TW202204866A - 應用於生物表面檢測之裝置及方法 - Google Patents
應用於生物表面檢測之裝置及方法 Download PDFInfo
- Publication number
- TW202204866A TW202204866A TW109125374A TW109125374A TW202204866A TW 202204866 A TW202204866 A TW 202204866A TW 109125374 A TW109125374 A TW 109125374A TW 109125374 A TW109125374 A TW 109125374A TW 202204866 A TW202204866 A TW 202204866A
- Authority
- TW
- Taiwan
- Prior art keywords
- detection
- layer
- reaction
- channel units
- biocompatible
- Prior art date
Links
- 239000010410 layer Substances 0.000 title claims abstract description 36
- 238000000034 method Methods 0.000 title claims abstract description 23
- 239000002344 surface layer Substances 0.000 title claims abstract description 22
- 238000001514 detection method Methods 0.000 claims abstract description 79
- 210000001124 body fluid Anatomy 0.000 claims abstract description 31
- 239000010839 body fluid Substances 0.000 claims abstract description 30
- 239000000126 substance Substances 0.000 claims abstract description 26
- 239000000463 material Substances 0.000 claims abstract description 19
- 239000013076 target substance Substances 0.000 claims abstract description 15
- 230000036541 health Effects 0.000 claims abstract description 9
- 230000008859 change Effects 0.000 claims abstract description 8
- 201000010099 disease Diseases 0.000 claims abstract description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 8
- 239000000560 biocompatible material Substances 0.000 claims description 21
- 150000007523 nucleic acids Chemical group 0.000 claims description 16
- 102000004169 proteins and genes Human genes 0.000 claims description 13
- 108090000623 proteins and genes Proteins 0.000 claims description 13
- 108020004707 nucleic acids Proteins 0.000 claims description 12
- 102000039446 nucleic acids Human genes 0.000 claims description 12
- 230000002209 hydrophobic effect Effects 0.000 claims description 10
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 claims description 8
- 102000004190 Enzymes Human genes 0.000 claims description 8
- 108090000790 Enzymes Proteins 0.000 claims description 8
- 230000003321 amplification Effects 0.000 claims description 7
- 238000003199 nucleic acid amplification method Methods 0.000 claims description 7
- 108091023037 Aptamer Proteins 0.000 claims description 6
- 238000007894 restriction fragment length polymorphism technique Methods 0.000 claims description 6
- 238000012360 testing method Methods 0.000 claims description 6
- 102000034287 fluorescent proteins Human genes 0.000 claims description 5
- 108091006047 fluorescent proteins Proteins 0.000 claims description 5
- 239000000017 hydrogel Substances 0.000 claims description 5
- 239000000178 monomer Substances 0.000 claims description 5
- PSGCQDPCAWOCSH-UHFFFAOYSA-N (4,7,7-trimethyl-3-bicyclo[2.2.1]heptanyl) prop-2-enoate Chemical group C1CC2(C)C(OC(=O)C=C)CC1C2(C)C PSGCQDPCAWOCSH-UHFFFAOYSA-N 0.000 claims description 4
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 4
- MYWOJODOMFBVCB-UHFFFAOYSA-N 1,2,6-trimethylphenanthrene Chemical compound CC1=CC=C2C3=CC(C)=CC=C3C=CC2=C1C MYWOJODOMFBVCB-UHFFFAOYSA-N 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- 238000004458 analytical method Methods 0.000 claims description 4
- 230000003197 catalytic effect Effects 0.000 claims description 4
- 238000001962 electrophoresis Methods 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- 230000001404 mediated effect Effects 0.000 claims description 4
- 229920000642 polymer Polymers 0.000 claims description 4
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 claims description 4
- 238000001262 western blot Methods 0.000 claims description 4
- RHNJVKIVSXGYBD-UHFFFAOYSA-N 10-prop-2-enoyloxydecyl prop-2-enoate Chemical compound C=CC(=O)OCCCCCCCCCCOC(=O)C=C RHNJVKIVSXGYBD-UHFFFAOYSA-N 0.000 claims description 3
- 102000014914 Carrier Proteins Human genes 0.000 claims description 3
- 108020004414 DNA Proteins 0.000 claims description 3
- 102000053602 DNA Human genes 0.000 claims description 3
- 108010053770 Deoxyribonucleases Proteins 0.000 claims description 3
- 102000016911 Deoxyribonucleases Human genes 0.000 claims description 3
- 108091008324 binding proteins Proteins 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- 230000000704 physical effect Effects 0.000 claims description 3
- 239000000376 reactant Substances 0.000 claims description 3
- 238000002965 ELISA Methods 0.000 claims description 2
- 102000004895 Lipoproteins Human genes 0.000 claims description 2
- 108090001030 Lipoproteins Proteins 0.000 claims description 2
- 108091034117 Oligonucleotide Proteins 0.000 claims description 2
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 claims description 2
- 229930003427 Vitamin E Natural products 0.000 claims description 2
- 238000003556 assay Methods 0.000 claims description 2
- 238000004737 colorimetric analysis Methods 0.000 claims description 2
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims description 2
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 2
- 239000003547 immunosorbent Substances 0.000 claims description 2
- 238000004255 ion exchange chromatography Methods 0.000 claims description 2
- 239000002207 metabolite Substances 0.000 claims description 2
- 238000007481 next generation sequencing Methods 0.000 claims description 2
- 230000035945 sensitivity Effects 0.000 claims description 2
- 238000012163 sequencing technique Methods 0.000 claims description 2
- 229940046009 vitamin E Drugs 0.000 claims description 2
- 235000019165 vitamin E Nutrition 0.000 claims description 2
- 239000011709 vitamin E Substances 0.000 claims description 2
- 108091092878 Microsatellite Proteins 0.000 claims 2
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 claims 1
- 238000001179 sorption measurement Methods 0.000 claims 1
- -1 ester acrylate Chemical class 0.000 description 5
- 244000052616 bacterial pathogen Species 0.000 description 4
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 210000000416 exudates and transudate Anatomy 0.000 description 3
- 210000003141 lower extremity Anatomy 0.000 description 3
- 230000008961 swelling Effects 0.000 description 3
- HHEHWCIYDICHCG-ODZAUARKSA-N (z)-but-2-enedioic acid;methoxyethene Chemical compound COC=C.OC(=O)\C=C/C(O)=O HHEHWCIYDICHCG-ODZAUARKSA-N 0.000 description 2
- 206010007882 Cellulitis Diseases 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 239000012491 analyte Substances 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 229920000573 polyethylene Polymers 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 238000003752 polymerase chain reaction Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 229920002101 Chitin Polymers 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 102000018120 Recombinases Human genes 0.000 description 1
- 108010091086 Recombinases Proteins 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- HVVWZTWDBSEWIH-UHFFFAOYSA-N [2-(hydroxymethyl)-3-prop-2-enoyloxy-2-(prop-2-enoyloxymethyl)propyl] prop-2-enoate Chemical compound C=CC(=O)OCC(CO)(COC(=O)C=C)COC(=O)C=C HVVWZTWDBSEWIH-UHFFFAOYSA-N 0.000 description 1
- GUCYFKSBFREPBC-UHFFFAOYSA-N [phenyl-(2,4,6-trimethylbenzoyl)phosphoryl]-(2,4,6-trimethylphenyl)methanone Chemical compound CC1=CC(C)=CC(C)=C1C(=O)P(=O)(C=1C=CC=CC=1)C(=O)C1=C(C)C=C(C)C=C1C GUCYFKSBFREPBC-UHFFFAOYSA-N 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 125000005396 acrylic acid ester group Chemical group 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000005202 decontamination Methods 0.000 description 1
- 230000003588 decontaminative effect Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 210000003722 extracellular fluid Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 229910001425 magnesium ion Inorganic materials 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000011895 specific detection Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
- A61B5/6801—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be attached to or worn on the body surface
- A61B5/683—Means for maintaining contact with the body
- A61B5/6832—Means for maintaining contact with the body using adhesives
- A61B5/6833—Adhesive patches
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B10/00—Instruments for taking body samples for diagnostic purposes; Other methods or instruments for diagnosis, e.g. for vaccination diagnosis, sex determination or ovulation-period determination; Throat striking implements
- A61B10/0045—Devices for taking samples of body liquids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
- A61B5/14546—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue for measuring analytes not otherwise provided for, e.g. ions, cytochromes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
- A61B5/1468—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means
- A61B5/1477—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means non-invasive
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/48—Other medical applications
- A61B5/4866—Evaluating metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B10/00—Instruments for taking body samples for diagnostic purposes; Other methods or instruments for diagnosis, e.g. for vaccination diagnosis, sex determination or ovulation-period determination; Throat striking implements
- A61B2010/0003—Instruments for taking body samples for diagnostic purposes; Other methods or instruments for diagnosis, e.g. for vaccination diagnosis, sex determination or ovulation-period determination; Throat striking implements including means for analysis by an unskilled person
- A61B2010/0006—Instruments for taking body samples for diagnostic purposes; Other methods or instruments for diagnosis, e.g. for vaccination diagnosis, sex determination or ovulation-period determination; Throat striking implements including means for analysis by an unskilled person involving a colour change
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B10/00—Instruments for taking body samples for diagnostic purposes; Other methods or instruments for diagnosis, e.g. for vaccination diagnosis, sex determination or ovulation-period determination; Throat striking implements
- A61B10/0045—Devices for taking samples of body liquids
- A61B2010/008—Interstitial fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B2562/00—Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
- A61B2562/02—Details of sensors specially adapted for in-vivo measurements
- A61B2562/028—Microscale sensors, e.g. electromechanical sensors [MEMS]
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Physics & Mathematics (AREA)
- Medical Informatics (AREA)
- Surgery (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pathology (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Animal Behavior & Ethology (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Optics & Photonics (AREA)
- Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
一種應用於生物表面檢測之裝置及方法，所述檢測裝置為可撓性片體結構，具有接觸面層、通道單元及反應層，接觸面層設有檢測圓凸部，檢測圓凸部係為微米大小之凸起且為親膚材質，反應層內含檢測分子及反應單元，透過將可撓性片體結構直接貼附於生物體的表面，透過檢測圓凸部吸取體液，待體液經由通道單元主動吸附至反應層後，透過可分析物質之目標物質會與反應層內部的檢測分子及反應單元進行反應，並依據反應單元的變化達到判別生物體健康或疾病狀態，以達到檢驗生物表面之目的。
Description
本發明為一種檢測裝置及方法，尤指一種應用於生物表面檢測之裝置及方法，透過將可撓性片體結構直接貼附於生物體表面，透過檢測圓凸部之特殊結構設計，導引且收集生物體之體液至反應層，使體液中之目標物質被檢測，以及改變反應層之顏色或產生螢光。
在目前檢測生物體的健康狀態，以從血液為主要的體液檢測標的物，此方法侵入性高、被檢測生物體疼痛不適感、後續須檢驗流程繁瑣，須對血液做檢驗前處理，另外，針對生物體表面局部性的健康狀態如發炎、病毒感染、未知紅腫熱痛病兆等，血液其對此健康狀態的反應性較差。
為了解決上述問題，已有業者使用敷料接觸於生物體表面，待生物體皮膚滲出液之中分析物降解或代謝成揮發性有機物質，此物質可被其敷料內之感測器檢測而出；然而，已知的技術有所局限，舉例來說，習用技術係以被動收集來自生物體之液體，假如生物體不具有滲出液，則此技術無法發揮功能；另外，滲出液中的分析物必須代謝或降解成揮發性有機物質，習用技術無法直接針對分析物進行感測。
本發明揭露一種應用於生物表面檢測之裝置，包括一可撓性
片體結構，具有一接觸面層、複數通道單元及一反應層，該接觸面層與該反應層之間設置該等通道單元，該等通道單元內具有微米結構的生物相容性材質，該接觸面層設置複數檢測圓凸部，該等檢測圓凸部係為微米大小之凸起且使用親膚材質的生物相容性材質，該反應層內含檢測分子及反應單元。
本發明另外揭露一種應用於生物表面檢測之方法，步驟如下：
步驟1.將一可撓性片體結構之複數檢測圓凸部以適當壓力貼附於生物體表面，由該等檢測圓凸部主動收集生物體之體液，上述體液含有可分析物質；
步驟2.上述體液經由該等檢測圓凸部主動吸附至一接觸面層，接著再由複數通道單元吸附該接觸面層的體液至一反應層，該等通道單元內具有微米結構的生物相容性材質，可分析物質之目標物質會與該反應層內部的檢測分子及反應單元進行反應，並依據該反應單元產生的變化判別生物體健康或疾病狀態，以達到檢驗生物表面之目的。
藉由上述結構及方法，本發明之功效如下：
1、針對生物體表面狀態檢驗：本發明之該可撓性片體結構僅需要貼附於生物體表面，可直接吸取生物體的體液，達到以無疼痛感的方式進行檢測生物體健康或疾病狀態。
2、主動性收集體液：由於該等檢測圓凸部為微米大小的凸起，因此能直接扎進生物體的表面毛細孔中且不會感受到疼痛，而上述生物相容性材質具有吸水性，能直接吸收生物體的表面液體，達到主動收集
體液之目的。
3、可檢測非揮發性有機物質：由於該反應層內含該檢測分子及該反應單元，因此除了能檢測揮發性有機物質，也能檢測非揮發性有機物質。
4、檢驗結果判別明顯：由於該檢測分子會放大生物體體液內含目標物質的核酸片段，會與該反應單元結合並於該反應層之表面產生反應，因此可直接透過該反應層的顏色變化或螢光的產生，達到判別生物體健康或疾病狀態。
10:可撓性片體結構
12:接觸面層
122:檢測圓凸部
14:通道單元
16:反應層
S1:步驟1
S2:步驟2
〔圖1〕為本發明之立體示意圖
〔圖2〕為本發明之俯視圖
〔圖3〕為本發明之仰視圖
〔圖4〕為〔圖2〕之4-4剖面示意圖
〔圖5〕為本發明之檢測方法流程圖
〔圖6〕為本發明之實施例示意圖
參閱圖1~圖4，本發明揭露一種應用於生物表面檢測之裝置，為一可撓性片體結構10具有一接觸面層12、複數通道單元14及一反應層16，該接觸面層12與該反應層16之間設置該等通道單元14，該接觸面層12設置複數檢測圓凸部122，該等檢測圓凸部122係為微米大小之凸起且使用親膚材質的生物相容性材質，該反應層16內含檢測分子及反應單元；所
述檢測分子為特殊酶蛋白、脫氧核醣核酸、單股酸結合蛋白、針對反應物設計引子、聚合酶蛋白或寡聚核酸；所述反應單元為分子信標、顯色蛋白、螢光蛋白或電磁訊號；藉由上述結構，可直接透過該反應層16的顏色變化或螢光產生，達到判別生物體健康或疾病狀態，上述疾病狀態係指感染症、癌症或自體免疫疾病。
繼續參閱圖3及圖4，其中該等檢測圓凸部122之表面為介於100-500微米大小之凸起，該等檢測圓凸部122係使用親膚材質的生物相容性材質，上述生物相容性材質為多層聚合物，且可為疏水性材質或親水性材質組成，使其具有吸收液體之物理特性。
當上述生物相容性材質與皮膚接觸面為疏水性材質時，上述生物相容性材質所形成微米大小之凸起，具有微通道約30-80微米寬，可利用外環疏水性材質的特性，讓體液經由毛細管原理或微型泵浦進入到該等檢測圓凸部122，上述疏水性材質可由具生物相容性之丙烯酸酯單體(Acrylate)所聚合而成，由不同比例之丙烯酸異冰片酯(Isobornyl acrylate)、1,10-癸二醇二丙烯酸酯(1,10-decanediol diacrylate)、季戊四醇三丙烯酸酯(pentaerythritol tetraacrylate)或酯丙烯酸酯齊聚體(acrylate oligomer)所組成，上述之疏水性物質以丙烯酸酯單體聚合時，其為由季戊四醇三丙烯酸酯(pentaerythritol tetraacrylate)與酯丙烯酸酯齊聚體(acrylate oligomer)以特定比例2：1至1：1範圍聚合，酯丙烯酸酯齊聚體比例越高其聚合物的鍵結越強，相對硬度越高。
若上述生物相容性材質與皮膚接觸面為親水性材質時，上述生物相容性材質所形成微米大小之凸起，係由水凝膠所組成，本身即具有
吸附體液之物理特性，水凝膠可為由100：1~1：1的比例之親水性單體所聚合而成：例如，甲基乙烯基醚-馬來酸肝(10-12%)和聚乙二醇(4-7%)組成，以甲基乙烯基醚-馬來酸肝和聚乙二醇之水凝膠，其比例可為2：1至2.5：1之間；如聚乙烯醇(Polyvinyl alcohol)及幾丁質(Chitosan)組成，其比例可為100：1至50：50之間，幾丁質的比例越高，其孔洞性越高；又或者，聚乙二醇二丙烯酸酯(Polyethylen glycol diacrylate)和二酰基膦氧化物(Phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide)組成，其比例可為100：1至20：1之間。
參閱圖5，揭露一種應用於生物表面檢測之方法，步驟如下：
步驟1 S1.先將待測生物體表面進行簡單的清潔與去汙，之後將圖1~圖4所揭露之一可撓性片體結構10之複數檢測圓凸部122以適當壓力貼附於生物體表面，利用生物體表面接觸該等檢測圓凸部122之凸起設計，且該等檢測圓凸部122為微米大小之凸起及使用親膚材質的生物相容性材質，使得該等檢測圓凸部122能扎到生物體表面毛細孔中且不會感受到疼痛，因此可使該等檢測圓凸部122具有主動收集生物體之體液的能力，上述體液為組織間液或傷口滲出液，其內含有可分析物質；另外，當生物體表面有特定之生理狀況時，會有局部區域的熱腫脹現象，此生理現象會導致微觀局部壓力和溫度升高，將促使生物體之體液更快速由該等檢測圓凸部122進入該可撓性片體結構10的一接觸面層12。
步驟2 S2.上述體液經由該等檢測圓凸部122主動吸附至該接觸面層12，接著再由複數通道單元14吸附該接觸面層12的體液至一反應層16，該等通道單元14內具有微米結構的生物相容性材質，可分析物質之目標物質會與該反應層16內部的檢測分子及反應單元進行反應，並依據
上述反應單元的變化判別生物體健康或疾病狀態，以達到檢驗生物表面之目的，上述可分析物質之目標物質為蛋白質、核酸或代謝分子，所述反應單元為分子信標、顯色蛋白、螢光蛋白或電磁訊號。
其中，上述可分析物質之目標物質為核酸時，係透過恆溫核酸放大原理、聚合酶連鎖反應(Polymerase Chain Reaction,PCR)、直接定序法、次世代定序法、短縱列重複序列(Short tandem repeats,STR)、酵素性核酸調控放大(catalytic nucleic acids mediated amplification)或限制性片段長度多態性(Restriction fragment length polymorphism,RFLP)進行檢測。舉例來說，若透過恆溫核酸放大原理，在37℃~42℃的溫度條件下，該反應層16內含上述檢測分子及反應單元，上述檢測分子主要為利用檢測液中之特殊酶蛋白，此特殊酶蛋白包含具有生物聚合酶功能之酵素、與單股核酸結合功能之蛋白及能結合特定序列之重組酶，其能完成從辨識特定序列到放大核酸片段的功能，因此上述檢測分子會與引子去與體液中目標分析物之去氧核酸特定片段接近，放大上述目標物質之目標區域的核酸片段，並且會與上述反應單元結合並於該反應層16之表面產生顏色改變或產生螢光的反應。
上述檢測分子為特殊酶蛋白、脫氧核醣核酸、單股酸結合蛋白、針對反應物設計引子、聚合酶蛋白或寡聚核酸，因此能讓此檢測之感測具有廣泛性。
上述反應單元為分子信標、顯色蛋白、螢光蛋白或電磁訊號；若反應單元為分子信標，僅需要上述目標物質的核酸片段與分子信標結合，即可改變分子信標顏色；若反應單元為螢光蛋白，則係藉由特定波
長激發，可在一定時間內激發可見光。
其中，上述可分析物質之目標物質為蛋白質時，係透過專一性適體(aptamer)、DNA酶、十二烷基硫酸鈉聚丙烯醯胺凝膠電泳(SDS-PAGE)、西方墨點法(Western blot)或酵素結合免疫吸附分析法(ELISA)進行檢測。
其中上述可分析物質之目標物質為代謝分子時，係透過專一性適體(aptamer)、DNA酶、酵素分析法(pyruvate)、呈色法(colorimetric method TG)、高效能液相分析法(HPLC vitamin E)、離子交換層析法(ion exchange chromatography 24hr VAM)或電泳分析(electrophoresis lipoprotein)進行檢測。
另外，該等通道單元14內生物相容性材質的微米結構會吸附上述可分析物質內多餘的物質，多餘的物質為蛋白質、脂質、碳水化合物或鎂離子等，減少進入該反應層16內的非檢測目標，藉由調整生物相容性材質的組成比例，能改變該等通道單元14對體液主動吸附後所被吸附的物質，達到過濾不同的成分之功效，進而改變最終檢測敏感度及特異性。
參閱圖6並配合圖1~圖4，利用本發明檢測之裝置及方法，以無傷口蜂窩性組織炎之致病菌檢測為例，此實施例可檢測下肢蜂窩性組織炎常見菌種之金黃色葡萄球菌。首先，在懷疑下肢有組織發炎且無明顯外傷的患者皮膚表面，將患者下肢表面進行消毒及表面去汙，接著將該可撓性片體結構10貼附於患者下肢表面具有紅腫熱痛的區域，該接觸面層12的該等檢測圓凸部122會主動收集來自發炎區域的體液，在此過程中，患者不會感受到疼痛或不舒適，當上述體液經由該等檢測圓凸部122經由該等通
道單元14至該反應層16後，該反應層16內特定的檢測分子及反應單元會抓取是否具有特定的致病菌存在，若上述反應單元致使該反應層16表面顏色變化，則表示具有致病菌存在，反之則無致病菌存在。
需注意的是，上述實施例僅為例示性說明本發明之原理及其功效，而非用於限制本發明之範圍。任何熟於此項技術之人均可在不違背本發明之技術原理及精神下，對實施例作修改與變化。因此本發明之權利保護範圍應如後述之申請專利範圍所述。
10:可撓性片體結構
12:接觸面層
122:檢測圓凸部
14:通道單元
16:反應層
Claims (10)
- 一種應用於生物表面檢測之裝置，包括：一可撓性片體結構，具有一接觸面層、複數通道單元及一反應層，該接觸面層與該反應層之間設置該等通道單元，該等通道單元內具有微米結構的生物相容性材質，該接觸面層設置複數檢測圓凸部，該等檢測圓凸部係為微米大小之凸起且使用親膚材質的生物相容性材質，該反應層內含檢測分子及反應單元。
- 如請求項1之應用於生物表面檢測之裝置，其中所述微米大小範圍介於100-500微米，上述生物相容性材質為多層聚合物，且可為疏水性材質或親水性材質組成。
- 如請求項1之應用於生物表面檢測之裝置，其中所述檢測分子為特殊酶蛋白、脫氧核醣核酸、單股酸結合蛋白、針對反應物設計引子、聚合酶蛋白或寡聚核酸；所述反應單元為分子信標、顯色蛋白、螢光蛋白或電磁訊號。
- 一種應用於生物表面檢測之方法，步驟如下：步驟1.將請求項1所揭露之一可撓性片體結構之複數檢測圓凸部貼附於生物體表面，該等檢測圓凸部係為微米大小之凸起且使用親膚材質的生物相容性材質，由該等檢測圓凸部主動收集生物體之體液，上述體液含有可分析物質；步驟2.將體液經由該等檢測圓凸部主動吸附至一接觸面層，接著再由複數通道單元吸附該接觸面層的體液至一反應層，該等通道單元內具有微米結構的生物相容性材質，可分析物質之目標物質會與該反應層內部的檢測分子及反應單元進行反應，並依據該反應單元的變化判別生物體健康或疾病狀態，以達到檢驗生物表面之目的。
- 如請求項4之應用於生物表面檢測之方法，其中該等通道單元內生物相容性材質的微米結構會吸附上述可分析物質內多餘的物質，減少進入該反應層內的非檢測目標，藉由調整上述生物相容性材質的組成比例，能改變該等通道單元對體液主動吸附後所被吸附的物質，進而改變最終檢測敏感度及特異性，上述生物相容性材質為疏水性材質或親水性材質。
- 如請求項5之應用於生物表面檢測之方法，其中上述生物相容性材質為疏水性材質時，上述生物相容性材質所形成微米大小之凸起具有微通道約30-80微米寬，可利用外環疏水性材質的特性，讓體液進入到該等檢測圓凸部，上述疏水性材質可由具生物相容性之丙烯酸酯單體(Acrylate)所聚合而成，由不同比例之丙烯酸異冰片酯(Isobornyl acrylate)、1,10-癸二醇二丙烯酸酯(1,10-decanediol diacrylate)、季戊四醇三丙烯酸酯(pentaerythritol tetraacrylate)或酯丙烯酸酯齊聚體(acrylate oligomer)所組成。
- 如請求項5之應用於生物表面檢測之方法，其中上述生物相容性材質為親水性材質時係由水凝膠所組成，本身即具有吸附體液之物理特性，水凝膠可為由100：1~1：1的比例之親水性單體所聚合而成。
- 如請求項4之應用於生物表面檢測之方法，其中上述可分析物質之目標物質為蛋白質時，係透過專一性適體(aptamer)、DNA酶、十二烷基硫酸鈉聚丙烯醯胺凝膠電泳(SDS-PAGE)、西方墨點法(Western blot)或酵素結合免疫吸附分析法(ELISA)進行檢測。
- 如請求項4之應用於生物表面檢測之方法，其中上述可分析物質之目標物質為核酸時，係透過恆溫核酸放大原理、PCR、直接定序法、次世代定序法、短縱列重複序列(Short tandem repeats,STR)、酵素性核酸調控放大(catalytic nucleic acids mediated amplification)或限制性片段長度多態性(Restriction fragment length polymorphism,RFLP)進行檢測。
- 如請求項4之應用於生物表面檢測之方法，其中上述可分析物質之目標物質為代謝分子時，係透過專一性適體(aptamer)、DNA酶、酵素分析法(pyruvate)、呈色法(colorimetric method TG)、高效能液相分析法(HPLC vitamin E)、離子交換層析法(ion exchange chromatography 24hr VAM)或電泳分析(electrophoresis lipoprotein)進行檢測。
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TW109125374A TWI758797B (zh) | 2020-07-28 | 2020-07-28 | 應用於生物表面檢測之裝置及方法 |
| US17/245,873 US11903735B2 (en) | 2020-07-28 | 2021-04-30 | Apparatus of examining surface of an organism and method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TW109125374A TWI758797B (zh) | 2020-07-28 | 2020-07-28 | 應用於生物表面檢測之裝置及方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW202204866A true TW202204866A (zh) | 2022-02-01 |
| TWI758797B TWI758797B (zh) | 2022-03-21 |
Family
ID=80003923
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW109125374A TWI758797B (zh) | 2020-07-28 | 2020-07-28 | 應用於生物表面檢測之裝置及方法 |
Country Status (2)
| Country | Link |
|---|---|
| US (1) | US11903735B2 (zh) |
| TW (1) | TWI758797B (zh) |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6837988B2 (en) * | 2001-06-12 | 2005-01-04 | Lifescan, Inc. | Biological fluid sampling and analyte measurement devices and methods |
| NZ564141A (en) * | 2005-05-09 | 2011-02-25 | Theranos Inc | Two way communication system for monitoring an analyte |
| CA2760680A1 (en) * | 2008-05-23 | 2009-11-26 | The University Of Queensland | Analyte detection by microneedle patch with analyte selective reagents |
| US9193816B2 (en) * | 2011-11-30 | 2015-11-24 | Wisconsin Alumni Research Foundation | Infrared light- and thermal-responsive graphene oxide hydrogel polymer composites |
| CN104245745B (zh) * | 2012-02-09 | 2017-03-29 | 生命技术公司 | 亲水性聚合物颗粒及其制备方法 |
| US20130280696A1 (en) * | 2012-04-23 | 2013-10-24 | Elliott Millenson | Devices and methods for detecting analyte in bodily fluid |
| WO2016038224A1 (en) * | 2014-09-12 | 2016-03-17 | Vib Vzw | Biological sampling and storage container |
| EP3435941B1 (en) * | 2016-03-30 | 2021-09-01 | ConvaTec Technologies Inc. | Detecting microbial infections in wounds |
| US20210338195A1 (en) * | 2016-09-02 | 2021-11-04 | University Of Utah Research Foundation | Smart hydrogel pillar and film resonators for biomedical sensing and methods of fabrication |
| WO2018237094A1 (en) * | 2017-06-21 | 2018-12-27 | Eccrine Systems, Inc. | Biofluid sensing devices with ph-buffered eab sensors |
| EP3673269B1 (en) * | 2018-06-01 | 2023-10-25 | Colgate-Palmolive Company | Methods, devices and systems for quantifying biomarkers |
| EP3883471A2 (en) * | 2018-11-20 | 2021-09-29 | University of Cincinnati | Fluid sensors based on measuring a swellable volume |
-
2020
- 2020-07-28 TW TW109125374A patent/TWI758797B/zh active
-
2021
- 2021-04-30 US US17/245,873 patent/US11903735B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| TWI758797B (zh) | 2022-03-21 |
| US11903735B2 (en) | 2024-02-20 |
| US20220031247A1 (en) | 2022-02-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Herrmann et al. | Hydrogels and their role in biosensing applications | |
| US20230110577A1 (en) | Device For Detecting A Medical Condition Of A Subject And Method For Manufacturing Thereof | |
| Brown et al. | Wearable technology for chronic wound monitoring: current dressings, advancements, and future prospects | |
| US8986940B2 (en) | Detecting infection in reduced pressure wound treatment | |
| JP4727725B2 (ja) | 分子インプリントポリマー及び診断デバイスにおけるその使用 | |
| JP2020508689A (ja) | 皮膚試料の収集および分析のための非侵襲的な方法 | |
| JP7089294B2 (ja) | 創傷の状態の決定 | |
| WO2018071296A1 (en) | Point of care isothermal diagnostic | |
| TWI758797B (zh) | 應用於生物表面檢測之裝置及方法 | |
| Miao et al. | Interfacing hydrogel microneedle patch for diagnosis | |
| Qiao et al. | Monolith and coating enzymatic microreactors of L-asparaginase: kinetics study by MCE–LIF for potential application in acute lymphoblastic leukemia (ALL) treatment | |
| US20170172935A1 (en) | Applications and tools based on silica particles coated with biological or synthetic molecules | |
| KR20230081571A (ko) | 다중 성 매개 감염병 진단용 조성물을 포함하는 가정용 랩온페이퍼 진단 칩 | |
| Toole | The Development of Optical Biosensors for the detection of proteins in solution | |
| KR101941040B1 (ko) | 스트립 및 그 스트립의 제조방법 | |
| Choi et al. | Editorial for the Special Issue on Point-of-Care Devices | |
| Wang et al. | A novel flexible sensor for infected wound bacterial identification and on-demand treatment | |
| WO2018060711A1 (en) | Microbial sensing devices | |
| US20240188941A1 (en) | Apparatus for and method of obtaining a biological sample from a surface | |
| HK40082108A (zh) | 用於检测对象的医疗状况的装置及其制造方法 | |
| CN120192841A (zh) | 一种用于检测角膜病原体的系统及方法 | |
| KR20230038926A (ko) | 염 매개의 핵산 고정화 방법, 상기 방법에 따라 고정화된 포획 핵산을 포함하는 고형 지지체, 상기 고형 지지체를 포함하는 측방 유동 분석 스트립, 및 표적 핵산 검출 방법 | |
| HK1157446A (zh) | 檢測減壓傷口治療中的感染 |