WO2020158832A1 - 生体分子回収デバイス並びに方法、生体分子分析デバイス並びに方法 - Google Patents

生体分子回収デバイス並びに方法、生体分子分析デバイス並びに方法 Download PDF

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Publication number
WO2020158832A1
WO2020158832A1 PCT/JP2020/003284 JP2020003284W WO2020158832A1 WO 2020158832 A1 WO2020158832 A1 WO 2020158832A1 JP 2020003284 W JP2020003284 W JP 2020003284W WO 2020158832 A1 WO2020158832 A1 WO 2020158832A1
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Prior art keywords
biomolecule
nanowires
recovery device
fluid chamber
wall
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Ceased
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PCT/JP2020/003284
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English (en)
French (fr)
Japanese (ja)
Inventor
隆一 小野瀬
豪 赤津
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Craif Inc
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Icaria Inc
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Publication date
Application filed by Icaria Inc filed Critical Icaria Inc
Priority to US17/426,420 priority Critical patent/US20220143613A1/en
Priority to JP2020569703A priority patent/JPWO2020158832A1/ja
Priority to EP20748065.8A priority patent/EP3919917B1/en
Priority to CN202080011574.2A priority patent/CN113597559A/zh
Publication of WO2020158832A1 publication Critical patent/WO2020158832A1/ja
Anticipated expiration legal-status Critical
Priority to JP2024062470A priority patent/JP7788174B2/ja
Ceased legal-status Critical Current

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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
    • G01N1/405—Concentrating samples by adsorption or absorption
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502746—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means for controlling flow resistance, e.g. flow controllers, baffles or throttle valves
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502761—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads or physically stretching molecules
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/1003—Extracting or separating nucleic acids from biological samples, e.g. pure separation or isolation methods; Conditions, buffers or apparatuses therefor
    • 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
    • C12Q1/6806—Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
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    • B01L2200/02—Adapting objects or devices to another
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    • B01L2200/027—Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
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    • B01L2200/06—Fluid handling related problems
    • B01L2200/0647—Handling flowable solids, e.g. microscopic beads, cells, particles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0647—Handling flowable solids, e.g. microscopic beads, cells, particles
    • B01L2200/0668—Trapping microscopic beads
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/10—Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0609—Holders integrated in container to position an object
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0832—Geometry, shape and general structure cylindrical, tube shaped
    • B01L2300/0845—Filaments, strings, fibres, i.e. not hollow
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0848—Specific forms of parts of containers
    • B01L2300/0851—Bottom walls
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0848—Specific forms of parts of containers
    • B01L2300/0858—Side walls
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0877—Flow chambers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0896—Nanoscaled
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/08—Regulating or influencing the flow resistance
    • B01L2400/084—Passive control of flow resistance
    • B01L2400/086—Passive control of flow resistance using baffles or other fixed flow obstructions
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y30/00—Nanotechnology for materials or surface science, e.g. nanocomposites
    • 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
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/158—Expression markers

Definitions

  • the present disclosure relates to biomolecule recovery.
  • biomolecules can be used as an index (for example, a bimarker) that represents a physiological state in the living body. Separation, extraction, recovery, etc. of biomolecules from solutions such as body fluids include physical methods such as centrifugation and filters, and chemical methods such as agglutination with reagents.
  • the present disclosure includes a biomolecule recovery device.
  • the method for measuring an antigen according to an embodiment of the present disclosure may include:
  • a biomolecule may be a biological substance.
  • the biological substance is a general term for high molecular weight organic compounds contained in the living body and functioning with respect to life phenomena, and examples thereof include proteins, lipids, nucleic acids, hormones, sugars, amino acids and the like.
  • the biomolecule may be a complex of biomolecules, for example, a complex of proteins or a multiprotein complex.
  • the biomolecule may be a nucleic acid.
  • the biomolecule may be a vesicle.
  • the substance to be recovered extraction, collection, etc.; hereinafter also referred to as recovery) may not be a biomolecule and may be a non-biomolecule.
  • the recovered substance may be an inorganic molecule, an organic molecule, or the like.
  • the biomolecule may be ribonucleic acid (RNA) or may include ribonucleic acid (RNA).
  • RNA includes, but is not limited to, messenger RNA (messenger RNA, mRNA), carrier RNA (transfer RNA, tRNA), ribosomal RNA (rRNA), non-coding RNA (ncRNA), micro RNA (miRNA), ribozyme, double strand. It may be RNA (dsRNA) or the like, and may include a plurality of them.
  • RNA may be modified.
  • RNA and miRNA may be involved in the onset and progression of cancer, cardiovascular disease, neurodegenerative disease, mental disease, chronic inflammatory disease and the like.
  • the miRNA may be a type of RNA that promotes carcinogenesis or positively controls (onco miRNA (oncogenic miRNA), a type of RNA that suppresses or negatively controls carcinogenesis).
  • onco miRNA oncogenic miRNA
  • Tuor Suppressor miRNA tumor-suppressing miRNA
  • the biomolecule may be an exosome or an exosome complex.
  • the nucleic acid may be deoxyribonucleic acid (DNA) or may include DNA.
  • the biomolecule may be an organelle or a vesicle.
  • Vesicles may be, but are not limited to, vacuoles, lysosomes, transport vesicles, secretions, gas vesicles, extracellular matrix vesicles, extracellular vesicles, etc., and may include multiples thereof. .. Extracellular vesicles may be, without limitation, exosomes, exotomes, shedding microvesicles, microvesicles, membrane particles, plasma membranes, blistering blisters and the like.
  • the vesicle may contain nucleic acid.
  • the biomolecule may be, but is not limited to, a cell.
  • the cells may be red blood cells, white blood cells, immune cells and the like.
  • the biomolecule may be a virus, a bacterium or the like.
  • the solution may be a body fluid or a liquid derived from a body fluid (diluting solution, treatment solution, etc.).
  • the solution may be a non-body fluid (non-body fluid-derived) solution, an artificially prepared liquid, or a body fluid or a mixed solution of a body fluid-derived solution and a non-body fluid-derived solution.
  • the solution may be a solution used for sample measurement or a solution used for calibration measurement.
  • the solution or the undiluted solution may be used as it is, or the undiluted solution may be a diluted or concentrated liquid.
  • the solution may be a standard solution or a calibration solution.
  • the sample to be measured may be a sample.
  • the solution may contain a physiological buffer such as phosphate buffered saline (PBS) or N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid buffer (TES) containing the substance to be recovered.
  • PBS phosphate buffered saline
  • TES N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid buffer
  • the body fluid may contain an additive. For example, a stabilizer or a pH adjuster may be added to the additive.
  • Body fluid may be a solution.
  • the body fluid may be in a liquid state or a solid state, for example, a frozen state.
  • the solution may or may not contain a substance to be recovered such as a biomolecule, and may contain a substance for measuring the substance to be recovered.
  • the body fluid may be animal body fluid.
  • the animal may be a reptile, a mammal, an amphibian. Mammals may be dogs, cats, cows, horses, sheep, pigs, hamsters, mice, squirrels, and primates such as monkeys, gorillas, chimpanzees, bonobos, and humans.
  • the body fluid may be lymph fluid or interstitial fluid such as interstitial fluid, intercellular fluid, interstitial fluid, body fluid, serous fluid, pleural fluid, ascites fluid, pericardial fluid, cerebrospinal fluid (cerebrospinal fluid). ), synovial fluid (synovial fluid), and aqueous humor (aqueous humor).
  • the body fluid may be digestive fluid such as saliva, gastric juice, bile, pancreatic juice, intestinal juice, etc., and may also be sweat, tears, runny nose, urine, semen, vaginal fluid, amniotic fluid, milk.
  • Urine means liquid waste produced by the kidneys. Urine may be a liquid or substance discharged to the outside through the urethra, or a liquid or substance accumulated in the bladder.
  • Saliva means the secretory fluid secreted from the salivary glands into the oral cavity.
  • the body fluid may be extracted or collected/collected from the body using an extractor such as a syringe.
  • the solution may be a body fluid of a healthy subject, or a body fluid of a particular disease (including but not limited to lung cancer, liver cancer, pancreatic cancer, bladder cancer, and prostate cancer). It may be a body fluid of a subject suspected of having a specific disease.
  • Extraction may be adsorption.
  • the substance to be measured may be trapped in the device or the fluid chamber, and may be adsorbed to a portion inside thereof.
  • a part or all of the fluid chambers and flow paths such as the substrates and spacers may be formed of an inorganic material or an organic material.
  • the inorganic material forming the substrate may be, for example, a metal, a semiconductor material such as silicon, an insulating material such as glass, ceramics or a metal oxide.
  • the fluid chambers and flow paths such as the substrates and spacers may be made of a polymer material.
  • the polymer material may be a natural resin, a synthetic resin, or a mixture thereof.
  • the synthetic resin may be a thermosetting resin, a thermoplastic resin, or another resin.
  • Thermosetting resins include, but are not limited to, phenol resin (PF), epoxy resin (EP), melamine resin (MF), urea resin (urea resin, UF), unsaturated polyester resin (UP), alkyd resin, It may be polyurethane (PUR), thermosetting polyimide (PI), or the like.
  • Thermoplastic resins include, but are not limited to, polyethylene (PE), high density polyethylene (HDPE), medium density polyethylene (MDPE), low density polyethylene (LDPE), polypropylene (PP), polyvinyl chloride (PVC), poly Vinylidene chloride, polystyrene (PS), polyvinyl acetate (PVAc), polyurethane (PUR), Teflon-(polytetrafluoroethylene, PTFE), ABS resin (acrylonitrile butadiene styrene resin), AS resin, acrylic resin (PMMA), etc.
  • PE polyethylene
  • HDPE high density polyethylene
  • MDPE medium density polyethylene
  • LDPE low density polyethylene
  • PP polypropylene
  • PVC polyvinyl chloride
  • PS polyvinyl chloride
  • PVAc poly Vinylidene chloride
  • PS polystyrene
  • PUR polyurethane
  • PA polyamide
  • PC polyacetal
  • m-PPE modified polyphenylene ether
  • PET polyethylene terephthalate
  • GF minus PET polybutylene terephthalate
  • PBT polybutylene terephthalate
  • COP cyclic polyolefin
  • PPS polyphenylene sulfide
  • PTFE polytetrafluoroethylene
  • PSF Polysulfone
  • PES polyethersulfone
  • PAR amorphous polyarylate
  • LCP liquid crystal polymer
  • PEEK polyetheretherketone
  • PI polyamideimide
  • PAI polyamideimide
  • a part or all of the members forming the flow path chamber may be a flat plate, may have a curved surface, or may have other shapes (for example, bent).
  • the flow channel chamber or flow channel may have a plurality of inner walls.
  • the flow channel chamber or flow channel may have a space substantially surrounded by a plurality of inner walls.
  • the flow channel chamber or the flow channel may have a polygonal cross section in a part thereof.
  • the polygon may be, for example, a triangle, a quadrangle, a pentagon, a hexagon, an octagon, or the like.
  • the plurality of inner walls may be configured by a flat inner wall, a curved inner wall, or a combination thereof.
  • the flow channel chamber or flow channel may have a member that constitutes the inner wall inside, in addition to the inner wall that defines the inner space.
  • a wall or a columnar structure may be provided in the flow path chamber. Those surfaces may form the inner inner wall.
  • the wall or columnar structure may have a structure projecting or denting from the inner wall, or may have a structure that partially crosses the inner space continuously from one inner wall to the opposing inner wall or another inner wall. ..
  • the flow channel chamber or flow channel may have a curved and continuous inner wall.
  • the flow channel chamber or flow channel may have a shape in which a part of the cross section is formed by a circle, an ellipse, or another curved line.
  • the flow path chamber may form a closed space surrounded by an inner wall.
  • the solution may be introduced through an openable/closable inlet.
  • the flow channel chamber may have a solution inlet and outlet.
  • the flow channel chamber is configured as a flow channel and may be in fluid communication with other chambers or components.
  • the fluid chamber may have air holes.
  • the nanowire may be arranged substantially perpendicular to the wall surface on which it is arranged.
  • the nanowire may be arranged non-perpendicular to the wall surface on which it is arranged.
  • the plurality of nanowires may be arranged at different angles with respect to the wall surface on which they are arranged.
  • the nanowire may be arranged parallel to the wall surface on which it is arranged.
  • the nanowire may have a branched chain.
  • the nanowire may have a single structure with or without branched chains.
  • the plurality of nanowires may include nanowires having branched chains and unbranched nanowires.
  • the nanowires may be periodically arranged at regular intervals on the wall surface on which they are arranged.
  • the nanowire may be randomly or aperiodically arranged on the wall surface on which the nanowire is arranged.
  • the nanowire may be formed by growing from a starting point on the wall surface.
  • the nanowire may be arranged to extend from the starting point on the wall surface.
  • the nanowires may be directly attached to the material forming the channel or fluid chamber. Nanowires may be grown directly from the wall.
  • the nanowires may be partially embedded in the wall.
  • the nanowire may be grown starting from the growth wire embedded in the wall surface.
  • the nanowires may be placed across the wall. In some embodiments, nanowires may be located on a portion of the wall.
  • the nanowire does not have to be physically and chemically fixed to the inner wall.
  • nanowires or aggregates thereof may be arranged in contact with the inner wall or in the vicinity of the inner wall.
  • the nanowire may or may not move macroscopically upon introduction of the solution.
  • the nanowires are mechanically substantially in contact with the inner wall, mechanically substantially in contact with the inner wall, or mechanically substantially fixed in the vicinity of the inner wall.
  • an aggregate of nanowires for example, a macroscopically or microscopically sheet-like aggregate
  • the substrate (inner wall) surface or the catalyst layer surface on which the nanowires are formed or grown may be subjected to surface treatment such as activation treatment, hydrophilization treatment, heat treatment, and hydrothermal treatment.
  • the surface treatment may be, for example, plasma treatment, particle (ion, radical, neutral atom, etc.) beam irradiation, light (electromagnetic wave) irradiation such as UV and EUV, electron beam irradiation, mechanical processing such as polishing, and the like.
  • the surface treatment may be, for example, a treatment for increasing the presence of oxygen that is combined with a metal to form a Lewis acid.
  • nanowire means a rod-shaped or wire-shaped structure having a cross-sectional shape on the order of nanometers or a size such as a diameter (for example, without limitation, a diameter of 1 to several hundreds of nanometers). ..
  • the material of the nanowire may be an inorganic material or an organic material.
  • the nanowire may be or may include a metal, a nonmetal, a semiconductor, a mixture or alloy thereof, or an oxide or nitride thereof.
  • the material of the nanowire may be a polymer material or may include a polymer material. Nanowires may be wires, whiskers, fibers, and mixtures or composites thereof.
  • Examples of the metal used for the material of the nanowire include, but are not limited to, typical metals (alkali metals: Li, Na, K, Rb, Cs, alkaline earth metals: Ca, Sr, Ba, Ra), magnesium group elements: Be.
  • alkali metals Li, Na, K, Rb, Cs, alkaline earth metals: Ca, Sr, Ba, Ra
  • magnesium group elements Be.
  • Mg, Zn, Cd, Hg aluminum group elements: Al, Ga, In, rare earth elements: Y, La, Ce, Pr, Nd, Sm, Eu, tin group elements: Ti, Zr, Sn, Hf, Pb, Th, iron group element: Fe, Co, Ni, earth acid element: V, Nb, Ta, chromium group element: Cr, Mo, W, U, manganese group element: Mn, Re, precious metal (copper group, currency metal) : Cu, Ag, Au, platinum group elements: Ru, Rh, Pd, Os, Ir, Pt, natural radioactive elements: radioactive decay products having U and Th as base materials: U, Th, Ra, Rn, actinides, super Uranium element: Np, Pu, Am, Cm, Bk, Cf, Es, Fm, Md, No, etc., elements after uranium, or alloys thereof may be used.
  • the nanowire may be an oxide of any one of the above metals or alloys or an alloy or mixture thereof, and may include an oxide.
  • the material of the nanowires or at least the surface of the nanowires is, for example and without limitation, ZnO, SiO 2 , Li 2 O, MgO, Al 2 O 3 , CaO, TiO 2 , Mn 2 O 3 , Fe 2 O. 3 , CoO, NiO, CuO, Ga 2 O 3 , SrO, In 2 O 3 , SnO 2 , Sm 2 0 3 , EuO and the like may be used.
  • Nanowires can be grown by pulsed laser deposition, physical vapor deposition such as VLS (Vapor-Liquid-Solid) method, CVD (Chemical-Vapor-Deposition) method, arc discharge method, laser evaporation method, metalorganic vapor phase selective growth method.
  • a hydrothermal synthesis method, a reactive ion etching method, a firing method, or a melting method may be used.
  • Nanowires may be charged.
  • the nanowire may have a charge opposite to that of the substance to be collected or extracted.
  • biomolecules such as extracellular vesicles and nucleic acids.
  • the nanowire may be fixed to the material forming the flow path or the fluid chamber via another material or member.
  • the material between the nanowires and the wall material may have a catalyst for nanowire growth or may be a non-catalytic material.
  • Nanowires may be grown via a catalyst layer, an adhesive layer, and a growth nucleus.
  • the "layer” may be a thin film.
  • the “layer” may be a continuous film.
  • “Layer” may be discontinuous.
  • a “layer” is a continuous membrane, which may have holes.
  • a “layer” may be a plurality of spaced apart thin films.
  • the “layer” may be an island or may include an island.
  • the “layer” may be particles or may include particles.
  • the catalyst layer, the adhesive layer, and the growth nucleus may be a metal, an alloy, a nonmetal, a semiconductor, or an oxide or nitride thereof. Or a mixture thereof.
  • Metals include, but are not limited to, typical metals (alkali metals: Li, Na, K, Rb, Cs, alkaline earth metals: Ca, Sr, Ba, Ra), magnesium group elements: Be, Mg, Zn, Cd, Hg, aluminum group element: Al, Ga, In, rare earth element: Y, La, Ce, Pr, Nd, Sm, Eu, tin group element: Ti, Zr, Sn, Hf, Pb, Th, iron group element: Fe , Co, Ni, earth acid element: V, Nb, Ta, chromium group element: Cr, Mo, W, U, manganese group element: Mn, Re, noble metal (copper group, currency metal): Cu, Ag, Au, Platinum group elements: Ru, Rh, Pd, Os, Ir, P
  • the growth nucleus of the nanowire may be formed of a material different from the wall material.
  • the growth core of the nanowire may be formed of a material different from that of the nanowire.
  • the growth core of the nanowire may be formed of a material substantially the same as the wall material.
  • the growth nuclei of the nanowire may be, for example, a surface having structurally unevenness.
  • the growth nuclei of the nanowire may be, for example, a surface that chemically has different properties in the subportions. Surfaces that are mechanically, structurally or chemically different (mottled) may be more likely to become growth nuclei for nanowires in some areas than in others.
  • the projections and depressions may be formed by lithography and dry/wet etching.
  • irradiation with ions, neutral atoms, or plasma may form mechanically, structurally, or chemically different (mottled) surfaces.
  • the length of the nanowire is, for example, without limitation, 500 nm, 1 ⁇ m, 1.5 ⁇ m, 2 ⁇ m, 3 ⁇ m, 4 ⁇ m, 5 ⁇ m, 6 ⁇ m, 7 ⁇ m, 8 ⁇ m, 9 ⁇ m, 10 ⁇ m, 11 ⁇ m, 12 ⁇ m, 13 ⁇ m, 14 ⁇ m, 15 ⁇ m, 17 ⁇ m, It may be larger than the value such as 20 ⁇ m or more.
  • the length of the nanowire is not limited to, for example, 1 ⁇ m, 1.5 ⁇ m, 2 ⁇ m, 3 ⁇ m, 4 ⁇ m, 5 ⁇ m, 6 ⁇ m, 7 ⁇ m, 8 ⁇ m, 9 ⁇ m, 10 ⁇ m, 11 ⁇ m, 12 ⁇ m, 13 ⁇ m, 14 ⁇ m, 15 ⁇ m, 17 ⁇ m, 20 ⁇ m, It may be smaller than or smaller than 50 ⁇ m, 100 ⁇ m, 200 ⁇ m, and the like.
  • the diameter (or size in the thickness direction) of the nanowire for example, without limitation, 5 nm, 10 nm, 15 nm, 20 nm, 25 nm, 30 nm, 40 nm, 50 nm, 60 nm, 70 nm, 80 nm, 90 nm, 100 nm, 150 nm, 200 nm, 250 nm, It may be larger than the value of 300 nm, 400 nm, 500 nm or the like, or may be larger than that.
  • the diameter (or size in the thickness direction) of the nanowire for example, without limitation, 10 nm, 15 nm, 20 nm, 25 nm, 30 nm, 40 nm, 50 nm, 60 nm, 70 nm, 80 nm, 90 nm, 100 nm, 150 nm, 200 nm, 250 nm, 300 nm, It may be smaller than the value of 400 nm, 500 nm, 1 ⁇ m, or the like, or may be smaller than that.
  • the polymer used for the nanowire material is, for example, without limitation, polymethylmethacrylate (PMMA), polystyrene (PS), polydimethylsiloxane (PDMS), conductive polymer poly(3,4-ethylenedioxythiophene). /Poly(4-styrenesulfonic acid) (PEDOT/PSS), polyethylene naphthalate (PEN), polyethylene terephthalate (PET), polyimide (PI), etc. may be used.
  • PMMA polymethylmethacrylate
  • PS polystyrene
  • PDMS polydimethylsiloxane
  • PEDOT/PSS Poly(4-styrenesulfonic acid)
  • PEN polyethylene naphthalate
  • PET polyethylene terephthalate
  • PI polyimide
  • the nanowire may be a fiber material or may include a fiber material.
  • the fibrous material may be synthetic fibers, natural fibers, mixtures thereof or mixed fibers.
  • the fibrous material may be, for example, without limitation, polyester, polypropylene, polyacrylic, polyamide, copolyester-based fibers, polyolefin-based fibers, polyvinyl alcohol-based fibers, and the like.
  • the fibrous material may be, for example and without limitation, vegetable fibers such as cotton, hemp, hemp and the like.
  • the fiber material used for the nanowire may be a woven fabric or a non-woven fabric.
  • nanowires can be a laminate of fibrous materials.
  • nanowires may be short fiber structures.
  • the length of the short fibers may be random or may be breathable.
  • the short fiber axes may be randomly arranged or may be regularly arranged.
  • synthetic fibers may be low melting point materials.
  • the low melting point material may be, for example, but not limited to, a copolyester fiber, a polyolefin fiber, a polyvinyl alcohol fiber, or the like.
  • the synthetic fibers may have a core structure with a low melting point polymer.
  • the distance between the pair of opposing wall surfaces having the nanowires may be twice the length of the nanowires (or the size in the direction perpendicular to the surface on which the nanowires are arranged, and the like below), or may be less than twice. Well, 1.5 times, 2 times or more, 3 times, 4 times, 5 times, 6 times, 7 times, 8 times, 9 times, 10 times, It may be larger than them.
  • the spacing between the pair of opposing wall surfaces having the nanowires may be less than or equal to 10, 9, 8, 7, 6, 6, 5, 4, 3, etc., or less than the length of the nanowires.
  • FIG. 1 shows a cross-sectional view of a flow channel device (fluid chamber) 100 according to an embodiment.
  • An internal space having a quadrangular cross section is formed in the substrate 110 of the channel chamber 100 of FIG.
  • Nanowires 131 and 132 are formed on the opposing inner walls 121 and 122.
  • a space may be formed inside one member, for example, as shown in FIG.
  • the internal space may form or define the internal space by combining multiple members.
  • FIG. 2 shows a sectional view of a fluid chamber 200 according to one embodiment.
  • the flow path chamber 200 of FIG. 2 is configured by a combination of a flat first substrate 211 and a second substrate 212 having a recess.
  • the internal space is defined by the combination of these substrates.
  • Nanowires 231 are formed on the inner wall surface 221 of the first substrate 211.
  • Nanowires 232 are formed on the inner wall surface 222 of the bottom surface of the recess of the second substrate 212 and at a position facing the inner wall surface 221 of the first substrate.
  • FIG. 3 shows a sectional view of a fluid chamber 300 according to one embodiment.
  • the fluid chamber 300 of FIG. 3 is configured by combining a flat first substrate 311 and a flat second substrate 312 with a spacer 313 sandwiched therebetween. That is, the internal space is defined by the first substrate 311, the second substrate 312, and the spacer.
  • Nanowires 331 are formed on the inner wall surface 321 of the first base 311.
  • Nanowires 332 are formed on the inner wall surface 322 of the second substrate 312 facing the inner wall surface 321 of the first substrate 311.
  • Nanowires may be formed on three or more inner wall surfaces. Nanowires may be formed on all interior wall surfaces that define a fluid chamber.
  • FIG. 4 shows a sectional view of a fluid chamber 400 according to one embodiment.
  • the fluid chamber 400 has an internal space formed inside the substrate 410 and has a rectangular cross section.
  • the substrate 410 has inner walls 421, 422, 423, 424, and these inner walls define the internal space.
  • nanowires 431, 432, 433, 434 are formed on these inner walls 421, 422, 423, 424, respectively.
  • the internal space may be curved.
  • FIG. 5 shows a sectional view of a fluid chamber 500 according to one embodiment.
  • the fluid chamber 500 has an internal space having a circular cross section in the substrate 510.
  • Nanowires 531 are formed on an inner wall 521 of a curved surface (spherical surface or cylindrical inner surface).
  • one or more inner walls may have irregularities.
  • FIG. 6 shows a sectional view of a fluid chamber 600 according to one embodiment.
  • the fluid chamber 600 is configured by combining a flat first substrate 611 and a macroscopically flat second substrate 612 having irregularities on the inner wall with a spacer 613 interposed therebetween.
  • Nanowires 631 are formed on the inner wall 621 of the first substrate 611.
  • the inner wall 622 of the second substrate 612 has a convex portion 622a and a concave portion or bottom surface 622b.
  • the nanowire 632a is formed on the convex portion 622a, and the nanowire 632b is also formed on the bottom surface 622b.
  • FIG. 7 shows a sectional view of a fluid chamber 700 according to one embodiment.
  • the fluid chamber 700 is configured by combining a flat first substrate 711 and a second substrate 712 that is macroscopically flat and has irregularities on the inner wall with a spacer 713 sandwiched therebetween. There is.
  • the nanowire is not formed on the convex portion 722a, and the nanowire 732 is formed on the bottom surface 722b.
  • nanowires may or may not be formed on all the inner wall surfaces having irregularities, and nanowires may be formed on a part of the irregular surface.
  • nanowires 632a and 632b are formed on the surface 622a of the convex portion facing the inner space and the concave or bottom surface 622b.
  • the nanowire 732 is formed in the recess 722b.
  • nanowires may be formed on the lateral surface of the uneven portion (not shown).
  • FIG. 8 shows a sectional view of a fluid chamber 800 according to one embodiment.
  • the fluid chamber 800 has a structure 814 in the internal space formed in the substrate 810, which is separate from the inner wall defining the internal space.
  • the structure body 814 is continuously formed from one inner wall to another inner wall or an opposing inner wall. Nanowires 834 are formed on the surface (which may be called an inner wall) 824 of the structure 814.
  • FIG. 9 shows a sectional view of a fluid chamber 900 according to one embodiment.
  • the fluid chamber 900 has a structure 914 in the internal space formed in the substrate 910, which is separate from the inner wall defining the internal space.
  • nanowires are not formed on the surface of the structure 924.
  • Nanowires 931 are formed on the inner wall 921.
  • irregularities and structures may be placed. All the surfaces of these uneven portions or structures and the inner wall that defines the outer frame of the inner space may be referred to as the inner wall.
  • the surface of the inner wall defining the outer frame of the inner space, the surface of the uneven portion or the structure may be defined as another inner wall.
  • Nanowires may be formed on all the surfaces of the uneven portion or structure and the inner wall that defines the outer frame of the internal space, or nanowires may be formed on part of the inner walls.
  • the inner wall on which the nanowire is formed may have the nanowire formed on the entire surface thereof, or may have the nanowire partially or partially formed.
  • the irregularities or structures arranged in the internal space may be so-called chaotic mixers (chaos mixers), which are non-linear and/or three-dimensional with respect to the fluid flowing in the internal space. It may have a structure that causes a dynamic flow. Such a structure may have, for example, a step, a change in cross-sectional area, or a change in the direction of the flow channel in the flow channel.
  • chaotic mixers chaos mixers
  • FIG. 10 shows a sectional view of a fluid chamber 1000 according to one embodiment.
  • the fluid chamber 1000 may be a flow path.
  • the solution flows in the direction of the arrow in FIG.
  • the flow channel 1000 has inner walls 1021 and 1022 facing each other.
  • the inner wall 1021 has a recess 1021.
  • the flow direction changes due to the level difference between the inner wall surface 1021a and the recess 1021b flowing in the direction of the arrow, resulting in a non-linear flow. It is considered that, by way of example, the probability that the substance in the solution contacts the nanowires 1031 and 1032 or reaches the vicinity thereof will increase.
  • the structure that changes the step, changes the cross-sectional area, and changes the direction of the flow path may be provided on one inner wall, at least one inner wall, or a plurality of inner walls.
  • FIG. 11 shows a sectional view of a fluid chamber 1100 according to one embodiment.
  • the fluid chamber 11 is provided with a step on the opposing inner wall.
  • Recesses 1121b and 1122b are arranged on both of the facing inner walls 1121a and 1122a, respectively, offset in the flow path direction.
  • Nanowires 1131a, 1131b, 1132a, 1132b are also arranged on the normal inner wall surfaces 1121a, 1122a and also in the recesses 1121b, 1122b.
  • An uneven structure or structure such as a chaotic mixer can have various configurations. For example, you may form a recessed part with respect to an inner wall.
  • the recess may be formed in a stripe shape (groove).
  • the recesses may be formed as a plurality of parallel stripes.
  • the stripe-shaped recesses may be parallel to the direction in which the solution flows, or may have an angle. The angle may be substantially vertical or may be between 0 and 90 degrees.
  • FIG. 12 shows a top view of one inner wall of the flow path 1200 according to the embodiment.
  • recesses or grooves 1221b are repeatedly formed in parallel in stripes.
  • the recess 1221b is arranged such that its longitudinal direction has an angle with respect to the direction in which the solution flows indicated by the arrow.
  • the concavo-convex structure or structure such as a chaotic mixer may have a linear shape or a bent shape.
  • FIG. 13 shows a top view of one inner wall of the flow path 1300 according to the embodiment.
  • recesses or grooves 1321b are formed in a stripe shape and are partially bent downward, and are repeatedly formed parallel to each other.
  • the recess 1321b is arranged such that its longitudinal direction has an angle with respect to the direction in which the solution flows indicated by the arrow. Such an arrangement may be called a herringbone shape.
  • FIG. 14 shows a top view of one inner wall of the flow channel 1400 according to the embodiment.
  • a structure in which a concave portion or a groove 1421b is formed in a stripe shape and is partially bent downward is formed continuously while the bent portions are displaced alternately.
  • the chaotic mixer with herringbone-shaped irregularities on the inner wall surface of the channel can promote the non-linear flow of fluid. This exemplarily allows the nanowires arranged on the plurality of inner wall surfaces or the inner wall surface of the curved surface to capture more biomolecules in the solution.
  • FIG. 15 shows a top view of one inner wall of the flow channel 1500 according to the embodiment.
  • Structures (walls) 1514 are repeatedly formed in parallel on the inner wall 1511.
  • the wall 1514 is arranged so that its longitudinal direction is at an angle with respect to the direction in which the solution flows indicated by the arrow.
  • FIG. 16 shows a top view of one inner wall of the flow channel 1600 according to the embodiment.
  • Structures (walls) 1614 are alternately and repeatedly formed on the inner wall 1611.
  • the wall 1614 is arranged such that its longitudinal direction forms an angle with the direction of flow of the solution indicated by the arrow.
  • FIG. 17 shows a top view of one inner wall of the flow path 1700 according to the embodiment.
  • a zigzag-shaped structure (wall) 1714 is formed on the inner wall 1711.
  • FIG. 18 shows a top view of one inner wall of the flow channel 1800 according to the embodiment.
  • Structures (pillars) 1814 are arranged on the inner wall 1811 in a lattice shape along the flow path direction of the arrow.
  • FIG. 19 shows a top view of one inner wall of the flow channel 1900 according to the embodiment.
  • Structures (pillars) 1914 are arranged on the inner wall 1911 while being staggered in the flow path direction of the arrow.
  • Structures such as walls and pillars arranged on the inner wall surface of the flow path may be formed continuously up to the inner wall facing each other, or may not be continuous to the inner wall and have an end portion in the internal space. May be. These structures can stir the flowing solution. Thereby, for example, the nanowires arranged on the plurality of inner wall surfaces or the inner wall surface of the curved surface can capture more biomolecules in the solution.
  • the flow path may be straight, curved, or curved.
  • the fluid chamber or flow channel device may be, or may be configured to be, connected to an analytical device.
  • the fluid chamber or flow channel device may be incorporated into an analytical device.
  • the analytical device may be, for example without limitation, an optical, magnetic, electrical, chemical, electrochemical, etc. analytical or measurement device.
  • the analytical device may be a measurement nucleic acid (RNA, DNA) sequencer. In some embodiments, it may be a microarray.
  • the present disclosure includes a biomolecule recovery, extraction, or collection method (also simply referred to as a collection method).
  • the recovery method includes introducing a solution into a fluid chamber or channel (hereinafter, also referred to as a fluid chamber), or bringing the solution into contact with a nanowire (also referred to as simply introducing the solution). May be included.
  • introducing the solution into the fluidic device may substantially allow the solution to rest within the fluidic device after introducing the solution. In some embodiments, introducing the solution into the fluidic device may continue to flow the solution into the fluidic device. For example, the solution may be continuously introduced from the inlet of the channel device and the solution passing through the channel device may be continuously discharged from the outlet. For example, the solution may be in constant contact with the nanowire while in a fluidic device.
  • nanowires When recovering charged molecules such as microRNA, nanowires may have a positive surface charge.
  • the body fluid may be contacted with the nanowire under pH conditions where the nanowire has a positive surface charge. This allows, for example, free and EV-encapsulated forms of microRNA to be trapped on the nanowires.
  • the pH of the body fluid may be adjusted so that the nanowire has a positive surface charge.
  • nanowires may be made of materials or methods that have a positive surface charge to match the pH of the solution.
  • the recovery method may include adjusting the pH of the solution.
  • the pH of the solution may be adjusted before, after, or during contact with the nanowire.
  • the pH of the body fluid may be adjusted to be greater than or greater than a value such as 2, 3, 4, or 5.
  • the pH of the bodily fluid may be adjusted to be below or below a value such as 10, 9, 8, 7, 6, or 5.
  • the pH of urine may be adjusted to 6-8.
  • the recovery method may introduce a dissociation agent (or a releasing agent, a dissociation solution, a solution for dissociation, etc.) after introducing the solution into the fluidic device. This allows, for example, molecules trapped within the nanowire or fluidic device to dissociate from the nanowire.
  • the recovery method may include recovering the supplemental substance with the dissociator.
  • the dissociation agent may include a buffering agent.
  • the dissociation agent may include a surface active agent.
  • the surface active agent may be, for example, a nonionic surface active agent or an ionic surface active agent.
  • the RNA contained in the EV captured by the nanowire, or the RNA in the solution in the free form and captured by the nanowire can be dissociated from the nanowire.
  • the dissociation agent may include an RNase inhibitor.
  • the recovery method may be washing after introducing the solution into the fluidic device.
  • the recovery method may include washing prior to introducing the liberating agent.
  • the washing may include introducing water, a buffer solution, a washing solution or the like (simply referred to as a washing solution) into the fluid device.
  • the cleaning liquid after cleaning may be discharged.
  • no washing may be done. For example, it may be unwashed.
  • the present disclosure also includes a method of measuring and analyzing the recovered molecule.
  • biomolecules collected in the fluidic device may be analyzed.
  • the expression level of RNA in body fluids may be analyzed.
  • the RNA may be microRNA.
  • the expression profile of RNA recovered in the fluidic device may be measured using a microarray or sequencer. The measurement may include introducing a solution containing the recovered RNA into a microarray or a sequencer.
  • the present disclosure also includes diagnostic methods. In some embodiments, based on the expression profile of RNA recovered by the fluidic device or the expression level of one or more specific RNAs, or their temporal changes, diagnosis of disease, risk of disease, and the like are performed. May be.
  • the present disclosure includes a program or software that implements a measurement method, an analysis method, and a diagnosis method.
  • the program or software may be recorded in a storage medium. It may include transmitting the expression profile of the RNA recovered by the fluidic device or the expression amount of one or more specific RNAs to a computing device (means) such as a PC, a server, or a CPU. .. Receiving the expression profile of the RNA recovered by the fluidic device or the expression level of one or more specific RNAs.
  • the reception and transmission may be performed by wire, may be performed wirelessly, and may be transmitted through the Internet. Data storage, storage, and transmission/reception may be performed via the cloud.
  • the analysis and diagnosis may be performed using artificial intelligence, machine learning, deep learning, or the like.
  • the present disclosure also includes the following embodiments: A01 A biomolecule recovery device, A fluid chamber having a plurality of inner walls; A plurality of nanowires disposed on two or more inner walls of the plurality of inner walls of the fluid chamber; A biomolecule recovery device comprising: A02 A biomolecule recovery device, A fluid chamber that is at least partially cuboid; Nanowires disposed on both at least one pair of opposing inner walls of the cuboid of the fluid chamber; A biomolecule recovery device comprising: A02b A biomolecule recovery device, A fluid chamber, at least a portion of which is rectangular in cross section, Nanowires disposed on both at least one pair of opposing inner walls of the cuboid of the fluid chamber; A biomolecule recovery device comprising: A03 The fluid chamber is A first substrate having a substantially flat surface and having nanowires disposed on the substantially flat surface; A second substrate having a frame having a surface in contact with the first substrate and a recess defined inside the frame, wherein a nanowire is arranged on the surface of
  • the fluid chamber is A pair of substrates having a substantially flat surface, wherein the nanowires are arranged on the flat surface, the pair of substrates being bonded such that the surfaces on which the nanowires are arranged face each other, A spacer sandwiched between the pair of substrates, between the opposing surfaces of the pair of substrates, a spacer configured to define a space of the nanowire, With The biomolecule recovery device according to embodiment A02. A11 At least one of the plurality of inner walls has a concave-convex structure. The biomolecule recovery device according to any one of embodiments A01 to A04.
  • the fluid chamber has an inlet for introducing a solution containing the biomolecule and an outlet for discharging the solution, and is configured as a flow path through which the solution flows.
  • the biomolecule recovery device according to any one of embodiments A01 to A11.
  • A22 The fluid chamber includes a chaotic mixer, The biomolecule recovery device according to any one of embodiments A1 to A21.
  • A23 The nanowires are disposed on at least a portion of the surface of the chaotic mixer, The biomolecule recovery device according to any one of embodiment A22.
  • A31 The nanowires are placed directly on the surface on which the nanowires are placed, The biomolecule recovery device according to any one of embodiments A1 to A23.
  • A32 The nanowire has one end embedded in an inner wall in which the nanowire is arranged, The biomolecule recovery device according to any one of embodiments A1 to A31.
  • A32b A part of the nanowire is embedded in an inner wall in which the nanowire is arranged, The biomolecule recovery device according to any one of embodiments A1 to A31.
  • A33 The inner wall on which the nanowires are arranged has a growth layer, The nanowires are formed by growing on the growth layer, The biomolecule recovery device according to any one of embodiments A1 to A31.
  • A34 The growth layer includes a catalyst for growing nanowires, The biomolecule recovery device according to embodiment A33.
  • B01 A biomolecule analysis device comprising the biomolecule device.
  • C01 A method for recovering biomolecules, comprising: A fluid chamber having a plurality of inner walls, and a plurality of nanowires disposed on two or more inner walls of the plurality of inner walls of the fluid chamber, Providing a biomolecule recovery device comprising: Introducing a solution containing a biomolecule into the biomolecule recovery device, A method comprising.
  • C02 A method for recovering biomolecules, comprising: Introducing a solution containing a biomolecule into the biomolecule recovery device continuously introduces a solution containing a biomolecule, The method according to embodiment C01.
  • C03 Introducing a dissociation agent into the biomolecule recovery device to dissociate the captured biomolecule from the nanowire, Is further provided, The method according to embodiment C01 or C02.
  • the biomolecule includes microRNA, The method according to any one of the embodiments C01 to C03.
  • C05 The solution is urine or saliva, The method according to embodiment C04.
  • D01 A method for analyzing RNA expression level, comprising: Providing RNA in recovered body fluid using a biomolecule recovery device comprising a fluid chamber having a plurality of inner walls and a plurality of nanowires arranged on two or more inner walls of the plurality of inner walls of the fluid chamber Or prepare and Measuring RNA recovered using the biomolecule recovery device; Estimating the expression level of the RNA in the body fluid based on the measured RNA data; With A method for analyzing RNA expression level.
  • D02 Estimating the expression level of the RNA in the body fluid includes determining an expression profile of the RNA in the body fluid, The method according to embodiment D01. D03 The body fluid is urine or saliva, The method according to embodiment D01 or D02.
  • 100 flow path device 110 substrate 121,122 inner wall 131,132 nanowire 200 fluid chamber 211 first substrate 212 second substrate 221 inner wall surface 231 nanowire 222 inner wall surface 232 nanowire 300 fluid chamber 311 first substrate 312 second substrate 321 inner wall surface 331 nanowire 322 inner wall surface 332 nanowire 400 fluid chamber 410 substrate 421, 422, 423, 424 inner wall 431, 432, 433, 434 nanowire 500 fluid chamber 510 substrate 521 inner wall 531 nanowire 600 fluid chamber 611 first substrate 612 second substrate 613 spacer 621 inner wall 631 nanowire 612 Second substrate 622 Inner wall 622a Convex portion 622b Recessed portion or bottom surface 632a Nanowire 632b Nanowire 700 Fluid chamber 711 First substrate 712 Second substrate 713 Spacer 722a Convex portion 722b Bottom surface 732 Nanowire 800 Fluid chamber 810 Substrate 814 Surface 814 Structure 834 nanowire 900 fluid chamber 910 substrate 914 structure 924 structure 921 inner wall 931 nanowire 1000

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