WO2022211319A1 - Ion-concentration-polarization-type bacteria detection device, and bacteria detection method using same - Google Patents

Ion-concentration-polarization-type bacteria detection device, and bacteria detection method using same Download PDF

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WO2022211319A1
WO2022211319A1 PCT/KR2022/003661 KR2022003661W WO2022211319A1 WO 2022211319 A1 WO2022211319 A1 WO 2022211319A1 KR 2022003661 W KR2022003661 W KR 2022003661W WO 2022211319 A1 WO2022211319 A1 WO 2022211319A1
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bacteria
ion
electrode
channel
ion concentration
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PCT/KR2022/003661
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French (fr)
Korean (ko)
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김성재
김원석
박재석
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서울대학교산학협력단
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/40—Concentrating samples
    • G01N1/4055—Concentrating samples by solubility techniques
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/30—Staining; Impregnating ; Fixation; Dehydration; Multistep processes for preparing samples of tissue, cell or nucleic acid material and the like for analysis
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/38—Diluting, dispersing or mixing samples
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/40—Concentrating samples
    • 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
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/52—Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper and including single- and multilayer analytical elements
    • 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
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/52—Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper and including single- and multilayer analytical elements
    • G01N33/521—Single-layer analytical elements
    • 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
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
    • 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
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
    • G01N33/56911—Bacteria
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/195—Assays involving biological materials from specific organisms or of a specific nature from bacteria

Definitions

  • the present invention relates to an ion concentration polarization type bacteria detection apparatus and a method for detecting bacteria using the same, and more particularly, by using the ion concentration polarization phenomenon to concentrate particles and simultaneously dissolve the concentrated particles in a temperature range where an enzyme reaction is promoted. It relates to an ion concentration polarization type bacteria detection device and a bacteria detection method using the same.
  • Particulate matter has a great impact on the human body and the global environment through various forms and routes. With the development of related industries and increasing interest in the environment, its importance is also gradually emerging. Molecules that affect us, from detecting specific particles that can obtain biometric information in living fluids, for example, bacteria in urine, to finding low-concentration environmental substances distributed in the air, depend on their size. and different concentrations. In order to efficiently measure and analyze this, various sensors and reactors have been developed.
  • a pre-treatment process of concentration to a desired level by these sensors and reactors is performed, and then a post-processing process for the concentrated one is performed.
  • the post-processing process needs to be performed by connecting separate devices for processing and analyzing particles in a multi-stage form, and this type has a complicated configuration and takes a lot of time and money to detect a specific particle. There is this.
  • An object of the present invention is to solve various problems including the above problems, and an object of the present invention is to provide an ion concentration polarization type bacteria detection device capable of simultaneously dissolving bacteria in the device and a bacteria detection method using the same.
  • these problems are exemplary, and the scope of the present invention is not limited thereto.
  • a channel unit including a first channel having an inlet into which a fluid is injected and a second channel connected to the first channel and having an outlet through which the fluid is discharged; an ion permeable membrane layer disposed on the channel portion to provide an ion transfer path; and an electrode unit including a first electrode to which a negative voltage is applied; Including, but the ion concentration polarization (ICP; Ion Concentration Polarization) phenomenon occurs in the vicinity of the branch point between the channel part and the ion permeable membrane layer, the bacteria from the fluid passing through the channel part is concentrated, the first electrode is the ion
  • ICP Ion Concentration Polarization
  • An ion concentration polarization type bacteria detection device may be provided which is disposed closely on one side of the permeable membrane layer and is provided to generate alkaline water by electrolyzing water in the fluid at a portion adjacent to the first electrode.
  • the alkaline water may dissolve the bacteria concentrated by the ion concentration polarization phenomenon.
  • the patch unit may store a dye sample for dyeing the bacteria dissolved by the alkaline water.
  • the channel part may include cellulose paper.
  • the pores inside the cellulose paper may have a size of 1 um to 100 um.
  • the electrode unit may further include a second electrode to which a ground or positive voltage is applied.
  • the method comprising: applying a negative voltage to the first electrode; injecting a fluid containing bacteria into the inlet; electrolyzing water in the fluid to generate alkaline water in an area adjacent to the first electrode; Concentrating the bacteria from the fluid by forming an ion depletion zone (ICP Zone) by generating the ion concentration polarization (ICP) phenomenon in a region adjacent to a branch point between the channel part and the ion permeable membrane layer; and dissolving the concentrated bacteria in the alkaline water; including, a method for detecting bacteria may be provided.
  • ICP Zone ion depletion zone
  • ICP ion concentration polarization
  • Dyeing the bacteria dissolved by the alkaline water with a dye sample stored in the patch, detecting the presence of the bacteria may further include.
  • an ion concentration polarization type bacteria detection apparatus capable of detecting a specific bacteria within a short time and a bacteria detection method using the same.
  • the scope of the present invention is not limited by these effects.
  • FIG. 1 is a diagram schematically illustrating an ion concentration polarization type bacteria detection apparatus according to an embodiment of the present invention.
  • Figure 4 (a) is the result of observing the color change in the picture shown by the detection of bacteria over time
  • Figure 4 (b) is the color change according to the presence or absence of Ion Concentration Polarization (ICP) phenomenon It is a graph showing the ratio according to the bacterial concentration
  • FIG. 5 is a step-by-step diagram illustrating a bacteria detection method using an ion concentration polarization type bacteria detection apparatus according to an embodiment of the present invention.
  • FIG. 1 is a diagram schematically illustrating an ion concentration polarization type bacteria detection apparatus 1000 according to an embodiment of the present invention.
  • the ion concentration polarization type bacteria detection apparatus 1000 includes a first channel 100 having an inlet into which a fluid is injected, and an outlet connected to the first channel 100 through which the fluid is discharged.
  • a channel portion having a second channel 200 provided therewith, an ion permeable membrane layer 500 disposed on the channel portion, a first electrode 10 to which a negative voltage is applied, and a second electrode to which a ground or positive voltage is applied ( 20) may be included.
  • An inlet into which the fluid is injected may be provided at one end of the first channel 100 , and an outlet through which the fluid remaining after passing through the channel is discharged may be provided at the other end of the second channel 200 .
  • the first channel 100 and the second channel 200 are connected and constitute one channel unit.
  • the ion permeable membrane layer 500 is disposed on the upper portion of the channel portion to provide a transfer path of ions in the fluid passing through the channel portion. That is, the ion concentration polarization type bacteria detection apparatus 1000 according to an embodiment of the present invention exists in the form of a single fluid tube rather than a structure in which the channel part is separated, so that ions present in the fluid when the fluid passes through the channel part It allows it to pass through the ion permeable membrane layer 500 at this high speed.
  • ICP ion concentration polarization
  • an ion concentration polarization (ICP) phenomenon occurs in an area adjacent to the branch point between the channel part and the ion permeable membrane layer 500 to form an ion depletion zone (ICP Zone), as described above
  • Bacteria may be concentrated from the fluid at a nearby point in the area.
  • the fluid may be understood as an arbitrary charged solution, for example, may include urine containing bacteria.
  • alkaline water is generated by electrolysis of water in the fluid passing through the channel in the adjacent portion of the first electrode 10 , and the first electrode 10 is disposed in close contact with the ion permeable membrane layer 500 .
  • Alkaline water generated from the first electrode 10 may dissolve bacteria concentrated in the region near the ion permeable membrane layer 500 .
  • the ion concentration polarization type bacteria detection apparatus 1000 may further include a patch unit 300 disposed adjacent to the first electrode 10 .
  • the patch unit 300 stores a staining sample 300a for staining bacteria dissolved by alkaline water. More specifically, when bacteria are dissolved by alkaline water, a specific enzyme is ejected, and the above-described staining sample 300a is provided to dye the ejected specific enzyme. That is, the presence or absence of specific bacteria in the fluid may be detected through the patch unit 300 .
  • the dye sample 300a may be, for example, a nitrocefin solution.
  • the periphery of the channel part may be coated with wax. Accordingly, it is possible to minimize the loss of fluid by suppressing a phenomenon in which water in the fluid passing through the channel part leaks around the channel part.
  • the channel portion may include cellulose paper.
  • cellulose paper due to the porous structure of the cellulose paper, electric convection phenomenon can be suppressed when an electric field is applied to the channel portion, and electrical instability can be minimized during ion concentration polarization.
  • the porous structure of the above-described cellulose paper enables the channel portion to have a high electrotreatment capacity, and thus the channel portion may exhibit stable ion transport efficiency even under a high voltage electric field.
  • the pores inside the cellulose paper may have a size of, for example, 1 um to 100 um.
  • the channel unit of the ion concentration polarization type bacteria detection apparatus 1000 may include, for example, cellulose paper having a porous structure having a pore size distribution of 1 ⁇ m to 100 ⁇ m.
  • the above-described porous structure performs the role of parallelized microchannels, it is possible to concentrate a large-capacity solution at the level of a body fluid.
  • the electrode unit includes a first electrode 10 to which a negative voltage is applied and a second electrode 20 to which a ground or positive voltage is applied.
  • the second electrode 20 may be provided as a positive (+) electrode due to a potential difference with the first electrode 10 .
  • the first electrode 10 is disposed closely on one side of the ion-permeable membrane layer 500 . That is, since the bacteria that have passed through the ion permeable membrane layer 500 are concentrated in the vicinity of the ion permeable membrane layer 500 , the corresponding concentration point and the first electrode 10 may also be disposed adjacent to each other. Accordingly, the bacteria may be concentrated by the ion concentration polarization phenomenon and, at the same time, dissolved by the alkaline water generated by the first electrode 10 .
  • FIG. 2 in a paper device in which a sample for measuring a change in pH is stored, for example, under each voltage applied to 140V, 160V, 180V, and 200V, the color of the sample gradually increases at the point where the bacteria are concentrated. It can be confirmed that it becomes darker, and as shown in the graph, this means that the pH value of the corresponding point is gradually increasing.
  • the ion concentration polarization type bacteria detection apparatus 1000 can quickly detect a specific bacteria in a fluid, and the detection can be performed through the patch unit 300 .
  • the above-described bacterial dissolution phenomenon requires that the temperature conditions for promoting the enzymatic reaction, for example, temperature conditions of 35 °C to 40 °C be satisfied.
  • the temperature conditions for promoting the enzymatic reaction for example, temperature conditions of 35 °C to 40 °C be satisfied.
  • FIG. 3 in the paper device in which the sample for measuring the temperature change is stored, it can be seen that the color of the sample gradually fades at the point where the bacteria are concentrated under a constant voltage. As shown in the graph, this means that the temperature of the corresponding point is gradually increasing.
  • a constant voltage for example, a voltage of 140 V is applied to the electrode unit. It can be confirmed that a predetermined temperature condition in which the enzymatic reaction is promoted can be achieved only by electrical resistance.
  • a channel was printed on nitrocellulose paper (Whatman filter paper num. 1, Sigma-Aldrich, USA) and heated at 130° C. for 3 minutes to constitute one channel part inside the paper.
  • Paraffin film (Parafilm M) was bonded above and below the channel to prevent external contamination and evaporation of the internal fluid.
  • the ion-permeable membrane layer 500 made of a nanoporous membrane sheet (Sigma-Aldrich, USA), an electrode part made of Ag, and a Nitrocefin (Sigma-Aldrich, USA) solution as a dyeing sample (300a) coated patch part (300)
  • urine was injected into the inlet part provided at one end of the first channel 100 of the channel part as a fluid passing through the channel part. Then, after 380 seconds (180 seconds of sample injection + 200 seconds of device operation) after urine was injected using a mobile phone, color changes were photographed, and the photographed pictures were analyzed.
  • Figure 4 (a) is the result of observing the color change in the photograph shown by the detection of bacteria over time
  • Figure 4 (b) is a photograph taken according to the presence or absence of Ion Concentration Polarization (ICP) phenomenon Among them, it is a graph showing the ratio of the color change according to the bacterial concentration.
  • ICP Ion Concentration Polarization
  • Bacteria concentrated by the ion concentration polarization (ICP) phenomenon may be dissolved by the alkaline water generated from the first electrode 10 at the same time as the concentration.
  • a specific enzyme is ejected, and the dye sample 300a stored in the patch part 300 stains the specific enzyme, so that the color change appears in the patch part 300 .
  • FIG. 4( a ) it can be seen that the color of the patch part 300 is changed within 3 minutes even when bacteria exist only at a low concentration level of about 10 4 cfu/mL.
  • the above-described bacteria are simply separated from the fluid by the ion concentration polarization (ICP) phenomenon and go through concentration, and the ion concentration polarization type bacteria detection device 1000 according to an embodiment of the present invention Even if the lysed bacteria are present only in low concentrations, the detection of the bacteria may be possible.
  • ICP ion concentration polarization
  • the ion concentration polarization type bacteria detection apparatus 1000 may be provided, for example, in the form of an automated small device.
  • FIG. 5 is a diagram illustrating a method for detecting bacteria according to an embodiment of the present invention.
  • Ion concentration polarization (ICP) Polarization may include a step of concentrating bacteria from the fluid by a phenomenon, dissolving the concentrated bacteria with alkaline water, and detecting the presence of bacteria through a patch part.
  • ICP ion concentration polarization
  • Ion concentration polarization (ICP) phenomenon is one of the electrochemical transfer phenomena observed around structures having nano-membrane.
  • the nano-membrane may be understood as the ion-permeable membrane layer 500 of the present invention.
  • the thickness of the electric double layer is similar to the size of the wall distance within the nanomembrane, the electric double layer overlaps inside the nanomembrane to show single ion permeability. Ions having the same type of charge as the wall charge of the nanomembrane do not pass through the nanomembrane due to diffusion and drift force, but only ions having the opposite type of charge to the wall charge pass through, and excessive depletion of ions at the nanomembrane interface phenomenon appears.
  • a strong electrical repulsive force acts between the ions that do not pass through the nano-membrane, so that both cations and anions are affected, and thus an ion concentration gradient appears.
  • charged bacteria, cells, and droplets are also affected by the electrical repulsive force of ions at the interface of the ion depletion zone (ICP Zone) and are pushed out around the nano-membrane.
  • the material may be electrically balanced by the force due to electroosmosis and the force due to electrophoresis, and the material may be concentrated at the equilibrium point of the force located near the ion depletion zone (ICP Zone).
  • the equilibrium point may be different depending on the size and charge amount of the molecular weight of each material.
  • the step of concentrating the bacteria by the above-described ion concentration polarization (ICP) phenomenon and the step of dissolving the bacteria may be simultaneously performed.
  • ICP ion concentration polarization
  • applying a negative voltage to the first electrode 10 and electrolyzing water in the fluid supplied to the inlet of the first channel 100 constituting the channel portion to the first electrode The step of generating alkaline water in the adjacent part of (10) is preceded, which is a process that proceeds continuously and automatically when a voltage is applied to the electrode.
  • alkaline water including hydroxide ions (OH - ) is generated through the electrolysis reaction of water (H 2 O) in the fluid, and the concentrated bacteria are in the already generated alkaline water. It can be dissolved simultaneously with concentration. Accordingly, the presence or absence of a specific bacteria can be detected within a short time through the method for detecting bacteria according to an embodiment of the present invention.
  • the bacteria dissolved by the alkaline water spout a specific enzyme, and the staining sample 300a stored in the patch unit 300 stains the specific enzyme spewed from the bacteria to detect the presence of the corresponding bacteria. Since the step of detecting the presence or absence of bacteria targets bacteria concentrated due to the ion concentration polarization phenomenon, the method for detecting bacteria according to an embodiment of the present invention enables detection of the bacteria even in the presence of only low-concentration bacteria. do.

Abstract

The present invention provides an ion concentration polarization (ICP)-type bacteria detection device, and a bacteria detection method using same, the device comprising: a channel unit including a first channel having an inlet part through which a fluid is injected, and a second channel having an outlet part connected to the first channel to discharge the fluid therethrough; an ion-permeable membrane layer disposed on the channel unit to provide an ion transfer path; and an electrode unit including a first electrode to which a negative voltage is applied, wherein ICP occurs in an area adjacent to a branch point between the channel unit and the ion-permeable membrane layer, and thus bacteria is concentrated from the fluid passing through the channel unit, and the first electrode is disposed closely to one side of the ion-permeable membrane layer and is provided so that water in the fluid is electrolyzed in an adjacent part of the first electrode to generate alkaline water.

Description

이온농도분극형 박테리아 검출장치 및 이를 이용한 박테리아 검출방법Ion concentration polarization type bacteria detection device and bacteria detection method using the same
본 발명은 이온농도분극형 박테리아 검출장치 및 이를 이용한 박테리아 검출방법에 관한 것으로서, 더 상세하게는 이온농도분극 현상을 이용하여 입자를 농축시킴과 동시에 농축된 입자들을 효소 반응이 촉진되는 온도 범위에서 용해시킬 수 있는 이온농도분극형 박테리아 검출장치 및 이를 이용한 박테리아 검출방법에 관한 것이다.The present invention relates to an ion concentration polarization type bacteria detection apparatus and a method for detecting bacteria using the same, and more particularly, by using the ion concentration polarization phenomenon to concentrate particles and simultaneously dissolve the concentrated particles in a temperature range where an enzyme reaction is promoted. It relates to an ion concentration polarization type bacteria detection device and a bacteria detection method using the same.
입자상 물질은 다양한 형태와 경로를 통해 인체와 지구환경에 큰 영향을 주고 있다. 관련 산업의 발전과 환경에 대한 관심의 증대에 따라 그 중요성도 점차 부각되고 있다. 생명 유체 내에서의 생체정보를 획득할 수 있는 특정 입자, 예를 들어, 소변 내 박테리아를 검출하는 것에서부터, 공기 중에 분포하는 저농도의 환경물질을 발견하는 것까지 우리에게 영향을 끼치는 분자들은 그 크기와 농도가 다양하다. 이를 효율적으로 측정하고 분석하기 위해서 다양한 센서 및 반응기들이 개발되어왔다.Particulate matter has a great impact on the human body and the global environment through various forms and routes. With the development of related industries and increasing interest in the environment, its importance is also gradually emerging. Molecules that affect us, from detecting specific particles that can obtain biometric information in living fluids, for example, bacteria in urine, to finding low-concentration environmental substances distributed in the air, depend on their size. and different concentrations. In order to efficiently measure and analyze this, various sensors and reactors have been developed.
특히, 생체 내 특정 입자를 검출하는 과정은 이러한 센서 및 반응기들에 의해 원하는 수준으로 농축하는 전처리 과정을 거친 후, 농축된 것에 대한 후처리 과정을 거치게 된다. In particular, in the process of detecting a specific particle in a living body, a pre-treatment process of concentration to a desired level by these sensors and reactors is performed, and then a post-processing process for the concentrated one is performed.
그러나 상기 후처리과정은 입자를 처리하고 분석하기 위한 별도의 장치들을 다단 형태로 연결하여 수행될 필요성이 존재하며, 이러한 형태는 구성이 복잡하고 특정 입자를 검출하기까지 많은 시간과 비용이 소요된다는 문제점이 있다.However, the post-processing process needs to be performed by connecting separate devices for processing and analyzing particles in a multi-stage form, and this type has a complicated configuration and takes a lot of time and money to detect a specific particle. There is this.
본 발명은 상기와 같은 문제점을 포함하여 여러 문제점들을 해결하기 위한 것으로서, 장치 내에서 박테리아의 농축과 동시에 용해가 가능한 이온농도분극형 박테리아 검출장치 및 이를 이용한 박테리아 검출방법을 제공하는 것을 목적으로 한다. 그러나, 이러한 과제는 예시적인 것으로, 이에 의해 본 발명의 범위가 한정되는 것은 아니다.An object of the present invention is to solve various problems including the above problems, and an object of the present invention is to provide an ion concentration polarization type bacteria detection device capable of simultaneously dissolving bacteria in the device and a bacteria detection method using the same. However, these problems are exemplary, and the scope of the present invention is not limited thereto.
본 발명의 일 관점에 따르면, 유체가 주입되는 입구부를 구비한 제1 채널 및 상기 제1 채널과 연결되어 상기 유체가 배출되는 출구부를 구비한 제2 채널을 포함하는 채널부; 상기 채널부의 상부에 배치되어 이온의 전달경로를 제공하는 이온투과막층; 및 음전압이 인가되는 제1 전극을 포함하는 전극부; 를 포함하되, 상기 채널부와 이온투과막층 사이 분기점의 인접한 부위에 이온농도분극(ICP;Ion Concentration Polarization) 현상이 발생함으로써 상기 채널부를 통과하는 유체로부터 박테리아가 농축되고, 상기 제1 전극은 상기 이온투과막층의 일측에 밀접 배치되고, 상기 제1 전극의 인접한 부위에서 상기 유체 내의 물을 전기분해하여 알칼리수가 생성되도록 마련되는, 이온농도분극형 박테리아 검출장치가 제공될 수 있다.According to an aspect of the present invention, a channel unit including a first channel having an inlet into which a fluid is injected and a second channel connected to the first channel and having an outlet through which the fluid is discharged; an ion permeable membrane layer disposed on the channel portion to provide an ion transfer path; and an electrode unit including a first electrode to which a negative voltage is applied; Including, but the ion concentration polarization (ICP; Ion Concentration Polarization) phenomenon occurs in the vicinity of the branch point between the channel part and the ion permeable membrane layer, the bacteria from the fluid passing through the channel part is concentrated, the first electrode is the ion An ion concentration polarization type bacteria detection device may be provided which is disposed closely on one side of the permeable membrane layer and is provided to generate alkaline water by electrolyzing water in the fluid at a portion adjacent to the first electrode.
상기 알칼리수는 상기 이온농도분극 현상에 의해 농축된 박테리아를 용해시킬 수 있다.The alkaline water may dissolve the bacteria concentrated by the ion concentration polarization phenomenon.
상기 제1 전극과 인접하게 배치된 패치부; 를 더 포함하되, 상기 패치부는 상기 알칼리수에 의해 용해된 박테리아를 염색하는 염색시료를 저장할 수 있다.a patch portion disposed adjacent to the first electrode; Further comprising, the patch unit may store a dye sample for dyeing the bacteria dissolved by the alkaline water.
상기 채널부는 셀룰로오스 종이를 포함할 수 있다.The channel part may include cellulose paper.
상기 셀룰로오스 종이 내부의 기공은 1 um 내지 100um의 사이즈를 가질 수 있다.The pores inside the cellulose paper may have a size of 1 um to 100 um.
상기 전극부는 그라운드 또는 양전압이 인가되는 제2 전극을 더 포함할 수 있다.The electrode unit may further include a second electrode to which a ground or positive voltage is applied.
본 발명의 다른 관점에 따르면, 상기 제1 전극에 음전압을 인가하는 단계;상기 입구부에 박테리아를 포함하는 유체를 주입하는 단계; 상기 유체 내의 물을 전기분해하여 상기 제1 전극의 인접한 부위에서 알칼리수를 생성하는 단계; 상기 상기 채널부와 이온투과막층 사이 분기점의 인접한 부위에 상기 이온농도분극(ICP;Ion Concentration Polarization) 현상이 발생함으로써 이온공핍영역(ICP Zone)이 형성되어 상기 유체로부터 상기 박테리아를 농축하는 단계; 및 상기 농축된 박테리아를 상기 알칼리수로 용해하는 단계;를 포함하는, 박테리아 검출방법이 제공될 수 있다.According to another aspect of the present invention, the method comprising: applying a negative voltage to the first electrode; injecting a fluid containing bacteria into the inlet; electrolyzing water in the fluid to generate alkaline water in an area adjacent to the first electrode; Concentrating the bacteria from the fluid by forming an ion depletion zone (ICP Zone) by generating the ion concentration polarization (ICP) phenomenon in a region adjacent to a branch point between the channel part and the ion permeable membrane layer; and dissolving the concentrated bacteria in the alkaline water; including, a method for detecting bacteria may be provided.
상기 알칼리수에 의해 용해된 박테리아를 패치부에 저장된 염색시료로 염색하여, 상기 박테리아의 존재여부를 검출하는 단계; 를 더 포함할 수 있다.Dyeing the bacteria dissolved by the alkaline water with a dye sample stored in the patch, detecting the presence of the bacteria; may further include.
상기한 바와 같이 이루어진 본 발명의 일 실시예에 따르면, 특정 박테리아를 단시간 내에 검출할 수 있는 이온농도분극형 박테리아 검출장치 및 이를 이용한 박테리아 검출방법을 구현할 수 있다. 물론 이러한 효과에 의해 본 발명의 범위가 한정되는 것은 아니다.According to an embodiment of the present invention made as described above, it is possible to implement an ion concentration polarization type bacteria detection apparatus capable of detecting a specific bacteria within a short time and a bacteria detection method using the same. Of course, the scope of the present invention is not limited by these effects.
도 1은 본 발명의 일 실시예에 따른 이온농도분극형 박테리아 검출장치를 개략적으로 도시한 도면이다.1 is a diagram schematically illustrating an ion concentration polarization type bacteria detection apparatus according to an embodiment of the present invention.
도 2는 박테리아가 농축되는 영역에 있어서, 전압을 인가하였을 때 시간경과에 따른 pH 변화를 관찰한 결과이다.2 is a result of observing the change in pH over time when a voltage is applied in a region where bacteria are concentrated.
도 3은 박테리아가 농축되는 영역에 있어서, 전압을 인가하였을 때 시간경과에 따른 온도변화를 관찰한 결과이다.3 is a result of observing the temperature change over time when a voltage is applied in a region where bacteria are concentrated.
도 4(a)는 박테리아가 검출됨으로써 나타내는 사진 속 색상변화를 시간 경과에 따라 관찰한 결과이고, 도 4(b)는 이온농도분극(ICP;Ion Concentration Polarization) 현상의 유무에 따라 색상 변화가 나타난 비율을 박테리아 농도에 따라 나타낸 그래프이다,Figure 4 (a) is the result of observing the color change in the picture shown by the detection of bacteria over time, Figure 4 (b) is the color change according to the presence or absence of Ion Concentration Polarization (ICP) phenomenon It is a graph showing the ratio according to the bacterial concentration,
도 5는 본 발명의 일 실시예에 따른 이온농도분극형 박테리아 검출장치를 이용한 박테리아 검출방법을 단계에 따라 도시한 도면이다. 5 is a step-by-step diagram illustrating a bacteria detection method using an ion concentration polarization type bacteria detection apparatus according to an embodiment of the present invention.
이하, 첨부된 도면들을 참조하여 본 발명의 실시예를 상세히 설명하면 다음과 같다. 그러나 본 발명은 이하에서 개시되는 실시예에 한정되는 것이 아니라 서로 다른 다양한 형태로 구현될 수 있는 것으로, 이하의 실시예는 본 발명의 개시가 완전하도록 하며, 통상의 지식을 가진 자에게 발명의 범주를 완전하게 알려주기 위해 제공되는 것이다. 또한 설명의 편의를 위하여 도면에서는 구성 요소들이 그 크기가 과장 또는 축소될 수 있다.Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings. However, the present invention is not limited to the embodiments disclosed below, but can be implemented in a variety of different forms. It is provided to fully inform In addition, in the drawings for convenience of description, the size of the components may be exaggerated or reduced.
본 명세서에서 사용된 용어는 특정 실시예를 설명하기 위하여 사용되며, 본 발명을 제한하기 위한 것이 아니다. 본 명세서에서 사용된 바와 같이, 단수 형태는 문맥상 다른 경우를 분명히 지적하는 것이 아니라면, 복수의 형태를 포함할 수 있다. 또한, 본 명세서에서 사용되는 경우 "포함한다(comprise)" 및/또는 "포함하는(comprising)"은 언급한 형상들, 숫자, 단계, 동작, 부, 요소 및/또는 이들 그룹의 존재를 특정하는 것이며, 하나 이상의 다른 형상, 숫자, 동작, 부, 요소 및/또는 그룹들의 존재 또는 부가를 배제하는 것이 아니다.The terminology used herein is used to describe specific embodiments, not to limit the present invention. As used herein, the singular form may include the plural form unless the context clearly dictates otherwise. Also, as used herein, “comprise” and/or “comprising” refers to specifying the presence of the recited shapes, numbers, steps, operations, parts, elements, and/or groups thereof. and does not exclude the presence or addition of one or more other shapes, numbers, acts, parts, elements and/or groups.
이하, 본 발명의 실시예들은 본 발명의 이상적인 실시예들을 개략적으로 도시하는 도면들을 참조하여 설명한다. 도면들에 있어서, 예를 들면, 제조 기술 및/또는 공차(tolerance)에 따라, 도시된 형상의 변형들이 예상될 수 있다. 따라서, 본 발명 사상의 실시예는 본 명세서에 도시된 영역의 특정 형상에 제한된 것으로 해석되어서는 아니 되며, 예를 들면 제조상 초래되는 형상의 변화를 포함하여야 한다.DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, embodiments of the present invention will be described with reference to the drawings schematically illustrating ideal embodiments of the present invention. In the drawings, variations of the illustrated shape can be envisaged, for example depending on manufacturing technology and/or tolerances. Accordingly, embodiments of the inventive concept should not be construed as limited to the specific shape of the region shown in the present specification, but should include, for example, changes in shape caused by manufacturing.
도 1은 본 발명의 일 실시예에 따른 이온농도분극형 박테리아 검출장치(1000)를 개략적으로 도시한 도면이다.1 is a diagram schematically illustrating an ion concentration polarization type bacteria detection apparatus 1000 according to an embodiment of the present invention.
본 발명의 일 실시예에 따른 이온농도분극형 박테리아 검출장치(1000)는 유체가 주입되는 입구부를 구비한 제1 채널(100) 및 상기 제1 채널(100)과 연결되어 유체가 배출되는 출구부를 구비한 제2 채널(200)을 구비한 채널부, 채널부의 상부에 배치된 이온투과막층(500), 음전압이 인가되는 제1 전극(10) 및 그라운드 또는 양전압이 인가되는 제2 전극(20)을 포함하는 전극부를 포함할 수 있다. The ion concentration polarization type bacteria detection apparatus 1000 according to an embodiment of the present invention includes a first channel 100 having an inlet into which a fluid is injected, and an outlet connected to the first channel 100 through which the fluid is discharged. A channel portion having a second channel 200 provided therewith, an ion permeable membrane layer 500 disposed on the channel portion, a first electrode 10 to which a negative voltage is applied, and a second electrode to which a ground or positive voltage is applied ( 20) may be included.
유체가 주입되는 입구부는 제1 채널(100)의 일단에 마련되고, 채널부를 통과하고 잔류한 유체가 배출되는 출구부는 제2 채널(200)의 타단에 마련될 수 있다. An inlet into which the fluid is injected may be provided at one end of the first channel 100 , and an outlet through which the fluid remaining after passing through the channel is discharged may be provided at the other end of the second channel 200 .
제1 채널(100)과 제2 채널(200)은 연결된 구조로서 하나의 채널부를 구성한다. 또한, 이온투과막층(500)은 채널부의 상부에 배치되어, 채널부를 통과하는 유체 내 이온의 전달경로를 제공한다. 즉, 본 발명의 일 실시예에 따른 이온농도분극형 박테리아 검출장치(1000)는 채널부가 분리된 구조가 아닌 하나의 유체관의 형태로 존재함으로써, 유체가 채널부를 통과할 때 유체 내 존재하는 이온이 빠른 속력으로 이온투과막층(500)을 통과할 수 있도록 한다. 즉, 채널부를 통과하는 유체 내 이온만이 채널부의 상부에 접촉되어 배치되는 이온투과막층(500)을 상대적으로 빠르게 통과하게 되며, 이러한 이온의 선택적인 빠른 속도에 의해 이온농도분극(ICP;Ion Concentration Polarization) 현상이 나타나게 된다.The first channel 100 and the second channel 200 are connected and constitute one channel unit. In addition, the ion permeable membrane layer 500 is disposed on the upper portion of the channel portion to provide a transfer path of ions in the fluid passing through the channel portion. That is, the ion concentration polarization type bacteria detection apparatus 1000 according to an embodiment of the present invention exists in the form of a single fluid tube rather than a structure in which the channel part is separated, so that ions present in the fluid when the fluid passes through the channel part It allows it to pass through the ion permeable membrane layer 500 at this high speed. That is, only ions in the fluid passing through the channel part pass through the ion permeable membrane layer 500 disposed in contact with the upper part of the channel part relatively quickly, and by the selective fast speed of these ions, ion concentration polarization (ICP) Polarization) occurs.
유체가 채널부를 통과할 때, 채널부와 이온투과막층(500) 사이 분기점의 인접한 부위에 이온농도분극(ICP;Ion Concentration Polarization) 현상이 발생함으로써 이온공핍영역(ICP Zone)이 형성되고, 상술한 영역의 인근 지점에서 유체로부터 박테리아가 농축될 수 있다. 여기서, 상기 유체는 임의의 전하를 띤 용액으로 이해될 수 있으며, 예를 들어, 박테리아를 포함한 소변을 포함할 수 있다. 후술할 바와 같이, 제1 전극(10)의 인접한 부위에서는 채널부를 통과하는 유체 내의 물을 전기분해하여 알칼리수가 생성되고, 제1 전극(10)은 이온투과막층(500)과 밀접하여 배치되기 때문에, 제1 전극(10)으로부터 생성된 알칼리수는 이온투과막층(500) 인근 영역에 농축된 박테리아를 용해시킬 수 있다. When the fluid passes through the channel part, an ion concentration polarization (ICP) phenomenon occurs in an area adjacent to the branch point between the channel part and the ion permeable membrane layer 500 to form an ion depletion zone (ICP Zone), as described above Bacteria may be concentrated from the fluid at a nearby point in the area. Here, the fluid may be understood as an arbitrary charged solution, for example, may include urine containing bacteria. As will be described later, alkaline water is generated by electrolysis of water in the fluid passing through the channel in the adjacent portion of the first electrode 10 , and the first electrode 10 is disposed in close contact with the ion permeable membrane layer 500 . , Alkaline water generated from the first electrode 10 may dissolve bacteria concentrated in the region near the ion permeable membrane layer 500 .
도 1의 확대된 A영역을 참조해보면, 본 발명의 일 실시예에 따른 이온농도분극형 박테리아 검출장치(1000)는 제1 전극(10)과 인접하게 배치된 패치부(300)를 더 포함할 수 있다.Referring to the enlarged area A of FIG. 1 , the ion concentration polarization type bacteria detection apparatus 1000 according to an embodiment of the present invention may further include a patch unit 300 disposed adjacent to the first electrode 10 . can
패치부(300)는 알칼리수에 의해 용해된 박테리아를 염색하는 염색시료(300a)를 저장한다. 보다 구체적으로, 박테리아가 알칼리수에 의해 용해되면 특정 효소를 분출하게 되고, 상술한 염색시료(300a)는 분출된 특정 효소를 염색시키도록 마련된다. 즉, 패치부(300)를 통해 유체 내 특정 박테리아의 존재여부를 검출할 수 있다. 염색시료(300a)는, 예를 들어, 니트로세핀(Nitrocefin) 용액일 수 있다.The patch unit 300 stores a staining sample 300a for staining bacteria dissolved by alkaline water. More specifically, when bacteria are dissolved by alkaline water, a specific enzyme is ejected, and the above-described staining sample 300a is provided to dye the ejected specific enzyme. That is, the presence or absence of specific bacteria in the fluid may be detected through the patch unit 300 . The dye sample 300a may be, for example, a nitrocefin solution.
채널부 주변은 왁스로 코팅처리 될 수 있다. 이에, 채널부를 통과하는 유체 내 물이 채널부 주변으로 새어나가는 현상을 억제시켜 유체의 손실을 최소화할 수 있다.The periphery of the channel part may be coated with wax. Accordingly, it is possible to minimize the loss of fluid by suppressing a phenomenon in which water in the fluid passing through the channel part leaks around the channel part.
채널부는 셀룰로오스 종이를 포함할 수 있다. 이 때, 셀룰로오스 종이의 다공성 구조에 의해, 채널부에 전기장 인가 시 전기대류 현상이 억제될 수 있고, 이온농도분극 시 전기적 불안정성을 최소화시킬 수 있다. 아울러 상술한 셀룰로오스 종이의 다공성 구조는 채널부로 하여금 높은 전기처리 용량을 보유할 수 있게 하며, 이로 인해 채널부는 고전압 전기장 하에서도 안정적인 이온 수송 효율을 보일 수 있다.The channel portion may include cellulose paper. At this time, due to the porous structure of the cellulose paper, electric convection phenomenon can be suppressed when an electric field is applied to the channel portion, and electrical instability can be minimized during ion concentration polarization. In addition, the porous structure of the above-described cellulose paper enables the channel portion to have a high electrotreatment capacity, and thus the channel portion may exhibit stable ion transport efficiency even under a high voltage electric field.
셀룰로오스 종이 내부의 기공은, 예를 들어, 1 um 내지 100um의 사이즈를가질 수 있다. 기존의 이온농도분극 장치 하에서는 대용량의 용액을 농축시키기 위해 추가적인 구조 공정이 요구되었으며, 이는 상당 수준의 비용 및 시간이 소요되는 문제점이 있었다. 본 발명의 일 실시예에 따른 이온농도분극형 박테리아 검출장치(1000)의 채널부는, 예를 들어, 1 um 내지 100um의 기공 사이즈 분포를 갖는 다공성 구조로 이루어진 셀룰로오스 종이를 포함할 수 있다. 여기서, 상술한 다공성 구조는 병렬화된 마이크로 채널의 역할을 수행하므로, 체액 수준의 대용량 용액을 농축할 수 있다.The pores inside the cellulose paper may have a size of, for example, 1 um to 100 um. Under the existing ion concentration polarization device, an additional structural process was required to concentrate a large-capacity solution, which had a problem in that it took a considerable amount of time and cost. The channel unit of the ion concentration polarization type bacteria detection apparatus 1000 according to an embodiment of the present invention may include, for example, cellulose paper having a porous structure having a pore size distribution of 1 μm to 100 μm. Here, since the above-described porous structure performs the role of parallelized microchannels, it is possible to concentrate a large-capacity solution at the level of a body fluid.
도 2는 박테리아가 농축되는 영역에 있어서, 전압을 인가하였을 때 시간경과에 따른 pH변화를 관찰한 결과이다.2 is a result of observing the pH change over time when a voltage is applied in a region where bacteria are concentrated.
전극부는 음전압이 인가되는 제1 전극(10) 및 그라운드 또는 양전압이 인가되는 제2 전극(20)을 포함한다. 음전압이 인가되어 제1 전극(10)이 음(-)전극이 됨에 따라, 제1 전극(10)과의 전위차에 의해 제2 전극(20)은 양(+) 전극으로 마련될 수 있다. The electrode unit includes a first electrode 10 to which a negative voltage is applied and a second electrode 20 to which a ground or positive voltage is applied. As a negative voltage is applied and the first electrode 10 becomes a negative (-) electrode, the second electrode 20 may be provided as a positive (+) electrode due to a potential difference with the first electrode 10 .
음전압이 인가된 제1 전극(10)의 인접한 부위에서는, 채널부를 통과하는 유체 내 물(H2O)의 전기분해반응을 통하여 수소가스(H2)와 수산화 이온(OH-)이 생성된다. 즉, 수산화 이온(OH-)을 포함한 알칼리수의 생성으로 인해 제1 전극(10) 주변의 pH가 증가하게 된다.In a region adjacent to the first electrode 10 to which a negative voltage is applied, hydrogen gas (H 2 ) and hydroxide ions (OH − ) are generated through an electrolysis reaction of water (H 2 O) in a fluid passing through the channel part. . That is, the pH around the first electrode 10 increases due to the generation of alkaline water including hydroxide ions (OH − ).
제1 전극(10)은 이온투과막층(500)의 일측에 밀접 배치된다. 즉, 이온투과막층(500)을 통과한 박테리아가 이온투과막층(500)의 인근 지점에 농축되기 때문에, 해당 농축 지점과 제1 전극(10) 역시 인접하여 배치될 수 있다. 이에, 박테리아는 이온농도분극 현상에 의해 농축됨과 동시에, 제1 전극(10)에서 생성된 알칼리수에 의해 용해될 수 있다. 도 2를 참조하면, pH 변화 측정을 위한 시료가 저장된 종이 장치에 있어서, 예를 들어, 140V, 160V, 180V, 200V로 인가된 각각의 전압 하에, 박테리아가 농축되는 지점에 해당 시료의 색이 점점 진해지는 것을 확인할 수 있고, 그래프에 도시된 바와 같이 이는 해당 지점의 pH값이 점점 증가하고 있음을 의미한다. The first electrode 10 is disposed closely on one side of the ion-permeable membrane layer 500 . That is, since the bacteria that have passed through the ion permeable membrane layer 500 are concentrated in the vicinity of the ion permeable membrane layer 500 , the corresponding concentration point and the first electrode 10 may also be disposed adjacent to each other. Accordingly, the bacteria may be concentrated by the ion concentration polarization phenomenon and, at the same time, dissolved by the alkaline water generated by the first electrode 10 . Referring to FIG. 2 , in a paper device in which a sample for measuring a change in pH is stored, for example, under each voltage applied to 140V, 160V, 180V, and 200V, the color of the sample gradually increases at the point where the bacteria are concentrated. It can be confirmed that it becomes darker, and as shown in the graph, this means that the pH value of the corresponding point is gradually increasing.
즉, 이온투과막층(500)을 통과하여 농축된 박테리아는 인접한 제1 전극(10)에서의 전기분해 반응으로 발생하는 pH 변화를 통해 농축과 동시에 용해될 수 있음을 확인할 수 있다. 이를 통해 본 발명의 일 실시예에 따른 이온농도분극형 박테리아 검출장치(1000)는 유체 내 특정 박테리아를 빠른 시간 내 검출할 수 있으며, 검출은 패치부(300)를 통해 수행할 수 있다.That is, it can be confirmed that the bacteria concentrated through the ion permeable membrane layer 500 can be dissolved simultaneously with concentration through the pH change generated by the electrolysis reaction in the adjacent first electrode 10 . Through this, the ion concentration polarization type bacteria detection apparatus 1000 according to an embodiment of the present invention can quickly detect a specific bacteria in a fluid, and the detection can be performed through the patch unit 300 .
도 3은 박테리아가 농축되는 영역에 있어서, 전압을 인가하였을 때 시간경과에 따른 온도변화를 관찰한 결과이다.3 is a result of observing the temperature change over time when a voltage is applied in a region where bacteria are concentrated.
상술한 박테리아 용해현상은 효소 반응이 촉진되는 온도 조건, 예를 들어, 35℃ 내지 40℃의 온도조건이 충족될 것이 요구된다. 도 3을 참조하면, 온도 변화 측정을 위한 시료가 저장된 종이 장치에 있어서, 일정 전압 하에 박테리아가 농축되는 지점에 해당 시료의 색이 점점 옅어짐을 확인할 수 있다. 그래프에 도시된 바와 같이 이는 해당 지점의 온도가 점점 증가하고 있음을 의미한다. The above-described bacterial dissolution phenomenon requires that the temperature conditions for promoting the enzymatic reaction, for example, temperature conditions of 35 °C to 40 °C be satisfied. Referring to FIG. 3 , in the paper device in which the sample for measuring the temperature change is stored, it can be seen that the color of the sample gradually fades at the point where the bacteria are concentrated under a constant voltage. As shown in the graph, this means that the temperature of the corresponding point is gradually increasing.
즉, 본 발명의 일 실시예에 따른 이온농도분극형 박테리아 검출장치(1000)는 전극부에 일정 전압, 예를 들어, 140V의 전압이 인가되기만 하면, 별도의 온도발생 장치 없이 인가된 전압에 의한 전기저항만으로도 효소 반응이 촉진되는 소정의 온도 조건을 달성할 수 있음을 확인할 수 있다. That is, in the ion concentration polarization type bacteria detection apparatus 1000 according to an embodiment of the present invention, as long as a constant voltage, for example, a voltage of 140 V is applied to the electrode unit, It can be confirmed that a predetermined temperature condition in which the enzymatic reaction is promoted can be achieved only by electrical resistance.
이하에서는, 본 발명의 이해를 돕기 위한 이온농도분극형 박테리아 검출장치(1000)의 제조예 및 실험예를 설명한다. 다만, 하기의 제조예 및 실험예는 본 발명의 이해를 돕기 위한 것일 뿐, 본 발명이 아래의 제조예 및 실험예만으로 한정되는 것은 아니다. Hereinafter, a manufacturing example and an experimental example of the ion concentration polarization type bacteria detection apparatus 1000 to help the understanding of the present invention will be described. However, the following Preparation Examples and Experimental Examples are provided only to aid the understanding of the present invention, and the present invention is not limited only to the Preparation Examples and Experimental Examples below.
<제조예 1> 니트로셀룰로오스 종이(Nitrocellulose paper)를 이용한 이온농도분극형 박테리아 검출장치(1000)의 제조<Preparation Example 1> Preparation of ion concentration polarization type bacteria detection device 1000 using nitrocellulose paper
Nitrocellulose paper (Whatman filter paper num. 1, Sigma-Aldrich, USA)에 채널을 프린트하고, 130℃에서 3분간 가열하여 종이 내부에 하나의 채널부를 구성하였다.A channel was printed on nitrocellulose paper (Whatman filter paper num. 1, Sigma-Aldrich, USA) and heated at 130° C. for 3 minutes to constitute one channel part inside the paper.
채널부의 위, 아래로 Paraffin film (Parafilm M)을 접합하여 외부의 오염과 내부 유체의 증발을 방지하도록 하였다.Paraffin film (Parafilm M) was bonded above and below the channel to prevent external contamination and evaporation of the internal fluid.
이후, Nanoporous membrane sheet (Sigma-Aldrich, USA)로 이루어진 이온투과막층(500), Ag로 이루어진 전극부 및 Nitrocefin (Sigma-Aldrich, USA)용액을 염색시료(300a)로서 코팅한 패치부(300)를 구성한 후, 각각의 지정된 장소에 삽입하고 열을 가해 이온농도분극형 박테리아 검출장치(1000)를 제조하였다. Then, the ion-permeable membrane layer 500 made of a nanoporous membrane sheet (Sigma-Aldrich, USA), an electrode part made of Ag, and a Nitrocefin (Sigma-Aldrich, USA) solution as a dyeing sample (300a) coated patch part (300) After constructing the ion concentration polarization type bacteria detection device 1000 by inserting it into each designated place and applying heat.
<실험예 1><Experimental Example 1>
제조예 1에 따른 이온농도분극형 박테리아 검출장치(1000)에 있어서 채널부를 통과하는 유체로서 채널부의 제1 채널(100) 일단에 마련된 입구부에 소변을 주입하였다. 이후, 휴대전화를 이용하여 소변을 주입시킨지 380 초(샘플 주입 180초 + 기기 작동 200초)가 지난 후부터 색상변화를 촬영하고, 촬영된 사진을 분석하였다. In the ion concentration polarization type bacteria detection apparatus 1000 according to Preparation Example 1, urine was injected into the inlet part provided at one end of the first channel 100 of the channel part as a fluid passing through the channel part. Then, after 380 seconds (180 seconds of sample injection + 200 seconds of device operation) after urine was injected using a mobile phone, color changes were photographed, and the photographed pictures were analyzed.
도 4(a)는 박테리아가 검출됨으로써 나타내는 사진 속 색상변화를 시간 경과에 따라 관찰한 결과이고, 도 4(b)는 이온농도분극(ICP;Ion Concentration Polarization) 현상의 유무에 따라, 촬영된 사진들 중 상기 색상 변화가 나타난 비율을 박테리아 농도에 따라 나타낸 그래프이다. Figure 4 (a) is the result of observing the color change in the photograph shown by the detection of bacteria over time, Figure 4 (b) is a photograph taken according to the presence or absence of Ion Concentration Polarization (ICP) phenomenon Among them, it is a graph showing the ratio of the color change according to the bacterial concentration.
이온농도분극(ICP;Ion Concentration Polarization) 현상에 의해 농축된 박테리아는 농축과 동시에 제1 전극(10)에서 생성된 알칼리수에 의해 용해될 수 있다. 이 때, 박테리아가 용해되면 특정 효소를 분출하게 되고, 패치부(300)에 저장된 염색시료(300a)가 상기 특정 효소를 염색시킴으로써 패치부(300)에 색상 변화가 나타나게 된다. 도 4(a) 참조하면, 박테리아가 약 10 4cfu/mL의 저농도 수준으로만 존재하여도 3분 이내로 패치부(300)의 색상이 변화되는 것을 확인할 수 있다. 도 4(b)를 참조하면, 이온농도분극(ICP;Ion Concentration Polarization) 현상 하에서는 약 10 4cfu/mL의 저농도의 박테리아만 존재하여도 색상변화가 나타나는 반면, 이온농도분극(ICP;Ion Concentration Polarization) 현상이 배재된 경우는 10 7cfu/Ml 이상의 고농도의 박테리아 존재하여야만 비로소 색상변화를 통한 특정 박테리아 검출이 가능해짐을 확인할 수 있다.Bacteria concentrated by the ion concentration polarization (ICP) phenomenon may be dissolved by the alkaline water generated from the first electrode 10 at the same time as the concentration. At this time, when the bacteria are dissolved, a specific enzyme is ejected, and the dye sample 300a stored in the patch part 300 stains the specific enzyme, so that the color change appears in the patch part 300 . Referring to FIG. 4( a ), it can be seen that the color of the patch part 300 is changed within 3 minutes even when bacteria exist only at a low concentration level of about 10 4 cfu/mL. Referring to FIG. 4(b), under the ion concentration polarization (ICP) phenomenon, a color change appears even in the presence of only bacteria at a low concentration of about 10 4 cfu/mL, whereas the ion concentration polarization (ICP) ) phenomenon is excluded, it can be confirmed that specific bacteria can be detected through color change only when bacteria with a high concentration of 10 7 cfu/Ml or more exist.
즉, 상술한 박테리아는 이온농도분극(ICP;Ion Concentration Polarization) 현상에 의해 유체로부터 단순 분리되는 것을 지나 농축까지 이루어진 것으로서, 본 발명의 일 실시예에 따른 이온농도분극형 박테리아 검출장치(1000)는 용해된 박테리아가 저농도로만 존재하여도 해당 박테리아의 검출이 가능할 수 있다.That is, the above-described bacteria are simply separated from the fluid by the ion concentration polarization (ICP) phenomenon and go through concentration, and the ion concentration polarization type bacteria detection device 1000 according to an embodiment of the present invention Even if the lysed bacteria are present only in low concentrations, the detection of the bacteria may be possible.
본 발명의 일 실시예에 따른 이온농도분극형 박테리아 검출장치(1000)는, 예를 들어, 자동화된 소형 장치 형태로 제공될 수 있다. The ion concentration polarization type bacteria detection apparatus 1000 according to an embodiment of the present invention may be provided, for example, in the form of an automated small device.
도 5는 본 발명의 일 실시예에 따른 박테리아 검출방법을 단계에 따라 도시한 도면이다. 5 is a diagram illustrating a method for detecting bacteria according to an embodiment of the present invention.
도 5를 참조하면, 본 발명의 일 실시예에 따른 박테리아 검출방법은 채널부의 제1 채널(100)의 일단에 마련된 입구부에 박테리아를 포함하는 유체를 주입한 후 이온농도분극(ICP;Ion Concentration Polarization) 현상에 의해 유체로부터 박테리아를 농축하는 단계, 농축된 박테리아를 알칼리수로 용해하는 단계 및 패치부를 통해 박테리아의 존재여부를 검출하는 단계를 포함할 수 있다. Referring to FIG. 5 , in the method for detecting bacteria according to an embodiment of the present invention, after injecting a fluid containing bacteria into the inlet provided at one end of the first channel 100 of the channel unit, Ion concentration polarization (ICP) Polarization) may include a step of concentrating bacteria from the fluid by a phenomenon, dissolving the concentrated bacteria with alkaline water, and detecting the presence of bacteria through a patch part.
본 발명의 일 실시예에 따른 이온농도분극(ICP;Ion Concentration Polarization) 현상은 다음과 같다. An ion concentration polarization (ICP) phenomenon according to an embodiment of the present invention is as follows.
이온농도분극(ICP;Ion Concentration Polarization) 현상은 나노막을 갖는 구조 주변에서 관찰되는 전기화학 전달 현상 중의 하나이다. 이 때, 상기 나노막은 본 발명의 이온투과막층(500)으로 이해될 수 있다. 전기 이중층의 두께가 상기 나노막 내 벽면 거리의 크기와 비슷하다고 가정할 때, 상기 나노막 내부에서 전기 이중층이 겹침으로써 단일 이온 투과성을 보인다. 나노막의 벽면 전하와 같은 종류의 전하를 갖는 이온들은 확산과 표류력에 의해 상기 나노막을 통과하지 못하고 벽면 전화와 반대 종류의 전하를 갖는 이온들만이 통과하게 되면서, 상기 나노막 경계면에서는 이온들의 공핍 과다 현상이 나타난다. 상기 나노막을 통과하지 못한 이온들 사이에서는 강한 전기적인 반발력이 작용하여 양이온과 음이온 모두 영향을 받게 되고, 이에 따라 이온 농도 구배 현상이 나타난다. 이 때, 전하를 띠고 있는 박테리아나 세포, 액적들도 이온공핍영역(ICP Zone) 경계면에서 이온들의 전기적 반발력에 영향을 받아 상기 나노막 주변에서 밀려나게 된다.Ion concentration polarization (ICP) phenomenon is one of the electrochemical transfer phenomena observed around structures having nano-membrane. At this time, the nano-membrane may be understood as the ion-permeable membrane layer 500 of the present invention. Assuming that the thickness of the electric double layer is similar to the size of the wall distance within the nanomembrane, the electric double layer overlaps inside the nanomembrane to show single ion permeability. Ions having the same type of charge as the wall charge of the nanomembrane do not pass through the nanomembrane due to diffusion and drift force, but only ions having the opposite type of charge to the wall charge pass through, and excessive depletion of ions at the nanomembrane interface phenomenon appears. A strong electrical repulsive force acts between the ions that do not pass through the nano-membrane, so that both cations and anions are affected, and thus an ion concentration gradient appears. At this time, charged bacteria, cells, and droplets are also affected by the electrical repulsive force of ions at the interface of the ion depletion zone (ICP Zone) and are pushed out around the nano-membrane.
즉, 임의의 전하를 띤 용액이 채널부 내에 주입되고, 채널부에 전압을 인가하게 되면, 이온농도 구배로 인한 이온농도분극(ICP;Ion Concentration Polarization) 현상에 의한 힘에 의해 특정 전하를 가진 물질이 이온공핍영역(ICP Zone)의 경계면에서 밀려날 수 있다. 이 때, 상기 물질은 전기삼투에 의한 힘과 전기영동으로 인한 힘에 의해 전기적으로 평형을 이룰 수 있으며, 이온공핍영역(ICP Zone) 인근에 위치한 힘의 평형 지점에서 물질이 농축될 수 있다. 한편, 각 물질의 분자량의 크기 및 전하량에 따라 평형을 이루는 지점은 각각 다를 수 있다.That is, when a solution having an arbitrary charge is injected into the channel part and a voltage is applied to the channel part, a substance having a specific charge by the force caused by the ion concentration polarization (ICP) phenomenon caused by the ion concentration gradient It can be pushed out at the interface of this ion depletion region (ICP Zone). At this time, the material may be electrically balanced by the force due to electroosmosis and the force due to electrophoresis, and the material may be concentrated at the equilibrium point of the force located near the ion depletion zone (ICP Zone). On the other hand, the equilibrium point may be different depending on the size and charge amount of the molecular weight of each material.
본 발명의 일 실시예에 따른 박테리아 검출방법은 전술한 이온농도분극(ICP;Ion Concentration Polarization) 현상에 의해 박테리아가 농축되는 단계 및 해당 박테리아가 용해되는 단계가 동시에 수행될 수 있다. 이를 위해, 박테리아를 농축하는 단계 이전에, 제1 전극(10)에 음전압을 인가하는 단계 및 채널부를 구성하는 제1 채널(100)의 입구부로 공급된 유체 내의 물을 전기분해하여 제1 전극(10)의 인접한 부위에서 알칼리수를 생성하는 단계가 선행되며, 이는 전극에 전압을 인가하면 연속적 그리고 자동적으로 진행되는 프로세스이다.In the method for detecting bacteria according to an embodiment of the present invention, the step of concentrating the bacteria by the above-described ion concentration polarization (ICP) phenomenon and the step of dissolving the bacteria may be simultaneously performed. To this end, before the step of concentrating the bacteria, applying a negative voltage to the first electrode 10 and electrolyzing water in the fluid supplied to the inlet of the first channel 100 constituting the channel portion to the first electrode The step of generating alkaline water in the adjacent part of (10) is preceded, which is a process that proceeds continuously and automatically when a voltage is applied to the electrode.
음전압이 인가된 제1 전극(10)의 주변에서는 유체 내 물(H2O)의 전기분해반응을 통하여 수산화 이온(OH-)을 포함한 알칼리수가 생성되고, 농축된 박테리아는 기 생성된 알칼리수에 의해 농축과 동시에 용해될 수 있다. 이에, 본 발명의 일 실시예에 따른 박테리아 검출방법을 통해 단시간 내에 특정 박테리아 존재여부의 검출이 가능하다.In the vicinity of the first electrode 10 to which the negative voltage is applied, alkaline water including hydroxide ions (OH - ) is generated through the electrolysis reaction of water (H 2 O) in the fluid, and the concentrated bacteria are in the already generated alkaline water. It can be dissolved simultaneously with concentration. Accordingly, the presence or absence of a specific bacteria can be detected within a short time through the method for detecting bacteria according to an embodiment of the present invention.
이후, 알칼리수에 의해 용해된 박테리아는 특정 효소를 분출하게 되고, 패치부(300)에 저장된 염색시료(300a)는 박테리아로부터 분출된 특정 효소를 염색하여 해당 박테리아의 존재여부를 검출할 수 있다. 박테리아의 존재여부를 검출하는 단계는 이온농도분극 현상으로 농축된 박테리아를 대상으로 하기 때문에, 본 발명의 일 실시예에 따른 박테리아 검출방법은 저농도의 박테리아만이 존재하여도 해당 박테리아의 검출을 가능하게 한다.Thereafter, the bacteria dissolved by the alkaline water spout a specific enzyme, and the staining sample 300a stored in the patch unit 300 stains the specific enzyme spewed from the bacteria to detect the presence of the corresponding bacteria. Since the step of detecting the presence or absence of bacteria targets bacteria concentrated due to the ion concentration polarization phenomenon, the method for detecting bacteria according to an embodiment of the present invention enables detection of the bacteria even in the presence of only low-concentration bacteria. do.
본 발명은 도면에 도시된 일 실시예를 참고로 설명되었으나 이는 예시적인 것에 불과하며, 당해 기술분야에서 통상의 지식을 가진 자라면 이로부터 다양한 변형 및 균등한 다른 실시예가 가능하다는 점을 이해할 것이다. 따라서 본 발명의 진정한 기술적 보호 범위는 첨부된 특허청구범위의 기술적 사상에 의하여 정해져야 할 것이다.Although the present invention has been described with reference to one embodiment shown in the drawings, this is merely exemplary, and it will be understood by those skilled in the art that various modifications and equivalent other embodiments are possible therefrom. Therefore, the true technical protection scope of the present invention should be determined by the technical spirit of the appended claims.

Claims (8)

  1. 유체가 주입되는 입구부를 구비한 제1 채널 및 상기 제1 채널과 연결되어 상기 유체가 배출되는 출구부를 구비한 제2 채널을 포함하는 채널부;a channel part including a first channel having an inlet part into which a fluid is injected and a second channel connected to the first channel and having an outlet part through which the fluid is discharged;
    상기 채널부의 상부에 배치되어 이온의 전달경로를 제공하는 이온투과막층; 및an ion permeable membrane layer disposed on the channel portion to provide an ion transfer path; and
    음전압이 인가되는 제1 전극을 포함하는 전극부; 를 포함하되,an electrode unit including a first electrode to which a negative voltage is applied; including,
    상기 채널부와 이온투과막층 사이 분기점의 인접한 부위에 이온농도분극(ICP;Ion Concentration Polarization) 현상이 발생함으로써 상기 채널부를 통과하는 유체로부터 박테리아가 농축되고,Bacteria are concentrated from the fluid passing through the channel part by the occurrence of an ion concentration polarization (ICP) phenomenon in a region adjacent to the branch point between the channel part and the ion-permeable membrane layer,
    상기 제1 전극은 상기 이온투과막층의 일측에 밀접 배치되고, 상기 제1 전극의 인접한 부위에서 상기 유체 내의 물을 전기분해하여 알칼리수가 생성되도록 마련되는,The first electrode is disposed closely on one side of the ion-permeable membrane layer, and is provided so that alkaline water is generated by electrolysis of water in the fluid at an adjacent portion of the first electrode,
    이온농도분극형 박테리아 검출장치.Ion concentration polarization type bacteria detection device.
  2. 제 1 항에 있어서,The method of claim 1,
    상기 알칼리수는 상기 이온농도분극 현상에 의해 농축된 박테리아를 용해시키는,The alkaline water dissolves the bacteria concentrated by the ion concentration polarization phenomenon,
    이온농도분극형 박테리아 검출장치.Ion concentration polarization type bacteria detection device.
  3. 제 2 항에 있어서,3. The method of claim 2,
    상기 제1 전극과 인접하게 배치된 패치부; 를 더 포함하되,a patch portion disposed adjacent to the first electrode; further comprising,
    상기 패치부는 상기 알칼리수에 의해 용해된 박테리아를 염색하는 염색시료를 저장하는,The patch unit stores a dye sample for dyeing the bacteria dissolved by the alkaline water,
    이온농도분극형 박테리아 검출장치.Ion concentration polarization type bacteria detection device.
  4. 제 1 항에 있어서,The method of claim 1,
    상기 채널부는 셀룰로오스 종이를 포함하는,The channel portion comprises a cellulose paper,
    이온농도분극형 박테리아 검출장치.Ion concentration polarization type bacteria detection device.
  5. 제 4 항에 있어서,5. The method of claim 4,
    상기 셀룰로오스 종이 내부의 기공은 1 um 내지 100um의 사이즈를 갖는,The pores inside the cellulose paper have a size of 1 um to 100 um,
    이온농도분극형 박테리아 검출장치.Ion concentration polarization type bacteria detection device.
  6. 제 1 항에 있어서,The method of claim 1,
    상기 전극부는 그라운드 또는 양전압이 인가되는 제2 전극을 더 포함하는,The electrode part further comprises a second electrode to which a ground or positive voltage is applied,
    이온농도분극형 박테리아 검출장치.Ion concentration polarization type bacteria detection device.
  7. 제 1 항 내지 제 6 항 중 적어도 어느 한 항에 의한 상기 이온농도분극형 박테리아 검출장치를 이용한 박테리아 검출 방법으로서,A method for detecting bacteria using the ion concentration polarization type bacteria detection device according to any one of claims 1 to 6,
    상기 제1 전극에 음전압을 인가하는 단계;applying a negative voltage to the first electrode;
    상기 입구부에 박테리아를 포함하는 유체를 주입하는 단계;injecting a fluid containing bacteria into the inlet;
    상기 유체 내의 물을 전기분해하여 상기 제1 전극의 인접한 부위에서 알칼리수를 생성하는 단계;electrolyzing water in the fluid to generate alkaline water in an area adjacent to the first electrode;
    상기 채널부와 이온투과막층 사이 분기점의 인접한 부위에 상기 이온농도분극(ICP;Ion Concentration Polarization) 현상이 발생함으로써 이온공핍영역(ICP Zone)이 형성되어 상기 유체로부터 상기 박테리아를 농축하는 단계; 및Concentrating the bacteria from the fluid by forming an ion depletion zone (ICP Zone) by generating the ion concentration polarization (ICP) phenomenon in a region adjacent to a branch point between the channel part and the ion permeable membrane layer; and
    상기 농축된 박테리아를 상기 알칼리수로 용해하는 단계; 를 포함하는,dissolving the concentrated bacteria in the alkaline water; containing,
    박테리아 검출방법.Bacteria detection method.
  8. 제 7 항에 있어서,8. The method of claim 7,
    상기 알칼리수에 의해 용해된 박테리아를 패치부에 저장된 염색시료로 염색하여, 상기 박테리아의 존재여부를 검출하는 단계; 를 더 포함하는,Dyeing the bacteria dissolved by the alkaline water with a dye sample stored in the patch, detecting the presence of the bacteria; further comprising,
    박테리아 검출방법.Bacteria detection method.
PCT/KR2022/003661 2021-04-02 2022-03-16 Ion-concentration-polarization-type bacteria detection device, and bacteria detection method using same WO2022211319A1 (en)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101754845B1 (en) * 2016-03-17 2017-07-19 한국과학기술연구원 Preconcentration system using location control of electrokinetic phenomenon
KR20190129403A (en) * 2018-05-11 2019-11-20 포항공과대학교 산학협력단 Multifunctional microfluidic apparatus for lysing cell and analyzing intracellular components based on ion contcentration polarization
JP2019536066A (en) * 2016-11-18 2019-12-12 カルス インコーポレイテッド Concentration kit for lateral flow assay strips
KR20200074832A (en) * 2018-12-17 2020-06-25 광운대학교 산학협력단 Sample Concentration and Separation Device by Controlling Speed and Position of Sample in Microchannel

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101754845B1 (en) * 2016-03-17 2017-07-19 한국과학기술연구원 Preconcentration system using location control of electrokinetic phenomenon
JP2019536066A (en) * 2016-11-18 2019-12-12 カルス インコーポレイテッド Concentration kit for lateral flow assay strips
KR20190129403A (en) * 2018-05-11 2019-11-20 포항공과대학교 산학협력단 Multifunctional microfluidic apparatus for lysing cell and analyzing intracellular components based on ion contcentration polarization
KR20200074832A (en) * 2018-12-17 2020-06-25 광운대학교 산학협력단 Sample Concentration and Separation Device by Controlling Speed and Position of Sample in Microchannel

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
DAS ARINDAM K., MANOHAR MURLI, SHAHI VINOD K.: "Cation-Exchange Membrane with Low Frictional Coefficient and High Limiting Current Density for Energy-Efficient Water Desalination", ACS OMEGA, ACS PUBLICATIONS, US, vol. 3, no. 8, 31 August 2018 (2018-08-31), US , pages 10331 - 10340, XP055972804, ISSN: 2470-1343, DOI: 10.1021/acsomega.8b01403 *

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