KR20170100884A - Method for detecting endocrine disruptors based on biomimetic material and total management system for field application - Google Patents

Method for detecting endocrine disruptors based on biomimetic material and total management system for field application Download PDF

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KR20170100884A
KR20170100884A KR1020160023313A KR20160023313A KR20170100884A KR 20170100884 A KR20170100884 A KR 20170100884A KR 1020160023313 A KR1020160023313 A KR 1020160023313A KR 20160023313 A KR20160023313 A KR 20160023313A KR 20170100884 A KR20170100884 A KR 20170100884A
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endocrine
substance
color sensor
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color
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손종렬
오현주
정나나
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고려대학교 산학협력단
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Abstract

The present invention relates to a biocompatible substance-based endocrine disruptor detection method, and a field applicable integrated management system by applying the same. More specifically, the present invention relates to a field applicable integrated management system for biocompatible substance-based endocrine disruptor detection. By using a bacteriophage-based color sensor and a molecularly imprinted polymer (MIP) cartridge which selectively binds to endocrine disruptors, real-time detection for endocrine disruptors consistently or intermittently emitted in living environments is possible. In addition, it is also possible to detect, analyze, and manage target endocrine disruptors by using smartphones.

Description

FIELD OF THE INVENTION [0001] The present invention relates to a method for detecting endocrine disrupters based on biocompatible materials,

The present invention relates to a biocompatible substance-based endocrine disrupter detection method capable of real-time sensing of endocrine disruptive substances released continuously or intermittently in a living environment and detecting concentration information of a target environmental hormone in real time, To an integrated management system for on-site application for the detection of endocrine disrupters.

As more than 1,000 new chemicals are synthesized each year, these chemicals are constantly threatening human health.

Endocrine disruptor is an endocrine disruptor that is similar to a steroid hormone among natural or synthetic chemicals encountered in the environment and everyday life. It is not easily decomposed and accumulated in the body compared with the hormone synthesized in vivo, The substances causing the system abnormalities are collectively called.

Endocrine disruptors, which have recently emerged as a social problem, are chemicals that interfere with the normal function of the endocrine system. They are also called 'environmental hormones' because the chemicals released into the environment act like hormones.

Typical examples of such endocrine disrupting substances are bisphenol A (bisphenol A) used in coating materials such as food or beverage cans, dichloro-diphenyl-trichloroethane (DDT), a pesticide used in the past to eradicate malaria mosquitoes, Phytate esters used as synthetic plasticizers, phtalate esters used as synthetic detergent raw materials, phtalate esters used as a synthetic detergent raw material, phytoestrogen existing in plants as well as styrene monomers such as styrolol, Best roll (diethylstilbestrol, DES) and polychlorinated biphenyls (PCBs).

Recently, it has been reported that polychlorinated biphenyls (PCBs) inhibit the action of male hormone, thyroid hormone and estrogen, and lower the insulin concentration in the blood while disturbing the hormone in vivo. Lavender and tea tree oil, which are often found in products such as shampoos, hair gels, body lotions and soaps used in children, Is being reported.

Therefore, although the concentration of endocrine disruptors in the living environment ranges from several ng / L to several mg / L, in general, very small amounts of environmental hormones have a fatal effect on the human body, Measurement of endocrine disruptors up to several ng / L is required.

Patent Registration No. 10-1300233 (Aug. 20, 2013)

Conventional endocrine disrupter detection technologies have high selectivity for detection target substances and low detection limits, but they are not easy to carry as device-oriented technologies in the laboratory environment.

In addition, when the amount of the endocrine disrupting substance to be detected is small, it takes a long time to detect it. That is, in the case of the endocrine disruptive substance detection system using the existing sensor, Therefore, when the amount of the endocrine disrupting substance is less than a certain amount, the speed of diffusion of the detection target substance is very slow and the time required for the detection is very long There is a problem.

Therefore, there is a need for a system for detecting and managing endocrine disruptive substances in the living environment that has a rapid response time to the endocrine disrupting substances in the living environment and can conduct concentration analysis in real time.

The present invention has been made in view of the above-mentioned problems, and it is an object of the present invention to provide a biocompatible bacteriophage-based color sensor and molecularly imprinted polymer (MIP) to dramatically improve selectivity and concentration sensitivity of a small amount of endocrine- And to detect the endocrine disruptors by color change and to measure the concentration of endocrine disruptors in the living environment and to manage them accordingly. The purpose is to provide.

In order to accomplish the above object, the present invention provides an integrated management system for on-site application for detecting an endocrine disruptive substance, comprising a sensor unit 10 for measuring an endocrine disrupting substance on a predetermined sample, A data memory unit 21 for storing a color sensor image of the endocrine disruptive material to be measured, and a display 23 of the smartphone terminal which is analyzed by converting the color sensor image into RGB color data and analyzing the RGB color data And a smart phone application 22 for displaying the smart phone application 22 on the display screen.

The sensor unit 10 includes a molecular-imprinted MIP cartridge 11 and a bacteriophage-based color sensor (not shown) filled with a molecular-weight polymer powder fixed to a particle-shaped support, 12), which is a receptor for detecting environmental hormones, including peptides and molecularly imprinted polymers, and thus can bind to target environmental hormones.

Wherein the color sensor 12 comprises a bacteriophage self assembly in the form of a smectic helicoidal nanofilament that expresses a peptide that selectively reacts with endocrine disruptors.

The smartphone application 22 compares the RGB color data for the pulling speed changes of the bacteriophage selfassembly measured on the color sensor with the RGB color data of a predetermined control to determine the concentration of endocrine disruptors Can be detected.

In addition, an integrated management system for detecting endocrine disruptors such as this can detect an endocrine disruptive substance above a preset reference value in the course of production such as plastic or canned food, Through the phone terminal, it is possible to obtain the real-time concentration detection result of the endocrine disruptive substance in the field, and it is possible to flexibly cope with emergency or unexpected situation on the spot.

In order to accomplish the above object, the present invention provides a method for detecting an endocrine disrupting substance using an integrated management system for on-site clinical use for detecting an endocrine disruptive substance, comprising a MIP cartridge (S710) for detecting a substance to be detected by adsorbing a substance to be detected on a molecule-impinging polymer powder by adding a sample containing the substance to be detected and desorbing the substance to be detected, A step S730 of detecting a color sensor of a color sensor in response to a virus-based color sensor, a step S730 of transmitting a color sensor image measured by a sensor unit measuring an endocrine disrupting substance to a predetermined terminal, , Stores the color sensor image transmitted from the sensor unit, converts the RGB data from the color sensor image, Analyzing the data (S740), and displaying the analysis result of the endocrine disrupting substance on the display of the terminal (S750).

Specifically, the step of detecting a molecular imprinted polymer (S710) is a step in which a molecule-imprinting polymer (MIP cartridge) filled with a molecule-imprinting polymer powder in which a molecule-imprinting polymer that specifically binds to a detection target is immobilized on a solid phase, And then the detection target substance is adsorbed on the polymer imprinted polymer powder, and then the extraction target solution is added to the polymer imprinted polymer cartridge to remove the detection target substance from the molecular imprinted polymer cartridge.

In the present specification, the substance to be detected is an endocrine disrupting substance harmful to the human body, such as Bisphenol A (BPA), 2,4-Dichlorobenzene, Chlorobenzene, Naphthalene, Is selected from the group consisting of benzo [a] pyrene, diethyl phthalate (DEP), diethylhexyl phthalate (DEHP), and polychlorinated biphenyl Or more.

The term 'endocrine disrupting agent' as used herein also means 'environmental hormone'.

The integrated detection and management system of endocrine disruptors based on biocompatible materials according to the present invention is a biosensor based sensing technology that can detect existing single detection sensation and other physical, chemical and biochemical pollutants in real time, Detection system, it is possible to provide a function of instantaneously and real-time grasping the concentration of an endocrine disrupting substance.

In addition, by detecting the endocrine disrupting substance more promptly and faster than in the conventional detection system which consumes a large amount of time and money, it is possible to quickly cope with damage such as endocrine hormone disturbance.

In addition, it is possible to connect with the pollutant management system in the living environment, and it is possible to secure an integrated management system for on-site application that can detect and analyze the endocrine disruptive substances using the smart phone so as to continuously monitor indoor / outdoor pollution conditions.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a block diagram showing a schematic configuration of a field-applied integrated management system for detecting endocrine disrupting substances based on biocompatible materials according to an example of the present invention. FIG.
2 is a schematic diagram of a method for producing a molecule-imprinting polymer for a specific target substance.
3 illustrates a molecular imprinted MIP cartridge according to an embodiment of the present invention.
4 is a schematic diagram of a bacteriophage selfassembly configured in a bacteriophage-based color sensor according to the present invention.
FIG. 5 shows the result of analyzing the RGB color pattern of the color sensor according to the concentration condition of bisphenol A. FIG.
6 shows an example in which the sensor of the present invention is applied in the form of a band or a sticker.
7 is a flowchart of a biocompatible material-based endocrine disrupter detection method of the present invention.
FIG. 8 shows the chemical formulas of the endocrine disrupting substance which can be detected according to the biocompatible substance-based endocrine disrupter detection method of the present invention and the on-site integrated management system for endocrine disruptor detection.

As shown in FIG. 1, the present invention provides a molecularly-labeled polymer cartridge using a molecule-imprinting polymer that specifically binds to an endocrine disrupting substance harmful to human body as a detection target, and a peptide that specifically binds to an endocrine disrupting substance A smart phone terminal 20 includes a data memory unit 21 and a smartphone application 22. The system includes a sensor unit 10 and a smartphone terminal 20, .

The sensor unit 10 is a solid-phase extraction unit using an affinity column. The molecule unit is specifically bound to a substance to be detected. A molecule-imprinting polymer is immobilized on a solid phase. A molecular-imprinted polymer cartridge filled with a polymer powder. ) 11 and a bacteriophage-based color sensor 12, which are receptors for detecting an endocrine disrupting substance, and can bind to a target endocrine disruptor because they contain a peptide and a molecule-imprinting polymer.

The polymer-imprinted polymer cartridge 11 will now be described.

The term " molecular imprinted polymer (MIP) " as used herein means that the target molecule is made of a template and imprinted with a ligand or space capable of bonding with the target molecule.

More specifically, it refers to a polymer having a space identical in shape to a template material by synthesizing a polymer using a monomer bonded to an appropriate template and removing the template material. Therefore, since only the morphologically identical template material can be interposed in the template material space, and molecules having a template structure and a different stereostructure can not be interrupted, a template polymer material having a template material space can be used to separate templates and other molecules have.

As shown in FIG. 2, the molecule-imprinting polymer of the present invention is prepared by reacting an endocrine disrupting substance, a template, with a ligand thereof, and then photopolymerizing or thermally polymerizing the cross-linker with an initiator to produce an endocrine disrupting substance A molecule-imprinting polymer capable of detecting a specific endocrine disrupting substance as a polymer to which a molecule-imprinted ligand is bound can be produced.

As the crosslinking agent, any one selected from the group consisting of EGD (ethylene glycol dimethacrylate), EGD (ethylene glycol dimethacrylate), TGD (triethyleneglycol dimethacrylate), PEG (polyethylene glycol dimethacrylate) and acrylamide may be used. It is not.

In one embodiment, the molecule-imprinting polymer was prepared by using bisphenol A, one of the environmental hormones, as described above. However, another endocrine disrupting substance was diethyl phthalate (DEP), diethylhexyl phthalate DEP) can also be used to manufacture molecularly imprinted polymers with the same principle.

The molecular-imprinted polymer cartridge 11 is obtained by applying the above-described molecular-imprinted polymer to a solid phase extraction (SPE) method. As shown in FIG. 3, the molecular-imprinted polymer cartridge includes a particle- (MIP powder), which is chemically bonded to form a molecular imprinted polymer powder (hereinafter referred to as " MIP powder ").

The color sensor 12 of the present invention is a color sensor comprising a peptide selectively binding to an endocrine disrupting substance. In order to exclude the peptide, an endocrine disrupting substance to be detected is immobilized on a solid surface with a linker, Is synthesized after confirming the peptide sequence from the phage display library. And a sensor chip in which such a peptide is immobilized.

Here, the phage-displayed library expresses a peptide that specifically binds to a desired substance by appropriately controlling the gene in the bacteriophage to change the combination of amino acids to a part of the peptide of the coat protein of the corresponding bacteriophage. It is a way to do it.

The color sensor 12 of the present invention is a color sensor based on a bacteriophage in which a Trp-His-Trp (WHW) peptide sequence is commonly expressed in pVII, which is a coat protein of M-13 bacteriophage.

As shown in FIG. 4, the structure of a bacteriophage in which a peptide selectively reactive with a harmful endocrine disrupting substance is expressed as a detection target substance produced through a phage display library is a self-assembly form of bacteriophages in which bacteriophages are regularly arranged, It consists of a smectic helicoidal nanofilament. This is because the structure of the spiral nanofiber structure selectively transmits and reflects visible light when the white light is irradiated from the outside, and thus the structure color appears in the photonic crystal.

That is, in the color sensor of the present invention, when the concentration of the endocrine disrupting substance in the ambient air is increased, the bundle of swollen phages expands and the interval between the bundles increases, so that the reflected wavelength becomes longer and becomes reddish. On the contrary, When the pH is lowered, the bundle of the phage contracts and the interval between the bundles narrows, and the reflected wavelength is shortened, so that the endocrine disrupter can be detected through the change of the color more blue.

FIG. 5 shows the result of color change of the color sensor due to the change in the concentration of bisphenol A, and the color sensor exposed to 50 ppb of Pisphenol A has a pulling speed of the bacteriophage self assembly having a smectic spiral nanofiber structure The RGB color value for the change is compared with the RGB color value of the predetermined control and the concentration of bisphenol A is measured through the RGB color value difference of the color sensor.

It has been confirmed that environmental hormones can be selectively measured by using such a color sensor.

Here, RGB means light of red (R), green (G), and blue (B), which are the three primary colors of light.

The color sensor causing color change used in the endocrine disrupter detection method of the present invention is not affected by environmental factors such as temperature and humidity.

According to an aspect of the present invention, the smartphone terminal 20 is provided with a sensor for measuring an endocrine disrupting substance and a predetermined environmental hormone analyzing module capable of analyzing a measurement result to measure the presence / It is possible to check whether or not the terminal user is exposed to an endocrine disruptive substance.

The present invention comprises a service operating system for providing an information service to a user through a smartphone application (22).

The smartphone application 22 calculates the endocrine disruptive substance concentration measurement through the smartphone terminal and displays it on the smartphone display and displays the data on the endocrine disruptive substance concentration information transmitted from the color sensor 12, Stored in the data memory unit configured in the application, and the stored information is displayed on the user interface so that the user can inquire and utilize the contamination information on the environmental hormone.

In addition, the smart phone application utilizes a terminal device connected to the Internet such as a PC, a web pad, a PDA, etc., as well as a smart phone terminal by a user, so that the user can obtain detailed information on the endocrine disruptive substance, Can be obtained in various ways.

In addition, the field integrated management system for detecting an endocrine disruptor of the present invention includes a facility 100 for producing a product group to be measured in which an endocrine disruptive substance such as a plastic production facility or a canning container production facility is generated, A sensor unit capable of detecting the endocrine disrupting substance of the present invention as shown in FIG. At this time, a band or sticker type sensor which is easy to attach and detach as shown in Fig. 6 can be applied to the operator.

The sensor unit includes a communication module 13. The communication module 13 transmits the endocrine disrupting substance information detected by the polymeric cartridge 11 and the color sensor 12 to the smartphone through wireless communication.

As described above, the smartphone application 22 receiving the endocrine disrupting substance information from the sensor unit determines whether the concentration of the endocrine disruptive substance detected by the sensor unit applied to the operator is out of the predetermined reference concentration information.

If an endocrine disruptor whose result is determined to be out of the predetermined reference concentration information is detected, the smartphone application generates a warning screen and an alarm through the display and the speaker of the smartphone, Warning alarms can be used to shut down plant facilities or take appropriate action in response to site conditions.

The integrated management system for on-site application for the detection of endocrine disrupting substances of the present invention is, for example, a server or production site workers (hereinafter referred to as " , A terminal for performing a similar function such as a PC or a smart phone terminal assigned to a user (also referred to as a " user ").

Therefore, it is directly connected to the facility management unit 30 connected to the smart phone and the wireless network as well as the smartphone, and receives a transmission signal for detecting the endocrine disrupter material transmitted from the smartphone terminal, It can be applied directly to the production site, which is presumed to be caused by endocrine disruptors that can be flexibly coped with.

FIG. 7 is a flowchart illustrating a method for detecting an endocrine disrupting substance of the present invention. Referring to FIG. 7, a method for detecting an environmental hormone using the endocrine disrupting agent detecting system will be described below.

A molecularly-imprinted polymer detection step (S710) of extracting a detection target substance with a molecular imprinted MIP cartridge that specifically binds to a detection target substance; A step S730 of detecting a color sensor, a step S730 of detecting a color sensor, a step S730 of transmitting a color sensor image measured by a sensor unit measuring an endocrine disrupting substance to a predetermined terminal, Converting the RGB data from the color sensor image, analyzing the RGB data (S740), and displaying the analysis result of the endocrine disrupting substance on the display of the terminal (S750).

The step S710 of detecting the molecule-impinging polymer is a method of applying a solid-phase extraction method using an affinity column. The molecule-impinging polymer, which is specifically bound to the substance to be detected, is immobilized on a solid phase. A sample containing the substance to be detected is placed in a molecular-imprinted MIP cartridge and reacted to adsorb the substance to be detected on the molecularly-imprinted polymer powder. Then, the substance to be detected is detached from the molecule-excluded polymer cartridge by adding an extraction solution Can be extracted.

In step S740, RGB data is converted into RGB data of three color signals of R, G, and B which are red, green, and blue from the color sensor color image. The concentration of a substance to be discriminated is compared with predetermined standard data.

Step S750 of displaying on the terminal display can display various environmental hormone information including the concentration information of each type of environmental hormone calculated through the smartphone application and preparation for the various types of information on the display of the smartphone terminal.

Meanwhile, the present invention relates to a system comprising a sensor containing a peptide specifically binding to an environmental hormone, bisphenol A (BPA), and a polymer impregnated with a polymer, as well as bisphenol A as well as 2,4-dichlorobenzene (2, 4-dichlorobenzene, chlorobenzene, naphthalene, benzo [a] pyrene, diethyl phthalate, diethylhexyl phthalate (DEHP) It is possible to provide a method for selectively detecting an endocrine disrupting substance such as polychlorinated biphenyl and a method for detecting or eliminating an endocrine disrupting substance in the present invention . The chemical formula for such an environmental hormone is shown in Fig.

It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the spirit or scope of the invention. Therefore, the scope of the present invention is not limited thereto. It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the spirit or scope of the invention.

10: Sensor unit
11: Molecular imprinted polymer cartridge
12: Color sensor
13: Communication module
20: Smartphones
21: Data memory unit
22: Smartphone applications
23: Display
100: On-site integrated management system for detection of endocrine disruptors
500: Facility that produces the product to be measured

Claims (5)

A sample containing the substance to be detected is placed in a molecular-imprinted MIP cartridge which specifically binds to the substance to be detected, and the substance to be detected is adsorbed on the molecularly-imprinted polymer powder, ;
Reacting the extracted detection target material with a virus-based color sensor to measure color change of the color sensor;
Transmitting a color sensor image measured by a sensor unit measuring an endocrine disrupting substance to a predetermined terminal;
Storing a color sensor image transmitted from the sensor unit, and converting RGB data from the color sensor image to analyze sensor measurement data;
And displaying the analysis result of the endocrine disrupting substance including the concentration of the endocrine disruptive substance type on the display of the terminal.
An integrated management system capable of detecting an endocrine disruptor based on a biocompatible material to which the method for detecting an endocrine disruptor based on biocompatible materials according to claim 1 is applied,
A sensor unit for measuring an endocrine disrupting substance on a predetermined sample; And
A data memory unit for storing a color sensor image of the endocrine disrupting substance measured from the sensor unit; And
And a smartphone application for converting the color sensor image into RGB color data, analyzing the RGB color data, and displaying the analyzed RGB color data on a display of the analyzed smartphone terminal,
The sensor unit is composed of a MIP cartridge and a bacteriophage-based color sensor in which a molecular imprinted polymer that selectively binds an endocrine disrupting substance selectively is fixed on a support of a particle type, Based integrated management system for detecting endocrine disruptors based on biocompatible materials.
3. The method of claim 2,
Wherein the color sensor comprises a bacteriophage self assembly in the form of a smectic helicoidal nanofilament that expresses a peptide that selectively reacts with an endocrine disrupting substance. Integrated management system for on - site application.
The method of claim 3,
Wherein the smartphone application compares and analyzes RGB color data for a change in pulling speed of the bacteriophage selfassembly measured by the color sensor with RGB color data of a predetermined control group. On - site integrated management system for detection of endocrine disrupters.
5. The method according to any one of claims 2 to 4,
The endocrine disrupting substance may be selected from the group consisting of Bisphenol A (BPA), 2,4-Dichlorobenzene, Chlorobenzene, Naphthalene, Benzo [a wherein the biocompatible material is at least one selected from the group consisting of pyrene, diethyl phthalate (DEP), diethylhexyl phthalate (DEHP), and polychlorinated biphenyl. On - site integrated management system for detection of endocrine disrupters.

KR1020160023313A 2016-02-26 2016-02-26 Method for detecting endocrine disruptors based on biomimetic material and total management system for field application KR20170100884A (en)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109772279A (en) * 2019-01-25 2019-05-21 重庆工业职业技术学院 A kind of method of modifying of multi-walled carbon nanotube
WO2023195628A1 (en) * 2022-04-08 2023-10-12 아주대학교산학협력단 Peptide for detecting ca125 and use thereof
WO2023195629A1 (en) * 2022-04-08 2023-10-12 아주대학교산학협력단 He4 detecting peptide and use thereof

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109772279A (en) * 2019-01-25 2019-05-21 重庆工业职业技术学院 A kind of method of modifying of multi-walled carbon nanotube
WO2023195628A1 (en) * 2022-04-08 2023-10-12 아주대학교산학협력단 Peptide for detecting ca125 and use thereof
WO2023195629A1 (en) * 2022-04-08 2023-10-12 아주대학교산학협력단 He4 detecting peptide and use thereof

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