Method and sensor device for determining the concentration of an analyte in a sample - Patents.com

Abstract

A method for determining the concentration of at least one analyte in a sample (112) is proposed, comprising: i. providing at least one sensor device (110), the sensor device (110) comprising: at least one field effect transistor (114) having at least one source electrode (116), at least one drain electrode (118), and at least one gate electrode (120); at least one sensing electrode (132) configured to contact the sample (112) and at least one of electrically connected to and / or integrated with the gate electrode (120) of the field effect transistor (114); and at least one controller (146) configured to apply operating parameters to the field effect transistor (114) and to monitor at least one signal value at the field effect transistor (114). The method includes providing a sensor device (110) for determining the concentration of at least one analyte in a sample (112), the sensor device (110) comprising: ii. at least one parameter selection step including selecting a set of operating parameters of the field effect transistor (114) for at least one subsequent measurement step, the parameter selection step including performing a plurality of evaluation measurements on the field effect transistor (114) using different candidate sets of operating parameters and selecting the set of operating parameters according to at least one optimization criterion monitored during the evaluation measurements; and iii. at least one measurement step including detecting a concentration of an analyte by applying the set of operating parameters selected in step ii to the field effect transistor (114) and determining at least one signal value at the field effect transistor (114). Further, a sensor device (110) for determining the concentration of at least one analyte in a sample (112) is proposed.

Description

[Technical field]

[0001] The present invention relates to a method for determining the concentration of at least one analyte in a sample. Furthermore, the present invention relates to a sensor device for determining the concentration of at least one analyte in a sample. By way of example, the device and method of the present invention may be used for diagnostic purposes, such as clinical or laboratory analysis, or for home monitoring purposes. The method and device of the present invention may in particular be used to determine the concentration of an analyte, such as potassium, in a body fluid or another liquid. However, other applications are also feasible. [Background technology]

[0002] So far, various sensor devices have been described for sensing analytes. Such sensor devices often rely on field-effect transistor-based measurements to qualitatively identify the analyte or quantitatively determine its concentration. The presence of the analyte leads to a change in the electric field and, as a result, a change in the charge carrier density in the conducting channel of the field-effect transistor. This in turn causes a measurable change in the current or potential between the source and drain of the field-effect transistor. In many cases, the source and drain contacts are protected from contact with the analyte and the gate surface is functionalized for specific binding of the analyte. However, other options are feasible.

[0003] EP 1 348 951 A1 discloses a sensing device comprising a sensing layer having at least one functional group that binds to a semiconducting channel layer and at least another functional group that functions as a sensor, a semiconducting channel layer having a first surface and a second surface opposite said surface, a drain electrode, a source electrode and a gate electrode, characterized in that the source electrode, the drain electrode and the gate electrode are arranged on the first surface of the semiconducting channel layer, the sensing layer is on the surface of the semiconducting channel layer, the sensing layer is in contact with the semiconducting channel layer, and the semiconducting channel layer has a thickness of less than 5000 nm.

[0004] JP 61-153559 A discloses a semiconductor enzyme sensor that uses a water-soluble photosensitive resin made of polyvinylpyrrolidone-diazide to directly form an enzyme immobilized membrane on the ion-sensitive surface of a pH-ISFET, thereby enabling easy reduction in size of the semiconductor enzyme sensor, forming a multi-sensor, and extending the life of the sensor. A pH-ISFET as a base electrode of the enzyme sensor is formed as a composite element, with a source and drain, a pseudo reference electrode, and a lead wire. Each element independently senses hydrogen ions to enable measurement of the pH in a solution. A membrane with an enzyme immobilized thereon, which changes the pH by reacting with a substrate, is attached to the channel of one element, but not to the other element. A water-soluble photosensitive resin made of polyvinylpyrrolidone-diazide is applied to cover the ion-sensitive surface of the channel of the element consisting of a source and a drain.

[0005] Japanese Patent Laid-Open Publication No. 60-29658 discloses a urea sensor that uses a photosensitive resin to directly form a urease immobilized membrane on a pH-ISFET, thereby enabling the miniaturization and manufacture of a multi-sensor in a simple process and aiming to extend the life of the sensor. The pH-ISFET element, which is the base electrode, is equipped with a source and a drain, a pseudo reference electrode, and a lead wire 7. This pH-ISFET element is a composite pH-ISFET element composed of one pH-ISFET (A) consisting of a source and a drain, and the other pH-ISFET (B) consisting of a source, a drain, and a (pseudo) reference electrode. The glucose sensor is manufactured by a method in which a urease immobilized membrane is attached to the pH-ISFET (A) and this membrane is not attached to the other pH-ISFET (B). When urea is present in the sample solution, the urea is decomposed, and a difference occurs in the pH of the sample solution itself, which is monitored by the pH-ISFET (B) that does not have a urease immobilized membrane, depending on the pH of the urease immobilized membrane.

[0006] US 2016 / 047775 discloses an embodiment of a sensing device including one or more integrated circuit (IC) dies, a housing, and a fluid barrier material. Each IC die includes an electrode-bearing surface and a contact surface. One of the dies includes an SFET having a sensing electrode proximate to the electrode-bearing surface. The same or a different die includes a reference electrode proximate to the electrode-bearing surface. The die further includes IC contacts located at the contact surface and a conductive structure connected between the SFET, the reference electrode, and the IC contacts. The housing includes a mounting surface and a housing contact formed at the mounting surface. The IC contacts are connected to the housing contacts. A fluid barrier material is disposed between the mounting surface and the IC die. The fluid barrier material provides a fluid barrier between the IC contacts and the housing contacts, and a space surrounding the sensing electrode and the reference electrode.

[0007] China Patent Publication No. 105301079 discloses a semiconductor device for detecting the ionic activity of an object to be detected and a detection method thereof. The semiconductor device comprises a substrate, a source, and a drain, the source and drain are disposed on the substrate, the semiconductor device further comprises a first ion-sensitive film and a second ion-sensitive film having different sensitivities to the ionic activity of the object to be detected, the object to be detected is disposed between the first ion-sensitive film and the second ion-sensitive film, the first ion-sensitive film is disposed on the substrate, the second ion-sensitive film is connected to a commercial power source, and in a preferred embodiment, a comb-shaped capacitor is also introduced. The semiconductor device for detecting the ionic activity of an object to be detected and the detection method thereof employing this structure eliminates the reference electrode and introduces two different ion-sensitive films to accurately measure the ionic activity of the object to be detected, has a simple structure, is low cost, and has a wide range of application for the semiconductor device.

[0008] European Patent Application Publication No. 3 588 075 discloses a highly sensitive biosensor. The object of this invention is to improve the detection specificity of the biosensor. This invention provides a biosensor comprising an identification substance capable of binding to a detection target substance and an electrode for capturing the charge of the identification substance, detecting a change in charge density of the electrode caused by binding of the detection target substance with the identification substance, the surface of the electrode being coated with polycatecholamine, a polymer layer having a molecular imprint having a structure complementary to the molecular structure of the detection target substance formed on all or a part of the electrode surface coated with polycatecholamine, the polymer layer containing the identification substance, and the polymer layer being an ultrathin film layer.

[0009] JP 2013-092479 A discloses a biosensor measuring device including a biosensor section, a measuring section, and a control section. The biosensor section includes a substrate, a drain electrode and a source electrode, a semiconductor film arranged on the substrate, an insulating film arranged on the semiconductor film, a sensitive film arranged on the insulator film and on which a measurement target is placed, a reference electrode that contacts the measurement target and receives a variable reference voltage, and a barrier. The measuring section includes a current source connected to the drain electrode and outputs a constant current, a reference potential section connected to the source electrode, a voltmeter that uses the junction between the drain electrode and the current source as an output terminal and measures an output voltage, and a reference voltage source that applies a reference voltage to the reference electrode. The control section includes a measurement setting section that controls the measurement by the measuring section, and a memory section that stores the output voltage measured by the voltmeter.

[0010] US 2016 / 0169835 discloses a biosensor for performing an analysis based on a sample collected non-invasively from the human body. The biosensor comprises an identification substance that binds to a substance to be detected and an electrode that is charged with the charge of the identification substance. The biosensor further comprises an inhibitor that inhibits substances that are not the target of detection from adhering to at least one of the identification substance and the electrode. The biosensor detects a change in the charge density of the electrode caused by the binding of the substance to be detected to the identification substance.

[0011] US Patent Application Publication No. 2019 / 0339229 discloses a semiconductor device comprising a first field effect transistor (FET) connected in series with a second FET and further comprising a third FET connected in series with the first FET and the second FET. The semiconductor device further includes a bias circuit connected to the first FET and the second FET and an output conductor connected to a terminal of the second FET, the output conductor obtaining an output signal from the second FET independent of the first FET.

[0012] Tatavarthi, SS et al., in “Rapid and Highly Sensitive Extended Gate FET-Based Sensors for Arsenite Detection Using a Handheld Device”, ECS Journal of Solid State Science and Technology, 2020, Vol. 9, No. 11, 115014, describe a FET-based ion-selective sensor for the detection of arsenite (As(III)) ions using a handheld device. The selective sensor exhibits a higher sensitivity (35.19 mV / log[As3+]) than the ideal Nernst slope. The dynamic range of the arsenite-based ion sensor is 10 -10 M~10 -4 The detection limit of this FET-based ion-selective sensor is 10 -10 Below M.

[0013] Schmoltner, K. et al., “Electrolyte-Gated Organic Field-Effect Transistor for Selective Reversible Ion Detection”, Advanced Materials, Volume 25, Issue 47, December 17, 2013, Pages 6895-6899, 10 -6 We describe an ion-sensitive electrolyte-gated organic field-effect transistor for the selective and reversible detection of sodium (Na+) up to M.

[0014] Melzer, K. et al., “Enzyme assays using sensor arrays based on ion-selective carbon nanotube field-effect transistors”, Biosensors and Bioelectronics, Volume 84, October 15, 2016, Pages 7-14, describe sensors based on spray-coated electrolyte-gated carbon nanotube field-effect transistors for selective and direct detection of the products of enzyme-substrate interactions, here for the important urea-urease system in metabolic processes. Selective and direct detection is achieved by immobilizing the enzyme urease on the sensor surface via a specific surface functionalization technique and further modifying the active interface with a polymeric ion-selective membrane and a pH-sensitive layer.

[0015] In general, there are various options for measuring the current or potential change between the source and drain in a sensor device based on a field effect transistor. The first common option is to measure the drain-source current I DS , the drain-source potential V DS While keeping constant, the applied gate potential V G The first approach is to measure the potential as a function of the drain-source potential V to obtain the transfer curve of the field-effect transistor. Typically, several transfer curves are recorded over time to monitor the change in the electric field. The range of the potential swept and the sampling rate determine the time resolution of the measurement. A second common choice is to measure the potential V as a function of the drain-source potential V DS and the gate potential V G With fixed drain-source current I DS over time, which allows for high time resolution.

[0016] Despite the advantages achieved by the known devices and methods, various technical challenges remain. In particular, in the case of the first option mentioned above, data processing is typically quite complicated. On the other hand, the second option mentioned above typically requires one gate potential V for one sample at a time.G This has drawbacks in multiplexing, since only one potential can be applied. Moreover, in the case of the second option mentioned above, the output of the measurement is a current, which would require a conversion to potential in order to compare data derived from different field effect transistors. In general, different measurement situations may require different measurement settings for best performance. Therefore, the measurement settings may have to be changed for different measurement situations, which can be a tedious process, especially when changing hardware components. Summary of the Invention

[0017] It is therefore desirable to provide a method for determining the concentration of at least one analyte in a sample and a sensor device for determining the concentration of at least one analyte in a sample, which at least partially addresses the above-mentioned problems of known devices and methods of similar type. In particular, it is desirable to provide a broadly applicable method and sensor device for determining the above-mentioned concentrations with high performance and reproducibility, which can, if possible, be achieved by means that are rapidly adaptable to different measurement situations and that are not too resource-intensive. More particularly, it is desirable to provide an approach that allows measurements with high time resolution and efficient multiplexing of different sensor devices.

[0018] This problem is addressed by a method for determining the concentration of at least one analyte in a sample and a sensor device for determining the concentration of at least one analyte in a sample having the features of the independent claims. Advantageous embodiments, which may be realized alone or in any combination, are set out in the dependent claims as well as in the specification as a whole.

[0019] When used below, the terms "having", "comprises" or "includes" or any grammatical variants thereof are used in a non-exclusive manner. These terms may therefore refer both to the situation where, apart from the features introduced by these terms, no further features are present in the entity described in this context, and to the situation where one or more further features are present. As an example, the expressions "A has B", "A comprises B" and "A includes B" may all refer to the situation where, apart from B, no other elements are present in A (i.e., the situation where A is exclusively composed of B), and to the situation where, apart from B, one or more further elements are present in entity A, such as element C, elements C and D, or even further elements.

[0020] Furthermore, it should be noted that the terms "at least one" or "one or more," or similar expressions, indicating that a feature or element may be present only once or multiple times, are typically used only once when introducing each feature or element. In the following, in most cases, when referring to each feature or element, the expressions "at least one" or "one or more" will not be repeated, despite the fact that each feature or element may be present once or multiple times.

[0021] Furthermore, when used hereinafter, the terms "preferably", "more preferably", "particularly", "more particularly", "particularly" or "more particularly" or similar terms are used in conjunction with optional features and do not limit the possibility of alternatives. Thus, features introduced by these terms are optional features and are not intended to limit the scope of the claims in any way. The present invention may be implemented by using alternative features, as would be understood by a person skilled in the art. Similarly, features introduced by "in an embodiment of the present invention" or similar expressions are intended to be optional features and do not entail any limitations on alternative embodiments of the present invention, any limitations on the scope of the present invention, or any limitations on the possibility of combining a feature introduced in such a manner with other optional or non-optional features of the present invention.

[0022] In a first aspect of the present invention, a method for determining the concentration of at least one analyte in a sample, particularly a body fluid sample, is disclosed.

[0023] As used herein, the term "analyte" is a broad term and should be given its common and ordinary meaning to those skilled in the art and should not be limited to a specific or special meaning. The term may specifically refer to any chemical or biological substance or species, such as, but not limited to, an ion, an atom, a molecule, or a compound. The analyte may specifically be an analyte that may be present in a body fluid or body tissue. The term analyte may specifically include atoms, ions, molecules, and macromolecules, in particular biological macromolecules such as nucleic acids, peptides and proteins, lipids, and metabolites. Further examples of analytes that may be considered for detection are given in more detail below.

[0024] As used herein, the term "concentration" is a broad term and should be given its common and ordinary meaning to those skilled in the art, and should not be limited to a special or special meaning. The term may specifically, but not limited to, refer to a numerical representation of the amount of a first entity in a second entity, specifically a numerical representation of the amount of an analyte in a sample. The amount may generally be indicated in a variety of ways known to those skilled in the art. The concentration may include at least one of molar concentration, equivalent concentration, mass concentration, volume concentration, and particle concentration. Further options and combinations are also contemplated. As an example, under ambient conditions, the sample may be a liquid sample, the analyte may be a solid analyte, and the concentration may be defined by the ratio of the mass of the solid analyte per volume of the liquid sample, e.g., g / L.

[0025] As used herein, the term "sample" is a broad term and should be given its common and ordinary meaning to those skilled in the art and should not be limited to a special or special meaning. The term may specifically refer to, but is not limited to, any entity or aliquot of at least one material that is the subject of analysis. Specifically, a sample may include at least one fluid, such as at least one liquid and / or at least one gas. A sample may be contained in a confined or definable space, or may be present in an open space, such as an open environment. A sample may be present in a stationary state or may flow continuously or discontinuously. A sample may be, by way of example, a pure liquid, or a homogeneous or heterogeneous mixture, such as a dispersion, emulsion, or suspension. Additionally or alternatively, a mixture of gases or a mixture of gases with liquids or solids may be used. Specifically, a sample may include atoms, ions, molecules and macromolecules, particularly biological macromolecules such as nucleic acids, peptides and proteins, lipids, and metabolites, as well as biological cells and cell fragments. However, the sample may also be or include a calibration solution, a reference solution, a reagent solution, or a solution containing a standardized analyte concentration (a so-called standard).

[0026] A typical sample to be analyzed may be a body fluid. As used herein, the term "body fluid" is a broad term and should be given its general and ordinary meaning to those skilled in the art, and should not be limited to a special or special meaning. The term may specifically refer to, but is not limited to, a fluid derived from at least one body, specifically at least one human body. Specifically, the body fluid may include at least one aqueous solution. By way of example, the body fluid may include at least one of blood, plasma, serum, urine, cerebrospinal fluid, tears, cell suspension, cell supernatant, cell extract, tissue lysate, saliva, tears, and interstitial fluid.

[0027] The method includes the following method steps: i. providing at least one sensor device, the sensor device comprising: at least one field effect transistor, in particular at least one MOSFET, having at least one source electrode, at least one drain electrode and at least one gate electrode, - at least one sensing electrode configured to be in contact with the sample and electrically connected to and / or integrated in a gate electrode of the field effect transistor; at least one control device configured to apply operating parameters to the field effect transistor and configured to monitor at least one signal value at the field effect transistor; providing a step of: ii. at least one selection step including selecting a set of operational parameters of the field effect transistor for at least one subsequent measurement step, the parameter selection step including performing a plurality of evaluation measurements on the field effect transistor using different candidate sets of operational parameters and selecting the set of operational parameters according to at least one optimization criterion monitored during the evaluation measurements; and iii. at least one measuring step comprising detecting the concentration of the analyte by applying the set of operating parameters selected in step ii to a field effect transistor and determining at least one signal value at the field effect transistor.

[0028] The method steps may be performed in a given order. However, it should be noted that different orders may be possible. Furthermore, one or more of the method steps may be performed once or repeatedly. Furthermore, two or more method steps may be performed simultaneously or overlapping in time. The method may include additional method steps not listed.

[0029] As used herein, the term "sensor device" is a broad term and should be given its common and ordinary meaning to those skilled in the art and should not be limited to a specific or special meaning. The term may specifically refer to a detector configured to determine at least one characteristic of another object or entity, such as, but not limited to, configured to qualitatively and / or quantitatively analyze at least one object of investigation. Specifically, the sensor device may be configured to detect at least one analyte in a sample qualitatively and / or quantitatively, specifically with high sensitivity. The sensor device is specifically configured to determine the concentration of at least one analyte in a sample.

[0030] The sensor device comprises at least one field effect transistor. As used herein, the term "field effect transistor" is a broad term and should be given its general and ordinary meaning to those skilled in the art and should not be limited to a special or special meaning. The term may specifically, but is not limited to, a functional semiconductor element comprising at least one source electrode, at least one drain electrode and at least one gate electrode. As used herein, the term "electrode" is a broad term and should be given its general and ordinary meaning to those skilled in the art and should not be limited to a special or special meaning. The term may specifically, but is not limited to, a functional element configured to perform current and / or voltage measurements and / or to apply a current and / or potential and / or voltage to an element in electrical contact with the electrode. In particular, the electrode may comprise a conductive and / or semiconducting material. By way of example, the electrode may comprise at least one metallic material and / or at least one organic or inorganic semiconducting material having at least one conductive or semiconducting surface. The surface itself may form an electrode or part of an electrode. By way of example, the electrodes may comprise at least one material, in particular at least one surface material, having a conductivity of at least 1 S / m, for example at least 1,000,000 S / m, which may be isotropic or anisotropic in at least one direction. At least one predefined potential may be individually applicable to each of the source, drain and gate electrodes of the field effect transistor. The potential may be a constant potential or a varying potential. In general, the potential may be applied with respect to ground. By way of example, a gate potential V G may be applied with respect to ground. However, as commonly used, the gate potential V G The drain-source voltage V can also refer to the potential difference between the source and gate electrodes of a field effect transistor. The potential difference between the two electrodes is generally referred to as the voltage. As an example, the drain-source voltage V DSGenerally, the drain-source current I DS generally refers to the current between the drain and source electrodes.

[0031] Generally, a field effect transistor further comprises at least one channel. As used herein, the term "channel" is a broad term and should be given its general and ordinary meaning to those skilled in the art and should not be limited to a special or special meaning. The term may specifically refer to, but is not limited to, a semiconductor component or a portion thereof configured to conduct a current between a source electrode and a drain electrode. The channel may have at least one semiconductor material and / or at least one doped semiconductor material. The semiconductor material may be at least one of an inorganic semiconductor material and an organic semiconductor material, or may include at least one of an inorganic semiconductor material and an organic semiconductor material. Typically, the semiconductor material is a 10 -6 S / m<σ<10 6 However, in the field of organic semiconductors, this description is often not entirely applicable due to the effects of low charge carrier mobility, molecular orbitals, and / or low charge carrier density. Therefore, organic conductive materials are often considered to have electrical conductivity of 10 6 S / m or higher, or 10 -6 Even if the resistivity is lower than S / m, it is often called an organic semiconductor.

[0032] In particular, the semiconductor material may comprise one or more regions, preferably 2 to 10 regions, more preferably 3 regions, each region may be n-type doped or p-type doped. In particular, the semiconductor material may comprise inorganic and / or organic semiconductor materials. The channel is capable of conducting a current between the source and drain electrodes only under certain external conditions. The conditions include the temperature of the channel and / or a voltage or potential applied to the channel, for example directly through the surface of the channel or through a gate electrode or an external electrode. In particular, the channel may be constituted by at least one semiconductor material, such as at least one semiconductor layer. By way of example, inorganic and / or organic semiconductor materials may be used. The gate electrode may be in direct physical contact with the channel. In this configuration, the field effect transistor may be commonly referred to as a "non-insulated gate field effect transistor" (NIGFET). In particular, the gate electrode may be at least partially identical to the channel or the surface of the channel. Alternatively, the gate electrode may be in indirect physical contact with the channel, for example by using one or more electrically insulating materials interposed between the gate electrode and the channel. In this configuration, the transistor is sometimes commonly referred to as an "insulated gate field effect transistor" (IGFET).

[0033] Insulated gate field effect transistors may specifically be implemented as "metal-insulator-semiconductor field effect transistors" (MISFETs). The gate electrode may include at least one metal that may be insulated from the channel by at least one electrically insulating material. The channel may include at least one semiconductor material. Thus, field effect transistors, specifically MISFETs, may include at least one insulating material, also called dielectric material or simply dielectric. Specifically, the insulation of the gate electrode from the channel may be constituted by an oxide. In this configuration, the field effect transistor may be generally referred to as a "metal oxide semiconductor field effect transistor" (MOSFET). However, other materials for the insulation of the gate electrode are also feasible. The channel of the field effect transistor may be in physical contact with an electrolyte that may constitute or form part of the gate electrode. An ionic double layer may be formed that may act as insulation of the gate electrode from the channel. In this configuration, the field effect transistor may be referred to as a "solution-gate or liquid-gate FET". The electrolyte may include a substance that, upon proximity or adsorption to the channel, may affect the potential applied to the channel and / or affect the insulation of the channel, thus enabling detection of chemical species. In this configuration, the field effect transistor may be referred to as a "chemical field effect transistor" or ChemFET. In particular, the ChemFET is configured to detect ionic species, such as H +and / or other ionic species to form an "ion-sensitive field effect transistor" (ISFET). A layer sensitive to ionic species such as Al2O3, Si3N4, or Ta2O5 may contact the channel or form part of the gate electrode of the ISFET and / or form part of the channel and gate electrode. In another configuration, the ChemFET may include a layer of immobilized enzyme as part of the gate electrode and / or channel of the field effect transistor. In this configuration, the field effect transistor may be referred to as an "enzyme field effect transistor" (ENFET). Binding of the enzyme to the analyte may affect the potential applied to the channel, allowing for the detection of the analyte. Thus, the ENFET is an example of a biosensor based on a field effect transistor (BioFET). As a BioFET, the field effect transistor may include a layer of immobilized biomolecules as a biorecognition element capable of binding to one or more molecular species (specifically biomolecules), and the binding reaction may directly or indirectly affect the potential applied to the channel.

[0034] Furthermore, the field effect transistor may be implemented as an "extended gate field effect transistor" (EGFET). As used herein, the term "extended gate field effect transistor" is a broad term and should be given its common and ordinary meaning to those skilled in the art and should not be limited to a special or special meaning. The term may specifically refer to, but is not limited to, a field effect transistor with a gate electrode configured to allow the channel of the field effect transistor to be spatially separated from a process or reaction that sets or affects the potential of the gate electrode. Such an electrode may be commonly referred to as an "extended gate electrode". Thus, by way of example, the gate electrode may include at least one portion that contacts the substance or sample to be sensed and may optionally include at least one portion that is in close proximity to the channel, for example by being separated from the channel only by at least one insulating material layer, such that the portions are electrically connected. Thus, the extended gate electrode of an extended gate field effect transistor may allow for a physical separation between the process of applying a potential to the channel and the process of applying a potential to the gate electrode.

[0035] The field effect transistor may comprise at least one substrate. The substrate may have purely mechanical properties and functions, such as carrying the above-mentioned components of the field effect transistor. Alternatively, however, the substrate may be completely or partially identical to one or more of the above-mentioned components. Thus, by way of example, at least one channel may be completely or partially embodied in the substrate.

[0036] The sensor device further comprises at least one sensing electrode. As used herein, the term "sensing electrode" is a broad term and should be given its general and ordinary meaning to those skilled in the art and should not be limited to a special or special meaning. The term may specifically, but not exclusively, refer to an electrode configured to be exposed to a sample having an analyte. As will be explained in more detail below, the sensing electrode may be specifically functionalized to interact with the analyte. As shown, the sensing electrode may be electrically connected to the gate electrode. In this case, direct contact between the sample and the gate electrode may be avoided. Additionally or alternatively, the sensing electrode may be integrated or incorporated into the gate electrode. Thus, the gate electrode may be or may include the sensing electrode. In particular, the sensing electrode may be an extended gate electrode of the EGFET. In either case, the voltage applied to the sensing electrode may be transferred to the gate electrode. However, the potential applied to the sensing electrode may be influenced by the analyte, especially when the sensing electrode is functionalized with respect to the analyte. The potential applied to the sensing electrode may be applied to the sensing electrode via the sample, in particular by using at least one electrolyte, more particularly at least one electrolytic solution. Thus, the concentration of the analyte in the sample may affect the potential applied to the gate electrode and thus the electric field experienced by the channel of the field effect transistor. As an example, the analyte may include ions that affect the electric field, for example by shielding the externally applied electric field. Thus, the concentration of the analyte may ultimately affect the electrical response of the field effect transistor, for example the specific drain-source voltage V DS The drain-source current I of a field-effect transistor occurring at DS may have an impact on

[0037] The sensor device further comprises at least one controller. As used herein, the term "controller" is a broad term and should be given its general and ordinary meaning to those skilled in the art and should not be limited to a special or special meaning. The term may specifically refer to, but is not limited to, any electronic device configured to at least one of monitor, regulate, and control one or more operations of a field effect transistor. The controller may be configured to control or set at least one voltage at an electrode of the field effect transistor. The controller may be configured to measure at least one current between two electrodes of the field effect transistor. The controller may be configured to control or set at least one current between two electrodes of the field effect transistor. The controller may be configured to measure at least one voltage at an electrode of the field effect transistor. Combinations of the above options may be feasible. The controller may comprise at least one source measurement unit (SMU). The controller may comprise at least one power source. The controller may comprise at least one of a multimeter, a voltmeter, an ammeter, and an ohmmeter.

[0038] The control device may in particular be or include at least one galvanostat, also known as an amperostat. The control device therefore controls at least one current, in particular the drain-source current I DS While keeping constant, at least one voltage, specifically the drain-source voltage V DS. Thus, the field effect transistor, which may in particular be a MOSFET as described above, may be connected or connectable to the galvanostat, for example by using at least one wired connection. More particularly, at least the source and drain electrodes of the field effect transistor may be connectable to the galvanostat. The control device may comprise at least one ground. The galvanostat may be grounded. The control device may comprise at least one output, in particular at least one analog output, which outputs at least one potential, in particular the gate potential V. G The analog output may be configured to apply a gate potential V G may be applied with respect to ground. The controller may include at least one digital output and / or interface, for example for communicating with at least one external device and / or user.

[0039] The control device may comprise at least one processing unit. As used herein, the term "processing unit" is a broad term and should be given its common and ordinary meaning to those skilled in the art and should not be limited to a special or special meaning. The term may specifically refer to any device configured to perform specified operations, preferably, but not limited to, by using at least one data processing device, more preferably, by using at least one processor and / or at least one application specific integrated circuit. As an example, the processing unit may comprise at least one data processing device that stores software code including several computer commands. The processing unit may provide one or more hardware elements for performing one or more of the specified operations and / or one or more processors that execute software to perform one or more of the specified operations. As an example, the processing unit may comprise one or more computers, application specific integrated circuits (ASICs), digital signal processors (DSPs), or one or more programmable devices such as field programmable gate arrays (FPGAs). However, in addition to or instead of this, the processing unit may be embodied fully or partially by hardware. The processing unit may be specifically configured to perform at least one measurement cycle. Information determined by the processing unit may be provided to at least one of the further devices and / or to a user, specifically in at least one of the following ways: electronically, visually, acoustically, or tactilely. Information determined by the processing unit may be stored in a memory storage and / or in a separate storage device and / or may be passed via at least one interface, such as a wireless interface and / or a wired interface. The processing unit may further be configured to control at least a part of the sensing device, specifically at least a part of the control device.

[0040] The control device is configured to apply the operating parameters to the field effect transistor. As used herein, the term "operating parameters" is a broad term and should be given its general and ordinary meaning to those skilled in the art and should not be limited to a special or special meaning. The term may specifically, but not limited to, refer to parameters (particularly, electrical parameters) characteristic of a particular operation of a device (particularly, a field effect transistor). In other words, the operating parameters may define the operation of the field effect transistor. Specifically, the operating parameters may define and / or specify at least one of: which voltage and / or potential is applied to which electrode of the field effect transistor, which current is applied to which electrode of the field effect transistor, which voltage and / or potential is measured between which electrodes of the field effect transistor, and which current is measured between which electrodes of the field effect transistor. Further options and combinations are also possible. The operating parameters may generally refer to both the type of parameter (e.g., voltage or current) and the value of the parameter (e.g., 1V or 1A). Further details and embodiments are outlined below. Additionally or alternatively, the operating parameters may refer to the shape of the parameter. As shown, the operating parameters may include, for example, voltage or current. As also outlined in more detail below, the voltage or current may be, for example, AC or DC, or may include a pulse or periodic signal that may define the shape of the voltage or current. The operating parameters related to the shape of the parameter may be, for example, but are not limited to, frequency or pulse time.

[0041] The control device is configured to monitor at least one signal value at the field effect transistor. As used herein, the term "signal" is a broad term and should be given its general and ordinary meaning to those skilled in the art and should not be limited to a specific or special meaning. The term may specifically refer to, but is not limited to, an entity or function used to convey information. Specifically, the signal may include at least one electrical signal. More specifically, the signal may include at least one of a voltage and a current. Thus, the signal may include at least one analog signal. Additionally or alternatively, the signal may include at least one digital signal, such as a processed signal or at least a pre-processed signal. The signal may change over time. The signal may include at least one AC signal. Additionally or alternatively, the signal may include at least one DC signal. As commonly used by those skilled in the art above and below, AC refers to alternating current and DC refers to direct current. The signal may respond, particularly electrically, to observable changes in the environment that affect the signal. As an example, the signal may be the drain-source current I of a field-effect transistor. DS which can be expressed as a function of the applied drain-source current V DS and the applied gate potential V G In addition, it can be affected by the presence of the test substance, which affects the actual electric field experienced by the channel of the field effect transistor.

[0042] As used herein, the term "signal value" is a broad term and should be given its ordinary and customary meaning to those skilled in the art, and should not be limited to a special or special meaning. The term may specifically refer to a value that represents a measurable characteristic of a signal, such as, but not limited to, the strength of the signal. As mentioned above, the signal may specifically include at least one electrical signal, more specifically at least one of a voltage and a current. As further mentioned above, the signal may include at least one DC signal. Thus, the signal value may include at least one of a voltage value and a current value, also called current strength. Also as mentioned above, the signal may include at least one AC signal. Thus, the signal value may include at least one of an amplitude, an average value such as a DC bias, a frequency, a phase, a phase difference, and a duty cycle. In general, the signal may suffer from noise, such as 1 / f noise, as known to those skilled in the art. The noise may distort the monitored signal value and thus reduce the reliability of the measurement. The noise may also depend specifically on the environment affecting the signal. Thus, as an example, it may be advantageous to find operating parameters that result in as little noise as possible.

[0043] The parameter selection step, i.e., step ii, includes performing a plurality of evaluation measurements on the field effect transistor using various candidate sets of operating parameters and selecting the set of operating parameters according to at least one optimization criterion monitored during the evaluation measurements. As used herein, the term "evaluation measurement" is a broad term and should be given its general and ordinary meaning to those skilled in the art and should not be limited to a special or special meaning. This term may specifically, but not exclusively, refer to a measurement or a preliminary measurement performed to find a suitable or optimal measurement setting for a subsequent actual measurement of interest. In particular, the evaluation measurement may be a preliminary measurement performed to find the best operating parameters for a subsequent determination of the concentration of the analyte in the sample. As an example, the evaluation measurement may be used to find the operating parameters that produce the least possible noise as described above.

[0044] As used herein, the term "candidate operating parameters" is a broad term and should be given its general and ordinary meaning to those skilled in the art and should not be limited to a special or special meaning. The term may specifically, but is not limited to, refer to the operating parameters applied during the evaluation measurement. Thus, the candidate operating parameters may be possible operating parameters for determining the concentration of the analyte, which possible operating parameters are pre-tested in at least one evaluation measurement. Specifically, as shown, the candidate operating parameters may be applied to the field effect transistor in a set. That is, one or more candidate operating parameters may be grouped together as a set and specifically applied simultaneously to the field effect transistor. As an example, in the evaluation measurement, a particular gate potential V G A particular drain-source voltage V in combination with DS may be applied to a field effect transistor, with the corresponding drain-source current I DS Further, in this example, such a procedure may be performed at a particular drain-source voltage V DS and the gate potential V GThis may be repeated for several sets of DS The particular set in which the noise is minimal may be selected for determining the concentration of the analyte. Several further options are possible, and further embodiments are outlined below.

[0045] As used herein, the term "optimization criterion" is a broad term and should be given its general and ordinary meaning to those skilled in the art and should not be limited to a special or special meaning. The term may specifically, but not limited to, refer to a criterion used to optimize at least one process (specifically, at least one measurement, such as the determination of the concentration of an analyte in a sample). The optimization criterion may be, or may include, as an example, at least one target condition that should be achieved as fully as possible. For optimization purposes, deviations from the achievement of the target condition may be used. In particular, one or more candidate sets of operating parameters may be compared according to the optimization criterion, and the particular set that provides the best results according to the optimization criterion may be selected. Thus, for each operating parameter set, at least one measurable value describing the deviation from the target result defined by the at least one target criterion may be determined for the results achieved by using that operating parameter set, and this measurable value may be used to select the optimal operating parameter set.

[0046] As used herein, the term "monitor" and any grammatical variations thereof are broad terms and should be given their common and ordinary meaning to those skilled in the art and should not be limited to a specific or special meaning. The term may specifically refer to at least one of measuring, tracking, tracing, observing, and recording at least one entity, such as, for example, the optimization criterion described above, particularly over a period of time, for example, continuously or repeatedly over at least one period. Specifically, monitoring the optimization criterion in the evaluation measurement may include evaluating the optimization criterion for at least one candidate operating parameter. Thus, by monitoring the optimization criterion, it may be possible to compare different candidate operating parameters. As an example, the optimization parameter may be a signal-to-noise ratio (SNR), which may be expressed as, for example, a signal-to-noise ratio (SNR) for a particular gate potential V. G and / or a particular drain-source voltage V DS etc. By monitoring the signal-to-noise ratio (SNR), for example, the candidate operating parameters that result in the highest signal-to-noise ratio (SNR) may be identified.

[0047] This allows the determination of the concentration of the analyte in the sample to be optimized according to the optimization criterion. Of course, if a different optimization criterion is selected, the set of candidate operating parameters selected as the operating parameters may also be different. As an example, as already indicated, the optimization criterion may be related to the signal noise, thereby selecting the optimized parameter set that results in the lowest signal noise in the comparison. Further details and embodiments are outlined below.

[0048] The measuring step, step iii, involves detecting the concentration of the analyte by applying the set of operating parameters selected in step ii to the field effect transistor and determining at least one signal value at the field effect transistor. In particular, a selected potential, voltage and / or current may be applied to selected electrodes of the field effect transistor. As an example, as already indicated, a selected drain-source voltage V DS and the gate potential V G may be applied to a field effect transistor, with a corresponding drain-source current I DS may be measured as a signal value. As mentioned above, further options are possible, and further embodiments are outlined below. Based on the determined signal value, the concentration of the analyte may be determined by using at least one known relationship (e.g., a look-up table or a transfer function) between the determined signal value and the concentration. The relationship may be determined, for example, in at least one calibration, in particular by using at least one calibrator. Further details are provided below.

[0049] The set of operating parameters selected in step ii is the gate potential V G and the drain-source current I of the field-effect transistor DS The gate potential V G can be applied in various forms. The gate potential V G may be applied as a constant or varying potential, where the varying potential may include, for example, a DC level or an AC voltage having a predetermined frequency. Additionally, constant current parameters such as acquisition rate, pulses, or steps may be varied. Thus, using a particular voltage or current as an operating parameter may specifically include using at least one of the magnitude, phase, and frequency of the voltage or current as an operating parameter. In general, at least one characteristic of the voltage or current may be used as an operating parameter.

[0050] The sensor device, such as the control device, is connected to the gate potential V G is applied to the gate electrode of the field effect transistor via the sample and sense electrodes, and a predetermined drain-source current I DS The drain-source voltage V required to achieve DS Therefore, the drain-source voltage V DS but in particular may be the signal value determined in step iii for deriving the concentration of the analyte. As mentioned above, the control device may comprise at least one analog output. By way of example, the control device, in particular the analog output, may be capable of applying a gate potential V to the sample, for example by using at least one electrode connected to the sample. G may be applied. As an example, the sample may contain an electrolyte and the electrode may be inserted into the electrolyte. Further options may be feasible. As already indicated, the sensing electrode may be specifically exposed to the sample and functionalized with respect to the analyte. Thus, the applied gate potential V G can be influenced by the sample, specifically the analyte. In particular, as already shown, the corresponding electric field in the channel of the field effect transistor can be influenced by the analyte. Thus, the resulting drain-source current I DS can be affected by the test material. As mentioned above, the selected operating parameter, the drain-source current I DS may be predefined. Thus, the drain-source current I DS can be kept in its predetermined state, i.e. constant, by using a control device. In other words, a control device, which may in particular comprise a galvanostat as described above, controls the predetermined drain-source current I selected in step ii. DS Specifically, as will be understood by those skilled in the art, the drain-source voltage V DS In other words, the controller can vary the drain-source voltage V DS By varying the drain-source current IDS As mentioned above, the control device may be configured to readjust or adjust a predetermined drain-source current I DS The drain-source voltage V required to achieve DS Additionally, as will be appreciated by those skilled in the art in light of the above description, the drain-source voltage V DS By monitoring the change in , the concentration of the analyte can be derived.

[0051] The control device controls the drain-source current I DS The drain-source voltage V required to achieve DS The system may include at least one feedback loop for controlling the drain-source current I. As used herein, the term "feedback loop" is a broad term and should be given its general and ordinary meaning to those skilled in the art and should not be limited to a special or special meaning. The term may specifically refer to, but is not limited to, an entity, specifically an electrical circuit or a portion of an electrical circuit, configured to feed back a signal response generated by using an input signal and the system to the input signal and / or by coupling the signal or a quantity derived from the signal to the source of the signal. As mentioned above, the drain-source current I DS can be affected by the analyte in the sample, but still be maintained by the controller as predetermined. The feedback loop regulates the drain-source current I DS , specifically the actual drain-source current I affected by the test material DS , and the measured drain-source current I DS may be configured to couple back to the controller. Thus, the controller may be configured to obtain a predetermined drain-source current I by using a feedback loop. DS The drain-source voltage V required to achieve DS may be configured to determine and apply

[0052] The set of operating parameters selected in step ii is the gate potential V of the field effect transistor applied to the sample when detecting the concentration of the analyte. G and the drain-source current I of the field-effect transistor applied to the field-effect transistor DS Step iii may include: DS The drain-source voltage V required to achieve DS as a signal value, and the drain-source voltage V DS Similarly to the above, the drain-source voltage V determined as the signal value may be used to derive the concentration of the analyte from DS The concentration of the analyte is determined based on the drain-source voltage V DS The concentration may be determined by using at least one known relationship (e.g., a look-up table or a transfer function) between the concentration and the concentration. The known relationship may be determined, for example, in at least one calibration, in particular by using at least one calibrator.

[0053] The optimization criterion may relate to at least one measurable optimization criterion value. In particular, the optimization criterion value may be quantifiable and / or comparable. The optimization criterion value may be selected from the group consisting of the signal-to-noise ratio SNR, the signal strength, the signal noise, the signal drift. As already indicated, a low signal noise can facilitate, for example, a reliable measurement. As the skilled person will appreciate, the relationship between the signal strength and the signal noise can be particularly decisive in this respect, which can generally be addressed by the signal-to-noise ratio SNR, i.e. the quotient of the signal strength to the noise strength. As an example, a higher noise may be acceptable for a reliable measurement if the signal strength is still significantly higher in comparison. Furthermore, as the skilled person will appreciate, the signal may drift over time for various reasons, such as changes in the ambient conditions or changes in at least one component in the sensor device (particularly the field effect transistor), for example due to material degradation. Such drifts, like the noise mentioned above, may also affect the monitored signal value and thus the reliability of the measurement.

[0054] The set of operating parameters in step ii may be selected by selecting the operating parameters of the evaluation measurement that result in one of the maximum and minimum optimization criterion values ​​monitored during the evaluation measurement. As an example, the set of operating parameters in step ii may be selected by selecting the operating parameters of the evaluation measurement that result in at least one of the maximum signal-to-noise ratio SNR, the maximum signal strength, the minimum signal noise, and the minimum signal drift. In particular, the set of operating parameters in step ii may be selected by selecting the operating parameters of the evaluation measurement that result in the maximum signal-to-noise ratio SNR. Such a selection may promote accurate and reliable measurements, in particular accurate and reliable determination of the concentration of the analyte in the sample. In this way, the most appropriate operating parameters may be found for each specific measurement by using resource-saving and rapidly adaptable means. In particular, rather complex changes of hardware components may be avoided.

[0055] Performing the evaluation measurements in step ii may include performing individual evaluation measurements in succession. Each evaluation measurement may involve varying one operating parameter while holding a further operating parameter constant. In this way, the effect of varying an operating parameter may be tracked in an isolated manner and therefore more reliably. As already outlined, the gate potential V of the field effect transistor G and the drain-source current I DS may be used as operational parameters and may be combined into a set of characterization measurements applied to the field effect transistor. At least one characterization measurement may be a gate potential V G In particular, the drain-source current I DS In this way, the gate potential V G The effect of varying the optimal gate potential V G Additionally or alternatively, the at least one characterization measurement may determine the drain-source current I of the field effect transistor. DS In particular, the gate potential V of a field effect transistor G Therefore, the drain-source current I DS The effect of varying the optimal drain-source current I DS Finally, the optimum gate potential V G and the determined optimal drain-source current I DS may be applied to the field effect transistor to determine the concentration of the analyte in the sample. Further types of evaluation measurements may be possible and the order of the evaluation measurements may vary.

[0056] In general, step ii may include selecting a first operating parameter for step iii by performing at least one first evaluation measurement, the at least one first evaluation measurement including varying the first operating parameter while holding a further operating parameter constant. Step ii may further include holding the selected first operating parameter constant in at least one further evaluation measurement performed to select the at least one further operating parameter for step iii. In general, the terms "first", "second" and further numbering, where applicable, are used herein merely as designations and do not indicate order or rank. As shown, the first operating parameter may be a gate potential V of a field effect transistor. G and further operating parameters may include the drain-source current I of the field effect transistor. DS may include:

[0057] Step ii may include performing the evaluation measurement under experimental conditions corresponding to step iii. In particular, step ii may include performing the evaluation measurement by using the same sample as step iii. Additionally or alternatively, step ii may include performing the evaluation measurement under the same ambient conditions (e.g., temperature or humidity) as step iii. Additionally or alternatively, step ii may include performing the evaluation measurement by using the same sensing device as step iii, in particular using at least one of the same field effect transistor, the same sensing electrode, and the same control device. Furthermore, step ii may include performing the evaluation measurement by using the same configuration and / or settings of the sensing device, in particular the control device. In particular, step ii may include performing the evaluation measurement by using the same measurement range as step iii.

[0058] Step ii may be performed again when changing the measurement range in step iii. As used herein, the term "measurement range" is a broad term and should be given its general and ordinary meaning to those skilled in the art and should not be limited to a specific or special meaning. The term may specifically, but not exclusively, refer to at least one interval in which a measurement is performed. The measurement range may include a start value and an end value and / or a minimum and a maximum value that define the interval. As already known to those skilled in the art, in particular for measurements involving field effect transistors, the measurement range may be determined by determining the gate potential V of at least one entity, e.g. G can be swept over a selected measurement range during a measurement, for example when recording the transfer curve of a field effect transistor. In this example, the gate potential V G In this case, the gate potential V G The measurement range may be varied, for example continuously or using discrete levels, from a start value to a final value that defines a measurement range of the field effect transistor. Similar considerations may be applied mutatis mutandis to other parameters of the field effect transistor and other parameters in general, as will be appreciated by those skilled in the art. The measurement range may affect the performance of the field effect transistor, in particular the performance of the field effect transistor for a selected set of operating parameters. In other words, different operating parameters may be better suited for different measurement ranges. Thus, when changing the measurement range in step iii, re-performing step ii and selecting a new set of at least possibly adapted operating parameters may facilitate accurate and reliable measurements.

[0059] Step ii may further include performing at least one calibration to determine a relationship between the concentration of the analyte and the signal value of the field effect transistor. As used herein, the term "relationship" is a broad term and should be given its general and ordinary meaning to those skilled in the art and should not be limited to a special or special meaning. The term may specifically, but not be limited to, refer to a connection or assignment between two entities. Specifically, a sensor device may be used to measure a signal value and the relationship may assign the measured signal value to a particular concentration of the analyte. The relationship may include at least one of a look-up table, a transfer function, an algorithm, and a model. Thus, the relationship may be determined, for example, by providing a number of test samples in which the concentration of the analyte is known, and may further include recording the corresponding signal values ​​of the field effect transistor for these test samples. Thereafter, the relationship, such as a calibration curve, may be determined, for example, by regression. Thus, the relationship may include at least one trained model, such as a model trained by regression or other methods known to those skilled in the art. The relationship may specifically be determined by performing a calibration prior to the actual measurement of the object of interest.

[0060] As used herein, the term "calibration" is a broad term and should be given its common and ordinary meaning to those skilled in the art and should not be limited to a special or special meaning. The term may specifically, but not exclusively, refer to the process of comparing a measurement value to a known standard, i.e., an entity having at least one precisely known characteristic. Calibration may include measuring the known standard and assigning the measurement value to the known characteristic. Specifically, as also outlined in more detail below, calibration may include determining at least one signal value in a field effect transistor for a sample with a known concentration of an analyte and assigning the determined signal value to the known concentration.

[0061] Calibration may include determining the sensitivity of the sensor device. As used herein, the term "sensitivity" is a broad term and should be given its common and ordinary meaning to one of ordinary skill in the art and should not be limited to a specific or special meaning. The term may specifically refer to, but is not limited to, the ratio of a change in an output value to a corresponding change in an input value. Specifically, sensitivity may represent the change in a signal value determined by using the sensing device to a change in concentration of the analyte. More specifically, sensitivity may represent the ratio of a determined drain-source voltage V to a given change in concentration of the analyte. DS , i.e., the ratio of voltage change to concentration change.

[0062] Calibration may include using at least one calibrator, specifically a set including a plurality of different calibrators. As used herein, the term "calibrator" is a broad term and should be given its general and ordinary meaning to those skilled in the art and should not be limited to a specific or special meaning. The term may specifically, but not exclusively, refer to a known standard, specifically a sample having known characteristics. More specifically, a calibrator may include a sample having a known concentration of an analyte. Thus, by analyzing a calibrator having a known concentration of an analyte, the electrical response of the sensor device to the analyte may be assigned to a corresponding concentration of the analyte, as already described above.

[0063] As further indicated above, the field effect transistor may be selected from the group consisting of an extended gate field effect transistor (EGFET), an ion sensitive field effect transistor (ISFET), a chemically sensitive field effect transistor (ChemFET), a biological field effect transistor (BioFET), an enzyme field effect transistor (ENFET), a solution or liquid gate field effect transistor, a graphene based field effect transistor. In particular, the field effect transistor may be an extended gate field effect transistor (EGFET). The sensing electrode may be an extended gate electrode. The sensing electrode may comprise at least one functional component on its surface. The functional component may comprise, by way of example, at least one compound deposited on at least one surface of the sensing electrode, such as the metal surface or the conductive carbon surface of the sensing electrode. The functional component may be chemically bound to the sensing electrode by, by way of example, at least one of covalent bonds, complex bonds, ionic bonds, hydrogen bonds, dipole bonds, van der Waals bonds, and the like. The functional component may be configured to directly and / or indirectly interact with the analyte. As used herein, the term "functional component" is a broad term and should be given its general and ordinary meaning to those skilled in the art and should not be limited to a special or special meaning. The term may specifically refer to, but is not limited to, a material such as a compound, molecule, chemical blend or mixture that may be electrically insulating itself but can form an electrostatic bond between the analyte and the sensing electrode such that the electrostatic potential of the sensing electrode is affected by the presence or absence of the analyte via the functional component. Thus, the functional component may, by way of example, comprise a spacer molecule that can be bound to the surface of the sensing electrode, for example by one or more of the above bonds, and that may comprise at least one binding site for binding with the analyte to be detected. The spacer molecule may be configured such that the electrostatic potential of the sensing electrode is different in the absence of the analyte and in the presence of the analyte. The functional component may be capable of binding to the analyte, such as by at least one of covalent bonds, complex bonds, ionic bonds, hydrogen bonds, dipole bonds, van der Waals bonds. To this end, the functional component may comprise at least one binding site.For further information on the functional moiety, one may refer to pages 1-14, especially page 8, of Grundler, Peter. Chemical sensors: An introduction for scientists and engineers. Springer Science & Business Media, 2007. The functional moiety may comprise at least one ionophore, especially valinomycin. Additionally or alternatively, the functional moiety may comprise at least one receptor compound. The receptor compound may be capable of interacting with at least one analyte, in particular capable of binding to at least one analyte, for example by one or more of the above-mentioned chemical bonds. The receptor compound may be capable of binding to at least one analyte selected from the group consisting of antibodies and fragments thereof, aptamers, peptides, enzymes, nucleic acids, receptor proteins or binding domains thereof.

[0064] The analyte may be selected from the group consisting of potassium and sodium. In general, any analyte may be feasible that is specifically configured to affect the surface charge density of the sensing electrode. This may more generally include proteins, DNA, and electrolytes. The sample may include at least one of bodily fluids, specifically blood, plasma, serum, urine, cerebrospinal fluid, tears, cell suspensions, cell supernatants, cell extracts, tissue lysates, saliva, tears, and interstitial fluid.

[0065] The method may be particularly at least partially implemented by a computer, and in particular at least one of steps ii and iii may be implemented by a computer. With respect to computer-implemented aspects of the present invention, one or more or all of the method steps of the method according to one or more of the embodiments disclosed herein may be implemented by using a computer or a computer network. Thus, in general, any method step that includes providing and / or manipulating data may be implemented by using a computer or a computer network. In general, these method steps may include any method step, except for method steps that typically require manual work, such as providing a sample and / or performing the actual measurement in certain aspects.

[0066] In a further aspect of the invention, a sensor device for determining the concentration of at least one analyte in a sample, in particular a body fluid sample, is disclosed. The sensor device comprises: at least one field effect transistor, in particular at least one MOSFET, having at least one source electrode, at least one drain electrode and at least one gate electrode, - at least one sensing electrode configured to be in contact with the sample and electrically connected to and / or integrated in a gate electrode of the field effect transistor; at least one control device configured to apply a set of operating parameters to the field effect transistor and configured to monitor at least one signal value at the field effect transistor; Equipped with the control device is configured to control steps ii and iii of the method according to any one of the embodiments disclosed in further detail above and below relating to a method for determining the concentration of at least one analyte in a sample.

[0067] The field effect transistor may be selected from the group consisting of extended gate field effect transistors (EGFETs), ion sensitive field effect transistors (ISFETs), chemically sensitive field effect transistors (ChemFETs), biological field effect transistors (BioFETs), enzyme field effect transistors (ENFETs), solution or liquid gate field effect transistors, graphene based field effect transistors. The field effect transistor may be an extended gate field effect transistor (EGFET). The sensing electrode may be an extended gate electrode. The sensing electrode may comprise at least one functional component on its surface. The functional component may be configured to directly and / or indirectly interact with the analyte. The functional component may comprise at least one ionophore, in particular valinomycin. Additionally or alternatively, the functional component may comprise at least one receptor compound. The receptor compound may be capable of binding to at least one analyte. The receptor compound may specifically be capable of binding to at least one test substance selected from the group consisting of antibodies and fragments thereof, aptamers, peptides, enzymes, nucleic acids, receptor proteins or binding domains thereof.

[0068] The sensor device may further comprise at least one fluid channel. The sensing electrode may be arranged in contact with the sample in the fluid channel. As mentioned above, the sample may in particular be a fluid sample. The sample may flow through the fluid channel. The sensing electrode may, for example, be inserted into the fluid channel such that the sample flows around the sensing electrode. The fluid channel may include at least one fluid inlet for bringing the sample into the fluid channel and at least one fluid outlet for leaving the sample from the fluid channel. The sensor device may further comprise at least one fluid pump for conveying the sample through the fluid channel.

[0069] For further definitions or embodiments regarding the sensor device, reference may be made to the above explanations regarding the method for determining the concentration of at least one analyte in a sample.

[0070] Further disclosed and proposed herein is a computer program comprising instructions, which when executed by a sensor device according to any one of the embodiments disclosed in more detail above or below with respect to the sensor device, cause the sensor device to perform at least one of steps ii and iii of the method according to any one of the embodiments disclosed in more detail above or below with respect to the method. In particular, the computer program may be stored on a computer-readable data carrier and / or a computer-readable storage medium.

[0071] As used herein, the terms "computer-readable data carrier" and "computer-readable storage medium" may specifically refer to non-transitory data storage means such as a hardware storage medium having computer-executable instructions stored thereon. A computer-readable data carrier or storage medium may specifically be or comprise a storage medium such as a random access memory (RAM) and / or a read-only memory (ROM).

[0072] Thus, in particular, one or more of the method steps ii and iii as set out above may be carried out using a computer or a computer network, preferably using a computer program.

[0073] Further disclosed and proposed herein is a computer program product having program code means for executing the method according to the invention in one or more of the embodiments contained herein when the program is executed on a computer or a computer network. In particular, the program code means may be stored on a computer readable data carrier and / or a computer readable storage medium.

[0074] Further disclosed and proposed herein is a data carrier storing a data structure which, after being loaded into a computer or computer network, such as a working memory or main memory of a computer or computer network, is capable of performing the methods according to one or more of the embodiments disclosed herein.

[0075] Further disclosed and proposed herein is a computer program product having program code means stored on a machine-readable carrier for executing the method according to one or more of the embodiments disclosed herein when the program is executed on a computer or computer network. As used herein, a computer program product refers to a program as a tradeable product. The product can generally be present in any format, such as a paper format, or on a computer-readable data carrier and / or a computer-readable storage medium. In particular, the computer program product may be distributed via a data network.

[0076] Further disclosed and suggested herein is a modulated data signal containing instructions readable by a computer system or computer network for carrying out a method according to one or more of the embodiments disclosed herein.

[0077] Further disclosed and proposed in this specification is a computer-readable storage medium comprising instructions which, when executed by a sensor device according to any one of the embodiments disclosed in further detail above or below with respect to the sensor device, cause the sensor device to perform at least one of steps ii and iii of a method according to any one of the embodiments disclosed in further detail above or below with respect to the method.

[0078] With respect to computer-implemented aspects of the present invention, one or more or all of the method steps of the method according to one or more of the embodiments disclosed herein may be performed by using a computer or a computer network. Thus, in general, any method step that includes providing and / or manipulating data may be performed by using a computer or a computer network. In general, these method steps may include any method step, except for those method steps that typically require manual work, such as providing a sample and / or certain aspects of performing the actual measurement.

[0079] Specifically, in this specification, a computer or computer network comprising at least one processor, the processor being configured to execute a method according to one of the embodiments described herein, - a computer-loadable data structure configured, when executed on a computer, to carry out a method according to one of the embodiments described herein; - a computer program configured, when it is run on a computer, to carry out a method according to one of the embodiments described in this specification, a computer program comprising program means for carrying out the method according to one of the embodiments described herein when said computer program is run on a computer or a computer network or a cloud, a computer program comprising program means according to the preceding embodiment, the program means being stored on a computer readable storage medium; - a storage medium storing a data structure, the data structure being configured to execute a method according to one of the embodiments described herein after being loaded into a main memory and / or a working memory of a computer or a computer network, and - a computer program product comprising program code means storable or stored on a storage medium, which, when executed on a computer or on a computer network, performs a method according to one of the embodiments described herein. is further disclosed.

[0080] The method and device according to the invention may offer a number of advantages over known methods and devices. In particular, it may allow efficient determination of optimal measurement settings for determining the concentration of an analyte in a sample. In particular, it may allow rapid finding of optimal operating parameters for determining the concentration of an analyte with high performance and reproducibility. In doing so, it may avoid changing hardware components, which may typically be a rather complicated process. In case a change of a hardware component is still required, for example due to the end of its useful life, adaptation to the new components may be efficiently achieved. Thus, the method and device according to the invention may be flexibly adaptable and widely applicable. Furthermore, it may particularly allow measurements with high time resolution, efficient multiplexing of different sensor devices, and efficient data processing.

[0081] As used herein, the term "multiplexing" is a broad term and should be given its general and ordinary meaning to those skilled in the art and should not be limited to a specific or special meaning. The term may specifically, but is not limited to, refer to the simultaneous detection of multiple analytes from a single sample. The term may specifically, but is not limited to, refer to a method for simultaneously, in situ detection of different analytes from a single sample. The term may specifically, but is not limited to, refer to the act of combining multiple signals and transmitting them through a shared medium, e.g., simultaneously or alternately. Specifically, the act of combining multiple signals through a single gate potential V gmay be transmitted through one sample to the multiple field effect transistors. The sensor device may include multiple sensing electrodes exposed to the sample. The sensing electrodes may, for example, each be connected to one field effect transistor. The different sensing electrodes may be configured to measure different analytes in the sample. As an example, a first sensing electrode may be configured to measure potassium, a second sensing electrode may be configured to measure magnesium, and a third sensing electrode may be configured to measure chloride. The sensing electrodes may, in particular, be connected to a gate potential V g The gate electrodes of the field effect transistors may be contacted with one liquid sample, which may then be applied with the same gate potential V g For each field effect transistor, an individual drain-source current I DS can be specifically determined as the optimal operating parameter for determining the concentration of the analyte. Thus, when determining the concentration of a certain analyte, the determined individual drain-source current I of the corresponding field effect transistor DS At the same time, the gate potential V g can be kept constant and monitored over time.

[0082] In summary, without excluding further embodiments, the following embodiments can be envisaged:

[0083] Embodiment 1: A method for determining the concentration of at least one analyte in a sample, in particular a sample of a body fluid, comprising: i. providing at least one sensor device, the sensor device comprising: at least one field effect transistor, in particular at least one MOSFET, having at least one source electrode, at least one drain electrode and at least one gate electrode, - at least one sensing electrode configured to be in contact with the sample and electrically connected to and / or integrated in a gate electrode of the field effect transistor; at least one control device configured to apply operating parameters to the field effect transistor and configured to monitor at least one signal value at the field effect transistor; Having or providing ii. at least one parameter selection step including selecting a set of operational parameters of the field effect transistor for at least one subsequent measurement step, the parameter selection step including performing a plurality of evaluation measurements on the field effect transistor using different candidate sets of operational parameters and selecting the set of operational parameters according to at least one optimization criterion monitored during the evaluation measurements; iii. at least one measuring step including detecting a concentration of the analyte by applying the set of operating parameters selected in step ii to a field effect transistor and determining at least one signal value at the field effect transistor; The method includes:

[0084] Embodiment 2: The set of operating parameters selected in step ii is the gate potential V G and the drain-source current I of the field-effect transistor DS 4. The method of claim 1, further comprising:

[0085] Embodiment 3: The sensor device applies a gate potential V to the gate electrode of the field effect transistor via the sample and sensing electrodes. G and configured to apply a predetermined drain-source current I DS The drain-source voltage V required to achieve DS 13. The method of any one of the preceding embodiments, further configured to monitor.

[0086] Embodiment 4: The control device controls the drain-source current I DS The drain-source voltage V required to achieveDS 4. The method of claim 1, further comprising at least one feedback loop for controlling

[0087] Embodiment 5: The set of operating parameters selected in step ii is the gate potential V of the field effect transistor applied to the sample when detecting the concentration of the analyte. G and the drain-source current I of the field-effect transistor applied to the field-effect transistor DS Step iii includes the signal value of the drain-source current I DS The drain-source voltage V required to achieve DS determining a determined drain-source voltage V DS 36. The method of any one of the preceding embodiments, further comprising deriving a concentration of the analyte from:

[0088] Embodiment 6: The method of any one of the preceding embodiments, wherein the optimization criterion relates to at least one measurable optimization criterion value.

[0089] Embodiment 7: The method according to any one of the preceding embodiments, wherein the optimization criterion value is selected from the group consisting of a signal-to-noise ratio SNR, a signal strength, a signal noise, and a signal drift.

[0090] Embodiment 8: A method according to any one of the preceding two embodiments, wherein the set of operating parameters in step ii is selected by selecting an operating parameter of the evaluation measurement that results in one of a maximum optimization criterion value and a minimum optimization criterion value monitored in the evaluation measurement.

[0091] Embodiment 9: A method according to any one of the preceding embodiments, wherein the set of operating parameters in step ii is selected by selecting the operating parameters of the evaluation measurement that results in the maximum signal-to-noise ratio SNR.

[0092] Embodiment 10: A method as in any one of the preceding embodiments, wherein performing the evaluation measurements in step ii includes performing individual evaluation measurements in succession, each evaluation measurement including varying one operating parameter while holding a further operating parameter constant.

[0093] At least one evaluation measurement is performed on the gate potential V of a field effect transistor. G In particular, the drain-source current I DS 4. The method of claim 1, further comprising:

[0094] Embodiment 12: At least one evaluation measurement is a drain-source current I of a field effect transistor. DS In particular, the gate potential V of a field effect transistor G 4. The method of any one of the preceding two embodiments, comprising varying while keeping constant

[0095] Embodiment 13: A method according to any one of the preceding embodiments, wherein step ii comprises selecting a first operating parameter for step iii by performing at least one first evaluation measurement, the at least one first evaluation measurement comprising varying the first operating parameter while holding a further operating parameter constant, and step ii further comprises holding the selected first operating parameter constant in at least one further evaluation measurement performed to select the at least one further operating parameter for step iii.

[0096] Embodiment 14: The first operating parameter is the gate potential V of the field effect transistor. G and a further operating parameter is the drain-source current I DS 3. The method of claim 2, further comprising:

[0097] Embodiment 15: The method of any one of the preceding embodiments, wherein step ii comprises carrying out evaluation measurements under experimental conditions corresponding to step iii.

[0098] Embodiment 16: The method of any one of the preceding embodiments, wherein step ii is re-executed when changing the measurement range in step iii.

[0099] Embodiment 17: The method of any one of the preceding embodiments, wherein step ii further comprises performing at least one calibration to determine a relationship between the concentration of the test substance and the signal value of the field effect transistor.

[0100] Embodiment 18: The method of the preceding embodiment, wherein the calibration includes determining the sensitivity of the sensor device.

[0101] Embodiment 19: The method of any one of the previous two embodiments, wherein the calibration comprises using at least one calibrator, in particular a set comprising a plurality of different calibrators.

[0102] Embodiment 20: The method of any one of the preceding embodiments, wherein the field effect transistor is selected from the group consisting of an extended gate field effect transistor (EGFET), an ion-sensitive field effect transistor (ISFET), a chemically sensitive field effect transistor (ChemFET), a biological field effect transistor (BioFET), an enzyme field effect transistor (ENFET), a solution or liquid gate field effect transistor, and a graphene-based field effect transistor.

[0103] Embodiment 21: The method of any one of the preceding embodiments, wherein the field effect transistor is an extended gate field effect transistor (EGFET) and the sensing electrode is an extended gate electrode.

[0104]

[0081] Embodiment 22: The sensing electrode comprises at least one functional component on a surface thereof, the functional component being configured to interact with the analyte, the functional component being: at least one receptor compound capable of binding to at least one test substance, in particular selected from the group consisting of antibodies and fragments thereof, aptamers, peptides, enzymes, nucleic acids, receptor proteins and binding domains thereof, and At least one ionophore, especially valinomycin 13. The method of any one of the preceding embodiments, comprising at least one of:

[0105] Embodiment 23: The method of any one of the preceding embodiments, wherein the test substance is selected from the group consisting of potassium and sodium.

[0106] Embodiment 24: The method of any one of the preceding embodiments, wherein the sample comprises a bodily fluid, in particular at least one of blood, plasma, serum, urine, cerebrospinal fluid, tears, a cell suspension, a cell supernatant, a cell extract, a tissue lysate, saliva, tears, and interstitial fluid.

[0107] Embodiment 25: The method of any one of the preceding embodiments, at least partially implemented by a computer, in particular at least one of steps ii and iii being implemented by a computer.

[0108] Embodiment 26: A sensor device for determining the concentration of at least one analyte in a sample, in particular a sample of a body fluid, comprising: at least one field effect transistor, in particular at least one MOSFET, having at least one source electrode, at least one drain electrode and at least one gate electrode, - at least one sensing electrode configured to be in contact with the sample and electrically connected to and / or integrated in a gate electrode of the field effect transistor; at least one control device configured to apply a set of operating parameters to the field effect transistor and configured to monitor at least one signal value at the field effect transistor; Equipped with - a control device configured to control steps ii and iii of the method according to any one of the preceding embodiments.

[0109] Embodiment 27: The sensor device of the preceding embodiment, wherein the field effect transistor is selected from the group consisting of extended gate field effect transistors (EGFETs), ion-sensitive field effect transistors (ISFETs), chemically sensitive field effect transistors (ChemFETs), biological field effect transistors (BioFETs), enzyme field effect transistors (ENFETs), solution or liquid gate field effect transistors, and graphene-based field effect transistors.

[0110] Embodiment 28: A sensor device described in any one of the preceding embodiments relating to a sensor device, wherein the field effect transistor is an extended gate field effect transistor (EGFET) and the sensing electrode is an extended gate electrode.

[0111]

[0081] Embodiment 29: The sensing electrode comprises at least one functional component on a surface thereof, the functional component being configured to interact with the analyte, the functional component being: at least one receptor compound capable of binding to at least one test substance, in particular selected from the group consisting of antibodies and fragments thereof, aptamers, peptides, enzymes, nucleic acids, receptor proteins and binding domains thereof, and At least one ionophore, especially valinomycin The sensor device of any one of the preceding embodiments relating to a sensor device, comprising at least one of:

[0112] Embodiment 30: A sensor device described in any one of the preceding embodiments relating to a sensor device, further comprising at least one fluid channel, the sensing electrode being arranged to contact a sample in the fluid channel.

[0113] Embodiment 31: A sensor apparatus as described in the preceding embodiment, further comprising at least one fluid pump for transporting the sample through the fluid channel.

[0114] Embodiment 32: A computer program comprising instructions, which when executed by a sensor device described in any one of the preceding embodiments relating to a sensor device, cause the sensor device to perform at least one of steps ii and iii of the method described in any one of the preceding embodiments relating to a method.

[0115] Embodiment 33: A computer-readable storage medium comprising instructions that, when executed by a sensor device described in any one of the preceding embodiments relating to a sensor device, cause the sensor device to perform at least one of steps ii and iii of the method described in any one of the preceding embodiments relating to a method. [Brief description of the drawings]

[0116] Further optional features and embodiments are disclosed in more detail in the following description of the embodiments, preferably in conjunction with the dependent claims, in which each optional feature may be realized in an independent manner as well as in any possible combination, as understood by a person skilled in the art. The scope of the present invention is not limited by the preferred embodiments. The embodiments are illustrated diagrammatically in the figures, where identical reference numbers in these figures refer to identical or functionally equivalent elements. [Figure 1] 1 shows a schematic diagram of an exemplary embodiment of a sensor device for determining the concentration of at least one analyte in a sample. [Diagram 2] 1 shows a flow chart of an exemplary embodiment of a method for determining the concentration of at least one analyte in a sample. [Figure 3A] 1 shows a flow chart of an exemplary embodiment of a calibration of a sensor device for determining a concentration of at least one analyte in a sample. [Figure 3B]1 shows a flow chart of an exemplary embodiment of a calibration of a sensor device for determining a concentration of at least one analyte in a sample. [Figure 3C] 1 shows a flow chart of an exemplary embodiment of a calibration of a sensor device for determining a concentration of at least one analyte in a sample. [Figure 4A] 1 shows experimental results of an exemplary embodiment of the evaluation measurement of step ii of the method for determining the concentration of at least one analyte in a sample, together with the corresponding concentration detection of potassium. [Figure 4B] 1 shows experimental results of an exemplary embodiment of the evaluation measurement of step ii of the method for determining the concentration of at least one analyte in a sample, together with the corresponding concentration detection of potassium. [Figure 4C] 1 shows experimental results of an exemplary embodiment of the evaluation measurement of step ii of the method for determining the concentration of at least one analyte in a sample, together with the corresponding concentration detection of potassium. [Figure 4D] 1 shows experimental results of an exemplary embodiment of the evaluation measurement of step ii of the method for determining the concentration of at least one analyte in a sample, together with the corresponding concentration detection of potassium. [Figure 4E] 1 shows experimental results of an exemplary embodiment of the evaluation measurement of step ii of the method for determining the concentration of at least one analyte in a sample, together with the corresponding concentration detection of potassium. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0117] 1 shows in a schematic diagram an exemplary embodiment of a sensor device 110 for determining the concentration of at least one analyte in a sample 112. The sample 112 may specifically include a body fluid, in particular at least one of blood, interstitial fluid, plasma, saliva, urine, and tears. The analyte may specifically be selected from the group consisting of potassium and sodium. However, in general, other analytes and / or samples are also possible, in particular any analyte configured to affect the charge density may be feasible. This may more generally include at least one of proteins, DNA, and electrolytes.

[0118] The sensor device 110 includes at least one field effect transistor 114. The field effect transistor 114 has at least one source electrode 116, at least one drain electrode 118, and at least one gate electrode 120. Furthermore, the field effect transistor 114 may include at least one semiconductor 122 and at least one dielectric 124, such as at least one layer of at least one solid dielectric medium. In the field effect transistor 114, a conductive channel 126 may be formed at an interface between the semiconductor 122 and the dielectric 124. In particular, the field effect transistor 114 may be a metal oxide semiconductor field effect transistor (MOSFET) 128. Thus, the dielectric 124 may in particular be or include at least one electrically insulating oxide. Generally, by way of example, the field effect transistor 114 may be selected from the group consisting of an extended gate field effect transistor (EGFET) 130, an ion sensitive field effect transistor (ISFET), a chemically sensitive field effect transistor (ChemFET), a biological field effect transistor (BioFET), an enzyme field effect transistor (ENFET), a solution or liquid gate field effect transistor, and a graphene-based field effect transistor.

[0119] The sensor device 110 further comprises at least one sensing electrode 132. The sensing electrode 132 is configured to contact the sample 112. The sensing electrode 132 is electrically connected to and / or integrated with the gate electrode 120 of the field effect transistor 114. As shown, the field effect transistor 114 may be an EGFET 130. The sensing electrode 132 may be an extended gate electrode 134. Thus, as shown in FIG. 1, the sensing electrode 132, which is an extended gate electrode 134, may be electrically connected to the gate electrode 120, particularly by using at least one wire 136 and / or at least one conductive path 138.

[0120] The sensing electrode 132 may include at least one functional component 140 on its surface. The functional component 140 may be configured to interact with the analyte. The functional component 140 may include at least one receptor compound 142. The receptor compound 142 may generally be capable of interacting with the analyte, and in particular may be capable of binding to the analyte, such as by at least one of covalent bonds, complex bonds, ionic bonds, hydrogen bonds, dipole bonds, van der Waals bonds, in this example or other examples. The receptor compound 142 may specifically be capable of binding to at least one analyte selected from the group consisting of antibodies and fragments thereof, aptamers, peptides, enzymes, nucleic acids, receptor proteins and binding domains thereof. Additionally or alternatively, the functional component 140 may include at least one ionophore 144, specifically valinomycin.

[0121] The sensor device 110 further comprises at least one controller 146. The controller 146 is configured to apply an operating parameter set to the field effect transistor 114 and to monitor at least one signal value at the field effect transistor 114. The controller 146 is configured to control steps ii and iii of the method according to any one of the embodiments of the method described above or in more detail below, for example according to FIG. 2 as described below. The controller 146 may comprise at least one source measurement unit (SMU) 148. The controller 146 may comprise at least one galvanostat 150. The field effect transistor 114 may be connected to the controller 146. In particular, the source electrode 116 and the drain electrode 118 may be directly connected to the controller 146. The controller 146 may be connected to a ground 152. The controller 146 may comprise at least one output 154, in particular at least one analog output 156. The analog output 156 may be connected to at least one contact electrode 158 in contact with the sample 112. The sample 112 may be in contact with the sensing electrode 132. Thus, by using the analog output 156, the controller 146 can transmit a gate potential V to the gate electrode 120 via the sample 112 and the sensing electrode 132. G The control device 146 may be configured to add: The control device 146 may comprise at least one processing unit 160 for signal processing and evaluation.

[0122] The sensor device 110 may further comprise at least one fluidic channel 162. The sensing electrode 132 may be positioned in the fluidic channel 162 to contact the sample 112. The sample 112 may flow through the fluidic channel 162 as indicated by arrows 164. The sensing electrode 132 may be inserted into the fluidic channel 162 such that the sample 112 passes the sensing electrode 132 as it flows through the fluidic channel 162. The sensor device 110 may further comprise at least one fluidic pump 166 for conveying the sample 112 through the fluidic channel 162.

[0123] 2 shows a flow chart of an exemplary embodiment of a method for determining the concentration of at least one analyte in a sample 112. The method includes: i. providing at least one sensor device 110, the sensor device 110 comprising: at least one field effect transistor 114, in particular at least one MOSFET 128, having at least one source electrode 116, at least one drain electrode 118 and at least one gate electrode 120; at least one sensing electrode 132 configured to be in contact with the sample 112 and electrically connected to and / or integrated in the gate electrode 120 of the field effect transistor 114; at least one controller 146 configured to apply operating parameters to the field effect transistor 114 and configured to monitor at least one signal value at the field effect transistor 114; providing a system for receiving a signal from a user (indicated by reference numeral 168); ii. at least one parameter selection step (denoted by reference numeral 170) including selecting a set of operating parameters of the field effect transistor 114 for at least one subsequent measurement step, the parameter selection step including performing a plurality of evaluation measurements on the field effect transistor 114 using different candidate sets of operating parameters and selecting the set of operating parameters according to at least one optimization criterion monitored during the evaluation measurements; iii. at least one measuring step (indicated by reference numeral 172) including detecting the concentration of the analyte by applying the set of operating parameters selected in step ii to the field effect transistor 114 and determining at least one signal value at the field effect transistor 114; Includes.

[0124] The method steps may be performed in a given order. However, it should be noted that different orders may be possible. Furthermore, one or more of the method steps may be performed once or repeatedly. Furthermore, two or more method steps may be performed simultaneously or overlapping in time. The method may include additional method steps not listed.

[0125] The set of operating parameters selected in step ii is the gate potential V G and the drain-source current I of the field effect transistor 114 DS The sensor device 110 applies a gate potential V to the gate electrode 120 of the field effect transistor 114 via the sample 112 and the sensing electrode 132. G The sensor device 110 may be configured to apply a predetermined drain-source current I DS The drain-source voltage V required to achieve DS The controller 110 may be further configured to monitor the drain-source current I DS The drain-source voltage V required to achieve DS As mentioned above, the control device 110 may specifically include at least one galvanostat 150. Thus, the control device 110 may specifically include at least one feedback loop for controlling the drain-source current I DS The set of operating parameters selected in step ii may be configured to maintain a gate potential V of the field effect transistor 114 applied to the sample 112 when detecting the concentration of the analyte. G and the drain-source current I of the field effect transistor 114 applied to the field effect transistor 114 DS Step iii may include the step of: DS The drain-source voltage V required to achieve DSStep iii may include determining the drain-source voltage V DS The method may further include deriving a concentration of the analyte from the

[0126] The optimization criterion may relate to at least one measurable optimization criterion value. The optimization criterion value may be selected from the group consisting of a signal-to-noise ratio SNR, a signal strength, a signal noise, a signal drift. The operating parameter set in step ii may be selected by selecting an operating parameter of the evaluation measurement that results in one of a maximum optimization criterion value and a minimum optimization criterion value monitored during the evaluation measurement. The operating parameter set in step ii may be selected by selecting an operating parameter of the evaluation measurement that results in a maximum signal-to-noise ratio SNR.

[0127] Performing the evaluation measurements in step ii may include performing individual evaluation measurements in succession. Each evaluation measurement may include varying one operating parameter while holding a further operating parameter constant. At least one evaluation measurement may include varying the gate potential V of the field effect transistor 114. G Specifically, the drain-source current I DS The at least one evaluation measurement may include varying the drain-source current I of the field effect transistor 114 while keeping constant DS Specifically, the gate potential V G Step ii may include selecting a first operating parameter for step iii by performing at least one first evaluation measurement, the at least one first evaluation measurement including varying the first operating parameter while holding the further operating parameter constant. Step ii may further include holding the selected first operating parameter constant in at least one further evaluation measurement performed to select the at least one further operating parameter for step iii. In particular, the first operating parameter may be a gate potential V of the field effect transistor 114.G and further operating parameters may include the drain-source current I of the field effect transistor 114. DS may include:

[0128] Step ii may include performing an evaluation measurement under experimental conditions corresponding to step iii. Specifically, step ii may include performing the evaluation measurement by using at least one of the same sample 112 as step iii, the same control device 146 as step iii, the same sensing electrode 132 as step iii, and the same field effect transistor 114 as step iii. Thus, step ii may specifically include performing the evaluation measurement by using at least one of the same sample 112 as step iii and the same sensor device 110 as step iii. The method may be at least partially, and in particular at least one of steps ii and iii, performed by a computer. With respect to computer-implemented aspects of the invention, one or more of the method steps of the method according to one or more of the embodiments disclosed herein may be performed by using a computer or a computer network. Thus, in general, any of the method steps including providing and / or manipulating data may be performed by using a computer or a computer network. In general, these method steps may include any method steps, except for those method steps that typically require manual operations, such as providing a sample and / or certain aspects of performing the actual measurement.

[0129] As illustrated in more detail below with respect to FIGS. 3A-3C, step ii may further include performing at least one calibration to determine a relationship between the concentration of the analyte and the signal value of the field effect transistor 114. Step ii may further include performing at least one calibration to determine a relationship between the concentration of the analyte and the signal value of the field effect transistor 114. The calibration may include determining the sensitivity of the sensor device 110. The calibration may include using at least one calibrator, in particular a set including a plurality of different calibrators. Step ii may be performed again when changing the measurement range in step iii. At least one individual calibration may be performed for each individual measurement range. In other words, the method may include performing at least one calibration to determine a relationship between the concentration of the analyte and the signal value of the field effect transistor 114 for each measurement range.

[0130] 3A-3C show a flow chart of an exemplary embodiment of a calibration of the sensor device 110 to determine the concentration of at least one analyte in the sample 112. Figure 3A shows an exemplary factory calibration of the sensor device 110. The factory calibration may include the following factory calibration steps: a) Gate potential V G selecting b) Drain-source current I (denoted by reference numeral 176) DS selecting c) determining the sensitivity and the signal to noise ratio SNR (denoted by reference numeral 178); d) characterizing the field effect transistor 114 (denoted by reference numeral 180); and e) Saving factory field effect transistor settings (designated by reference numeral 182).

[0131] The factory calibration steps may be performed in a given order. However, it should be noted that a different order may be possible. Furthermore, one or more of the factory calibration steps may be performed only once or repeatedly. Furthermore, two or more factory calibration steps may be performed simultaneously or overlapping in time. The factory calibration may include additional steps not listed.

[0132] In particular, the factory calibration steps a) to c) may be performed iteratively. Thus, the selected gate potential V G and the selected drain-source current I DS After determining the sensitivity and the signal-to-noise ratio SNR based on G and the new drain-source current I DS Specifically, the optimization algorithm selects the gate potential V G and / or the drain-source current I DS , for example in ascending order at predetermined intervals, for example within the measurement range of the sensor device 110. G and / or the drain-source current I DS Different values ​​of the gate potential V G and / or the drain-source current I DS Additionally or alternatively, the gate potential V may be selected by using at least one predetermined step size for successively increasing or decreasing the value of V. G and / or the drain-source current I DS The optimization algorithm may, for example, select predetermined discrete values ​​of the gate potential V G and / or the drain-source current I DS The optimization algorithm may thus include, in particular, comparing the sensitivity and / or the signal-to-noise ratio SNR for different values ​​of V G and / or an optimized drain-source current IDS , specifically, a gate potential V that results in an optimized sensitivity and / or an optimized signal-to-noise ratio SNR, e.g., a maximum sensitivity and / or a maximum signal-to-noise ratio SNR. G and / or the drain-source current I DS In general, other options for the optimization algorithm may be feasible. Once the gate potential V has been optimized in the factory calibration steps a) to c), G and the optimized drain-source current I DS Once found, the field effect transistor 114, which may specifically be a MOSFET 128, may be characterized, for example, to determine at least one of the field effect mobility, the on-off ratio, and the threshold voltage. Finally, the results of the characterization of the field effect transistor 114 may be saved as the setting of the field effect transistor at the factory.

[0133] 3B illustrates an exemplary initial calibration of the sensor device 110 for three measurement ranges. In general, fewer or more measurement ranges may be feasible. The initial calibration may include the following initial calibration steps: a) Gate potential V G selecting b) Drain-source current I (denoted by reference numeral 186) DS selecting c) using a first calibrator (denoted by reference numeral 188); d) using a second calibrator (designated with reference numeral 190); e) determining the sensitivity and signal to noise ratio (denoted by reference numeral 192); and f) storing the optimized sensitivity and the optimized signal-to-noise ratio SNR (denoted by reference numeral 194).

[0134] The initial calibration steps may be performed in a given order. However, it should be noted that a different order may be possible. Furthermore, one or more of the initial calibration steps may be performed only once or repeatedly. Furthermore, two or more initial calibration steps may be performed simultaneously or overlapping in time. The initial calibration may include additional steps not listed.

[0135] Specifically, the initial calibration steps a) to e) may be performed iteratively. Thus, the gate potential V selected by using the first calibrator and the second calibrator may be G and the selected drain-source current I DS After determining the sensitivity and the signal-to-noise ratio SNR based on G and the new drain-source current I DS As already shown, the optimization algorithm specifically selects the gate potential V G and / or the drain-source current I DS , for example in ascending order at predetermined intervals, for example within the measurement range of the sensor device 110. G and / or the drain-source current I DS Different values ​​of the gate potential V G and / or the drain-source current I DS Additionally or alternatively, the gate potential V may be selected by using at least one predetermined step size for successively increasing or decreasing the value of V. G and / or the drain-source current I DS The gate potential V may be selected, for example, in sequence. G and / or the drain-source current I DS Different values ​​of may in particular be used in at least the first calibrator and / or the second calibrator. The optimization algorithm may in particular G and / or the drain-source current IDS The optimization algorithm may thus include, in particular, comparing the sensitivity and / or the signal-to-noise ratio SNR for different values ​​of V G and / or an optimized drain-source current I DS , specifically, a gate potential V that results in an optimized sensitivity and / or an optimized signal-to-noise ratio SNR, e.g., a maximum sensitivity and / or a maximum signal-to-noise ratio SNR. G and / or the drain-source current I DS In general, other options for the optimization algorithm may be feasible. Once the gate potential V has been optimized in the initial calibration steps a) to e), G and the optimized drain-source current I DS Once found, the optimized sensitivity and the optimized signal-to-noise ratio SNR may be saved.

[0136] An initial calibration may be performed for each measurement range separately. The first measurement range is indicated with reference numeral 196, the second measurement range with reference numeral 198, and the third measurement range with reference numeral 200. The initial calibration may be performed initially when the sensor device 110 is installed and operational in the field, e.g. in a test lab. Thereafter, further calibrations may be performed at regular or irregular time intervals, e.g. daily.

[0137] 3C shows an exemplary daily calibration of the sensor device 110 for three measurement ranges. By way of example, the daily calibration may be performed similarly to the initial calibration. However, in principle, modifications or adjustments may also be feasible. Thus, the daily calibration may include the following daily calibration steps: a) Gate potential V G selecting b) Drain-source current I (denoted by reference numeral 204) DS selecting c) using a first calibrator (denoted by reference numeral 206); d) using a second calibrator (denoted by reference numeral 208); e) determining the sensitivity and the signal-to-noise ratio (denoted by reference numeral 210); and f) storing the optimized sensitivity and the optimized signal-to-noise ratio SNR (denoted by reference numeral 212).

[0138] The daily calibration steps may be performed in a given order. However, it should be noted that a different order may be possible. Furthermore, one or more of the daily calibration steps may be performed only once or repeatedly. Furthermore, two or more daily calibration steps may be performed simultaneously or overlapping in time. The daily calibration may include additional steps not listed.

[0139] Specifically, the daily calibration steps a) to e) may be performed iteratively. Thus, the gate potential V selected by using the first calibrator and the second calibrator may be G and the selected drain-source current I DS After determining the sensitivity and the signal-to-noise ratio SNR based on G and the new drain-source current I DS As already shown, the optimization algorithm specifically selects the gate potential V G and / or the drain-source current I DS , for example in ascending order at predetermined intervals, for example within the measurement range of the sensor device 110. G and / or the drain-source current I DS Different values ​​of the gate potential V G and / or the drain-source current I DS Additionally or alternatively, the gate potential V may be selected by using at least one predetermined step size for successively increasing or decreasing the value of V. G and / or the drain-source current IDS The gate potential V may be selected, for example, in sequence. G and / or the drain-source current I DS Different values ​​of may in particular be used in at least the first calibrator and / or the second calibrator. The optimization algorithm may in particular G and / or the drain-source current I DS The optimization algorithm may thus include, in particular, comparing the sensitivity and / or the signal-to-noise ratio SNR for different values ​​of V G and / or an optimized drain-source current I DS , specifically, a gate potential V that results in an optimized sensitivity and / or an optimized signal-to-noise ratio SNR, e.g., a maximum sensitivity and / or a maximum signal-to-noise ratio SNR. G and / or the drain-source current I DS In general, other options for the optimization algorithm may be feasible. Once the gate potential V has been optimized in the routine calibration steps a) to e), G and the optimized drain-source current I DS Once found, the optimized sensitivity and the optimized signal-to-noise ratio SNR may be stored. As mentioned above, the daily calibration may be performed separately for each measurement range. As can be appreciated, at least one of the factory calibration, the initial calibration, and the daily calibration may be performed for a set of operating parameters, in particular a particular gate potential V G and the drain-source current I DS The method may include selecting:

[0140] 4A-4E show experimental results of an evaluation measurement of an exemplary embodiment of step ii of the method for determining the concentration of at least one analyte in a sample 112, together with the corresponding concentration detection of potassium. Thus, FIGS. 4A-4D illustrate the results of an exemplary evaluation measurement for selecting an operating parameter set. The evaluation measurement was performed by using an EGFET 130 with a MOSFET 128 by Microchip Technology Inc. and an extended gate electrode 134 as the sensing electrode 132. The Ag / AgCl contact electrode 158 was biased at a constant gate potential V g The electrical measurements were carried out using a multichannel control device 146 of the IVIUM n-stat type equipped with a galvanostat 150. A constant drain-source current I DS The drain-source voltage V required to maintain DS was monitored over time. The sample 112 was pumped through the sensor electrodes using a fluid pump 166, model Aladdin AL4000-220Z, World Precision Instruments, Germany.

[0141] For the experimental results shown in Fig. 4A and Fig. 4B, the gate potential V G is fixed at -600mV, and the drain-source current I DS The gate potential V was varied from 5 nA through 50 nA to 100 nA. Figure 4A shows the gate potential V V held constant for a time period of over 120 minutes. G and the respective drain-source current I DS The drain-source voltage V required to achieve DS 1, where the concentration of the analyte in sample 112 is varied after about 35 minutes, 75 minutes, and 115 minutes. G Drain-source current I of 5 nA at DS The drain-source voltage V required to achieve DS is shown at 214. A fixed gate potential V G Drain-source current I of 50 nA DSThe drain-source voltage V required to achieve DS is shown at 216. A fixed gate potential V G Drain-source current I of 100 nA DS The drain-source voltage V required to achieve DS is shown with reference numeral 218. Clearly different levels are visible in FIG. 4A as the concentration of the analyte in the sample 112 is changed. However, each level in FIG. 4A also shows a deviation corresponding to the signal-to-noise ratio SNR. FIG. 4B shows the respective drain-source current I DS The figure shows the logarithm of the signal-to-noise ratio (SNR) for a drain-source current of 50 nA, I DS It is shown that the highest signal-to-noise ratio SNR can be found at

[0142] For the experimental results shown in Fig. 4C and Fig. 4D, the drain-source current I DS is fixed at 50nA, and the gate potential V G As before, Fig. 4C shows the gate potential V G At a fixed drain-source current I DS The drain-source voltage V required to achieve DS The gate potential V of -501mV is shown. G Fixed drain-source current I of 50 nA at DS The drain-source voltage V required to achieve DS is shown with reference numeral 220. A gate potential V G Fixed drain-source current I of 50 nA at DS The drain-source voltage V required to achieve DS is shown with reference numeral 222. A gate potential V G Fixed drain-source current I of 50 nA at DS The drain-source voltage V required to achieve DS is shown with reference numeral 224. A gate potential V G Fixed drain-source current I of 50 nA atDS The drain-source voltage V required to achieve DS is shown with reference numeral 226. Again, clearly different levels are discernible for each concentration of the test substance. Potassium was used as the test substance. The experiment started with a concentration of 1 mM, which was first increased to 4 mM, then to 8 mM, and then finally back to 1 mM. Figure 4D shows the results at a gate potential V of -550 mV. G Thus, using the signal-to-noise ratio SNR as the optimization criterion, the exemplary evaluation measurements are performed with an overall drain-source current I of 50 nA as the operating parameter. DS and a gate potential V of -550 mV G This resulted in a choice of

[0143] FIG. 4E shows an example concentration measurement of potassium (K+) over 9 hours with the operating parameters selected as described above in the evaluation measurements. Thus, the gate potential V G and the source-drain current I DS is selected as the operating parameter, and the source-drain current I DS The source-drain voltage V required to achieve DS The drain-source current I of 50 nA was monitored. DS and a gate potential V of -550 mV G In FIG. 4E, the source-drain voltage V DS is shown at 232. The corresponding potassium concentration is shown at 234. [Explanation of symbols]

[0144] 110 Sensor device 112 Samples 114 Field-effect transistor 116 Source Electrode 118 Drain electrode 120 Gate electrode 122 Semiconductors 124 Dielectric 126 Channels 128 Metal Oxide Semiconductor Field Effect Transistor (MOSFET) 130 Extended Gate Field Effect Transistor (EGFET) 132 Sensing electrode 134 Extended gate electrode 136 Wire 138 Conductive Path 140 Functional ingredients 142 Receptor Compounds 144 Ionophore 146 Control Device 148 Source Measurement Units 150 Galvanostat 152 Grounding 154 Output 156 Analog Output 158 Contact electrode 160 Processing Units 162 Fluid Channels 164 Arrows showing fluid flow 166 Fluid Pump 168 Method Step i 170 Method Step II 172 Method Step III 174 Factory Calibration Step a) 176 Factory Calibration Step b) 178 Factory Calibration Step c) 180 Factory Calibration Steps d) 182 Factory Calibration Step e) 184 Initial calibration step a) 186 Initial calibration step b) 188 Initial calibration step c) 190 Initial calibration step d) 192 Initial calibration step e) 194 Initial calibration step f) 196 First Measurement Range 198 Second Measurement Range 200 3rd measurement range 202 Daily calibration step a) 204 Daily calibration step b) 206 Daily calibration step c) 208 Daily calibration step d) 210 Daily Calibration Step e) 212 Daily calibration step f) 214 -600mV V G I of 5nA at DS V required to achieve DS 216 -600mV V G I of 50 nA at DS V required to achieve DS 218 -600mV V G I of 100 nA at DS V required to achieve DS 220 -501mV V G I of 50 nA at DS V required to achieve DS 222 -520mV V G I of 50 nA at DS V required to achieve DS 224 -550mV V G I of 50 nA at DS V required to achieve DS 226 -600mV V G I of 50 nA at DS V required to achieve DS 232 V in the first exemplary embodiment of the components of the sensor device DS 234 Concentration of potassium in the first exemplary embodiment of the component of the sensor device

Claims

1. 1. A method for determining the concentration of at least one analyte in a sample (112), comprising: i. providing at least one sensor device (110), said sensor device (110) comprising: at least one field effect transistor (114) having at least one source electrode (116), at least one drain electrode (118), and at least one gate electrode (120); at least one sensing electrode (132) configured to be in contact with the sample (112) and electrically connected to the gate electrode (120) of the field effect transistor (114) and / or integrated in the gate electrode (120) of the field effect transistor (114); and at least one control device (146) configured to apply operating parameters to said field effect transistor (114) and to monitor at least one signal value at said field effect transistor (114); the providing comprising: ii. at least one parameter selection step including selecting an operating parameter set for the field effect transistor (114) for at least one subsequent measurement step, the parameter selection step including performing a plurality of evaluation measurements on the field effect transistor (114) using different candidate operating parameter sets and selecting the operating parameter set according to at least one optimization criterion monitored during the evaluation measurements; iii. at least one measuring step including detecting the concentration of the analyte by applying the set of operating parameters selected in step ii to the field effect transistor (114) and determining at least one signal value at the field effect transistor (114); Including, the method, wherein step ii comprises selecting a first operating parameter for step iii by performing at least one first evaluation measurement, the at least one first evaluation measurement comprising varying the first operating parameter while holding a further operating parameter constant; step ii further comprises holding the selected first operating parameter constant in at least one further evaluation measurement performed to select the at least one further operating parameter for step iii; step ii comprises performing the evaluation measurement under experimental conditions corresponding to step iii; and step ii comprises performing the evaluation measurement by using the same sample as the sample in step iii.

2. The first operating parameter is the gate potential V of the field effect transistor. Ｇ and the further operating parameter comprises a drain-source current I of the field effect transistor. ＤＳ The method of claim 1 , comprising:

3. The set of operating parameters selected in step ii is the gate potential V Ｇ and the drain-source current I of the field effect transistor (114) ＤＳ The method of claim 1 , comprising at least two operating parameters selected from the group consisting of:

4. The sensor device (110) applies a gate potential V to the gate electrode (120) of the field effect transistor (114) via the sample (112) and the sensing electrode (132). Ｇ configured to apply a predetermined drain-source current I ＤＳ The drain-source voltage V required to achieve ＤＳ and the control device (110) is further configured to monitor the drain-source current I ＤＳ The drain-source voltage V required to achieve ＤＳ The method of claim 1 , further comprising at least one feedback loop for controlling:

5. The set of operating parameters selected in step ii) is a gate potential V of the field effect transistor (114) applied to the sample (112) when detecting the concentration of the analyte. Ｇ and the drain-source current I of the field effect transistor (114) applied to the field effect transistor (114). ＤＳ and step iii includes determining, as the signal value, the drain-source current I ＤＳ The drain-source voltage V required to achieve ＤＳ determining the drain-source voltage V ＤＳ 10. The method of claim 1, further comprising deriving the concentration of the analyte from

6. 2. The method of claim 1, wherein the optimization criterion relates to at least one measurable optimization criterion value, the optimization criterion value being selected from the group consisting of a signal-to-noise ratio (SNR), a signal strength, a signal noise, and a signal drift.

7. 2. The method of claim 1, wherein performing the evaluation measurements in step ii comprises subsequently performing individual evaluation measurements, each evaluation measurement comprising varying one operating parameter while holding a further operating parameter constant.

8. At least one evaluation measurement is the gate potential V of the field effect transistor. Ｇ and at least one evaluation measurement is a drain-source current I of the field effect transistor. ＤＳ The method of claim 1 , comprising varying

9. The method of claim 1 , wherein step ii) is re-executed when the measurement range in step iii) is changed.

10. 2. The method of claim 1, wherein step ii further comprises performing at least one calibration to determine a relationship between the concentration of the test substance and the signal value of the field effect transistor (114), the calibration comprising determining a sensitivity of the sensor device (110).

11. 2. The method of claim 1, wherein the field effect transistor (114) is an extended gate field effect transistor (EGFET) (130) and the sensing electrode (132) is an extended gate electrode (134).

12. The sensing electrode (134) includes at least one functional component (140) on a surface thereof, the functional component (140) being configured to interact with the analyte, the functional component (140) comprising: at least one receptor compound (142) capable of binding to said at least one analyte, and - at least one ionophore (144) The method of claim 1 , comprising at least one of:

13. The method of claim 1 , wherein the sample (112) comprises a bodily fluid.

14. The method of claim 1 , wherein the method is at least partially computer-implemented.

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