LAB-ON-A-CHIP SYSTEM WITH FUNCTIONALIZED WAVEGUIDE

Abstract

A lab-on-a-chip system (100) comprises an optical detection waveguide (122) that has an at least partially periodic structure (123, 501, 502, 503, 504) that is configured to couple light (152) from surroundings of the optical detection waveguide (122) into the optical detection waveguide (122). The lab-on-a-chip system (100) furthermore also comprises a microfluidic network (212), wherein the microfluidic network (212) has multiple lines and at least one reaction chamber (211, 211-1, 211-2, 211-3).

Claims

1. A lab-on-a-chip system, comprising: an optical detection waveguide that has an at least partially periodic structure that is configured to couple light from surroundings of the optical detection waveguide into the optical detection waveguide, and a microfluidic network, wherein the microfluidic network has multiple lines and at least one reaction chamber, wherein the lab-on-a-chip system is configured such that the at least one reaction chamber, of the microfluidic network can be arranged in the surroundings of the optical detection waveguide.

2. The lab-on-a-chip system according to claim 1, furthermore comprising: a multi-pixel detector having a sensitive surface, wherein the optical detection waveguide has an output coupling region that is arranged adjacent to the multi-pixel detector and that is configured to couple the light out of the optical detection waveguide in the direction of the multi-pixel detector, wherein the at least partially periodic structure and the output coupling region are configured to generate an image of the at least one reaction chamber on the sensitive surface.

3. The lab-on-a-chip system according to claim 2, wherein the at least one reaction chamber comprises a multiplicity of reaction chambers, wherein the at least partially periodic structure and the output coupling region are configured to image pixels of the image, which correspond to object points in different reaction chambers of the multiplicity of reaction chambers, onto different pixels of the multi-pixel detector.

4. The lab-on-a-chip system according to claim 2, wherein the at least partially periodic structure and the output coupling region are configured to image pixels of the image, which correspond to object points at different positions within one of the at least one reaction chambers, onto different pixels of the multi-pixel detector.

5. The lab-on-a-chip system according to claim 4, furthermore comprising: a computing unit that is configured to count objects of a predefined type in an image of the multi-pixel detector.

6. The lab-on-a-chip system according to claim 1, wherein the optical detection waveguide and the microfluidic network are arranged on a common substrate.

7. The lab-on-a-chip system according to claim 1, wherein the optical detection waveguide and the microfluidic network are arranged on different substrates, wherein the lab-on-a-chip system optionally furthermore comprises: a guide element that is configured to enable a relative movement of the different substrates in relation to one another.

8. The lab-on-a-chip system according to claim 1, wherein the at least partially periodic structure is configured to transmit the light with an imaging optical function, wherein different pixels that are defined by the imaging optical function are associated with different wavelengths of the light.

9. The lab-on-a-chip system according to claim 1, furthermore comprising: an optical illumination waveguide that comprises a further at least partially periodic structure that is configured to emit the light or additional light into the reaction chamber.

10. The lab-on-a-chip system according to claim 9, furthermore comprising: a light source that is optically coupled to the optical illumination waveguide and that is configured to emit the light and/or the additional light with an adjustable wavelength, and a computing unit that is configured to actuate the light source in order to feed the light and/or the additional light into the optical illumination waveguide, wherein the computing unit is furthermore configured to select the adjustable wavelength of the light and/or of the additional light on the basis of a wavelength dependency of an optical imaging function of the at least partially periodic structure and/or of the further at least partially periodic structure.

11. The lab-on-a-chip system according to claim 1, wherein the at least partially periodic structure is implemented by a holographic optical element, HOE, which optionally comprises one or more volume holograms integrated into the detection waveguide or a hologram applied to the detection waveguide.

12. The lab-on-a-chip system according to claim 1, wherein the at least partially periodic structure shapes the light through refraction and/or reflection.

13. The lab-on-a-chip system according to claim 1, wherein the at least partially periodic structure shapes the light through diffraction as a diffractive optical element, DOE.

14. The lab-on-a-chip system according to claim 1, wherein the at least partially periodic structure is at least partially transparent to visible light.

15. The lab-on-a-chip system according to claim 1, wherein the at least partially periodic structure is configured to couple the light into the optical detection waveguide with a wavelength dependency, wherein the at least one reaction chamber is integrated on a substrate, wherein the wavelength dependency does not allow coupling of additional light that is produced by fluorescence of the substrate into the optical detection waveguide, or allows this only with suppression.

16. A method, comprising: using the lab-on-a-chip system as claimed in one of the preceding claims to obtain a measurement image based on the light coupled into the optical detection waveguide, and using a microscopy device to obtain a further measurement image of the at least one reaction chamber at the same time as capturing the measurement image.

17. A lab-on-a-chip system, comprising: an optical illumination waveguide that has an at least partially periodic structure that is configured to couple light out of the optical illumination waveguide into surroundings of the optical illumination waveguide, and a microfluidic network, wherein the microfluidic network has multiple lines and at least one reaction chamber, wherein the lab-on-a-chip system is configured such that the at least one reaction chamber of the microfluidic network is able to be arranged in the surroundings of the optical illumination waveguide.

18. The lab-on-a-chip system according to claim 17, wherein the at least partially periodic structure is configured to emit at least part of the output-coupled light to the at least one reaction chamber.

19. A use of a lab-on-a-chip system according to claim 1 for microscopic blood analysis or a fluorescence measurement.

Description

BRIEF DESCRIPTION OF THE FIGURES

[0042] The properties, features and advantages of this invention described above and the way in which they are achieved will become clearer and more clearly understood in association with the following description of the exemplary embodiments which are explained in greater detail in association with the drawings.

[0043] FIG. 1 is a schematic view of a lab-on-a-chip system according to various examples.

[0044] FIG. 2 shows a top view of one exemplary implementation of a lab-on-a-chip system according to various examples.

[0045] FIG. 3 is a side view of the exemplary implementation of the lab-on-a-chip system from FIG. 2.

[0046] FIG. 4 is a side view of a variant of the exemplary implementation of the lab-on-a-chip system from FIG. 2.

[0047] FIG. 5 shows the use of a microscopy device for the exemplary implementation of the lab-on-a-chip system from FIG. 2 in the side view according to FIG. 3.

[0048] FIG. 6 is a flowchart of one exemplary method.

[0049] FIG. 7 illustrates one exemplary implementation of an at least partially periodic structure in the form of a diffractive grating according to various examples.

[0050] FIG. 8 illustrates one exemplary implementation of an at least partially periodic structure in the form of a volume hologram according to various examples.

[0051] FIG. 9 illustrates one exemplary implementation of an at least partially periodic structure in the form of a refractive grating structure according to various examples.

[0052] FIG. 10 illustrates one exemplary implementation of an at least partially periodic structure in the form of a combination of a reflective grating structure with a diffractive grating according to various examples.

[0053] FIG. 11 illustrates a reference implementation of a reflective structure for the input coupling or output coupling of light.

[0054] FIG. 12 schematically illustrates assembly line positioning of multiple laboratory chips with respect to a photonic chip.

DETAILED DESCRIPTION OF EMBODIMENTS

[0055] The present invention is explained in greater detail below on the basis of preferred embodiments with reference to the drawings. In the figures, identical reference signs denote identical or similar elements. The figures are schematic representations of various embodiments of the invention. Elements illustrated in the figures are not necessarily illustrated as true to scale. Rather, the various elements illustrated in the figures are rendered in such a way that their function and general purpose become comprehensible to a person skilled in the art. Connections and couplings between functional units and elements as illustrated in the figures may also be implemented as an indirect connection or coupling. A connection or coupling may be implemented in a wired or wireless manner. Functional units may be implemented as hardware, software or a combination of hardware and software.

[0056] Techniques in connection with lab-on-a-chip systems are described below. The lab-on-a-chip systems described herein use one or more functionalized optical waveguides to provide integrated optical excitation and/or detection. In particular, according to the various examples described herein, it may be possible for the functionalized optical waveguides to have input coupling regions and/or output coupling regions that implement an imaging optical function. Spatially resolved measurements may also thereby be performed. The imaging optical function may have wavelength selectivity. It is also possible to selectively address different reaction chambers in a wavelength-resolved manner.

[0057] Compared to conventional labs-on-a-chip, various effects may be achieved. Some effects are listed below. For example, it is possible to achieve a particularly high degree of integration, that is to say a particularly high level of miniaturization/compactness. Local targeted optical excitation is possible; this is not possible for example using classic freely propagating optical illuminationfor instance using a separate microscopy devicein line with reference implementations. Local targeted detection is also possible; this is not possible using a classic camera function or microscope function in line with reference implementations. It is also possible to eliminate the potential fluorescence of the substrate caused by excitation, currently not possible due to undifferentiated excitation/illumination. To this end, the partially periodic structure may be designed such that it does not forward or image the wavelength range of the fluorescent light of the substrate, but on the contrary reflects or transmits it, for instance, while at the same time the fluorescent light from the reaction chamber is forwarded or imaged. The Limit of Detection (LOD) may be increased.

[0058] Various examples relate to the implementation of a lab-on-a-chip through a microfluidic network and at least one reaction chamber. In connection with labs-on-a-chip, in particular the space-saving should be mentioned as an advantage, since complex processes have to take place in the smallest of spaces. Due to the size of the miniaturized laboratory, it is also very easy to transport, which makes it interesting, inter alia, for medical first aid outside GP surgeries and hospitals.

[0059] Generally speaking, a lab-on-a-chip thus comprises a microfluidic network and one or more reaction chambers. Liquids may be moved through the microfluidic network, for example by capillary forces. Extensive biological, chemical and/or physical processes may take place on an LOC according to the examples described hereinin particular in the one or more reaction chambers. The functionality of the microfluidic network may be increased by active components such as microvalves, pumps and/or sensors that are integrated into the microfluidic network.

[0060] The labs-on-a-chip have a wide range of applications. For example, there may be applications in the following fields: medical-biological research, chemical analysis or in-line process control for pharmacy, biotechnology and modern chemistry. The lab-on-a-chip may be characterized according to various physical properties. These include in particular: type of microfluidics; method of excitation; detection technology.

[0061] Exemplary applications for a lab-on-a-chip that may be implemented through such processes comprise: microarray analysis and next generation sequencing (NGS). Some applications comprise analyzing liquids or biological samples with the optical detection and analysis of fluorescent biomolecules. Other applications comprise blood analysis, malaria detection, fluorescence measurements, cell separation, etc. In the various examples described herein, all such applications or else other applications may be implemented by the lab-on-a-chip. The specific implementation of the lab-on-a-chip or the specific application or applications that are provided by the lab-on-a-chip are not essential to the techniques described herein. In other words, the techniques described herein may be combined with a wide variety of implementations of the lab-on-a-chip.

[0062] According to various examples, a description is given of an ultra-compact, multifunctional lab-on-a-chip system. The lab-on-a-chip system comprises a microfluidic network having one or more reaction chambers. The lab-on-a-chip system also comprises one or more multifunctional waveguides for integrated optical excitation and/or integrated optical detection of samples in the one or more reaction chambers.

[0063] For example, lateral input coupling into at least one of the one or more multifunctional waveguides could take place.

[0064] According to the various examples, a transparent detection function may be made possible, that is to say the light from the reaction chamber may be received by the at least one waveguide and guided to a detector. This may take place without significant degradation of the microfluidic function.

[0065] As may be seen in FIGS. 1-5, light from the one or more reaction chambers, in other words light that is emitted from the one or more reaction chambers, is at least partially coupled into the detection waveguide by an at least partially periodic structure. The input coupling results in the light being steered in the direction of a propagation direction, such that it is propagated along the propagation direction in the waveguide in the direction of a detector. The at least partially periodic structure may be arranged on an end face of the waveguide perpendicular to the propagation direction, or on an interface of the waveguide that extends along the propagation direction, for example on an interface of the detection waveguide facing and/or opposite the reaction chamber. The detector may be arranged on an end face along the propagation direction of the light, or not along the propagation direction, for example at an angle, for example, perpendicular, to the propagation direction.

[0066] As may also be seen in FIGS. 1-5, light is coupled out, through an at least partially periodic structure, from the illumination waveguide into surroundings of the illumination waveguide in which a microfluidic network is arranged, such that at least part of the output-coupled light impinges on the at least one reaction chamber.

[0067] According to various examples described herein, provision may thus be made for integrated optical excitation and/or integrated optical detection. This means that, according to various examples, it is not necessary to use external equipmentsuch as for example a microscope with an illumination modulefor optical detection and analysis.

[0068] However, in some examples, it is in this case also additionally possible to carry out external optical excitation and/or detection in addition to the integrated optical excitation and/or optical detection. This means that a lab-on-a-chip system, as described herein, may be used for integrated optical detection, for example with an integrated multi-pixel detector, in order to obtain a corresponding measurement image of at least one reaction chamber; and at the same time an external microscopy device may be used to capture a further measurement image of the same at least one reaction chamber.

[0069] This may be enabled through the transparent design of the least one waveguidefor example in a predetermined wavelength range, for instance in the visible wavelength rangesuch that wavelength-multiplexed measurements may be carried out using the microscope and an on-chip detector.

[0070] The integrated excitation/illumination function based on an optical waveguide enables spectrally selective illumination of the one or more reaction chambers, both spatially and temporally. The integrated transparent detection function enables in-situ detection.

[0071] Using the techniques described herein, it is thus possible to implement spectrally selective illumination or excitation of the liquid or biological samples to be analyzed using an integrated multifunctional illumination waveguide.

[0072] As an alternative or in addition, it is also possible to implement a transparent detection function by using a corresponding optical detection waveguide. This could be integrated for example into a cover of the microfluidic network.

[0073] Using such techniques, it may be possible to capture an image of the one or more reaction chambers in one detection step in the near field.

[0074] The lab-on-a-chip described herein is also particularly suitable for detecting a low photon flux, as is typically the case with fluorescence from biological samples of a limited quantity. Input coupling into a detection waveguide may in particular be made particularly efficient.

[0075] The lab-on-a-chip system may be integrated on one or more substrates. Such substrates may be made from: silicon, plastic and/or glass.

[0076] For example, it would be conceivable for both one or more optical waveguideswhich are used for the optical excitation and/or detectionand a microfluidic network to be integrated on a common substrate.

[0077] In one variant, the optical partthat is to say the one or more optical waveguidesmay be implemented separately from the microfluidic platethat is to say from the microfluidic network. The lab-on-a-chip system effectively becomes a plug-in card that is plugged in between an illumination and imaging plate. Due to the compact design of illumination and imaging, the entire system may be implemented in the size of a card reader.

[0078] FIG. 1 is a schematic view of a lab-on-a-chip system 100. In the illustrated example, it has two substrates 101, 201, wherein optical elements are arranged on the substrate 101 (hereinafter photonic chip 101) and serve for illumination and detection, and a microfluidic network 212 having one or more reaction chambers 211 is formed on the substrate 201 (hereinafter laboratory chip 201). In some examples, the photonic chip 101 and the laboratory chip 201 could also be integrated on a single substrate.

[0079] As a general rule, the photonic chip 101 and the laboratory chip 201 may be arranged in incident light geometry (cf. FIG. 12) or transmitted light geometry (cf. FIGS. 2 to 5) (the schematic illustration from FIG. 1 is not intended to be limiting in this respect). In incident light geometry, contactless measurements may be carried out, which may enable rapid measurement of multiple laboratory chips in succession. In incident light geometry, it may furthermore be possible to design the back of the laboratory chip 201 to be absorbent; which may make it possible for example to place elements of the lab-on-a-chip there in a flexible manner. In transmitted light geometry, the photonic chip 101 may be positioned precisely in relation to the laboratory chip 201. A mechanical guide element 299 could for example be provided for this purpose

[0080] In the example of FIG. 1, provision is also made for a mechanical guide element 299. This is configured to enable a relative movement of the two substrates 101, 201 with respect to one another. It is thereby possible for example to reuse the photonic chip 101 in connection with multiple laboratory chips 201. As a general rule, a mechanical guide element 299 may be used both in incident light geometry and in transmitted light geometry.

[0081] A stop position may be defined by the guide element 299, in which the laboratory chip 201 and the photonic chip 101 are positioned so as to allow optical excitation and/or optical detection of liquids in the reaction chambers.

[0082] Next, details in connection with the photonic chip 101 will be described. In the example of FIG. 1, this comprises a detection waveguide 122 and an illumination waveguide 112. As a general rule, it would be conceivable for the photonic chip 101 to comprise either the detection waveguide 122 or the illumination waveguide 112.

[0083] The detection waveguide 120 has an at least partially periodic structure 123 that is implemented for example by a multiplicity of volume holograms or a relief grating on a surface of the detection waveguide 120. The partially periodic structure 123 could also be adhesively bonded by way of a film. The at least partially periodic structure 123 could have a refractive and/or reflective beam shaping component; for example, the at least partially periodic structure 123 could implement a Fresnel lens in such a case. Various examples regarding the implementation of the partially periodic structure 123 were discussed above in connection with Table 1.

[0084] In this case, the at least partially periodic structure 123 is configured to couple light 152 from surroundings of the detection waveguide 122 into the detection waveguide 122. For example, the at least partially periodic structure may be configured to transmit the light 152 with an imaging optical function. In this case, different pixels of this imaging optical function may be associated with different wavelengths of the light 152. Depending on the angle of incidence, the coupling efficiency may be selectively high for specific wavelengths (wavelength selectivity). This means that, for example, different processes may be detected in different reaction chambers in a wavelength-resolved manner.

[0085] In the relative positioning of the laboratory chip 201 with respect to the photonic chip 101 as illustrated in FIG. 1, the one or more reaction chambers 211 are located in these surroundings. This means that the light 152 from the one or more reaction chambers is coupled into the detection waveguide 122. This light 152 then passes through the detection waveguide 122 and is guided, via an output coupling structure 124, to a detector 121for example a multi-pixel detector. The detector may be actuated by a computing unit 180 so as to capture images.

[0086] The at least partially periodic structure 123 thus forms an input coupling region. The at least partially periodic structure 123 and the output coupling region 124 are configured to generate an image of the one or more reaction chambers 211 on a sensitive surface of the detector 121.

[0087] The illumination waveguide 112 is arranged between a light source 111which may also be actuated by the computing unit 180 so as to emit light 151and the one or more reaction chambers 211. The illumination waveguide 112 comprises an at least partially periodic structure 113see Table 1 for different options. The at least partially periodic structure 113 is configured to couple the light 151 out of the illumination waveguide 112 into the surroundings of the illumination waveguide 112, wherein the one or more reaction chambers 211 are located in the surroundings.

[0088] The at least partially periodic structure 113 may in principle be designed so as to be identical to or correspond to the at least partially periodic structure 123.

[0089] The illumination waveguide 112 may also comprise an input coupling structure close to the light source 111 in order to couple the light 151 into the illumination waveguide 112 (not shown in FIG. 1). The input coupling structure could in turn be designed as an at least partially periodic structurecf. Table 1.

[0090] The at least partially periodic structure 113for example in combination with an input coupling structure of the illumination waveguide 112may be configured to transmit the light 151 with an imaging optical function. Different pixels of the imaging optical function may in this case be positioned at different positions of a specific reaction chamber 211; or else also in different reaction chambers. Different pixels of the imaging optical function may be associated with different wavelengths of the light 151, that is to say provision may be made for wavelength selectivity. This means that, for example, different processes may be excited in different reaction chambers in a wavelength-resolved manner.

[0091] The example of FIG. 1 illustrates that the light 151 is emitted by the light source 111 and the light 152 is detected by the detection waveguide 122. For example, the light 152 could be generated by fluorescence of material in one of the reaction chambers 211, with the fluorescence being stimulated by the light 151. In other examples, it would also be conceivable for the light 151 emitted by the light source 111 to be guided directly from the detection waveguide 122 to the detector 121. A corresponding selection may in turn be made based on the wavelength dependency of the imaging optical functions of the partially periodic structures 113, 123. For example, the computing unit 180 could be configured to actuate the light source 111 in a time-dependent manner in order to feed the light 151 into the optical illumination waveguide 112 with an adjustable wavelength that is selected depending on the wavelength dependency of the optical imaging function of the partially periodic structure 113 and optionally the partially periodic structure 123. Corresponding pixels of the multi-pixel detector 121 that are assigned to the same wavelength could be read out in a temporally correlated manner. This thus means that the computing unit 180 is able to take into account the wavelength selectivity of the partially periodic structures 113, 123.

[0092] FIG. 1 also illustrates that the computing unit 180 is able to control the microfluidic network 212, this generally being optional. For example, specific microvalves, etc. could be controlled. This may take place in a manner coordinated with the actuation of the light source 111 and/or of the detector 121.

[0093] FIG. 1 illustrates that additional light 153 passes through the at least partially periodic structure 123 and passes through the one or more reaction chambers 211. This additional light 153 may be emitted for example by an illumination module of a microscopy device and may enter a lens of the microscopy device. Measurements may thereby be carried out using the detector 121 and at the same time images may be captured using the microscopy device. This is made possible because the at least partially periodic structure 123 is at least partially transparent to light in the corresponding wavelength range, for example to visible light.

[0094] Based on the schematic illustration of the lab-on-a-chip system 100, one possible structural implementation is discussed below in connection with FIGS. 2 and 3. In this case, FIG. 2 shows a top view of the lab-on-a-chip system 100, and FIG. 3 shows a side view. In this case, the illustrated structural implementationhere in transmitted light geometry, that is to say the microfluidic network 212 is arranged between the waveguides 112, 122is only an example. It could also be measured in incident light geometry.

[0095] In the illustrated example, the microfluidic network 212 comprises multiple feed lines 221, 222 to multiple reaction chambers 211-1-211-3 (the sources are not illustrated in FIG. 2).

[0096] It may be seen from FIG. 3 that, by virtue of imaging optical functions of the partially periodic structure 113 and of the partially periodic structure 123for instance in combination with the corresponding wavelength dependency (this wavelength dependency would mean that the different beams in FIG. 3 indicate the propagation of light with different wavelengths)different reaction chambers 211-1-211-3 are able to be illuminated selectively (for example by actuating the light source 111 so as to emit corresponding light) and the light 152 emitted by the different reaction chambers is able to be imaged onto different pixels (indicated in FIG. 3) of a sensitive surface of the detector 121.

[0097] Another situation is illustrated in FIG. 4. FIG. 4 corresponds, in principle, to FIG. 3, wherein the lab-on-a-chip system 100 illustrated in FIG. 4 comprises a single reaction chamber 211. The at least partially periodic structure 123 and the output coupling region 124 are configured so as to image pixels of the image, which correspond to object points at different positions within the reaction chamber 211, onto different pixels of the multi-pixel detector 121.

[0098] FIG. 5which corresponds, in principle, to FIG. 3illustrates how, due to the partially transparent design of the optical waveguides 112, 122, measurements may be carried out in parallel with additional light 153 from a microscopy device.

[0099] FIG. 6 is a flowchart of one exemplary method.

[0100] First of all, in optional box 3005, the laboratory chip 201 may be arranged in relation to the photonic chip 101. For example, the guide element 299 could be used for this purpose, for instance to insert the laboratory chip 201 between the two waveguides 112, 122. The lab-on-a-chip system 100 is thereby formed. An automated arrangement could take place, for example in an assembly line application (cf. FIG. 12).

[0101] Box 3005 may be omitted if the microfluidic network 212 and the one or more waveguides 112, 122 are integrated on a single substrate.

[0102] Optionally, it would then be possible, in box 3010, to fix the lab-on-a-chip system 100 on a sample holder of a microscopy device, cf. FIG. 5.

[0103] The measurement may then be performed, as shown in box 3015. To this end, the computing unit 180 could actuate both the light source 111 and the detector 121.

[0104] This may take place synchronously. For example, depending on the used wavelength of the light source 111, a different reaction chamber could be addressed, which corresponds to reading out a corresponding pixel of the multi-pixel detector 121. In this case, the wavelength dependency of the imaging optical functions of the output coupling and input coupling regions is taken into account. This may be achieved through appropriate formation of volume holograms. Another variant would be to use a Fresnel lens, that is to say with a refractive component, in addition to the diffractive component.

[0105] At the same time as box 3015, an image capture could also take place using the microscopy device in optional box 3020.

[0106] In optional box 3025, an evaluation may take place. For example, it would be possible to count objects of a predefined type in the image of the multi-pixel detector, as obtained from box 3015for instance by way of the computing unit 180.

[0107] Applications such as blood analysis or else malaria detection may thereby be implemented, for example.

[0108] Next, various variants for implementing an at least partially periodic structure according to the various examples described herein will be explained in connection with the following figures. In this case, various variants are explained in connection with the detection waveguide 122, such that this implements an input coupling region. However, corresponding variants may also be used in connection with another optical waveguide, for instance the illumination waveguide 112.

[0109] Corresponding variants may also implement an output coupling region.

[0110] FIG. 7 illustrates aspects in connection with a partially periodic structure 501 that is implemented in the form of a diffractive grating structure (cf. Table 1: Example I, Example IV). In this case, the diffractive grating structure 501a DOEis integrated on a top side 122-1 of the detection waveguide 122, that is to say in the form of a surface relief (produced for instance by heat-induced material removal by way of laser scribing, or by stamping methods). Using the diffractive grating structure 601 in the example of FIG. 7, light is able to be input-coupled via the bottom side 122-2. As an alternative or in addition, the diffractive grating structure 501 could also be arranged on the bottom side 122-2that is to say facing the reaction chamber.

[0111] For example, a side of the diffractive grating structure 501 that faces away from the detection waveguide 122 could be coated with a reflective material or an absorbent material. An intrinsic wavelength selectivity of the diffractive grating structure 501 may thereby be modified.

[0112] The thickness of the diffractive grating structure 501 is small in comparison with the thickness of the detection waveguide 122. A high degree of integration may thereby be achieved.

[0113] FIG. 8 illustrates aspects in connection with a partially periodic structure 502, implemented here in the form of a diffractive volume hologram (cf. Table 1, Example II). A diffractive, beam-shaping effect may be achieved by modulating the refractive index. The volume hologram 502 is embedded in the detection waveguide 122. Multiple volume holograms could also be used adjacently (multiplexing).

[0114] FIG. 9 illustrates aspects in connection with a partially periodic structure 503, implemented here in the form of a refractive Fresnel structure (cf. Table 1: Example V). It is apparent from comparing FIG. 7 with FIG. 9 that the refractive periodic structure 503 has a greater periodicity and, moreover, the thickness of the structure perpendicular to the width of the detection waveguide 122 is greater than the corresponding parameters of the grating structure 501. In particular, the thickness of the refractive grating structure 503 is not small in comparison with the thickness of the detection waveguide 122.

[0115] For example, typical thicknesses of the DOE 501 in FIG. 7 would be in the range of 0.5 to 10 m; and typical thicknesses of the refractive structure 503 from FIG. 9 would be in the range of 80 m or greater.

[0116] The various Fresnel units of the Fresnel structure may each have curved surfaces (not shown in FIG. 9) in order to produce a refractive imaging effect.

[0117] The periodicity of the reflective periodic structure 503 may correspond to a spatial resolution of an imaging optical function. This means that a corresponding pixel may be obtained for each Fresnel unit. This thus means that the various Fresnel units of a Fresnel structure may be assigned for example to different reaction chambers that are to be imaged by different pixels (cf. FIG. 3). In contrast thereto, many grating unit cells of the diffractive grating structure 501 from FIG. 7 may interact in a phase-coherent manner (through constructive or destructive interference) in order to define a location point of a corresponding imaging optical function.

[0118] It would be possible for one or more filter layers to be applied to the Fresnel structure 503. For example, different prism units of the Fresnel structure 503 could be coated with different filters, that is to say for example filters that absorb different wavelengths. A wavelength dependency of the input coupling of light may thereby be achieved, in particular, for example, a different wavelength dependency for different location points of an imaging function.

[0119] FIG. 10 illustrates aspects in connection with a partially periodic structure 504, designed here in the form of a combined diffractive-refractive structure (cf. Table 1, Example III). In the example of FIG. 10, a grating structure is provided on the bottom side 122-2 of the detection waveguide 122 and a Fresnel structure is provided on the top side 122-1. The grating structure and the Fresnel structure could also be integrated together on the same side. For example, aberrations in the Fresnel structure could be reduced or compensated for by the diffractive structure.

[0120] FIG. 11 illustrates aspects in connection with a non-periodic structure, for reference. The non-periodic structure is comparatively thick and thereby prevents a high level of integration of the input coupling region, in comparison with the variants of the at least partially periodic structures in FIG. 7 to FIG. 10.

[0121] FIG. 12 illustrates aspects in connection with one possible implementation of the lab-on-a-chip system 100. In the example of FIG. 12, the laboratory chip 201 and the photonic chip 101 are not arranged in a sandwich structure according to the examples from FIG. 2 to FIG. 5, but are arranged laterally to one another. This corresponds to a reflected light geometry, in contrast to a transmitted light geometry according to FIG. 2 to FIG. 5. This means that measurements may be carried out in reflections; this means that light emitted from the illumination waveguide is reflected into one or more reaction chambers 211, and then collected in reflection via the detection waveguide.

[0122] Such a reflected light geometry has certain advantages. For example, it may not be necessary to set up a mechanical intervention by way of a guide element 299 between the laboratory chip 201 and the photonic chip 101. The guide element may be omitted. It could be possible to place multiple laboratory chips 201, 201-1, 201-2 in a measurement position in relation to the photonic chip 101 in serial automated processing (indicated in FIG. 12 by the horizontal arrow), for example using a conveyor belt or a pick and place machine. The optical coupling takes place only via an interface, which makes relative positioning easier. A high throughput of different measurements may be achieved.

[0123] In summary, a description has been given above of techniques that enable a particularly high level of integration of a lab-on-a-chip system. In particular, the optical detection and/or the optical illumination or excitation may be provided with a high degree of integration. This may be made possible through the use of one or more at least partially periodic optical structures that enable functionalization of an illumination waveguide and/or of a detection waveguide. Classic separate lens elements or separate prisms, which would typically take up a comparatively large amount of space, may thereby be dispensed with. At the same time, efficient input coupling and/or output coupling of light into and/or out of corresponding waveguides may be achieved through a suitable design of the at least partially periodic optical structures. This efficient input coupling and/or output coupling may be supplemented with further functionalization, such as a tailored wavelength dependency that is adapted to the microfluidic laboratory to be examined. In addition, images from different location points within a reaction chamber could be used to enable complicated counting applications as well. Interfering lightfor instance caused by fluorescence of the substratemay be filtered. A description has also been given above of different structural implementations of the lab-on-a-chip system that are suitable for different application casesfor instance individual testing or mass testswherein the decoupling of optics and microfluidics is able to be adapted here to the corresponding application case by way of an appropriate mechanical configuration (guide element, incident light geometry versus transmitted light geometry).

[0124] It goes without saying that the features of the embodiments and aspects of the invention described above may be combined with one another. In particular, the features may be used not only in the combinations described but also in other combinations or on their own without departing from the scope of the invention.

[0125] For example, a description has been given above of various implementations of a lab-on-a-chip system having a detection waveguide with a partially periodic structure for input coupling of light. It would also be possible to use a lab-on-a-chip system only having an illumination waveguide with an appropriately configured partially periodic structure. It would also be possiblefor example, if illumination and detection are performed at different timesfor the same optical waveguide to be used both for illumination and for detection, that is to say for the same at least partially periodic structure to be used once for output coupling of light and once for input coupling of light. It is then possible to use a beam splitter to guide the detected light to a detector and to receive the light to be emitted from a light source.