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WO2002052260A2 - Biocapteur et son procede de production - Google Patents

Biocapteur et son procede de production Download PDF

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Publication number
WO2002052260A2
WO2002052260A2 PCT/EP2001/015225 EP0115225W WO02052260A2 WO 2002052260 A2 WO2002052260 A2 WO 2002052260A2 EP 0115225 W EP0115225 W EP 0115225W WO 02052260 A2 WO02052260 A2 WO 02052260A2
Authority
WO
WIPO (PCT)
Prior art keywords
layer
protective layer
biosensor
plasmon
hydrogel
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.)
Ceased
Application number
PCT/EP2001/015225
Other languages
German (de)
English (en)
Other versions
WO2002052260A3 (fr
WO2002052260A9 (fr
Inventor
Andreas Hofmann
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Jandratek GmbH
Original Assignee
Jandratek GmbH
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Jandratek GmbH filed Critical Jandratek GmbH
Priority to AU2002237253A priority Critical patent/AU2002237253A1/en
Publication of WO2002052260A2 publication Critical patent/WO2002052260A2/fr
Publication of WO2002052260A9 publication Critical patent/WO2002052260A9/fr
Publication of WO2002052260A3 publication Critical patent/WO2002052260A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—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

Definitions

  • the invention relates to a biosensor with a support, a plasmon-supporting layer arranged on the support made of a metal with free electrons or a semiconductor, an intermediate layer and an external hydrogel layer with the possibility of connecting receptors for the binding of analytes and the like Property to avoid unspecific adsorption.
  • Such a biosensor is e.g. known from DE 198 17 180 C2.
  • the biosensor whose hydrogel layer consists of a polymer, for example dextran, amose or celulose and whose receptors are formed, for example, by proteins (e.g. antibodies, antigens, membrane proteins), glycoproteins, nykleotids or DNA, to which an analyte ( Binding partner) can serve to detect certain molecules (in particular biomolecules) in a sample to be examined, for which purpose an optical plasmon resonance measurement is carried out.
  • proteins e.g. antibodies, antigens, membrane proteins
  • glycoproteins e.g. antibodies, antigens, membrane proteins
  • nykleotids or DNA to which an analyte ( Binding partner) can serve to detect certain molecules (in particular biomolecules) in a sample to be examined, for which purpose an optical plasmon resonance measurement is carried out.
  • a covalently bound organic compound predominantly sulfur compound
  • the plasmon-bearing noble metal layer in particular gold layer
  • the intermediate layer made of a polymer
  • a further linker is used to bind the hydrogel (main polymer).
  • the object of the invention is to create a biosensor which is comparatively simple to manufacture and which is insensitive to disturbing contamination of the plasmon-bearing layer.
  • the intermediate layer contains a protective layer covering the plasmone-bearing layer, which is physisorbed onto the plasmone-bearing layer and to which the hydrogel layer is connected.
  • the physisorption provided according to the invention makes chemical binding in the manner of a linker to the plasmon-carrying layer superfluous.
  • the physisorbed protective layer for example a very thin silicon oxide layer, protects the plasmon-bearing layer in an excellent manner against impurities, in particular in combination with the hydrogel layer it prevents the so-called unspecific adsorption. This result is already achieved with a thin protective layer of less than 10 nm, in particular less than 5 nm, which seals the plasmon-carrying layer, without this protective layer losing the physical effect relevant for the measurements.
  • the hydrogel layer can be more easily connected to the physisorbed protective layer and that known and proven coating methods can be adopted from other areas. Furthermore, when the plasmon-bearing noble metal layer is applied by vapor deposition or sputtering onto the carrier, the protective layer can also be applied in one step in a labor-saving manner.
  • the invention also relates to a method for producing the biosensor according to the invention, in which a plasmon-carrying layer is applied to a carrier, which is then covered with a hydrogel layer with the interposition of an intermediate layer.
  • this method is characterized in that after the plasmon-carrying layer has been applied to the intermediate layer, a protective layer is physisorbed, whereupon the hydrogel layer is attached to the intermediate layer.
  • FIGS. 3 and 4 the result of optical plasmon resonance measurements (detector response curves) with a biosensor according to FIG. 1 with a physisorbed protective layer (FIG. 4) and without such a protective layer ( Figure 3) show.
  • a plasmon-carrying layer 2 is arranged on a carrier 1, for example a glass prism, which can be a noble metal layer, in particular a gold layer, a silver layer or a semiconductor layer. Between the Carrier 1 and layer 2 can be provided with an adhesion promoter (not shown). As shown in FIG. 1, there is an intermediate layer 3 on layer 2.
  • An ultra-thin silicon monoxide was applied to layer 2 by means of an adhesion promoter, for example nickel / chromium, titanium, chromium, by means of thermal evaporation, sputtering, electron beam evaporation, sol gel technology or plasma polymerization Layer (Sio layer) of less than 5 nm thickness applied.
  • the SiO is oxidized to SiC> 2 in air and forms a protective layer 4 on the plasmon-carrying layer 2.
  • a hydrogel layer 6 e.g. Dextran, amylose or cellulose.
  • This hydrogel layer 6 can be provided with receptors 7 in a known manner, e.g. Proteins (e.g. antibodies, antigens, membrane proteins), glycoproteins, nucleotides, DNA, to which only the analytes to be detected, mainly biomolecules, attach, provided that they are in a sample to be applied to the hydrogel layer 6.
  • FIG. 2 shows a biosensor modified compared to FIG. 1, but which in the same way has a carrier 1, a plasmon-carrying layer 2 and a hydrogel layer 6 with receptors 7.
  • the intermediate layer 8 has a protective layer 9, for the formation of which a polymer, for example polyacrylic acid, was applied to the surface of the layer 2 by means of plasma polymerization.
  • the hydrogel layer 6 is attached to this polymer layer 9 serving as a protective layer by means of a linker 10.

Landscapes

  • Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Cell Biology (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)

Abstract

L'invention concerne un biocapteur comprenant un support (1) (prisme de verre), une couche (2) porteuse de plasmons, constituée d'une couche métallique à électrons libres, en particulier de l'or ou de l'argent, ou d'une couche semi-conductrice, et une couche d'hydrogel (6) constituée d'un polymère, en particulier du dextrane auquel des récepteurs (7) peuvent se lier. Ce biocapteur comprend en outre une couche de protection (4) composée d'oxyde de silicium ou d'un oxyde métallique, ou une couche de protection (9) composée d'un polymère et étant physisorbée sur la couche (2) porteuse de plasmons. La couche d'hydrogel (6) peut être liée par l'intermédiaire d'un lieur (5, 10) ; par exemple, si la couche de protection (4) est composée d'oxyde de silicium, le lieur (5) peut être du silane. La couche de protection (4) présente une épaisseur inférieure à 10 nm, de préférence inférieure à 5 nm, et protège efficacement la couche active (2) porteuse de plasmons contre des impuretés perturbatrices sans que l'effet optique physique produit par la résonance plasmonique de surface n'ait lieu à l'extérieur de la zone mesurable, de sorte que la fonction de biocapteur est préservée.
PCT/EP2001/015225 2000-12-22 2001-12-21 Biocapteur et son procede de production Ceased WO2002052260A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2002237253A AU2002237253A1 (en) 2000-12-22 2001-12-21 Biosensor and method of producing the same

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE2000164146 DE10064146A1 (de) 2000-12-22 2000-12-22 Biosensor und verfahren zu seiner Herstellung
DE10064146.6 2000-12-22

Publications (3)

Publication Number Publication Date
WO2002052260A2 true WO2002052260A2 (fr) 2002-07-04
WO2002052260A9 WO2002052260A9 (fr) 2002-09-19
WO2002052260A3 WO2002052260A3 (fr) 2002-11-14

Family

ID=7668367

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2001/015225 Ceased WO2002052260A2 (fr) 2000-12-22 2001-12-21 Biocapteur et son procede de production

Country Status (3)

Country Link
AU (1) AU2002237253A1 (fr)
DE (1) DE10064146A1 (fr)
WO (1) WO2002052260A2 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1724584A1 (fr) * 2005-05-19 2006-11-22 Agilent Technologies, Inc. Capteur d'onde évanescente avec un ligand attaché
EP1953553A3 (fr) * 2007-02-01 2008-08-13 FUJIFILM Corporation Substrat de biocapteur
US7463358B2 (en) * 2005-12-06 2008-12-09 Lumera Corporation Highly stable surface plasmon resonance plates, microarrays, and methods
EP2042609A1 (fr) * 2007-09-26 2009-04-01 Fujifilm Corporation Biocapteur
WO2010139869A1 (fr) 2009-06-05 2010-12-09 Ecole Polytechnique / Dgar Utilisation d'une couche de silicium amorphe et procédés d'analyse

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2004061211A (ja) * 2002-07-26 2004-02-26 Shimadzu Corp 蛍光検出方法及び装置
WO2007061981A2 (fr) 2005-11-21 2007-05-31 Lumera Corporation Detecteur a resonance de plasmon en surface avec mecanisme de balayage d’angle entraine par actionneur
US8004669B1 (en) 2007-12-18 2011-08-23 Plexera Llc SPR apparatus with a high performance fluid delivery system

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB8618133D0 (en) * 1986-07-24 1986-09-03 Pa Consulting Services Biosensors
GB8705650D0 (en) * 1987-03-10 1987-04-15 Pa Consulting Services Assay technique
DE19805809C2 (de) * 1998-02-12 2000-02-17 Biotul Bio Instr Gmbh Bestimmung der Oberflächenplasmonen-Resonanz mit Hilfe von örtlich oder zeitlich modifizierten Schichten
JP2000039401A (ja) * 1998-03-24 2000-02-08 Dainippon Printing Co Ltd 表面プラズモン共鳴バイオセンサ―用測定セル及びその製造方法
DE19853428A1 (de) * 1998-11-19 2000-05-25 Biotul Bio Instr Gmbh Biosensor mit modifizierter Edelmetalloberfläche und Verfahren zu seiner Herstellung
DE19817180C2 (de) * 1998-04-17 2000-04-27 Biotul Bio Instr Gmbh Biosensor mit modifizierter Edelmetalloberfläche und Verfahren zu seiner Herstellung
DE19818360C2 (de) * 1998-04-24 2000-05-31 Suisse Electronique Microtech Dextranbeschichtete Oberfläche

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1724584A1 (fr) * 2005-05-19 2006-11-22 Agilent Technologies, Inc. Capteur d'onde évanescente avec un ligand attaché
US7463358B2 (en) * 2005-12-06 2008-12-09 Lumera Corporation Highly stable surface plasmon resonance plates, microarrays, and methods
EP1953553A3 (fr) * 2007-02-01 2008-08-13 FUJIFILM Corporation Substrat de biocapteur
EP2042609A1 (fr) * 2007-09-26 2009-04-01 Fujifilm Corporation Biocapteur
WO2010139869A1 (fr) 2009-06-05 2010-12-09 Ecole Polytechnique / Dgar Utilisation d'une couche de silicium amorphe et procédés d'analyse

Also Published As

Publication number Publication date
DE10064146A1 (de) 2002-07-04
WO2002052260A3 (fr) 2002-11-14
WO2002052260A9 (fr) 2002-09-19
AU2002237253A1 (en) 2002-07-08

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