HK1081650A - Holographic sensor based on a volume hologram in a porous medium - Google Patents

Description

Holographic sensor based on volume hologram in porous medium

Technical Field

The invention relates to a sensor based on a hologram sensitive element.

Background

WO-A-9526499 discloses A holographic sensor based on volume holography. The sensor comprises an analyte-sensitive matrix having an optical transducing structure disposed throughout its volume. Due to the physical arrangement of such transducing structures, the optical signal generated by the sensor is very sensitive to volume changes or structural rearrangements in the analyte sensitive matrix due to interaction or reaction with the analyte.

An alternative method for producing A holographic sensor is disclosed in WO-A-9963408. A sequential processing technique is used in which a polymer film is first prepared, followed by the addition of photosensitive silver halide particles. These particles are introduced by dispersing soluble salts into a polymer matrix where they react to form an insoluble photosensitive deposit. The holographic pattern is then recorded.

Disclosure of Invention

One aspect of the invention is a sensor for detecting an analyte that includes a holographic element. The element comprises a hologram disposed throughout the volume of a support medium, wherein the optical properties of the hologram vary with changes in physical properties occurring throughout the volume of the medium. The medium may be obtained by in situ formation, preferably by polymerization of the monomers in the presence of a porogen. Although the reagent is present and active in the polymerization reaction, such reagent is not present in the sensor and/or does not react with the analyte or sensor. The reagent may be a gas, liquid or solid; the solid can be pulled out to create the pores.

The formation of additional and/or larger pores in the matrix may allow greater diffusion of the analyte throughout the support medium, thereby making the sensor more sensitive to analyte concentration changes.

Detailed Description

Holographic sensors typically include a holographic support medium and a hologram disposed throughout the volume of the medium. The carrier medium interacts with the analyte resulting in a change in the physical properties of the medium. This change causes a change in an optical characteristic of the holographic element, such as its polarization, reflectivity, refractive index or absorbance. If a change occurs while the hologram is being replayed by incident broad band, non-ionising electromagnetic radiation, a colour or intensity change is observed.

There are a number of basic methods of changing physical properties and thus optical properties. The physical property that can be changed is preferably the size of the holographic element. This may be achieved by introducing specific groups into the support matrix, wherein these groups undergo a conformational change upon interaction with the analyte and cause the support medium to expand or contract. Such groups are preferably specific binding conjugates of the analyte species. Other methods may be to vary the active water content of the carrier medium.

By simply changing the composition of the support medium, the holographic sensor can be used to detect a variety of different analytes. The medium preferably comprises a polymer matrix, but its composition must be optimized to obtain a high quality film, i.e. a film having a uniform matrix in which holographic fringes can be formed. The matrix is preferably formed by copolymerization of (meth) acrylamide and/or (meth) acrylate derived monomers and may be crosslinked. In particular, the monomer HEMA (hydroxyethyl methacrylate) is readily polymerizable and crosslinkable. Polyhema is a versatile carrier material due to its swellability, hydrophilicity and broad biocompatibility.

Other examples of holographic support media are gelatin, K-carageenan, agar, agarose, polyvinyl alcohol (PVA), sol-gels (general classification), hydrogels (general classification) and acrylates. Other materials are polysaccharides, proteins and protein-containing materials, oligonucleotides, RNA, DNA, cellulose acetate, silicones, polyamides, polyimides and polyacrylamides. Gelatin is a standard matrix material for supporting photosensitive species such as silver halide particles. Gelatin can also be photo-crosslinked between carboxyl groups on the gel bundle by chromium III ions.

When the analyte is relatively large relative to the pore size of the polymer matrix and/or the polymer has little or no associated porosity, the analyte is inhibited from diffusing into and throughout the matrix. Thus, the sensor response to changes in analyte concentration becomes slower.

The sensor of the invention comprises a holographic support medium which can be formed by polymerisation of a monomer or co-monomer in the presence of an agent capable of producing a porous polymeric matrix. The agent may be optimally selected in order to produce pores of a particular size. This is important when the steric hindrance of the analyte is bulky, for example large biomolecules such as hemoglobin.

The pore former or porogen may be a liquid, gas or solid, such as particles of bicarbonate, carbonate or PVC. When solid particles are used, they are preferably insoluble in the polymerization mixture so that they remain in the matrix after polymerization and can subsequently be removed therefrom by reaction (e.g. acid), dissolution or washing. When the reagents are gases, they may be bubbled through the polymerization reaction mixture.

One example of a pore former is water. By introducing water into the monomer mixture, such as HEMA monomer, small voids can be created during the polymerization reaction, resulting in a more porous polymer matrix.

For example, the agent may be a non-solvent for the polymer. Another example is a salt, which can be present in high concentrations during the polymerization. Metal alginate may be used which can be removed by washing with EDTA/acid (to remove the metal) and then dissolved. Proteins or liquids can be removed by enzymatic means. The agent may also be removed by physical means, such as laser irradiation or ablation. With a local temperature difference, the UV absorber can be locally heated to cause pore formation.

The reagent may be a gas capable of being generated in situ. Electrolysis or physical migration may simulate the formation of a gas in a suitable system. If the matrix incorporates a solvent saturated with gas, removal of the solvent will generate bubbles. Bubble formation can be stabilized by surfactants such as Pluronic.

The following examples illustrate the invention.

Example 1

The polymer matrix was formed by polymerization of HEMA monomer in water and 4% methanol (w/v). As a reference, another polymer was made by polymerization of HEMA monomer in isopropanol. Once formed, each polymer was soaked in 50mg/ml hemoglobin for 2 hours and the respective absorption spectra were measured, as shown in FIG. 1. The absorption spectrum of the 0.25mg/ml hemoglobin reference is also given for comparison.

The presence of water in the polymerization mixture results in a more porous polymer matrix. As can be seen from the absorption spectrum, the increased porosity of the matrix allows for better diffusion of the relatively larger hemoglobin molecules, resulting in an absorption that is more correlated with the absorption of the hemoglobin solution.

Example 2

A pair of holographic polymer matrices were prepared, each having a monomer composition of 70% HEMA, 20% ethylene glycol dimethacrylate (EDMA) and 10% methacrylic acid (MAA). One of the polymers is prepared by polymerization of the monomers in propanol; the other was prepared in water and 8% methanol (w/v). A holographic recording material is then provided on each support and a hologram is recorded.

The developed hologram was immersed in the analyte sample. The response time for increasing analyte concentration is shown in figure 2. The presence of water in the polymerization reaction mixture creates a microporous polymer structure, resulting in a more sensitive holographic sensor.

Claims (9)

1. A sensor for detecting an analyte comprising a holographic element, said element comprising a medium and a hologram disposed throughout the volume of the medium, wherein the optical properties of said hologram change as a function of a physical property change that occurs throughout the volume of the medium, wherein said medium is formable in situ in the presence of a pore-forming agent, wherein said agent is not present in said sensor or is not reactive with the analyte and the sensor.

2. The sensor of claim 1, wherein the physical property is a size of the medium.

3. The sensor of claim 1 or 2, wherein the optical property is the reflectance, refractive index or absorbance of the holographic element.

4. The sensor of any preceding claim, wherein the reagent is a gas.

5. The sensor of any one of claims 1-3, wherein the reagent is a liquid.

6. The sensor of any preceding claim, wherein the reagent is water.

7. The sensor of any one of claims 1-3, wherein the reagent is a solid that is obtainable by extruding the reagent after formation.

8. The sensor of any preceding claim, wherein the medium is a polymer obtainable by in situ monomer polymerisation.

9. The sensor of claim 8, wherein the monomer comprises hydroxyethyl methacrylate.