Sensor device and method for operating sensor device

Abstract

The present application discloses a sensor device and a method for operating the sensor device. The sensor device comprises: a chamber; a first electrode connected to a common voltage end, wherein the potential difference between the first electrode and a corresponding second electrode is used for driving an analyte to be detected to penetrate through a corresponding nanopore and generate a sensing electrical signal; a bias voltage generation module used for generating a bias voltage less than or equal to a common voltage provided by the common voltage end; a first multi-path selection module, wherein the first multi-path selection module is connected to a plurality of second electrodes and can select one of the second electrodes to output a sensing electrical signal while the rest second electrodes are connected to the bias voltage generation module or the common voltage end; and a signal processing module, wherein the signal processing module is connected to the first multi-path selection module and can obtain the state of the nanopore on the basis of the sensing electrical signal.

Description

Sensor device and method for operating the same

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to Chinese patent application No. 202410068766.7, filed on January 17, 2024, entitled “Sensor device and operating method of sensor device,” the entire contents of which are incorporated herein by reference. Technical Field

[0003] The present application relates to the field of biological detection technology, and in particular to a sensor device and an operating method of the sensor device. Background Art

[0004] In nanopore sequencing, a certain electric potential is applied to drive biopolymers through the nanopore sequencing channel on the thin film. The current changes caused by different molecules passing through the nanopore sequencing channel are used to identify the biopolymers passing through the nanopore sequencing channel.

[0005] Taking single-stranded DNA as an example, the film can separate the chamber into two chambers, each of which has an electrode, and the two electrodes have different potentials, which can drive the single-stranded DNA through the nanopore. When the single-stranded DNA passes through the nanopore, the blockage of the nanopore on the base pair film will increase the resistance of the nanopore to the current between the electrodes, that is, change the equivalent resistance value of the nanopore. Due to the differences in the properties of different bases, the degree of blockage of the nanopore of the film by different base pairs is different, that is, the degree of change in the equivalent resistance value of the nanopore is also different. By reading the changes in the current between the electrodes, the genetic sequence information of the single-stranded DNA can be obtained.

[0006] To improve the efficiency of nanopore gene sequencing and minimize the impact of membrane nanopore damage on sequencing, a redundant nanopore array design is often employed. This design allows for selective connection of multiple nanopores on the membrane to a detection channel for gene sequencing. However, the remaining nanopores not connected to the detection channel can accumulate charge, generating pulsed currents that can affect the accuracy of nanopore sequencing and even damage the membrane and nanopores. Summary of the Invention

[0007] The embodiments of the present application provide a sensor device and a method for operating the sensor device, which can solve the technical problem that unused nanopores generate charge accumulation, thereby affecting nanopore sequencing.

[0008] In a first aspect, an embodiment of the present application provides a sensor device, the sensor device comprising:

[0009] Chamber; in the case where the chamber is provided with a thin film containing a plurality of nanopores, the chamber is divided into a first chamber and a second chamber by the thin film, the second chamber includes a plurality of second sub-chambers separated from each other, and each second sub-chamber is connected to the first chamber through a corresponding nanopore;

[0010] A first electrode is disposed in the first chamber and connected to a common voltage terminal;

[0011] A plurality of second electrodes are respectively disposed in the plurality of second sub-chambers; the potential difference between the first electrode and the second electrode is used to drive the analyte to be measured to pass through the corresponding nanopore and generate a sensing electrical signal;

[0012] A bias voltage generating module, configured to generate a bias voltage, wherein the bias voltage is less than or equal to a common voltage provided by the common voltage terminal;

[0013] a first multi-way selection module connected to the plurality of second electrodes, capable of selecting one second electrode from the plurality of second electrodes to be connected to the output terminal of the first multi-way selection module to output a sensing electrical signal, and connecting the second electrode not connected to the output terminal of the first multi-way selection module to the bias voltage generation module or the common voltage terminal;

[0014] The signal processing module has an input end connected to the first multiplex selection module, and the signal processing module can obtain the state of the nanopore according to the sensing electrical signal output by the first multiplex selection module.

[0015] In some embodiments, the first multi-path selection module includes:

[0016] a first switch module, wherein the first terminals of the first switch module are respectively connected to the second electrodes, and the second terminal of the first switch module is connected to the output terminal of the first multi-way selection module; the first switch module is used to output a sensing electrical signal of one of the second electrodes;

[0017] The second switch module has a plurality of first ends connected to the plurality of second electrodes respectively, and a second end connected to the bias voltage generating module.

[0018] In some embodiments, the first switch module includes:

[0019] a plurality of sensing switches, each sensing switch being connected between a corresponding second electrode and an output terminal of the first multi-way selection module; at any one time, at most one of the plurality of sensing switches is in an on state;

[0020] The second switch module includes:

[0021] A plurality of first bias switches are provided, each of the first bias switches being connected between a corresponding second electrode and the bias voltage generating module.

[0022] In some embodiments, the third terminal of the second switch module is connected to the common voltage terminal; the second switch module further includes:

[0023] A plurality of second bias switches are provided, each second bias switch being connected between a corresponding second electrode and a common voltage terminal, wherein the bias voltage generated by the bias voltage generating module is smaller than the common voltage provided by the common voltage terminal.

[0024] In some embodiments, the sensor device further comprises:

[0025] The signal detection circuit is connected between the first multi-channel selection module and the signal processing module, and is used to amplify the sensing electrical signal from the first multi-channel selection module.

[0026] In some embodiments, the sensor device includes a plurality of first multiplexing modules;

[0027] The signal detection circuit includes:

[0028] A plurality of current amplifying units, wherein the input end of the current amplifying unit is connected to the corresponding first multi-way selection module; the current amplifying unit is used to amplify the sensing electrical signal output by the corresponding first multi-way selection module;

[0029] The sensor device further comprises:

[0030] a second multiplex selection module connected to output terminals of the plurality of current amplifying units and configured to output an amplified sensing electrical signal from one of the plurality of current amplifying units; and

[0031] The analog-to-digital conversion module has an input end connected to the output end of the second multiplex selection module, and an output end of the analog-to-digital conversion module connected to the input end of the signal processing module.

[0032] In some embodiments, the sensor device further comprises:

[0033] A controller module, wherein the input end of the controller module is connected to the output end of the signal processing module, and the selection signal end of the controller module is connected to the first multi-way selection module; the controller module is used to generate a selection signal corresponding to one of the multiple second electrodes and send it to the first multi-way selection module.

[0034] In some embodiments, the controller module is connected to the bias voltage generation module;

[0035] When at least one nanopore is in a damaged state and the second switch module does not include a second bias switch, the controller module is configured to drive the bias voltage generation module to generate a bias voltage equal to the common voltage.

[0036] In some embodiments, when at least one nanopore is in a damaged state and the second switch module includes a second bias switch, the controller module is configured to drive the first multiplexing module to switch the second electrode corresponding to the damaged nanopore to be connected to the common voltage terminal.

[0037] In a second aspect, an embodiment of the present application provides an operating method for a sensor device, which is applied to the sensor device of the first aspect, and the method includes:

[0038] acquiring states of the plurality of nanopores, and determining a target nanopore according to the states of the plurality of nanopores;

[0039] The second electrode corresponding to the target nanopore is electrically connected to the signal processing module, and the second electrodes corresponding to the remaining nanopores are connected to the bias voltage generation module or the common voltage terminal, so as to analyze and process the analyte to be measured through the sensing electrical signal generated when the analyte to be measured passes through the target nanopore.

[0040] In some embodiments, obtaining states of the plurality of nanopores and determining the target nanopore according to the states of the plurality of nanopores includes:

[0041] The first multiplex selection module electrically connects the second electrode corresponding to each nanopore to the signal processing module in sequence;

[0042] Determine the state of each nanopore according to the sensing electrical signal corresponding to each nanopore;

[0043] The nanopore in the normal state is selected as the target nanopore.

[0044] In some embodiments, the method of operating the sensor device further includes:

[0045] monitoring the state of the target nanopore according to the sensing electrical signal generated by the target nanopore when the second electrode corresponding to the target nanopore is electrically connected to the signal processing module;

[0046] When the target nanopore is damaged, the second electrode corresponding to the target nanopore is switched to be connected to the bias voltage generating module or the common voltage terminal.

[0047] Compared with the related art, the sensor device and the operating method of the sensor device provided in the embodiment of the present application can generate a bias voltage less than or equal to the common voltage by setting a bias voltage generation module. When the first multi-way selection module selects a second electrode from a plurality of second electrodes to be connected to the output end of the first multi-way selection module to output a sensing electrical signal, the remaining second electrodes can be connected to the bias voltage generation module or to the common voltage end. At this time, the nanopore corresponding to the selected second electrode can generate a sensing electrical signal when the analyte to be measured passes through, and the signal processing module can analyze and process the analyte to be measured based on the sensing electrical signal. The second electrodes corresponding to the other redundant nanopores can receive the bias voltage or the common voltage instead of being in a floating state, thereby improving the problem that the second electrodes of each redundant nanopore in the floating state cause the nanopores on the film to generate charge accumulation and may cause pulse current, thereby improving the stability and safety of the sensor device. In addition, when the bias voltage is set lower than the common voltage, the electrodes or electrolytes of the consumed redundant nanopores can also be repaired by a reduction reaction, thereby extending the service life of the electrodes or electrolytes. BRIEF DESCRIPTION OF THE DRAWINGS

[0048] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the following briefly introduces the drawings required for use in the embodiments of the present application. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0049] FIG1 is a schematic diagram of a module structure of a sensor device provided in one embodiment of the present application;

[0050] FIG2 is a schematic diagram of a partial structure of a sensor device provided in another embodiment of the present application;

[0051] FIG3 is a schematic diagram of the circuit structure of a first multi-way selection module provided in an embodiment of the present application;

[0052] FIG4 is a schematic diagram of a module structure of a sensor device provided in another embodiment of the present application;

[0053] FIG5 is a schematic diagram of the circuit structure of a first multi-way selection module provided in another embodiment of the present application;

[0054] FIG6 is a schematic diagram of a module structure of a sensor device provided in yet another embodiment of the present application;

[0055] FIG7 is a schematic diagram of a module structure of a sensor device provided in yet another embodiment of the present application;

[0056] FIG8 is a flow chart of an operating method of a sensor device according to an embodiment of the present application;

[0057] FIG9 is a flow chart of an operating method of a sensor device provided in another embodiment of the present application;

[0058] FIG10 is a schematic diagram of voltage variation of the bias voltage during the nanopore switching process provided in one embodiment of the present application.

[0059] In the accompanying drawings: e1, first electrode; e2, second electrode; np, nanopore; 10, first multiplexer module; 11, first switch module; 12, second switch module; 20, bias voltage generation module; 30, signal processing module; 40, signal detection circuit; 41, current amplification unit; 42, second multiplexer module; 43, analog-to-digital conversion module; 50, controller module; VCOM, common voltage terminal; S1, sensing switch; S21, first bias switch; S22, second bias switch. DETAILED DESCRIPTION

[0060] The features and exemplary embodiments of various aspects of the present application will be described in detail below. In order to make the purpose, technical solutions and advantages of the present application clearer, the present application will be further described in detail below in conjunction with the accompanying drawings and specific embodiments. It should be understood that the specific embodiments described herein are only intended to explain the present application, rather than to limit the present application. For those skilled in the art, the present application can be implemented without the need for some of these specific details. The following description of the embodiments is merely to provide a better understanding of the present application by illustrating the examples of the present application.

[0061] It should be noted that, in this document, relational terms such as first and second, etc., are used only to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any actual relationship or order between these entities or operations. Moreover, the terms "comprises," "comprising," or any other variants thereof are intended to cover non-exclusive inclusion, so that a process, method, article, or device comprising a series of elements includes not only those elements, but also other elements not explicitly listed, or elements inherent to such process, method, article, or device. In the absence of further limitations, the elements defined by the phrase "comprising..." do not exclude the presence of other identical elements in the process, method, article, or device comprising the elements.

[0062] It should be noted that, in the absence of conflict, the embodiments and features in the embodiments of the present application can be combined with each other. The embodiments will be described in detail below with reference to the accompanying drawings.

[0063] In nanopore sequencing, a certain electric potential is applied to drive biopolymers through the nanopore sequencing channel on the thin film. The current changes caused by different molecules passing through the nanopore sequencing channel are used to identify the biopolymers passing through the nanopore sequencing channel.

[0064] Taking single-stranded DNA as an example, the film can separate the chamber into two chambers, each of which has an electrode, and the two electrodes have different potentials, which can drive the single-stranded DNA through the nanopore. When the single-stranded DNA passes through the nanopore, the blockage of the nanopore on the base pair film will increase the resistance of the nanopore to the current between the electrodes, that is, change the equivalent resistance value of the nanopore. Due to the differences in the properties of different bases, the degree of blockage of the nanopore of the film by different base pairs is different, that is, the degree of change in the equivalent resistance value of the nanopore is also different. By reading the changes in the current between the electrodes, the genetic sequence information of the single-stranded DNA can be obtained.

[0065] To improve the efficiency of nanopore gene sequencing and minimize the impact of membrane nanopore damage on sequencing, a redundant nanopore array design is often employed. This design allows for selective connection of multiple nanopores on the membrane to a detection channel for gene sequencing. However, the remaining nanopores not connected to the detection channel can accumulate charge, generating pulsed currents that can affect the accuracy of nanopore sequencing and even damage the membrane and nanopores.

[0066] In order to solve the above technical problems, the embodiments of the present application provide a sensor device and an operating method of the sensor device.

[0067] 1 shows a schematic structural diagram of a sensor device provided by an embodiment of the present application, which includes a chamber, a first electrode e1 , a plurality of second electrodes e2 , a bias voltage generating module 20 , a first multiplexing module 10 , and a signal processing module 30 .

[0068] A membrane (not shown) containing multiple nanopores np may be disposed in the chamber (not shown). When the membrane containing multiple nanopores np is disposed in the chamber, the membrane containing multiple nanopores np may separate the chamber into a first chamber and a second chamber. The second chamber includes multiple mutually separated second sub-chambers, each of which may communicate with the first chamber via a corresponding nanopore np.

[0069] The first electrode e1 may be disposed in the first cavity, and the first electrode e1 is connected to the common voltage terminal VCOM.

[0070] The plurality of second electrodes e2 can be respectively disposed in the plurality of second sub-chambers. Each nanopore np on the membrane can serve as a channel between the first chamber and the second sub-chamber, allowing the analyte to pass from the first chamber through the nanopore np to the second sub-chamber.

[0071] Each nanopore np can correspond to a first electrode e1 and a second electrode e2. As shown in Figure 1, each nanopore np can be equivalent to a parallel connection of a resistor and a capacitor, where the resistor is the equivalent resistance of the nanopore np, and the capacitor is the equivalent parallel parasitic capacitance of the film at the location of the nanopore np. The first end of each nanopore np can be connected to the first electrode e1, and the second end of each nanopore np can be connected to the corresponding second electrode e2.

[0072] The first electrode e1 is connected to a common voltage terminal VCOM. The common voltage terminal VCOM can provide a common voltage, so that the potential of the first electrode e1 is the common voltage.

[0073] Taking a single nanopore np as an example, there is a potential difference between the first electrode e1 and the second electrode e2 corresponding to the nanopore np. This potential difference can drive the analyte to be tested in the first chamber to pass through the nanopore np to reach the second sub-chamber, and generate a sensing electrical signal in the process of passing through the nanopore np.

[0074] The nanopore np in the thin film can be considered an equivalent resistor. As the analyte passes through the nanopore np, the bases of the analyte block the nanopore np, thereby changing the equivalent resistance of the nanopore np. In other words, as the analyte passes through the nanopore np, the nanopore np acts as a variable resistor. Because different bases have different effects on the equivalent resistance of the nanopore np, the corresponding four bases, A, T, C, and G, can be determined by detecting changes in the sensed electrical signal as the analyte passes through the nanopore np. For example, single-stranded DNA can be sequenced as it passes through the nanopore np.

[0075] The bias voltage generating module 20 can generate a bias voltage through the bias voltage terminal VBias. The bias voltage can be set to be consistent with the common voltage provided by the common voltage terminal VCOM, or the bias voltage can be less than the common voltage. As an optional embodiment, the bias voltage generating module 20 can be a digital-to-analog conversion module.

[0076] The first multiplexer module 10 can be connected to a plurality of second electrodes e2. The first multiplexer module 10 can select one second electrode e2 from the plurality of second electrodes e2 and connect the second electrode e2 to the output terminal of the first multiplexer module 10 to output a sensing electrical signal.

[0077] The first multiplexing module 10 may further connect the second electrodes e2 that are not connected to the output terminal of the first multiplexing module 10 to the bias voltage generation module 20 or the common voltage terminal VCOM. That is, among the plurality of second electrodes e2 connected to the first multiplexing module 10, at most one second electrode e2 is connected to the output terminal of the first multiplexing module 10, and the remaining second electrodes e2 are connected to the bias voltage generation module 20 or the common voltage terminal VCOM.

[0078] The input end of the signal processing module 30 is connected to the first multiplexer module 10. When the first multiplexer module 10 outputs a sensing electrical signal through the output end, the signal processing module 30 can receive the sensing electrical signal output by the first multiplexer module 10 and obtain the state of the nanopore np based on the sensing electrical signal.

[0079] The state of the nanopore NP can be normal or damaged. The signal processing module 30 can determine the state of the nanopore NP based on the sensed electrical signal. If the nanopore NP is in a damaged state, the nanopore NP can be determined to be damaged. If the nanopore NP is in a normal state, the signal processing module 30 can analyze and process the analyte to be tested based on the sensed electrical signal and obtain corresponding analysis results. For example, the signal processing module 30 can determine the genetic sequence of the analyte to be tested based on the sensed electrical signal.

[0080] It should be noted that, among the plurality of second electrodes e2, the nanopore np corresponding to the second electrode e2 connected to the output end of the first multiplexer module 10 is the nanopore np that analyzes and processes the analyte to be detected, while the remaining nanopores np are redundant nanopores np and are not analyzed and processed at this time.

[0081] If the second electrode e2 of the remaining redundant nanopores np is in a floating state when not sequencing, the corresponding equivalent resistance of the nanopore np is relatively large, typically reaching the GΩ level. Since multiple nanopores np are in a floating state, the membrane surface will be affected by the sensed electrical signal, causing charge accumulation. This accumulated charge cannot be discharged due to the lack of an effective charge discharge channel.

[0082] When the nanopore np performing analysis and processing of an analyte is switched, the second electrode e2 of the switched nanopore np, when connected to the output terminal of the first multiplexing module 10, may release the accumulated charge and generate a large instantaneous pulse current, thereby affecting the analysis and processing process. This pulse current may even damage the nanopore np on the membrane. Therefore, the redundant nanopore np should be kept from floating when not performing analysis and processing.

[0083] In the above embodiment, except for the second electrode e2 connected to the output terminal of the first multiplexing module 10, the other second electrodes e2 can be connected to the bias voltage generating module 20 or the common voltage terminal VCOM. In other words, the second electrode e2 of each redundant nanopore np is not in a floating state, but receives a bias voltage or a common voltage.

[0084] Because the second electrode e2 of each redundant nanopore np can receive a common voltage or a bias voltage, each redundant nanopore np has a charge discharge channel, preventing significant charge accumulation when not performing analysis processing. When switching a nanopore np, the redundant nanopore np has minimal charge accumulation, preventing significant pulse current.

[0085] It should be noted that in order to allow the analyte to move from the first chamber to the second chamber, the potential of the first electrode e1 should be set to be at least not lower than the potential of the second electrode e2, that is, the common voltage provided by the common voltage terminal VCOM is greater than or equal to the bias voltage generated by the bias voltage generating module 20.

[0086] When the common voltage and the bias voltage are the same, the potentials between the first electrode e1 and the second electrode e2 of the redundant nanopore np are equal. At this time, the first electrode e1 and the second electrode e2 will not drive the analyte to be measured to pass through the redundant nanopore np.

[0087] When the common voltage is greater than the bias voltage, the electrodes or electrolyte can also be repaired.

[0088] Taking the electrode as an oxidizable electrode material as an example, during the nanopore NP sequencing process, the second electrode will be connected to a potential lower than the common voltage of the first electrode, and the electrode in the second chamber will be continuously oxidized. For example, when the electrode material is silver, the oxidation process of the electrode is: Ag→Ag + +e;

[0089] That is, the second electrode e2 will be oxidized into silver ions and electrons, resulting in electrode loss during the nanopore np sequencing process.

[0090] Similarly, when the electrode is made of an inert material, the electrode will not be lost during the nanopore NP sequencing process. However, in order to generate the sensing electrical signal, an electrolyte needs to be injected into the second chamber. At this time, the ions in the electrolyte will be continuously consumed during the nanopore NP sequencing process. For example, when the electrode material is platinum and the electrolyte is potassium ferrocyanide (K4[Fe(CN)6]) solution, although the electrode will not be lost during the sequencing process, the iron ions in the electrolyte will be continuously oxidized: Fe 2+ →Fe 3+ +e;

[0091] As can be seen from the above examples, whether an oxidizable electrode or an electrolyte is used to provide a sensing electrical signal, the electrode or the electrolyte will be consumed during the nanopore NP sequencing process.

[0092] When the Ag in the electrode or the Fe in the electrolyte 2+ When ions are nearly completely consumed due to continuous oxidation, the sensing signal will drop significantly, making it impossible to continue nanopore NP sequencing. Therefore, during the nanopore NP sequencing process, if a nanopore NP has been sequencing for a period of time and the electrode or electrolyte is severely consumed, causing the sensing signal to drop beyond the measurable range, the nanopore NP performing sequencing can be switched and the electrodes or electrolyte consumed during the sequencing process can be repaired.

[0093] In the above embodiment, when the bias voltage is set to be lower than the common voltage, the consumed electrode or electrolyte can be repaired. For example, when the electrode uses an oxidizable electrode, the electrode will be continuously oxidized during the sequencing process. For the redundant nanopore NP, the second electrode will be connected to a bias voltage lower than the common voltage and a reduction reaction will occur. Taking the electrode material as silver as an example, the electrode reduction process is: Ag + +e→Ag;

[0094] Similarly, when the electrode material is an inert material, such as platinum, and the electrolyte is potassium ferrocyanide solution, the reduction process of iron ions in the electrolyte is: Fe 3+ +e→Fe 2+ ;

[0095] Through the above-mentioned reduction process, when the electrode is consumed or the ions in the electrolyte are consumed due to nanopore NP sequencing before the redundant nanopore NP, the reduction process of the electrode or the reduction process of the ions in the electrolyte can be achieved through the potential difference between the common voltage and the bias voltage, so that the metal electrode or electrolyte consumed in the sequencing can be repaired, thereby extending the service life of the electrode or electrolyte.

[0096] In this embodiment, a bias voltage generation module 20 is provided to generate a bias voltage less than or equal to the common voltage. When the first multiplexer module 10 selects one second electrode e2 from among multiple second electrodes e2 and connects it to the output terminal of the first multiplexer module 10 to output a sensing electrical signal, the remaining second electrodes e2 can be connected to the bias voltage generation module 20 or to the common voltage terminal VCOM. The nanopore np corresponding to the selected second electrode e2 can then generate a sensing electrical signal when an analyte passes through it, and the signal processing module 30 can analyze and process the analyte based on the sensing electrical signal. The remaining redundant nanopores np can be connected to the bias voltage generation module 20 or the common voltage terminal VCOM via the first multiplexer module 10. The second electrodes e2 corresponding to each redundant nanopore np can receive a bias voltage or a common voltage, rather than being left floating. This mitigates the issue of charge accumulation on the nanopore np in the membrane, which can potentially induce pulsed currents, when the second electrodes e2 of each redundant nanopore np are left floating. This improves the stability and safety of the sensor device. Furthermore, when the bias voltage is set to be lower than the common voltage, the consumed electrode or electrolyte of the redundant nanopore NP can be repaired through a reduction reaction, thereby extending the service life of the electrode or electrolyte.

[0097] It should be noted that when the bias voltage is set lower than the common voltage, any electrode or electrolyte consumption incurred when the redundant nanopore np was previously connected to the output of the first multiplexing module 10 for sequencing can be repaired. If the redundant nanopore np was not previously connected to the output of the first multiplexing module 10 and was not consumed, connecting its second electrode e2 to a bias voltage lower than the common voltage will not restore or repair the redundant nanopore, but will also not have any adverse effects.

[0098] Referring to FIG. 2 , in some embodiments, the first multi-way selection module 10 may include a first switch module 11 and a second switch module 12 .

[0099] The first terminals of the first switch module 11 can be connected to the second electrodes e2, respectively, and the second terminal of the first switch module 11 can be connected to the output terminal of the first multiplexer module 10. The first switch module 11 can connect one of the second electrodes e2 to the output terminal of the first multiplexer module 10 to output a sensing electrical signal of one of the second electrodes e2.

[0100] The multiple first ends of the second switch module 12 can be respectively connected to the multiple second electrodes e2, and the second end of the second switch module 12 can be connected to the bias voltage generation module 20. The second switch module 12 can connect the remaining second electrodes e2 among the multiple second electrodes e2, except the second electrode e2 connected to the output end of the first multiplexer module 10, to the bias voltage generation module 20 to provide a bias voltage to the remaining second electrodes e2, thereby preventing the remaining second electrodes e2 from being in a floating state.

[0101] Through the first switch module 11 and the second switch module 12, multiple nanopores np can be selectively operated. One of the multiple nanopores np can output a sensing electrical signal through the corresponding second electrode e2, and the second electrodes e2 of the remaining redundant nanopores np that are not in operation can receive a bias voltage, ensuring that there is a charge discharge channel in the film where each redundant nanopore np is located, thereby avoiding the accumulation of excessive charge on the surface of the film.

[0102] Referring to FIG. 3 , in some embodiments, the first switch module 11 may include a plurality of sensing switches S1 , and the second switch module 12 may include a plurality of first bias switches S21 .

[0103] Each of the plurality of sensing switches S1 can be connected between the corresponding second electrode e2 and the output terminal of the first multiplexer module 10. When the sensing switch S1 is turned on, the corresponding second electrode e2 is connected to the output terminal of the first multiplexer module 10.

[0104] At any time, at most one of the plurality of sensing switches S1 is in the on state, that is, at most one of the plurality of second electrodes e2 can be connected to the output terminal of the first multiplex selection module 10 and output a sensing electrical signal.

[0105] Among the multiple first bias switches S21, each first bias switch S21 can be connected between the corresponding second electrode e2 and the bias voltage generation module 20. When the first bias switch S21 is turned on, it is equivalent to connecting the corresponding second electrode e2 to the bias voltage generation module 20, and the second electrode e2 can receive the bias voltage.

[0106] It should be noted that, at any moment, in order to prevent the second electrode e2 corresponding to the redundant nanopore np from being in a floating state, except for the second electrode e2 connected to the output end of the first multi-way selection module 10, the first bias switches S21 corresponding to the remaining second electrodes e2 are all in a conducting state, that is, the remaining second electrodes e2 all receive the bias voltage and are not in a floating state.

[0107] 4 and 5 , in some embodiments, the second switch module 12 further includes a third terminal, which can be connected to the common voltage terminal VCOM. The second switch module 12 further includes a plurality of second bias switches S22 .

[0108] Each of the plurality of second bias switches S22 can be connected between the corresponding second electrode e2 and the common voltage terminal VCOM. When the second bias switch S22 is turned on, the corresponding second electrode e2 is connected to the common voltage terminal VCOM, and the second electrode e2 can receive the common voltage.

[0109] Taking a second electrode e2 as an example, when the first bias switch S21 corresponding to the second electrode e2 is turned on, the second electrode e2 can receive a bias voltage; and when the second bias switch S22 corresponding to the second electrode e2 is turned on, the second electrode e2 can receive a common voltage. To distinguish the functions of the first bias switch S21 and the second bias switch S22, the bias voltage generated by the bias voltage generation module 20 can be set to be lower than the common voltage provided by the common voltage terminal VCOM. That is, when the first bias switch S21 is turned on, the second electrode e2 receives a bias voltage lower than the common voltage. At this time, a certain potential difference exists between the first electrode e1 and the second electrode e2. This potential difference can promote the reduction process of the electrodes or the reduction process of ions in the electrolyte, thereby repairing the metal electrodes or electrolyte consumed during sequencing, thereby extending the service life of the electrodes or electrolyte. When the second bias switch S22 is turned on, the voltage received by the second electrode e2 is the common voltage. At this time, the potential difference between the first electrode e1 and the second electrode e2 is substantially 0, and thus the analyte cannot be driven to pass through the nanopore np corresponding to the second electrode e2.

[0110] Referring to FIG. 6 , in some embodiments, the sensor device may further include a signal detection circuit 40 .

[0111] The signal detection circuit 40 may be connected between the first multiplexer module 10 and the signal processing module 30 . The signal detection circuit 40 may amplify the sensing electrical signal from the first multiplexer module 10 .

[0112] The signal detection circuit 40 is capable of receiving the sensing electrical signal outputted from the output terminal of the first multiplexer module 10 and performing signal amplification and signal conversion processing on the sensing electrical signal, thereby converting the sensing electrical signal into a signal type that can be collected by the signal processing module 30. For example, the power supply voltage of the signal detection circuit 40 can be greater than the common voltage provided by the common voltage terminal VCOM. In this case, the signal detection circuit 40 can amplify the sensing electrical signal, thereby increasing the amplitude of the sensing electrical signal with a lower amplitude to a voltage range detectable by the signal processing module 30. The signal detection circuit 40 can also perform analog-to-digital conversion on the sensing electrical signal to convert the analog signal into a digital signal that can be recognized by the signal processing module 30.

[0113] 7 , in some embodiments, the sensor device may include multiple first multiplexing modules 10, and the sensor device signal detection circuit 40 may include multiple current amplifying units 41. Furthermore, the sensor device may further include a second multiplexing module 42 and an analog-to-digital conversion module 43.

[0114] Because a single first multiplexing module 10 can only select a limited number of channels, multiple first multiplexing modules 10 are typically required when a large number of nanopores NPs are present on the membrane. For example, a first multiplexing module 10 may include four first signal input terminals, and each first multiplexing module 10 may be connected to the second electrodes e2 corresponding to four nanopores NPs. If a large number of nanopores NPs are present on the membrane, for example, 20 nanopores NPs are provided on the membrane, at least five first multiplexing modules 10 are required.

[0115] When the sensor device is provided with a plurality of first multiplexing modules 10 , the signal detection circuit 40 may include a plurality of current amplifying units 41 .

[0116] Multiple current amplifying units 41 can correspond to multiple first multiplexing modules 10, respectively. The input end of each current amplifying unit 41 can be connected to the corresponding first multiplexing module 10. The current amplifying unit 41 can amplify the signal amplitude of the sensing electrical signal output by the corresponding first multiplexing module 10 so that the sensing electrical signal, after amplification, can meet the sampling range of the signal processing module 30. The current amplifying unit 41 can also perform noise removal and filtering on the sensing electrical signal.

[0117] It is understandable that if the sensing electrical signal output by the second electrode e2 to the output end of the first multiplexing module 10 can already meet the sampling range of the signal processing module 30 without signal amplification, the current amplifying unit 41 can be omitted.

[0118] The common voltage provided by the common voltage terminal VCOM can be determined based on the supply voltage of the current amplifying unit 41. That is, the common voltage should be set between the highest and lowest potentials that the current amplifying unit 41 can provide. For example, when the supply voltage of the current amplifying unit 41 is 3.3V, the common voltage can be set to any voltage value between 0 and 3.3V, such as 0.5V, 0.8V, 1.0V, 1.2V, 1.5V, 2.0V, 2.5V, etc., and is typically set to 1.6V.

[0119] The second multiplexer selection module 42 can be connected to the output ends of the multiple current amplifying units 41 . The second multiplexer selection module 42 can select one current amplifying unit 41 from the multiple current amplifying units 41 and output the sensing electrical signal amplified by the current amplifying unit 41 .

[0120] The input end of the analog-to-digital conversion module 43 can be connected to the output end of the second multiplexer module 42, and the output end of the analog-to-digital conversion module 43 can be connected to the input end of the signal processing module 30. The analog-to-digital conversion module 43 can convert the amplified sensing electrical signal output by the second multiplexer module 42 from an analog signal to a digital signal, so that the signal processing module 30 can analyze and process the sensing electrical signal by reading the digital signal.

[0121] As an exemplary embodiment, a membrane is provided with 20 nanopores NPs. The sensor device includes five first multiplexer modules 10, each of which can be connected to the second electrodes e2 of four nanopores NPs. The five first multiplexer modules 10 are connected to a second multiplexer module 42 via five current amplification units 41. The second multiplexer module 42 can selectively connect to one of the five first multiplexer modules 10, and this connected first multiplexer module 10 can selectively connect to one of the second electrodes e2 of the corresponding four nanopores NPs. Through the selective connection between the first multiplexer modules 10 and the second multiplexer modules 42, selective connection to one of the 20 nanopores NPs can be achieved, that is, the nanopore NP sequencing process can be selected from one of the multiple nanopores NPs.

[0122] Continuing with FIG. 7 , in some embodiments, the sensor device may further include a controller module 50 .

[0123] The controller module 50 includes an input terminal and a gate signal terminal. As shown in FIG7 , the input terminal of the controller module 50 can be connected to the output terminal of the signal processing module 30 , and the gate signal terminal Gate1 of the controller module 50 can be connected to the first multiplexer module 10 .

[0124] The controller module 50 can generate a strobe signal corresponding to one of the plurality of second electrodes e2 and send the strobe signal to the first multiplexer module 10. Based on the strobe signal, the first multiplexer module 10 connects the corresponding second electrode e2 to the output terminal of the first multiplexer module 10 to output the sensing electrical signal, and connects the remaining second electrodes e2 to the bias voltage generating module 20 or the common voltage terminal VCOM, so that the second electrodes e2 that do not output the sensing electrical signal receive the bias voltage or the common voltage.

[0125] In some embodiments, the controller module 50 may be connected to the bias voltage generating module 20 .

[0126] If at least one of the multiple nanopores np is damaged and the second switch module does not include the second bias switch S22, the sensor device can only provide a bias voltage to the second electrode e2, but not the common voltage, because the second switch module only includes the first bias switch S21. In this case, if the bias voltage is lower than the common voltage, the potential difference between the common voltage and the bias voltage may generate a large current in the damaged nanopore np, causing further damage to the damaged nanopore np and surrounding healthy nanopores np. Therefore, when a damaged nanopore np is present and only a bias voltage can be provided to the second electrode e2, the controller module 50 can drive the bias voltage generation module 20 to generate a bias voltage equal to the common voltage, so that the potential difference between the common voltage and the bias voltage is substantially zero, thereby preventing the generation of a large transient current in the damaged nanopore np, which could cause further damage.

[0127] In other embodiments, if at least one of the multiple nanopores np is damaged and the second switch module includes a second bias switch S22, the controller module 50 can drive the first multiplexer module 10 to switch the second electrode e2 corresponding to the damaged nanopore np to be connected to the common voltage terminal VCOM. In this case, among the multiple nanopores np not connected to the output terminal of the first multiplexer module 10, the normal nanopores np can receive the bias voltage via the conductive first bias switch S21, while the damaged nanopore np can receive the common voltage via the conductive second bias switch S22. For the damaged nanopore np, the potential difference between the first electrode e1 and the second electrode e2 at its ends is essentially zero, resulting in a large transient current flowing through the intact nanopore np, thus preventing further damage.

[0128] It should be noted that, in the above embodiment, the controller module 50 may send a bias voltage control signal to control the bias voltage generating module 20 to generate a suitable bias voltage.

[0129] When all redundant nanopores NPs are in a normal state, the controller module 50 can control the bias voltage generation module 20 to generate a bias voltage lower than the common voltage. In this case, the potential difference between the bias voltage and the common voltage can reduce and repair ions in the consumed electrode or electrolyte. When at least one of the redundant nanopores NPs is damaged, since the equivalent resistance of the damaged nanopore NP is significantly lower than that of a normal nanopore NP, to avoid generating large transient current pulses in the damaged nanopore NP, the controller module 50 can control the bias voltage generation module 20 to generate a bias voltage consistent with the common voltage. In this case, the potential difference between the bias voltage and the common voltage is zero or close to zero. This small potential difference does not generate a large current in the damaged nanopore NP, thereby preventing further damage to the damaged nanopore NP and surrounding normal nanopore NPs, and does not affect the nanopore NP sequencing process.

[0130] In some embodiments, the signal processing module 30 obtains the status of each nanopore np by driving the first multiplexer module 10 to sequentially connect each second electrode e2 to the output terminal of the first multiplexer module 10 before selecting a nanopore np for sequencing.

[0131] When each second electrode e2 is connected to the output terminal of the first multiplexing module 10, the signal processing module 30 can receive the sensing electrical signal corresponding to the second electrode e2. When the analyte to be measured has not passed through the nanopore np, the normal nanopore np can be equivalent to a large resistance. In this case, the sensing electrical signal received by the signal processing module 30 should be the empty pore current.

[0132] The equivalent resistance of a damaged nanopore np is significantly lower than that of a normal nanopore np. Therefore, when the signal processing module 30 connects the second electrode e2 corresponding to the damaged nanopore np to the output terminal of the first multiplexing module 10, the received sensing electrical signal will be greater than the empty pore current. Based on the current magnitude of the sensing electrical signal corresponding to different second electrodes e2, the signal processing module 30 can determine whether each nanopore np is in a normal or damaged state.

[0133] After sequentially determining the status of each nanopore NP, if at least one nanopore NP is damaged, the controller module 50 can drive the bias voltage generation module 20 to generate a first bias voltage to prevent the potential difference between the common voltage and the bias voltage from being applied to the damaged nanopore NP and generating a large pulse current. This first bias voltage can be consistent with the common voltage. In other words, when a damaged nanopore NP is present, the bias voltage cannot be set lower than the common voltage, but should be set to the same voltage as the common voltage to prevent the damaged nanopore NP from generating a large current and affecting the accuracy of nanopore NP sequencing.

[0134] In the above embodiment, the sensing switch S1, the first bias switch S21, and the second bias switch S22 can be analog switch integrated circuits, or single MOSFETs (Metal-Oxide-Semiconductor Field-Effect Transistors) in an integrated circuit, or complementary switch circuits composed of two different types of transistors.

[0135] Referring to FIG. 8 , an embodiment of the present application further provides an operating method for a sensor device, which is applied to the sensor device in the above embodiment. The method includes:

[0136] S110, acquiring states of the plurality of nanopores, and determining a target nanopore according to the states of the plurality of nanopores;

[0137] S120, electrically connecting the second electrode corresponding to the target nanopore to the signal processing module, and connecting the second electrodes corresponding to the remaining nanopores to the bias voltage generation module or the common voltage terminal, so as to analyze and process the analyte to be measured through the sensing electrical signal generated when the analyte to be measured passes through the target nanopore.

[0138] The operating method of the sensor device provided in the embodiments of the present application is applicable to the sensor device in the above-mentioned embodiments. The sensor device can select one of the multiple nanopores to analyze the analyte to be detected. The other redundant nanopores not undergoing analysis can be connected to a bias voltage generation module or a common voltage terminal to provide a bias voltage or a common voltage to the redundant nanopores. This prevents the second electrode of the redundant nanopore from being in a floating state, and can provide a stable charge discharge channel to prevent the accumulation of large amounts of charge on the membrane, which may affect the accuracy of nanopore sequencing or cause damage to the membrane and nanopore.

[0139] In this embodiment, by determining the states of multiple nanopores, the target nanopore can be determined from the nanopores in the normal state, the second electrode of the target nanopore is electrically connected to the signal processing module, the potential difference between the two ends of the target nanopore is used to drive the analyte to pass through the target nanopore, and the analyte to be tested is analyzed and processed according to the sensing electrical signal generated during the analyte to be tested passing through the target nanopore. For example, the gene sequence of the analyte to be tested can be inferred by sensing the electrical signal, thereby realizing nanopore sequencing. For other redundant nanopores that have not been sequenced, the second electrode corresponding to each redundant nanopore can be connected to the bias voltage generation module or the common voltage terminal to provide a bias voltage or a common voltage for the redundant nanopore, thereby preventing the second electrode of the redundant nanopore from being in a floating state for a long time, forming an effective charge discharge channel, and preventing the large instantaneous current generated when the nanopore is switched from interfering with the sequencing process.

[0140] In S110 , based on the sensor device in the above embodiment, the analyte to be detected in the chamber may be analyzed and processed.

[0141] During analysis and processing, the controller module in the sensor device may obtain the states of the multiple nanopores and determine the target nanopore according to the states of the multiple nanopores.

[0142] To improve the efficiency of nanopore sequencing, a redundant nanopore array is often used. Specifically, a membrane is provided with multiple nanopores, and a single nanopore is selected as a target nanopore. This nanopore is then connected to a sequencing circuit to sequence the genetic sequence of the analyte. After determining the status of the multiple nanopores, a controller module selects the target nanopore from among those in a healthy state, while any damaged nanopores are not selected as targets.

[0143] Referring to FIG. 9 , as an optional embodiment, the above S110 may include:

[0144] S210, enabling the first multiplexer module to electrically connect the second electrode corresponding to each nanopore to the signal processing module in sequence;

[0145] S220, determining the state of each nanopore according to the sensing electrical signal corresponding to each nanopore;

[0146] S230 , selecting a nanopore in a normal state as a target nanopore.

[0147] In this embodiment, the controller module can control the first multiplexing module to sequentially electrically connect the second electrode of each nanopore to the signal processing module. Based on the sensed electrical signals corresponding to each nanopore, it can be determined whether each nanopore is in a normal state or a damaged state. After determining the state of each nanopore, one of the multiple normal nanopores can be selected as a target nanopore.

[0148] In S210 , the controller module may detect the status of each nanopore by sequentially connecting the second electrode of each nanopore to the signal processing module via the first multiplexing module, so as to construct a sequencing circuit through each nanopore.

[0149] In S220 , since a normal nanopore is equivalent to a relatively high resistor, a damaged nanopore will have a significantly lower resistance. By electrically connecting the second electrode of each nanopore to the signal processing module, the sensing electrical signal of each nanopore can be collected. Based on the sensing electrical signal corresponding to each nanopore, the equivalent resistance range of each nanopore can be determined. If the sensing electrical signal of a nanopore is too large, it indicates that the equivalent resistance of the nanopore is low, and the nanopore may be damaged.

[0150] By determining whether the sensing electrical signal corresponding to each nanopore is in an appropriate current range, it is possible to determine whether the state of each nanopore is normal.

[0151] It should be noted that the above process of detecting the status of each nanopore is before the sequencing process of the analyte to be tested. At this time, no analyte to be tested is added to the chamber, and the equivalent resistance of the nanopore will remain stable.

[0152] In S230 , after the states corresponding to the plurality of nanopores are determined, a nanopore in a normal state may be determined from the plurality of nanopores, and one of the nanopores in the normal state may be selected as a target nanopore.

[0153] In S120, after selecting the target nanopore from multiple nanopores, the second electrode corresponding to the target nanopore can be electrically connected to the signal processing module, that is, the first multi-way selection module is controlled to connect the second electrode corresponding to the target nanopore to the output end of the first multi-way selection module, and the second electrodes corresponding to the remaining nanopores are connected to the bias voltage generation module or the common voltage end.

[0154] The first electrode of the target nanopore has a common voltage. The potential difference between the first and second electrodes drives the analyte from the first chamber through the target nanopore to the corresponding second sub-chamber of the target nanopore. As the analyte passes through the target nanopore, the analyte's base pairs block the nanopore, causing a change in the equivalent resistance of the target nanopore, which in turn changes the sensed electrical signal received by the signal processing module. Based on the detected sensed electrical signal, the signal processing module infers the base type that passed through the target nanopore and, consequently, determines the genetic sequence of the analyte, thereby sequencing the analyte.

[0155] As an optional embodiment, the operating method of the sensor device may further include:

[0156] S310, monitoring the state of the target nanopore according to the sensing electrical signal generated by the target nanopore, when the second electrode corresponding to the target nanopore is electrically connected to the signal processing module;

[0157] S320 , when the target nanopore is damaged, switching the second electrode corresponding to the target nanopore to be connected to the bias voltage generating module or the common voltage terminal.

[0158] In this embodiment, during the process of analyzing the analyte through the target nanopore, the state of the target nanopore can also be monitored based on the sensing electrical signal generated by the target nanopore. When the target nanopore is damaged, it is necessary to replace it with a new nanopore for analysis and processing, and switch the second electrode corresponding to the target nanopore to be connected to the bias voltage generating module or the common voltage terminal. When the target nanopore is damaged, it can be promptly replaced.

[0159] In S310, after determining the target nanopore, the sensor device may electrically connect the second electrode corresponding to the target nanopore to the signal processing module. When the second electrode corresponding to the target nanopore is electrically connected to the signal processing module, the sensor device may also monitor the state of the target nanopore based on the sensing electrical signal generated by the target nanopore.

[0160] The signal processing module in the sensor device not only analyzes and processes the analyte based on the electrical signal generated by the target nanopore, but also determines whether the target nanopore is damaged. During the analysis and processing of the analyte using the target nanopore, the target nanopore's status must be monitored, allowing the sensor to switch to a functioning nanopore in a timely manner if damage occurs.

[0161] As an optional embodiment, when no analyte to be measured passes through the nanopore, the sensing electrical signal of the nanopore is usually around 100 picoamperes, and the normal current range of the nanopore is the empty pore current range; when the analyte to be measured passes through the nanopore, the sensing electrical signal of the nanopore decreases compared to the empty pore current and is only a fraction of the empty pore current. At this time, the normal current range of the nanopore is the sequencing current range.

[0162] If the sensing signal remains within the empty pore current range and the sequencing current range, the target nanopore is in a normal state. If the sensing signal exceeds the empty pore current range, the equivalent resistance of the target nanopore is too low, indicating that the target nanopore is damaged.

[0163] In S320, when monitoring the state of the target nanopore based on the sensing electrical signal generated by the target nanopore, if the sensing electrical signal abnormally increases to exceed a preset range, it can be determined that the target nanopore is damaged. At this time, the sensor device can switch the second electrode corresponding to the target nanopore to be connected to the bias voltage generation module or the common voltage terminal.

[0164] When a target nanopore is damaged, analysis of the analyte cannot be performed through it, requiring a switch to another functioning nanopore. The sensor device can disconnect the damaged target nanopore from the output of the first multiplexing module and connect it to a bias voltage generation module or a common voltage terminal. This makes the damaged target nanopore a redundant nanopore. By providing a bias voltage or a common voltage, the redundant nanopore can be prevented from floating.

[0165] It should be noted that since the target nanopore is in a damaged state, if the second electrode corresponding to the target nanopore is connected to the common voltage end, it can ensure that the potential difference between the two ends of the target nanopore is basically 0, and no large current pulse will be generated on the damaged target nanopore; if the second electrode corresponding to the target nanopore is to be connected to the bias voltage generation module, the bias voltage provided by the bias voltage generation module also needs to be adjusted to be consistent with the common voltage.

[0166] In some embodiments, during the above-mentioned process of replacing a new nanopore for analysis and processing when the target nanopore is damaged, if the bias voltage is inconsistent with the common voltage, the voltage change rate of the bias voltage should be set lower than the preset slope value during the time interval for raising the bias voltage to be consistent with the common voltage, that is, to avoid the voltage change rate of the bias voltage being too fast, thereby reducing the instantaneous current peak during the bias voltage change process.

[0167] As shown in Figure 10, before time t0, the bias voltage at the bias voltage terminal is VR, which is lower than the common voltage VC provided by the common voltage terminal. At this time, the electrode or electrolyte corresponding to the redundant nanopore connected to the bias voltage terminal is in the reduction stage. At time t0, the switching of the target nanopore begins. In the interval from t0 to t1, the controller module can control the bias voltage generation module to raise the bias voltage VR to the common voltage VC. During this raising process, the voltage change rate of the bias voltage is:

[0168] In order to prevent the bias voltage from changing too quickly, a preset slope value SR1 can be set. When the controller module controls the bias voltage generation module to raise the bias voltage VR, the following conditions should be met:

[0169] That is, in order to avoid an excessively large instantaneous current peak during the bias voltage change process, the voltage change rate can be limited.

[0170] The present application also provides a nanopore sequencing device, comprising the sensor device of the above embodiment and a membrane comprising a plurality of nanopores. An analyte to be tested is added to the first chamber separated by the membrane, and nanopore sequencing of the analyte to be tested is performed using the sensor device.

[0171] The functional blocks shown in the above-described block diagram can be implemented as hardware, software, firmware or a combination thereof. When implemented in hardware, they can be, for example, electronic circuits, application specific integrated circuits (ASICs), appropriate firmware, plug-ins, function cards, etc. When implemented in software, the elements of the present application are programs or code segments that are used to perform the required tasks. The program or code segment can be stored in a machine-readable medium, or transmitted on a transmission medium or a communication link by a data signal carried in a carrier wave. "Machine-readable medium" can include any medium that can store or transmit information. Examples of machine-readable media include electronic circuits, semiconductor memory devices, ROMs, flash memories, erasable ROMs (EROMs), floppy disks, CD-ROMs, optical disks, hard disks, optical fiber media, radio frequency (RF) links, etc. The code segment can be downloaded via a computer network such as the Internet, an intranet, etc.

[0172] It should be noted that, in this article, the terms "comprises", "includes" or any other variations thereof are intended to cover non-exclusive inclusion, so that a process, method, article or apparatus that includes a series of elements includes not only those elements, but also includes other elements not explicitly listed, or also includes elements that are inherent to such process, method, article or apparatus.

[0173] This article uses specific examples to illustrate the principles and implementation methods of this application. The above examples are only used to help understand the method and core ideas of this application. The above are only optional implementation methods of this application. It should be pointed out that due to the limitations of textual expression, there are objectively infinite specific structures. For ordinary technicians in this technical field, without departing from the principles of this application, they can also make several improvements, modifications or changes, and can also combine the above technical features in an appropriate manner; these improvements, modifications, changes or combinations, or the direct application of the concept and technical solution of this application to other occasions without improvement, should be regarded as the scope of protection of this application.

Claims

1. A sensor device, the sensor device comprising: A chamber; when a thin film including a plurality of nanopores is disposed in the chamber, the chamber is separated by the thin film into a first chamber and a second chamber, the second chamber including a plurality of mutually separated second sub-chambers, each of the second sub-chambers communicating with the first chamber through a corresponding nanopore; A first electrode disposed in the first chamber, the first electrode being connected to a common voltage terminal; A plurality of second electrodes respectively disposed in the plurality of second sub-chambers; The potential difference between the first electrode and the second electrode is used to drive an analyte to be measured through the corresponding nanopore and generate a sensing electrical signal; A bias voltage generation module for generating a bias voltage, wherein the bias voltage is less than or equal to the common voltage provided by the common voltage terminal; A first multiplexing module connected to the plurality of second electrodes, capable of selecting one of the plurality of second electrodes to communicate with the output terminal of the first multiplexing module to output a sensing electrical signal, and connecting the second electrodes not communicating with the output terminal of the first multiplexing module to the bias voltage generation module or the common voltage terminal; A signal processing module, the input terminal of the signal processing module being connected to the first multiplexing module, the signal processing module being capable of obtaining the state of the nanopore according to the sensing electrical signal output by the first multiplexing module.

2. The sensor device according to claim 1, wherein, The first multiplexing module includes: A first switch module, a plurality of first ends of the first switch module being respectively connected to the plurality of second electrodes, a second end of the first switch module being connected to the output terminal of the first multiplexing module; the first switch module is used to output the sensing electrical signal of one of the plurality of second electrodes; A second switch module, a plurality of first ends of the second switch module being respectively connected to the plurality of second electrodes, a second end of the second switch module being connected to the bias voltage generation module.

3. The sensor device according to claim 2, wherein, The first switch module includes: A plurality of sensing switches, each sensing switch being connected between the corresponding second electrode and the output terminal of the first multiplexing module; at any moment, at most one of the plurality of sensing switches is in a conducting state; The second switch module includes: A plurality of first bias switches, each first bias switch being connected between the corresponding second electrode and the bias voltage generation module.

4. The sensor device according to claim 3, wherein, A third end of the second switch module is connected to the common voltage terminal; the second switch module further includes: A plurality of second bias switches, each second bias switch being connected between the corresponding second electrode and the common voltage terminal, wherein the bias voltage generated by the bias voltage generation module is less than the common voltage provided by the common voltage terminal.

5. The sensor device according to claim 1, wherein, The sensor device further includes: A signal detection circuit connected between the first multiplexing module and the signal processing module for amplifying the sensing electrical signal from the first multiplexing module.

6. The sensor device according to claim 5, wherein, The sensor device includes a plurality of the first multiplexing modules; The signal detection circuit includes: A plurality of current amplification units, the input end of the current amplification unit being connected to the corresponding first multiplexing module; the current amplification unit is used for amplifying the sensed electrical signal output by the corresponding first multiplexing module; The sensor device further includes: A second multiplexing module, the second multiplexing module being connected to the output ends of the plurality of current amplification units, and being used for outputting the amplified sensed electrical signal from one of the plurality of current amplification units; and, An analog-to-digital conversion module, the input end of the analog-to-digital conversion module being connected to the output end of the second multiplexing module, and the output end of the analog-to-digital conversion module being connected to the input end of the signal processing module.

7. The sensor device according to claim 3 or 4, wherein, The sensor device further includes: A controller module, the input end of the controller module being connected to the output end of the signal processing module, and the gating signal end of the controller module being connected to the first multiplexing module; the controller module is used for generating a gating signal corresponding to one of the plurality of second electrodes and sending it to the first multiplexing module.

8. The sensor device according to claim 7, wherein, The controller module is connected to the bias voltage generation module; In the case that at least one nanopore is in a damaged state and the second switch module does not include a second bias switch, the controller module is used for driving the bias voltage generation module to generate a bias voltage equal to the common voltage.

9. The sensor device according to claim 7, wherein, In the case that at least one nanopore is in a damaged state and the second switch module includes a second bias switch, the controller module is used for driving the first multiplexing module to switch the second electrode corresponding to the damaged nanopore to be connected to the common voltage terminal.

10. An operation method of a sensor device, applied to the sensor device according to any one of claims 1-9, the method includes: Obtaining the states of a plurality of nanopores, and determining a target nanopore according to the states of the plurality of nanopores; Electrically connecting the second electrode corresponding to the target nanopore to the signal processing module, and connecting the second electrodes corresponding to the remaining nanopores to the bias voltage generation module or the common voltage terminal, so as to analyze and process the analyte to be measured through the sensed electrical signal generated when the analyte to be measured passes through the target nanopore.

11. The method of operating a sensor device according to claim 10, wherein, The obtaining the states of a plurality of nanopores and determining a target nanopore according to the states of the plurality of nanopores includes: Making the first multiplexing module sequentially electrically connect the second electrode corresponding to each nanopore to the signal processing module; Respectively determining the state of each nanopore according to the sensed electrical signal corresponding to each nanopore; Selecting the nanopore in the normal state as the target nanopore.

12. The method of operating a sensor device according to claim 10, wherein, The operation method of the sensor device further includes: When the second electrode corresponding to the target nanopore is electrically connected to the signal processing module, monitoring the state of the target nanopore according to the sensed electrical signal generated by the target nanopore; When the target nanopore is damaged, switching the second electrode corresponding to the target nanopore to be connected to the bias voltage generation module or the common voltage terminal.

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