HK1156561B - Plasmonic assisted systems and methods for interior energy-activation from an exterior source - Google Patents

Description

Plasmon-assisted system and method for internal energy activation from an external source

Cross Reference to Related Applications

This application relates to provisional application 60/910,663 entitled "METHOD OF TREATING CELL PROLIFERATION DISORDERS", filed on 8.4.2007 and non-provisional application 11/935,655 entitled "METHOD OF TREATING CELL PROLIFERATION DISORDERS", filed on 6.11.2007, each of which is incorporated herein by reference. This application relates to provisional application 61/035,559 entitled "SYSTEMS AND METHODS FOR INTERIORERGY-ACTIVATION FROM AN EXTERIOR SOURCE", filed on 11.3.2008, the entire contents of which are incorporated herein by reference. This application relates to provisional application 61/030,437 entitled "METHODS AND SYSTEMS FOR recording cellular components associated with photostutectatic tissue damage (PEPST) AND EXCITON-PLAMONENHANCED PHOTOTHERAPY (EPEP)" filed on 21.2.2008, which is incorporated herein by reference in its entirety. The present application relates to a non-provisional application 12/389,946 entitled "METHODS AND SYSTEMS FOR recording cellular components associated with a cellular component process Project (PEST) AND exterior-related-plossproject project (EPEP)" filed 2, 20, 2009, the entire contents of which are incorporated herein by reference. This application is related to and claims priority FROM provisional application 61/035,559 entitled "SYSTEMS and METHODS FOR interactive food FROM AN EXTERIOR SOURCE", filed on 11.3.2008, 35U.S. C.119(e), the entire contents of which are incorporated herein by reference. This application is related to and claims priority FROM provisional application 61/080,140 entitled "PLASMONICASSISTED SYSTEMS AND METHOD FOR NTERIONERGRY-ACTIVATION FROM AN EXTERIOR SOURCE", filed on 11.7.2008, 35U.S. C.119(e), the entire contents of which are incorporated herein by reference.

Background

Technical Field

The present invention relates to methods and systems for generating radiant energy inside a medium or object to alter the properties of the medium or object by exposure to the radiation.

Background

Currently, light (i.e., electromagnetic radiation from radio frequencies, ranging from visible to x-ray and gamma ray wavelengths) activated processes are used in a variety of industrial processes, from photoresist curing to ozone preparation on demand, sterilization, promotion of polymer crosslinking activation (e.g., in adhesives and surface coatings), and the like. Today, photo-activated processing is considered to have significant advantages over conventional approaches in these areas. For example, conventional sterilization by steam autoclaving or pasteurization in food processing may unduly overheat the medium to be sterilized. Thus, light activated curable coatings are one of the fastest growing areas in the coating industry. In recent years, this technology has entered many industrial fields such as optical fibers, photosensitive adhesives and pressure-sensitive adhesives, and automotive applications such as cured topcoats and curable powder coatings. The drive for this development is primarily the need to increase the productivity of the coating and curing process, since conventional non-light activated adhesives and surface coatings typically require: 1) solvent removal from the adhesive and surface coating to produce cure, and 2) time/temperature cure, which delays the manufacturing process and increases costs.

Furthermore, the use of solvent-based products in adhesive and surface coating applications is becoming increasingly unattractive due to increased energy costs and stringent regulations for solvent emissions into the environment. Both energy saving and ecological benefits are achieved by radiation curable adhesive and surface coating compositions. Radiation curable polymer crosslinking systems have been developed that do not require high oven temperatures and do not require expensive solvent recovery systems. In this system, radiation initiates free radical crosslinking in the presence of a generic photosensitizer.

However, in adhesive and surface coating applications, as well as in many other such applications, light activated processing is limited by the depth of penetration of light into the processing medium. For example, in water sterilization, a uv light source is combined with a shaking and stirring mechanism to ensure that any bacteria in the aqueous medium are exposed to uv light. In light-activated adhesive and surface coating processes, a major limitation is that the material to be cured must be directly exposed to light, including both type (wavelength or spectral distribution) and intensity. In adhesive and surface coating applications, any "masked" areas require a secondary cure history, such that the cure time is increased on non-masked areas and delayed due to the presence of a sealing surface layer through which subsequent curing must occur (i.e., known as the cocoon effect).

Disclosure of Invention

The present invention overcomes these problems and disadvantages of the prior art, as described in several embodiments below.

In one embodiment, a method and system for producing a change in a medium disposed within an artificial container is provided. The method (1) disposing at least one of a plasmonics agent and an energy modulation agent in proximity to a medium, and (2) applying initiation energy to the medium through the artificial container from an application initiation energy source. The applied initiation energy interacts with the plasmonics agent or energy modulation agent to produce a change in the medium, either directly or indirectly. The system comprises: an artificial container configured to contain a medium containing an energy modulation agent or a plasmonics agent. The system also includes an application initiation energy source configured to apply initiation energy to the medium through the artificial container to activate at least one of the plasmonics agent and the energy modulation agent.

In another embodiment, a method and system for curing a radiation-curable medium is provided. The method applies application energy throughout a composition comprising an uncured radiation-curable medium and at least one of a plasmonics agent and an energy modulation agent. The applied initiation energy interacts with the plasmonics agent or energy modulation agent to cure the medium directly or indirectly through polymerization of the polymer in the medium. The system includes an initiation energy source configured to apply initiation energy to the composition.

It is to be understood that both the foregoing general description and the following detailed description are exemplary, but are not restrictive, of the invention.

Drawings

A full appreciation of the invention and various attendant advantages thereof will be readily obtained as the same becomes better understood by reference to the following detailed description when considered in connection with the accompanying drawings, wherein:

FIG. 1 provides an exemplary electromagnetic spectrum in meters (1nm equals 10)^-9Rice);

FIG. 2 is a list of photoactivatable agents;

FIG. 3A is a schematic view of a system in which an initiation energy source is directed at a self-contained medium to produce a change in the medium, according to one embodiment of the invention;

FIG. 3B is a schematic diagram of a system according to another embodiment of the invention, wherein an initiation energy source is directed to a vessel containing a medium having an energy modulation agent dispensed within the medium;

FIG. 3C is a schematic diagram of a system according to another embodiment of the invention, wherein an initiation energy source is directed to a vessel containing a medium having an energy modulation agent sequestered within the medium;

FIG. 3D is a schematic diagram of a system according to another embodiment of the invention, wherein an initiation energy source is directed to a vessel containing a medium having an energy modulation agent isolated within the medium in a fluidized bed configuration;

FIG. 4 illustrates an exemplary computer system for implementing various embodiments of the present invention;

FIGS. 5A and 5B illustrate plasmonic nanostructures and their theoretical electromagnetic enhancement at different excitation wavelengths;

FIGS. 6A-6G provide representative embodiments of plasmonic photosensitive probes for use in the present invention;

fig. 7A and 7B are diagrams illustrating a plasmon enhancement effect of the present invention;

8A-8J illustrate representative embodiments of plasmonic active nanostructures;

FIGS. 9A-9C illustrate various embodiments of PEPST probes having linkers cleavable by photon irradiation;

FIG. 10 is a diagram of a "window" in an aqueous medium;

FIG. 11 illustrates one embodiment of an energy conditioner (or initiating energy converter/EEC) -Photoactivator (PA) system of the present invention;

12A-12F illustrate several embodiments of plasmonic photoactive energy modulator-PA probes;

FIGS. 13A-13B show the structure of various preferred embodiments of gold complexes exhibiting XEOL;

FIG. 14 shows the structure of another embodiment of a compound exhibiting XEOL, namely a tris-8-hydroxyquinoline-aluminum complex;

FIG. 15 shows a plasmon enhancement mechanism for a photoactive energy modulator-PA probe of the present invention;

FIGS. 16A-16C illustrate embodiments of PEPST energy modulator-PA systems with detachable linkages;

FIG. 17 shows one embodiment of a PEPST probe for dual plasmon excitation;

FIGS. 18A-18D provide a diagram of a sequence of use of encapsulated photosensitizers;

FIG. 19 is a graph showing Eu-doped XEOL in a BaFBr matrix;

FIG. 20 shows various embodiments of EIP probes of the invention;

FIGS. 21A-21B show other embodiments of EIP probes of the invention;

FIGS. 22A-22C show other embodiments of schematic designs of EIP probes;

figures 23A and 23B show various embodiments of basic EPEP probes;

FIG. 24 shows one embodiment of an EPEP probe with NPs, NWs and NR;

FIG. 25 shows one embodiment of an EPEP probe with NPs, NWs, NRs and biological receptors;

FIG. 26 shows one embodiment of an EPEP probe with NPs and multiple NWs;

FIG. 27 shows one embodiment of a sterilization system of the present invention;

FIG. 28 shows another embodiment of the present sterilization system utilizing plasmons;

FIG. 29 illustrates another embodiment of the sterilization system of the present invention utilizing a photosensitive material;

FIG. 30 illustrates another embodiment of a sterilization system of the present invention utilizing a photosensitive material and a dielectric medium;

FIG. 31 illustrates another embodiment of a sterilization system of the present invention utilizing an X-ray energy conversion agent with embedded metal nanoparticles that function as plasmons;

FIG. 32 shows another embodiment of the sterilization system of the present invention utilizing embedded metal nanoparticles introduced on the inside of a re-enterable (re-enterant) structure through which the medium to be sterilized will flow;

FIG. 33 illustrates another embodiment of the present sterilization system utilizing an X-ray energy conversion agent having embedded metal nanoparticles illustrated in FIG. 31 comprising an inner layer of a container through which a medium to be sterilized will flow;

fig. 34 shows another embodiment of the sterilization system of the present invention utilizing embedded metal nanoparticles introduced on the inside of a re-enterable wall structure through which the medium to be sterilized will flow;

FIG. 35 shows another embodiment of a sterilization system of the present invention utilizing chemical receptors on the interior of the container through which the medium to be sterilized will flow;

FIG. 36 shows another embodiment of a sterilization system of the present invention utilizing embedded metal nanoparticles in one layer and chemical receptors in a further inner layer of the interior of the container through which the medium to be sterilized will flow;

FIG. 37 shows another embodiment of a sterilization system of the present invention that utilizes a photosensitive material and a chemical receptor on the interior of the container through which the medium to be sterilized will flow;

FIG. 38 shows another embodiment of a sterilization system of the present invention that utilizes a photosensitive material, a dielectric layer incorporating embedded metal nanoparticles, and chemical receptors on the surface of a probe inside a container where the medium to be sterilized will flow;

FIG. 39 illustrates one embodiment of a sterilization probe system of the present invention;

FIG. 40 illustrates another embodiment of a sterilization probe system of the present invention that utilizes a dielectric layer incorporating embedded metal nanoparticles;

FIG. 41 illustrates another embodiment of a sterilization probe system of the invention that utilizes an X-ray energy conversion agent and chemical receptors on the surface of the probe inside the container through which the medium to be sterilized will flow;

FIG. 42 shows another embodiment of a sterilization probe system of the present invention utilizing an X-ray energy conversion agent and an additional dielectric layer bonded to embedded metal nanoparticles on the probe surface inside the container where the medium to be sterilized will flow through;

FIG. 43 shows another embodiment of a sterilization system of the present invention utilizing a paramagnetic core material;

FIGS. 44A-44G illustrate different plasmonic probes of the present invention.

Detailed Description

The present invention discloses a novel method for effecting, specific and enabling alteration of a mediator activity.

In general, the present invention provides a method of producing a change in a medium after generation of radiant light inside the medium. In the method, an initiation energy source provides initiation energy through the medium and induces internal radiation to produce a desired effect in the medium.

In one embodiment, the initiation energy source is applied directly or indirectly to the medium. In the context of the present invention, the expression "indirect application" (or different variations of this expression etc.) when referring to the application of initiation energy means: the initiation energy penetrates into the medium below the surface of the medium and reaches the activatable agent or energy modulation agent inside the medium. In one embodiment, the initiation energy interacts with a previously supplied energy modulation agent and then activates the activatable agent.

While not intending to be bound by any particular theory or in any way, the theoretical discussion and definition of the following scientific principles are provided to assist the reader in understanding and appreciation of the present invention.

As used herein, an "activatable agent" is an agent that is typically present in an inactive state in the absence of an activation signal. When an agent is activated by an activation signal under activation conditions, the agent is capable of producing a desired pharmacological, cellular, chemical, electrical, or mechanical effect (i.e., a predetermined change) in a medium. For example, when a photocatalyst is irradiated with visible or ultraviolet light, these agents cause polymerization and "curing" of the photosensitive adhesive.

Signals that may be used to activate the respective agent may include, but are not limited to: photons of a particular wavelength (e.g., x-rays or visible light), electromagnetic energy (e.g., radio frequency or microwave), thermal energy, acoustic energy, or any combination thereof. Activation of an agent may be described simply as delivering a signal to the agent or may also require a set of activation conditions. For example, the activatable agent, such as a photosensitizer, may be activated by UV-A radiation (e.g., by UV-A radiation generated internally in the medium). Once activated, the reagent in the activated state may directly produce the predetermined change.

When other conditions may be required for activation, merely transmitting the activation signal may not be sufficient to produce the predetermined change. For example, a photoactive compound that achieves its effect by binding a structure in its active state may need to be in physical proximity to the target structure when transmitting an activation signal. For such activatable agents, delivery of an activation signal under non-activating conditions does not produce the desired effect. Some examples of activation conditions may include, but are not limited to: temperature, pH, location, medium status, and the presence or absence of co-factors.

The choice of activatable agent depends largely on many factors such as the desired change, the desired form of activation, and the physical and biochemical constraints that can be imposed. Exemplary activatable agents may include, but are not limited to: agents that are activated by photonic energy, electromagnetic energy, acoustic energy, chemical or enzymatic reactions, thermal energy, microwave energy, or any other suitable activation mechanism.

When activated, the activatable agent may produce a change, including but not limited to: increasing the activity of an organism, fermentation, decreasing the activity of an organism, apoptosis, metabolic pathway alteration, sterilization of a medium, cross-linking polymerization and solidification of a medium, or low temperature pasteurization of a medium.

The mechanism by which the activatable agent can achieve its desired effect is not particularly limited. Such mechanisms may include direct action on the intended target as well as indirect action via altering biochemical pathways. In one embodiment, the activatable agent is capable of chemically binding to an organism in the medium. In this embodiment, the activatable agent is exposed in situ to activation energy emitted by an energy modulation agent, which in turn receives energy from an initiation energy source.

Suitable activatable agents include, but are not limited to: photoactive reagents, acoustic-active agents (sono-active), thermal-active agents, and radio frequency/microwave-active agents. The activatable agent may be a small molecule; biomolecules such as proteins, nucleic acids, or lipids; a supramolecular assembly; a nanoparticle; or any other molecular entity capable of producing a predetermined activity upon activation.

The activatable agent may be obtained from natural or synthetic sources. Any such molecular entity that can be activated by a suitable activation signal source to produce a predetermined cellular alteration can be advantageously employed in the present invention.

Suitable photoactive agents include, but are not limited to: psoralens and psoralen derivatives, pyrenyl cholesterol oleate, acridine, porphyrins, fluorescein, rhodamine, 16-diazocortisone, ethidine, transition metal complexes of bleomycin, transition metal complexes of deglycobleomycin, organo-platinum complexes, alloxazines such as 7, 8-dimethyl-10-ribityl isoalloxazine (riboflavin), 7, 8, 10-trimethylisoalloxazine (photopigment), 7, 8-dimethylisoalloxazine (photopigment), isoalloxazine-adenine dinucleotide (flavin adenine dinucleotide [ FAD ]), alloxazine mononucleotides (also known as flavin mononucleotide [ FMN ] and riboflavin-5-phosphate), vitamin K, vitamin L, their metabolites and precursors, and naphthoquinones, naphthalenes, naphthols, and derivatives thereof having a planar molecular conformation, porphyrins, dyes such as neutral red, methylene blue, acridine, toluidine, riboflavin (acriflavine hydrochloride) and phenothiazine derivatives, coumarins, quinolones, quinones, and anthraquinones, aluminum phthalocyanine tetrasulfonate (111), hematoporphyrins and phthalocyanines, and compounds which preferentially adsorb to nucleic acids without affecting or with little effect on proteins. The term "alloxazine" includes isoalloxazines.

Endogenous derivatives include synthetically derived analogs and homologs of endogenous photoactivated molecules, which may have or lack lower (1-5 carbon) alkyl or halogen substituents of the photosensitizer from which they are derived, and which retain functionality and are substantially non-toxic. Endogenous molecules are themselves non-toxic and do not produce toxic photoproducts after light irradiation.

FIG. 1 provides an exemplary electromagnetic spectrum in meters (1nm equals 1 nanometer). As used herein, an "energy modulation agent" refers to an agent that is capable of receiving energy input from a source and then re-emitting a different energy to a receiving target. The intermolecular energy transfer can be performed in various ways. The energy form may be electrical, thermal, electromagnetic, kinetic or chemical in nature. Energy may be transferred from one molecule to another (intermolecular transfer) or from one part of a molecule to another part of the same molecule (intramolecular transfer). For example, the modulating agent may receive electromagnetic energy and re-emit the energy as thermal energy.

Table 1 in fig. 2 provides a list of photoactivatable agents that can be used as primary or secondary internal light sources. For example, the photoactivatable agent may be a receptor that induces emission of X-rays from the nanoparticle (described below) and, in turn, secondary light. In some media, it may be that the excitation wavelengths in table 1 are transparent to the particular medium and the emission wavelengths are highly absorbed (due to, for example, molecular or solid state bandgap transitions). In this case, the photoreactive reagents in table 1 may be the primary source for internal light generation.

In various embodiments, the energy modulation agent receives higher energy (e.g., x-rays) and re-emits at lower energy (e.g., UV-a). Some modulators may have very short energy retention times (on the order of femtoseconds, e.g., fluorescent molecules), while others may have very long half-lives (on the order of minutes to hours, e.g., luminescent or phosphorescent molecules). Suitable energy modulation agents include, but are not limited to: biocompatible fluorescent metal nanoparticles, fluorescent dye molecules, gold nanoparticles, water-soluble quantum dots encapsulated by polyamidoamine dendrimers, luciferase, biocompatible phosphorescent molecules, combined electromagnetic energy harvesting molecules (harvetter molecules) and lanthanide chelates capable of intense luminescence. Generally, energy modulation agents cause a photoreactivity change in the medium and are not used for the purpose of specifically heating the medium.

A number of exemplary applications are shown in the following embodiments.

Modulators may also be combined with carriers for targeting purposes. For example, biocompatible molecules such as fluorescent metal nanoparticles emitting the UV-A band or fluorescent dye molecules may be selected as energy modulation agents. The energy modulation agent may preferably be directed to the desired location by systemic administration into the medium. For example, the UV-A emission energy modulation agent may be distributed in the medium by physical insertion and/or mixing, or by associating the UV-A emission energy modulation agent with a specific carrier (e.g., a lipid, chitin or chitin derivative, chelate or other functionalized carrier capable of focusing the UV-A emission source in a specific target region of the medium).

Further, the energy modulation agents can be used alone or as a series of two or more energy modulation agents such that the energy modulation agents provide an energy cascade. Thus, a first energy modulation agent in a cascade may absorb the activation energy, converting it to a different energy, which is then absorbed by a second energy modulation agent in the cascade, and so on until the end of the cascade is reached, the last energy modulation agent in the cascade emitting the energy necessary to activate the activatable agent. Alternatively, more than one energy modulation agent in a cascade may also activate other activatable agents.

While the activatable agent and the energy modulation agent may be different and separate, it is to be understood that the two agents need not be separate and separate entities. In fact, the two agents may be related to each other via a number of different configurations. When two reagents are independent of each other and can move separately from each other, they typically interact with each other via diffusion and accidental encounters within a common surrounding medium. When the activatable agent and the energy modulation agent are not separated, they may be combined into a single entity.

The initiation energy source can be any energy source capable of providing energy at a level sufficient to directly activate the activatable agent or to provide an input to the energy modulation agent necessary to emit activation energy for the activatable agent (indirect activation). Preferred initiation energy sources include, but are not limited to: ultraviolet lamps such as UV-a and UV-B lamps, halogen lamps, fiber optic lines, light needles, endoscopes, self-ballasted mercury vapor lamps, ballasted HID lamps, and any device capable of producing x-rays, y-rays, gamma rays, or an electron beam.

In one embodiment, the initiation energy is capable of passing completely through the medium. In the context of the present invention, the expression "capable of passing completely through the medium" is used to denote any distance required for energy to be able to pass through the container to activate the activatable agent within the medium. The actual applied energy need not pass completely through the medium, so long as it is capable of allowing penetration to any desired distance that activates the activatable agent. The type of energy source selected depends on the medium itself. Exemplary initiation energy sources capable of passing completely through a passing medium include, but are not limited to, x-rays, gamma rays, electron beams, microwaves, and radio waves.

In one embodiment, the initiation energy source may be radio wave emitting nanotubes such as those described by K.Jensen, J.Weldon, H.Garcia and A.Zettl of the University of California at Berkeley physical line (see http:// socrantates. Berkeley. edu/. about. argon/nanoradioradio. html, which is incorporated herein by reference in its entirety). These nanotubes can be introduced into a medium and preferably combined with an activatable agent or an energy modulation agent or both, such that upon application of initiation energy, the nanotubes can receive initiation energy (preferably radio waves) and then emit radio waves in close proximity to the activatable agent or to the energy modulation agent, which then causes activation of the activatable agent. In such an embodiment, the nanotubes actually act as a radio wave focusing or amplifying device in close proximity to the activatable agent or energy modulation agent.

Alternatively, the energy-emitting source can be an energy modulation agent that emits energy in a form suitable for absorption by a transfer agent or for direct interaction with a component of the medium. For example, the initiation energy source may be acoustic energy, and one energy modulation agent may be capable of receiving the acoustic energy and emitting photonic energy (e.g., sonoluminescent molecules) that is received by another energy modulation agent capable of receiving the photonic energy. Other examples include transfer agents that receive x-ray wavelength energy and emit UV wavelength energy, preferably UV-a wavelength energy. As described above, a plurality of such energy modulation agents may be used to form a cascade, whereby energy from an initiation energy source is transferred via a series of energy modulation agents to activate an activatable agent.

The photoactivatable agent may be excited by an energy source to an activation energy state capable of producing a predetermined desired change by a mechanism such as irradiation, resonance energy transfer, exciton migration, electron injection, or chemical reaction. One advantage is that the wavelength of the emitted radiation can be used to selectively excite more than one photoactivatable agent or energy modulation agent capable of exciting more than one photoactivatable agent. The energy modulation agent is adapted to be excited at a wavelength and energy that does not cause a change in the medium or changes very little.

In another embodiment, the photoactivatable agent is excited via resonance energy transfer. Resonance Energy Transfer (RET) is an energy transfer mechanism between two molecules with overlapping emission and absorption bands. Electromagnetic emitters are capable of converting the arriving wavelength to a longer wavelength. For example, the UV-B energy absorbed by the first molecule can be transferred to a UV-a emitting molecule in close proximity to the absorbing UV-B molecule via dipole-dipole interactions. One advantage is that multiple wavelengths of emitted radiation can be utilized to selectively excite one or more photoactivatable agents or energy modulation agents capable of exciting the one or more photoactivatable agents. With RET, the energy modulation agent is preferably excited at a wavelength and energy that does not affect or minimally affects the surrounding medium, while energy from more than one energy modulation agent is transferred to the photoactivatable agent, for example, by frester resonance energy transfer.

Alternatively, the material that absorbs the shorter wavelengths may be selected to provide RET to non-emissive molecules that have an absorption band that overlaps with the emission band of the transfer molecule. Alternatively, phosphorescence, chemiluminescence, or bioluminescence may be used to transfer energy to the photoactivatable molecules.

Alternatively, a source of initiation energy may be applied to the medium. In the context of the present invention, applying an initiation energy source refers to applying an agent that itself generates initiation energy, such that the agent is allowed to reach a target structure within the medium. Application may take any form. Furthermore, in this embodiment, the initiation energy source may be of any form, including but not limited to: tablets, powders, liquid solutions, liquid suspensions, liquid dispersions, gases or vapors, and the like. In this embodiment, the initiation energy source includes, but is not limited to: chemical energy sources, nano-emitters, nano-chips, and other nanomachines that generate and emit energy at a desired frequency.

Recent advances in nanotechnology provide examples of a variety of devices that generate or emit energy at the nanoscale, such as the molecular switching (or molecularing) work of doctor Keith pharman, EC Research and Development Project, or the work of Cornell et al (1997), which describes a nanomachine-based structure surrounding an ion channel switch of size only 1.5nm, using ion channels formed in artificial membranes by two gramicidin molecules: one gramicidin molecule is attached to the gold electrode in the lower layer of the membrane and one gramicidin molecule is attached to the biological receptor such as an antibody or nucleotide in the upper layer. When the receptor captures a target molecule or cell, the ion channel is disrupted, its conductivity is reduced, and thus a biochemical signal is converted into an electrical signal. These nanodevices may also be combined with the invention to provide targeting of target cells to directly deliver the initiation energy at the desired location.

In another embodiment, the invention comprises the application of an activatable agent with a source of chemical energy, such as chemiluminescence, phosphorescence or bioluminescence. The chemical energy source may be a chemical reaction between two or more compounds or may be caused by activation of a chemiluminescent, phosphorescent or bioluminescent compound outside or within the medium with a suitable activation energy, which allows activation of the activatable agent in the medium. The application of the activatable agent and the chemical energy source may be performed sequentially in any order or may be performed simultaneously.

In the case of this particular chemical energy source, the application of the chemical energy source may be carried out after external activation of the medium, for example for certain types of phosphorescent materials, the lifetime of the energy emission is at most a few hours.

When the molecules absorb the excitation light, electrons undergo transition from the ground state to an excited state of the electrons. The electron-induced energy is then attenuated via radiative emission (luminescence) and non-radiative decay channels. When the molecule absorbs the initiation energy, it is driven from S₀Some vibrational level, i.e. S, lifted to one of the excited singlet states₁，...，S_nS in (1)_n. In condensed medium (tissue), S _nIn the state of 10^-13To 10^-11Rapid deactivation within S via Vibrational Relaxation (VR) processes to ensure that they are at the lowest possible vibrational level S_n. Since the VR process is faster than the electronic transition, any excess vibrational energy is rapidly lost as the molecule deactivates to the lower vibrational level of the corresponding electronic excited state. This excess VR energy is released as thermal energy to the surrounding medium. From S_nState, rapid deactivation of molecules via Internal Conversion (IC) processes to lower electronic states of equi-energetic vibrational levels such as S_n-1. An IC process is a transition between the same multiple states.

The molecule is then deactivated via the VR process to the lowest electron vibrational level S_n-1. Through a series of VR processes followed by IC processes, the molecule is rapidly inactivated to the ground state S₁. This process generates excess VR and IC energy that is released as thermal energy into the surrounding medium, resulting in light absorptionThe local environment surrounding the drug molecule is overheated. The heat generated causes local changes in the medium.

In various embodiments, the light absorbing substance can include natural chromophores in tissue or exogenous dye compounds such as indocyanine green, naphthalocyanine, and porphyrins coordinated to transition metals, metal nanoparticles, and metal nanoshells. However, the natural chromophore absorption is very low. The choice of exogenous photothermal agents is made based on their strong absorption cross-section and efficient photo-thermal conversion. This feature significantly minimizes the amount of laser energy required to cause local changes in the medium.

One problem associated with the use of dye molecules is their photobleaching under laser irradiation. Therefore, nanoparticles such as gold nanoparticles and nanoshells have recently been used. The promising role of nanoshells in medical applications has been elucidated [ Hirsch, l.r., Stafford, r.j., Bankson, j.a., sersen, s.r., river, b., Price, r.e., Hazle, j.d., Halas, n.j., and West j.l., Nanoshell-mediated near-isolated thermal therapy of vascular magnetic resonance regulation. 13549-13554, which is incorporated by reference herein in its entirety. The use of plasmon-enhanced photothermal properties of metal nanoparticles for photothermal therapy has been reviewed (Xiaohua Huang & prashan k. jain & Ivan h. el-Sayed mostab a. el-Sayed, "plasma photothermal therapy (ppt) using gold nanoparticles," Lasers in Medical Science, month 8 2007) and incorporated herein by reference in its entirety.

Another example is nanoparticles or nanoclusters into which certain atoms can be introduced such that they are capable of resonance energy transfer over a relatively large distance, for example over a distance of more than 1 nanometer, more preferably more than 5 nanometers, further preferably at least 10 nanometers. Functionally, the resonant energy transfer can have a sufficiently large "Foerster" distance (R) ₀) Such that the nanoparticles in a portion of the medium are capable of activating activation of a photoactivatable agent disposed in a distal portion of the medium, provided that the distance does not substantially exceed R₀And (4) finishing. For example, gold nanospheres having a size of 5 gold atoms have recently been indicated to have an emission band in the ultraviolet range.

Any photoactivatable agent may be exposed to a source of initiation energy provided in the medium. The photoactive reagent may be directed to the acceptor site by a support having a strong affinity for the acceptor site. In the context of the present invention, "strong affinity" is preferably the equilibrium dissociation constant K_iAt least in the nanomolar nM or higher range. The carrier may be a polypeptide and may, for example, form a covalent bond with a photoactive reagent. Alternatively, the photoactive reagent may have a strong affinity for the target molecule in the medium without binding to the support.

In one embodiment, multiple sources for supplying electromagnetic radiation energy or energy transfer are provided by providing more than one molecule to the medium. The molecules may emit the excitation radiation in the correct wavelength band to excite the photoactivatable agent, or the molecules may transfer energy directly to the photoactivatable agent through resonance energy transfer or other mechanisms or indirectly via a cascade effect via other intermolecular interactions.

In another embodiment, the biocompatible light-emitting source that emits the UV-A band is selected, for example, a fluorescent metal nanoparticle or a fluorescent dye molecule. UV-a and other UV bands are known to be effective as bactericides.

In one embodiment, the UV-a emitting source is a gold nanoparticle comprising clusters of 5 gold atoms, such as a polyamidoamine dendrimer encapsulated water soluble quantum dot. Clusters of gold atoms can be formed, for example, by slow reduction of gold salts (e.g., HAuCl)₄Or AuBr₃) Or other encapsulated amines. One advantage of such gold nanoparticles is the Forster distance (i.e., R)₀) And, increasingly, it can be greater than 100 angstroms. The formula for determining the Forster distance is significantly different from the formula for molecular fluorescence, which is limited to use within distances of less than 100 angstroms. Gold nanoparticles are believed to be governed by the nanoparticle surface to dipole equation, and 1/R⁴Distance dependent rather than 1/R⁶The distances are related. Example (b)This allows, for example, energy transfer from the cytoplasm to the nucleus between the metal nanoparticle and the photoactivatable molecule.

In another embodiment, a UV or luminescent luciferase is selected as the emission source for exciting the photoactivatable agent. Luciferases can be bound to molecules and then oxidized by other molecules to excite luminescence at a desired wavelength. Alternatively, a phosphorescent emitter source may be used. Phosphorescent materials may have longer relaxation times than fluorescent materials because relaxation of the triplet state facilitates forbidden energy state transitions, energy is stored in the excited triplet state, and only a limited number of quantum mechanical energy transfer processes are available to return to the lowest energy state. The energy emission is delayed or extended by fractions of a second to hours. Otherwise, the energy emitted during phosphorescent relaxation is different from fluorescence, and the wavelength range can be selected by selecting a particular phosphor.

In another embodiment, a combined electromagnetic energy harvesting molecule is designed, such as the combined light harvester disclosed in j.am.chem.soc.2005, 127, 9760-9768, which is incorporated herein by reference in its entirety. By combining a set of fluorescent molecules in a molecular structure, a resonance energy transfer cascade can be utilized to collect broadband electromagnetic radiation that results in emission of narrow-band fluorescent energy. Further energy resonance transfer excites the photoactivatable molecules by pairing the combined energy harvester with the photoactivatable molecules when they are close to the excited combined energy harvesting molecules. Another example of a capture molecule is disclosed in fig. 4 of the master paper by Worcester polytechnical institute, m.o. guler (5/18 2002) "single let-single triple Energy Transfer in bichromotic Cyclic Peptides", the entire content of which is incorporated herein by reference.

In another embodiment, the stokes shift of a light emitting source or a series of light emitting sources in a stepped arrangement is selected to convert shorter wavelength energy, such as X-rays, into longer wavelength fluorescent emission, such as light or UV-a, which is used to excite photoactivatable molecules in a medium.

In another embodiment, the photoactivatable agent may be a photocaged complex having an activating agent contained within the photocage (which may be a cytotoxic agent if cytotoxicity is desired, or may be an activatable agent). In various embodiments, when the activating agent is a cytotoxic agent, the photocage molecule releases the cytotoxic agent into the medium where it can attack a "target" substance that is not beneficial in the medium. The activator may be surrounded by other molecules that prevent it from binding to a particular target, thereby masking its activity. When the photocage complex is photoactivated, the enclosure is reduced, exposing the activator. In such a photocage complex, the photocage molecules may be photoactive (i.e., when photoactivated, causing them to separate from the photocage complex, thereby exposing the internal activator), or the activator may be a photoactivatable agent (which when photoactivated causes the photocage to decrease), or both the photocage and the activator may be photoactivated using the same or different wavelengths. Suitable light cages include those disclosed by Young and Deiters in "Photochemical control of Biological Processes", org. biomol chem., 999-1005 (2007) and "Photochemical Hammerhead Ribozyme Activation", bioorganic chemical Letters, 16(10), 2658-2661 (2006), the entire contents of which are incorporated herein by reference.

The work shows that: the amount of singlet oxygen required to cause cell lysis and thus cell death was 0.32X 10^-3More than or equal to 10 mol/L⁹More than one singlet oxygen molecule per cell. In one embodiment of the invention, the level of singlet oxygen production upon activation, caused by the initiation energy or the activatable agent, is sufficient to cause a change in the medium, wherein the medium becomes free of any microorganisms. Microorganisms include, but are not limited to, bacteria, viruses, yeasts, or fungi. For this purpose, a sufficient amount of singlet oxygen as described above can be used for sterilizing the medium.

For example, medical bottle caps require sterilization between the bottom cap material and the adhesive sealing material that contacts the bottom of the medical bottle. Since a steam autoclave is not sufficient for this purpose, one embodiment of the present invention uses UV-luminescent particles contained in an adhesive layer when a sealing material is applied to a bottle cap. X-ray irradiation can then cure the adhesive and generate ultraviolet radiation inside the adhesive medium for direct sterilization or generate singlet oxygen or ozone for biological sterilization.

Activatable agents and derivatives thereof, as well as energy modulation agents, may be incorporated into compositions suitable for delivery of a particular medium. The composition may also comprise at least one additive having a complementary effect with the medium, such as a lubricant or sealant.

The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), and suitable mixtures thereof. Suitable fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants.

Referring to fig. 3A, an exemplary system according to one embodiment of the invention may have an initiation energy source 1 directed at a medium 4. The activatable agent and the energy modulation agent 3 are dispersed throughout the medium 4. The initiation energy source 1 may also be connected via a network 8 to a computer system 5 capable of directing the delivery of the initiation energy. In various embodiments, energy modulation agent 3 is an encapsulated energy modulation agent 6, such as a silica encapsulated energy modulation agent as shown in fig. 3A. As shown in fig. 3A, the initiation energy 7 in the form of radiation from the initiation energy source 1 passes through the entire medium 4. Computer system 5 is described more fully below with reference to fig. 4. As described in more detail below, the initiation energy source 1 may be an external energy source or an energy source located at least partially within the medium 4. As described in more detail below, the activatable agent 2 and/or the energy modulation agent 3 may include a plasmonics agent that boosts the applied energy or energy emitted from the energy modulation agent 3 to produce a change in the medium, either directly or indirectly.

In various embodiments, the initiation energy source 1 may be a linear accelerator equipped with image-guided computer control capability to deliver a precisely collimated beam of radiation to preselected coordinates. Of such linear acceleratorsOne example is SmartBeam from the Varian medical systems, Inc. Palo Alto California^TMIMRT (intensity modulated radiation therapy) systems. In other embodiments, the initiation energy source 1 can be a commercially available component of an X-ray machine or a non-medical X-ray machine. X-ray machines producing X-rays of 10 to 150keV are available on the market. For example, the General Electric Definium series or the Siemens MULTIX series are two examples of commonly used X-ray machines designed for the medical industry, while the EaglePack series from Smith Detection is one example of a non-medical X-ray machine. Thus, the invention is capable of performing its intended function when used in conjunction with commercial X-ray equipment.

In other embodiments, the initiation energy source 1 may be a radio frequency or microwave source that emits radio waves of a frequency that pass through the medium and initiate or generate secondary radiant energy emissions within the medium by interacting with the energy modulation elements 6 in the medium. In other embodiments, the initiation energy source 1 can be an ultraviolet, visible, Near Infrared (NIR), or Infrared (IR) emitter that emits at a frequency that passes through the medium 4 and initiates or generates secondary radiant energy emission within the medium 4 by interacting with the energy modulation element 6 in the medium.

Fig. 3B is a schematic diagram of another system according to another embodiment of the invention, wherein the initiation energy source 1 of fig. 3A is directed to an energy modulation element 6, and the energy modulation element 6 is disposed adjacent to a fluid medium 4 (e.g., a liquid or other fluid-like medium) and inside a container 9. The container 9 is made of a material that is "transparent" to the radiation 7. For example, a plastic, quartz, glass, or aluminum container may be sufficiently transparent to X-rays, while a plastic or quartz or glass container may be transparent to microwave or radio frequency light. The energy modulation elements 6 may be uniformly dispersed throughout the medium, or may be isolated in different portions of the medium, or further physically separated from the medium by an encapsulating structure 10. The supply 11 supplies the medium 4 into the container 9.

Alternatively, as shown in fig. 3C, the luminescent particles may be present in the encapsulating structure 10 in a medium. In one embodiment, the encapsulating structure 10 is aligned to be in line with the direction of the external initiation energy source 1. In this configuration, each encapsulating structure 10 has its own "line of sight" to the external initiation energy source 1 shown in fig. 3C, without being obscured by other encapsulating structures 10. In other embodiments, the encapsulating structure 10 is not aligned in this direction, but is aligned perpendicular to the direction shown in fig. 3C or may be disposed arbitrarily. In fact, the supply of fluid medium 4 itself may be used to agitate the enclosing structure 10 and mix the fluid medium 4 within the container 9.

The system of fig. 3C may also be used without an energy modulation agent. In this embodiment, the energy of the initiation energy source 1 may, for example, be adapted to drive a physical, chemical and/or biological process in the fluid medium 4. The plasmonics agent contained in the encapsulating structure 10 effectively amplifies light from the initiation energy source 1 due to its interaction with the medium 4. In one aspect of the invention, the initiation energy source 1 can be an ultraviolet light source, as with many conventional ultraviolet sterilization systems, and the encapsulating structure 10 of fig. 3C is a light rod that directs ultraviolet light from an external source to the interior region of the medium 4. In one aspect of the invention, the initiation energy source 1 may even be disposed within the medium and may be an ultraviolet light source, as in many conventional UV sterilization systems.

Fig. 3D is a schematic diagram of a system according to another embodiment of the invention, wherein an initiation energy source is directed to a vessel containing a medium having an energy modulation agent isolated within the medium in a fluidized bed 20 configuration. The fluidized bed 20 includes enclosing structures 10 configured such that fluid to be treated passes between the enclosing structures 10. As described herein, the encapsulated structure 10 may comprise both an energy modulation agent and a plasmonics agent.

In other embodiments of the invention, robotic manipulation devices may also be included in the systems of fig. 3A, 3B, 3C and 3D to deliver and disperse the energy modulation elements 6 in the medium 4 or to move old products out of the system and introduce new products to be processed into the system.

In the present invention, the intermolecular energy transfer can be performed in various ways. The energy form may be electrical, thermal, electromagnetic, kinetic or chemical in nature. The energy may be adjusted upward to emit energy from the energy modulation agent that is higher than the input initiation energy, or may be adjusted downward to emit energy from the energy modulation agent that is lower than the input initiation energy. Energy can be transferred from one molecule to another (intermolecular transfer) or from one part of a molecule to another part of the same molecule (intramolecular transfer). For example, the modulating agent may receive electromagnetic energy and re-emit the energy in a different energy form. In various embodiments, the energy modulation agent receives higher energy (e.g., x-rays) and re-emits lower energy (e.g., UV-A). In other embodiments, the energy modulation agent receives lower energy (e.g., infrared or near infrared) and emits higher energy (e.g., visible or ultraviolet). The process of energy transfer is also known as molecular excitation. Some modulators may have very short energy retention times (about fs-ns, e.g., fluorescent molecules), while others may have very long half-lives (about seconds-hours, e.g., inorganic luminescent or phosphorescent molecules). Suitable energy modulation agents include, but are not limited to: metal nanoparticles or biocompatible metal nanoparticles, metals coated or uncoated with a biocompatible outer layer, chemiluminescent molecules with enhanced light emission by microwave activation, fluorescent dye molecules, gold nanoparticles, water-soluble quantum dots encapsulated by polyamidoamine dendrimers, luciferase, biocompatible phosphorescent molecules, biocompatible fluorescent molecules, biocompatible scattering molecules, combined electromagnetic energy harvesting molecules, and lanthanide chelates capable of intense luminescence. A number of exemplary uses of these are described.

The modulator may also be combined with a carrier for targeted use. For example, biocompatible molecules such as fluorescent metal nanoparticles emitting the UV-A band or fluorescent dye molecules may be selected as energy modulation agents.

The energy modulation agent may preferably be directed to the desired site (e.g., proximate to the photoactive material such as a photocatalyst or photoinitiator) by predistributing the energy modulation agent in the medium to be exposed to the activation energy. For example, the UV-A luminescent energy modulation agent may be enriched at the junction where the two parts are bonded together, by physical insertion and/or mixing, or by combining the UV-A luminescent energy modulation agent with a photoactivatable resin.

Furthermore, the energy modulation agents can be used alone or as a series of two or more energy modulation agents, wherein the energy modulation agents provide an energy cascade. Thus, a first energy modulation agent in a cascade may absorb the activation energy, converting it to a different energy, which is then absorbed by a second energy modulation agent in the cascade, and so on until the end of the cascade is reached, the last energy modulation agent in the cascade emitting the energy required to activate the photoactivatable agent in the medium.

While the photoactivatable agent and the energy modulation agent may be different and separate, it is to be understood that the two agents need not be separate and separate entities. In fact, the two agents may be related to each other via a number of different configurations. When the two reagents are independent of each other and move separately, they typically interact with each other via diffusion and accidental encounters within a common surrounding medium. When the photoactivatable agent and the energy modulation agent are not separated, they may be combined into one single entity.

The initiation energy source can be any energy source capable of providing energy at a level sufficient to directly activate the activatable agent or to provide the energy modulation agent with the input required to emit activation energy for the activatable agent (indirect activation). Preferred activation energy sources include, but are not limited to: UV-a lamps or fiber optic lines, light needles, endoscopes, and linear accelerators that generate x-rays, gamma rays, or electron beams. The energy used may be of any type including, but not limited to, gamma rays, x-rays, ultraviolet rays, near ultraviolet rays, visible light, near infrared rays, microwaves, radio waves, and the like. In a preferred embodiment, the initiation energy is capable of penetrating the object completely. Exemplary initiation energy sources capable of fully penetrating an object include, but are not limited to: x-rays, gamma rays, electron beams, microwaves and radio waves.

Plasmon and fundamental principles of enhanced electromagnetic fields

The plasmon enhancement principle is theoretically based on the enhancement mechanism of the electromagnetic field effect. These theories are set forth herein in advance to illustrate the invention and are not necessarily intended to limit any embodiment to this particular theory. There are two main sources of electromagnetic enhancement: (1) first, the laser electromagnetic field is enhanced due to the field increase caused by the polarization of the metal particles; (2) the amplified emission (luminescence, raman, etc.) field due to molecular radiation is enhanced, which further polarizes the metal particles, thereby further amplifying the raman/luminescence signal as an antenna.

Electromagnetic enhancement is divided into two main types: a) enhancement only in the presence of a radiation field, and b) enhancement even without a radiation field. The first type of enhancement is further divided into several processes. Plasmon resonances on the substrate surface, also known as surface plasmons, have a significant contribution to electromagnetic enhancement. One effective plasmonic active substrate includes nanostructured metal particles, protrusions, or rough surfaces of metal materials. Incident light illuminating these surfaces excites conduction electrons in the metal and causes excitation of surface plasmons resulting in raman/luminescence enhancement. At plasmon frequencies, the metal nanoparticles (or other nanostructure roughening structures) become polarized, resulting in large field-induced polarization and thus large local fields on the surface. These local fields cause an increase in luminescence/raman emission intensity, which is proportional to the square of the applied field at the molecule.

As a result, the effective electromagnetic field experienced by analyte molecules on these surfaces is significantly larger than the actual applied field. The field leaves the surface with 1/r³And decreases. Thus, in an electromagnetic model, the luminescent/raman-activated analyte molecules do not have to be in contact with the metal surface, but can be located anywhere within the enhanced local field range, which can polarize the molecules. Dipole vibration at the wavelength λ of raman or luminescence may in turn polarize the metallic nanostructure, and if λ resonates with the local surface of the plasmon, the nanostructure may enhance the observed emitted light (raman or luminescence).

Thus, the plasmonically activated metal nanoparticles also exhibit strongly enhanced visible and near infrared light absorption, with several orders of magnitude improvement in intensity compared to conventional laser phototherapy agents. The use of plasmonic nanoparticles as highly enhanced light absorbing agents thus provides an alternative and efficient strategy for efficient use of internally generated light.

Thus, the present invention utilizes several important mechanisms:

(A) increasing absorption of excitation light by the plasmonic metal nanoparticles such that photoactivation of the photoinitiator or photocatalyst is enhanced;

(B) increasing the absorption of excitation light by plasmonic metal nanoparticles acting as a more efficient energy modulation system, generating more light for increased photoinitiator or photocatalyst excitation;

(C) increasing absorption of the excitation light by a dielectric material on or near the plasmonic metal nanoparticles;

(D) increasing the light absorption of energy modulation agent molecules adsorbed on or near the metal nanoparticles;

(E) amplifying light emission from energy modulation agent molecules attached to or near the metal nanoparticles; and

(F) the absorption of the light emission from the energy modulation agent is increased by a photoinitiator or photocatalyst.

As described above, raman scattering, which can enhance one of several phenomena of light emission (raman or luminescence) efficiency from molecules adsorbed on or near the metal nanostructure, is a Surface Enhanced Raman Scattering (SERS) effect. In 1984, one of the present inventors first reported that SERS is generally applicable as an analytical technique, and that SERS measures the possibility for various chemicals including polyaromatic compounds of several homocyclic and heterocyclic rings [ t.vo-Dinh, m.y.k.hiromoto, g.m.begun and r.l.moody, "Surface-enhanced ramanSpectroscopy for tracking analysis, "anal. chem., Vol.56, 1667, 1984]The entire contents of which are incorporated herein by reference. Since the mid-80 s of the twentieth century, much research has been devoted to understanding and modeling raman enhancement in SERS. For example, figure 5 shows that early work by Kerker simulated electromagnetic field enhancement of spherical silver nanoparticles and metal nanoshells around a dielectric core as early as 1984, [ m.m. Kerker, acc.chem.res., 17, 370(1984)]The entire contents of which are incorporated herein by reference. The figure shows theoretical calculations of electromagnetic enhancement at different excitation wavelengths for isolated spherical nanospheres and nanoshells. For compounds adsorbed on a SERS substrate, the intensity of the weak raman scattering process is typically increased by 10 ¹³Or 10¹⁵This allows for single molecule detection. Nanoparticles have gained increased utility as fluorescent and raman nanoprobes as a result of the enhanced electromagnetic field generated near the nanostructured metal surface.

Theoretical models indicate that the size of the nanoparticles and nanoshells can be tuned to the excitation wavelength. Experimental evidence shows that: 10⁶-10¹⁵The fold raman enhancement originates mainly from two mechanisms: a) the electromagnetic "lightning rod" effect, often referred to as "surface plasmons," generated near the metal surface structure associated with the large local field due to electromagnetic resonance, and b) the effect associated with direct energy transfer between the molecule and the metal surface.

According to classical electromagnetic theory, when light is incident on the metal nanostructures, the electromagnetic field can be locally amplified. These field enhancements can be quite large (typically 10)⁶To 10⁷Multiple, but maximum 10 at "hot spot¹⁵Fold enhancement). When the nanostructured metal surface is illuminated by an electromagnetic field (e.g., a laser beam), electrons within the conduction band begin to vibrate at a frequency equal to the incident light. These vibrating electrons, called "surface plasmons," generate a secondary electric field that increases the incident field. If the electron space of these vibrations is limited, as is the case with isolated metal nanospheres or roughened metal surfaces (nanostructures), then characteristic frequencies exist The ratio (plasmon frequency) at which there is a resonant response to collective vibration of the incident field. This condition produces a strong local field enhancement that can interact with molecules on or near the metal surface. In an effect similar to a "lightning rod," the "secondary magnetic field" is typically most concentrated at high curvature points on the roughened metal surface.

Design, fabrication, and operation of plasmon-enhanced structures

Fig. 6A-6G show a number of different embodiments of Plasmon Enhanced Probe Structures (PEPST), which can be designed as:

(A) photoactivatable (PA) molecules bound to metal (e.g., gold) nanoparticles;

(B) a Photoactivatable (PA) molecule coated with a metal nanoparticle;

(C) metal nanoparticles covered with a PA nanobelt;

(D) PA-containing nanoparticles capped with a metallic nanobelt;

(E) metal nanoparticles covered with a PA nanoshell;

(F) PA-containing nanoparticles covered with a metal nanoshell; and

(G) PA-containing nanoparticles covered with a metal nanoshell with a protective coating.

A basic embodiment of PEPST is shown in fig. 6A. The PEPST includes PA molecules bound to metal (e.g., gold) nanoparticles. FIG. 7 illustrates a plasmon enhancement effect for use in the present invention that enhances the interaction of a primary excitation light source with an energy modulation agent or enhances the interaction of a secondary generated light with a medium to cause a change in the medium. The PEPST structure is excited using suitable energetic radiation, which in turn activates, for example, the surrounding photoinitiators.

For example, light from a HeNe laser (632.8-nm excitation) can be used for excitation. In this case, the metal nanoparticles are designed to exhibit a strong plasmon resonance band around 632.8 nm. The surface plasmon resonance effect amplifies the excitation light at the nanoparticles, resulting in increased photoactivation of the photoinitiator or photocatalyst and improved reaction kinetics. Furthermore, for sterilization applications, this effect increases the likelihood of a sterilization event in the medium surrounding the nanoparticles. While light such as HeNe laser light can be scattered and absorbed in the medium, the presence of PEPST structures enhances the interaction of the transmitted light beyond those enhancements that are generally considered useful. The plasmon enhancement mechanism can be used with the other PEPST probes in fig. 6B, 6C, 6D, 6E, 6F, and 6G.

Structure of plasmon-activated metal nanostructures

Plasmon resonances occurring inside the metal nanoparticles arise from collective vibrations of free electrons driven by an incident optical field. The plasmonic response of nanoparticles plays a role in an increasing number of applications, including Surface Enhanced Raman Scattering (SERS), chemical sensing, drug delivery, photo-thermal cancer therapy, and new photonic devices. The study and application of plasmonics nanomaterials for SERS detection has been used by one of the present inventors for 20 years [ t.vo-Dinh, "Surface-enhanced raman Spectroscopy Using Metallic Nanostructures," Trends in anal. chem., 17, 557(1998), the entire contents of which are incorporated herein by reference. In 1984, one of the present inventors first reported practical analytical applications using SERS technology for trace analysis of various chemicals including polyaromatic compounds of several homocyclic and heterocyclic rings [ t.vo-Dinh, m.y.k.hiromoto, g.m.begun and r.l.moody, "Surface-enhanced Raman spectroscopy for trace organic analysis," anal.chem., volume 56, 1667, 1984], the entire contents of which are incorporated herein by reference. Since then, the development of SERS technology for chemical sensing, biological analysis, and medical diagnostics has begun. The substrate comprises nanoparticles and a semi-nanoshell with a one-sided metal (e.g., silver) coated nanoparticle layer (the nanosheet or half-shell). Several groups have indicated that: the plasmon resonance of the spherical shell can be tuned by controlling the shell thickness and aspect ratio of the nanoshell structure [ m.m. kerker, acc.chem.res., 17, 370 (1984); jackson, s.l.westcott, l.r.hirsch, j.l.west and n.h.halas, "controlling the surface enhanced raman effect via the nanoshell geometry", appl.phys.lett, vol 82, 257-259, 2003, the entire contents of which are incorporated herein by reference; norton and T.Vo-Dinh, "plasma resonances of nanoshells of Marine Shape", IEEE trans. nanotechnology, 6, 627-638(2007), the entire contents of which are incorporated herein by reference. These shells typically have a metal layer on a dielectric core. In one embodiment of the invention, these shells comprise spherical shells, since plasmon resonances (longitudinal and transverse modes) are affected by shell thickness and aspect ratio. A large number of researchers have studied the plasmon response of solid spherical particles in their analysis of surface enhanced raman scattering, although spherical shells appear to have not been studied. The invention also includes elongated and oblate spherical shells whose plasmon resonances exhibit some interesting property features. The spherical shell exhibits two degrees of freedom for adjustment: shell thickness and shell length to diameter ratio [ s.j.norton and t.vo-Dinh, "plasma resources of nanoshells of sphenoid Shape", IEEE trans. nanotechnology, 6, 627-638(2007) ], the entire contents of which are incorporated herein by reference.

Fig. 7 shows some different embodiments of plasmon-activated nanostructures, and most preferred embodiments of the invention, which can be designed as:

(A) a metal nanoparticle;

(B) a dielectric nanoparticle core covered with a metallic nanoparticle cap;

(C) a spherical metal nanoshell overlying a dielectric spherical core;

(D) an oblate spheroidal metal nanoshell overlying a dielectric spheroidal core;

(E) a metal nanoparticle core covered with a dielectric nanoshell;

(F) a metal nanoshell having a protective coating;

(G) a multilayer metal nanoshell overlying a dielectric spherical core;

(H) a multi-nanoparticle structure;

(I) metal nanocubes and nanocrisms/nanoprisms; and

(J) a metal pillar.

PEPST probes with remotely activated photoactivatable molecules

In another embodiment of the invention, PA molecules can be incorporated into a material (e.g., a biocompatible polymer) that can form a nanoshield on metal (gold) nanoparticles. The material may be a biocompatible polymer or gel that may have long-term continuous release properties. Suitable gels or biocompatible polymers include, but are not limited to: polyesters based on Polylactide (PLA), Polyglycolide (PGA), Polycaprolactone (PCL) and their copolymers, as well as polyhydroxyalkanoates of the PHB-PHV type, other polyesters, natural polymers, in particular modified polysaccharides such as starch, cellulose and chitosan, polyethylene oxide, polyetherester block copolymers and ethylene-vinyl acetate copolymers. The release mechanism can also be triggered by non-invasive techniques such as RF, MW, ultrasound, photons (fig. 8).

Fig. 9 shows other possible embodiments, where the PA molecule is bound to the metal nanoparticle via a linker, which can be cleaved by photon radiation. Such linkers include, but are not limited to, biochemical bonds (FIG. 9A), DNA bonds (FIG. 9B), or antibody-antigen bonds (FIG. 9C). In another embodiment, the linker is a chemically labile bond that can be cleaved by the chemical environment inside the cell. In various embodiments, metal nanoparticles may be more difficult to access to a target site in a medium than smaller molecules. In these embodiments, a PEPST probe with a releasable PA molecule is desired.

Agglomeration of metal (e.g., silver or gold) nanoparticles (nanospheres, nanorods, etc.) is a common problem, particularly with citrate-coated gold nanospheres, cetyl trimethylammonium bromide (CTAB) -coated gold nanospheres, and nanorods and nanoshells, because of their poor stability due to the agglomeration effect of salt ions when they are dispersed in a buffer solution. By coating the nanoparticles with polyethylene glycol (PEG), which is conjugated to the metal nanoparticles through thiol-functionalized PEG, biocompatibility can be improved and nanoparticle agglomeration can be prevented.

Immobilization of biomolecules and metal nanoparticles

Biomolecules (PA molecules, drugs, proteins, enzymes, antibodies, DNA, etc.) can be immobilized to a carrier using various methods disclosed in the literature. For example, in one embodiment of the invention, the encapsulating structure 10 of fig. 3C and 3D may be modified such that the PEPST structure is immobilized on an externally exposed surface such that any light from the encapsulating structure may be enhanced in interaction with the medium. Moreover, in one embodiment, the encapsulating structure 10 does not comprise an energy modulation agent. Instead, light from an external source, such as a flash lamp or LED array or laser or UV source, may be transmitted through the empty encapsulating structure 10 and into the medium. Reactive groups such as amino (-NH) groups, which are naturally occurring or can be introduced into the structure of biomolecules, can be used₂) Or thioether (-SH) groups are bonded by covalent bonds. Amines can be chemically reacted with carboxylic acid or ester moieties in high yields to form stable amide bonds. Thiols can participate in maleimide coupling to give stable dialkyl sulfides.

One support of interest for the present invention is a metal (preferably gold or silver) nanoparticle. Most immobilization schemes involving metal surfaces such as gold or silver are to pre-derivatize the surface with alkyl thiols to form stable bonds. Alkyl thiols tend to form self-assembled monolayers (SAMs) on silver surfaces at micromolar concentrations. The end of the alkyl thiol chain can be used to bind biomolecules or can be easily modified to bind biomolecules. It has been found that the length of the alkyl thiol chain is an important parameter for keeping the biomolecules away from the surface, preferably the alkyl length of 4 to 20 carbons.

There are a number of methods that involve the preparation of stable oligonucleotides bound to gold particles by using thiol-functionalized biomolecules that have previously been described to form strong gold-thiol bonds. Oligonucleotides having a 5' -terminal alkanethiol functional group as anchor can be bound to the surface of gold nanoparticles, and the resulting labels are robust and stable to both high and low temperature conditions [ R.Elghanin, J.J.Storhoff, R.C.Mucic, R.L.Letsinger and C.A.Mirkin, Selectivity assay of polynucleotides based on the distance-dependent properties optical properties of gold nanoparticles, science 277(1997), pp.1078-1081 ], the entire contents of which are incorporated herein by reference. Cyclic dithiane-epiandrosterone disulfide bonds have been developed for binding oligonucleotides to gold surfaces [ r.elghanian, j.j.storhoff, r.c.mucic, r.l.letsinger and c.a.mirkin, selective colorimetric detection of polynucleotides based on the distance-dependent properties of gold nanoparticles.science 277(1997), pages 1078-1081 ], the entire contents of which are incorporated herein by reference. Li et al reported that trithiol-coated oligonucleotides can stabilize gold metal nanoparticles with a diameter of 100nm while maintaining comparable hybridization performance to acyclic or dithiol-oligonucleotide modified particles [ z.li, r.c.jin, c.a.mirkin and r.l.letsinger, Multiple thio-capped DNA-gold nanoparticlespondence. nucleic Acids res.30(2002), pages 1558-1562 ].

In general, silver nanoparticles cannot be effectively passivated by alkylthiol modified oligonucleotides using established experimental protocols developed for gold particles. A method of producing core-shell particles with a silver core and a gold thin shell that facilitates the functionalization of silver nanoparticles with alkanethiol-oligonucleotides using validated methods that have been used in the past to prepare pure gold particle-oligonucleotide conjugates [ y.w.cao, r.jin and c.a.mirkin, DNA-modified core-shell Ag/nanoparticles.j.am.chem.soc.123 (2001), pages 7961-7962 ], the entire contents of which are incorporated herein by reference.

It has been found that silver surfaces exhibit controlled self-assembly kinetics when exposed to dilute ethanol solutions of alkyl thiols. The angle of inclination formed between the surface and the hydrocarbon tail is 0-15 deg. There is also a greater amount of thiol bulk density on silver when compared to gold [ Burges, j.d.; hawkridge, f.m. langmuir1997, 13, 3781-6], the entire contents of which are incorporated herein by reference. After forming a self-assembled monolayer (SAM) on the gold/silver nanoparticles, the alkyl thiol may be covalently bound to a biomolecule. Most synthetic techniques for covalent immobilization of biomolecules utilize free amine groups of polypeptide (enzymes, antibodies, antigens, etc.) or ammonia-labeled DNA strands or reaction with carboxylic acid moieties that form amide bonds.

This combination scheme has application not only by providing a mechanism by which nanoparticles can be controllably dispersed and delivered within a medium, but can also have a role in the formation of the encapsulated structures of the present invention, as described above.

Spectral range of light for PEPST

The plasmon enhancement effect can occur in the entire electromagnetic region if appropriate nanostructures, nano-dimensions, metal types are used. Thus, the PEPST principle can be applied to the entire electromagnetic spectrum, i.e., energy ranging from gamma rays and X-rays through to ultraviolet, visible, infrared, microwave and radio frequency energy. However, for practical reasons, for silver and gold nanoparticles, visible and NIR light is used, since plasmon resonances for silver and gold occur in the visible and NIR regions, respectively. Especially for gold nanoparticles, the NIR region is very suitable for feeding energy into the medium, otherwise optical scattering at shorter wavelengths may cause problems, for example in wastewater treatment with high concentrations of suspended solids or sterilization of food products.

Photon excitation

Several methods of the present invention use light to excite a photoactive compound in a medium. One approach may use light having a wavelength within a so-called "window" (designed to penetrate any container holding the medium to be treated and/or to transmit through the medium). Furthermore, while certain aspects of the present invention prefer that the excitation light be nominally non-absorbing in the medium, the present invention may also be used in media where there is significant scattering and absorption due to the advantages of plasmons. For example, in the UV application described above, a plasmon enhanced PEPST probe may be introduced into the medium and ultraviolet light may be used as the activation source. While the PEPST probe may not play a dominant role in the region of the medium near the surface, in regions deep into the surface where the ultraviolet light becomes dilute, the PEPST probe may play an important role in photoinitiation or photocatalysis.

The ability of light to penetrate a medium depends on absorption and scattering. Inside the aqueous medium, the window is 600 to 1300nm, i.e. from the orange/red region of the visible spectrum into the NIR. At the short wavelength end, it becomes important to absorb biomolecules including DNA and amino acids such as tryptophan and tyrosine. At the Infrared (IR) end of the window, penetration is limited due to the absorbency of water. Inside the window, scattering dominates over absorption, so the propagating light is scattered, although not necessarily into the scattering limit. Fig. 10 shows a diagram of a window for an aqueous medium. The following sections discuss the use of single photon and multiple photon techniques.

The optical excitation method comprises the following steps: single and multiple photon excitation

Two methods can be used, single or multiple photon excitation. If two-photon techniques are used, the PA molecules can be excited with light that can penetrate deep inside the medium from 700 to 1000nm to excite absorbing molecules in the 350-500nm spectral region. The method can excite compounds which absorb in the 290-350nm spectral region and emit in the visible region. By using a single photon method, Photoactivator (PA) molecules can directly absorb excitation light of 600-1300 nm. In this case, we can design systems with additional aromatic rings or in combination with others to change the ability to absorb different wavelengths.

X-ray excitation

While X-rays can non-invasively excite compounds in a medium, X-rays are not readily absorbed by many compounds where energy modulation is desired. The present invention provides a solution to this problem by providing a molecular system that can absorb X-ray energy and convert those energies to other energies that can be used. More specifically, one example of a molecular system that can absorb and alter X-ray energy in the present invention is a PEPST probe comprising nanoparticles (as described above).

In this embodiment, the invention uses X-rays for excitation. Since X-rays can penetrate deep into the medium, there is an advantage in being able to non-invasively excite molecules. In one embodiment of the present invention, the PA molecule (e.g., photoinitiator) binds to a molecular entity called an "energy modulation agent" that can interact with X-rays and then emits light that can be absorbed by the PA molecule. (FIG. 11)

PEPST probe for X-ray excitation

In the previous section, the advantages of gold nanoparticles as plasmonic activation systems have been discussed. Furthermore, gold nanoparticles, because they are biocompatible and have proven to be a possible X-ray contrast agent, are also suitable energy modulation systems [ Hainfeld et al, the British Journal of radiology, 79, 248, 2006], the entire contents of which are incorporated herein by reference. The concept of dose escalation for cancer radiotherapy has been the use of high-Z materials for over 20 years. Gold nanoparticles appear to be more promising as a dose enhancer than earlier attempts using microspheres and other materials for two main reasons. First, gold has a higher Z number than iodine (I, Z53) or gadolinium (Gd, Z64), and exhibits minimal toxicity to rodent or human tumor cells until at least 3 wt%. Gold nanoparticles are non-toxic to mice and are largely cleared from the body via the kidneys. The new use of small gold nanoparticles allows materials that accidentally ingest some of these nanoparticles to remain safe for human consumption.

Fig. 12 shows a number of different embodiments of PEPST probes that may be preferred for X-ray excitation of energy modulator-PA systems. These probes include:

(A) PA molecules bound to an energy modulation agent and plasmonic metal nanoparticles;

(B) plasmonic metal nanoparticles with an energy modulation agent nanoshell covering the PA molecules;

(C) PA-covered nanoparticles with plasmonic metal nanoparticles;

(D) nanoparticles containing an energy modulation agent covered with PA molecules and plasmonic metal nanoshields;

(E) a plasmonic metal nanoparticle core with a PA molecule-covered energy modulation agent nanoshell; and

(F) PA molecules bound to energy modulation agent (attached to plasmonic metal nanoparticles) nanoparticles through cleavable biochemical bonds.

Examples of PEPST systems based on energy Modulator-PA

For simplicity, the following discussion focuses on gold as the metal material and CdS as the energy modulation agent material (which may also be used as DNA stabilized CdS), see Ma et al, Langmuir, 23(26), 12783-12787(2007), the entire contents of which are incorporated herein by reference. However, it is understood that many other embodiments of the metallic material, energy modulation agent and PA molecule are possible within the scope of the present invention, and the following description is for exemplary purposes only.

In the embodiment of fig. 12A, the PEPST system includes: gold nanoparticles, energy modulation agent nanoparticles (e.g., CdS) linked to PA drug molecules (e.g., psoralen). X-ray irradiation of CdS [ Hua et al, rev. sci. instrum., 73, 1379, 2002, the entire contents of which are incorporated herein by reference ], which absorbs X-rays and emits CdS XEOL light (350-400nm) enhanced by gold nanoparticle plasmons. The enhanced XEOL light can be used to photoactivate PA molecules. In this case, the nanostructure of the gold nanoparticles is designed to enhance XEOL light of 350-400 nm.

In the embodiment of fig. 12B, the PEPST system includes plasmon-activated metal (gold) nanoparticles with energy modulation agent nanotags (CdS) covered by PA molecules. CdS is irradiated with X-rays, which absorb the X-rays and emit XEOL light enhanced by gold nanoparticle plasmons. The enhanced XEOL light is used to photoactivate the PA molecules.

In the embodiment of fig. 12C, the PEPST system includes: PA (e.g., psoralen) covered CdS nanoparticles with smaller plasmonic metal (gold) nanoparticles. CdS is irradiated with X-rays, which absorb the X-rays and emit light enhanced by gold nanoparticle plasmons. The enhanced XEOL light is used to photoactivate the PA molecules.

In the embodiment of fig. 12D, the energy modulation agent core comprises CdS or CsCl nanoparticles covered with a gold nanoshell. CdS or CsCl is irradiated with X-rays, which absorb X-rays [ [ Jaegle et al, j.appl.phys., 81, 2406, 1997] and emit XEOL light that is plasmon-enhanced by a gold nanoshell structure. The enhanced XEOL light is used to photoactivate the PA molecules.

Similarly, the embodiment in fig. 12E includes a spherical gold core covered with a shell of CdS or CsCl. CdS or CsCl materials are irradiated with X-rays, which absorb X-rays [ Jaegle et al, j.appl.phys., 81, 2406, 1997, the entire contents of which are incorporated herein by reference ] and emit XEOL light that is plasmonically enhanced through gold nanospheres. The enhanced XEOL light is used to photoactivate the PA molecules.

In the embodiment of fig. 12F, the PEPST system includes gold nanoparticles, and energy modulation agent nanoparticles (e.g., CdS) linked to PA drug molecules (e.g., psoralen) through bonds that can be broken using radiation. CdS is irradiated with X-rays, which absorb the X-rays and emit XEOL light (350-400nm) plasmon-enhanced through gold nanoparticles. The enhanced XEOL light is used to photoactivate psoralens (PA molecules). In this case, the nanostructure of the gold nanoparticles is designed to enhance XEOL light of 350-400 nm.

In an alternative embodiment, the metal nanoparticle or single nanoshell is replaced with a multilayered nanoshell [ Kun Chen, Yang Liu, Guillermo orange, Vadim Backman, optimal design of structured nanospheres for ultrashort light-scattering reactions as molecular imaging multilayers, journal of biological Optics, 10(2), 024005 (3/4/2005), the entire contents of which are incorporated herein by reference ].

In other alternative embodiments, the metal nanoparticles are covered with a layer (1-30nm) of dielectric material (e.g., silicon dioxide). The dielectric layer (or nanoshell) is designed to prevent quenching of light emitted by the energy modulation agent (also referred to as EEC) molecules due to direct contact of the metal with the energy modulation agent molecules. In other alternative embodiments, the energy modulation agent molecule or material is linked to (or adjacent to) the metal nanoparticle via a spacer (linker). The spacer is designed to prevent quenching of light emitted by the energy modulation agent molecule or material.

Other useful materials

The energy modulation agent material may include any material that can absorb X-rays and emit light to excite the PA molecules. Energy modulation agent materials include, but are not limited to:

Metals (gold/silver, etc.);

quantum dots;

a semiconductor material;

an alternating light and a phosphor material;

a material exhibiting X-ray stimulated luminescence (XEOL);

organic solids, metal complexes, inorganic solids, crystals, rare earth materials (lanthanides), polymers, light-alternating materials, phosphor materials, and the like; and

a material exhibiting excitonic properties.

Quantum dots, semiconductor nanostructures. Various materials related to quantum dots, semiconductor materials, and the like may be used as the energy modulation agent system. Nanostructures such as those associated with CdS have been shown to exhibit X-ray stimulated luminescence in the UV-visible region [ Hua et al, rev.

The cross-gloss material acts as an energy conditioner system. Various types of phototropic materials can be used as energy modifiers because they absorb X-rays and emit light emissions that can be used to excite PA systems. For example, a single crystal of molybdate may be excited by X-rays and emit light at about 400nm [ Mirkhin et al, Nuclear instruments, meth.in Physics res.a, 486, 295, 2002, the entire contents of which are incorporated herein by reference ].

Solid materials as energy conditioner system: various solid materials can be used as energy modulation agents due to their X-ray stimulated luminescence properties. For example CdS (or CsCl) exhibits luminescence when excited by soft X-rays [ Jaegle et al, j.appl.phys., 81, 2406, 1997, the entire contents of which are incorporated herein by reference ].

Xeol material: lanthanide or rare earth materials; see L.Soderholm, G.K.Liu, Mark R.antonioc, F.W.lytle, X-ray isolated optical luminescence.XEOL.detection of X-ray absorbance fine structure. XAFZ, J.chem.Phys, 109, 6745, 1998, all of which are incorporated herein by reference, or Masachi Ishiia, Yoshihtitanaka and Tetsuya Ishikawa, Shuji Komura and Takitaro Morrikawa, Yoshinobu Aoygi, Site-selective X-ray absorbance fine structure of interactive activity center in-Er amplified micro-luminescence X-luminescence-183, light emission X-luminescence, light emission X-183, all of which are incorporated herein by reference, light emission X-183, light emission X-ray absorption fine structure, and light emission X-emission, light emission X-emission, light emission X-183, light emission X-emission, light emission X-emission, light emission X-.

Some examples of XEOL-exhibiting metal complexes useful as energy modulation systems are shown in fig. 13 and 14. This structure can be modified by replacing metal atoms with metal nanoparticles to make plasmon enhanced PEPST probes. In the present invention, experimental parameters including nanostructure size, shape and metal species may be selected based on excitation radiation (NIR or X-ray excitation), photo-activation radiation (UVB) and/or emission processes from the energy modulation agent system (visible NIR).

Principle of plasmon enhancement effect using X-ray excited PEPST probe

One embodiment of the basic PEPST probe embodiments includes: PA molecules bound to energy modulation agents and to plasmonic metal (gold) nanoparticles. Metal nanoparticles can play two roles:

(A) enhancement of X-ray electromagnetic fields

(B) Enhancement of the radiation signal of the energy modulation agent system.

The X-ray radiation used to excite the energy modulation agent system is amplified by the metal nanoparticles due to plasmon resonance. As a result, the energy modulator system exhibits more luminescence that is used to photoactivate the PA molecules and make them photoactivated. In this case, the metal nanoparticles are designed to exhibit strong plasmon resonance at or near the X-ray wavelength. The surface plasmon resonance effect amplifies the excitation light at the nanoparticles, allowing increased photoactivation of the PA drug molecules and improving the therapeutic effect. Plasmon enhancement mechanisms can also be used with PEPST probes as described above.

Fig. 15 shows the plasmon enhancement effect of the PEPST probe. Photon energy for X-rays used in medical diagnostic imaging is about 10-150 keV, which corresponds to wavelengths of 1.2-0.0083 angstroms. [ lambda (Angstrom) ═ 12.4/E (keV) ]. Soft X-rays may be up to 10 nm. Plasma laserThe size of the meta-active nanoparticles is generally about equal to or less than the wavelength of the radiation used. Note that the approximate atomic radius of gold is about 0.15 nanometers. Below this limit, the smallest "nanoparticle" size for gold is 0.14nm (only 1 gold atom). Nanoparticles hundreds of nm in size may have about 10⁶-10⁷A gold atom. Thus, the gold nanoparticles described in the present invention may range from 1 to 10⁷A gold atom.

Gold nanoparticles may also enhance the energy modulation agent emission signal, which is used to excite the PA molecule. For psoralens, this spectral range is the UVB region (320-400 nm). Silver or gold nanoparticles, nanoshells, and nanobuds that exhibit strong plasmon resonances in this region have been fabricated. FIG. 16 shows excitation and fluorescence emission spectra of psoralen compound (8-methoxypsoralen).

Nanoparticle chains for the double plasmon effect

As mentioned previously, there is a need to develop nanoparticle systems that can have dual (or multiple) plasmon resonance modes. Fig. 17 shows one embodiment of a PEPST probe of the present invention having a string of metal particles of different sizes and bound to each other, which can exhibit dual plasmon-based enhancement. For example, the parameters (size, metal type, structure, etc.) of the larger nanoparticles (fig. 17, left) can be tuned to NIR, VIS or UV light, while the smaller particles (fig. 17, right) can be tuned to X-rays. There is also a coupling effect between these particles.

These nanoparticle chains serve to provide both plasmonic enhancement of the incident radiation used (e.g. x-ray activation of CdS) and plasmonic enhancement of the emitted radiation that subsequently activates the PA. Similar nanoparticle systems have been used as Nanolens [ Self-Similar Chain of metallic nanospheres as an effective Nanolens, Kuiru Li, Mark I.Stockman and David J.Bergman, Physical Review Letter, Vol.91, No. 22, 227402-1, 2003, the entire contents of which are incorporated herein by reference ].

Production of gold nanoparticles: frees method [ Frees, G., Controlled circulation for The regulation of The particulate size in monodispersese Gold solutions. Nature (London) Phys Sci, 1973.241: pages 20-22, which are incorporated herein by reference in their entirety]Can be used in the present invention to synthesize a solution of gold nanoparticles having a diameter of 8 to 10 nm. Briefly, 5.0 × 10^-6Molar HAuCl₄Dissolved in 19ml of deionized water to give a pale yellow solution. The solution was heated in a rotary evaporator with vigorous stirring for 45 minutes. 1ml of 0.5% sodium citrate solution was added and the solution was stirred for a further 30 minutes. The solution color gradually changed from an initial yellowish color to a clear, gray, purple color and finally to an appealing wine-red color similar to mellot. The sodium citrate used has a dual role, the first acting as a reducing agent and the second generating negative citrate ions that adsorb on the gold nanoparticles to introduce surface charges to repel the particles to prevent nanocluster formation.

Another method for synthesizing nanoparticles comprising gold stabilized by equine apoferritin (HSAF) has been reported to use NaBH₄Or 3- (N-morpholino) propanesulfonic acid (MOPS) as a reducing agent [ Lei Zhang, Joe Swift, Christopher A. buttons, Vij ay Yerbandi and Ivan J. Dmochowski, Structure and activity of antibiotic-stabilized gold nanoparticles, Journal of organic Biochemistry, Vol.101, 1719-1729, 2007, the entire contents of which are incorporated herein by reference]. Preparation of gold sulfite (Au) in the lumen of a cage protein, apoferritin₂S) nanoparticles. Diameter of cavity of apoferritin 7nm, Au produced₂The diameter of the S nanoparticles is almost the same as the size of the cavity and the size distribution is small. [ KeikoYoshizawa, Kenji Iwahori, Kenji Sugimoto and Ichiro Yamashita, contamination of Gold Nanoparticles Using the Protein Cage of Apoferrin, Chemistry Letters, Vol.35 (2006), p.10, page 1192, the entire contents of which are incorporated herein by reference]. Thus, in one embodiment, PA or energy modulation agent-PA compounds are encapsulated in a desferriferous eggInside the white shell.

Excitons in solid materials

Excitons are often defined as "quasi-particles" within a solid material. In solid materials such as semiconductors, molecular crystals, and conjugated organic materials, photoexcitation at a suitable wavelength (e.g., X-rays, UV, and visible radiation, etc.) can excite an electron from the valence band to the conduction band. This newly formed conduction electron is attracted to the positively charged hole it left on the valence band by coulomb interaction. As a result, the electrons and holes together form a bound state called an exciton. (Note: the neutral binding complex is a particle with integer spin that can behave as a Bose-Einstein statistic; when the temperature of the Bose gas drops below a certain value, a large number of Bose "coalesces" into a single quantum state-i.e., a Bose-Einstein agglomerate (BEC)). Exciton generation involves X-ray excitation of solid materials. In the manufacture of light emitters and phosphors, wide bandgap materials are often used to convert x-rays to ultraviolet/visible photons [ Martin Nikl, science detectors for x-rays, meas. sci. technol.17(2006) R37-R54, the entire contents of which are incorporated herein by reference ]. Exciton theory is well known in materials research and in the manufacture and application of semiconductors and other materials.

During the initial conversion, multi-step interactions of high energy X-ray photons with the crystal lattice of the light-intersecting material occur through the photoelectric effect and Compton scattering effect; for X-ray excitation at photon energies below 100keV, the photoelectric effect is the dominant process. Many excitons (i.e., electron-hole pairs) are generated and thermally distributed in the conduction band (electrons) and the valence band (holes). This first process occurs in less than 1 ps. During subsequent transport, excitons migrate through the material, where repeated trapping can occur at the defect, resulting in energy loss due to non-radiative recombination, etc. The final phase, luminescence, involves the sequential trapping of electron-hole pairs at the luminescence center and their radiative recombination. The electron-hole pairs can be trapped and recombine at the defect, producing light emission. Luminescent dopants may also be used as traps for excitons.

Exciton traps

Exciton traps can be created using impurities in the host matrix of the crystal. In an impurity-containing crystal having dipolar guest molecules, an electron trapping state may occur when electrons are localized on adjacent impurity molecules. Such traps have been observed in carbazole-doped anthracene [ Kadshchuk, a.k., Ostapenko, n.i., Skryshevskii, yu.a., Sugakov, v.i., and Susokolova, t.o., mol.cryst.and liq.cryst., 201, 167(1991), the entire contents of which are incorporated herein by reference ]. These traps are formed due to the interaction of the dipole moment of the impurities with the carriers. As the dopant (or impurity) concentration increases, the spectrum exhibits additional spectral structure due to carriers being trapped on clusters of impurity molecules. Sometimes, impurities and dopants are not necessary: electrons or excitons will become trapped on Structural Defects in such Crystals due to electrostatic interactions with the reoriented dipole moments of the perturbing crystal molecules [ s.v.izvekov, v.i.sugakov, exiton and electron tracks on Structural Defects in Molecular Crystals with DipolarMolecules, Physica script, volume T66, 255-257, 1996 ]. Structural defects that act as exciton traps can be engineered into molecular crystals. The development of GaAs/AlGaAs nanostructures and the use of nanofabrication techniques may allow the manipulation of exciton traps with new quantum mechanical properties in the materials used in the present invention.

Design, fabrication and operation of EIP probes

Fig. 18A-D show various embodiments of EIP probes, which can be designed as:

(A) probes comprising PA molecules bound (via a linker, which may be immobilized or detachable) to energy modulation agent particles that can generate excitons upon excitation by radiation of a suitable wavelength (e.g., X-rays). In this preferred embodiment, the energy modulation agent material has structural defects that serve as traps for excitons.

(B) Probes comprising PA molecules bound (linker, which may be immobilized or detachable) to energy modulation agent particles that can generate excitons upon excitation by radiation of a suitable wavelength (e.g., X-rays). In this preferred embodiment, the energy modulation agent material has an impurity or dopant molecule that acts as a trap for excitons.

EIP probe with tunable radiation：

The probe as described in (B) above can provide the ability to modulate the energy conversion from the X-ray excitation source to a wavelength that is of interest for exciting the PA molecules. In 1976, D' silvera et al indicated that: polycyclic Aromatic Hydrocarbon (PAH) molecules doped with a coagulated n-alkane solid can be excited by X-rays and produce luminescence characterized by visible wavelengths in their luminescence spectrum. P.p.d' Silva, g.j.oesterech, and v.a.fassel, X-ray excited optical luminescence of nuclear aromatic hydrocarbons, anal.chem.; 1976; pages 48(6)915-917, the entire contents of which are incorporated herein by reference ]. Tunable EIP probes are designed to include such luminescent dopants, for example, highly luminescent PAHs that exhibit light emission in the range of 300-400nm suitable for activating psoralens. One embodiment of an EIP with tunable radiation includes a solid substrate (semiconductor, glass, quartz, conjugated polymer, etc.) doped with naphthalene, phenanthrene, pyrene or other compounds exhibiting luminescence (fluorescence) in the 300-400nm range [ t.vo-Dinh, multicomponent analysis by chromatography luminescence spectrometry, anal.chem.; 1978; pages 50(3)396-401, which are incorporated herein by reference in their entirety ]. The EEC substrate may be a semiconductor material, preferably transparent at the wavelengths of light (excitation and radiation) of interest.

Other dopant species, such as rare earth materials, may also be used as dopants. FIG. 19 shows X-ray excited optical luminescence (XEOL) with europium doping in the matrix of BaFBr, emitting at 370-420 nm. U.S. patent application publication 2007/0063154, which is incorporated herein by reference, describes these and other nanocomposites (and methods of making them) suitable for XEOL.

Fig. 20 shows various embodiments of EIP probes, which can be designed as:

(A) probes comprising PA molecules bound around energy modulator particles or embedded in a shell around energy modulator particles that can generate excitons upon excitation by radiation of a suitable wavelength (e.g., X-rays). In this preferred embodiment, the energy modulation agent material has structural defects that serve as traps for excitons.

(B) Probes comprising PA molecules bound around energy modulator particles or embedded in a shell around energy modulator particles that can generate excitons upon excitation by radiation of a suitable wavelength (e.g., X-rays). In this preferred embodiment, the energy modulation agent material has an impurity or dopant molecule that acts as a trap for excitons.

The fundamental core concept in photophysics is the formation of new quasiparticles from a mixture of strongly coupled states. This mixed state may have unusual properties not possessed by the original particles. The coupling between excitons and plasmons may be weak or strong. When the light-substance interaction cannot be considered as a perturbation, the system is a strongly coupled system. Strong coupling between Surface Plasmon (SP) modes and organic excitons has been demonstrated; the organic semiconductor used was a concentrated cyanine dye in a polymer matrix deposited on a silver film [ see: the mass of the seed is J.Bellessa, ^*Bonnan, and j.c. plenet, j.mungnier, string coupling surface plasmids and exitons in an organic semiconductor, phys.rev.lett, 93(3), 036404-1, 2004, the entire contents of which are incorporated herein by reference]. Other work describes the photophysical properties of excitons of hybrid complexes composed of semiconductors and metal nanoparticles. The interaction between the individual nanoparticles can produce an enhancement or suppression of radiation. The radiation enhancement comes from the electric field amplified by plasmon resonance, while the radiation suppression is a result of energy transfer from the semiconductor to the metal nanoparticles. [ Alexander O.Govorov, Garnett W.Bryant,wei Zhang, Timur Skeini, Jaebeom Lee, Nichlas A.Kotov, Joseph M.Slocik, | and Rajesh R.Naik, Exciton-plasma Interaction and Hybrid interactions in semiconductor device Metal nanoparticles assays, Nano Lett., Vol.6, No. 5, No. 984, 2006, the entire contents of which are incorporated herein by reference]. Other work describes the theory of interaction between excited states and surface electromagnetic modes in small diameter (< 1nm) semiconducting single-walled Carbon Nanotubes (CN). Bondarev, K.Tatur and L.M.Woods, Strong exton-plasmocoupling in semiconductor constructing carbon nanotube, the entire contents of which are incorporated herein by reference ]。

Other work reports on the synthesis and optical properties of composite metal-insulator-semiconductor nanowire systems, including those composed of controlled thickness of SiO₂A core of wet-chemically grown silver wire surrounded by a shell and a subsequent outer shell of highly luminescent CdSe nanocrystals [ Yuri Feditek, Vasil Temnov, UlrikeWogon, Elena Utinovich, and Mikhail Artemyev, Exceptin-plasma interaction in a composite metal-insulator-semiconductor nanowineglass, J.Am.Chem.Soc., 129(48), 14939-14945, 2007, the entire contents of which are incorporated herein by reference]. For SiO with a thickness of-15 nm₂Spacers, which observe efficient excitation of surface plasmons by excitation radiation of CdSe nanocrystals. For small d, i.e., well below 10nm, the radiation is strongly suppressed (PL quenching), which is consistent with the expected advantage of dipole-dipole interaction of damped mirror dipoles G.W Ford and W.H.Weber, Electromagnetic interactions of molecules with metal surfaces, Phys.Rep.113, 195-287(1984), the entire contents of which are incorporated herein by reference]. For nanowires with a length of up to-10 μm, composite metal-insulator-semiconductor nanowires ((Ag) SiO) ₂CdSe) as a waveguide for 1D-surface plasmons at optical frequencies with efficient photon out-coupling at the nanowire ends, which is desirable for efficient exciton-plasmon-photon conversion and surface plasmon waveguides on a sub-micron scale in the visible light spectral range.

Experiments with colloidal solutions of Ag nanoparticles capped with J-agglomerates show that strong scattering cross-sections and enhanced fields associated with surface plasmons can be used to generate excitation radiation from J-agglomerate excitons at very low excitation power. Gregory a. wurtz,^*paul r. evans, William Hendren, Ronald Atkinson, Wayne Dickson, Robert J. pollard, and anataly v.zayats, Molecular plasma with mobile exposure-plasma coupled Strength in J-Aggregate hybrid Au nanorodassages, Nano let, volume 7, stage 5, 1297, 2007, the entire contents of which are incorporated herein by reference]. Their coupling to surface plasmon excitation therefore provides a particularly attractive method for generating low power optics. This process can result in effective X-ray coupling for phototherapy. Furthermore, the coupling of J-aggregates to plasmonic structures represents a real fundamental meaning of generating mixed plasmonic-exciton states.

Design, manufacture and operation of EPEP probes

Fig. 21 shows various embodiments of EPEP probes of the present invention exhibiting exciton-plasmon coupling:

(A) a probe comprising a PA molecule or group of PA molecules bound (via a linker, which may be fixed or detachable) to an energy modulation agent particle that can generate excitons upon excitation by radiation of a suitable wavelength (e.g., X-rays). The energy modulation agent particles are bonded to (or adjacent to) metal nanoparticles that are coated with a silica (or other dielectric material) nanoshell. The silicon dioxide layer (or nanoshell) (see fig. 25A and 25B; white nanoshell layer between the energy modulation material and the metal nanostructure) is designed to prevent quenching of the emitted luminescence of the X-ray excited energy modulation agent particles. Metal nanoparticles (Au, Ag, etc.) are designed to induce plasmons that enhance X-ray excitation, which in turn induce an increase in the optical radiation of the energy modulation agent, ultimately leading to an increase in the efficiency of photoactivation, i.e., phototherapy. The structure of the nanoparticles can also be designed such that the plasmon effect also enhances the energy modulation agent emitting light. These processes are due to strong coupling between excitons (plasmons in the energy modulation agent material and in the metal nanoparticles); and

(B) A probe comprising a PA molecule or group of PA molecules bound (via a linker, which may be fixed or detachable) to an energy modulation agent particle that can generate excitons upon excitation by radiation of a suitable wavelength (e.g., X-rays). The energy modulation agent particles are bound to (or adjacent to) the metal nanoparticles via a spacer (linker). The spacer is designed to prevent quenching of the luminescence emitted by the X-ray excited energy modulation agent particles.

Fig. 22 shows other embodiments of EPEP probes of the present invention:

(A) probes comprising PA molecules or groups of PA molecules bound (via linkers, which may be fixed or detachable) to energy modulation agent particles that can generate excitons upon excitation by radiation of a suitable wavelength (e.g., X-rays). The energy conditioner particles are covered with a nanoshell of silicon dioxide (or other dielectric material) covered with a layer of isolated metal (Au, Ag) nanostructures (nano-islands, nanorods, nanocubes, etc.). The silicon dioxide layer (or other dielectric material) is designed to prevent quenching of the luminescence emitted by the X-ray excited EEC (also called energy modulation agent) particles. Metallic nanostructures (Au, Ag, etc.) are designed to induce plasmons that enhance X-ray excitation, which subsequently cause an increase in EEC light radiation, ultimately leading to an increase in the efficiency of light activation, i.e., phototherapy. The structure of the nanoparticles can also be designed such that the plasmon effect also enhances the energy modulation agent emitting light. These processes are due to strong coupling between excitons (plasmons in the energy modifier material and in the metal nanostructure).

(B) A probe comprising a set of PA molecules in a particle bound (via a linker, which may be fixed or detachable) to an energy modulation agent particle that can generate excitons upon excitation by radiation of a suitable wavelength (e.g., X-rays). The particles containing PA are covered with a layer of metal nanostructures (Au, Ag). Metallic nanostructures (Au, Ag, etc.) are designed to induce plasmons that enhance the optical radiation of the energy modulation agent, ultimately leading to an increase in the efficiency of photoactivation, i.e., phototherapy.

(C) A probe comprising a PA molecule or group of PA molecules bound (via a linker, which may be fixed or detachable) to an energy modulation agent particle that can generate excitons upon excitation by radiation of a suitable wavelength (e.g., X-rays). The energy conditioner particles are covered with a nanoshell of silicon dioxide (or other dielectric material) covered with a layer of metallic nanostructures (Au, Ag). The silicon dioxide layer (or other dielectric material) is designed to prevent quenching of the luminescence emitted by the X-ray excited energy modulation agent particles. Metallic nanostructures (Au, Ag, etc.) are designed to induce plasmons that enhance X-ray excitation, which in turn leads to increased energy modulator light emission, ultimately leading to increased efficiency of light activation. The PA-containing particles are covered with a layer of metal nanostructures (Au, Ag). Metallic nanostructures (Au, Ag, etc.) are designed to induce plasmons that enhance EEC light radiation, ultimately leading to increased efficiency of light activation.

Hybrid EPEP nano superstructure

EPEP probes may also include hybrid self-assembled superstructures made of biological and non-biological nanoscale components that can provide a variety of different molecular architectures with unique electronic, surface, and spectral properties for phototherapy.

Biopolymers and nanoparticles can be integrated into superstructures, which provide unique functionality because of the physical properties of the inorganic nanomaterials and the chemical flexibility and specificity of the polymers that can be used. It is worth noting that two types of excitation, e.g. excitons and plasmons, common in nanomaterials are combined to give a coupled excited complex system. Containing a member comprising a metal, a semiconductor Nanoparticle (NP), a Nanorod (NR) or a Nanowire (NW)The molecular architecture can produce EPEP probes with a combination of photonic properties and enhanced interactions that are important for the field of phototherapy. Some examples of the assembly of NW nanostructures and NPs have been reported in biosensing. Nanoscale superstructures made from CdTe Nanowires (NWs) and metal Nanoparticles (NPs) were prepared via a bio-coupling reaction. The prototype biomolecule, such as the D-biotin and streptavidin pair, was used to link NP and NW in solution. Au NPs were found to form a dense shell around CdTe NW. Superstructures exhibit extraordinary optical effects associated with the long-range interaction of semiconductor and noble metal nanocolloids. Compared to the uncoupled NW, the NW/NP complex showed a 5-fold increase in the luminescence intensity and a blue shift of the emission peak Jaebeom Lee, Alexander o. John Dulka, and Nicholas A.Kotov, Bioconj ugates of CdTe N anowires and Autop articles: plasma-Exciton Interactions, luminescences enhancement, and Collective Effects, Nano letter Lett., Vol.4, No. 12, 2323, 2004, the entire contents of which are incorporated herein by reference]。

Fig. 23 shows various embodiments of EPEP probes of the present invention comprising a superstructure of NP, NW and NR:

(A) a probe comprising a PA molecule or group of PA molecules bound (via a linker, which may be fixed or detachable) to an energy modulation agent particle that can generate excitons upon excitation by radiation of a suitable wavelength (e.g., X-rays). The energy modulation agent particles are bound to (or adjacent to) the metal nanowires (or nanorods) of the nanoshell pillars being coated with silicon dioxide (or other dielectric material). The silica nanoshell columns are designed to prevent quenching of the luminescence emitted by the X-ray excited energy modulation agent particles. Metal nanoparticles (Au, Ag, etc.) are designed to induce X-ray excited plasmons that subsequently cause an increase in the energy modulator light emission, ultimately leading to an increase in the efficiency of photoactivation, i.e., phototherapy. The structure of the nanoparticles can also be designed such that the plasmon effect and/or exciton-plasmon coupling (EPC) effect also enhances the energy modulation agent emission. These processes should be due to strong coupling between excitons (plasmons in the energy modulation agent material and in the metal nanoparticles); and

(B) A probe comprising a PA molecule or group of PA molecules bound (via a linker, which may be fixed or detachable) to an energy modulation agent particle that can generate excitons upon excitation by radiation of a suitable wavelength (e.g., X-rays). The energy modulation agent particles are bound to (or adjacent to) the metal nanoparticles via a spacer (linker). The spacer is designed to prevent quenching of the luminescence emitted by the X-ray excited energy modulation agent particles. The same effects as in the above (A).

Fig. 24 and 25 show another set of embodiments of EPEP probes of the present invention comprising a superstructure of NP, NW and NR with biological receptors (antibodies, DNA, surface cell receptors, etc.). The use of biological receptors for target tumor cells has been previously discussed for PEPST probes. Note that in this embodiment, the PA molecules are attached along the NW axis to be excited by the emitted light from the NW.

Fig. 26 shows another embodiment of an EPEP probe of the present invention comprising a superstructure of NPs linked to multiple NWs.

For some embodiments, there is a significant improvement by adding metal nanostructures designed for specific interaction with excitons in the energy conditioner system:

(1) Introducing other radiation pathways from exciton to photon conversion

(2) The metallic nanostructures may be designed to amplify (due to the plasmon effect) excitation radiation (e.g., X-rays) and/or emit radiation (e.g., UV or visible light) to excite light-activated (PA) molecules, thereby enhancing PA effectiveness.

The various metal nanostructures that can be used in the EPEP probe of embodiments of the invention are the same as those illustrated in fig. 4 for the PEPST probe.

EPEP probe with microresonator

In one embodiment, the energy modulation agent system can be designed for use as a microresonator of micron or submicron size. Previous work has described resonant microcavities, particularly those involving strong optical species interactions [ m.lipson; l.c. kimerling; the resonant microcavities are typically formed in a substrate, such as silicon, and have dimensions on the order of a few microns or a fraction of a micron. The resonant microcavity contains a photoactive material (i.e., a light-emitting substance) and a reflector that limits the entry of light into the photoactive material. The confined light interacts with the photo-active species to produce a photo-species interaction. The photonic-species interaction in the microcavity is characterized by being either strong or weak. Weak interactions do not change energy levels in the species, while strong interactions change energy levels in the species. In a strong photophobic interaction arrangement, confined light can be made to resonate with these energy level transitions to alter microcavity performance.

Experimental methods

Preparation of nanoparticles (Ag, Au)

There are many methods to prepare metal nanoparticles for EPEP or PEPST probes. The process of preparing gold and silver colloids comprises: electro-explosion, electro-deposition, gas phase condensation, electrochemical processes, and solution phase chemical processes. Although methods for preparing uniform size spherical colloidal gold with a diameter of 2-40 nm are well known [ N.R. Jana, L.Gearheart and C.J.Murphy, feeding growth for sizing control of 5-40 nm diameter gold nanoparticles.Langmuir 17(2001), pp.6782-6786, the entire contents of which are incorporated herein by reference ], particles of this size are commercially available. An efficient chemical reduction method for the preparation of silver particles (with uniform optical scattering properties) or gold particles (with improved control over size and shape monodispersity) is based on the use of small diameter, uniformly sized gold particles as nucleation centers for further growth of the silver or gold layer.

A widely used method involves citrate reduction of gold salts to produce 12-20nm gold particles with a relatively narrow size distribution. One common method of producing smaller gold particles is found in Brust, m.; walker, m.; bethell, d.; schiffrin, d.j.; whyman, R.chem.Commun.1994, 801, the entire contents of which are incorporated herein by reference. The method is based on carrying out borohydride reduction of gold salts in the presence of alkanethiol coating agents to produce 1-3 nm particles. The size of the nanoparticles can be controlled between 2-5 nm by changing the concentration of thiol [ Hostetler, M.J.; wingate, j.e.; zhong, c.j.; harris, j.e.; vachet, r.w.; clark, m.r.; londono, j.d.; green, s.j.; stokes, j.j.; wignall, g.d.; glish, g.l.; porter, m.d.; evans, n.d.; murray, r.w.langmuir 1998, 14, 17, the entire contents of which are incorporated herein by reference ]. Phosphine-stabilized gold clusters have also been produced and subsequently converted to thiol-coated clusters by ligand exchange to improve their stability [ Schmid, g.; pfeil, r.; boese, R.; bandrmann, f.; meyer, s.; calis, g.h.m.; van der Velden, j.w.a.chem.be.1981, 114, 3634; warner, m.g.; reed, s.m.; hutchison, j.e.chem.mater.2000, 12, 3316, the entire contents of which are incorporated herein by reference and a similar protocol to Brust method was used to prepare phosphine-stabilized monodisperse gold particles [ week, w.w.; reed, s.m.; warner, m.g.; hutchison, j.e.j.am.chem.soc.2000, 122, 12890, the entire contents of which are incorporated herein by reference ]. See also: ziyi Zhong, Benoit Male, Keith B.Luong, John H.T., More Recent Progress in the Preparation of Au nanostrucrures, Properties, and Applications, Analytical Letters; 2003, volume 36, No. 15, pages 3097-3118, the entire contents of which are incorporated herein by reference.

Fabrication of metal nanoparticles coated with a dye nanoshell

The manufacture of metal nanoparticles coated with nanoshells of dye molecules can be carried out using the methods described in the following documentsThe method comprises the following steps: akito Masuhara, Satoshi Ohhashi, Hitoshi Kasai; ShujiOkada, FABRICATION AND OPTIC PROPERTIES OFNANOCOROMPLEXES COMPOSITES OF METAL NANOPROARTICLES ANDORGANIC DYES, Journal OF Nonlinear OPTICAL Physics&Materials volume 13, volume 3&Stage 4 (2004)587-592, the entire contents of which are incorporated herein by reference. Preparation of a crystalline solid from Ag or Au as core and 3-carboxymethyl-5- [2- (3-octadecyl-2-benzothiazolinylidene) ethylidene as shell by co-reprecipitation]Rhodanine (MCSe) or copper (II) phthalocyanine (CuPc). In the case of Ag-MCSe nanocomposites, 0.5mM MCSe in acetone was injected into 10ml by using NaBH₄Reducing AgNO₃In the prepared aqueous dispersion of Ag nanoparticles: Au-MCSe nanocomposites can also be fabricated in a similar manner. Reduction of HAuCl by use of sodium citrate in aqueous Au nanoparticle dispersions₄And (4) preparation. Subsequently, 2M NH was added₄OH (50. mu.l) and heat treating the mixture at 50 ℃. This amine treatment often promotes the formation of J-aggregates of mcse.6ag-CuPc, and Au-CuPc nanocomposites are also fabricated in the same way: a1 mM solution of CuPc in 1-methyl-2-pyrrolidone (NMP) (200. mu.l) was injected into an aqueous dispersion of Ag or Au nanoparticles (10 ml).

Preparation of silver nanoparticles

Silver (or gold) colloids were prepared according to the standard Lee-Meisel method: 200mL of 10-3M AgNO were stirred vigorously₃The aqueous solution was boiled and then 5mL of 35mM sodium citrate solution was added and the resulting mixture was kept boiling for 1 hour. The process is reported to produce colloidal particles of uniform size-1011 particles/mL, with diameters of-35-50 nm and a maximum absorption at 390 nm. The colloidal solution was stored at 4 ℃ and protected from room light. Further dilution of the colloidal solution was performed using distilled water.

Fabrication/preparation of metallic Nanocamp

One approach involves the use of nanospheres spin-coated on a solid support to create and control the desired roughness. The nanostructure carrier is then covered with a silver layer that provides the conduction electrons needed for the surface of the plasmonic mechanism. Among the solid substrate based technologies, the method using simple nanomaterials such as polytetrafluoroethylene or emulsion nanospheres seems to be the simplest preparation method. Polytetrafluoroethylene and emulsion nanospheres of various sizes are commercially available. The shapes of these materials are very regular and their dimensions can be chosen for optimal reinforcement. These materials include isolated dielectric nanospheres (30 nm in diameter) coated with silver that create a half-nanoshell system, which is referred to as a nanoshield.

Fabrication of gold nanoshells

Gold nanoshells have been prepared using methods described in the following references: hirsch LR, StaffordRJ, Bank JA, Sershenn SR, Price RE, Hazle JD, Halas NJ, West JL (2003) Nanoshell-media attached thermal therapy of turboms under MRGuidian. Proc Natl Acad Sci 100: 13549-13554 the method uses a mechanism involving nucleation and then continuous growth of gold nanoparticles around a silicon dioxide dielectric core. Gold nanoparticles prepared as described above using the fress method were used as seeds to grow gold shells. Silica nanoparticles (100nm) used as the core of the nanoshell were monodisperse in a solution of 1% APTES in EtOH. Molecular attachment via amino groups gold "seed" colloids were grown on the surface of silica nanoparticles synthesized using the fress method. The "seeds" cover the surface of the aminated silica nanoparticles, first a discontinuous gold metal layer, and gradually grow to form a continuous gold shell.

Commercial applications

In the following commercial application of the invention described herein, an energy modulation agent 3 (e.g., a particle or photon emitter) is provided and distributed in a medium 4 for inactivation or activation of an agent in the medium to produce a physical, chemical or biological change in the medium. In one embodiment, a plasmonics agent as described above is added to the medium. The plasmonics agent may enhance the applied initiation energy such that the enhanced initiation energy activates the at least one activatable agent to produce a change in the medium upon activation, and may also enhance the light converted by the energy modulation agent.

Examples of the light-emitting particles may include gold particles (e.g., gold nanoparticles as described above), BaFBr: Eu particles, CdSe particles, Y₂O₃:Eu³⁺Particles and/or other known excited light materials such as ZnS: Mn²⁺；ZnS:Mn²⁺，Yb³⁺，Y₂O₃:Eu³⁺；BaFBr:Tb³⁺And YF₃:Tb³⁺。

In one embodiment of the invention described herein, other potentially useful luminescent particles (or energy modulation agents) include, for example, carbon nanotubes as described by Wang et al in "electronic excitation of nano-carbon in vacuum", OPTICS EXPRESS, Vol.13, No. 10, 5/10/2005, the entire contents of which are incorporated herein by reference. Such carbon nanotubes exhibit a blackbody emission and a discontinuous linear emission in visible light when subjected to microwave radiation.

Other potentially useful luminescent particles for use in the invention described herein include: chemiluminescent reactions/substances described in "multicolor microwave-thickened Metal-Enhanced cheminescence" published in J.AM.CHEM.SOC. by Aslan et al, 09/23/2006, on the web, the entire contents of which are incorporated herein by reference. These chemiluminescent reactions/species are formed using silver nanoparticles that enhance the chemiluminescent reaction when subjected to microwave radiation. Aslan et al utilize the chemiluminescent material of a commercially available glow stick in which, for example, hydrogen peroxide oxidizes phenyl oxalate to a peroxy ester and a phenol. The unstable peroxyester decomposes into a peroxy compound and a phenol, which chemically produces an electronically excited state in response to light irradiation. While these chemiluminescent species may have a limited lifetime, it is still possible in the curing applications of the invention described herein, wherein the curing process occurs in one go and an external microwave source promotes curing by accelerating visible light generation.

The emission wavelength and/or efficiency of a luminescent particle often depends on the particle size. Particle sizes in the nanometer size range used in the invention described herein exhibit strong luminescence in many cases, as described in U.S. patent application publication 2007/0063154, which is incorporated herein by reference in its entirety. Furthermore, in one embodiment of the invention described herein, the luminescent particles may be bound to a molecular complex such as polyethylene glycol, vitamin B12 or DNA, which serves to prevent agglomeration of the luminescent particles (especially nanoparticles) and serves to render the luminescent particles biocompatible. More specifically, one method for synthesizing CdSe nanocrystals presented herein is from U.S. patent application publication No. 2007/0063154. Thus, citrate stabilized CdSe nanocrystals suitable for the invention described herein can be prepared according to the following procedure:

0.05g of sodium citrate (Fluka) and 2ml of 4X 10 are added to 45ml of water^-2Cadmium perchlorate (Aldrich). The pH was adjusted to 9.0 using 0.1M NaOH (Alfa). The solution was bubbled with nitrogen for 10 minutes, then 2ml of 1X 10 was added^-2N, N-dimethylselenourea (Alfa) of M. The mixture was heated in a conventional 900 watt microwave oven for 50 seconds. In this method, the molar ratio of Cd to Se is 4: 1, which gives CdSe nanoparticles with a diameter of-4.0 nm; by increasing the concentration of Cd, smaller CdSe nanoparticles can be synthesized.

Furthermore, the luminescent particles used in the invention described herein may be coated with an insulator material, such as silicon dioxide, which may reduce the likelihood of any chemical interaction between the luminescent particle and the medium. For biological applications of inorganic nanoparticles, one major limiting factor is their toxicity. In general, all semiconductor nanoparticles are more or less toxic. For biomedical applications, it is desirable that the toxicity of the nanoparticles is as low as possible, otherwise the nanoparticles must remain isolated from the medium. Pure TiO₂ZnO and Fe₂O₃Is biocompatible. CdTe and CdSe are toxic, while ZnS, CaS, BaS, SrS and Y₂O₃The toxicity is low. Furthermore, the toxicity of the nanoparticles can come from their inorganic stabilizers, such as TGA, or from dopants, such as TGAEu²⁺、Cr³⁺Or Nd³⁺. Other suitable energy modulation agents that appear to be most biocompatible are zinc sulfide, ZnS: Mn²⁺Iron oxide, titanium dioxide, zinc oxide, containing a small amount of Al₂O₃And AgI nanoclusters encapsulated in a molecular sieve. For non-medical applications, toxicity may not be as much of a concern, and the following materials (and listed elsewhere) are considered suitable: thulium activated oxyhalides of lanthanum and gadolinium; er ³⁺Doped BaTiO₃Nanoparticles of Yb³⁺Doped CsMnCl₃And RbMnCl₃，BaFBr:Eu²⁺Nanoparticles, cesium iodide, bismuth germanate, cadmium tungstate, and CsBr doped with divalent Eu.

In various embodiments of the present invention, the following luminescent polymers are also suitable as energy modulation agents: polyphenyleneacetylene, polyphenyleneethylene, polyparaphenylene, polythiophene, polyvinylpyridine, polypyrrole, polyacetylene, polyvinylcarbazole, polyfluorene, and copolymers and/or derivatives thereof.

Although many of the energy modulation agents of the present invention are down conversion agents (i.e., where higher energy excitation produces lower energy emission), U.S. Pat. No. 7,008,559 (the entire contents of which are incorporated herein by reference) describes the up conversion properties of ZnS, where excitation at 767nm produces luminescence in the visible region. U.S. Pat. No. 7,008,559 describes compositions containing ZnS and Er³⁺Doped BaTiO₃Nanoparticles and Yb³⁺CsMnCl doping₃Are suitable for various embodiments of the present invention.

Other materials designated for up-conversion include CdTe, CdSe, ZnO, CdS, Y₂O₃MgS, CaS, SrS and BaS. Such an up-converting material may be any semiconductor, and more specifically but not limited to: sulfides, tellurides, selenides, and oxide semiconductors and their nanoparticles, e.g. Zn _1-xMn_xS_y、Zn_1-xMn_xSe_y、Zn_1-xMn_xTe_y、Cd_1-xMnS_y、Cd_1-xMn_xSe_y、Cd_1-xMn_xTe_y、Pb_1-xMn_xS_y、Pb_1-xMn_xSe_y、Pb_1-xMn_xTe_y、Mg_1-xMnS_y、Ca_1-xMn_xS_y、Ba_1-xMn_xS_yAnd Sr_1-xAnd the like (wherein x is more than 0 and less than or equal to 1, and y is more than 0 and less than or equal to 1). Coordination compounds of the above-mentioned semiconductors may also be used in the present invention, for example (M)_1-zN_z)_1-xMn_xA_1-yB_y(M ═ Zn, Cd, Pb, Ca, Ba, Sr, Mg; N ═ Zn, Cd, Pb, Ca, Ba, Sr, Mg; A ═ S, Se, Te, O; B ═ S, Se, Te, O; 0 < x.ltoreq.1, 0 < y.ltoreq.1, 0 < z.ltoreq.1.) two examples of such coordination compounds are Zn_0.4Cd_0.4Mn_0.2S and Zn_0.9Mn_0..1S_0.8Se_0.2. Other conversion materials include insulating and non-conductive materials such as BaF₂BaFBr and BaTiO₃A few examples of exemplary compounds are given. Semiconductors co-doped with transition metals and rare earth ions suitable for the present invention include sulfide, telluride, selenide and oxide semiconductors and nanoparticles thereof, such as ZnS; mn; er; ZnSe; mn, Er; MgS; mn, Er; CaS; mn, Er; ZnS; mn, Yb; ZnSe; mn, Yb; MgS; mn, Yb; CaS; mn, Yb, etc. and their complex compounds: (M)_1-zN_z)_1-x(Mn_qR_1-q)_xA_1-yB_y(M＝Zn，Cd，Pb，Ca，Ba，Sr，Mg；N＝Zn，Cd，Pb，Ca，Ba，Sr，Mg；A＝S，Se，Te，O；B＝S，...0＜z≤1，0＜q≤1)。

In fact, some nanoparticles such as ZnS: Tb³⁺，Er³⁺；ZnS:Tb³⁺；Y₂O₃:Tb³⁺；Y₂O₃:Tb³⁺，Er³⁺；ZnS:Mn²⁺；ZnS:Mn，Er³⁺It is well known in the art to have two functions, i.e. to be able to be used for both down-conversion and up-conversion luminescence.

To reduce toxicityOr render the nanoparticles biologically inert or biocompatible, one embodiment of the invention described herein coats the nanoparticles with silica. Silica is used as a coating material in a wide range of industrial colloidal products ranging from paints and magnetic fluids to high quality paper coatings. In addition, silica is both chemically and biologically inert, and is optically transparent. The citrate stabilized CdTe of the invention described herein, Mn, CdTe, is suitable for use in the methods (from M.A. Correa-Duart, M.Giesig, and L.M.Liz-Marzan, Stabilization of CdS semiconductor nanoparticles against photodegradation by a silica coating process, chem.Phys.Lett., 1998, 286: 497, the entire contents of which are incorporated herein by reference) ²⁺/SiO₂Nanocrystals can be prepared with a silica coating:

(1) in CdTe: Mn²⁺To a nanoparticle solution (50ml) was added under vigorous stirring a freshly prepared aqueous solution (0.5ml, 1mM) (Sigma) of (3-mercaptopropyl) trimethoxysilane (MPS). The function of MPS is that its thiol group can bind directly to the surface Cd sites of CdTe, leaving the silane groups towards the solution, from where the silicate ions approach the particle surface; (2) adding 2ml of sodium silicate (Alfa) solution with pH 10.5 under vigorous stirring; (3) the resulting dispersion (pH 8.5) was allowed to stand for 5 days to allow the silica to slowly polymerize onto the particle surface; and (4) transferring the dispersion to ethanol so that excess dissolved silicate can precipitate out to increase the shell thickness of the silica.

Alternatively, as shown in fig. 3C and 3D, the light emitting particles in the encapsulating structure 10 may be in the vicinity of the medium. In one embodiment of the invention described herein, the luminescent particles are coated on the inside of the quartz or glass tube 9 and sealed. In another embodiment, the luminescent particles may be coated on the surface of a sphere or tube and then encapsulated with silicon dioxide (or other suitable passivation layer) using a vapor deposition or sputtering process or a spin-on-glass process of the above-described solution processes to produce an encapsulated structure 10, which encapsulated structure 10 may be part of a re-entrant structure extending from the vessel wall (as shown in fig. 3C) or may be part of a fluidized bed structure (as shown in fig. 3D). In another embodiment, the plasmonics agent is fixed to the outer surface of the glass tube 9. External light applied to the tube and scattered to the outer surface is enhanced at the plasmonics agent, so that the medium is more efficiently treated without having to use energy modulation agents.

In either configuration, the medium to be treated will flow through the enclosing structure 10 or along the enclosing structure 6, and the separation distance between the enclosing structures 6, 10 can be set to a distance that is less than the UV skin depth in the medium.

A suitable light source, such as one of the x-ray sources described above, may be used to excite the luminescent particles in the encapsulating structure 10. In one embodiment of the invention described herein, the concentration of the luminescent particles in the medium or the spacing between the encapsulating structures 10 is set such that the luminescent particles are spaced apart from each other in the medium by less than the skin depth of the UV into the medium. Higher concentrations can of course be used and higher UV fluxes can be generated if the energy source has sufficient intensity to "illuminate" all the luminescent particles.

For relatively clear aqueous media, solar UV-B radiation decays to 1% after penetrating 0.2m to 1m in the water sample, while UV-A penetrates about several meters. For such media, the concentration of the luminescent particles is more determined by the time required for the desired UV flux to inactivate or activate the reagent in the medium, rather than having to be set based on the concentration of the luminescent particles, where the medium itself does not block the UV excitation radiation from passing through the entire medium. The luminescent particles are disposed in and proximate to the medium without being limited by the optical density of the medium.

Eu as X-ray absorption per keV²⁺Published data for emission of an average of 5.2 spontaneous photons (M.Thoms, H.von Seggern, Method for the determination of photostimulable defect centers, production rates, and efficiency formation energies, J.Appl.Phys.1994, 75: 4658-4661, the entire contents of which are incorporated herein by reference), it is expected that CdTe nanoparticles emit about 50 photons for X-ray absorption per 50 keV.

U.S. patent application publication 2007/0063154-based method for stabilizing CdTe particles using 0.8ml of L-cysteine in 0.2g BaFBr Eu²⁺Concentrated preparation of CdTe/BaFBr: Eu in phosphor²⁺X-ray spectroscopy results of the nanocomposites, Eu, with increasing X-ray exposure time²⁺390nm of the intensity of the X-ray luminescence increases. This phenomenon is described in W.Chen, S.P.Wang, S.Westcott, J.Zhang, A.G.Joly, and D.E.McCready, Structure and luminescence science of BaFBr: Eu²⁺and BaFBr:Eu²⁺，Tb³⁺phosphors and thin films, j.appl.phys.2005, 97: 083506, the entire contents of which are incorporated herein by reference.

Thus, in one embodiment of the invention, for particles having a diameter of 200nm, per cm ³About 10⁹A minimum baseline concentration of nanoparticles is expected to be sufficient to produce altered UV radiation in the medium. The present invention is not limited to this concentration range, but this range is given as an illustrative example. Indeed, higher concentrations can increase UV emission per unit time and provide faster interaction, which is generally considered useful for industrial applications where product throughput is a concern.

Sterilization and low temperature pasteurization of fluids

Table 1 below shows the appropriate strength of the germicidal destruction

TABLE 1 Sterilization energy required for destruction

Thus, the energy modulation agent (or luminescent particles) of the present invention (as described above with reference to fig. 3B and 3C) may be provided inside a sealed quartz or glass tube or may be provided coated on the surface of a sphere or tube and further encapsulated with a silicon dioxide or passivation layer. The plasmonics agent may be formed using an energy modulation agent. In any of the structures of the invention described herein, the medium can flow through the enclosing structure 6, 10 such that the separation distance between the enclosing structure or quartz or glass tube is less than the UV skin depth.

For example, Ultraviolet (UV) light at a wavelength of 254nm is known to be prone to inactivation of most types of microorganisms. Most juices are opaque to UV due to the high concentration of suspended solids therein, so conventional UV treatment, which is commonly used for water treatment, cannot be used to treat the juice. In order to make the process efficient, thin film reactors constructed of glass have been used, with the juice flowing along the inner surface of a vertical glass tube as the membrane. See "Ultraviolet Treatment of Orange Juice" (Vol. 5, No. 4, 12 months 2004, pages 495-502) published in Innovative Food science embedding Technologies by Tran et al, the entire contents of which are incorporated herein by reference. Wherein Tran et al report: the decimal reduction dose required for reconstituting orange juice (OJ; 10.5 ℃ Brix) for standard Aerobic Plate Count (APC) and yeast and mold was 87 + -7 and 119 + -17 mJ/cm, respectively ². In this article, under limited UV exposure (73.8 mJ/cm)²) The shelf life of the freshly squeezed orange juice is prolonged to 5 days. The effect of UV on vitamin C concentration was investigated using HPLC and titration measurements. At 100mJ/cm²At high UV exposure, vitamin C is degraded to 17%, similar to what is normally present in heat sterilization. The enzyme Pectin Methylesterase (PME) activity was also measured as the major cause of haze loss in juice. Energy required for UV treatment of orange juice (2.0kW h/m)³) Much less than the energy required for heat treatment (82kW h/m)³). The color and pH of the juice was not significantly affected by the treatment.

The advantages of the invention described herein over this process are: the energy modulation agent can be placed inside a fixture such as quartz or glass (sealing structure 8) within the orange juice (or other fluid medium) and irradiated with x-rays (or other penetrating radiation) through, for example, a plastic or aluminum container 9 to activate the energy modulation agents 3 and 6 within the orange juice. Thus, the expense and fragility of thin film reactors constructed from other similarly constructed glasses is avoided.

Although illustrated with respect to orange juice, any other medium to be sterilized, including food products, medical products, and cosmetic products, may be treated using the inventive techniques described herein.

Sterilization of medical and pharmaceutical products

As described above, the medical bottle cap requires sterilization between the bottom cap material and the sealing material contacting the bottom of the medical bottle. Steam pressure tanks are not sufficient for this purpose because once glued, the steam cannot penetrate into the glued joint.

Gamma radiation has been conventionally used to sterilize the following articles: medical caps and other medical, pharmaceutical and cosmetic articles, such as surgical disposable articles (e.g., surgical bandages, dressings, gauntlets, diapers, delivery devices, and the like), metal products (e.g., scalpels, implants, aluminum caps, containers, and the like), and plastic and rubber articles (e.g., petri dishes, centrifuge tubes, blood collection devices, scalp needles, shunt valves, rubber gloves, contraceptives, gowns, packaging covers, sheets, and the like). The present invention can be used to sterilize any "interior" surface of these and other products.

In one embodiment of the invention described herein, the UV-luminescent particles may be included in the adhesive layer when the sealing material is applied to the bottle cap. X-ray irradiation can then cure the adhesive (if, for example, the adhesive is a light-sensitive adhesive as set forth in more detail below) and can generate ultraviolet radiation within the adhesive medium for direct sterilization or for generating singlet oxygen or ozone for biological sterilization. In addition, plasmonics agents may be included to enhance the effect of incident radiation or internally generated radiation.

Although described herein with respect to medical bottle caps, other adhesive configured devices may also benefit from these procedures, wherein the adhesive medium is cured and/or sterilized during activation of the energy modulation agents 3 and 6.

Of blood productsSterilization

U.S. patent 6,087,141, the entire contents of which are incorporated herein by reference, describes a uv-activated psoralen process for sterilization of transfusion products. Here, the invention can be applied in devices such as shown in fig. 3C and 3D for the treatment or inactivation of AIDS and HIV or other viruses or pathogens in blood transfusion products. In this embodiment, the at least one photoactivatable agent is selected from: psoralens, pyrenyl cholesterol oleate, acridines, porphyrins, fluoresceins, rhodamines, 16-diazocortisones, ethidines, transition metal complexes of bleomycin, transition metal complexes of deglycobleomycin, organo platinum complexes, alloxazines, vitamin Ks, vitamin L, vitamin metabolites, vitamin precursors, naphthoquinones, naphthalenes, naphthols and their derivatives with planar molecular conformations, porphyrins, dyes and phenothiazine derivatives, coumarins, quinolones, quinones and anthraquinones. These photoactivatable agents are introduced into a blood product (or the bloodstream of a patient). Applying penetrating energy to the blood product (or to the patient). The energy modulation agent (either contained in the blood product or in the encapsulating structure 10) generates secondary light, such as UV light, that activates the photoactivatable agent in the blood product.

In a particular example, the photoactivatable agent is a psoralen, a coumarin, or a derivative thereof, and as described above, blood product sterilization can be performed in vivo (i.e., in a patient) or in a blood product (e.g., donated blood) container. The treatment can be used to treat an abnormality, such as cancer cells, tumor cells, autoimmune deficiency syndrome virus, or blood-borne bactericides, by treating the abnormality with a psoralen, a coumarin, or a derivative thereof.

Detoxification of waste water

Photocatalysis may also be used as a tertiary treatment of wastewater to meet regulatory emission limits and to oxidize persistent compounds that are not oxidized in biological treatment. Photocatalysis has been very successfully applied to the elimination of a variety of pollutants (e.g., alkanes, alkenes, phenols, aromatics, pesticides). In many cases, alreadyComplete mineralization of the organic compound was observed. Various photocatalysts such as CdS, Fe have been studied₂O₃、ZnO、WO₃And ZnS, but using TiO₂P₂₅The best results have been obtained. These photocatalysts may be used in the invention described herein.

Refinery wastewaters come from water washing equipment used in the process, undesirable waste and sanitary sewage. These effluents have a high oil and fat content, in addition to other organic compounds in the solution. These pollutants form a residual Chemical Oxygen Demand (COD) that can pose a serious toxic hazard to the environment.

Photocatalysis is known to be useful for wastewater reduction remediation. U.S. patent 5,118,422 to Cooper et al, the entire contents of which are incorporated herein by reference, describes a uv-driven photocatalytic post-treatment technique for purifying a water feedstock containing oxidizable contaminant compounds. In this work, a water feedstock is mixed with photocatalytic semiconductor particles (e.g., TiO) having a particle size of about 0.01 to about 1.0 micron and in an amount of about 0.01 to about 0.2 weight percent of the water₂、ZnO、CdS、CdSe、SnO₂、SrTiO₃、WO₃、Fe₂O₃And Ta₂O₅Granules) are mixed. The water comprising the semiconductor mixture is exposed to band gap photons for a time sufficient to oxidize the oxidizable contaminants to purify the water. The purified water is separated from the semiconductor particles using cross-flow membrane filtration. Cooper et al indicate that: the carbon content of the organic impurities of simulated recovered water at a nominal 40PPM level can be reduced to parts per billion using a recirculating batch reactor.

Cooper et al identified that an important aspect of the photocatalytic process is the adsorption of organic molecules onto a very large surface area by a finely divided powder dispersed in water. Cooper et al also indicate that: in photochemical applications, the fact that the solid phase (metal oxide semiconductor) is also photoactivated and the generated charge carriers are used directly for the oxidation of the organic matter is advantageous. Adsorption of band gap photons by the semiconductor particles results in electrons (e) ^-) Hole (h)⁺) And (4) forming pairs. Cooper et al consider in the pilotElectrons generated in the band and forming a dioxyanion (O)^2-) Solution oxygen reaction of species, dioxyanion (O)^2-) The species then undergoes further reaction, resulting in the production of the strongly oxidizing hydroxyl radical species OH. These strong oxidizers are known to oxidize organic compounds themselves. In addition, Cooper et al believe that the strong oxidative holes generated in the valence band have sufficient energy to oxidize all organic bonds.

In the Cooper et al reactor, turbulence is necessary to ensure exposure of wastewater contaminants and photocatalytic titanium dioxide particles to UV light. Cooper et al consider that the most fundamental consideration is photocatalyst photoabsorption and its relationship to convective mixing. For 0.1 wt% photocatalyst loading, experiments show that: absorb 90% of the light within 0.08 cm. This is mainly due to the large UV absorption coefficient of the photocatalyst, and therefore most of the photoelectrochemistry occurs in this illuminated region. By operating the reactor of Cooper et al at a Reynolds number (Re) of 4000, it was ensured that a significant portion of the photoactive region was within a well-mixed turbulent region.

"photocatalytic as a tertiary treatment for petroleum refinery waste water" (the entire contents of which are incorporated herein by reference) as published in braz.j.chem.eng. 23, vol.4, 2006 by Santos et al reports satisfactory reduction of the amount of pollutants to prescribed emission limit levels and oxidation of persistent compounds that are not oxidized in the biological treatment. The processing sequence adopted by refineries (REDUC/PETROBASRS, Brazilian refineries) is an oil/water separation followed by a biological treatment. Although the process is efficient in terms of Biological Oxygen Demand (BOD) removal, residual and persistent COD and phenol content remains. The refining capacity of the oil refinery is 41,000m ³A day, yield 1,100m³Waste water/h, which was discharged directly into the gulanaba bay (Rio de Janeiro). Residual and persistent COD is still preferred.

Santos et al performed a first set of experiments in a 250mL open reactor containing 60mL of wastewater. In a second set of experiments, Pyrex containing 550mL of wastewater was usedA loop reactor (DePaoli and Rodrigues, 1978) is shown in FIG. 1. The reaction mixture in the reactor was kept in suspension by magnetic stirring. In all experiments, air was continuously bubbled through the suspension. A250W Phillips HPL-N medium-pressure mercury lamp (with its outer bulb removed) was used as UV-light source (radiant flux 108 J.m at > 254 nm)^-2·s^-1). In one set of experiments, the lamp was located at a fixed height (12cm) above the liquid surface. In a second set of experiments, a lamp was inserted into the well. All experiments by Santos et al were performed at 25. + -. 1 ℃. The concentration of the catalyst is 0.5-5.5 g L^-1And the initial pH is 3.5 to 9.

In the invention described herein, the luminescent particles or other energy modulation agents can be placed within quartz or glass fixtures or can be placed on silica encapsulated structures within the wastewater, such as photocatalytic TiO₂The energy modulation agent(s) may be introduced into the wastewater during irradiation. In addition, plasmonics agents may be included to enhance the effect of incident radiation or internally generated radiation.

Activation of the luminescent particles (i.e., energy modulation agents) generates UV light in the vicinity of the photocatalytic agent upon irradiation with x-rays (or other penetrating radiation) through, for example, a plastic or aluminum container. In other words, for the invention described herein, luminescent particles or other energy modulation agents are mixed with photocatalytic semiconductor particles in the wastewater fluid stream, and an external activation energy source passes through a container (e.g., a plastic or aluminum container) and irradiates the bulk of the wastewater, generating UV light throughout the wastewater, which in turn drives the photocatalytic reaction. In one embodiment, the plasmonics agent is complexed with the luminescent particle or other energy modulation agent prior to addition to the fluid stream.

Thus, the invention described herein provides many advantages over the above-described solutions, including the elimination of the need for expensive wastewater holding tanks, the avoidance of having to pump the wastewater at higher pressures or flow rates to create sufficient turbulence and the generation of UV light throughout the wastewater thereby providing faster batch treatment of the wastewater.

Optical excitation

Optical excitation is a field where light is applied to change physical properties. For example, there is an increasing interest in the use of biodegradable polymers in the consumer and biomedical fields. Polylactic acid (PLA) plastics and Polyhydroxyalkanoate (PHA) plastics have played an important role in achieving this goal. Their relatively hydrophobic surfaces limit their use in various applications. Therefore, surface modification of these film surfaces is required. Due to the lack of any modifiable side chain groups, researchers have used sequential two-step photografting techniques to surface modify these biopolymers. In step 1, benzophenone is photo-grafted on the surface of the film, and in step 2, hydrophilic monomers such as acrylic acid and acrylamide are photo-polymerized from the surface of the film.

Researchers have found that ultraviolet radiation can achieve effective graft copolymerization. UV assisted photografting in ethanol has been used to grow hydrophilic polymers (e.g., polyacrylic acid and polyacrylamide) from the surface of PLA, PHA, and PLA/PHA blend films. In this work, a functional Polyurethane (PU) surface was prepared by photo-grafting N, N-dimethylaminoethyl methacrylate (DMAEM) onto the film surface. Graft copolymerization is carried out by a combination of photooxidation and irradiation grafting. The PU film was photo-oxidized to introduce hydrogen peroxide groups on the surface, and then the film previously immersed in the monomer solution was irradiated with UV light. The results show that: prior to the present invention, UV irradiation was effective in effecting graft copolymerization.

In the invention described herein, these processes are accelerated by including luminescent particles or other energy modulation agents in a dispersion in a fluid medium for photoexcitation. In addition, plasmonics agents may be included to enhance the effect of incident radiation or internally generated radiation. In one embodiment, the plasmonics agent is complexed with a luminescent particle or other energy modulation agent previously added to the fluid medium.

Upon irradiation with x-rays (or other penetrating radiation) through, for example, a plastic or aluminum container, activation of the luminescent particles (i.e., energy modulation agent) can generate UV light throughout the volume of the medium (without any shadowing effect) and allow batch or bulk type processing to be performed in parallel throughout the container.

In other examples, the generation of endogenous light within the bulk medium can be used to stimulate a chemical or biological process through direct interaction of light with an activatable agent in the medium or indirectly by generating heat, and the present invention can provide a controlled and uniform manner of heating the drum of material in a biological or chemical process through the dispersed energy modulation agent.

Light inactivation

In many industrial processes, in particular in the food and beverage industry, yeast is used to produce changes in a medium, such as conversion of sugars in raw materials. One particularly important example is the wine industry. Stopping the wine from fermenting in one step can keep the current sweetness. Likewise, allowing wine to continue fermenting further only makes wine less and less sweet as the day goes by. Finally, the wine will dry out completely, at which time the fermentation will stop by itself. This is because yeast converts sugar to alcohol during fermentation.

The desire to stop the fermentation is in itself good. Unfortunately, however, there is indeed no practical way to successfully stop the fermentation completely. Additives such as sulfites and sorbates may be added to stabilize the fermentation product and stop additional fermentation. Many brewers will turn to the use of sulfites such as sodium bisulfite or compton tablets for this purpose. However, both additives do not reliably kill enough yeast to ensure complete cessation of activity-at least in amounts that are not normal for keeping the wine still drinkable.

Once most of the sulfite from any of these components dissipates from the wine into the air-like sulfite-if given sufficient time, the remaining few viable yeast cells will start to multiply and re-ferment. This usually occurs at the most unfortunate time, such as after the wine has been bottled and stored.

Potassium sorbate is another ingredient considered by many brewers when attempting to stop wine from further fermentation. There are many misunderstandings about this product. It is usually used in home-based wine books when the wine is to be sweetened. At this point the fermentation is complete and ready for bottling. Potassium sorbate is added with the sugar added for sweetening.

Potassium sorbate prevents the yeast from fermenting the newly added sugar. Thus, many brewers believe that potassium sorbate can also stop active fermentation, but potassium sorbate does not kill the yeast at all, but rather renders the yeast incapable of reproduction. In other words, it impairs the ability of the yeast to self-propagate. However, it does not prevent the ability of yeast to ferment sugars to alcohol.

Ultraviolet light is known to destroy yeast cultures, but has limited application because ultraviolet light cannot penetrate fluid media. While heat may be used to destroy yeast activity, the cooked product may be premature or may produce undesirable changes in consistency and taste. For liquid or fluid food products, the same techniques described above for liquid pasteurization can be used with the invention described herein. For non-liquid products, energy conditioners (e.g. iron oxide or titanium dioxide) with low and preferably no toxicity may be added. Here, the concentration of these additives would be limited by any unexpected taste change.

Photoactivated crosslinking and curing of polymers

In this application, luminescent particles (or energy modulation agents) are provided and distributed into an uncured polymer-based medium to activate photosensitizers in the medium to promote crosslinking and curing of the polymer-based medium. In addition, plasmonics agents may be included to enhance the effect of incident radiation or internally generated radiation. In one embodiment, the plasmonics agent is complexed with the luminescent particle or other energy modulation agent prior to addition to the polymer.

As noted above, for adhesive and surface coating applications, light activation treatment is limited by the penetration depth of UV light into the treatment medium. In light-activated adhesive and surface coating processes, the main limitation is that the material to be cured must be irradiated with light, including type (wavelength or spectral distribution) and intensity. This limitation means that a medium must generally transmit suitable light. In adhesive and surface coating applications, any "masked" areas will require a secondary cure mechanism, such that the cure time on the unmasked areas is increased and further delayed due to the presence of a sealing skin layer through which subsequent curing must occur.

Conventionally, moisture cure mechanisms, thermal cure mechanisms, and photo-initiated cure mechanisms are used to initiate curing, i.e., crosslinking, of reactive compositions such as reactive silicones, polymers, and adhesives. These mechanisms are based on condensation reactions where moisture hydrolyzes certain groups or addition reactions that can be initiated by forms of energy such as electromagnetic radiation or heat.

The invention described herein may use any of the following light-activated curing polymers, as well as other light-activated curing polymers known in the art, to which the luminescent particles (or energy modulation agents) are added.

For example, one suitable photoactive polymer includes a UV-curable silicone having acrylate functionality. U.S. patent 4,675,346 to Lin, the entire contents of which are incorporated herein by reference, relates to a UV-curable silicone composition comprising at least 50% of a specific type of silicone resin, at least 10% of a fumed silica filler, and a photoinitiator, and cured compositions thereof. Other known UV-curable silicone compositions suitable for the present invention include (meth) acrylate functional group-containing polyorganosiloxanes, photosensitizers, and solvents, which cure to a hard film. Other known UV-curable silicone compositions suitable for the present invention include: a polyorganosiloxane having an average of at least one acryloxy and/or methacryloxy group per molecule, a low molecular weight polyacryl crosslinker, and a photosensitizer.

Loctite Corporation designed and developed UV-curable and UV/moisture dual-curable silicone compositions that also exhibited high flame retardancy, wherein the flame retardant ingredient was a combination of hydrated alumina and an ingredient selected from the group consisting of a transition metal organic ligand complex, a transition metal organosiloxane ligand complex, and combinations thereof. See U.S. patent nos. 6,281,261 and 6,323,253 to Bennington. These formulations are also suitable for use in the present invention.

Other known UV light activatable silicones include silicones functionalized with, for example, carboxylic acid esters, maleic acid esters, cinnamic acid esters, and combinations thereof. These formulations are also suitable for use in the present invention. Other known UV light-activatable silicones suitable for use in the present invention include benzoin ethers ("UV free radical generators") and free radically polymerizable functional silicone polymers as described in U.S. patent 6,051,625, which is incorporated herein by reference in its entirety. The UV free-radical generator (i.e., benzoin ether) is contained in an amount of 0.001 to 10 wt% based on the total weight of the curable composition. The free radical generator may be added in a catalytic amount relative to the polymerizable functional groups in the target composition by irradiating the composition to generate free radicals that serve as initiators for the polymerization reaction. These silicone resins may further contain silicon-bonded dioxy compounds, which may form siloxane bonds, while the remaining oxygen may be bonded to another silicon in each case to form siloxane bonds, or may be bonded to a methyl group or an ethyl group to form alkoxy groups, or may be bonded to hydrogen to form silanol. Such compounds may include trimethylsilyl, dimethylsilyl, phenyldimethylsilyl, vinyldimethylsilyl, trifluoropropyldimethylsilyl, (4-vinylphenyl) dimethylsilyl, (vinylphenyl) dimethylsilyl, and (vinylphenethyl) dimethylsilyl.

The photoinitiator component of the present invention is not limited to those free radical generators described above, but may be any photoinitiator known in the art, including: the aforementioned benzoins and substituted benzoins (e.g., alkyl esters of substituted benzoins), Michler's ketone, dialkoxyacetophenones such as diethoxyacetophenone ("DEAP"), benzophenone and substituted benzophenones, acetophenone and substituted acetophenones, and xanthones and substituted xanthones. Other suitable photoinitiators include: DEAP, benzoin methyl ether, benzoin ethyl ether, benzoin isopropyl ether, diethoxy xanthone, chloro-thio-xanthone, azobisisobutyronitrile, N-methyldiethanol aminobenzophenone, and mixtures thereof. Visible light initiators include camphorone, peroxyester initiators, and non-fluorenylcarboxylic acid peroxyesters.

Commercially available examples of photoinitiators suitable for the present invention include those available under the trade names IRGACURE and DAROCUR from Vantico Inc, Brewster, N.Y., in particular IRGACURE184 (1-hydroxycyclohexyl phenyl ketone), 907 (2-methyl-1- [4- (methylthio) phenyl ] -2-morpholinopropan-1-one), 369 (2-benzyl-2-N, N-dimethylamino) -1- (4-benzomorpholino ] -1-butanone, 500 (a combination of 1-hydroxycyclohexyl phenyl ketone and benzophenone), 651(2, 2-dimethoxy-2-phenylacetophenone), 1700 (the group of bis (2, 6-dimethoxybenzoyl-2, 4, 4-trimethylpentyl) phosphine oxide and 2-hydroxy-2-methyl-1-phenyl-propan-1-one) And 819[ bis (2, 4, 6-trimethylbenzoyl) phenylphosphine oxide ] and DAROCUR 1173 (2-hydroxy-2-methyl-1-phenyl-1-propane) and 4265 (a combination of 2, 4, 6-trimethylbenzoyl-phosphine oxide and 2-hydroxy-2-methyl-1-phenyl-propan-1-one); and IRGACURE 784DC (bis (η 5-2, 4-cyclopentadien-1-yl) -bis [2, 6-difluoro-3- (1H-pyrrol-1-yl) phenyl ] titanium).

Generally, the amount of photoinitiator (or free radical generator) should be from about 0.1% to about 10% by weight, for example from about 2 to about 6% by weight. The concentration of free radical generator for the benzoin ether is generally 0.01 to 5 wt%, based on the total weight of the curable composition.

A moisture cure catalyst may also be included in an amount effective to cure the composition. For example, from about 0.1 to about 5 wt%, such as from about 0.25 to about 2.5 wt% of a moisture cure catalyst may be used in the present invention to promote curing processes other than light activated curing. Examples of such catalysts include organic compounds of titanium, tin, zirconium, and combinations thereof. Tetraisopropyl titanate and tetraisobutyl titanate are suitable as moisture curing catalysts. See U.S. Pat. No. 4,111,890, incorporated herein by reference in its entirety.

Included in conventional silicone compositions (and other inorganic and organic adhesive polymers) suitable for the present invention are various inorganic fillers. For example, hollow microspheres under the trade name Q-CEL supplied by Kish are white free-flowing powders. Typically, these borosilicate hollow microspheres are used as extenders in active resin systems, often to replace heavy fillers such as calcium carbonate, thereby reducing the weight of the composite material formed therefrom. The Q-CEL 5019 hollow microspheres were composed of borosilicate and had a liquid displacement density of 0.19g/cm ²The average particle size is 70 microns, and the particle size range is 10-150 microns. Other Q-CEL products are shown in the following table. Another commercially available hollow glass bead is sold by Kish under the name SPHERICEL. SPHEREICEL 110P8 had an average particle size of about 11.7 microns and a crush strength of greater than 10,000 psi. Other commercially available hollow glass microspheres are sold under the trade name PERLITE by Schundler Company, Metuchen, N.J., Whitehouse Scientific Ltd., Chester, UK and 3M, Minneapolis, Minn., under the trade name SCOTCHLITE.

Typically, these inorganic filler components (as well as other components such as fumed silica) add structural properties to the cured composition, but also impart flowable properties to the composition in the uncured state and increase transmission of UV curing radiation. When present, fumed silica can be used at levels up to 50 weight percent, with about 4 to at least about 10 weight percent being suitable. While the precise level of silica can vary with the characteristics of the particular silica and the desired properties of the composition and its reaction products, one skilled in the art should note that the compositions of the present invention are made to have a suitable level of transmittance to allow UV curing to occur.

Desirable hydrophobic silicas include hexamethyldisilazane-treated silicas such as those commercially available under the trade name HDK-2000 from Wacker-Chemie, Adrian, Mich. Other include polydimethylsiloxane-treated silicas such as those sold under the tradename CAB-O-SIL N70-TS by Cabot Corporation or AEROSIL R202 by Degussa Corporation. Other silicas include trialkoxyalkylsilane-treated silicas such as trimethoxyoctylsilane-treated silicas commercially available from Degussa under the trade name aersil R805; and 3-dimethyldichlorosilane-treated silica commercially available from Degussa under the trade names R972, R974 and R976.

While these inorganic fillers have extended the use of conventional UV-cured silicone systems to allow curing of materials outside the skin depth of the UV penetration, these inorganic fillers do not overcome the shadowing effect by themselves and are subject to UV scattering which is effective to promote smaller skin depths. In the invention described herein, the inclusion of these inorganic fillers with the luminescent particles provides a mechanism by which uniform light activated curing can occur deep into the interior of the adhesive curing assembly in areas where external UV or other light sources are typically shielded or otherwise inaccessible.

Thus, in this example of the invention described herein, conventional silicone and polymeric adhesive or release or coating compositions are prepared using conventional mixing, heating and incubation methods. Luminescent particles are included in these conventional compositions. These compositions comprising luminescent particles can then be applied to the surfaces of objects to be fixed together, or to surfaces where a hard coating is desired, or to cast prepared mouldings in curable form. The luminescent particles in these compositions, when activated, can generate radiant light for photo-activated curing of the polymer composition comprising the luminescent particles. The density of the luminescent particles in these compositions can depend on the "light transmittance" of the composition comprising the luminescent particles. In the case where these compositions contain a significant amount of the above-described inorganic filler, the concentration of luminescent particles can be reduced as compared to compositions having a black pigment in which light transmittance can be significantly reduced.

One advantage of the invention described herein is seen in this example: pigments can now be incorporated into photocurable resins without significantly sacrificing cured product performance. These pigments may include more than one colored pigment known to those skilled in the art. Such pigments are typically metal oxides and include, but are not limited to: titanium dioxide, iron oxides, organic complexes, mica, talc and quartz. One pigment may be used or a combination of two or more pigments may be used. By selecting suitable pigments and combining them in a similar manner as set forth in the examples below and making the necessary corrections common in the coatings industry, different colors can be obtained. Thus, in one embodiment of the invention, these pigments, including carbon black, may also be included as an opaque material to limit the propagation of internal light from the point of generation.

U.S. patent application 7,294,656 to Bach et al, the entire contents of which are incorporated herein by reference, describes a non-aqueous composition curable by ultraviolet radiation that consists essentially of a mixture of two UV-curable urethane acrylates, which has several advantages over conventional radiation-curable compositions. The composition of Bache et al can be cured in a relatively short time using UV-C (200-280nm), UV-B (280-320nm), UV-A (320-400nm), and visible light (above 400nm) radiation. In particular, the compositions of Bache et al can be cured using radiation having a wavelength of 320nm or greater. When fully cured (regardless of the radiation used), the Bach et al composition exhibits hardness and impact resistance at least comparable to conventional coatings.

In the invention described herein, a luminescent particle (or energy modulation agent) as described above may be added to the Bach et al composition, optionally including multiple pigments in one embodiment. Thicker surface coatings can be achieved due to the fact that the external energy source passes completely through the entire composition of Bach et al. Furthermore, the coating can be used, for example, for the preparation of complex surfaces with depressions or protrusions. Curing around the recesses and protrusions without the limitations of conventional UV shielding can provide a surface coating with enhanced adhesion to the workpiece.

Furthermore, in one embodiment of the present invention, an external energy source that initiates energy may direct structural elements in which gaps (or cracks) are filled with uncured radiation-curable medium (such as those described above). The uncured radiation-curable medium in the endogenous photocurable gaps (or cracks) thereby repairs the irradiated structure.

Currently, there are commercially available epoxy systems for the restoration of concrete structures using epoxy resin injection. Epoxy injection is often the only option for a complete replacement of the structure. Thus resulting in a significant cost reduction. In addition to filling cracks, epoxy resin injection is known to protect the rebar and water resistance in concrete. Commercially, epoxy injection resins provide a system for welding cracks that repairs the original strength and load of the original design in the concrete. Typically, a low viscosity resin is pressed into the cracks. Holes are typically drilled around or in the fracture to provide a conduit for pumping resin into the fracture.

However, it takes time to infiltrate the resin into the thin and even hairline cracks. Unfortunately, in current commercial systems, the upper cure time limit is set for the length of time that a low viscosity resin can flow into the fracture due to the limited time that results from premixing the resin with the hardener. Moreover, the time to complete repair is problematic in many industrial repairs because the hardener is typically at a high enough concentration to allow the resin to set within twenty-four (24) hours, for example. Further, with conventional resin methods, since all areas of the resin are cured, curing cannot occur in a particular area of interest.

The present invention provides a number of advantages. First, the resin of the present invention can be a light-activated resin that does not substantially cure until the x-ray source generates internal light to activate the photoinitiator. This provides greater flexibility in pumping and waiting for the fracture to fill completely. Second, once the photoactivatable resin is in place, its curing is activated and occurs at a rate that is not controlled by conventional hardening reactions. Third, the x-rays transmit through the concrete and the crack area will provide a more uniform resin curing mechanism, where deep cracks are likely to be fully cured as narrow cracks that may extend deep into the material. Furthermore, the invention allows the possibility to cure only specific areas of interest, i.e. the areas irradiated with X-rays.

In another embodiment of the present invention, the external energy source may be a directed or focused beam of initiation energy that cures the uncured radiation-curable medium to produce patterned elements. In this embodiment, the structure that houses or at least partially encloses the uncured radiation curable medium may be a structure that is opaque to visible light. In this way, uncured radiation-curable media (which are typically photoactivated when exposed to ambient light) can be delivered without premature curing. In this embodiment, curing is activated by directing one or more focused beams of x-rays, the overlap of the beams creating the following regions in the structure that contains or at least partially encloses the uncured radiation-curable medium: wherein the UV or visible light generated from the energy modulation agent in the medium has sufficient intensity to activate the photoinitiator. In this way, precise three-dimensional and two-dimensional patterns can be achieved. In a similar embodiment, upconverting energy modulators may be used when the structure is transmissive to, for example, infrared or microwave frequencies. The initiation energy from the infrared laser is directed and focused into a structure that contains or at least partially encapsulates the uncured radiation-curable medium.

As an example in another embodiment, a patterned element such as a device (e.g., a plug that closes a particular internal hole or channel) can be fabricated (e.g., cured) inside a structure (e.g., a building material, an artificial or natural underground storage tank, internal organs of the human body, etc.) from the outside of the structure using energy excitation (e.g., X-rays). Another application of this technique may involve the manufacture of an orthopedic structure in vivo, wherein a curable resin is introduced locally at the site of the orthopedic structure to be formed and a directed or focused x-ray beam is introduced to cure the structure.

Accordingly, in another embodiment of the present invention, a method (and associated system) of generating patterned elements within a structure is provided. The method provides a radiation-curable medium including at least one of a plasmonics agent and an energy modulation agent within a structure. The energy modulation agent is configured to emit light into the medium upon interaction with the initiation energy. The method applies initiation energy to the medium from a directed or focused energy source. The applied initiation energy interacts with the plasmonics agent or energy modulation agent to generate light at a localized region inside the structure, thereby locally curing the radiation-curable medium.

As described above, the method may form plugs as patterned elements to close holes or passages in structures, such as in building materials, artificial or natural underground storage tanks, or in human or animal body viscera. The method may form a prosthetic device as a patterned element at a localized point in a human or animal body.

The method may also reduce the propagation of light generated from the point of generation by disposing an optically dense material (such as the above-described pigments) in the radiation curable medium.

Computer aided control

In one embodiment of the invention, a computer-implemented system is provided for designing and selecting a suitable combination of an initiation energy source, an energy modulation agent, and an activatable agent. For example, the computer system 5 may include: a Central Processing Unit (CPU) having a storage medium, provided thereon: a database of excitable compounds, a first calculation module for a photoactivatable agent or energy transfer agent, and a second calculation module that predicts the energy flux required to fully activate the energy transfer agent or photoactivatable agent.

FIG. 4 illustrates a computer system 1201 for implementing various embodiments of the present invention. The computer system 1201 may serve as the computer system 5 to perform any or all of the functions described above. The computer system 1201 includes a bus 1202 or other communication means for communicating information, and a processor 1203 connected with the bus 1202 for processing the information. The computer system 1201 also includes: a main memory 1204, such as a Random Access Memory (RAM) or other dynamic storage device (e.g., Dynamic Random Access Memory (DRAM), Static Random Access Memory (SRAM), and Synchronous DRAM (SDRAM)), is coupled to the bus 1202 for storing information and instructions to be processed by the processor 1203. In addition, the main memory 1204 may be used for storing temporary variables or other intermediate information during execution of instructions from the processor 1203. The computer system 1201 also includes: a Read Only Memory (ROM)1205 or other static memory such as a Programmable Read Only Memory (PROM), Erasable Programmable Read Only Memory (EPROM), and Electrically Erasable Programmable Read Only Memory (EEPROM) coupled to the bus 1202 may be used to store static information and instructions for the processor 1203.

The computer system 1201 also includes: a disk controller 1206 coupled to the bus 1202 to control one or more memories for storing information and instructions, such as a magnetic hard disk 1207, and a removable media drive 1208 (e.g., floppy disk drive, read-only compact disk drive, read/write compact disk drive, compact disk access cartridge, tape drive, and removable magneto-optical drive). Suitable device interfaces (e.g., Small Computer System Interface (SCSI), integrated electronics (IDE), enhanced IDE (E-IDE), Direct Memory Access (DMA), or hyper-DMA) may be used.

The computer system 1201 may also include special purpose logic devices such as Application Specific Integrated Circuits (ASICs) or configurable logic devices such as Simple Programmable Logic Devices (SPLDs), Complex Programmable Logic Devices (CPLDs), and Field Programmable Gate Arrays (FPGAs).

The computer system 1201 may further include: a display controller 1209, such as a Cathode Ray Tube (CRT), coupled to the bus 1202 for controlling the display, displays information to the computer user. The computer system includes input devices, such as a keyboard and pointing device, for interacting with a computer user and providing information to the processor 1203. The pointing device, which may be, for example, a mouse, trackball, or pointing stick, is used to communicate direction information and command selections to the processor 1203 and to control cursor movement on the display. In addition, a printer may provide printed listings of data stored and/or generated by the computer system 1201.

The computer system 1201 performs a portion or all of the processing steps of the invention (such as those described with reference to fig. 5) in response to the processor 1203 executing one or more sequences of one or more instructions contained in a memory, such as the main memory 1204. Such instructions may be read into the main memory 1204 from another computer readable medium, such as a magnetic hard disk 1207 or a removable media drive 1208. Sequences of instructions contained in main memory 1204 may also be executed using more than one processor in a multi-processing sequence. In alternative implementations, hardware circuitry may be used in place of, or in combination with, software instructions. Thus, embodiments are not limited to any specific combination of hardware circuitry and software.

As mentioned above, the computer system 1201 includes at least one computer readable medium or memory for holding instructions programmed according to the teachings of the invention and for containing data structures, tables, records, or other data described herein. Examples of computer readable media are compact discs, hard disks, floppy disks, magneto-optical disks, PROMs (EPROM, EEPROM, flash EPROM), DRAM, SRAM, SDRAM, or any other magnetic medium, compact discs (e.g., CD-ROM) or any other optical medium, punch cards, paper tape, or other tangible medium having patterns of holes, a carrier wave (described below), or any other medium from which a computer can read.

Stored on any one or on a combination of computer-readable media, the present invention includes software for controlling the computer system 1201, for driving one or more devices for implementing the invention, and for enabling the computer system 1201 to interact with a user. Such software may include, but is not limited to, device drivers, operating systems, development tools, and application software. Such computer-readable media also includes the computer program product of the present invention for implementing all or a portion (if processing is distributed) of the processing implemented in the invention as described below.

The computer encoder of the present invention may be any interpretable or executable code mechanism, including but not limited to scripts, interpretable programs, Dynamic Link Libraries (DLLs), Java classes, and complete executable programs. Furthermore, portions of the processing of the present invention may be distributed for better performance, reliability, and/or cost.

The term "computer-readable medium" as used herein refers to any medium that participates in providing instructions to the processor 1203 for execution. Computer-readable media can take many forms, including but not limited to, non-volatile media, and transmission media. Non-volatile media includes, for example, optical, magnetic disks, and magneto-optical disks, such as magnetic hard disk 1207 or removable media drive 1208. Volatile media includes dynamic memory, such as the main memory 1204. Transmission media includes coaxial cables, copper wire and fiber optics, including the wires that comprise bus 1202. Transmission media can also be in the form of acoustic or optical waveforms, such as those generated during radio wave and infrared data communications.

Various forms of computer readable media may be involved in carrying out one or more sequences of one or more instructions to processor 1203 for execution. For example, the instructions may initially be carried on a magnetic disk of a remote computer. The remote computer may load the instructions for implementing all or a portion of the present invention remotely into a dynamic memory and transmit the instructions over a telephone line using a modem. A modem local to the computer system 1201 may receive the data on the telephone line and use an infrared transmitter to convert the data to an infrared signal. An infrared detector coupled to the bus 1202 can receive the data carried in the infrared signal and place the signal on the bus 1202. The bus 1202 carries the data to the main memory 1204, from which main memory 1204 the processor 1203 retrieves and executes the instructions. The instructions received by the main memory 1204 may optionally be stored in memory 1207 or 1208 either before or after execution by the processor 1203.

The computer system 1201 also includes: a communication interface 1213 coupled to bus 1202. The communication interface 1213 provides a two-way data communication coupling to a network connection 1214 that connects to, for example, a Local Area Network (LAN)1215 or other communication network 1216 such as the internet. For example, the communication interface 1213 may be a network interface card to attach to any packet switched LAN. As another example, the communication interface 1213 may be an Asymmetric Digital Subscriber Line (ADSL) card, an Integrated Services Digital Network (ISDN) card or a modem to provide a data communication connection to a corresponding type of communication line. Wireless connections may also be implemented. In any such implementation, the communication interface 1213 sends and receives electrical, electromagnetic or optical signals that carry digital data streams representing various types of information.

The network connection 1214 typically provides data communication through more than one network to other data devices. For example, the network connection 1214 may connect to another computer through a local network 1215 (e.g., a LAN) or through equipment operated by a facilitator which provides communication services through a communications network 1216. The local network 1214 and the communications network 1216 use, for example, electrical, electromagnetic, or optical signals that carry digital data streams, and the associated physical layer (e.g., CAT 5 cable, coaxial cable, optical fiber, etc.). The signals through the various networks and the signals on the network connection 1214 and through the communication interface 1213, which carry the digital data to and from the computer system 1201 maybe implemented in baseband signals, or carrier wave based signals. The baseband signal conveys the digital data as unmodulated electrical pulses that are descriptive of a stream of digital data bits, where the term "bit" is to be construed broadly to mean a symbol, where each symbol conveys at least one more information bit. A carrier wave can also be modulated with digital data, such as amplitude, phase, and/or frequency shift keyed signals that are transmitted over a conductive medium or transmitted as electromagnetic waves through a propagation medium. Thus, the digital data may be transmitted as unmodulated baseband data over a "wire" communication channel and/or within a predetermined frequency band, other than baseband, by modulating a carrier wave. The computer system 1201 can receive/transmit data, including program code, through the networks 1215 and 1216, the network link 1214, and the communication interface 1213. In addition, the network connection 1214 may provide a connection through a LAN1215 to a mobile device 1217 such as a Personal Digital Assistant (PDA) laptop computer or mobile telephone.

The exemplary power spectrum previously shown in fig. 1 may also be used in this computer-implemented system.

Reagents and chemicals used in the methods and systems of the invention may be packaged into kits to facilitate the use of the invention. In an exemplary embodiment, the kit may comprise: the apparatus may include at least one activatable agent capable of producing a predetermined cellular change, at least one energy modulation agent capable of activating the at least one activatable agent when excited, at least one plasmonics agent that may enhance an applied initiation energy such that the enhanced initiation energy activates the at least one activatable agent to produce a change in a medium upon activation thereof. And a container adapted to store the agent in a stable form, and further comprising instructions for applying the at least one activatable agent and the at least one energy modulation agent to the medium and applying initiation energy from the initiation energy source to activate the activatable agent. The instructions may be in any desired form, including but not limited to electronic storage instructions printed on a sleeve, printed on one or more containers, and provided on an electronic storage medium, such as a computer-readable storage medium. A software package on a computer readable storage medium is also optionally included that enables the user to integrate the information and calculate a control dose to calculate and control the irradiation source intensity.

System implementation

In one embodiment of the invention, a first system for producing a change in a medium disposed in an artificial container is provided. The first system includes: means arranged to supply at least one of a plasmonics agent and an activatable agent in a medium. The plasmonics agent enhances or alters the energy in its vicinity. In one example, the plasmonics agent enhances or modifies the applied initiation energy such that the enhanced initiation energy produces a modification in the medium, either directly or indirectly. The system includes an initiation energy source configured to apply initiation energy through the artificial container to the medium to activate the at least one activatable agent in the medium.

In one embodiment, the energy modulation agent converts the applied initiation energy and generates light having an energy different from the applied initiation energy. The plasmonics agent may enhance light from the at least one energy modulation agent. In one embodiment, the applied initiation energy source is an external initiation energy source. In one embodiment, the source of initiation energy applied is a source at least partially located in a vessel containing the medium.

In one embodiment, the medium is substantially transparent to the initiation energy. For example, if the medium is a liquid or fluid food product having a large amount of suspended solids, such as orange juice, then UV light, such as that described above, and even visible light, may be substantially absorbed and/or scattered by the orange juice medium. Moreover, microwave energy may likewise be absorbed by the medium. However, the initiation energy source, such as an X-ray source, may be substantially completely transparent to, for example, orange juice media. The effect is that the medium can now be fully illuminated using an external initiation energy source.

Other sources tuned to specific wavelengths may also be used as initiation energy sources. These sources may utilize "optical windows" in the medium where, for example, light of a particular wavelength is not absorbed. Water selectively scatters and absorbs certain wavelengths of visible light. The long wavelengths of the spectrum-red, yellow and orange-can penetrate about 15, 30 and 50 meters (49, 98 and 164 feet), respectively, while the short wavelengths of the spectrum-violet, blue and green-can penetrate deeper. Thus, for many water-based systems, a high-energy X-ray source may not be required. In those cases, energy modulation agents and plasmonics agents may be added, whose interaction with the incident light may produce, for example, catalyst photoactivation in an aqueous medium. The light generated by the energy modulation agent may also be enhanced by the plasmonics agent in the medium.

Thus, depending on the medium and the energy modulation agent and activatable agent, the initiation energy source may comprise at least one of an X-ray source, a gamma-ray source, an electron beam source, an ultraviolet radiation source, a visible light source and an infrared source, a microwave source, or a radio wave source. The initiation energy source may be an energy source that emits one of electromagnetic energy, acoustic energy, or thermal energy. The initiation energy source may be an energy source that emits a wavelength whose skin depth passes through the entire medium. In one embodiment, the initiation energy may be scattered or absorbed in the medium, but the plasmonics agent utilizes the remaining light. The medium to be treated can be a medium to be fermented, to be sterilized or to be pasteurized at low temperature. The medium to be treated may comprise bacteria, viruses, yeasts and fungi.

The activatable agent may be a photoactivatable agent such as a photocage (among others)Described herein) such that upon exposure to an initiation energy source, the photocage decomposes to render the activator available. The activatable agent may comprise an agent selected from the group consisting of: psoralens, pyrenyl cholesterol oleate, acridines, porphyrins, fluoresceins, rhodamines, 16-diazocortisones, ethidines, transition metal complexes of bleomycin, transition metal complexes of deglycobleomycin, organo platinum complexes, alloxazines, vitamin Ks, vitamin L, vitamin metabolites, vitamin precursors, naphthoquinones, naphthalenes, naphthols and their derivatives with planar molecular conformations, porphyrins, dyes and phenothiazine derivatives, coumarins, quinolones, quinones and anthraquinones. The activatable agent may include a photocatalyst such as TiO₂、ZnO、CdS、CdSe、SnO₂、SrTiO₃、WO₃、Fe₂O₃And Ta₂O₅And (3) granules.

The first system may include a device configured to provide at least one energy modulation agent in the medium that converts the initiation energy into activation energy for activating the activatable agent. The energy modulation agent may be a photon emitter such as a phosphorescent compound, a chemiluminescent compound, and a bioluminescent compound. The energy modulation agent may be an up-conversion or down-conversion agent. The energy modulation agent may be a luminescent particle that emits light upon exposure to the initiation energy. The energy modulation agent can be nanotubes, nanoparticles, chemiluminescent particles, and bioluminescent particles, and mixtures thereof. The luminescent particles may be nanoparticles of semiconductor or metallic materials. The luminescent particles may be chemiluminescent particles that exhibit enhanced chemiluminescence upon exposure to microwaves.

The first system may include a device configured to provide a plasmonic agent in a medium, the plasmonic agent including a metal nanostructure such as a nanosphere, a nanorod, a nanocube, a nanocone, a nanoshell, a multi-layered nanoshell, and combinations thereof. The form and structure of these plasmonics agents may include the probe structures detailed above.

Depending on the initiation energy source, the system may comprise a container for a medium that is permeable to the applied initiation energy. For example, for an X-ray source, the container may be made of aluminum, quartz, glass, or plastic. For microwave sources, the container may be made of quartz, glass or plastic. Moreover, the container may be a container that receives and conducts the initiation energy to the fluid product to pasteurize the fluid product, or may be a container that receives and conducts the initiation energy to the fluid product to remediate contaminants in the fluid product.

In another embodiment of the present invention, a second system for curing a radiation-curable medium is provided. The second system includes: means arranged to supply an uncured radiation curable medium comprising at least one plasmonics agent and at least one activatable agent which, when activated, produces a change in the radiation curable medium, and further comprising: an application initiation energy source configured to apply initiation energy to a composition comprising an uncured radiation curable medium, a plasmonics agent, and an energy modulation agent. The energy modulation agent absorbs the initiation energy and converts the initiation energy into activation energy capable of curing the uncured medium (i.e., causing polymerization of the polymer in the uncured medium). The plasmonics agent enhances the applied initiation energy such that the enhanced initiation energy directly or indirectly cures the medium through polymerization of the polymer in the medium. For example, the plasmonics agent may enhance the activation energy light such that the enhanced light activates the at least one photoactivatable agent to polymerize the polymer in the medium. In another example, activation of the energy modulation agent generates light that activates at least one photoactivatable agent to polymerize the polymer in the medium.

The second system has similar characteristics to the first system described above and may also allow the at least one activatable agent to comprise a photoinitiator such as one of the following: benzoin, substituted benzoin, alkyl ester substituted benzoin, Michler's ketone, dialkoxyacetophenone, diethoxyacetophenone, benzophenone, substituted benzophenone, acetophenone, substituted acetophenone, xanthone, substituted xanthone, benzoin methyl ether, benzoin ethyl ether, benzoin isopropyl ether, diethoxyacetophenone, chlorothioxanthone, azobisisobutyronitrile, N-methyldiethanolamine aminobenzophenone, camphorone, peroxyester initiator, non-fluorene carboxylic acid peroxyester, and mixtures thereof.

The second system may further include a device configured to provide a plasmonic agent in the medium, the plasmonic agent including a metal nanostructure such as a nanosphere, a nanorod, a nanocube, a nanocone, a nanoshell, a multi-layered nanoshell, and combinations thereof. The form and structure of these plasmonics agents may include the probe structures detailed above.

The second system may include a container for an uncured radiation curable medium that is transparent to the applied initiation energy. The container may be configured as a mold containing the uncured radiation curable medium or a mold containing the uncured radiation curable medium. The container as described above may be an aluminum container, a quartz container, a glass container or a plastic container depending on the initiation energy applied.

In one embodiment, the energy source (e.g., an external energy source) is configured to irradiate the uncured radiation curable medium in the attachment region (or regions) that bonds one region of the appliance to another region of the appliance. In another embodiment, the energy source is arranged to irradiate the connection area and thereby sterilize the connection area due to the generation of intrinsic UV light inside the connection area. In another embodiment, the energy source is configured to irradiate the surface coating. In another embodiment, the energy source is configured to irradiate a mold of the radiation curable medium.

The radiation curable medium in the surface coating or mold or in another medium may contain pigments to add color to the finished cured product. The radiation curable medium in the surface coating or in the mold or in another medium may comprise fumed silica to enhance the distribution of internal light and to promote strength. The radiation curable medium in the surface coating or in the mold or in another medium may contain moisture cure promoters to supplement curing.

A second system provides an apparatus for preparing a new radiation-cured article comprising a radiation-curing medium, at least one plasmonics agent, and at least one energy modulation agent distributed throughout the medium. An energy modulation agent is a substance that is capable of converting applied energy into light that is capable of causing curing of a radiation-curable medium. The plasmonics agent enhances the applied initiation energy such that the enhanced initiation energy activates the energy modulation agent. The light generated by the energy modulation agent may also be enhanced by the plasmonics agent in the medium. The article may comprise luminescent particles such as nanotubes, nanoparticles, chemiluminescent particles and bioluminescent particles and mixtures thereof. The article may comprise nanoparticles of semiconductor or metallic materials. The article may comprise chemiluminescent particles. The article may comprise a pigment or fumed silica. The article may comprise a plasmonics agent including metal nanostructures such as nanospheres, nanorods, nanocubes, nanoshells, multi-layered nanoshells, and combinations thereof. The form and structure of these plasmonics agents may include the probe structures detailed above.

In another embodiment of the invention, a third system for creating a change in a medium placed in an artificial container is provided. The third system includes: means arranged to provide the medium with 1) an activatable agent and 2) at least one of a plasmonics agent and an energy modulation agent. The energy modulation agent converts the initiation energy into an activation energy, which then activates the at least one activatable agent. The third system further comprises an application initiation energy source configured to apply initiation energy through the artificial container to the medium to activate the at least one activatable agent in the medium. The plasmonics agent enhances or alters the energy in its vicinity. In one example, the plasmonics agent enhances or modifies the applied initiation energy such that the enhanced initiation energy produces a modification in the medium, either directly or indirectly.

The third system has similar features to the first and second systems described above, and further includes an encapsulating structure comprising at least one of an energy modulation agent and a plasmonics agent. The encapsulating structure may comprise nanoparticles of an energy modulation agent encapsulated by a passivation layer or may comprise a sealed quartz or glass tube with an energy modulation agent inside. The encapsulating structure may include a sealed tube (which may or may not be directly exposed to the medium) with a plasmonics agent disposed on the exterior of the sealed tube.

In another embodiment of the present invention, a fourth system for producing photoexcited changes in a medium disposed in an artificial container is provided. The fourth system includes: means arranged to provide at least one of a plasmonics agent and an energy modulation agent in a medium. The energy modulation agent converts the initiation energy into activation energy, which then produces a photoexcitation change. The fourth system further comprises an initiation energy source configured to apply initiation energy to the medium to activate the at least one energy modulation agent in the medium. The plasmonics agent enhances or alters the energy in its vicinity. In one example, the plasmonics agent enhances or modifies the applied initiation energy such that the enhanced initiation energy produces a modification in the medium, either directly or indirectly. The system may include an encapsulated structure having an energy modulation agent contained therein. The encapsulating structure may include nanoparticles of an energy modulation agent encapsulated by a passivation layer. The encapsulating structure may include a sealed tube (which may or may not be directly exposed to the medium) with a plasmonics agent disposed on the exterior of the sealed tube.

The fourth system may include a container that receives initiation energy and conducts the initiation energy to the product within the medium. The product may comprise a plastic, wherein the activation energy changes the surface structure of the plastic. The product may include polylactic acid (PLA) plastics and Polyhydroxyalkanoate (PHA) plastics. In this embodiment, the activation energy may photograft molecular species onto the plastic surface.

Sterilization method and system components

Optical techniques have been frequently used in sterilization procedures to render undesirable or harmful aquatic microorganisms incapable of reproduction by means of ultraviolet light, in particular in the UV-C spectral region, in the range of 200 to 280 nm. The ultraviolet rays of UV-C are considered to be the most lethal range (capable of altering DNA of living microorganisms and preventing microorganisms from reproducing) as a bactericidal disinfectant. UV-C with a peak germicidal wavelength of 264 nm is called the germicidal spectrum. Although the UV-C method is simple and effective, it is not particularly effective in samples (gases, liquids, particles) enclosed by containers that are opaque to UV light. The present invention provides techniques and systems that can use externally applied radiation, such as X-rays, for sterilization. Although described below with respect to X-ray radiation, as noted above, other suitable forms of energy may be used if the container and medium to be sterilized are sufficiently transparent to the medium to be fully irradiated. Examples of alternative sources and materials for up-converting luminescence to higher energies have been set forth above.

Fig. 27-44 illustrate various embodiments of sterilization systems and probes that can utilize X-ray excitation. These systems are suitable for many of the applications described above, as well as other sterilization applications. The system can therefore be used for industrial applications of wastewater detoxification, blood sterilization, low temperature pasteurization and light inactivation as set forth in the above section. These systems (as in fig. 3B-3D) show the use of artificial containers in which the medium to be treated is arranged.

Fig. 27 shows an embodiment of the sterilization system of the present invention, comprising: a container and a material containing an X-ray energy converter. The container contains a sample (e.g., liquid, gas, or particles) to be sterilized. X-ray radiation that is able to penetrate the container wall excites a material comprising an X-ray induced energy converter (EEC), which is arranged to emit radiation light. The EEC material is selected such that the emitted light or luminescence is in a spectral region (e.g. the ultraviolet spectral range) that is useful for sterilization.

Fig. 28 shows an embodiment of another sterilization system of the present invention, which utilizes plasmons and comprises: a container, a material comprising an X-ray energy converter, a dielectric layer (e.g. silicon dioxide), and metal nanostructures (e.g. Au, Ag). The container contains a sample (e.g., liquid, gas, or particles) to be sterilized. X-ray radiation that is able to penetrate the container wall excites the material comprising the X-ray induced energy converters (EECs), which in turn emit radiation light. The EEC material is selected such that the emitted light or luminescence is in a spectral region (e.g. the ultraviolet spectral range) that is useful for sterilization. The metallic nanostructures are designed to amplify the luminescence due to the plasmon enhancement effect described above. The dielectric layer is designed to separate the X-ray energy converter from the metal nanostructure to minimize or prevent possible luminescence quenching. The optimal thickness of the dielectric layer is about 1-5 nm, so that the dielectric layer does not significantly change the plasmon effect.

Fig. 29 shows another embodiment of a sterilization system of the present invention, comprising: a container, a material comprising an X-ray energy converter, and a photo-activated (PA) material. X-ray radiation that is able to penetrate the container wall excites the material comprising the X-ray induced energy converters (EECs), which in turn emit radiation light. The EEC material is selected such that the emitted light or luminescence is in a spectral region that can be used to further excite the photo-activated (PA) material. The photo-active material may be adapted to emit light for sterilization purposes (e.g. luminescence) after excitation by the EEC luminescence. Alternatively, the PA material is replaced or is itself a material with upper/lower energy conversion properties of EEC generated light to generate radiation of a wavelength suitable for sterilization purposes (e.g., UV light to kill bacteria).

Fig. 30 shows another embodiment of the sterilization system of the present invention, comprising: a container, a material comprising an X-ray energy converter, a dielectric layer (e.g., silicon dioxide), metallic nanostructures (e.g., Au, Ag), and a photo-activated (PA) material. X-ray radiation that is able to penetrate the container wall excites the material comprising the X-ray induced energy converters (EECs), which in turn emit radiation light. The EEC material is selected such that the emitted light or luminescence is in a spectral region that can be used to further excite the photo-activated (PA) material. The photo-active material may be adapted to emit light for sterilization purposes (e.g. luminescence) after excitation by the EEC luminescence. Alternatively, the PA material is replaced by or is itself a material with up/down energy conversion properties of the EEC radiation light to generate radiation of a wavelength suitable for sterilization purposes (e.g., UV light to kill bacteria). In this embodiment, the metal nanostructures are designed to amplify the luminescence due to the plasmon enhancement effect. The dielectric layer is designed to separate the material comprising the X-ray energy converter from the metal nanostructures to minimize or prevent possible luminescence quenching.

Fig. 31 shows another embodiment of the sterilization system of the present invention, comprising: a container and a material comprising an X-ray energy converter that does not contain embedded metal nanoparticles as part of the container wall. The container contains the sample to be sterilized, which may be a liquid, a gas or particles. X-ray radiation that is able to penetrate the container wall excites the material comprising the X-ray induced energy converters (EECs), which in turn emit radiation light. The EEC material is selected such that the emitted light or luminescence is in a spectral region (e.g. the ultraviolet spectral range) that is useful for sterilization. In this embodiment, the EEC material is contained in a matrix also having metal nanoparticles (1-100 nm in diameter). The metal nanoparticles serve as a plasmon activation system designed to enhance EEC radiation light.

Fig. 32 shows another embodiment of the sterilization system of the present invention, comprising: a container and a material comprising an X-ray energy converter that does not contain embedded metal nanoparticles as part of the container wall and is contained on a reentrant structure. This embodiment is designed such that the sample flow can have maximum contact with the wall of the sterilization system, including the re-enterable structure. The sample flowing through the container may be a liquid, a gas, or a particulate. X-ray radiation that is able to penetrate the container wall excites the material comprising the X-ray induced energy converters (EECs), which in turn emit radiation light. The EEC material is selected such that the emitted light or luminescence is in a spectral region (e.g. the ultraviolet spectral range) that is useful for sterilization. In this embodiment, the EEC material is contained in a matrix also having metal nanoparticles (1-100 nm in diameter). The metal nanoparticles serve as a plasmon activation system designed to enhance EEC radiation light.

Fig. 33 shows another embodiment of a sterilization system of the present invention, comprising: a container, a material comprising an X-ray energy converter, and a photoactivatable material. The container contains the sample to be sterilized, which may be a liquid, a gas or particles. X-ray radiation that is able to penetrate the container wall excites the material comprising the X-ray induced energy converters (EECs), which in turn emit radiation light. The EEC material is selected such that the emitted light or luminescence is in a spectral region that can be used to further excite the photo-activated (PA) material. The photo-active material may be adapted to emit light for sterilization purposes (e.g. luminescence) after excitation by the EEC luminescence. Alternatively, the PA material is replaced by or is itself a material with up/down energy conversion properties of the EEC radiation light to generate radiation of a wavelength suitable for sterilization purposes (e.g., UV light to kill bacteria). In this embodiment, the PA material (or upper/lower energy conversion material) is not contained in a matrix that also has metal nanoparticles (1-100 nm in diameter). The metal nanoparticles are used as plasmon activation systems designed to enhance the radiated light.

Fig. 34 shows another embodiment of a sterilization system of the present invention, comprising: a container and a material comprising an X-ray energy converter that does not contain embedded metallic nanoparticles as part of the container wall and is contained on a reentrant structure, and a photo-active material. The container contains the sample to be sterilized, which may be a liquid, a gas, or particles. This embodiment is designed such that the sample flow can be in frequent contact with the wall of the sterilization system. X-ray radiation that is able to penetrate the container wall excites the material comprising the X-ray induced energy converters (EECs), which in turn emit radiation light. The EEC material is selected such that the emitted light or luminescence is in a spectral region that can be used to further excite the photo-activated (PA) material. The photo-active material may be adapted to emit light for sterilization purposes (e.g. luminescence) after excitation by the EEC luminescence. Alternatively, the PA material is replaced by or is itself a material with up/down energy conversion properties of the EEC radiation light to generate radiation of a wavelength suitable for sterilization purposes (e.g., UV light to kill bacteria). In this embodiment, the PA material (or upper/lower energy conversion material) is not contained in a matrix that also has metal nanoparticles (1-100 nm in diameter). The metal nanoparticles are used as plasmon activation systems designed to enhance the radiated light.

Fig. 35 shows another embodiment of the sterilization system of the present invention, comprising: a container, a material comprising an X-ray energy converter, and a chemical or biological receptor for capturing a target. The container contains the sample to be sterilized, which may be a liquid, a gas or particles. X-ray radiation that is able to penetrate the container wall excites the material comprising the X-ray induced energy converters (EECs), which in turn emit radiation light. The EEC material is selected such that the emitted light or luminescence is in a spectral region (e.g. the ultraviolet spectral range) that is useful for sterilization. A layer of chemical receptors (e.g., ligands specific for chemical groups) or biological receptors (e.g., antibodies, surface cell receptors) is used to capture biochemical targets of interest. In this embodiment, a particular target compound selectively binds to the surface and is more efficiently irradiated by the irradiating light.

Fig. 36 shows another embodiment of the sterilization system of the present invention, comprising: a container, a material containing an X-ray energy converter, a dielectric layer (e.g., silicon dioxide), metal nanostructures (e.g., Au, Ag), and a chemical or biological receptor for capturing a target. The sample inside the container may be a liquid, a gas or a particle. X-ray radiation that is able to penetrate the container wall excites the material comprising the X-ray induced energy converters (EECs), which in turn emit radiation light. The EEC material is selected such that the emitted light or luminescence is in a spectral region (e.g. the ultraviolet spectral range) that is useful for sterilization. The metal nanostructures are designed to amplify luminescence (or emitted light) due to the plasmon enhancement effect described above. The dielectric layer is designed to separate the material comprising the X-ray energy converter from the metal nanostructures to minimize or prevent possible luminescence quenching. The optimal thickness of the dielectric layer is about 1-5 nm, so that the dielectric layer does not influence the effect of plasmon remarkably. A layer of chemical receptors (e.g., ligands specific for chemical groups) or biological receptors (e.g., antibodies, surface cell receptors) is used to capture biochemical targets of interest. In this embodiment, a particular target compound selectively binds to the surface and is more efficiently irradiated by the irradiating light.

Fig. 37 shows another embodiment of the sterilization system of the present invention, comprising: a container, a material comprising an X-ray energy converter, a photo-activated (PA) material, and a chemical or biological receptor for capturing a target. X-ray radiation that is able to penetrate the container wall excites the material comprising the X-ray induced energy converters (EECs), which in turn emit radiation light. The EEC material is selected such that the emitted light or luminescence is in a spectral region that can be used to further excite the photo-activated (PA) material. The photo-active material may be adapted to emit light for sterilization purposes (e.g. luminescence) after excitation by the EEC luminescence. A layer of chemical receptors (e.g., ligands specific for chemical groups) or biological receptors (e.g., antibodies, surface cell receptors) is used to capture biochemical targets of interest. In this embodiment, a particular target compound selectively binds to the surface and is more efficiently irradiated by the irradiating light. Alternatively, the PA material is replaced by or is itself a material with up/down energy conversion properties of the EEC radiation light to generate radiation of a wavelength suitable for sterilization purposes (e.g., UV light to kill bacteria).

Fig. 38 shows another embodiment of the sterilization system of the present invention, comprising: a container, a material comprising an X-ray energy converter, a photo-activated (PA) material, metallic nanostructures (e.g., Au, Ag), a dielectric layer (e.g., silicon dioxide), and a chemical or biological receptor for capturing a target. X-ray radiation that is able to penetrate the container wall excites the material comprising the X-ray induced energy converters (EECs), which in turn emit radiation light. The EEC material is selected such that the emitted light or luminescence is in a spectral region that can be used to further excite the photo-activated (PA) material. The photo-active material may be adapted to emit light for sterilization purposes (e.g. luminescence) after excitation by the EEC luminescence. Alternatively, the PA material is replaced by or is itself a material with up/down energy conversion properties of the EEC radiation light to generate radiation of a wavelength suitable for sterilization purposes (e.g., UV light to kill bacteria). The metallic nanostructures are designed to amplify the luminescence due to the plasmon enhancement effect described above. The dielectric layer is designed to separate the material comprising the X-ray energy converter from the metal nanostructures to minimize or prevent possible luminescence quenching. A layer of chemical receptors (e.g., ligands specific for chemical groups) or biological receptors (e.g., antibodies, surface cell receptors) is used to capture biochemical targets of interest. In this embodiment, a particular target compound selectively binds to the surface and is more efficiently irradiated by the irradiating light.

The present invention may use these chemical and biological receptors on the inner wall in contact with the medium to be sterilized in another system shown herein.

Fig. 39 illustrates one embodiment of a sterilization probe system of the present invention, comprising: a container which can contain the medium to be sterilized and a probe made of a material containing an X-ray energy converter. The sample inside the container may be a liquid, a gas or a particle. X-ray radiation that is able to penetrate the container wall excites the probe with a material comprising an X-ray induced energy converter (EEC), which in turn emits radiation light. The EEC material is selected such that the emitted light or luminescence is in a spectral region (e.g., the ultraviolet spectral region) that is useful for sterilization. The probe may be removed and reinserted into the container and reused.

Fig. 40 shows one embodiment of a sterilization probe system of the present invention, comprising: a container that can contain the medium to be sterilized, a probe made of a material comprising an X-ray energy converter, a dielectric layer (e.g. silicon dioxide), and metal nanostructures (e.g. Au, Ag). The sample inside the container may be a liquid, a gas or a particle. X-ray radiation that is able to penetrate the container wall excites the probe with a material comprising an X-ray induced energy converter (EEC), which in turn emits radiation light. The EEC material is selected such that the emitted light or luminescence is in a spectral region (e.g., the ultraviolet spectral region) that is useful for sterilization. The metallic nanostructures are designed to amplify the luminescence due to the plasmon enhancement effect described above. The dielectric layer is designed to separate the material comprising the X-ray energy converter from the metal nanostructures to minimize or prevent possible luminescence quenching. The optimal thickness of the dielectric layer is about 1-5 nm, so that the dielectric layer does not influence the effect of plasmon remarkably. The probe may be removed and reinserted into the container and reused.

Fig. 41 illustrates one embodiment of a sterilization probe system of the present invention, comprising: a container that can hold a medium to be sterilized, a probe made of a material containing an X-ray energy converter, and a chemical or biological receptor for capturing a target. The sample inside the container may be a liquid, a gas or a particle. The probe with the material comprising the X-ray induced energy converter (EEC) is excited by X-ray radiation that is transmitted through the container wall, which in turn emits radiation light. The EEC material is selected such that the emitted light or luminescence is in a spectral region (e.g., the ultraviolet spectral region) that is useful for sterilization. A layer of chemical receptors (e.g., ligands specific for chemical groups) or biological receptors (e.g., antibodies, surface cell receptors) is used to capture biochemical targets of interest. In this embodiment, a specific target compound selectively binds to the probe surface and is more efficiently irradiated by the irradiation light. The probe may be removed and reinserted into the container and reused.

Fig. 42 illustrates one embodiment of a sterilization probe system of the present invention, comprising: a container that can contain the medium to be sterilized, a probe made of a material comprising an X-ray energy converter, a dielectric layer (e.g. silicon dioxide), and metal nanostructures (e.g. Au, Ag). The sample inside the container may be a liquid, a gas or a particle. X-ray radiation that is able to penetrate the container wall excites the probe with a material comprising an X-ray induced energy converter (EEC), which in turn emits radiation light. The EEC material is selected such that the emitted light or luminescence is in a spectral region (e.g., the ultraviolet spectral region) that is useful for sterilization. The metallic nanostructures are designed to amplify the luminescence due to the plasmon enhancement effect described above. The dielectric layer is designed to separate the material comprising the X-ray energy converter from the metal nanostructures to prevent possible luminescence quenching. The optimal thickness of the dielectric layer is about 1-5 nm, so that the dielectric layer does not influence the effect of plasmon remarkably. A layer of chemical receptors (e.g., ligands specific for chemical groups) or biological receptors (e.g., antibodies, surface cell receptors) is used to capture biochemical targets of interest. In this embodiment, a specific target compound selectively binds to the probe surface and is more efficiently irradiated by the irradiation light. The probe may be removed and reinserted into the container and reused.

Fig. 43 shows an embodiment of a sterilization probe system of the present invention, comprising: a container that can contain a medium to be sterilized, nanoparticles having 1) a paramagnetic core and 2) a shell comprising a material comprising an X-ray energy converter. The sample inside the container may be a liquid, a gas or a particle. An externally applied magnetic field can be used to deliver nanoparticles into a container, the nanoparticles having a paramagnetic core covered with a nanoshell of a material comprising an X-ray energy converter. X-ray radiation, which is able to penetrate the container wall, excites the nanoparticle shell comprising the X-ray induced energy converters (EECs), which in turn emit the radiation light. The EEC material is selected such that the emitted light or luminescence is in a spectral region (e.g., the ultraviolet spectral region) that is useful for sterilization. After sterilization is complete, the nanoparticles can be removed from the container using an applied magnetic field. The magnetic field unit serves as a means for introducing and collecting magnetic nanoparticles. The nanoparticles can be reinserted into the container and reused. In another embodiment, the nanoparticles may also be covered with a layer of chemical receptors (e.g. ligands specific for chemical groups) or biological receptors (e.g. antibodies, surface cell receptors). This layer is used to capture biochemical targets of interest. In this embodiment, a specific target compound selectively binds to the probe surface and is more efficiently irradiated by the irradiation light.

Fig. 44 shows an example of a plasmon probe having paramagnetic nuclei. In FIG. 44A, the magnetic core is surrounded by a metal layer, which in turn is surrounded by a dielectric layer. In FIG. 44B, the magnetic core is surrounded by an X-ray induced energy converter (EEC) material, which in turn is surrounded by a dielectric layer. The metal nanoparticles are attached to the dielectric. In FIG. 44C, the magnetic core is surrounded by a metal layer, which in turn is surrounded by a dielectric layer. An X-ray induced energy converter (EEC) material is formed as part of a cap over the dielectric layer. In FIG. 44D, the magnetic core is surrounded by X-ray induced energy converter (EEC) material, which in turn is surrounded by a dielectric layer. The metal layer is formed as part of a cap on the dielectric layer. In FIG. 44E, the magnetic core is surrounded by a metal layer, which in turn is surrounded by a dielectric layer, which in turn is surrounded by an X-ray induced energy converter (EEC) material. In FIG. 44F, the magnetic core is surrounded by X-ray induced energy converter (EEC) material, which in turn is surrounded by a dielectric layer, which in turn is surrounded by a metal layer. In FIG. 44G, the magnetic core is surrounded by an X-ray induced energy converter (EEC) material, which in turn is surrounded by a dielectric layer, which in turn is surrounded by a metal layer, which in turn is surrounded by a layer of a chemical acceptor.

Design and fabrication of plasmon-activated materials and surfaces

The plasmon-activated surface and probe in the embodiments described above can be prepared using one of the following procedures to generate nanostructures of metals or thin layers of metals exhibiting plasmon properties.

For nanostructures produced on metal electrode systems, electrochemical cells using silver and other metal electrodes have been used to produce nanostructure-like morphologies on the electrode Surface for SERS studies (Pettinger b., u.wenning, and h.wetzel, Surface-plated Raman-scattering frequency and.. Ag and Cu electrolytes, 1980, surf.sci., 101, 409; Fleishman m., p.r.graves, and j.robinson, the man-Spectroscopy of the hydride and plating-electrolytes, 1985, j.electroananal.m., 182, 87). The manufacturing procedures described in these references, the entire contents of which are incorporated herein by reference, are also applicable to the present invention. During the first half cycle, by reacting Ag- > Ag + + e^-Oxidizing the silver at the electrodes. By reaction of Ag + + e during the reduction half-cycle^-Ag again creates a rough silver surface. The redox process typically produces surface protrusions on the electrode surface with dimensions in the range of 25-500 nm. The working electrode can then typically be positioned such that the laser excitation can be concentrated on its surface and the raman scattered light can be efficiently collected by suitable optical elements. Strong SERS signals typically only implement electricity on metal electrodes The chemical redox cycle occurs after, and is often referred to as an "activation cycle". The fabrication procedures for the various electrodes described in these references, the entire contents of which are incorporated herein by reference, are applicable to the present invention.

Other metal electrodes such as platinum (lo BH., Surface-enhanced Raman-spectroscopy of platinum, 1983, j.phys.chem., 87, 3003) have also been investigated as plasmonic substrates. Experimental factors such as the effect of laser irradiation of copper electrodes on the SERS signal of pyridine and benzotriazole during oxidation/reduction treatment have been studied (Thierry d. and c. leygraf, the influence of catalysis on surface-enhanced. raman scattering from coater electrodes, 1985, surface sci., 149592). Beer, k.d.; tanner, w.; garrell, R l. at j.electroanal. Ex-situ electrode roughening procedures for SERS on gold and silver electrode surfaces were studied in chem.1989, 258, 313-325. The manufacturing processes for the individual electrodes described in these references (which are incorporated herein by reference in their entirety) are suitable for use in the present invention.

For chemical, electrochemical etching of metals and other rough surfaces, chemical etching procedures can also be used to create plasmon-activated metal surfaces (Miller s.k., a.baiker, m.meier, and a.wokaun, Surface-enhanced Raman scattering and the preparation of copper substrates for catalytic reactants, 1984, j.chem.soc.far. trans.i., 80, 1305). In one procedure, at room temperature 2mol ^-3The copper foil was etched in nitric acid for 40 minutes. Another procedure involves the use of Al at 4 atmospheres₂O₃The copper foil was sand blasted and then etched for 2 minutes. SEM photographs of the metal surface show that two etching processes can produce surface roughness structures with dimensions of 10-100 nm. Electrochemically roughened Silver Oxide Substrates have been developed to detect vapors of chemical Nerve Agent mimics (Taranenko N., J.P.Alarie, D.L.Stokes and T.Vo Dinh, Surface-Enhanced Raman Detection of New Agent Simulant (DMMPand DIMP) Vapor on electrochemical Prepared Silver oxides Substrates, 1996, J.Raman Spectrum.,27, 379-384). These procedures are consistent with and similar to electroplating methods. The manufacturing processes described in these references, the entire contents of which are incorporated herein by reference, are suitable for use in the present invention.

Various procedures for coating solid substrates with metal Nanostructures have been previously described for metal Nanostructures on solid substrates [ Vo-Dinh, Surface-Enhanced Raman spectroscopy Using Metallic Nanostructures, 1998, Trends in analytical chemistry, 17, 557(1998) ]. These procedures can be used to generate plasmonically activated surfaces and embodiments. The manufacturing processes described in this reference, which is incorporated herein by reference in its entirety, are suitable for use in the present invention.

In various embodiments of the invention, the inner wall may also have a suitable protective coating that is optically transparent to the emitted light used for sterilization.

For metal nanoparticle island films, the simplest metal nanostructures can be created by directly evaporating a thin layer (e.g., less than 10nm thick) of a metal, such as silver, on a solid substrate support. Under these conditions, the silver layer forms nanoparticles of isolated metal islands on the support. As the thickness of the deposited silver increases, the particles begin to agglomerate and form a continuous film. By varying the thickness of the deposited metal (measured by a quartz crystal monitor perpendicular to the evaporation source), the size and shape of the metal nanoparticles can be influenced. SERS measurements using silver nanoparticle island films were compared to those obtained with other nanostructured materials. SERS from copper and zinc phthalocyanine complexes (Jennings c., r. aroca, a.m.hor and r.o.loutfy, Surface-enhanced Raman scattering from coppers and zinc phthalocyanine by silver and indium films, 1984, anal. chem., 56, 203) from silver and indium island films are reported. The silver and indium films are vacuumed (p < 10) ^-6Torr) was evaporated onto a tin oxide slide and then at 5 x 10^-7Copper and zinc phthalocyanine complexes were coated in a vacuum system at a base pressure of torr. The metal thickness was about 7.5nm on the substrate to create islands of metal nanoparticles. Another one isAn alternative approach involves sputtering a metal-deposited film as a plasmonic substrate (Ni f., r.sheng and t.m.cotton, Flow-injection analysis and real-time.. bases by surface-enhanced raman-spectroscopy, 1990, anal.chem., 62, 1958). The manufacturing processes described in these references, the entire contents of which are incorporated herein by reference, are suitable for use in the present invention.

For metal coated nanosphere substrates, one early difficulty in the development of SERS technology for analytical applications was to prepare surfaces or media with easily controlled protruding dimensions (roughness) and reproducible structures. One approach involves the use of nanospheres applied to a solid surface (such as the wall of a container) to create and control the desired roughness. The nanostructure carrier is then covered with a silver layer that provides the conduction electrons needed for the surface plasmon mechanism. Among the solid substrate based technologies, the method using simple nanomaterials such as polytetrafluoroethylene or emulsion nanospheres appears to be the easiest to prepare. Polytetrafluoroethylene and emulsion spheres are commercially available in various sizes. The shapes of these materials are very regular and their dimensions can be chosen for optimal reinforcement. The effect of the ball size and the metal layer thickness indicates that: for each sphere size, there is an optimal silver layer thickness at which the maximum SERS signal is observed. (Moody R.L., T.Vo Dinh and W.H.Fletcher, invasion of Experimental Parameters for Surface-Enhanced Raman Spectroscopy, 1987, appl.Spectr., 41, 966). Silver coated nanospheres were found to have the strongest substrate enhancing effect with an enhancement factor comparable to or greater than that of the electrochemically roughened surface. The manufacturing processes described in this reference, which is incorporated herein by reference in its entirety, are suitable for use in the present invention.

For metal-coated alumina nanoparticles, SERS studies show that nanoparticles with irregular shapes (instead of regularly shaped nanospheres) can also be used to spin-coat solid substrates. For example, alumina appears to be one of the most effective materials for making plasmon-activated substrates. The preparation of the substrate is similar to that of a substrate using fumed silica (Bello J.M., D.L.Stokes and T.Vo Dinh, Silver-Coated Aluminum as a New Medium for surface-Enhanced Raman Scattering Analysis, 1989, appl.Spectroscc., 43.1325). An important advantage of alumina over polytetrafluoroethylene or emulsion nanospheres is its extremely low cost. The surface of the aluminum oxide is composed of surface aggregates which are randomly distributed and 10-100 nm of protrusions. These structures generate large electromagnetic fields on the surface when the incident photon energy resonates with localized surface plasmons. Alumina-based substrates have various practical applications due to their efficiency, low cost, and ease of preparation. Moreover, the repeatability of the alumina-based SERS substrate is excellent; the relative standard deviation was found to be less than 5% (Sutherland, A Portable Surface-enhanced Raman Spectrometer, Instrumentation Science & Technology, Vol.22, No. 3 August 1994, page 231-. The manufacturing processes described in these references, the entire contents of which are incorporated herein by reference, are suitable for use in the present invention.

For silver coated titanium dioxide nanoparticles, titanium dioxide is an alternative material that can be used to create nanostructured roughness when coated on a surface. The procedure for preparing these substrates is similar to those used for nanosphere and alumina particles. The titanium dioxide material is first deposited on glass and cellulose substrates and then coated with a 50-100 nm silver layer by thermal evaporation as previously described. Before deposition, the titanium dioxide is prepared as a suspension in water (10% strength by weight). The silver coated titania surface obtained by this method provides an effective plasmonically activated substrate (see us patent 7,267,948, the entire contents of which are incorporated herein by reference). Titanium dioxide provides the nano-sized structures with the necessary surface for the plasmonic effect. The detection limit of various compounds is at the parts per billion (ppb) level and indicates the analytical usefulness of the substrate for trace analysis.

For Silver Coated Silica nanoparticles, another Substrate that has comparable plasmon activation and is easy to prepare is a Fumed Silica-based Substrate (Alak A. and T.Vo Dinh, Silver-Coated fused Silica as New Substrate Materials for surface-Enhanced Raman Scattering, 1989, anal. chem., 61, 656). Fumed silica has been used as a thickener in a number of industrial processes, including coatings and cosmetic preparations. In the preparation of plasmons, the selection of an appropriate type of fumed silica is important. Fumed silica is prepared in different grades, which vary with surface area, particle size, and degree of compression. Fumed silica particles were suspended in a 10% aqueous solution and coated on a glass plate or filter paper. And then coating a silver layer with the thickness of 50-100 nm on the substrate through thermal evaporation. With such a substrate, the vapor-phase-method silica material having a nano-sized structure provides a rough surface effect for a plasmon process. The manufacturing processes described in this reference, which is incorporated herein by reference in its entirety, are suitable for use in the present invention.

It has been investigated that plasmonically activated surfaces can be fabricated using lithographic techniques to produce controllable surface roughness structures. (Liao P.F., and M.B.Stern, Surface-enhanced Raman scattering on gold and aluminum particulate arrays, 1982, Opt.Lett., 7, 483). These surfaces comprise a uniform array of isolated silver nanoparticles of uniform shape and size. These surfaces produce 10⁷Orders of magnitude raman enhancement and has been used to test electromagnetic models for SERS. The effectiveness of cross-grid plasmonic substrates has been linked to CaF₂Rough films, island films, and etched quartz are comparable (Vo Dinh t., m.meier and a.wokaun, 1986, surface enhanced Raman Spectroscopy with Silver Particles on charustic postsubststrates, anal.chim.acta, 181, 139). The manufacturing processes described in these references, the entire contents of which are incorporated herein by reference, are suitable for use in the present invention.

Plasma etching of substrates may also be used with the present invention. It is often difficult to produce periodic structures over large areas by lithographic techniques. Procedure using etched quartz columns by using island-like films as SiO₂An etch mask on the substrate thus avoids this difficulty (elow p.d., m.c. buntick, r.j.waterrock and t.vo Dinh, protection of Nitro p olynuclear AromaticCompounds by Surface Enhanced Raman Spectroscopy，1986，Anal.Chem.，58，1119)。SiO₂The preparation of the prolate nanorods is a multi-step operation that involves plasma etching of SiO using the silver island film as an etch mask₂. Since fused quartz etches more slowly than thermally deposited quartz, 500nm of SiO is first thermally evaporated on fused quartz at a rate of 0.1-0.2 nm/s₂And (3) a layer. The resulting crystalline quartz was annealed to fused quartz at about 950 c for 45 minutes. Then in hot SiO₂A 5nm silver layer was evaporated on top of the layer and the substrate was rapidly heated at 500 c for 20 seconds. This heating causes the thin silver layer to spheroidize into small spheres, which act as an etch mask. Then in CHF₃Etching the substrate in plasma for 30-60 minutes to produce submicron, prolate SiO₂A column, which is then coated with a continuous 80nm silver layer at normal evaporation angles. Another method includes varying the angle of evaporation to produce silver nanoparticles on the quartz cylinder tip. (Vo Dinh T., M.Meier and A.Wokaun, Surface enhanced Raman Spectroscopy with Silver Particles on Stochastic Post Substrates, 1986, anal.Chim.acta, 181, 139). The manufacturing processes described in these references, the entire contents of which are incorporated herein by reference, are suitable for use in the present invention.

Metal coated cellulosic substrates may also be used in the present invention. These substrates can be used as (disposable) liners for containers. Direct metal coating of special filter paper coated with silver may provide a substrate for use. Certain types of microporous filter paper coated with a thin layer of evaporated silver appear to provide an effective plasmon-activated substrate. Scanning electron micrographs of these cellulosic materials show that: these surfaces consist of a 10nm fiber bundle with many whiskers that provide the necessary protrusions needed for SERS enhancement.

Silver films may also be used in the present invention. These films may also be used in container liners. One of the simplest types of solid substrates is a silver film for air particle sampling (Vo Dinh T., 1989, Surface-Enhanced Raman Spectrometry, in Chemical Analysis of multicyclic aromatic Compounds, Wiley, T.vo-Dinh, Ed., New York.). The filter already has the necessary nanopores/micropores to produce SERS and the voids to provide the nano/micro features (e.g., nano/micro alignment). Since these films contain silver, these films can be used directly as plasmon-activated substrates without the addition of additional silver. The manufacturing processes described in this reference, which is incorporated herein by reference in its entirety, are suitable for use in the present invention.

There are various micro/nano fabrication techniques that can be used to create nanostructures on metal substrates. These techniques include, but are not limited to 1) photolithography such as electron beam lithography; photolithography and nanoimprint lithography, 2) dry etching such as Reactive Ion Etching (RIE), Inductively Coupled Plasma (ICP) etching, and plasma etching, 3) thin film deposition and processing, 4) Focused Ion Beam (FIB), 5) electron beam and thermal evaporation, 6) Plasma Enhanced Chemical Vapor Deposition (PECVD), 7) sputtering, and 8) nanoimprint.

In addition, sol-gel matrices embedded with silver or other metal nanoparticles may also be used in the present invention. An optically translucent material has been prepared for use as a plasmon-activated substrate [ M.Volcan, D.L.Stokes and T.Vo-Dinh, A Sol-Gel Derived AgPhotochromophoric Coating on Glass for SERS Chemical Sensor Application, Sensors and Actuators B, 106, 660-667(2005) ]. The material is a silica matrix, synthesized by a sol-gel process, and contains in-situ precipitated AgCl particles, which serve as precursors for nanoparticles of elemental silver. Reduction of AgCl to silver nanoparticles was achieved by UV irradiation. The plasmon activating medium is distributed on the solid, thereby producing a thin, strong and optically translucent substrate. The procedure may further be adapted to produce the above-described coating with embedded metal nanoparticles. The manufacturing processes described in this reference, which is incorporated herein by reference in its entirety, are suitable for use in the present invention.

Having generally described this invention, a further understanding can be obtained by reference to certain specific examples provided herein which are provided for purposes of illustration only and are not intended to be limiting unless otherwise specified.

Many modifications and variations of the present invention are possible in light of the above teachings. It is, therefore, to be understood that within the scope of the appended claims, the invention may be practiced otherwise than as specifically described herein.

Claims (204)

1. A method for producing a change in a medium disposed in an artificial container, comprising:

(1) placing within the medium an energy modulation agent and a photoactivatable agent, the energy modulation agent configured to emit light into the medium upon interaction with initiation energy from a source that emits at least one of x-rays, gamma rays, and an electron beam;

(2) applying the initiation energy comprising at least one of the x-rays, gamma rays, electron beams to the medium; and

(3) inducing a photoreactive change in the photoactivatable agent by light emitted into the medium,

wherein at least one of the x-rays, gamma rays, and electron beams interacts with the energy modulation agent to produce the light emitted into the medium, the light producing a change in the medium, wherein the change in the medium comprises a change in organism activity.

2. The method of claim 1, further comprising introducing a plasmonics agent in the medium.

3. The method of claim 1, further comprising: emitting the light from the energy modulation agent, the light having an energy different from the initiation energy applied.

4. The method of claim 3, further comprising introducing a plasmonics agent in the medium, wherein the plasmonics agent 1) enhances or modifies the light from the energy modulation agent or 2) enhances or modifies the initiation energy.

5. The method of claim 1, wherein applying comprises:

applying the initiation energy from an external energy source; or

The initiation energy is applied from a source at least partially located in the artificial container containing the medium or exposed through an opening in the artificial container.

6. The method of claim 2, wherein the plasmonics agent comprises a metal structure.

7. The method of claim 6, wherein the metal structure comprises at least one of nanospheres, nanorods, nanocubes, nanocones, nanoshells, multi-layer nanoshells, and combinations thereof.

8. The method of claim 1, wherein the energy modulation agent comprises at least one of a sulfide, a telluride, a selenide, and an oxide semiconductor.

9. The method of claim 8, wherein the energy modulation agent comprises Y₂O₃；ZnS；ZnSe；MgS；CaS；Mn，ErZnSe；Mn，ErMgS；Mn，ErCaS；Mn，ErZnS；Mn，YbZnSe；Mn，YbMgS；Mn，YbCaS；Mn，YbZnS：Tb³⁺，Er³⁺；ZnS：Tb³⁺；Y₂O₃：Tb³⁺；Y₂O₃：Tb³⁺，Er3⁺；ZnS：Mn²⁺；ZnS：Mn，Er³⁺At least one of (a).

10. The method of claim 2, wherein:

the energy modulation agent is disposed adjacent to at least one metal nanoparticle serving as the plasmonics agent;

the energy modulation agent is at least partially coated with a metal that acts as the plasmonics agent;

the energy modulation agent comprises a magnetic substance; or

The energy modulation agent includes a chemical or biological receptor.

11. The method of claim 2, wherein:

the metal nanoparticles used as the plasmonics agent are at least partially covered with the energy modulation agent;

the metal nanoparticles include a magnetic substance; or

The metal nanoparticles include chemical or biological receptors.

12. The method of claim 2, wherein:

the plasmonics agent comprises a dielectric-metal composite; or

The plasmonics agent includes a plurality of different sized metal nanoparticles disposed adjacent to one another as a composite plasmonics agent.

13. The method of claim 1, wherein the change in activity comprises at least one of sterilization of the medium or inactivation of fermentation within the medium.

14. The method of claim 1, wherein the change in activity comprises low temperature pasteurization of the medium.

15. The method of claim 1, wherein applying comprises sterilizing a medium comprising at least one organism selected from the group consisting of bacteria, viruses, yeast, and fungi.

16. The method of claim 1, wherein the photoactivatable agent comprises an active agent contained within a photocage, wherein upon exposure to the initiation energy source, the photocage is configured to separate from the active agent such that the active agent is available to the medium.

17. The method of claim 1, wherein the photoactivatable agent is selected from the group consisting of: psoralens, pyrenyl cholesterol oleate, acridines, porphyrins, fluoresceins, rhodamines, 16-diazocortisones, ethidines, transition metal complexes of bleomycin, transition metal complexes of deglycobleomycin, organo platinum complexes, alloxazines, vitamin Ks, vitamin L, vitamin metabolites, vitamin precursors, naphthoquinones, naphthalenes, naphthols and their derivatives with planar molecular conformations, porphyrins, dyes and phenothiazine derivatives, coumarins, quinolones, quinones and anthraquinones.

18. The method of claim 1, wherein the photoactivatable agent comprises a psoralen, a coumarin, or a derivative thereof.

19. The method of claim 18, wherein at least one of a cancer cell, a tumor cell, an autoimmune deficiency syndrome virus, or a blood-borne bactericide is treated with psoralen, coumarin, or a derivative thereof.

20. The method of claim 1, wherein the photoactivatable agent comprises a photocatalyst.

21. The method of claim 20, wherein the photocatalyst comprises TiO₂、ZnO、CdS、CdSe、SnO₂、SrTiO₃、WO₃、Fe₂O₃And Ta₂O₅At least one of (a).

22. The method of claim 2, wherein:

the energy modulation agent comprises a photon emitter configured to emit the light at a wavelength that activates at least one photoactivatable agent in the medium, and

the plasmonics agent enhances the light emitted by the energy modulation agent such that the enhanced radiation light activates the at least one photoactivatable agent.

23. The method of claim 22, wherein the photon emitter comprises a plurality of luminescent agents.

24. The method of claim 23, wherein the luminescent agent is selected from chemiluminescent compounds and bioluminescent compounds that emit the light upon exposure to the initiation energy.

25. The method of claim 23, wherein the luminescent agent is selected from phosphorescent compounds and bioluminescent compounds that emit the light upon exposure to the initiation energy.

26. The method of claim 23, wherein the luminescent agents comprise nanotubes, nanoparticles, chemiluminescent particles, and bioluminescent particles, and mixtures thereof.

27. The method of claim 23, wherein the luminescent agent comprises a semiconductor or metallic material.

28. The method of claim 23, wherein the luminescent agent comprises a chemiluminescent agent having enhanced chemiluminescence upon exposure to microwave energy.

29. The method of claim 23, wherein the luminescent agent comprises carbon nanotubes.

30. The method of claim 29, wherein the carbon nanotubes emit light when exposed to microwave or radio frequency energy.

31. The method of claim 23, further comprising: magnetically introducing the energy modulation agent into the medium or collecting the energy modulation agent from the medium.

32. The method of claim 1, wherein applying comprises:

applying the initiation energy throughout the entire volume of the artificial container.

33. The method of claim 1, wherein applying comprises:

transmitting the initiation energy through the artificial container, the artificial container comprising at least one of an aluminum container, a quartz container, a glass container, a plastic container, or a combination thereof.

34. The method of claim 1, wherein the energy modulation agent is provided within the medium at a density where the light produced by the energy modulation agent is not blocked throughout the medium.

35. The method of claim 2, wherein placing comprises providing the energy modulation agent or the plasmonics agent in an isolated state within the medium.

36. The method of claim 35, wherein providing an isolated state within the medium comprises providing encapsulation of the energy modulation agent or the plasmonics agent in the medium.

37. The method of claim 36, wherein providing encapsulation comprises providing the encapsulation at a density where light is not blocked throughout the medium.

38. The method of claim 36, wherein providing an encapsulation comprises:

providing said encapsulation in a fluidized bed;

providing the envelope in a re-enterable structure extending into the artificial container containing the medium; or

Providing said envelope on an inner wall of said artificial container containing said medium.

39. The method of claim 1, wherein the initiation energy comprises x-ray energy and UV/VIS energy that activate a photoactivatable agent in the medium.

40. The method of claim 1, wherein the initiation energy comprises infrared energy and UV/VIS energy that activate the photoactivatable agent in the medium.

41. The method of claim 1, wherein the initiation energy comprises radio wave or microwave energy and UV/VIS energy that activates the photoactivatable agent in the medium.

42. The method of claim 1, wherein applying comprises applying the initiation energy to wastewater to reduce contaminants in the wastewater.

43. The method of claim 1, wherein applying comprises sterilizing a portion of a connection region of an appliance that connects one region of the appliance to another region of the appliance.

44. The method of claim 1, wherein applying comprises applying the initiation energy to a fluid to sterilize the fluid.

45. The method of claim 44, wherein applying comprises at least one of:

Sterilizing a blood product or food; or

Pasteurizing the fluid or the food product.

46. The method of claim 1, wherein applying comprises applying an initiation energy having an energy higher than the energy produced by the energy modulation agent or applying an initiation energy having an energy lower than the energy produced by the energy modulation agent.

47. A method of producing a change in a medium disposed in an artificial container, comprising:

(1) placing within a medium to be treated a plasmonics agent and a photoactivatable agent that when activated generates a modification in the medium, the plasmonics agent configured to enhance or modify energy conducted in the vicinity of the plasmonics agent; and

(2) applying initiation energy to the medium from an energy source emitting at least one of x-rays, gamma-rays, and electron beams,

(3) inducing a change in photoreactivity of the photoactivatable agent by the enhanced or altered energy;

wherein at least one of the x-rays, gamma rays, and electron beams interact with the plasmonics agent to produce the enhanced or altered energy that produces the change in the medium, wherein the change in the medium comprises a change in organism activity.

48. The method of claim 47, further comprising emitting light by an energy modulation agent disposed proximate the medium, the light having an energy different from the applied initiation energy.

49. The method of claim 48, wherein the plasmonics agent 1) enhances or modifies the light from the energy modulation agent or 2) enhances or modifies the initiation energy.

50. The method of claim 47, wherein applying comprises:

applying the initiation energy from an external energy source; or

The initiation energy is applied from a source at least partially located in the artificial container containing the medium or exposed through an opening in the artificial container.

51. The method of claim 47, wherein the plasmonics agent comprises a metal structure.

52. The method of claim 51, wherein the metal structure comprises at least one of nanospheres, nanorods, nanocubes, nanocones, nanoshells, multi-layer nanoshells, and combinations thereof.

53. The method of claim 47, further comprising: providing an energy modulation agent in the medium, the energy modulation agent comprising at least one of a sulfide, a telluride, a selenide and an oxide semiconductor.

54. The method of claim 53, wherein the energy modulation agent comprises Y₂O₃；ZnS；ZnSe；MgS；CaS；Mn，ErZnSe；Mn，ErMgS；Mn，ErCaS；Mn，ErZnS；Mn，YbZnSe；Mn，YbMgS；Mn，YbCaS；Mn，YbZnS：Tb³⁺，Er³⁺；ZnS：Tb³⁺；Y₂O₃：Tb³⁺；Y₂O₃：Tb³⁺，Er3⁺；ZnS：Mn²⁺；ZnS：Mn，Er³⁺At least one of (a).

55. The method of claim 47, wherein:

the photoactivatable agent is disposed adjacent to at least one metal nanoparticle serving as the plasmonics agent;

the photoactivatable agent is at least partially coated with a metal that acts as the plasmonics agent;

the photoactivatable agent comprises a magnetic substance; or

The photoactivatable agents include chemical or biological receptors.

56. The method of claim 47, wherein:

the metal nanoparticles used as the plasmonics agent are at least partially covered with the photoactivatable agent;

the metal nanoparticles include a magnetic substance; or

The metal nanoparticles include chemical or biological receptors.

57. The method of claim 47, wherein:

the plasmonics agent comprises a dielectric-metal nanocomposite; or

The plasmonics agent includes a plurality of different sized metal nanoparticles disposed adjacent to one another as a composite plasmonics agent.

58. The method of claim 47, wherein the change in activity comprises at least one of sterilization of the medium or inactivation of fermentation within the medium.

59. The method of claim 47, wherein the change in activity comprises low temperature pasteurization of the medium.

60. The method of claim 47, wherein applying comprises applying the initiation energy to sterilize a medium comprising at least one organism selected from the group consisting of bacteria, viruses, yeast, and fungi.

61. The method of claim 47, wherein the photoactivatable agent comprises an active agent contained within a photocage, wherein upon exposure to the initiation energy source, the photocage is configured to detach from the active agent such that the active agent is available to the medium.

62. The method of claim 47, wherein the photoactivatable agent is selected from the group consisting of: psoralens, pyrenyl cholesterol oleate, acridines, porphyrins, fluoresceins, rhodamines, 16-diazocortisones, ethidines, transition metal complexes of bleomycin, transition metal complexes of deglycobleomycin, organo platinum complexes, alloxazines, vitamin Ks, vitamin L, vitamin metabolites, vitamin precursors, naphthoquinones, naphthalenes, naphthols and their derivatives with planar molecular conformations, porphyrins, dyes and phenothiazine derivatives, coumarins, quinolones, quinones and anthraquinones.

63. The method of claim 47, wherein the photoactivatable agent comprises a psoralen, a coumarin, or a derivative thereof.

64. The method of claim 63, wherein the cancer cells, tumor cells, autoimmune deficiency syndrome virus or blood-borne bactericides are treated with psoralen, coumarin or a derivative thereof.

65. The method of claim 47, wherein the photoactivatable agent comprises a photocatalyst.

66. The method of claim 65, wherein the photocatalyst comprises TiO₂、ZnO、CdS、CdSe、SnO₂、SrTiO₃、WO₃、Fe₂O₃And Ta₂O₅At least one of (a).

67. The method of claim 47, further comprising: providing the medium with an energy modulation agent that converts the initiation energy into activation energy that activates the photoactivatable agent.

68. The method of claim 67, wherein the energy modulation agent comprises a photon emitter configured to emit light at a wavelength that activates the photoactivatable agent, and

the plasmonics agent enhances the light such that the enhanced light activates the photoactivatable agent.

69. The method of claim 68, wherein the energy modulation agent receives infrared or near infrared and emits visible or ultraviolet light.

70. The method of claim 68, wherein the photon emitter comprises a plurality of luminescent agents.

71. The method of claim 70, wherein said luminescent agent is selected from the group consisting of chemiluminescent compounds and bioluminescent compounds that emit said light upon exposure to said initiation energy.

72. The method of claim 70, wherein said luminescent agent is selected from the group consisting of phosphorescent and bioluminescent compounds that emit said light upon exposure to said initiation energy.

73. The method of claim 70, wherein said luminescent agents comprise nanotubes, nanoparticles, chemiluminescent particles and bioluminescent particles and mixtures thereof.

74. The method of claim 70, wherein the luminescent agent comprises a semiconductor or metallic material.

75. The method of claim 70, wherein the luminescent agents comprise chemiluminescent agents having enhanced chemiluminescence upon exposure to microwave energy.

76. The method of claim 70, wherein said luminescent agents comprise carbon nanotubes.

77. The method of claim 76, wherein said carbon nanotubes emit light upon exposure to microwave or radio frequency energy.

78. The method of claim 68, further comprising: magnetically introducing the energy modulation agent into the medium or collecting the energy modulation agent from the medium.

79. The method of claim 47, wherein applying comprises:

applying the initiation energy throughout the entire volume of the artificial container.

80. The method of claim 47, wherein applying comprises:

transmitting the initiation energy through the artificial container, the artificial container comprising at least one of an aluminum container, a quartz container, a glass container, a plastic container, or a combination thereof.

81. The method of claim 47, wherein disposing comprises providing a dispersed energy modulation agent within the medium that converts the initiation energy into light that activates the photoactivatable agent.

82. The method of claim 81, wherein providing dispersion within the medium comprises: providing the energy modulation agent at a density wherein the light is not blocked throughout the medium.

83. The method of claim 47, wherein placing comprises providing an isolated energy modulation agent or the plasmonics agent within the medium.

84. The method of claim 83, wherein providing isolation inside the medium comprises providing encapsulation of an energy modulation agent or the plasmonics agent in the medium.

85. The method of claim 84, wherein providing encapsulation comprises providing the encapsulation at a density where the light is not blocked throughout the medium.

86. The method of claim 84, wherein providing an encapsulation comprises:

providing said encapsulation in a fluidized bed;

providing the envelope in a re-enterable structure extending into the artificial container containing the medium; or

Providing said envelope on an inner wall of said artificial container containing said medium.

87. The method of claim 47, wherein the initiation energy comprises x-ray energy and UV/VIS energy that activate the photoactivatable agent.

88. The method of claim 47, wherein the initiation energy comprises infrared energy and UV/VIS energy that activate the photoactivatable agent.

89. The method of claim 47, wherein the initiation energy comprises radio waves or microwave energy and UV/VIS energy that activate the photoactivatable agent.

90. The method of claim 47, wherein applying comprises applying the initiation energy to wastewater to reduce contaminants in the wastewater.

91. A method as in claim 47, wherein applying comprises sterilizing a portion of a connection region of an appliance, the connection region connecting one region of the appliance to another region of the appliance.

92. The method of claim 47, wherein applying comprises applying the initiation energy to a fluid to sterilize the fluid.

93. The method of claim 92, wherein applying comprises sterilizing the blood product or food.

94. The method of claim 47, wherein applying comprises applying the initiation energy to a fluid or food to pasteurize the fluid or food.

95. The method of claim 47, wherein applying comprises applying the initiation energy at an energy higher than that produced by an energy modulation agent in the medium, or applying the initiation energy at an energy lower than that produced by an energy modulation agent in the medium.

96. A system for producing a change in a medium disposed in an artificial container, comprising:

A device configured to provide within a medium to be treated (1) a photoactivatable agent and 2) an energy modulation agent configured to emit light into the medium upon interaction with initiation energy from a source emitting at least one of x-rays, gamma rays, and electron beams; and

an initiation energy source configured to apply the initiation energy to the medium,

wherein the photoreactivity change of the photoactivatable agent is induced by light emitted into the medium to be treated;

wherein at least one of the x-rays, gamma rays and electron beams interact with the energy modulation agent to produce the light emitted into the medium to be treated, the light producing a change in the medium, wherein the change in the medium comprises a change in organism activity.

97. The system of claim 96, further comprising a plasmonics agent in the medium, the plasmonics agent configured to enhance or modify energy conducted in the vicinity of the plasmonics agent.

98. The system of claim 96, wherein the energy modulation agent is configured to emit the light at an energy different from the initiation energy.

99. The system of claim 97, wherein the plasmonics agent 1) enhances or modifies the light from the energy modulation agent or 2) enhances or modifies the initiation energy.

100. The system claimed in claim 96 and wherein:

the initiation energy source comprises an external energy source; or

The initiation energy source comprises an energy source located at least partially in the artificial container containing the medium or an energy source exposed through an opening in the artificial container.

101. The system of claim 96, wherein the initiation energy source further comprises: at least one of a UV radiation source, a microwave source, or a radio wave source.

102. The system of claim 97, wherein the plasmonics agent comprises a metallic structure.

103. The system of claim 102, wherein the metal structure comprises at least one of nanospheres, nanorods, nanocubes, nanocones, nanoshells, multi-layer nanoshells, and combinations thereof.

104. The system of claim 96, wherein the energy modulation agent comprises at least one of a sulfide, a telluride, a selenide and an oxide semiconductor.

105. The system of claim 104, wherein the energy modulation agent comprises Y₂O₃；ZnS；ZnSe；MgS；CaS；Mn，ErZnSe；Mn，ErMgS；Mn，ErCaS；Mn，ErZnS；Mn，YbZnSe；Mn，YbMgS；Mn，YbCaS；Mn，YbZnS：Tb³⁺，Er³⁺；ZnS：Tb³⁺；Y₂O₃：Tb³⁺；Y₂O₃：Tb³⁺，Er3⁺；ZnS：Mn²⁺；ZnS：Mn，Er³⁺At least one of (a).

106. The system of claim 96, wherein the medium comprises a medium to be fermented.

107. The system of claim 96, wherein the medium comprises a fluid medium to be sterilized or pasteurized.

108. The system of claim 107, wherein the medium comprises a blood product or a food product.

109. The system of claim 108, wherein the medium comprises at least one organism selected from the group consisting of bacteria, viruses, yeast, and fungi.

110. The system of claim 96, wherein the photoactivatable agent comprises an active agent contained within a photocage that, when exposed to the initiation energy source, detaches from the active agent such that the active agent is available for use.

111. The system of claim 96, wherein the photoactivatable agent is selected from the group consisting of: psoralens, pyrenyl cholesterol oleate, acridines, porphyrins, fluoresceins, rhodamines, 16-diazocortisones, ethidines, transition metal complexes of bleomycin, transition metal complexes of deglycobleomycin, organo platinum complexes, alloxazines, vitamin Ks, vitamin L, vitamin metabolites, vitamin precursors, naphthoquinones, naphthalenes, naphthols and their derivatives with planar molecular conformations, porphyrins, dyes and phenothiazine derivatives, coumarins, quinolones, quinones and anthraquinones.

112. The system of claim 96, wherein the photoactivatable agent comprises a psoralen, a coumarin, or a derivative thereof.

113. The system of claim 112, wherein the cancer cells, tumor cells, autoimmune deficiency syndrome virus or blood-borne bactericides are treated with a psoralen, a coumarin, or a derivative thereof.

114. The system of claim 96, wherein the photoactivatable agent comprises a photocatalyst.

115. The system of claim 114, wherein the photocatalyst comprises TiO₂、ZnO、CdS、CdSe、SnO₂、SrTiO₃、WO₃、Fe₂O₃And Ta₂O₅At least one of the particles.

116. The system of claim 96, further comprising a magnetic device configured to provide the energy modulation agent to the medium or collect the energy modulation agent from the medium.

117. The system of claim 116, wherein the energy modulation agent comprises a photon emitter selected from a chemiluminescent compound and a bioluminescent compound.

118. The system of claim 116, wherein the energy modulation agent comprises a photon emitter selected from a phosphorescent compound and a bioluminescent compound.

119. The system of claim 117 or 118, wherein the energy modulation agent comprises a plurality of luminescent agents.

120. The system of claim 119, wherein the luminescent agent is selected from the group consisting of chemiluminescent compounds and bioluminescent compounds that emit light upon exposure to the initiation energy.

121. The system of claim 119, wherein the luminescent agent is selected from phosphorescent compounds and bioluminescent compounds that emit light upon exposure to the initiation energy.

122. The system of claim 119, wherein the luminescent agents comprise nanotubes, nanoparticles, chemiluminescent particles and bioluminescent particles and mixtures thereof.

123. The system of claim 119, wherein the luminescent agent comprises a semiconductor or metallic material.

124. The system of claim 119, wherein the luminescent agent comprises a chemiluminescent agent that chemiluminesces upon exposure to microwave energy.

125. The system of claim 96, wherein the energy modulation agent is provided within the medium at a density where the light from the energy modulation agent is not occluded throughout the medium.

126. The system of claim 96, wherein the energy modulation agent converts the initiation energy into light that activates the photoactivatable agent.

127. The system of claim 96, further comprising: encapsulation of the energy modulation agent in the medium.

128. The system of claim 127, wherein the encapsulation comprises a density where the light emitted from the encapsulation is not blocked throughout the medium.

129. The system of claim 127, wherein the encapsulation comprises:

a fluidized bed;

a re-entrant structure extending into a container containing the medium; or

An inner wall of the artificial container containing the medium.

130. The system of claim 96, wherein the artificial container comprises a container that is permeable to the initiation energy.

131. The system of claim 96, wherein the artificial container is at least one of an aluminum container, a quartz container, a glass container, a plastic container, or a combination thereof.

132. The system of claim 96, wherein the artificial container comprises a container that receives and transmits the initiation energy to a fluid product to pasteurize the fluid product.

133. The system of claim 96, wherein the artificial container comprises a container that receives and conducts the initiation energy to a fluid product to treat contaminants in the fluid product.

134. The system claimed in claim 97 and wherein:

the photoactivatable agent is disposed adjacent to at least one metal nanoparticle serving as the plasmonics agent;

the photoactivatable agent is at least partially coated with a metal that acts as the plasmonics agent;

the photoactivatable agent comprises a magnetic substance; or

The photoactivatable agents include chemical or biological receptors.

135. The system claimed in claim 97 and wherein:

the metal nanoparticles used as the plasmonics agent are at least partially covered with the photoactivatable agent;

the metal nanoparticles include a magnetic substance; or

The metal nanoparticles include chemical or biological receptors.

136. The system claimed in claim 97 and wherein:

the plasmonics agent comprises a dielectric-metal nanocomposite; or

The plasmonics agent includes a plurality of different sized metal nanoparticles disposed adjacent to one another as a composite plasmonics agent.

137. The system of claim 96, wherein the initiation energy is higher or lower than the energy produced by the energy modulation agent.

138. A system for producing a change in a medium disposed in an artificial container, comprising:

means arranged to provide a plasmonics agent and a photoactivatable agent within a medium to be treated, the plasmonics agent being arranged to enhance or alter energy conducted in the vicinity of the plasmonics agent; and

an initiation energy source arranged to apply an initiation energy of at least one of x-rays, gamma-rays and an electron beam to said medium,

wherein the photoreactivity of the photoactivatable agent is induced to change by the enhanced or altered energy;

wherein at least one of the x-rays, gamma rays, and electron beams interact with the plasmonics agent to produce the enhanced or altered energy that produces the alteration in the medium, wherein the alteration in the medium comprises a change in organism activity.

139. The system of claim 138, wherein the initiation energy is higher than the energy produced by an energy modulation agent that converts the initiation energy to a different energy.

140. The system of claim 139, further comprising an encapsulating structure, wherein the encapsulating structure contains a plasmonics agent and comprises:

A fluidized bed;

a re-enterable structure extending into the artificial container containing the medium; or

An inner wall of the artificial container containing the medium.

141. The system of claim 139, further comprising an encapsulating structure, wherein the encapsulating structure comprises energy modulation agent nanoparticles encapsulated by a passivation layer.

142. The system of claim 139, further comprising an encapsulating structure, wherein the encapsulating structure comprises a sealed tube containing an energy modulation agent and a plasmonics agent.

143. The system of claim 139, further comprising an encapsulated structure, wherein the encapsulated structure comprises a sealed tube with the plasmonics agent disposed on an exterior of the sealed tube proximate the medium.

144. The system of claim 138, wherein the plasmonics agent comprises a metallic structure.

145. The system of claim 144, wherein the metal structure comprises at least one of nanospheres, nanorods, nanocubes, nanocones, nanoshells, multi-layer nanoshells, and combinations thereof.

146. The system claimed in claim 144 and wherein:

An energy modulation agent disposed adjacent to at least one metal nanoparticle serving as the plasmonics agent;

the energy modulation agent is at least partially coated with a metal that acts as the plasmonics agent;

the energy modulation agent comprises a magnetic substance; or

The energy modulation agent includes a chemical or biological receptor.

147. The system claimed in claim 144 and wherein:

the metal nanoparticles used as the plasmonics agent are at least partially covered with an energy modulation agent;

the metal nanoparticles include a magnetic substance; or

The metal nanoparticles include chemical or biological receptors.

148. The system claimed in claim 144 and wherein:

the plasmonics agent comprises a dielectric-metal nanocomposite; or

The plasmonics agent includes a plurality of different sized metal nanoparticles disposed adjacent to one another as a composite plasmonics agent.

149. The system claimed in claim 138 and wherein:

the initiation energy source comprises an external energy source; or

The initiation energy source comprises an energy source located at least partially in the artificial container containing the medium or an energy source exposed through an opening in the artificial container.

150. The system claimed in claim 138 and further comprising: an energy modulation agent in the medium, the energy modulation agent comprising at least one of a sulfide, a telluride, a selenide and an oxide semiconductor.

151. The system of claim 150, wherein the energy modulation agent comprises Y₂O₃；ZnS；ZnSe；MgS；CaS；Mn，ErZnSe；Mn，ErMgS；Mn，ErCaS；Mn，ErZnS；Mn，YbZnSe；Mn，YbMgS；Mn，YbCaS；Mn，YbZnS：Tb³⁺，Er³⁺；ZnS：Tb³⁺；Y₂O₃：Tb³⁺；Y₂O₃：Tb³⁺，Er3⁺；ZnS：Mn²⁺；ZnS：Mn，Er³⁺At least one of (a).

152. The system of claim 138, wherein the photoactivatable agent is selected from the group consisting of: psoralen, pyrenyl cholesterol oleate, acridine, porphyrin, fluorescein, rhodamine, 16-diazocortisone, ethidine, transition metal complexes of bleomycin, transition metal complexes of deglycobleomycin, organo platinum complexes, alloxazines, vitamin Ks, vitamin L, vitamin metabolites, vitamin precursors, naphthoquinones, naphthalenes, naphthols and derivatives thereof having a planar molecular conformation, porphyrins, dyes and phenothiazine derivatives, coumarins, quinolones, quinones and anthraquinones.

153. The system of claim 152, wherein the photoactivatable agent comprises a psoralen, a coumarin, or a derivative thereof.

154. The system of claim 153, wherein the cancer cells, tumor cells, autoimmune deficiency syndrome virus, or blood-borne bactericides are treated with a psoralen, a coumarin, or a derivative thereof.

155. The system claimed in claim 138 and further comprising: a magnetic device arranged to provide said plasmonics agent to or collect said plasmonics agent from said medium.

156. A system for producing a light excitation modification to a medium placed in an artificial container, comprising:

a device configured to provide an energy modulation agent and a photoactivatable agent within a medium to be treated, the energy modulation agent configured to emit light into the medium upon interaction with an initiation energy of at least one of an x-ray, a gamma ray, and an electron beam; and

an initiation energy source configured to apply the initiation energy to the medium,

wherein the photoreactivity change of the photoactivatable agent is induced by light emitted into the medium to be treated;

wherein at least one of the x-rays, gamma rays and electron beams interact with the energy modulation agent to produce the light emitted into the medium to be treated, the light producing a light-excited change, wherein the change in the medium comprises a change in organism activity.

157. The system of claim 156, further comprising a plasmonics agent in the medium, the plasmonics agent configured to enhance or modify energy conducted in the vicinity of the plasmonics agent.

158. The system of claim 156, wherein the initiation energy is higher than the energy produced by the energy modulation agent.

159. The system of claim 157, further comprising an encapsulating structure, wherein the encapsulating structure includes at least one of the energy modulation agent or the plasmonics agent, and includes:

a fluidized bed;

a re-enterable structure extending into the artificial container containing the medium; or

An inner wall of the artificial container containing the medium.

160. The system of claim 156 or 157, further comprising an encapsulating structure, wherein the encapsulating structure comprises the energy modulation agent encapsulated by a passivation layer.

161. The system of claim 157, further comprising an encapsulated structure, wherein the encapsulated structure comprises a sealed tube with the plasmonics agent disposed on an exterior of the sealed tube proximate the medium.

162. The system of claim 157, wherein the plasmonics agent comprises a metallic structure.

163. The system of claim 162, wherein the metal structure comprises at least one of nanospheres, nanorods, nanocubes, nanocones, nanoshells, multi-layer nanoshells, and combinations thereof.

164. The system of claim 156, wherein the artificial container comprises a container that receives and conducts the initiation energy to the medium-internal product.

165. The system of claim 164, wherein the product comprises plastic.

166. The system of claim 165, wherein the light from the energy modulation agent alters the surface structure of the plastic.

167. The system of claim 165, wherein the plastic comprises polylactic acid (PLA) plastic and Polyhydroxyalkanoate (PHA) plastic, the energy modulation agent converts the initiation energy into activation energy that photografts molecular species on a surface of the plastic.

168. The system claimed in claim 157 and wherein:

the energy modulation agent is disposed adjacent to at least one metal nanoparticle serving as the plasmonics agent;

the energy modulation agent is at least partially coated with a metal that acts as the plasmonics agent; or

The energy modulation agent comprises a magnetic substance; or

The energy modulation agent includes a chemical or biological receptor.

169. The system claimed in claim 157 and wherein:

The metal nanoparticles used as the plasmonics agent are at least partially covered with the energy modulation agent;

the metal nanoparticles include a magnetic substance; or

The metal nanoparticles include chemical or biological receptors.

170. The system claimed in claim 157 and wherein:

the plasmonics agent comprises a dielectric-metal nanocomposite; or

The plasmonics agent includes a plurality of different sized metal nanoparticles disposed adjacent to one another as a composite plasmonics agent.

171. The system claimed in claim 156 and wherein:

the initiation energy source comprises an external energy source; or

The initiation energy source comprises an energy source located at least partially in the artificial container containing the medium or an energy source exposed through an opening in the artificial container; or

The initiation energy source comprises an external energy source directed to the structural elements in which the gap is pre-filled with uncured radiation curable medium, thereby curing the uncured radiation curable medium in the gap; or

The initiation energy source comprises a directed or focused beam of the initiation energy that cures the uncured radiation-curable medium to produce patterned elements.

172. The system of claim 156, wherein the energy modulation agent comprises at least one of a sulfide, a telluride, a selenide and an oxide semiconductor.

173. The system of claim 172, wherein the energy modulation agent comprises Y₂O₃；ZnS；ZnSe；MgS；CaS；Mn，ErZnSe；Mn，ErMgS；Mn，ErCaS；Mn，ErZnS；Mn，YbZnSe；Mn，YbMgS；Mn，YbCaS；Mn，YbZnS：Tb³⁺，Er³⁺；ZnS：Tb³⁺；Y₂O₃：Tb³⁺；Y₂O₃：Tb³⁺，Er3⁺；ZnS：Mn²⁺；ZnS：Mn，Er³⁺At least one of (a).

174. A sterilization system, comprising:

an initiation energy source configured to apply initiation energy of at least one of x-rays, gamma-rays, and electron beams to a medium to be sterilized; and

a plasmonics agent and a photoactivatable agent disposed within a medium to be treated, the plasmonics agent configured to enhance or alter energy conducted in proximity to the plasmonics agent; and

wherein at least one of the x-rays, gamma rays, and electron beams interact with the plasmonics agent to generate the enhanced or altered energy, wherein a photoreactivity change of the photoactivatable agent is induced by the enhanced or altered energy to sterilize the medium, thereby generating an alteration of an organism's activity.

175. The system claimed in claim 174 and further comprising: an encapsulation structure comprising the plasmonics agent.

176. The system of claim 175, wherein the encapsulating structure comprises:

a fluidized bed;

a re-entrant structure extending into a container containing the medium; or

An inner wall of a container containing the medium.

177. The system of claim 175, wherein the encapsulating structure comprises an energy modulation agent encapsulated by a passivation layer.

178. The system of claim 175, wherein the encapsulated structure comprises a sealed tube containing the plasmonics agent.

179. The system of claim 175, wherein the encapsulated structure comprises a sealed tube with the plasmonics agent disposed on an outside of the sealed tube.

180. The system of claim 174, wherein the plasmonics agent comprises a metallic structure.

181. The system of claim 180, wherein the metal structure comprises at least one of nanospheres, nanorods, nanocubes, nanocones, nanoshells, multi-layer nanoshells, and combinations thereof.

182. The system claimed in claim 174 and wherein:

an energy modulation agent disposed adjacent to at least one metal nanoparticle serving as the plasmonics agent;

The energy modulation agent is at least partially coated with a metal that acts as the plasmonics agent;

the energy modulation agent comprises a magnetic substance; or

The energy modulation agent includes a chemical or biological receptor.

183. The system claimed in claim 174 and wherein:

the metal nanoparticles used as the plasmonics agent are at least partially covered with an energy modulation agent; or

The metal nanoparticles include a magnetic substance; or

The metal nanoparticles include chemical or biological receptors.

184. The system claimed in claim 174 and wherein:

the plasmonics agent comprises a dielectric-metal nanocomposite; or

The plasmonics agent includes a plurality of different sized metal nanoparticles disposed adjacent to one another as a composite plasmonics agent.

185. The system of claim 174, wherein the initiation energy is higher or lower than the energy produced by the energy modulation agent.

186. The system of claim 174, further comprising an energy modulation agent comprising at least one of a sulfide, a telluride, a selenide and an oxide semiconductor.

187. The system of claim 186, in which the energy modulation agent comprises Y₂O₃；ZnS；ZnSe；MgS；CaS；Mn，ErZnSe；Mn，ErMgS；Mn，ErCaS；Mn，ErZnS；Mn，YbZnSe；Mn，YbMgS；Mn，YbCaS；Mn，YbZnS：Tb³⁺，Er³⁺；ZnS：Tb³⁺；Y₂O₃：Tb³⁺；Y₂O₃：Tb³⁺，Er3⁺；ZnS：Mn²⁺；ZnS：Mn，Er³⁺At least one of (a).

188. The system of claim 174, wherein the photoactivatable agent is selected from the group consisting of: psoralen, pyrenyl cholesterol oleate, acridine, porphyrin, fluorescein, rhodamine, 16-diazocortisone, ethidine, transition metal complexes of bleomycin, transition metal complexes of deglycobleomycin, organo platinum complexes, alloxazines, vitamin Ks, vitamin L, vitamin metabolites, vitamin precursors, naphthoquinones, naphthalenes, naphthols and derivatives thereof having a planar molecular conformation, porphyrins, dyes and phenothiazine derivatives, coumarins, quinolones, quinones and anthraquinones.

189. The system of claim 188, wherein the photoactivatable agent comprises a psoralen, a coumarin, or a derivative thereof.

190. The system of claim 189, wherein the cancer cells, tumor cells, autoimmune deficiency syndrome virus, or blood borne sterilant is treated with psoralen, coumarin, or a derivative thereof.

191. The system of claim 174, further comprising a container to receive and conduct the initiation energy, the container configured to contain at least one of:

A blood product or food to be sterilized; or

A fluid or food product with pasteurization.

192. The system claimed in claim 174 and further comprising: conducting light from the initiation energy source to a sealed tube in the medium to be sterilized.

193. The system of claim 192, wherein the plasmonics agent is disposed on a side of the sealed tube that is in contact with the medium.

194. The system of claim 192, wherein the initiation energy source comprises a UV light source.

195. The system of claim 192, wherein the initiation energy source comprises a broadband light source.

196. The system of claim 174, further comprising an energy modulation agent contained in proximity to the medium, wherein

The initiation energy source further comprises a source that produces at least one of UV radiation, visible light, infrared radiation, microwaves, chemical energy, or radio waves, and

the energy modulation agent converts energy from the initiation energy source into sterilizing light.

197. The system of claim 174, further comprising an energy modulation agent contained in proximity to the medium, wherein

The initiation energy source further comprises a source that generates at least one of UV radiation, visible light, infrared radiation, microwaves, chemical energy, or radio waves; and

The energy modulation agent converts energy from the initiation energy source into light that activates at least one photoactivatable agent contained in the medium to be sterilized.

198. The system of claim 197, wherein the at least one photoactivatable agent is selected from the group consisting of: psoralens, pyrenyl cholesterol oleate, acridines, porphyrins, fluoresceins, rhodamines, 16-diazocortisone, ethidium, transition metal complexes of bleomycin, transition metal complexes of desugared bleomycin organo-platinum complexes, alloxazines, vitamin Ks, vitamin L, vitamin metabolites, vitamin precursors, naphthoquinones, naphthalenes, naphthols and their derivatives with planar molecular conformations, porphyrins, dyes and phenothiazine derivatives, coumarins, quinolones, quinones and anthraquinones.

199. The system claimed in claim 174 and further comprising: a magnetic device configured to provide the plasmonics agent to the medium or to collect the plasmonics agent from the medium.

200. A method for producing a change in a medium, wherein the medium is not contained in a container, the method comprising:

(1) placing within a medium to be treated an energy modulation agent and a photoactivatable agent, the energy modulation agent configured to emit light into the medium upon interaction with an initiation energy of at least one of x-rays, gamma rays, and an electron beam; and

(2) Applying the initiation energy from an energy source to the medium,

(3) inducing a photoreactivity change of the photoactivatable agent by light emitted into the medium to be treated,

wherein at least one of the x-rays, gamma rays and electron beams interact with the energy modulation agent to produce the light emitted into the medium to be treated, the light producing a change in the medium, wherein the change in the medium comprises a change in organism activity.

201. A method of producing a change in a medium, wherein the medium is not contained in a container, the method comprising:

(1) placing within a medium to be treated a plasmonics agent and a photoactivatable agent that when activated generates a modification in the medium, the plasmonics agent configured to enhance or modify energy conducted in the vicinity of the plasmonics agent; and

(2) applying an initiation energy of at least one of x-rays, gamma rays, and an electron beam from an energy source to the medium,

(3) inducing a change in photoreactivity of the photoactivatable agent by the enhanced or altered energy;

wherein at least one of the x-rays, gamma rays, and electron beams interact with the plasmonics agent to produce the enhanced or altered energy that produces the change in the medium, wherein the change in the medium comprises a change in organism activity.

202. A system for producing a change in a medium, wherein the medium is not contained in a container, the system comprising:

a device configured to provide within a medium to be treated 1) a photoactivatable agent and 2) an energy modulation agent configured to emit light into the medium upon interaction with an initiation energy of at least one of an x-ray, a gamma ray, and an electron beam; and

an initiation energy source configured to apply the initiation energy to the medium,

wherein the photoreactivity of the photoactivatable agent is induced by light emitted into the medium to be treated,

wherein at least one of the x-rays, gamma rays and electron beams interact with the energy modulation agent to produce the light emitted into the medium to be treated, the light producing a change in the medium, wherein the change in the medium comprises a change in organism activity.

203. A system for producing a change in a medium, wherein the medium is not contained in a container, the system comprising:

means arranged to provide a plasmonics agent and a photoactivatable agent within a medium to be treated, the plasmonics agent being arranged to enhance or alter energy conducted in the vicinity of the plasmonics agent; and

An initiation energy source configured to apply initiation energy of at least one of x-rays, gamma-rays and electron beams to the medium,

wherein the photoreactivity of the photoactivatable agent is induced to change by the enhanced or altered energy;

wherein at least one of the x-rays, gamma rays, and electron beams interact with the plasmonics agent to produce the enhanced or altered energy that produces the change in the medium, wherein the change in the medium comprises a change in organism activity.

204. A system for producing a light-activated change in a medium, wherein the medium is not contained in a container, the system comprising:

a device configured to provide an energy modulation agent and a photoactivatable agent within a medium to be treated, the energy modulation agent configured to emit light into the medium upon interaction with an initiation energy of at least one of an x-ray, a gamma ray, and an electron beam; and

an initiation energy source configured to apply the initiation energy to the medium,

wherein the photoreactivity of the photoactivatable agent is induced by light emitted into the medium to be treated,

wherein at least one of the x-rays, gamma rays and electron beams interact with the energy modulation agent to produce the light emitted into the medium to be treated, the light producing the light-excited change, wherein the change in the medium comprises a change in organism activity.