Classifications

• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
  • G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
  • G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
  • G01N21/7703—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator using reagent-clad optical fibres or optical waveguides
• • G—PHYSICS
  • G02—OPTICS
  • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
  • G02B1/00—Optical elements characterised by the material of which they are made; Optical coatings for optical elements
  • G02B1/04—Optical elements characterised by the material of which they are made; Optical coatings for optical elements made of organic materials, e.g. plastics
  • G02B1/045—Light guides
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
  • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
  • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
  • G01N21/64—Fluorescence; Phosphorescence
  • G01N21/645—Specially adapted constructive features of fluorimeters
  • G01N21/648—Specially adapted constructive features of fluorimeters using evanescent coupling or surface plasmon coupling for the excitation of fluorescence

Definitions

• the invention relates to integrated optical waveguide sensors based on photoaddressable polymers and their use as bio or chemosensors.
• Bio- or chemical sensors are devices that can detect an analyte qualitatively or quantitatively with the help of a signal converter and a recognition reaction.
• the recognition reaction is generally the specific binding or reaction of a so-called analyte with a so-called recognition element. Examples of recognition reactions are the binding of ligands to complexes, the complexation of ions, the binding of ligands to (biological)
• Receptors from antigens or haptens to antibodies, from substrates to enzymes, from DNA or RNA to certain proteins, the hybridization of DNA / RNA / PNA or the processing of substrates by enzymes.
• Analytes can be: ions, proteins, natural or artificial antigens or haptens, hormones, cytokines, mono- and oligosaccharides, metabolites, or other biochemical markers that are used in diagnostics, enzyme substrates, DNA, RNA, PNA, potential active substances, drugs , Cells, viruses.
• recognition elements are: complexing agents for metals / metal ions, cyclodextrins, crown ethers, antibodies, antibody fragments, anticalins (Beste, G .; Schmidt, FS; Stibora, T .; Skerra A .; Proc. Natl. Acad. Sei. USA (1999 ) 96, 1898-1903), enzymes, DNA,
• RNA, PNA DNA / RNA binding proteins, enzymes, receptors, membrane receptors, ion channels, cell adhesion proteins, gangliosides, mono- or oligosaccharides.
• bio or chemical sensors can be used in environmental analysis, the food sector, human and veterinary diagnostics and crop protection to determine analytes qualitatively and / or quantitatively.
• Detection reaction makes it possible to analyze analytes in complex samples such as Ambient air, contaminated water or body fluids without qualitative or quantitative determination without or with little previous purification.
• bio- or chemosensors can also be used in (bio-) chemical research and drug discovery to determine the interaction between two different ones
• the recognition reaction can be integrated with the signal converter to form a bio- or chemical sensor by immobilizing the recognition element or the analyte on the surface of the signal converter.
• the detection reaction ie the binding or reaction of the analyte with the detection element, changes the optical properties of the medium directly on the surface of the signal converter (e.g.
• Optical waveguides are a class of signal converters that can be used to detect the change in the optical properties of a medium that borders on a waveguiding layer. If light is transported as a guided mode in the waveguiding layer, the light field at the medium / waveguide interface does not drop abruptly, but decays exponentially in the so-called detection medium adjacent to the waveguide. This exponentially falling light field is called the evanescent field. Do the optical properties of the medium adjoining the waveguide change (e.g. change in the optical refractive index (Tiefenthaler et.
• the chips should be storable for 2 years (in the dark);
• the polymer surface and subsequent physisorption of the biomolecules are conceivable (e.g. as with the coating of microtiter plates, which are first plasma-treated and then coated with proteins.
• the sensitivity can only be made sufficiently high by using very long optical paths. Since the refractive index of the proposed material is only small ⁇ 1.66, very large measuring sections result, and thus the requirements with regard to sensitivity and dimension cannot be met at the same time.
• a known waveguide consists of hard dielectric materials.
• glass can also be structured by pressing, casting and embossing, but these processes are very complex and difficult to control. Wear and aging of the tools used are also a problem.
• Section 3 describes the manufacture.
• the chips were produced by replication in polycarbonate substrates (foils) and subsequent coating with an inorganic wave-guiding layer.
• a 260 ⁇ m thick SiNx layer was deposited as a waveguide onto the replicated surface relief in the polycarbonate by means of a “plasma-enhanced chemical vapor deposition” (PECVD) process.
• PECVD plasma-enhanced chemical vapor deposition
• the manufacturing process is complex, in particular the deposition processes as such, and additionally the application of adhesion promoters, barrier layers, etc.
• the object of the invention is to provide a detection platform which avoids the disadvantages mentioned above, the two most important properties of the waveguides, i.e. simple manufacture, high sensitivity are in the foreground.
• the invention relates to integrated optical detection platforms and a layer structure for this purpose, which have at least one layer, or more generally an area, which consists of a photo-addressable polymer (PAP).
• PAP photo-addressable polymer
• the invention relates to an optical layer structure with at least two
• Layers comprising at least one substrate layer and at least one (light) wave-guiding layer and a coupling element for coupling the optical radiation, in particular an optical grating, a prism or a planar or curved transparent end face of the wave-guiding layer, the layer adjacent to the wave-guiding layer having a smaller refractive index than the wave-guiding layer, characterized in that at least one layer consists of a photo-addressable polymer.
• the photoaddressable polymer according to the invention is preferably polymeric or oligomeric organic material, particularly preferably a side chain polymer.
• the main chains of the side chain polymer come from the following basic structures: polyacrylate, polymethacrylate, polyacrylamide, polymethacrylamide, polysiloxane, polyurea, polyurethane, polyester, polystyrene or cellulose. Polyacrylate, polymethacrylate and polyacrylamide are preferred.
• the polymers and oligomers according to the invention preferably have glass transition temperatures T g of at least 40 ° C., particularly preferably of at least 90 ° C.
• the glass transition temperature can be determined, for example, according to B. Vollmer, Grundriß der Makromolekularen Chemie, pp. 406-410, Springer-Verlag, Heidelberg 1962.
• the polymers and oligomers according to the invention have a weight average molecular weight of 5,000 to 2,000,000 g / mol, preferably 8,000 to 1,500,000 g / mol, determined by gel permeation chromatography (calibrated with polystyrene).
• azo dye- are used as the side chain of the photoaddressable polymers
• azo dyes are covalently bound to the main polymer chain, generally via flexible spacers.
• the azo dyes interact with the electromagnetic radiation and change their spatial orientation.
• the mesogens are usually bound in the same way as the azo dyes. You don't necessarily have to absorb the actmic light because they act as a passive group of molecules. So they are not photoactive in the above sense. Your job is to to enhance light-inducible birefringence and to stabilize after the 'exposure to light.
• the reorientation of the dyes after exposure to actinic light results, for example, from investigations on polarized absorption spectroscopy:
• a sample previously exposed to actinic light 5 is placed between two polarizers in a UV / VIS spectrometer (eg company CARY 4G, UV- / VI8 Spectrometer) in the spectral range of the absorption of the dyes.
• UV / VIS spectrometer eg company CARY 4G, UV- / VI8 Spectrometer
• the molecular longitudinal axis can be determined, for example, on the basis of the molecular shape by molecular modeling (eg CERIUS 2 ).
• the grouping that interacts with the electromagnetic radiation 5 is an azo dye.
• the material according to the invention consequently contains at least one azo dye.
• azo dyes have the following structure of formula (I)
• R 1 and R 2 independently of one another represent hydrogen or a nonionic substituent and m and n independently of one another represent an integer from 0 to 4, preferably 0 to 2.
• X r -R 3 and X 2 ' -R 4 can represent hydrogen, halogen, cyano, nitro, CF 3 or CC1 3 ,
• R 6 and R 7 independently of one another for hydrogen, halogen, C to C 2 o-alkyl, - to C 20 alkoxy, C 3 - to C ⁇ 0 cycloalkyl, C 2 - to C 20 alkenyl or C 6 - to Cio -Aryl stand.
• the alkyl, cycloalkyl, alkenyl and aryl radicals can in turn be substituted by up to 3 radicals from the series halogen, cyano, nitro, Q- to C 20 -alkyl, - to C 20 -alkoxy, C 3 - to Cjo-cyclo- alkyl, C 2 - to C 2 o-alkenyl or C 6 - to C 10 -aryl can be substituted and the alkyl and alkenyl radicals can be straight-chain or branched.
• Halogen is to be understood as fluorine, chlorine, bromine and iodine, in particular fluorine and chlorine.
• the dyes in particular the azo dyes of the formula (I), are covalently bound to the polymer skeletons, generally via a spacer.
• X 1 (or X 2 ) then stands for such a spacer, in particular with the meaning X 1 ' - (Q 1 ) i -T 1 -S 1 -,
• R 9 represents hydrogen, methyl, ethyl or propyl
• R, 1 1'0 represents methyl or ethyl
• R 5 to R 8 have the meaning given above.
• Preferred dye monomers for polyacrylates or methacrylates then have the formula (II)
• R represents hydrogen or methyl
• X 3 denotes CN, and all other known electron-withdrawing substituents, and then preferably R 1 is also CN,
• the polymeric or oligomeric organic, amorphous material according to the invention can carry formanisotropic groupings in addition to the dyes, for example of the formula (I). These, too, are usually covalently bound to the polymer frameworks via a spacer.
• Shape-anisotropic groupings have, for example, the structure of the formula (III)
• A represents O, S or NC r to C 4 alkyl
• X 3 stands for -X J - (Q j - -S -,
• X 4 stands for X r * 4 - rR.1 1 3 J ,
• X 4 4 '- -RD 13 can represent hydrogen, halogen, cyan, nitro, CF 3 or CC1 3
• R 6 and R 7 independently of one another are hydrogen, halogen, - to C 20 alkyl, - to C 20 alkoxy , C 3 - to Cio-cycloalkyl, C 2 - to C 20 -alkenyl or C 6 - to Cio-aryl,
• Y for a simple bond, -COO-, OCO-, -CONH-, -NHCO-, -CON (CH 3 , -N (CH 3 ) CO-, -O-, -NH- or -N (CH 3 ) -
• R 9 represents hydrogen, methyl, ethyl or propyl
• R 10 represents methyl or ethyl.
• Preferred monomers with such shape-anisotropic groupings for polyacrylates or methacrylates then have the formula (IV)
• R represents hydrogen or methyl and the other radicals have the meaning given above.
• alkyl, cycloalkyl, alkenyl and aryl radicals can in turn be substituted by up to 3 radicals from the series halogen, cyano, nitro, - to C 2 o -alkyl, C to C 20 alkoxy, C 3 - to Cio-cycloalkyl, C 2 - to C 20 -alkenyl or C 6 - to Cio-aryl may be substituted and the alkyl and alkenyl radicals may be straight-chain or branched.
• Halogen is to be understood as fluorine, chlorine, bromine and iodine, in particular fluorine and chlorine.
• Particularly preferred shape-anisotropic monomers of the formula (IV) are, for example:
• the oligomers or polymers according to the invention can also contain building blocks which are used primarily to lower the percentage content of functional building blocks, in particular of dye building blocks. Next this task they can also be responsible for other properties of the oligomers or polymers, e.g. B. the glass transition temperature, liquid crystallinity, film formation property, etc.
• such monomers are acrylic or methacrylic acid esters of the formula (V)
• R represents hydrogen or methyl
• X 5 stands for -O- or - (NR 15 ) -
• R 14 and R 15 independently of one another represent optionally branched C -C 20 - are or alkyl or an at least one further acrylic unit containing group together form a bridge member - (CH 2) r.-CH 2 -CH 2 -O- CH 2 - CH 2 - or. -CH 2 -CH 2 -N (R) - CH 2 -CH 2 - form where
• f 2 to 6.
• the quantitative ratio between II, IV and V is arbitrary. Depending on the absorption coefficient of II, the concentration of II is preferably between 0.1 and 100% based on the respective mixture.
• the ratio between II and IV is between 100: 0 and 1:99, preferably between 100: 0 and 20:80, very particularly preferably between 100: 0 and 50:50. '
• the structure of the polymers and oligomers adjusts the intermolecular interactions of the structural elements of the formulas (II) with one another or between the formulas (IV) and (V) with one another in such a way that the formation of liquid-crystalline order states is suppressed and optically isotropic, transparent, non-scattering films, Foils, plates or cuboids can be produced.
• the intermolecular interactions of the structural elements of the formulas (II) with one another or between the formulas (IV) and (V) with one another in such a way that the formation of liquid-crystalline order states is suppressed and optically isotropic, transparent, non-scattering films, Foils, plates or cuboids can be produced.
• the intermolecular interactions of the structural elements of the formulas (II) with one another or between the formulas (IV) and (V) with one another in such a way that the formation of liquid-crystalline order states is suppressed and optically isotropic, transparent, non-scattering films,
• interaction forces occur between the side groups of the repeating units of the formula (II) or between those of the formula (IV) that are sufficient for the photo-induced configuration change of the side groups of the formula (II) to result in a so-called - so-called cooperative - reorientation of the other side groups (IV ) causes.
• optical anisotropy can be induced in the optically isotropic amorphous photochromic polymers ( ⁇ n to 0.4). Due to the influence of actinic light, order states are generated and modified in the polymers or oligomers and thus the optical properties are modulated.
• Polarized light is used as the light, the wavelength of which lies in the region of the absorption band, preferably in the region of the long-wave n- ⁇ * band of the repeating units of the formula (II).
• the optical anisotropy can be increased further by tempering the sample oriented with polarized light at temperatures between 70 and 150 ° C., preferably between 100 and 140 ° C.
• the polymers and oligomers can be prepared by methods known from the literature, for example according to DD 276 297, DE-A 3 808 430, Macromolecular Chemistry 187, 1327-1334 (1984), SU 887 574, Europ. Polym. 18, 561 (1982) and Liq. Cryst. 2, 195 (1987).
• Particularly suitable materials contain at least one of the polymers of the formulas VI to XI
• PAP photo-addressable polymers
• PAP waveguides are therefore very well suited for sensor arrays in which several analytes at different wavelengths can be detected simultaneously (multiplexing).
• PAP layers that are applied directly to a wave-guiding layer can also be used only as a coupling-in or coupling-out grating. Due to the very sensitive light-induced refractive index change, exposure or refractive index gratings, also referred to as phase gratings, can be produced in the PAP layer very easily and inexpensively, both in volume or near the surface, the surface corresponding to the side of the PAP layer that facing actinic light.
• the waveguiding then takes place in the waveguiding layer, which can consist of organic or inorganic materials.
• This waveguiding layer can also be a PAP material which has different optical properties from the PAP layer into which optical gratings have been written.
• PAP layers show strongly pronounced surface gratings in holographic experiments, which appear as regular profiles in the PAP film surface and which can be used as coupling-in / coupling-out gratings for the sensor. They are temperature and long-term stable.
• the absorption of the PAP materials can be adjusted over a wide wavelength range, so that a high degree of transparency ( ⁇ 3 dB / cm) can be achieved with the technically used laser wavelength.
• PAP layers lie above all in the light-induced generation of optical waveguide and grating structures. No photolithographic steps and etching steps are necessary to create these structures. Thin layers (10 nm to 1000 nm) of PAP can be applied to a suitable substrate material using generally known techniques, for example spin coating, spraying, knife coating, dip coating etc. These processes are simpler and less expensive to produce than the sputtering or vapor deposition of inorganic waveguides on substrates in a high vacuum.
• these PAP areas have at least one of the following functions:
• This function is used for the flexible definition of areas on the platform that are used for coupling and decoupling light with great efficiency (eg for grid-based sensors, and for defining sensor and reference measurement fields. Furthermore, structures can also be used are produced to guide laterally limited light waves on the
• the main advantage of the invention is a drastic reduction in costs and simplification of production, since only a few process steps are required and the quality of the layers will be high due to the few process steps in production (e.g. coupling of detection layers etc.).
• functional groups are incorporated by copolymerization, or proteins are absorbed by plasma treatment of the surface. Similar to microtiter plates, light-induced coupling via photochemistry is also possible.
• Macroscopic area e.g. writing in strip waveguides and defining sensor fields with dimensions from micrometers to millimeters and centimeters.
• a layer structure is preferred which is characterized in that the photo-addressable polymer has a refractive index of> 1.65, preferably of> 1.75.
• a layer structure is also preferred, which is characterized in that the wave-guiding layer has a plurality of light-induced, microscopic and / or macroscopic light-guiding substructures. These have a refractive index that differs clearly from that of the surrounding areas.
• the waveguides can optionally be produced in a light-induced manner.
• the substrate layer is optically transparent.
• Optically transparent in the sense of the invention means that the material for radiation with a wavelength in the range from 450 to 900 mm has a range with a transmittance of min. 90%.
• the substrate layer is not optically transparent, but an additional buffer layer arranged above the substrate layer is optically transparent.
• the coupling element is a grid.
• the coupling element is a grid which is attached in the layer which has the photoaddressable polymer.
• the wave-guiding layer is based on photoaddressable polymers.
• a layer structure is particularly preferred in which the wave-guiding layer is based on a material selected from the series tantalum pentoxide, titanium dioxide, hafnium dioxide, zinc oxide, niobium pentoxide or zirconium oxide, alone or in a mixture, in particular on titanium oxide.
• the layer structure a plurality of gratings with different grating constants are present as coupling elements.
• the refractive index of the waveguiding layer is> 1.6, particularly preferably> 1.67.
• a structure of the layer structure is advantageous in which the layer thickness of the waveguiding layer is smaller than the wavelength of the radiation which is guided in the waveguide.
• a layer structure is very particularly preferred, which is characterized in that the wave-guiding layer can be operated in single-mode operation.
• a coupling-out unit for coupling out the optical radiation is additionally provided, in particular an optical grating.
• the thickness of the wave-guiding layer is 30 to 300 nanometers.
• Another particularly preferred embodiment of the layer structure is characterized in that an intermediate layer with a lower refractive index than that of the waveguide layer is provided between the waveguiding layer and the substrate layer.
• the intermediate layer is based on an optically transparent polymer.
• shock absorber is also particularly preferred, which is characterized in that a layer of photoaddressable polymers contains the coupling element and an adjacent, in particular a layer located above the layer with the coupling element is the waveguiding layer.
• a particularly preferred detection platform consists of a transparent substrate and one or more optically anisotropic layers based on PAP, into which at least one sensor structure, consisting of an optical waveguide structure and at least one optical grating structure, has been inscribed via one or more suitable exposure steps Distinguish from the unexposed part of the PAP in that they have a different refractive index and light that is coupled in via the grating structures is transported in the waveguide structure, in its evanescent field at the interface from the waveguide to a sample in contact with it, the optical properties of the sample such as refractive index, Luminescence, absorption etc. is detected with a suitable detection device.
• a preferred integrated optical waveguide for use as a bio or chemical sensor consists, for example, of a transparent substrate and an optically anisotropic layer based on PAP, into which at least one sensor structure consisting of an optical waveguide and at least one is used via one or more suitable exposure steps optical grating structure, which differ from the rest of the PAP in that they have a different refractive index and light coupled via the grating structures is transported in the waveguide structure via total reflection or as a guided mode.
• a detection platform consisting of a transparent substrate on which a planar optical waveguide and a thin optically anisotropic one are preferably also possible
• Layer based on PAP are applied, in which at least one optical grating structure has been inscribed via one or more suitable exposure steps, which differ from the rest of the PAP in that they have a different refractive index and couple light into the adjacent waveguide via the grating structures and is transported in it, and in the evanescent light field at the interface of
• optical properties of the sample such as refractive index, luminescence, absorption, etc.
• a suitable detection device for a sample in contact with it can be detected using a suitable detection device for a sample in contact with it.
• An integrated optical waveguide for use as a bio or chemical sensor consisting of a transparent substrate and an optically anisotropic layer based on PAP, into which at least one sensor structure consisting of an optical waveguide and at least one optical grating structure, which differ from the rest of the PAP in that they have a different refractive index and light coupled in via the grating structures in the guide structure
• a preferred detection platform consists, for example, of a transparent substrate and an optically anisotropic layer based on PAP, into which at least one sensor structure, consisting of an optical waveguide structure and at least one optical grating structure, has been written via one or more suitable exposure steps, which is different from the rest of the PAP differ in that they have a different refractive index and that light coupled in via the grating structures is transported in the waveguide structure, the evanescent field of which at the interface of Waveguide to a sample in contact with it stimulates luminescent substances to luminescence and the luminescence emitted into the room is detected with a suitable detection device.
• a particularly preferred detection platform consists of a transparent substrate and an optically anisotropic layer based on PAP, into which at least one sensor structure, consisting of an optical waveguide structure, which lies between two optical grating structures, has been written in via one or more suitable exposure steps Differentiate the rest of the PAP in that they have a different refractive index and that light is coupled into the waveguide structure via one of the lattice structures, the evanescent field of which at the interface of
• Waveguide to a sample in contact with it stimulates luminescent substances to luminescence and the light fed back into the waveguide is coupled out again at the second grating and detected with a suitable detection device.
• Chemosensors mean that the change in the optical properties of the medium is only detected very close to the surface of the waveguide. If the recognition element or the analyte is immobilized on the interface of the waveguide, the binding to the recognition element or the reaction of the recognition element can be detected in a surface-sensitive manner if the optical properties of the recognition element
• an integrated optical waveguide sensor consisting of a transparent substrate and an optically anisotropic layer based on PAP, into which at least one sensor structure consisting of an optical waveguide structure and at least one optical grating structure has been written via one or more suitable exposure steps differ from the rest of the PAP in that they have a different refractive index and that light coupled in via the grating structures is transported in the waveguide structure.
• Another object of the invention is a sensor comprising a sensor layer, a light source and a detection layer and an optical detector for luminescence, scattered light, absorption or change in the refractive index having a layer structure according to the invention.
• Devices that can detect an analyte qualitatively or quantitatively with the help of a signal converter (sensor layer) and a recognition reaction are referred to as bio or chemical sensors.
• the specific binding or reaction of a so-called analyte with a so-called recognition element is generally referred to as the recognition reaction.
• recognition reactions are the binding of ligands to complexes, the complexation of ions, the binding of ligands to (biological) receptors, membrane receptors or ion channels, from antigens or haptens to antibodies, from substrates to enzymes, from DNA or RNA to certain proteins, the hybridization of DNA / RNA / PNA or the processing of substrates by enzymes.
• Analytes can be: ions, proteins, natural or artificial antigens or haptens, hormones, cytokines, mono- and oligosaccharides, metabolic products, or other biochemical markers that are used in diagnostics, enzyme substrates, DNA, RNA, PNA, potential active substances, drugs , Cells, viruses.
• recognition elements are: complexing agents for metals / metal ions, cyclodextrins, crown ethers, antibodies, antibody fragments, anticalins, enzymes, DNA, RNA, PNA, DNA / RNA-binding proteins, enzymes, receptors, membrane receptors, ion channels, cell adhesion proteins, gangliosides, mono- or oligosaccharides.
• the integration of the detection reaction with the signal transducer to a biological or chemical sensor can be done by immobilizing the recognition element or the analyte on the surface of the transducer for example of the layer structure according to the invention directly or via an organic intermediate layer '.
• the recognition reaction ie the binding or the reaction of the analyte with the recognition element
• the optical properties of the medium change directly on the surface of the signal converter (e.g. change in the optical refractive index, absorption, fluorescence, phosphorescence, luminescence etc.), which is converted into a measurement signal by the signal converter.
• the invention also relates to the use of the aforementioned sensor for analyzing biomolecules, brands and active substances in environmental analysis, the food sector, human and veterinary diagnostics, (bio) chemical research and the search for active substances.
• bio or chemical sensors can be used in environmental analysis, the food sector, human and veterinary diagnostics and crop protection to determine analytes qualitatively and / or quantitatively.
• the specificity of the recognition reaction makes it possible to analyze analytes in complex samples such as B. ambient air, to determine dirty water or body fluids without or only with little previous purification qualitatively or quantitatively.
• bio or chemical sensors can also be used in (bio) chemical research and drug discovery to investigate the interaction between two different substances (e.g. between proteins, DNA, RNA, or biologically active substances and proteins, DNA,
• the invention further relates to a method for recognizing biomolecules using a sensor according to the invention.
• the results apply to the propagation of a TMO mode with a wavelength of 633 nm.
• the figure clearly shows that it is essential to use a layer 1 with a Refractive index nf of significantly more than 1.6
• the figure shows the optimum thickness hf of layer 1 and the maximum sensitivity that can be achieved.
• Fig. 3 The coupling factor for fluorescence emission from emitting centers (eg molecules) in the waveguide.
• the exact definition of the coupling factor is in the publication [G. novin et al., "Si3N4 / SiO2 / Si waveguide grating for fluorescent biosensors", Proc. SPIE, Vol. 3620 (1999)].
• the layer structure data are the same as for FIG. 2, ie a sensor chip is implemented with the same layer structure a fluorescence-based sensor is used to measure the fluorescence emission from centers that are close to the waveguide surface.
• the factor is a measure of the fraction of the fluorescence radiation which is emitted into the waveguide, i.e. a 2x larger factor means that 2x more energy gets into the waveguide.
• the molecules were thought to be directly on the waveguide.
• FIG. 3 (a) shows the fluorescence coupling factor for the radiation in the TM mode at 633 nm wavelength
• FIG. 3 (b) shows the conditions for the radiation in the TE mode.
• FIG. 1 (a) shows a variant of the layer structure in which the PAP layer 1 is at the same time the wave-guiding layer and is applied directly to an optically transparent substrate 2.
• the lattice structure 3 has been produced directly in layer 1. Only two process steps are required for production, namely the application of layer 1 and the exposure of the lattice structure 3.
• Preferred materials for the substrate are plastics and glass.
• FIG. 1 (b) shows a variant in which there is yet another layer 4 with a high refractive index between the PAP layer 1 and the substrate. Advantages of this variant are that the properties of layer 1 can be adapted to the optimal inscription of the lattice structure 3, while for the wave-guiding layer 4 a highly refractive index
• Polymer layer can be used, the properties of which can be optimized with a view to low attenuation of the modes propagating therein and / or low scatter.
• Layer 4 can also be a PAP layer, but need not.
• the refractive indices of layers 1 and 4 can be the same or different. Layer 4, however, must have a higher refractive index than substrate layer 2.
• Figure 1 (c) shows a variant in which the order of layers 1 and 4 is interchanged. Essentially, what was said in FIG. (B) applies, but here layer 1 must have a higher refractive index than layer 2.
• an advantage can arise if the surface properties of layer 4 are optimized especially for the coupling of a biochemical detection layer can be optimized, while the layer 1 can be optimized for a high refractive index and for the generation of the lattice structure 3. Furthermore, it can be advantageous to protect the PAP layer with the coupling structure 3 from environmental influences (layer 1 is not in contact with the analyte medium here, which is only in contact with layer 4).
• Figure 1 (d) shows an embodiment in which between the layer 1 and the
• Substrate 2 is an optically transparent buffer layer 5.
• the PAP layer 1 is here the wave-guiding layer, while the buffer layer 5 has the function of creating a distance between substrate 2 and layer 1, so that the evanescent wave propagates below layer 1 in layer 5 and not in substrate 2
• the refractive index of the buffer layer can be selected to be very small, so that the evanescent wave on the analyte side (above layer 1) extends far into the analyte medium, and thus larger areas near the waveguide surface can also be defined as sample volume.
• Such arrangements are also referred to as "reverse symmetry waveguides" and were e.g. by Horvath et al. (see Appl. Phys. Lett, Vol. 81/12, pp. 2166-2168 (September 16, 2002).
• the substrate layer does not have to be transparent.
• Semiconductors such as silicon, III-V compounds or opto-electronic polymers are used and thus also active electrical circuits in the substrate can be realized, which can be used to evaluate the sensor signals (possibly detectors for optical reading directly in the
• Substrate metals or other materials can also be used, i.e. the sensor chips can be applied to any objects.
• the signals are read optically from the side of layer 1 or through holes or transparent areas in substrate layer 2.
• FIG. 1 (e) shows a somewhat more complicated variant of (d), in which a layer 4 with a high refractive index is used between buffer layer 5 and PAP layer 1.
• a layer 4 with a high refractive index is used between buffer layer 5 and PAP layer 1.
• Different versions are possible. It is of particular interest to apply layer 1 to the production of coupling structure 3 and the coupling of detection layers optimize while layer 4 can be optimized as a waveguide.
• the further advantages are the same as in the arrangement according to FIG. 1 (d), in particular a non-transparent substrate can be used with the additional advantages connected therewith.
• FIG. 1 (f) shows a further variant where an inorganic high-index layer 6 is used as the wave-guiding layer.
• an inorganic high-index layer 6 is used as the wave-guiding layer.
• materials to choose from for example from the series tantalum pentoxide, titanium dioxide, hafnium dioxide, zinc oxide, niobium, pentoxide or zirconium oxide, alone or in a mixture, in particular tantalum pentoxide.
• This variant has advantages above all to achieve the highest possible sensitivity, since very high refractive indices are available, which can be higher than 2.3. Below can 'such
• the coupling structures 3 can be conveniently generated in the overlying PAP layer 1 without further process steps. Even in this case, only a few process steps are necessary, namely (i) deposition of layer 6 on substrate 2, (ii) deposition of layer 1 and (iii) exposure of coupling structure 3.

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