SENSOR FOR CONVERSION OF CHEMICAL AND/OR BIOCHEMICAL INFORMATION FROM AN ANALYTE

Abstract

A sensor is provided for conversion of chemical and/or biochemical information from an analyte in a sample to an electrical signal. The sensor includes a test cantilever having a base and a deformable part, with a receptor layer for selective uptake of the analyte applied at least atop the deformable part, with a first and second test transducer arranged atop the test cantilever, and a reference cantilever having a base and a deformable part, with a reference layer for selective non-uptake of the analyte applied at least atop the deformable part, with a first and second test transducer arranged atop the reference cantilever. The transducers output an electrical signal corresponding to the occurrence and/or the concentration and/or the amount of the analyte in the sample.

Claims

1. A sensor for conversion of at least one of chemical and biochemical information from an 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 of the analyte applied at least atop the deformable part, with a first and second test transducer arranged atop the test cantilever; a reference cantilever having a base and a deformable part, with a reference layer configured for selective non-uptake of the analyte applied at least atop the deformable part, with a first and second test transducer arranged atop the reference cantilever, wherein the respective transducers are configured to output an electrical signal corresponding to at least one of an occurrence, a concentration and an amount of the analyte in the sample, wherein, based on the selective non-uptake of the analyte by the reference layer, an interaction of the reference cantilever with the sample with analyte corresponds to an interaction of the test cantilever with the sample without analyte, and wherein the first and second test transducers are arranged on the deformable part of the test cantilever, and the first and second reference transducers are arranged on the deformable part of the reference cantilever.

2. The sensor according to claim 1, wherein the respective transducers are each configured to ascertain a change in a surface tension of the reference cantilever and test cantilever.

3. The sensor according to claim 1, wherein a force to be detected is at least one of a bending force, an extension force, a shear force, and a surface tension, or is based on a bending stiffness of the reference and test cantilevers.

4. The sensor according to claim 1, wherein at least one of the concentration and the amount of the analyte can be inferred by comparing at least one of deformations, forces and surface tensions detected by the respective transducers.

5. The sensor according to claim 1, wherein: the deformable parts of the reference and test cantilevers have identical geometric dimensions, respective width of the deformable part of the reference and test cantilevers corresponds to a length of the deformable part of the reference and test cantilevers, the deformable parts of the reference and test cantilevers have a width of less than 200 m, a length of less than 200 m and a thickness of less than 1 m, or the deformable parts of the reference and test cantilevers have a V-shaped geometry or a triangular geometry or a different geometry or a geometry with holes.

6. The sensor according to claim 1, wherein the reference and test cantilevers comprise at least one of Si3N4, SiO2, Si3N4/SiO2, SiC, Si, and aluminium oxide, or are composed of at least one of Si and at least one polymer.

7. The sensor according to claim 1, wherein the respective transducers have identical intrinsic physical properties and are configured to adjust their electrical properties according to respective forces acting on the reference and test cantilevers.

8. The sensor according to claim 1, wherein the reference and test cantilevers and the active and passive reference and test transducers are in a mirror-symmetric arrangement relative to one another.

9. The sensor according to claim 1, further comprising at least four electrodes that are configured to make electrical contact with the respective transducers, and the respective transducers are electrically connected in a full bridge that is configured to establish a cross-bridge voltage based on electrical properties of the transducers.

10. The sensor according to claim 9, further comprising a cross-bridge voltage detector configured to detect a cross-bridge voltage (VB) of the full bridge, wherein, by the detected cross-bridge voltage (VB), at least one of a size and the concentration of the occurrence, selectively taken up by the receptor layer, is inferred.

11. The sensor according to claim 1, wherein the first and second test transducers are each arranged in one depression or are arranged in a common depression in the test cantilever, and the first and second reference transducers are each arranged in one depression or are arranged in a common depression in the reference cantilever.

12. The sensor according to claim 11, wherein: the depressions in the test cantilever and in the reference cantilever increase an elasticity of the test cantilever and of the reference cantilever, or the test transducers in the depressions in the test cantilever reduce an elasticity of the test cantilever, and the reference transducers in the depressions in the reference cantilever reduce an elasticity of the reference cantilever.

13. The sensor according to claim 12, wherein: the at least one depression has a depth of more than 50% of a thickness of the cantilever, a distance of at least one transducer from a neutral axis of the cantilever is less than 20% of the thickness of the cantilever, or a height of at least one transducer corresponds at least to the depth of the depression.

14. The sensor according to claim 11, wherein the depressions are arranged on at least one of upper and lower surfaces of the respective cantilever.

15. The sensor according to claim 1, wherein the first and second transducers of a same cantilever are configured to detect longitudinal and transverse force components.

16. The sensor according to claim 15, wherein the first and second transducers have an alignment with regard to a longitudinal axis of the corresponding cantilever.

17. The sensor according to claim 15, wherein the first and second transducers of the same cantilever are aligned at an angle orthogonally to one another.

18. The sensor according to claim 15, wherein: the first transducer is aligned along a longitudinal axis of the cantilever and the second transducer is aligned perpendicular to the longitudinal axis of the cantilever, the first transducer is aligned along the longitudinal axis of the cantilever and the second transducer is aligned along the longitudinal axis of the cantilever, or the first transducer is aligned perpendicular to the longitudinal axis of the cantilever and the second transducer is aligned perpendicular to the longitudinal axis of the cantilever.

19. The sensor according to claim 15, wherein the first and second transducers are arranged at sites of maximum and minimum surface tension of the cantilever.

20. The sensor according to claim 1, wherein upper surfaces of the reference and test cantilevers are activated by an activation layer that is configured to provide a greater surface tension compared to non-activated surface of the reference and test cantilevers, the activation layer comprising gold.

21. The sensor according to claim 1, wherein upper or lower surfaces of the reference and test cantilevers are passivated by a passivation layer that is configured to minimize non-specific protein adhesion on the reference and test cantilevers, the passivation layer comprising at least one of trimethoxysilane and a blocking substance.

22. The sensor according to claim 1, wherein the reference and test cantilevers have an additional layer comprising a self-assembly monolayer.

23. The sensor according to claim 1, wherein the receptor layer comprises antibodies for an antigen, and the reference layer comprises an antigen-specific isotype control antibody targeting the antibody of the reference layer.

24. The sensor according to claim 1, wherein: the receptor layer provides molecule-specific binding forces, and the reference layer does not provide molecule-specific binding forces, 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, 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, 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, the receptor layer comprises scFv antibodies and the reference layer comprises scFv antibody-specific isotype control antibodies; 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.

25. The sensor device according to claim 3, wherein a relative deformation is a transverse extension of the cantilever parallel to the base of the cantilever.

26. The sensor device according to claim 3, wherein a relative deformation of the cantilever is a longitudinal extension perpendicular to the base of the cantilever.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0148] Preferred further embodiments of the invention are elucidated in detail by way of the description of the figures that follows. The figures show:

[0149] FIG. 1 is a schematic diagram of the sensor;

[0150] FIG. 2A-2F are schematic diagrams of the sensor with various depressions;

[0151] FIG. 3A-3D are schematic diagrams of the cantilever with longitudinal extents and transverse extents;

[0152] FIGS. 4A and 4B are additional schematic diagrams of the sensor and configurations of the transducers;

[0153] FIGS. 5A and 5B are additional schematic diagram of the sensor together with sensor electrodes; and

[0154] FIG. 6 is a schematic diagram of the binding of antigens to antibodies.

DETAILED DESCRIPTION

[0155] 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.

[0156] 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 has a base 20 and a deformable part 22. Arranged atop the deformable part 22 are a first test transducer 200 and a second test transducer 220. Analogously, the sensor 1 also has a reference cantilever 3, which in turn has a base 30 and a deformable part 32. Arranged atop the deformable part 32 are a first reference transducer 300 and a second reference transducer 320.

[0157] The transducers 200, 220, 300, 320 are each connected, via electrodes 40, to electronics 4 that are capable of recording or of forwarding the measured signals 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.

[0158] The sensor 1 has the function of indicating the occurrence and preferably the amount of an analyte 90 in a sample 9. In FIG. 1, the sample 9 is a liquid, for example lymph or a diluted lymph fluid. Alternatively, the sample 9 may be saliva or blood or another body fluid. It may also be the case that the sample 9 stems from a tissue sample or has been obtained and/or synthesized from another sample taken. The analyte 90 may be dissolved here in the sample, or be in undissolved form, as a suspension or dispersion or emulsion.

[0159] 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 the analyte 90. 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.

[0160] The interaction alters the surface tension of the section, coated with the receptor layer 24, of the deformable part 22 of the test cantilever 2 changing, which leads to deformation of the deformable part 22 of the test cantilever 2. The first and second test transducers 200, 220 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.

[0161] However, even the interaction with the sample liquid 9 can result in registration of deformation by the test transducers 200, 220, for example in that merely the surface tension of the liquid acts on and bends the deformable part 22 of the test cantilever 2. The presence of an analyte 90 is accordingly not responsible for such a deformation.

[0162] In order to establish the magnitude of this basic effect of the sample 9 on the test cantilever 2, the reference cantilever 3 is 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. This enables differentiation from the measurement signal from the test cantilever 2. There will accordingly be a difference in the measured signals from the transducers 200, 220, 300, 320 if an analyte 90 occurs in the sample 9.

[0163] However, the test cantilever 2 and the reference cantilever 3 are at different positions in the sample 9, such that different ambient conditions, for example fluctuations in temperature or concentration gradients etc., can influence measurement accuracy.

[0164] However, these different ambient conditions can be corrected for by a comparison of the measured values from the transducers 200, 220, 300, 320. The sensor 1 can accordingly be used to analyse the occurrence of an analyte 90 in a sample 9 in isolation, since the influence of interactions that are not associated with the analyte 90 is reduced and isolated due to a multitude of measurement points on the reference and test cantilevers 3, 2. This enables high measurement accuracy of the occurrence of the analyte 90 in the sample 9. The magnitude of the difference of the measured signals from the transducers 200, 220, 300, 320 of the test cantilever 2 and of the reference cantilever 3 can thus be used in the simplest case to directly infer the amount of occurrence of the analyte 90 in the sample 9.

[0165] 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 260 and a lower surface 260. 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 fixed part (that transitions into the base of the test cantilever) toward the freely mobile part of the deformable part 22. The depicted deflection L 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.

[0166] The deformation of the deformable part 22 of the test cantilever 2 is shown for example for the test cantilever 2 in FIG. 2B. However, the description is analogous in respect of the reference cantilever 3. The reason for this is that the upper surface 260 and the upper surface 262 of the test cantilever 2 are extended to different degrees because of the interaction with the analyte 90, resulting in deformation of the test cantilever 2. Because of the great extent D at the upper surface 260, the first and second test transducers 200, 220 applied thereto can register an extension force F. The registered extension force F can be converted here to an electronic signal by the test transducers 200, 220 or influence an existing electronic signal, for example an applied voltage. This can be accomplished, for example, in that the test transducers 200, 220 change resistance if they experience an extension force F that in turn results in extension of the test transducers 200, 220.

[0167] As shown in FIG. 2B, the first and second test transducers 200, 220 may be arranged in a depression in the test cantilever 2. The depression increases the elasticity of the test cantilever 2, whereas the first and second test transducers 200, 220 increase the stiffness of the test cantilever 2. The combination of the two effects can achieve the effect that the first and second test transducers 200, 220 measure the extension of a test cantilever with high elasticity, which can generate a particularly large measurement signal with the test transducers 200, 220. If the test transducers 200, 220 were arranged solely on the surface of the cantilever 2, 3 and not in a depression, the test cantilever 2 would be stiffer, especially in the region of the respective transducers, and so a weaker measurement signal would be generated.

[0168] The depressions may have a depth of more than 5%, preferably more than 20%, more preferably more than 50%, of the thickness of the test cantilever 2. In the present case, in FIG. 2B, the depth is about 80% of the thickness of the cantilever 2, 3.

[0169] In addition, the height of the first and second test transducers 200, 220 corresponds to the depth of the respective depression, such that the upper surface of the test transducers 200, 220 concludes flush with the upper surface 260 of the test cantilever 2. It is also possible that the test transducers 200, 220 project beyond the upper surface 260, as shown in FIG. 2C, or lie partly beneath the upper surface 260, as shown in FIG. 2D, or lie entirely beneath the upper surface 260 (not shown).

[0170] Moreover, the neutral axis N is drawn in in FIGS. 2C and 2D, along which no material stress occurs in the ground state, taking account in particular of the layer structure as well. The neutral axis N may be determined, for example, via computer simulations of the layer system having the geometry of the cantilever.

[0171] The first and second test transducers 200, 220 of the test cantilever 2 may also be arranged in depressions arranged on the lower surface of the test cantilever 2, as shown in 2E. In particular, it is also possible that the depression for the first test transducer 200 is arranged on the upper surface of the test cantilever 2, while the depression for the second test transducer is arranged on the lower surface (or vice versa), as shown in FIG. 2F. In particular, the test transducers 200, 220 may also have different thicknesses.

[0172] Beam theory makes it possible, for example, to predict the points on the deformable part 22 at which the extension D will be at its greatest. It is possible to arrange the test transducers 200, 220 at these points in order to achieve an optimal signal-to-noise ratio and in order to have maximum sensitivity to the extensions. In the exact positioning of the test transducers, however, other boundary conditions should also be taken into account. In particular, the test transducers 200, 220 may also be arranged at the sites on the test cantilever 2 with the greatest changes in extension on contact with a sample.

[0173] In particular, the alignment of the test transducers 200, 220 relative to the alignment of the cantilevers plays an important role. FIG. 3A shows, for example, a test cantilever in the ground state. If the test cantilever 2 comes into contact with the analyte 90, the surface tension changes and there is deformation of the material, as shown in FIG. 3B. FIG. 3B illustrates that the test 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 test cantilever 2 makes it possible to determine the direction in which a greater extension D is brought about. In particular, the test transducers 200, 220 be aligned in these directions in order to generate a particularly large measured signal.

[0174] FIG. 3C shows for example that a first test transducer 200 is arranged at the site of the greatest longitudinal extent of the test cantilever 2, while a second test transducer 220 is arranged at the site of the greatest transverse extent of the test cantilever 2. The test transducers 200, 220 are in elliptical form here, but they may also have a rectangular profile, as shown in FIG. 2. In particular, the two test transducers 200, 220 are aligned differently with regard to the longitudinal axis of the test cantilever 2. The orientation of the test transducers 200, 220 may be guided, for example, by the long axis of the elliptical test transducer 200, 220. Accordingly, an isotropic transducer material, by virtue of the geometric configuration, can detect a longitudinal or transverse extension or else a mixed state.

[0175] The orientation of the transducers results from a preferential direction of the transducers in which these have the greatest possible sensitivity. This is typically at its highest in the direction of the greatest extent of the transducers. In the case of a configuration of the transducers with a rectangular base area, the preferential direction extends correspondingly along the longer side of the rectangle. In the case of the elliptical base area of the transducer indicated here, the preferential direction extends along the main axis.

[0176] The first test transducer 200 here is aligned parallel to the longitudinal axis of the test cantilever 2, while the second test transducer 220 is aligned perpendicular to the longitudinal axis of the test cantilever 2. In particular, the two test transducers 200, 220 are thus oriented perpendicular to one another and form an angle of 90. However, the angle may also be smaller or greater, according to the nature and characteristics of the test cantilever and the test transducers 200, 220.

[0177] FIG. 3D shows a schematic of the progression of the extension of the test cantilever in FIG. 3C along the x axis. The extension here disappears along the base 20 and falls in terms of magnitude from the bending edge in the deformable part 22. In particular, the longitudinal extent along the x axis and the transverse extent along the y axis of different magnitudes.

[0178] The above description of FIGS. 2 and 3 is analogously applicable to the manner of function of the reference cantilever 3 with the first and second reference transducers 300, 320.

[0179] FIG. 4A shows an embodiment of the sensor 1 in which the reference cantilever 3 and the test cantilever 2 have identical geometric dimensions and have a mirror-symmetric configuration relative to one another. 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 equal 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.

[0180] For example, the width B of the cantilevers is equal to the height H of the cantilevers 2, 3, which enables 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 150 m, a length of less than 150 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 0.5 m.

[0181] In the embodiment of the sensor 1 in FIG. 4A, the bases 30, 20 of the reference and test cantilevers 3, 2 are additionally arranged on the same overall base, which allows the cantilevers 2, 3 to be arranged closer to one another in order to reduce different environmental conditions.

[0182] FIG. 4B shows a further embodiment in which the first transducers 200, 300 are aligned perpendicular to the longitudinal axis of the cantilever 2, 3, and the second transducers 220, 320 are aligned parallel to the longitudinal axis of the cantilever 2, 3. For comparison, FIG. 4A shows the first transducers 200, 300 aligned parallel to the longitudinal axis of the cantilevers 2, 3, while the second transducers are aligned perpendicular to the longitudinal axis of the cantilevers 2, 3.

[0183] Because the first transducers 200, 300 measure, for example, a transverse extent of the cantilevers 2, 3 and the second transducers 220, 320 measure a longitudinal extent, the difference in the measurement signals from the first transducers 200, 300 or the second transducers 220, 320 is attributable solely to the interaction or non-interaction of the analyte with the cantilevers.

[0184] In particular, the transducers 200, 220, 300, 320 shown may be arranged and aligned not only on the surface of the cantilevers 2, 3, but may also be arranged in a corresponding depression.

[0185] FIG. 5A shows a further embodiment of the sensor 1. The transducers 200, 220, 300, 320 are in electrically connected via the electrodes 401, 402, 403, 404. In particular, the second test transducer 220 is connected to the second reference transducer 320 via the electrode 401. In addition, the first test transducer 200 is connected to the first reference transducer 300 via the electrode 403. The second test transducer 220 is additionally connected to the first test transducer 200 via the electrode 402, while the second reference transducer 320 is connected to the first reference transducer 300 via the electrode 404. The result is thus a total of four electrodes 200, 220, 300, 320 via which the transducers are electrically contact-connected to one another.

[0186] 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. 5B. In the full bridge, a DC voltage or AC voltage is applied between the electrodes 403, 401. The first and second 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 first test transducer 200 to the second test transducer 220 of the test cantilever 2 is equal to the ratio of the resistances of the first reference transducer 300 to the second reference transducer 320 of the reference cantilever 3. Even the variance of one resistance is thus sufficient in order to change the resistance ratios, and thus in order to establish a voltage between the electrodes 402, 404.

[0187] 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.

[0188] Because the resistances of the first and second transducers change differently because of the different alignment, for example, a particularly large change in 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 first and second test transducers 200, 220 relative to the first and second reference transducers 300, 320 can be displayed 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.

[0189] A cross-bridge voltage detector 44 can display 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. It may also be the case that the detector 44 detects the signals at the electrodes 402 and 404 in isolation from one another, such that it is possible to draw a conclusion as to the respective deflections of the deformable parts 32, 22.

[0190] FIG. 6 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 configuration of the cantilever, is very substantially identical.

[0191] 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. A task of the activation layer 240 is furthermore to bring about an asymmetric layer structure of the cantilever 3, 2, such that there is the greatest possible difference in the extent of the upper surface of the cantilever and the lower surface of the cantilever.

[0192] A so-called self-assembly monolayer 241 may then be applied to the gold layer 240, and this can compensate for the surface unevenness of the gold layer and at the same time provides adhesion promotion for a further layer, specifically the reference and receptor layers 34, 24.

[0193] The structure of the reference and receptor layer 34, 24 is different. However, both layers are based on a layer that may comprise a so-called protein A 242, which firstly binds to the self-assembly monolayer 241, 341, but also has and is able to bind, on its surface, antibodies 243 or isotype control antibodies 343.

[0194] 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. 6 shows that the antibody 243 can interact with the antigen 5 and the similar antigens 50 to some degree.

[0195] In contrast to the antibody 243, the isotype control antibody 343 is a protein that preferentially does not interact with the antigen 5 with ultrahigh specificity. This makes it possible to virtually rule out any interaction with a specific antigen 5. This is shown in FIG. 6 in that the isotype control antibody 343 can interact only with two similar antigens 50, but not with the antigen 5 which is shown schematically as a square here. As a result, the relative change in surface tension of the cantilevers 22, 32 is attributable solely to the specific antigen 5.

[0196] 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, is able to interact solely with the test cantilever 2. This ensures that the relative deformation brought about by the analyte 90 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.

[0197] In contrast to the upper surface of the cantilevers 2, 3, the lower surface of the cantilevers is passivated. Such a passivation 244 and 344 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.

[0198] 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

[0199] 1 sensor [0200] 10 bending edge [0201] 2 test cantilever [0202] 20 base [0203] 200 first test transducer [0204] 22 deformable part [0205] 220 second test transducer [0206] 24 receptor layer [0207] 240 activation layer [0208] 241 self-assembly monolayer [0209] 242 protein A [0210] 243 antibody [0211] 244 passivation layer [0212] 26 surface [0213] 260 upper surface [0214] 262 lower surface [0215] 3 reference cantilever [0216] 30 base [0217] 300 first reference transducer [0218] 32 deformable part [0219] 320 second reference transducer [0220] 34 reference layer [0221] 340 activation layer [0222] 341 self-assembly monolayer [0223] 342 protein A [0224] 343 isotype control antibody [0225] 344 passivation layer [0226] 36 surface [0227] 360 upper surface [0228] 362 lower surface [0229] 4 electronics [0230] 40 electrode [0231] 400, 401, 402, 403 electrodes [0232] 42 cross-bridge voltage detector [0233] 44 A/D converter [0234] 440 A/D converter logic unit [0235] 5 antigen [0236] 50 similar antigen [0237] 9 sample [0238] 90 analyte [0239] F force [0240] L deflection [0241] D extension [0242] AT distance between active and passive transducer [0243] AE distance between electrodes [0244] S axis of symmetry [0245] VB cross-bridge voltage [0246] N neutral axis