EP1190253A1 - Biocapteurs utilisant des polymeres conjugues a charge neutre - Google Patents

Biocapteurs utilisant des polymeres conjugues a charge neutre

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Publication number
EP1190253A1
EP1190253A1 EP00939709A EP00939709A EP1190253A1 EP 1190253 A1 EP1190253 A1 EP 1190253A1 EP 00939709 A EP00939709 A EP 00939709A EP 00939709 A EP00939709 A EP 00939709A EP 1190253 A1 EP1190253 A1 EP 1190253A1
Authority
EP
European Patent Office
Prior art keywords
conjugated polymer
biomolecule
neutral conjugated
charge neutral
electrodes
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.)
Withdrawn
Application number
EP00939709A
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German (de)
English (en)
Inventor
Changming Li
Song Shi
Vi-En Choong
George Maracas
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.)
Motorola Solutions Inc
Original Assignee
Motorola Inc
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 Motorola Inc filed Critical Motorola Inc
Publication of EP1190253A1 publication Critical patent/EP1190253A1/fr
Withdrawn legal-status Critical Current

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—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
    • 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
    • C12Q1/6813—Hybridisation assays
    • C12Q1/6816—Hybridisation assays characterised by the detection means
    • C12Q1/6825—Nucleic acid detection involving sensors
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B01J2219/00612—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports the surface being inorganic
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B01J2219/00614—Delimitation of the attachment areas
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B01J2219/00623—Immobilisation or binding
    • B01J2219/00626—Covalent
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B01J2219/00632—Introduction of reactive groups to the surface
    • B01J2219/00637—Introduction of reactive groups to the surface by coating it with another layer
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00653—Making arrays on substantially continuous surfaces the compounds being bound to electrodes embedded in or on the solid supports
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00659—Two-dimensional arrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00709—Type of synthesis
    • B01J2219/00713—Electrochemical synthesis
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/0072—Organic compounds

Definitions

  • the invention is in the field of arrays of sensing electrodes on a chip for conducting analysis of biological substances such as DNA.
  • a device for biomolecule detection is generally comprised of supporting matrix for probe molecule attachment or entrapment, a sensing probe located on/in the supporting matrix.
  • a complementary biomolecule target or analyte
  • the biosensing device When exposed to a complementary biomolecule target (or analyte), the biosensing device produces detectable change in radioactive, optical, or electrical signal to confirm the existence of a specific biomolecule target.
  • the biomolecule target to be detected needs to be labeled with a marker (or reporter) such as 32 P, fluorescent dye, or redox, depending on whether the detection means is autoradiography, fluorescent microscope or electric tools.
  • An alternative biosensing device includes a second reporting molecule.
  • the second reporting molecule is introduced after the probe molecule has interacted with its complementary biomolecule target. Like the probe molecule, the second reporting molecule also interacts with the biomolecule target by either binding to the target or forming a complex.
  • Lavache, et al Analytical Biochemistry 258, 188-194 describes an oligonucleotide array constructed on a silicon chip having a matrix of addressable microelectrodes. Each electrode is coated with polypyrrole copolymer where some of the pyrroles in the copolymer have an oligonucleotide bound to the pyrrole.
  • the polymers are made by electrochemical techniques. This copolymer is deposited on microelectrodes. Hepatistis C genotypes were detected by hybridization of the probe DNA on the electrode to test sample DNA which was PCR amplified to contain a fluorescent marker group.
  • WO 95/29199 describes functionalized polypyrrole copolymers where the functional groups are designed to bind biological molecules such as DNA or polypeptides.
  • US Patent 5,837,859 assigned to Cis Bio International describes the preparation of electrically conductive pyrrole/nucleotide/derivatized/pyrrole copolymers useful for nucleic acid synthesis, sequencing and hybridization. The copolymers are produced electrochemically and coated on microelectrodes for DNA analysis.
  • US Patent 5,202,261 describes conductive sensors and their use in diagnostic assays.
  • US Patent 5,403,451 describes the detecting of a target analyte with conductive polymer coupled with periodic alternating voltage.
  • the target DNA is usually labeled with a marker (or reporter) such as 32 P, fluorescent dye, or redox.
  • a marker such as 32 P, fluorescent dye, or redox.
  • a radioactive signal or fluorescence, or electric signal is detected.
  • fluorescent or redox labeling is preferred due to the stringent experiment conditions required for radioactive labeling.
  • fluorescent dyes in the vicinity of conductive polymers or copolymers are subject to signal quenching.
  • conductive polymers or copolymers contribute to significant background noise when used for redox labeled target detection.
  • the invention is directed to a method of detecting biological molecule
  • biomolecule such as DNA, RNA and polypeptides with the aid of a neutralized conjugated polymer or copolymer on electrodes.
  • the present invention makes use of a functionalized polymer or copolymer in its neutral state, instead of conductive state as the supporting matrix for biomolecule probe attachment or entrapment in a biomolecule detection device.
  • aromatic monomers and functionalized aromatic monomers are electrochemically polymerized and deposited on an electrode surface to generate a functionalized polymer or copolymer.
  • the as-deposited conjugated polymer or copolymer is in a charged, conductive state.
  • the charged, functionalized polymer or copolymer is electrochemically reduced to a neutral state to form (charge neutral conjugated polymer) before it is used in any biomolecule detection.
  • the charge neutral functionalized polymer or copolymer has low electric background when used in electric detection of biomolecules. It also does not quench fluorescent signal when used in fluorescent detection of biomolecules. In both cases, the resulting devices have significantly improved signal to noise ratio, thus enhancing the sensitivity of biomolecule detection.
  • the invention includes a charge neutral conjugated polymer which have functional groups for binding biomolecule probes to the polmyer.
  • the invention includes electrodes in electrical communication with such polmyers, arrays of such electrodes.
  • the invention includes biosensors which a biomolecule probe is covalently linked to the functional group of the charge neutral conjugated polymer on electrode and a binding of a biomolecule to be detected is measured by an electrical detection means, such as AC impedence.
  • Figure 1 represents a schematic diagram for preparing the array of polypyrrole coated electrodes and detecting by AC impedance.
  • Figure 2 illustrates polypyrrole copolymer formulation
  • FIG. 3 illustrates the electrochemically reduced neutral polypyrrole copolymer.
  • Figure 4 illustrates the relationship of capacitance vs. frequency on oxidized polypyrrole-based electrodes with and without DNA Attachment.
  • Figure 5 illustrates the relationship of capacitance vs. frequency on neutral polypyrrole-based electrode with and without DNA attachment.
  • Figure 6 illustrates the comparison of response of capacitance vs. frequency between oxidized and neutralized polypyrrole-based electrodes with DNA attachment.
  • Figure 7 AC impedance planes measured in perfect match hybridized DNA and single stranded DNA system.
  • Figure 8 is a Frequency Complex diagram obtained from neutralized polypyrrole Electrodes.
  • Figure 9 is impedance planes measured in 3-bas mismatch hybridized DNA and single stranded DNA systems.
  • Figure 10 is a plot of Resistance vs. ⁇ "1 ' 2 for AC impedance measured in 3- base mismatch hybridized DNA and single stranded DNA systems.
  • the invention is directed to a method of detecting biological molecule with the aid of a charge neutral conjugated polymer on electrodes.
  • Charge neutral conjugated polymer is meant a polymer with zero charge (negative or positive) on its backbone, yet with delocalized pi electron on its backbone.
  • a conjugated polymer is characterized by its backbone with regular alternation of single and double chemical bonds. Examples of conjugated polymers include: polypyrrole, polyphenylene, polyacetylene, polydiacetylene, polythiophene, polyfuran, polyaniline, polycarbazole, poly(phenylene vinyl ene). More specifically, the invention encompasses a charge neutral conjugated polymers containing one or more functional groups capable of binding a probe molecule.
  • the as-deposited conjugated polymer or copolymer is conductive and is usually in its charged state with its charge being balanced by counter ions from the polymerization solution.
  • the charged state is the source of signal quenching for nearby fluorescent markers as in the case of fluorescence detection. It is also the source of noise for electric detection.
  • the polymer or copolymer deposited on the electrode used in present invention is reduced to its charge-neutral state from the as-deposited charged state by reverse biasing right after the polymer or copolymer is initially deposited on the surface electrodes.
  • the polymer or copolymer in its neutral state is an insulator or semiconductor, which does not quench fluorescence of nearby fluorescent markers in fluorescence detection and also give rise to only limited background noise in electric detection of biomolecule target.
  • the functional group used in present invention includes, but not limited to, amine, hydrazine, ester, amide, carboxylate, halide, hydroxyl, vinyl, vinyl carboxylate, thiol, phosphate, silicon containing organic compounds, and their derivatives.
  • the functional group is used to bind biomolecule probes such as DNA, RNA, peptides, polypeptides, proteins, antibody, antigen and hormones to the polymer or copolymer on the electrode.
  • biomolecule probes such as DNA, RNA, peptides, polypeptides, proteins, antibody, antigen and hormones
  • an oligonucleotide which is in part complementary to a target DNA is covalently linked to a neutral polypyrrol copolymer through an amine functional group.
  • the electrode used in the present invention is made of at least one of the following materials: metals such as gold, silver, platinum, copper, and alloys; conductive metal oxide such as indium oxide, indium-tin oxide, zinc oxide; other conductive materials such carbon black, conductive epoxy and combinations thereof.
  • the preferred sensing method in this embodiment is electric or electrochemical methods. After exposure to a target molecule, the biosensor senses a change in electric signal, and reports the change by a readout means such as display, printout.
  • the electric or/and electrochemical methods may be selected from, but are not limited to, AC impedance, cyclic voltammetry (CV), pulse voltammetry, square wave voltammetry, AC voltammetry (ACV), hydrodynamic modulation voltammetry, potential step method, potentiometric measurements, amperometric measurements, current step method, and combinations thereof. It is more advantageous to detect a biomolecule target without the need of labeling the target.
  • Present invention provides a highly sensitive method for detection of biomolecule target without the need of labeling the target.
  • biomolecules are electrically active and may produce undesired background noise when a detection is performed by passing charge through those biomolecules.
  • guanine and adenine can be oxidized around 0.75 V and
  • the invention includes a method for determining an analyte in a test sample comprising: (a) depositing a polymer or copolymer film on an electrode by electrochemically polymerizing an aromatic monomer and a monomer with functional group in a solution via a positive bias with supporting electrolyte;
  • the biosensor may include an array of electrodes in electrical contact with a matrix of charge neutral conjugated polymer having different sensing probes for sensing multiple biomolecule targets. It is also within the scope of the present invention to fabricate a high density biosensor with column and row addressable electrodes coated with thousands of sensing probes for screening applications. In the case of a high density array, it is more practical to place various biomolecule probes on each electrode with a robotic tool.
  • the invention is illustrated by neutral polypyrrole conjugated polymer electrode arrays used in conjunction with AC impedance detecting methods.
  • the process to make such arrays is schematically shown in Fig. 1.
  • the chips J_0 are made by microelectric technology on a silicon support j_l.
  • the probe arrays 05 and electrodes J_6 are made of inert metals such as gold or platinum.
  • Polypyrrole J_2, with DNA linking group J_3 is electrochemically deposited on the probe array J_4 in 0.1 M pyrrole + 5 ⁇ M 3-acetate N-hydroxysuaccinimido pyrrole + 0.1 M LiCIO /acetonitrile (0/5% water). Then the polypyrrole-film is electrochemically neutralized 17.
  • every probe can be sequentially attached to a different oligonucleotide 18 ODNl and ODN2.
  • AC impedance analyzer 20 is used to detect the impedance change for a specific DNA sequence 2L
  • the biomolecule probe can also be attached to the aromatic functional monomer before it is electrochemically polymerized with aromatic monomer to yield a conjugated polymer.
  • Electrode surface was polished by gamma alumina powder (CH Instruments, Inc.) with 0.3 and 0.005 ⁇ m in sequence followed by deionized water washing. After polishing, the electrodes were immersed in 1 M HsSO for 20 minutes and then vigorously washed by DI water. CH 660 potentiostat was used for polypyrrole deposition. Platinum wire and
  • the electrolyte was purged by nitrogen gas during whole electrochemical deposition.
  • the deposited polypyrrole film with the linking function group was uniform and blue in color.
  • the polypyrrole film is in oxidized form (charged conductive state).
  • the electrode was placed in the electrolyte again and cycled over a potential range of -0.2 to 0.3 vs Ag/AgCl, which is the reduction zone for this electrochemical system.
  • the neutralization of the polypyrrole film is illustrated in Figure 3.
  • the neutralized polypyrrole film coated electrodes were vigorously washed for probe oligonucleotide attachment.
  • the oligonucleotide CCC TCA AGC AGA with a terminal amino group on it s 5'-phosphorylated position was used.
  • the oxidized polypyrrole film was modified by oligonucleotide in the same procedure mentioned above.
  • Fig. 4 shows the capacitance changes of the electrode surface vs. frequency, indicating that the oxidized polypyrrole-based electrode surface with oligonucleotide attachment has larger capacitance response than the surface without oligonucleotide attachment at the low frequency range. However, the ratio of signal to noise is not great.
  • Fig. 5 demonstrates that the capacitance of neutralized polypyrrole-based electrode surface with oligonucleotide attachment is significantly greater than that of the surface without oligonucleotide attachment.
  • Fig. 6 shows that the capacitance on the neutralized polypyrrol-based electrode surface with oligonucleotide attachment is greater than that of oxidized polypyrrole-based surface by about 4 times.
  • the neutralized polypyrrole film coated electrodes were vigorously washed for
  • the oligonucleotide CCC TCA AGC AGA with a terminal amino group on its 5'- phosphorylated position was used as an example.
  • the microelectrode was washed with DI water thoroughly before a baseline AC impedance was measured.
  • the probe attached to polypyrrole on a microelectrode was exposed to 35 uL of target molecule of different concentration
  • the counter and reference electrodes were platinum and Ag/AgCl, respectively.
  • OCV open circuit voltage
  • the measured complex impedance versus frequency is shown in Fig. 8 for single and hybridized DNA, indicating significant difference of the impedance before and after hybridization.
  • this type of electrodes can detect 0.1 amol of target DNA in solution due to the neutralized form of polyrrole film.
  • This invention can be used in any solution containing metal or polymerized cations, which are ion-conductive and can react with DNA.
  • the above examples are intended to illustrate the present invention and not to limit it in spirit or scope.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Organic Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Urology & Nephrology (AREA)
  • Hematology (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Physics & Mathematics (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biomedical Technology (AREA)
  • Cell Biology (AREA)
  • General Engineering & Computer Science (AREA)
  • Pathology (AREA)
  • General Physics & Mathematics (AREA)
  • Medicinal Chemistry (AREA)
  • Food Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Investigating Or Analyzing Materials By The Use Of Electric Means (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Polyoxymethylene Polymers And Polymers With Carbon-To-Carbon Bonds (AREA)
  • Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
  • Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

La présente invention concerne un polymère conjugué à charge neutre ou des copolymères qui possèdent un groupe fonctionnel permettant la liaison d'une sonde biomoléculaire. Cette invention concerne aussi des électrodes et un réseau d'électrodes en contact électrique avec ces polymères, et une sonde biomoléculaire est liée de façon covalente au polymère. Cette invention comprend des biocapteurs qui utilisent les électrodes revêtues du polymère conjugué, et la liaison de la sonde biomoléculaire est détectée par une composante électrique telle qu'une impédance relative au courant alternatif.
EP00939709A 1999-06-10 2000-06-09 Biocapteurs utilisant des polymeres conjugues a charge neutre Withdrawn EP1190253A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US13843799P 1999-06-10 1999-06-10
US138437P 1999-06-10
PCT/US2000/015832 WO2000077523A1 (fr) 1999-06-10 2000-06-09 Biocapteurs utilisant des polymeres conjugues a charge neutre

Publications (1)

Publication Number Publication Date
EP1190253A1 true EP1190253A1 (fr) 2002-03-27

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EP (1) EP1190253A1 (fr)
JP (1) JP2003508730A (fr)
AU (1) AU776997B2 (fr)
CA (1) CA2376532A1 (fr)
WO (1) WO2000077523A1 (fr)

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AU776997B2 (en) 2004-09-30
WO2000077523A1 (fr) 2000-12-21

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