HK1083240A - Broad spectrum optically addressed sensor - Google Patents

Description

Broad-spectrum optical sensor

Technical Field

The present invention relates to a broad spectrum sensor and a method of manufacturing such a sensor which can detect chemical, biological, biochemical or other environmental stimuli in a manner which is acute in the influence of these substances on the mechanical-optical properties of the sensor material.

Background

The chemical sensor is a gel matrix with crystal domains of colloidal particles embedded therein. Suitably prepared gels, such as hydrogels, can augment or correlate with feedback in a physicochemical environment. The lattice constant of the implanted colloidal crystal increases with the swelling of the sol and its optically derived properties change, which can be detected. These responses can be optimized with specific stimuli by introducing functional groups into the gel that can react with the stimuli and reduce the desired structural changes to the gel.

In an example of this technique, the necessary functional groups have been incorporated directly into the polymer from which the gel is made (see, U.S. patent No.6,544,800, and ash et al, U.S. patent nos.5,187,599, 5,854,078, and 5,898,004-heretofterther "ash patents"). Once the gel is functionalized in this way, it will swell in response to a specific stimulus and the colloidal particles that have been implanted will be used as a passive tracer (marker) of the mechanical state or degree of swelling of the functionalized hydrogel. As described in Asher, the extent of agglutination swelling is monitored by measuring the optical properties of the colloidal crystals implanted in the gel. The change in lattice constant will cause a measurable change in the colloidal crystal diffraction pattern.

In particular, as described in Asher's patent, uniformly sized colloidal spheres can be clustered into a crystalline shape, and then a hydrogel that has been integrated into a concentrated, substitutional functional group will polymerize around the shaped crystals. Once formed, this functional gel crystal will be used as a quantitative sensor for stimuli, where the response of the functional group can be monitored for diffraction by an optical spectrometer. The integration of different functional groups with different gels will lead to different sensitivities of the sensor material to different specific environmental stimuli, all being sensitive to one specific stimulus.

However, the above method, as described in the Asher patent, is effective only when one stimulus is detected at the same time, and it does not readily scale up the spectrum of the potential stimulus. Furthermore, combining several sensor crystals into one system would pose great difficulties in detecting and distinguishing different stimuli, thus requiring a comprehensive system, which would become a difficult step. However, in the existing methods, there is no method for synthesizing a clear functional domain in a gel, similar to the related art.

Still further, allowing colloidal spheres to self-assemble into a colloidal gel and then forming the gel around the lattice, as described in Asher's patent, introduces undesirable variations into the optical properties of the sensor due to the structural disadvantages of the self-assembled colloidal crystal and also due to the crystal lattice constant being only slightly more controllable than its control of its formation.

Finally, if the optical properties of self-agglutinated individuals are not readily discernible or predictable, detection of different responses to different stimuli in a sensor array would require location-sensitive detection, which can be costly. Having a characteristic optical signal sensor domain would greatly reduce the expense, but is difficult to achieve, but is very difficult and possibly impossible to control during colloidal crystallization.

Therefore, there is a need for a sensor that can simultaneously detect and monitor a large number of different environmental stimuli, and that is easy to operate and inexpensive to manufacture.

Summary of The Invention

The present invention relates to a sensor for detecting chemical, biological, biochemical or other environmental stimuli, comprising a plurality of colloidal particles having chemical receptors attached to their surfaces, wherein said plurality of colloidal particles is comprised of a material having a first dielectric constant, and wherein said particles form a one-, two-or three-dimensional lattice structure.

The lattice structure is surrounded by a gel matrix having a second dielectric constant and which may swell or condense in response to specific changes in the local environment.

When a target stimulus is directed at the sensor, and more specifically at the chemical receptor, the gel matrix will compress or expand, which will change the lattice constant and thus cause a measurable pattern of diffraction patterns, which in turn can be detected by the spectrometer.

In another embodiment of the invention, a plurality of colloidal particles are combined with holographic optical tweezers and polymerized to form an integrated sensor array, which diffracts light in a characteristic state such that each particle crystal domain of a one-, two-, or three-dimensional spatial structure or each particle crystal domain diffracts a different color in a specific direction.

In another embodiment of the invention, monolayer and thin three-dimensional sensors allow easy access of the target stimulus and improve the sensitivity of the crystal domain on the gel sensor.

In another embodiment of the invention, a characteristic sensor domain may be stacked in one of three dimensions to detect and correct for the lattice constant of sensor domains that are biased by environmental factors, and may be used to distinguish between similarly related stimuli. Domains that are not functionalized and difficult to functionalize can still be used to the same effect in one-, two-or three-dimensional distributions.

In another embodiment of the invention, a dual or multiple detection technique, wherein the sensor is first exposed to a potential stimulus and then detects the stimulus, may be used to the same effect.

In another embodiment of the present invention, gelled sensor arrays can be placed at the end of an optical fiber for optical readout with a fiber spectrometer and integrated into a portable system for the detection of chemical, biological, biochemical or other environmental stimuli.

In another embodiment of the invention, the gelled sensor may be in the form of a bundle or a "brush" that allows an operator to detect a large area by sweeping the sensor bundle or brush across the target area. The distribution of the brushes provides communication between the sensor elements and the target in situ without the use of a chip for transporting the sample.

In another embodiment of the invention, instead of gelled sensor arrays, beads are used to respond to specific target stimuli, and such beads may be treated at the end of each optical fiber that may be aligned with a brush to provide a response to the target stimuli.

In embodiments of the invention, a sleeve may be placed around the brush to provide sufficient stiffness structure to insert the sensor into a loose fill material. Further, a hardened permeable screen may be provided on the tip of the optical fibers of the brush, so that the gelled sensor array is not worn during use.

In another embodiment of the invention, a target stimulus can be introduced to a gelled sensor array, and the target stimulus can interact with functional groups on the sphere, such that the specifically functionalized spheres are attached together. After this time, the gel may expand non-specifically by a change in the chemical ambient temperature. The spheres attached together by the stimulus response will not separate due to expansion and therefore the diffraction properties of the crystalline domains will not change. In contrast, the different functionalized spheres will not separate due to the swelling of the gel, and will not respond to the stimulus, thereby causing a change in the diffraction characteristics. In this embodiment, the detection of the target stimulus does not include the change in color caused by the swelling of the gel. This method is useful, for example, for the specific detection of antigens by their ability to attach to spheres to functionalize the relevant antibodies.

As mentioned above, some of the features of the present invention will be described in detail in the specification section, which can be more easily understood, and the contribution to the art will represent a thank you. Again, additional features of the invention will be described hereinafter and will be subject of the dependent claims.

In this regard, before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not limited in its application to the details of construction and to the arrangements of the components set forth in the following description or illustrated in the drawings. The method and apparatus of the present invention are capable of other embodiments and of being practiced or of being carried out in various ways. Also, it is to be understood that the phraseology and terminology employed herein, as well as the abstract, are for the purpose of description and should not be regarded as limiting.

Those skilled in the art will appreciate that the conception upon which this disclosure is based may readily be utilized as a basis for the designing of other structures, methods and systems for carrying out the several purposes of the present invention. It is important that the claims be regarded as including such equivalents within their scope as do not depart from the scope of the method and apparatus claimed herein.

Drawings

FIG. 1 is a schematic representation of functionalized colloidal particles according to one embodiment of the present invention.

FIG. 2 is a schematic representation of a single cell lattice of colloidal crystals of functionalized colloidal particles according to one embodiment of the present invention.

FIG. 3 is a diagram of a gelled sensor crystal according to one embodiment of the invention.

FIG. 4 is a schematic representation of the principle of stimulus detection by gelled crystal domains, the stimulus being introduced into the gel according to one embodiment of the present invention.

FIG. 4B is a schematic representation of the principle of stimulus detection by gelled crystal domains, attaching individual molecules of a stimulus of interest to individual particles according to one embodiment of the invention.

FIG. 5 is a diagram of a holographic optical tweezers system, according to one embodiment of the present invention.

FIG. 6 is a diagram of a sensor array with characteristic functionalized domains distributed in an integrated state, according to an embodiment of the present invention.

Fig. 7A and 7b are illustrations of a sensor array consisting of characteristic one-dimensional particle chains and characteristic two-dimensional particle domains in a monolayer, according to one embodiment of the invention.

FIG. 8 is a schematic representation of a three-dimensional particle domain, according to an embodiment of the present invention.

Fig. 9 illustrates that in a three-dimensional domain, a single sensor material is combined with several different domains, superimposed on top of each other, which write the sensor material to have sensitivity to different stimuli, according to an embodiment of the invention.

Fig. 10a illustrates a sensor field that appears to be superimposed by functionalized particles on top of the same field on a particle whose surface is not functionalized, according to an embodiment of the invention.

FIG. 10B illustrates the superimposed particle of FIG. 10A showing the response of the upper functionalized domain relative to the lower unfunctionalized domain, according to one embodiment of the invention.

Fig. 11A-11 c illustrate a gelled sensor for use with a dual or multiplex detection technique.

FIG. 12 illustrates an optical reader that places a gelled sensor at the end of an optical fiber for use with a fiber optic spectrometer to form an integrated optical sensor system, according to one embodiment of the invention.

Fig. 13 illustrates placement of multiple samples in a portable sensor system to interact with other deployments in the domain to provide a panoramic environmental condition and its progression over time, according to one embodiment of the invention.

Fig. 14 illustrates a method of using a brush to sense and detect biological, chemical, and radiological threats on a wide variety of samples, according to one embodiment of the present invention.

Detailed Description

The invention relates to a colloidal crystal sensor and a production method of the colloidal crystal sensor, and the method comprises the following steps: (1) functionalizing colloidal particles rather than implanting them into a gel; (2) holographic optical trapping technology is used to bind one or more functionalized colloidal particles to delicate domains with chemical and optical properties.

In more detail, the colloidal crystal sensor can be functionalized for the detection of chemical, biochemical and physical factors by adding functional chemical groups on the surface of the colloidal particles, said groups being arranged to respond to a substituted stimulus by a change in the chemical environment of the gel, for example by changing the ionic strength, temperature, chemical composition or PH of the gel. The expansion or contraction of the gel, thereby causing the colloidal particles or spheres in the colloidal crystal to separate. The lattice constant of the functionalized crystal is changed so that its diffraction characteristics can be detected by the spectrometer, whereby the presence of the target stimulus can be detected. The target stimulant may be one of a nucleic acid, a protein, a carbohydrate, or an oil.

The functionalized colloidal particle 120, e.g., a colloidal sphere 100, is illustrated in fig. 1 with a specific chemical receptor 110 attached to its surface. The colloidal particles 100 themselves may be silicon, polystyrene, titanium oxide fire gas, or other material having the desired suitable optical properties and not having a specific or non-specific response to any predetermined target environmental stimulus.

The ligand or chemical receptor 110 should specifically react with the selected stimulus, for example, by chemically binding the target molecule or by catalyzing a chemical reaction when reacting with the stimulus. The ligands 110 will be irreversibly attached to the surface of the particle or sphere. Different numbers of ions or spheres 120 can be made by adding different ligands 110 to the surface of the sphere 120. These quantities can be distinguished by the size, shape and material composition of the particles. In the present case, the size of the spherical particles can be represented by the diameter "a" (as shown in fig. 1).

Fig. 2 illustrates a unit cell 200 of colloidal crystals, which is composed of functionalized particles 120, shown as spheres 120, from an individual tissue into a periodic lattice 200, represented by the characteristic space "D". The crystal lattice 200 is represented as a simple two-dimensional square array of unit cells 200, but those skilled in the art will appreciate that the crystal lattice may take the form of a generally horizontal single-layer or multi-layer crystal structure.

For the lattice or array 200 to be a diffractive optical element, the particles or spheres 100 should be of a material having a dielectric constant that is distinguishable from the dielectric constant of the surrounding medium 150. In this case, light is dispersed by the particles or spheres 100 through the medium 150, and scattered light is adjusted from the regular positions of the particles or spheres 100 so as to obtain desired diffracted light. More specifically, the wavelength λ impinges on the particle or sphere 100 distributed in this way, and is diffracted by the lines (two-dimensional) or the planes (three-dimensional) of the particle or sphere 100, and the angle of diffraction is θ:

Sinθ＝nλ/D

wherein n is an integer, and n is 1, 2, 3.

Conversely, the wavelength giving the angle of the scattered light can be derived from the following equation:

λ＝DSinθ/n

the particles or spheres 100 may influence the observed diffraction pattern and will require the principles of kinetic diffraction to predict the diffraction pattern of light at a particular wavelength. Even so, the wavelength will scatter in a particular direction depending on the lattice constant.

Fig. 3 shows a gelled crystal sensor 250 in which a lattice 200 of functionalized particles or spheres 120 is implanted into a gelled matrix 210. The gel 210 may be derived from a hydrogel, in which case the flowing medium supporting the sphere 120 and the gel 120 is water. Other gels or solvents may be used as desired for particular applications, as will be recognized by those skilled in the art. The gel 210 is placed around the already assembled colloidal crystals 250 and may be polymerized, for example, by photochemical polymerization, chemically induced polymerization, thermally induced polymerization, or by other methods known to those skilled in the art.

The gel 210 will be illustrated such that an increase or decrease in its specific volume (or expansion or contraction) will be responsive to its surrounding environment, and thus the spacing D of the spheres in the colloidal crystal 250. Relevant changes include changes in salt concentration, changes in the intensity of ambient ions, changes in the PH value, or changes in the concentration of chemicals in the solution.

Preferably, the gel 210 itself will not react strongly to any target stimulus directed to the sensor array 200. Furthermore, the target stimuli should interact with the ligands 110 attached to the particles or spheres 100 so as to affect the response of the gel 210 to the chemical change. The colloidal particles or spheres 100, ligand 110, gel 210 and solvent 120 will be selected as appropriate. For example, by chemically attaching crown ethers to the surface of the particle or sphere 120, specific adsorption can result in the generation of ions in the aqueous solution, thereby increasing the strength of the surrounding ions and shrinking the surrounding hydrogel.

The lattice constant of the implanted colloidal crystal 200 changes due to contraction or expansion of the gel 120. These in turn will affect the diffraction characteristics of the colloidal crystal 200. The resulting change in lattice constant of the functionalized crystal 210 can be detected by injecting white light and measuring the wavelength of the backscattered light. Very accurate results can be measured using a hand-held fiber optic spectrophotometer where economic conditions permit.

FIGS. 1A and 4B show a graphical representation of a gelled crystal sensor 250 detecting its particular target stimulus 300, such as a smaller sphere 120. An individual's stimulator molecule 260 (see fig. 4A) is attached to the ligand 110 and adheres to the individual's particle or sphere 120 (see fig. 4B). This reaction is caused by a specific chemical change on the particle or sphere 100 and propagates into the surrounding gel 210. By design, these chemical changes cause the gel crystal 200 to expand, changing the lattice constant of the implanted colloidal crystal from D to D'. These, in turn, will change the wavelength of light scattered at a particular location, and thus the presence of target stimulus 120 can be detected.

Thus, the functional ligand 110 is attached to the colloidal particle 100, rather than to the surrounding gel 210. These advantages over the prior art are that different particles 100 may form different kinds of sensors 250, using the same chemical gel. Still further, it provides a method of manufacturing multiple self-calibrating sensors on a single device.

By functionalizing the particles or spheres 100 instead of the gel 210, multiple detectors can be integrated on a single agglomerate 210, thereby creating a high density, relatively inexpensive sensor 250.

In another embodiment of the invention, rather than self-coalescing the desired colloidal particles into colloidal domains, the coalescing of colloidal particles is manipulated with holographic optical tweezers 300 (as shown in FIG. 5).

In conventional sensors, colloidal particles are allowed to self-assemble into colloidal crystals, which in turn create a gel around them to form a lattice, so that the resulting sensor has various optical properties, since the self-assembled colloidal crystals may suffer structural damage and it may be difficult to control the resulting lattice constant and its symmetry.

However, by using holographic optical tweezers 300 (shown in FIG. 5), particles can be screened or trapped from a library of particles, moved to a collection domain, and then quickly, economically and efficiently organized into any desired configuration, including a three-dimensional array of structures. This construction need not be associated with any self-aggregating colloidal particles; the lattice space in which the tweezers make up the crystal is also not necessarily associated with the natural equilibrium forces between the particles. Thus, the particles can be optimized for their optical and chemical properties without having to consider their interactions. Therefore, the particles used for this purpose need to be spherical, rather than having to be of a precise specific size.

Holographic optical tweezers 300 are well known in the art and are described in patent U.S. patent No.6,055,106 to griier et al, which may be incorporated herein by reference. In the present application, as shown in FIG. 5, for example, holographic optical tweezers 300 insert a transparent chemically fabricated colloidal particle 200 into a three-dimensional array through flow cavities 315. A sample 310 located in cavity 315 is illuminated by an illuminator 320. The optical carrier is made by inputting a computer controlled laser beam 330 into a fan-shaped diverging beam 350, wherein the diverging beam 350 passes through a series of mirrors 360, each of the diverging beams 350 being directly reflected by a mirror 355 and focused directly into a high power objective 370. Each colloidal particle in the tissue sample is organized with holographic optical tweezers and occupies a corresponding position according to the capture of the exact optical position.

The light, after treatment by the optical tweezers 300, is viewed by the camera 380 and at the same time the resulting colloidal particle array (polystyrene in this case) is observed microscopically, dispersed in water and organized by capturing into a square array.

Ordinary micellar-like colloidal particle subarrays are known as colloidal crystals and have conventional scattering properties for visible light. They can be considered as diffraction gratings of three-dimensional spatial structure whose characteristic pattern of diffraction varies according to the symmetry and lattice constant of the crystal. The distinctive optical characteristics of the crystals can be optimized by constructing precise structures of colloidal arrays, and they are used here as a means of measuring concentration and in conjunction with environmental stimuli.

In another embodiment of the present invention, different colloidal particles from different sources can be organized in this way to form different domains simultaneously and can be distinguished by their chemical function and their optical properties, as shown in FIG. 6. These separate domains can be placed in absolute proximity, i.e., rearranged using a dynamic holographic optical tweezer 300 (fig. 5). Once the desired colloidal particles or spheres are obtained in the domains, the entire system can be polymerized to produce an integrated sensor array 400, as shown in fig. 6.

Fig. 6 shows two domains 410, 420 of a sensor array 400 formed by the side-by-side distribution of functionalized colloidal particles or spheres 120 with different surface ligands and crystal lattice structures in the same gel matrix.

Even if only one or two target stimuli are desired, current sensor arrays may have the advantage of competing with the prior art, and more particularly, the multiple characteristic domains provide continuity of the in situ criteria, reduce redundant cross-detection, and have superior recognition of nearby related target stimuli.

In another embodiment of the invention, the sensor array is again composed of characteristic row one-dimensional chains of particles in a monolayer, or characteristic two-dimensional domains of particles, and still scatter light under certain conditions, each chain and each domain scattering a certain color by setting a certain direction.

Thus, crystals 700, 710, 720 of three one-dimensional functional colloidal spheres, as shown in fig. 7A, are distributed in a sensor configuration 770 using holographic optical tweezers. Each chain of spheres 700, 710, 720 has a distinct spatial and distinguishable scatter signal.

Further, FIG. 7B shows four two-dimensional functionalized colloidal crystals 730, 740, 750, and 750, distributed in sensor configuration 780 using holographic optical tweezers, each domain having a characteristic spacing, as in 730, 750, and 760, or both having a characteristic row spacing and symmetry, as in 740.

Such as the three-dimensional domain shown in fig. 8, which scatters light more strongly than other lower-dimensional structures and provides a strong backscattering capability (e.g., 180 degrees of scattering). Strong backscattering is required in some optical detection schemes and can be emphasized by increasing the mismatch in dielectric constant between the colloidal particles and the surrounding liquid gel. High dielectric constant materials, such as titanium oxide, may be preferred for the particles in such cases. The use of high dielectric constant particles will greatly reduce the depth of penetration of the scattered wavelength through the crystal, so that two to three layers will be sufficient to achieve the necessary complete backscattering.

Monolayer molecular and thin three-dimensional sensors, in which a target stimulus can be allowed to easily enter the inside thereof and thus can exhibit a strong response to relatively few target stimuli, are superior to thick sensors. These increase the sensitivity of the gelled sensor crystal domain.

In this case, fig. 8 shows a unit cell of a three-dimensional face-centered cubic lattice of colloidal spheres. Such three-dimensional crystal structures have a characteristic diffraction pattern, the apex of which depends on the size of the space between the particles. Different crystal symmetries and lattice spaces result in different resolvable diffraction patterns.

Following this approach, as described above, several different domains sensitive to several different stimuli can be combined on a single sensor material (see fig. 6). This material can be viewed using a spectrophotometer, such as a hand-held fiber optic spectrophotometer (available from ocean optics). The diffraction pattern of each domain will be resolved because one or more distinct diffraction peaks can be recorded by the spectrophotometer.

Introduction of a stimulus into a domain causes its characteristic diffraction peak to change wavelength. This change in wavelength can be resolved by a spectrophotometer, and the spectrophotometer can also inform of the presence of the specific stimulus and its concentration. The use of gelled sensor arrays integrated into an optical detection system will be further described below (see FIG. 12).

In another embodiment of the invention, the domains of the distinctive sensor may also be superimposed on each other in a three-dimensional structure at the top (see fig. 9), if the properties of the domains of the sensor are designed to allow illumination light to pass through all the domains and scattered light to pass through the monitor.

As shown in fig. 9, three optically characteristic colloidal crystal domains are superimposed in a three-dimensional spatial structure (note that there is no actual space between the domains, and certain spatial intervals are shown in the figure for the understanding of the invention). In particular, domain 1000 is intended to reflect the wavelength of beam 1050, but may transmit the wavelengths of beams 1060 and 1070. Similarly, the domain 1010 reflects the wavelength of the beam 1060 and transmits the wavelength of the beam 1070. Finally, beam 1070 is reflected by domain 1020. Thus, if the lattice constant of any one of the domains 1000, 1010 or 1020 is changed, the change in the diffraction pattern of this domain, and even the other two domains, will be clearly visible.

Superimposing the detection domains in this way will counteract the advantage of increased sensitivity and allow the reaction time to be determined by a thin sensor. In some applications, however, the superposition of the resulting system may provide other additional advantages.

For example, a sensor consists of a functionalized particle superimposed on the same domain of other non-functionalized particles on the surface (see FIG. 10A). As shown in fig. 10A, two colloidal particle crystal domains 1100 and 1110, both designed to reflect the wavelength of light beam 1150, but may transmit the wavelength of other light beams, such as light beam 1160. The only difference is that domain 1110 is functionalized to swell in response to stimulus 1190, but domain 1100 is not. Thus, in the absence of a stimulus, both layers of domains may scatter light, but when a stimulus is present, the upper layer of functionalized domains will be reflected, while the lower unfunctionalized domains will not. Further, one-dimensional chains of unfunctionalized particles will be used between the functionalized domains to monitor cross-interference of the internal domains.

FIG. 10B shows a response to stimulus 1190. The functionalized domain 1110 swells in response to a stimulus. As a result, the lattice constant of domain 1110 will change such that the wavelength of beam 1160 cannot be transmitted, but is reflected. The reflected light will pass through the domains 1100 whose lattice is not functionalized, and therefore the diffraction pattern of the domains 1100 will undergo a slight change for the stimulus 1190. Any passively induced change in the lattice constant of domains 1100 and 1110 will be apparent as a general model transformation at the scattering wavelengths of beams 1150 and 1160. The concentration of the stimulus will emerge from the differential shift of the diffraction peak.

Thus, as in the case of FIG. 10B, the response to the stimulus can be measured when the individual diffraction peaks are broadened or even bisected by a measurable amount. Such differential measurements will be used to compensate for deviations in lattice constant due to unusual changes in the environment, such as changes in temperature or humidity, and in other embodiments of the invention, stacking different functionalization products in the same domain will be used to resolve closely similar stimuli, one will have a stronger effect on the upper domain and the other will have a stronger effect on the lower domain.

In other embodiments of the invention, many of the same advantages are achieved by arranging the unfunctionalized or differentially functionalized domains in two or even three dimensions. The ultimate limitation to this would be a graded crystal sensor with a functionalization process and lattice constant that varies continuously through its length, range, or volume.

The sensor array detects environmental stimuli directly through the influence of the stimuli on the ligands attached to the particles. In other embodiments of the invention, the sensor array may also be used as a dual or multiple detection technique.

For example, in FIG. 11A, a gelled sensor array 1100 has a stimulus 1110 attached to it, but this is not immediately apparent in the lattice constant D of the array. Thus, another chemical or physical treatment, indicated at 1120 in FIG. 11B, transfers the stimulus to a new entity 1130, as shown in FIG. 11C, and this process affects the lattice constant of the array so that it is detectable. A transformation introduced by 1120, which transformation may comprise attaching an antibody to a previous protein stimulus; the selectivity is to use chemical oxidation or reduce the attached irritants; or an optical derivation transformation in which entity 1130 will be understood to appear as a reaction of the beam on the attached target 1110. Other possible transformations of the attached stimulus may also include thermal processes.

The present invention provides several advantages over conventional detection methods for detecting materials in mixed samples of proteins, carbohydrates and other related organisms. These advantages include the detection of each target molecule with a substituted adsorption site on the colloidal particles that are easily prepared. The substitution of these adsorption sites can be selected to optimize sensitivity and recognition for the same target without regard to the conditions that optimize the system for none of the types of adsorbed molecules. The resulting sensor array 1140 (FIG. 11C) can be exposed to the unknown sample in a number of ways, including immersion and surface contact with a solid sample. Thus, array 1140 can be rinsed and chemically activated to detect the presence of only the attached molecules, but not to an equivalent thereof. For example, detecting the presence of adsorbed proteins can be accomplished by exposing the array to a solution of biochemical enzymes or ATP. Any domain attached to the target protein will swell because the attached protein will undergo a metabolic change and their presence can be detected by a change in the diffraction wavelength in their crystal domain.

Thus, the position, size and spherical shell of the particles, as well as their spacing and symmetry, plus their chemical functionalization, will affect their response to the target stimulus.

Therefore, the colloidal sensor array as described above should have applications as gene chip, protein chip, carbohydrate chip, and the ability to rapidly detect and resolve a large number of similar molecules. In the detection of food, pharmaceuticals, cosmetics and other goods, there is an application for detection, and pathogens easily enter the goods, and a detection method which can be used frequently and is very economical is required. The gelled sensor will be dipped with a sample of the product and can be tested for characteristics such as heavy metal contamination, salt concentration and PH. In turn, it can be selectively tested using multi-step assays to find pathogens or metabolites of pathogens. More general multi-step detection methods can be applied to other applications using the same principles.

The gelled sensor array can be placed at the end of an optical fiber and used with the optical readout of a fiber spectrometer to form the entire all-optical sensor 1290, as shown in fig. 12. The colloidal sensor array can monitor diffraction peaks of the domain features. For example, two-layer domains produce diffraction signals from colloidal spheres that are easily measured. Thus, several hundred characteristic domains can be integrated into an optical detection system as shown in FIG. 12.

As shown in fig. 2, white light 1200 emitted from a light source 1280 is projected into a multimode optical fiber 1220 by the projection optical system 1210. Optical fiber 1220 shapes white light 1200 into a beam shape and then emits through optics 1230 onto the back of colloidal sensor array 1240. The colloidal sensor 1240 scatters light in various directions. Only a limited amount of light is collected by the beam shaping optics 1230 and returned to the optical fiber 1260. Each sensor field in array 1240 is designated to diffract only specific wavelengths at specific angles and these returned light 1250 will include only these specific wavelengths. This light is conducted through an optical fiber or bundle of light to a spectrometer 1270 which has the ability to resolve the wavelengths of these diffracted light and report the results to the end user, or to an automated readout system. The overall system 1290 is comprised of a light source 1280, projection optics 1210, collection optics 1230, and a spectrometer 1270, which make up an integrated all-optical sensor system 1290.

The spectrometer 1270 may be selected from a hand-held fiber spectrometer for package portability. Analysis of diffraction patterns for different individual wavelengths therefore requires minimal computational support for the variety of exposure to environmental stimuli and can be handled by a simple implanted processor or interfaced to a manually operated computing device. In this case, the entire system 1290 can be integrated into a handheld, broad-spectrum sensor system. Such a sensor system can be easily integrated into a more general portable information processing system. Such information handling systems include handheld computing capabilities, wireless communication and global positioning reception capabilities. The integrated optical detection system described herein can be easily integrated into such a system. The integrated system may report its location and detection status to a central data analysis station.

Many probes currently cannot detect a wide range of environmental threats and report their detection results, and location enables natural quantitative assessment, detecting the extent and time of anomalies. Thus, each portable sensor system interacts with other devices to a certain extent to provide a panoramic view of the environmental conditions and their value in the assessment of time. FIG. 13 provides a simplified illustration of interoperation in the field, wherein the multiplicity of reporting unit devices in the field provides a quantitative distribution map over the breadth of the context of environmental contaminants. These will have wide application in war command and control of industrial environmental detection methods and pollution detection and remediation.

The colloid sensor 1240, because of its high degree of customization, can have many applications. For example, sensor crystals may be filled with food, pharmaceuticals and other products, and their byproducts of spoilage and adulteration detected during shipping. The gelled sensor array recognizes the product and detects its by-products, etc., and thus can detect the change in the possibility during transportation of the sample through the scanning system at a later time. Therefore, reading of the gelled sensor array does not necessarily require reading of the reaction at a uniform time of detection.

The use as described above can be extended to the protection of consumer products and to the detection of long term storage stability.

A single gelled sensor can simultaneously monitor a range of stimuli, from airborne chemicals and biologies to doses of ionizing radiation.

The sensor element can be used arbitrarily and can be easily replaced when contaminated or when a different test is selected.

The reader may be provided as a handheld device under appropriate economic conditions and may be constructed to transmit data to a critical location over an unlimited connection. Such a device can present a continuous and even analysis to all operators of all trials.

Optical signals in devices are not susceptible to contaminants and interferents by their natural nature. Such equipment is well suited for hazardous environments and can be deployed or operated remotely by throwing out the aircraft.

In another embodiment of the invention, the gelled sensor may be provided as a bundle or "brush" 1300 (see FIG. 14), and the operator may detect a large field area by sweeping the bundle or brush 1300 across the target field. The brush arrangement provides communication between the sensor element and the target in situ, since no sample is transferred to the chip.

Each fiber 1320 in the brush 1300 is a sensor element that can be swept across a surface or in air and flowing water. The fibers or bristles of the brush are free and flexible. With the brush method, the sensor is not confined to the surface and it can be inserted into cracks and placed normally where it is difficult to read.

Further, instead of using a gelled sensor array, beads 1340 (shown in FIG. 14), which can respond to a specific target stimulus, can be treated or placed at the end of each of the fibers 1320 of the brush 1300 to provide a response to the target stimulus.

A sleeve 1310 may be disposed around the brush 1300 such that the sleeve 1310 provides sufficient stiffness to insert the sensor into a soft, filled material. The sleeve can be made of any material, and is made of plastic, metal and the like, so that sufficient rigidity can be provided. Once the sensors are inserted into the material, the cartridge can be removed so that the gelled sensor array can sense the material, react to the stimulus, and the reaction can be read.

The response of the different sensors to different stimuli may be reflected by different fibers or bristles 1320 of the brush 1300 (e.g., testing on separate fibers).

Further, measurements of the same target stimulus can be distributed over the bristles at different sensitivity levels for semi-quantification and cross-quantification, and provide a statistical basis and greatly reduce active and passive error messages.

Further, a hardened see-through metal or nylon screen 1350, or other suitable material, may be provided at the end of each fiber 3120 in the brush 1300 (e.g., a sensor pad), so that the gel of the sensor array 1330 is not enlarged during use (see fig. 14).

The operational group may sweep the specified contamination field with a brush. The results can be reported on-the-fly or read later and then associated with the field to create a pattern and intensity analysis.

In another embodiment of the invention, the groups attached to the colloidal ions may be reactive to a selected stimulus, for example, the exothermic reaction that occurs may be measured by various methods. Other biological, chemical or radiological changes in the gel can be detected to ascertain the presence of the target stimulus. It is noted that the gel must be permeable to the stimulus to be detected.

In another embodiment of the invention, the sensor crystals are clustered by holographic optical tweezers, particles or spheres are embedded in a gel and closely associated with each other, the spheres can be exposed to a stimulus, such as an antigen, or a DNA chain, or a carbohydrate, etc., after which specific antibodies can be attached to the spheres, in particular, different spheres of different sizes can be used to react to many different antibodies.

Thus, the spheres are selectively attached to specific spheres and can bridge small gaps between the spheres. Thus, spheres are linked together, but domains without attached antibodies are not linked.

If temperature or other chemical reactions do not occur, the gel in the antibody-attached domain will swell, but the sphere will not swell in the antibody-unattached domain. Similarly, when the temperature changes, for example, the gel expands, separation occurs between the spheres and the diffracted wavelength will become red. Thus, this change in color can be measured by a spectrometer.

In another embodiment of the invention, as one of ordinary skill in the art would appreciate, the invention may be used for the hybridization of nucleic acids. In more detail, the binding agent may be used to link two objects together through a whole, for example using a hybrid DNA array, leptin, carbohydrate or biotin, etc. In nucleic acid hybridization, the nucleic acid will contain a specific code that will search for a specific sequence. Thus, the mat can be wrapped with a probe having a sequence wrapped with one or more nucleic acids and a gene sequence comprising at least one domain directed to a particular nucleic acid.

In addition, the material can be used to treat the target so that it more easily enters the detector and reacts on the pad. For example, nucleic acid hybridization can be combined with restriction enzymes in a gel to fragment the target DNA into pieces that can more easily enter the pad. Further, other substances may be bound to the gel to facilitate the reaction, such as crystals.

It should be emphasized that the above-described embodiments are merely possible examples of implementations of the invention, so that the invention may be better understood. Various modifications and changes may be made without departing from the principles and spirit of the invention. All such modifications are intended to be included within the scope of this invention and the following claims.

Claims (78)

1. A sensor, comprising:

a plurality of colloidal particles having a specific chemoreceptor adsorbed onto said particles, and such particles being functionalized to react with a target stimulus;

the particles are integrated in an array.

2. The sensor of claim 1, wherein each particle is a spacer.

3. The sensor of claim 1, wherein each of said particles is comprised of silicon, polystyrene, and titanium oxide.

4. The sensor of claim 1, wherein each of said particles does not respond specifically or non-specifically to said target stimulus.

5. The sensor of claim 1, wherein each of said chemoreceptors is specifically reactive with each of said target stimuli.

6. The sensor of claim 1, wherein different species of the particles are formed by attaching different chemical receptors to the surface of the particles.

7. The sensor of claim 1, further comprising a gel, wherein the particles are embedded in the gel.

8. The sensor of claim 7, further comprising a medium in which said gel-implanted particles are disposed.

9. The sensor of claim 8, wherein the response of the particles to the target stimulus includes a change in local ionic strength, a change in temperature, a change in chemical composition, and a change in PH of the gel and the medium.

10. The sensor of claim 7, wherein the gel causes the functionalized particles to change the spacing between particles as a result of the target stimulus.

11. The sensor of claim 10, wherein the lattice constant of the array changes in response to a target stimulus.

12. The sensor of claim 10, wherein the response to the target stimulus is a color change response.

13. The sensor of claim 11, wherein the change in the lattice constant is measured with a spectrometer.

14. The sensor of claim 13, wherein the spectrometer is configured to measure the wavelength of backscattered light generated by illuminating the array with white light.

15. The sensor of claim 1, the array being on at least one layer.

16. The sensor of claim 8, wherein the particles are made of a material having a dielectric constant that is different from at least one of the dielectric and the gel.

17. The sensor of claim 7, wherein the gel is a hydrogel.

18. The sensor of claim 1, wherein the diffraction pattern of the array changes in response to a target stimulus.

19. The sensor of claim 1, further comprising a gel, said particles being embedded in said gel, said gel being formed around said array by one of photopolymerization, chemically-induced polymerization, and thermally-induced polymerization.

20. The sensor of claim 1, wherein the particles are polymerized into the array using holographic optical tweezers.

21. The sensor of claim 20, wherein the particles are aggregated to form a multi-dimensional array.

22. The sensor of claim 20, wherein the holographic optical tweezer comprises: a laser source that emits a laser beam; a diffractive optical element that diffracts the laser beam; an objective lens focused on the laser beam; a flowing chamber illuminated with a light beam, in which chamber each particle can be optically trapped.

23. The sensor of claim 22, further comprising a camera for viewing said optical capture.

24. The sensor of claim 6, wherein different particles from said different species can be organized to form separate domains that can be distinguished by their chemical function and optical properties.

25. The sensor of claim 24, wherein said domains are arranged in close proximity as an assembly using holographic optical tweezers.

26. The sensor of claim 25, wherein the modules can be grouped into an integrated sensor array.

27. The sensor of claim 1, wherein the sensor is comprised of distinct one-dimensional chains of particles and distinct two-dimensional domains of particles in a monolayer.

28. The sensor as claimed in claim 27 wherein each of the chains and domains diffracts different light into a particular direction.

29. The sensor of claim 27, further comprising non-functionalized one-dimensional chains and disposed between functionalized domains of the particles to monitor interaction within the domains.

30. The sensor of claim 27, wherein said array is a multi-dimensional array comprising a two-dimensional array and a three-dimensional array, wherein said one-dimensional chain, said two-dimensional domain, and said three-dimensional array are distributed such that said instances have different spatial and different diffraction signals.

31. The sensor of claim 26, wherein the integrated sensor array comprises different domains having sensitivity to different target stimuli.

32. The sensor of claim 30, wherein each of said responses to a target stimulus comprises a change in the wavelength of a characteristic diffraction peak of said different domains.

33. The sensor of claim 32, wherein a spectrometer is used to detect the change in the wavelength.

34. The sensor of claim 25, wherein the domains are superimposed on each other in three-dimensional space.

35. The sensor of claim 34, wherein the domains are stacked in a staggered manner.

36. A sensor as claimed in claim 34 wherein the illumination light passes through the associated superimposed fields and the diffracted light passes through the detector.

37. The sensor as claimed in claim 34 wherein each of said superposed domains reflects a specific wavelength and transmits a specific wavelength.

38. The sensor of claim 34, wherein the surface of one domain comprises functionalized particles and the surface of the other domain comprises unfunctionalized particles.

39. The sensor of claim 11, wherein the array uses a multiplex detection method.

40. The sensor of claim 39, wherein the multi-step method, the array is linked with a target stimulus that has no effect on the array lattice constant, and then the target stimulus is transferred to a new entity in the array with a subsequent step, the entity affecting the lattice constant of the array.

41. The sensor of claim 40, wherein the method comprises: antibodies are attached to the previously attached target stimuli, optionally with chemical oxides and reduction of the previously attached target stimuli, image-derived transformations and thermal methods.

42. The sensor of claim 1, wherein the target stimulus is one of a nucleic acid, a protein, a carbohydrate, and a liquid.

43. The sensor of claim 1, wherein each of said arrays is at the active end of a plurality of flexible optical fibers.

44. The sensor of claim 43, further comprising a ferrule and said optical fiber is encased therein.

45. The sensor of claim 44, wherein the sleeve is retractable.

46. The sensor of claim 43, wherein each of said fiber end arrays is responsive to a different target stimulus.

47. The sensor of claim 43, wherein each of said fiber end arrays exhibits a different degree of sensitivity in response to the same target stimulus.

48. The sensor of claim 43, further comprising a screen positioned at an end of said optical fiber to protect said array.

49. The sensor of claim 1, wherein the target stimulus causes sphere-specific functionalization to interconnect.

50. A sensor according to claim 49 wherein the target stimulus is an antigen and the antibody-adsorbed particles will react with it in such a way that the diffraction signal is detected by the spectrometer.

51. The sensor as claimed in claim 43, wherein at least one of a plurality of products can be filled into said array to detect spoiled by-products and counterfeit goods.

52. The sensor of claim 49, wherein the response to the target stimulus is a chemical, biological, or radiological change.

53. A sensor as claimed in claim 2, wherein each array is located at a movable end of a plurality of flexible optical fibres.

54. An apparatus for detecting a target stimulus, comprising:

a plurality of flexible optical fibers comprising a gelled sensor array comprising a plurality of functionalized colloidal particles for reacting with a target stimulus, said array being located at a movable end of each of said optical fibers.

55. The apparatus of claim 54, further comprising a ferrule in which said optical fiber is located.

56. The apparatus of claim 55, wherein the cannula is retractable.

57. The apparatus of claim 54, wherein each of said arrays of fiber ends is responsive to a different stimulus

58. The apparatus of claim 54, wherein each of said arrays of fiber ends exhibits a different sensitivity level in response to the same target stimulus.

59. The apparatus of claim 54, further comprising a screen positioned at an end of said optical fiber to include said array.

60. An apparatus for detecting a target stimulus, comprising

A plurality of flexible optical fibers having an array of functionalized spacers, each disposed on a movable end of an optical fiber, are responsive to a target stimulus.

61. The apparatus of claim 60, further comprising a sleeve in which said optical fiber is located.

62. The apparatus of claim 60, further comprising a screen positioned at an end of each of said optical fibers to protect said array.

63. An optical detection system comprising:

a light source emitting a laser beam; a projection optics system that focuses the laser on a sensor array having a plurality of functionalized colloidal particles thereon that are reflective of a target stimulus; an analytical collection optics for collecting and transmitting light scattered by the sensor array; a spectrometer is used to detect changes in the sensor that occur due to the presence of the target stimulus.

64. The system of claim 63, wherein the optical detection system is portable.

65. The system of claim 63, which can simultaneously detect airborne chemical and biological agents and ionizing radiation.

66. The system of claim 66, wherein the detection of the change in the diffraction signal is performed either instantaneously or delayed.

67. A method of focusing a device for detecting a target stimulus, comprising: an array is placed at the end of each of a plurality of mobile flexible optical fibers, the array comprising a plurality of colloidal particles, each particle having a specific chemoreceptor adsorbed onto the particle, the examples being functionalized to respond to a target stimulus.

68. The method of claim 67, further comprising gathering the optical fibers together to form a brush shape.

69. The method of claim 67, further comprising positioning a sleeve over the brush.

70. The method of claim 67, further comprising positioning a monitor screen over said array.

71. A method of detecting a response to a target stimulus, comprising: providing a plurality of colloidal particles, each colloidal particle comprising a specific chemical receptor attached to said particle, the particles being functionalized to react with the stimuli; the particles are collected on an array, and a target stimulus is introduced onto the particles of the array.

72. The method of claim 71, wherein said aggregating step comprises forming a multi-dimensional array.

73. The method of claim 77, further comprising: applying a method to the array after introduction of the target stimulus to transfer the target stimulus to a new entity; measuring a change in the lattice constant of the array.

74. The method of claim 71, wherein the aggregating step comprises forming different domains and superimposing the domains.

75. The method of claim 71, further comprising: an antigen is introduced into the array and changes in the lattice constant of the array are measured.

76. The apparatus of claim 53, further comprising means for protecting said optical fiber.

77. The apparatus of claim 53, further comprising means for including said array.

78. The sensor of claim 43, further comprising means for protecting the array and optical fiber.