WO2017149579A1

WO2017149579A1 - Chemical-substance-sensing system

Info

Publication number: WO2017149579A1
Application number: PCT/JP2016/055966
Authority: WO
Inventors: 真斗永田; 健三黒土; 安藤　正彦; 希倫何; 典史亀代
Original assignee: 株式会社日立製作所
Priority date: 2016-02-29
Filing date: 2016-02-29
Publication date: 2017-09-08

Abstract

The purpose is to provide a chemical-substance-sensing system having high sensitivity and a long service life. The present invention is provided with: a chemical substance sensor provided with a detector for detecting a chemical substance in the air; a first solution that contacts the detector; a second solution having a greater solubility with respect to the chemical substance, which is to be measured, than does the first solution; and an atomization device for atomizing the second solution.

Description

Chemical substance sensing system

The present invention relates to a chemical substance sensing system that collects chemical substances contained in the atmosphere or various gases.

Chemical substances sensors that measure molecules in the atmosphere are called gas sensors or odor sensors. In particular, semiconductor gas sensors that use sintered metal oxides are widely used in applications such as flammable gas and poison gas alarms. in use.

Oxygen in clean air is adsorbed and present as oxygen ions on the metal oxide surface in the semiconductor gas sensor heated by the heater. Since oxygen draws electrons from the metal oxide when ionized, the carrier density decreases in the region near the surface, a depletion layer is formed, and the resistance value of the metal oxide increases.

If the air in contact with the metal oxide is not clean and contains a reducing gas, it reacts with oxygen ions adsorbed on the surface of the metal oxide and emits electrons to increase the carrier density. The resistance value of objects is reduced compared to clean air. Since this resistance value varies depending on the concentration of reducing gas such as methane, butane, hydrogen, carbon monoxide contained in the air, the semiconductor gas sensor can be used as a combustible gas sensor and a poison gas sensor.

The semiconductor gas sensor is small and inexpensive, but it responds if it is a reducing gas that reacts with oxygen ions. Therefore, gas chromatography (GC: Gas Chromatography) is used when there is a contaminated component in the gas or when multi-component analysis of a mixed gas is performed.

GC is separated by selectively delaying each component as it flows through the column due to the difference in adsorption characteristics depending on the boiling point and polarity of the stationary phase or packing material in the column. It is an analytical technique that is introduced and measures the concentration of each component. As the detector, a flame ionization detector, a thermal conductivity detector, a mass spectrometer, or the like can be used, but the operation principle of each detector is omitted. An analyzer using GC is larger and more expensive than a semiconductor gas sensor, and a delay time is provided for component separation, making it difficult to measure in real time.

The chemical substance sensor mentioned above is difficult to satisfy all in terms of device size, molecular selectivity, and response speed, but the olfaction in the living body is a small organ of several centimeters to several millimeters, Using hundreds to thousands of different olfactory receptors, components in the atmosphere can be distinguished with a response speed of 1 second or less. As for sensitivity, any measurement method depends on the measurement component, but since the living body can be felt even at a concentration of several ppt (part per trillion: 1/1 trillion) or less, the sensitivity of the living body is the GC. The sensitivity is equal to or higher than the sensitivity of a gas chromatograph mass spectrometer (GC-MS) using a mass spectrometer as a detector.

Biosensors using biomaterials such as cells, proteins, or lipid membranes have been studied in order to realize a highly selective sensor with a small size, high sensitivity, and fast response equivalent to the olfactory sense of the living body. Since biomaterials function in water, it is necessary to immerse the sensor in water. Therefore, it is necessary to dissolve in water to detect airborne substances.

However, in general, volatile odor molecules have a strong tendency to be hydrophobic and have low solubility in water. In living organisms, scent-binding proteins are synthesized and used to dissolve hydrophobic molecules in body fluids, but it is not possible to extract and purify odor-binding proteins suitable for various odor molecules in large quantities from living organisms. It's not easy. Therefore, there is a need for molecular solubilization techniques that can replace odor-binding proteins.

As an alternative method known at present, Patent Document 1 discloses a technique for atomizing a highly soluble solution in order to efficiently dissolve molecules in the air (see Patent Document 1). .

JP 2004-233061 A

As in Patent Document 1, when a high-solubility solution intended to efficiently collect molecules in the air is used, the chemical substance sensor is denatured, causing changes in characteristics and shortening of the lifetime. In particular, for living cells, in order to dissolve hydrophobic molecules in aqueous solution, it is known that even a commonly used solvent shows toxicity as the solvent concentration increases, and biological substances are used. It has become an issue of increasing the sensitivity of biosensors.

An object of the present invention is to provide a chemical substance sensing system with high sensitivity and long life.

In order to achieve the above object, the present invention provides a chemical substance sensor having a detection unit for detecting a chemical substance in a gas, a first liquid in contact with the detection unit, and a measurement object rather than the first liquid. A second liquid having a high solubility of the certain chemical substance and an atomizing device for atomizing the second liquid are provided.

According to the present invention, a highly sensitive and long-life chemical substance sensing system can be provided.

It is a schematic block diagram of the air molecule collection sensing system which is one Embodiment of this invention. 1 is a schematic configuration diagram of a spraying type gas molecule continuous collection and sensing system of Example 1. FIG. 6 is a schematic configuration diagram of an electric field type intermittent gas molecule collection / sensing system of Example 2. FIG. FIG. 5 is a schematic configuration diagram of a droplet type gas molecule intermittent collection and sensing system of Example 3.

In this embodiment, as shown in the schematic configuration diagram of the air molecule sensing system shown in FIG. 1, a detection unit S1 that operates in a liquid such as a biomolecule, and a conversion unit that converts a change in the detection unit S1 into an electrical signal. In the chemical substance sensor provided with S2, in order to detect air molecules difficult to dissolve in the sensor solution L1 necessary for the detection unit S1 to function with high sensitivity, It is effective to introduce the molecules into the sensor solution L1 after dissolving the molecules.

On the other hand, since the collection liquid L2 is mixed into the sensor solution L1 and the lifetime of the sensor is reduced, the atomization of the collection liquid L2 with the atomizer AT1 causes the gas and the collection liquid L2 to be atomized. By increasing the contact area and improving the collection efficiency, it is possible to reduce the amount of collected liquid mixed in the sensor solution while maintaining the sensor sensitivity, and to suppress a decrease in sensor life.

Hereinafter, an embodiment of the present invention will be described in detail using examples.

In the present embodiment, a spraying type gas molecule continuous collection sensing system, which is one form of the chemical substance sensing system, will be described. FIG. 2 is a schematic configuration diagram of the chemical substance sensing system in the present embodiment.

In FIG. 2, the gas taken in from the outside of the apparatus through the air inlet P1 by the air pump AP1 is introduced into the mixing tube T2 together with the mist solution L3 introduced from the mist introducing tube T1. Here, the atomized solution L3 is generated by finely dividing and collecting the collected liquid L2 discharged from the liquid feed pump LP1 by mechanical vibration excited on the surface of the atomizing device AT2. In this embodiment, a SAW device (Surface Acoustic Wave: surface acoustic wave) is used as the atomizing device.

The diameter of the generated mist solution L3 can be controlled by the interdigital electrode pattern on the surface of the SAW device AT2 and the frequency of the applied voltage. The number of mists introduced into the mixing tube T2 together with the gas taken in from the outside can be controlled by the power supplied to the SAW device AT2 and the length and cross-sectional area of the mist introducing tube L3. Note that not only the SAW device but also an ultrasonic atomizing unit, a coaxial type or a direct type nebulizer can be used for the atomizing apparatus.

The mist solution L3 passes through the inside of the mixing tube T2 (mixing region) while dissolving molecules in the gas introduced together, and is sprayed on the surface of the sensor solution L1. The time for the atomized solution L3 to dissolve the molecules in the air can be controlled by the length of the mixing tube T2 and the air flow rate of the air pump AP1. That is, the air pump AP1 functions as a control unit that controls the mixing time of the molecules in the gas and the mist solution L3 in the mixing tube T2.

Here, while the length of the mixing tube T2 is a fixed value, the air flow rate of the air pump AP1 is variable, so that the measurement sensitivity and response speed can be optimized for each measurement condition. For example, if the concentration of molecules in the gas to be measured cannot be detected due to low concentration, the air flow rate of the air pump AP1 is decreased and the mixing time is extended to remove more molecules in the gas in a mist solution. It can be dissolved in L3 to increase the detection accuracy. However, since the response speed of the measurement decreases as the mixing time is lengthened, it is necessary to increase the air supply flow rate of the air pump AP1 in applications where real-time measurement is important, such as odor source search.

Therefore, the air pump AP1 can be used as a control unit in order to set the detection accuracy and response speed according to the intended use.

The collected liquid L2 to be atomized has a high solubility of the measurement target substance contained in the gas, has low toxicity with respect to the detection unit C1 provided with detection cells, and is a sensor solution L1 mainly composed of water. It is desirable that it is easy to mix. Dimethyl sulfoxide (DMSO) or ethanol is known as a material that satisfies such conditions, and a solvent suitable for the measurement object may be selected. For example, when the object to be measured is alkane, it is preferable to use ethanol because of its low solubility in DMSO.

The mist solution L3 is mixed when sprayed on the surface of the sensor solution L1, and separated from the gas component not dissolved in the mist solution L3, and the remaining gas component is discharged from the exhaust port P2.

The component collected in the sensor solution L1 comes into contact with a receptor expressed in the cell membrane of the detection unit C1 (detection unit including cells and cell membranes) in contact with the sensor solution L1, and changes the ion concentration inside and outside the cell, This change is detected by utilizing the change in the electrical characteristics of the ISFET (Ion Sensitive Field Effect Transistor) I1 in the vicinity of the cell.

Detection of collected components is not limited to changes in ion concentration, but uses changes in ionic current that flow inside and outside the cell as a receptor opens and closes in the cell membrane, changes in cell membrane potential, and changes in fluorescence intensity due to fluorescent proteins in the cell. May be detected.

The detection unit C1 may be configured to include a protein, a lipid membrane, or a sensitive membrane (a sensitive membrane modified with a polymer or functional group having selectivity for a chemical substance to be measured). As described above, high molecular selectivity can be obtained by using biologically derived substances such as proteins, lipid membranes, and cells. However, since the lifetime is shorter than that of the sensitive membrane, the configuration of the detection unit C1 is set according to the purpose of use. You can choose.

If the mist solution L3 is continuously mixed in the sensor solution L1, the concentration of the collection liquid L2 with respect to the sensor solution L1 increases, the toxicity of the detection unit C1 having cells increases, and the sensor life is shortened. . Therefore, the concentration of the collected liquid L2 with respect to the sensor solution L1 is maintained below a certain level by replenishing the sensor solution L1 as needed by the liquid feed pump LP2 and discharging it from the waste liquid port P3. Therefore, the liquid feed pump LP2 has a function as a liquid control unit that replaces or circulates the sensor solution L1.

It is desirable that the collected liquid L2 has low toxicity to cells. Specifically, a solution that does not denature proteins under conditions of 1% by volume or more with respect to water, or the inhibition rate after 24 hours of living cells is 50%. The following solutions are used. If the solubility is 1% by volume or more, it is possible to introduce more molecules in the gas into the water than it is less than that, and the dissolution rate is fast even if the concentration is lower than 1% by volume. It is possible to detect molecules introduced into water earlier. Therefore, the collection liquid L2 has a solubility of 1 atm and a volume of 1% by volume or more under the conditions of 25 ° C.

Specifically, methanol, ethanol, ethylene glycol, acetonitrile, acetone, dimethylformamide, isopropyl alcohol, n-propanol, tetrahydrofuran, dioxane, hexamethylphosphoric triamide, dimethyl sulfoxide, methyl ethyl ketone, triethylamine, ethyl acetate, etc. may be used. A solution having high molecular solubility in the gas to be measured is selected as the collection liquid L2. For example, when the object to be measured is alkane, the solubility in DMSO is low. Therefore, by selecting ethanol, alkane can be detected with high sensitivity.

In the configuration of the present embodiment, since the gas to be measured can be continuously inhaled using the air pump AP1 and measured in real time, it is suitable for applications where a short measurement interval is important, such as odor source search. ing.

In this embodiment, an electric field type intermittent gas molecule collection sensing system, which is one form of the chemical substance sensing system, will be described. FIG. 3 is a schematic configuration diagram of the chemical substance sensing system in the present embodiment.

The difference from the spray-type gas molecule continuous collection and sensing system shown in Example 1 is that the mixing tube T2 is eliminated, and the SAW device AT2 that is an atomizer and the ion-responsive electric field that is a measurement unit of the chemical substance sensor. The effect transistor I1 and the detection unit C1 including cells are disposed in the same space, and the large electrode E1 and the small electrode E2 covered with the insulating film IF1. In this embodiment, an electric field gradient is generated between the large electrode E1 and the small electrode E2.

In this embodiment, the size of the entire apparatus can be reduced by eliminating the mixing tube T2, but the function of adjusting the mixing time depending on the length of the mixing tube T2 is lost. Therefore, the function of controlling the mixing time according to the operation cycle of the air pump AP1 is substituted by intermittently performing the intake operation by the air pump AP1.

The gas introduced into the collection space SP1 (mixing region) by short-time intake by the air pump AP1 is mixed with the mist solution generated by the SAW device AT2, and is retained in the collection space SP1 for an arbitrary time. That is, the air pump AP1 functions as a control unit that controls the mixing time of the solution in the collection space SP1.

After the air molecules are sufficiently dissolved in the atomized solution, an electric field gradient is generated inside the collection space SP1 by generating a potential difference between the large electrode E1 and the small electrode E2 using the external power source V1. Since the atomized solution in the electric field is polarized in each droplet and generates a dipole moment, the atomized solution receives an attractive force in the direction of the strong electric field and is attracted to the sensor solution L1 side and collected.

In FIG. 3, the small electrode E2 covered with the insulating film IF1 is arranged on the opposite side of the collection space SP1 across the ion-responsive field effect transistor I1, but the electric field generated by the ion-responsive field effect transistor I1. If the shielding effect of is large, it may be arranged at the boundary between the ion-responsive field-effect transistor I1 and the detection unit C1 including cells, or at the boundary between the detection unit C1 and the sensor solution L1.

In the configuration of the present embodiment, by applying a voltage to the large electrode E1 and the small electrode E2, the mixing time can be accurately controlled, and the mixing time of the molecules in the gas and the atomized solution L3 can be made uniform. Therefore, it is suitable for applications in which measurement accuracy of molecular concentration is important, such as component analysis.

In this embodiment, a droplet type intermittent gas molecule collection sensing system, which is a form of a chemical substance sensing system, will be described. FIG. 4 is a schematic configuration diagram of the chemical substance sensing system in the present embodiment.

The difference from the droplet-type gas molecule intermittent collection and sensing system of Example 2 is that the large and small electrodes E1 and E2 are eliminated, and the liquid supply system that supplies the solution to the atomizer (SAW device) AT2 is the collection liquid L2. In addition to LP1 that supplies the sensor solution, LP3 that supplies the sensor solution L1 is provided.

The sedimentation speed L of the collected liquid L2 that has become fine droplets by the SAW device AT2 is slow, and it is about several tens of μm / s using Stokes' formula for determining the terminal speed when the microparticles in the fluid settle. It is.

Since the terminal velocity of sedimentation is proportional to the square of the droplet diameter, the larger the droplet diameter generated by the atomizer, the faster the sedimentation. However, in order to dissolve the air molecules in the droplet The smaller the diameter of the collected liquid L2 droplet, the more convenient in terms of the contact area. Therefore, if a droplet having a larger diameter can be separately generated, the liquid of the collection L2 can be maintained without adopting the configuration including the electric field application electrode as in Example 2 while keeping the collection area large. Drops can be collected and introduced into the sensor solution.

If the recovery droplet is the same as the collection liquid L2, the concentration of the collection liquid L2 in the sensor solution L1 increases and the sensor life decreases, so the sensor solution L2 is supplied to the SAW device AT2 and atomized. Thus, an increase in concentration can be avoided. If the droplet diameter for recovery is 100 μm, the sedimentation termination speed is several tens of cm / s, and the collected liquid can be recovered sufficiently quickly.

Each embodiment described above enables solubilization of hydrophobic molecules, which is a common problem faced by gas sensors and odor sensors that must operate in liquids, such as biosensors using biomaterials. At the same time, it is possible to avoid shortening the service life of the sensor by minimizing contamination of the solution by the collected liquid.

In addition, according to the present embodiment, in order to improve the detection sensitivity of air molecules in the chemical substance sensor, a solution having a higher solubility than the solution in contact with the chemical substance sensor can be efficiently collected. Can collect airborne molecules. In addition, by atomizing the collection solution and increasing the contact area with the gas, it is possible to efficiently collect air molecules with a small amount of solution, and the concentration of the collection solution with respect to the solution in contact with the chemical substance sensor By reducing the above, it is possible to suppress the denaturation of the material used for the detection part of the chemical substance sensor and extend the life.

In order to analyze components present in the atmospheric environment with high sensitivity, a large-scale device such as GC-MS is conventionally required. However, this example provides portable high sensitivity and high selectivity. Provided chemical sensor, and use it for detection of explosives, narcotics and victims who had to rely on the smell of animals such as trained dogs and mice, and for home use of medical breath analysis be able to.

In the configuration of the present embodiment, the mixing tube T2 in the first embodiment and the external power supply V2 in the second embodiment are not necessary, and the size of the entire system can be reduced. Suitable for applications where safety and low power consumption are important.

AP1: Air pump AT1: Atomizer AT2: SAW device C1: Detection unit E1: Large electrode E2: Small electrode I1: ISFET
IF1: Insulating film L1: Sensor solution L2: Collection liquid L3: Atomized solution LP1: Collection liquid feed pump for atomizer LP2: Sensor solution feed pump LP3: Sensor solution feed pump P1 for atomizer Intake port P2: Exhaust port P3: Waste liquid port S1: Chemical substance sensor detection unit S2: Chemical substance sensor conversion unit T1: Fog introduction tube T2: Mixing tube V1: External power supply

Claims

A chemical substance sensor comprising a detection unit for detecting a chemical substance in the gas;
A first liquid in contact with the detection unit;
A second liquid having a higher solubility of the chemical substance to be measured than the first liquid;
A chemical substance sensing system comprising an atomizing device for atomizing the second liquid.
The said chemical substance sensor is equipped with the sensitive film | membrane modified with the polymer or functional group which has selectivity with respect to the chemical substance used as a cell, protein, a lipid membrane, or a measuring object, The claim 1 characterized by the above-mentioned. Chemical substance sensing system.
The chemical substance sensing system according to claim 1, wherein the chemical substance sensor includes an ion-responsive field effect transistor.
The chemical substance sensing system according to claim 1, further comprising a liquid control unit that exchanges or circulates the first liquid.
The chemical substance sensing system according to claim 1, wherein the solubility of the second liquid in water is 1% by volume or more under the conditions of 1 atm and 25 ° C.
2. The chemical substance sensing system according to claim 1, wherein the second liquid does not denature the protein under the condition of 1% by volume or more, or the inhibition rate after 24 hours of living cells is 50% or less.
The second liquid component includes any of methanol, ethanol, ethylene glycol, acetonitrile, acetone, dimethylformamide, isopropyl alcohol, n-propanol, tetrahydrofuran, dioxane, hexamethylphosphoric triamide, dimethyl sulfoxide, methyl ethyl ketone, triethylamine, and ethyl acetate. The chemical substance sensing system according to claim 1, further comprising:
The chemical substance sensing system according to claim 1, further comprising a mixing region for introducing or holding a gas containing a second liquid atomized by the atomizing unit and a substance to be measured.
The chemical substance sensing system according to claim 8, further comprising a control unit that controls a mixing time in the mixing region.
The chemical substance sensing system according to claim 8, further comprising a control unit that controls a diameter of a mist introduced or held in the mixing region.
The chemical substance sensing system according to claim 8, further comprising a control unit that controls a liquid amount of mist introduced or held in the mixing region.