KR102059488B1 - DNA motion control system using a nanopore sensor and its processing method - Google Patents

DNA motion control system using a nanopore sensor and its processing method Download PDF

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KR102059488B1
KR102059488B1 KR1020180025333A KR20180025333A KR102059488B1 KR 102059488 B1 KR102059488 B1 KR 102059488B1 KR 1020180025333 A KR1020180025333 A KR 1020180025333A KR 20180025333 A KR20180025333 A KR 20180025333A KR 102059488 B1 KR102059488 B1 KR 102059488B1
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김정석
박유경
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가천대학교 산학협력단
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    • G—PHYSICS
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    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
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    • G01N33/48721—Investigating individual macromolecules, e.g. by translocation through nanopores
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    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
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    • G01N27/327—Biochemical electrodes, e.g. electrical or mechanical details for in vitro measurements
    • G01N27/3275—Sensing specific biomolecules, e.g. nucleic acid strands, based on an electrode surface reaction
    • G01N27/3278—Sensing specific biomolecules, e.g. nucleic acid strands, based on an electrode surface reaction involving nanosized elements, e.g. nanogaps or nanoparticles
    • 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
    • G01N33/5308—Immunoassay; Biospecific binding assay; Materials therefor for analytes not provided for elsewhere, e.g. nucleic acids, uric acid, worms, mites

Abstract

본 발명은 나노기공센서를 통과하는 DNA를 자기장 제어하여 DNA 통과속도를 높이고 시간해상도를 향상시키는 DNA 동작제어 시스템 및 방법을 제공한다.The present invention provides a DNA motion control system and method for magnetic field control of DNA passing through a nanoporous sensor to increase DNA passage speed and improve time resolution.

Description

나노기공센서를 사용한 DNA 동작제어 시스템 및 방법 {DNA motion control system using a nanopore sensor and its processing method}DNA motion control system using a nanopore sensor and its processing method

본 발명은 나노기공센서를 이용한 DNA 염기분석 기술분야에 관한 것이다.The present invention relates to the field of DNA nucleotide analysis using nanopore sensors.

DNA 염기는 아데인, 구아닌, 시토신, 티민으로 구성되고, 이 염기 서열들의 서열에 따라 고유한 유전형질이 발현된다.DNA base is composed of adene, guanine, cytosine, thymine, and unique genotypes are expressed according to the sequence of these base sequences.

이에 다른 DNA 염기서열 분석은 정확한 질병 진단, 불치병 예측, 맞춤형 신약개발, DNA 보유개체의 성격파악, 범죄자 검거 등 다양한 분양에 활용된다.Other DNA sequencing analysis is used for a variety of distribution, such as accurate disease diagnosis, incurable disease prediction, customized drug development, characterization of DNA-bearing individuals, criminal arrest.

현존하는 DNA 염기분석 기법 중 나노기공(Nanopore)센서를 활용한 염기서열 분석이 차세대 유전자 검사 방법으로 주목받고 있는바, 여기서 나노기공센서는 자연에 존재하는 단백질을 사용하거나, 인위적으로 나노물질을 합성하여 만들 수 있다.Among the existing DNA sequencing techniques, sequencing using nanopore sensors is drawing attention as the next generation genetic test method, where nanopore sensors use proteins existing in nature or artificially synthesize nanomaterials. You can make

도 1은 나노기공센서의 일례로서, (a)는 KCL 용액이 채워진 cis 챔버와 trans 챔버 사이에 나노기공이 존재하는 구조이며, 일정한 전압을 클램핑(

Figure 112018021560513-pat00001
)하면 나노기공 사이에 전기장이 발생하여 이온 전류들(
Figure 112018021560513-pat00002
와
Figure 112018021560513-pat00003
)이 흐르기 시작하고, cis 챔버에 위치한 음전하를 띤 외가닥 DNA가 전기영동법에 의해 trans 챔버로 이동하게 된다. 1 is an example of a nano-pore sensor, (a) is a structure in which nano-pores exist between the cis chamber and the trans chamber filled with KCL solution, clamping a constant voltage (
Figure 112018021560513-pat00001
) Creates an electric field between the nanopores
Figure 112018021560513-pat00002
Wow
Figure 112018021560513-pat00003
) Begins to flow, and negatively charged single-stranded DNA located in the cis chamber is transferred to the trans chamber by electrophoresis.

이로써 외가닥 DNA가 나노미터 크기를 가진 구멍을 통과할 때 염기 종류에 따라 미세하게 변조된 이온전류가 발생하는데, (b)와 같이 이 전류의 순차적인 변화를 측정하여 염기서열을 판독할 수 있다.As a result, when the stranded DNA passes through the nanometer-sized pores, an ion current that is finely modulated according to the base type is generated.

나노기공센서를 이용한 염기분석 기법은 판독시간이 빠르고, 분석 비용이 저렴하며, DNA 염기 정보 처리량이 높은 장점을 가지나, DNA 분자의 속도가 너무 빠르기 때문에 시간해상도가 낮아 정확한 DNA 염기서열의 신호를 판독하기 어려운 문제가 있다.The nucleotide analysis method using nano-pore sensor has the advantage of fast reading time, low analysis cost, and high throughput of DNA base information, but because of the speed of DNA molecule is too fast, time resolution is low and accurate DNA sequence signal is read. There is a problem that is difficult to do.

관련 선행기술인 등록 특허 제1777483호(자성입자 제어를 통한 분자 인식 가속시스템 및 방법)는 분자 반응 챔버 외부에 설치된 자기장 발생부에 의해 자성입자 제어를 통한 분자 인식 가속 시스템에 관한 것으로서, 브라운 노이즈 스펙트럼형(복합체의 자연적인 브라운 운동 형상을 그대로 증폭)의 자기장을 발생하여, DNA 시퀀싱, 약물 스크리닝, 앱타머 선별 등의 어레이형 분자결합 판별에 이용하고자 한다.Related prior art Patent No. 1777483 (Method for accelerating molecular recognition through magnetic particle control system and method) relates to an accelerating system for molecular recognition through magnetic particle control by a magnetic field generating unit installed outside the molecular reaction chamber. A magnetic field of (amplifying the natural Brownian motion of the complex as it is) is generated and used for array type molecular binding determination such as DNA sequencing, drug screening and aptamer selection.

이는 나노기공센서의 챔버구조에서의 자기장의 세기와 방향을 조절하여 DNA 분자 속도를 제어하려는 본 발명과는 구성 및 작용 효과는 상이하다.This is different from the configuration and effect of the present invention to control the DNA molecule speed by adjusting the strength and direction of the magnetic field in the chamber structure of the nanoporous sensor.

본 발명은 나노기공센서를 통과하는 DNA 분자를 자기장 세기와 방향으로 제어하여 DNA 통과속도를 낮춰서 시간해상도를 향상시키는 DNA 동작제어 시스템 및 방법을 제공한다.The present invention provides a DNA motion control system and method for improving the time resolution by lowering the DNA passage rate by controlling the DNA molecules passing through the nanoporous sensor in the magnetic field strength and direction.

본 발명은 자기비드가 연결된 DNA가 통과하는 나노기공을 포함하여 DNA 통과시 이온전류의 변화를 발생하는 나노기공센서; 상기 나노기공센서에 일정 전압을 클램핑하는 전압인가부; 상기 나노기공센서의 나노기공의 방향과 축 방향이 일치하도록 상기 나노기공센서 외부 양측에 상호 연결되게 설치됨으로써 마그네틱 피드백 루프를 형성하는 한 쌍의 코일; 및 상기 나노기공센서, 전압인가부 및 코일에 연결되어, 상기 전압인가부 및 상기 코일의 구동 또는 전압을 제어하며, 상기 나노기공을 통과하는 DNA에 의해 발생하는 신호를 수집 분석하는 제어부; 를 포함하여, 상기 제어부에 의해 상기 전압인가부의 전압이 증가하여 DNA 통과속도가 상승할 때 상기 코일이 구동되어 상기 나노기공센서 내에 자기장을 형성함으로써 상기 DNA 통과속도가 감소하도록 제어되는 것을 특징으로 하는, 나노기공센서를 사용한 DNA 동작제어 시스템을 제공한다.The present invention includes a nano-pore sensor for generating a change in the ion current when passing through the DNA, including nano-pores through which the magnetic beads are connected; A voltage applying unit for clamping a predetermined voltage to the nanoporous sensor; A pair of coils which are installed to be connected to both sides of the nanoporous sensor outside so as to coincide with the direction of the nanopores of the nanoporous sensor to form a magnetic feedback loop; And a controller connected to the nanopore sensor, the voltage applying unit and the coil to control driving or voltage of the voltage applying unit and the coil, and collecting and analyzing a signal generated by the DNA passing through the nanopores. Including, the coil is driven by the controller when the voltage of the voltage applying unit is increased to increase the DNA passage rate is controlled to form a magnetic field in the nano-pore sensor is controlled to reduce the DNA passage rate To provide a DNA motion control system using nano-pore sensors.

본 발명의 다른 특징에 의하면, 마그네틱 성분이 있는 나노비드를 시퀀싱 타겟인 DNA 분자와 연결하는 자기 비드 연결단계; 자기 비드가 연결된 DNA 시료를 나노기공센서의 cis 챔버에 넣는 DNA분자 cis 챔버 투입단계; 전압인가부에 의해 나노기공센서의 trans 챔버에 인가하는 trans 챔버 전압인가단계; 전기영동법에 의해 DNA 분자들이 trans 챔버로 이동하면서 나노기공을 통과하는 trans 챔버 이동단계; 코일을 동작시켜 나노기공센서 내에 자기장을 형성하는 자기장 형성단계; 및 상기 단계에서 형성된 자기장에 의해 자기 비드가 cis 챔버쪽으로 이동하면서 나노기공을 통과하는 cis 챔버 이동단계;를 포함하여, 코일 자기장의 세기와 전기영동법의 전기장 세기를 조절함으로써 DNA 분자들이 나노기공에서 움직이는 속도와 시간을 제어하는 것을 특징으로 하는, 나노기공센서를 사용한 DNA 동작제어 방법을 제공한다.According to another feature of the invention, the magnetic bead linking step of connecting the nanobeads with a magnetic component with a DNA molecule as a sequencing target; A DNA molecule cis chamber input step of putting a DNA sample connected with magnetic beads into the cis chamber of the nanoporous sensor; A trans chamber voltage applying step of applying the trans chamber to the nanoporous sensor by the voltage applying unit; Trans chamber transfer step of passing through the nano-pores while moving the DNA molecules to the trans chamber by the electrophoresis method; A magnetic field forming step of operating a coil to form a magnetic field in the nanoporous sensor; And moving the cis chamber through the nanopores while the magnetic beads move toward the cis chamber by the magnetic field formed in the step. The DNA molecules move in the nanopores by controlling the strength of the coil magnetic field and the electric field strength of the electrophoresis method. It provides a method for controlling DNA motion using nano-pore sensors, characterized in that the speed and time are controlled.

본 발명에 따르면, 자기장에 의한 DNA 이동제어가 효과적으로 수행되어, 전압을 상승시켜 DNA 분자 속도를 높이더라도 높은 시간 해상도를 제공하는바, 나노기공 염기서열 측정을 가능하게 한다.According to the present invention, the DNA movement control by the magnetic field is effectively performed to provide high time resolution even by increasing the voltage to increase the DNA molecule rate, thereby enabling nanopore sequence measurement.

또한, 나노기공의 방향과 코일의 축 방향이 일치하여 DNA 이동제어의 효율성이 극대화된다.In addition, the direction of nanopores coincides with the axial direction of the coil to maximize the efficiency of DNA movement control.

도 1은 종래 나노기공센서의 구성 및 작용관계를 나타낸 도면이다.
도 2는 본 발명에 따른 나노기공센서의 구성 및 작용관계를 나타낸 도면이다.
도 3은 본 발명에 따른 시스템의 구성 블록도이다.
도 4는 본 발명에 따른 시스템의 플랫폼 아키텍쳐이다.
도 5는 본 발명에 따른 시스템의 처리 방법을 나타낸 흐름도이다.1 is a view showing the configuration and working relationship of the conventional nano-pore sensor.
2 is a view showing the configuration and working relationship of the nano-pore sensor according to the present invention.
3 is a block diagram illustrating the configuration of a system according to the present invention.
4 is a platform architecture of a system according to the present invention.
5 is a flowchart illustrating a processing method of a system according to the present invention.

이하에서는, 도면을 참조하여 본 발명의 기술적 특징을 상세히 설명한다.Hereinafter, with reference to the drawings will be described in detail the technical features of the present invention.

나노기공 염기서열 분석에 있어서, DNA 신호의 SNR(신호대잡음비)과 시간해상도가 반비례 관계에 있기 때문에, DNA 신호의 SNR과 시간해상도를 동시에 향상시키는 것은 어렵다.In nanopore sequencing, since the SNR (signal-to-noise ratio) and time resolution of a DNA signal are inversely related, it is difficult to simultaneously improve the SNR and time resolution of a DNA signal.

도 2를 참조하면, 본 발명은 나노기공센서 외부에 한 쌍의 코일로서 헬름홀츠코일을 설치하며,

Figure 112018021560513-pat00004
증가 → DNA 신호의 SNR 향상 → 통과속도 상승 → 헬름홀츠코일 작동 → 센서내 자기장 형성 → 자기비드 제어 → 통과속도 감소 → 시간해상도 증가의 과정으로 DNA 통과속도를 제어한다.2, the present invention installs a Helmholtz coil as a pair of coils outside the nano-pore sensor,
Figure 112018021560513-pat00004
Increase the SNR of the DNA signal → Increase the passage speed → Helmholtz coil operation → Form the magnetic field in the sensor → Control the magnetic beads → Decrease the passage speed → Control the DNA passage speed by increasing the time resolution.

즉, 헬름홀츠코일을 사용하여 마그네틱 피드백 루프 시스템을 구성하는 것인데, 전압

Figure 112018021560513-pat00005
를 변화시켜 자기장의 세기와 방향을 조절할 수 있다. 나노기공센서는 전압
Figure 112018021560513-pat00006
에 의한 전기장뿐 아니라 전압
Figure 112018021560513-pat00007
에 의한 자기장 영향에 놓이게 된다. In other words, the Helmholtz coil is used to construct a magnetic feedback loop system.
Figure 112018021560513-pat00005
To change the intensity and direction of the magnetic field. Nano pore sensor uses voltage
Figure 112018021560513-pat00006
Electric field as well as voltage by
Figure 112018021560513-pat00007
Subject to magnetic field effects.

그 결과 DNA 분자 움직임은 전압

Figure 112018021560513-pat00008
에 의해 속도
Figure 112018021560513-pat00009
로 제어되고, 자기 비드(bead) 움직임은
Figure 112018021560513-pat00010
에 의해 속도
Figure 112018021560513-pat00011
으로 제어되며, 이로써 DNA 통과속도를 낮춰 시간해상도를 향상시킬 수 있다. 이때 DNA 통과 속도는 VDNA=VE-VM 혹은 VE-VM 으로 정의가 된다. 여기서 +과 -는 방향을 가르키며 이는 코일에 걸리는 자기장의 방향으로 결정된다.As a result DNA molecule movements are voltage
Figure 112018021560513-pat00008
Speed by
Figure 112018021560513-pat00009
Controlled by magnetic bead movement
Figure 112018021560513-pat00010
Speed by
Figure 112018021560513-pat00011
This can be used to improve the time resolution by lowering the DNA passage rate. DNA passage rate is defined as V DNA = V E -V M or V E -V M. Where + and-indicate the direction, which is determined by the direction of the magnetic field across the coil.

도 3은 본 발명에 따른 나노기공센서를 사용한 DNA 동작제어 시스템의 구성 블록도로서, 나노기공센서(10), 전압인가부(20), 코일(30) 및 제어부(40)를 포함한고, 도 4는 도 3의 구성을 기반으로 한 플랫폼 아키텍쳐를 나타낸다.3 is a block diagram of a DNA motion control system using a nanoporous sensor according to the present invention, which includes a nanopore sensor 10, a voltage applying unit 20, a coil 30, and a controller 40. 4 shows a platform architecture based on the configuration of FIG. 3.

나노기공센서(10)는 자기 비드가 연결된 DNA가 통과하는 나노기공을 포함하여 DNA 통과시 이온전류의 변화 등의 신호를 발생하는 센서이다.The nano-pore sensor 10 is a sensor that generates a signal such as a change in the ion current when passing through the DNA, including nano-pores through which the DNA is connected magnetic beads.

상기 자기 비드는 streptavidin 코딩된 자기비드를 사용하고, biotin을 사용하여 DNA와 자기비드를 연결할 수 있다.The magnetic beads may be streptavidin-encoded magnetic beads, and biotin may be used to connect DNA and magnetic beads.

전압인가부(20)는 나노기공센서(10)에 일정 전압을 클램핑하여 이온전류를 생성하고 감지하는 장치로서 초저잡음 전위가변장치(퍼텐쇼스탯,potentiostat)가 적용될 수 있다. The voltage applying unit 20 is a device for generating and detecting an ion current by clamping a predetermined voltage to the nanoporous sensor 10, and an ultralow noise potential variable device (potentiostat) may be applied.

코일(30)은 헬름홀츠코일과 같이, 전기적으로 연결된 한 쌍으로 구성되어 나노기공센서(10)의 외부에 설치되어, 마그네틱 피드백 루프를 형성한다.The coil 30 is composed of a pair electrically connected to each other, such as a Helmholtz coil, and is installed outside the nano-pore sensor 10 to form a magnetic feedback loop.

코일(30)은 그 축 방향이 나노기공센서(10)의 나노기공의 방향과 일치하도록 설치함으로써, 자기비드를 부착한 DNA의 분자속도제어(비드제어)의 효율성을 높일 수 있다.The coil 30 is installed so that its axial direction coincides with the direction of the nanopores of the nanoporous sensor 10, thereby increasing the efficiency of molecular rate control (bead control) of DNA having magnetic beads.

제어부(40)는 나노기공센서(10), 전압인가부(20) 및 코일(30)에 연결되어, 전압인가부(20) 및 상기 코일(30)의 구동 또는 전압을 제어하고, 상기 나노기공을 통과하는 DNA에 의해 발생하는 신호를 수집 분석한다.The control unit 40 is connected to the nano-pore sensor 10, the voltage applying unit 20 and the coil 30, to control the driving or voltage of the voltage applying unit 20 and the coil 30, the nano-pores Collect and analyze the signals generated by the DNA passing through them.

제어부(40)는 전압인가부(20)를 구동하고, 적정 전압을 승인하여 DNA 통과속도를 제어하며, 이때 센서 내 자기장을 형성하기 위해 코일(30)의 전압-전류 컨버터를 구동하여 헬름홀츠코일을 작동시키고 적정전압을 승인한다.The controller 40 drives the voltage applying unit 20 and controls the DNA passage speed by approving an appropriate voltage. At this time, the voltage-current converter of the coil 30 is driven to form a magnetic field in the sensor to operate the Helmholtz coil. Activate and approve the proper voltage.

헬름홀츠코일의 작동에 의한 자기장은 DNA 에 부착된 자기 비드에 작용하여, 도 2에서와 같이,

Figure 112018021560513-pat00012
과
Figure 112018021560513-pat00013
를 조절함으로써 DNA의 통과속도를 요구되는 수준에 맞출 수 있게 된다. Magnetic field by the operation of the Helmholtz coil acts on the magnetic beads attached to the DNA, as shown in Figure 2,
Figure 112018021560513-pat00012
and
Figure 112018021560513-pat00013
By controlling the rate of passage of the DNA can be adjusted to the required level.

즉, 상기 제어부(40)에 의해 전압인가부(20)의 전압이 증가하여 DNA 통과속도가 상승할 때 상기 코일이 구동되어 나노기공센서(10) 내에 자기장을 형성함으로써 상기 DNA 통과속도가 감소하도록 제어되는 것이다.That is, when the voltage of the voltage applying unit 20 is increased by the controller 40 and the DNA passage speed is increased, the coil is driven to form a magnetic field in the nanopore sensor 10 so that the DNA passage speed is decreased. It is controlled.

제어부(40)는 나노기공센서(10)의 나노기공을 통과하는 DNA에 의해 발생하는 신호를 수집 분석하는 컴퓨팅 수단과 연결되어 수집 및 분석작업을 제어한다.The controller 40 is connected to computing means for collecting and analyzing signals generated by DNA passing through the nanopores of the nanopore sensor 10 to control the collection and analysis.

도 5는 본 발명의 DNA 동작제어 시스템의 제어방법(처리과정)을 나타낸 흐름도로서, 자기 비드 연결단계(s10), DNA분자 cis 챔버 투입단계(s20), trans 챔버 전압인가단계(s30), trans 챔버 이동단계(s40), 자기장 형성단계(s50) 및 cis 챔버 이동단계(s60)를 포함한다.Figure 5 is a flow chart showing a control method (process) of the DNA motion control system of the present invention, magnetic bead connection step (s10), DNA molecule cis chamber input step (s20), trans chamber voltage application step (s30), trans The chamber movement step (s40), the magnetic field forming step (s50) and cis chamber movement step (s60).

자기 비드 연결단계(s10)는 상술한 바와 같이, 마그네틱 성분이 있는 나노비드를 시퀀싱 타겟인 DNA 분자와 연결한다.As described above, the magnetic bead linking step (s10) connects the nanobeads with the magnetic component with the DNA molecules that are the sequencing targets.

DNA분자 cis 챔버 투입단계(s20)는 자기 비드가 연결된 DNA 시료를 나노기공센서(10)의 cis 챔버에 넣는다.In the DNA molecule cis chamber input step (s20), a DNA sample in which magnetic beads are connected is put in the cis chamber of the nano-pore sensor 10.

trans 챔버 전압인가단계(s30)는 전압인가부(20)에 의해 나노기공센서(10)의 trans 챔버에 인가한다.Trans chamber voltage application step (s30) is applied to the trans chamber of the nano-pore sensor 10 by the voltage application unit (20).

trans 챔버 이동단계(s40)는 전기영동법에 의해 DNA 분자들이 trans 챔버로 이동하면서 나노기공을 통과한다.In the trans chamber moving step (s40), DNA molecules move to the trans chamber by electrophoresis and pass through the nanopores.

자기장 형성단계(s50)는 코일(30)을 동작시켜 나노기공센서(10) 내에 자기장을 형성한다.Magnetic field forming step (s50) to operate the coil 30 to form a magnetic field in the nano-pore sensor 10.

cis 챔버 이동단계(s60)는 상기 단계에서 형성된 자기장에 의해 자기 비드가 cis 챔버쪽으로 이동하면서 나노기공을 통과한다.In the cis chamber moving step (s60), the magnetic beads move through the cis chamber by the magnetic field formed in the step and pass through the nanopores.

이때 자기장의 세기와 전기영동법의 전기장 세기를 조절하여 DNA 분자들이 나노기공에서 움직이는 속도와 시간을 제어한다. At this time, by controlling the strength of the magnetic field and the electric field strength of the electrophoresis method to control the speed and time the DNA molecules move in the nano-pores.

본 발명은 현재 나노기공 상용화의 가장 큰 걸림돌인 DNA 통과속도의 제어를 가능하게 하며, 차세대 염기서열 분석 장치의 핵심 구성이 될 것으로 기대된다.The present invention enables the control of DNA passage rate, which is the biggest obstacle to the current nanopore commercialization, and is expected to be the core configuration of the next generation sequencing apparatus.

10 : 나노기공센서 20 : 전압인가부
30 : 코일 40 : 제어부10: nano pore sensor 20: voltage applied part
30 coil 40 control part

Claims (4)

자기비드가 연결된 DNA가 통과하는 나노기공을 포함하여 DNA 통과시 이온전류의 변화를 발생하는 나노기공센서;
상기 나노기공센서에 일정 전압을 클램핑하는 전압인가부;
상기 나노기공센서의 나노기공의 방향과 축 방향이 일치하도록 상기 나노기공센서 외부 양측에 상호 연결되게 설치됨으로써 마그네틱 피드백 루프를 형성하는 한 쌍의 코일; 및
상기 나노기공센서, 전압인가부 및 코일에 연결되어, 상기 전압인가부 및 상기 코일의 구동 또는 전압을 제어하며, 상기 나노기공을 통과하는 DNA에 의해 발생하는 신호를 수집 분석하는 제어부; 를 포함하여,
상기 제어부에 의해 상기 전압인가부의 전압이 증가하여 DNA 통과속도가 상승할 때 상기 코일이 구동되어 상기 나노기공센서 내에 자기장을 형성함으로써 상기 DNA 통과속도가 감소하도록 제어되는 것을 특징으로 하는, 나노기공센서를 사용한 DNA 동작제어 시스템.Nano-pore sensor for generating a change in the ion current when passing through the DNA, including nano-pores through which the magnetic beads are connected;
A voltage applying unit for clamping a predetermined voltage to the nanoporous sensor;
A pair of coils which are installed to be connected to both sides of the nanoporous sensor outside so as to coincide with the direction of the nanopores of the nanoporous sensor to form a magnetic feedback loop; And
A control unit connected to the nanopore sensor, a voltage applying unit and a coil to control driving or voltage of the voltage applying unit and the coil, and collecting and analyzing a signal generated by DNA passing through the nanopores; Including,
The nano-pore sensor is controlled to reduce the DNA passage speed by driving the coil to form a magnetic field in the nano-pore sensor when the voltage of the voltage applying unit is increased by the controller to increase the DNA passage speed. DNA motion control system using. 제1항에 있어서,
상기 코일은 헬름홀츠코일인 것을 특징으로 하는 시스템.The method of claim 1,
The coil is a Helmholtz coil. 제1항에 있어서,
상기 전압인가부는 퍼텐쇼스탯인 것을 특징으로 하는 시스템.The method of claim 1,
The voltage application unit is characterized in that the potentiometer. 마그네틱 성분이 있는 나노비드를 시퀀싱 타겟인 DNA 분자와 연결하는 자기 비드 연결단계;
자기 비드가 연결된 DNA 시료를 나노기공센서의 cis 챔버에 넣는 DNA분자 cis 챔버 투입단계;
전압인가부에 의해 나노기공센서의 trans 챔버에 인가하는 trans 챔버 전압인가단계;
전기영동법에 의해 DNA 분자들이 trans 챔버로 이동하면서 나노기공을 통과하는 trans 챔버 이동단계;
코일을 동작시켜 나노기공센서 내에 자기장을 형성하는 자기장 형성단계; 및
상기 단계에서 형성된 자기장에 의해 자기 비드가 cis 챔버쪽으로 이동하면서 나노기공을 통과하는 cis 챔버 이동단계;를 포함하여,
코일 자기장의 세기와 전기영동법의 전기장 세기를 조절함으로써 DNA 분자들이 나노기공에서 움직이는 속도와 시간을 제어하는 것을 특징으로 하는, 나노기공센서를 사용한 DNA 동작제어 방법.



Magnetic bead linking step of connecting the nanobead with the magnetic component to the DNA molecule as the sequencing target;
A DNA molecule cis chamber input step of putting a DNA sample connected with magnetic beads into the cis chamber of the nanoporous sensor;
A trans chamber voltage applying step of applying the trans chamber to the nanoporous sensor by the voltage applying unit;
Trans chamber transfer step of passing through the nano-pores while moving the DNA molecules to the trans chamber by the electrophoresis method;
A magnetic field forming step of operating a coil to form a magnetic field in the nanoporous sensor; And
And moving the cis chamber through the nanopores while moving the magnetic beads toward the cis chamber by the magnetic field formed in the step.
A method for controlling DNA motion using a nanoporous sensor, characterized in that the speed and time of DNA molecules moving in the nanopores are controlled by controlling the strength of the coil magnetic field and the electric field of electrophoresis.



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