JP3243937B2 - Biomimetic sensor - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a biomimetic sensor for measuring and identifying chemical substances in the fields of food, medicine, chemical industry, environmental measurement and the like.

[0002]

2. Description of the Related Art In recent years, research and development of chemical sensors that simulate the stoichiometry of human senses such as taste and smell have been promoted, and some of them have been commercialized. Was. For example, a sensor in which a lipid bimolecular membrane is formed as a sensitive membrane on an electrode surface of a quartz oscillator or a surface acoustic wave (SAW) element is known as a sensor for measuring and identifying a certain kind of odorant. Utilizing the fact that the resonance frequency changes in proportion to the increase in the mass of odor molecules adsorbed on the sensitive film formed on the electrode of the quartz oscillator.

[0003] These sensors are connected to an oscillating circuit, the frequency change of which is measured by a frequency counter, the data is transferred to a computer, and the response pattern of the sensor is recognized to identify the odor. Using an inexpensive commercially available quartz oscillator, a gas sensor having various characteristics depending on the type of the sensitive film can be obtained, and further, it is easy to handle.

[0004]

Although the above-mentioned sensor is useful, it still has the following problems. That is, a multiple sensor system coated with different sensitive membranes still has insufficient selectivity, especially for odorous substances. Since the concentration of odor is extremely low, the detection sensitivity is low.

The present invention has been made to solve these problems, and an object of the present invention is to detect a target chemical substance, particularly an odor substance, with high sensitivity, and to enhance the selectivity of the detection substance. An object of the present invention is to provide a biomimetic (biological function imitation) sensor.

[0006]

In order to solve the above-mentioned problems, the biomimetic sensor of the present invention performs a polymerization reaction in the presence of a target chemical substance to change the three-dimensional molecular structure of the target chemical substance. A thin film having a molecular recognition function similar to an antibody of a living body, in which a target chemical substance is extracted from an organic polymer to be stored, is converted into various transducers, for example, a quartz oscillator or a surface acoustic wave (hereinafter, referred to as SAW) element, or a surface plasmon ( The sensor is fixed to the surface of an element, and can detect molecules of a target chemical substance by a change in frequency or a change in resonance angle of light.

[0007]

[Function] When, for example, methacrylic acid (functional monomer) and ethylene glycol dimethyl acrylate (crosslinking monomer) undergo a polymerization reaction in the presence of a target chemical substance to be detected, the three-dimensional molecular structure of the target chemical substance is stored. The resulting polymer is produced. Since this polymer has a site having almost the same shape as the three-dimensional molecular structure of the target chemical substance, it can be used as a selective receptor having a molecular recognition function similar to that of a biological antibody. Therefore, by forming a thin film of the above-mentioned polymer on the surface of the quartz oscillator or SAW element, the weight change caused by the selective adsorption of the molecule of the target chemical substance is converted into a frequency shift, or the SPR element surface It can be used as a sensor that can detect the target chemical substance with high sensitivity by converting it into a change in the resonance angle of light caused by the selective adsorption of the target chemical substance and the polymer thin film.

[0008]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below based on embodiments. An object of the present invention is to provide a polymer capable of recognizing a three-dimensional molecular structure of a target chemical substance (Molecular Inp.).
printing polymer (hereinafter referred to as MIP), for example, methacrylic acid (hereinafter, referred to as MIP).
MAA) and ethylene glycol dimethyl acrylate (hereinafter referred to as EDMA), for example, a monomer (MAA) collected around molecules such as geosmin or 2-methylisoborneol (hereinafter referred to as 2-MIB) which is a musty substance. And EDMA) are polymerized at once,
An MIP film in which a three-dimensional molecular structure of geosmin or 2-MIB is stored can be produced.

Embodiment 1 FIG. 1 is a schematic plan view showing a configuration of a main part of a biomimetic sensor 1a of the present invention using a quartz oscillator. The sensor 1a includes a gold electrode 2 formed on both front and back surfaces of a crystal unit 1, a MIP thin film 3 formed thereon, and a lead 5 passing from the gold electrode 2 through a support 4.
The main points of the fabrication are as follows.

First, for example, 0.9 g of geosmin, 1.8 methacrylic acid (MAA) in 50 ml of chloroform.
g, ethylene glycol dimethyl acrylate (EDM
A) 18.7 g of a polymerization initiator 2,2'-azobis (2
0.24 g of -methylpropionitrile) (AIBN)
Add. After defoaming in a vacuum while irradiating the mixed solution with ultrasonic waves, the mixed solution is replaced with nitrogen gas for 5 minutes.

[0011] Then, the oscillation frequency 10 MHz _Z, on both sides of the crystal resonator 1 of the AT-cut, by depositing a gold electrode 2 having a diameter of 5 mm, after applying the solution to this, a nitrogen gas atmosphere at 60 ° C. For 10 hours to polymerize MAA and EDMA to form a MIP thin film 3. Next, this is washed in an acetic acid-methanol mixed solution, and the geosmin in the MIP thin film 3 is extracted and then dried to obtain the biomimetic sensor 1a of the present invention.

FIGS. 2 (a) to 2 (c) show that M is a pseudo antibody.
It is a schematic diagram which shows the preparation process of the IP film 3, (a) the state where MAA7 and EDMA8 coexist around the geosmin molecule 6, (b) the state which polymerized MAA7 and EDMA8, (c) Extracts the geosmin molecule 6,
This shows that IP9 is obtained.

FIGS. 3A and 3B are schematic diagrams showing states before and after the geosmin molecule 6 is adsorbed on the MIP film 3, and FIG. 3A shows a state near the gold electrode 2 on the crystal unit 1. And (b) show a state in which only the geosmin molecule 6 is adsorbed on the MIP film 3, respectively.

FIG. 4 is a schematic diagram showing a main configuration of a measuring apparatus using the sensor 1a of the present invention. In FIG. 4, the apparatus is configured to receive distilled water or a measurement sample solution 12 for about 10 minutes.
The sensor 1 a is arranged in a 0 ml glass container 13 and connected to a resonance frequency measuring device 14 and a recorder 15 outside the glass container 13. Measurement is 10ml first
After measuring the resonance frequency using a container containing distilled water, the sample solution 12 was replaced with a glass container 13 containing 10 ml, and the measurement was performed for 10 minutes. Do.

FIG. 5 shows the measurement results. FIG. 5 is a diagram showing the relationship between the response of the sensor of the present invention to the geosmin standard solution prepared with distilled water, the horizontal axis represents time, and the vertical axis represents frequency shift. They are also indicated by arrows. From FIG. 4, it can be seen that this diagram is a repetition in which the frequency change increases when distilled water is changed to a geosmin solution, and it is possible to measure geosmin, which is a target odor substance, with high sensitivity.

The method for obtaining the sensor 1a of the present invention is as follows.
In addition to the above, the above mixture was allowed to stand at 60 ° C. in a nitrogen gas atmosphere for 10 hours, and the polymer obtained by the polymerization reaction was pulverized into particles of several μm to several tens μm, and then acetic acid-methanol was added. The geosmin in the particles is extracted in the mixed solution, and the dried one is applied on the surface of the gold electrode 2, or the particles are put into a film material such as PVC (vinyl chloride) to cover and form the film. Alternatively, the obtained sensor 1a can obtain the same effect as described above.

Embodiment 2 FIG. Next, the biomimetic sensor 1b of the present invention using a SAW element will be described. Figure 6 is a schematic plan view showing the main configuration, in FIG. 6, the sensor 1b is a SAW device having a resonance frequency 90MH _Z made quartz ST-cut, gold electrodes 2a and the comb electrodes on both ends The MIP film 3a is formed in the (IDT) 16 and the surface wave propagation region 17 indicated by the dotted line,
Frequency counter 1 from T16 through high frequency amplifier 18
9 is connected.

The MIP film 3a of the sensor 1b is manufactured as follows. First, in 40 ml of chloroform,
For example, 2-methylisoborneol (2-MIB) 1.
2 g, 2.3 g of MAA, 26 g of EDMA, AIBN 0.
5 g was added and mixed, and the mixture was degassed in vacuum while applying ultrasonic waves, and then replaced with nitrogen gas for 5 minutes. Next, this mixed solution is applied to the surface wave propagation region 17 of the SAW element shown in FIG. 6 and irradiated with ultraviolet light having a wavelength of 366 nm at 5 ° C. for 5 hours to polymerize MAA and EDMA to form the MIP thin film 3a. . Then, this is washed in an acetic acid-methanol mixed solution, 2-MIB extraction in the MIP thin film 3a is dried, and the biomimetic sensor 1b of the present invention can be obtained. In Example 1 , the polymer obtained by the polymerization reaction may be used in the form of particles. It is the same as described above.

FIG. 7 is a schematic diagram showing a main configuration of a measuring device of the biomimetic sensor 1b of the present invention using a SAW element. In FIG. 7, this device fixes a sensor 1 b at an upper part in a flow cell 22 installed in a constant temperature water tank 21 at a temperature of about 40 ° C. by a temperature controller 20, and can switch between distilled water and a measurement sample solution 12. Then, these liquids are passed through the flow cell 22 while being heated by the heat exchanger 23, and the distilled water and the sample liquid 12 are alternately sent at an interval of 10 minutes.
Each of the frequency (f _1, f) performs measurements by the frequency counter 19, frequency shift the response of the sensor (f ₁ -
f ₂ ).

FIG. 8 shows the measurement results. FIG. 8 shows a sensor 1b of the present invention for a 2-MIB standard solution prepared with distilled water.
FIG. 6 is a diagram showing the relationship between the responses of FIG. 5A and FIG. 5B. As in FIG. 5, the horizontal axis represents time, the vertical axis represents frequency shift, and the switching points between distilled water and the sample liquid are indicated by arrows. FIG. 8 shows that, similarly to the diagram shown in FIG. 5, 2-MIB, which is the target odor substance in this case, can be measured with high sensitivity.

Embodiment 3 FIG. Next, the biomimetic sensor 1c of the present invention using an SPR element will be described. FIG. 9 is a schematic plan view showing the configuration of the main part. In FIG. 9, the sensor 1c has a refractive index 1.5243.
A 50 μm gold electrode 2 b is formed on the bottom surface of the K prism 24, and a MIP film 3 b is formed on the gold electrode 2 b. The change in the resonance angle θ that changes with the irradiation of the laser beam 25 whose incidence direction is indicated by an arrow is detected. Things.

The production of the MIP film 3b of this sensor is basically the same as described above. First, for example, 1.2 g of 2-MIB, 2.3 g of MAA, and ED in 40 ml of chloroform.
After adding 26 g of MA and 0.5 g of AIBN, mixing and degassing in vacuum while applying ultrasonic waves, the atmosphere is replaced with nitrogen gas for 5 minutes. Next, this mixed solution is applied to the surface of the deposited gold electrode 2b on the bottom surface of the prism 24 of the SPR element shown in FIG. 9 and irradiated with ultraviolet light having a wavelength of 366 nm at 5 ° C. for 5 hours to polymerize MAA and EDMA. , The MIP thin film 3b is formed. Next, this is washed in an acetic acid-methanol mixed solution, 2-MIB extracted in the MIP thin film 3b, and dried to obtain the biomimetic sensor 1c of the present invention. Also in this case, as described in Example 1 and Example 2 , the polymer obtained by the polymerization reaction may be used in the form of particles.

FIG. 10 is a schematic diagram showing a main configuration of a measuring device of the biomimetic sensor 1c of the present invention using an SPR element. In FIG. 10, in this apparatus, a 2-MIB measurement sample solution 26 having a concentration adjusted with distilled water
Flow from one side of the flow cell 27 and discharge it from the other, and separately send air 28 to the first flow cell 27 to carry gas containing 2-MIB to the second flow cell 29 to which the sensor 1c is fixed, And exhaust from the other side. He-N emitted from the laser oscillator 30 at the same time
The sensor 1c is irradiated with the e-laser light 25. At this time, the laser light 25 passes through a polarizer 31 and is branched by a beam splitter 32. One of the laser light 25 is incident on the sensor 1c , and then a first photodiode (signal detector) ) 33, the signal is sent to the arithmetic circuit 34, and the other signal enters the arithmetic circuit 34 via the second photodiode (reference detector) 35. The data processed by the arithmetic circuit 34 is sent to a recorder (not shown). FIG.
, The traveling directions of the sample liquid 26, the air 28, and the laser beam 25, and the signal paths from the photodiodes 33 and 35 are all indicated by arrows.

FIG. 11 shows the measurement results. Distilled water and 2-M
The measurement of the IB sample solution alternately at 10 minute intervals and the measurement of the change are the same as in the case described above.
FIG. 11 is a diagram showing the change in the resonance angle of the sensor 1c of the present invention with respect to the 2-MIB sample solution of each concentration, while using the sample solution prepared with distilled water while changing the concentration of 2-MIB. is there. The dotted line in FIG. 11 is an unmeasured range. From the diagram of FIG. 11, it can be seen that as the 2-MIB concentration increases, the resonance angle θ
Increases linearly, and the target musty odor substance 2-MI
It can be seen that B can be measured with high sensitivity.

[0025]

As described above, the biomimetic sensor of the present invention can produce, by organic synthesis, a polymer having a function similar to an antibody in a living body against chemical substances, especially musty odor substances. Therefore, target chemical substances can be detected with high sensitivity by thinning it and forming it on the surface of various transducers or fixing it as fine particles on the surface of various transducers, and the accuracy and selectivity of detection by sensors It can be applied to water purification plants, etc. to achieve great effects.

[Brief description of the drawings]

FIG. 1 is a schematic plan view showing a configuration of a main part of a biomimetic sensor of the present invention using a quartz oscillator.

2A and 2B show a process for producing a MIP film, wherein FIG. 2A shows a state in which geosmin molecules, MAA molecules, and EDMA molecules coexist; FIG. 2B shows a state in which MAA and EDMA are polymerized;
(C) is a schematic diagram showing that a geosmin molecule is extracted and MIP is obtained, respectively.

3A and 3B show states before and after a geosmin molecule is adsorbed on a MIP film, wherein FIG. 3A shows a state in which another smell molecule including a geosmin molecule is floating near a gold electrode, and FIG.
Schematic diagrams showing the state where only the geosmin molecule is adsorbed on the IP membrane, respectively.

FIG. 4 is a schematic view showing a main configuration of a measuring apparatus using the sensor of the present invention shown in FIG. 1;

FIG. 5 is a diagram showing the relationship between the response of the sensor of the present invention measured by the apparatus of FIG. 4;

FIG. 6 is a schematic plan view showing a main configuration of a biomimetic sensor of the present invention using a SAW element.

FIG. 7 is a schematic diagram showing a main configuration of a measuring device using the sensor of the present invention in FIG. 6;

FIG. 8 is a diagram showing the relationship between the response of the sensor of the present invention measured by the apparatus of FIG. 7;

FIG. 9 is a schematic plan view showing a main configuration of a biomimetic sensor of the present invention using an SPR element.

FIG. 10 is a schematic diagram showing a main configuration of a measuring device using the sensor of the present invention in FIG. 9;

11 is a diagram showing the relationship between the response of the sensor of the present invention measured by the apparatus of FIG. 10;

[Description of Signs] 1a Quartz Crystal Resonator Sensor 1b SAW Element Sensor 1c SPR Element Sensor 1 Quartz Crystal Unit 2 Gold Electrode 2a Gold Electrode 2b Gold Electrode 3 MIP Thin Film 3a MIP Thin Film 3b MIP Thin Film 4 Support 5 Lead 6 Geosmin Molecule 7 MAA Reference Signs List 8 EDMA 9 MIP 10 Other odor molecules 11 Other odor molecules 12 Sample liquid 13 Glass container 14 Resonance frequency measuring device 15 Recorder 16 IDT 17 Surface wave propagation area 18 High frequency amplifier 19 Frequency counter 20 Temperature controller 21 Constant temperature water bath 22 Flow cell Reference Signs List 23 heat exchanger 24 prism 25 laser light 26 sample liquid 27 first flow cell 28 air 29 second flow cell laser light 30 laser oscillator 31 polarizer 32 beam splitter 33 first photodiode 34 arithmetic circuit 35 second photo Diode

────────────────────────────────────────────────── ─── Continued on the front page (58) Fields surveyed (Int. Cl. ⁷ , DB name) G01N 21/75-21/83 G01N 33/48-33/98 H03H 9/02 CA (STN) JICST file ( JOIS)

Claims (6)

(57) [Claims] 1. A thin film obtained by extracting said target chemical substance from an organic polymer having a three-dimensional molecular structure of said target chemical substance polymerized in the presence of a target chemical substance, and said thin film is attached And a device capable of converting a desorption reaction between the organic polymer and the target chemical substance into a change in frequency or a change in resonance angle of light. 2. The biomimetic sensor according to claim 1, wherein the target chemical is geosmin or 2-methylisoborneol (2-MIB). 3. The biomimetic sensor according to claim 1, wherein the organic polymer comprises methacrylic acid (MAA) and ethylene glycol dimethyl acrylate (EDMA). 4. The biomimetic sensor according to claim 1, wherein the organic polymer is used as fine particles. 5. The biomimetic sensor according to claim 1, wherein the element capable of converting to a frequency change is a quartz oscillator or a surface acoustic wave (SAW) element. 6. The sensor according to claim 1, wherein the element capable of converting a change in resonance angle of light is a surface plasmon (SPR).
A biomimetic sensor, which is an element.