Micro-optical sensor.

The invention relates to a micro-optical method for detection of chemical substances, which comprises contacting a sample containing the substance to be detected with the waveguiding layer of an optical layer waveguide in contact coupled coherent light into the waveguiding layer, guided as a light wave in this and this coupled out again from the layer is, as well as a micro-optical sensor for carrying out this process with a waveguide layer of a waveguiding layer on a substrate and an in-plane of the waveguiding layer diffraction grating for coupling in and out of coherent light.

Chemical changes, eg molecular deposits, for example, be detected by measuring the relative intensity of the coupled light beams at or in the immediate vicinity of the waveguide layer. An alternative method of detection is (polarized zBorthogonal) simultaneously couple two coherent beams of light in the film waveguide, and by interference of two decoupled partial beams, which of the two in the waveguide jointly controlled (orthogonally polarized) light waves are generated, the relative phase angle (phase difference) the two (orthogonally polarized) to measure out-coupled light rays.

In biomedical diagnostics based many of the common testing procedures on the use of solid carrier substrates, for example balls, which are loaded with a chemically sensitive molecular layer. For the analysis, the patient sample, eg serum or plasma is brought into contact with the carrier substrate, which enter into the sample dissolved detected (bio) molecules specifically binds to the chemically sensitive layer.

The detection of the bound to the chemo-sensitive layer molecules takes place in conventional tests usually indirectly by means of a second in solution the reaction partner, which is labeled with a radioisotope, a fluorophore or an enzyme. The labeled molecules have specific Taken shaft to occupy the remaining free binding sites on the chemo-sensitive layer, or so-called after. To couple "sandwich" principle to the free end of the chemosensitive bound molecules to be detected. The surface concentration of the labeled molecules is determined using a suitable measuring method. It is concluded on the concentration of the substance to be detected in the sample.

Optical layer waveguide consist of a thin dielectric layer on a transparent support substrate. (For an introduction tutorische see eg T. Tamir, Integrated Optics, Springer, Berlin, 1985). That the waveguide layer covering medium, the so-called superstrate, as may be gaseous or liquid. A coupled into the waveguide light beam, eg a laser beam is guided by total internal reflection in the waveguide layer, provided that the substrate and superstrate having a lower refractive index than the intermediate dielectric layer. The propagation of these guided optical wave takes the form of distinct modes. The phase velocity of the guided light wave is c / n, where c is the speed of light in vacuum, and N is the effective refractive index of the guided mode in the waveguide. The effective refractive index N depends on the configuration of the waveguide, ie. Of layer thickness and refractive index of the thin waveguiding layer and the refractive indices of the substrate and superstrate The transverse field distribution of modes falls outside of the waveguide layer rapidly. The effective layer thickness d_eff the waveguide is defined as the sum of the geometric layer thickness d of the waveguide layer and the penetration depth of the evanescent optical fields in the substrate and the superstrate. By using suitable high refractive index materials for the waveguide layer to the waveguide can be a d_eff of less than realize a wavelength of the guided light beam. The penetration depth of the evanescent field in the substrate and the superstrate is in this case only a fraction of the wavelength.

That at the substrate surface spatially highly concentrated field of guided modes is ideally for sampling of chemical changes that take place on or in the immediate vicinity of the waveguide layer. In a waveguide structure based optical measuring method, also referred to as "integrated optical" method, win for surface analysis and optical sensors are becoming increasingly important. Methods are known in which changes in the propagation constant (effective refractive index) of the guided modes, and / or changes in the light intensity due exploited by absorption of the guided modes to (chemical) changes at the interface between the waveguiding layer and superstrate and / or in volume prove the waveguide layer.

For the selective detection of specific substances in the waveguide covering a sample chemosensitive additional layer on the wave-guiding layer is required, which selectively binds the molecules to be detected and thereby causes, for example, a change in the effective refractive index. The interaction of the guided mode with the sample takes place via the transversely damped field whose penetration depth is typically greater in the superstrate than the thickness of the (molecular) chemosensitive additional layer.

According to the known prior art, the coupling of the light into the waveguide is accomplished by focusing a laser beam on its front side, or with the aid of a diffraction grating (so-called. Grating), the coupled in beam from the side of the substrate or superstrate is incident on the wave-guiding layer , The frontal coupling makes high demands on the mechanical positioning and stability, particularly for extremely thin, surface-sensitive waveguide having a d_eff of less than one micrometer. With grating couplers can be a laser beam or one couple out in a simple manner in a waveguide, wherein one does not require focusing optics.

are known arrangements, in which are laterally limited grating structures used in the waveguide layer for coupling or decoupling of the beam. A laser beam is coupled, provided that it is incident at a specific, dependent on the grating period and the effective refractive index, angle of incidence on the grating structure provided with the region of the waveguide. The coupled ray passes through, for example, a period between two spatially separated regions grating portion of the waveguide and is coupled when impinging on the second grating region.

If the input light beam by molecules which are located on the surface of the waveguide is absorbed, so this can be detected by measuring the intensity of the extracted beam with high sensitivity. The coupling of the incident wave of the guided wave occurs in the region of the grating region. The coupling and decoupling on the grid has the character of a resonance. The resonance angle for optimum coupling is dependent on the grating period and the effective refractive index of the guided mode. Changes in the effective refractive index, for example, caused by attachment of molecules to the waveguide surface, cause a shift of the incident angle type resp failure angle at which carried out the coupling and decoupling of the laser beam. By measuring the angle at which the guided wave can be stimulated, a molecular surface coating can be detected in the grating region of the waveguide layer with submonomolekularer sensitivity (see. This K. Tiefenthaler and W. Lukosz, "Integrated optical switches and gas sensors", Optics Letters Vol 9, No. 4, 1984, pp. 137 -139, and K. Tiefenthaler and W. Lukosz, US patent 4,815,843, 1989).

Another known method for the detection of adsorbate based on the excitation of surface plasmons of metal layer interfaces with or without the use of diffraction gratings. The coherent excitation of conduction electrons in the form of a running along on the metal surface the surface acoustic wave is called a surface plasmon. The electromagnetic field of the surface plasmon is tranversal spatially highly concentrated to the metal surface. The transverse field distribution has a maximum at the surface and falls in metal and superstrate exponentially. The plasmon wave is attenuated by resistive losses in the metal. The Propagationsdistanz of the surface plasmon is, for example for pure silver 22 microns at a wavelength of 514 nm. Adsorbing molecules on the metal surface, then the propagation constant (phase velocity) of the moving along at the interface surface plasmon changes.

The sensitivity with which this change in the propagation constant can be detected is limited by the relatively short Propagationsdistanz of Plasmon. various optical arrangements which utilize the resonant excitation of surface plasmons in order to metal shell detect molecular adsorbate surfaces are known (compare B. Song Mountain, C. Nylander, and I. Lundstrom, "Surface plasmon resonance for gas detection and biosensing," Sensors and Actuators 4, 1983, pp. 299 -304 and EP 0112721).

A universal method for characterization of thin films on planar surfaces is ellipsometry, which is based on the measurement of the polarization state of the reflected light at the surface. An oblique aptly to the surface beam undergoes when reflected a change in the relative amplitude and phase of the parallel and perpendicular to the incident plane polarized components of the electromagnetic field. The incident light beam is preferably circular polarization or linear. The polarization state of elliptically polarized in general, the reflected beam is analyzed, resulting in the thickness and refractive index of the thin film can be determined.

In simple reflection of the light beam on the surface to be analyzed caused by molecular adsorbate changes the polarization state are very small, which can be explained by the fact that the interaction of the incident light beam is limited by the adsorbate at a distance of the order of magnitude of the layer thickness. Slight changes in the polarization state during the passage of the incident and reflected beam by the assigned the adsorbate substrate, or by a on the substrate cell, limiting the accuracy of ellipsometric measurements. (See. For this purpose R. Azzam et al., Physics in Medicine and Biology 22, 1977, 422-430, Cuypers PA et al., Analytical Biochemistry 84, 1978, 56-67)

The present invention has for its object to provide a highly sensitive optical measuring methods are available, with which molecular changes at surfaces and interfaces can be detected in a simple manner.

According to the invention, this object is achieved by a method of the aforementioned type, which is characterized in that coupling and decoupling using an in-plane of the layer called. Multidiffractive lattice structure occurs. The inventive device for implementing the method is characterized in that the diffraction grating consists of a multi-diffractive grating structure.

Multidiffractive is a lattice structure when its frequency spectrum comprises several fundamental components. By appropriate selection of the geometry of the multi-diffractive grating structure, the diffraction angle and the intensities of individual diffraction orders can be varied independently.

Of particular interest here is the bidiffraktive grating having two independent diffraction orders. The two fundamental frequency components of bidiffractive lattice structure preferably differ by less than a factor of two from each other. Bidiffraktive grating structures for example can be realized by superimposing two gratings with different periodicity. For example, this can be done using a two-step lithographic process, in which two surface relief gratings of different periodicity are etched in a substrate surface in sequence.

Grating according to the known prior art consist of a "classic" diffraction grating whose diffraction orders associated with multiples of the fundamental frequency of the grid. The first diffraction order is generated from the fundamental frequency of the grating, which is given by the reciprocal value of the lattice constants.

The inventive method has the advantage that at least one fed-out sub-beam is created, which does not coincide with a direct order of diffraction of the incident on the grating structure beam. The use of a multi-diffractive grating structure thus makes it possible to separate the guided in the waveguide decoupled component beam of reflected, transmitted, respectively directly diffracted partial beams, although the regions partially overlap on the waveguide layer in which the coupling and uncoupling of the light beams occurs.

In the following preferred embodiments of the invention will be described with reference to the accompanying drawings. Show it<ul><li>1a - 1e are schematic representations of various forms of planar waveguides with multi-diffractive grating couplers in section,</li><li>2a and 2b pespektivische illustrations of embodiments of planar waveguides with multidiffractive grating couplers,</li><li>3a and 3b are schematic representations of the optical properties of a diffraction grating and an ordinary bidiffractive grating having two diffraction orders,</li><li>4 is a schematic sectional view of a sensor according to the invention,</li><li>5 is a schematic sectional view of another form of a sensor,</li><li>6 is a sectional view of a sensor with a grating similar to that in FIGURE 1b</li><li>7 shows a section through a sensor with a grating similar to that in Fig.1c</li><li>8 shows a section through a sensor with superstrat mutual light coupling,</li><li>9 shows a section through a sensor with a grating similar to that in Fig. 1c</li><li>10 shows a section through a sensor with simultaneous superstrat mutual coupling of two light beams.</li></ul>

The film waveguide. 1a schematically shown in Figure in sectional view 1 is composed of a wave-guiding layer 2 on a planar substrate 3. The surface of the waveguiding layer 2 and the interface between the waveguiding layer 2 and substrate 3 are modulated with a respective surface relief grating. The two optical diffraction grating can also be located in the volume of the waveguide layer.

The film waveguide 1b shown in Fig. In section Figure 1 also consists of a wave-guiding layer 2 on a substrate 3. In this alternative form, however only the interface between the waveguiding layer 2 and the substrate 3 is modulated with a biperiodischen lattice structure. The biperiodische lattice structure consists for example of a superposition (mixture superposition) of two sinusoidal gratings with different periodicity.

Similarly, there is the film waveguide shown in Fig.1c of the wave-guiding layer 2 and the substrate 3 and an optical diffraction grating. The bidiffraktive property of the grid is achieved by appropriate selection of the grating structure. In this case, the profile of consecutive grating grooves are periodically varied in width (pulse width modulation) and / or in depth (pulse amplitude modulation). The grating grooves are hereinafter subsumed under the term grid elements.

The slab waveguide shown in Fig. 1D comprises a wave-guiding layer 2 on a substrate 3, again the interface is modulated with a lattice structure. The lattice structure is made up of alternating sections G_a and G_b two grid composed with different periodicity.

Similarly, the film waveguide shown in Fig. 1e 1 again has a wave-guiding layer 2 and a substrate 3, and a bidiffraktive lattice structure. In this embodiment, but is between the waveguiding layer and the substrate an intermediate layer 2a, the interface thereof having the grating for waveguiding layer 2nd For the production of the lattice structure, the layer 2a is applied to the planar substrate 3, first, in which an embossing process with a surface relief grating is produced. Alternatively, for embossing the surface relief can be produced by means of a microlithography-photographic process. On the surface relief, the high-index waveguide layer 2 is applied.

Both the preparation of a master grating for the embossing process such as the production of multi-diffractive grating structure may also be holographic.

The 2a schematically shown in perspective in FIG. 1 film waveguide is modulated with two gratings. The two superimposed line gratings are oriented parallel to each other and have different period lengths.

The illustrated in Fig. 2b film waveguide 1 is also modulated with two superimposed gratings. In contrast to the embodiment according to Fig. 2a, but the superimposed line gratings are oriented differently. Such gratings are called crossed grating.

The launching of a light beam in the wave-guiding layer 2 is carried out with diffraction gratings whose grating constant is smaller than the vacuum wavelength of the incoupled light. The diffraction orders of such fine grids are transverse-damped (so-called. Evanescent) waves which run along the grid. If the angle of incidence chosen correctly, the incident on the grating light beam on one of these evanescent diffraction orders is coupled into the waveguide. If such a grating -As in Fig. 3a and however 3b angedeutet- in a high-index immersion liquid 1 immersed (eg diiodomethane with refractive index n = 1.73), so take the place of the evanescent waves to freely propagating light beams whose diffraction angles are observed.

In Fig. 3a, the operation of a bidiffractive diffraction grating is explained with an example. Diffraction at the grating structure of the incident light beam is split into several partial beams. The θ at the angles_a and θ_b diffracted partial beams from the grating G_a resp. G_b generated. The unabgebeugt continuous beam corresponds to the zero diffraction order in transmission. By appropriate selection of the geometry of the lattice structure, the diffraction angle θ can_a and θ_b the diffracted partial beams are independently selected.

FIG. 3b shows the optical properties of a grating coupler with a diffraction grating according to the known prior art. Where a light beam onto the grating, so come in addition to the first-order diffraction on more discrete orders which from the higher Fourier components (harmonics) of eg rectangular grid caused. The diffraction angle θ_j of individual orders arising from the grating diffraction equation sin (θ_j) = J (λ / nl), in which the diffraction order j, the vacuum wavelength λ, the refractive index n of the grid surrounding medium I and the lattice constant of 1 (small letter L) arrives.

If in Fig. 3a and 3b, the high-index immersion through a medium I with a smaller refractive index n replaced (eg., Water with n = 1:33 or air with n = 1), so take the place of the diffracted partial beams transverse-damped waves at the interface run along between the waveguide layer 2 and the I medium. The incident light beam is coupled into the waveguiding layer 2 if it is incident at a specific, dependent on the grating period and the effective refractive index of the waveguide on the grating angle.

The sensor 4 shown in Fig. In cross-section consists of layer 1 and a waveguide mounted thereon sample cell 5 with side walls and a cover. The cover has openings through which the interior of the sample cell 5, and thus the sensitive surface of the waveguide is fed with the substance to be examined. 4

Figure 4 and the following figures also show the path of the light in the measurement. As Figure 4 shows, a substrate side incident light beam 6 from one of the two gratings G_a and G_b partially coupled into the waveguide 1; the coupled partial beam 7 passes through a guided mode of the distance L of the waveguide layer 2 and occurs with the sample 4 in interaction. The direction of one of the two coupled-out partial beam 9a and 9b is different from the direction of the reflected on the layer not coupled portion 8 of the incident beam 6. The partial beam 8 corresponds to the zeroth diffraction order in reflection. The diameter of the incident beam 6 is fitted into the waveguide layer 2 of the Propagationsdistanz the injected Teilstarhls. 7 Typically, the beam width W and the lateral propagation path L of the same magnitude. The sensitivity of the sensor depends on the configuration of the waveguide, ie. Of layer thickness and refractive index of the thin waveguiding layer, and the refractive indices of the substrate and superstrate For the detection of chemical changes that take place on or in the immediate vicinity of the waveguide layer, it is advantageous if the thickness of the highly refractive waveguiding layer 2 is smaller than the wavelength of the injected light.

In the shown in FIG. 5 in an enlarged schematic longitudinal section, with two gratings G_a and G_b modulated film waveguide on a planar substrate is provided with a thin chemosensitive additional layer 10, the waveguide layer. 2 The sample to be analyzed 4 is placed in the sample cell 5 with the chemo-sensitive layer 10 in contact. The resonance angle .phi.A and .phi.b, is taking place in which the coupling respectively decoupling the light beams depend on the period lengths of the two gratings, and of the effective refractive index of the guided in the waveguide mode 7. The addition of a molecular adsorbate 11 to the chemo-sensitive layer 10 causes changes in the effective refractive index and / or absorption of the guided mode.

Even with that shown in Fig. 6 in a schematic longitudinal section biperiodisch modulated film waveguide on a planar substrate with the sample cell, the wave-guiding layer 2 is provided with a chemosensitive additional layer 10 which is in contact with the sample 4. The resonance angle for coupling or decoupling, the light beams depend on the period lengths of the Fourier components of biperiodischen grid G, and of the effective refractive index of the guided in the waveguide mode 7. The adsorption of a molecular layer 11 on the surface of the chemo-sensitive layer 10 effected as an attenuation by absorption of the guided mode, which can be detected by measuring the intensity of the coupled beam 9b.

In the shown in Fig. 7 in a schematic longitudinal section biperiodisch modulated film waveguide on a planar substrate with the sample cell, the resonance angle depends on the coupling or decoupling of light from the period lengths of the two gratings in the alternating grid sections G_a and G_b, And on the effective refractive index of the guided in the waveguide mode. 7 The width of the alternating grid sections G_a and G_b with different periodicity (vgl.Fig.1d) is preferably smaller than the diameter W of the incident light beam 6. The addition of a molecular adsorbate 11 to the chemo-sensitive layer 10 causes changes in the effective refractive index and / or a deterioration by absorption of the guided mode ,

The bidiffraktive feature of this structure is based on that of the light coupled into the waveguide 2 Mode 7 with both grid G_a and with grid G_b interacts, wherein the coupled-out partial beam 9a and 9b are formed.

For the reproducibility of the measurement, it is advantageous if the efficiency for the coupling and decoupling of light is not sensitive to a translation of the waveguide in the plane of the layer relative to the incident light beam 6. This can be achieved in good approximation by the width the arranged alternately, strip grating sections G_a and G_b is selected smaller than the diameter W (lateral extent) of the incident, partially coupled light beam 6th

Since it is in coupling a beam of light into a waveguide by a process in which the coherence of the light plays an important role, it is advantageous, if the lattice structure having high coherence. As indicated in Figure 1d and 7, this is assured if the distance between the grating elements of different grating sections G_a (Respectively G_b), Always an integer multiple of the period length of the grating type G_a (Respectively G_b) Is.

The film waveguide shown in Fig. 8 in a schematic longitudinal section 1 is provided with two grids modulates an d with a thin chemosensitive additional layer 10 loaded. The resonance angle for coupling or decoupling, of superstrat each incident light beam 6 from hanging from the period lengths of the grid and of the effective refractive index of the guided in the waveguide mode 7. The presence of an adsorbed layer 11 can be determined by measuring the intensity of the coupled partial beam as 9b quantify.

Also in the film waveguide shown in longitudinal section in FIG. 9, the coupling and decoupling of the light beams occurs superstrat other. The incident light beam 6 is coupled via one of the lattice generated by the evanescent waves. The coupled portion 7 passes through a guided mode of the waveguide layer 2, and is thereby decoupled from the grid structure bidiffractive continuously again, the partial beams 9a and 9b are formed. The propagation directions of the beams 9b and 8 are different; Beam 8 corresponds to the zero diffraction order in reflection. This direction separation makes it possible to detect by measuring the intensity of the beam 9b the run and out-coupled in the waveguide layer light background-free and it to close as the presence of an absorbing additive layer 11th

Also, the film waveguide shown in a schematic longitudinal section in FIG. 10 is modulated with two screens and loaded with a chemosensitive additional layer 10. By simultaneous coupling of two coherent orthogonally polarized light beams two jointly guided TE and TM modes of different polarization are generated. The coupled-out partial beams are mutually coherent and can be placed with a polarizer for interference. By measuring the relative phase angle (phase difference) of two partial beams, which are generated by the two mutually orthogonal polarized modes 7 (TE and TM), the presence of an adsorbed layer 11 can be detected with very high sensitivity.

The chemosensitive additional layer 10 in Figures 5-10 is as chemoselective layer.

An alternative detection method is to measure the relative intensity of two coupled-beam components; the coupling of the two modes 7 in Fig. 10 and measuring the (relative) intensity of the partial beam 9b can be carried out sequentially.

Where a light beam, eg a laser beam on a with a grating structure modulated, wave-guiding layer, as occur in addition to the reflected and transmitted partial beams more discrete diffraction orders on, both in reflection and in transmission. If the angle of incidence chosen correctly, the beam through a diffraction order in the waveguide is coupled. The coupled partial beam propagates as guided mode in the waveguiding layer and occurs a second time with the diffraction grating interacts; the guided mode is coupled back continuously when passing through the modulated by the grating structure waveguide.

The Propagationsdistanz, which is required for complete decoupling of the mode depends on the diffraction efficiency of the grating. The grating regions, in which the coupling and uncoupling occurs are offset from each other and partially overlap. As shown in Fig. 4 schematically, the partial beams are coupled out 9a and 9b with respect to the incident beam 6 laterally offset. The ratio of lateral displacement L to the beam width W is the profile of the light incident on the wave-conducting layer beam and the diffraction efficiency of the grating depends [this compare T. Tamir and HL Bertoni, "Lateral displacement of optical beams at multilayered and periodic structures", J. opt. Soc. At the. 61 (1971), pp. 1397-1413 and T. Tamir and ST Peng, "Analysis and Design of Grating Couplers", Appl. Phys. 14, pp. 235-254 (1977)].

If the coupling and uncoupling of the guided in the waveguide modes on one and the same grid, so the out-coupled beams are parallel to one of the direct orders of diffraction of the incident light beam. By using two (or more) superimposed gratings of different periodicity and / or orientation, however, succeeds in a beam of light into a planar waveguide on and couple out, the direction of at least one decoupled component beam is different from the directions of the reflected, transmitted, respectively directly diffracted portion of the incoming light beam.

In the figures 4-10 is illustrated schematically for various biperiodische grating structures: The incident light beam 6 on the first diffraction order of the grating G_a coupled into the waveguide; the coupled beam 7 passes through the wave-guiding layer and is continuously of the two superimposed gratings G_a and G_b coupled so that two partial beams 9a and 9b are formed with different propagation directions. The direction of separation of the run and out-coupled in the waveguide light beam 9b from the reflected portion 8 of the incident light beam 6 enables decoupled light to detect background-free, although the mesh regions in which the engaging and disengaging occurs, partially overlap.

As mentioned in the foregoing description of various embodiments of the invention already partly run in the implementation of the method the following actions occur:<ul><li>1. An optical film waveguide of a waveguide layer on a planar substrate, which biperiodischen with a multi-diffractive, eg, grid structure is modulated is brought superstrat side with a sample to be analyzed into contact. The multidiffraktive lattice structure consists for example of two gratings with different periodicity and / or orientation, which placed one above the other or alternately, or overlaid (superimposed) are.</li><li>2. Use the multi-diffractive grating structure beams are switched on and coupled into the waveguide layer; thereby decoupled component beams are generated whose propagation direction does not coincide with a direct order of diffraction of the incident on the grating structure beam. In particular, the directions of these decoupled component beams are different from the zero diffraction order, that is (by the layer transmitted respectively) of the directions of the light reflected at the layer portions of the incident light beams.</li><li>3. Although the regions partially overlap on the waveguide layer, in which the coupling and uncoupling of the light beams occurs, can (respectively through the layer transmitted) beams from the guided and coupled out from the layer partial beams are separated the light reflected on the layer.</li><li>4. The multidiffraktive grid modulation of the waveguiding layer is homogeneous in the plane of the layer; the efficiency of the coupling and decoupling of light is, therefore, not sensitive to a translation of the waveguide in the plane of the layer relative to the incident light beam.</li><li>5. The coupled light beams propagate. As guided modes in the waveguide layer and come here with a chemo-sensitive surface layer and / or with a sample interaction which superstrat side the film waveguide covered</li><li>6. Chemical changes (eg molecular deposits) on or in the immediate vicinity of the waveguide layer can be detected by measuring the (relative) intensity of one or more fed-out sub beams. </li><li>7. Two coherent (zBorthogonal polarized) light beams are simultaneously switched on and coupled with the help of multi-diffractive grating structure in the film waveguide, and the decoupled component beams of different polarizations are brought to interference (eg with a polarizer). The detection of chemical changes (eg molecular deposits) on or carried out in the immediate vicinity of the waveguide layer by measuring the relative phase angle (phase difference) of two decoupled partial beams, which are generated by the two simultaneously conducted, orthogonally polarized, fashions.</li><li>8. Chemical or physical effects on the wave-guiding layer, which take place outside of the inputs and Auskoppelregionen, do not affect the in the waveguide run and used for the measurement light.</li><li>9. The integration of various measuring points on the surface of a modulated multidiffractive layer waveguide (for example in a 2-dimensional grid) of several substances are detected in parallel or sequentially on a test substrate in a sample.</li></ul>