Sensor system and method of evaluating sensor element

Abstract

To provide a sensor system which enables evaluation of the quality of a sensor element, and a method of evaluating the sensor element.SOLUTION: A sensor system is provided, comprising a sensing unit, probe molecules provided on a surface of the sensing unit, a sensor element comprising first and second electrodes electrically connected to the sensing unit, and a processing unit configured to apply a voltage between the first and second electrodes to evaluate the quality of the sensor element from electrical characteristics of the sensor element.SELECTED DRAWING: Figure 2

Description

[Technical field]

[0001] SUMMARY OF THE DISCLOSURE The present invention relates to a sensor system and a method for evaluating a sensor element. [Background technology]

[0002] For example, a sensor element in which the surface of graphene is functionalized with probe molecules has been proposed, but an inspection system for detecting defective elements has not yet been established. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Patent Publication No. 2022-132804 Summary of the Invention [Problem to be solved by the invention]

[0004] An object of the embodiments of the present invention is to provide a sensor system capable of evaluating the quality of a sensor element and a method for evaluating a sensor element. [Means for solving the problem]

[0005] According to an embodiment of the present invention, a sensor system includes a sensor element having a sensitive part, a probe molecule located on a surface of the sensitive part, and a first electrode and a second electrode electrically connected to the sensitive part, and a processing device that applies a voltage between the first electrode and the second electrode and evaluates the quality of the sensor element based on the electrical characteristics of the sensor element.

[0006] According to an embodiment of the present invention, a method for evaluating a sensor element includes a method for evaluating the quality of a sensor element based on the electrical characteristics of the sensor element in which a probe molecule is located on the surface of a sensitive part and a voltage is applied between a first electrode and a second electrode electrically connected to the sensitive part. [Brief description of the drawings]

[0007] [Figure 1] 1 is a schematic configuration diagram of a sensor system according to an embodiment. [Diagram 2] FIG. 2 is a schematic configuration diagram of a sensor unit according to an embodiment. [Diagram 3] 3(a) is a graph showing the Id-Vg characteristics of a good element, and (b), (c), and (d) are schematic diagrams showing the states of the probe molecules at points b, c, and d in FIG. 3(a), respectively. [Figure 4] 4(a) is an Id-Vg characteristic diagram for a defective element, and (b), (c), and (d) are schematic diagrams showing the state of the probe molecules at points b, c, and d in FIG. 4(a), respectively. [Diagram 5] 1 is a graph showing the measurement results of ΔId for Samples 1 to 5. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0008] Each embodiment will be described below with reference to the drawings. The drawings are schematic or conceptual, and the relationship between the thickness and width of each part, the size ratio between parts, etc. are not necessarily the same as those in reality. Even when the same part is shown, the dimensions and ratios of each part may be different depending on the drawing. Furthermore, the same reference numbers are used to refer to the same or similar elements.

[0009] 1, the sensor system of the embodiment includes a sensor unit 30 and a processing device 100. The processing device 100 includes, for example, a calculation device such as a CPU, a storage device, a power supply device that generates a voltage to be applied to the sensor unit 30, and a device that reads the electrical characteristics of the sensor unit 30. The processing device 100 processes an input signal and controls the operation of the sensor unit 30 according to, for example, software stored in the storage device. The processing device 100 determines whether the sensor element 50 is good or bad.

[0010] As shown in FIG. 2, the sensor unit 30 has a sensor element 50. The sensor element 50 has a sensitive part 20, a probe molecule 32, a first electrode 41, and a second electrode 42. The sensitive part 20 has electrical sensitivity to the proximity of a target molecule. For example, the sensitive part 20 includes graphene, and the sensor element 50 has a graphene field effect transistor (GFET) structure. Note that, as the sensitive part 20, for example, a carbon nanotube can be used in addition to graphene.

[0011] The sensitive part 20, the first electrode 41, and the second electrode 42 are supported on a substrate 10. The substrate 10 is, for example, a silicon substrate. The sensitive part 20 can be provided on the substrate 10 via an undercoat film. For example, a silicon oxide film can be used as the undercoat film. The undercoat film can also have a function of a chemical catalyst for forming graphene.

[0012] The first electrode 41 can function as a drain electrode in the FET, and the second electrode 42 can function as a source electrode in the FET. The first electrode 41 and the second electrode 41 are electrically connected to the sensitive part 20. When a voltage is applied between the first electrode 41 and the second electrode 42 by the power supply 44, a current (drain current) Id flows between the first electrode 41 and the second electrode 42 through the sensitive part 20. The sensor system can include a measuring device 45 that measures the drain current Id.

[0013] The probe molecule 32 is located on the surface of the sensitive part 20. The probe molecule 32 is located on the surface of the sensitive part 20 means that the probe molecule 32 is bound, adsorbed, or close to the surface of the sensitive part 20 by chemical or charge attraction, π-π interaction, cation-π interaction, hydrophobic interaction, or the like, and the probe molecule 32 is constrained on the surface of the sensitive part 20. The probe molecule 32 includes at least one of a protein, a peptide, an antibody, a DNA aptamer, or a biomolecule derived from these, for example. The probe molecule 32 can be located on the surface of the sensitive part 20 via, for example, a linker (or a scaffold molecule) 33. For example, pyrene can be used as the linker 33.

[0014] As described later, a solution containing the sample atmosphere is supplied to the surface of the sensitive part 20. Alternatively, the sample atmosphere may be supplied as a gas phase to the surface of the sensitive part 20. The probe molecule 32 can specifically recognize a target molecule that may be contained in the sample atmosphere, or can specifically interact with the target molecule. When the probe molecule 32 recognizes or captures the target molecule, the target molecule approaches the surface of the sensitive part 20, and the electronic state of the sensitive part 20 changes due to the charge of the target molecule or the structural change of the probe molecule 32 caused by capturing the target molecule. By detecting this as a change in the drain current Id, the presence and concentration of the target molecule in the sample atmosphere can be known.

[0015] The processing device 100 controls the power supply 44 to apply a voltage between the first electrode 41 and the second electrode 42. The processing device 100 also evaluates the quality of the sensor element 50 from the electrical characteristics of the sensor element 50 obtained by the measuring device 45. This makes it possible to remove defective elements and suppress erroneous detection of the presence and concentration of target molecules in the sample atmosphere.

[0016] A specific example of a method for evaluating the electrical characteristics and quality of the sensor element 50 will be described below.

[0017] The sensor system of the embodiment may further include a first liquid supply mechanism that supplies the liquid 31 to the surface of the sensitive part 20, and a gate electrode 43 that applies a voltage to the liquid 31 supplied to the surface of the sensitive part 20. The first liquid supply mechanism will be described later with reference to FIG.

[0018] 2, the surface of the sensitive part 20 and the probe molecule 32 are immersed in a liquid 31. This can improve the ability of the probe molecule 32 to capture a target molecule when the probe molecule 32 is a molecule derived from a living organism. The liquid 31 is, for example, an aqueous solution, and more specifically, a buffer solution.

[0019] The first electrode 41 and the second electrode 42 are covered with, for example, an insulating film (not shown) so that the first electrode 41 and the second electrode 42 are not in direct contact with the liquid 31.

[0020] When the above-mentioned drain current is Id and the voltage of the gate electrode 43 is Vg, the Id-Vg characteristic can be used as an electrical characteristic that serves as an index for evaluating the quality of the sensor element 50.

[0021] An example of the Id-Vg characteristics is shown in FIG. 3(a) and FIG. 4(a).

[0022] The processing device 100 evaluates the quality of the sensor element 50, for example, by comparing a first Id-Vg characteristic I (solid line) when Vg is swept from a negative voltage to a positive voltage with a second Id-Vg characteristic II (dashed line) when Vg is swept from a positive voltage to a negative voltage.

[0023] For example, the second electrode 42 is grounded, and a voltage of 5 mV is applied to the first electrode 41 from the power supply 44. In this state, the voltage Vg of the gate electrode 43 is swept from −500 mV to +350 mV in 10 mV steps, and Id is measured to obtain a first Id-Vg characteristic I. Also, the voltage Vg is swept from +350 mV to −500 mV in 10 mV steps, and Id is measured to obtain a second Id-Vg characteristic II.

[0024] Fig. 3(a) is an example of the Id-Vg characteristics of a good element, and Fig. 4(a) is an example of the Id-Vg characteristics of a bad element. It was confirmed that in the bad element, the difference ΔId in Id when Vg in the first Id-Vg characteristics I and the second Id-Vg characteristics II is the same value tends to be larger than ΔId in the good element.

[0025] Therefore, the processing device 100 can evaluate the quality of the sensor element 50 from the difference ΔId in Id when Vg in the first Id-Vg characteristic I and the second Id-Vg characteristic II is the same value. The processing device 100 can output the quality of the sensor element 50 through an interface (not shown). When the sensor element 50 is evaluated as a good product, the processing device 100 executes a sensing operation using the sensor element 50. When the sensor element 50 is evaluated as a defective product, the processing device 100 does not execute a sensing operation using the sensor element 50 or stops the sensing operation.

[0026] ΔId was measured for five samples 1 to 5. The results are shown in Figure 5. In each sample, the sensor element has a GFET structure using graphene as the sensing part. A cocaine aptamer (a nucleic acid aptamer capable of specifically recognizing or interacting with cocaine molecules) was used as the probe molecule. The graphene surface and the probe molecule were immersed in phosphate buffered saline.

[0027] The difference ΔId in Id when Vg was 0 mV between the first Id-Vg characteristic I and the second Id-Vg characteristic II measured under the above-mentioned conditions was measured. The ΔId of sample 1 was 0.0009 μA, the ΔId of sample 2 was 0.0036 μA, the ΔId of sample 3 was 0.068 μA, the ΔId of sample 4 was 0.090 μA, and the ΔId of sample 5 was 0.15 μA.

[0028] After measuring the ΔId, methyl benzoate was dissolved in phosphate buffered saline for each of Samples 1 to 5. The molar concentration of methyl benzoate in this methyl benzoate solution was 100 μM. Samples 1 and 2 showed a large change in Id before and after the addition of methyl benzoate, and responded to methyl benzoate. Therefore, Samples 1 and 2 can be considered as good elements. Samples 3 to 5 did not show a large change in Id before and after the addition of methyl benzoate, and did not respond to methyl benzoate. Therefore, Samples 3 to 5 can be considered as bad elements.

[0029] From the results of FIG. 5, the quality of the sensor element can be evaluated by the magnitude of ΔId in the first Id-Vg characteristic I and the second Id-Vg characteristic II. For example, in the example of FIG. 5, ΔId=0.04 μA can be set as the threshold for determining quality. The processing device 100 compares the threshold stored in the storage device 200 with the actually measured ΔId, and determines that the element is good if ΔId is equal to or less than 0.04 μA, and determines that the element is bad if ΔId is greater than 0.04 μA. Preferably, ΔId=0.01 μA can be set as the threshold for determining quality. If more accuracy is required, ΔId=0.006 μA can be set as the threshold for determining quality.

[0030] 4(a), which shows the Id-Vg characteristics for a defective element, ΔId between the first Id-Vg characteristics I and the second Id-Vg characteristics II when Vg is 0 or negative is larger than ΔId between the first Id-Vg characteristics I and the second Id-Vg characteristics II when Vg is positive. Therefore, the processing device 100 can improve the accuracy of the pass / fail judgment by evaluating the pass / fail of the sensor element 50 from the difference ΔId in Id when Vg is 0 or negative.

[0031] The minimum value of the Id-Vg characteristic is the charge neutral point (CNP), which is the point where the carriers (electrons or holes) contributing to conduction change. According to FIG. 4(a), in a region where Vg is lower than the value at the charge neutral point, the difference between the first Id-Vg characteristic I and the second Id-Vg characteristic II becomes large. Therefore, it is preferable to evaluate the quality of the sensor element 50 from ΔId in a region where Vg is lower than the value at the charge neutral point.

[0032] Furthermore, the processing device 100 may evaluate the quality of the sensor element 50 from the difference ΔVg between Vg when Id in the first Id-Vg characteristic I and the second Id-Vg characteristic II is the same value. As a threshold for determining quality, ΔVg=10 mV when Id=1 μA can be set. When ΔVg is 10 mV or less or less than 10 mV, the element is determined to be good, and when ΔVg is greater than 10 mV, the element is determined to be bad. More preferably, as a threshold for determining quality, ΔVg=2 mV when Id=1 μA can be set.

[0033] The sensor system of the embodiment may further include a storage device 200 (shown in FIG. 1) that stores the result of evaluation of the quality of the sensor element 50 by the processing device 100. A threshold value for determining quality may also be stored in the storage device 200.

[0034] FIG. 3(b) is a schematic diagram showing the state of the probe molecule 32 at point b (Vg<0) of the first Id-Vg characteristic I shown in FIG. 3(a). FIG. 3(c) is a schematic diagram showing the state of the probe molecule 32 at point c (Vg=near CNP) of the first Id-Vg characteristic I shown in FIG. 3(a). FIG. 3(d) is a schematic diagram showing the state of the probe molecule 32 at point d (Vg<0) of the second Id-Vg characteristic II shown in FIG. 3(a).

[0035] As shown in Figures 3(a) to 3(d), in a good element, even if Vg varies, the probe molecule 32 remains in close proximity to the surface of the sensitive part (graphene) 20, and it is considered that the sensitive part 20 is likely to respond to the target molecule captured by the probe molecule 32.

[0036] FIG. 4(b) is a schematic diagram showing the state of the probe molecule 32 at point b (Vg<0) of the first Id-Vg characteristic I shown in FIG. 4(a). FIG. 4(c) is a schematic diagram showing the state of the probe molecule 32 at point c (Vg=near CNP) of the first Id-Vg characteristic I shown in FIG. 4(a). FIG. 4(d) is a schematic diagram showing the state of the probe molecule 32 at point d (Vg<0) of the second Id-Vg characteristic II shown in FIG. 4(a).

[0037] 4(a) to 4(d), in a defective element, the binding force of the probe molecule 32 to the surface of the sensitive part (graphene) 20 is weak, and it is considered that the probe molecule 32 having a charge (e.g., a negative charge) approaches or moves away from the surface of the sensitive part 20 due to electrostatic attraction in the liquid 31 as Vg varies. If the trap site of the target molecule of the probe molecule 32 is away from the surface of the sensitive part 20, it is considered that even if the target molecule is captured at the trap site, it is difficult for the sensitive part 20 to respond to the charge of the target molecule.

[0038] 1, the sensor system of the embodiment may further include a target molecule capturing unit 62 that exposes a specimen atmosphere containing hydrophobic target molecules to a hydrophilic organic solvent, a mixing unit 91 that mixes the organic solvent containing the target molecules with an aqueous solution to prepare a specimen liquid, and a second liquid supply mechanism that supplies the specimen liquid to the surface of the sensitive part 20. The second liquid supply mechanism may include, for example, a pipe 95 that connects the mixing unit 91 and the sensor unit 30, and a valve 94 connected to the pipe 95.

[0039] The target molecule capturing unit 62 is connected to a pipe 61 and a pipe 64. An intake and exhaust device 63 is connected to the pipe 64. The intake and exhaust device 63 is, for example, a pump or a fan. When the intake and exhaust device 63 is driven, the sample atmosphere is taken into the target molecule capturing unit 62 via the pipe 61. In this embodiment, the detection target of the sensor element is hydrophobic target molecules contained in the sample atmosphere.

[0040] The target molecule capturing unit 62 is connected to a supply source of an organic solvent. For example, the target molecule capturing unit 62 is connected to an organic solvent tank 65 in which an organic solvent is stored, via a pipe 69, a valve 68, and a pipe 66. The organic solvent is a hydrophilic organic solvent, and is, for example, any one selected from the group consisting of lower alcohols such as ethanol and methanol, DMSO (Dimethyl Sulfoxide), DMF (N,N-dimethylformamide), acetone, and acetonitrile.

[0041] An organic solvent is supplied from an organic solvent tank 65 to the target molecule capturing unit 62. The target molecule capturing unit 62 exposes the sample atmosphere, which may contain hydrophobic target molecules, to the hydrophilic organic solvent.

[0042] The target molecule capturing unit 62 is connected to a pipe 77 for draining liquid, and a valve 76 is connected to the pipe 77. The target molecule capturing unit 62 is also connected to a metering unit 78 via a pipe 73, a valve 72, and a pipe 74.

[0043] The organic solvent tank 65 is connected to a metering unit 78 via a pipe 66 , a valve 68 , a pipe 71 , a valve 72 , and a pipe 74 .

[0044] The metering unit 78 is connected to a pipe 79 for draining liquid, and a valve 81 is connected to the pipe 79. The metering unit 78 is also connected to a mixing unit 91 via a pipe 83, and a valve 82 is connected to the pipe 83.

[0045] A supply source of an aqueous solution is connected to the mixing unit 91. For example, the mixing unit 91 is connected to an aqueous solution tank 84 in which an aqueous solution is stored via a measuring unit 87. A valve 86 is connected to a pipe 85 connecting the aqueous solution tank 84 and the measuring unit 87. A valve 88 is connected to a pipe 89 connecting the mixing unit 91 and the measuring unit 87. The aqueous solution is, for example, a phosphate buffer solution, a HEPES buffer solution, a Tris-HCl buffer solution, or the like.

[0046] The mixing unit 91 is supplied with an organic solvent that may contain the target molecules from the target molecule capturing unit 62, and further supplied with an aqueous solution from the aqueous solution tank 84. Then, the mixing unit 91 mixes the organic solvent that may contain the target molecules with the aqueous solution to prepare a specimen liquid.

[0047] The mixing unit 91 is connected to the sensor unit 30 via a pipe 95. A valve 94 is connected to the pipe 95. The mixing unit 91 is connected to a pipe 93 for draining liquid, and a valve 92 is connected to the pipe 93.

[0048] The surface of the sensitive part 20 in the sensor unit 30 is exposed to a flow path through which a sample liquid is supplied. The surface of the sensitive part 20 and the probe molecules 32 are exposed to the sample liquid. The sensor unit 30 is connected to a pipe 97 for draining the liquid, and a valve 96 is connected to the pipe 97.

[0049] For example, the target molecule capturing unit 62 has a tank for bubbling the sample atmosphere into an organic solvent. This tank is connected to an organic solvent tank 65 via a pipe 69, a valve 68, and a pipe 66. A pump 67 is connected to the pipe 66. By opening the valve 68 to the pipe 69 side and driving the pump 67, the organic solvent stored in the organic solvent tank 65 is supplied into the tank of the target molecule capturing unit 62.

[0050] An atmosphere collection port is formed at one end of the pipe 61. The other end of the pipe 61 is located in the organic solvent in the tank of the target molecule capturing unit 62. One end of the pipe 64 is located in the gas phase above the organic solvent in the tank of the target molecule capturing unit 62, and the other end of the pipe 64 serves as an exhaust port. An intake and exhaust device 63 is connected between the tank of the target molecule capturing unit 62 and the exhaust port of the pipe 64. By driving the intake and exhaust device 63, the specimen atmosphere taken into the pipe 61 from the atmosphere collection port is bubbled into the organic solvent in the tank of the target molecule capturing unit 62, and the target molecules in the specimen atmosphere are dissolved in the organic solvent.

[0051] The tank of the target molecule capturing unit 62 is connected to a metering unit 78 via a pipe 73, a valve 72, and a pipe 74. By opening the valve 72 to the pipe 73 side and driving a pump 75 connected to the pipe 74, an organic solvent that may contain the target molecules in the tank of the target molecule capturing unit 62 is supplied to the metering unit 78.

[0052] A method for detecting a target molecule using the sensor system of the embodiment may include the steps described below.

[0053] (First Step) The suction and exhaust device 63 is driven to take in the specimen atmosphere into the target molecule capturing unit 62 through the pipe 61. Furthermore, the valve 68 is switched to a state in which the pipes 66 and 69 communicate with each other, and the pump 67 is driven to supply the organic solvent from the organic solvent tank 65 to the target molecule capturing unit 62. In this target molecule capturing unit 62, the target molecules in the specimen atmosphere are dissolved in the organic solvent.

[0054] Hydrophobic target molecules are poorly soluble in aqueous solutions but are soluble and dispersible in organic solvents, so they can be efficiently captured from air into liquids.

[0055] (Second step) Valve 72 is switched to a state in which pipes 73 and 74 communicate with each other, and pump 75 is driven to supply the organic solvent in which the target molecules are dissolved from target molecule capturing unit 62 to measuring unit 78. In addition, valve 86 is opened to supply the aqueous solution from aqueous solution tank 84 to measuring unit 87.

[0056] The aqueous solution may contain, for example, a labeling molecule that has an affinity with the target molecule. The labeling molecule is hydrophilic and dissolved in the aqueous solution. The aqueous solution may be, for example, a phosphate buffer, a HEPES buffer, a Tris-HCl buffer, or the like. The number of the labeling molecule is greater than the number of the target molecule. The labeling molecule is either a molecule having a larger molecular weight than the target molecule, a molecule having a charge, or a polar molecule having a polarization. The labeling molecule is, for example, arginine, arginine methyl ester, argininamide, a nucleic acid aptamer, or a peptide.

[0057] (Third Step) Valve 82 is opened to supply a first predetermined amount of organic solvent (which may contain the target molecule) measured in measuring unit 78 to mixing unit 91. Also, valve 88 is opened to supply a second predetermined amount of aqueous solution measured in measuring unit 87 to mixing unit 91. As a result, a specimen liquid is prepared in mixing unit 91 in which the first predetermined amount of organic solvent which may contain the target molecule is mixed with the second predetermined amount of aqueous solution.

[0058] The hydrophilic organic solvent diffuses in the aqueous solution, and the organic solvent and the aqueous solution are miscible. When the organic solvent contains target molecules, the target molecules rapidly dissipate into the aqueous solution, and a specimen solution is obtained. Since the target molecules are hydrophobic, they are left behind in an unstable state in the specimen solution. Although the target molecules are hydrophobic, they are dispersed in the hydrophilic organic solvent when mixed with the aqueous solution. Since this hydrophilic organic solvent mixes with the aqueous solution, the target molecules can be efficiently dispersed in the aqueous solution with less energy than if the hydrophobic target molecules were directly incorporated into the aqueous solution without going through the organic solvent.

[0059] As described above, the labeled molecules are dispersed in the aqueous solution. Therefore, the labeled molecules are also dispersed in the sample solution. The sample solution is an aqueous solution in which an organic solvent is diluted with an aqueous solution, and the hydrophobic target molecules in the sample solution are in an unstable state. This unstable target molecule associates with a nearby labeled molecule. For example, limonene as a target molecule and arginine amide as a labeled molecule are bound by π-π interaction to form an association.

[0060] (Fourth step) By opening valve 94, the specimen liquid is supplied from mixing unit 91 through piping 95 to sensor unit 30. Then, in sensor unit 30, electrical characteristics (for example, the above-mentioned Id-Vg characteristics) corresponding to target molecules in the specimen liquid are measured.

[0061] When a target molecule is captured by the probe molecule 32 and approaches the surface of the sensitive part 20, the electronic state of the surface of the sensitive part 20 changes, causing a change in Id. This change in Id makes it possible to detect the presence and concentration of the target molecule in the sample liquid.

[0062] In addition, when the target molecule is uncharged and has a small molecular weight (for example, when the molecular weight is 300 or less), it may be difficult to detect a change in the electronic state of the surface of the sensitive part 20 due to the approach of the target molecule. According to this embodiment, as described above, the target molecule is associated with a labeling molecule, so when the target molecule is captured by the probe molecule 32, the labeling molecule also approaches the surface of the sensitive part 20. Here, when the labeling molecule has a strong charge like argininamide, or has a large molecular weight (for example, 500 or more) like nucleic acid or peptide, a change in the electronic state of the sensitive part 20 due to the approach of the labeling molecule (for example, the approach of the charge of the labeling molecule or the change in the distribution of ions at the solution interface due to the approach of a large labeling molecule) can be detected. As a result, even when it is difficult to detect only by the approach of the target molecule, it is possible to detect the presence and concentration of the target molecule in the sample liquid by detecting the approach of the labeling molecule.

[0063] (5th step) Valve 76 is opened to discharge the remaining organic solvent to which the sample atmosphere in target molecule capturing unit 62 has been exposed from target molecule capturing unit 62 through pipe 77. Also, valve 92 is opened to discharge the remaining sample liquid in mixing unit 91 from mixing unit 91 through pipe 93.

[0064] (Sixth step) Valves 68 and 72 are opened to the pipes 69 and 73, respectively, and valve 81 is further opened to drain the organic solvent from the organic solvent tank 65 to the pipe 79 via the target molecule capturing unit 62 and the metering unit 78. The target molecule capturing unit 62 and the metering unit 78 are washed with the organic solvent in the organic solvent tank 65 to which the sample atmosphere is not exposed. The target molecules are discharged from the target molecule capturing unit 62 and the metering unit 78.

[0065] (Seventh step) Valves 68 and 72 are opened to the piping 71 side, and the organic solvent is supplied from the organic solvent tank 65 to the metering unit 78 through the piping 71. The organic solvent is supplied from the organic solvent tank 65 to the metering unit 78 without passing through the target molecule capturing unit 62. In addition, valve 86 is opened, and the aqueous solution is supplied from the aqueous solution tank 84 to the metering unit 87 through the piping 85.

[0066] (Step 8) Valve 82 is opened to supply the mixing unit 91 with the same first predetermined amount of organic solvent (which does not contain target molecules) as above measured in the measuring unit 78. Also, valve 88 is opened to supply the mixing unit 91 with the same second predetermined amount of aqueous solution as above measured in the measuring unit 87. As a result, in the mixing unit 91, a control solution is prepared in which the first predetermined amount of organic solvent not containing target molecules is mixed with the second predetermined amount of aqueous solution. The solution supplied from the mixing unit 91 to the sensor unit 30 through the piping 95 becomes the liquid 31. The aqueous organic solvent solution that has taken up the target molecules is called a specimen liquid.

[0067] (9th step) By opening a valve 94, the control solution is supplied from the mixing unit 91 through a pipe 95 to the sensor unit 30. By comparing the measurement signal (electrical characteristic) of the sensor element 50 exposed to the control solution not containing the target molecule with the measurement signal (electrical characteristic) of the sensor element 50 exposed to the sample liquid, when the target molecule is contained in the sample liquid, it is possible to perform highly accurate detection of the target molecule with correction for disturbance noise.

[0068] According to this embodiment, hydrophobic target molecules are concentrated and taken up in an organic solvent, and the organic solvent aqueous solution (specimen liquid) containing the target molecules is exposed to the surface of the sensitive part 20, thereby making it possible to increase the detection sensitivity of the target molecules compared to the case where the hydrophobic target molecules are directly taken up in an aqueous solution.

[0069] Biological molecules (e.g., peptides, DNA aptamers, etc.) function in aqueous solutions. Therefore, when a biological molecule is used as the probe molecule 32, if the surface of the sensitive part 20 is exposed to an organic solvent, the structure of the biological probe molecule 32 is changed or destroyed, and the ability of the probe molecule 32 to capture the target molecule is reduced.

[0070] In addition, graphene is hydrophobic and therefore has a high affinity with organic solvents, and may be damaged when the surface of the graphene serving as the sensitive part 20 is exposed to the organic solvent. This damage may cause the organic solvent to penetrate into the adhesive surface between the graphene and the undercoat film, or into the interfaces between the first and second electrodes 41, 42 and the protective insulating film covering them, which may induce peeling of the graphene or the protective insulating film.

[0071] In this embodiment, the above problem does not occur because the sample liquid, which is an aqueous solution obtained by diluting an organic solvent with an aqueous solution, is exposed to the surface of the sensitive part 20.

[0072] The control solution can be used as the liquid 31 supplied to the surface of the sensitive part 20 when evaluating the quality of the sensor element 50. Alternatively, only the aqueous solution in the aqueous solution tank 84 may be used as the liquid 31 supplied to the surface of the sensitive part 20. The first liquid supply mechanism that supplies the liquid 31 to the surface of the sensitive part 20 includes at least the aqueous solution tank 84, and pipes 85, 89, and 95 that connect the aqueous solution tank 84 and the sensor unit 30.

[0073] In the method for evaluating a sensor element according to the embodiment, a solution containing probe molecules 32 in a solvent can be supplied to the surface of the sensitive part 20, the solvent can be evaporated, and then the liquid 31 can be supplied to the surface of the sensitive part 20. For example, the solution containing the probe molecules 32 can be supplied to the surface of the sensitive part 20, and the surface of the sensitive part 20 can be dried at room temperature for a predetermined time or more to evaporate the solvent. This makes it easier for the probe molecules 32 to be confined close to the surface of the sensitive part 20 as shown in Figs. 3(b) to (d) described above, making it easier to make a good sensor element. For example, a buffer solution can be used as the solvent.

[0074] Furthermore, in the sensor element evaluation method of the embodiment, when the sensor element 50 is evaluated as good, the electrical characteristics can be measured by supplying target molecules to the surface of the sensitive part 20. If it is confirmed in the measurement of the electrical characteristics that the sensitive part 20 is sensitive to the target molecules, the sensor element can be determined to be a good element.

[0075] Embodiments may include the following sensor systems and methods for evaluating sensor elements.

[0076] [Configuration 1] a sensor element having a sensitive portion, a probe molecule located on a surface of the sensitive portion, and a first electrode and a second electrode electrically connected to the sensitive portion; a processing device that applies a voltage between the first electrode and the second electrode and evaluates the quality of the sensor element based on an electrical characteristic of the sensor element; and A sensor system comprising: [Configuration 2] The sensor system of embodiment 1, wherein the sensitive portion includes graphene. [Configuration 3] a first liquid supply mechanism that supplies a liquid to the surface of the sensitive part; a gate electrode that applies a voltage to the liquid supplied to the surface of the sensitive part; Further equipped with The sensor system of configuration 1 or 2, wherein the electrical characteristic is an Id-Vg characteristic, where Id is the current flowing between the first electrode and the second electrode through the sensitive portion, and Vg is the voltage of the gate electrode. [Configuration 4] The sensor system of configuration 3, wherein the processing device evaluates the quality of the sensor element by comparing a first Id-Vg characteristic when the Vg is swept from a negative voltage to a positive voltage with a second Id-Vg characteristic when the Vg is swept from a positive voltage to a negative voltage. [Configuration 5] The sensor system of configuration 4, wherein the processing device evaluates the quality of the sensor element from the difference in Id when the Vg in the first Id-Vg characteristic and the second Id-Vg characteristic have the same value. [Configuration 6] The sensor system according to configuration 5, wherein the processing device evaluates the quality of the sensor element from a difference in Id when the Vg is 0 or negative. [Configuration 7] The sensor system of configuration 4, wherein the processing device evaluates the quality of the sensor element from the difference in Vg when the Id in the first Id-Vg characteristic and the second Id-Vg characteristic are the same value. [Configuration 8] a target molecule capturing unit that exposes a sample atmosphere containing hydrophobic target molecules to a hydrophilic organic solvent; a mixing unit for mixing the organic solvent containing the target molecule with an aqueous solution to prepare a sample solution; a second liquid supply mechanism that supplies the sample liquid to the surface of the sensitive part; The sensor system according to any one of configurations 1 to 7, further comprising: [Configuration 9] The sensor system according to any one of configurations 1 to 8, further comprising a storage device that stores a result of the evaluation of the quality of the sensor element by the processing device. [Configuration 10] 10. The sensor system according to any one of configurations 1 to 9, wherein the probe molecule includes at least one of a protein, a peptide, an antibody, a DNA aptamer, or a biomolecule derived therefrom. [Configuration 11] A method for evaluating a sensor element, in which a probe molecule is positioned on the surface of a sensitive part and a voltage is applied between a first electrode and a second electrode electrically connected to the sensitive part, to evaluate the quality of the sensor element based on the electrical characteristics of the sensor element. [Configuration 12] Supplying a liquid to the surface of the sensitive portion; applying a voltage from a gate electrode to the liquid supplied to the surface of the sensitive part; A method for evaluating a sensor element according to configuration 11, in which the Id-Vg characteristic is measured as the electrical characteristic, where Id is the current flowing between the first electrode and the second electrode through the sensitive part, and Vg is the voltage of the gate electrode. [Configuration 13] The method for evaluating a sensor element according to configuration 12, further comprising the steps of: comparing a first Id-Vg characteristic obtained when the Vg is swept from a negative voltage to a positive voltage with a second Id-Vg characteristic obtained when the Vg is swept from a positive voltage to a negative voltage to evaluate the quality of the sensor element. [Configuration 14] A method for evaluating a sensor element according to configuration 13, comprising: evaluating the quality of the sensor element from the difference in Id when the Vg in the first Id-Vg characteristic and the second Id-Vg characteristic are the same value. [Configuration 15] 15. The method for evaluating a sensor element according to claim 14, wherein the processing device evaluates the quality of the sensor element from a difference in Id when the Vg is 0 or negative. [Configuration 16] A method for evaluating a sensor element according to configuration 13, which evaluates the quality of the sensor element from the difference in Vg when the Id in the first Id-Vg characteristic and the second Id-Vg characteristic are the same value. [Configuration 17] supplying a solution containing the probe molecules in a solvent to the surface of the sensitive part; 17. The method for evaluating a sensor element according to any one of Configurations 12 to 16, further comprising the step of: supplying the liquid to the surface of the sensitive part after volatilizing the solvent. [Configuration 18] 18. The method for evaluating a sensor element according to any one of configurations 11 to 17, further comprising the steps of: supplying target molecules to the surface of the sensitive part and measuring the electrical characteristics if the sensor element is evaluated as good.

[0077] Although some embodiments of the present invention have been described, these embodiments are presented as examples and are not intended to limit the scope of the invention. These novel embodiments can be implemented in various other forms, and various omissions, substitutions, and modifications can be made without departing from the spirit of the invention. These embodiments and their modifications are included in the scope and spirit of the invention, and are included in the scope of the invention and its equivalents described in the claims. [Explanation of symbols]

[0078] 10...substrate, 20...sensitive part, 30...sensor unit, 31...liquid, 32...probe molecule, 41...first electrode, 42...second electrode, 43...gate electrode, 50...sensor element, 100...processing device, 200...storage device

Claims

1. a sensor element having a sensitive portion, a probe molecule located on a surface of the sensitive portion, and a first electrode and a second electrode electrically connected to the sensitive portion; a processing device that applies a voltage between the first electrode and the second electrode and evaluates the quality of the sensor element based on an electrical characteristic of the sensor element; and A sensor system comprising:

2. The sensor system according to claim 1 , wherein the sensitive portion includes graphene.

3. a first liquid supply mechanism that supplies a liquid to the surface of the sensitive part; a gate electrode that applies a voltage to the liquid supplied to the surface of the sensitive part; Further equipped with The sensor system according to claim 1, wherein the electrical characteristics are Id-Vg characteristics, where Id is the current flowing between the first electrode and the second electrode through the sensitive portion, and Vg is the voltage of the gate electrode.

4. The sensor system of claim 3, wherein the processing device evaluates the quality of the sensor element by comparing a first Id-Vg characteristic when the Vg is swept from a negative voltage to a positive voltage with a second Id-Vg characteristic when the Vg is swept from a positive voltage to a negative voltage.

5. The sensor system according to claim 4, wherein the processing device evaluates the quality of the sensor element from a difference in Id when the Vg in the first Id-Vg characteristic and the second Id-Vg characteristic have the same value.

6. The sensor system according to claim 5 , wherein the processing device evaluates the quality of the sensor element from a difference in Id when the Vg is 0 or negative.

7. The sensor system according to claim 4, wherein the processing device evaluates the quality of the sensor element from the difference in Vg when the Id in the first Id-Vg characteristic and the second Id-Vg characteristic have the same value.

8. a target molecule capturing unit that exposes a sample atmosphere containing hydrophobic target molecules to a hydrophilic organic solvent; a mixing unit for mixing the organic solvent containing the target molecule with an aqueous solution to prepare a sample solution; a second liquid supply mechanism that supplies the sample liquid to the surface of the sensitive part; The sensor system of claim 1 further comprising:

9. The sensor system according to claim 1 , further comprising a storage device that stores a result of the quality evaluation of the sensor element by the processing device.

10. The sensor system according to claim 1 , wherein the probe molecule includes at least one of a protein, a peptide, an antibody, a DNA aptamer, or a biomolecule derived therefrom.

11. A method for evaluating a sensor element, in which a probe molecule is positioned on the surface of a sensitive part and a voltage is applied between a first electrode and a second electrode electrically connected to the sensitive part, to evaluate the quality of the sensor element based on the electrical characteristics of the sensor element.

12. Supplying a liquid to the surface of the sensitive portion; applying a voltage from a gate electrode to the liquid supplied to the surface of the sensitive part; The method for evaluating a sensor element according to claim 11, further comprising measuring an Id-Vg characteristic as the electrical characteristic, where Id is a current flowing between the first electrode and the second electrode through the sensitive part, and Vg is a voltage of the gate electrode.

13. The method for evaluating a sensor element according to claim 12, further comprising the steps of: comparing a first Id-Vg characteristic obtained when the Vg is swept from a negative voltage to a positive voltage with a second Id-Vg characteristic obtained when the Vg is swept from a positive voltage to a negative voltage; and evaluating the quality of the sensor element from the comparison.

14. The method for evaluating a sensor element according to claim 13, further comprising the step of evaluating the quality of the sensor element from a difference in Id when the Vg in the first Id-Vg characteristic and the Vg in the second Id-Vg characteristic have the same value.

15. The method for evaluating a sensor element according to claim 14 , wherein the processing device evaluates the quality of the sensor element from a difference in Id when the Vg is 0 or a negative value.

16. The method for evaluating a sensor element according to claim 13, further comprising the step of evaluating the quality of the sensor element from a difference in Vg when the Id in the first Id-Vg characteristic and the Vg in the second Id-Vg characteristic are the same value.

17. supplying a solution containing the probe molecules in a solvent to the surface of the sensitive part; The method for evaluating a sensor element according to claim 12, further comprising the step of: supplying the liquid to the surface of the sensitive part after volatilizing the solvent.

18. The method for evaluating a sensor element according to claim 11 , further comprising the steps of: supplying target molecules to the surface of the sensitive portion and measuring the electrical characteristics if the sensor element is evaluated as being good.

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