Chemical Sensor System

Abstract

To provide a chemical sensor system capable of improving the detection sensitivity of a target substance.SOLUTION: A chemical sensor system includes: a chemical sensor having a sensor element and probe molecules located on a surface of the sensor element; a collection unit for a sample atmosphere; a humidifier for generating humidified air having a higher humidity than the sample atmosphere; a switching mechanism connected to the collection unit, the humidifier, and the chemical sensor, for switching between a state in which the sample atmosphere is supplied to the surface of the sensor element and a state in which the humidified air is supplied to the surface of the sensor element; and a cooling mechanism for cooling the sensor element.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] FIELD OF THE INVENTION Embodiments of the present invention relate to chemical sensor systems. [Background technology]

[0002] There is a demand for improved sensitivity in chemical sensors that detect target substances in the gas phase. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Japanese Patent Application Publication No. 2019-168663 [Patent Document 2] Japanese Patent Publication No. 2021-031382 Summary of the Invention [Problem to be solved by the invention]

[0004] An object of an embodiment of the present invention is to provide a chemical sensor system that can improve the detection sensitivity of a target substance. [Means for solving the problem]

[0005] According to an embodiment of the present invention, a chemical sensor system includes a chemical sensor having a sensor element and probe molecules located on the surface of the sensor element, a sample atmosphere collection unit, a humidifying device that generates a humidified fluid with a higher humidity than the sample atmosphere, a switching mechanism connected to the collection unit, the humidifying device, and the chemical sensor that switches between a state in which the sample atmosphere is supplied to the surface of the sensor element and a state in which the humidifying fluid is supplied to the surface of the sensor element, and a cooling mechanism that cools the sensor element. [Brief explanation of the drawings]

[0006] [Figure 1] 1 is a schematic diagram illustrating a configuration of a chemical sensor system according to an embodiment. [Figure 2] FIG. 2(a) is a schematic diagram of a sensor element according to an embodiment, and FIG. 2(b) is a schematic diagram of the surface of the sensor element. [Figure 3] FIG. 2 is a schematic diagram of a chemical sensor and a cooling mechanism according to an embodiment. [Figure 4] FIG. 10 is a schematic diagram illustrating another example of a cooling mechanism according to the embodiment. [Figure 5] FIG. 10 is a diagram showing experimental results. [Figure 6] FIG. 10 is a diagram showing experimental results. [Figure 7] FIG. 10 is a diagram showing experimental results. [Figure 8] FIG. 10 is a diagram showing experimental results. [Figure 9] FIG. 10 is a diagram showing experimental results. [Figure 10] FIG. 10 is a diagram showing experimental results. [Figure 11] FIG. 10 is a diagram showing experimental results. [Figure 12] FIG. 10 is a diagram showing experimental results. [Figure 13] FIG. 1 is a schematic diagram showing the configuration of a chemical sensor system used in an experiment. [Figure 14] FIG. 1 is a schematic diagram showing the configuration of a chemical sensor system used in an experiment. DETAILED DESCRIPTION OF THE INVENTION

[0007] Hereinafter, embodiments will be described with reference to the drawings, in which the same components are denoted by the same reference numerals.

[0008] 1, the chemical sensor system 1 of the embodiment includes a first collection unit 101 into which a sample atmosphere is taken in, and a chemical sensor 10. The chemical sensor system 1 can also include, for example, a first pipe 102, an exhaust pipe 105, and an exhaust device 120 as mechanisms for supplying the sample atmosphere taken in from the first collection unit 101 to the chemical sensor 10. The sample atmosphere is, for example, air.

[0009] The first pipe 102 is connected between the first collection unit 101 and the chemical sensor 10. The chemical sensor 10 is connected between the first pipe 102 and the exhaust pipe 105. The exhaust device 120 is connected to the exhaust pipe 105. The exhaust device 120 is, for example, a fan. The first collection unit 101 has a first collection port 101a that opens to the outside of the first pipe 102. By driving the exhaust device 120, a gas flow is formed from the first collection port 101a, through the first pipe 102 and the chemical sensor 10, to the exhaust pipe 105. The exhaust device 120 may be an air pump.

[0010] The chemical sensor 10 includes a sensor element 31 shown in Fig. 2(a). The sensor element 31 has, for example, a GFET (graphene field effect transistor) structure, and a surface 31a of the sensor element 31 includes graphene. For example, the sensor element 31 can include a substrate 37, graphene 32 supported on the substrate 37, a first electrode 35, and a second electrode 36.

[0011] The substrate 37 is, for example, a silicon substrate. The graphene 32 is provided on the substrate 37 via, for example, an underlayer 38. The underlayer 38 may be, for example, a silicon oxide film. The underlayer 38 may also function as a chemical catalyst for forming the graphene 32.

[0012] One of the first electrode 35 and the second electrode 36 functions as a drain electrode, and the other functions as a source electrode. The first electrode 35 and the second electrode 36 are in electrical contact with the graphene 32. A current (drain current) flows between the first electrode 35 and the second electrode 36 through the graphene 32. The chemical sensor system 1 may include a measurement device 90 (shown in FIG. 1 ) that measures the drain current.

[0013] 2(b), the chemical sensor 10 has a probe molecule 33 located on the surface 31a of the sensor element 31. The probe molecule 33 being located on the surface 31a of the sensor element 31 means that the probe molecule 33 is bound, adsorbed, or comes close to the surface 31a of the sensor element 31 by chemical or charge attraction, π-π interaction, cation-π interaction, hydrophobic interaction, or the like, and the probe molecule 33 is confined to the surface 31a of the sensor element 31. The probe molecule 33 can be any substance that exhibits binding properties to a target substance, such as a protein, a peptide, an antibody, a DNA aptamer, or a derivative thereof.

[0014] When the probe molecule 33 recognizes or captures a target substance, the target substance approaches the surface of the graphene 32, and the charge of the target substance or the structural change of the probe molecule 33 caused by capturing the target substance changes the electronic state of the graphene 32. By detecting this as a change in the current (drain current) flowing between the first electrode 35 and the second electrode 36, the presence and concentration of the target substance in the sample atmosphere can be determined.

[0015] As shown in Fig. 3, the sensor element 31 can be mounted on a cartridge substrate 21. A substrate 37 of the sensor element 31 is adhered to the surface of the cartridge substrate 21 by, for example, a thermally conductive adhesive 22. An input / output terminal 23 is provided at one end of the cartridge substrate 21. One end of the cartridge substrate 21 is inserted into a socket 24, and the input / output terminal 23 is electrically connected to an electrode 25 provided on the socket 24. The socket 24 is electrically connected to the measuring device 90 shown in Fig. 1.

[0016] A first wiring 11 electrically connected to the first electrode 35 and a second wiring 12 electrically connected to the second electrode 36 are provided on a substrate 37 of the sensor element 31. The first wiring 11 and the second wiring 12 are each electrically connected to a wiring portion 27 provided on the cartridge substrate 21 via a gold wire 13. The wiring portion 27 is electrically connected to the input / output terminal 23. The gold wire 13, the joint between the gold wire 13 and the first wiring 11, the joint between the gold wire 13 and the second wiring 12, and the joint between the gold wire 13 and the wiring portion 27 are covered and protected by an insulating resin 14.

[0017] A window 102a is formed in the sensor element placement portion of the first pipe 102, and a packing 15 is provided around the outer periphery of the window 102a. When the sensor element 31 mounted on the cartridge substrate 21 is positioned in the window 102a, the surface 31a of the sensor element 31 is airtightly sealed off from the outside by the packing 15 and is exposed to the inside of the first pipe 102. This configuration allows the sensor element 31 to be attached and detached as a replacement part or a consumable part.

[0018] The chemical sensor system 1 further includes a cooling mechanism 50 that cools the sensor element 31. In the example shown in Fig. 3, the cooling mechanism 50 includes a Peltier element 51 and a cold storage body 52 that contacts a surface (heat absorbing surface) 51a of the Peltier element 51.

[0019] The Peltier element 51 is electrically connected to the drive wiring 54. The cold storage body 52 has thermal conductivity and electrical conductivity. For example, Al or Cu can be used as the material of the cold storage body 52. ​​The cold storage body 52 is fixed to, for example, ground potential via a voltage control device 70 shown in FIG. 1 as necessary. In addition, the temperature of the cold storage body 52 can be detected by a thermocouple 53, and the detection result can be fed back to drive the Peltier element 51.

[0020] The cold storage body 52 is disposed between the cartridge substrate 21 and the Peltier element 51. The lower surface of the cold storage body 52 contacts the surface 51a of the Peltier element 51. The upper surface of the cold storage body 52 contacts the thermally conductive member 28 provided on the lower surface of the cartridge substrate 21. The thermally conductive member 28 is connected to a plurality of thermally conductive vias 26 that penetrate the cartridge substrate 21. The thermally conductive member 28 may be, for example, a highly thermally conductive sheet containing carbon, metal, ceramic powder, or thermal grease. The thermally conductive vias 26 may be made of, for example, a board wiring material such as Cu plating, or a highly thermally conductive paste containing metal or ceramic powder.

[0021] Between the surface 51 a of the Peltier element 51 and the sensor element 31 , a heat conduction path is formed by the cold storage body 52 , the heat conduction member 28 , the heat conduction vias 26 , and the heat conduction adhesive 22 .

[0022] As shown in FIG. 4, the cooling mechanism 50 may have a cooling pipe 55 that is in contact with the lower surface of the cooling storage body 52 and through which cooling water flows, and a non-polarizable electrode 56 that is at least partially located within the cooling pipe 55.

[0023] The non-polarizable electrode 56 is electrically connected to the voltage control device 70 shown in Fig. 1. The non-polarizable electrode 56 comes into contact with the cooling water flowing in the cooling pipe 55 and fixes the potential of the cooling water. For example, the cooling water containing chloride ions flows in the cooling pipe 55, and the non-polarizable electrode 56 is an Ag / AgCl electrode.

[0024] As shown in FIG. 1, the chemical sensor system 1 further includes a humidifier 40 that generates a humidified fluid with a higher humidity than the sample atmosphere. The humidified fluid may be, for example, humidified air or humidified nitrogen. The humidifier 40 may be, for example, an impinger containing a humidification source, a pipe with a nonwoven fabric wetted with the humidification source attached to its inner wall, a bubbling device, or a spray device. The humidifier 40 is a device that increases the vapor pressure of a predetermined substance contained in the fluid. The predetermined substance may be, for example, a hydrophilic or amphiphilic substance that binds to probe molecules. The predetermined substance may, for example, not denature the probe molecules and maintain the three-dimensional structure of the probe molecules in a desired form. The predetermined substance may, for example, be a volatile liquid or gas at room temperature and normal pressure. In addition to water, the predetermined substance may be, for example, a carbonyl compound such as acetone or an alcohol such as methanol or ethanol.

[0025] The chemical sensor system 1 includes a first collection unit 101, a first wiring 102, a humidifier 40, and switching mechanisms 110-112 connected to the chemical sensor 10. In the first piping 102, the switching mechanism 111 is located between the first collection unit 101 and the switching mechanism 112, the switching mechanism 112 is located between the switching mechanism 111 and the switching mechanism 110, and the switching mechanism 110 is located between the switching mechanism 112 and the chemical sensor 10. As the switching mechanisms 110-112, for example, ball valves can be used.

[0026] The humidifier 40 is connected to the second pipe 104. The upstream end of the second pipe 104 is connected to the switching mechanism 112, and the downstream end of the second pipe 104 is connected to the switching mechanism 110.

[0027] Furthermore, second collection unit 103 can be connected to switching mechanism 111 via third piping 106. For example, a reference atmosphere located away from the sample atmosphere can be taken into third piping 106 from second collection port 103a of second collection unit 103. By switching switching device 111 and switching device 112 to a state connecting third piping 106 and second piping 104 and switching device 110 to a state connecting second piping 104 and chemical sensor 10, the reference atmosphere can be humidified by humidifier 40, and the humidified fluid humidified by humidifier 40 can be supplied to chemical sensor 10.

[0028] That is, by switching the switching mechanisms 110 to 112, it is possible to switch between a state in which the sample atmosphere is supplied to the surface of the sensor element 31 (detection phase) and a state in which the humidifying fluid is supplied to the surface of the sensor element 31 (humidification phase). During the detection phase, the humidifying fluid is not supplied to the surface of the sensor element 31. During the humidification phase, the sample atmosphere is not supplied to the surface of the sensor element 31.

[0029] Furthermore, by switching the switching mechanisms 110 to 112, a dew condensation removal phase in which the reference atmosphere is supplied to the chemical sensor 10 without passing through the humidifier 40 can be executed.

[0030] The chemical sensor system 1 may further include a control device 80. The control device 80 may control the humidifier 40, the switching mechanisms 110 to 112, the measuring device 90, the chemical sensor 10, the fan 120, the cooling mechanism 50, and the voltage control device 70.

[0031] Under the control of the control device 80, the humidification phase is executed for a predetermined time, then stopped, and the system transitions to a dew condensation phase as needed. After the dew condensation phase is executed for a predetermined time, the system transitions to a detection phase, where target substances in the sample atmosphere are detected. In the humidification phase, the probe molecules 33 located on the surface of the sensor element 31 are humidified, activating the probe molecules 33. This improves the target substance capture ability of the probe molecules 33, thereby improving the target substance detection sensitivity. However, if water droplets are formed due to condensation during the humidification phase, this can cause noise. In this case, the water droplets are removed in the dew condensation phase. In the dew condensation removal phase (water droplet removal phase), the water droplets are evaporated and removed, but the hydrophilic portions of the probe molecules 33 remain humidified, allowing the capture ability to be expressed.

[0032] In this embodiment, the sample atmosphere itself is not humidified, but the surface of the sensor element 31 is humidified before the detection phase, and in the detection phase, the unhumidified sample atmosphere is supplied to the surface of the sensor element 31. As shown in the experimental results described later, this improves the detection sensitivity of the target substance compared to when the sample atmosphere is humidified and supplied to the surface of the sensor element 31 in the detection phase.

[0033] Furthermore, by cooling the sensor element 31 with the cooling mechanism 50, the temperature of the sample atmosphere supplied to the surface of the sensor element 31 is lowered, and the target substance is more likely to be adsorbed onto the surface (including the probe molecules 33) of the sensor element 31. This further improves the detection sensitivity of the target substance.

[0034] Cooling can prevent the substance supplied in the humidification phase, such as water, from evaporating from the sensor element 31. Cooling also prevents the water bound to the probe molecules 33 from being released, maintaining the three-dimensional structure of the probe molecules 33. As a result, the probe molecules 33 can maintain a high binding affinity to the target substance for a long period of time.

[0035] Furthermore, by fixing the potentials of the cold storage body 52 and the cooling water, noise due to potential fluctuations can be reduced and stable detection can be performed.

[0036] Next, we will explain the experimental results. In the following experiments, a GFET was used as the sensor element. A nine-residue peptide was used as the probe molecule. The peptide has the sequence RRWLPLWRR-GGGC, with the first nine residues being the probe site. GGG is the spacer sequence, and C is the linker site for binding to the maleimide group of the scaffold molecule.

[0037] Figure 13 is a schematic diagram showing the configuration of the system used in the experiment. An empty impinger 203 and an impinger 202 containing a target substance were connected between a nitrogen gas (N2 gas) cylinder 201 and a GFET 31, and it was possible to switch between a state in which nitrogen gas was supplied to the GFET 31 via the impinger 202 containing the target substance and a state in which nitrogen gas was supplied to the GFET 31 via the empty impinger 203. In the graphs shown below, the horizontal axis represents time (minutes), and the vertical axis represents the drain current (relative value) of the GFET.

[0038] In the experiment whose results are shown in Figure 5, PEA (phenylethylamine) was used as the target substance. While nitrogen gas was being supplied to the GFET 31 via the empty impinger 203, nitrogen gas was also supplied to the GFET 31 via the impinger containing PEA for time T. Also, in Figure 5, "with downstream humidification" represents a state in which nitrogen gas was supplied to the GFET 31 with the humidifier 40 connected downstream of the impinger 202 containing PEA and the empty impinger 203. The humidifier 40 contains a nonwoven fabric containing water. "without downstream humidification" represents a state in which nitrogen gas was supplied to the GFET 31 from the impinger 202 containing PEA and the empty impinger 203 via the dryer tube 204 without passing through the humidifier 40. The connection between the humidifier 40 and the impinger 202 and the connection between the humidifier 40 and the impinger 203 could be manually switched. Furthermore, the connection between the GFET 31 and the humidifier 40 and the connection between the GFET 31 and the dryer tube 204 can also be manually switched.

[0039] The results in Figure 5 show that the drain current response at time T is greater without downstream humidification than with downstream humidification, i.e., the detection sensitivity of PEA is higher. With downstream humidification, humidified nitrogen gas containing PEA is supplied to the GFET. When water vaporizes in the nitrogen gas containing PEA, the partial pressure of water vapor in the total gas pressure increases, causing a vapor pressure competition with the partial pressure of PEA. However, since there is no new evaporation source for PEA, only the partial pressure of water increases, resulting in a partial liquefaction of some of the PEA, which is thought to reduce the detection sensitivity of PEA.

[0040] Next, in the experiment whose results are shown in Figures 6 and 7, borneol was used as the target substance. This experiment used the system shown in Figure 14. Humidifier 40 and dryer tube 204 are connected upstream of impingers 202 and 203. For time T, nitrogen gas is supplied to GFET 31 via impinger 202 containing borneol. Figure 6 shows the experimental results at room temperature, and Figure 7 shows the experimental results when GFET 31 was cooled using cooling water (pure water and its ice) from cooling device 50.

[0041] In the room temperature experiment results shown in Figure 6, a large drain current response is observed immediately after switching the nitrogen gas flow path from the empty impinger 203 to the impinger 202 containing borneol. This is thought to be due to the fact that the gas containing borneol at a high concentration that filled the impinger 202 was supplied to the GFET 31. After that, no large drain current response is observed, even though the gas containing borneol is supplied to the GFET 31. Furthermore, no large drain current response is observed even when the supply of borneol is stopped. This is thought to be because borneol was not adsorbed to the GFET 31 in the first place in the latter half of time T, and therefore borneol did not desorb from the GFET 31 after the supply of borneol was stopped.

[0042] In contrast, in the experimental results for the cooled case shown in Figure 7, it can be seen that the amount of borneol adsorbed to GFET 31 increases during time T while borneol is being supplied to GFET 31, resulting in an increase in the drain current. Furthermore, because a sufficient amount of borneol is adsorbed to GFET 31 during time T, after the supply of borneol is stopped, the desorption of borneol from GFET 31 is seen as a decrease in the drain current. In other words, cooling the sensor element can improve the detection sensitivity of the target substance.

[0043] Next, in the experiment shown in Figures 8 and 9, nitrogen gas containing borneol was supplied to a GFET cooled with cooling water, and the drain current was measured. Figure 8 shows the results when pure water and its ice were used as the cooling water and the potential of the cooling water was not fixed (the potential of the cooling water was floating), while Figure 9 shows the results when 150 mM KCl and its ice were used as the cooling water and the potential of the cooling water was fixed at 0 mV (more precisely, the potential applied to the Ag / AgCl electrode) using an Ag / AgCl electrode.

[0044] The results shown in Figure 8 show drift-like noise and spike-like noise that are thought to be caused by fluctuations in the potential of the cooling water. The results shown in Figure 9, where the potential of the cooling water was fixed, show that noise other than the response to borneol is reduced.

[0045] Next, in the experiment whose results are shown in Figures 10 to 12, nitrogen gas containing borneol was supplied to the GFET for time T1, and nitrogen gas was supplied to the GFET via an empty impinger and a humidification tube for time T2 (humidification phase). During the humidification phase, condensation was observed on the surface of the GFET, and condensation remained on the surface of the GFET for several minutes after the humidification phase. The GFET was at room temperature.

[0046] Figure 11 shows the results of measuring the drain current again 8 minutes after the measurement shown in Figure 10. Figure 12 shows the results of measuring the drain current again 4 minutes after the measurement shown in Figure 11.

[0047] The drain current response to borneol after the humidification phase at time T2 was greater than the drain current response to borneol before the humidification phase (when the GFET surface was dry), indicating that humidifying the sensor element surface in advance can improve the detection sensitivity of the target substance. Furthermore, the results in Figures 11 and 12 indicate that the highly active state of the GFET surface is maintained even after the condensation on the GFET surface disappears, and this highly active state was confirmed to be maintained for at least 1.5 hours in this experiment. This is consistent with the fact that the drain current, which increased due to humidification, remains high. Therefore, it is possible to determine whether the highly active state is maintained using the drain current value.

[0048] Although several 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 embodied 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 within the scope and spirit of the invention, and are also included in the scope of the invention and its equivalents as defined in the claims. [Explanation of symbols]

[0049] 1...chemical sensor system, 10...chemical sensor, 31...sensor element, 32...graphene, 33...probe molecule, 37...substrate, 40...humidifier, 50...cooling mechanism, 51...Peltier element, 52...cold storage body, 55...cooling piping, 56...non-polarizable electrode, 110...switching mechanism,

Claims

1. a chemical sensor having a sensor element and a probe molecule located on a surface of the sensor element; a sample atmosphere collection section; a humidifying device that generates a humidified fluid having a higher humidity than the atmosphere of the specimen; a switching mechanism connected to the collection unit, the humidifying device, and the chemical sensor, for switching between a state in which the sample atmosphere is supplied to the surface of the sensor element and a state in which the humidifying fluid is supplied to the surface of the sensor element; a cooling mechanism for cooling the sensor element; A chemical sensor system comprising:

2. 2. The chemical sensor system according to claim 1, wherein the cooling mechanism includes a cooling pipe through which cooling water flows.

3. The chemical sensor system of claim 2 , further comprising a non-polarizable electrode located at least partially within the cooling piping.

4. The cooling water containing chlorine ions flows through the cooling pipe, 4. The chemical sensor system according to claim 3, wherein the non-polarizable electrode is an Ag / AgCl electrode.

5. The chemical sensor system according to claim 1 , wherein the cooling mechanism includes a Peltier element.

6. 6. The chemical sensor system according to claim 5, further comprising a cooling storage body in contact with the surface of the Peltier element.

7. The chemical sensor system according to claim 6 , wherein the regenerator is capable of fixing a potential.

8. The chemical sensor system according to any one of claims 1 to 7, wherein the surface of the sensor element comprises graphene.

9. 8. The chemical 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 from these.

10. a pipe connecting the collection unit and the switching mechanism; a pipe connecting the humidifier and the switching mechanism; a pipe connecting the chemical sensor and the switching mechanism; The chemical sensor system according to any one of claims 1 to 7, comprising:

11. The chemical sensor system according to claim 10 , wherein the piping connecting the chemical sensor and the switching mechanism includes a fan or a pump for causing a gas to flow from the switching device toward the chemical sensor.

12. 8. The chemical sensor system according to claim 1, wherein the humidifying fluid includes water.

13. 2. The chemical sensor system according to claim 1, further comprising a regenerator having a fixed potential.

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