WO2019068034A2 - NANOPORA DEVICE AND METHOD FOR MANUFACTURING THE SAME - Google Patents

NANOPORA DEVICE AND METHOD FOR MANUFACTURING THE SAME Download PDF

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Publication number
WO2019068034A2
WO2019068034A2 PCT/US2018/053624 US2018053624W WO2019068034A2 WO 2019068034 A2 WO2019068034 A2 WO 2019068034A2 US 2018053624 W US2018053624 W US 2018053624W WO 2019068034 A2 WO2019068034 A2 WO 2019068034A2
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WO
WIPO (PCT)
Prior art keywords
nanopore
layer
electrode
dielectric
electrodes
Prior art date
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Ceased
Application number
PCT/US2018/053624
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English (en)
French (fr)
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WO2019068034A3 (en
Inventor
Kyung Joon Han
Jungkee YOON
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Biothlon Inc
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Biothlon Inc
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Filing date
Publication date
Application filed by Biothlon Inc filed Critical Biothlon Inc
Priority to EP18792689.4A priority Critical patent/EP3688464A2/en
Priority to KR1020207012259A priority patent/KR102433301B1/ko
Priority to JP2020518642A priority patent/JP7254366B2/ja
Priority to CN202211439098.1A priority patent/CN116042789B/zh
Priority to CN201880063003.6A priority patent/CN111194408B/zh
Publication of WO2019068034A2 publication Critical patent/WO2019068034A2/en
Publication of WO2019068034A3 publication Critical patent/WO2019068034A3/en
Anticipated expiration legal-status Critical
Priority to JP2023044919A priority patent/JP7823898B2/ja
Ceased legal-status Critical Current

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Classifications

    • 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
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D57/00—Separation, other than separation of solids, not fully covered by a single other group or subclass, e.g. B03C
    • B01D57/02—Separation, other than separation of solids, not fully covered by a single other group or subclass, e.g. B03C by electrophoresis
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D67/00—Processes specially adapted for manufacturing semi-permeable membranes for separation processes or apparatus
    • B01D67/0002—Organic membrane manufacture
    • B01D67/0023—Organic membrane manufacture by inducing porosity into non porous precursor membranes
    • B01D67/0032—Organic membrane manufacture by inducing porosity into non porous precursor membranes by elimination of segments of the precursor, e.g. nucleation-track membranes, lithography or laser methods
    • B01D67/0034—Organic membrane manufacture by inducing porosity into non porous precursor membranes by elimination of segments of the precursor, e.g. nucleation-track membranes, lithography or laser methods by micromachining techniques, e.g. using masking and etching steps, photolithography
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D67/00—Processes specially adapted for manufacturing semi-permeable membranes for separation processes or apparatus
    • B01D67/0039—Inorganic membrane manufacture
    • B01D67/0053—Inorganic membrane manufacture by inducing porosity into non porous precursor membranes
    • B01D67/006—Inorganic membrane manufacture by inducing porosity into non porous precursor membranes by elimination of segments of the precursor, e.g. nucleation-track membranes, lithography or laser methods
    • B01D67/0062—Inorganic membrane manufacture by inducing porosity into non porous precursor membranes by elimination of segments of the precursor, e.g. nucleation-track membranes, lithography or laser methods by micromachining techniques, e.g. using masking and etching steps, photolithography
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D67/00—Processes specially adapted for manufacturing semi-permeable membranes for separation processes or apparatus
    • B01D67/0079—Manufacture of membranes comprising organic and inorganic components
    • B01D67/00791—Different components in separate layers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D69/00—Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor
    • B01D69/12—Composite membranes; Ultra-thin membranes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D71/00—Semi-permeable membranes for separation processes or apparatus characterised by the material; Manufacturing processes specially adapted therefor
    • B01D71/02—Inorganic material
    • B01D71/0215—Silicon carbide; Silicon nitride; Silicon oxycarbide
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D71/00—Semi-permeable membranes for separation processes or apparatus characterised by the material; Manufacturing processes specially adapted therefor
    • B01D71/02—Inorganic material
    • B01D71/022—Metals
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D71/00—Semi-permeable membranes for separation processes or apparatus characterised by the material; Manufacturing processes specially adapted therefor
    • B01D71/06—Organic material
    • B01D71/70—Polymers having silicon in the main chain, with or without sulfur, nitrogen, oxygen or carbon only
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D71/00—Semi-permeable membranes for separation processes or apparatus characterised by the material; Manufacturing processes specially adapted therefor
    • B01D71/06—Organic material
    • B01D71/70—Polymers having silicon in the main chain, with or without sulfur, nitrogen, oxygen or carbon only
    • B01D71/701—Polydimethylsiloxane
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82B—NANOSTRUCTURES FORMED BY MANIPULATION OF INDIVIDUAL ATOMS, MOLECULES, OR LIMITED COLLECTIONS OF ATOMS OR MOLECULES AS DISCRETE UNITS; MANUFACTURE OR TREATMENT THEREOF
    • B82B1/00—Nanostructures formed by manipulation of individual atoms or molecules, or limited collections of atoms or molecules as discrete units
    • B82B1/001—Devices without movable or flexible elements
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82B—NANOSTRUCTURES FORMED BY MANIPULATION OF INDIVIDUAL ATOMS, MOLECULES, OR LIMITED COLLECTIONS OF ATOMS OR MOLECULES AS DISCRETE UNITS; MANUFACTURE OR TREATMENT THEREOF
    • B82B3/00—Manufacture or treatment of nanostructures by manipulation of individual atoms or molecules, or limited collections of atoms or molecules as discrete units
    • B82B3/0009—Forming specific nanostructures
    • B82B3/0014—Array or network of similar nanostructural elements
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82B—NANOSTRUCTURES FORMED BY MANIPULATION OF INDIVIDUAL ATOMS, MOLECULES, OR LIMITED COLLECTIONS OF ATOMS OR MOLECULES AS DISCRETE UNITS; MANUFACTURE OR TREATMENT THEREOF
    • B82B3/00—Manufacture or treatment of nanostructures by manipulation of individual atoms or molecules, or limited collections of atoms or molecules as discrete units
    • B82B3/0009—Forming specific nanostructures
    • B82B3/0019—Forming specific nanostructures without movable or flexible elements
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y40/00—Manufacture or treatment of nanostructures
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • 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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D2313/00—Details relating to membrane modules or apparatus
    • B01D2313/34—Energy carriers
    • B01D2313/345—Electrodes
    • 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
    • C12Q2565/00—Nucleic acid analysis characterised by mode or means of detection
    • C12Q2565/60—Detection means characterised by use of a special device
    • C12Q2565/607—Detection means characterised by use of a special device being a sensor, e.g. electrode
    • 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
    • C12Q2565/00—Nucleic acid analysis characterised by mode or means of detection
    • C12Q2565/60—Detection means characterised by use of a special device
    • C12Q2565/631—Detection means characterised by use of a special device being a biochannel or pore

Definitions

  • a nanopore is a small hole (e.g., with a diameter of about 1 nm to about 1000 nm) that can detect the flow of electrons through the hole by the change in the ionic current and/or tunneling current.
  • a nucleic acid e.g., adenine, cytosine, guanine, thymine in DNA, uracil in RNA
  • measuring changes in the current flowing through a nanopore during translocation results in data that can be used to directly sequence a nucleic acid molecule passing through the nanopore.
  • Nanopore technology is based on electrical sensing, which is capable of detecting nucleic acid molecules in concentrations and volumes much smaller than that required for other conventional sequencing methods.
  • Advantages of nanopore based nucleic acid sequencing include long read length, plug and play capability, and scalability.
  • current biological nanopore based nucleic acid sequencing techniques can require a fixed nanopore opening (e.g., with a diameter of about 2 nm), have poor sensitivity (i.e., unacceptable amount of false negatives), high cost that renders production worthy manufacturing a challenge, and strong temperature and concentration (e.g., pH) dependency.
  • the method also includes depositing a second metal or polysilicon layer on the first metal or polysilicon electrode layer.
  • the method further includes depositing a second Si 3 N 4 layer on a second dielectric layer.
  • the method also includes etching and patterning the second metal or polysilicon electrode layer.
  • the method further includes depositing and patterning the multiple layers of metal or polysilicon electrode layers.
  • a method of detecting a charged particle uses a 3D nanopore device having top, middle and bottom chambers, and a 3D nanopore array disposed in the middle chambers such that the top and bottom chambers are fluidly coupled by a plurality of nanopores in the 3D nanopore array.
  • the method includes adding electrolyte solution including the charged particle to the top, middle, and bottom chambers.
  • the method also includes placing top and bottom electrodes in the top and bottom chambers respectively.
  • the method further includes applying an electrophoretic bias between the top and bottom electrodes.
  • the method also includes applying a rate-control bias in the rate- control electrode.
  • the method further includes applying a sensing bias in the sensing electrode.
  • the method includes detecting a change in an electrode current in the electrolyte.
  • the method includes detecting a change in a tunneling current in the electrodes.
  • the rate-control electrode has a thickness ranges from about 2 nm to about 1000 nm.
  • the rate-control electrode may include Ta, Cr, Al, Au-Cr, Graphene, or Al-Cu. It may include heavily doped (n- or p-type) polysilicon or salicided polysilicon .
  • the 3D nanopore channel pillar array may include a biological layer having the rate- control electrode, such that the 3D nanopore channel pillar array is a hybrid.
  • the top and bottom chambers may contain at least some of the electrolyte solution.
  • the electrolyte solution may include KCI and LiCI 2 .
  • the electrodes for top and bottom chamber may include Ag/AgCI 2 .
  • the 3D nanopore channel pillar array is manufactured using ALD and/or CVD deposition of dielectric layers, High aspect ratio Reactive Ion Etch deep trench process (nanopore channel opening etch), ALD and/or CVD deposition of trimming dielectric layers, and/or ALD and/or CVD deposition of membrane dielectric layers.
  • the dielectric-electrode stack also includes a bottom dielectric layer.
  • the bottom dielectric layer may have a thickness of about 100 nm to 1000 nm.
  • the bottom dielectric layer may include Si0 2 , glass, or SOI to reduce substrate coupled low level noise.
  • the dielectric-electrode stack may also include a top dielectric layer.
  • the top dielectric layer may have a thickness of about 5 nm to about 50 nm.
  • the top dielectric layer may include Si0 2 , Si 3 N 4 , or Al 2 0 3 .
  • the top dielectric layer may determine a final nanopore channel opening width.
  • Figure 3 schematically illustrates a 3D nanopore device according to one embodiment including some details of its operation.
  • Figure 4 is a table summarizing the voltage operation of the nanopore device depicted in Figure 3.
  • Figure 5 schematically illustrates a 3D nanopore device according to one embodiment including some of the electrodes therein.
  • Figures 6A-6E illustrate a method for manufacturing a 3D nanopore device according to one embodiment.
  • Figures 7A-7E illustrate a method for manufacturing a 3D nanopore device according to another embodiment.
  • FIG. 2A-2D schematically depict various views of a nanopore device 200 incorporating solid-state nanopore technology with a three dimensional (“3D") array architecture according to one embodiment.
  • the device 200 includes a plurality of 2D arrays or layers 202A-202E stacked along a Z axis 204. While the 2D arrays 202A-202E are referred to as "two dimensional," each of the 2D arrays 202A-202E has some thickness along the Z axis.
  • Figure 2B depicts a top view of the top 2D array 202A depicted in Figure 2A.
  • Figures 2C and 2D schematically depict front and right side views of the nanopore device 200 depicted in Figure 2A.
  • Electrophoretic charged particle translocation can be driven by applying a bias to electrodes disposed in a top chamber (not shown) adjacent the top 2D array 202A of the nanopore device 200 and a bottom chamber (not shown) adjacent the bottom 2D array 202E of the nanopore device 200.
  • the nanopore device 200 is disposed in a middle chamber (not shown) such that the top and bottom chambers are fluidly and electrically coupled by the nanopore pillars 210 in the nanopore device 200.
  • the top, middle, and bottom chambers may contain the electrolyte solution.
  • Figure 3 schematically depicts a nanopore device 300 according to another embodiment.
  • Figure 3 depicts the top 2D array 302 in a cross- sectional (x-z plane) view showing the 3D nanopore 310 and nano-electrode schemes.
  • Each nanopore 310 is surrounded by nano-electrodes 312, allowing the nanopore 310 channel to operate under an electric bias field condition generated using the nano-electrodes 312.
  • Cross-patterned nanogap nano-electrodes 312CS-312Cn, 312RS-312Rn are disposed in two layers on top of the nanopore device 300.
  • nano-electrodes 312CS- 312Cn, 312RS-312Rn are column and row inhibitory nano-electrodes 312CS- 312Cn, 312RS-312Rn for the nanopore array, respectively.
  • the cross- patterned nano-electrodes 312CS-312Cn, 312RS-312Rn as shown in the top 2D array 302 (x-y plane view) may be formed/patterned at the metal lithography steps.
  • Nano-electrodes 312 in the remaining 2D arrays in the 3D stack may be formed by plane depositing metals.
  • Nano-electrode 312 mediated ionic translocation suppression can be substantially complete or the electrical bias can be modulated to only reduce the rate of ionic translocation.
  • the electrical biases in a stack of 3D nanopore nano-electrodes 312 can be modulated to control the biomolecular translocation speed.
  • 3D nanopore devices allow either direct or targeted sequencing in an array while minimizing form-factor overhead, because the 2D arrays 202, 302 in the nanopore devices 200, 300 can be stacked vertically instead of positioned horizontally, thereby allowing for high density applications.
  • 3D nanopore devices e.g. , 200, 300
  • 3D nanopore devices are scalable, with medium to large 3D nanopore devices having more than 1 ,000 nanopore 210, 310 pillars. Consequently, a larger number of sequencing sensors can be accommodated within the same form-factor.
  • 3D nanopore devices e.g. , 200, 300

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  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
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  • Physics & Mathematics (AREA)
  • Nanotechnology (AREA)
  • Inorganic Chemistry (AREA)
  • Manufacturing & Machinery (AREA)
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  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
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  • Biomedical Technology (AREA)
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  • General Health & Medical Sciences (AREA)
  • Biophysics (AREA)
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  • Optics & Photonics (AREA)
  • General Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
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  • General Physics & Mathematics (AREA)
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  • Urology & Nephrology (AREA)
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PCT/US2018/053624 2017-09-29 2018-09-28 NANOPORA DEVICE AND METHOD FOR MANUFACTURING THE SAME Ceased WO2019068034A2 (en)

Priority Applications (6)

Application Number Priority Date Filing Date Title
EP18792689.4A EP3688464A2 (en) 2017-09-29 2018-09-28 Nanopore device and method of manufacturing same
KR1020207012259A KR102433301B1 (ko) 2017-09-29 2018-09-28 나노포어 디바이스 및 이를 제조하는 방법
JP2020518642A JP7254366B2 (ja) 2017-09-29 2018-09-28 ナノポア装置およびその製造方法
CN202211439098.1A CN116042789B (zh) 2017-09-29 2018-09-28 纳米孔设备及其制造方法
CN201880063003.6A CN111194408B (zh) 2017-09-29 2018-09-28 纳米孔设备及其制造方法
JP2023044919A JP7823898B2 (ja) 2017-09-29 2023-03-22 ３ｄナノポアデバイス

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201762566313P 2017-09-29 2017-09-29
US62/566,313 2017-09-29
US201762593840P 2017-12-01 2017-12-01
US62/593,840 2017-12-01

Publications (2)

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WO2019068034A2 true WO2019068034A2 (en) 2019-04-04
WO2019068034A3 WO2019068034A3 (en) 2019-06-27

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US (3) US11041844B2 (https=)
EP (1) EP3688464A2 (https=)
JP (2) JP7254366B2 (https=)
KR (1) KR102433301B1 (https=)
CN (2) CN111194408B (https=)
WO (1) WO2019068034A2 (https=)

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US11067561B2 (en) 2017-12-31 2021-07-20 Palogen, Inc. Nanopore device and methods of electrical array addressing and sensing
JP2023513126A (ja) * 2020-02-06 2023-03-30 パロゲン，インコーポレイテッド ナノポアセンサデバイスおよびその製造方法

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US11686701B2 (en) 2019-07-16 2023-06-27 Palogen, Inc. Nanopore device and methods of detecting and classifying charged particles using same
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JP2022015499A (ja) 2020-07-09 2022-01-21 キオクシア株式会社 記憶装置
WO2022020206A1 (en) * 2020-07-24 2022-01-27 Palogen, Inc. Nanochannel systems and methods for detecting pathogens using same
CN112251343A (zh) * 2020-11-11 2021-01-22 深圳市儒翰基因科技有限公司 一种dna测序装置、固态纳米孔组件及其制备方法
JP2022129253A (ja) 2021-02-24 2022-09-05 キオクシア株式会社 記憶装置
KR102416152B1 (ko) 2021-03-12 2022-07-06 고려대학교 산학협력단 나노 층상 구조막이 결합된 나노포어 소자
KR102547706B1 (ko) 2021-03-16 2023-06-29 주식회사 멤스팩 신속 바이오 진단키트
CN115141749A (zh) * 2021-03-29 2022-10-04 上海近观科技有限责任公司 基于电致发光材料的纳米孔阵列结构及其制备方法
CN115125132B (zh) * 2021-03-29 2026-03-31 上海近观科技有限责任公司 基于固态纳米孔阵列的测序芯片及其制备方法
CN113552332B (zh) 2021-09-22 2022-04-22 成都齐碳科技有限公司 用于感测包含在液体中的分析物的装置和设备
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