MXPA97008698A - Sensor platform and method for the parallel detection of a plurality of analysts using luminescence evanescently excit - Google Patents

Abstract

The invention relates to a sensor platform based on at least two separate inorganic dielectric waveguide regions separated on a common substrate, and to a method for parallel evanescent excitation and detection of the luminescence of identical or different analytes. The invention also relates to a sensor platform having the separate flat inorganic dielectric waveguide regions, and to one or more organic phases immobilized thereon. A further object of the invention is the use of the modified sensor platform, in a luminescence detection method, for quantitative affinity detection, and for the selective quantitative determination of the luminescent constituents of optically opaque solutions.

Description

SENSOR PLATFORM AND METHOD FOR THE PARALLEL DETECTION OF A PLURALITY OF ANALYTICES USING LUMINESCENCE EVANESCENTLY EXCITED The invention relates to a sensor platform based on at least two separate inorganic dielectric waveguide regions separated on a common substrate, and to a method for parallel evanescent excitation and detection of the inescence of identical or different analytes. The invention also relates to a modified sensor platform consisting of the sensor platform having the separate flat inorganic dielectric waveguide regions, and to one or more organic phases immobilized thereon. A further object of the invention is the use of the sensor platform or the modified sensor platform, in a luminescence detection method, for quantitative affinity detection, and for the selective quantitative determination of the optically luminescent constituents of solutions opaque If a wave of light is coupled to a plane wave guide that is surrounded by a lower refractive index, it is confined by the total reflection at the boundaries of the waveguide layer. In the simplest case, a flat waveguide consists of a three layer system: substrate, waveguide layer, superstrate (or the sample to be investigated), the waveguide layer having the refractive index higher. The additional intermediate layers may further improve the action of the flat wave guide. In that configuration, a fraction of the electromagnetic energy enters the middle of the lower refractive index. This portion is called the evanescent field (= decay).

The force of the evanescent field depends to a very high degree. of the thickness of the waveguide layer itself, and of the ratio of the refractive indices of the waveguide layer and the surrounding medium. In the case of thin waveguides, that is, with layer thicknesses that are equal to or smaller than the wavelength to be guided, separate modes of the guided light can be distinguished. Using an evanescent field, it is possible, for example, to excite the luminescence in the middle of a relatively low refractive index, and to excite that luminescence in the immediate vicinity of the region of the waveguide only.

This principle is known as the evanescent luminescence excitation. The evanescent luminescence excitation is of great interest in the field of analysis, since the excitation is limited to the immediate vicinity of the waveguide layer. Methods and apparatuses are known for determining the evanescently excited luminorescence of antibodies or antigens marked with luminescent dyes. / SP describe, for example, in I United States Patent Number US-A-4,582,809. The configuration claimed therein utilizes an optical fiber for evanescent luminescence excitation. These optical fibers typically have a diameter of up to 1 millimeter, and guide a large number of modes when the laser light is coupled to them. The evanescently excited luminescence can easily be measured only by means of the portion coupled back into the fibers. A further drawback is that the apparatus is relatively large, and comparatively large sample volumes are required. There is very little scope for any further substantial reduction in the size of the configuration, leaving only its miniaturization to produce integrated optical sensors. Any increase in sensitivity is usually associated with an increase in the size of the configuration. In the same way. photo-electric instruments are known for determining the luminescence of biosensors under evanescent excitation conditions, using flat optical waveguides, and are described, for example, in Puhl i Nation International Number W0 90/06503. The waveguide layers used in that description are from 160 nanometers to 1,000 nanometers thick, and the excitation wave is coupled without grid couplers. Various attempts have been made to increase the sensitivity of the luminescent to evanescently excited, and to produce integrated optical sensors. For example, a report in Biosepsor &; Bioelectropics 6 (1991), 595-607. describes monomodal flat or low-mode waveguides that are produced in a two-step ion exchange process, and where the excitation wave is coupled using prisms. The affinity system used is human-G protein / fluorescein-labeled Inhibin A, the antibody being immobilized on the waveguide, and fluorescein-labeled protein A being added to be detected, in a phosphate buffer, to an alcohol film. poly with which the measurement region of the waveguide is covered. A considerable disadvantage of this method is that only small differences in the refractive index can be reached between the waveguide layer and the substrate layer, with the result that the sensitivity is relatively low. The sensitivity is given as 20 nM of protein A labeled with fluoresceypa. This is still not satisfactory for the determination of very small traces, and therefore, a further increase in sensitivity is required. In addition. The coupling of light using prisms is difficult to reproduce and to perform in practice, due to the high degree to which the efficiency of the coupling depends on the quality and size of the contact surface between the prism and the waveguide. In the Patent of the United States of North America, US-A-5, 081.012, a different principle is proposed. The flat wave guide layer is 200 nanometers to 1,000 nanometers thick, and contains two gratings, one of which is in the form of a reflecting grid, with the result that the coupled light wave has to pass at least twice through the sensor region between the grids. This is supposed to produce greater sensitivity. One drawback is that the reflected radiation can lead to an undesirable increase in the intensity of the background radiation. International Publication Number WO 91/10122 discloses a thin layer spectroscopic sensor comprising an internal coupling grid. and a physically remote external coupling grid. It is especially suitable for the measurement of absorption if an inorganic metal oxide of a high refractive index is used as the waveguide layer. Various modalities are described which are suitable for the internal coupling and the external coupling of multi-chromatic light sources. The preferred thickness of the waveguide layer is greater than 200 panometers. and the depth of the grid should be approximately 100 nanometers. These conditions are not suitable for luminescence measurements in affinity detection, since only a low sensitivity is obtained. This is confirmed in Appl. Optics Volume 29. Number 31 (1990). 583-4589, by the data of the global efficiency of these systems: 0.3 percent to 6 ^ nanó etros, and 0.03 percent to 514 nanómetros.

In another embodiment of the same sensor, a plurality of polymeric waveguide layers that can be used as a gas mixing analyzer are applied to a substrate. In this case, use is made of the change in the effective refractive index, or of the change in the thickness of the layer of the polymer waveguide with which they are in contact, for example, solvent vapors. The structure of the waveguide is physically altered by the same. However, these changes are totally inadequate for luminescence measurements in affinity detection, since inward coupling is altered, an increase in dispersion occurs, and there may be a significant decrease in sensitivity. The production of flat waveguides is a process where the planarity of the substrate, the constant thickness, and the homogeneity of the waveguide layer and the refractive index of the material used for it are of extreme importance. This is described, for example, in European Patent Number EP-A-0.533,074, and that description proposes the application of inorganic waveguides for plastic substrates. This offers the advantage that, for example, the structuring of the grid coupler can be effected in an economical manner, by printing the structure on the plastic. However, on the other hand, the requirements regarding the optical quality of plastic substrates are also high. Flat waveguides offer considerable advantages for industrial production over waveguides based on optical fiber. In particular, it is generally necessary, in the case of fibers, to polish the cut ends, in order to achieve a perfect optical quality. The flat wave guides. on the other hand, they can be produced in sheet form, and then they can be stamped, broken, or cut to the desired size. The finishing of the edges is unnecessary in most cases, making mass production more economical. Other advantages of flat waveguides having grid couplers are a simple adjustment in the measuring apparatus or in the measurement configuration, and a simple application of a coating, for example. for the immobilization of an analyte. Conventional coatings technology processes can be used, which allow the production of constant and reproducible layer thicknesses. For that purpose. Examples are spraying, knife application, centrifugal coating, and immersion. Quality control can also be carried out in a simple way using very precise methods known. Suitable are, for example, microscopic or interferometric methods, and ellipsometry or contact angle measurements. These methods can not be used, or can only be used with difficulty, for curved surfaces, such as those found in waveguides based on optical fiber. Along with the waveguide layer itself, the nature of the coupling of the light wave in the waveguide layer represents a major problem. The requirements for gratings for coupling light in waveguides that are thinned for integrated optical sensors are indicated, for example, in Chemical, Biochemical and Environmental Fiber Sensors V, Proc. SPIE, Volume 2068, 313-325, 1994. The modulation depth of the grid and the thickness of the waveguide layer are described as critical characteristics. The systems proposed in this publication can be used, for example, as integrated optical light indicators, although no reference is made to any luminescence to be detected. If you are going to use these flat waveguides that have integrated grating couplers to measure luminescence, the essential characteristics for their utility and for the achievement of a high degree of sensitivity are an adequate internal coupling efficiency, such a strong evanescent field as possible, and a low attenuation of the guided wave. These characteristics are critically determined by the combination of the refractive index of the waveguide layer and the substrate, and of any intermediate layers, the layer thickness of the waveguide, and the structure, depth of modulation, and period of grid coupler grid. In addition to this, there is the required optical quality of the surfaces and the plaparity or roughness of the same. A drawback of all methods for the evanescently excited luminescence detection described in the prior art is that only one sample can be analyzed at a time on the sensor platform in the form of a homogeneous film. In order to make other measurements on the same sensor platform, laborious washing and cleaning steps are necessary. This is especially the case when an apalite is detected that is different from the analyte of the first measurement. In the case of an immunoassay, it generally means that the entire immobilized layer has to be replaced on the sensor platform, or that a new sensor platform has to be used. Accordingly, there is a need to develop a method that allows a plurality of samples to be analyzed in parallel, i.e., in a simultaneous manner, or one immediately after another, without additional cleaning steps. International Publication Number WO 95/03538 proposes, for example, to configure on top of a continuous waveguide layer, a plurality of sample cells in the form of cavities in a sample plate, on top of the guide layer cool. Beneath each sample cell is a grid that externally couples a portion of the light guided through the waveguide layer. The detection of the analytes is based on the change in the external coupling angle as a function of the concentration of the analyte. Methods based on changes in the refractive index are generally distinctly less sensitive than luminescence methods. International Publication Number WO 94/27137 proposes, for example, an apparatus and a method for performing immunoassays using evanescently excited fluorescence. The apparatus consists of a continuous optical waveguide having two parallel flat surfaces and one lateral edge acting in conjunction with a lens as the internal coupling element. A plurality of specific link partners are immobilized on at least one surface. In a preferred embodiment, the specific link partners are configured on the continuous waveguide, such that they are physically separated from each other. In the working example, they are distributed in the form of points on the surface of the waveguide. Based on the disclosed modalities, it must be assumed that the efficiency achieved through internal coupling by means of the lateral edge is lower than in the case of internal coupling by means of grids: in addition, due to the great thickness of the layer ( self-supported waveguide). the force of the evanescent field, and consequently the efficiency of the excitation, are considerably lower than in the case of monomadal waveguides dp a relatively small layer thickness. Above all, the sensitivity of the configuration is limited as a result. The configurations which apply several specific binding partners to a continuous waveguide layer also have the drawback that the excitation light excites all molecules labeled with fluorophore. Therefore, the selection of the measurement sites according to the location is not possible. In addition, fluorescent photons evanescently retro-coupled, can contribute to the signal from the neighboring point, and consequently, lead to measurement errors. In the integrated optics for application in telecommunications, flat optical components based on glass containing waveguides in the form of channels are known. The waveguide channels are produced by the exchange of individual ions on the surface, with the help of masks (Glastechnische Berichte, Volume 62, page 285, 1989). It results in a physically interconnected layer that exhibits a slight increase in the refractive index, in the channels that have been added with ions. The increase is generally less than 5 percent. These components are complicated and expensive to produce. In the SPIE publication, volume 1587, ChemicaL, Biochemical and Environmental Fiber Sensors TTT (1991), pages 88-113. RE. Kunz describes optical waveguides that bifurcate and then come together again, and that PSDPGÍ almentp are suitable for integrated optical instruments, such as interferometers.not.

These structures are not suitable for the measurement of evanescently excited luminescence, since the elements can not be directed individually, and because the configuration of a plurality of bifurcations one after the other, quickly leads to large losses of intensity for the light wave internally coupled at the first fork. Since the opening angle of these bifurcations is small (typical of 3o), the distances between the two branches of a bifurcation, in the case of small components, are short, or otherwise, the dimensions of the components are what to do correspondingly bigger. which is generally undesirable. In addition, the fixed phase relationship between bifurcated waves is not required for luminescence measurements. In International Publication Number WO 92/19976, R. Kunz again describes a configuration comprising a plurality of integrated measuring strips for detecting a complex signal; this can be especially, the detection of an odor by means of an artificial nose. The use of substantially monomodal flat inorganic waveguides for luminescence detection methods is mentioned only generically in the prior art, without any description of the specific requirements associated with excitation and luminescence detection. In particular, there is no indication of the layer thickness ranges, or the modulation depths with which good or very good results can be obtained. It has now been discovered that it is possible to produce, in a simple manner, a sensor platform based on at least two separate flat inorganic dielectric waveguide regions, on a common substrate, whose platform is suitable for excitation and parallel evanescent detection of the luminescence of identical or different apallites. These separate waveguide regions may each have one or more coupling grids. A substantial advantage of this sensor platform is that, for example, several sample solutions with a high degree of sensitivity can be analyzed simultaneously. No washing or cleaning steps are required between individual measurements. with the result that a high production of samples per unit of time is achieved. This is of great significance, especially for routine analysis, or in the field of genetic engineering analysis. In addition to the analysis of a plurality of sample solutions in a simultaneous manner, it is also possible for SP to test a sample solution to determine several of its analytes simultaneously in succession on a sensor platform. This is convenient, especially in the case of the blood or serum test, which in this way can be performed in a particularly fast and economical way. When several sample solutions are analyzed simultaneously, the separate waveguide regions prevent interference between the luminescence signals from different samples. With this method a high degree of selectivity and low error rates are achieved. The separation of the waveguide regions also makes it possible to increase the selectivity and the sensitivity even more. through the targeted use of light sources of different wavelengths. An additional advantage of the sensor platform is that the individual separated waveguide regions can be selectively addressed in an optical, chemical, or fluid manner. A sensor platform having physically or optically separated flat waveguide regions, in which only one mode or a small number of modes is guided, is especially suitable. It is distinguished by an especially high degree of sensitivity and an extremely small structure. As a rule. this degree of sensitivity is not achieved with the multimodal waveguides of a flat construction. The excitation light can be coupled internally, for example, using lenses, prisms, or grids, or directly on the end face of the waveguide layer. The internal coupling, and when appropriate, the external coupling, using grids, is generally simpler and more efficient than with lenses or prisms, with the result that the intensity of the light wave coupled internally in the same way is older; this, together with a low degree of attenuation of the guided light wave, contributes to the very high sensitivity of this configuration. The sensitivity can be further increased by using an evanescent field as strong as possible. This offers the possibility of determining even very small amounts of luminescent material on the surface of the waveguide layer. An object of the invention is a sensor platform consisting of a continuous transparent substrate, and a transparent flat inorganic dielectric waveguide layer, wherein: a) the transparent inorganic dielectric waveguide layer is divided at least in the measurement region, in at least two waveguide regions, by virtue of the fact that the effective refractive index in the regions where the wave is guided is greater than in the surrounding regions, or the division in the waveguide layer. Waveguide is formed by a material on its surface that absorbs the light coupled inward; b) the waveguide regions are provided with an internal coupling grid each. or with a common internal coupling grid, such that the propagation direction of the wave vector is maintained after the internal coupling, and c) where appropriate, the waveguide regions are provided with an external coupling grid each one, with a common external coupling grid. The invention does not include configurations of two waveguide grids which, for example, initially branch out in the form of a Y, and then join together again at both ends, since in that case, the propagation direction of the vector of the wave changes after the internal coupling. These configurations are already known and are used, for example, as interferometers. In the present invention, the purpose of the separate waveguide regions is to provide a sensor platform for the simultaneous detection of evanescently excited luminescence from one or more analytes. The terms "measurement section" and "measurement region" are used as synonyms within the context of the present invention. The geometric shape of the separated waveguide regions is itself optional. It is conveniently regulated by the structure of the device as a whole, where the sensor platform is installed. Examples of geometric shapes are lines, strips, rectangles, circles, ellipses, chessboard patterns, lattices, honeycomb patterns, or irregular tiles. The divisions between the individual waveguide regions are essentially straight lines. For example, they can reach a point at the ends, and can be made wider to narrower than in the measurement region.

The waveguide regions are preferably configured in the form of separate strips, rectangles, circles, ellipses, and checkerboard patterns. The waveguide regions are especially configured in the form of parallel strips. A further preferred embodiment is obtained when the waveguide regions are configured in the form of parallel strips which are joined together at one or both ends, the direction of propagation of the wave vector after inward coupling being unchanged. Another convenient embodiment is one in which the strips are joined together at one end, and the other end is left open, leaving unchanged the propagation direction of the wave vector after the internal coupling. Figures a to Id, and 2a to 2d, illustrate several additional possible modalities. The reference numerals denote: 1 the waveguide layer that has been applied to a substrate: 2 the divisions, which are formed either by an absorbent material on the surface of the waveguide layer, or by a reduction in the effective refractive index in the plane of the layer, which in the simplest case, is achieved by means of an air gap instead of the waveguide layer: 3, 3 'the coupling grids towards in and outward coupling, respectively. In Figure la, the waveguide regions (= measurement regions) are interrupted by divider regions. These divider regions do not come into contact with the coupling element. In the case of Figure Ib, internal coupling and external coupling grids are present which are common to all measurement regions. There is no contact with the dividing regions. In Figure 1, the divisor regions extend beyond the coupling element. However, this does not affect the internal coupling in the waveguide regions. Figure Id comprises two coupling grids, but otherwise corresponds to Figure le. Figures 2a to 2d show a configuration in which the coupling grids are not continuous, but where each waveguide region has its own individual grid. Physically or optically separated waveguide regions can be produced using known methods. There are two possible basic methods. For example, a) SP layers can be physically constructed separately from the beginning in a vapor deposition method using masks, or b) a continuous layer is produced, and then structured using suitable methods. An example of method a) is the vapor deposition of the inorganic waveguide material, with a suitably structured mask covering part of the sensor platform. These masks are known from the production of integrated circuits. The masks should be in direct contact with the sensor platform. You can use positive and negative masks. It is also possible to apply a suspension of the inorganic wave guide material to the sensor platform through a suitably structured mask, and produce the wave guide layer by the sol-gel technique. In this way, separate waveguide regions are formed, the division being carried out in the simplest case by means of an air gap. However, this clear can be subsequently filled with a material different from a refractive index lower than that of the waveguide layer. If the division into several waveguide regions is done in this manner, the difference in effective refractive index between the waveguide region and the adjacent material is preferably greater than 0.2, especially greater than 0.6 units. An example of method b) is the vapor deposition of an inorganic waveguide material, to form a continuous layer, which is then divided into individual waveguide regions by mechanical scraping, machining of the material with laser, lithographic processes. fiels, or plasma processes. The steam tank is usually made under vacuum conditions. In the same way, it is possible to deposit plasma. Special mention must be made to machining using a driven excimer, and solid state laser devices or continuous gas laser devices. In the case of driven high-energy laser devices, the structuring can be carried out over a large area through a mask. In the case of laser devices that operate continuously, the focused beam is generally passed over the waveguide layer to be structured, or the waveguide layer moves relative to the beam. Suitable lithographic processes are recording techniques, such as those used in the production of printed circuit boards or microelectronic components. These processes allow to have an extraordinarily wide variety of geometric patterns, and a fineness of the structure in the micras or submicron range. It is important, in the case of any ablative machining process, that the waveguide layer be removed partially or completely, but without the sensor platform being completely divided. In the same way, any intermediate layers that may be present can be completely or partially removed. In a modified form of method b), first a continuous layer of an inorganic dn pnria material and guide is applied, and then, in a second step, using an absorbent material that interrupts the waveguide, a structure is applied to that layer , such that the waveguide regions are divided by the absorbent regions, and therefore, without waveguide. The absorbent materials can be inorganic materials, such as metals having a high optical absorption coefficient, for example, gold, silver, chromium, or nickel, or organic compounds, for example dyed and pigmented polymers. These materials can be applied to the wave guide layer in the form of continuous layers, or as is the case with metals, in the form of aqueous colloidal solutions. A selection of different methods is available. Depositing processes for structuring carried out under vacuum conditions have already been mentioned above. In the same way, colloidal materials can be used in water or in organic solvents, such as gold in water, to structure the waveguide regions. The deposit of colloidal gold on the surfaces by means of spontaneous "assembly" has been described, for example, by R. Griffith et al., Science 1995. 267. 1629-1632. For example, streams of laminar parts physically or fluidly separated from a colloidal gold solution can be allowed to flow over the waveguide layer, the gold particles being deposited, for example, in the form of strips. The surface is dried, and separate waveguide regions are obtained according to the invention. The deposited gold colloids must have a minimum size of 10 to 15 nanometers, in order that the desired absorption is present. They are preferably from 15 to 35 nanometers in diameter. The deposition of colloidal gold can also be done by stamping on the surface. The stamping of dissolved organic materials is described by Whitesides as "icrocontact printing", and has been used to structure gold surfaces using liquid alkanethiols (J.L. Wilbur et al., Adv. Mater. 1994, 6, 600-604; Y. Xia and G.M. Whitesides, J. Am. Chem. Soc. 1995, 117, 3274-3275). For example, the colloidal gold solution can be internally aspirated from an elastomeric cushion having the desired pattern of structuring, and the pattern of structuring can be transferred to the waveguide surface by application of the pattern. The methods that use organic solvents or water are very flexible and quick to use. These allow the structuring of the waveguide to take place immediately before a luminescepcia test is performed. In some cases, the surface of the waveguide layer has to be modified in such a way that before the colloidal deposit of. for example, gold, there is good adhesion between the colloidal particles and the modified surface. Adhesion can be achieved by means of hydrophobic interaction. van der Waals forces, dipole-dipole interaction. Simple electrostatic interaction, or by means of covalent bond. The interaction can be produced by functionalizing the colloids and / or the surface of the waveguide layer. A suitable method for modifying the surface, and for achieving adhesion, is, for example, silanization, as described in Advapces in Colloid and Inferid Science 6, L. Boksányi, 0. Liardop and E. Kováts, (1976) 95 -137. This silanization is also used to improve the adhesion of the recognition elements in affinity detection. In particular, the mercapto-terminated silane is suitable. such as (mercaptomethyl) dimethylethoxysilane, to cause the adhesion of the gold by means of the formation of a covalepte bond of sulfur-gold. Another modification of method b) consists in applying to the continuous layer of inorganic waveguide material, in a second step, the same inorganic material in the form of a structure, with the result that, by increasing the thickness of the In this case, an increase in the effective refractive index is achieved, and consequently, the propagation of the light wave mode is concentrated in the resulting measurement regions. These "plate waveguides" and methods for producing them are described by H.P. Zappe in "Introduction to Semiconductor Integrated Optics", Artech House Inc., 1995. The width of the strip of the wave guide layers is preferably 5 microns to 5 millimeters, especially 50 microns to 1 millimeter. If the width of the waveguide regions is reduced too much, the available sensor area will also be reduced. Conveniently, the width of the strip and the required sensor area are coupled with one another. The size and width of the individual waveguide regions can be varied within a wide range, and depend substantially on the intended use and the structure of the system as a whole. When in the form of strips, the individual waveguide regions are preferably from 0.5 to 50 millimeters, especially from 1 to 20 millimeters, and most especially from 2 to 10 millimeters in length. The number of strips on the sensor platform of preference is from 2 to 1,000. especially from 2 to 100. The individual waveguide regions can be configured, for example, as strips on the substrate in two or more groups of at least two strips each, thereby forming a multiple detection region. The great practical advantage of these assembled multiple sensing regions is that the sensor platform does not need to be cleaned or replaced between the successive measurements of multiple analytes, but merely that P has to be removed. relationship with the excitation, fluid, and detection units.

An additional advantage is that these multiple detection regions are more economical to produce. A very substantial advantage is the fact that it does not require a large consumption of time and high cost for the separation, in divided sensor platforms. Each multiple detection region preferably consists of 2 to 50, especially 2 to 20 separate waveguide regions. Preferably there are from 2 to 100, especially from 5 to 50 multiple detection regions on the sensor platform. Figures 3a and 3b show a possible configuration of a sensor platform having a plurality of multiple detection regions, wherein the substrate is in the form of a disc, and which can be produced by press molding in a similar manner to the one currently used for compact discs. The overall configuration may consist of a disc-shaped sensor platform having a plurality of multiple detection regions, and a fluid disk comprising the fluid supply lines and the real cell spaces. The two parts unite, for example they adhere, to each other, and form a unit. However, cell spaces in the form of cavities can alternatively be preformed in the disk-shaped sensor platform. Then this modality is covered with a flat lid. The reference numerals 1 to 3 are as defined above, 4 denotes a complete multiple detection region, 5 is the substrate, and 6 is a central cut portion that can accommodate an axis to make it possible to pass the multiple detection regions 4, by rotation, under the excitation and detection optics. 7 and 7 'denote the inlet and outlet openings for the solutions required during the course of the test, said solutions are generally brought into contact, by means of a transverse flow cell having at least two openings, with the immobilized recognition elements. over the waveguide regions. Alternatively, the multiple detection regions can be configured in concentric circles. The distances between the individual multiple detection regions. for example, they may be such that rotation through an angle of 5 to 20 degrees brings a new multiple detection region under the excitation and detection optics. FIGS. 4 a and b show an analogous construction of the sensor platform on a disk, with the difference that, compared to FIG. 3, the individual multiple detection regions 4 are configured radially rather than tangentially, which leads to better use of the surface area. An additional configuration is shown in Figures 5a and 5b. The individual multiple detection regions 4 are configured in the form of a rectangular checkerboard pattern. However, the multiple detection regions can also be configured in the manner of individual images in a film strip. The film strip can be in the form of a flat element, or it can be wound. The individual multiple detection regions can be transported under the excitation and detection optics in a manner analogous to a film. The preferences indicated for the separate waveguide regions also apply in the case of multiple detection regions. A sensor platform within the context of the present invention is a self-supporting element that can be constructed in the form of a strip, a plate, a disk, or any other desired geometric shape. It is essentially flat. The geometric shape selected by itself is not critical, and can be selected to fit the structure of the appliance as a whole, where the sensor platform is installed. However, the sensor platform can also be used as an independent element, physically separated from an excitation light source and from the optoelectronic detection system. Preference is given to configurations that allow substantial miniaturization. Suitable substrates are, for example, glass of all types, or quartz. Preferably, glass is used, having the lowest possible optical refractive index, and the lowest possible intrinsic luminescence degree, and allowing the simplest possible optical machining, such as recording, grinding, and polishing. The substrate is preferably transparent, at least at the excitation and emission wavelengths. The microscopic roughness of the substrate should be as low as possible. They can also be used as transparent thermoplastic plastic substrates, such as those described, for example, in European Patent Number EP-A-0, 533, 074. The substrates can be further covered with a thin layer having a higher refractive index. low that, or equal to, that of the substrate, and that is not thicker than 0.01 millimeters. That layer can be used to prevent the problematic excitation of fluorescence in the substrate, and also to reduce the surface roughness of the substrate, and can consist of thermally crosslinkable or structurally crosslinked plastics, or alternatively in inorganic materials such as Si02. In the presence of an intermediate layer, with a refractive index lower than one of the waveguide layer, and with a layer thickness considerably greater than the penetration depth of the evanescent field (ie, >; > 100 nanometers). the transparency of only this intermediate layer, at the excitation and emission wavelength, is sufficient if the excitation light is thrown from the upper side of the sensor platform. In this case, the substrate can also be absorbent. Especially preferred substrate materials consisting of transparent thermoplastic plastics are polycarbonate, poly-iron, or polymethyl methacrylate. The refractive index of preference is the same for all waveguide layers, that is, all waveguide layers are preferably made of the same material. The refractive index of the waveguide layers must be greater than that of the substrate and any intermediate layers that are used. The transparent flat wave guide layer preferably consists of a material having a refractive index greater than 2. Inorganic materials, especially inorganic metal oxides, such as TiO 2, are suitable, for example. ZnO, Nb3 s Ta Q, 5HfO f ZrO. 2 Ta33 s and TiO2 are preferred. The thickness of the waveguide layers is preferably 40 to 1,000 nanometers, especially 40 to 300 nanometers, and most especially 40 to 160 nanometers. In a preferred embodiment, the wave guide layers are of the same thickness. The depth of modulation of the grids is preferably from 3 to 60 nanometers. especially from 3 to 30 nanometers. The ratio of the depth of modulation to the thickness of the layers is preferably equal to, or less than, 0.5 and especially equal to, or less than, 0.2. The grids for the internal coupling of the excitation light, or for the external coupling of the luminescence light back-mounted, are in the form of optical diffraction gratings, preferably in the form of release grids. The release structure can have different forms. Sine, rectangular, or sawtooth structures are suitable, for example. The processes for the production of these grids are known. Photolithographic or holographic processes and recording techniques are used predominantly for their production, such as those described, for example, in Chemical, Biochemical and Environmetal Fiber Sensors V. Proc. SPIE, Volume 2068, 313-325. 1994. Molding or stamping processes for organic substrates can also be used. The structure of the grid can be produced on the substrate, and then it can be transferred to the waveguide layer, where then the grid structure is reproduced, or the grid is produced in the waveguide layer itself. The period of the grid can be from 200 to 1,000 nanometers, the grid having in a convenient manner only one periodicity, that is to say, being monodifractive. The period of the selected grid is preferably one which allows the excitation light to be coupled in the first diffraction order. The depths of modulation of the grids are preferably of the same magnitude. The grids preferably have a bar to space ratio of 0.5 to 2. "Bar to space ratio" should be understood, for example, in the case of a rectangular grid, as the ratio of the width of the bars to the width of the spaces . The grids can be used both for the coupling of the excitation light in the individual waveguide layers, and for the external coupling of the retro-coupled luminescence light in the waveguide layers. For the analysis of samples of different luminescences, it may be convenient that all or some of the internal coupling and external coupling grids have different grid constants. In a preferred embodiment, the grid constants are the same for all grids. If some of the grids are used for internal coupling, and some for external coupling, the light, the grate constant of the grid or of the grids, is preferably different from the grid constant of the grid or of the coupling grids. external. The grid separation is preferably B <; 3 X¡ / € X_ / e which is the length in which the intensity I $ le the guided radiation has fallen to Io e In a preferred group of sensor platform modalities: transparent flat inorganic dielectric waveguide regions over the The sensor platform is divided at least one along the measuring section, by a jump in the refractive index of at least 0.6, and each region has one or two separate grid couplers, or all regions have joints one or two common grid couplers, the transparent planar inorganic dielectric waveguide regions having a thickness of 40 to 160 nanometers, the depth of modulation of the gratings being from 3 to 60 nanometers, and the ratio of the modulation depth being to the thickness equal to, or less than, 0.5. The simplest method to achieve a jump in the refractive index of 0.6 or more is that the waveguide layer is completely divided and contains a clear air, or during the measurement, optionally water. The waveguide layers of preference guide only 1 to 3 modes, and are especially monomodal waveguides. A further object of the invention is a modified sensor platform, wherein one or more specific binding patterns are immobilized on the surface of the waveguide regions as chemical or biochemical recognition elements for one or more identical or different analytes . Different specific link partners can be applied to the surface of a waveguide region, the physical separation of the same within each waveguide region is not important. For example, they may be present thereon in the form of a random mixture. This is convenient when analytes having different emission wavelengths are to be simultaneously determined by means of an external coupling grid. The specific link partners on the surface of each waveguide region of preference are physically separated from each other. The specific binding partners can be immobilized at different sites on the waveguide regions, for example, by photochemical crosslinking, as described in International Publication Number WO 94/27137. Another method comprises the drip application of the specific binding participants to be immobilized, using a multi-pipette head. This can also be done using a modified ink jet printhead, with piezoelectric actuators. This has the advantage that the method can be carried out quickly, and that very small quantities can be used. This is a precondition for the production of thin strips or other finely structured geometrical patterns. Another preferred method for the physically separate detachment of the specific link partners over the waveguide regions, which is very simple to perform, is based on the use of a flow cell, it being possible for the separation to be carried out in the cell of flow, either mechanically in the form of divider bars, or fluidly in the case of a laminar flow. In this method, the geometrical configuration of the partial currents supplied by the link participants substantially corresponds to the configuration of the waveguide regions on the sensor platform. This method of immobilization using a flow cell is particularly advantageous when specific binding partners are to be embedded in an environment that is stable only in the fluid medium, as is the case, for example, with the receptors linked to the lipid membrane. . In particular, it is possible in this way to deposit specific binding partners that are covalently linked to the gold colloids. in the same way as described above for the production of non-waveguide regions. In order to obtain the waveguide in the immobilization regions, it is necessary to use dp gold colloids with very small diameters of less than 10 nanometers. and especially less than 5 nanometers. An additional method that is simple to perform in the same way, is based on stamping the surface with the specific link participants, or with specific link partners linked to metals, in a manner analogous to that described above for the production of the regions that are not waveguide. A preferred metal is gold. The preferred physically separated patterns are strips, rectangles, circles, ellipses, or chessboard patterns. Preference is given especially to a modified sensor platform where only one specific link partner is configured on the surface of each waveguide region. Another preferred embodiment of the modified sensor platform is obtained if an adhesion promoting layer is located between the waveguide regions and the immobilized specific binding participants. The thickness of the adhesion promoter layer is preferably equal to, or less than. 50 nanometers, especially less than 20 nanometers. In addition, it is possible that the adhesion promoter layers are selectively applied only in the nano-guide regions. or that are attenuated in regions that are not waveguide, for example, by means of photochemical activation, or by using wet chemical methods, such as multi-pipette head, inkjet printers, flow cells with mechanical separation or flow of the streams, deposit of colloids, or stamping of the surface. Methods for direct immobilization of specific recognition elements onto an optionally chemically modified or functionalized surface have been previously described. The selective immobilization of the specific recognition elements exclusively on the waveguide regions, either directly or in the manner of adhesion promoter layers, when a sample cell is used that covers both the waveguide regions and those which not be waveguide, may lead to an increase in the sensitivity of the detection method, since it reduces the non-specific binding of analytes in regions not used for signal generation. The preferences described hereinabove for the sensor platform are applied in the same manner to the modified sensor platform. The modified sensor platform is preferably completely or partially regenerable. and it can be used several times. Under suitable conditions, for example, at a low pH, at an elevated temperature. using organic solvents, or using the so-called cauteric reagents (salts), the affinity complexes can be selectively dissociated without substantially impairing the binding capacity of the immobilized recognition elements. The precise conditions depend a lot on the individual affinity system. A specific form of luminescence detection in an assay consists of the immobilization of the inescent lu substances that are used for the detection of the analyte directly on the surface of the waveguide regions. These substances can be, for example, a plurality of luminophores linked to a protein, which can thus be excited up to the luminescence on the surface of the waveguide regions. If you pass the participants who have affinity for the proteins on that immobilized layer. the luminescence can be altered by the same, and in this way the number of partners that have affinity can be determined. In particular, it is also possible for both participants of an affinity complex to be labeled with luminophores, for example, in order to make determinations of the concentration based on the transfer of energy between the two, for example, in the form of a extinction of luminescence. Another preferred form of immobilization for chemical or biochemical affinity dp tests consists of immobilization on the surface of the sensor platform, from one or more specific link participants as chemical or biochemical recognition elements for the analytes themselves, or for one of the link participants. The tests may consist of one or more stages in the course of which, in successive steps, one or more solutions may be passed containing specific binding partners for the recognition elements immobilized on the surface of the sensor platform, on the surface of the sensor platform, the analytes linking in one of the partial steps. The apallites are detected by the link of the participants lumiplescentemepte marked in the affinity test. The substances marked with luminescence can be any one or more of the binding partners of the affinity assay, or an analog of the analytes provided with a phosphor. The only precondition is that the presence of analytes must selectively lead to a luminesce signal. or selectively to a change in the luminescence signals. In order to increase the surface of the chemically active sensor, it is also possible to immobilize the chemical or biochemical recognition elements on microparticles, called "granules", which can be fixed on the sensor platform by suitable methods. The prerequisites for the use of granules, which may consist of different materials, such as plastics, are that, first, the interaction with the analytes should proceed. to a significant degree, within the penetration depth of the evanescent field, and that, secondly, it does not interfere significantly with the waveguide properties. In principle, the recognition elements can be immobilized, for example, by hydrophobic adsorption or covalepte bonding directly on the waveguide regions, or after the chemical modification of the surface, for example, by silanization or the application of a layer polymeric In addition, for the purpose of facilitating the immobilization of the recognition elements directly on the waveguide, a thin intermediate layer may be applied, for example. consisting of Si02. as the adhesion promoter layer. Silanization of glass and metal surfaces has been comprehensively described in the literature, for example, in Advances in Colloid and Interface Science 6. L. Boksányi, 0. Liardop and E. Kováts, (1976) 95-137. The possible specific methods to perform the immobilization have already been described previously in the present. The appropriate recognition elements are. for example, antibodies for aptigens, binding proteins, such as protein A and G, for immunoglobulins, biological and chemical receptors for ligands, chelators for components with histidine tag. for example proteins marked with histidine. or oligopucleotides, and simple strands of RNA or DNA for their complementary strands, avidin for biotin, enzymes for enzymatic substrates. cofactors or inhibitors of enzymes, or lectins for carbohydrates. Knowing which of the relevant affinity patterns has been immobilized on the surface of the sensor platform depends on the architecture of the assay. The elements of recognition can be natural, or they can be produced or synthesized through genetic engineering or biotechnology. The expressions "element of recognition" and "specific link participants" are used as synonyms. The assays themselves may be one-step complex formation processes, for example, competitive assays, or multi-step processes, for example, sandwich assays. In the simplest example of a competitive assay, the sample, which comprises the analyte at an unknown concentration, and a known amount of a compound that is identical, apart from being labeled by luminescence, is contacted with the surface of the platform of the sensor, where the molecules marked by luminescence and unmarked compete for binding sites on their immobilized recognition elements. In this test configuration, a maximum luminescence signal is obtained when the sample does not contain analyte. As the concentration of the substance to be detected increases, the luminescence signals that can be observed decrease. In a competitive immunoassay. the immobilized recognition element on the surface of the sensor platform does not have to be the antibody. but alternatively it can be the antigen. In general it is a matter of choice in the chemical affinity or biochemical tests, which of the participants is immobilized. This is one of the main advantages of luminescence-based assays over methods such as surface plasmon resonance or interferometry. which rely on a change in the mass adsorbed in the evanescent field of the waveguide region. In addition, competition in the case of competitive trials, need not be limited to binding sites on the surface of the sensor platform. For example, a known amount of an antigen can be immobilized on the surface of the sensor platform, and then an unknown quantity, which is to be detected, of the same antigen can be contacted with the sample comprising as analyte, and also antibodies marked by luminescenc a. In that case, the competition to bind the antibodies takes place between the antigens immobilized on the surface, and the antigens in solution. The simplest example of a multi-step test. is a sandwich assay, in which a primary antibody is immobilized on the surface of the sensor platform. The binding of the antigen to be detected, and of the secondary antibody labeled by luminescence used for detection, with a second antigen. It can be carried out either by contacting, in succession, the solution comprising the antigen, and a second solution comprising the antibody labeled with luminescence, or after previously joining the two solutions, in such a way that finally the partial complex consisting of antigen and antibody marked by luminescepcia. The affinity assays may also comprise additional additional link steps. For example, in the case of sandwich immunoassays, protein A can be immobilized on the surface of the sensor platform in a first step. The protein specifically binds the immunoglobulins with their so-called Fc portion, and then they serve as primary antibodies in a subsequent sandwich assay, which can be performed as described. There are many other forms of affinity assay, for example, using the known avidin-biotin affinity system. Examples of affinity assay forms will be found in J. H. Rittenburg. Fundamentáis of Immunoassay: in Development and Application of Immunoassay for Food Analysis, J.H. Rittenburg (Ed.), Elsevier, Essex 1990, or in P. Tijssen, Practice and Theory of Enzyme Immunoassays, R.H. Burdon. P.H. van Knippenberg (Eds). Elsevier Amsterdam 1985. A further object of the invention is a method for the parallel determination of one or more luminescence. using a sensor platform, or a modified sensor platform according to the invention, said method comprises placing one or more liquid samples in contact with one or more waveguide regions on the same sensor platform, coupling the excitation light in the waveguide regions, causing it to pass through the regions of the waveguide. waveguide, thus exciting in parallel in the evanescent field the luminescent substances of the samples, or the luminescent substances immobilized on the waveguide regions, and, using optoelectronic components, measure the luminescences produced by them. The preferences described hereinabove for the sensor platform, and the modified sensor platform, also apply to the method. Only substantially parallel light is suitable for luminescence excitation. "Substantially parallel" should be understood within the context of this invention, to mean a divergence of less than 5o. This means that the light could be slightly divergent or slightly convergent. The use of coherent light is preferred for luminescence excitation, especially laser light having a wavelength of 300 to 1,100 nanometers. more especially from 450 to 850 nanometers, and most especially from 480 to 700 nanometers. Examples of the laser devices that can be used are dye laser devices, gas laser devices, solid state laser devices. and semiconductor laser devices. If necessary, the emission wavelength can also be duplicated by means of non-linear crystal optics. By using optical elements, the beam can also be focused additionally. polarized or attenuated by means of neutral gray filters. Especially suitable laser devices are argon / ion laser devices and helium / neon laser devices, which emit at wavelengths of 457 nanometers to 514 panometers, and from 543 nanometers to 633 nanometers. respectively. Diode laser devices, or dual frequency diode laser devices of a semiconductor material that emit a fundamental wavelength of 630 nanometers to 1100 panometers, are very particularly suitable. Due to their small dimensions and low energy consumption, they allow a substantial miniaturization of the sensor system as a whole. "Sample" should be understood within the context of the present invention, as the entire solution to be analyzed, which may comprise a substance to be detected - the analyte. The detection can be carried out in a single step or multiple step test during which the surface of the sensor platform is brought into contact with one or more solutions. At least one of the solutions used comprises a luminescent substance that can be detected according to the invention. If a luminescent substance has already been adsorbed on the waveguide region, the sample may also be free of luminescent constituents. The sample may contain other constituents, such as pH regulators, salts, acids, bases, surfactants, additives that have an influence on the viscosity, or dyes. In particular, a saline physiological solution can be used as a solvent. If the luminescent portion is itself liquid, the addition of a solvent can be omitted. In that case, the luminescent substance content in the sample can be up to 100 percent. The sample may also be a biological medium, such as egg yolk, a body fluid or the components thereof, especially blood, serum, plasma, or urine. It can also be surface water, solutions of extracts from natural or synthetic media, such as soils or parts of plants, liqueurs of biological processes, or synthetic liquors. The sample can be used either undiluted or with added solvent. Suitable solvents are water, aqueous buffer solutions, and protein solutions, and organic solvents. Suitable organic solvents are alcohols, ketones, esters and aliphatic hydrocarbons. Preference is given to the use of water, aqueous regulators, or a mixture of water and an iscible organic solvent. However, the sample may also comprise constituents that are not soluble in the solvent, such as pigment particles, dispersants, and natural and synthetic oligomers or polymers. Then the sample is in the form of an optically opaque dispersion or emulsion. Like the luminescent compounds, functionalized luminescepts dyes having a luminescence of a wavelength in the scale from 330 nanometers to 1,000 nanometers can be used, such as rhodamines, fluorescein derivatives, coumarin derivatives, biphenyls, diethyrim, stybene derivatives , phthalocyanines, naphthalocyanines, polypyridyl / ruthenium complexes, such as ruthenium chloride tris (2,2'-bipyridyl), ruthenium chloride tris (1.10-phenanthroline) ruthenium chloride tris (, 7-diphenyl-1 .10-phenanthroline) ), and polypyridine / phenazine / ruthenium complexes, platinum / porphyrin complexes. such as octaethyl-platinum-porphyrin complexes. of europium and long-lived terbium, or rip cyanine dyes. The dyes having wavelengths of absorption and emission on the scale of 600 to 900 nanometers are especially suitable for blood or serum analysis. Dyes, such as fluorescein derivatives, are very particularly suitable. containing functional groups through which they can be linked in a covalent manner. such as fluorescein isothiocyanate. Functional fluorescent dyes that are commercially available from Biological Detectio Systems Inc., for example, the mono- and bi-functional Cy5.5MR dyes, which are also described, for example, in Clinical Chemistry 40 (9) are also very suitable: 1819-1822, 1994. The preferred luminescence is fluorescence. The use of different fluorescent dyes that can all be excited by light of the same wavelength, but having different emission wavelengths, may be convenient, especially when using external coupling grids. The luminescent dyes used can also be linked chemically with polymers, or with one of the binding partners in biochemical affinity systems, for example antibodies or fragments of antibodies, antigens, proteins, peptides, receptors or their ligands, hormones or hormone receptors, oligonucleotides. DNA strands and RNA strands, DNA or RNA analogs, binding proteins, such as proteins A and G. avidin or biotin, enzymes, cofactors or inhibitors of enzymes, lectins, or carbohydrates. The use of covalepte luminescence labeling mentioned at the end is preferred for reversible or irreversible affinity (bio) chemical tests. It is also possible to use spheroids, lipids. and chelators marked by luminescence. In the case especially of hybridization tests with DNA strands or oligonucleotides, it is also particularly suitable to intercalate 1 or inescent dyes, especially when different ruthenium complexes are present - they exhibit improved luminescence when intercalated. When these labeled compounds are contacted by luminescence, with their affinity partners immobilized on the surface of the sensor platform, their linkage can be quantitatively determined easily using the measured luminescence intensity. Likewise, it is possible to make a quantitative determination of the analytes, measuring the change in the luminescence when the sample interacts with the luminophores, for example in the form of. extinction of luminescence by oxygen, or improvement of luminescence resulting from conformational changes in proteins. In the method according to the invention, the samples can be brought into contact with the waveguide regions when they are stationary, or they can be passed on continuously, being possible that the circulation is open or closed. An additional important form of application of the method is based primarily on limiting the generation of signals - in the case of a backward coupling that also applies to signal detection - to the evanescent field of the waveguide, and second , on the reversibility of affinity complex formation as an equilibrium process. Using appropriate flow rates in a cross-flow system, the link or desorption, ie, dissociation, of the link, of the affinity participants tagged with luminescence in the evanescent field, can be followed in real time. Therefore, the method is suitable for kinetic studies to determine different association or dissociation constants, or for displacement assays. The evanescently excited luminescence can be detected by known methods. Photodiodes, photocells, photomultipliers, CCD cameras, and detector arrays, such as CCD arrays and CCD arrays, are suitable. Luminescence can be projected onto the latter by means of optical elements, such as mirrors, prisms, lenses, Fresnel lenses. and lenses of graduated index, being possible that the elements are configured individually or in the form of fixes. In order to select the emission wavelength, known elements can be used, such as filters, prisms, monochromators, dichroic mirrors, and diffraction gratings. Especially when a relatively large number of physically separate separate link participants is present, it is convenient to use detector arrays configured in the immediate vicinity of the sensor platform. They are conveniently arranged between the sensor platform and the optical elements of the detector array to separate excitation and luminescence light, such as holographic or interference filters. One form of the method is to detect luminescence evanescently e / cited, isatropicarnentp radiated.

In another form of the method, the evanescently excited luminescence retro-coupled in the waveguide region is detected on one edge of the sensor platform, or by means of an external coupling grid. The intensity of the retro-coupled luminescence is surprisingly high, with the result that in the same way a very good sensitivity is achieved using this procedure. In another form of the method, both the isotropically radiated, evanescently excited luminescence and the luminescence coupled backward in the waveguide are detected, one independently of the other, but in a simultaneous manner. Due to the different selectivity of these two luminescence detection methods, whose selectivity is a function of the distance between the luminophores and the waveguide region, this form of the method can be used to obtain additional information regarding the physical distribution of the luminophores. This also makes it possible to distinguish between the photochemical bleaching of the luminophores, and the dissociation of the affinity complexes carried by the luminophores. Another advantage of the method is that. In addition to the detection of luminescence, the absorption of the radiated excitation light can be determined simultaneously. Compared with multimodal waveguides of a fiber optic or planar construction, in this case a substantially better signal ratio to p is achieved. The effects of luminescence extinction can be detected with great sensitivity by means of the simultaneous measurement of luminescence and absorption. The method can be carried out by radiating in the excitation light in a continuous wave operation (oc), that is, the excitation is carried out with light of an intensity that is constant over time. However, the method can also be performed by radiating the excitation light in the form of a timed pulse having an impulse length of, for example, from a picosecond to 100 seconds, and detecting the luminescence in a time-resolved manner. - in the case of short impulse wavelengths - or intervals from seconds to minutes. This method is especially convenient when, for example, the rate of bond formation is to be monitored analytically, or the reduction in a luminescence signal resulting from photochemical bleaching is to be prevented by using short exposure times. In addition, the use of appropriately short pulse lengths, and adequate resolution of detection time, makes it possible to discriminate scattered light, Ra an emission, and short-lived luminescence of any undesired luminescent constituents of the sample or the material of the sensor that may be present, of the luminescence of the marker molecule (which in this case is as long as possible), since the emission of the analyte is only detected once the radiation has decayed Short life In addition. the detection of resolved luminescence in the time after the excited excitation, and, in the same way, the excitation and modulated detection, allow the investigation of the influence of the analyte binding on the behavior of the decay of the molecular luminescence. The decay time of the molecular luminescence can be used, together with the recognition of the specific analyte by the immobilized recognition elements and the physical limitation of the generation of signals towards the evanescent field of the waveguide, as an additional selectivity criterion . The method can also be performed by radiating the excitation light in a modulated intensity manner, at one or more frequencies, and detecting the resulting phase change and modulation of the luminescence of the sample. The parallel coupling of the excitation light in a plurality of waveguide regions can be performed in several ways: a) a plurality of laser light sources are used; b) the beam is enlarged from a laser light source using known suitable optical components, in such a way as to cover a plurality of waveguide regions and internally coupled grids; c) the beam is divided from a laser light source using diffraction or holographic optical elements in a plurality of individual beams, which are then coupled in the wave guide regions by means of the gratings, or d) is used an array of solid-state laser devices. A convenient method is also obtained by using a controllable baffle mirror, which can be used to internally or externally couple the waveguide regions with a time delay. In an alternative way, the sensor platform can be moved properly. Another preferred method is to excite luminescences with different laser light sources of identical or different wavelengths. Particular preference is given to the use of a single row of laser diode devices (laser arrangement) for the excitation of the luminescences. These components have the special advantage that they are very compact and economical to produce, and the individual laser diodes can be controlled individually. The preferences described for the sensor platform also apply in the case of the fluorescence detection method. Figure 6 is a diagrammatic representation of a possible complete construction. Reference numerals 1 and 3 are as previously defined herein, and other reference numerals are as follows: 8. sensor platform. 9. filters. 10. seal. 11. cross flow cell. 12. sample space. 13. excitation optics. 14. Optical / electronic detection.

The excitation light, for example, from a laser diode device 13, is ced by means of a first grid 3 in a waveguide region 1 of the sensor platform 8. On the underside of the sensor platform 8, and compressed tightly against the sensor platform, is a transveral flow cell 11. The solutions required for the test are flooded through space 12 in the cross flow cell 11, which may have one or more inlet openings, and one or more exit openings. The fluorescence of a binding partner is detected in the detector 14. on which the retro-ced fluorescence light is externally ced in the waveguide region by means of a second grid 3. The filters 9 serve to filter scattered light. The method is preferably used to analyze samples such as egg yolk, blood, serum, plasma, or urine. Another preferred method is obtained in the analysis of samples such as surface water, dirt or plasma extracts, and liquors of biological or synthetic processes. The present invention also relates to the use of the sensor platform, or modified sensor platform according to the invention, for the quantitative determination of biochemical substances in affinity detection. Since the generation and detection of the signal are limited to the chemical or biochemical recognition surface on the waveguide, and the noise signals are discriminated from the medium, the link of the substances with the recognition elements can be followed immobilized in real time. The use of the method according to the invention in the affinity selection or in the displacement tests, especially in the development of pharmaceutical products. by means of the direct determination of the association and dissociation velocities in a transverse flow system at suitable flow rates, therefore, it is also possible. The present invention also includes: a) the use of the sensor platform, or modified sensor platform according to the invention, for the quantitative determination of antibodies or antigens; b) the use of the sensor platform, or the modified sensor platform, for the quantitative determination of receptors or ligands, oligonucleotides, DNA or RNA strands, DNA or RNA analogs, enzymes, enzyme substrates, or factors or inhibitors of enzymes, lectins and carbohydrates, and c) the use of the sensor platform, or modified sensor platform according to the invention, for the selective quantitative determination of luminescent constituents of optically opaque fluids. The optically opaque fluids may be, for example, biological fluids, such as egg yolk, and body fluids, such as blood, serum, or plasma, but also samples of environmental analysis, such as surface water, dissolved soil extracts. , or extracts of dissolved plants. Also relevant are reaction solutions, such as those obtained, for example, in chemical production, especially dye solutions or reaction solutions of optical brighteners. All types of dispersions and preparations used, for example, in the textile industry are also relevant. in the understanding that they comprise one or more luminescent components. Therefore, the method can also be used for quality control. The following examples illustrate the invention. In all of the following examples, the M unit of concentration, denotes moles / liter.

Examples A: Production of different sensor platforms Example Al. Production using masks in the vapor deposition. A polycarbonate (PC) substrate is coated with Ti0 by means of steam deposition (process, sputtering, deposition rate: 0.5 A / second, thickness: 150 panometers). Between the target and the substrate, in the immediate vicinity of the substrate, a mask made of aluminum is introduced in which six strips of 30 millimeters in length and 0.6 millimeters in width have been cut. The six resulting waveguide regions (measurement regions) have a trapezoidal profile with a uniform thickness of 150 panometers in the central region, which is 600 microns wide, and a layer thickness that decreases on the sides in the form of a gradient (shading). The internally coupled laser light is confined to the waveguide region, since the effective refractive index is higher in the central region, because that region has the highest layer thickness.

Example A2 Production through subsequent division. The operation is performed using an ArF excimer laser device at 193 nanometers. The rectangular beam is concentrated using a cylindrical lens for a beam profile of 200 microns wide and 20 millimeters long focused on the sensor platform. The sensor platform has a continuous layer of Taf) s of 100 nanometers thick. At an energy density greater than 1 J / cm2, the entire layer is cut with a single laser pulse (10 nanoseconds).

Example A3 Production through subsequent division. The operation is performed using an Ar-ion laser device at 488 nanometers. The round laser beam is concentrated using a microscope lens (40x) for a diameter of 4 microns focused on the waveguide layer. The sensor platform has a continuous layer of TaO s 100 nanometers thick, and is located on a motor-driven positioning element (Newport PM500). Under a continuous laser irradiation, the platform is driven perpendicular to the beam at 100 millimeters / second. With an output of 700 mW, the entire waveguide layer is cut at the focus, with the result that two separate waveguide regions are formed.

Example A4. Production by applying a layer of absorbent cover structured by the vacuum method. Five parallel strips of a chrome / gold layer system. sp dppositan enn vapor on the wave guide of metal oxide (continuous) consisting of Ta D 5 (installation by tank with steam: Balzers BAK 400); first 5 panometers of Cr at 0.2 nanometers / second, then 45 nanometers of Au at 0.5 nanometers / second. The internally coupled modes are interrupted in the absorbent layers.

Example A5. Production by applying a layer of absorbent cover structured by the aqueous method. The surface of a metal oxide waveguide consisting of Taß 5 is silanized with (mercaptomethyl) dimethylethylsilane in the gas phase at 180 ° C. With the aid of a thin pipette, colloidal solution A (GoldSol) is applied. supplied by Aurion, average colloid diameter = 28.9 nanometers, concentration: A52o ~ 1, aqueous solution) to the modified surface in the form of droplets or strips, and incubated for 1 hour. After incubation, the surface is washed with water. Guided modal light is absorbed in the incubated sites. Downstream of the incubated sites, there is no longer any modal light present. The same applies in the case of the colloidal solution of Au B coated with protein A (P-9785 supplied by Sigma) average diameter = 18.4 nanometers A520 * 5.5, in 50 percent glycerol, 0.15 M NaCl, sodium phosphate 10 M, pH 7.4, PFi 20 0.02 percent, sodium azide 0.02 percent). The absorption patterns on the surface of the waveguide are still intact, even after rinsing several times with water and with ethanol. which shows the stability of the structures produced. By the manual application of rows of microdroplets (1 icrolitre) of the colloidal solution A, continuous light-absorbing strips can be produced.

Example A6. Production by applying a layer of absorbent cover structured by the aqueous method. The surface of a metal oxide waveguide consisting of TI02 is silanized with (mercaptomethyl) -dimethylethoxysilane in the gas phase at 50 ° C. A portion of the surface of the waveguide is then incubated in front of, and including a, the second external coupling grid, for 3 hours, with colloidal solution B (P-9785 supplied by Sigma) average diameter = 18.4 nanometers, A52F 5.5, in 50 percent glycerol, 0.15 M NaCl, 10 sodium phosphate mM, pH 7.4, PEG 20 0.02 percent, sodium azide 0.02 percent). The propagation of the wave in the incubated sites is completely interrupted. The surface of the incubated site is examined using an atomic force microscope, and the presence of colloids and the density of the gold particles anchored in the surface that is necessary for the absorption of observed light are determined. The average separation of the particles is in the region of approximately 100 panometers.

Example A7. Production by applying a layer of absorbent cover structured by the aqueous method. The surface of a metal oxide waveguide consisting of Taf) 5 is silanized with (mercaptomethyl) di ethylethosilane (in the gas phase at 180 ° C). The integrated circuit of the waveguide is connected to a transverse flow cell having parallel, smoothly separated, laminar partial streams, which allow up to five different streams of fluid to pass in parallel, one adjacent to another, along the length of the the waveguide, by means of separate, individually steerable flow openings (1-5). The intention is to produce three waveguide strips separated by two thinner strips of Au colloids deposited. The transverse flow cell is charged at inlets 1, 3, and 5 with pH regulator (phosphate-regulated sodium chloride solution, pH 7.0), and at entrances 2 and 4 with the colloidal solution of Au. A colloidal solution whose surface is blocked with bovine serum albumin (BSA Gold Tracer, supplied by Aurion, mean colloid diameter = 25 nanometers, OD5 &2.0) is used. The selected flow rates (per channel) are: 0.167 milliliters / minute for the pH regulator streams 1, 3, and 5, and 0.05 milliliters / minute for the two colloidal streams 2 and 4. This results in a width of approximately 1 millimeter for the colloidal current, and approximately 3 millimeters for the pH regulator stream. The ratio of the width of the colloidal current to the width of the pH regulator stream can generally be selected freely by the ratio of the currents. The currents are applied for 20 minutes (corresponding to a colloid amount of 1 milliliter per channel). After an incubation of 20 minutes, the integrated circuit of the waveguide is removed, washed with water, and dried with a stream of nitrogen. The colloid immobilized strips completely absorb the guided modal light, and this results in three separate light guide modes of approximately 3 millimeters wide.

Application Examples B Example B: Parallel detection of two different fluorescein-labeled oligonucleotides. with complementary strands immobilized on two physically separated regions in a hybridization assay.

Bl. 1 Optical sensor platform having two waveguide regions, obtained according to Example A3. Geometry: 16 mm x 48 mm x 0.5 mm. Waveguide layer: T 5 n = 2.31"? To 4RR nanopters, thickness 150 + 5 nanometers.

Substrate: Corning Glass C7059, n = 1,538 to 488 nanometers. Grid: rectangular grid that has a modulation depth of 6-7 nanometers, grid period: 750 nanometers.

Result of inward coupling with excitation at 633 nanometers. Coupling angle: 4th -5th (second order diffraction). Internal coupling efficiency: 7 percent on the grid dp site. Attenuation: 2.5 dB / cm.

Bl .2 Optical design The excitation light from an argon ion laser device (excitation wavelength of 488 nanometers) is expanded to 10 millimeters, using a cylindrical lens, and is directed with the help of a rotating mirror from the back of the substrate, on the two grids of the waveguide regions. It is compressed on top of the waveguide layer from above, and sealed by a ring 0, a thermostatically controlled transverse flow cell, q ??? It has a capacity of approximately 0.07 milliliters, and it extends over both waveguide regions. The l nes of the two samples, excited in the evanescent field, register in a simultaneous way by means of two physically separate detectors. The two detectors each consist of a photodiode (SR 1133, Hamamatsu), on which they are guided, by means of an identical glass fiber optic with filtration using an interference filter, the lumcepceces radiated into the cell space. The signals are amplified by means of two trapsimpedance amplifiers. The individual elements used for the design are known and commercially available.

B1.3 Solutions used; 1) Hybridization regulator (pH of 7.75), consisting of 0.069 M phosphate buffer (Na ^ PO "0.041 M + 0.028 M NaHf0), 0.176 M KCl, 1 milliliter of POE- (20) sorbitol monolaurate (Tween 20 , IC1), 1 gram of polyacrylic acid PAA 5,100, 500 milligrams / liter of sodium azide, filling up to 1 liter with distilled water. 2) Sample solution 1 (16 * cfl): fluorescein-labeled oligomer, consisting of 16 base pairs (fluorescein-5'-GTTGTGTGGAATTGTG-3 '(lO'Cl) in hybridization buffer 1), complementary to the immobilized oligomer on the first waveguide region. 3) Sample solution 2 (15 * cfl): fluorescein-labeled oligomer, consisting of 15 base pairs (fluorescein-5'-TTTTTCTCTCTCTGT-3 '(lO'ft) in hybridization buffer 1), complementary to the immobilized oligomer on the second waveguide region. 4) Regeneration solution: 50 percent (weight / weight) urea in an aqueous solution. The solutions are supplied by means of Cavro pumps (volume of the 10 milliliter sample in each case).

Bl.U Immobilization process: Using an oligonucleotide synthesizer (Applied Biosystems 394B), the specific binding participants are synthesized (3'CAACACACCTTAACAC-5 'on the first waveguide region, 3 * AAAAAGAGAGAGAGA on the second guide region of wave) directly on the sensor platform silanized with 3-glycidyloxypropyltrimethoxysilane, using a method that is conventional for the synthesis of oligonucleotides on particles. However, in contrast to the conventional synthesis method, a stable hexaethylene glycol displacer is used to anchor the oligonucleotides to the surface, at P! 3 'end. The sensor platforms, along with the immobilized specific binding participants, are washed with water, and then used in the assay.

B1.5 Measurement procedure: Variant 1 of the measurement method (which supplies two different analytes, one after the other, chronologically, on the two waveguide regions in a simultaneous manner), consists of the following individual steps: wash for 2 minutes with hybridization regulator 1) (0.5 milliliters / minute), recording the background signal; - supply sample solution 2) for 10 minutes (0.5 milliliters / minute) (after flooding for 5 seconds at 5 milliliters / minute); flood for 2 minutes with '-'- »hybridization 1); - supply the regeneration solution 4) during 3 minutes (0.5 milliliters / minute); flood for 4 minutes with the hybridization regulator 1); supply the sample solution 3) for 10 minutes (0.5 milliliters / minute) (after flooding for 5 seconds at 5 milliliters / minute); flood for 2 minutes with the hybridization regulator 1); supply the regeneration solution 4) for 3 minutes (0.5 milliliters / minute); Flood for 2 minutes with the hybridization regulator 1).

The fluorescence isotropically radiated from the two waveguide regions is collected during the procedure by means of light guide beams of a rectangular input cross-section (10 millimeters * 1 millimeter) placed directly below the sensor platform. The rectangular cross section of the light guide beams is transformed into circular outlets (diameter of 6 millimeters). Immediately downstream of the outputs of the light guide beams, are similar interference filters (maximum transmission at 530 nanometers, bandwidth of 30 nanometers). The spectrally filtered fluorescent light is measured by means of two photodiodes. After 10 minutes of supplying the 16-mer complementary sample labeled with fluorescein, a 42 mV fluorescence signal is observed from the first waveguide region, and no signal is observed from the second waveguide dp region. (1 mV). By contrast, after 10 minutes of supplying the 15-mer complementary sample labeled with fluorescein, a fluorescence signal of 43 V is measured in the second waveguide region, and no signal is measured (0 mV) in the first region of waveguide. The signal noise is approximately 2 mV. Variant II of the measurement procedure (which delivers two different analytes to two physically separate waveguide regions in a simultaneous manner using separate cells), consists of the following individual steps: wash for 2 minutes with the hybridization regulator 1 (0.5 milliliters / minute) in both regions of waveguide, recording the background signals of both channels; (after flooding for 5 seconds at 5 milliliters / minute), supply sample solution 2) (0.5 milliliters / minute) to the first waveguide region, and sample solution 3) (0.5 milliliters / minute) to the second waveguide region for 10 minutes; flooding both waveguide regions for 2 minutes with the hybridization regulator 1); supply the regeneration solution 4) (0.5 milliliters / minute) to both waveguide regions for 3 minutes; flood both waveguide regions for 4 minutes with the hybridization regulator 1).

The fluorescence isotropically radiated from the two waveguide regions, is collected during the procedure by means of light guide beams of a rectangular input cross-section (10 millimeters * 1 millimeter), placed directly below the sensor platform. The rectangular cross section of the light guide beams is transformed into circular outlets (diameter of 6 millimeters). Immediately downstream of the outputs of the light guide beams are similar interference filters (maximum transmission at 350 nanometers, bandwidth of 30 nanometers). The spectrally filtered fluorescent light is measured by means of two photodiodes. Clear signals are obtained from both waveguide regions.

Example B2 Detection of recognition elements on 5 parallel strips.

B2.1 Immobilization of the recognition elements Human antibodies labeled with Cy 5.5 are immobilized. protein A, and bovine serum albumin, as recognition elements and control molecules in strips on 5 regions of the sensor platform described in Example A4. The analyte for all recognition elements is a human antibody labeled with Cy 5.5 which exhibits an affinity reaction with protein A strips only. All the strips are 0.6 mm * 15 mm.

The distance between the strips is 0.6 mm. The strips start 1 millimeter to the right of the continuous internal mesh grid. For the structured immobilization of the recognition elements and the control molecules on the surface of the sensor platform, a multi-channel cell having the following geometry is used. Six channels that tipnpn the dimensions: width of 0.6 mm * length of 15 mm, and a cavity of size rte the sensor platform used, are cut into a straight Teflon parallelepiped (dimensions: 100 mm * 60 mm * 18 mm). At both ends of the channels, drilled holes are made in the Teflon using a 0.6 millimeter bit, in order to provide access to the individual channels from the underside of the Teflon block. As a result of the special configuration of the channels made in the teflóp, and of the selected geometry around the channels, the channels are in the form of "lips" projecting approximately 0.2 millimeters from the cut cavity for the waveguide . The waveguide layers, whose surface has been chemically modified previously by means of silanization in gas phase with 3-mercaptopropyl-dimethylmethoxysilane, are placed in the cavity of the multi-channel cell, in such a way that the guide layer wave gives towards the channels. By compressing the sensor platform against the Teflon lips of the multi-channel cell, a sealed connection occurs between the surface of the waveguide regions and the Teflon block. The following solutions are injected into the individual channels by means of the drilled holes.

Channel 1: 1 nM of a solution of a human antibody labeled with Cy 5.5. Channel 2: 1 milligram / milliliter of protein A in water. Channel 3: 10 milligrams / milliliter of bovine serum albumin in water.

Channel 4 1 milligram / milliliter of protein A in water. Channel 5 1 milligram / milliliter of protein A in water, Channel 6 Not used.

After an incubation period of 2 hours, the channels are washed by injecting demineralized water into them, and dried by blowing nitrogen through them. Then the sensor platform of the multi-channel cell is removed, and SP moistens the waveguide surface with approximately 400 microliters of a solution of bovine serum albumin having a concentration of 10 milligrams / milliliter, in order to saturate any remaining active binding sites on the surface silanized with a protein (bovine serum albumin). Bovine serum albumin exhibited no affinity for the human antibody labeled with Cy 5.5 used as the analyte in this experiment. After an incubation period of 2 hours, the sensor platform is washed with demineralized water.

B2 .2 Experimental setup for the automatic flijorescence measurement of the recognition elements and their binding partners immobilized in strips. The configuration of the measurement consists of three main components: A) a vertically adjustable support element for the sensor platform, with an integral transverse flow cell for the fluid contact of the waveguide regions with different solutions. B) An optical configuration having a support element for a laser source, and optical elements for the definition of the excitation light beam. C) An optical configuration which, by means of a combination of lenses and a mechanical shield, projects a strip-shaped region of the waveguide surface onto a detector. The flow cell is mounted on a computer controlled rotation and translation unit, in such a way that the internal coupling grid is located exactly on the rotating axis of the rotation unit. Using the translation unit, the flow cell can be placed, along with the waveguide, along that rotary axis, and in this way the internal mode can be coupled, in the region of the five molecular strips immobilized on the wave guide. The flow cell consists in principle of an aluminum plate that has the following dimensions: 75 millimeters * 40 millimeters * 5 millimeters, in whose center a 0 ring is established, in such a way that when compressing the sensor platform against the 0 ring , a surface chamber having the following dimensions is formed: 28 millimeters * 6 millimeters * 0.2 millimeters. For fluid contact. the PS camera accessible by means of three holes of 1 millimeter diameter drilled in the aluminum. Two of these perforated holes, which serve as entrances to the flow cell, are made in the centers of the end faces inside the chamber. When the sensor platform is pressed against the 0 ring, the two grids on the sensor platform are located between the inlets to the flow cell. The third perforated hole serves as an outlet from the flow cell, and is configured in such a way that the inwardly engaging grid is located symmetrically between one of the inlets and the outlet of the flow cell. A pH regulator is pumped into the cell by means of the inlet of the internal coupling grid, and the internal analyte of the flow cell is pumped through the inlet of the external acnplamipntn grid. This construction prevents the internal coupling grid from being contaminated by the constituents of the analyte solution (counter-flow principle). A sealing connection is achieved between the waveguide and the flow cell by means of a ring 0 established in the flow cell. The medium of the flow cell can be replaced by hose connections using the principle of counter-flow. A diode laser device is used to produce a converging beam of light. The laser beam, which has a diameter of 0.4 millimeters, which comes from the laser optics, forms a constant right angle with the face of the sensor platform evtrpmo. By using a polarizer and a? / 2 plate, the intensity and polarization of the laser beam can be adjusted. A bandpass filter having a wavelength of 670 panometers, eliminates the photons that are emitted by the diode laser device in the wavelength scale of the fluorophores to be detected (from 690 to 740 nanometers ), and that would interfere with fluorescence detection. The angle between the laser beam and the longitudinal axis of the waveguide can be freely adjusted using the rotation element, and is used to adjust the internal coupling angle for the TE0 mode. The detection optics (C) are focused on the center of the longitudinal side of the waveguide and at the level of the TE0 mode, and produces on the detector a mode image on the waveguide surface. Using a strip mesh immediately in front of the detector, only the image of the region corresponding to the geometry of the molecules immobilized in strips is taken, that is, a region of 0.6 millimeters * 15 millimeters. The optic of the selected detector is such that it produces a 1: 1 image of the waveguide surface in the plane of the detector. A combination of filters substantially eliminates excitation light, and allows virtually only fluorescence photons to pass through the detector (2 * bandpass 725 nanometers).

B2.3 Execution of a multiple test First the flow cell is filled with PBS 7.0, and the internal coupling angle is adjusted using the rotation unit. The following solutions are pumped in succession through the flow cell per measurement cycle: 1) 1 milliliter of wash buffer PBS 7.0, flow rate of 500 icroliters / minute. 2) 1 milliliter of analyte - human antibodies labeled with Cy 5.5 5.5 pM, flow rates of 250 microliters / minute. 3) 1 milliliter of PBS 7.0 wash regulator, flow rate of 250 microliters / minute. 4) 1 milliliter of chaotropic regulator (glycine, pH 2.6), flow rate of 250 microliters / minute. 5) 1 milliliter of PBS 7.0 wash regulator, flow rate of 500 microliters / minute. counter-flow: 5 milliliters of PBS 7.0, flow rate of 300 microliters / minute. Using multiple valves and piston pumps controlled by computer, the different solutions are pumped through the flow cell in the previous sequence and at the previous flow rates during the 15 minute measurement cycle. The vertical position of the flow cell is adjusted initially by means of the translation unit, in such a way that the mode runs exactly in the upper region of the waveguide surface, on whose region the antibody has been immobilized in advance. human labeled with Cy 5.5. Since this strip is permanently fluorescent as a result of excitation by the laser beam, the vertical position is adjusted in such a way that the counter-photon produces a maximum value. This identifies the position of the human antibody labeled with immobilized Cy 5.5. Then the automatic measurement is started where, by increasing changes in the vertical position of the flow cell by means of the translation unit, whose changes correspond to the distance between the immobilized strips, the five strips are moved upwards one after the other. the other in the sequence of 1 to 5 in a rhythm of 8 seconds in the focus of the detector. As a result of the described geometry, in the same way the TE mode is produced or only in the selected regions. Although the flow cell, along with the waveguide, is held in one position, the value measured by the counter-photon in the selected region in one second is recorded as a function of time. The automatic movement between the five different regions of the waveguide continues through the entire duration of 15 minutes of measurement. During that period, the solutions indicated above are pumped through the measuring cell at the appropriate flow rates. The data obtained can be displayed as a function of time. The region on which the human antibody labeled with Cy 5.5 (strip / channel 1) is immobilized fluoresces during the entire measurement cycle, and exhibits no interaction with the 10 pM solution of a human antibody labeled with Cy 5.5 pumped as analyte in the measurement cell. In the case of regions 2, 4, and 5 of the sensor platform, on which protein A has been immobilized in advance, an increase in the fluorescence signal is initiated from 4 to 5 times the initial value after 150 seconds. The start of the increase correlates with the point in time at which the analyte is pumped into the flow dp cell. The signal, in the case of these channels, remains virtually unchanged at a high value, even when, after 40 seconds, 1 milliliter of the wash regulator is pumped through the flow cell at a flow rate of 250 microliters. /minute. This behavior is consistent with the specific binding of the antibody labeled with protein A. In region 3 of the sensor platform, bovine serum albumin has been immobilized beforehand as the control. As expected, this strip / channel exhibits a very low value throughout the entire measurement, since the human antibodies marked with Cy 5.5 used as analyte. they react from a non-specific one with bovine serum albumin.

Claims (60)

1. CLAIMS 1. A sensor platform consisting of a continuous substrate and a transparent planar inorganic dielectric waveguide layer, wherein: a) the transparent inorganic dielectric waveguide layer is divided at least in the measurement region, at least two waveguide regions, by virtue of the fact that the effective refractive index in the regions where the wave is guided is greater than in the surrounding regions, or the division in the waveguide layer is formed by a material on its surface that absorbs the internally coupled light; b) the waveguide regions are provided with an internal coupling grid each, or with a common internal coupling grid, such that the propagation direction of the wave vector is maintained after internal coupling, and c) where appropriate, the waveguide regions are provided with an external coupling grid each or with a common outwardly engaging grid. A sensor platform according to claim 1, wherein the waveguide regions are configured in the form of strips, rectangles, circles, ellipses, or separate checkerboard patterns. 3. A sensor platform according to claim 2, wherein the waveguide regions are configured in the form of parallel strips. 4. A sensor platform according to claim 1, wherein the waveguide regions are configured in the form of parallel strips that are joined together at one or both ends. A sensor platform according to claim 1, wherein the division into a plurality of waveguide regions is achieved by means of a change in the effective refractive index between the waveguide region and the adjacent material , the difference in the effective refractive index being greater than 0.2 units. 6. A sensor platform according to claim 1, wherein the division into a plurality of rip waveguide regions is effected by means of an absorbent material on the surface of the waveguide layer. 7. A sensor platform according to claim 6, wherein the division into a plurality of dp waveguide regions is effected by metals colloidally deposited on the surface of the waveguide layer. 8. A sensor platform according to claim 7, wherein the division into a pluralida1 c> waveguide regions is effected by gold colloidally deposited on the surface of the waveguide layer. A sensor platform according to claim 7, wherein the division into a plurality of waveguide regions is effected by metals colloidally deposited on the surface of the waveguide layer whose surface has been modified by means of an adhesion promoter layer 10. A sensor platform according to claim 1, wherein the width of the strip of the waveguide regions is from 5 microns to 5 millimeters. according to claim 10, wherein the width of the strip of the waveguide regions is 50 microns to 1 millimeter 12. A sensor platform according to claim 1, wherein the individual waveguide regions. Duals, when in the form of strips, are 0.5 to 50 millimeters in length. 13. A sensor platform according to claim 1, wherein the number of strips on the sensor platform is from 2 to 1,000. A sensor platform according to claim 1, wherein the individual waveguide regions on the substrate are configured to form multiple detection regions. 15. A sensor platform according to claim 14, wherein each multiple detection region consists of from 2 to 50 separate waveguide regions. 16. A sensor platform according to claim 14, which has from 2 to 100 multiple detection regions on the sensor platform. 17. A sensor platform according to claim 14, which is in the form of a disk that can rotate freely around a central cutout portion (6), and on which a plurality of multiple detection regions are configured (4). ) in a tangential or radial manner, so that when the disk is rotated around the cut portion (6) under the excitation and detection optics, a plurality of multiple detections can be performed in succession. 18. A sensor platform according to claim 14, which is in the form of a rectangle or strip on which multiple detection regions (4) are configured, such that, when the sensor platform is moved laterally under the optics of excitation and detection, a plurality of multiple detections may be carried out in succession. 19. A sensor platform according to claim 1, wherein the substrate is glass, quartz, or a transparent thermoplastic plastic material. 20. A sensor platform according to claim 19, wherein the substrate consists of polycarbonate, poly-i ida, or polymethyl methacrylate. 21. A sensor platform according to claim 1, wherein the refractive index is the same for all waveguide regions. 22. A sensor platform according to claim 1, wherein the refractive index of the waveguide regions is greater than 2. 23. A sensor platform according to claim 22, wherein the guide regions waveforms consist of Ti02, ZnO, Nb gd Ta 02, sHfO or2 ZrO. 2 24. A sensor platform according to claim 23, wherein the waveguide regions consist of Ti02 or Ta?)? 25. A sensor platform according to claim 1, wherein the thickness of the waveguide regions is from 40 to 300 nanometers. 26. A sensor platform according to claim 25, wherein the thickness of the dp waveguide regions is from 40 to 160 nanometers. 27. A sensor platform according to claim 1, wherein the depth of modulation of the gratings is from 3 to 60 nanometers. 28. A sensor platform according to claim 1, wherein the ratio of the modulation depth to the thickness of the waveguide layers is equal to or less than 0.5. 29. A sensor platform according to claim 1, wherein the ratio of the modulation depth to the thickness of the waveguide layers is equal to, or less than, 0.2. 30. A sensor platform according to claim 1, wherein the period of .- ^ • f -.t1- ~ - <; -. -, 1, 000 nanometers. 31. A sensor platform according to claim 1, wherein: a) transparent planar inorganic dielectric waveguide regions on the sensor platform, are separated from one another along the measurement section by a jump at the refractive index of at least 0.6, and b) each region has one or two separate grid couplers, or all the regions together have one or two common grid couplers, and c) the transparent flat inorganic dielectric waveguide regions have a thickness of 40 to 160 nanometers, the depth of modulation of the gratings is from 3 to 60 nanometers, and the ratio of the depth of modulation to thickness is equal to, or less than, 0.5. 32. A signaling platform according to claim 1, wherein the waveguide regions guide from 1 to 3 modes. A method for the production of the sensor platform according to claim 1, which comprises vaporizing the inorganic waveguide material under a suitably structured mask in a vacuum. 34. A method for producing the sensor platform according to claim 1, which comprises, in a first step, vaporizing an inorganic waveguide material, to form a continuous layer, and then dividing the layer in individual waveguide regions by mechanical scraping, laser material machining, lithographic processes, or plasma processes. 35. A method for the production of the sensor platform according to claim 1, which comprises depositing an inorganic absorbent metal on the surface, from a colloidal solution, in a suitably structured manner. 36. A method for the production of the sensor platform according to claim 1, which comprpndp deposit gold having a particle size of at least 10 nanometers, on the surface, from a colloidal solution, in a manner properly structured. 37. A method for the production of the sensor platform according to claim 36, wherein the particle size is from 15 to 35 nanometers. 38. A modified sensor platform, wherein, on the surface of the waveguide regions according to claim 1, one or more specific binding partners are immobilized as chemical or biochemical recognition elements, for one or more identical analytes or different 39. A modified sensor platform according to claim 38, wherein the specific binding partners on the surface of each waveguide region are physically separated from each other. 40. A modified sensor platform according to claim 38, wherein only a specific link partner is configured on the surface of each waveguide region. 41. A modified sensor platform according to claim 38, wherein an adhesion promoter layer is located between the waveguide regions and the immobilized specific binding participants. 42. A modified sensor platform according to claim 38, wherein the dp pnlanp specific participants covalently linked to the gold colloids are located on the waveguide regions, the gold colloids being less than 10 nanometers. 43. A method for the production of the modified sensor platform in accordance with the requirement of 38, which comprises passing the specific bond partners dissolved over the separate waveguide regions, by means of a cell Transverse flow of multiple channels, the channels of the multi-channel cell being separated in a fluid or physical manner. 44. A method for the production of the modified sensor platform according to claim 38, which comprises applying the dissolved specific link partners to the separate waveguide regions, by means of a stamping. 45. A method for the parallel determination of one or more luminescences, using a sensor platform or a modified sensor platform according to claim 1 or claim 38, said method comprises placing one or more liquid samples in contact with a or more waveguide regions on the sensor platform, coupling excitation light in the waveguide regions, causing it to pass through the waveguide regions, thus exciting in parallel in the evanescent field the substances luminescent of the samples, or the luminescent substances immobilized on the waveguide regions, and, using optoelectronic components, measure the luminescences produced by the same. 46. A method for the parallel determination of one or more luminescences according to claim 45, wherein coherent light having a wavelength of 300 to 1,100 nanometers is used for the luminescence excitation. 47. A method for the parallel determination of one or more luminescences according to claim 46, wherein laser light having a wavelength of 450 to 850 nanometers is used for the luminescence excitation. 48. A method for the parallel determination of one or more luminescences according to claim 45, wherein a functionalized luminescent dye is selected from the group consisting of rhodamines, fluorescein derivatives, cu-aline derivatives, diethylaryl biphenyls, derivatives of stilbene, phthalocyanines, naphthalocyanines, polypyridyl / ruthenium complexes, such as ruthenium chloride tris (2,2 * -bipyridyl), ruthenium chloride tris (1, 10-phenanthroline), ruthenium chloride tris (4,7-diphenyl) -l, 10-phenanthroline), and polypyridyl / phenazine / ruthenium complexes, platinum / porphyrin complexes, europium and terbium complexes, and cyanine dyes. 49. A method for the parallel determination of one or more luminescences according to claim 48, wherein fluorescein isothiocyanate is used as the luminescent dye. 50. A method according to claim 45, where isotropically radiated luminescences are detected, evanescently excited. 51. A method according to claim 45, wherein the evanescently excited luminescences are retro-coupled in the waveguiding layer, by means of an external coupling grid, or on one edge of the sensor platform. 52. A method according to claim 45, wherein both the isotropic radiated luminescence and the retro-coupled luminescence are detected, independently of one another, but in a simultaneous manner. 53. A method according to claim 45, wherein the absorption of the radiated excitation light is simultaneously determined. 54. A method according to claim 45, wherein the luminescences are excited by different laser light sources of identical or different wavelengths. 55. A method according to claim 45, wherein the luminescences are excited by a single row of diode laser devices. 56. A method according to claim 45, wherein the samples to be analyzed are egg yolk, blood, serum, plasma, or urine. 57. A method according to claim 45, wherein the sample to be analyzed is surface water, a dirt or plant extract, or a liquor from a biological or synthetic process. 58. The use of the sensor platform or the modified sensor platform according to claim 1 or claim 38, for the quantitative determination of biochemical substances in affinity detection. 59. The use of the sensor platform or the modified sensor platform according to the claim 1 or with claim 38, for the quantitative determination of antibodies or antigens, receptors or ligands, chelators or histidine-labeled compounds, oligonucleotides, DNA or RNA strands, DNA or RNA analogs, enzymes, enzyme substrates, cofactors or inhibitors of enzymes, lectins and carbohydrates. 60. The use of the sensor platform or the modified sensor platform according to claim 1 or claim 38, for the selective quantitative determination of the luminescent constituents of optically opaque fluids.