JP7849335B2 - Evaluation method for sensor systems and sensor elements - Google Patents

Description

Embodiments of the present invention relate to a sensor system and a method for evaluating sensor elements.

For example, sensor elements with graphene surfaces functionalized with probe molecules have been proposed, but a testing system for detecting defective elements has not yet been established.

Japanese Patent Publication No. 2022-132804

The embodiments of this invention aim to provide a sensor system capable of evaluating the quality of a sensor element and a method for evaluating a sensor element.

According to an embodiment of the present invention, the sensor system comprises a sensing portion, a probe molecule located on the surface of the sensing portion, a sensor element having a first electrode and a second electrode electrically connected to the sensing portion, 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 its electrical characteristics.

According to an embodiment of the present invention, the evaluation method for a sensor element involves a probe molecule positioned on the surface of a sensing portion, and the quality of the sensor element is evaluated based on its electrical characteristics when a voltage is applied between a first electrode and a second electrode electrically connected to the sensing portion.

This is a schematic diagram of the sensor system according to the embodiment. This is a schematic diagram of the sensor unit according to the embodiment. (a) is the Id-Vg characteristic curve for a good element, and (b), (c), and (d) are schematic diagrams showing the state of the probe molecule at points b, c, and d in Figure 3(a), respectively. (a) is the Id-Vg characteristic curve for a defective element, and (b), (c), and (d) are schematic diagrams showing the state of the probe molecule at points b, c, and d in Figure 4(a), respectively. This graph shows the measurement results of ΔId for samples 1 to 5.

Each embodiment will be described below with reference to the drawings.
Drawings are schematic or conceptual, and the relationships between the thickness and width of each part, as well as the ratios of the sizes of different parts, are not necessarily identical to those of reality. Even when representing the same part, the dimensions and ratios may be depicted differently in different drawings.
Furthermore, identical or similar elements are assigned the same symbol.

As shown in Figure 1, the sensor system of this embodiment comprises a sensor unit 30 and a processing unit 100. The processing unit 100 includes, for example, a arithmetic unit such as a CPU, a storage device, a power supply device that generates the voltage applied to the sensor unit 30, and a device for reading the electrical characteristics of the sensor unit 30. The processing unit 100 processes the input signal according to software stored in the storage device, for example, and controls the operation of the sensor unit 30. The processing unit 100 determines whether the sensor element 50 is good or bad.

As shown in Figure 2, the sensor unit 30 has a sensor element 50. The sensor element 50 includes a sensing portion 20, a probe molecule 32, a first electrode 41, and a second electrode 42. The sensing portion 20 is electrically sensitive to the proximity of a target molecule. For example, the sensing portion 20 contains graphene, and the sensor element 50 has a GFET (graphene field effect transistor) structure. Note that, in addition to graphene, materials such as carbon nanotubes can also be used as the sensing portion 20.

The sensing element 20, the first electrode 41, and the second electrode 42 are supported on the substrate 10. The substrate 10 is, for example, a silicon substrate. The sensing element 20 can be provided on the substrate 10 via an underlayer. For example, a silicon oxide film can be used as the underlayer. Furthermore, the underlayer can also function as a chemical catalyst for graphene formation.

The first electrode 41 can function as the drain electrode in the FET, and the second electrode 42 can function as the source electrode in the FET. The first electrode 41 and the second electrode 42 are electrically connected to the sensing unit 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 sensing unit 20. The sensor system may include a measuring device 45 for measuring the drain current Id.

The probe molecule 32 is located on the surface of the sensing portion 20. The location of the probe molecule 32 on the surface of the sensing portion 20 means that the probe molecule 32 is bound, adsorbed, or in close proximity to the surface of the sensing portion 20 by chemical, charge-induced attraction, π-π interaction, cation-π interaction, or hydrophobic interaction, thereby constraining the probe molecule 32 to the surface of the sensing portion 20. The probe molecule 32 includes, for example, at least one of the following: a protein, peptide, antibody, DNA aptamer, or a biomolecule derived from these. The probe molecule 32 can be located on the surface of the sensing portion 20 via, for example, a linker (or scaffold molecule) 33. For example, pyrene can be used as the linker 33.

As described later, a solution containing the sample atmosphere is supplied to the surface of the sensing element 20. Alternatively, the sample atmosphere may be supplied to the surface of the sensing element 20 as a gas phase. The probe molecule 32 is capable of specifically recognizing or specifically interacting with target molecules that may be present in the sample atmosphere. When the probe molecule 32 recognizes or captures a target molecule, the target molecule approaches the surface of the sensing element 20. Therefore, the electronic state of the sensing element 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 determined.

The processing unit 100 controls the power supply 44 and applies a voltage between the first electrode 41 and the second electrode 42. The processing unit 100 also evaluates the quality of the sensor element 50 based on its electrical characteristics obtained by the measuring device 45. This allows for the removal of defective elements and suppresses false detection of the presence or concentration of target molecules in the sample atmosphere.

The following describes specific examples of methods for evaluating the electrical characteristics and quality of the sensor element 50.

The sensor system of this embodiment may further include a first liquid supply mechanism that supplies liquid 31 to the surface of the sensing element 20, and a gate electrode 43 that applies a voltage to the liquid 31 supplied to the surface of the sensing element 20. The first liquid supply mechanism will be described later with reference to Figure 1.

As shown in Figure 2, the surface of the sensing element 20 and the probe molecule 32 are immersed in the liquid 31. This improves the target molecule capture ability of the probe molecule 32, especially when the probe molecule 32 is of biological origin. The liquid 31 is, for example, an aqueous solution, and more specifically, a buffer solution.

The first electrode 41 and the second electrode 42 are coated with, for example, an insulating film (not shown), so that the first electrode 41 and the second electrode 42 do not come into direct contact with the liquid 31.

When the drain current is denoted as Id and the voltage of the gate electrode 43 as Vg, the Id-Vg characteristic can be used as an electrical characteristic to evaluate the quality of the sensor element 50.

An example of the Id-Vg characteristics is shown in Figures 3(a) and 4(a).

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

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. Measuring Id during this sweep yields the first Id-Vg characteristic I, and measuring Id during the same sweep from +350 mV to -500 mV in 10 mV steps yields the second Id-Vg characteristic II.

Figure 3(a) shows an example of the Id-Vg characteristics in a good element, and Figure 4(a) shows an example of the Id-Vg characteristics in a defective element. In the defective element, a tendency was observed where the difference in Id ΔId between the first Id-Vg characteristic I and the second Id-Vg characteristic II, when Vg is the same value, was larger than that of the good element.

Therefore, the processing unit 100 can evaluate the quality of the sensor element 50 from the difference ΔId of Id when Vg is the same value in the first Id-Vg characteristic I and the second Id-Vg characteristic II. The processing unit 100 can output the quality of the sensor element 50 via an interface (not shown). When the processing unit 100 evaluates the sensor element 50 as good, it executes a sensing operation using that sensor element 50. When the processing unit 100 evaluates the sensor element 50 as defective, it either does not execute a sensing operation using that sensor element 50 or stops the sensing operation.

ΔId was measured for five samples (1-5). The results are shown in Figure 5. In each sample, the sensor element had a GFET structure using graphene as the sensing element. Cocaine aptamers (nucleic acid aptamers capable of specifically recognizing or specifically interacting with cocaine molecules) were used as probe molecules. The graphene surface and probe molecules were immersed in phosphate-buffered saline.

The difference in Id values (ΔId) when Vg is 0 mV was measured between the first Id-Vg characteristic I and the second Id-Vg characteristic II, which were measured under the conditions described above. The ΔId for sample 1 was 0.0009 μA, for sample 2 it was 0.0036 μA, for sample 3 it was 0.068 μA, for sample 4 it was 0.090 μA, and for sample 5 it was 0.15 μA.

After measuring ΔId as described above, methyl benzoate was dissolved in phosphate-buffered saline for each of the samples 1-5. The molar concentration of methyl benzoate in this solution was 100 μM. Samples 1 and 2 showed a significant change in Id before and after the addition of methyl benzoate, indicating a response to methyl benzoate. Therefore, samples 1 and 2 can be considered good devices. Samples 3-5 did not show a significant change in Id before and after the addition of methyl benzoate, indicating no response to methyl benzoate. Therefore, samples 3-5 can be considered defective devices.

From the results in Figure 5 above, the quality of the sensor element can be evaluated based on the magnitude of ΔId in the first Id-Vg characteristic I and the second Id-Vg characteristic II. For example, in the example in Figure 5, ΔId = 0.04 μA can be set as the threshold for quality determination. The processing unit 100 compares the threshold stored in the storage unit 200 with the measured ΔId, and determines that the element is good if ΔId is 0.04 μA or less, or less than 0.04 μA, and determines that the element is defective if ΔId is greater than 0.04 μA. Preferably, ΔId = 0.01 μA can be set as the threshold for quality determination. If even greater accuracy is required, ΔId = 0.006 μA can be set as the threshold for quality determination.

Figure 4(a), which shows the Id-Vg characteristics for a defective element, reveals that the ΔId between the first Id-Vg characteristic I and the second Id-Vg characteristic II when Vg is 0 or negative is greater than the ΔId between the first Id-Vg characteristic I and the second Id-Vg characteristic II when Vg is positive. Therefore, the processing unit 100 can improve the accuracy of its quality determination by evaluating the quality of the sensor element 50 based on the difference in Id ΔId when Vg is 0 or negative.

Furthermore, 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. As shown in Figure 4(a), the difference between the first Id-Vg characteristic I and the second Id-Vg characteristic II becomes large in the region where Vg is lower than the value at the charge neutral point. Therefore, it is preferable to evaluate the quality of the sensor element 50 from ΔId in the region where Vg is lower than the value at the charge neutral point.

Furthermore, the processing unit 100 may evaluate the quality of the sensor element 50 from the difference ΔVg between the first Id-Vg characteristic I and the second Id-Vg characteristic II when Id is the same value. A threshold value of ΔVg = 10mV when Id = 1μA can be set for quality determination. If ΔVg is 10mV or less, or less than 10mV, it can be determined to be a good element; if ΔVg is greater than 10mV, it can be determined to be a defective element. More preferably, a threshold value of ΔVg = 2mV when Id = 1μA can be set for quality determination.

The sensor system of this embodiment may further include a storage device 200 (shown in Figure 1) that stores the evaluation results of the sensor element 50 by the processing device 100. The threshold value for pass/fail judgment can also be stored in the storage device 200.

Figure 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 Figure 3(a).
Figure 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 Figure 3(a).
Figure 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 Figure 3(a).

As shown in Figures 3(a) to 3(d), in a good element, even when Vg fluctuates, the probe molecule 32 maintains a close proximity to the surface of the sensing part (graphene) 20, making it easier for the sensing part 20 to sense the target molecule captured by the probe molecule 32.

Figure 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 Figure 4(a).
Figure 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 Figure 4(a).
Figure 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 Figure 4(a).

As shown in Figures 4(a) to 4(d), in the defective element, the restraining force of the probe molecules 32 on the surface of the sensing part (graphene) 20 is weak. It is thought that, with fluctuations in Vg, the charged (e.g., negatively charged) probe molecules 32 move closer to or away from the surface of the sensing part 20 in the liquid 31 due to electrostatic attraction. If the target molecule trapping site of the probe molecule 32 is far from the surface of the sensing part 20, even if the target molecule is trapped at the trapping site, the sensing part 20 is unlikely to be sensitive to the charge of the target molecule.

The sensor system of this embodiment, as shown in Figure 1, may further include a target molecule incorporation unit 62 that exposes a sample 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 create a sample solution, and a second liquid supply mechanism that supplies the sample solution to the surface of the sensing unit 20. The second liquid supply mechanism may, for example, include a pipe 95 connecting the mixing unit 91 and the sensor unit 30, and a valve 94 connected to the pipe 95.

The target molecule acquisition unit 62 is connected to piping 61 and piping 64. A suction/exhaust device 63 is connected to piping 64. The suction/exhaust device 63 is, for example, a pump or fan. The suction/exhaust device 63 drives the sample atmosphere into the target molecule acquisition unit 62 via piping 61. In this embodiment, the sensor element detects hydrophobic target molecules contained in the sample atmosphere.

The target molecule incorporation unit 62 is connected to a source of organic solvent. For example, the target molecule incorporation unit 62 is connected to an organic solvent tank 65 containing the organic solvent via piping 69, a valve 68, and piping 66. The organic solvent is a hydrophilic organic solvent, selected from the group consisting of, for example, lower alcohols such as ethanol and methanol, DMSO (Dimethyl Sulfoxide), DMF (N,N-dimethylformamide), acetone, and acetonitrile.

The organic solvent is supplied from the organic solvent tank 65 to the target molecule incorporation unit 62. The target molecule incorporation unit 62 exposes the sample atmosphere, which may contain hydrophobic target molecules, to the hydrophilic organic solvent.

The target molecule intake unit 62 is connected to a drainage pipe 77, to which a valve 76 is connected. The target molecule intake unit 62 is also connected to a metering unit 78 via pipes 73, valve 72, and 74.

The organic solvent tank 65 is connected to the metering unit 78 via piping 66, valve 68, piping 71, valve 72, and piping 74.

The measuring unit 78 is connected to a drainage pipe 79, to which a valve 81 is connected. The measuring unit 78 is also connected to a mixing unit 91 via a pipe 83, to which a valve 82 is connected.

The mixing unit 91 is connected to a source of aqueous solution. For example, the mixing unit 91 is connected to an aqueous solution tank 84 containing the aqueous solution via a metering unit 87. A valve 86 is connected to the piping 85 connecting the aqueous solution tank 84 and the metering unit 87. A valve 88 is connected to the piping 89 connecting the mixing unit 91 and the metering unit 87. The aqueous solution can be, for example, a phosphate buffer, a HEPES buffer, or a Tris-HCl buffer.

The mixing unit 91 is supplied with an organic solvent potentially containing the target molecule from the target molecule incorporation unit 62, and further supplied with an aqueous solution from the aqueous solution tank 84. The mixing unit 91 then mixes the organic solvent potentially containing the target molecule with the aqueous solution to create a sample solution.

The mixing unit 91 is connected to the sensor unit 30 via piping 95. A valve 94 is connected to piping 95. The mixing unit 91 is also connected to drainage piping 93, and a valve 92 is connected to piping 93.

The surface of the sensing element 20 in the sensor unit 30 is exposed to the flow path through which the sample liquid is supplied. The surface of the sensing element 20 and the probe molecules 32 are exposed to the sample liquid. The sensor unit 30 is connected to a drainage pipe 97, and a valve 96 is connected to the pipe 97.

For example, the target molecule incorporation unit 62 has a tank that bubbles the sample atmosphere into an organic solvent. This tank is connected to the organic solvent tank 65 via piping 69, a valve 68, and piping 66. A pump 67 is connected to piping 66. By opening valve 68 towards piping 69 and driving the pump 67, the organic solvent stored in the organic solvent tank 65 is supplied into the tank of the target molecule incorporation unit 62.

An atmosphere collection port is formed at one end of piping 61. The other end of piping 61 is located in the organic solvent in the tank of the target molecule intake unit 62. One end of piping 64 is located in the gas phase above the organic solvent in the tank of the target molecule intake unit 62, and the other end of piping 64 is an exhaust port. An intake and exhaust device 63 is connected between the tank of the target molecule intake unit 62 and the exhaust port of piping 64. By operating the intake and exhaust device 63, the sample atmosphere taken into piping 61 from the atmosphere collection port is bubbling into the organic solvent in the tank of the target molecule intake unit 62, and the target molecules in the sample atmosphere dissolve in the organic solvent.

The tank of the target molecule intake unit 62 is connected to the metering unit 78 via piping 73, valve 72, and piping 74. By opening valve 72 to piping 73 and driving the pump 75 connected to piping 74, the organic solvent containing the target molecule from the tank of the target molecule intake unit 62 is supplied to the metering unit 78.

The method for detecting target molecules using the sensor system of this embodiment may include the steps described below.

(Step 1)
The intake and exhaust device 63 is activated, and the sample atmosphere is introduced into the target molecule intake unit 62 through the piping 61. The valve 68 is then switched to a state that connects piping 66 and piping 69, and the pump 67 is activated to supply organic solvent from the organic solvent tank 65 to the target molecule intake unit 62. In this target molecule intake unit 62, the target molecules in the sample atmosphere dissolve in the organic solvent.

Hydrophobic target molecules are poorly soluble in aqueous solutions, but they dissolve in organic solvents and disperse within them. Therefore, hydrophobic target molecules can be efficiently incorporated into liquids from the air.

(Step 2)
The valve 72 is switched to a state that connects the pipes 73 and 74, and the pump 75 is driven to supply the organic solvent containing the target molecules from the target molecule intake unit 62 to the metering unit 78. In addition, the valve 86 is opened to supply the aqueous solution from the aqueous solution tank 84 to the metering unit 87.

The aqueous solution may contain, for example, a labeled molecule that has affinity for the target molecule. The labeled molecule is hydrophilic and dissolved in the aqueous solution. Examples of aqueous solutions include phosphate buffer, HEPES buffer, and Tris-HCl buffer. The number of labeled molecules is greater than the number of target molecules. The labeled molecule is either a molecule with a larger molecular weight than the target molecule, a charged molecule, or a polar molecule with polarization. Examples of labeled molecules include arginine, arginine methyl ester, arginine amide, nucleic acid aptamer, or peptide.

(Step 3)
The valve 82 is opened to supply the first predetermined amount of organic solvent (which may contain the target molecule) measured in the metering unit 78 to the mixing unit 91. The valve 88 is also opened to supply the second predetermined amount of aqueous solution measured in the metering unit 87 to the mixing unit 91. As a result, in the mixing unit 91, a sample solution is prepared 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.

Hydrophilic organic solvents diffuse in aqueous solutions, and the organic solvent and the aqueous solution become miscible. When the organic solvent contains target molecules, the target molecules rapidly disperse into the aqueous solution, yielding the sample solution. Because the target molecules are hydrophobic, they remain in an unstable state in the sample solution. However, when mixing the target molecules with an aqueous solution, they are dispersed within the hydrophilic organic solvent. Since this hydrophilic organic solvent mixes with the aqueous solution, it requires less energy to efficiently disperse the target molecules into the aqueous solution compared to directly incorporating the hydrophobic target molecules without the organic solvent.

Furthermore, as mentioned 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 obtained by diluting an organic solvent with an aqueous solution, and the hydrophobic target molecules in the sample solution are in an unstable state. These unstable target molecules associate with nearby labeled molecules. For example, limonene, as the target molecule, and arginine amide, as the labeled molecule, bind via π-π interactions, forming an aggregate.

(Step 4)
The sample solution is supplied from the mixing unit 91 to the sensor unit 30 via the piping 95 by opening the valve 94. The sensor unit 30 then measures the electrical properties (for example, the Id-Vg properties described above) corresponding to the target molecules in the sample solution.

When the target molecule is captured by the probe molecule 32 and approaches the surface of the sensing element 20, the electronic state of the surface of the sensing element 20 changes, causing a fluctuation in Id. This fluctuation in Id makes it possible to detect the presence and concentration of the target molecule in the sample solution.

Furthermore, if the target molecule is uncharged and has a small molecular weight (for example, a molecular weight of 300 or less), it may be difficult to detect changes in the electronic state of the surface of the sensing part 20 due to the proximity of the target molecule. According to this embodiment, as described above, since the target molecule associates with the label molecule, when the target molecule is captured by the probe molecule 32, the label molecule also approaches the surface of the sensing part 20. Here, if the label molecule has a strong charge, such as arginine amide, or a large molecular weight (for example, 500 or more), such as nucleic acids or peptides, it is possible to detect changes in the electronic state of the sensing part 20 due to the proximity of this label molecule (for example, the proximity of the charge of the label molecule or changes in the ion distribution at the solution interface due to the proximity of a large label molecule). This makes it possible to detect the presence and concentration of the target molecule in the sample solution by detecting the proximity of the label molecule, even when detection is difficult with only the proximity of the target molecule.

(Step 5)
Valve 76 is opened to discharge the remaining organic solvent that the sample atmosphere in the target molecule intake unit 62 has been exposed to through pipe 77. Valve 92 is also opened to discharge the remaining sample solution in the mixing unit 91 through pipe 93.

(Step 6)
Valves 68 and 72 are opened to the sides of pipes 69 and 73, respectively, and valve 81 is also opened to drain the organic solvent from the organic solvent tank 65 into pipe 79 via the target molecule intake unit 62 and the metering unit 78. The target molecule intake unit 62 and the metering unit 78 are washed with the organic solvent in the organic solvent tank 65, which is not exposed to the sample atmosphere. Target molecules are discharged from the target molecule intake unit 62 and the metering unit 78.

(Step 7)
Valves 68 and 72 are opened to the side of piping 71 to supply the organic solvent from the organic solvent tank 65 to the metering unit 78 through piping 71. The organic solvent is supplied from the organic solvent tank 65 to the metering unit 78 without passing through the target molecule intake unit 62. In addition, valve 86 is opened to supply the aqueous solution from the aqueous solution tank 84 to the metering unit 87 through piping 85.

(Step 8)
Valve 82 is opened to supply the same first predetermined amount of organic solvent (which does not contain the target molecule) measured in the metering unit 78 to the mixing unit 91. Valve 88 is also opened to supply the same second predetermined amount of aqueous solution (which does not contain the target molecule) measured in the metering unit 87 to the mixing unit 91. As a result, a control solution is created in the mixing unit 91 in which the first predetermined amount of organic solvent (which does not contain the target molecule) 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 liquid 31. The aqueous solution of organic solvent that has incorporated the target molecule is called the sample solution.

(Step 9)
The control solution is supplied from the mixing unit 91 to the sensor unit 30 via the piping 95 by opening the valve 94. By comparing the measurement signal (electrical characteristics) of the sensor element 50 exposed to the control solution that does not contain the target molecule with the measurement signal (electrical characteristics) of the sensor element 50 exposed to the sample solution, if the target molecule is present in the sample solution, high-precision detection of the target molecule with corrected disturbance noise can be performed.

According to this embodiment, hydrophobic target molecules are concentrated and incorporated into the organic solvent, and the aqueous solution of the organic solvent (sample solution) containing these target molecules is exposed to the surface of the sensing unit 20. Therefore, the detection sensitivity of the target molecules can be increased compared to the case where hydrophobic target molecules are directly incorporated into the aqueous solution.

Biomolecules (e.g., peptides, DNA aptamers, etc.) function in aqueous solutions. Therefore, when a biomolecule is used as a probe molecule 32, exposure of the surface of the sensing element 20 to an organic solvent alters or destroys the structure of the biomolecule probe molecule 32, reducing its ability to capture target molecules.

Furthermore, because graphene is hydrophobic, it has a high affinity for organic solvents, and exposure of the graphene surface as the sensitive part 20 to organic solvents may cause damage. This damage raises concerns that organic solvents may penetrate the adhesion surface between the graphene and the underlying film, and the interface between the first and second electrodes 41 and 42 and the protective insulating film covering them, potentially inducing delamination of the graphene and the protective insulating film.

In this embodiment, the sample solution, which is an aqueous solution obtained by diluting an organic solvent with an aqueous solution, is exposed to the surface of the sensing part 20, thus preventing the above-mentioned problem.

When evaluating the quality of the sensor element 50, the control solution described above can be used as the liquid 31 supplied to the surface of the sensing unit 20. Alternatively, only the aqueous solution in the aqueous solution tank 84 may be used as the liquid 31 supplied to the surface of the sensing unit 20. The first liquid supply mechanism that supplies the liquid 31 to the surface of the sensing unit 20 may include at least the aqueous solution tank 84 and the piping 85, 89, and 95 connecting the aqueous solution tank 84 and the sensor unit 30.

In the sensor element evaluation method of the embodiment, a solution containing probe molecules 32 in a solvent can be supplied to the surface of the sensing part 20, the solvent can be evaporated, and then liquid 31 can be supplied to the surface of the sensing part 20. For example, after supplying the solution containing probe molecules 32 to the surface of the sensing part 20, the solvent is evaporated by drying the surface of the sensing part 20 at room temperature for a predetermined time or longer. This makes it easier for the probe molecules 32 to be confined in close proximity to the surface of the sensing part 20, as shown in Figures 3(b) to (d) above, making it easier to produce a high-quality sensor element. For example, a buffer solution can be used as the solvent.

Furthermore, in the sensor element evaluation method of this embodiment, if the sensor element 50 is evaluated as good, target molecules can be supplied to the surface of the sensing part 20 and its electrical characteristics can be measured. If it can be confirmed that the sensing part 20 responds to the target molecules during this electrical characteristic measurement, then the sensor element can be confirmed as a good element.

The embodiments may include the following sensor systems and methods for evaluating sensor elements.

[Structure 1]
A sensor element having a sensing portion, a probe molecule located on the surface of the sensing portion, and a first electrode and a second electrode electrically connected to the sensing 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 its electrical characteristics,
A sensor system equipped with the following features.
[Structure 2]
The sensing element is a sensor system according to configuration 1, including graphene.
[Structure 3]
A first liquid supply mechanism that supplies liquid to the surface of the sensing part,
A gate electrode that applies a voltage to the liquid supplied to the surface of the sensing part,
Furthermore,
The sensor system according to configuration 1 or 2, wherein when the current flowing between the first electrode and the second electrode through the sensing portion is Id and the voltage of the gate electrode is Vg, the electrical characteristics are Id-Vg characteristics.
[Structure 4]
The sensor system according to configuration 3, wherein the processing device evaluates the quality of the sensor element by comparing a first Id-Vg characteristic obtained when Vg is swept from a negative voltage to a positive voltage with a second Id-Vg characteristic obtained when Vg is swept from a positive voltage to a negative voltage.
[Structure 5]
The sensor system according to configuration 4, wherein the processing device evaluates the quality of the sensor element based on the difference in Id when Vg is the same value in the first Id-Vg characteristic and the second Id-Vg characteristic.
[Composition 6]
The sensor system according to configuration 5, wherein the processing device evaluates the quality of the sensor element based on the difference in Id when Vg is 0 or negative.
[Structure 7]
The sensor system according to configuration 4, wherein the processing device evaluates the quality of the sensor element based on the difference in Vg when Id is the same value in the first Id-Vg characteristic and the second Id-Vg characteristic.
[Structure 8]
A target molecule incorporation unit that exposes a sample atmosphere containing hydrophobic target molecules to a hydrophilic organic solvent,
A mixing unit that mixes 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 solution to the surface of the sensing part,
A sensor system according to any one of configurations 1 to 7, further comprising the above.
[Structure 9]
The sensor system according to any one of configurations 1 to 8, further comprising a storage device for storing the evaluation results of the quality of the sensor element by the processing device.
[Composition 10]
The sensor system according to any one of configurations 1 to 9, wherein the probe molecule comprises at least one of a protein, peptide, antibody, DNA aptamer, or a biomolecule derived thereof.
[Structure 11]
A method for evaluating a sensor element, in which a probe molecule is positioned on the surface of a sensing part, and a voltage is applied between a first electrode and a second electrode electrically connected to the sensing part, and the quality of the sensor element is evaluated based on the electrical characteristics of the sensor element.
[Structure 12]
A liquid is supplied to the surface of the sensing part.
A voltage is applied from the gate electrode to the liquid supplied to the surface of the sensing part.
A method for evaluating a sensor element according to configuration 11, wherein the current flowing between the first electrode and the second electrode through the sensing portion is Id, and the voltage of the gate electrode is Vg, and the Id-Vg characteristic is measured as the electrical characteristic.
[Composition 13]
A method for evaluating a sensor element according to configuration 12, which evaluates the quality of the sensor element by comparing a first Id-Vg characteristic obtained when Vg is swept from a negative voltage to a positive voltage with a second Id-Vg characteristic obtained when Vg is swept from a positive voltage to a negative voltage.
[Structure 14]
A method for evaluating a sensor element according to configuration 13, wherein the quality of the sensor element is evaluated based on the difference in Id when Vg is the same value in the first Id-Vg characteristic and the second Id-Vg characteristic.
[Composition 15]
The processing apparatus evaluates the quality of the sensor element according to configuration 14, based on the difference in Id when Vg is 0 or negative.
[Composition 16]
A method for evaluating a sensor element according to configuration 13, wherein the quality of the sensor element is evaluated based on the difference in Vg when Id is the same value in the first Id-Vg characteristic and the second Id-Vg characteristic.
[Composition 17]
A solution containing the probe molecule in a solvent is supplied to the surface of the sensing part.
A method for evaluating a sensor element according to any one of configurations 12 to 16, wherein the solvent is evaporated and the liquid is supplied to the surface of the sensing part.
[Composition 18]
A method for evaluating a sensor element according to any one of configurations 11 to 17, wherein if the sensor element is evaluated as good, a target molecule is supplied to the surface of the sensing part and the electrical characteristics are measured.

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 novel embodiments can be implemented in various other forms, and various omissions, substitutions, and modifications are possible without departing from the spirit of the invention. These embodiments and their variations are included within the scope and spirit of the invention, as well as within the scope of the invention and its equivalents as described in the claims.

10…Substrate, 20…Sensing element, 30…Sensor unit, 31…Liquid, 32…Probe molecule, 41…First electrode, 42…Second electrode, 43…Gate electrode, 50…Sensor element, 100…Processing device, 200…Memory device

Claims (14)

A sensor element having a sensing portion, a probe molecule located on the surface of the sensing portion, and a first electrode and a second electrode electrically connected to the sensing 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 its electrical characteristics,
A first liquid supply mechanism that supplies liquid to the surface of the sensing part,
A gate electrode that applies a voltage to the liquid supplied to the surface of the sensing part,
Equipped with ,
When the current flowing between the first electrode and the second electrode through the sensing portion is Id and the voltage of the gate electrode is Vg, the electrical characteristics are Id-Vg characteristics.
The processing device is a sensor system that evaluates the quality of the sensor element by comparing a first Id-Vg characteristic obtained when Vg is swept from a negative voltage to a positive voltage with a second Id-Vg characteristic obtained when Vg is swept from a positive voltage to a negative voltage . The sensor system according to claim 1, wherein the sensing element includes graphene. The sensor system according to claim 1 or 2, wherein the processing device evaluates the quality of the sensor element based on the difference in Id when Vg is the same value in the first Id-Vg characteristic and the second Id-Vg characteristic. The sensor system according to claim 3 , wherein the processing device evaluates the quality of the sensor element from the difference in Id when Vg is 0 or negative. The sensor system according to claim 1 or 2, wherein the processing device evaluates the quality of the sensor element from the difference in Vg when Id is the same value in the first Id-Vg characteristic and the second Id-Vg characteristic. A target molecule incorporation unit that exposes a sample atmosphere containing hydrophobic target molecules to a hydrophilic organic solvent,
A mixing unit that mixes 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 solution to the surface of the sensing part,
The sensor system according to claim 1 or 2, further comprising: The sensor system according to claim 1 or 2 , further comprising a storage device for storing the evaluation results of the quality of the sensor element by the processing device. The sensor system according to claim 1 or 2 , wherein the probe molecule comprises at least one of a protein, peptide, antibody, DNA aptamer, or a biomolecule derived thereof. A method for evaluating a sensor element, wherein a probe molecule is positioned on the surface of the sensing part, and a voltage is applied between a first electrode and a second electrode electrically connected to the sensing part, and the quality of the sensor element is evaluated based on the electrical characteristics of the sensor element ,
A liquid is supplied to the surface of the sensing part.
A voltage is applied from the gate electrode to the liquid supplied to the surface of the sensing part.
When the current flowing between the first electrode and the second electrode through the sensing part is Id and the voltage of the gate electrode is Vg, the Id-Vg characteristic is measured as the electrical characteristic.
A method for evaluating a sensor element, which involves comparing a first Id-Vg characteristic obtained when Vg is swept from a negative voltage to a positive voltage with a second Id-Vg characteristic obtained when Vg is swept from a positive voltage to a negative voltage, to evaluate the quality of the sensor element . The method for evaluating a sensor element according to claim 9 , wherein the quality of the sensor element is evaluated based on the difference in Id when Vg is the same value in the first Id-Vg characteristic and the second Id-Vg characteristic. The method for evaluating a sensor element according to claim 10, wherein the quality of the sensor element is evaluated based on the difference in Id when Vg is 0 or negative. The method for evaluating a sensor element according to claim 9 , wherein the quality of the sensor element is evaluated based on the difference in Vg when Id is the same value in the first Id-Vg characteristic and the second Id-Vg characteristic. A solution containing the probe molecule in a solvent is supplied to the surface of the sensing part.
A method for evaluating a sensor element according to any one of claims 9 to 12 , wherein the liquid is supplied to the surface of the sensing part after the solvent has evaporated. If the sensor element is evaluated as good, a method for evaluating a sensor element according to any one of claims 9 to 12, wherein a target molecule is supplied to the surface of the sensing part and the electrical characteristics are measured.