DIGITAL SENSOR DEVICE FOR DETECTING ANALYTES IN A SAMPLE

Abstract

A sensor device is provided for the detection of an occurrence and/or a concentration and/or an amount of an analyte in a sample. The device includes a sensor, connection electronics and a housing. The sensor is configured to convert chemical and/or biochemical information from an analyte, preferably a virus, in a sample to an electrical signal. The sensor includes a test cantilever having a base and a deformable part, where a receptor layer for selective uptake of the analyte has been applied at least atop the deformable part. The sensor further includes a reference cantilever having a base and a deformable part, where a reference layer for selective non-uptake of the analyte has been applied atop the deformable part.

Claims

1. A sensor for conversion of at least one of chemical and biochemical information from at least one analyte in a sample to an electrical signal, the sensor comprising: a test cantilever having a base and a deformable part, with a receptor layer configured for selective uptake the analyte applied at least atop the deformable part, the test cantilever having a test converter layer that includes a passive test transducer on the base and an active test transducer on the deformable part, and wherein a test function layer is disposed between the test converter layer and the receptor layer; and a reference cantilever having a base and a deformable part, with a reference layer configured for selective non-uptake of the analyte applied atop the deformable part, the reference cantilever having a reference converter layer that includes a passive reference transducer on the base and an active reference transducer on the deformable part, and wherein a reference function layer is disposed between the reference converter layer and the reference layer.

2. The sensor according to claim 1, wherein the active and passive reference transducers and the active and passive test transducers are configured to output an electrical signal corresponding to at least one of the occurrence, the concentration and the amount of the analyte in the sample.

3. The sensor according to claim 1, wherein the test function layer covers at least one of the active test transducer and the passive test transducer, and the reference function layer covers at least one of the active reference transducer and the passive reference transducer.

4. The sensor according to claim 1, wherein the test function layer forms a flat surface that accommodates the receptor layer.

5. The sensor according to claim 1, wherein the reference function layer forms a flat surface that accommodates the reference layer.

6. The sensor according to claim 1, wherein the test function layer and the reference function layer comprise a same material.

7. The sensor according to claim 1, wherein a material of at least one of the test function layer and the reference function layer is configured to adjust a surface energy in order to facilitate at least one of a binding of the receptor layer to the test function layer and a binding of the reference layer to the reference function layer.

8. The sensor according to claim 1, wherein at least one of the test function layer and the reference function layer comprises an electrically insulating material.

9. The sensor according to claim 1, wherein at least one of the test function layer and the reference function layer comprises a porous material that enables partial permeability to at least one of selected substances and analytes.

10. The sensor according to claim 1, wherein the test converter layer comprises electrodes configured to contact at least one of the passive test transducer and the active test transducer, and the electrodes are covered by the test function layer.

11. The sensor according to claim 1, wherein the reference converter layer comprises electrodes configured to contact at least one of the passive reference transducer and the active reference transducer, and the electrodes are covered by the reference function layer.

12. The sensor according to claim 1, further comprising a passivation layer arranged atop a lower surface of at least one of the test cantilever and a lower surface of the reference cantilever.

13. The sensor according to claim 12, wherein the passivation layer is configured to minimize adhesion of the analyte on the underside of the at least one of the test cantilever and the reference cantilever.

14. The sensor according to claim 13, further comprising at least one of a receptor layer and a reference layer for selective uptake of that analyte and that is arranged on the underside of the at least one of the test cantilever and the reference cantilever, respectively.

15. The sensor according to claim 14, wherein a change in a surface tension of the upper layer as a result of binding of the analyte to the at least one of the receptor layer and the reference layer is opposite of a change in a surface tension of the lower layer.

16. The sensor according to claim 1, wherein material properties of at least one of the test function layer and the reference function layer are configured to maximize a deformation in the at least one of the test transducer and the reference transducer induced by deformation of the deformable part of the test cantilever or the deformable part of the reference cantilever, respectively.

17. The sensor according to claim 16, wherein the material properties are one of a thickness and a modulus of elasticity of the respective layer.

18. The sensor according to claim 1, wherein at least one of the test function layer and the reference function layer are geometrically structured so as to maximize a deformation in at least one of the test transducer and the reference transducer, respectively, that is induced by deformation of the respective deformable part.

19. The sensor according to claim 1, wherein at least one of the test transducer and the reference transducer are structured in the horizontal plane of the cantilevers, such that a sensitivity of the respective transducers is optimized by a maximization of a deformation or change in length at a site of the respective transducers.

20. The sensor according to claim 1, wherein at least one of the test transducer and the reference transducer is geometrically structured such that a sensitivity of the respective transducers is optimized by a maximization of a deformation or a change in length at a site of the respective transducers, and wherein at least one of a spatially long side of the test transducer and a spatially long side of the reference transducer are aligned parallel to a main component of a deformation of the deformable part of the respective cantilever.

Description

BRIEF DESCRIPTION OF THE DRAWING

[0241] Exemplary embodiments of the invention are elucidated in detail by way of the description of the figures that follows. The figures show:

[0242] FIG. 1 is a schematic diagram of a first embodiment of the sensor;

[0243] FIGS. 2A, 2B, 2C and 2D are schematic diagrams of the cantilevers;

[0244] FIGS. 3A and 3B are schematic diagrams of a second embodiment of the sensor;

[0245] FIG. 4 is a schematic diagram of a third embodiment of the sensor;

[0246] FIGS. 5A, 5B, and 5C are schematic diagrams of additional embodiments of the sensor, and a circuit diagram of a full bridge;

[0247] FIG. 6 is a schematic diagram of a chip with multiple cantilever pairs;

[0248] FIG. 7 is a schematic diagram of the binding of antigens to antibodies;

[0249] FIG. 8 is schematic diagram of the sensor in the form of a cantilever with a function layer that covers the sensor layer;

[0250] FIG. 9A is a schematic diagram of selected layers of a cantilever without function layer, with neutral axis drawn in;

[0251] FIG. 9B is a schematic diagram of selected layers of a cantilever with additional function layer and a neutral axis shifted downward;

[0252] FIG. 10 is a schematic diagram of selected layers of a cantilever with additional function layer and a neutral axis shifted downward at the structuring site;

[0253] FIG. 11A is a top view of the converter layer of a cantilever with transducers structured in the plane; and

[0254] FIG. 11B is a lateral view of selected layers of a cantilever with structured height profile of the transducers

DETAILED DESCRIPTION

[0255] Exemplary embodiments are described below with reference to the figures. Elements that are identical, similar or have the same effect are given the same reference numerals here in the various figures, and repeated description of these elements is omitted in some cases in order to prevent redundancy.

[0256] FIG. 1 shows a schematic of a first embodiment of the proposed sensor 1 for converting chemical and/or biochemical information. The sensor 1 comprises a test cantilever 2, which in turn has a base 20, and a deformable part 22. A passive test transducer 200 is arranged on the base 20, while an active test transducer 220 is arranged on the deformable part 22.

[0257] In a similar manner, the sensor 1 also has a reference cantilever 3, which in turn has a base 30 with a passive reference transducer 300, and a deformable part 32 that has an active reference transducer 320.

[0258] The transducers 200, 220, 300, 320 are each connected, via electrodes 40, to electronics 4 that are capable of recording or of forwarding a measured signal from the transducers 200, 220, 300, 320, while the electronics 4 are likewise capable of supplying the transducers 200, 220, 300, 320 with current and/or voltage.

[0259] The sensor 1 has the objective of indicating the occurrence and/or the concentration and/or the amount of an analyte 90 in a sample 9.

[0260] In FIG. 1, the sample 9 is a fluid that has been produced, for example by treatment of a swab, in particular a nose swab or a throat swab, from a test subject. However, it may also be the case that the sample 9 is saliva or blood or another bodily fluid. However, it may also be the case that the sample 9 is a gargling fluid that the test subject has gargled. It may also be the case that the sample 9 has been obtained and/or synthesized from a tissue sample or another substance taken from the test subject. The analyte 90 may be dissolved here in the sample, or be in undissolved form, as a suspension or dispersion or emulsion.

[0261] In any case, the sensor 1 should be used to examine the sample 9 for the occurrence and/or a concentration and/or an amount of an analyte 90 in the sample 9. For this purpose, a receptor layer 24 is applied to the test cantilever 2, with which an analyte 90 can interact, or a receptor layer 24 that can adsorb or absorb the analyte 90. In the case of adsorption, the analyte 90 would adhere to the surface of the receptor layer 24, while in the case of absorption the analyte 90 would penetrate into the interior of the reference layer 90.

[0262] If the sample 9 includes an analyte 90, this analyte may thus interact with the receptor layer 24. This can have the effect that there is a change in the surface tension of the section coated with the receptor layer 24 in the deformable part 22 of the test cantilever 2. This change in surface tension can be registered by the active test transducer 220, which is in turn interpreted in the electronics 4 as the measured signal.

[0263] This change in the surface tension of the section coated with the receptor layer 24 in the deformable part 22 of the test cantilever 2 can also lead to deformation of the deformable part 22 of the test cantilever 2. The active test transducer 220 can therefore also register a deformation of the deformable part of the test cantilever 2, which is in turn interpreted in the electronics 4 as the measured signal.

[0264] However, a force exerted by the active test transducer 220 may already be registered owing to the interaction with the sample fluid 9, for example in that merely the surface tension of the fluid acts on the deformable part 22 of the test cantilever 2. Accordingly, in this case, it is not the presence of an analyte 90 that is responsible for a correspondingly resulting the formation or change in surface tension.

[0265] In order to establish the magnitude of this basic effect of the sample 9 on the test cantilever 2, the reference cantilever 3 is also brought into contact with the sample 9 at the same time as the test cantilever 2. For this purpose, the reference cantilever 3 has a reference layer 34, with which an analyte 90 cannot interact, or a reference layer 24 that is not able to adsorb or absorb the analyte 90. In this case, any interaction with the analyte 90 should be avoided in order to enable differentiation with regard to the measured signal from the test cantilever 2.

[0266] Since both the test cantilever 2 and the reference cantilever 3 interact with the sample 9, both cantilevers 2, 3 interact similarly with the sample 9. The difference in this case is however that the test cantilever 2 is additionally able to interact with any analyte 90 present via its reference layer 24. Accordingly, the measured signals from the active transducers 220, 320 differ, if an analyte 90 occurs in the sample 9. The magnitude of the difference between the measured signals can accordingly, in the simplest case, be used to infer the amount of the occurrence of the analyte 90 in the sample 9.

[0267] However, the test cantilever 2 and the reference cantilever 3 measure the occurrence of the analyte 19 in the sample 9 at different positions. There may be different environmental conditions at different positions of the sample, for example fluctuations in temperature or concentration gradients, etc. These different environmental conditions may be measured by the passive transducers 200, 300.

[0268] The passive transducers 200, 300 are arranged on the base and preferably do not detect any measured signal in the event of a deformation or change in the surface tension of the deformable part 22, 32 of the reference or test cantilevers 2, 3. However, the base level of the measured signal from the passive transducers 200, 300 may be influenced due to these different environmental conditions. Because the passive transducers 200, 301 provide a comparison value for each measured value from the active transducers 220, 23 that gives a view of the environmental conditions in isolation, the influence of the environmental conditions on the measured signals from the active transducers 220, 320 may be determined and reduced, or factored out or isolated.

[0269] The sensor 1 can accordingly be used to analyse the occurrence of an analyte 90 in a sample 9 in isolation, since due to a multitude of measurement points on the reference and test cantilevers 3, 2 the influence of interactions that are not associated with the analyte 90 is reduced and isolated. This enables high measurement accuracy of the occurrence of the analyte 90 in the sample 9.

[0270] FIG. 2A shows the comparison of the deformable parts 32, 22 of the reference and test cantilevers 3, 2 in the event of a deformation and longitudinal extension. The deformable part 32 of the reference cantilever 3 has an upper surface 360 and a lower surface 362. The deformable part 22 of the test cantilever 2 likewise has an upper surface 262 and a lower surface 262. If an analyte 90 in the sample 9 interacts with the test cantilever 2, or with the receptor layer 24, there is a change in surface tension and, for example, deformation of the deformable part 22 from the stationary part (that merges into the base of the test cantilever) toward the freely mobile part of the deformable part 22. The deflection L shown here results from the relative deflection between the deformable part 32 of the reference cantilever 3 and the deformable part 22 of the test cantilever 2 due to the interaction with the analyte 90.

[0271] The deformation of the deformable part 22 of the test cantilever 2 is shown in FIG. 2B. The cause of this is that the upper surface 260 and the lower surface 262 extend to different degrees. Because of the large extension D on the upper surface 260, an active transducer 220 applied thereto may register a change in surface tension and/or an extension force F. The registered change in surface tension and/or the extension force F may be converted here to an electronic signal by the active transducer 220 or influence an existing electronic signal, for example an applied voltage. This can be accomplished, for example, in that the resistance of the transducer changes if it experiences an extension force F, which in turn results in an extension of the transducer 220.

[0272] The transducer would also be able to detect a contraction of the surface on which it is arranged. In the embodiments disclosed, however, the transducers are always arranged on surfaces where an extension is expected.

[0273] However, the extension and/or change in surface tension and/or force detected by the transducer may also be a bending force or a shear force, or be brought about by a bending force or shear force, or generally be based on the modulus of elasticity of the respective cantilever. In particular, the attachment of the deformable part 22, 32 to the base 20, 30 has the result that the deformable part 22, 32 becomes aligned along a bending curve due to a force exerted by a change in the surface tension of the test cantilever. The resulting bending curve results in particular from the geometry, in particular the surface moment of inertia, of the cantilever, and by the mass of the cantilever and the modulus of elasticity. The bending curves may be described, for example, in accordance with beam theory.

[0274] The different surface tensions on the lower side and the upper side of the cantilever accordingly result in the described deformation or extension of the cantilever.

[0275] Beam theory makes it possible, for example, to predict the point on the deformable part 22, 32 at which the extension D will be at its greatest. It is possible to arrange the active transducer 220, 320 at this point in order to achieve an optimum signal-to-noise ratio and in order to have maximum sensitivity to the extensions. In the exact positioning of the transducers, however, other boundary conditions should also be taken into account.

[0276] In particular, the alignment of the transducers relative to the alignment of the cantilevers plays an important role. For example, FIG. 2C shows a non-deflected cantilever. If the cantilever comes into contact with the analyte, the surface tension changes and there is deformation of the material, as shown in FIG. 2D. FIG. 2D illustrates that the cantilever undergoes deformation perpendicular to the base 20, or to the bending edge. This is accompanied by a longitudinal extension DI of the upper surface. At the same time, deformation takes place parallel to the base 20, or to the bending edge, which is accompanied by a transverse extension Dq of the upper surface. The geometry of the cantilever makes it possible to determine the direction in which a greater extension D is brought about. The transducer may in particular be aligned in this direction in order to generate a particularly large measured signal.

[0277] By virtue of an increased mechanical extension at the site of the transducer, it is possible to even further improve the signal found by the transducer. Such an increased mechanical extension can be achieved, for example, via the arrangement and shape of the electrodes.

[0278] FIG. 3A shows a further embodiment of the sensor 1. In particular, the reference cantilever 3 and the test cantilever 2 have identical geometric dimensions; in particular, the height, width and thickness of the reference cantilever 3 correspond to the height, width and thickness of the test cantilever 2. This generates an extension D on the upper surfaces 260, 360. Because the geometrical dimensions of the cantilevers 2, 3 are identical, an identical dependence of the measured signal on the extension is accordingly also expected.

[0279] The width B of the cantilevers is preferably equal to the height H of the cantilevers 2, 3, thereby allowing a particularly large extension D on the upper surface 260, 360 of the cantilever 2, 3. For example, the cantilevers here have a width of less than 100 m, a length of less than 100 m and a thickness of less than 1 m, in particular a width of 50 m, a length of 50 m long and a thickness of 0.3 m.

[0280] In the embodiments of the sensor 1 in FIG. 3, the bases 30, 20 of the reference and test cantilever 3, 2 are additionally arranged on the same overall base. There is accordingly a direct mechanical connection and interaction of the cantilevers via the overall base. This enables, for example, to reduce the different environmental influences on the cantilevers 22, 3, since the cantilevers 2, 3 can be arranged closer to one another. In particular, the bases 30, 20 of the reference and test cantilevers 3, 2 can also be formed as one piece. This ensures that the bases also have the same material-specific binding properties, such that the measurement results from the passive and active transducers 200, 220, 300, 320 have good comparability with one another.

[0281] The distance A between the active transducers 320, 220 and the passive transducers 300, 200 is measured in the height direction H of the cantilevers. The distance A is in particular less than 100 m, thereby ensuring that the transducers are arranged as close as possible to one another, such that, for example, spatial environmental influences on the transducers are reduced.

[0282] FIG. 3B shows a further embodiment in which the transducers 200, 220, 300 and 320 are aligned perpendicular to the base 20, 30. While a transverse extension of the cantilevers 22, 23 is measured along the bending edge in FIG. 3A with the transverse alignment of the transducers, a longitudinal extension of the cantilevers 22, 23 is measured in FIG. 3B.

[0283] FIG. 4 shows one preferred embodiment in this regard, in which the active transducers 320, 220 and the passive transducers 300, 200 each adjoin the bending edge 10 of the cantilevers 3, 2. Since all the transducers 320, 300, 220, 200 adjoin the bending edge 10, the smallest possible distance A between the transducers 320, 300, 220, 200 is achieved. Furthermore, in this embodiment, the electrodes 40 and the transducers 320, 300, 220, 200 have mirror-symmetric orientation with a mirror axis of symmetry S. In particular, the transducers 320, 300, 220, 200 thus have mirror-symmetric orientation relative to one another.

[0284] FIG. 5A shows a further embodiment of the sensor 1. The transducers 300, 320, 200, 220 are contact-connected via the electrodes 401, 402, 403, 404. In particular, the active transducer 220 is connected to the active transducer 320 via the electrode 401. In addition, the passive transducer 200 is connected to the passive transducer 300 via the electrode 403. The active transducer 220 is additionally connected to the passive transducer 200 via the electrode 402, while the active transducer 320 is connected to the passive transducer 300 via the electrode 404. The result is thus a total of four electrodes via which the transducers are electrically contact-connected to one another. An electrical contact connection may especially be achieved here in that the transducers are applied to the electrodes so as to establish a conductive connection. Since the transducers have a thickness, it may in particular be the case that, when electrodes are applied subsequently, no conductive contact connection to the electrodes would be achievable at the edges of the transducers. This is ensured only when the thickness of the electrodes is greater than the thickness of the transducers.

[0285] FIG. 5B shows a further embodiment of the sensor 1. The electrodes that contact-connect the transducers 200, 220, 300, 320 have an overall mirror-symmetric structure. Currents flow through the electrodes, or there are voltages across them, such that, when these electrodes have an asymmetric design, there may be asymmetric crosstalk of electrical signals to the other electrodes. This mutual influencing may lead to the generation of a control signal between the electrodes, but this can be avoided by the symmetrical structure.

[0286] The transducers 200, 220, 300, 320 are in particular electrically interconnected in what is called a full bridge. The circuit of the full bridge is shown in FIG. 5C. In the full bridge, a DC voltage or AC voltage is applied between the electrodes 403, 401. The passive and active transducers act as a voltage divider between these electrodes due to their electrical resistances. A full bridge in the form shown has the advantage that no voltage is established between the electrodes 402, 404 if the ratio of the resistances of the passive transducer 200 to the active transducer 220 of the test cantilever 2 is identical to the ratio of the resistances of the passive transducer 300 to the active transducer 320 of the reference cantilever 3. The deviation of one resistance is in particular sufficient to change the resistance ratios, and thus in order to establish a voltage between the electrodes 402, 404.

[0287] When the reference cantilever 3 and the test cantilever 2 interact with the sample 9 and the analyte 90, both deformable parts 22, 32, for example, experience a change in surface tension, which is greater for the deformable part 22 of the test cantilever 2 than for the deformable part 32 of the reference cantilever 3. The resistance of the active test transducer 220 of the deformable part 22 of the test cantilever 2 will accordingly vary to a greater extent than for the reference transducer 320 of the deformable part 32 of the reference cantilever 3. If the resistances of the passive transducers 200, 300 do not change or at least change identically, a change in the resistance ratios results from the deformation of the deformable part 22 of the test cantilever 2 due to the interaction with the analyte 90 in the sample 9, which interacts specifically with the reference layer 24 of the test cantilever 2. In the event of such an interaction, a voltage is accordingly established between the electrodes 402, 404, such that a force exerted on the active test transducer 220 relative to the active reference transducer 320 can be indicated in the form of a cross-bridge voltage VB. The cross-bridge voltage VB is preferably proportional to the occurrence of the analyte 90 in the sample 9, thereby enabling a quantitative assessment of the measured signal.

[0288] A cross-bridge voltage detector 44 can indicate the cross-bridge voltage VB externally or forward it, such that the existence of a cross-bridge voltage VB is made visible to the user of the sensor 1. In particular, such a cross-bridge voltage detector 44 may also be formed by an A/D converter, where the A/D converter converts the cross-bridge voltage VB to a digital signal that can be forwarded to an external measuring device. In particular, the A/D converter may be operated in two different measurement modes. The first measurement mode is the differential measurement mode, in which the cross-bridge voltage VB is measured and a relative measured value for the deformation of the two reference and test cantilevers 3, 2 is thus generated. In this differential measurement mode, the measured signals from all the transducers 200, 22, 300, 23 are taken into account, such that the output signal from the A/D converter is a measured signal corrected for environmental influences, which can be used to infer the relative deformation of the deformable parts 32, 22 and thus the occurrence of an analyte 90.

[0289] The second measurement mode is the so-called the absolute measurement mode. In the absolute measurement mode, the cross-bridge voltage is not detected; instead, the signals at the electrodes 402 and 404 are tapped off in an isolated manner, such that it is possible to draw a conclusion as to the respective deflections of the deformable parts 32, 22. This information remains unavailable to the user in the differential measurement mode.

[0290] FIG. 6 shows a further embodiment of the sensor 1. The sensor 1 here comprises multiple cantilever pairs, where each cantilever pair here comprises a reference cantilever 3 and a test cantilever 2. The reference cantilever 3 and test cantilever 2, or the corresponding transducers, are, as in FIGS. 5A to C, electrically connected to one another via an electrode circuit, such that a cross-bridge voltage VB can be tapped off for each cantilever pair. The cross-bridge voltage VB may be tapped off from each cantilever pair by the A/D converter 440, or by the cross-bridge voltage detector 44. In particular, the measured signal from a specific cantilever pair may, for example, be output in the A/D converter 440 via an A/D converter logic unit, or the integrated measured signal from all cantilever pairs may be output, or a combination thereof. It is thus possible in particular to average the measured signals over various cantilever pairs, such that the occurrence of an analyte 90 is indicated with higher statistical significance. However, it is also possible for various reference and receptor layers 34, 24 to be applied to the different cantilever pairs, such that such a sensor 1 may be used to analyse the sample 9 for different analytes 90 at the same time. For example, however, it is also possible for a single reference cantilever 3 to serve as reference for multiple test cantilevers 2.

[0291] In particular, the sensor 1 is formed with the multitude of cantilever pairs on a chip 100. A chip here may mean that the sensor 1 has been fabricated from a single substrate, such that, for example, the various cantilevers 2, 3 are mechanically connected to one another. However, it may also be the case that the chip 100 comprises a further electronic circuit, which is, for example, a CMOS circuit, i.e. a semiconductor circuit that taps off the cross-bridge voltage VB and directly processes it further. Such a semiconductor circuit in combination with a sensor is also called a system-on-a-chip.

[0292] FIG. 7 shows a schematic of the structure of the various deformable parts 22, 32 of the reference and test cantilevers 3, 2. The construction of the cantilevers is identical apart from the receptor layer and the reference layer, meaning that an interaction with the sample or the surrounding medium, along with the mechanical design of the cantilever, is very substantially identical.

[0293] A reference converter layer 340 or a test converter layer 240 have respectively been applied atop the deformable part 32, 22 of the reference cantilever or test cantilever 3, 2, and these firstly form electrodes for reference or test transducer (not shown in FIG. 7) and secondly optionally promote adhesion between the surface of the deformable part 32, 22 and a reference function layer 390 or test function layer 290.

[0294] A monolayer 341, 241 may respectively have been applied atop the surface of the reference function layer 390 or test function 290, and a receptor layer 242 or a reference layer 342 may have been applied thereon.

[0295] The function layer 390, 290 has the function of creating an asymmetric layer structure of the cantilever 3, 2, so as to give a maximum difference in the upper surface area of the cantilever and a lower surface area of the cantilever. The converter layer 340, 240 may especially comprise gold or consist of gold, where the transducers are correspondingly contact-connected via the electrodes arranged in the converter layer 340, 240.

[0296] By means of the function layer 390, 290, an electrical insulation may also be applied atop the converter layer 340, 240, especially the converter layer 340, 240 comprising gold or consisting of gold, in order to provide insulation from the environment.

[0297] The function layer 390, 290 may also serve to compensate for the surface unevenness or trenches caused by the structuring of the electrodes of the converter layer 340, 240 and/or the formation of the transducers.

[0298] It is possible to apply a so-called self-assembly monolayer 341, 241 atop the function layer 390, 290, which is able to compensate for the remaining surface unevenness of the function layer 390, 290 beneath and simultaneously provides for promotion of adhesion for further layers, namely the reference or receptor layers 34, 24.

[0299] The structure of the reference layer or receptor layer 34, 24 may be different and may be matched to the respective demands of the analysis.

[0300] In a preferred embodiment, however, both layers are based on a layer that may comprise so-called protein A 242, which binds firstly to the self-assembly monolayer 241, 341, but also has and can bind to antibodies 243 or isotype control antibodies 343 on its surface.

[0301] The antibodies 243 are proteins that react or bind to an antigen 5 and hence, for example, mark virus cells in the human immune system, such that the immune system is accordingly able to destroy the marked virus in order, for example, to stem or to prevent a viral outbreak. The antibodies 243 are very substantially specific to the antigen 5, but may also interact with other similar antigens 50. FIG. 7 shows that the antibody 243 can interact with the antigen 5 and the similar antigens 50 to some degree.

[0302] In contrast to the antibody 243, the isotype control antibody 343 is a protein that preferentially with ultrahigh specificity does not interact with the antigen 5. This makes it possible to virtually rule out any interaction with a specific antigen 5. This is shown in FIG. 7 in that the isotype control antibody 343 can interact only with two similar antigens 50, but not with the one shown schematically as a square here.

[0303] Because the test cantilever 2 has an antibody 243 and the reference cantilever 3 has an isotype control antibody 343, it is ensured that, in the sample 9, the analyte 90, if the analyte 90 is an antigen 5, can only interact here with the test cantilever 2. This ensures that the relative deformation brought about by the analyte in the test cantilever 2, in comparison with the deformation of the reference cantilever 3, is based solely on the presence of the analyte 90 or of the antigen 5. Accordingly, it is possible with this sensor 1 to reliably and quickly detect an antigen 5.

[0304] In contrast to the upper surface of the cantilevers, the lower surface of the cantilevers is passivated. Such a passivation may have the effect that an interaction, or binding, or absorption or adsorption, of an analyte 90 in the sample 9 in or on the cantilevers is avoided. However, such a passivation layer in particular also contributes to an increase in the asymmetry of the layer structure in order to bring about the greatest possible extension effect on the upper surface of the cantilever 3, 2. In particular, the passivation layer may comprise trimethoxysilane and/or a blocking substance.

[0305] The sensor shown can in particular be used to detect the antigens 5 of a Sars-CoV2 virus or of another virus. For this purpose, the receptor layer 24 of the test cantilever 2 comprises Sars-CoV2 antibodies, for example, while the reference layer 34 comprises Sars-CoV2-specific isotype control antibodies. A measured signal is accordingly generated by the sensor 1 when the antigens 5 of a Sars-CoV2 virus are present in the sample 9 and these accumulate on the test cantilever 2 or the receptor layer 24.

[0306] FIG. 8 shows a schematic of a reference cantilever 3 or test cantilever 2. The cantilever 3, 2 is divided into base 30, 20 and a deformable part 32, 22, where the boundary between the base 30, 20 and the deformable part 32, 22 is at the bending edge 31, 21.

[0307] In the embodiment shown, the reference cantilever 3 or test cantilever 2 comprises or is composed of multiple layers. The cantilever 3, 2 here comprises a main body 301, 201 which comprises or has been manufactured from silicon, for example, atop which has been applied a first carrier layer 321, 221, consisting of SiN for example, that project beyond the edge of the main body 301, 201 and hence extends beyond base 30, 20 and the deformable part 32, 22, and hence in structural terms also forms the deformable part 32, 22 of the cantilever 3, 2.

[0308] In addition, the cantilever 3, 2 comprises a test converter layer 240 or reference converter layer 340 which is formed as a conductive layer and is formed to electrically connect a passive reference or test transducer 300, 200 on the base 30, 20 and an active reference or test transducer 320, 220 on the deformable part 32, 22. In the test converter layer 240 or reference converter layer 340, it is possible to provide correspondingly structured conductor tracks that form the intended conductor structure for contact connection of the respective transducers.

[0309] The respective transducers 300, 320, 200, 220 may be accommodated in the respective converter layer 340, 240. In other words, the structure of the conductor tracks of the converter layer may be formed in such a way that the transducers 300, 320, 200, 220 are in direct contact with or have been applied atop the first carrier layer 321, 221, and the conductor tracks adjoin them laterally.

[0310] The converter layer 340, 240, which is in the form of a conductive layer in the design shown, for the purpose of increased surface extension in the converter layer, may simultaneously serve as activation layer, such that the sensitivity of the active reference or test transducer 320, 220 is increased on deformation of the cantilever.

[0311] As indicated in the figure by the gaps in the converter layer 340, 240 at the sites of the active and passive reference or test transducer 300, 200 and 320, 220, the converter layer 340, 240 formed as a conductive layer is structured for suitable electrical contact connection of the reference or test transducer 320, 220, 300, 200 to electrodes.

[0312] The cantilever 3, 2 also comprises a test function layer or reference function layer 390, 290 arranged between the converter layer 340, 240 and a receptor layer or reference layer 34, 24. In the embodiment shown, the function layer 390, 290 covers the complete area of the converter layer 340, 240, including the active and passive reference or test transducer 320, 220 and 300, 200. The receptor layer or reference layer 32, 22 has been applied on the outer surface of the function layer 390, 290 in order to ensure direct contact with a sample to be examined.

[0313] The test function layer 290 or reference function layer 390 can thus, for example, compensate for or at least reduce the surface unevenness caused by the structuring of the electrodes in the converter layer 340, 240.

[0314] The test function layer 290 or reference function layer 390 can thus also achieve, for example, electrical insulation of the electrodes in the converter layer 340, 240 and of the transducers 200, 220, 300, 320 with respect to the receptor layer or reference layer 32, 22.

[0315] For example, FIG. 9A shows a layer structure of the cantilever, especially comprising a carrier layer 321, 221 and a converter layer 340, 240, and also passive transducers 300, 200 and active transducers 320, 220.

[0316] In addition, a neutral axis 35, 25 of the cantilever 3, 2 is drawn in the form of a dotted line.

[0317] The neutral axis 35, 25 is characterized in that no change in length takes place along said axis on bending of the cantilever. As shown for example in the figure, the line of the neutral axis is influenced significantly by the layer structure. In the case of inhomogeneous material, especially a material with a homogeneous module of elasticity, the neutral axis runs along the geometric middle of the material (considering bending/deformation of the material transverse to this neutral axis).

[0318] In the case of multiple layers and possibly different moduli of elasticity and thicknesses of the layers involved, the neutral axis may also lie away from the geometric middle of the layer structure, as illustrated by the corresponding equation in the general part of the description.

[0319] The neutral axis 35, 25 should preferably be as far as possible away from the active transducers in order to maximize the sensitivity of the sensor. In other words, the neutral axis 35, 25 preferably lies such that the change in surface tension or change in length at the position of the active transducers is at a maximum.

[0320] However, the neutral axis 35, 25 in FIG. 9A shows a deviation at those positions where the transducers 300, 200 and 320, 220 are positioned. Typically, the effect of the material of the transducers is a shift in the neutral axis directed toward the transducers. This creates a comparatively reduced change in length compared to the rest of the layer structure at the positions of the transducers on bending or variation of the surface tension, which reduces the sensitivity of the sensor.

[0321] In order to counter this unwanted effect, in FIG. 9B, according to a preferred embodiment, a function layer 390, 290 has been applied atop the converter layer 340, 240. The applying of the function layer 390, 290 can move the neutral axis 35, 25 within the layer structure.

[0322] This is shown in FIG. 9B. By comparison with the neutral axis 35, 25 from FIG. 9A, the neutral axis in FIG. 9B has been shifted downward. In order to move the neutral axis 36, 25 downward by means of this additional function layer 340, 240, in this embodiment, the modulus of elasticity of the function layer 340, 240 must be much smaller than the modulus of elasticity of the layer structure beneath. In addition, the thickness of the function layer 340, 240 must be sufficiently small in order to induce the shift shown of the neutral axis 35, 25 away from the transducers.

[0323] FIG. 10 shows essentially the same arrangement as FIG. 9B, except that structuring of the height profile of the function layer 390, 290 is shown in schematic form here, which is represented for example as a recess 391, 291 at the site of the active reference or test transducer 320, 220. As shown in FIG. 10, the change in the height profile of the function layer 390, 290 can influence the line of the neutral axis 35, 25 in such a way that the neutral axis is at a distance from the transducer at the site thereof.

[0324] The recess 391, 291 achieves a controlled influence on the stress distribution of the cantilever 3, 2, which is preferably such that the extension under deformation of the deformable part 32, 22 of the cantilever 3, 2 is at a maximum at the site of the active reference or test transducer 320, 220.

[0325] It should be pointed out that it is possible also to apply a receptor layer 34, 24 atop the structured function layer 390, 290.

[0326] FIG. 11A shows a top view of a cantilever, in particular of the carrier layer 321, 221, and of the converter layer 340, 240 on top, into which the passive transducers 300, 200 and the active transducers 320, 220 have been embedded.

[0327] For example, the converter layer 340, 240 may consist of gold or comprise gold, and comprise electrodes, i.e. an electrical connection for the transducers. As shown in FIG. 11, the transducers are structured in a non-trivial form. A trivial form here would correspond typically to a rectangular shape. The structuring can achieve a non-homogeneous distribution of stress in the transducers.

[0328] FIG. 11B shows a cantilever layer structure comprising a carrier layer 321, 221 and a converter layer 340, 240, where the passive transducers 300, 200 and the active transducers 320, 220 have a non-trivial form with regard to their height profile. A trivial form here would correspond to a flat height profile of the transducers. Such structuring of the height profile of the transducers can bring about a controlled influence on the stress distribution and an influence on the neutral axis at the site of the transducers themselves. It is possible here to configure the structuring in such a way that the stress distribution at the respective site of the transducers is optimized, i.e. the change in length in particular is maximized on bending of the cantilevers at the site of the transducers.

[0329] Where applicable, all individual features that are illustrated in the embodiments may be combined with one another and/or exchanged for one another without departing from the scope of the invention.

LIST OF REFERENCE SIGNS

[0330] 1 sensor [0331] 10 bending edge [0332] 2 test cantilever [0333] 20 base [0334] 201 main body [0335] 21 bending edge [0336] 200 passive test transducer [0337] 22 deformable part [0338] 221 carrier layer [0339] 220 active test transducer [0340] 24 receptor layer [0341] 25 neutral axis of the test cantilever [0342] 240 test converter layer [0343] 241 self-assembly monolayer [0344] 242 protein A [0345] 243 antibody [0346] 244 passivation layer [0347] 26 surface [0348] 260 upper surface [0349] 262 lower surface [0350] 290 test function layer [0351] 291 recess [0352] 3 reference cantilever [0353] 30 base [0354] 301 main body [0355] 31 bending edge [0356] 300 passive reference transducer [0357] 32 deformable part [0358] 321 carrier layer [0359] 320 active reference transducer [0360] 34 reference layer [0361] 35 neutral axis of the reference cantilever [0362] 340 reference converter layer [0363] 341 self-assembly monolayer [0364] 342 protein A [0365] 343 isotype control antibody [0366] 344 passivation layer [0367] 36 surface [0368] 360 upper surface [0369] 362 lower surface [0370] 390 reference function layer [0371] 391 recess [0372] 4 electronics [0373] 40 electrode [0374] 400, 401, 402, 403 electrodes [0375] 42 cross-bridge voltage detector [0376] 44 A/D converter [0377] 440 A/D converter logic unit [0378] 5 antigen [0379] 50 other antigen [0380] F force [0381] L deflection [0382] D extension [0383] AT distance between active and passive transducer [0384] AE distance between electrodes [0385] S axis of symmetry [0386] VB cross-bridge voltage