DE102021210044A1 - Measurement system, specimen, electrode device and method for measuring a variety of analytes - Google Patents

Abstract

A sample body comprises a first plurality of wells arranged in the sample body and designed to receive an analyte sample, and a second plurality of sensor devices, wherein at least one sensor device assigned to the well is arranged in each well and is designed to measure the in the associated well arranged analyte samples to perform. The sample body also includes a circuit structure which is connected to the plurality of sensor devices and is designed to supply each of the plurality of sensor devices with an electrical potential in an electrically insulated manner from other sensor devices of the plurality of sensor devices.

Description

The present invention relates to a sample body, an electrode device that can be used together in a measuring system, as well as a corresponding measuring system and a method for measuring a large number of analytes. More particularly, the present invention relates to multi-pH measurement and apparatus for rapid pH measurement in multiple samples.

When measuring the pH value in small volumes and very large numbers of samples, a rapid measurement of the pH value is required in order to prevent the sample from drying out and to prevent the analyte samples from being altered, for example by CO ₂ from the environment. This problem occurs in particular with pH measurement in biochemical assays, which are often only available with small amounts of analyte (25 µl - 100 µl) on 96-well microtiter plates. 8th 1002a, 1002b and 1002c shows a photograph of various known commercial microtiter plates or well plates. The microtiter plate 1002a has, for example, 96 depressions or wells, the microtiter plate 1002b has 384 wells and the microtiter plate 1002c has 1536 wells.

1. 1. Kalibration der Einstabmesskette an zwei Punkten, beispielsweise pH 4 und pH 7
2. 2. Anfahren des Messortes beziehungsweise Wells
3. 3. Eintauchen in die Analytlösung
4. 4. Durchführung der Messung
5. 5. Reinigen/Spülen der Einstabmesskette
6. 6. Anfahren der Ausgangsposition/Kalibrationsstation

The analyte samples are currently being pipetted into the well plates. For this purpose, there are automatic pipetting robots that put a certain amount, e.g. B. Pipette 75 µl, analyte. The loaded corrugated sheet is then placed in the chamber. A pH glass electrode with an integrated Ag/AgCl/3M KCl reference electrode (combined electrode) is now used for pH measurement and the following work steps are repeated for each of the 96 samples:

1. 1. Calibration of the combination electrode at two points, for example pH 4 and pH 7
2. 2. Approaching the measurement location or well
3. 3. Immersion in the analyte solution
4. 4. Carrying out the measurement
5. 5. Cleaning/rinsing the combination electrode
6. 6. Approaching the starting position/calibration station

Points 1 and 5 can be modified depending on the nature and accuracy requirements. An example of a pH measuring robot from Hudson Robotics designed for such a measurement sequence is shown in 9 shown.

Disadvantages of the process described are that it takes a lot of time, which can lead to the analyte samples drying out and changing, a relatively large sample volume, since the electrode (pH and reference electrode) must be completely wetted, and the risk of glass breakage, since the pH electrode is off a very thin glass membrane with a thickness of around 50 µm and there is a risk of contamination/carryover through the pH electrode and reference electrode if the rinsing is insufficient.

Accordingly, it would be desirable to have test bodies, an electrode device, a measuring system and a method for measuring a large number of analyte samples that overcome the disadvantages mentioned and, in particular, enable the analyte samples to be measured quickly.

It is therefore an object of the present invention to create sample bodies, electrode devices, measuring systems and methods for measuring a large number of analytes which enable rapid evaluation of the analytes.

This object is solved by the subject matter of the independent patent claims.

A core idea of the present invention is that analyte samples can be measured quickly, for example in microtiter plates, by introducing a respective sensor device directly and individually into the corresponding well and contacting several wells or the analytes introduced there with a common reference electrode , which on the one hand enables an individual evaluation of the analyte samples and on the other hand a small number of movements of the reference electrode, since the reference electrode can remain stationary during a sequential measurement of the analytes in contact with it. This achieves a significant saving in time, which is advantageous.

According to one embodiment, a sample body comprises a first plurality of wells arranged in the sample body and designed to receive an analyte sample and a second plurality of sensor devices, wherein at least one sensor device assigned to the well is arranged in each well and is designed to measure the in to carry out the analytes arranged in the associated well. The sample body comprises a circuit structure which is connected to the plurality of sensor devices and is designed to supply each of the plurality of sensor devices with an electrical potential, electronically isolated from other sensor devices of the plurality of sensor devices.

According to one exemplary embodiment, the sensor devices are arranged in a respective bottom area of the depressions, which makes it possible for the sensor devices to take up little volume of the depression.

According to one embodiment, the sensor devices include ion-sensitive field effect transistors, ISFETs. These are particularly suitable for measurements on analyte samples, for example for pH measurement.

According to one embodiment, an edge area of the ISFETs and/or a carrier board of the ISFETs is covered with an electrical potting compound. This makes it possible to avoid contacting the covered areas with the analyte sample in order to obtain precise measurement results in that the analyte sample only contacts the inner contact surface of the ISFET, its sensitive area.

According to one embodiment, the sensor devices are sensitive to at least one of a pH value of the analyte sample, an electrical conductivity of the analyte sample, an electrical impedance of the analyte sample, an electrical capacitance of the analyte sample and a characteristic property of a biological cell arranged in the analyte sample. This enables the property of the analyte sample to be measured in each case, with different sensor devices of the sample body also being able to be formed with different sensitivity for different properties, which can make it possible to introduce identical analyte samples into different wells for different measurement by differently designed sensor devices and to carry out different measurements without greater expenditure of time to be carried out on the identical analyte samples, in particular if a same or identical reference electrode is used, whereby these advantages are also obtained independently.

According to one embodiment, the circuit structure is at least partially integrated in a substrate of the sample body, which makes it possible to protect the circuit structure from contact with cleaning agents or analyte samples.

According to one embodiment, the substrate is a solvent resistant and/or analyte resistant substrate, allowing the substrate to be cleaned and reused.

According to one exemplary embodiment, the circuit structure is designed in such a way that it has a contacting section that has a plurality of contacting areas that are set up for contacting with an electrical connector, each contacting area being uniquely assigned to a sensor device. This means that a sensor device can be contacted individually and electrically separately from another sensor device or from any other sensor device via the contacting areas, which enables independent measurements.

According to one exemplary embodiment, each sensor device is contacted via an electrical contact with a number of electrical contacts. For each sensor device, the contacting section has the number of electrical contacts uniquely assigned to the sensor device, so that each sensor device can be uniquely addressed, which avoids ambiguities.

According to one embodiment, the electrical connector is formed as a plug connector, which allows to contact the specimen with different connectors and vice versa different boards or specimens to a same connector. In addition, it is possible to separate the specimen from the measuring system, for example for cleaning or filling purposes.

According to one exemplary embodiment, areas of the circuit structure outside of the contacting section are protected against contact with a cleaning agent, and the contacting section is arranged in a lateral area of the sample body that is free of sensor devices. This means that, for example, in an immersion bath, the sensor devices or the depressions with the sensor devices are immersed in the immersion bath with the cleaning agent, but the lateral section with the contacting section remains outside the cleaning agent in order to protect contacts of the contacting section.

According to one exemplary embodiment, the sensor devices are fixed in the sample body by means of a casting compound, with the casting compound having an opening for the sensor device to come into contact with the analyte sample. This enables a robust configuration of the sample body and a reliable fixation of the sensor devices in the sample body.

According to one embodiment, the plurality of wells are arranged in a matrix pattern having a plurality of rows and a plurality of columns. This allows easy repositioning of reference electrodes in the wells by simply shifting the reference electrode laterally.

According to one exemplary embodiment, the plurality of wells is equipped with a measuring volume of 2 μl to 5000 μl set up for receiving the analyte samples.

According to one embodiment, an electrode device for a sample body has a device body with a cavity. As stated in non-limiting but illustrative manner 4 As shown, the cavity is for receiving an electrically conductive liquid in a cavity flow. Furthermore, an opening is provided in the device body, which is designed to connect a reference electrode to the cavity volume and to apply an electrical potential of the reference electrode to the electrically conductive liquid. The device body has a plurality of contacting areas connected to the cavity volume, each contacting area being configured to receive the electrically conductive liquid from the cavity on a first side, such as an inside, and on a second side, such as an outside, to contact with a measurement medium, for example the analyte sample. The plurality of bonding portions are spaced from each other on the device body. This makes it possible to apply the electrical potential of the electrode to the plurality of contacting regions of the device body, so that a reference potential can be applied to a plurality of depressions of a sample body, for example, at the same time.

According to one embodiment, each of the sensing areas includes at least one of a frit, a diaphragm, and a capillary contact and is configured to be saturated with the electrically conductive liquid, such as to direct the electrically conductive liquid to the outside or second side.

According to one exemplary embodiment, the measuring area is formed as a frit and in particular as a ceramic frit, which enables robust and yet precise manufacture.

According to one exemplary embodiment, the plurality of contacting areas is arranged in at least one row and at least one column. This enables the electrode device to be moved precisely and easily in order to contact further measurement volumes after the measurement has been completed.

According to one embodiment, the reference electrode is an electrode of the first type or an electrode of the second type.

According to one embodiment, the reference electrode is releasably attached by means of a positioning device and the reference electrode is exchangeable. This enables adaptation of the electrode device by changing the property of the electrode as well as reliable and long-term use of the electrode device by replacing the reference electrode, perhaps based on wear.

According to one embodiment, a measurement system includes a sample body described herein and an electrode device described herein. An arrangement of the contacting areas of the electrode device is adapted to an arrangement of the depressions of the sample body. The electrode device is designed to introduce a contact area into a third plurality of the first plurality of wells, and to simultaneously apply the electrical potential to analyte samples in the third plurality of wells. Together with the sample body, this enables independent measurements in the third plurality of wells without having to move the electrode device between the individual measurements, which enables the measurements to be performed quickly.

According to one exemplary embodiment, the measuring system is designed to sequentially activate the sensor devices of the third plurality of wells in order to prevent an analyte sample of a first well from influencing a measurement of a sensor device of a second well. This enables precise measurement results.

According to one embodiment, the measuring system is designed to introduce the plurality of contact areas into the third plurality of wells for measuring analyte samples located therein in a first measuring position of the electrode device, and to then move the electrode device into a second measuring position in which the contact areas in a fourth plurality of wells of the specimen are inserted, and to measure the analyte samples in the fourth plurality of wells. This means that the electrode device does not have to contact all the depressions of the sample body at the same time, but the third or fourth plurality of depressions that are contacted at the same time still saves a corresponding amount of time.

According to one exemplary embodiment, the contact areas of the electrode device are cleaned between the first measurement position and the movement into the second measurement position. This makes it possible to avoid contamination.

According to one exemplary embodiment, the measuring system is designed to apply a pressure to the electrically conductive liquid, that is to say a fluidic pressure. As a result, a portion of the electrically conductive liquid is pressed out of the cavity through the contact areas in order to carry out the cleaning of the contact areas. This enables simple cleaning of the contact areas, which is also reliable since any analyte sample that may have entered is pressed out of the contact area again.

According to one embodiment, the measurement system is designed to calibrate the electrode device and/or the sensor devices between the first measurement position and the second measurement position, which also leads to precise measurement results.

According to one embodiment, a cross-sectional area of the contact areas of the electrode device is adapted to a cross-sectional area of the depressions of the sample body and a distance between side walls of the contact areas and side walls of the depressions is configured such that it is at most 2000 μm, preferably at least 1 μm and at most 100 μm. In this way it can be avoided that an unnecessarily large amount of analyte sample escapes from the wells since the corresponding surface is covered by the contact areas. It becomes clear here that even in wells that are currently not being measured, it is nevertheless possible to prevent the analyte samples from escaping, for example through evaporation, even if no measurement is being carried out at the time.

According to an embodiment, the electrode device is a reference electrode for measurements in the third plurality of wells and a relative position between the sample body and the electrode device is variable.

According to one embodiment, a method for measuring a plurality of analyte samples, which are arranged in a corresponding plurality of wells of a sample body, comprises the following steps: contacting the plurality of analyte samples each with an associated sensor device and contacting the plurality of analyte samples simultaneously with a common one reference electrode. Furthermore, the method comprises measuring the analyte samples sequentially one after the other using the respectively assigned sensor device and the reference electrode.

Further advantageous embodiments are the subject of further dependent patent claims.

• 1 eine schematische perspektivische Ansicht eines Probenkörpers gemäß einem Ausführungsbeispiel;
• 2a eine schematische Draufsicht auf einen ISFET-Chip, der einen ISFET-Kanal aufweist und gemäß einem Ausführungsbeispiel in einer Sensoreinrichtung verwendet wird;
• 2b eine schematische Draufsicht auf eine Sensoreinrichtung gemäß einem Ausführungsbeispiel;
• 3 eine schematische Draufsicht auf einen Probenkörper gemäß einem Ausführungsbeispielbei dem Vertiefungen durch eine elektrisch isolierende Vergussmasse bereitgestellt werden;
• 4 eine schematische Seitenschnittansicht einer Referenzelektrodenvorrichtung gemäß einem Ausführungsbeispiel;
• 5 eine schematische Draufsicht auf ein Messsystem gemäß einem Ausführungsbeispiel;
• 6 eine schematische Seitenschnittansicht eines Teils des Messsystems aus 5;
• 7 ein schematisches Flussdiagramm eines Verfahrens gemäß einem Ausführungsbeispiel;
• 8 eine Ablichtung verschiedener bekannter kommerzieller Mikrotiterplatten oder Wellplatten; und
• 9 eine Abbildung eines für eine Messreihenfolge ausgelegten bekannten pH-Messroboters.

Particularly preferred embodiments of the present invention are explained below with reference to the accompanying drawings. show:

• 1 a schematic perspective view of a sample body according to an embodiment;
• 2a a schematic plan view of an ISFET chip having an ISFET channel and used according to an embodiment in a sensor device;
• 2 B a schematic plan view of a sensor device according to an embodiment;
• 3 a schematic plan view of a sample body according to an embodiment in which depressions are provided by an electrically insulating potting compound;
• 4 a schematic side sectional view of a reference electrode device according to an embodiment;
• 5 a schematic plan view of a measurement system according to an embodiment;
• 6 a schematic side sectional view of a part of the measuring system 5 ;
• 7 a schematic flowchart of a method according to an embodiment;
• 8th a photocopy of various known commercial microtiter plates or well plates; and
• 9 an illustration of a known pH measuring robot designed for a measuring sequence.

Before exemplary embodiments of the present invention are explained in more detail below with reference to the drawings, it is pointed out that identical elements, objects and/or structures that have the same function or have the same effect are provided with the same reference symbols in the different figures, so that the elements shown in different exemplary embodiments Description of these elements is interchangeable or can be applied to each other.

Exemplary embodiments described below are described in connection with a large number of details. However, example embodiments can also be implemented without these detailed features. Furthermore, for the sake of comprehensibility, exemplary embodiments are described using block diagrams as a substitute for a described in detail. Furthermore, details and/or features of individual exemplary embodiments can be combined with one another without further ado, as long as it is not explicitly described to the contrary.

1 shows a schematic perspective view of a sample body 10 according to an embodiment. The sample body 10 can provide a titer plate or microtiter plate that is modified compared to known titer plates. A plurality of depressions 12 ₁ to 12 _N are arranged in the sample body and are designed to receive an analyte sample. Volumes of the wells 12 ₁ to 12 _N can be separated from one another, so that analyte samples can be filled into the wells 12 ₁ to 12 _N independently of one another. Each of the wells 12 ₁ to 12 _N can have a measurement volume designed to receive the analyte sample. This comprises, for example, at least 2 μl and at most 5000 μl, preferably at least 20 μl and at most 80 μl and particularly preferably around 25 μl. The volume can be adjusted as a function of the sensor dimensions used, the measurement task and properties of the analyte samples, such as a viscosity of the same, a surface tension, a boiling point or a course of the reaction or the like.

In 1 1, the specimen 10 is shown in a sectional view to clearly show the nature of the indentations 12 ₁ to 12 _N .

The sample body 10 also includes sensor devices 14 ₁ , 14 ₂ and 14 ₃ which are arranged in the wells 12 ₁ to 12 _N in order to carry out a measurement of the analyte sample arranged in the associated well. In other words, an individual and dedicated sensor device 14 is arranged in each depression 12 provided for a measurement.

The sample body 10 comprises a circuit structure 16 which is connected to the plurality of sensor devices 14 and is designed to supply each of the plurality of sensor devices 14 with an electrical potential in an electrically insulated manner from other sensor devices of the plurality of sensor devices 14 . This means that electrical _potentials can be applied to sensor devices 14 ₁ , 14 ₂ , .

The arrangement or integration of sensor devices 14 in the respective depression 12 already makes it possible that the corresponding electrode for such a measurement does not have to be inserted into the depression 12 through an opening thereof, which can already save space. In addition, the circuit structure 16 means that the sensor devices 14 ₁ to 14 ₃ can be operated electrically isolated from one another, which means that the measurement is independent, which offers advantages both in the case of identically formed sensor devices 14 and in the case of sensor devices 14 of different sensitivity.

According to exemplary embodiments, each of the sensor devices 14 ₁ to 14 ₃ is for at least one of a pH value of the analyte samples, an electrical conductivity of the analyte, an electrical impedance of the analyte samples, an electrical capacitance of the analyte and a characteristic property of a biological cell arranged in the analyte samples sensitive. This means that, for example, with sensor devices 14 ₁ to 14 ₃ of the same design, different analyte samples can be examined and/or that an identical analyte sample can be evaluated with regard to different properties for sensor devices of different sensitivity.

A characterizing property of a biological cell assigned in the analyte samples can be understood, for example, as the fact that cells can be checked for their vitality by means of impedance spectroscopy. For example, dead cells lose their contents via the cell wall and thus their cell response to the impedance measurement. This characteristic property of the cell can be determined by appropriate measurements.

2a 1 shows a schematic plan view of an ISFET chip 20, which has an ISFET channel 18 and can be electrically contacted, for example via contacts 22 ₁ and 22 ₂ , for example bond contacts and/or bond wires. The ISFET chip can, for example, have a dimension of approximately 5 mm along an x-direction and 5 mm along a y-direction, although any other dimensions are also possible. The ISFET channel 18 can provide a sensitive surface of the ISFET chip 20, so that a potential change at the contacts 22 ₁ and/or 22 ₂ depending on a contact of a medium, such as an analyte sample, on the ISFET channel 18 indicates its presence or property can be evaluated.

In other words shows 2a a schematic representation of an ISFET chip with channel, bonding areas and bonding wires.

2 B shows a schematic plan view of a sensor device 25 according to an embodiment. This has, for example, the ISFET chip 20 off 2a on, wherein an edge area of the ISFET chip can be covered with an electrically insulating potting compound 24 . For example, the electrically insulating potting compound 24 may be solvent resistant to provide an additional function to electrically insulating passivation and to be robust to cleaning cycles or the like, which may allow for repeated use of the ISFET chip 20 .

The electrically insulating potting compound 24 can at the same time form or provide the depression 12 , so that the ISFET chip and consequently the sensor device are arranged in a bottom region of the depression 12 .

In other words shows 2 B an ISFET chip with passivation that forms a "well", i.e. the cavity into which the analyte can be dispensed.

3 shows a schematic plan view of a sample body 30 according to an exemplary embodiment, to which the explanations relating to the sample body 10 apply without further ado. The indentations 12 ₁ and 12 ₂ and possible further indentations can be provided by electrically insulating potting compound 24, wherein in a bottom region of the indentations 12 ₁ and 12 ₂ in connection with 2a described ISFET channel 18 can be arranged in order to implement the respective sensor element 14 ₁ to 14 ₃ of the sample body 10 .

In other words, the sensor devices 12 can, for example, be applied to a substrate during manufacture or integrated therein and then partially covered by the potting compound in order to protect certain areas of the sensor devices from media and/or to fix the sensor devices 12 in place. By applying the potting compound, the ISFET or the sensor device can at least partially form a bottom of the depression and to this extent can be arranged in a bottom region. However, this does not rule out other attachment locations, with regard to a reference electrode inserted from the opening of the depression, in particular, accommodating the sensor device as spaced apart from it as possible and thus arranged in the bottom area is advantageous

The sample body 30 can have a contacting section 26 which can form part of the circuit structure 16, for example. The contacting section 26 can have contacting areas 28 ₁ to 28 _M , which can be formed as contact pads, for example. Although electrical signals are used for evaluating and operating the sensor devices 14 and 18 in connection with the exemplary embodiments described herein, other signals, for example optical signals, are also possible as an alternative.

In the exemplary configuration of the sensor structure 14 as an ISFET channel 18, for example, two contacts 22 ₁ and 22 ₂ can be made 2a be sufficient to contact the sensor element. The corresponding line can be coupled to a respectively unambiguously assigned contact area 28, either directly or with the interposition of further circuit elements.

Each contact area 28 is thus uniquely assigned to a sensor device 14 or 18 . The contacting area 26 can be designed to enable contacting with an electrical or alternatively optical connector, preferably a plug connector. This connector can be mated with different specimens and alternatively the specimen 30 can be coupled with different connectors.

Although a large number of different configurations of sensor devices 14 are possible, so-called ion-sensitive field effect transistors, ISFETs, are preferred in the exemplary embodiments described herein.

The number of two electrical contacts 22 ₁ and 22 ₂ for the ISFET channel 18 ₁ is merely an example. Other configurations of the sensor structure, for example an EIS sensor (Electrolyte-Insulator-Semiconductor, electrolyte-insulator-semiconductor) can be operated with a single contact, for example, while other configurations of the sensor element 14, for example as an OFET (organic field-effect transistor, organic field effect transistor) can use three connections for source, drain and gate and/or four connections can be used for an impedance measurement or a 4-point measurement. The connections provided are routed to the contacting area 26 accordingly. Each of the electrical contacts can include a uniquely assigned contacting area 28 in the contacting section 26 . This enables a clear assignment of the contact areas 28 to the respective sensor element, which can be helpful for a later measuring system.

The number of indentations and/or sensor elements can, as specified in 3 is shown as an example, in one or more columns 32 ₁ , 32 ₂ and/or rows 34 . In the case of a single row or a single column, all of the at least two wells arranged in a one-line array. In contrast, a two-dimensional field or a matrix arrangement offers advantages, in particular with regard to handling. In such a two-dimensional array, the plurality of depressions and/or sensor devices can be arranged in a matrix pattern with a plurality of rows and a plurality of columns.

According to an embodiment and as in 3 shown, the contacting section 26 can be arranged in a lateral area 36 of a substrate 38 of the sample body 30 . The substrate 38 may comprise, for example, a glass substrate, a ceramic substrate, or a circuit board such as a sealed FR4 board. In particular, the substrate can be solvent-resistant and/or analyte-resistant. In particular, this means the properties of the substrate as a whole, for example with regard to FR4 circuit boards. Sometimes their individual layers may not be solvent-resistant, but they may be covered by a solvent-resistant substrate. This results in a solvent-resistant and/or analyte-resistant, ie media-resistant property for the substrate itself. The circuit structure may be at least partially integrated into the substrate 38 to also protect the circuit structure from solvents and/or analytes.

The lateral area 36 can be free of sensor devices along at least one direction x or y. The lateral area 36 can, for example, define an area that remains free of the cleaning bath or is not introduced into an immersion bath during an immersion bath for cleaning the depressions 12 and/or sensor devices from analyte samples or other substances. For example, areas of the circuit structure 16 outside of the lateral area 36 and/or outside of the contacting section 26 can be protected against contact with the cleaning agent by suitable measures. Such measures include, for example, covering the circuit structure 16 with materials that are resistant to the cleaning material, for example lacquers or the like, and/or embedding the circuit structure 16 in the substrate 38 Embodiments exposed the contacting areas 28, which is why the arrangement of the contacting areas 28 in the lateral area 36 offers advantages.

The sensor devices, ie the ISFET chips or their ISFET channels, can be fixed in the sample body 30 by means of the potting compound 24, the potting compound having or providing an opening for contact of the sensor device with the analyte.

In other words shows 3 a schematic representation of the arrangement of the ISFETs on a circuit board in the microtiter grid. The circuit board with connections is designed in such a way that it can be completely immersed in a cleaning tank, possibly with the exception of the contact strip, the contacting section 26 . A circuit board section with a contact strip and two encapsulated ISFETs are shown as an example, arranged in a well-plate grid as an example.

The inventive solution idea for the sample bodies is based, among other things, on the use of pH-sensitive ISFETs, which are used as the bottom of the respective wells. The required contacts are electrically connected, e.g. by wire bonding, to an underlying solvent-resistant board, e.g. ceramic or sealed FR4 boards. The contacts for the electrical contacting of all ISFETs are grouped together at the edge of the circuit board, so that they can be easily electrically connected, for example via a connector. The ISFETS are then encapsulated in such a way that a depression is formed in such a way that the analyte samples can be dispensed into. The casting compound must be tailored to the solvent and analyte samples as well as the entire measurement task, for example with regard to resistances or durability.

4 12 shows a schematic side sectional view of an electrode device 40 according to an embodiment. The electrode device 40 can, for example, be adapted for a test body, such as the test body 10 and/or 30, although this is not absolutely necessary.

The electrode device 40 comprises a device body 42 with a cavity 44 which can also be referred to as the inner volume of the device body 42 . The cavity 44 is set up to receive an electrically conductive liquid 46 . A 3-molar potassium chloride solution (3M KCl) solution can be used, for example, as the electrically conductive liquid, although other solutions are also possible.

An electrode 52 can be brought into communication with the cavity volume 44 through an opening 48 of the device body 42, such as by directly adjoining, partially inserting or fully inserting the electrode 52 into the cavity volume 44 so that electrical contact between the electrically conductive liquid bility 46 and the electrode 52 is obtained. The electrode 52 is, for example, a 3M silver chloride coated wire (3M AgCl coated Ag wire).

The device body includes a plurality of 2 or more bonding areas 54 ₁ to 54 ₄ which may be arranged as a one-dimensional array or as a two-dimensional array. In the schematic side sectional view of the 4 Four contacting areas 54 ₁ to 54 ₄ are arranged, which does not exclude additional columns or rows that are covered in the depth direction. A different number of contacting areas 54 in a row, ie 1 or more, is also readily possible.

The contacting areas 54 are connected to the cavity volume 44 and are designed to receive the electrically conductive liquid 46 on a first side 54A, for example an inside of the volume body, from the cavity 54 and on a second side 54B, for example an outside, to a measuring medium to contact. This means that although the contact areas create a certain degree of tightness, they are at least permeable for an exchange of ions between the sides 54A and 54B. The contact areas 54 ₁ to 54 ₄ can comprise, for example, a frit, in particular a ceramic frit, a diaphragm and/or a capillary contact and can be designed to be saturated with the electrically conductive liquid 46 .

The contacting areas 54 are arranged at a distance from one another on the device body 42, which enables, for example, simultaneous contacting of a plurality of depressions 12 with the electrically conductive liquid 46 or the potential present thereon. A distance between the contact areas 54 can be adapted to a distance between the depressions 12, for example.

An electrical potential applied to the electrode 52 at an electrode connection 56 can thus be applied simultaneously to the contact regions 54 by means of the electrically conductive liquid 46 . At the same time, the use of the electrically conductive liquid enables a simple replacement of the liquid compared to the use of viscous or solid materials, which can nevertheless be used within the scope of exemplary embodiments. For example, by removing the electrode 52 through the opening 48, the electrically conductive liquid 46 can also be removed or renewed.

The electrode device 40 can optionally be designed to exert a pressure P on the electrically conductive liquid 46 . For this purpose, for example, an additional opening can be provided in the device body 42 through which the pressure can be applied. Alternatively, the device body 42 or a part thereof can also be deformed, for example in order to reduce the volume of the cavity 44 . The pressure P may cause the electrically conductive liquid 46 to be forced through the permeable contact areas 54 such that a portion of the electrically conductive liquid from the cavity 44 is forced through the contact areas 54 to perform cleaning of the contact areas 54, such as thereafter the contact areas 54 were in contact with an analyte sample.

The electrode 52 can also be part of the electrode device. The electrode 52 can be an electrode of the first type, ie an electrode whose electrical potential depends directly on the concentration of the electrolyte solution surrounding it. Alternatively, the electrode can also be an electrode of the second type, that is, an electrode whose electrical potential depends only indirectly on the concentration of the electrolyte solution surrounding it. The electrode can be detachably fastened by means of a positioning device (not shown), for example by means of a ground joint or a seal in the device body, which is made of a glass body, for example. The detachability allows the electrode 52 to be replaceable, that is, it can be taken out of the device body 42 and replaced with another electrode without causing damage. This enables the electrode device to be used for a long time.

According to one exemplary embodiment, the electrode device can be designed in such a way that the device body 42 has a local depression 58 in the cavity volume 44 , which is designed to receive electrode slime from the electrode 52 . For this purpose, the local indentation 58 is arranged in a region of the electrode 52 and is arranged below the electrode 52 in relation to an orientation of the electrode device during normal operation of the same, it being possible for the local indentation 58 to be larger than the electrode 52 itself. On the electrode 52 resulting and detaching electrode sludge 62, such as AgCl sludge, can thus be absorbed in the local depression 58, which serves as a collection volume for the electrode sludge 62, which reduces or prevents the electrode sludge 62 from being distributed in the further volume 44, which measurement accuracy is beneficial.

In other words shows 4 a multiple reference electrode in a schematic representation position, whereby the number and size of the ceramic frits can vary depending on the application. Four connection options for analytes are shown in the example.

5 shows a schematic plan view of a measurement system 50 according to an embodiment. The measuring system 50 comprises, for example, the sample body 30, with the sample body 10 also being able to be provided as an alternative or in addition. The sample body 30 is designed, for example, in such a way that it has the depressions 12 ₁ to 12 _N arranged in four rows 31 ₁ to 34 ₄ and in eight columns 32 ₁ to 32 ₈ .

Measuring system 50 also includes an electrode device, such as electrode device 40. This has eight contact areas 54 ₁ to 54 ₈ , for example, arranged in two columns and four rows, for example, with any other arrangement having at least one row and/or at least one column is possible with the exception of a 1x1 arrangement. The arrangement of the contact areas 54 is adapted to an arrangement of the depressions 12 of the sample body, in particular with regard to the dimensions, diameters, depths and distances.

The electrode device 40 can serve as a reference electrode for measurements in the respective set of depressions, ie for the sensor devices. A relative position between the sample body and the electrode device can be variable.

The electrode device 40 is designed, for example, to introduce a contact area 54 into a subset or into all of the depressions 12 in order to simultaneously apply the electrical potential present at the electrode 52 to analyte samples in the quantity of depressions thus applied. The measuring system 50 also has a connector 64, for example a plug connector, in order to apply electrical potentials to the contacting areas 28 ₁ to 28 _M or to tap them off. In this way, the measurement system 50 can sequentially control the sensor devices to which the potential of the electrode 52 is applied, in order to measure the analyte samples located therein. It is thus possible to prevent the analyte samples in a first well, for example well 12 ₂ , from influencing a measurement of a sensor device in another well, for example well 12 ₃ . For example, the potential of the electrode 52 can serve as a reference electrode, so that the electrode device 40 provides a multiple reference electrode. Individual measurements can thus be carried out by sequential measurement of the analyte samples in the analyte samples to which the reference potential has been applied, which is possible without any problems due to the circuit structure. Once all desired or all applied indentations that can be reached via the current position of the electrode structure 40 have been measured, the electrode device 40 can be brought into a different position, for example by lateral displacement along the positive or negative x-direction. With a larger array of depressions 12, for example with a larger number of rows 34 and/or with a smaller number of contacting regions of the electrode structure 40, a movement along the y-direction can also be provided as an alternative or in addition.

In this way, for example, in the measurement position shown, a measurement of the indentations reached or the analyte samples located therein can be carried out and in a second measurement position obtained afterwards, the same contact areas 54 can be inserted into other indentations in order to measure a changed plurality of indentations or analyte samples located therein. Between the different positions, the contact areas of the electrode device 40 can be cleaned by the measuring system, for example by inserting them into a cleaning basin, by applying cleaning agents from the outside and/or by applying the in 4 illustrated pressure P to the electrically conductive liquid 46 in order to push a subset of the electrically conductive liquid 46 out of the cavity 44 through the contact areas 54 in order to carry out the cleaning of the contact areas.

Alternatively or additionally, the electrode device and/or the sensor devices can be calibrated by the measuring system 50 between the different measuring positions.

6 shows a schematic sectional side view of part of the measurement system 50. For this purpose, a contact area 54 is introduced into a depression 12 of the sample body, so that the contact area 54 contacts the analyte sample 66 introduced into the depression 12. The analyte sample 66 also contacts the sensor element, for example the ISFET sensor 20. A dimension 68 of the recess 12, for example a diameter or an edge length along the x-direction, and a dimension 72 of the contact area 54 are matched to one another. Thus, dimension 72 is preferably geometrically similar to dimension 68, for example also a diameter or the like. The dimension 72 is smaller than the dimension 68, for example also a diameter or the like. The dimension 72 is smaller than the dimension 68 in order to enable the contact area 54 to be inserted into the depression 12 . This can result in a distance between the side walls of the contact areas 54 and the side walls of the depressions 12 . Such a distance 74 is, for example, at most 2000 μm and preferably at least 1 μm and at most 100 μm. The contact area 54 thus covers the analyte 66 which prevents the analyte sample 66 from evaporating or evaporating or escaping from the well 12 . This beneficial effect occurs both during the measurement and during a period of time outside of the measurement being made, but while the contact area 54 is inserted into the well 12, for example to measure another well. This makes it clear that multiple application of the electrode device to a plurality of depressions at the same time also has a positive effect on the escape of the electrolyte, since each depression is at least temporarily covered during the overall measurement of all depressions.

7 shows a schematic flow chart of a method 700 according to an embodiment. The method 700 can be used to measure or measure a large number of analyte samples which are arranged in a corresponding plurality of wells of a sample body, for example in the sample body 10 or 30. An electrode device according to the exemplary embodiments described herein can be used for this purpose.

In a step 710, the multiplicity of analytes are each contacted with an assigned sensor device. A step 720 includes contacting the plurality of analytes simultaneously with a common reference electrode.

A step 730 comprises measuring the analyte samples sequentially one after the other using the respective associated sensor device and the reference electrode.

The embodiments described herein allow for rapid measurements of analyte samples. For the measurements, as is known, the analyte sample is dispensed into the wells. Compared to known concepts, smaller volumes, for example 25 μl, are sufficient for this, since the active layer, the sensor device, is located on the bottom of the well, so that no corresponding electrode has to be included in the volume, as in known measuring methods.

Then a reference electrode, such as in 4 , showing a multiple reference electrode. This reference electrode is equipped with an AgCl-coated Ag wire or comparable and is filled with a 3 molar (3M) KCl solution, for example. There is also an inlet/outlet for the exchange of KCI solution, which may be via port 48 or other port. Furthermore, there is, for example, below the Ag/AgCl wire a collecting basin 58 for any electrode sludge, as is to be expected after prolonged use. A number N of analyte samples with ISFETs, which are electrically separated from one another, can now be electrically connected via a number N of contact areas, for example ceramic frits. Now the ISFETs can be used one after the other with the reference potential of the reference electrode for pH measurement. After the N measurements have been taken, the reference electrode may be rinsed, possibly assisted by applying pressure to the KCl solution, to flush any residual analyte sample that may have entered the frit. Depending on requirements, a calibration step can follow to recalibrate the cleaned electrode. After that, the reference electrode is ready for contacting the next N analyte samples.

Since the ceramic frits are aligned with their opening downwards, very small amounts of analyte sample, e.g. 50 µl, can be used, as shown in the cross-section in 6 shown. This shows a cross-section of the measurement setup using an ISFET and a ceramic frit as an example. Due to the simultaneous contacting of N analyte samples, approaching the measuring position, rinsing and, if necessary, calibration are eliminated N-1 times. This also reduces the risk of electrode and analyte sample contamination.

After the measurement has been carried out, the microtiter plate can be easily cleaned with conventional cleaning procedures, calibrated if necessary and reused. The same applies to the multiple reference electrode.

• • Deutlich schnellere Messungen durch einen Wegfall von vielen Positionier-, Kalibrier- und Reinigungsschritten der Referenzelektrode, sowie eine schnellere Messung durch die Verwendung von ISFETs anstelle von Glaselektroden;
• • ein Gewinn an Zuverlässigkeit, da weniger Kontaminationen zu erwarten sind und Glasbruch der Glaselektrodenmembranen bei Verwendung entsprechender Referenzelektroden nicht mehr auftreten kann; und
• • geringere Analytprobenmengen durch verbesserte Messgeometrie.

Exemplary embodiments provide several advantages over known concepts, including:

• • Significantly faster measurements by eliminating many positioning, calibration and cleaning steps of the reference electrode, as well as faster measurement by using ISFETs instead of glass electrodes;
• • a gain in reliability, since less contamination is to be expected and glass electrode membranes can no longer break when using corresponding reference electrodes; and
• • Lower amounts of analyte sample due to improved measurement geometry.

1. 1. Probenkörper, Elektrodenvorrichtung, Messystem und/oder Verfahren zur pH-Messung in L Analytproben mittels M ISFETs, angeordnet auf einem Träger und dort kontaktiert, sowie einer N-fach Referenzelektrode. M, N sind ganze Zahlen. Die N-fach Referenzelektrode kann zum Träger der ISFETs ausgerichtet und positioniert werden. Hierbei kann die Referenzelektrode oder aber der Träger mit den ISFETs, z.B. mit einem x-y-Tisch bewegt werden. Anschließend wird entweder die N-fach Referenzelektrode in die mit Analyt beladenen ISFETs so eingetaucht, dass die Analytprobe sowohl die ISFET-Sensorfläche als auch die Referenzelektrodenkontaktfläche (Fritte) benetzen. Jetzt werden nacheinander die pH-Werte der L Analytproben bzw. M ISFETs mit der N-fach Referenzelektrode gemessen. Nachdem jede Kontaktfläche der N-fach Referenzelektrode, die zur Messung vorgesehen war, verwendet wurde, kann sich ein Reinigungs- und/oder Kalibrierschritt anschließen. Dieser Vorgang kann sich beliebig wiederholen, z.B. solange bis alle M ISFETs die Messung abgeschlossen haben.
2. 2. Probenkörper, Elektrodenvorrichtung, Messystem und/oder Verfahren zur nach Aspekt 1 mit ISFETs angeordnet auf dem Träger in einem Raster, wie in Std.- Multititerplatten.
3. 3. Probenkörper, Elektrodenvorrichtung, Messystem und/oder Verfahren zur nach Aspekt 1 oder 2 mit Positioniermarken und/oder Vorrichtungen zur Positionierung und Positionserkennung von Referenzelektroden zur Analytprobenposition.
4. 4. Probenkörper, Elektrodenvorrichtung, Messystem und/oder Verfahren zur nach einem der Aspekte 1 bis 3 mit N-Fach Referenzelektrode, wobei die N sich am Raster der ISFETs orientiert.
5. 5. Probenkörper, Elektrodenvorrichtung, Messystem und/oder Verfahren zur nach einem der Aspekte 1 bis 4 mit ISFETs, deren Chip-Rand und Kontakte mit einer Vergussmasse passiviert sind.
6. 6. Probenkörper, Elektrodenvorrichtung, Messystem und/oder Verfahren zur nach Aspekt 4 oder 5mit einer Vergussmasse, die eine Kavität bildet und den ISFET Sensor-Kanal so einfasst, dass er vom Analyt sicher benetzbar ist
7. 7. Probenkörper, Elektrodenvorrichtung, Messystem und/oder Verfahren zur nach einem der Aspekte 1 bis 6, welches andere Parameter als den pH Wert misst, wie beispielsweise Leitfähigkeit, Impedanz, Kapazität, biologische Zellcharakterisierung (Vitalität), etc.
8. 8. Probenkörper, Elektrodenvorrichtung, Messystem und/oder Verfahren zur nach einem der Aspekte 1 bis 7, bei dem die Referenzelektrode auf eine Silber/Silberchlorid oder Kalomel-Referenzelektrode zurückzuführen ist. (Elektroden 2. Art), Elektroden 1. Art (NHE wäre auch möglich)
9. 9. Probenkörper, Elektrodenvorrichtung, Messystem und/oder Verfahren zur nach einem der Aspekte 1 bis 8, bei dem der Chlorid beschichtete Silberdraht wechselbar ist, z.B. über einen Schliff oder eine Dichtung in dem Glaskörper.
10. 10. Probenkörper, Elektrodenvorrichtung, Messystem und/oder Verfahren zur nach einem der Aspekte 1 bis 9, bei dem die elektrische Anbindung des chlorierten Silberdrahtes über eine Kaliumchloridlösung, 0,1 Mol/L bis ges. Lösung, vorzugsweise 3 Mol/L und einer semipermeablen Vorrichtung (z.B. Diaphragma, Keramikfritte...). Die Porengröße kann in Abhängigkeit der Messaufgabe angepasst werden.
11. 11. Probenkörper, Elektrodenvorrichtung, Messystem und/oder Verfahren zur nach einem der Aspekte 1 bis 10, bei der die Verdunstung der Analytprobenlösung durch die Referenzelektrode minimiert wird.
12. 12. Probenkörper, Elektrodenvorrichtung, Messystem und/oder Verfahren zur nach einem der Aspekte 1 bis 12, bei dem im Spülvorgang ein Überdruck an die Referenzelektrode angelegt wird, um eventuell eingedrungene Analytprobenreste aus der Fritte herauszudrücken und abzuspülen.

Aspects of the present invention further relate to:

1. 1. Sample body, electrode device, measuring system and/or method for pH measurement in L analyte samples using M ISFETs, arranged on a carrier and contacted there, and an N-fold reference electrode. M, N are integers. The N-fold reference electrode can be aligned and positioned to the carrier of the ISFETs. Here, the reference electrode or the carrier with the ISFETs can be moved, for example with an xy table. Then either the N-fold reference electrode is immersed in the ISFETs loaded with analyte in such a way that the analyte sample wets both the ISFET sensor surface and the reference electrode contact surface (frit). The pH values of the L analyte samples or M ISFETs are now measured one after the other with the N-fold reference electrode. After each contact surface of the N-fold reference electrode that was provided for the measurement has been used, a cleaning and/or calibration step can follow. This process can be repeated as desired, for example until all M ISFETs have completed the measurement.
2. 2. Sample body, electrode device, measuring system and/or method according to aspect 1 with ISFETs arranged on the carrier in a grid, as in standard multititer plates.
3. 3. Sample body, electrode device, measuring system and/or method according to aspect 1 or 2 with positioning marks and/or devices for positioning and position detection of reference electrodes for the analyte sample position.
4. 4. Sample body, electrode device, measuring system and/or method according to one of aspects 1 to 3 with N-fold reference electrode, the N being based on the grid of the ISFETs.
5. 5. Sample body, electrode device, measuring system and/or method according to one of aspects 1 to 4 with ISFETs whose chip edge and contacts are passivated with a casting compound.
6. 6. Sample body, electrode device, measuring system and/or method according to aspect 4 or 5 with a casting compound that forms a cavity and encloses the ISFET sensor channel in such a way that it can be reliably wetted by the analyte
7. 7. Sample body, electrode device, measuring system and/or method according to one of aspects 1 to 6, which measures parameters other than the pH value, such as conductivity, impedance, capacity, biological cell characterization (vitality), etc.
8. 8. Sample body, electrode device, measuring system and/or method according to one of aspects 1 to 7, in which the reference electrode can be traced back to a silver/silver chloride or calomel reference electrode. (electrodes of the 2nd type), electrodes of the 1st type (NHE would also be possible)
9. 9. Sample body, electrode device, measuring system and/or method according to one of aspects 1 to 8, in which the chloride-coated silver wire can be changed, eg via a joint or a seal in the glass body.
10. 10. Test body, electrode device, measuring system and/or method according to one of aspects 1 to 9, in which the electrical connection of the chlorinated silver wire is via a potassium chloride solution, 0.1 mol/L to sat. Solution, preferably 3 mol/L and a semi-permeable device (e.g. diaphragm, ceramic frit...). The pore size can be adjusted depending on the measurement task.
11. 11. Sample body, electrode device, measuring system and/or method according to one of aspects 1 to 10, in which the evaporation of the analyte sample solution through the reference electrode is minimized.
12. 12. Sample body, electrode device, measuring system and/or method according to one of aspects 1 to 12, in which overpressure is applied to the reference electrode during the rinsing process in order to press out any analyte sample residues that have penetrated the frit and rinse them off.

Although some aspects have been described in the context of a device, it is understood that these aspects also represent a description of the corresponding method, so that a block or a component of a device is also to be understood as a corresponding method step or as a feature of a method step. Similarly, aspects described in connection with or as a method step also constitute a description of a corresponding block or detail or feature of a corresponding device.

In some embodiments, a programmable logic device (e.g., a field programmable gate array, an FPGA) may be used to perform some or all of the functionality of the methods described herein. In some embodiments, a field programmable gate array may cooperate with a microprocessor to perform any of the methods described herein. In general, the procedures in some execution tion examples performed by any hardware device. This can be hardware that can be used universally, such as a computer processor (CPU), or hardware that is specific to the method, such as an ASIC.

The embodiments described above are merely illustrative of the principles of the present invention. It is understood that modifications and variations to the arrangements and details described herein will occur to those skilled in the art. Therefore, it is intended that the invention be limited only by the scope of the following claims and not by the specific details presented in the description and explanation of the embodiments herein.

Claims (30)

A specimen with: a first plurality of wells (12) disposed in the specimen (10; 30) and adapted to receive an analyte (66); a second plurality of sensor devices (14; 18), with at least one sensor device (14; 18) associated with the depression (12) being arranged in each depression (12) and being designed to measure the in the associated depression (12) to perform arrayed analyte samples (66); and a circuit structure (16) which is connected to the plurality of sensor devices (14; 18) and is designed to electrically insulate each of the plurality of sensor devices (14; 18) from further sensor devices (14; 18) of the plurality of sensor devices ( 14; 18) with an electrical potential. Specimen (10; 30) according to claim 1 , In which the sensor devices (14; 18) are arranged in a respective bottom region of the depressions (12). Specimen (10; 30) according to claim 1 or 2 , In which the sensor devices (14; 18) comprise ion-sensitive field effect transistors, ISFETs. Specimen (10; 30) according to claim 3 , in which an edge area of the ISFETs and/or a carrier board of the ISFETs are covered with an electrically insulating potting compound (24). Sample body (10; 30) according to any one of the preceding claims, wherein the sensor devices (14; 18) sensitive to at least one of a • pH of analyte samples (66); • an electrical conductivity of the analyte samples (66); • an electrical impedance of the analyte samples (66); • an electrical capacitance of the analyte samples (66); a characterizing property of a biological cell located in the analyte samples (66). Sample body (10; 30) according to one of the preceding claims, in which the circuit structure (16) is at least partially integrated into a substrate (38) of the sample body (10; 30). Specimen (10; 30) according to claim 6 wherein the substrate (38) is a solvent resistant and/or analyte sample resistant substrate (38). Specimen (10; 30) according to one of the preceding claims, in which the circuit structure (16) has a contacting section (26) which has a plurality of contacting areas (28) which are set up for contacting an electrical connector (64); each contact area (28) being uniquely assigned to a sensor device (14; 18). Specimen (10; 30) according to claim 8 , in which each sensor device (14; 18) is contacted via an electrical contact with a number of electrical contacts and the contacting section (26) for each sensor device (14; 18) has the number of electrical contacts and clearly assigned contacting areas (28). Specimen (10; 30) according to claim 8 or 9 wherein the electrical connector (64) is formed as a plug connector. Specimen (30) according to one of Claims 8 until 10 in which areas of the circuit structure (16) outside of the contacting section (28) are protected from contact with a cleaning agent; and the contacting section (28) is arranged in a lateral area (36) of the sample body (30) which is free of sensor devices (14; 18). Sample body (30) according to one of the preceding claims, in which the sensor devices (14; 18) are fixed in the sample body (30) by means of a casting compound (24), the casting compound (24) having an opening for contact of the sensor device (14; 18 ) with the analyte (66). A specimen (10; 30) according to any one of the preceding claims, wherein the plurality of wells (12) are arranged in a matrix pattern having a plurality of rows (34) and a plurality of columns (34). Sample body (10; 30) according to one of the preceding claims, in which the plurality of wells (12) has a measurement volume of 2 to 5000 µl, preferably 20 to 80 µl, adapted to receive the analyte (66). Electrode device (40) for a specimen (10; 30) with: a device body (42) having a cavity (44) configured to receive an electrically conductive liquid (46) in a cavity volume; and an aperture in the device body (42) configured to connect a reference electrode (52) to the cavity volume for applying an electrical potential of the reference electrode (52) to the electrically conductive liquid (46); the device body (42) having a plurality of contacting areas (54) connected to the cavity volume; each contacting area being designed to receive the electrically conductive liquid (46) on a first side (54A) of the cavity (44) and to contact a measuring medium on a second side (54B); and wherein the plurality of bonding areas (54) are spaced apart from each other on the device body (42). Electrode device according to claim 15 wherein each measurement region (54) comprises a frit, diaphragm, capillary contact adapted to be saturated with the electrically conductive liquid (46). Electrode device according to Claim 16 , wherein at least one frit is a ceramic frit. Electrode device according to one of Claims 15 until 17 , In which the plurality of contacting areas (54) are arranged in at least one row and at least one column. Electrode device according to one of Claims 15 until 18 , in which the reference electrode (52) is an electrode of the first type or an electrode of the second type. Electrode device according to one of Claims 15 until 19 , in which the reference electrode (52) is detachably fixed by means of a positioning device; and the electrode (52) is replaceable. Electrode device according to one of Claims 15 until 20 wherein the device body (42) has a local depression (58) in the cavity volume, which is designed to receive electrode slime (62) of the reference electrode (52). Measuring system (50) with: a specimen (10; 30) according to one of Claims 1 until 14 ; and an electrode device (40) according to any one of Claims 15 until 21 ; wherein an arrangement of the contacting areas (54) is adapted to an arrangement of the depressions (12); and the electrode device (40) is designed to introduce a respective contact region (54) into a third plurality of the first plurality of depressions (12); and to simultaneously apply the electrical potential to analyte samples (66) in the third plurality of wells (12). measurement system according to Claim 22 , which is designed to activate the sensor devices (14; 18) of the third plurality of wells (12) sequentially one after the other in order to prevent an analyte sample (66) of a first well (12 ₁ ) from influencing a measurement of a sensor device of a second well (12 ₂ ) to prevent. measurement system according to Claim 22 or 23 which is designed to introduce the plurality of contact areas (54) into the third plurality of wells (12) for measuring the analytes (66) located therein in a first measuring position of the electrode device (40); and thereafter to move the electrode device (40) into a second measuring position in which the contact areas (54) are inserted into a fourth plurality of depressions (12) of the sample body (10; 30); and to measure the analyte samples (66) in the fourth plurality of wells (12). measurement system according to Claim 24 , which is designed to carry out a cleaning of the contact areas of the electrode device (40) between the first measuring position and the movement into the second measuring position. measurement system according to Claim 25 , which is designed to apply a pressure (P) to the electrically conductive liquid (46) in order to push a subset of the electrically conductive liquid (46) out of the cavity (44) through the contact areas (54) in order to clean the Run contact areas (54). Measuring system according to one of claims 24 until 26 , which is designed to carry out a calibration of the electrode device (40) and/or the sensor devices (14; 18) between the first measurement position and the second measurement position. Measuring system according to one of Claims 22 until 27 , wherein a cross-sectional area of the contact areas of the electrode device (40) to a Cross-sectional area of the depressions (12) of the sample body (10; 30) is adapted and a distance (74) between side walls of the contact areas and side walls of the depressions (12) is at most 2000 μm, preferably 1 μm to 100 μm. Measuring system according to one of Claims 22 until 28 wherein the electrode means (40) provides a reference electrode for measurements in the third plurality of wells (12); and a relative position between the sample body (10; 30) and the electrode device (40) is variable. Method (700) for measuring a multiplicity of analytes, which are arranged in a corresponding multiplicity of wells of a sample body, with the following steps: contacting (710) the plurality of analyte samples each with an associated sensor device; and contacting (720) the plurality of analyte samples simultaneously with a common reference electrode; and measuring (730) the analyte samples sequentially one after the other using the respective associated sensor device and the reference electrode.

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