WO2018107127A1

WO2018107127A1 - An etalon or interferometer based sensor assembly

Info

Publication number: WO2018107127A1
Application number: PCT/US2017/065473
Authority: WO
Inventors: Michael Serpe
Original assignee: The Governors Of The University Of Alberta
Priority date: 2016-12-09
Filing date: 2017-12-08
Publication date: 2018-06-14

Abstract

An etalon or interferometer based sensor assembly is provided that includes a monolithic polymeric gel layer. A metal-containing overlayer is formed over a top surface of the polymeric gel layer. A metal-containing base layer supports a bottom surface of the polymeric gel layer. The base layer in turn supported by a substrate. An enclosure about a perimeter of the aforementioned components of the sensor assembly functions to limit diffusion to through the overlayer. The gel layer having a thickness that induces a color change in the sensor as the thickness changes. A process of preparing such a etalon or interferometer based sensor assembly is also provided.

Description

AN ETALON OR INTERFEROMETER BASED SENSOR ASSEMBLY

RELATED APPLICATIONS

[0001] This application claims priority benefit of United States Provisional Application Serial Number 62/432,286 filed 9 December 2016; the contents of which are hereby incorporated by reference.

TECHNICAL FIELD

[0002] The present invention generally relates to the substance sensing, and more specifically to an etalon or interferometer based sensor assembly.

BACKGROUND

[0003] Interferometry is a technique in which waves, usually electromagnetic, are superimposed in order to extract information. Interferometers are widely used in science and industry for the measurement of small displacements, refractive index changes and surface irregularities. In analytical science, interferometers are used in continuous wave Fourier transform spectroscopy to analyze light containing features of absorption or emission associated with a substance or mixture. A form of interferometer is an etalon which is typically made of a transparent plate with two reflecting surfaces. The complexity and associated cost of formation of etalons has preclude the use of such devices in a variety of applications.

[0004] While there have been many advances in sensor technologies there continues to be a need for improved sensors with increased sensitivity and improved accuracy that are less costly and easy to produce. SUMMARY OF THE INVENTION

[0005] An etalon or interferometer based sensor assembly is provided that includes a monolithic polymeric gel layer. A metal-containing overlayer is formed over a top surface of the polymeric gel layer. A metal-containing base layer supports a bottom surface of the polymeric gel layer. The base layer is in turn supported by a substrate. An enclosure or the overlayer extends about a perimeter of the polymeric gel layer to limit diffusion into the polymeric gel layer to be predominantly through the overlayer. The gel layer having a thickness that induces a color change in the sensor as the thickness changes.

[0006] A process of preparing such an etalon or interferometer based sensor assembly is also provided.

BRIEF DESCRIPTION OF THE DRAWINGS

[0007] The present invention is further detailed with respect to the following drawings that are intended to show certain aspects of the present of invention, but should not be construed as limit on the practice of the invention, wherein:

[0008] FIG. 1 is a cross-sectional view of a sensor assembly in accordance with embodiments of the invention; and

[0009] FIG. 2 is a cross-sectional view of a sensor assembly of FIG. 1 showing the effects of surface blocking for biosensing in accordance with embodiments of the invention.

DETAILED DESCRIPTION OF THE INVENTION

[0010] The present invention has utility as a sensor for detecting biological agents, environmental contaminants, and other target substances able to induce a change in thickness in the polymeric gel layer that is discemable through optical interference. Embodiments of an inventive sensor assembly are formed by sandwiching a polymeric gel layer between comparatively thin layers denoted as a base layer and an overlayer. In some inventive embodiments, these metal-containing layers have nanometer scale thicknesses to form the sensor assembly. In some inventive embodiments, these metal-containing layers allow for partial light transmission either through forming the layers with a controlled thickness. The bottom metal-containing layer rests on a support, illustratively including glass, or an optically transparent planar polymer such as polycarbonate. The metal-containing overlayer lies directly on the polymeric gel layer. When the sandwich structure is immersed in water, or an aqueous solution, the polymeric gel layer swells, and increases the distance between the two outer metal layers thereby yielding a color change. The color of the device depends on lateral separation of the metal-containing sandwiching layers. The separation distance can be influenced by exposing the assembly to a salt solution containing a salt, such as NaCl. The salt is able to penetrate into the polymeric gel layer and change the polymeric gel layer thickness via osmolality changes in the polymeric gel layer, which in turn changes the separation distance and hence the color correlates with the swell of the assembly by a substance to be sensed. The color of the device may be quantified and calibrated by determining the intensity of certain wavelengths of light before exposure to a stimulant to establish a baseline and then after exposure of the device to achieve an effect of functioning as a measuring device or sensor. The ability to detect and measure the presence of biological agents, environmental contaminants, and other targeted substances with an inventive sensor assembly is related to the amount of salt absorbed by the polymeric gel layer in the metal sandwich structure. If an interferent substance is present on the outer layer of the metal- containing overlayer, the substance prevents the salt from penetrating the polymeric gel layer, and the response to salt will be diminished relative to the sensor assembly absent an interferent attached to the top of the metal-containing overlayer on the polymer. For example, if bacteria are present in a water sample, the binding of the bacteria or other interferent to the metal layer, as might be facilitated by bacteria specific interactions with molecular-scale receptors that are attach to the metal layer, will block the salt from entering the polymeric gel layer and therefore the device will have a response to salt that is much less than the device with no bacteria on the surface (and hence no bacteria in the water). Therefore, by quantifying the extent of the response of the device to salt, a determination may be made of how much bacteria is bound to the surface that in turn correlates to detect multiple species of interest in a matter of minutes so as to achieve ease of use and low the amount of bacteria in a sample. This approach may be used to detect a variety of biologies that illustratively include pathogens, viruses, cells, solutes, nanoparticles, colloids, macromolecules and combinations thereof. In some inventive embodiments, a single device is that modified to cost. Non- limiting examples of applications for an inventive sensor illustratively include pathogen species such as E.coli, botulinum toxin, erythrogenic toxins; water quality and food safety monitoring, blood-alcohol levels, medical testing to pathogens, and countless other applications where pathogens, viruses, cancer cells are required to be detected.

[0011] It is to be understood that in instances where a range of values are provided that the range is intended to encompass not only the end point values of the range but also intermediate values of the range as explicitly being included within the range and varying by the last significant figure of the range. By way of example, a recited range of from 1 to 4 is intended to include 1-2, 1-3, 2-4, 3-4, and 1-4.

[0012] In a specific inventive embodiment of the etalon or interferometer sensor assembly, the side edges of the polymeric gel layer perimeter are enclosed either by the overlayer or a separate enclosure formed of like materials relative to the overlayer so as to limit fluid diffusion into the polymeric gel layer as coming only through the metal-containing overlayer, or enclosure.. By adding a capturing agent (e.g., an antibody), this diffusion may be slowed or prevented by the biomolecule binding to the capturing agent. [0013] Embodiments of the polymeric gel layer are formed as a colloidal polymer in solution with at least a monomer having at least one nitrogen, fluorine, chlorine, or phosphorus atom per monomer unit. The nitrogen, fluorine, chlorine, or phosphorus in the monomer assists in binding the polymeric gel layer to the metal layers. The polymer used for the polymeric gel layer may be any hydrogel or organogel (crosslinked polymer network that can be swollen with an organic solvent), but for the polymer to be color tunable, the polymer must be responsive to a stimulus. In some inventive embodiments, the polymer includes hydrophilic groups. Hydrophilic groups operative herein illustratively include acrylamides, acrylates, silicones, ethylene oxides, ethylene glycols, polyamines, polyethers, and combinations thereof.

[0014] A monomer with the at least one nitrogen, fluorine, chlorine, or phosphorus per monomer unit may be the main monomer in a co-polymer. A co-polymer can be formed from one or more co-monomers in addition to the monomer. The monomers in a co-polymer may be individually non-responsive to a stimulus, or one or more of the co-monomers may be responsive to one or more stimuli. Different monomers in the co-polymer may be responsive to different stimuli.

[0015] Any cross-linker suitable for the polymer forming the polymeric gel layer may also be used for cross-linking monomers in the gel. Examples include N, N- methylenebisacrylamide (effectively two acrylamide monomers joined at the N's by a methylene group). In some embodiments, the cross-linker may be omitted if the monomer units sufficiently bond to each other. For example, linear (uncrosslinked) poly(Nisopropylacrylamide) (pNIPAm) may be deposited by spin or dip coating pNIPAm on a metal such as gold (Au), followed by Au or other metal deposition on top. Alternatively, NIP Am or other gel monomer may be spread on a gold or other metal surface and photopolymerized to make a polymeric gel layer, in this example a pNIPAm layer, onto which Au or other metal may be deposited. Photopolymerization allows the polymeric gel layer to be patterned, however, other patterning methods may also be used such as ink jet printing and mesh screen templating. Patterning may be useful in, for example, display devices.

[0016] The polymeric gel layer is formed of particles that are closely packed or squeezed together to form a monolithic gel. The gel assembly should be monolithic, that is, as close to planar as possible. To achieve a monolithic structure with gel particles, the gel particles need to be jammed or squeezed together, which means the center to center particle distance is closer than what would be expected from the gel particle diameter alone. By way of example, with 1 micron diameter particles closely packed but not jammed together on a surface, the center to center distance would be 1 micron, whereas an inventive monolithic layer of microgels have center to center distances less than 1 micron, and thus define polymer that is denoted herein as "jammed together" or synonymously as "squeezed together".

[0017] Embodiments of the polymeric gel layer may be formed of colloidal particles having an effective diameter of between 0.05 micron and 250 microns (a microgel falls within this size range), but smaller or larger particles are also be suitable. While monolithic gels in the examples have included the range of between 0.229 micron to 1.5 microns, it is appreciated that the inventive device and process of detection therewith is not particularly sensitive to gel particle size and may use a wider range of gel particle sizes of between 0.05 micron and 250 microns and even beyond this range by an addition 20 diameter percent as measured in an unsqueezed state.

[0018] The polymers used in the polymeric gel layer may be formed of one or more stimulus responsive polymers selected from a group illustratively including thermoresponsive polymers, pH responsive polymers, electroresponsive polymers, magnetoresponsive polymers, ionic strength responsive polymers, and photoresponsive polymers. The stimulus responsive polymers may change volume in response to a stimulus. The stimulus may be for example temperature (thermoresponsive material), pH or ionic concentration (salt). The polymers may be responsive to more than one stimulus. Thus, for example a thermoresponsive polymer may also be hydroresponsive. Polymers in some inventive embodiments are rendered magnetosensitive by inclusion of magnetic materials.

[0019] The metal layers that sandwich polymeric gel layer are generally parallel with 20 degrees of angle of parallelism to one another and are reflective. The metal layers in some inventive embodiments are sufficiently thin to be partially transparent to an interrogating wavelength of light. The metal-containing layers may have a different refractive index from the polymeric gel layer. In this instance, the gel assembly forms an etalon (reflection from two surfaces of a single layer) or interferometer (reflection from two separate layers). The thickness of the polymeric gel layer and the relative refractive indices of the metal layers determine the color of the etalon. Each metal-containing layer may be formed of any metal illustratively including Fe, Ni, Ag, Au, Al, Ti, Cu, Cr, and alloys thereof, and interme tallies thereof, in which one of the aforementioned metals or combination thereof constitute the atomic percent majority of the alloy or interme tallic. It is appreciated that the metal layers need not be the same metal on either side of the gel, and each layer may independent of the other metal layer include more than one metal. In some inventive embodiments, one or both such layers are Cr/Au.

[0020] The metal layers may be formed as coatings on the polymeric gel layer. Illustrative methods that may be used to provide the metal layers on the polymeric gel layer may include, but are not limited to, physical vapor deposition (PVD), chemical vapor deposition (CVD), wet chemical methods, atomic layer deposition, thermal evaporation, electron beam evaporation, sputtering, electroless deposition, pulsed laser deposition, reduced temperature melting of a nanocrystal film, and direct transfer of a metal layer from another substrate. [0021] In a specific embodiment, by combining a stimulus responsive material with metal layers having a different refractive index from the polymeric gel layer, the gel assembly forms a tunable etalon or interferometer. When the wavelengths in which the gel assembly is operative are visible wavelengths then the gel assembly forms a color tunable etalon or interferometer. Advantages of the gel assembly and hydrogel etalon may include easy and simple fabrication, thermoresponsive, and functionalization to respond to various stimuli (other than temperature), for example biomolecules.

[0022] Referring now to the figures, FIG. 1 is a cross-sectional view of an embodiment of an etalon or interferometer based sensor assembly is provided generally at 10 with a metal- containing overlay er 12 formed over the microgel layer 14 that is formed on a metal- containing base layer 16. The base layerl6 is formed on a glass substrate 18. The layers (12, 14, 16) may be formed by sequential layer deposition. FIG. 2 is a cross-sectional view of the an etalon or interferometer based sensor assembly 10 of FIG. 1 showing the effects of surface blocking for biosensing. In a specific inventive embodiment, the overlay er 12 and the base layer 16 are formed from the materials and by techniques as detailed above.

[0023] A process for forming the inventive detection and sensing device with the gel layer in some inventive embodiments includes providing the colloidal polymer in solution, drying the solution to form the polymeric gel layer and forming metal layers on either side of the polymeric gel layer. In the gel assembly process, the polymeric gel layer may be spread under pressure across a surface before being dried. Various tools may be used for spreading illustratively including a roller, blade, or brush. This process has particular utility for hydrogel particles (e.g., microgels). Spreading occurs sufficiently rapidly and continuously to avoid different areas of the polymer drying at different times. EXAMPLES

[0024] The present invention is further described with respect to the following non- limiting examples. These examples are intended to illustrate specific formulations according to the present invention and should not be construed as a limitation as to the scope of the present invention.

Example 1

[0025] Based on the properties of the materials tested and gel assemblies made of other materials may be formed in like manner and yield like results. The examples provided here are predicted to work based on the similar properties of stimulus responsive materials to the tested materials. Additional materials used to form the gel layer may include: oligoethyleneglycol methacrylate - T and pH, O

2-dimethylaminoethyl methacrylate - T and pH, O

2-oxazoline-T, N and O

hydroxypropyl acrylate -T, O

2-2(methoxyethoxy)ethylmethacrylate-T, O

NIPAm-T-N

hydroxypropyl cellulose-T,0

vinylcaprolactone-T,0

(l-hydroxymethyl)propyl methacrylamide, T, N,0

Ν,Ν'-diethylacrylamide, Τ,Ν,Ο

hexafluorobutyl methacrylate, T, O, F

propylene oxide/glycol, T,0

2-(methacryloyloxy)ethyl phosphoryl choline-Ε,Τ,Ο,Ν,Ρ

Spiropyran, pH, L,N,0

azobenzene, L,N

spirooxazine, pH, L,N,0

naphthopyran, L, O

Cinnamate, L, O

ethyleneamine, pH, IS, N

4-vinylbenzoate, pH, IS, O

chitosan, pH, IS, Ο,Ν

acrylic acid, pH, IS, O

2-dimethyl aminoethyl methacrylate, pH, IS, N, O, L,N,0

diethyl aminoethyl methacrylate, pH, IS, N, O

propylacrylic acid, pH, IS, O

vinylpyridine, pH, IS, N

2-(diisopropylamino)ethylmethacrylate, pH, IS, N,0 methacrylic acid, H, IS, O

glutamic acid, pH, IS, N, O

vinyl imidazole, pH, IS, N

allylamine, pH, IS, N

alginate, pH, IS, O

chondroitin, pH, IS, O

hyaluronic acid, pH, IS, O

2-chloroacrylic acid, pH, IS, O, CI

saccharides, weak acids and bases, pH, IS

where pH=pH sensitive,T=temperature sensitive, IS=ionic strength sensitive, L=light or photo sensitive, E=electrosensitive and 0=oxygen containing, N=nitrogen containing, F=fluorine containing, Cl=chlorine containing, and P=phosphorus containing.

The polymers disclosed here are all hydrophilic polymers, which can be crosslinked to give hydrogels and microgels. These materials may be immobilized between Au (or any metal) layer(s), just like the pNIPAm based system describe above. The polymers may be swollen with solvent, and change volume in response to the indicated stimuli, therefore changing the color of the etalon. The listed polymers should all stick to the metal because polymers have elements with free electrons.

Other Embodiments

[0026] The film uniformity of the gel layer provided by the spreading technique described herein makes it easier to control release of substances that may be loaded into the polymer gel. For example, gold may be deposited on top of a drug-loaded hydrogel to control drug release, for use for example in implantable devices. In the example of slow or controlled drug release, a multilayer structure of polymeric gel layers and intervening metal layers formed by repetitive units of the gel assembly may be formed in which drug-loaded hydrogel is sandwiched between consecutive layers of gold. This would allow the release of a different drug after one drug is exhausted and could be useful to avoid bacterial resistance in the case of antibiotic drugs.

[0027] In a gel assembly loaded for drug delivery, the polymeric gel may be spread onto a metal substrate. A solution containing drug is then added to the polymeric gel layer and allowed to dry. A metal overlayer is then deposited on to the polymer and drug. The assembly is then exposed to a stimulus such as water in the case of a hydrosensitive polymer being used for the polymeric gel layer, and the drug released from the gel assembly. The release may also be triggered with temperature. That is, at high temperature, the gel particles in the gel assembly collapse, effectively squeezing out the drug on the polymer between the two metal layers. There may be other mechanisms of release for drug from a gel assembly loaded with drug. For example, polymer de-swelling may cause cracks to form in the metal layer, which may facilitate more drug release at high temperature.

[0028] Embodiments of the inventive sensor may be used in a device to test blood/alcohol levels. The device may utilize a blood sample taken for example by a pin prick to obtain an alcohol level, or by analyzing the breath of a subject as in a breathalyzer.

[0029] Embodiments of the etalon described herein may be used as a tunable filter— for example, by heating it up, one can decrease the wavelength of the light that will be reflected; this is useful as filters for fluorescent microscopes so as to avoid the need to switch to a different filter for a different wavelength used to excite a different fluorophore.

[0030] Embodiments of the etalon may be fabricated where there is only one reflectance peak in the visible spectrum, thereby providing a level of spectral purity that may be used in colorimetric sensors with a visual readout. Furthermore, the wide color range (from near-infra red (IR) to ultra violet (UV) provides the colorimetric sensor with a vivid display readout evident in more costly spectrometers. The wide color range is mostly achieved from a changing mirror-to-mirror distance though a change in the index of refraction.

[0031] While at least one exemplary embodiment has been presented in the foregoing detailed description, it should be appreciated that a vast number of variations exist. It should also be appreciated that the exemplary embodiment or exemplary embodiments are only examples, and are not intended to limit the scope, applicability, or configuration of the described embodiments in any way. Rather, the foregoing detailed description will provide those skilled in the art with a convenient roadmap for implementing the exemplary embodiment or exemplary embodiments. It should be understood that various changes may be made in the function and arrangement of elements without departing from the scope as set forth in the appended claims and the legal equivalents thereof.

Claims

1. An etalon or interferometer based sensor assembly comprising

a monolithic polymeric gel layer defining a perimeter and a thickness;

a metal-containing overlayer formed over a top surface of the monolithic polymeric gel layer;

a metal-containing base layer supporting a bottom surface of the monolithic polymeric gel layer;

a substrate on which the metal-containing base layer is formed; and an enclosure or the metal-containing overlayer about the perimeter to limit diffusion to be predominantly through the metal-containing overlayer, the gel layer having a thickness that induces a color change as the thickness changes.

2. The assembly of claim 1 wherein the monolithic polymeric gel layer is formed as a colloidal polymer in solution with at least a monomer having at least one nitrogen, fluorine, chlorine, or phosphorus atom per monomer unit.

3. The assembly of claim 2 wherein the colloidal polymer is a hydrogel or organo-gel.

4. The assembly of claim 2 wherein the colloidal polymer has hydrophilic groups including one or more of acrylamides, acrylates, silicones, ethylene oxides, ethylene glycols, poly amines, polyethers, and combinations thereof.

5. The assembly of claim 2 further comprising a co-monomer and the colloidal polymer is a co-polymer.

6. The assembly of claim 5 wherein the monomers in the co-polymer are individually non-responsive to a first stimulus, or the co-monomer is responsive to the first stimulus or other stimuli.

7. The assembly of claim 2 wherein the colloidal polymer further comprises a cross-linker.

8. The assembly of claim 2 further comprising uncrosslinked

poly(Nisopropylacrylamide) (pNIPAm) .

9. The assembly of any one of claims 1 to 8 wherein the monolithic polymeric gel layer is formed of colloidal particles having an effective diameter of between 0.05 micron and 250 microns.

10. The assembly of any one of claims 1 to 8 wherein the monolithic polymeric gel layer is formed of colloidal particles having an effective diameter of between 0.229 micron to 1.5 microns.

11. The assembly of claim 1 wherein the monolithic polymeric gel layer is formed of one or more stimulus responsive polymers of thermoresponsive polymers, pH responsive polymers, electroresponsive polymers, magnetoresponsive polymers, ionic strength responsive polymers, or photoresponsive polymers.

12. The assembly of claim 11 wherein the one or more stimulus responsive polymers change volume in response to a stimulus.

13. The assembly of any one of claims 1 to 8 wherein the metal-containing overlayer and the metal-containing base layer are parallel to each other and are optically reflective.

14. The assembly of any one of claims 1 to 8 further comprising an interferant adhered to the metal-containing overlayer.

15. The assembly of claim 14 wherein at least one of the metal-containing overlayer and the metal-containing base layer has optical transparency to an interrogating wavelength.

16. The assembly of claim 14 wherein the metal-containing overlayer and the metal-containing base layer are each independently formed of Fe, Ni, Ag, Au, Al, Ti, Cu, Cr, alloys thereof, or intermetallics thereof, in which one of the aforementioned metals or a combination thereof constitute an atomic percent majority of the alloy or the intermetallic.

17. The assembly of claim 14 wherein the metal-containing overlayer and the metal-containing base layer are deposited as a coating via at least one of physical vapor deposition, chemical vapor deposition, wet chemical methods, thermal evaporation, electron beam evaporation, sputtering, electroless deposition, pulsed laser deposition, nanocrystal film melting, and direct transfer of a metal layer from another substrate.

18. A process of making the assembly of any one of claims 1 to 8 comprising: providing a colloidal hydrophilic polymer in a solution;

drying the solution to form the polymeric gel layer on a metal-containing base layer in turn supported on a substrate; and

forming a metal-containing overlayer formed over the top surface of the polymeric gel layer; and

forming an enclosure about the perimeter of the sensor assembly.