JP2020525795A - 検出システムおよびその製造方法 - Google Patents
検出システムおよびその製造方法 Download PDFInfo
- Publication number
- JP2020525795A JP2020525795A JP2019572624A JP2019572624A JP2020525795A JP 2020525795 A JP2020525795 A JP 2020525795A JP 2019572624 A JP2019572624 A JP 2019572624A JP 2019572624 A JP2019572624 A JP 2019572624A JP 2020525795 A JP2020525795 A JP 2020525795A
- Authority
- JP
- Japan
- Prior art keywords
- membrane
- channel region
- medium
- electrode
- detector
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000001514 detection method Methods 0.000 title claims abstract description 64
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 21
- 239000012528 membrane Substances 0.000 claims abstract description 104
- 239000011148 porous material Substances 0.000 claims abstract description 76
- 238000000034 method Methods 0.000 claims abstract description 28
- 238000005259 measurement Methods 0.000 claims description 31
- 239000012491 analyte Substances 0.000 claims description 27
- 238000007306 functionalization reaction Methods 0.000 claims description 26
- 239000003792 electrolyte Substances 0.000 claims description 25
- 108091023037 Aptamer Proteins 0.000 claims description 20
- 239000012790 adhesive layer Substances 0.000 claims description 17
- 102000007066 Prostate-Specific Antigen Human genes 0.000 claims description 16
- 108010072866 Prostate-Specific Antigen Proteins 0.000 claims description 16
- 230000035945 sensitivity Effects 0.000 claims description 8
- 239000012048 reactive intermediate Substances 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 238000002847 impedance measurement Methods 0.000 claims description 3
- 230000002862 amidating effect Effects 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 238000010030 laminating Methods 0.000 claims description 2
- 239000010410 layer Substances 0.000 description 32
- 239000000758 substrate Substances 0.000 description 16
- 239000002985 plastic film Substances 0.000 description 14
- 229920006255 plastic film Polymers 0.000 description 14
- 239000000543 intermediate Substances 0.000 description 10
- 239000003446 ligand Substances 0.000 description 9
- 239000000853 adhesive Substances 0.000 description 8
- 230000001070 adhesive effect Effects 0.000 description 8
- 230000010354 integration Effects 0.000 description 8
- 150000002500 ions Chemical class 0.000 description 8
- 206010060862 Prostate cancer Diseases 0.000 description 6
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000002090 nanochannel Substances 0.000 description 4
- 229920002120 photoresistant polymer Polymers 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 3
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 238000005530 etching Methods 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 3
- 229910052737 gold Inorganic materials 0.000 description 3
- 239000010931 gold Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 229910052709 silver Inorganic materials 0.000 description 3
- 239000004332 silver Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- ISCMYZGMRHODRP-UHFFFAOYSA-N 3-(iminomethylideneamino)-n,n-dimethylpropan-1-amine Chemical compound CN(C)CCCN=C=N ISCMYZGMRHODRP-UHFFFAOYSA-N 0.000 description 2
- 239000004593 Epoxy Substances 0.000 description 2
- 108091008103 RNA aptamers Proteins 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 229920001222 biopolymer Polymers 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 150000001735 carboxylic acids Chemical group 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 238000005370 electroosmosis Methods 0.000 description 2
- 238000005240 physical vapour deposition Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- GVJXGCIPWAVXJP-UHFFFAOYSA-N 2,5-dioxo-1-oxoniopyrrolidine-3-sulfonate Chemical compound ON1C(=O)CC(S(O)(=O)=O)C1=O GVJXGCIPWAVXJP-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 108091008102 DNA aptamers Proteins 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 238000004026 adhesive bonding Methods 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 125000003277 amino group Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 238000010923 batch production Methods 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 150000007942 carboxylates Chemical group 0.000 description 1
- 125000003262 carboxylic acid ester group Chemical class [H]C([H])([*:2])OC(=O)C([H])([H])[*:1] 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000002800 charge carrier Substances 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 239000011651 chromium Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000000151 deposition Methods 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000013399 early diagnosis Methods 0.000 description 1
- 230000005684 electric field Effects 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 231100000317 environmental toxin Toxicity 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 102000035122 glycosylated proteins Human genes 0.000 description 1
- 108091005608 glycosylated proteins Proteins 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000002484 inorganic compounds Chemical class 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 239000011229 interlayer Substances 0.000 description 1
- 238000003698 laser cutting Methods 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 208000010658 metastatic prostate carcinoma Diseases 0.000 description 1
- 239000002581 neurotoxin Substances 0.000 description 1
- 231100000618 neurotoxin Toxicity 0.000 description 1
- 108091008104 nucleic acid aptamers Proteins 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- RPENMORRBUTCPR-UHFFFAOYSA-M sodium;1-hydroxy-2,5-dioxopyrrolidine-3-sulfonate Chemical compound [Na+].ON1C(=O)CC(S([O-])(=O)=O)C1=O RPENMORRBUTCPR-UHFFFAOYSA-M 0.000 description 1
- 238000004544 sputter deposition Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 238000007039 two-step reaction Methods 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 238000007740 vapor deposition Methods 0.000 description 1
- 238000004832 voltammetry Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000004457 water analysis Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
Classifications
-
- 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
- B01L3/502707—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 manufacture of the container or its components
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
-
- 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
- B01L3/50273—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 or forces applied to move the fluids
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B81—MICROSTRUCTURAL TECHNOLOGY
- B81B—MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
- B81B1/00—Devices without movable or flexible elements, e.g. microcapillary devices
- B81B1/006—Microdevices formed as a single homogeneous piece, i.e. wherein the mechanical function is obtained by the use of the device, e.g. cutters
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B81—MICROSTRUCTURAL TECHNOLOGY
- B81C—PROCESSES OR APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OR TREATMENT OF MICROSTRUCTURAL DEVICES OR SYSTEMS
- B81C1/00—Manufacture or treatment of devices or systems in or on a substrate
- B81C1/00015—Manufacture or treatment of devices or systems in or on a substrate for manufacturing microsystems
- B81C1/00023—Manufacture or treatment of devices or systems in or on a substrate for manufacturing microsystems without movable or flexible elements
- B81C1/00119—Arrangement of basic structures like cavities or channels, e.g. suitable for microfluidic systems
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B81—MICROSTRUCTURAL TECHNOLOGY
- B81C—PROCESSES OR APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OR TREATMENT OF MICROSTRUCTURAL DEVICES OR SYSTEMS
- B81C1/00—Manufacture or treatment of devices or systems in or on a substrate
- B81C1/00015—Manufacture or treatment of devices or systems in or on a substrate for manufacturing microsystems
- B81C1/00206—Processes for functionalising a surface, e.g. provide the surface with specific mechanical, chemical or biological properties
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume, or surface-area of porous materials
- G01N15/06—Investigating concentration of particle suspensions
- G01N15/0656—Investigating concentration of particle suspensions using electric, e.g. electrostatic methods or magnetic methods
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/416—Systems
- G01N27/447—Systems using electrophoresis
- G01N27/44704—Details; Accessories
- G01N27/44717—Arrangements for investigating the separated zones, e.g. localising zones
- G01N27/44739—Collecting the separated zones, e.g. blotting to a membrane or punching of gel spots
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/416—Systems
- G01N27/447—Systems using electrophoresis
- G01N27/44756—Apparatus specially adapted therefor
- G01N27/44791—Microapparatus
-
- 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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/54366—Apparatus specially adapted for solid-phase testing
- G01N33/54373—Apparatus specially adapted for solid-phase testing involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
- G01N33/5438—Electrodes
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57407—Specifically defined cancers
- G01N33/57434—Specifically defined cancers of prostate
-
- 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
- B01L2200/12—Specific details about manufacturing devices
-
- 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
- B01L2300/06—Auxiliary integrated devices, integrated components
- B01L2300/0627—Sensor or part of a sensor is integrated
- B01L2300/0645—Electrodes
-
- 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
- B01L2300/06—Auxiliary integrated devices, integrated components
- B01L2300/0681—Filter
-
- 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
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
- B01L2400/0415—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B81—MICROSTRUCTURAL TECHNOLOGY
- B81B—MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
- B81B2201/00—Specific applications of microelectromechanical systems
- B81B2201/05—Microfluidics
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B81—MICROSTRUCTURAL TECHNOLOGY
- B81B—MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
- B81B2203/00—Basic microelectromechanical structures
- B81B2203/03—Static structures
- B81B2203/0323—Grooves
- B81B2203/0338—Channels
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B81—MICROSTRUCTURAL TECHNOLOGY
- B81B—MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
- B81B2203/00—Basic microelectromechanical structures
- B81B2203/04—Electrodes
Abstract
Description
−第1のチャネル領域を備えた第1の検出器部および第2のチャネル領域を備えた第2の検出器部を提供するステップと、
−少なくとも1つの細孔を備えた膜を提供するステップと、
−第1のチャネル領域および第2のチャネル領域の少なくとも一部が膜によって分離され、第1のチャネル領域および第2のチャネル領域は、媒体が膜の少なくとも1つの細孔を通る流路を形成するために、互いに接続されて、チャネルシステムを形成するように、第1の検出器部および第2の検出器部を膜の両側に配置するステップと、を含み、
膜を通る流路に沿って、バイオレセプターを膜(例えば、細孔領域内に)上に形成して、流路に沿った流れを測定することによって媒体中の生体分子の濃度を決定する。
a)NH2−C6−CCGUCAGGUCACGGCAGCGAAGCUCUAGGCGCG
GCCAGUUGC−OH、
b)NH2−C6−TTTTTAATTAAAGCTCGCCATCAAATAGCTTT−OH、
c)NH2−C6−ACGCTCGGATGCCACTACAGGTTGGGGTCGGGCATGCGTCCGGAGAAGGGCAAACGAGAGGTCACCAGCACGTCCATGAG−OHのうちの1つのアプタマーでよい。
(i)NH2−C6−CCGUCAGGUCACGGCAGCGAAGCUCUAGGCGCG
GCCAGUUGC−OH、
(ii)NH2−C6−TTTTTAATTAAAGCTCGCCATCAAATAGCTTT−OH、
(iii)NH2−C6−ACGCTCGGATGCCACTACAGGTTGGGGTCGG
GCATGCGTCCGGAGAAGGGCAAACGAGAGGTCAC
CAGCACGTCCATGAG−OHのうちの少なくとも1つを含む。
−第1のチャネル領域を備えた第1の検出器部および第2のチャネル領域を備えた第2の検出器部を提供すること(S110)と、
−少なくとも1つの細孔を備えた膜を提供すること(S120)と、
−第1のチャネル領域および第2のチャネル領域の少なくとも一部は膜によって分離され、第1のチャネル領域および第2のチャネル領域は、媒体が膜の少なくとも1つの細孔を通る流路を形成するために、互いに接続されて、チャネルシステムを形成するように、第1の検出器部および第2の検出器部を膜の両側に配置すること(S130)と、を含む。
1.RNAアプタマー(参照:Jeong S、Han SR、Lee YJ、Lee SW, 2010,Selection of RNA aptamers specific to active prostate−specific antigen,Biotechnol Lett 32:379−385)配列(5’−3’):
NH2−C6−CCGUCAGGUCACGGCAGCGAAGCUCUAGGCGCGGCCAGUUGC−OH
2.DNA Aptamer−01(参照:Savory N、Abe K、Sode K、Ikebukuro K.2010,Selection of DNA aptamer against prostate specific antigen using a genetic algorithm and application to sensing,Biosens Bioelectron 26:1386−1391)配列(5’−3’):
NH2−C6−TTTTTAATTAAAGCTCGCCATCAAATAGCTTT−OH
3.DNAアプタマー−02(参照:Duan M、Long Y、Yang C、Wu X、Sun Y、Li J、Hu X、Lin W、Han D、Zhao Y、Liu J、Ye M、Tan W.2016,Selection and characterization of DNA aptamer for metastatic prostate cancer recognition and tissue imaging,Oncotarget 7:36436−36446)配列(5’−3’):
NH2−C6−ACGCTCGGATGCCACTACAGGTTGGGGTCGG
GCATGCGTCCGGAGAAGGGCAAACGAGAGGTCACCAGCACGTCCATGAG−OH。
−大/全表面細孔プラスチックフィルム120は、2つの流体チャネル215、225の間のラボオンチップシステムに統合される(例えば、バッチプロセスで)。
−フィルム120は、レーザー切断、電子写真法、またはエッチングにより、流体チャネル215、225の領域で除去される(右の図6L、6Mを参照)。
使用される細孔フィルム120は、再現可能な幾何学的形状を有する円錐状細孔110を含む。
−粘着層680は、細孔110を一体化することおよび細孔を機能不全にする(閉じる)ことの両方に役立つ。統計的に言えば、1つのみの細孔が電解質と接触できる。単孔プラスチックフィルム120の高感度は、複数孔プラスチックフィルムの助けにより達成される。
−細孔110の機能化は、チップ製造後に行われるが、機能化の前に行うこともできる。
−統合後のマルチポアプラスチックフィルム120の機能化には、少量のレセプター分子112のみが必要である。
−以前に機能化された細孔を統合することにより、細孔を汚染または詰まらせる可能性がある。
−新しいシステムは、Micro Total Analysis System(μTAS)に拡張される可能性を有する。これにより、複数のリガンド分子114の同時検出が可能になる。
−マイクロシステムの感度は、単細孔測定に匹敵する。
−従来の粘着層は液体UV粘着剤である。これは、細孔の目詰まりを引き起こすため、細孔または機能化細孔の統合には適していない。これらの従来の方法の助けを借りて、システムの不浸透性を保証することはできない。フィルムの機能化は、UV暴露によっても破壊される。これとは反対に、本発明の例示的な実施形態では、多孔質プラスチックフィルム120は熱的に一体化される(T=65℃で)。
−使用されるマルチポアプラスチックフィルムは、統合後と統合前の両方で機能化できる。この方法で100%の収率が達成された。
(i)細孔110を通る流量測定、
(ii)インピーダンス測定、
および(iii)界面動電測定(電気泳動、電気浸透など)。
−任意の種類の低分子有機および無機化合物
−環境毒素
−農薬
−ホルモン
−タンパク質
−抗生物質
−神経毒
−バクテリア
−ウイルス
−寄生虫。
50 媒体
110 細孔
112 バイオレセプター
114 生体分子
120 膜
125 検出範囲
130 流路
210、220 検出器部
215、225 チャネル地域
310、320 電圧特性
315 第1の電極
325 第2の電極
500A、500B 検出器領域
510 接続電極
520 電解質注入口
521 チャネル
530 分析物注入口
610 基板
620 フォトレジスト層
630 中間層(例えばクロム製)
640 電極層(例えば銀または金製)
660 粘着中間層
670 マスク層
680 粘着層
Claims (15)
- 媒体(50)中の生体分子(114)の検出システムを製造する方法であって、
第1のチャネル領域(215)を備えた第1の検出器部(210)および第2のチャネル領域(225)を備えた第2の検出器部(220)を提供するステップ(S110)と、
少なくとも1つの細孔(110)を備えた膜(120)を提供するステップ(S120)と、
前記第1のチャネル領域(215)および前記第2のチャネル領域(225)の少なくとも一部が前記膜(120)によって分離され、前記第1のチャネル領域(215)および前記第2のチャネル領域(225)は、前記媒体(50)が前記膜(120)の前記少なくとも1つの細孔(110)を通る流路(130)を形成するために、互いに接続されて、チャネルシステムを形成するように、前記第1の検出器部(210)および前記第2の検出器部(220)を前記膜(120)の両側に配置するステップ(S130)と、を含み、
前記膜を通る前記流路(130)に沿って、バイオレセプター(112)を前記膜(120)上に形成して、前記流路(130)に沿った流れを測定することによって前記媒体(50)中の前記生体分子(114)の濃度を決定する、方法。 - 前記配置ステップ(S130)が、
前記第1の検出器部(210)または前記第2の検出器部(220)上に前記膜(120)を配置することと、次いで
検出器領域(125)の外側の前記膜(120)の一部を除去することと、を含む、請求項1に記載の方法。 - 前記膜(120)と接触する粘着層(680)を形成することを更に含み、前記粘着層(680)は、前記細孔(110)の少なくとも数個を前記粘着層(680)によって閉じられるような様式で前記膜(120)と接触させ、それにより前記媒体(50)の流量測定のための前記細孔(110)の数を減らすことによって前記膜(120)の感度を上げる、請求項1または2に記載の方法。
- 機能化によって前記膜(120)に前記バイオレセプター(112)を付着させることを更に含み、前記機能化は、前記膜(120)の両側の前記第1の検出器部(210)および前記第2の検出器部(220)の前記配置の前または後に行われる、請求項1〜3のいずれか1項に記載の方法。
- 前記機能化は、少なくとも以下の機能化ステップ:
−アミン反応性中間体を得るためにカルボキシ末端基を活性化するステップと、
−前記膜(120)上に所望のバイオレセプター(112)を形成するために前記アミン反応性中間体をアミド化するステップと、を含み、
前記機能化が前記膜(120)のすべての領域で同じ様式で起こるか、あるいは、前記膜(120)が異なった生体分子(114)に感受性となるように、前記機能化中に、異なったバイオレセプター(112)が異なった領域内の前記細孔(110)で形成される、請求項4に記載の方法。 - 前記第1の検出器部(210)および/または前記第2の検出器部(220)上に前記膜(120)を積層することを更に含む、請求項1〜5のいずれか1項に記載の方法。
- 前記第1の検出器部(210)および前記第2の検出器部(220)が、少なくとも50℃または少なくとも65℃の温度での熱処理によって前記膜(120)の両側で互いに接続される、請求項1〜6のいずれか1項に記載の方法。
- 前記媒体(50)中の前記生体分子(114)の前記濃度が、以下の測定:(i)前記少なくとも1つの細孔(110)を通る流量測定、(ii)インピーダンス測定、および(iii)動電測定、特に電気泳動測定または電気浸透測定、のうちの少なくとも1つによって決定される、請求項1〜7のいずれか1項に記載の方法。
- 前記生体分子(114)が、前立腺特異的抗原(PSA)を含み、前記バイオレセプター(112)が、特に以下のアプタマー:
d)NH2−C6−CCGUCAGGUCACGGCAGCGAAGCUCUAGGCGCG
GCCAGUUGC−OH、
e)NH2−C6−TTTTTAATTAAAGCTCGCCATCAAATAGCTTT−OH、
f)NH2−C6−ACGCTCGGATGCCACTACAGGTTGGGGTCGGGCATGCGTCCGGAGAAGGGCAAACGAGAGGTCACCAGCACGTCCATGAG−OHのうちの1つであるアプタマーを含む、請求項1〜8のいずれか1項に記載の方法。 - 媒体(50)中の生体分子(114)のための検出システムであって、
前記媒体(50)を導入することができ、かつ、第1の電極(315)および第2の電極(325)を有する第1のチャネル領域(215)および第2のチャネル領域(225)と、
少なくとも1つの細孔(110)を含み、前記第1のチャネル領域(215)を前記第2のチャネル領域(225)から分離し、前記第1の電極(315)と前記第2の電極(325)との間に流動的に配置される、膜(120)と、を含み、
バイオレセプター(112)が前記細孔(110)上またはその中に形成され、特に以下のアプタマー:
(iv)NH2−C6−CCGUCAGGUCACGGCAGCGAAGCUCUAGGCGCGGCCAGUUGC−OH、
(v)NH2−C6−TTTTTAATTAAAGCTCGCCATCAAATAGCTTT−OH、
(vi)NH2−C6−ACGCTCGGATGCCACTACAGGTTGGGGTCGG
GCATGCGTCCGGAGAAGGGCAAACGAGAGGTCAC
CAGCACGTCCATGAG−OHのうちの1つを含み、
それによって、前記媒体(50)中のPSA濃度が、前記第1の電極(315)と前記第2の電極(325)との間の前記媒体(50)の流路(130)に沿った抵抗測定によって測定できる、検出システム。 - 前記膜(120)内の前記少なくとも1つの細孔(110)が前記流路(130)に沿ってテーパー状または円筒状のプロファイルを有する、請求項10に記載の検出システム。
- 異なった生体分子(114)の同時検出を可能にするために、異なった領域の前記膜が異なったレセプター(112)またはアプタマーを含む、請求項10または11に記載の検出システム。
- 前記第1のチャネル領域(215)および/または前記第2のチャネル領域(225)は、前記流路(130)に垂直な、最大1mmまたは最大50ミクロンもしくはせいぜい10ミクロンの最大チャネル幅を有する、請求項10〜12のいずれか1項に記載の検出システム。
- 検出に必要な媒体(50)の量を減らすために、媒体(50)を分析物注入口(530)に、また電解質を電解質注入口(520)に導入できるように、前記第2の電極(325)に前記電解質注入口(520)および前記第1の電極(315)に前記分析物注入口(530)を更に含む、請求項10〜13のいずれか1項に記載の検出システム。
- 前記電極(315)と前記第2の電極(325)との間の電気抵抗の関数である電気変数を測定することによって、媒体(50)中の生体分子(114)を検出するための、請求項10〜14のいずれか1項に記載の検出システムの使用。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE102017114349.1 | 2017-06-28 | ||
DE102017114349.1A DE102017114349A1 (de) | 2017-06-28 | 2017-06-28 | Detektionssystem und Verfahren zu dessen Herstellung |
PCT/EP2018/065542 WO2019001952A1 (de) | 2017-06-28 | 2018-06-12 | Detektionssystem und verfahren zu dessen herstellung |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2020525795A true JP2020525795A (ja) | 2020-08-27 |
JP2020525795A5 JP2020525795A5 (ja) | 2021-07-26 |
Family
ID=62620862
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2019572624A Pending JP2020525795A (ja) | 2017-06-28 | 2018-06-12 | 検出システムおよびその製造方法 |
Country Status (6)
Country | Link |
---|---|
US (1) | US20210114023A1 (ja) |
EP (1) | EP3646029B1 (ja) |
JP (1) | JP2020525795A (ja) |
CN (1) | CN111051885A (ja) |
DE (1) | DE102017114349A1 (ja) |
WO (1) | WO2019001952A1 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2024029557A1 (ja) * | 2022-08-02 | 2024-02-08 | テルモ株式会社 | 分離装置及び分離方法 |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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 |
CN114551952A (zh) * | 2021-12-31 | 2022-05-27 | 南开大学 | 一种超微型空气阴极的单室mfc反应器及制作方法 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6863833B1 (en) * | 2001-06-29 | 2005-03-08 | The Board Of Trustees Of The Leland Stanford Junior University | Microfabricated apertures for supporting bilayer lipid membranes |
US20080025875A1 (en) * | 2004-09-29 | 2008-01-31 | Martin Charles R | Chemical, Particle, and Biosensing with Nanotechnology |
WO2016181465A1 (ja) * | 2015-05-11 | 2016-11-17 | 株式会社日立製作所 | 分析デバイス及び分析方法 |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SE0203773D0 (sv) * | 2002-12-19 | 2002-12-19 | Capture Device Ab | Method and device for capturing charged molecules traveling in a flow stream |
CA2530607A1 (en) * | 2003-06-27 | 2005-04-07 | Purdue Research Foundation | Device for detecting biological and chemical particles |
US8592225B2 (en) * | 2006-09-28 | 2013-11-26 | The Board Of Trustees Of The Leland Stanford Junior University | Array-based bioactivated nanopore devices |
DE102007043132B4 (de) * | 2007-09-11 | 2012-07-26 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Biosensor und Verfahren zum Messen einer Konzentration eines Analyten in einem Medium |
KR101026468B1 (ko) * | 2008-09-10 | 2011-04-01 | 한국전자통신연구원 | 생분자 검출 장치 및 검출 방법 |
WO2010111605A2 (en) * | 2009-03-27 | 2010-09-30 | Nabsys, Inc. | Devices and methods for analyzing biomolecules and probes bound thereto |
EP2484630B1 (en) * | 2011-02-04 | 2019-11-06 | Ecole Polytechnique | A Method for detecting and quantifying charged molecules by using in situ stripping voltammetry and use of a nanosensor |
US9347929B2 (en) * | 2011-03-01 | 2016-05-24 | The Regents Of The University Of Michigan | Controlling translocation through nanopores with fluid wall |
DE102011112638B4 (de) * | 2011-09-05 | 2013-11-14 | Karlsruher Institut für Technologie | Mikrofluidischer Chip mit mikrofluidischem Kanalsystem |
DE102014209193B4 (de) * | 2014-05-15 | 2015-12-31 | Robert Bosch Gmbh | Mikrofluidische Vorrichtung zum Nachweisen von Zellen aus einem Fluid, Verfahren zum Betreiben einer solchen Vorrichtung und Verfahren zum Herstellen einer solchen Vorrichtung |
WO2015179712A1 (en) * | 2014-05-22 | 2015-11-26 | University Of Notre Dame Du Lac | Integrated membrane sensor for rapid molecular detection |
-
2017
- 2017-06-28 DE DE102017114349.1A patent/DE102017114349A1/de not_active Withdrawn
-
2018
- 2018-06-12 CN CN201880055872.4A patent/CN111051885A/zh active Pending
- 2018-06-12 WO PCT/EP2018/065542 patent/WO2019001952A1/de unknown
- 2018-06-12 US US16/627,181 patent/US20210114023A1/en not_active Abandoned
- 2018-06-12 EP EP18731411.7A patent/EP3646029B1/de active Active
- 2018-06-12 JP JP2019572624A patent/JP2020525795A/ja active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6863833B1 (en) * | 2001-06-29 | 2005-03-08 | The Board Of Trustees Of The Leland Stanford Junior University | Microfabricated apertures for supporting bilayer lipid membranes |
US20080025875A1 (en) * | 2004-09-29 | 2008-01-31 | Martin Charles R | Chemical, Particle, and Biosensing with Nanotechnology |
WO2016181465A1 (ja) * | 2015-05-11 | 2016-11-17 | 株式会社日立製作所 | 分析デバイス及び分析方法 |
Non-Patent Citations (3)
Title |
---|
MARIO EI KHOURY, ET AL.: "Integration of Nanochannels for Lab-on-Chip-Systems", MIKRO-NANO-INTEGRATION;6.GMM WORKSHOP DUISBURG 5-6 OCTOBER 2016, JPN6022019632, 2016, pages 175 - 178, ISSN: 0004947519 * |
NASA SAVORY ET AL.: "Selection of DNA aptamer against prostate specific antigen using a genetic algorithm and application", BIOSENSORS AND BIOELECTRONICS, vol. 26, JPN6022019633, 2010, pages 1386 - 1391, ISSN: 0004776933 * |
WOLFGANG ENSINGER: "Ion Conducting Nanopores for (Bio)molecular Sensing: the iNAPO Project", PROCEEDING OF THE 2ND WORLD CONGRESS ON NEW TECHNOLOGIES(NEW TECH'16), vol. ICNFA129-1~129-7, JPN6022019635, 18 August 2016 (2016-08-18), ISSN: 0004947520 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2024029557A1 (ja) * | 2022-08-02 | 2024-02-08 | テルモ株式会社 | 分離装置及び分離方法 |
Also Published As
Publication number | Publication date |
---|---|
CN111051885A (zh) | 2020-04-21 |
EP3646029A1 (de) | 2020-05-06 |
US20210114023A1 (en) | 2021-04-22 |
EP3646029B1 (de) | 2022-05-25 |
DE102017114349A1 (de) | 2019-01-03 |
WO2019001952A1 (de) | 2019-01-03 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
KR101709762B1 (ko) | 생체분자 농축 기능 일체형 센서 및 그 제조방법 | |
Tseng et al. | Recent advances in microfluidic paper-based assay devices for diagnosis of human diseases using saliva, tears and sweat samples | |
US7777476B2 (en) | Dynamic modulation for multiplexation of microfluidic and nanofluidic based biosensors | |
CN104203808B (zh) | 具有纳米结构电极的生物传感器 | |
US20200124625A1 (en) | Systems and methods for detecting a target analyte in a breath sample | |
JP2006516721A (ja) | 多孔質層上に試薬を含む複層化された電気化学系微小流体センサー | |
JP2009533658A (ja) | 最適化電流測定検出を用いる小型バイオセンサー | |
Lin et al. | Urine analysis in microfluidic devices | |
KR20120013316A (ko) | 분석물의 생물검정을 위한 일회용 마이크로유체 시험 카트리지 | |
JP2020525795A (ja) | 検出システムおよびその製造方法 | |
Borberg et al. | Light-controlled selective collection-and-release of biomolecules by an on-chip nanostructured device | |
Noh et al. | Biosensors in microfluidic chips | |
Liu et al. | Label-free specific detection of femtomolar cardiac troponin using an integrated nanoslit array fluidic diode | |
KR101218987B1 (ko) | 바이오칩 및 그 제조 방법, 이를 이용한 분석 대상 물질 검출 방법 | |
KR20110083460A (ko) | 전기습윤 기반의 유체 분석 장치 및 방법 | |
US20160178649A1 (en) | Method and system for sensing and detecting a target molecule | |
KR101770557B1 (ko) | 생체분자 농축 장치 | |
Tzouvadaki et al. | Large-scale nano-biosensing technologies | |
Kim et al. | Nanofluidic concentration of selectively extracted biomolecule analytes by microtubules | |
KR101789043B1 (ko) | 종이접기를 통한 생체 시료 농축 장치 | |
Vu-Dinh et al. | Enhanced immunoassay in a nanofluidic preconcentrator utilizing nano-interstices among self-assembled gold nanoparticles | |
KR101718951B1 (ko) | 생체 분자 농축 장치 및 그 제조방법 | |
KR101830758B1 (ko) | 시료 분리 장치 | |
US20220291211A1 (en) | Microfluidic microparticle-labeled impedance sensor array for enhancing bioassay sensitivity | |
El Khoury et al. | Integration of Nanochannels for Lab-on-Chip-Systems |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20210614 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20210614 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20220520 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20220527 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20221220 |