Sensor module system

Abstract

To provide a sensor module system capable of inspecting the presence or absence of probe molecules on a sensor chip before measurement.SOLUTION: A sensor module system comprises a first sensor module including a probe molecule that responds to light irradiation with charge, and a second sensor module including no probe molecule. A first flow path is connected to one end side of the first sensor module, and a second flow path is connected to the other end side. A third flow path branching from the first flow path is connected to one end side of the second sensor module, and a fourth flow path joining the first flow path is connected to the other end side. A valve capable of opening and closing the third flow path is connected to a junction of the first flow path and the third flow path.SELECTED DRAWING: Figure 1A

Description

Technical Field

[0001] Embodiments of the present invention relate to a sensor module system.

Background Art

[0002] Before measuring a sensor chip, a system for inspecting the presence or absence of probe molecules on the sensor chip is required.

Summary of the Invention

Problems to be Solved by the Invention

[0003] Embodiments of the present invention provide a sensor module system capable of inspecting the presence or absence of probe molecules on a sensor chip before measurement.

Means for Solving the Problems

[0004] A sensor module system according to an embodiment includes a first sensor module 2 including probe molecules that respond to charges upon light irradiation, and a second sensor module 3 not including probe molecules. A first flow path is connected to one end side of the first sensor module, and a second flow path is connected to the other end side. A third flow path branched from the first flow path is connected to one end side of the second sensor module, and a fourth flow path that merges with the first flow path is connected to the other end side. A valve capable of opening and closing the third flow path is connected to a confluence portion of the first flow path and the third flow path.

Brief Description of the Drawings

[0005] [Figure 1A] FIG. 1A is a schematic diagram showing the configuration of a sensor module system according to the first embodiment. [Figure 1B] FIG. 1B is a schematic diagram showing a further configuration of the sensor module system according to the first embodiment. [Figure 1C] FIG. 1C is a schematic diagram showing another further configuration of the sensor module system according to the first embodiment. [Figure 2]Figure 2 is a diagram illustrating the configuration of the sensor module system of the first embodiment, where (a) is a schematic cross-sectional view of the first sensor module and (b) is a schematic cross-sectional view of the second sensor module. [Figure 3] Figure 3 is a schematic diagram showing the configuration of the sensor module system of the second embodiment. [Figure 4] Figure 4 is a schematic diagram showing the configuration of the sensor module system of the third embodiment. [Figure 5] Figure 5 is a schematic diagram showing another configuration of the sensor module system of the third embodiment. [Figure 6A] Figure 6A is a schematic diagram showing the configuration of the sensor module system of the fourth embodiment. [Figure 6B] Figure 6B is a schematic diagram showing another configuration of the sensor module system of the fourth embodiment. [Figure 7] Figure 7 is a flowchart illustrating a method for analyzing a target substance using the sensor module systems of the first to fourth embodiments. [Figure 8] Figure 8 is a graph showing the results of the buffer ion residue test using the second sensor module in the experimental results of Example 1. (a) shows the measurement results of the second sensor module equipped with a liquid film made of HEPES solution, (b) shows the measurement results of the second sensor module equipped with a liquid film made of pure water, and (c) shows the measurement results of the second sensor module equipped with a liquid film made of sodium chloride aqueous solution. [Figure 9] Figure 9 is a graph showing the results of the negative control experiment for buffer ion residue testing using the second sensor module, from the experimental results of Example 1. (a) shows the results of the negative control experiment for the second sensor module equipped with a liquid film made of HEPES solution, and (b) shows the results of the negative control experiment for the second sensor module equipped with a liquid film made of pure water. [Figure 10]Figure 10 is a graph showing the experimental results for Example 2, where (a) shows the results of a negative control experiment using a second sensor module equipped with a liquid film made of pure water, and (b) shows the measurement results of probe molecule testing using a second sensor module equipped with a probe molecule to which a fluorescent dye is bound. [Modes for carrying out the invention]

[0006] Various embodiments of the present invention will be described below with reference to the drawings. Each figure is an embodiment and a schematic diagram to facilitate understanding of it, and its shape, dimensions, ratios, etc. may differ from those of the actual product. These can be appropriately modified in the design, taking into consideration the following description and known technology.

[0007] (First Embodiment) The following explanation will use Figure 1, a schematic diagram showing the sensor module system of the first embodiment.

[0008] The sensor module system 1 according to the first embodiment comprises a first sensor module 2 equipped with a probe molecule that responds to light irradiation, and a second sensor module 3 not equipped with a probe molecule. A first flow path 4 is connected to one end of the first sensor module 2, and a second flow path 5 is connected to the other end. A third flow path 6 branching off from the first flow path 4 is connected to one end of the second sensor module 3, and a fourth flow path 7 merging with the first flow path 4 is connected to the other end. A valve 8 is provided at the junction of the first flow path 4 and the third flow path 6, allowing the third flow path 6 to be opened and closed. A valve 8 that allows the fourth flow path 7 to be opened and closed may also be connected at the junction 9 of the first flow path 4 and the fourth flow path 7. One end of the first flow path 4 is connected to the first module 2, and the other end is a liquid inlet for allowing liquid to flow into the interior.

[0009] The first sensor module 2 comprises a substrate 10, a sensitive film 11 disposed on the substrate 10, and a liquid film 12 disposed to cover the sensitive film 11, with probe molecules 13 solidified on the surface of the sensitive film 11. For example, if the first sensor module 2 is a type of FET sensor, the sensitive film 11 is disposed such that the gate electrode 14 is in contact with it via the liquid film 12, and a source electrode 15 is electrically connected to one end and a drain electrode 16 is electrically connected to the other end (see Figure 2(a)). A circuit for applying a voltage (i.e., gate voltage) is also connected to the gate electrode 14. A circuit for applying a voltage is also formed between the source electrode 15 and the drain electrode 16, and an ammeter (not shown) for measuring the drain current flowing through this circuit is placed there. The source electrode 15 and the drain electrode 16 are covered with an insulating protective film 17.

[0010] Unlike the first sensor module 2, the second sensor module 3 does not have probe molecules 13 immobilized on the surface 11a of the sensitive film. However, the other configurations are the same as those of the first sensor module 2. Specifically, the second sensor module 3 comprises a substrate 10, a sensitive film 11 disposed on the substrate 10, and a liquid film 12 disposed to cover the sensitive film 11 (see Figure 2(b)). Also, for example, if the first sensor module 2 is a type of FET sensor, the second sensor module 3 has a similar configuration. That is, the sensitive film 11 of the second sensor module 3 is disposed such that the gate electrode 14 is in contact with it via the liquid film 12, and a source electrode 15 is electrically connected to one end and a drain electrode 16 is electrically connected to the other end. A circuit for applying voltage (i.e., gate voltage) is connected to the gate electrode 14, and a circuit for applying voltage is also formed between the source electrode 15 and the drain electrode 16, and an ammeter (not shown) for measuring the drain current flowing through the circuit is arranged. The source electrode 15 and the drain electrode 16 are covered with an insulating protective film 17.

[0011] The first sensor module 2 and the second sensor module 3 are configured to be removable and replaceable from the sensor module system 1. In other words, the first sensor module 2 and the second sensor module 3 are components used as disposable chips or cassettes.

[0012] The liquid film 12 is positioned so that its surface 12a is in contact with the sample containing the target substance, and so as to cover the sensitive membrane 11 and immerse the probe molecules 13, which are immobilized on the surface 11a of the sensitive membrane. The liquid constituting the liquid film 12 may be a liquid with a composition depending on the usage state and purpose of the sensor module system 1. For example, when the sensor module system 1 is used to measure a target substance, the liquid film 12 may be composed of a liquid capable of dissolving the target substance. For example, when the sensor module system 1 is stored, the liquid film 12 may be composed of a liquid containing any reagents necessary for storage (e.g., stabilizers and pH adjusters).

[0013] The probe molecule 13 is a nucleic acid, peptide, or protein that functions as an aptamer, and may be of natural or artificial origin. Specifically, the probe molecule 13 may be a nucleic acid probe composed of, for example, single-stranded or double-stranded nucleic acids, or a probe composed of, for example, an enzyme peptide or protein. However, the probe molecule 13 in this embodiment has the characteristic of responding to charge when irradiated with light (for example, monochromatic light), as will be described later, and it is preferable that the electrical change is large. For example, the probe molecule 13 may be labeled with a fluorescent dye, or its backbone may contain a site that acts as a buffer ion or a site that has fluorescent properties.

[0014] In addition, the sensor module system 1 includes a light source 18 used for the buffer ion residue inspection and probe molecule inspection described later. The light source 18 is configured to irradiate the sensitive film surface 11a included in the first sensor module 2 and the second sensor module 3 with monochromatic light. Monochromatic light refers to light consisting of a single wavelength, and the wavelength in the embodiment is approximately 500 nm to 800 nm. The light source 18 may be common to the first sensor module 2 and the second sensor module 3, or may be separate for the first sensor module 2 and the second sensor module 3. That is, the sensor module system 1 may include a plurality of light sources. Further, the light source 18 may be incorporated and integrated into the first sensor module 2 and the second sensor module 3, or may be configured as a separate module. In other words, the light source 18 may be configured as part of an exchangeable chip.

[0015] The valve 8 is configured to be able to switch the open / closed state of a branch flow path (i.e., the third flow path 6) respectively connected to the downstream side of the first flow path 4, and includes, for example, a switching member. The switching member is configured to open or block the third flow path 6, for example, by a rotating operation. Further, by connecting a valve controller or the like to the valve 8 provided with such a switching member, it is possible to switch the open / closed state of the third flow path 6 by electrical control.

[0016] As shown in FIG. 1B, a cleaning liquid container 19 and a sample liquid container 20 may be provided upstream of the first flow path 4. A branch flow path is connected between the upstream end of the first flow path 4, the cleaning liquid container 19, and the sample liquid container 20, and a flow path switching valve 21 may be provided in the branch flow path. The valve controller of the flow path switching valve 21 is connected to the control circuit 22.

[0017] The cleaning liquid container 19 is a container that stores a liquid containing no buffer ions (for example, pure water), and may include a pump for transporting the cleaning liquid. The cleaning liquid flows from the cleaning liquid container 19 to the more downstream branch flow path and the first flow path 4.

[0018] The container 20 for the sample liquid is a container that houses the liquid to be inspected or the solution containing the inspection object for which the sensor module system 1 performs sensing as the sample liquid, and may include a pump for transporting the sample liquid. The sample liquid may contain a target substance or buffer ions. Since the inclusion of buffer ions in the sample liquid stabilizes the properties as a solution, noise components in sensing by the sensor module can be reduced. The sample liquid flows from the container 20 for the sample liquid to the downstream branch flow path and then to the first flow path 4.

[0019] Various operations of the sensor module system 1 (for example, analysis of the target substance, switching of the valve, and transportation of the liquid, etc.) can be realized by inputting a control signal to the valve controller. The control signal is output from a computer provided outside the sensor module system 1 or from the control circuit 22 included in the sensor module system 1. The control circuit 22 is composed of, for example, a CPU, a memory, a non-volatile storage storing various reference values and programs, etc. The control circuit 22 or the computer provided outside is connected to the output terminals of the sensor module (for example, various electrode terminals such as the source electrode 15 and the drain electrode 16).

[0020] The control circuit 22 or the computer provided outside can analyze the sensing data obtained by the measurement using the sensor module, and can determine whether the sample liquid contains the target substance, and can also determine whether the sensor module contains buffer ions. Furthermore, the determination results can be output in an arbitrary output format.

[0021] For example, the control circuit 22 (or the computer provided outside) can perform the controls described in the following (1) to (5): (1) The control circuit 22 controls the valve controller to adjust the flow path switching valve 21 so that the flow path connecting the first flow path 4 and the cleaning liquid container 19 becomes conductive (as a result, the cleaning liquid, i.e., a liquid that does not contain buffer ion components, is introduced into the first sensor module 2 and the second sensor module 3). (2) The control circuit 22 controls the light source to flash on the sensitive film of the first sensor module 2, or on the sensitive films of the first sensor module 2 and the second sensor module 3, at a desired time interval. (3) The control circuit 22 analyzes the sensing data obtained using the second sensor module 3 and determines whether or not buffer ion components are present in the first sensor module 2 and the second sensor module 3. For example, the control circuit 22 compares the value of the output signal obtained by sensing using the second sensor module 3 during light irradiation (e.g., current value or voltage value) with the value of the output signal obtained by sensing when light is not irradiated, and determines that buffer ion components remain in the second sensor module 3 if there is a difference between the two. Here, the determination of whether or not there is a difference may be performed by comparing the measured value of the fluctuation amount (or fluctuation amount per unit time) with a preset reference value. If it is determined that buffer ion components are present in the first sensor module 2, the control circuit 22 controls the valve controller to continue introducing cleaning fluid into the first sensor module 2 and the second sensor module 3. This control is maintained until it is determined that buffer ion components are not present in the first sensor module 2. If it is determined that buffer ion components are not present in the first sensor module 2, the control circuit 22 executes the control in (4) below. Furthermore, immediately before executing the control in (4), the control circuit 22 may control the valve controller to adjust the flow path switching valve 21 to close the flow path between the first flow path 4 of the branched flow path and the cleaning fluid container 22. (4) The control circuit 22 analyzes the sensing data of the first sensor module 2 and the second sensor module 3 and determines whether the probe molecule state of the first sensor module 2 is normal (probe molecule inspection). The determination is made, for example, by whether or not a reference amount of probe molecules is present. Specifically, the determination may be made by calculating the difference between the current value or voltage value of the signal obtained by sensing of the first sensor module 2 during light irradiation and the current value or voltage value of the signal obtained by sensing of the second sensor module 3 under the same conditions, and comparing the difference with a reference value. Alternatively, the state of the probe molecule of the first sensor module 2 may be determined to be normal if the current value or voltage value of the signal obtained by sensing of the first sensor module 2 fluctuates between the time of light irradiation and the time of non-light irradiation. In this case, the determination is made by comparing the amount of fluctuation (or the amount of fluctuation per unit time) with a reference value. (5) If the state of the probe molecule is determined to be normal in the control described in (4) above, the control circuit 22 controls the valve controller to adjust the flow path switching valve 21 to make electrical contact between the sample liquid container 20 and the first sensor module 2. As a result, the sample liquid is introduced into the first sensor module.

[0022] As shown in Figure 1C, a sample intake unit 23 may be provided as an alternative to the sample liquid container 20 shown in Figure 1B. The sample intake unit 23 is connected to the upstream end of the branched channel to which the washing solution container 19 and valve 21 are connected. The sample intake unit 23 brings a buffer-free liquid (e.g., pure water) introduced from the washing solution container 19 into contact with the sample (e.g., an atmosphere that may contain the target substance), and incorporates a portion of the sample into the buffer-free liquid. Thus, a buffer-free sample liquid is prepared in the sample intake unit 23. Note that the sample intake unit 23 can also be considered as the sample liquid container 20 if it contains the sample liquid.

[0023] The sensor module system 1, having the above configuration, includes a first sensor module 2 equipped with a probe molecule 13. By supplying a sample liquid containing the target substance to the sensor module system 1, it is possible to analyze whether or not the target substance is present in the sample. In this case, by closing the third channel 6 with the valve 8, the supply of liquid to both channels and, consequently, to the second sensor module system 3 is stopped. Therefore, the sample liquid that may contain the target substance, which is sent to the first channel 4, is introduced only into the first sensor module 2. After that, the liquid used for analysis in the first sensor module 2 is discharged to the outside through the second channel 5.

[0024] As described above, the sensor module system 1, which has been used to analyze a target substance in a sample liquid by supplying liquid, can be used to analyze another sample by replacing the first sensor module 2 and the second sensor module 3 with unused ones and cleaning the inside. In other words, the sensor module system 1 is configured to be reusable and capable of repeated measurements by replacing the tip and cleaning. Cleaning of the sensor module system 1 is performed by sending cleaning solution from the cleaning solution container 19 to the first channel 4, replacing the liquid contained in the sensor module system 1 with the cleaning solution, and filling any empty spaces with the cleaning solution. As will be described later, the sensor module system 1 after cleaning is subjected to buffer ion residue testing and then probe molecule testing. For this reason, a liquid that does not contain buffer ion components (e.g., pure water) is used as the cleaning solution.

[0025] The buffer ion residue test, as described later, is a measurement performed to determine whether or not buffer ion components are contained in the liquid flowing through or contained within the sensor module system 1, and is carried out using the second sensor module 3. Therefore, the second sensor module 3 is supplied with a liquid of the same quality as the liquid flowing through the other flow channels that make up the sensor module system 1 (for example, the first sensor module 2, the first flow channel 4, the second flow channel 5, the third flow channel 6, and the fourth flow channel 7, etc.). To achieve this, during the cleaning of the sensor module system 1, the valve 8 is controlled to open the third flow channel 6 and the fourth flow channel 7 to the first flow channel 4, and cleaning liquid is also supplied to the second sensor module 3.

[0026] Therefore, to explain the flow of the cleaning fluid during cleaning of the sensor module system 1, the cleaning fluid discharged from the liquid outlet is divided at valve 8 into a flow that continues through the first flow path 4 and a flow that goes to the third flow path 6. The cleaning fluid that branches off to the third flow path 6 passes through the second sensor module 3 and then the fourth flow path 7, and rejoins with the first flow path 4. The cleaning fluid that rejoins and flows through the first flow path 4 passes through the first sensor module 2 and is discharged through the second flow path 5.

[0027] The buffer ion residue inspection performed using sensor module system 1 will be described in detail below.

[0028] The buffer ion residue test is performed by applying a constant voltage to the sensor element of the second sensor module 3, which does not have a probe molecule, and irradiating it with monochromatic light, and measuring whether the current flowing through the sensor element changes before and after irradiation with monochromatic light. The determination is made if the current value of the sensor element changes when the irradiation of monochromatic light starts, the changed current value is maintained while the monochromatic light is irradiated, and the change in the current value disappears after the irradiation of monochromatic light ends, then it is determined that buffer ion components are present in the liquid film. Conversely, if no change in the current value of the sensor element is observed from the start to the end of the irradiation of monochromatic light, then it is determined that buffer ion components are not present in the liquid film. In other words, in the buffer ion residue test, the monochromatic light is controlled to blink at predetermined time intervals, and it is confirmed that the time interval of the blinking coincides with the time interval of the change in the current value.

[0029] Next, we will explain the principle by which the current flowing through a sensor element changes when monochromatic light is irradiated in the presence of buffer ions.

[0030] First, when monochromatic light is irradiated, it is thought that the charge near the surface of the sensor element will change. Here, buffer ions are ions that can stably exist in multiple charge states of different valencies. Therefore, when charge transfer occurs between them and graphene due to light irradiation, the state in which the valency has been changed by the exchanged charge is maintained for a certain period of time. In other words, the buffer ion component can hold the charge that has moved into the liquid film.

[0031] A change in the charge near the surface of a sensor element induces an electrostatic charge change in the sensor element in the opposite direction. This effect changes the electron occupancy of the sensor element, i.e., the Fermi level. The Fermi level indicates which electron orbitals (i.e., up to which energy level) are filled when electrons fill the electron orbitals starting from the lower energy levels. When the sensor element is made of graphene, a change in the Fermi level changes the carrier density, and consequently, the current value also changes (in other words, to change the Fermi level of graphene, for example, one can change the charge near the graphene surface).

[0032] Although buffer ions are released into the liquid and not fixed near the graphene surface, the change in current value is maintained if the above phenomenon continues to occur continuously. Therefore, it is thought that the change in current value is maintained while monochromatic light is irradiated. After that, when the light irradiation is turned off, the buffer ions with changed valence are released into the liquid, and the Fermi level, i.e., the current value, returns to its original state.

[0033] Furthermore, the reverse charge transferred by graphene is thought to disappear instantaneously because graphene is connected to both the source and drain electrodes. Therefore, the current change due to the transfer of charge by graphene is presumed to be too small to be observed. Consequently, if a current change occurs in graphene and that change is maintained, the most reasonable interpretation is that the Fermi level of the graphene is being modulated.

[0034] On the other hand, the surface of the sensor element of the first sensor module 2 is either labeled with a fluorescent dye or has probe molecules immobilized on it that contain buffer ion sites or sites with fluorescent properties. For example, when monochromatic light is shone on the surface of the sensor element of the first sensor module 2 equipped with probe molecules labeled with a fluorescent dye, electrons move from the highest occupied molecular orbital (HOMO) of the fluorescent dye to the graphene, or electrons move from the graphene to the lowest unoccupied molecular orbital (LUMO) of the fluorescent dye. In other words, the fluorescent dye becomes charged by light irradiation.

[0035] Because fluorescent dyes in this charged state do not possess electron-hole pairs, electron-hole recombination does not occur. Therefore, the fluorescent dye, and consequently the probe molecule, can maintain its charge for a certain period of time. As a result, the Fermi level in the graphene to which the probe molecule is bound is modulated, as described above, and the current value changes. Although electrons and holes do not recombine, they are still present in the liquid and can be discharged into the liquid after a certain period of time. Therefore, it is thought that the current value returns to its original value when light irradiation is turned off.

[0036] The above explains the presumed mechanism by which the buffer ion component generates the above-mentioned photoresponse. As will be discussed later, experimental results have been obtained that support this mechanism, making the hypothesis quite plausible.

[0037] The sensor module system 1 of this embodiment may be provided in its final product form with probe molecules solidified on the sensor element, and further with a water-soluble protective film coated on the sensor element to protect the probe molecules. However, depending on the storage conditions, the sensor module system 1 may unintentionally enter an undesirable state with respect to its probe molecules. Undesirable states include, for example, a state in which the solidified probe molecules peel off from the surface of the sensor element, a state in which the probe molecules deteriorate (change in quality), and a state in which the protective film removal is not completely completed and the probe molecules remain partially covered. Therefore, in order to ensure the reliability of the sensor, such as its sensitivity and accuracy, it is desirable to inspect the state of the probe molecules on the sensitive film 11 before analyzing a target substance using the sensor.

[0038] Conventionally, methods for confirming the state of probe molecules have been proposed that involve detecting changes in current values ​​that occur when probe molecules are immobilized on a sensor element, or conducting probe molecule detection experiments (i.e., positive controls) using a sample containing the target substance. However, these methods make it difficult to perform inspections on demand. In the case of inspections using positive controls, probe molecules that have captured the target substance contained in the positive control lose their capture ability. That is, when analysis is performed on a sample after inspection using a positive control, there are problems in that the sensitivity to the target substance in the sample decreases, and there is a risk of false detection. Furthermore, even if the sensor used for the positive control is cleaned in an attempt to eliminate such sensitivity reduction, there is a risk that the probe molecules may detach due to this cleaning operation.

[0039] Therefore, the inventors have found a method to detect probe molecules by their photoresponse, as described above, as a way to solve the problems of conventional probe molecule testing methods. Since the method of detecting probe molecules by photoresponse is non-contact and non-destructive, it can preserve the performance of the probe molecules, and it is simple and can be performed at any time. Accordingly, this method is very effective for quality assurance and stabilizing the detection of target substances in samples.

[0040] However, the inventors have now revealed that the photoresponse detection method also detects buffer ion components contained in the measurement environment (as described later in the examples). In other words, it is suggested that it is difficult to distinguish between the signals of both in a measurement environment where both are present.

[0041] Therefore, the inventors found that a sensor module system 1 according to the embodiment is used for detecting probe molecules. According to the sensor module system 1 according to the embodiment, since it has a first sensor module 2 and a second sensor module 3 configured as described above, buffer ion residue inspection and probe molecule inspection can be performed in the same flow path, and the influence of buffer ion residue as noise can be eliminated.

[0042] Specifically, by cleaning the sensor module system 1 until the disappearance of buffer ion residue is confirmed in the photoresponse detection using the second sensor module 3, the influence of buffer ion residue on the photoresponse detection in the first sensor module 2 can be eliminated. Consequently, in the first sensor module 2 of the sensor module system 1 according to the embodiment, it is possible to accurately confirm the state of the probe molecules, in particular whether or not the probe molecules are bound to the sensitive film.

[0043] In a further embodiment, the sensor module system 1 may be equipped with a feedback cleaning function that automatically cleans based on the results obtained from the buffer ion residue inspection. Specifically, the sensor module system 1 may include a measurement unit that monitors the current value of the sensitive membrane 11, a storage unit that stores the current value obtained from the measurement unit, a comparison unit that compares the value detected by the measurement unit with the value stored in the storage unit, and a control unit that controls whether or not to supply cleaning liquid (e.g., pure water) to the liquid outlet of the sensor module system 1 based on the results obtained from the comparison unit (none of which are shown). With such a configuration, the sensor module system 1 can be automatically cleaned, and contamination by buffer ion residue can be effectively prevented.

[0044] Furthermore, in a further embodiment, if only samples that are certain to be free of buffer ion components are supplied to the sensor module system 1, buffer ion residue testing is unnecessary, and therefore the sensor module system 1 does not need to include a second sensor module 3. In such a case, the sensor module 1 may be equipped with a first sensor module 2, a first channel 4, a second channel 5, and a light source for probe molecule testing and sample analysis.

[0045] (Second embodiment) Figure 3 is a schematic diagram showing the sensor module system of the second embodiment. In Figure 3, components similar to those described in Figure 1 in the first embodiment are denoted by the same reference numerals and their descriptions are omitted.

[0046] The sensor module system 200 of the second embodiment differs in that the second sensor module 3 is located downstream of the first sensor module 2. More specifically, in the second sensor module 3 of the sensor module system 200, a valve 8 is provided in the second flow path 5. Similar to the first embodiment, a third flow path 6 branches off from the second flow path 5 at the valve 8, and the third flow path 6 is connected to the upstream end of the first sensor module 3. The downstream end of the first sensor module 3 is connected to a fourth flow path 7, and the fourth flow path 7 merges with the second flow path 5 at a merging section 9.

[0047] When analyzing a target substance in a sample using the sensor module system 200, the supply of liquid to the second sensor module system 3 and subsequently to the fourth channel 7 is stopped by closing the third channel 6 with valve 8. Therefore, the liquid containing the sample delivered to the first channel 4 is introduced only into the first sensor module 2. After that, the liquid used for analysis in the first sensor module 2 is discharged to the outside through the second channel 5. Thus, when analyzing a target substance in a sample, the liquid containing the sample flows through the same channel as the sensor module system 1 of the first embodiment.

[0048] However, the flow of the cleaning fluid during cleaning of the sensor module system 200 differs from that of the sensor module system 1 in the first embodiment. The cleaning fluid discharged from the liquid outlet passes through the first flow path 4 and subsequently the first sensor module 2, and flows into the second flow path 5. At the valve 8, the flow branches into one that continues through the second flow path 5 and another that flows into the third flow path 6. The cleaning fluid that branches into the third flow path 6 passes through the second sensor module 3 and subsequently the fourth flow path 7, and rejoins the second flow path 5 at the confluence 9. The cleaning fluid flowing through the second flow path 5 passes through the second flow path 5 and is discharged from its downstream end.

[0049] In the second embodiment, the second sensor module 3 of the sensor module system 200 is located downstream of the first sensor module 2, so it can detect buffer ion residue in the liquid that has already passed through the first sensor module 2. Therefore, the second sensor module 3 can perform inspections that reflect the influence of buffer ion residue within the sensor module system 200 (including the first sensor module 2) upstream of the second sensor module 3.

[0050] In the first embodiment, the second sensor module 3 is located upstream of the first sensor module 2, so the liquid sent to the first sensor module 2 is used for detecting buffer ion residue. In other words, the detection of buffer ion residue performed by the first sensor module 2 in the first embodiment does not reflect the influence of buffer ion residue in the subsequent second sensor module 3.

[0051] However, when cleaning the sensor module systems of the first and second embodiments, a sufficient amount of cleaning solution is supplied and the cleaning is carried out over a sufficient period of time. Therefore, if buffer ion components are not detected on the upstream side, the possibility of buffer ion residue being present on the downstream side is low. Similarly, if buffer ion components are not detected on the downstream side, the possibility of buffer ion residue being present on the upstream side is low. Thus, although the objects on which buffer ion residue is detected differ strictly between the sensor module system 1 of the first embodiment and the sensor module system 20 of the second embodiment, both configurations have the same effect in that they allow for the understanding of the state of buffer ion residue throughout the entire sensor module system during probe molecular testing of the sensitive membrane.

[0052] (Third embodiment) Figure 4 is a schematic diagram showing the sensor module system of the third embodiment. In Figure 4, components similar to those described in Figure 1 in the first embodiment are denoted by the same reference numerals and their descriptions are omitted.

[0053] The sensor module system 300 of the third embodiment differs from the sensor module system 1 of the first embodiment in that the third sensor module 31 is provided in parallel with the second sensor module 2. More specifically, in the sensor module system 300, similar to the first embodiment, the third flow path 6 branches off from the first flow path 4 at a valve 8 provided in the first flow path 4. In addition, the third flow path 6 branches further and is connected to the upstream end of the first sensor module 3 and the upstream end of the third sensor module 31. Similarly, the fourth flow path 7 also branches and is connected to the downstream end of the first sensor module 3 and the downstream end of the third sensor module 31.

[0054] When analyzing a target substance in a sample using the sensor module system 300, valve 8 is closed to stop the supply of liquid to the third channel 6, the second sensor module system 3, and consequently, the fourth channel 7. Therefore, the liquid containing the sample delivered to the first channel 4 is introduced only into the first sensor module 2. After that, the liquid used for analysis in the first sensor module 2 is discharged to the outside through the second channel 5. Thus, when analyzing a target substance in a sample, the liquid containing the sample flows through the same channels as the sensor module system 1 of the first embodiment.

[0055] However, the flow of the cleaning fluid during cleaning of the sensor module system 300 differs from that of the sensor module system 1 in the first embodiment. The cleaning fluid discharged from the liquid outlet is divided at the valve 8 into a flow that continues through the first flow path 4 and a flow that goes to the third flow path 6. The cleaning fluid discharged to the third flow path 6 is further divided and goes to the second sensor module 3 and the third sensor module system 31. The liquids that have passed through the second sensor module 3 and the third sensor module system 31 merge and pass through the fourth flow path 7, and then merge with the first flow path 4. After that, the cleaning fluid passes through the first sensor module 2 and is discharged through the second flow path 5.

[0056] The third sensor module 31 is a sensor module for performing a reference measurement of the buffer ion residue inspection performed by the first sensor module 1. Here, the reference measurement in this embodiment refers to the measurement of the negative control of the buffer ion residue inspection. Specifically, in the reference measurement, the drain current flowing by applying the same voltage as in the buffer ion residue inspection is measured without irradiating with monochromatic light. Therefore, it is preferable that the third sensor module 31 has the same conditions as the first sensor module 1, except that it does not irradiate with light. Thus, it is preferable that the third sensor module 31 has the same configuration as the first sensor module 1. However, since light irradiation is not performed in the reference measurement, the third sensor module 31 does not need to be equipped with a light source.

[0057] Reference measurements allow us to confirm that the change in current value is due to irradiation with monochromatic light, thus enabling highly accurate buffer ion residue testing.

[0058] In a further embodiment, the third sensor module 31 may be connected in series with the first sensor module system 1, and may be positioned upstream or downstream of the first sensor module system 1. By connecting them in series, the liquid that has passed through one sensor module passes through the other sensor module, so that a more homogeneous liquid can be used for measurement. However, if the third sensor module 31 and the first sensor module system 1 are directly connected, there will be a time difference between when the liquid passes through one sensor module and when it reaches the other sensor module, and during that time it may be affected by stirring or other factors. In this respect, it is preferable to connect the third sensor module 31 and the first sensor module system 1 in parallel.

[0059] In a further embodiment, the third sensor module 31 of the sensor module system of the third embodiment may be configured to be provided in parallel with the second sensor module 2 of the sensor module system 200 of the second embodiment (see Figure 5). With such a configuration, as described in the second embodiment, it is possible to perform inspections that reflect the influence of buffer ion residue in the sensor module system 300 upstream of the second sensor module 3 (i.e., including the first sensor module 2).

[0060] (Fourth embodiment) Figures 6A and 6B are schematic diagrams showing a sensor module system according to the fourth embodiment. In Figures 6A and 6B, components similar to those described in Figure 1 in the first embodiment are denoted by the same reference numerals and their descriptions are omitted.

[0061] The fourth embodiment relates to a chemical sensor comprising multiple sensor modules, each of which was described in the first to third embodiments, on the same substrate or on the same chip.

[0062] The sensor module system 400 comprises multiple sensor elements on the same substrate 10, and each sensor element has the same configuration as the first sensor module 2 or the second sensor module 3 described in the first to third embodiments. That is, when each sensor element is a FET, each sensor element is provided with a source electrode 15 and a drain electrode 16, as described in the first embodiment. Also, as shown in Figure 6A, a first pad electrode Pd1 is connected to the source electrode 15, and a second pad electrode Pd2 is connected to the drain electrode 16.

[0063] Figure 6A shows a case where the sensor module system 400 has a total of three sensor elements (specifically, two first sensor modules 2 (CH2 and CH3 in Figure 4) and one second sensor module 3 (CH1 in Figure 4)), but there may be only one first sensor module 2 and one second sensor module 3. Also, the sensor module system 400 may have two or more first sensor modules 2 and two or more second sensor modules 3.

[0064] Furthermore, in the sensor module system 400, a portion of the first flow path 4, second flow path 5, third flow path 6, fourth flow path 7, and junction 9 described in the first to third embodiments may be formed on the same substrate 10. In the sensor module system 40, a valve 8 described in the first to third embodiments may be formed on the same substrate 10. Moreover, as shown in Figure 6B, the sensor module system 400 may be configured such that the second sensor module 3 is integrated with the first sensor module 2 and connected to the first flow path 4 and the second flow path 5, without providing the third flow path 6 and the fourth flow path 7.

[0065] As described in the first embodiment, the difference in configuration between the first sensor module 2 and the second sensor module 3 lies in whether or not they have probe molecules. When incorporating probe molecules into a sensor module, they can be formed by coating the surface of the sensitive film of a sensor module that does not have probe molecules (i.e., has the same configuration as the first sensor module) with a material containing probe molecules. Therefore, by preparing materials that contain probe molecules and materials that do not, and appropriately coating the sensor elements with these materials, it is possible to mount the first sensor module 2 and the second sensor module 3 on the same substrate. Alternatively, a material containing probe molecules may be prepared, and the sensor elements coated with this material may be mounted as the first sensor module 2, while the sensor elements without the coating may be mounted as the second sensor module 3.

[0066] The sensor module system of the fourth embodiment is provided with multiple first sensor modules 2 and second sensor modules 3 mounted on the same substrate, thus eliminating the need to assemble the system and making it easy to use. Furthermore, since it can be manufactured by the simple operation described above, it is also advantageous in terms of manufacturing costs. In addition, by making the chip characteristics between the two sensor modules the same, the reliability of the difference values ​​of each signal obtained from sensing by the first sensor module 2 and the second sensor module 3 is improved.

[0067] As a further embodiment, for example, a sensor module system may be manufactured by preparing materials containing different types of probe molecules and coating each sensor element with them, thereby providing multiple first sensor modules 2 with different target substances on the same substrate. For example, two types of materials, PG1 and PG2, may be prepared and used to coat sensor elements CH2 and CH3 in different ways.

[0068] Such a sensor module system allows for the detection of multiple types of target substances and the performance of buffer ion residue testing using a single sensor module system. This eliminates the need to assemble multiple systems and makes the system easier to use. Furthermore, because it can be manufactured through the simple operations described above, it is also advantageous in terms of manufacturing costs.

[0069] (Fifth embodiment) The method according to the fifth embodiment is a method for measuring a target substance using the sensor module systems according to the first to fourth embodiments in repeated use. The method according to the fifth embodiment will be described in detail with reference to Figure 7.

[0070] The method according to the fifth embodiment involves (S1) preparing a sensor module system comprising a first sensor module equipped with a probe molecule that responds to light irradiation, a second sensor module connected to the first sensor module and not equipped with a probe molecule, a valve for adjusting the liquid supply to the second sensor module, and a light source for irradiating the first and second sensor modules with monochromatic light; (S2) adjusting the valve of the sensor module system prepared in (S1) to shut off the liquid supply to the second sensor module; (S3) after (S2) supplying a sample to the first sensor module and measuring the target substance in the sample; (S4) after (S3) replacing the first sensor module and adjusting the valve to shut off the liquid supply to the second sensor module. (S5) The process includes enabling the supply of liquid; irradiating the second sensor module of the sensor module system, in which the first and second sensor modules were replaced in (S4), with monochromatic light to perform a buffer ion residue test, and supplying cleaning solution to the sensor module system until no buffer ion residue is detected in the test; (S6) After (S5), irradiating the first sensor module with monochromatic light to perform a probe molecule test, and comparing the obtained measurement value with a reference value; (S7) Adjusting the valve of the sensor module system, which was confirmed to meet the reference value in (S6), to shut off the liquid supply to the second sensor module; and (S8) After (S7), supplying a sample to the sensor module system and measuring the target substance in the sample.

[0071] Note that the sensor module in (S1) may be in contact with a solution containing buffer ions. The sample in (S3) may be a liquid containing buffer ions. If the sensor module is to be cleaned and reused after measurement, the sample remaining in the sensor module is removed by supplying the cleaning solution in (S5) without replacing the sensor module in (S4).

[0072] The buffer ion residue test and probe molecule test in the determination method according to the fifth embodiment can be performed using the procedure described in the first embodiment. Specifically, the buffer ion residue test can be performed by applying a voltage to the second sensor module, measuring a value indicating the electrical characteristics of the sensor element (e.g., the magnitude of the current), and detecting whether the electrical characteristics have changed before and after irradiating the sensor element with monochromatic light from the light source. On the other hand, the probe molecule test can be performed by applying a voltage to the first sensor module, measuring a value indicating the electrical characteristics of the sensor element (e.g., the magnitude of the current), and detecting whether the electrical characteristics have changed before and after irradiating the sensor element with monochromatic light from the light source.

[0073] Furthermore, the buffer ion residue test and probe molecule test may take the form of a qualitative measurement that determines the presence or absence of buffer ion components or probe molecules, or it may take the form of a quantitative measurement that determines their concentrations. In the qualitative measurement, a threshold obtained from preliminary experiments may be set, and the presence or absence of buffer ion components or probe molecules may be determined when the value exceeds this threshold. In the quantitative measurement, the correlation between known amounts of buffer ion components or probe molecules and the measured values ​​may be determined from the measured values ​​using this correlation.

[0074] As described in the first embodiment, buffer ion components can become noise in probe molecule testing. According to the determination method of the fifth embodiment, the first and second sensor modules are replaced in (S3), and the sensor module system is cleaned with a cleaning solution in (S4) while confirming that there is no influence from buffer ion residue. Subsequently, probe molecule testing is performed in (S5), so that probe molecules can be detected with higher accuracy. Consequently, the target substance can be detected accurately even when the sensor module system is used repeatedly.

[0075] Furthermore, the reference value in (S5) is an indicator that the sensor module system can accurately detect the target substance. The reference value is, for example, the value of the change in electrical characteristics obtained in a preliminary experiment using a sensor module system equipped with a sensor element that can detect the target substance with the desired accuracy and has a known probe molecule density. Alternatively, the correlation between the value of the change in electrical characteristics and the density may be determined in such a preliminary experiment, and the value determined from this correlation may be used as the reference value. Therefore, in (S5), by setting such a reference value and comparing it with the measured value obtained from the probe molecule test, it can be confirmed that the sensor module system prepared in (S4) can accurately detect the target substance if the measured value meets the reference value.

[0076] [example] The sensor module system described in the embodiment will be explained below using experimental data.

[0077] Example 1: Buffer ion residue inspection using a second sensor module • Preparation of three types of second sensor modules Three FET sensor elements, similar in structure to the second sensor module of the first embodiment, i.e., the sensor modules shown in Figure 2(b), were prepared. The sensor element in each sensor module is a single-layer graphene film. A voltage application circuit is connected to each sensor module, allowing a gate voltage to be applied between the gate electrode and the source electrode, and a drain voltage between the drain electrode and the source electrode. Although not shown, each sensor module is also equipped with an ammeter for measuring the drain current and a light source capable of emitting monochromatic light with a wavelength of approximately 350 nm to 800 nm. The slit length of the light source is 1.2 mm.

[0078] Each of the three second sensor modules prepared had a liquid film made of a different solute solution, which was used to coat a single-layer graphene film. Specifically, the three second sensor modules were: one with a liquid film made of pure water, one with a liquid film made of an aqueous sodium chloride solution, and one with a liquid film made of a buffer solution, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) solution. Ultrapure water was used as the pure water.

[0079] • Measurement using the second sensor module prepared. As described above, a constant voltage (=650mV) was applied to the three types of second sensor modules, and the change in drain current over time was measured. In addition, in measuring the change in drain current over time, monochromatic light of different wavelengths was irradiated for 30 seconds each, with a time interval of approximately 1 minute between irradiations, in the order of 800nm, 700nm, 600nm, and 500nm, and it was measured whether the value of the drain current changed.

[0080] ·result The results of the buffer ion residue test described above are shown in Figure 8. Figure 8(a) shows the measurement results for the second sensor module equipped with a liquid film made of HEPES solution, (b) shows the measurement results for the second sensor module equipped with a liquid film made of pure water, and (c) shows the measurement results for the second sensor module equipped with a liquid film made of sodium chloride aqueous solution.

[0081] Figures 8(a), (b), and (c) show a common trend: the drain current gradually decreases over time, independently of the timing of monochromatic light irradiation. This is a drift specific to the measurement of electrochemical phenomena.

[0082] However, referring to Figure 8(a), it was observed that when irradiation with monochromatic light of 800 nm, 700 nm, 600 nm, or 500 nm was started, the drain current value decreased, and this decreased state was maintained while each monochromatic light was irradiated, and the decreased value increased when the irradiation ended. On the other hand, referring to Figures 8(b) and (c), it can be seen that when monochromatic light was irradiated onto a second sensor module equipped with a liquid film made of pure water and a second sensor module equipped with a liquid film made of an aqueous sodium chloride solution, the drain current value did not change. Therefore, it was found that when buffer ion components are contained in the liquid film, the drain current value changes when irradiated with monochromatic light.

[0083] • Negative control experiment for buffer ion residue testing In the buffer ion residue inspection using the second sensor module in Example 1, a constant voltage (=650mV) was applied as a negative control to measure the change in drain current over time. A system without monochromatic light irradiation was also prepared and implemented. The negative control was performed on the second sensor module equipped with a liquid film made of pure water, and the second sensor module equipped with a liquid film made of HEPES solution.

[0084] ·result The results of the negative control experiment for Example 1 are shown in Figure 9. Figure 9(a) shows the results of the negative control experiment for the second sensor module equipped with a liquid film made of HEPES solution, and (b) shows the results of the negative control experiment for the second sensor module equipped with a liquid film made of pure water.

[0085] In both Figure 9(a) and (b), a gradual decrease in drain current was observed over time. However, compared to Figure 8(a) and (b), no significant change in current value was observed, unlike the change observed at the timing of light irradiation. Therefore, the change in current value observed in the buffer ion residue test in Example 1 was caused by irradiation with monochromatic light.

[0086] Example 2: Probe molecular inspection using the first sensor module • Preparation of two types of first sensor modules Two FET sensor elements, similar in structure to the first sensor module of the first embodiment, i.e., the sensor modules shown in Figure 2(a), were prepared. The sensor element in each sensor module is a single-layer graphene film, with several tens of base nucleic acid probes immobilized on its surface as probe molecules. A voltage application circuit is connected to each sensor module, allowing a gate voltage to be applied between the gate electrode and the source electrode, and a drain voltage between the drain electrode and the source electrode. Although not shown, each sensor module is also equipped with an ammeter for measuring the drain current and a light source capable of emitting monochromatic light with a wavelength of approximately 350 nm to 800 nm. The slit length of the light source is 1.2 mm.

[0087] • Negative control experiment for probe molecular testing As described above, pure water was supplied to the first sensor module, a constant voltage (=650mV) was applied, and the change in drain current over time was measured. In addition, in measuring the change in drain current over time, monochromatic light of different wavelengths was irradiated for 30 seconds each at intervals of approximately 1 minute, in the order of 800nm, 700nm, 600nm, and 500nm, and it was measured whether the value of the drain current changed.

[0088] ·result Figure 10(a) shows the results of the negative control experiment for probe molecular analysis. The negative control experiment shows that there is no significant change in the drain current before and after irradiation with monochromatic light.

[0089] • Binding of the fluorescent dye to the probe molecule of the first sensor module. An aqueous solution containing 100 μM rhodamine 6G (prepared with pure water) was added to the first sensor module used in the aforementioned negative control experiment. Since rhodamine 6G is a fluorescent dye, the addition of this aqueous solution allows rhodamine 6G to bind to the probe molecule of the first sensor module. Furthermore, after adding the rhodamine 6G-containing aqueous solution, the first sensor module was washed by supplying a sufficient amount of 8 mM sodium chloride aqueous solution to remove any rhodamine 6G that was not bound to the probe molecule. In other words, a first sensor module equipped with a probe molecule to which rhodamine 6G had been bound was prepared.

[0090] • Probe molecular testing using the first sensor module As described above, a constant voltage (=650mV) was applied to the first sensor module to which a fluorescent dye was bonded, and the change in drain current over time was measured. In addition, in measuring the change in drain current over time, monochromatic light of different wavelengths was irradiated for 30 seconds each at intervals of approximately 1 minute, in the order of 800nm, 700nm, 600nm, and 500nm, and it was measured whether the value of the drain current changed.

[0091] ·result The results of the probe molecule analysis are shown in Figure 10(b). Referring to Figure 10(b), it can be seen that a significant change in drain current occurred before and after irradiation with monochromatic light, which was not observed in the negative control experiment. Therefore, it was demonstrated that by binding a fluorescent dye to the probe molecule, detection of the probe molecule by irradiation with a single light source is possible.

[0092] While several embodiments of the present invention have been described, these embodiments are presented as examples only and are not intended to limit the scope of the invention. These embodiments can be carried out in a variety of other forms, and various omissions, substitutions, modifications, and combinations are possible without departing from the spirit of the invention. These embodiments and their variations are included in the scope and spirit of the invention, as well as in the claims and their equivalents. The invention as described in the original claims of the patent application is listed below. [1] A first sensor module comprising a probe molecule that responds to light irradiation with charge, A second sensor module that does not include the aforementioned probe molecule and A first flow path connected to one end of the first sensor module, A second flow path connected to the other end of the first sensor module, A third flow path branches off from the first flow path and is connected to one end of the second sensor module, A fourth flow path is connected to the other end of the second sensor module and merges with the first flow path, A valve capable of opening and closing the third flow path is positioned at the junction of the first flow path and the third flow path. A sensor module system equipped with the following features. [2] The third channel and the fourth channel each further include branch channels, The system further comprises a third sensor module connected to the branch channel of the third channel and the branch channel of the fourth channel. The sensor module system described in [1]. [3] A first sensor module comprising a probe molecule that responds to light irradiation with charge, A second sensor module that does not include the aforementioned probe molecule and A first flow path connected to one end of the first sensor module, A second flow path connected to the other end of the first sensor module, A third flow path branches off from the second flow path and is connected to one end of the second sensor module, A fourth channel is connected to the other end of the second sensor module and merges with the second channel, A valve capable of opening and closing the third flow path is positioned at the junction of the second flow path and the third flow path. A sensor module system equipped with the following features. [4] The third channel and the fourth channel each further include branch channels, The system further comprises a third sensor module connected to the branch channel of the third channel and the branch channel of the fourth channel. The sensor module system described in [3]. [5] The first sensor module includes a first sensitive film and a first source electrode and a first drain electrode connected to both ends of the first sensitive film. The second sensor module includes a second sensitive membrane and a second source electrode and a second drain electrode connected to both ends of the second sensitive membrane. The system further comprises a light source for irradiating the first sensitive film and the second sensitive film with light. A sensor module system described in any one of [1] to [4]. [6] A second valve connected to the other end of the first flow path, A first branch channel and a second branch channel are connected to the other end of the first channel via the second valve, A first container for containing a sample is connected to the other end of the first branch channel, A second container for containing cleaning fluid is connected to the other end of the second branch channel, Furthermore, The sensor module system according to [5], wherein the cleaning solution is a liquid that does not contain buffer ion components. [7] A control circuit, a valve controller for opening and closing the second valve, It further possesses, The control circuit controls the valve controller, as described in [6], the sensor module system. [8] The aforementioned control circuit is To open the second branch channel and connect the first channel and the second container, Control the valve controller, The sensor module system according to [7], which determines whether the signal value output from the second sensor module has changed between the time of light irradiation and the time of non-light irradiation, and controls the valve controller to close the second branch channel and prevent conduction between the first channel and the second container if it is determined that the signal value has not changed. [9] The aforementioned control circuit is To open the second branch channel and connect the first channel and the second container, Control the valve controller, The signal value output from the second sensor module changes between the time of light irradiation and the time of non-light irradiation. Determine whether or not it moved. The signal value output from the first sensor module changes between the time of light irradiation and the time of non-light irradiation. Determine whether or not it moved, and, It is determined that the signal value of the second sensor module does not change, and the first When it is determined that the signal value of the sensor module has changed, the first branch channel is opened. The valve controller is used to connect the first flow path and the first container. control The sensor module system described in [7].

[10] The aforementioned control circuit is The signal value output from the second sensor module is the same for when light is irradiated and when light is not irradiated. The signal value output from the first sensor module does not fluctuate between light illumination and non-light illumination, and the signal value output from the first sensor module does not fluctuate between light illumination and non-light illumination. When the probe fluctuates between the time of injection and the time of injection, it is determined that the probe is in a normal state, [7] The sensor module system described.

[11] The sample is a liquid containing buffer ion components, as described in [7]. Tem.

[12] The sensor module system according to [7], wherein the light source emits monochromatic light.

[13] The first sensor module and the second sensor module are provided on the same substrate. The sensor module system described in [1] or [3].

[14] A sensor module system for measuring a target substance in a sample, The device comprises a sensitive film having probe molecules that capture a target substance and respond to light irradiation with charge. A first sensor module and a second sensor module comprising a sensitive film that does not have the probe molecule A circuit board with a sensor module mounted on it, A light source that irradiates the sensitive film with monochromatic light, A first flow path connected to one end of the first sensor module, A second flow path connected to the other end of the first sensor module, The other end of the first flow path is connected to a container for holding cleaning fluid, A module system.

[15] (S1) A sensor module system comprising: a first sensor module equipped with a probe molecule that responds to light irradiation; a second sensor module connected to the first sensor module and not equipped with the probe molecule; a valve for adjusting the liquid supply to the second sensor module; and a light source for irradiating the first sensor module and the second sensor module with monochromatic light; (S2) Adjust the valve of the sensor module system prepared in (S1) above to shut off the liquid supply to the second sensor module; (S3) After (S2), supply a sample to the first sensor module and measure the target substance in the sample; (S4) After (S3), adjust the valve to enable the supply of liquid to the second sensor module; (S5) After (S4), the second sensor module is irradiated with monochromatic light to perform a buffer ion residue inspection, and cleaning solution is supplied to the sensor module system until no buffer ion residue is detected in the inspection; (S6) After (S5), the first sensor module is irradiated with monochromatic light to perform probe molecular testing, and the obtained measured value is compared with the reference value; (S7) Adjust the valve of the sensor module system that has been confirmed to meet the reference value in (S6) above to shut off the liquid supply to the second sensor module; and (S8) After (S7), supply a sample to the sensor module system and measure the target substance in the sample; A method for analyzing target substances, including [specific details omitted]. [Explanation of Symbols]

[0093] 1...Sensor module system, 2...First sensor module, 3...Second sensor module, 4...First channel, 5...Second channel, 6...Third channel, 7...Fourth channel, 8...Valve, 9...Confluence

Claims

1. A first sensor module comprising a probe molecule that responds to light irradiation with charge, A second sensor module that does not include the aforementioned probe molecule, A first flow path whose downstream end is connected to one end of the first sensor module, A second flow path whose upstream end is connected to the other end of the first sensor module, A third flow path, the upstream end of which branches off from the first flow path and the downstream end of which is connected to one end of the second sensor module, A fourth flow path whose upstream end is connected to the other end of the second sensor module, and whose downstream end merges with the first flow path, A valve capable of opening and closing the third flow path is positioned at the junction of the first flow path and the third flow path. A sensor module system equipped with the following features.

2. The third channel and the fourth channel each further include branch channels, The system further comprises a third sensor module connected to the branch channel of the third channel and the branch channel of the fourth channel. The sensor module system according to claim 1.

3. A first sensor module comprising a probe molecule that responds to light irradiation with charge, A second sensor module that does not include the aforementioned probe molecule, A first flow path whose downstream end is connected to one end of the first sensor module, A second flow path whose upstream end is connected to the other end of the first sensor module, A third flow path, the upstream end of which branches off from the second flow path and the downstream end of which is connected to one end of the second sensor module, A fourth flow path whose upstream end is connected to the other end of the second sensor module, and whose downstream end merges with the second flow path, A valve capable of opening and closing the third flow path is positioned at the junction of the second flow path and the third flow path. A sensor module system equipped with the following features.

4. The third channel and the fourth channel each further include branch channels, The system further comprises a third sensor module connected to the branch channel of the third channel and the branch channel of the fourth channel. The sensor module system according to claim 3.

5. The first sensor module includes a first sensitive membrane and a first source electrode and a first drain electrode connected to both ends of the first sensitive membrane. The second sensor module includes a second sensitive membrane and a second source electrode and a second drain electrode connected to both ends of the second sensitive membrane. The system further comprises a common light source for irradiating the first sensitive film and the second sensitive film with light, or a plurality of separate light sources. A sensor module system according to any one of claims 1 to 4.

6. A second valve connected to the upstream end of the first flow path, A first branch channel and a second branch channel are connected to the upstream end of the first channel via the second valve, A first container for containing a sample is connected to the other end of the first branch channel, A second container for containing cleaning fluid is connected to the other end of the second branch channel, Furthermore, The sensor module system according to claim 5, wherein the cleaning solution is a liquid that does not contain buffer ion components.

7. A control circuit, a valve controller for opening and closing the second valve, It further possesses, The sensor module system according to claim 6, wherein the control circuit controls the valve controller.

8. The aforementioned control circuit is The valve controller is controlled to open the second branch channel and connect the first channel and the second container. The sensor module system according to claim 7, which determines whether the signal value output from the second sensor module has changed between the time of light irradiation and the time of non-irradiation, and controls the valve controller to close the second branch channel and prevent conduction between the first channel and the second container when it is determined that the signal value has not changed.

9. The aforementioned control circuit is The valve controller is controlled to open the second branch channel and connect the first channel and the second container. The system determines whether the signal value output from the second sensor module has changed between the time of light irradiation and the time of non-light irradiation. The system determines whether the signal value output from the first sensor module has changed between the time of light irradiation and the time of non-light irradiation, and When it is determined that the signal value of the second sensor module does not change, and when it is determined that the signal value of the first sensor module has changed, the valve controller is controlled to open the first branch channel and connect the first channel and the first container. The sensor module system according to claim 7.

10. The aforementioned control circuit is The sensor module system according to claim 7, wherein the probe molecule is determined to be in a normal state when the signal value output from the second sensor module does not fluctuate between light irradiation and non-light irradiation, and the signal value output from the first sensor module fluctuates between light irradiation and non-light irradiation.

11. The sensor module system according to claim 7, wherein the sample is a liquid containing buffer ion components.

12. The sensor module system according to claim 7, wherein the common light source or the separate plurality of light sources emit monochromatic light.

13. The sensor module system according to claim 1 or 3, wherein the first sensor module and the second sensor module are provided on the same substrate.

14. A sensor module system for measuring a target substance in a sample, A substrate on which a first sensor module having a sensitive film that captures a target substance and has probe molecules that respond to light irradiation with charge, and a second sensor module having a sensitive film that does not have the probe molecules are mounted, A common light source that irradiates monochromatic light onto the sensitive film of the first sensor module and the sensitive film of the second sensor module, or a plurality of separate light sources, A first flow path whose downstream end is connected to one end of the first sensor module, A second flow path, the upstream end of which is connected to the other end of the first sensor module, A sensor module system comprising a container for containing cleaning fluid, connected to the upstream end of the first flow path.

15. (S1) A sensor module system comprising: a first sensor module equipped with a probe molecule that responds to light irradiation; a second sensor module fluidly connected to the first sensor module and not equipped with the probe molecule; a valve for adjusting the liquid supply to the second sensor module; and a common light source or a plurality of separate light sources for irradiating the first sensor module and the second sensor module with monochromatic light; (S2) Adjust the valve of the sensor module system prepared in (S1) above to shut off the liquid supply to the second sensor module; (S3) After (S2), supply a sample to the first sensor module and measure the target substance in the sample; (S4) After (S3), adjust the valve to enable the supply of liquid to the second sensor module; (S5) After (S4), the second sensor module is irradiated with monochromatic light to perform a buffer ion residue inspection, and cleaning solution is supplied to the sensor module system until no buffer ion residue is detected in the inspection; (S6) After (S5), the first sensor module is irradiated with monochromatic light to perform probe molecular testing, and the obtained measured value is compared with the reference value; (S7) Adjust the valve of the sensor module system that has been confirmed to meet the reference value in (S6) above to shut off the liquid supply to the second sensor module; and (S8) After (S7), supply a sample to the sensor module system and measure the target substance in the sample; A method for analyzing target substances, including [specific details omitted].

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