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WO2015025993A1 - Système et procédé d'analyse de séquence moléculaire en temps réel utilisant un nanoruban empilé - Google Patents

Système et procédé d'analyse de séquence moléculaire en temps réel utilisant un nanoruban empilé Download PDF

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Publication number
WO2015025993A1
WO2015025993A1 PCT/KR2013/007477 KR2013007477W WO2015025993A1 WO 2015025993 A1 WO2015025993 A1 WO 2015025993A1 KR 2013007477 W KR2013007477 W KR 2013007477W WO 2015025993 A1 WO2015025993 A1 WO 2015025993A1
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Prior art keywords
nanoribbons
nanoribbon
real
sequence analysis
nanopores
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English (en)
Korean (ko)
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최중범
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Nanochips Inc
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Nanochips Inc
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Priority to PCT/KR2013/007477 priority Critical patent/WO2015025993A1/fr
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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6869—Methods for sequencing
    • 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
    • G01N33/483—Physical analysis of biological material
    • G01N33/487—Physical analysis of biological material of liquid biological material
    • G01N33/48707—Physical analysis of biological material of liquid biological material by electrical means
    • G01N33/48721—Investigating individual macromolecules, e.g. by translocation through nanopores
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y15/00—Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors

Definitions

  • the present invention relates to a real-time molecular sequence analysis system using stacked nanoribbons, and more particularly, at least four nanoribbons are stacked on a substrate with an insulating layer interposed therebetween, the substrate, the insulating layer and the nano
  • a nanopore is formed penetrating the center of the ribbon in a vertical direction, and the nanoribbons are formed by the interaction between the unit molecules and the nanoribbons constituting the biopolymer while the biopolymer passes through the nanopore.
  • a molecular sequence analysis system that detects the change of the unit spherical component in real-time by sensing the current flowing through the measured and measured change through a measurement electrode formed at each end of the longitudinal length of the nanoribbon, and It's about how.
  • Decoding the unit molecule sequence (amino acid molecule sequence of the protein, DNA base molecule sequence) constituting the biological polymer means decoding the biometric information, the molecular genetic understanding can make early diagnosis of human disease It is very important in that it is.
  • DNA is composed of nucleotide units, and each nucleotide has the same one deoxyribose and phosphate group and has four different bases: adenine (A), guanine (G), and cytosine (C). ), Thymine (T) is present, and A and G are Purine series having two cyclic structures, and C and T are Pyrimidine series having one cyclic structure.
  • mRNA messenger RNA
  • proteins are synthesized through the binding of amino-acids in ribosomes. If there is a mutated nucleotide sequence different from the original nucleotide sequence, protein synthesis may not be possible or abnormal proteins may be synthesized and expressed, resulting in physiological problems. For this reason, the meaning of deciphering the information possessed by DNA is very important from a pathological point of view for the early diagnosis and treatment of diseases.
  • the present invention has been made to solve the conventional problems as described above, according to an embodiment of the present invention, to solve the problems of the conventional unit molecular sequence analysis system using nanotechnology, molecular sequence analysis It reduces excessive time and harmful chemicals that are invested in preliminary work, and enables real-time unit molecular analysis at high speed using semi-permanent solid elements, unlike conventional methods, which provides a cheaper molecular sequence analysis system.
  • the movement means having a piezoelectric element inherent electricity of different unit molecules constituting the biopolymer while controlling the movement speed of the biopolymer (biological polymer) passing through the nanopore
  • the movement means having a piezoelectric element inherent electricity of different unit molecules constituting the biopolymer while controlling the movement speed of the biopolymer (biological polymer) passing through the nanopore
  • An object of the present invention is a nanoribbon having a specific width in which a current change is induced by interaction with the nearest unit molecules of the biomolecules; Measuring electrodes formed at each of both ends of the longitudinal direction of the nanoribbon to measure a change in current; An insulating layer formed on the upper and lower surfaces of the nanoribbons to electrically insulate the nanoribbons from each other; And nanopores that penetrate the insulating layer and the nanoribbons in the vertical direction and allow unit molecules forming the biopolymer to pass through.
  • the real-time molecular sequence analysis system using the stacked nanoribbons may include the nanopores.
  • the apparatus may further include a substrate for supporting the nanoribbons, the measuring electrode, and the insulating layer, and the nanopores may be formed by penetrating the substrate, the insulating layer, and each of the nanoribbons in a vertical direction.
  • Four or more nanoribbons may be configured to be stacked on a substrate with an insulating layer interposed therebetween.
  • Each nanoribbon may have a unit molecule coating part coated with different unit molecules at a position where the nanopores are formed to induce complementary bonding between the unit molecule and the coating part passing through the nanopores.
  • Nanoribbons include zig-zag graphene or two-dimensional topological insulators, so the inside of the nanoribbon is characterized by being electrically insulating and having edges that are conductive. Can be.
  • the measuring electrode may be made of a conductor including at least one of gold, silver, copper, platinum, palladium, titanium, nickel, and cobalt, and may be electrically connected to the nanoribbon.
  • the insulating layer consists of an electrical insulator comprising at least one of a silicon oxide film, a silicon nitride film, an aluminum oxide film, a silver oxide film, a zinc oxide film, and a hafnium oxide film, and insulates the nanoribbons from the electrolyte and other nanoribbons. It can be characterized.
  • a hydrogen atom or a nitrogen atom may be bonded to a carbon atom having a dangling bond.
  • the thickness of the nanoribbons may be characterized in that less than 5 kPa.
  • the width of the nanoribbons may be characterized in that less than 10nm.
  • the diameter of the nanopores may be characterized in that less than 10nm.
  • the method may further include a voltage applying unit for applying a voltage to the measurement electrode.
  • the method may further include analyzing means for acquiring the current change data based on the current measured by the measuring electrode, and determining the sequence of the unit molecules of the biopolymer based on the current change data.
  • an object of the present invention is to apply a voltage to a measurement electrode connected to both ends of a length of each nanoribbon such that a current flows through the nanoribbon; Applying a voltage difference or a fluid pressure difference between one side and the other side of the substrate to allow the biopolymer to pass through the nanopores; Changing the current flowing through the nanoribbons by interacting with the nanoribbons of the unit molecules forming the biopolymer; Detecting a change in current flowing through the nanoribbon; And determining the sequence of unit molecules by combining and analyzing the current change flowing through each nanoribbon. This may be achieved as a real-time molecular sequence analysis method using stacked nanoribbons.
  • the current flowing through the nanoribbon may be characterized as including an edge current.
  • the nanoribbons are stacked on the substrate with four or more insulating layers interposed therebetween, and each nanoribbon is provided with unit molecular coatings coated with different unit molecules at positions where nanopores are formed.
  • Complementary bonding of the unit molecule and the coating portion passing through the nanopores may be characterized in that the current flowing through the nanoribbons is changed.
  • the detecting and determining may be based on a change in current flowing through the nanoribbons detected by the measuring electrode, and the analysis means may identify the sequence of unit molecules by combining and analyzing the change in current flowing through the nanoribbons. Can be.
  • nanoribbons are stacked on a substrate with an insulating layer interposed therebetween, and each unit molecule of a biopolymer that moves nanopores vertically penetrating the center of the substrate, the insulating layer, and the nanoribbons
  • each unit molecule of a biopolymer that moves nanopores vertically penetrating the center of the substrate, the insulating layer, and the nanoribbons
  • T, C can be maximized the detection efficiency and reliability by maximizing the current change of the nanoribbon through complementary bonding with base molecules moving into the nanopore, and through a single ss-DNA movement 4 All nucleotide sequences consisting of two base molecules can be analyzed.
  • ss-DNA which is an example of a biopolymer
  • the probe to pass through the nanochannel by driving the moving unit and the tension, compression of the piezoelectric element.
  • FIG. 1 is a perspective view of a real-time molecular sequence analysis system using stacked nanoribbons applied to DNA base molecule sequence decoding according to an embodiment of the present invention
  • FIG. 2 is a cross-sectional view taken along line A-A of FIG.
  • FIG. 3 is a partial cross-sectional view of a real-time molecular sequence analysis system using a laminated nanoribbon having a piezoelectric element according to an embodiment of the present invention
  • FIG. 4 is a flowchart of a method for real-time molecular sequence analysis using stacked nanoribbons according to an embodiment of the present invention
  • FIG. 5 is a graph showing current change data measured using nanoribbons coated with four different bases applicable according to one embodiment of the present invention
  • FIG. 6 is a flowchart illustrating a real-time molecular sequence analysis method using stacked nanoribbons having piezoelectric elements according to an embodiment of the present invention.
  • nanoribbon 200A A-coated nanoribbon
  • the real-time molecular sequence analysis system using the stacked nanoribbons according to the present invention decodes the unit molecule sequence (for example, amino acid molecules of proteins, or base molecule sequences of DNA, etc.) constituting various biopolymers such as proteins or DNA. It can be used to As a specific example, specific contents applied to DNA nucleotide sequence analysis will be described below.
  • FIG. 1 illustrates a perspective view of a real-time molecular sequence analysis system using stacked nanoribbons applied to DNA base molecule sequence decoding according to an embodiment of the present invention
  • FIG. 2 is a cross-sectional view of FIG.
  • the real-time molecular sequence analysis system using a stacked nanoribbon is largely nanopore 100, nanoribbon (200: 200A, 200G, 200T, 200C) ,
  • the measurement electrode 300, the insulating layer 400, the substrate 500, and the like, may be included.
  • a predetermined voltage is applied to the measurement electrode 300 to flow a predetermined current through the nanoribbons 200, and the other side of the substrate 500 Single-stranded DNA (hereinafter referred to as ss-DNA) by a voltage difference or a fluid pressure difference applied between (between the upper side and the lower side of the substrate 500 as shown in FIGS. 1 and 2), 10 passes through the nanopores (100).
  • the sequence of nucleotides constituting the ss-DNA 10 may be analyzed by analyzing a change in edge current flowing through the edge of the ribbon 200.
  • each of the nanoribbon 200 at the position where the nanopore 100 is formed is coated with any one of the different bases A, G, T, C through the nanopore 100
  • the complementary bond AT or GC nucleotides ss-DNA (10) to maximize the current change flowing through the edge of the nanoribbons (200).
  • the nanopores 100 are formed to vertically penetrate through the centers of the substrate 500, the plurality of insulating layers 400, and the plurality of nanoribbons 200.
  • ss-DNA (10) has a diameter that can pass without twisting or overlapping, usually in the range of 2nm or less.
  • the ss-DNA 10 passes the nanopores 100 by a voltage difference or a fluid pressure difference applied between one side and the other side of the substrate 500.
  • ss-DNA (10) is used to induce a change in the charge distribution of the nanoribbons 200 from the electric dipoles of different nucleotides by exposing the base to the outside, DNA is a double helix structure for one strand Since the other strand has a complementary sequence, it is possible to grasp the entire DNA structure by analyzing the nucleotide sequence with one ss-DNA (10).
  • the nanoribbons 200 are used to detect the actual nucleotides. Since the distance between the different bases forming the ss-DNA 10 is 5 m or less, the thickness of the nanoribbons 200 should also be 5 m or less. When analyzing nucleotides it is possible not to be greatly interfered with other adjacent nucleotides.
  • nanoribbons 200 in order to induce a change in the effective current of the nanoribbons 200 from the base electric dipole should have a width of less than 10nm.
  • zig-zag graphene or two-dimensional topological insulators satisfying the above conditions may serve as the nanoribbons 200.
  • 200A is coated with deoxyribonucleotide (dATP) having adenine or adenine as a base on the nanopore 100
  • 200G is similarly deoxyribonucleotide having a guanine or guanine as a base.
  • dGTP is coated with thymine or deoxyribonucleotide (dTTP) with thymine as base
  • dCTP deoxyribonucleotide
  • the nanoribbons through the complementary bond (AT or CG) of the base constituting the ss-DNA 10 and the base coated on the nanoribbons 200.
  • the change of the charge distribution is maximized, and thus the change of the edge current of the nanoribbon is maximized.
  • the measuring electrode 300 may be composed of a conductor including gold, silver, copper, platinum, palladium, titanium, nickel, cobalt, the longitudinal direction of the nanoribbon 200 It is electrically connected to both ends, and the voltage is applied by the voltage applying unit.
  • the stacked nanoribbons 200 are formed on the upper and lower surfaces of the nanoribbons 200 for the analysis of each nucleotide, and an insulating layer 400, which is an electrical non-conductor, is formed in a length direction with one nanoribbon 200.
  • the measuring electrodes 300 formed at both ends are electrically insulated from an external electrolyte or other nanoribbons 200.
  • the substrate 500 is mechanically supported by the nanoribbons 200 on which the insulating layer 400 and the measurement electrode 300 are formed.
  • the real-time molecular sequence analysis system using a laminated nanoribbon includes an electrode element 5, a probe 70, a piezoelectric element 60, a moving unit 50, a control means, The movement speed of the ss-DNA 10 passing through the nanopores can be controlled.
  • Figure 3 shows a cross-sectional view of a real-time molecular sequence analysis system using a stacked nanoribbons having a piezoelectric element according to an embodiment of the present invention.
  • the substrate 500 serves as a separation wall separating both ends of the measuring tank 4 in which the electrolyte for maintaining the ss-DNA 10 is maintained therein.
  • the electrode elements 5 are installed at both sides of the substrate at specific intervals to form a potential difference at both ends of the substrate 500 so that the ss-DNA 10 can be supplied to move the nanopores 100. do. That is, the electrode elements 5 are provided in pairs and installed at the upper end and the lower end of the measuring bath 4, respectively. Then, the voltage is supplied to the electrode element 5 so that the lower end has a + pole and the upper end has a-pole, thereby forming a potential difference between the upper end and the lower end of the substrate 500. Therefore, since the ss-DNA 10 is basically -charged, the ss-DNA 10 can be moved from the upper end to the lower end through the nanopores 100 by this potential difference.
  • the real-time molecular sequence analysis system using the stacked nanoribbons having the piezoelectric element 60 further includes a moving means.
  • the moving means includes a head 40 installed on one side of the measuring tank 4 and a moving part 50 moving in the x, y, and z axis directions with respect to the head, and a piezoelectric element 60 that is tensioned or compressed by an applied voltage. And, it may be provided as a control means (not shown) for controlling the driving of the piezoelectric element 60 and the moving unit 50.
  • the moving unit 50 moves the piezoelectric element 60 and the probe 70 in the x-axis, the y-axis, and the z-axis in the vertical direction with respect to the head 40 at a level of 0.1 to several tens of micrometers.
  • the moving unit 50 may be composed of a piezo motor or the like.
  • the piezoelectric element 60 is tensioned or compressed in the z-axis, x-axis, and y-axis directions in the range of 0.1 to 10 ⁇ m by the applied voltage.
  • the ss-DNA 10 is nanopored by driving the piezoelectric element 60 and the moving unit 50 by bonding the end of the ss-DNA 10 to the end surface of the probe 70. It is possible to adjust the moving speed passing through (100).
  • FIG. 4 is a flowchart illustrating a real-time molecular sequence analysis method using stacked nanoribbons according to an embodiment of the present invention.
  • a voltage is applied to the measurement electrodes 300 provided at both ends of each nanoribbon 200 by a voltage applying unit so that a predetermined current flows through the nanoribbon 200 (S10). Then, a voltage difference or a fluid pressure difference is applied between one surface and the other surface of the substrate 500 to allow the biopolymer to pass through the nanopores 100 (S20).
  • the unit molecules forming the biopolymer interact with each nanoribbon 200 to change a current flowing through the nanoribbon 200.
  • most of the current flowing through the nanoribbons 200 corresponds to an edge current.
  • the change of the current flowing through the nanoribbons 200 is sensed by the measuring electrodes 300 provided at both ends of each of the nanoribbons 200 (S30).
  • the nanoribbons 200 are stacked on the substrate 500 with four or more insulating layers 400 interposed therebetween, and each of the nanoribbons 200 has different units at positions where the nanopores 100 are formed. Comprising a unit molecule coating unit coated with a molecule, the complementary bonding of the unit molecule and the base coating portion passing through the nanopores 100 can be induced to maximize the current change flowing through the nanoribbons 200.
  • the analysis means obtains the current change data by the unit molecules constituting the biopolymer passing through the nano-pores (100) (S40). In addition, the analyzing means may determine the sequence of the unit molecules by combining and analyzing the obtained current change data (S50).
  • the analysis means based on the current change flowing through the nanoribbons 200 sensed by the measuring electrode 300, the analysis means identifies the sequence of unit molecules by combining and analyzing the current change data flowing through the nanoribbons 200. Done.
  • FIG. 5 is a graph showing current change data measured in real-time using nanoribbons 200 coated with four different bases applicable according to an embodiment of the present invention. That is, FIG. 5 shows four independent nanoribbons 200 coated with ss-DNA 10 having the same base sequence CTGACTGA ... as in FIG. 2 passing through the nanopore 100 with each other base. Shows the measured data in real time that can be predicted by edge current modulation.
  • the graph shown at the top left in FIG. 5 is the current change data measured in the nanoribbons 200A coated with base A, and the graph shown at the top right is the current change measured in the nanoribbons 200G coated with base G.
  • Data, the graph shown at the bottom left is a base T coated nanoribbons 200T, and the graph shown at the bottom right is a base C coated nanoribbons 200C.
  • the analytical means can analyze the base sequence of the ss-DNA 10 that passed through the nanochannel by combining-analyzing these four data in real time, and if the analysis of the graph shown in FIG. It can be read that the sequence becomes CTGACTGA ... in real time as in FIG. 2.
  • the real-time molecular sequence analysis system using the stacked nanoribbons according to an embodiment of the present invention, the electrode element 5, the probe 70, the piezoelectric element 60, the moving part 50, Including the control means, it is possible to adjust the moving speed of the ss-DNA 10 passing through the nanopores.
  • FIG. 6 illustrates a flowchart of a real-time molecular sequence analysis method using stacked nanoribbons having piezoelectric elements.
  • control means drives the moving part 50 of the moving means to attach the end of the ss-DNA 10 to the end surface of the probe 70 while moving the moving part 50 in the x, y and z axis directions. It becomes (S100).
  • the control means drives the moving unit 50 to adjust the direction and position the end of the probe 70 close to the nano-pores (100) (S200).
  • the step of attaching the end of the ss-DNA (10) to the end surface of the probe 70 (S100) and the position of the ss-DNA (10) in close proximity to the nanopore 100 (S200) For easy identification, labeling DNA stained with fluorescent material at the end of the ss-DNA 10 to be analyzed can be conjugated (ligation) using a lyase.
  • the position of the ss-DNA 10 can be more easily identified, and the moving part 50 is moved to probe the upper end of the labeling DNA 70. ) It will be attached to the end surface.
  • a voltage is applied to the measurement electrodes 300 provided at both ends of each nanoribbon 200 by a voltage applying unit so that a predetermined current flows through the nanoribbon 200 (S300). Then, a voltage difference or a fluid pressure difference is applied between one surface and the other surface of the substrate 500 to allow the biopolymer to pass through the nanopores 100 (S400).
  • a voltage is applied to the electrode element 5.
  • the electrode element 5 located at the upper end of the measuring tank 4 has a positive pole, and the electrode element 5 located at the lower part has a negative pole. Therefore, a potential difference is formed between both ends of the substrate 500 such that the ss-DNA 10 attached to the end surface of the probe 70 passes through the nanopores 100 (S400).
  • the control means moves the ss-DNA 100 attached to the probe 70 in the longitudinal direction of the nanopores while controlling the piezoelectric element 60 and the moving unit 50 (S500).
  • the unit molecules constituting the biopolymer interact with each nanoribbon 200 to change a current flowing through the nanoribbon 200 (S600). At this time, most of the current flowing through the nanoribbons 200 corresponds to an edge current.
  • the current flowing through the nanoribbons 200 is sensed by the measuring electrodes 300 provided at both ends of the nanoribbons 200.
  • the nanoribbons 200 are stacked on the substrate 500 with four or more insulating layers 400 interposed therebetween, and each of the nanoribbons 200 has different units at positions where the nanopores 100 are formed. Comprising a unit molecule coating unit coated with a molecule, the complementary bonding of the unit molecule and the base coating portion passing through the nanopores 100 can be induced to maximize the current change flowing through the nanoribbons 200.
  • the analyzing means obtains the current change data by the unit molecules forming the biopolymers passing through the nanopores 100 (S700). In addition, the analyzing means may determine the sequence of the unit molecules by combining and analyzing the obtained current change data (S800).
  • the analysis means based on the current change flowing through the nanoribbons 200 sensed by the measuring electrode 300, the analysis means identifies the sequence of unit molecules by combining and analyzing the current change data flowing through the nanoribbons 200. Done.

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Abstract

La présente invention concerne un système pour analyser une séquence moléculaire qui permet l'analyse en temps réel d'une séquence moléculaire unitaire formant un biopolymère au moyen d'un nanoruban empilé, et est constitué de nanopores, d'un nanoruban, d'électrodes de mesure, d'une couche d'isolation, et d'un substrat. Les électrodes de mesure sont électriquement connectées au nanoruban aux deux extrémités dans une direction longitudinale du nanoruban, un courant amené à circuler dans le nanoruban au moyen d'une tension prédéterminée appliquée par l'intermédiaire des électrodes de mesure est modifié par les dipôles électriques inhérents respectivement différents de molécules unitaires de biopolymère qui traverse les nanopores formés au centre du nanoruban, et les degrés des changements sont détectés, de sorte que les séquences des molécules unitaires formant le biopolymère puissent être analysées en temps réel.
PCT/KR2013/007477 2013-08-21 2013-08-21 Système et procédé d'analyse de séquence moléculaire en temps réel utilisant un nanoruban empilé Ceased WO2015025993A1 (fr)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2221874A1 (fr) * 2009-02-24 2010-08-25 S.a.r.l. FIRMUS Procédé de fabrication de dispositifs nano électroniques fabriqués à partir de cristaux de carbone en 2D comme graphène et dispositifs obtenus avec ce procédé
KR101118461B1 (ko) * 2008-10-10 2012-03-06 나노칩스 (주) 초고속 고감도 dna 염기서열 분석 시스템
KR20120125159A (ko) * 2011-05-04 2012-11-14 충북대학교 산학협력단 나노채널을 이용한 실시간 분자서열 분석시스템 및 방법
WO2013016486A1 (fr) * 2011-07-27 2013-01-31 The Board Of Trustees Of The University Of Illinois Capteurs à nanopore pour la caractérisation biomoléculaire
US20130186758A1 (en) * 2011-12-09 2013-07-25 University Of Delaware Current-carrying nanowire having a nanopore for high-sensitivity detection and analysis of biomolecules

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101118461B1 (ko) * 2008-10-10 2012-03-06 나노칩스 (주) 초고속 고감도 dna 염기서열 분석 시스템
EP2221874A1 (fr) * 2009-02-24 2010-08-25 S.a.r.l. FIRMUS Procédé de fabrication de dispositifs nano électroniques fabriqués à partir de cristaux de carbone en 2D comme graphène et dispositifs obtenus avec ce procédé
KR20120125159A (ko) * 2011-05-04 2012-11-14 충북대학교 산학협력단 나노채널을 이용한 실시간 분자서열 분석시스템 및 방법
WO2013016486A1 (fr) * 2011-07-27 2013-01-31 The Board Of Trustees Of The University Of Illinois Capteurs à nanopore pour la caractérisation biomoléculaire
US20130186758A1 (en) * 2011-12-09 2013-07-25 University Of Delaware Current-carrying nanowire having a nanopore for high-sensitivity detection and analysis of biomolecules

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