WO2019156180A1 - Système de dissolution pour composé organique peu soluble dans l'eau, procédé de dissolution d'un composé organique peu soluble dans l'eau et système de détection d'odeur - Google Patents

Système de dissolution pour composé organique peu soluble dans l'eau, procédé de dissolution d'un composé organique peu soluble dans l'eau et système de détection d'odeur Download PDF

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Publication number
WO2019156180A1
WO2019156180A1 PCT/JP2019/004475 JP2019004475W WO2019156180A1 WO 2019156180 A1 WO2019156180 A1 WO 2019156180A1 JP 2019004475 W JP2019004475 W JP 2019004475W WO 2019156180 A1 WO2019156180 A1 WO 2019156180A1
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soluble organic
organic compound
aqueous solution
container
water
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PCT/JP2019/004475
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English (en)
Japanese (ja)
Inventor
大悟 照月
秀文 光野
健志 櫻井
亮平 神崎
暢之 間瀬
浩平 佐藤
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国立大学法人東京大学
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Priority to JP2019571154A priority Critical patent/JPWO2019156180A1/ja
Publication of WO2019156180A1 publication Critical patent/WO2019156180A1/fr

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F21/00—Dissolving
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F25/00—Flow mixers; Mixers for falling materials, e.g. solid particles
    • B01F25/50—Circulation mixers, e.g. wherein at least part of the mixture is discharged from and reintroduced into a receptacle
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F25/00—Flow mixers; Mixers for falling materials, e.g. solid particles
    • B01F25/70—Spray-mixers, e.g. for mixing intersecting sheets of material
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F31/00—Mixers with shaking, oscillating, or vibrating mechanisms
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F35/00—Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
    • B01F35/90—Heating or cooling systems
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M1/00—Apparatus for enzymology or microbiology
    • C12M1/34—Measuring or testing with condition measuring or sensing means, e.g. colony counters

Definitions

  • the present invention relates to a dissolution technique, and relates to a dissolution system for a poorly water-soluble organic compound, a dissolution method for a poorly water-soluble organic compound, and an odor detection system.
  • an object of the present invention is to provide a dissolution system for a poorly water-soluble organic compound, a dissolution method for a poorly water-soluble organic compound, and an odor detection system that can dissolve a poorly water-soluble organic compound in the air.
  • droplets containing bubbles having a diameter of 1 ⁇ m or less are sprayed toward a container that can store a gaseous sparingly water-soluble organic compound and a gas containing the sparingly water-soluble organic compound in the container.
  • a dissolution system for a poorly water-soluble organic compound comprising a spraying device, and storing an aqueous solution containing the poorly water-soluble organic compound in a container.
  • the dissolution system of the slightly water-soluble organic compound described above further includes a suction device that sucks the aqueous solution stored in the container and sends it to the spray device, and the spray device generates droplets from the aqueous solution sent from the suction device. May be.
  • the suction device may continuously send the aqueous solution to the spray device.
  • the above-described system for dissolving a slightly water-soluble organic compound may further include an aqueous solution stirring element for stirring the aqueous solution in the container.
  • the above-described dissolution system for hardly water-soluble organic compounds may further include a heating device for heating the container so that the hardly water-soluble organic compounds in the gas are not condensed.
  • the heating device may include a hot tub for warming the container.
  • the above-mentioned dissolution system of a poorly water-soluble organic compound may further include a warm bath liquid stirring element for stirring the warm bath liquid in the warm bath.
  • the poorly water-soluble organic compound may be an odor substance.
  • the spray device may be configured to spray droplets containing bubbles having a diameter of 1 ⁇ m or less by ultrasonic vibration.
  • a liquid containing bubbles having a diameter of 1 ⁇ m or less toward the gas containing the poorly water-soluble organic compound in the container and storing the gaseous hardly water-soluble organic compound in the container.
  • a method for dissolving a poorly water-soluble organic compound comprising spraying droplets and storing an aqueous solution containing the poorly water-soluble organic compound in a container.
  • an aqueous solution stored in a container may be sucked to generate droplets from the aqueous solution.
  • the aqueous solution stored in the container may be continuously sucked to generate droplets from the aqueous solution.
  • the method for dissolving the slightly water-soluble organic compound may further include stirring the aqueous solution in the container.
  • the method for dissolving the hardly water-soluble organic compound may further include heating the container so that the hardly water-soluble organic compound in the gas is not condensed.
  • the container may be heated using a hot tub for warming the container.
  • the above-described method for dissolving a slightly water-soluble organic compound may further include stirring the warm bath liquid in the warm bath.
  • the poorly water-soluble organic compound may be an odor substance.
  • droplets containing bubbles having a diameter of 1 ⁇ m or less may be sprayed by ultrasonic vibration.
  • a container capable of storing a gaseous odor substance
  • a spray device that sprays droplets containing bubbles having a diameter of 1 ⁇ m or less toward the gas containing the odor substance in the container
  • an odor detection system including an odor sensor to which an aqueous solution containing an odor substance stored in a container is supplied.
  • the odor sensor may include a cell that reacts to an odor substance.
  • the cell may emit fluorescence in response to the odor substance.
  • the odor sensor includes a transistor having a gate electrode containing aluminum or aluminum oxide, an insect cell having an olfactory receptor disposed on the gate electrode, and the insect cell reacts to an odor substance in an aqueous solution. And a detection device for detecting a current generated in the transistor when the transistor is used.
  • the odor sensor includes a transistor having a gate electrode containing aluminum or aluminum oxide, a chamber for placing an insect cell having an olfactory receptor disposed on the transistor, and an insect on the gate electrode. And a detection device that detects a current generated in the transistor when the cell reacts to an odorous substance in the aqueous solution.
  • the insect cell may express an olfactory receptor by a transgene.
  • the insect cell may express an insect olfactory receptor.
  • the olfactory receptor may be an ion channel type receptor.
  • the olfactory receptor may be selected from BmOR1, BmOR3, Or13a, Or56a, Or85b, and PxOR1.
  • the insect cell may be a moth-derived cell.
  • the insect cell may be selected from Sf21, Sf9, High Five, and Tni-derived cells.
  • the insect cell may be a Drosophila-derived cell.
  • the insect cell may be a Drosophila S2 cell.
  • the insect cell may express a fluorescent protein whose fluorescence intensity changes according to the ion concentration.
  • the transistor may be a field effect transistor.
  • the gate electrode may be an extended gate electrode.
  • aluminum or aluminum oxide may be exposed on the surface of the gate electrode.
  • the odor detection system may further include a Faraday cage that covers the transistor.
  • the spray device may be configured to spray droplets containing bubbles having a diameter of 1 ⁇ m or less by ultrasonic vibration.
  • a dissolution system for a poorly water-soluble organic compound a dissolution method for a poorly water-soluble organic compound, and an odor detection system capable of dissolving a slightly water-soluble organic compound in the air in an aqueous solution.
  • FIG. 1 is a chemical formula of 1-octen-3-ol according to Example 1.
  • 3 is a graph showing the change over time of the concentration of 1-octen-3-ol in the air according to Example 1.
  • 6 is a graph showing the change over time of the concentration of 1-octen-3-ol in liquids according to Example 1 and Comparative Example 1.
  • Example 3 is a graph showing a change over time in the dissolution rate of 1-octen-3-ol according to Example 1 and Comparative Example 1.
  • 6 is a graph showing the change over time of the concentration of 1-octen-3-ol in the air according to Example 2.
  • 6 is a graph showing the change over time of the concentration of 1-octen-3-ol in the liquid according to Example 2.
  • 6 is a graph showing changes in the dissolved concentration of 1-octen-3-ol over a long period of time according to Example 3.
  • 10 is a table showing changes in the dissolution concentration of 1-octen-3-ol over a long period of time according to Example 3.
  • 10 is a graph showing the change over time of the concentration of 1-octen-3-ol in the air according to Example 4.
  • 10 is a graph showing the change over time of the concentration of 1-octen-3-ol in the liquid according to Example 4.
  • 10 is a graph showing changes over time in concentrations of 3-octaneone, 3-octanol and 1-octen-3-ol in the air according to Example 5.
  • 10 is a graph showing changes over time in the concentrations of 3-octaneone, 3-octanol and 1-octen-3-ol in a liquid according to Example 5. It is a graph which shows the relationship between the distance from the nozzle tip which concerns on Example 6, and the water surface of aqueous solution, and the number of particles.
  • 10 is a graph showing the fluorescence intensity generated in Sf21 cells in response to 1-octen-3-ol according to Example 7.
  • FIG. 10 is a graph showing the fluorescence intensity generated in Sf21 cells in response to 1-octen-3-ol according to Example 7. It is a microscope picture which shows the time-dependent change of the Sf21 cell on the aluminum substrate based on Example 8.
  • FIG. It is a graph which shows the time-dependent change of the survival rate of the Sf21 cell on the aluminum substrate based on Example 8.
  • It is a microscope picture which shows the time-dependent change of HEK293T cell on the aluminum substrate based on Example 8.
  • the dissolution system for a poorly water-soluble organic compound includes a container 1 that can store a gaseous hardly water-soluble organic compound, and the poorly water-soluble organic compound in the container 1.
  • a spraying device 20 that sprays droplets containing bubbles having a diameter of 1 ⁇ m or less toward the gas, and the aqueous solution 2 containing the poorly water-soluble organic compound is stored in the container 1.
  • the container 1 may be made of a transparent material such as glass and resin, or may be made of an opaque material.
  • the container 1 has, for example, a cylindrical shape, but is not particularly limited.
  • an aqueous solution 2 for dissolving the hardly water-soluble organic compound is placed on the bottom of the container 1.
  • the aqueous solution 2 is, for example, a buffer solution, a culture solution, and a fragrance solvent, but is not particularly limited.
  • the aqueous solution 2 includes water and pure water.
  • an index representing the water solubility of an organic compound is a partition coefficient.
  • the partition coefficient is a value obtained from the concentration ratio of the organic compound in each phase when the organic compound is dissolved in two phases of water and an organic solvent such as 1-octanol.
  • LogP Log 10 (C O / C W ) (1)
  • C 2 O represents the concentration of the organic compound in the organic solvent phase
  • C W represents the concentration of the organic compound in the aqueous phase.
  • the higher the partition coefficient the more fat the organic compound is and the lower the water solubility.
  • an organic compound having a partition coefficient of 2.0 or more is referred to as a hardly water-soluble compound.
  • the poorly water-soluble organic compound is, for example, an odor substance.
  • other examples of poorly water-soluble organic compounds include alcohols, aldehydes, ketones, amines, terpenes, aromatic compounds, esters, acids, hydrocarbons, ethers, lactones, amides, and lactams.
  • the gas containing the poorly water-soluble organic compound introduced into the container 1 is, for example, air, but is not particularly limited.
  • the container 1 is provided with an inlet for introducing a gas containing the aqueous solution 2 and the poorly water-soluble organic compound.
  • the inlet is sealed. Therefore, the container 1 can be sealed.
  • the spraying device 20 is provided on the upper surface or side surface of the container 1, for example.
  • the spraying device 20 includes, for example, a spray nozzle and a piezo that applies ultrasonic waves to the spray nozzle. Due to the ultrasonic vibration, droplets containing bubbles having a diameter of 1 ⁇ m or less are generated from the liquid supplied to the spray nozzle. Spraying using ultrasonic waves does not require pressurization and can be operated with a small amount of liquid feeding, and is also useful for miniaturization with low power consumption. However, the spraying method can be other than ultrasonic waves.
  • the spraying device 20 is not particularly limited as long as it can spray droplets containing bubbles having a diameter of 1 ⁇ m or less.
  • the droplets have the same composition as the aqueous solution 2.
  • Bubbles having a diameter of 1 ⁇ m or less contained in the droplet shown in FIG. 2 are also called ultrafine bubbles.
  • the diameter of the bubbles is, for example, 10 nm or more, 20 nm or more, or 30 nm or more.
  • the diameter of the bubbles is, for example, 700 nm or less, 800 nm or less, or 900 nm or less.
  • the bubble diameter may be not less than 100 nm and not more than 200 nm.
  • the droplet sprayed by the spray device 20 shown in FIG. 1 falls toward the aqueous solution 2 according to gravity. Bubbles having a diameter of 1 ⁇ m or less contained in the droplets falling on the aqueous solution 2 diffuse into the aqueous solution 2. Bubbles having a diameter of 1 ⁇ m or less cannot be visually observed in the droplet or in the aqueous solution 2. If the aqueous solution 2 before containing bubbles is colorless and transparent, the aqueous solution 2 remains colorless and transparent even if bubbles having a diameter of 1 ⁇ m or less are included. However, bubbles having a diameter of 1 ⁇ m or less can be observed with a liquid particle observation device. As a liquid particle observation apparatus, for example, Nanosite LM10 (Malvern Instruments Limited) can be used.
  • the surface of bubbles with a diameter of 1 ⁇ m or less is usually negatively charged. Therefore, aggregation of bubbles is difficult to occur.
  • the buoyancy of bubbles having a diameter of 1 ⁇ m or less is extremely small, the bubbles having a diameter of 1 ⁇ m or less do not float up to the surface of the aqueous solution 2, but Brown moves in the aqueous solution 2 and tends to stay in the aqueous solution 2 for a long time.
  • the slightly water-soluble organic compound dissolution system further includes a suction device 30 that sucks the aqueous solution 2 stored on the bottom of the container 1 and sends it to the spraying device 20.
  • the suction device 30 sucks the aqueous solution 2 in the container 1 through, for example, a pipe 31 connected to the side wall of the container 1.
  • the suction device 30 sends the aqueous solution 2 to the spraying device 20 via a pipe 32 connected to the spraying device 20.
  • the spray device 20 generates droplets from the aqueous solution 2 sent from the suction device 30.
  • the aqueous solution 2 circulates in the container 1 and the path including the suction device 30 and the spray device 20.
  • a pump can be used as the suction device 30, a pump can be used.
  • the pump include a tube pump such as a peristaltic pump (registered trademark), a roller pump, and a peristaltic pump. Or a ceramic pump is mentioned as an example of a pump.
  • the suction device 30 continuously sends liquid to the spray device 20, for example. Pumps that send the liquid in the tube by compressing the tube, such as a tube pump, a roller pump, and a peristaltic pump, are suitable for continuous liquid feeding.
  • the slightly water-soluble organic compound dissolution system may further include an aqueous solution stirrer 40 that stirs the aqueous solution 2 in the container 1 and a magnetic stirrer that rotates the aqueous solution stirrer 40.
  • an aqueous solution stirrer 40 that stirs the aqueous solution 2 in the container 1
  • a magnetic stirrer that rotates the aqueous solution stirrer 40.
  • the dissolution system of a hardly water-soluble organic compound according to the embodiment may further include a heating device 3 that heats the container 1 so that the hardly water-soluble organic compound in the gas in the container 1 is not condensed and liquefied.
  • the heating device 3 may include a hot tub 51 that warms the container 1.
  • the slightly water-soluble organic compound dissolution system may further include a warm bath agitator 4 that agitates the warm bath fluid 52 in the warm bathtub 51.
  • a warm bath agitator 4 that agitates the warm bath fluid 52 in the warm bathtub 51.
  • the odor detection system according to the second embodiment includes a container 1 capable of storing a gaseous odor substance shown in FIG. 1 and a droplet containing bubbles having a diameter of 1 ⁇ m or less toward the gas containing the odor substance in the container 1. 3, and a odor sensor 500 shown in FIG. 3 to which an aqueous solution containing an odor substance stored in the container 1 is supplied. Since the dissolution system of the slightly water-soluble organic compound according to the second embodiment is the same as that of the first embodiment, description thereof is omitted.
  • the odor sensor 500 includes a transistor 10 having a gate electrode 14 containing aluminum or aluminum oxide, an insect cell 50 having an olfactory receptor disposed on the gate electrode 14, and a transistor 10 when the insect cell 50 reacts to an odor. And a detection device 80 for detecting a current generated in the above.
  • the transistor 10 includes a semiconductor substrate 11.
  • the transistor 10 is, for example, a field effect transistor (FET), and may be a MOSFET.
  • FET field effect transistor
  • a source electrode 12 and a drain electrode 13 are provided at an interval.
  • a gate electrode 14 is disposed between the source electrode 12 and the drain electrode 13 of the semiconductor substrate 11 with an oxide insulating film interposed therebetween.
  • the gate electrode 14 may be an extended gate electrode.
  • the gate electrode 14 is made of aluminum, and an oxide film made of aluminum oxide (Al 2 O 3 ) is formed in the vicinity of the surface. An oxide film made of aluminum oxide (Al 2 O 3 ) may not be formed near the surface.
  • the gate electrode 14 which is an extended gate electrode has a region where the insect cells 50 are arranged. The size of the region where the insect cells 50 are arranged is, for example, 100 ⁇ m ⁇ 100 ⁇ m, but is not limited thereto. The number of insect cells 50 arranged on the gate electrode 14 is, for example, 10 or less, but is not limited thereto.
  • the insect cell 50 is disposed on the gate electrode 14 of the transistor 10.
  • the insect cell 50 adheres to the gate electrode 14 by giving a solution containing the insect cell 50 on the gate electrode 14 and allowing it to stand for several tens of minutes to several hours.
  • Insect cells 50 express olfactory receptors on their cell membranes.
  • the olfactory receptor may be naturally expressed or may be expressed by a transgene.
  • the insect cells may be cells derived from moths such as Spodoptera frugiperda and Trichoplusia ni.
  • Sf21 and Sf9 are mentioned as an example of a cell derived from a mushroom.
  • Sf21 cells are derived from ovarian cells. Sf21 cells can divide indefinitely and establish a stable expression line that permanently expresses the introduced gene. In addition, Sf21 cells can survive in a wide temperature range of 18 ° C. to 40 ° C., and carbon dioxide for adjusting the pH of the culture solution is unnecessary. Sf21 cells originally do not have olfactory receptors, but can express olfactory receptors by introducing olfactory receptor genes.
  • Sf9 cells are clones of Sf21. Examples of cells derived from nettle guava include High Five and Tni. Tni-derived cells are derived from ovarian cells.
  • the insect cell may be a Drosophila-derived cell.
  • Drosophila-derived cells include Drosophila S2 cells.
  • the olfactory receptor may be a G protein-coupled receptor or an ion channel receptor.
  • the ion channel type receptor has a part that interacts with a ligand that is an odor substance and a part into which ions flow.
  • a cation such as sodium ion or calcium ion flows into the insect cell 50.
  • ion influx can occur in the order of tens of milliseconds after ligand binding.
  • the amount of ions flowing in is large, and it is said that the amount of ions flowing into the cell is 10 7 with respect to the binding of one ligand.
  • certain types of olfactory receptors have specificity for certain odorants.
  • only one type of olfactory receptor corresponding to one type of odor substance may be expressed, or a plurality of types of olfactory receptors corresponding to a plurality of types of odor substances may be expressed.
  • the detection sensitivity of the odor sensor may be adjusted by adjusting the amount of the olfactory receptor to be expressed.
  • olfactory receptors examples include BmOR1, which is a Bombykol receptor for Bombykol, a BmOR3 receptor for Bombykal, a Drosophila receptor, which is a Bombykal pheromone.
  • Or13a which is a receptor for 1-octen-3-ol which is a musty odor
  • a receptor for Drosophila which is a receptor for a mold odor
  • ore 56a which is a receptor for Drosophila
  • Or85b which is a general odor receptor for Drosophila melanogaster
  • PxOR1 which is the female sex pheromone receptor, but is not limited to.
  • a gene encoding the olfactory receptor When expressing an olfactory receptor in insect cells 50 by genetic engineering, for example, a gene encoding the olfactory receptor is incorporated into a vector, and the constructed vector is transfected into a host cell.
  • a gene encoding an olfactory receptor can be isolated by, for example, extracting mRNA from an olfactory organ of an insect and synthesizing cDNA. From the isolated cDNA, it is possible to amplify a part of the gene encoding the olfactory receptor by PCR using PCR primers.
  • Part of the gene encoding the olfactory receptor can also be obtained by incorporating the synthesized double-stranded cDNA into an appropriate vector and transforming Escherichia coli etc. using the vector to prepare a cDNA library. it can.
  • the cDNA can be incorporated into the vector by a conventional method using a restriction enzyme and ligase, for example, by cleaving the obtained cDNA with a restriction enzyme, inserting it into a restriction enzyme site of vector DNA, and ligating it to the vector.
  • the fluorescent protein may be expressed together with the olfactory receptor.
  • ions such as calcium ions flow in the insect cell 50 when an odorant is bound to the ion channel type olfactory receptor. Therefore, by introducing into the insect cell 50 a gene that expresses a fluorescent protein whose fluorescence intensity changes according to the ions, it is confirmed whether the insect cell 50 detects an odor substance from the change in the fluorescence intensity. It becomes possible.
  • fluorescent proteins include GCaMP3, GCaMP6s and aequorin.
  • At least a part of the gate electrode 14 of the odor sensor according to the embodiment is disposed in the chamber 60.
  • An aqueous solution 70 that may contain an odorous substance to be detected is placed in the chamber 60.
  • the aqueous solution 70 may appropriately contain substances necessary for the survival of the insect cells 50.
  • the reference electrode 15 is disposed in the chamber 60 so as to be in contact with the aqueous solution 70.
  • the chamber 60 may be provided with an inlet for feeding an aqueous solution that may contain an odor substance into the chamber 60 and an outlet for discharging the aqueous solution in the chamber 60.
  • An introduction pump for feeding the aqueous solution into the chamber 60 is connected to the introduction port of the chamber 60.
  • a discharge pump for discharging the aqueous solution from the chamber 60 is connected to the discharge port of the chamber 60.
  • a fixed liquid feed pump can be used as the introduction pump and the discharge pump.
  • the insect cell 50 When an odorous substance corresponding to the olfactory receptor of the insect cell 50 is present in the aqueous solution 70, the insect cell 50 reacts with the odorous substance and the gate potential of the gate electrode 14 is displaced, so that the source electrode 12 and the drain electrode 13 Modulation occurs in the drain current flowing between them. Therefore, it is possible to detect the presence of an odorous substance by detecting the modulation of the drain current of the transistor 10.
  • the detection device 80 is connected to, for example, the source electrode 12, the drain electrode 13, the back gate 16, and the reference electrode 15 of the transistor 10, and detects modulation of the drain current of the transistor 10.
  • a source major unit (SMU) or the like can be used as the detection device 80.
  • the detection device 80 may be connected to a computer system 300 for analyzing the detected current or displaying it on a display.
  • the reason why the insect cell 50 reacts to the odor substance and the gate potential of the gate electrode 14 is displaced is considered to be that when the insect cell 50 reacts to the odor substance, an inward ion flow is generated in the insect cell 50. It is not bound by the theory.
  • the odor sensor according to the embodiment may include a Faraday cage that covers the transistor 10. Since the Faraday cage shields the transistor 10 from the electric field, it is possible to reduce the noise of the drain current in the odor sensor.
  • the electrode of the transistor is formed of gold or coated with a biocompatible material, and the cell is disposed thereon.
  • these methods are costly.
  • the present inventors have conducted intensive research, and insect cells are not damaged by aluminum or aluminum oxide and can survive for a long period of time even when placed on the electrode where aluminum or aluminum oxide is exposed. I found out. Therefore, according to the embodiment, it is possible to provide a highly reliable and low-cost odor sensor using, for example, a commercial CMOS foundry.
  • the insect cell 50 can survive for 5 days or longer, for example.
  • the odor sensor according to the embodiment can be reused repeatedly by cleaning the odor sensor after use.
  • a cleaning method for example, a commercially available detergent may be dropped on the surface of the transistor 10.
  • Example 1 A dissolution system for poorly water-soluble organic compounds as shown in FIG. 4 was prepared.
  • a liquid odor substance container 201 made of glass is placed in a 500 mL beaker 110, and 1 mL of liquid odor substance 1-octen-3-ol (Sigma Aldrich, content 98%) is placed in the liquid odor substance container 201.
  • 1-octen-3-ol has a smell of mold, a mushroom, and a person's sweat.
  • the chemical formula of 1-octen-3-ol is as shown in FIG. 1-octen-3-ol is a poorly water-soluble organic compound.
  • the liquid odor substance container 201 shown in FIG. 4 includes a lid, but has a structure that allows the odorous substance that has volatilized to communicate between the inside and outside of the container.
  • a stirrer 140 was placed in the beaker 110.
  • the beaker 110 was sealed with a lid 112.
  • the lid 112 is provided with an atomizer 120 (Sonaer Inc.) capable of spraying droplets containing bubbles having a diameter of 1 ⁇ m or less in the beaker 110. Further, a pipe 131 for sucking distilled water 111 in the beaker 110 was provided through the lid 112, and the pipe 131 was connected to the suction port of the ceramic pump 130 (CPA-2, ASONE). Further, a pipe 132 connecting the discharge port of the ceramic pump 130 and the liquid supply port of the atomizer 120 is disposed.
  • the beaker 110 was put in a hot tub 151 containing a warm bath solution 152 as water.
  • a stirrer 160 was placed in the warm bath liquid 152.
  • the hot tub 151 was placed on a hot magnet stirrer 153 (CMAGHS100 digital, IKA) having a temperature feedback function.
  • the room temperature was 21.5 ° C.
  • the hot bath liquid 152 was kept at 30 ° C. with a hot magnet stirrer 153 equipped with a temperature feedback function. In this state, the liquid 1-octen-3-ol in the liquid odor substance container 201 was volatilized in the beaker 110. Next, 50 mL of distilled water, which is the amount that does not allow the liquid odor substance container 201 to sink, is put into the beaker 110 by the syringe 210 provided on the lid 112, and the ceramic pump 130 is driven after rotating the stirring bars 140 and 160.
  • distilled water 111 in the beaker 110 was sucked at a flow rate of about 13 mL / min, supplied to the atomizer 120, and droplets containing bubbles having a diameter of 1 ⁇ m or less were sprayed from the atomizer 120.
  • an aqueous solution in which 1-octen-3-ol is dissolved in distilled water 111 in the beaker 110 is sucked with a syringe 210, and the sucked aqueous solution is analyzed with a gas chromatography device (GC-2010, Shimadzu Corporation).
  • the concentration of 1-octen-3-ol contained in the sucked aqueous solution was measured.
  • FIG. 7 1 minute after the start, the concentration of 1-octen-3-ol in the aqueous solution reached an average of 39 ⁇ mol / L, and thereafter, with the passage of time, 1-octen- It was confirmed that the concentration of 3-ol was increased.
  • the dissolution rate of 1-octen-3-ol in the aqueous solution reached nearly 20% 30 minutes after the start of spraying of droplets containing bubbles having a diameter of 1 ⁇ m or less.
  • a temperature-controlled water bath (Thermax, ASONE) with temperature feedback is used instead of the hot tub 151 and the hot magnet stirrer 153, and the ceramic pump 130 and the atomizer 120 are stopped.
  • 1-octen-3-ol was dissolved in distilled water 111, and the concentration of 1-octen-3-ol contained in the aqueous solution was measured.
  • a container placed in the beaker was charged with 2 mL of liquid 1-octen-3-ol.
  • the room temperature was 26 ° C.
  • the concentration of 1-octen-3-ol in the aqueous solution was not detected by the gas chromatography apparatus for the first 5 minutes.
  • the concentration of 1-octen-3-ol in the aqueous solution increased after 10 minutes, but was lower than that in Example 1.
  • the dissolution rate of 1-octen-3-ol in the aqueous solution was low compared to Example 1 even 30 minutes after the start of spraying of the droplets containing bubbles having a diameter of 1 ⁇ m or less.
  • Example 2 1 ⁇ L of 1-octen-3-ol (Sigma Aldrich, content 98%) was dissolved in 999 ⁇ L of distilled water and stirred with a vortex mixer to prepare 1 mL of diluted odorant solution.
  • the diluted odor substance solution was placed in the liquid odor substance container 201 shown in FIG. Except for this point and that the room temperature is 23 ° C., 1-octen-3-ol is dissolved in distilled water 111 in the same manner as in Example 1, and the concentration of 1-octen-3-ol contained in the aqueous solution is adjusted. Measured. As a result, as shown in FIG. 9, it was confirmed that the concentration of 1-octen-3-ol in the gas decreased with the passage of time.
  • Example 3 Using the system for dissolving poorly water-soluble organic compounds shown in Example 1, 1-octen-3-ol was dissolved in distilled water to obtain an odorant solution.
  • a gas chromatography apparatus GC-2010, Shimadzu Corporation
  • the concentration of 1-octen-3-ol in the odorant solution immediately after the odorant was dissolved was as shown in FIG. 11 and FIG. It was 418 ⁇ mol / L.
  • the concentration of 1-octen-3-ol in the odorant solution was high even after 2 and 6 months.
  • Example 4 4 except that the stirring bars 140 and 160 shown in FIG. 4 were not used, a temperature-controlled water bath with temperature feedback (Thermax, ASONE) was used instead of the hot tub 151 and the hot magnet stirrer 153, and the room temperature was 30.5 ° C.
  • distilled water 111 was supplied to the atomizer 120 using a ceramic pump, and 1-octen-3-ol was dissolved in the distilled water 111.
  • a thermostatic water bath with temperature feedback (Thermax, ASONE) is used, the room temperature is 30.0 ° C, and instead of the ceramic pump 1-octen-3-ol was dissolved in distilled water 111 in the same manner as in Example 1 except that a peristaltic pump (registered trademark, AC-2120 peristal biomini pump, ATTO) with a flow rate of 17 mL / min was used. It was. As a result, as shown in FIGS.
  • FIG. 4 shows 333 ⁇ L of 3-octaneone (Sigma Aldrich, content of 98% or more), 333 ⁇ L of 3-octanol (Sigma Aldrich, content of 99%), and 333 ⁇ L of 1-octen-3-ol (Sigma Aldrich, content of 98%).
  • a total of 999 ⁇ L of odorant mixed solution was prepared in the liquid odorant container 201 shown. Except for this point and the room temperature of 30.5 ° C., three kinds of odorous substances were dissolved in distilled water 111 in the same manner as in Example 1, and the concentration of each odorous substance contained in the aqueous solution was measured.
  • the concentration of odorous substance in the gas before the operation of the apparatus was highest at 1-4.7 ppm for 3-octaneone, 2.2 ppm for 3-octanol, and 2.7 ppm for 1-octen-3-ol.
  • FIG. 15 it was confirmed that the concentration of the odorous substance in the gas decreased with the passage of time.
  • FIG. 16 it was confirmed that all odorous substances were dissolved in the aqueous solution 1 minute after the operation of the apparatus, and the concentration increased with the passage of time.
  • the solution concentration in aqueous solution was highest for 3-octaneone, which has a large volatilization amount, and it was confirmed that 3-octanol and 1-octen-3-ol, which had the same volatilization amount, had the same dissolution concentration. It was. This indicates that not only the aliphatic unsaturated alcohol 1-octen-3-ol but also the aliphatic ketone 3-octaneone and the aliphatic saturated alcohol 3-octanol can be dissolved in an aqueous solution in a short time. . It also shows that various odorous substances are dissolved in an aqueous solution while maintaining the ratio existing in the air.
  • Example 6 It is expected that the larger the amount of bubbles contained in the droplets sprayed from the ultrasonic spray nozzle, the more efficient dissolution of the gaseous odor substance is expected. Therefore, the amount of bubbles contained in the droplets was investigated based on the difference in distance between the nozzle tip and the liquid level of the aqueous solution. Using a funnel, a glass bottle, a 200 mL beaker, and a 500 mL beaker, the distance from the nozzle tip to the liquid level of the aqueous solution was changed to 0 mm, 3.8 mm, and 11.7 mm in three stages for spraying. At the time of spraying, the aqueous solution was perfused using the ceramic pump 130 shown in FIG.
  • the hot tub 151 was not used, and the room temperature was 23 ° C. Moreover, it verified about the influence which stirring of aqueous solution with a stirring bar has on the quantity of the bubble which exists in aqueous solution.
  • a hot magnet stirrer 153 was used for stirring with a stir bar.
  • the ceramic pump 130 was driven at a flow rate similar to that of Example 1 for 5 minutes, distilled water was 50 mL, and the room temperature was about 23 ° C.
  • the distance between the nozzle tip and the liquid surface of the aqueous solution was 0 mm and stirring was performed, particles of 8.7 ⁇ 10 8 particles / mL were confirmed.
  • Sf21 cells expressing the Or13a receptor and the co-receptor DmOrco were obtained by the lipofection method.
  • the Or13a receptor is an olfactory receptor that responds to 1-octen-3-ol.
  • Sf21 cells were passaged from 1 to 3 days. Thereafter, using a cell counter, the concentration of Sf21 cells was adjusted from 1.0 ⁇ 10 6 cells / mL to 1.5 ⁇ 10 6 cells / mL, and Sf21 cells were adhered to a petri dish.
  • the room temperature is 25.5 ° C.
  • the amount of 1-octen-3-ol in the liquid odor substance container 201 is 2 mL
  • the stirrers 140 and 160 are not inserted, and a constant temperature water bath with temperature feedback (Thermax, ASONE 1-octen-3-ol was dissolved in distilled water 111 by the same method as in Example 1 except that the above was used.
  • the aqueous solution in which 1-octen-3-ol was dissolved was analyzed with a gas chromatography apparatus (GC-2010, Shimadzu Corporation), and the concentration of 1-octen-3-ol in the aqueous solution was determined. Based on the determined concentration, an aqueous solution in which 1-octen-3-ol is dissolved is diluted with an assay buffer solution, and the concentration of 1-octen-3-ol is 1 ⁇ mol / L, 3 ⁇ mol / L, 10 ⁇ mol / L, And 30 micromol / L aqueous solution was prepared as a sample.
  • a gas chromatography apparatus GC-2010, Shimadzu Corporation
  • the composition of the assay buffer was 140 mmol / L NaCl, 5.6 mmol / L KCl, 4.5 mmol / L CaCl 2 , 11.26 mmol / L MgCl 2 , 11.32 mmol / L MgSO 4 , 9.4 mmol / L D-glucose. And 5 mmol / L HEPES, and the pH of the assay buffer was 7.2.
  • DMSO dimethyl sulfoxide
  • the stirrers 140 and 160 shown in FIG. 4 are not put into the beaker 110 and the hot bath liquid 152, but a constant temperature water bath (Thermax, ASONE) with temperature feedback is used instead of the hot tub 151 and the hot magnet stirrer 153 to smell liquid.
  • Example 8 An aluminum film having a film thickness of 500 nm was formed on the surface of the silicon substrate by a sputtering apparatus to obtain an aluminum substrate. In addition, wild type Sf21 cells into which no olfactory receptor was introduced were prepared.
  • Sf21 cells on the aluminum substrate were subjected to life / death judgment every day for 5 days after the Sf21 cells were seeded on the aluminum substrate.
  • a dye exclusion test method using trypan blue was used for viability determination. According to the dye exclusion test method, dead cells are stained blue with the dye, so that the ratio of viable cells can be determined by microscopic observation.
  • HEK293T cells derived from human fetal kidney were prepared. As shown in FIG. 22, the viability of the HEK293T cells on the aluminum substrate was determined every day for 5 days after the HEK293T cells were seeded on the aluminum substrate. A dye exclusion test method using trypan blue (Wako Pure Chemical Industries, Ltd.) was used for viability determination. As a result, HEK293T cells were observed to grow slowly on the aluminum substrate over time, and the cells were killed by corrosion of the aluminum substrate.
  • FIG. 23 shows an increase curve of Sf21 cells and HEK293T cells on an aluminum substrate. Sf21 cells were confirmed to grow on the aluminum substrate. In contrast, the number of HEK293T cells increased or decreased on the aluminum substrate, and the number of cells was not stable.

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Abstract

Un système de dissolution pour un composé organique peu soluble dans l'eau, qui est pourvu : d'un récipient 1 qui est apte à contenir un gaz qui contient un composé organique peu soluble dans l'eau qui se présente sous la forme d'un gaz; et un dispositif de pulvérisation 20 qui pulvérise des gouttelettes contenant des bulles d'air ayant un diamètre de 1 µm ou moins vers le gaz qui contient un composé organique peu soluble dans l'eau à l'intérieur du récipient 1. Ce système de dissolution pour un composé organique peu soluble dans l'eau est configuré de telle sorte qu'une solution aqueuse 2 qui contient le composé organique peu soluble dans l'eau est retenue à l'intérieur du récipient 1.
PCT/JP2019/004475 2018-02-09 2019-02-07 Système de dissolution pour composé organique peu soluble dans l'eau, procédé de dissolution d'un composé organique peu soluble dans l'eau et système de détection d'odeur WO2019156180A1 (fr)

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WO2021045233A1 (fr) * 2019-09-06 2021-03-11 国立大学法人東京大学 Kit de détection d'odeur, procédé de fabrication de kit de détection d'odeur et procédé de détection d'odeur
WO2024034377A1 (fr) * 2022-08-10 2024-02-15 キヤノン株式会社 Procédé de fabrication et dispositif de fabrication de liquide contenant de fines bulles

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JP2006150221A (ja) * 2004-11-29 2006-06-15 Riko Kagaku Sangyo Kk 磁気駆動撹拌装置
JP2008198974A (ja) * 2007-01-15 2008-08-28 Shibaura Mechatronics Corp 基板の処理装置及び処理方法
JP2008255209A (ja) * 2007-04-04 2008-10-23 Japan Steel Works Ltd:The メタンガスの濃縮方法および装置
JP2012096216A (ja) * 2010-11-04 2012-05-24 Yasutaka Sakamoto 気泡微小化ノズル、それを用いた微小気泡発生装置、微小気泡含有水製造方法、物品洗浄装置、物品洗浄方法、水産物の養殖方法、水耕栽培方法及びシャワー装置
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WO2024034377A1 (fr) * 2022-08-10 2024-02-15 キヤノン株式会社 Procédé de fabrication et dispositif de fabrication de liquide contenant de fines bulles

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