Sensor and measurement method for converting chemical and / or biochemical information of at least one analyte

Abstract

The invention relates to a sensor (1) for converting chemical and / or biochemical information of at least one analyte (90) in a sample (9) into a measurement signal, comprising: at least three cantilevers (2, 3) wherein each of the cantilevers (2, 3) has a base and a deformable portion, and wherein a first and a second transducer (200, 220, 300, 320) are arranged on each of the cantilevers (2, 3), wherein at least two of the at least three cantilevers (2, 3) together with the associated transducer (200, 220, 300, 320) form a measurement tuple; a multiplexer (10) configured to receive the control signal of the control signal generator (8) so as to contact the transducers (200, 220, 300, 320) of the cantilevers (2, 3) corresponding to the measurement tuple of the control signal; and an evaluation unit (12) which converts chemical and / or biochemical information of the analyte (90) into a measurement signal based on the detected electrical signal of the contacted measurement tuple and outputs the measurement signal.

Description

Technical Field

[0001] The present invention relates to sensors and methods for converting chemical and / or biochemical information of at least one analyte in a sample into a measurement signal, and to a method for manufacturing sensors. Background Technology

[0002] It is known to use elastic elements or cantilever arms to detect analytes in samples. In this case, the interaction between the cantilever and the sample liquid, and the adhesion of the analyte in the sample to the coating of the cantilever, are utilized to induce deformation of the cantilever. The presence of the analyte can then be inferred from the deformation via strain gauges.

[0003] For example, in Rasmussen, PA, Hansen, O., & Boisen, A. (2005). Cantileversurface stress sensors with single-crystalline silicon piezoresistors, Applied Physics Letters, 86(20), 203502. https: / / doi.org / 10.1063 / 1.1900299 The deformation of the cantilever caused by different surface stresses is described in the paper.

[0004] WO 2007 / 088018 A1 further proposes a flexible element for use in biosensors, such as DNA analysis.

[0005] DE 10 2021 107 255 A1 discloses a sensor for converting chemical and / or biochemical information of an analyte in a sample into an electrical signal, so as to derive qualitative and / or quantitative conclusions about the presence of the analyte in the sample based on the generated electrical signal.

[0006] However, if multiple different analytes are to be examined in a sample, a large number of different sensors are required according to existing techniques, all of which must contact the sample sequentially. This approach, however, is time-consuming, sample-intensive, and cost-intensive because only one analyte can be examined per sample. Summary of the Invention

[0007] Therefore, based on the known prior art, the object of the present invention is to provide an improved sensor and its manufacture, as well as a corresponding measurement method.

[0008] The objective is achieved by a sensor having the features of claim 1. Advantageous improvements are derived from the dependent claims, the specification, and the drawings.

[0009] Correspondingly, a sensor for converting the chemical and / or biochemical information of at least one analyte in a sample into a measurement signal is proposed. The sensor comprises: at least three cantilever arms, each cantilever arm having a base and a deformable portion, and wherein first and second transducers are disposed on each cantilever arm, wherein at least two of the at least three cantilever arms, together with their respective transducers, form a measurement unit; a multiplexer configured to receive a control signal from a control signal generator to contact the transducers of the cantilever arms corresponding to the measurement unit of the control signal; and an evaluation unit that converts the chemical and / or biochemical information of the analyte into a measurement signal based on the detected electrical signal of the contacted measurement unit and outputs it.

[0010] In this context, a sample represents a finite amount of substance extracted from a relatively large quantity of matter, such as from a reservoir, where the composition of the sample represents the composition of the substance in the reservoir, and correspondingly, the presence of the substance in the reservoir can be inferred from the presence and composition of the substance in the sample.

[0011] For example, a sample can be a saliva sample or a blood sample or a swab, especially a throat swab, a nasal swab, or a sinus swab, or a extracted tissue. Samples include any type of biological sample, especially animal samples. Samples can also be non-biological samples, such as chemical samples.

[0012] In particular, one sample form can be transformed into another, enabling the detection of analytes or their presence in a simple and reliable manner. For example, a swab can be dissolved in a liquid, such that the swab dissolved in the liquid is the actual sample. The sample, for example, can be or contain lymph fluid or lymph.

[0013] Therefore, the sample contains chemical and / or biochemical information about the analyte. Here, the analyte is a substance whose presence in the sample should be qualitatively and / or quantitatively demonstrated or should be detected by means of a sensor. The analyte is particularly capable of being present directly in the sample, or dissolved in or adhered to the sample or a portion thereof, especially sample particles. The analyte can also interact chemically, biologically, and / or physically with the sample, such that the analyte can only be detected indirectly through the corresponding interaction.

[0014] Chemical information can include, for example, the type of analyte, its concentration, presence, weight, reactivity, and density. Biochemical information includes the same characteristics as chemical information; however, the substance can be produced through biological processes. In particular, biochemical information is used if the analyte has a specific effect on biological cycles, such as metabolism or the immune system.

[0015] To convert the chemical and / or biochemical information of an analyte into an electrical signal, the sensor includes a cantilever. In this case, the cantilever is an elastic element with a base and a deformable portion.

[0016] In this configuration, the substrate is the immovable portion of the cantilever, which is specifically fixedly connected to and / or supported by and / or machined from the substrate. The substrate of the cantilever is configured as a rigid substrate, such that only the deformable portion of the cantilever is deformably configured.

[0017] The deformable portion of the cantilever extends longitudinally out of the substrate, on which the base is disposed. In other words, the deformable portion of the cantilever is suspended on one side of the base and is not supported by the substrate. Because the deformable portion extends out of the substrate, it can bend, deflect, and extend. The following spatial boundary, called the bending edge, is the starting point from which the cantilever can bend or transition from the base into the deformable portion. When the cantilever extends out of the substrate, the bending edge is typically the edge of the substrate.

[0018] If the cantilever deforms, measurable material stresses and forces are generated in or on the cantilever material. As long as these material stresses and / or forces can be measured, the deformation of the cantilever can be inferred from them. The deformation can be convex or concave. However, the cantilever itself can also deform, for example, by arching, undulating, or twisting.

[0019] Here, the transducer serves the purpose of determining or measuring the deformation of the cantilever. The transducer can be mounted on the base and deformable portion of the cantilever, or only on the deformable portion. For example, deformation of the cantilever can cause an increase or decrease in the resistance of the transducer, while no deformation of the cantilever will cause no change in the resistance of the transducer. This can be achieved, for example, by a transducer configuration based on the principle of a strain gauge, whereby the deformation of the cantilever is represented by a change in the length of the strain gauge applied to it, and thus the deformation of the cantilever can be directly detected by the change in the resistance of the strain gauge.

[0020] Therefore, the chemical and / or biochemical information of the analyte can be detected by the deformation of the cantilever, followed by recording by the transducer, and finally by changes in the electrical properties of the transducer.

[0021] The transducer of the cantilever of the measuring element can be configured and configured to output an electrical signal corresponding to the presence and / or concentration and / or amount of the analyte in the sample.

[0022] A receptor layer for selectively receiving analytes can be applied to a deformable portion of at least one of the cantilever arms, thereby forming a test cantilever arm, and / or a reference layer for selectively not receiving analytes can be applied to a deformable portion of at least one of the cantilever arms, thereby forming a reference cantilever arm.

[0023] In this configuration, the test cantilever can have a coating that allows it to bend or change its surface stress when interacting with a specific analyte. The reference cantilever can have another coating that allows it to bend or change its surface stress when interacting with another analyte. In this configuration, the test cantilever can also be used as a reference for the bending of the reference cantilever. In other words, not only the reference cantilever but also the test cantilever can be used separately for different analytes.

[0024] However, it is also possible that the reference cantilever has a coating that does not show the interaction with the analyte, so that the bending of the reference cantilever is attributed only to physical environmental conditions.

[0025] For example, the first transducer of the reference cantilever can induce a first reference electrical state through the influence of environmental conditions and interaction with the sample, while the interaction between the test cantilever and the environmental conditions of the sample induces a first test electrical state of the first transducer of the test cantilever.

[0026] For example, the reference cantilever can bend to a first value under the influence of environmental conditions, such that the deflection causes a first reference state in the first transducer and a second reference electrical state in the second transducer.

[0027] Conversely, the test cantilever is able to bend at a second magnitude due to the influence of environmental conditions, and at a third magnitude due to additional interaction with the analytes in the sample, which induces a first test electrical state in the first transducer and a second test electrical state in the second transducer.

[0028] A comparison of the electrical states of the first and second transducers indicates a measure of the cantilever's deformation. Simultaneously, a comparison of the corresponding first and / or second transducers yields a measure of the difference in cantilever deformation. From this, it is feasible to infer the specific effects of the analyte on the tested cantilever.

[0029] The four-transducer configuration has the following advantages: localized sensor calibration can be performed at the location where the sample and analyte influence each other.

[0030] A measurement element is a set of cantilever arms along with their associated transducers. A measurement element can, for example, include two cantilever arms along with their associated transducers. However, a measurement element can also include adjacent cantilever arms along with their associated transducers. A measurement element can also include any four cantilever arms along with their associated transducers. The cantilever arms and their associated transducers can belong to different measurement elements. The transducers of the cantilever arms of a measurement element can communicate with each other via electrical connections.

[0031] The measurement tuple may include, for example, all cantilever arms along with transducers, which are sensitive to specific analytes or can be used as reference cantilever arms for the analytes. Thus, the presence of a corresponding analyte in the sample can be detected using the measurement tuple.

[0032] The measurement unit preferably consists of cantilever arms that have substantially the same resistance and / or other characterizing physical or chemical properties as their transducers. In other words, the cantilever arms and transducers in the measurement unit have similar physical and chemical properties, or different but previously known properties, such as the uniformity and coverage density of the functional coating. Correspondingly, the measurement unit is not limited to the geometric arrangement of the cantilever arms on the sensor chip. More precisely, it is possible to achieve logical associations between the different cantilever arms of the sensor, independent of the geometry and positional arrangement of the cantilever arms.

[0033] One hundred cantilever arms can be divided into measurement groups of 5 x 20, 2 x 50, 50 x 2, or 100 x 1. In this case, the cantilever arms can be arbitrarily distributed within the sensor's range. Statistical evaluation can be performed based on different signals from the measurement groups used for the analyte. In particular, statistical evaluation can also be performed based on different combinations of signals from the measurement groups used for the analyte.

[0034] Substrate inhomogeneities can be compensated for by using measurement tuples, where inhomogeneities can interfere with measurements if only adjacent cantilevers on the wafer substrate are test and reference cantilevers. Consequently, the quality of the cantilevers and transducers only meets the required quality standards with a certain statistical probability. Therefore, with a large number of cantilevers and transducers, the probability of adjacent cantilevers having different qualities increases. However, by using measurement tuples in the proposed manner, it is possible to find a corresponding ideal reference cantilever for the test cantilever regardless of its position. In other words, the corresponding reference and test cantilevers can be combined into measurement tuples independent of their original production.

[0035] The sensor's multiplexer is configured to receive control signals from the control signal generator and access the measurement tuples corresponding to the control signals.

[0036] Accordingly, a multiplexer is a device capable of establishing electrical connections with multiple transducers for an electrical signal, and enabling the multiple transducers to be electrically connected to each other. Accordingly, the multiplexer enables alternating contact with different transducers on a sensor. This achieves sequential or simultaneous contact with multiple measurement elements using the multiplexer.

[0037] The first measurement unit, for example, can detect a first analyte and output an electrical signal. The second measurement unit, for example, can detect a second analyte and output an electrical signal. Similarly, it is possible to have multiple measurement units for specific analytes.

[0038] For example, a first measurement element may be sensitive to a first analyte, while a second measurement element may be sensitive to a second analyte that is different from the first analyte. Preferably, multiple measurement elements are provided, with at least one measurement element being sensitive to a specific analyte. Correspondingly, different analytes can be measured using a sensor, and particularly preferably, multiple analytes can be measured.

[0039] The cantilever of different measurement units can have different geometries and / or different materials.

[0040] For example, the first measurement element can have a first cantilever geometry, and the second measurement element can have a second cantilever geometry, wherein the first and second measurement elements are sensitive to the same analyte. These two cantilever geometries can offer specific advantages for detection, resulting in more persuasive weighting and processing of the electrical signal.

[0041] Different cantilever geometries and / or different materials can result in varying cantilever curvatures within the same sample. For example, the cantilever geometries of the first and second measurement units can be configured such that the output of the first measurement unit is two or three times larger than the measurement value of the second measurement unit. For example, the detection of the analyte can be verified by known or predictable curvature characteristics because the measurements of the measurement units are within specific numerical proportions to each other.

[0042] This also applies to different materials, which, through their different elastic moduli, also affect the bending characteristics of the cantilever. Different physical influences, such as flow or temperature, will in any case produce other proportions in the measured values.

[0043] The sensor has an evaluation unit that converts the chemical and / or biochemical information of at least one analyte into a measurement signal and outputs it based on the electrical signal of the contacted measurement element.

[0044] The transducers in the measurement unit can, for example, transmit electrical signals to the evaluation unit. The evaluation unit can then focus, process, and / or aggregate the signals and output the corresponding measurement signals. The evaluation unit can, for example, summarize the electrical signals or consider the shape, form, and geometry of the cantilever when generating the measurement signals. The evaluation unit can also, for example, consider physical and / or chemical properties.

[0045] The advantage of this invention is that it enables the analysis of different analytes using different measurement units. By contacting each measurement unit, in the sense of the transducer of the cantilever of the measurement unit, significantly faster, more automated, more reliable, more stable, and / or safer detection of analytes in the sample can be performed.

[0046] A receptor layer for selectively receiving analytes can be applied at least on the deformable portion of the test cantilever, and a reference layer for selectively not receiving analytes can be applied at least on the deformable portion of the reference cantilever.

[0047] In this case, the acceptor layer is the substance capable of interacting with the analyte. This means that the acceptor layer is specifically selected for each analyte. Similarly, the reference layer is the substance that cannot interact with the analyte. Therefore, the reference layer is also specifically selected for the analyte.

[0048] In this context, interaction means that the analyte and the receptor layer undergo chemical and / or biochemical and / or physical interactions. In particular, interactions can occur during the binding of the analyte to the receptor layer. Furthermore, interactions can occur during the absorption, adsorption, or chemisorption of the analyte to the receptor layer.

[0049] Preferably, the receptor layer and the reference layer are chemically identical with respect to possible interfering effects, and are preferably distinguished only by their interaction with the analyte. Substances that are not analytes interact with the receptor layer in a manner as strong or as weak as their interaction with the reference layer.

[0050] The selective reception of the analyte at the test cantilever causes forces to act on the test cantilever through the analyte, making the cantilever respond sensitively to the analyte. Conversely, other substances in the sample besides the analyte contribute only to the background noise at the test cantilever, which is characterized by basic bending. For example, the higher the concentration of the analyte in the sample or the faster the surface of the cantilever is occupied by the analyte, the faster the forces acting on the test cantilever increase. The maximum possible force is achieved for the corresponding configuration when the cantilever is fully occupied.

[0051] Conversely, selectively excluding the analyte at the reference cantilever causes forces not to act on the reference cantilever through the analyte, so that only substances that are not analytes contribute to the background noise of the reference cantilever in the form of basic bending.

[0052] This force induces deformation in the deformable portion of the test cantilever, while the deformable portion of the reference cantilever remains unchanged. The deflection of the cantilever is based on the alteration of surface stress through interaction with the analyte. This change in surface stress causes stretching or contraction of the upper (or lower) surface of the cantilever. The different stretching or contraction at the upper and lower sides induces internal forces or material stresses in the material, which in turn cause deformation.

[0053] According to existing technology, the reference cantilever lacks a receptor layer that sensitively responds to the analyte. While this allows for the determination of effects such as turbulence in the sample and thermal drift of the sensor system, in such a reference cantilever, the analyte can bind to the reference layer of the cantilever non-specifically. Therefore, the analyte itself contributes to background noise. Thus, in sensors according to existing technology, it is necessary to perform reference measurements in a reference sample, i.e., a sample without the analyte. Only in this way can the effects of non-specific binding of substances that are not analytes be determined.

[0054] In the sensor according to the invention, the measurement method is significantly simplified by selectively not receiving analytes at the reference cantilever, since the reference cantilever is insensitive to analytes and thus contributes nothing to the background noise. Here, only substances that are not analytes contribute to the background noise of the reference cantilever. By selectively not receiving analytes at the reference cantilever, it is possible to induce, to a certain extent, that the reference cantilever experiences the same turbulence, the same thermal drift, and the same effects as in the reference liquid from all substances that are not analytes. However, the difference lies in the fact that the reference signal is determined directly in the sample liquid.

[0055] In particular, reference cantilever with a reference layer and test cantilever with a receptor layer result in significantly more specific analysis of the analyte compared to a reference cantilever without a receptor layer alone, because not only the reference layer but also the receptor layer has specific interactions or non-interactions with the analyte.

[0056] The construction of a sensor with a measurement element having a reference cantilever and a test cantilever has the following advantages: it enables two measurements to be performed simultaneously in a sample, where the measurement of the reference cantilever can calibrate the measurement of the test cantilever. This reduces the environmental influences on the corresponding measurements, such as chemical, thermal, mechanical, electrical, fluid, and gaseous interferences, making it possible to infer the presence of the analyte from the comparison of measurements at the test cantilever and the reference cantilever.

[0057] The forces or material stresses acting on the cantilever, such as stretching or contraction, can ultimately be detected by a transducer, wherein different intensities of stress are detected by the transducer through stretching or contraction of varying strengths.

[0058] At least one measurement tuple can include at least one test cantilever and at least two reference cantilever.

[0059] This means that, for example, there are two reference cantilever arms for a single test cantilever arm. This multiple reference can improve the specificity of the sensor.

[0060] At least one measurement tuple can include at least two test cantilever arms and at least one reference cantilever arm.

[0061] This means that, for example, two test cantilever arms can be referenced by a single reference cantilever arm. Conversely, multiple test cantilever arms can be referenced by a single reference cantilever arm, thereby enabling multiple test sensors to be mounted on the sensor.

[0062] At least one measurement tuple can include at least two test cantilever arms and at least two reference cantilever arms.

[0063] For example, the sensor can have first and second test cantilevers and first and second reference cantilevers, the first and second test cantilevers being chemically and physically very similar, and the first and second reference cantilevers also being chemically and physically very similar. For example, the first test cantilevers can be referenced by either the first or the second reference cantilevers. However, it is also possible for both test cantilevers to be referenced by both reference cantilevers.

[0064] By using a combination of test and / or reference cantilevers, particularly convincing measurement signals can be generated.

[0065] The first measurement element can output an analyte-specific measurement signal, while the second measurement element can output a measurement signal that interferes with the analyte-specificity.

[0066] Interfering analytes can interact with analytes bound to the test layer, but not with the test layer or the analytes themselves.

[0067] However, it's also possible that the interfering analyte binds to the receptor layer, potentially leading to false positive results. Conversely, it's also possible that the interfering analyte binds to the analyte, preventing it from binding to the receptor layer, thus causing false negative results. Finally, it's possible that the interfering analyte binds to the receptor layer, thereby preventing the analyte from binding to the receptor layer.

[0068] This so-called cross-reaction can be revealed by using a second measurement tuple that is sensitive to interfering analytes.

[0069] The sensor has at least two measurement elements that are sensitive to two different analytes.

[0070] For example, a first measurement tuple can be used to detect a first analyte, while a second measurement tuple can be used to detect a second analyte.

[0071] In this case, the probe can be a time-resolved measurement of the bending state of the cantilever, so as to obtain information about the reaction kinetics of the analyte in the sample.

[0072] This allows for the detection of different analytes using a single sensor, thereby improving the sensor's cost-effectiveness. In particular, this sensor design enables rapid analysis of various analytes.

[0073] The cantilever of different measurement tuples can have different geometries.

[0074] For example, the first measurement tuple can have a rectangular cantilever, while the second measurement tuple has a triangular cantilever.

[0075] Triangular and rectangular cantilever arms, for example, have different natural frequencies. Different natural frequencies can, for example, better filter out mechanical interference, such as sound propagating through air or sound in a sample liquid.

[0076] For example, the first measurement tuple can have a first rectangular shape, and the second measurement tuple can have a second rectangular shape.

[0077] Cantilever arms of different sizes exhibit different bending behaviors rather than being identical. Furthermore, the temporal response of the cantilever arm to the analyte is strongly dependent on the size of the interacting surfaces.

[0078] Correspondingly, other parasitic effects can also be identified.

[0079] However, it is also feasible to use cantilever thicknesses for the same analyte. This allows for the coverage of a very large dynamic range within which the sensor provides a reliable signal of the analyte. For example, a thicker cantilever can be used to detect large amounts of analyte, while a thinner cantilever can be used to detect small amounts.

[0080] The sensor can have a control signal generator with a database of measurement tuples and is configured to send control signals to a multiplexer.

[0081] The database can store, for example, the shape and configuration of the cantilever. It can also store the resistance of each transducer and / or the position of the cantilever on the sensor and / or the type of analyte or the analyte that can be measured using the corresponding cantilever. Furthermore, a list of compatible cantilevers can be stored for each cantilever. In this respect, cantilevers can be associated with measurement sets. In particular, a single cantilever and its transducer can also be associated with different measurement sets.

[0082] The control signal generator sends control signals to the multiplexer, enabling at least one measurement element to be accessed. In other words, the control signal ultimately determines which measurement element should be used, and thus, which analyte should be identified.

[0083] The sensor can be flexibly configured by controlling the signal generator. For example, different analytes can be measured in a sequence.

[0084] For example, it is also possible to sample the measurement signals of different analytes differently. For instance, the first analyte can interact rapidly with the first receptor layer, while the second analyte interacts slowly with the second receptor layer. In the first case, to determine the reaction kinetics, more measurement points can be recorded, for example, per minute, per second, or per millisecond.

[0085] The aforementioned objective is also achieved by a method having the features of claim 9 for converting chemical and / or biochemical information of at least one analyte in a sample into a measurement signal using a sensor according to the invention. Advantageous modifications of the method are derived from the dependent claims, as well as from this specification and the accompanying drawings.

[0086] Correspondingly, a method for converting the chemical and / or biochemical information of an analyte in a sample into a measurement signal using one of the aforementioned sensors includes the following steps: selecting at least one measurement unit specific to the analyte using a signal generator; contacting the cantilever of the measurement unit with a multiplexer; detecting the electrical signal of the transducer of the contacted measurement unit using an evaluation unit; converting the chemical and / or biochemical information of the analyte obtained using the corresponding analyte-specific measurement unit into a measurement signal using the evaluation unit; and outputting the measurement signal using the evaluation unit.

[0087] In other words, the sensor is capable of measuring a variety of analytes, where, for each analyte, one or more measurement tuples are available.

[0088] Therefore, in the first step, a measurement tuple suitable for the desired analyte is selected. In this case, the step "selection" can involve controlling the signal generator or locating the desired analyte in the corresponding database.

[0089] In another step, one or more desired measurement elements are contacted via a multiplexer through a control signal. This allows contact with the individual transducers of the cantilever, but also connects the individual transducers of the cantilever to each other. Therefore, it is feasible, for example, to measure the resistance value of each transducer directly or with the aid of a compensation circuit, wherein the resistance value includes typical characteristic data of the transducer, such as temperature-dependent resistance. However, it is also feasible to connect the transducers in a bridge circuit via a multiplexer so that only the relative change in resistance value is output.

[0090] In the third step, the evaluation unit can receive the detected electrical signals from the measurement elements. Accordingly, the evaluation unit can receive, for example, the individual resistance values ​​or resistance changes within the measurement elements.

[0091] In the fourth step, the evaluation unit can output a measurement signal.

[0092] This has the following advantages: data processing is already performed in the evaluation unit, so that the signal connection between the evaluation unit and, for example, an external computer is not overloaded.

[0093] The method can be performed on all measurement tuples or only on specific measurement tuples.

[0094] For example, a sensor can have multiple first measurement elements, by which a first analyte can be measured, and multiple second measurement elements, by which a second analyte can be measured. For instance, it is possible to select only the measurement elements for the first analyte for measurement, making the measurement faster. However, it is also possible to select all measurement elements of the multiple first measurement elements and then subsequently select the multiple second measurement elements for measurement.

[0095] Preferably, the method can be performed sequentially, wherein measurement tuples are selected and measured step by step. Furthermore, it is also possible to first measure a plurality of first measurement tuples in this sequence, and then measure a plurality of second measurement tuples subsequently.

[0096] In particular, the measurement tuple can include only a single cantilever along with its associated transducer. In this respect, it is possible to detect measurements for each individual cantilever by measuring the measurement tuple sequentially.

[0097] For example, the measurement value of each such measurement tuple can be routinely detected, and then processed. Thus, arbitrary combinations of measurement tuples can be synthesized. However, it is also possible to obtain a first choice for a specific measurement tuple by performing such measurements on all cantilevers, for example, in cases where an unknown substance should be examined using a sensor. For example, the presence of a specific nucleotide sequence can be inferred during DNA sequencing.

[0098] The measurement signals can be output as a whole based on multiple measurement elements for the analyte, or the individual measurement signals of a single measurement element can be output.

[0099] Because different measurement tuples can be used for a single analyte, the electrical signals of the transducers associated with the measurement tuples can be computed against each other to obtain better statistical significance and better accuracy.

[0100] For example, the first measurement tuple can provide a first measurement signal, and the second measurement tuple can provide a second measurement signal. However, it is also possible for the evaluation unit to first receive the electrical signal of the first measurement tuple, and then receive the electrical signal of the second measurement tuple, and to weight and calculate the electrical signals together.

[0101] The output of the measurement signal can include statistical analysis.

[0102] Therefore, the measurement signals can have higher statistical relevance. For example, multiple test cantilevers of a measurement tuple can be calculated together with multiple reference cantilevers, allowing the output of a separate measurement signal for each test cantilever. However, it is also possible to output only a single measurement signal for each measurement tuple. Similarly, it is possible to output only a unique measurement signal for each analyte, even if the measurement signal is determined by multiple measurement tuples.

[0103] The evaluation unit can output measurement signals, for example, via an interface, such as a wireless interface or via a cable. Such an interface can, for example, connect a computer, smartphone, or other mobile device to the sensor.

[0104] The above objective is also achieved by a method for manufacturing a sensor having the features of claim 13. Advantageous improvements to the method are derived from the dependent claims, this specification, and the accompanying drawings.

[0105] Correspondingly, a method for manufacturing a sensor is proposed, the method comprising the following steps: manufacturing a cantilever; manufacturing a transducer on the cantilever; characterizing the cantilever and the associated transducer; associating the cantilever together with the transducer with a measurement tuple based on the characterization; and depositing a reference layer or test layer on the cantilever of the measurement tuple for a specific analyte.

[0106] The method is based on the idea that, due to the fluctuations in manufacturing technology when producing cantilever arms, it is meaningful to detect analytes using only cantilever arms that interact with the analytes in a similar manner.

[0107] Correspondingly, multiple cantilever arms are first manufactured.

[0108] Therefore, the sensor cantilever can be manufactured from a single substrate. This has the advantage that the manufacturing process only needs to be performed once, ensuring a time-efficient manufacturing method.

[0109] Sensors can be composed of cantilevers made of the same substrate. For example, all cantilevers can be fabricated from silicon substrates of different wafers. The individual cantilevers can be cleaved from different wafers and assembled into a sensor in a subsequent "pick and place" process.

[0110] Some processes, such as wet chemical processes, can also be performed at the wafer scale. If, for example, multiple analytes need to be detected, the cantilever can be derived from different wafers.

[0111] This has the following advantages: for sensors, only cantilever arms with a predetermined mass can be used. Furthermore, cantilever arms derived from individual coatings of a single wafer can be constructed for different testing systems.

[0112] The sensor can be composed of cantilevers made of different substrates. This has the advantage of allowing analyte-specific cantilevers. For example, an analyte might interact strongly with the first substrate, which could distort the measurement signal. Correspondingly, chemically inert substrates can be selected for these specific analytes.

[0113] In particular, the cantilever arms of the measurement elements can be arranged sequentially, or nested with the cantilever arms of another measurement element. Such an arrangement can optimize the structural space, for example.

[0114] The characterization of the cantilever and the associated transducer can include the quality parameters and / or performance parameters of the cantilever and / or the associated transducer.

[0115] Performance parameters may include the sensitivity and / or specificity and / or gain of the cantilever and / or transducer. It is crucial for sensor users that the corresponding analytical results are consistent and reliable, or that the analytical results are accompanied by indications of probability or safety.

[0116] A quality parameter could be, for example, the natural frequency of the cantilever, which provides a conclusion about its mechanical integrity. However, this parameter could also be the actual area or stiffness determined by the manufacturing process. For example, different cantilever arms can have the same stiffness when using different substrates and surface geometries. A quality parameter could also be the self-similarity of the transducer's resistance. If transducers have the same resistance, then the transducers are self-similar.

[0117] It is known that the self-similarity of the resistance of a resistive bridge is a good indicator of the quality of a transducer, and thus can also be used as at least one of the quality parameters that can be used to select the appropriate transducer.

[0118] Based on the measured parameters, each cantilever, along with its transducer, can be associated with a measurement tuple. Thus, within the measurement tuple, there exist, for example, all cantilevers with similar physical and / or similar chemical properties.

[0119] However, artificial intelligence can also associate cantilever and / or the transducer to which it belongs with specific measurement tuples based on their mass and / or performance parameters. For this purpose, thresholds can be determined for the mass and / or performance parameters, where the thresholds correspond to probabilities that determine the correctness of the measurement results obtained by means of the cantilever and / or transducer. Based on the measured mass parameters, correspondingly trained artificial intelligence can associate, for example, cantilever and / or transducers with similar performance parameters with specific performance levels. Finally, cantilever and / or transducers with similar performance parameters can be associated with the same measurement tuples, thereby ensuring, for example, the specificity of the measurement.

[0120] In other words, if a list of quality parameters and / or performance parameters exists, then a cantilever and / or transducer can be selected for the measurement tuple, with the selection taking into account the application scenario.

[0121] Subsequently, the cantilever in this measurement tuple can be covered with a test layer or a reference layer. In this case, for example, the first portion of the cantilever of the measurement tuple can be covered with a first test layer, the second portion of the cantilever of the measurement tuple can be covered with a second test layer, the third portion of the cantilever of the measurement tuple can be covered with a first reference layer, and the fourth portion of the cantilever of the measurement tuple can be covered with a second reference layer. Thus, for example, it is possible to achieve that there are as many cantilevers with reference layers as there are cantilevers with test layers in the measurement tuple.

[0122] The positional parameters of the cantilever, namely its position on the sensor, the type of coating layer, and the performance parameters determined in the characterization, can be stored in a database, allowing for the selection of the appropriate measurement device for a specific analyte.

[0123] Measurement tuples and their associated analytes can be stored in a database on the control signal generator. This allows the control signal generator to select the appropriate measurement tuple to probe a specific analyte with remarkable ease and without user intervention.

[0124] However, it is also feasible to store the database in the cloud, provided that the control signal generator can access the cloud. The database could also be stored, for example, in an EEPROM, in an encrypted chip on a biosensor, or in control software stored on the terminal device.

[0125] Here, storage can preferably be performed in an encrypted manner.

[0126] Encryption is particularly important for data integrity. Because the output measurement signals may contain, for example, health-related data, data encryption is crucial. Encryption helps prevent sensors from providing false negative results to computers. Attached Figure Description

[0127] Preferred further embodiments of the present invention will be described in detail below with reference to the accompanying drawings. As shown herein:

[0128] Figure 1 A schematic construction of a sensor according to the prior art is shown;

[0129] Figure 2 A schematic construction of a sensor according to the present invention is shown;

[0130] Figure 3 A schematic construction of a sensor according to one embodiment of the present invention is shown;

[0131] Figure 4 A schematic flowchart illustrating the measurement method is shown;

[0132] Figure 5 A schematic apparatus and method for measuring erythrocyte sedimentation rate (ESR) are shown; and

[0133] Figure 6 A schematic flowchart of the manufacturing method is shown. Detailed Implementation

[0134] Preferred embodiments are described below with reference to the accompanying drawings. Here, the same, similar, or identical elements in different drawings are given the same reference numerals, and repeated descriptions of these elements are omitted in part to avoid redundancy.

[0135] exist Figure 1 The image schematically illustrates one embodiment of a sensor 1 for converting chemical and / or biochemical information according to the prior art. Sensor 1 includes a test cantilever 2 having a substrate and a deformable portion. A first transducer 200 and a second transducer 220 are disposed on the test cantilever 2. Similarly, sensor 1 also has a reference cantilever 3 having a substrate and a deformable portion. A first transducer 300 and a second transducer 320 are disposed on the reference cantilever 3.

[0136] The transducers 200, 220, 300, and 320 are connected via electrodes 40 to an electronic device 4 capable of recording or forwarding the measurement signals of the transducers 200, 220, 300, and 320. The electronic device 4 can also supply current and / or voltage to the transducers 200, 220, 300, and 320.

[0137] Sensor 1 has the following task: to display the presence of analyte 90 in sample 9, and preferably to display the amount present. Figure 1 In this sample, sample 9 is a liquid, such as lymph or diluted lymph fluid. However, it is also possible that sample 9 is saliva, blood, or other bodily fluids. It is also possible that sample 9 is derived from tissue extracts, or obtained from other extracted substances and / or synthesized. In such cases, analyte 90 can be soluble in the sample or exist in an insoluble manner and method as a suspension, dispersion, or emulsion.

[0138] In any case, the sample 9 should be examined using sensor 1 to determine the presence and / or concentration and / or amount of analyte 90. For this purpose, an acceptor layer to which analyte 90 can interact or to which analyte 90 can be adsorbed or absorbed is applied to the test cantilever 2.

[0139] Through this interaction, the surface stress of the section of the deformable portion of the test cantilever 2 covered with the receptor layer changes, causing deformation of the deformable portion of the test cantilever 2. Therefore, transducers 200 and 220 record the deformation of the deformable portion of the test cantilever 2, which is then interpreted as a measurement signal in the electronic device 4.

[0140] However, since the interaction with the sample liquid 9 can even cause deformation recorded by transducers 200 and 220, for example, in such a way that only the surface stress of the liquid acts on the deformable portion 22 of the test cantilever 2 and causes said deformable portion to deform. Accordingly, the presence of analyte 90 is not the cause of this deformation, but rather the deformation is caused solely by the sample liquid 9.

[0141] To determine, balance, or compensate for the magnitude of this fundamental effect of sample 9 on test cantilever 2, reference cantilever 3 contacts both test cantilever 2 and sample 9. For this purpose, reference cantilever 3 has a reference layer to which analyte 90 precisely does not interact, while the analyte explicitly interacts with the acceptor layer of test cantilever 2. By selectively not receiving analyte 90 in the reference layer, a difference in measurement signals between test cantilever 2 and test cantilever 2 is achieved. Correspondingly, as long as analyte 90 is present in sample 9, the measurement signals of transducers 200, 220, 300, and 320 are different. Therefore, the measurement signals between test cantilever 2 and reference cantilever 3 differ precisely from the effect caused by analyte 90.

[0142] However, the test cantilever 2 and the reference cantilever 3 are located at different positions within sample 9, causing different environmental conditions, such as temperature fluctuations or concentration gradients, to affect the measurement accuracy. These different environmental conditions can be addressed by comparing the measurements from transducers 200, 220, 300, and 320. Accordingly, the presence of analyte 90 in sample 9 can be analyzed independently via sensor 1 by reducing and isolating the effects of interactions not associated with analyte 90 through multiple measurement points on the reference and test cantilever arms 3 and 2. This achieves high measurement accuracy for the presence of analyte 90 in sample 9. Therefore, in the simplest case, the magnitude of the difference between the measurement signals from transducers 200, 220, 300, and 320 of test cantilever 2 and reference cantilever 3 can directly infer the amount of analyte 90 present in sample 9.

[0143] Transducers 200, 220, 300, and 320 are in contact with each other via electrodes 401, 402, 403, and 404. Specifically, the second transducer 220 is connected to the second transducer 320 via electrode 401. Furthermore, the first transducer 200 is connected to the first transducer 300 via electrode 403. The second transducer 220 is also connected to the first transducer 200 via electrode 402, and the second transducer 320 is connected to the first transducer 300 via electrode 404. This results in a total of four electrodes, through which transducers 200, 220, 300, and 320 are electrically in contact with each other. Transducers 200, 220, 300, and 320 are electrically connected, in particular, in a so-called full-bridge configuration.

[0144] Now Figure 2 The sensor 1 presented herein is schematically shown. Here, the sensor 1 has, for example, at least one test cantilever 2 and a reference cantilever 3, whose transducers are respectively capable of contacting the multiplexer 10.

[0145] exist Figure 2 In this sensor, there are three test cantilever arms 2, 2' that are sensitive to different analytes 90 or 90'. Furthermore, the sensor 1 has two reference cantilever arms 3, 3', which, for example, selectively do not receive analytes 90 or 90' respectively.

[0146] The multiplexer 10 enables different cantilever arms 2, 2', 3, 3' to make near-simultaneous or close-to-ground contact.

[0147] In this way, the cantilever arms to which the measurement tuples belong can make targeted contact.

[0148] A measurement unit is a predetermined quantity of cantilever arms along with their corresponding transducers. In the simplified illustration above, the first measurement unit for measuring the first analyte 90 includes at least one test cantilever 2 and at least one reference cantilever 3, while the second measurement unit for measuring the second analyte 90' ​​similarly includes at least one test cantilever 2' and at least one reference cantilever 3'. A measurement unit can also have at least two test cantilever arms 2 and exactly one reference cantilever 3, or exactly one test cantilever 2 and at least two reference cantilever arms 3.

[0149] Multiplexer 10, for example, can access test arm 2 and reference arm 3. Test arm 2 and reference arm 3 then form a first measurement tuple.

[0150] A multiplexer, for example, can simultaneously access both test arms 2' and reference arms 3', allowing both test arms to be referenced via the same reference arm 3'. These two test arms 2' and reference arms 3' then form a second measurement tuple.

[0151] However, test cantilever 2 and test cantilever 2' can also be connected to each other, such that test cantilever 2' can be used as a reference for the measurement values ​​of test cantilever 2. Test cantilever 2' and test cantilever 2 then form a third measurement tuple.

[0152] The electrical signals of the transducers of different measurement elements can be received and evaluated into measurement signals by means of the evaluation unit 12.

[0153] In this configuration, different measurement tuples can be selected by the signal generator 8 of the multiplexer 10. The signal generator 8 can, for example, access a database storing different measurement tuples. In this configuration, different measurement tuples are suitable, for example, for probing a specific analyte 90.

[0154] Each cantilever and / or measurement element can be rapidly and sequentially contacted with the multiplexer 10, enabling the evaluation unit 12 to detect the electrical signals of the measurement elements. The electrical signals can then be processed in the evaluation unit. The evaluation unit 12 can, for example, synthesize a full-bridge signal from a single resistor of the transducer. Alternatively, it is possible to first average the signals from different test cantilever arms 2' and then perform calculations using a reference cantilever arm 3'.

[0155] exist Figure 3 Another embodiment of sensor 1 is shown. In this case, although the test cantilever is sensitive to the same analyte 90, the test cantilever 2 and 2' differ in their geometry or different performance and / or mass parameters.

[0156] Correspondingly, cantilever arms 2' and 3' can be associated with the first measurement set. Furthermore, cantilever arms 2 and 3 can be associated with the second measurement set.

[0157] The electrical signals of the measurement elements can be read sequentially by the evaluation unit 12, for example. Subsequently, the evaluation unit 12 can output the measurement signals of each measurement element, or output a single integrated value. The integrated value can, for example, include another data processing that takes into account different geometries and / or different performance and / or quality parameters.

[0158] In another embodiment, 20 individualized test cantilever arms 2 and 20 individualized reference cantilever arms 3 are, for example, capable of detecting a single analyte 90. In a first variant, the electrical signals of the test cantilever arms 2 and the electrical signals of the reference cantilever arms 3 can be averaged, wherein the measured signal is the difference between the averaged signals. In a second variant, each test cantilever arm 2 can be combined with each reference cantilever arm 3 to form a full bridge, wherein the measured signal is the average of the full bridge measurements.

[0159] Further statistical analysis can help improve the persuasiveness of measurements, such as by ignoring outliers when outputting measurements or by identifying erroneous calculations or measurements.

[0160] exist Figure 4 The diagram schematically illustrates a method for converting chemical and / or biochemical information according to the present invention.

[0161] In the first step U1, at least one measurement element is selected using the signal generator 8. In the second step U2, the measurement element is brought into contact with the multiplexer 10. In this case, the cantilever of the measurement element or the measurement element itself can be brought into contact simultaneously or sequentially. In the third step U3, the electrical signal of the contacted measurement element is detected using the evaluation unit, and in the fourth step U4, the evaluation unit converts the electrical signal into a measurement signal. In the fifth step U5, the evaluation unit 12 outputs the measurement signal.

[0162] For example, it is possible to perform sequential measurements on multiple selected measurement tuples (via...). Figure 4 (As shown by the dashed lines in the diagram). A new measurement element can be accessed after each probe detects the electrical signal of the previously accessed measurement element. In this case, the measured value is temporarily stored in the evaluation unit after each probe process, and then subsequently converted into a measurement signal, for example.

[0163] However, it is also possible to measure different analytes simultaneously. For example, the sample liquid arrives at all cantilever arms approximately at the same time, thus initiating the interaction between the analyte and the test and reference layers simultaneously. Therefore, simultaneous measurement of all cantilever arms and their transducers is particularly advantageous.

[0164] In terms of measurement technology, the simultaneous measurement can be achieved by having a multiplexer cyclically connect the individual transducers of the cantilever—preferably by directly and sequentially connecting the cantilever arms constituting the measurement unit. In this regard, for example, although all cantilever arms are measured simultaneously within the period length of the measurement cycle, sequential measurements are still performed.

[0165] exist Figure 5 A feasible implementation of the method is shown below. For example, the erythrocyte sedimentation rate (ESR) should be determined using sensor 1. ESR (erythrocyte sedimentation rate) describes how quickly red blood cells settle in an anticoagulated blood sample. The ESR is affected by the number, shape, and deformability of red blood cells.

[0166] For this purpose, a processed blood sample 9 is introduced into a tube, in which a sensor 1 according to the invention is also disposed. However, it is also possible that the blood sample 9 is unprocessed, wherein interfering parameters are technically isolated by means of another measurement unit. Every other cantilever of the cantilever 2 shown can be used, for example, to detect red blood cells, thereby forming, for example, measurement units for each cantilever 2.

[0167] In the first scenario, specific measurement units suitable for detecting blood cells can be progressively accessed. Specifically, such measurement units can refer to those with only one cantilever along with its associated transducer. From measurements of chemical and / or biological information, the presence of blood cells at the corresponding cantilever position can be read out.

[0168] However, it is also feasible to combine adjacent cantilevers into a single measurement tuple, and the cantilevers are simultaneously contacted. Thus, for example, a local gradient of blood cell concentration can be measured as a measurement value, such as the resistance difference indicated by the transducer's bridge circuit.

[0169] The measurement of erythrocyte sedimentation rate can also be displayed dynamically and at time resolution in the manner described above.

[0170] Particularly feasible is to repeat the measurement after a specific time interval. This allows for the correlation between the gradient or temporal development of blood cell distribution and the location of the cantilever. This directly leads to the determination of the sedimentation rate of blood cells.

[0171] For example, it is possible to measure markers indicating a specific disease in another measurement tuple, making it possible, for example, to associate sedimentation rates with specific proteins or inflammatory pathogens.

[0172] exist Figure 6The diagram schematically illustrates a method for manufacturing a sensor 1 according to the present invention. In the first step S1, multiple cantilever arms can be manufactured initially. The cantilever arms can, for example, be produced from a single substrate. However, it is also possible for the cantilever arms to be manufactured from different substrates and / or with different geometries.

[0173] In the second step S2, the transducer can be mounted on the cantilever.

[0174] In the third step S3, the cantilever and transducers can be characterized. For example, the natural frequency of the cantilever can be determined, and this natural frequency is then used for characterization. Alternatively or supplementarily, the resistance values ​​of each transducer can be determined, such that the resistance values ​​can be used to characterize the cantilever. Furthermore, information such as optical images characterizing the cantilever in terms of purity or pre-bending can be incorporated into the evaluation. For example, wafer characteristics measured by microindentation methods can also be incorporated into the characterization. In principle, all characteristics, measurement data generated during production, and all combinations thereof, along with the overall knowledge gained, can also be included in the characterization.

[0175] Then, in step S4, the cantilever, along with its associated transducer, can be associated with the measurement set. For example, cantilevers with similar geometries and / or similar natural frequencies and / or whose transducers have as similar resistance values ​​as possible can be associated with the measurement set.

[0176] By associating individualized cantilever arms with measurement units, the characteristics of the measurement units used for planned measurements of the corresponding analytes can be advantageously predetermined. For example, the electrical characteristics of the measurement units consisting of test and reference cantilever arms can be particularly advantageous when the specific resistances of all transducers are very similar. In other words, when the transducer resistance values ​​are very similar, and / or when other characteristics of the cantilever arms are clearly matched to the corresponding analytical plan, the measurement units can have particularly high measurement accuracy, such as sensitivity and / or specificity, for a particular analyte.

[0177] By associating individualized cantilever arms with measurement tuples, particularly advantageous measurement characteristics can be achieved for the corresponding analytes.

[0178] Here, the interconnection of the cantilever arms constituting the measurement unit does not need to be predetermined by the spatial arrangement of the cantilever arms. Instead, it can be connected into a measurement unit independently of its spatial arrangement using a multiplexer. In other words, cantilever arms that are not side-by-side or are arranged far apart from each other can also be connected into a measurement unit.

[0179] In step S5, the cantilever associated with the measurement tuple can be fitted with a reference layer and a test layer.

[0180] In another step or during the corresponding aforementioned steps, the measured values ​​of the cantilever and the characterization and laying parts of the measurement elements can be stored in the database of the control signal generator.

[0181] In particular, it enables the re-characterization to be performed during the quality control process after the appropriate test or reference layer is laid on the cantilever, and the results of the characterization are taken into account in the decision-making process used to construct the measurement tuple.

[0182] In the corresponding measurement method using the sensor according to the invention, for example in Figure 2 As shown, the sensor 1 can be connected to a computer (not shown) via interface 40, such as cable 42. The computer can, for example, preset the analysis of a specific analyte 90. Through the data communication connection, the desired analyte can be searched for and selected in the database of the signal generator 10.

[0183] The corresponding analytes in the database of the signal generator 10 can be associated with at least one measurement tuple. Correspondingly, the cantilever can also be geometrically positioned and the corresponding electrical contacts of the transducers can be made via the measurement tuples.

[0184] The multiplexer contacts the measurement elements and accordingly constructs an electrical connection with the cantilevered transducer.

[0185] The transducer of the measurement unit generates an electrical signal, which is ultimately received by the evaluation unit 12, wherein the chemical and / or biochemical information of the analyte is converted into a measurement signal by means of the evaluation unit.

[0186] The measurement signal is then output back to the computer.

[0187] Communication with the computer can be encrypted. Communication with databases and sensors can also be encrypted. This encryption can be implemented, for example, through control devices used for encryption. This encryption serves two purposes. First, it encrypts the precise positioning of the cantilever of the measurement tuple to prevent targeted tampering of the cantilever. Second, encryption should also be present at interface 40 so that tampered false positive or false negative measurement signals cannot be output to the computer.

[0188] Wherever applicable, all individual features shown in the embodiments can be combined and / or substituted with each other without departing from the scope of the invention.

[0189] List of reference numerals

[0190] 1 sensor

[0191] 2 Test cantilever

[0192] 200 transducers

[0193] 220 transducer

[0194] 3 Reference Cantilever

[0195] 300 transducer

[0196] 320 transducer

[0197] 4 electronic devices

[0198] Electrodes 401, 402, 403, and 404

[0199] 8 signal generator

[0200] 9 samples

[0201] 90 analytes

[0202] 10-channel multiplexer

[0203] 12 assessment units

[0204] 14 signal encryption units

[0205] 40 interface

[0206] 42 cable

Claims

1. A sensor (1) for converting chemical and / or biochemical information of at least one analyte (90) in a sample (9) into a measurement signal, said sensor comprising: At least three cantilever arms (2, 3), each of the cantilever arms (2, 3) having a base and a deformable portion, and wherein a first and second transducer (200, 220, 300, 320) is provided on each of the cantilever arms (2, 3). At least two of the at least three cantilever arms (2, 3), together with their respective transducers (200, 220, 300, 320), form a measurement unit. A multiplexer (10) configured to receive control signals from a control signal generator (8) to contact the transducers (200, 220, 300, 320) of the cantilever (2, 3) corresponding to the measurement elements of the control signals, and Evaluation unit (12) converts the chemical and / or biochemical information of the analyte (90) into a measurement signal and outputs it based on the electrical signal detected by the contacted measurement unit.

2. The sensor (1) according to claim 1, characterized in that, The cantilever (2, 3) of the different measurement tuples has different geometries and / or different materials.

3. The sensor (1) according to claim 1 or 2, characterized in that, A control signal generator (8) is provided, the control signal generator having a database containing the measurement tuple and configured to send control signals to the multiplexer (10), wherein preferably, the database and / or the control signals are encrypted.

4. The sensor (1) according to any one of the preceding claims, characterized in that, The transducers (200, 220, 300, 320) of the cantilever (2, 3) of the measurement unit are configured and arranged to output an electrical signal corresponding to the presence and / or concentration and / or amount of the analyte (90) in the sample (9).

5. The sensor (1) according to any one of the preceding claims, characterized in that, A receptor layer for selectively receiving the analyte is applied to the deformable portion of at least one of the cantilever arms (2), thereby forming the test cantilever arm (2), and / or A reference layer is applied to the deformable portion of at least one of the cantilever arms (3) to selectively not receive the analyte, thereby forming a reference cantilever arm (3).

6. The sensor (1) according to claim 5, characterized in that, At least one test cantilever (2) and at least one reference cantilever (3), together with their respective transducers (200, 220, 300, 320), form a measurement tuple that is specific to the analyte.

7. The sensor (1) according to claim 6, characterized in that, - The measurement tuple includes at least one test cantilever (2) and at least two reference cantilever (3) along with their respective transducers, and / or - The measurement tuple includes at least two test cantilever arms (2) and at least one reference cantilever arm (3) along with their respective transducers, and / or - The measurement tuple includes at least two test cantilever arms (2) and at least two reference cantilever arms (3) along with their respective transducers.

8. The sensor (1) according to any one of the preceding claims, characterized in that, The first measurement set is sensitive to the first analyte (90), and the second measurement set is sensitive to the second analyte (90') which is different from the first analyte (90). Preferably, there are multiple measurement sets, wherein at least one measurement set is sensitive to the specific analyte.

9. A method for converting chemical and / or biochemical information of an analyte (90) in a sample (9) into a measurement signal using a sensor (1) according to any one of the preceding claims, the method comprising the steps of: - Using a signal generator (8), at least one measurement element that is specific to the analyte is selected. - Make the cantilever (2, 3) of the measurement tuple contact the multiplexer (10), - The electrical signals of the transducers (200, 220, 300, 320) of the contacted measurement elements are detected by the evaluation unit (12). - The evaluation unit (12) converts the chemical and / or biochemical information of the analyte obtained by means of the measurement tuples specific to the corresponding analyte into a measurement signal, and - The evaluation unit (12) outputs a measurement signal.

10. The method according to claim 9, characterized in that, The method is performed for at least two different analytes using at least two measurement tuples that are specific to the different analytes, wherein the contact of the different measurement tuples is preferably performed sequentially or simultaneously.

11. The method according to claim 9 or 10, characterized in that, The measurement signal is output as a whole for the analyte based on multiple measurement elements, or the measurement signals of each measurement element are output.

12. The method according to any one of claims 9 to 11, wherein the output of the measurement signal includes statistical analysis.

13. A method for manufacturing a sensor according to any one of claims 1 to 8, the method comprising the following steps - Create the cantilever (2, 3). - Manufacture the transducers (200, 220, 300, 320) on the cantilever (2, 3). - Characterize the cantilever (2, 3) and the associated transducer (200, 220, 300, 320). - Based on the aforementioned characterization, the cantilever (2, 3) along with the transducers (200, 220, 300, 320) are associated with the measurement tuple. - Lay a reference layer or test layer for a specific analyte (90) on the cantilever (2, 3) of the measurement tuple.

14. The method according to claim 13, characterized in that, - The cantilever (2, 3) of the sensor (1) is manufactured in one piece from the substrate, or - The sensor (1) is composed of cantilever (2, 3) made of the same substrate, or - The sensor (1) is composed of cantilever (2, 3) made of different substrates.

15. The method according to claim 13 or 14, characterized in that, The characterization includes: determining the natural frequency of the cantilever (2, 3); and / or determining the resistance of the transducer (200, 220, 300, 320); and / or determining the geometry of the cantilever (2, 3).

16. The method according to any one of claims 13 to 15, the method comprising the following steps: - The measurement tuple and its associated analyte are stored in a database accessed by the control signal generator (8), preferably on the control signal generator (8), wherein the storage is preferably performed in encrypted form.

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