WO2017122338A1 - 人工嗅覚センシングシステム - Google Patents
人工嗅覚センシングシステム Download PDFInfo
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- WO2017122338A1 WO2017122338A1 PCT/JP2016/051063 JP2016051063W WO2017122338A1 WO 2017122338 A1 WO2017122338 A1 WO 2017122338A1 JP 2016051063 W JP2016051063 W JP 2016051063W WO 2017122338 A1 WO2017122338 A1 WO 2017122338A1
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/0004—Gaseous mixtures, e.g. polluted air
- G01N33/0009—General constructional details of gas analysers, e.g. portable test equipment
- G01N33/0027—General constructional details of gas analysers, e.g. portable test equipment concerning the detector
- G01N33/0031—General constructional details of gas analysers, e.g. portable test equipment concerning the detector comprising two or more sensors, e.g. a sensor array
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- 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
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/403—Cells and electrode assemblies
- G01N27/414—Ion-sensitive or chemical field-effect transistors, i.e. ISFETS or CHEMFETS
- G01N27/4141—Ion-sensitive or chemical field-effect transistors, i.e. ISFETS or CHEMFETS specially adapted for gases
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/27—Association of two or more measuring systems or cells, each measuring a different parameter, where the measurement results may be either used independently, the systems or cells being physically associated, or combined to produce a value for a further parameter
Definitions
- the present invention relates to an artificial olfactory sensing system that combines biological material and semiconductor technology.
- Sensing technology that artificially reproduces the five senses and has performance superior to that of living organisms is an indispensable technology for protecting safety, health, and security in the complicated and diversified human society and the global environment. If an odor sensor (artificial olfactory sensing system) that is as sensitive as a living organism is realized, information that could not be used before can be used, and it may be applied to robots, automated driving, medical treatment, etc. (for example, non-patented) Reference 1).
- Non-Patent Document 3 a result of detecting a response of a mouse olfactory epithelial cell to a volatile odor substance as an electric signal using an ion-sensitive field effect transistor is disclosed (for example, see Non-Patent Document 3).
- Non-Patent Document 2 As a technology combining biotechnology and semiconductor technology, a configuration in which an optical or electrical response generated when an olfactory receptor of an olfactory cell extracted from a living organism recognizes an odor molecule is measured using a field effect transistor. And a technique related to the method is disclosed (for example, see Non-Patent Document 2).
- Patent Document 1 and Non-Patent Documents 2 and 3 are olfactory sensing systems specialized for specific odor molecules, which are so-called specialist type olfactory sensing systems. Specifically, Patent Document 1 and Non-Patent Document 2 can detect only insect pheromone molecules, and Non-Patent Document 3 can detect only VOC (volatile substance) that is a cancer-related biomarker.
- VOC volatile substance
- the mammalian olfactory nervous system is roughly divided into three parts: (1) the olfactory epithelium 81, (2) the olfactory bulb 82, and (3) the brain 83.
- a plurality of types of olfactory cells 84 exist in the olfactory epithelium 81 inside the nasal cavity, and a plurality of olfactory cells 84 of the same type are connected to a single corresponding glomerulus 85 on the olfactory bulb 82 by axons 86.
- axons 86 has been.
- There is a gradual key-keyhole relationship between the odor molecule 87 and the olfactory cell 84, and signals emitted from a plurality of olfactory cells 84 that have recognized the odor molecule 87 are added by the glomerulus 85,
- the firing pattern of the glomerulus 85 corresponding to the odor pattern is displayed.
- the brain 83 searches the odor memory in the brain and identifies the odor by comparing it with the firing pattern displayed on the olfactory bulb 82.
- the brain 83 By adding the signals of the plurality of olfactory cells 84 by the glomerulus 85, noise is canceled and the SN ratio is improved.
- olfactory cells 84 that emit different response signals to the odor molecule 87 are present on the olfactory epithelium 81.
- a plurality of types of olfactory cell groups 84 that recognize odor molecules 87 and emit different response signals, or odor molecule sensor groups corresponding thereto (2) A glomerulus 85 for adding response signals of a plurality of olfactory cells of the same type, or an odor signal adding mechanism corresponding to the glomerulus 85, and (3) an odor pattern emitted by a plurality of glomeruli 85 or a plurality of odor signal addition mechanisms.
- 83, or a search algorithm that substitutes the brain function, and a searcher equipped with the search algorithm are required.
- Patent Document 2 As a technology related to such a generalist type sensor.
- a generalist-type olfactory sensing system is configured using olfactory cells and glomeruli extracted from living organisms.
- Non-Patent Document 4 In general, in living organisms, as described above, about 1000 olfactory cells of the same type are connected to the same glomerulus and are not erroneously connected to different types of olfactory cells. It has become clear (see, for example, Non-Patent Document 4).
- Patent Document 2 it is actually very difficult to take out a three-dimensionally connected nerve cell network such as a glomerulus in which a plurality of olfactory cells are nerve-connected from an organism. is there.
- glomeruli corresponding to individually extracted olfactory cells are selectively connected according to the configuration disclosed in Non-Patent Document 4, but this configuration is realized in environments other than living organisms. Is difficult.
- An object of the present invention is to provide an artificial olfactory sensing system capable of sniffing various odors with high sensitivity.
- the present invention includes a plurality of sensor cells in which an olfactory receptor is expressed on a lipid membrane, and a plurality of ion-sensitive field effect transistors (ISFETs) that correspond one-to-one with the sensor cells.
- ISFETs ion-sensitive field effect transistors
- FIG. 1 It is a block diagram of the artificial olfactory sensing system which is one Example of this invention. It is a schematic sectional drawing explaining the principal part structure of the sensor cell of FIG. It is the schematic which shows the example by which the some sensor cell was arrange
- FIG. 1 is a configuration diagram of an artificial olfactory sensing system in the present embodiment.
- sensor cells Cij are arranged on a total of 1 million sensor cells Sij.
- the scanning wiring Wi is connected to the scanning circuit 15, the signal wiring Bj is connected to the signal circuit 16, the signal circuit Bj is connected to the memory arithmetic circuit (odor signal adding unit) 17, and the memory arithmetic circuit is connected to the odor identifying unit 18.
- FIG. 2 is a cross-sectional view showing a detailed configuration of the sensor cell 13 and the sensor cell 14 shown in FIG.
- the sensor cell 13 includes an ion sensitive field effect transistor (ISFET) 21 and a well 22 disposed thereon, and at least one sensor cell 14 is disposed in the well 22.
- the ion sensitive transistor 21 includes a gate electrode 23, a drain electrode 24, a source electrode 25, an insulating film 26, and a semiconductor 27, and the semiconductor 27 that contacts the insulating film 26 at the interface by a gate voltage applied to the gate electrode 23. Carrier charges are accumulated, and a current corresponding to the voltage applied between the drain electrode 24 and the source electrode 25 flows.
- the sensor cell 14 is in contact with the gate electrode 23 via a contact electrode 28 made of a noble metal such as gold or platinum and an alloy thereof provided on the gate electrode 23 as necessary.
- the sensor cell 14 mainly includes an insect olfactory receptor 29 and is immersed in a physiological aqueous solution 210 adjusted in pH. Ca ions 211 and odor molecules 212 are dispersed in the physiological aqueous solution 210. When the olfactory receptor 29 recognizes the odor molecules 212, the ion channel of the olfactory receptor 29 is opened and Ca ions are generated in the sensor cell 14. It flows in, and the potential of the sensor cell 14 surface changes.
- This potential change is transmitted to the gate electrode 23 to cause carrier charge accumulation at the interface of the insulating film 26 / semiconductor 27, and current flows between the drain electrode 24 / source electrode 25, so that the olfactory receptor 29 recognizes the odor molecule 212.
- a response signal indicating that it has been converted into an electrical signal.
- the sensor cell 14 the sensor cell disclosed in Patent Document 1 or Non-Patent Document 2 can be used.
- At least one sensor cell 14 can be arranged in a well 22 having a diameter of about 20 ⁇ m by selecting a sensor cell 14 composed of the above host cells having a diameter of about 20 ⁇ m using a porous filter.
- the sensor cell 14 is maintained by the action of an ion pump expressed on the surface of the lipid membrane 213 in a state where the intracellular Ca concentration is separated from the outside by the lipid membrane 213 and the intracellular Ca concentration is lower than that outside the cell.
- an ion pump expressed on the surface of the lipid membrane 213 in a state where the intracellular Ca concentration is separated from the outside by the lipid membrane 213 and the intracellular Ca concentration is lower than that outside the cell.
- the olfactory receptor 29 similarly expressed on the lipid membrane 213 recognizes the odor molecule 212
- its ion channel opens and Ca ions 211 flow into the cell from outside the cell.
- the potential change of the lipid membrane 213 of the sensor cell 14 is transmitted to the gate electrode 23 through the contact electrode 28, the ISFET 21 is turned on, and the magnitude of this on state is converted into an electrical signal.
- FIG. 3 is a schematic view in which a plurality of types of sensor cells (here, four types) are arranged on an ISFET two-dimensional matrix array.
- FIG. 3A four types of sensor cells 41 to 44 are arranged in the well 22 that is formed on the ISFET 21 and exposes the contact electrode 28 (FIG. 1) covering the gate electrode 23 of the ISFET 21 at the bottom thereof.
- the structure is characterized in that the same type of sensor cells are arranged on the ISFET 21 connected to the same scanning wiring (FIG. 1).
- the output signal (or current pulse width) caused by the sensor cells arranged on the same scanning wiring is turned on. Is received by the signal circuit 16 (FIG. 1) and then added by the memory arithmetic circuit 17, so that the output signals of the same type of sensor cells in the scanning cycle can be added. Output signals from the same type of sensor cells arranged on different scanning wirings may be added after being stored in the memory arithmetic circuit 17.
- sensor cells of the same type are arranged on the same scanning wiring, there is an advantage that the output signals of the sensor cells can be added simultaneously.
- FIG. 3B shows a configuration in which four types of sensor cells 41 to 44 are arranged in the well 22 which is formed on the ISFET 21 and exposes the contact electrode 28 (FIG. 1) covering the gate electrode 23 of the ISFET 21 at the bottom thereof.
- each type of sensor cell is randomly arranged on the ISFET 21 connected to the same scanning wiring. Therefore, in order to add the output signals from the same type of sensor cells, the output signals from the sensor cells output in time series by the line-sequential scanning drive of the scanning wiring are temporarily stored in the memory arithmetic circuit, and then It is necessary to selectively add only the signal outputs from the same type of sensor cells after the cycle scan is completed.
- FIG. 3A since the arrangement of each sensor cell is determined in advance, it is not necessary to check the arrangement of the various sensor cells after the arrangement if it can be accurately arranged.
- FIG. 3B since the arrangement of various sensor cells is random, it is necessary to measure the type and arrangement of sensor cells after arrangement and store them for later addition processing. This method will be described below with reference to FIG.
- FIG. 4 is a schematic diagram showing three types of sensor cells A51, sensor cells B52, and sensor cells C53 randomly arranged on a 6 ⁇ 6 two-dimensional matrix ISFET array.
- Each of the three types of sensor cells has different olfactory receptors that distinguish and respond strongly to different odor molecule groups.
- the odor molecule groups are a, b, and c, respectively.
- a sensor cell A51 that responds particularly greatly and can be distinguished from the responses of other sensor cells B52 and C53 is used for the odor molecule group a.
- the odor molecule groups b and c are selected on the same basis.
- the arrangement of the sensor cells A51, B52, and C53 is specified by the following procedure using the odor molecule groups a, b, and c prepared as described above.
- the artificial olfactory sensing system is operated for a certain time using only the odor molecule group a.
- the output signal addition value of the sensor cell in which the sensor cell A is arranged after 3 to 4 cycles depends on the odor molecule concentration.
- a value that is clearly larger than the output signal addition value of the sensor cell in which the cells B and C are arranged is displayed.
- positioning of the sensor cell A can be specified.
- the arrangement of the sensor cells B and C can also be specified by the same procedure using the odor molecule groups b and c.
- the output signals of the same type of sensor cells can be added during general odor molecule measurement.
- the cumulative added output signal strength in the same type of sensor cells may differ for the same concentration of odor molecule groups. For this reason, it is necessary to normalize before adding the output signal intensity with respect to odor molecule group stimulation of the same concentration using the method shown below.
- FIG. 5 shows temporal changes in optical response and electrical response of two types of sensor cells A and B, each of which has high sensitivity to stimulation of two types of odor molecule groups a and b.
- Sensor cell A has three types of sensor cells A1, A2, and A3 that have different response current intensities for the same odor molecule stimulation. Further, as can be seen from the dependence of the response current intensity of the sensor cells A and B on the odor molecule type shown in the lowermost graph of FIG. 5, the sensor cells A and B have the largest responses to the odor molecules a and b, respectively. While the sensor cells A and B are sensitive to the odor molecules b and a, respectively, while having a current, the sensor cells A and B are sensitive to the odor molecules a and b. It cannot be determined.
- FIG. 5 is used to explain the standardization method and the selection method of the signal intensity of the sensor cell.
- the fluorescence responses of the sensor cells A1, A2 and A3 to the stimulation of the odor molecules a and b shown in the uppermost graph of FIG. 5 are almost the same as shown in the second graph from the top of FIG. It was. From this, it can be seen that A1 to A3 are sensor cells that show the same response to the same odor stimulus.
- the response current intensity with respect to the odor molecule a is larger than the threshold value indicated by the dotted line (the third graph from the top in FIG. 5, the left graph in the fourth graph).
- the response current values of all the sensor cells A are normalized so that the response current value of the sensor cell A2 matches the response current value of the sensor cell A1, and then cumulative addition is performed by the memory arithmetic circuit.
- This normalization factor is extracted in the protocol for specifying the position of each sensor cell shown in FIG. 4 and stored in the memory arithmetic circuit, and multiplied by the response signal of each sensor cell at the time of actual odor measurement. Perform cumulative addition from.
- the search time is limited by limiting the sensor cell type used for the search to the minimum necessary according to the type of odor molecule group to be searched.
- it has the unique characteristics of an artificial olfactory sensing system that living organisms do not have. This will be described with reference to FIG.
- FIG. 6 is a conceptual diagram showing that five kinds of odor groups (memory) correspond to five kinds of odor molecule groups via five kinds of sensor cell groups.
- the five types of odor groups correspond to the five types of odor molecule groups via the five types of sensor cell groups. ). Therefore, when the odor molecule group to be searched for odors is limited to three types of molecule groups 2 to 4 as shown in FIG. 6, the search process after the electric signal conversion is performed among the five types of sensor cells of the artificial olfactory sensing system. By limiting the signals to be used to the corresponding sensor cells 2 to 4, it is possible to save time and energy required for the search accompanying the signal processing of the sensor cells 1 and 4 outside the search region.
- This is a method of saving information processing time and energy that cannot be executed in the nervous system of a living organism in which signal processing proceeds only in one direction from the input side to the output side from the olfactory cell ⁇ olfactory bulb ⁇ brain cortex as shown in FIG. 1000 ⁇ 1000 1,000,000 living organisms, and an advantageous characteristic of an artificial olfactory sensing system using sensor cells of the same number and type.
- SYMBOLS 11 Scan wiring 12 Signal wiring 13 Sensor cell 14 Sensor cell 15 Scan circuit 16 Signal circuit 17 Memory arithmetic circuit (odor signal addition part) 18 Odor Identification Unit 21 ISFET (Ion Sensitive Transistor) 22 well 23 ISFET gate electrode 24 ISFET drain electrode 25 ISFET source electrode 26 insulator 27 semiconductor 28 contact electrode 29 olfactory receptor 210 physiological aqueous solution 211 Ca ion 212 odor molecule 213 lipid membrane
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Abstract
Description
12 信号配線
13 センサセル
14 センサ細胞
15 走査回路
16 信号回路
17 メモリ演算回路(匂い信号加算部)
18 匂い識別部
21 ISFET(イオン感応性トランジスタ)
22 ウェル
23 ISFETのゲート電極
24 ISFETのドレイン電極
25 ISFETのソース電極
26 絶縁体
27 半導体
28 接触電極
29 嗅覚受容体
210 生理水溶液
211 Caイオン
212 匂い分子
213 脂質膜
Claims (8)
- 嗅覚受容体が脂質膜上に発現した複数のセンサ細胞と、
前記センサ細胞と一対一で対応する複数のイオン感応性電界効果トランジスタ(ISFET)とを備え、
前記センサ細胞の嗅覚受容体が匂い分子を認識したことを示す応答信号が、当該センサ細胞に対応するISFETにおいて電気信号に変換されることを特徴とする人工嗅覚センシングシステム。 - 前記センサ細胞は複数種類あり、同一種類のセンサ細胞に対応するISFETにおいて変換された電気信号を加算することを特徴とする請求項1記載の人工嗅覚センシングシステム。
- 前記複数のISFETが2次元アレイ状に配置されており、
前記ISFETに配置されるセンサ細胞が、隣接するISFETと電気的に隔離する隔壁を前記各ISFETに備えることを特徴とする請求項1記載の人工嗅覚センシングシステム。 - 所定の匂い分子に対するISFETの出力信号強度を計測することによって、同一種類のセンサ細胞が配置されたISFETを特定することを特徴とする請求項1記載の人工嗅覚センシングシステム。
- 所定の匂い分子に対するISFETの出力信号強度の所定時間の平均値に基づいて、同一種類のセンサ細胞が配置されたISFETの出力信号強度を規格化することを特徴とする請求項4記載の人工嗅覚センシングシステム。
- 所定の匂い分子に対するISFETの出力信号の中から、同一種類のセンサ細胞が配置されたISFETの出力信号を選択的に加算することを特徴とする請求項4記載の人工嗅覚センシングシステム。
- 前記人工嗅覚センシングシステムは、走査配線と信号配線を含み、
前記2次元マトリクス状ISFETアレイに含まれるISFETが、前記走査配線と前記信号配線の交差部分に配置されており、
同一の走査配線に接続されたISFETに、同一種類のセンサ細胞を配置することを特徴とする請求項3記載の人工嗅覚センシングシステム。 - 検知対象となる匂い分子群を識別するセンサ細胞が配置されたISFETの出力信号のみを処理することを特徴とする請求項4記載の人工嗅覚センシングシステム。
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US15/760,777 US10338046B2 (en) | 2016-01-15 | 2016-01-15 | Artificial olfactory sensing system |
JP2017561478A JP6556870B2 (ja) | 2016-01-15 | 2016-01-15 | 人工嗅覚センシングシステム |
PCT/JP2016/051063 WO2017122338A1 (ja) | 2016-01-15 | 2016-01-15 | 人工嗅覚センシングシステム |
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JP2019124651A (ja) * | 2018-01-19 | 2019-07-25 | 株式会社日立製作所 | 人工嗅覚センシングシステムおよびその製造方法 |
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JPWO2017122338A1 (ja) | 2018-05-31 |
JP6556870B2 (ja) | 2019-08-07 |
US10338046B2 (en) | 2019-07-02 |
US20180267005A1 (en) | 2018-09-20 |
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