DIGITAL SENSOR DEVICE FOR DETECTING AN ANALYTE IN A SAMPLE

Abstract

A sensor device is provided for detecting an incidence and/or a concentration and/or an amount of an analyte in a sample. The sensor device includes a sensor, connection electronics and a housing. The sensor converts chemical and/or biochemical information of an analyte in a sample into an electrical signal. The sensor includes a test cantilever that has a base and a deformable part, where a receptor layer for selective reception of the analyte is applied at least to the deformable part. The sensor also includes a reference cantilever that has a base and a deformable part, where a reference layer for selective non-reception of the analyte is applied to the deformable part.

Claims

1. A sensor device for detecting at least one of an incidence, a concentration and an amount of an analyte in a sample, the sensor device comprising: a sensor configured to convert at least one of chemical and biochemical information of an analyte in a sample into an electrical signal; connection electronics; and a housing, wherein the sensor comprises a test cantilever that has a base and a deformable part, wherein a receptor layer for selective reception of the analyte is applied at least to the deformable part of the test cantilever, and wherein the sensor further comprises a reference cantilever that has a base and a deformable part, wherein a reference layer for selective non-reception of the analyte is applied to the deformable part of the reference cantilever.

2. The sensor device according to claim 1, further comprising: a passive test transducer arranged on the base of the test cantilever and an active test transducer arranged on the deformable part of the test cantilever; and a passive reference transducer arranged on the base of the reference cantilever and an active reference transducer arranged on the deformable part of the reference cantilever, wherein the respective active and passive reference transducers are configured to output an electrical signal corresponding to the at least one of the incidence, concentration and the amount of the analyte in the sample.

3. The sensor device according to claim 2, wherein the selective reception of the analyte by the receptor layer and the selective non-reception of the analyte by the reference layer causes at least one of a deformation and a change in a surface stress of the test cantilever with respect to the reference cantilever, and the at least one of the incidence, the concentration and the amount of the analyte is inferred by comparing forces detected by the respective transducers or by comparing surface stresses detected by the respective transducers.

4. The sensor device according to claim 1, wherein the deformable parts of the reference and test cantilevers have identical geometric dimensions, wherein a width of the deformable parts of the reference and test cantilevers corresponds to a length of the deformable parts of the reference and test cantilevers, and wherein the bases of the reference and test cantilevers are arranged on a same overall base and the bases are formed in one piece with one another.

5. The sensor device according to claim 2, wherein the respective transducers are electrically interconnected in a full bridge that is configured to build up a transverse bridge voltage (VB) based on electrical properties of the respective transducers.

6. The sensor device according to claim 5, further comprising an A/D converter configured to convert the transverse bridge voltage (VB) into a digital signal and that is configured to be operated in at least one of a differential measuring mode and in an absolute measuring mode using an A/D converter logic unit.

7. The sensor device according to claim 1, further comprising: a passivation layer applied to lower surfaces of the reference and test cantilevers; an activation layer applied to upper surfaces of the reference and test cantilevers; a self-assembling monolayer applied to the activation layer; and at least one of a reference layer or receptor layer applied to the self-assembling monolayer of the reference and test cantilever, respectively, wherein the receptor layer comprises antibodies for an antigen and the reference layer comprises an antigen-specific isotype control antibody according to the antibody of the receptor layer.

8. The sensor device according to claim 1, wherein: the receptor layer comprises single-strand DNA (ssDNA) and/or other DNA fragments that bind specifically to DNA fragments in the sample and the reference layer comprises single-strand DNA and/or other DNA fragments that do not bind to any chemical and/or biochemical and/or physical species in the sample, but correspond to the receptor layer in terms of characteristic parameters, or the receptor layer comprises single-strand RNA and/or other RNA fragments that bind specifically to RNA fragments in the sample and the reference layer comprises single-strand RNA and/or other RNA fragments that do not bind to any chemical and/or biochemical and/or physical species in the sample, but correspond to the receptor layer in terms of characteristic parameters, or the receptor layer comprises antibodies and/or other and/or further proteins that are able to specifically bind target proteins and the reference layer comprises specific isotype control antibodies and/or other and/or further proteins that do not bind to any chemical and/or biochemical and/or physical species in the sample, or the receptor layer comprises scFv antibodies and the reference layer comprises scFv antibody-specific isotype control antibodies; or the receptor layer comprises Sars-CoV2 antibodies and the reference layer comprises Sars-CoV2-specific isotype control antibodies; or the receptor layer and the reference layer comprise hydrogels.

9. The sensor device according to claim 6, wherein the connection electronics comprise a printable circuit board that is configured to ensure the electrical communication between a connection socket and the sensor.

10. The sensor device according to claim 9, wherein the connection socket and the printable circuit board are configured to perform at least one of: implementing a voltage supply for the full bridge, reading the transverse bridge voltage (VB), reading the output signal from the A/D converter, setting the measuring mode of the A/D converter logic unit, and implementing ESD protection.

11. The sensor device according to claim 9, wherein the connection socket is a magnetic connection socket.

12. The sensor device according to claim 1, wherein: the housing encloses the sensor and the connection electronics, the housing has an opening for connecting the connection electronics, and the housing has a measurement opening through which at least the deformable parts of the cantilevers of the sensor protrude from the housing.

13. The sensor device according to claim 12, wherein the openings are sealed by rubber seals.

14. The sensor device according to claim 12, wherein the housing comprises two parts that are connected to one another by a snap-in connection.

15. The sensor device according to claim 12, wherein the measurement opening is surrounded by a thread that corresponds to a thread of a sample vial.

16. The sensor device according to claim 12, wherein the housing has a protective cap for the deformable parts of the reference and test cantilevers, with the protective cap configured to protect the deformable parts against any direct mechanical action of the sample and allows a controlled supply of the sample to the deformable parts of the reference and test cantilevers.

17. The sensor device according to claim 9, wherein the printable circuit board has an ESD protection contact or grounding contact, at least part of the sensor housing has a conductivity of less than 1 GΩ and the at least one conductive housing part is electrically conductively connected to the printable circuit board.

18. The sensor device according to claim 6, wherein: the sensor device is connected to an evaluation station that is configured to evaluate the measured signals from at least one of the transverse bridge voltage detector and the A/D converter, and the evaluation station is configured to communicate with a computer system in a wired or wireless manner, wherein a display of the evaluation is displayed on the computer system.

19. The sensor device according to claim 3, wherein at least one of the deformation and the change in the surface stress is achieved in a transverse direction of at least one of the test cantilever and the reference cantilever, with the transverse direction running parallel to the base of the test cantilever and/or of the reference cantilever.

20. The sensor device according to claim 3, wherein at least one of the deformation and the change in the surface stress is achieved in a longitudinal direction of at least one of the test cantilever and the reference cantilever, wherein the longitudinal direction runs perpendicular to the base of the test cantilever and/or the reference cantilever.

Description

BRIEF DESCRIPTION OF THE FIGURES

[0229] Preferred further embodiments of the invention are explained in more detail by way of the following description of the figures, in which:

[0230] FIG. 1 shows a schematic illustration of a first embodiment of the sensor;

[0231] FIGS. 2A, B, C, D show a schematic illustration of the cantilevers;

[0232] FIGS. 3A, B show a schematic illustration of a second embodiment of the sensor;

[0233] FIG. 4 shows a schematic illustration of a third embodiment of the sensor;

[0234] FIGS. 5A, B, C show further illustrations of further embodiments of the sensor, and also a circuit diagram of a full bridge;

[0235] FIG. 6 shows a schematic illustration of a chip with multiple cantilever pairs;

[0236] FIG. 7 shows a schematic illustration of the binding of antigens to antibodies;

[0237] FIG. 8 shows an exploded drawing of the sensor device; and

[0238] FIGS. 9A, B show a schematic illustration of the sensor device in connection with an evaluation station and a computer.

DETAILED DESCRIPTION OF EMBODIMENTS

[0239] Preferred embodiments are described below based on the figures. In this case, elements that are identical, similar or have the same effect are provided with identical reference signs in the various figures and a repeated description of these elements is partly omitted in order to prevent redundancies.

[0240] FIG. 1 schematically shows a first embodiment of the sensor 1 according to the invention for converting chemical and/or biochemical information. The sensor 1 comprises a test cantilever 2, which in turn has a base 20, and also 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.

[0241] 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.

[0242] 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.

[0243] The sensor 1 is tasked with indicating the incidence and/or the concentration and/or the amount of an analyte 90 in a sample 9.

[0244] In FIG. 1, the sample 9 is a fluid that has been produced by a test subject, for example by treating a swab, in particular a nose swab or a throat swab. 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 in this case be dissolved in the sample, or be present in undissolved form, as a suspension or dispersion or emulsion.

[0245] In any case, the sensor 1 should be used to examine the sample 9 with regard to the incidence 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 is able to 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.

[0246] If the sample 9 contains an analyte 90, this analyte may thus interact with the receptor layer 24. This may cause the surface stress of the portion of the deformable part 22 of the test cantilever 2 coated with the receptor layer 24 to change, resulting in a deformation of the of the deformable part 22 of the test cantilever 2. The active test transducer 220 therefore registers a deformation and/or change in the surface stress of the deformable part of the test cantilever 2, which is in turn interpreted as a measured signal in the electronics 4.

[0247] However, a force exerted by the active test transducer 220 may already be registered due to the interaction with the sample fluid 9, for example since only the surface stress of the fluid acts on the deformable part 22 of the test cantilever 2 and bends it. The presence of an analyte 90 is accordingly not responsible for such a deformation.

[0248] In order to establish the magnitude of this basic action 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 receptor layer an analyte 90 can 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 allow differentiation with regard to the measured signal from the test cantilever 2.

[0249] 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 that is present via its reference layer 24. The measured signals from the active transducers 220, 320 accordingly differ if an analyte 90 occurs in the sample 9. The magnitude of the difference between the measured signals may accordingly, in the simplest case, be used to infer the amount of the incidence of the analyte 90 in the sample 9.

[0250] The test cantilever 2 and the reference cantilever 3 however measure the incidence of the analyte 90 in the sample 9 at different positions. There may be different environmental conditions at different positions of the sample, such as for example temperature fluctuations or concentration gradients, etc. These different environmental conditions may be measured by the passive transducers 200, 300.

[0251] The passive transducers 200, 300 are arranged on the base and preferably do not detect any measured signal in the event of a deformation 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. Since, for each measured value from the active transducers 220, 230, a comparison value is provided by the passive transducers 200, 300, this comparison value considering 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.

[0252] The sensor 1 may accordingly be used to analyze the incidence of an analyte 90 in a sample 9 in isolation, since the influence of interactions that are not associated with the analyte 90 are reduced and isolated due to a large number of measurement points on the reference and test cantilevers 3, 2. This allows a high measurement accuracy of the incidence of the analyte 90 in the sample 9.

[0253] 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 stretching. 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 260 and a lower surface 262. If an analyte 90 of the sample 9 interacts with the test cantilever 2, or with the receptor layer 24, the deformable part 22 deforms from the stationary part (that transitions into the base of the test cantilever) toward the freely movable part of the deformable part 22. The deflection L that is shown is in this case given by 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.

[0254] The deformation of the deformable part 22 of the test cantilever 2 is shown in FIG. 2B. Deformation. The cause of this is that the upper surface 260 and the lower surface 262 expand to different extents. Due to the large stretching D on the upper surface 260, an active transducer 220 applied thereto may register a change in surface stress and/or a stretching force F. The registered change in the surface stress and/or the stretching force F may in this case be converted into an electronic signal by the active transducer 220 or influence an existing electronic signal, for example an applied voltage. This may for example take place by the transducer changing the resistance if it experiences a stretching force F, which in turn results in a stretching of the transducer 220.

[0255] The transducer could also detect a contraction of the surface on which it is arranged. In the embodiments shown, the transducers are however always arranged on surfaces for which a stretching is expected.

[0256] The stretching and/or change in surface stress and/or force detected by the transducer may however 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. The attachment of the deformable part 22, 32 to the base 20, 30 in particular results in the deformable part 22, 32 being oriented along a bending curve due to a force exerted by a change in the surface stress of the test cantilever. The resulting bending curve is described in particular by 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.

[0257] The different surface stresses on the lower side and the upper side of the cantilever accordingly result in the described deformation or stretching of the cantilever.

[0258] Beam theory makes it possible for example to predict the point of the deformable part 22, 32 at which the stretching D will be largest. 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 react as sensitively as possible to the stretching. When positioning the transducers precisely, however, other boundary conditions should also be taken into consideration.

[0259] The orientation of the transducers relative to the orientation of the cantilevers plays a particularly important role. FIG. 2C shows a non-deflected cantilever for example. If the cantilever comes into contact with the analyte, then the surface stress changes and there is a deformation of the material, as shown in FIG. 2D. FIG. 2D illustrates that the cantilever experiences a 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, a deformation takes place parallel to the base 20, or to the bending edge, which is accompanied by a transverse extrention Dq of the upper surface. The geometry of the cantilever makes it possible to define the direction along which a larger extension D is brought about. The transducer may in particular be oriented along this direction in order to generate a particularly large measured signal.

[0260] Over-dimensioning a mechanical stretching at the location of the transducer makes it possible to improve the signal ascertained by the transducer even further. Such over-dimensioning may for example be achieved through the arrangement and form of the electrodes.

[0261] FIG. 3A shows a further embodiment of the sensor 1. The reference cantilever and the test cantilever 2 in particular 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. An stretching D is thereby generated on the upper surfaces 260, 360. Since the geometrical dimensions of the cantilevers 2, 3 are identical, an identical dependency of the measured signal on the stretching is accordingly also expected.

[0262] The width B of the cantilevers is preferably identical to the height H of the cantilevers 2, 3, thereby allowing a particularly large stretching D on the upper surface 260, 30 of the cantilevers 2, 3. For example, the cantilevers are in this case less than 100 μm wide, less than 100 μm long and less than 1 μm thick, in particular 50 μm wide, 50 μm long and 0.3 μm thick.

[0263] In the embodiment 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 makes it possible for example to reduce the various environmental influences on the cantilevers 2, 3, since the cantilevers 2, 3 can be arranged closer to one another. The bases 30, 20 of the reference and test cantilevers 3, 2 may in particular also be formed in one piece with one another. 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 can be compared well with one another.

[0264] The distance A between the active transducers 320, 220 and the passive transducers 300, 200 is measured along the height direction H of the cantilevers. The distance A is in particular less than 100 μm, 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.

[0265] FIG. 3B shows a further embodiment in which the transducers 200, 220, 300 and 320 are oriented perpendicular to the base 20, 30. While a transverse stretching of the cantilevers 2, 3 is measured along the bending edge in FIG. 3A with the transverse orientation of the transducers, a longitudinal stretching of the cantilevers 2, 3 is measured in FIG. 3B.

[0266] One preferred embodiment in this regard is shown in FIG. 4, in which the active transducers 320, 220 and the passive transducers 300, 200 each lie against the bending edge 10 of the cantilevers 3, 2. Since all of the transducers 320, 300, 220, 200 lie against the bending edge 10, the smallest possible distance A between the transducers 320, 300, 220, 200 is realized. Furthermore, in this embodiment, the electrodes 40 and the transducers 320, 300, 220, 200 are oriented mirror-symmetrically to a mirror axis of symmetry S. The transducers 320, 300, 220, 200 are thus in particular oriented mirror-symmetrically to one another.

[0267] FIG. 5A shows a further embodiment of the sensor 1. The transducers 300, 320, 200, 220 are connected via the electrodes 401, 402, 403, 404. The active transducer 220 is in particular connected to the active transducer 320 via the electrode 401. The passive transducer 200 is furthermore 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, whereas the active transducer 320 is connected to the passive transducer 300 via the electrode 404. This gives a total of four electrodes via which the transducers are electrically contact-connected to one another. An electrical connection may in this case in particular be achieved by applying the transducers to the electrodes, so as to create a conductive connection. Since the transducers have a thickness, it may in particular be the case that, when electrodes are applied subsequently, no conductive connection to the electrodes would be able achieved at the edges of the transducers. This is only ensured when the thickness of the electrodes is larger than the thickness of the transducers.

[0268] FIG. 5B shows a further embodiment of the sensor 1. The electrodes that connect the transducers 200, 220, 300, 320 have an overall mirror-symmetric structure. Currents flow through the electrodes or voltages are present there, such that, when these electrodes have an asymmetric design, there may be asymmetric crosstalk of electrical signals on the other electrodes. This mutual influencing may lead to the generation of a control signal between the electrodes, but this may however be avoided by the symmetrical structure.

[0269] The transducers 200, 220, 300, 320 are in particular electrically interconnected in what is known as 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 built up 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 thus in particular sufficient to change the resistance ratios, and thus to build up a voltage between the electrodes 402, 404.

[0270] When the reference cantilever 3 and the test cantilever 2 interact with the sample 9 and the analyte 90, then both deformable parts 22, 32 for example experience a change in surface stress, which is larger 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 of the deformable part 22 of the test cantilever 2 will accordingly vary to a larger 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 builds up 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 transverse bridge voltage VB. The transverse bridge voltage VB is preferably scaled with the incidence of the analyte 90 in the sample 9, thereby allowing a quantitative assessment of the measured signal.

[0271] A transverse bridge voltage detector 44 is able to indicate the transverse bridge voltage VB externally or forward it, such that the fact that a transverse bridge voltage VB is present becomes visible to the user of the sensor 1. Such a transverse bridge voltage detector 44 may in particular also be formed by an A/D converter, wherein the A/D converter converts the transverse bridge voltage VB into a digital signal that may be forwarded to an external measuring device. The A/D converter may in particular be operated in two different measuring modes. The first measuring mode is the differential measuring mode, in which the transverse 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 measuring mode, the measured signals from all of the transducers 200, 22, 300, 23 are taken into consideration, such that the output signal from the A/D converter is a measured signal without environmental influences, through which it is possible to infer the relative deformation of the deformable parts 32, 32 and thus the incidence of an analyte 90.

[0272] The second measuring mode is the so-called absolute measuring mode. In the absolute measuring mode, the transverse bridge voltage is not detected, but rather the signals at the electrodes 402 and 404 are tapped off in a manner isolated from one another, such that it is possible to make a statement about the respective deflections of the deformable parts 32, 22. This information remains unavailable to the user in the differential measuring mode.

[0273] FIG. 6 shows a further embodiment of the sensor 1. The sensor 1 in this case comprises multiple cantilever pairs, wherein here each cantilever pair 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 transverse bridge voltage VB′ can be tapped off for each cantilever pair. The transverse bridge voltage VB′ may be tapped off from each cantilever pair by the A/D converter 440, or by the transverse bridge voltage detector 44. The measured signal from a specific cantilever pair may in particular 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 in particular possible to average the measured signals over various cantilever pairs, such that the incidence 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 various cantilever pairs, such that such a sensor 1 may be used to examine the sample 9 for different analytes 90 at the same time. By way of example, however, it is also possible for a single reference cantilever 3 to serve as reference for multiple test cantilevers 2.

[0274] The sensor 1 is in particular embodied with the multiplicity of cantilever pairs on a chip 100. A chip may in this case 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, that is to say a semiconductor circuit that taps off the transverse 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.

[0275] FIG. 7 schematically shows the structure of the various deformable parts 22, 32 of the reference and test cantilevers 3, 2. The structure 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 largely identical.

[0276] An activation layer 34, 24 is applied to the deformable part 32, 22 of the reference and test cantilever 3, 2, respectively. An activation layer 240 is configured to promote adhesion between the surface of the deformable part 32, 22 and a further layer 241, 341. The activation layer 240 is furthermore tasked with bringing about an asymmetric layer structure of the cantilever 3, 2, such that there is the greatest possible difference in the stretching of the upper surface of the cantilever and the lower surface of the cantilever. The adhesion promotion layer, or the activation layer 240, may in particular comprise gold or consist of gold.

[0277] A so-called self-assembling monolayer 241 may then be applied to the gold layer 240, which can compensate for the surface unevennesses of the gold layer and at the same time provides adhesion promotion for a further layer, specifically the reference and receptor layers 34, 24.

[0278] The structure of the reference and receptor layer 34, 24 is different. Both layers are however based on a layer that may comprise so-called protein A 242, which firstly binds to the self-assembling monolayer 241, 341, but also has and is able to bind, on its surface, antibodies 243 or isotype control antibodies 343.

[0279] The antibodies 243 are proteins that react to an antigen 5, or bind thereto and thus 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 largely specific to the antigen 5, but may however 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 extent.

[0280] In contrast to the antibody 243, the isotype control antibody 343 is a protein that preferably does not interact with the antigen 5 in an ultra-high-specific manner. This makes it possible to virtually rule out any interaction with a specific antigen 5. This is shown in FIG. 7 by the fact 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.

[0281] Since 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 interact only with the test cantilever 2. This ensures that the relative deformation, brought about by the analyte, of the test cantilever 2, in comparison with the deformation of the reference cantilever 3, is based only of the presence of the analyte 90 or of the antigen 5. It is accordingly possible to use this sensor 1 to detect an antigen 5 reliably and quickly.

[0282] In contrast to the upper surface of the cantilevers, the lower surface of the cantilevers is passivated. Such passivation may lead to an interaction, or binding, or absorption or adsorption of an analyte 90 in the sample 9 in or on the cantilevers being avoided. However, such a passivation layer in particular also contributes to increasing the asymmetry of the layer structure in order to bring about the largest possible stretching effect on the upper surface of the cantilever 3, 2. The passivation layer may in particular comprise trimethoxysilane and/or a blocking substance.

[0283] The sensor that is shown may 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 for example comprises Sars-CoV2 antibodies, while the reference layer 34 comprises Sars-CoV2-specific isotype control antibodies. A measured signal is accordingly produced by the sensor 1 when the antigens 5 of a Sars-CoV2 virus are present in the sample 9 and accumulate on the test cantilever 2 or the receptor layer 24.

[0284] FIG. 8 schematically illustrates the sensor device 6 in an exploded drawing. The sensor device 6 in this case comprises a sensor housing 62, the connection electronics 60 and the sensor 1.

[0285] The connection electronics 60 in particular have a printable circuit board 600 that enables the electrical communication between the connection socket 602 and the sensor 1. For this purpose, conductor tracks may be provided on the printable circuit board, these being produced for example from a conductive layer of the printable circuit board in an etching process, or by writing the conductor tracks to the substrate of the printable circuit board in a writing process. The conductor tracks are connected to the electrodes 40 of the sensor 1 at one end, for example by virtue of an electrically conductive wire being bonded both to the conductor tracks and to the electrodes 40. At the other end, the conductor tracks may for example be soldered to the connection pins of the connection socket 602. The printable circuit board 600 thus takes on at least the role of promoting the electrical conduction between the connection socket 602, which has macroscopic dimensions, and the electrodes 40 and the transducer of the sensor 1, which may have microscopic dimensions.

[0286] In order to ensure ESD protection, the parts of the sensor device 6 may be slightly conductive, for example have a resistance of less than 1 GΩ, and be grounded via an ESD protection contact on the printable circuit board 600.

[0287] The printable circuit board 600 may additionally also have a crypto-chip on which production parameters are stored. This makes it possible to achieve reliable and correct detection of the analyte in the sample fluid.

[0288] The connection socket 602 has eight connection pins in FIG. 8. For example, two pins of these may allow electrical conduction from a current source or a voltage source to the full bridge. By way of example, two further pins may directly tap off the transverse bridge voltage VB and provide it to a voltmeter connected via the connection socket 602. For example, two further connection pins may tap off the signal from the A/D converter 44, while two further pins may be used to communicate with the A/D converter logic unit. However, it is also possible for the connection pins to have another assignment.

[0289] For example, the connection socket 602 may thus also be used to set the measuring mode of the A/D converter logic unit 440.

[0290] It may in particular be the case that the connection socket 602 is a magnetic connection socket. For this purpose, the connection socket may contain magnets the polarity of which, on the connection side of the connection socket 602, corresponds to the reverse polarity of the connection magnets in the connection side of the socket of the plug.

[0291] The exploded drawing furthermore shows that the housing 62 consists of two parts 62′, 62″. The two parts of the housing may be connected to one another via a snap-in connection and thereby enclose the connection electronics 60, such that these are protected for example against mechanical shocks, against moisture or against electromagnetic radiation. The housing may in particular be slightly conductive in order to ensure ESD protection for the components inside it. In order to allow a connection of measuring devices and voltage sources to the connection socket 602, and thus indirectly to the sensor 1, one part 62′ has an opening 620, such that the connection socket 602 is externally accessible. The opening 620 may in particular provide a mechanically stabilizing effect for the connection cable.

[0292] The housing 62 in particular also has a measurement opening 622 through which at least the deformable parts 32, 22 of the cantilevers 3, 2 protrude externally. This ensures that the cantilevers 3, 2 are also able to interact with the environment, in particular with the sample 9.

[0293] In order to enable further sealing of the sensor device 6, the housing 62 is sealed off with rubber seals 624. For example, it is also possible to seal off the housing with only one rubber seal 624 that is embedded in the thread 626. The rubber seals 624 are in particular arranged on the housing side of the measurement opening 622, such that no sample fluid penetrates into the housing 62 of the sensor device 6 so as for example to trigger a short circuit on the printable circuit board 600. A thread 626 may be arranged around the measurement opening 622, wherein the thread 626 corresponds to the thread of a sample vial 92, such that sample fluid is able to be supplied to the cantilevers 3, 2. The thread may in particular have a thread stop in order to avoid overscrewing of the thread. In FIG. 8, the thread is arranged in a cylindrical component that can be jointly enclosed and fastened in a durable manner when the parts of the housing 62′, 62″ are connected.

[0294] A sample vial may finally be screwed into this thread 626. In order to protect the cantilevers 3, 2 against any direct mechanical action of the sample 9, the housing 62 has a protective cap 628, which both protects the cantilevers 3, 2 from the direct mechanical action of the sample, but also ensures a controlled supply of the sample 9 to the deformable parts 32, 22 of the reference and test cantilevers 3, 2.

[0295] If the sample vial 92 is connected to the housing 62 and the sample vial 92 is turned with the housing 62 such that the sample 9 falls in the direction of the sensor 1, the protective cap 628 acts as a protective shield. However, a controlled supply of the sample 9 may be achieved through a subsequent rise in the level of the sample fluid in the direction of the deformable parts 32, 22 of the cantilevers 3, 2. It is thus possible for the cantilevers 3, 2 to detect the accumulation of an analyte, or of a virus, for a transverse bridge voltage VB to arise across the full bridge, for this transverse bridge voltage VB to be routed to the connection socket 602 via the printable circuit board and to be transmitted from there by a connection plug and a downstream cable to an evaluation station 7 in which the measured signals can be interpreted.

[0296] The sample vial 92 may in this case be embodied for a specific sample volume, such that the cantilevers 3, 2 are underneath the sample fluid surface and are covered completely with sample fluid.

[0297] The sample vial 92 may in particular be held in the housing 62 such that no potentially infectious sample fluid is able to escape.

[0298] FIG. 9A shows a sensor device 6 that is connected to a sample vial 92 via a thread 626 with a thread stop. The sample vial 92 is in particular closed at the top and open on the thread side, such that the sample 9 is able to reach at least the deformable parts 32, 22 of the reference and test cantilevers 3, 2. Any direct mechanical interaction is in this case prevented by the protective cap 628, but a controlled supply of the sample to the cantilevers 3, 2 and a subsequent mechanical interaction is made possible.

[0299] The measured signals produced by the transducers of the cantilevers 3, 2 in the full bridge are transmitted to an evaluation station 7 via the magnetic connection socket 602 and via a cable. The magnetic connection socket 602 may in particular be used to create a twist-proof and polarity reversal-proof connection. ESD protection may furthermore be ensured by the connection cable, by virtue for example of contact-connecting the grounding connection of the printable circuit board.

[0300] The evaluation station 7 is configured to evaluate and to interpret the measured signals, for example the transverse bridge voltage VB and/or the digital signals from the A/D converter 44. For this purpose, the evaluation station 7 may in particular comprise a memory, comprise a processor, and comprise communication interfaces, such that the evaluation station 7 is capable of processing and outputting data. The evaluation station 7 may also verify the functionality of the sensor using a crypto-chip installed therein. It is additionally also possible to incorporate the connection cable into the verification process using a crypto-chip in order to ensure reliable and correct analysis of the sample fluid.

[0301] The evaluation station 7 may in particular communicate with a computer system 70, in particular with a smartphone, via a wired or wireless interface. For example, the interface that is shown may be a Bluetooth interface or a WLAN interface or an interface based on microwaves (RFID) or magnetic fields (NFC). The evaluation of the measured signal from the evaluation station 7 may finally be displayed on the computer system 70, such that a user is for example made aware of a contaminated sample, that is to say a sample 9 that contains an analyte 90 or a virus 902.

[0302] The computer system 70 may in particular also have an interface that is compatible with infection chain tracking programs. A possible test result may in particular be uploaded to a database in order to allow further tracking of the infection chains.

[0303] FIG. 9B shows an alternative embodiment of the sensor device 6. In this case, the sensor 1, or the deformable parts 23, 22 of the cantilevers 3, 2, are guided in the direction of the sample 9 via a dipstick 64, wherein the protective cap 628 once again protects the cantilevers 3, 2 against sudden interaction with the sample 9. The dipstick 64 is part of the housing 62, meaning that the measurement opening 622 is located at the end of the dipstick 64. The dipstick 64 may furthermore comprise part of the printable circuit board 600, such that the sensor 1 is able to be arranged at the end of the dipstick 64.

[0304] If applicable, all individual features that are illustrated in the exemplary embodiments may be combined with one another and/or exchanged without departing from the scope of the invention.

LIST OF REFERENCE SIGNS

[0305] 1 Sensor [0306] 10 Bending edge [0307] 2 Test cantilever [0308] 20 Base [0309] 200 Passive test transducer [0310] 22 Deformable part [0311] 220 Active test transducer [0312] 24 Receptor layer [0313] 240 Activation layer [0314] 241 Self-assembling monolayer [0315] 242 Protein A [0316] 243 Antibody [0317] 244 Passivation layer [0318] 26 Surface [0319] 260 Upper surface [0320] 262 Lower surface [0321] 3 Reference cantilever [0322] 30 Base [0323] 300 Passive reference transducer [0324] 32 Deformable part [0325] 320 Active reference transducer [0326] 34 Reference layer [0327] 340 Activation layer [0328] 341 Self-assembling monolayer [0329] 342 Protein A [0330] 343 Isotype control antibody [0331] 344 Passivation layer [0332] 36 Surface [0333] 360 Upper surface [0334] 362 Lower surface [0335] 4 Electronics [0336] 40 Electrode [0337] 400, 401, 402, 403 Electrodes [0338] 42 Transverse bridge voltage detector [0339] 44 A/D converter [0340] 440 A/D converter logic unit [0341] 6 Sensor device [0342] 60 Connection electronics [0343] 600 Printable circuit board [0344] 602 Connection socket [0345] 62 Housing [0346] 620 Opening [0347] 622 Measurement opening [0348] 624 Rubber seal [0349] 626 Thread [0350] 628 Protective cap [0351] 64 Dipstick [0352] 7 Evaluation station [0353] 70 Smartphone [0354] 700 Display [0355] 72 Wireless connection [0356] 9 Sample [0357] 90 Analyte [0358] 900 Antigen [0359] 902 Virus [0360] 92 Sample container [0361] F Force [0362] L Deflection [0363] D Stretching [0364] AT Distance between active and passive transducer [0365] AE Distance between electrodes [0366] S Axis of symmetry [0367] VB Transverse bridge voltage