WO1995016206A1 - Composition et procede servant a detecter des analytes - Google Patents

Composition et procede servant a detecter des analytes Download PDF

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Publication number
WO1995016206A1
WO1995016206A1 PCT/US1994/014094 US9414094W WO9516206A1 WO 1995016206 A1 WO1995016206 A1 WO 1995016206A1 US 9414094 W US9414094 W US 9414094W WO 9516206 A1 WO9516206 A1 WO 9516206A1
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WO
WIPO (PCT)
Prior art keywords
binding
analyte
channel
membrane
proteins
Prior art date
Application number
PCT/US1994/014094
Other languages
English (en)
Inventor
Stephen J. Kennedy
Original Assignee
Biosystems Technology Corporation
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 Biosystems Technology Corporation filed Critical Biosystems Technology Corporation
Priority to JP7516329A priority Critical patent/JPH09509481A/ja
Priority to EP95904843A priority patent/EP0733209A1/fr
Publication of WO1995016206A1 publication Critical patent/WO1995016206A1/fr

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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

Definitions

  • binding agents are labeled with an electron transfer mediator, such as ferrocene. Complexation enhances or interferes with a redox reaction taking place at the surface of the electrode.
  • an electron transfer mediator such as ferrocene.
  • Complexation enhances or interferes with a redox reaction taking place at the surface of the electrode.
  • binding agents and analyte analogs are connected together and bound to a sensing surface.
  • receptors transduce the binding of specific ligand into an increase in enzyme activity or the activation of a secondary molecule such as a G protein. What is needed is a means to provide membrane bound receptors with functional binding diversity as great as that of antibodies, and means for coupling the response of receptors to changes in the activity of other agents to produce a measurable signal.
  • the binding element can also be a naturally occurring protein that functions as a receptor for molecules such as hormones, growth factors, cytokines, neurotransmitters, odorants, vitamins, antibodies, bacteria, viruses, serum lipoproteins, other proteins, toxins, or binding agent-ligand pairs such as antibody-antigen complexes, carbohydrate-lectin complexes, and complexes of metal-binding molecules with metal ions.
  • molecules such as hormones, growth factors, cytokines, neurotransmitters, odorants, vitamins, antibodies, bacteria, viruses, serum lipoproteins, other proteins, toxins, or binding agent-ligand pairs such as antibody-antigen complexes, carbohydrate-lectin complexes, and complexes of metal-binding molecules with metal ions.
  • the signaling element can also be a member of the naturally occurring group of voltage-gated ion channel proteins or a member of the naturally occurring group of ligand-gated ion channel proteins.
  • the signaling element can also be a genetically engineered member ofthe superfamily of voltage-gated ion channel proteins, or the superfamily of ligand-gated ion channel proteins.
  • the genetically engineered feature of the channel is an alteration of the naturally occurring form. This may be a change in the type of ion which traverses the channel, a change in the voltage- dependence or gating kinetics of the channel, the addition, deletion, or modification of a channel blocking region or domain, a change in the number of protein domains or subunits associated to form the channel, a change in the types of protein domains or subunits associated to form the channel, or a change in other aspects of the protein domains or subunits associated to form the channel.
  • the membrane is selected from a group consisting of lipid bilayers and lipid monolayers. The lipid membrane can optionally be crosslinked, and may contain molecules other than lipids.
  • One object of the present invention is to provide membrane bound receptors with functional binding diversity as great as that of antibodies.
  • composition of the present invention can be used to provide an assay system to accurately measure analytes in a fluid.
  • the fluid can be a mixture such as blood, serum or other bodily fluids.
  • the present invention can be used to monitor changes in the concentrations of analytes in a sample as a diagnostic determinant, over the course of a disease, during surgical procedures, or over the course of treatment.
  • the present invention can be used to detect the presence and/or determine the amount of infectious agents, hormones, drugs, metabolites, or other chemicals in diagnostic samples from humans, animals, or other organisms.
  • the present invention can be used to screen candidate pharmaceutical compounds in the search for new drugs and therapeutic agents.
  • Figure 3 is a schematic cross sectional representation of a typical voltage-gated ion channel.
  • Figure 4 is a schematic representation of univalent binding elements interacting with the specific analyte to form a dimer and trigger the signal element.
  • Figure 5 is a schematic representation ofthe normal functioning of a voltage-gated ion channel. The open, closed and inactivated stages are illustrated.
  • Figure 6 is a schematic representation of binding of an analyte to inhibit the inactivation stage of the voltage-gated ion channel.
  • Figure 7 is a schematic representation of the inhibition ofthe functioning of the ion channel by an attached toxin molecule. With the addition of a specific binding element, the presence of an analyte prevents the inhibition by the attached toxin molecule.
  • Figure 8 is a schematic representation of the support structure for the lipid membrane.
  • the immunoglobin superfamily includes, but is not limited to, antibodies including all classes of antibodies including, but not limited to, IgG, IgE, IgM and IgA, cellular adhesion molecules, the T-cell receptor, T-cell accessory molecules such as CD2, CD3, CD4 and CD8, the B-cell receptor, Fc receptors, certain receptor tyrosine kinases, certain receptor tyrosine phosphatases, and others.
  • the distinguishing feature of these molecules is a characteristic domain structure known as the immunoglobin fold.
  • the three dimensional structure of the immunoglobin fold is well characterized and genetic engineering techniques can be used to modify antibody binding properties.
  • the binding sites of these proteins are formed by polypeptide strands known as Complementarity Determining Regions or CDRs.
  • PLC phospholipase C
  • DAG diacylglycerol
  • IP 3 inositol 1,4,5-triphosphate
  • the same process can be used to fine tune the size of the blocking particle or its affinity for the channel.
  • the same process can be used to produce analyte analogs that bind to a particular binding element.
  • the ion channel and its associated blocking protein functions as the signaling element and the channel contains an inserted domain that functions as the binding element.
  • the genetic code for the binding element and signaling element may be combined in the genome of an appropriate expression vector and used to transform an appropriate host cell line.
  • the hydrophobic portion 35 may be a hydrocarbon, a peptide, or other compound of appropriate size and hydrophobicity.
  • the reactive groups 34 may be sulfhydryl, amino or other groups suitable for covalent reaction with the surface of the annular ring.
  • the photolabile linkage 37 may be an ortho-nitro ester or the like.
  • Polar groups 36 and 40 may be carboxylate, sulphate, phosphate, carbohydrate, and the like, and combinations thereof.
  • Nonpolar cleavable groups 38 may be aliphatic or aromatic esters or the like. Vesicles or cells can also be fixed within the cylindrical apertures through the use of hydrostatic pressure, or hydrophobic molecules as described above.
  • the recombinant cDNA plasmids containing the modified K + channel cDNAs are linearized by digestion with Hind III, extracted with 1:1 pheno chloroform, made 0.3 M in sodium acetate, and precipitated with 2.5 volumes of ethanol. Linearized template DNA is quantitated by spectrophotometry at 260 nm.

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  • 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)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

L'invention se rapporte à une composition de biocapteur comprenant un élément de liaison associé à une membrane lipidique, en combinaison avec un élément de signalisation afin de détecter qualitativement ou quantitativement un analyte dans un mélange. Cette composition est conçue de manière que la fixation d'un analyte par un élément de liaison produise un changement mesurable dans l'élément de signalisation. Cette composition peut éventuellement contenir un élément intermédiaire afin de coupler la réponse de l'élément de liaison à l'élément de signalisation au moyen de réactions chimiques intermédiaires.
PCT/US1994/014094 1993-12-06 1994-12-06 Composition et procede servant a detecter des analytes WO1995016206A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
JP7516329A JPH09509481A (ja) 1993-12-06 1994-12-06 分析物検出用の組成物及び方法
EP95904843A EP0733209A1 (fr) 1993-12-06 1994-12-06 Composition et procede servant a detecter des analytes

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US16287093A 1993-12-06 1993-12-06
US08/162,870 1993-12-06

Publications (1)

Publication Number Publication Date
WO1995016206A1 true WO1995016206A1 (fr) 1995-06-15

Family

ID=22587474

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1994/014094 WO1995016206A1 (fr) 1993-12-06 1994-12-06 Composition et procede servant a detecter des analytes

Country Status (3)

Country Link
EP (1) EP0733209A1 (fr)
JP (1) JPH09509481A (fr)
WO (1) WO1995016206A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996012957A1 (fr) * 1994-10-19 1996-05-02 Fritz Pittner Biodetecteur de modulation de flux d'ions, regule par bioreconnaissance
WO1997025616A1 (fr) * 1996-01-11 1997-07-17 Australian Membrane And Biotechnology Research Institute Groupage sanguin par capteur a canal ionique
WO1997029366A1 (fr) * 1996-02-08 1997-08-14 Australian Membrane And Biotechnology Research Institute Biocapteurs de detection des enzymes
WO1999047923A2 (fr) * 1998-03-20 1999-09-23 The Rockefeller University Essais de recherche systematique de composes en interaction avec des proteines de canal cation, proteines de canal cation procaryotes mutantes, et utilisations correspondantes
WO2002066596A2 (fr) * 2001-01-08 2002-08-29 Niels Fertig Dispositif et procede d'analyse de canaux ioniques dans des membranes

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
USH201H (en) * 1985-08-23 1987-01-06 United States Of America Biosensors from membrane proteins reconstituted in polymerized lipid bilayers

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
USH201H (en) * 1985-08-23 1987-01-06 United States Of America Biosensors from membrane proteins reconstituted in polymerized lipid bilayers

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
ANALYTICAL CHIMICA ACTA, Vol. 281, issued 24 September 1993, ADACHI et al., "NA+,K+-ATPase-Based Bilayer Lipid Membrane Sensor for Adenosine 5'-Triphosphate", pages 577-584. *
ROITT, "Essential Immunology", Published 1991 by BLACKWELL SCIENTIFIC PUBLICATIONS , (OXFORD, ENGLAND), pp. 56, 57, 117, 118. *
SENSORS AND ACTUATORS B, Vol. 7, issued 1992, KLEE et al., "A Biosensor Based on the Membrane Protein Lactose Permease", pp. 376-379. *

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996012957A1 (fr) * 1994-10-19 1996-05-02 Fritz Pittner Biodetecteur de modulation de flux d'ions, regule par bioreconnaissance
WO1997025616A1 (fr) * 1996-01-11 1997-07-17 Australian Membrane And Biotechnology Research Institute Groupage sanguin par capteur a canal ionique
WO1997029366A1 (fr) * 1996-02-08 1997-08-14 Australian Membrane And Biotechnology Research Institute Biocapteurs de detection des enzymes
AU708021B2 (en) * 1996-02-08 1999-07-29 Ambri Limited Enzyme detection biosensors
WO1999047923A2 (fr) * 1998-03-20 1999-09-23 The Rockefeller University Essais de recherche systematique de composes en interaction avec des proteines de canal cation, proteines de canal cation procaryotes mutantes, et utilisations correspondantes
WO1999047923A3 (fr) * 1998-03-20 2002-10-03 Univ Rockefeller Essais de recherche systematique de composes en interaction avec des proteines de canal cation, proteines de canal cation procaryotes mutantes, et utilisations correspondantes
US6641997B1 (en) 1998-03-20 2003-11-04 The Rockefeller University Assays for screening compounds which interact with cation channel proteins, mutant prokaryotic cation channel proteins, and uses thereof
WO2002066596A2 (fr) * 2001-01-08 2002-08-29 Niels Fertig Dispositif et procede d'analyse de canaux ioniques dans des membranes
WO2002066596A3 (fr) * 2001-01-08 2003-03-27 Niels Fertig Dispositif et procede d'analyse de canaux ioniques dans des membranes

Also Published As

Publication number Publication date
JPH09509481A (ja) 1997-09-22
EP0733209A1 (fr) 1996-09-25

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