WO2003051506A1 - Membrane - Google Patents

Membrane Download PDF

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Publication number
WO2003051506A1
WO2003051506A1 PCT/GB2002/005795 GB0205795W WO03051506A1 WO 2003051506 A1 WO2003051506 A1 WO 2003051506A1 GB 0205795 W GB0205795 W GB 0205795W WO 03051506 A1 WO03051506 A1 WO 03051506A1
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WO
WIPO (PCT)
Prior art keywords
membrane according
membrane
bilayer
dimension
substrate
Prior art date
Application number
PCT/GB2002/005795
Other languages
English (en)
Inventor
James Richard Bushby
John Colyer
Stephen J. Evans
Original Assignee
University Of Leeds
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 University Of Leeds filed Critical University Of Leeds
Priority to AU2002358214A priority Critical patent/AU2002358214A1/en
Publication of WO2003051506A1 publication Critical patent/WO2003051506A1/fr

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y30/00—Nanotechnology for materials or surface science, e.g. nanocomposites
    • 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
    • C12Q1/001—Enzyme 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
    • G01N33/543—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
    • 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
    • B01J2219/00277—Apparatus
    • B01J2219/00497—Features relating to the solid phase 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
    • B01J2219/00277—Apparatus
    • B01J2219/00497—Features relating to the solid phase supports
    • B01J2219/00527—Sheets
    • 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
    • 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
    • G01N27/28—Electrolytic cell components
    • G01N27/40—Semi-permeable membranes or partitions

Definitions

  • the present invention relates to a novel form of membrane, methods of preparing such membranes, uses of such membranes and devices comprising such membranes.
  • Biological membranes play a crucial role in regulating cellular activity. They consist of a flexible phospholipid bilayer that is given shape/support by the cytoskeleton and which is impervious to the flow of ions and large molecules. Such bilayers contain numerous proteins, peptides, sugars, carbohydrates, etc. These proteins are involved in a wide range of cellular activities, such as, signal transduction and immunoresponse, for example, the opening of an acetylcholine receptor channel permits Na + to diffuse into a cell.
  • One way to mimic events happening in natural cells is to incorporate membrane proteins and receptors into artificial lipid bilayers, attached onto solid supports (sBLM) or suspended over an aperture (BLM). The activities of proteins and receptors can then be detected using electrical techniques.
  • sBLM solid supports
  • BBM suspended over an aperture
  • SAMs Self-assembled monolayers
  • a mixed SAM will comprise mixtures of anchor molecules and packing molecules, the packing molecules will often be hydrophilic in character.
  • the anchor molecule will generally contain two parts, a hydrophobic moiety (e.g. cholesterol, fatty acid or phospholipid moiety), whose function is to insert into the hydrophobic region of the inner leaflet of the bilayer and to anchor or tether the bilayer to the surface, and a hydrophilic, "spacer” segment, which is used to create a hydrophilic region between the bilayer leaflet and the substrate surface.
  • the "packing" molecules serve to control the density of anchor groups present on the surface of the substrate as well as to help maintain the hydrophilic nature of the substrate surface.
  • patterned SAMs have been prepared, for example using microcontact printing and used to support biomembranes.
  • Such patterned SAMs generally comprise regions of free standing lipid bilayers separated by lipid monolayers on top of anchor molecules ( Figure 2).
  • a membrane adapted to be supported on a patterned substrate characterised in that the pattern comprises bilayer regions the size of which is less than 20 ⁇ m in at least one dimension.
  • the bilayer regions need not be circular in section.
  • the diameter of the bilayer regions should be understood to mean that a substantial proportion of the bilayer regions have the diameter quoted and/or are seeded.
  • the diameter is generally a mean diameter, that is, for example, at least 50% of the bilayer regions may have a mean diameter of 20 ⁇ m or less, preferably 60%, more preferably 70%, most preferably 80% and especially at least 90%.
  • the membrane of the invention may, preferentially comprise a size of less than 20 ⁇ m wherein, this represents the largest (in plane) dimension, i.e. in the plane of the substrate.
  • The, size of the smallest dimensions (in plane) of the bilayer regions may vary, but they are preferentially less than 15 ⁇ m, more preferably less lO ⁇ m, most preferably less than 5 ⁇ m and especially less than l ⁇ m.
  • the smallest (in plane) dimension of the bilayer region may be from lnm to lOOOnm and especially from 500nm to 750nm.
  • the dimensions above represent the largest (in plane) dimension of the bilayer region.
  • the dimension referred to may comprise the largest respective dimension.
  • anchoring and/or packing molecules include, by way of example only, anchoring molecules, such as thiol derivatives of cholesterol and lipid disulphides; packing molecules, such as mercapto alcohols, e.g. mercapto ethanol, or thiol derivatives of polyethylene oxide.
  • the anchoring and/or packing molecules may include thiol, disulphide, sulphide groups (for anchoring to Au, Ag and other noble metals), organosilanes (for anchoring to SiO 2 , or other hydroxylated surfaces) and alkenes (for anchoring to Si[H]).
  • the anchor molecules will generally comprise a lipophilic "head” region and a hydrophilic tail region, functionalised to bond the substrate.
  • the lipophilic head group region may comprise one or more of the groups normally associated with naturally occurring or synthetic lipids.
  • Naturally occurring lipid molecules include cholesterol or other sterols, phosphatidyl choline, phosphatidyl ethanolamine, mono-, di- or tri-methylated phosphatidyl ethanolamine, phosphatidic acid, phosphatidyl serine, phosphatidyl glycerol, phosphatidyl inositol, distributed head groups as found in cardiolipins, ganglioside head groups, sphingomyelin head groups, plasmalogen head groups, glycosyl, galactosyl, digalactosyl, sulfosugar, phosphosugar, N-acetyl neuramic acid, sialic acid, aminosugar head groups carbohydrate head groups, gal(betal-3)galNAc(betal-4) [NAcNeu(alpha2-3] gal (betal-4) gl
  • the hydrophilic tail region may comprise saccharides, polysaccharides, oligomers of ethylene glycol, ethylene glycol, oligomers of propylene glycol, propylene glycol, amino acids, oligomers of amino acids, combinations of oligomers of ethylene glycol or propylene glyco functionalised with amino acids or other ionic species or any combination or derivative of the above.
  • the hydrophilic region of the packing molecules may comprise one or more hydrophilic compounds.
  • the hydrophilic region of the packing molecule may be composed of ethers, peptides, amides, amines, esters, saccharides, polyols, charged groups (positive and/or negative), electroactive species or combinations thereof.
  • the main requirement of the hydrophilic region of the packing molecule is that it provides a water-filled space between the bilayer (or the anchor:lipid hybrid layer) and the substrate.
  • the membranes of the invention are advantageous in that, inter alia, the stability, function and quality of the membrane bilayer is improved over prior art membranes.
  • Prior art mixed SAMs have generally comprised random array bilayer regions.
  • the use of a pre-defined patterned SAM in a controlled, i.e. non-random, fashion is especially advantageous.
  • the controlled patterned SAMs in the membranes of the invention will generally comprise bilayer regions and monolayer regions.
  • the monolayer or hydrophilic regions may be "seeded" with a proportion of a ligand. This is a novel and especially advantageous aspect of the present invention which improves bilayer formation on the substrate and improves the stability of such bilayers.
  • a membrane adapted to be supported on a patterned substrate, characterised in that the membrane supporting regions of the substrate are provided with a proportion of ligands.
  • the membrane may therefore be adapted to be anchored to a substrate surface and may, optionally, comprise a self-assembled monolayer (SAM).
  • SAM self-assembled monolayer
  • the ligands may vary.
  • the ligands may comprise lipophilic anchor molecules as hereinbefore described.
  • the ligands may comprise fusogens.
  • the ligands may comprise a mixture of lipophilic anchors and fusogens.
  • the fusogens may be non- fusogenic compounds that become fusogenic by triggering, for example, chemical triggering by exposure to low pH or an oxidative environment.
  • the patterned bilayer regions may comprise a random pattern or an ordered e.g. controlled pattern.
  • the size of bilayer regions may vary and may be up to lOO ⁇ m in their smallest dimension.
  • the "seeded" bilayer regions need not be limited to a minimum dimension of less than 20 ⁇ m.
  • the "seeded" bilayer regions may still be less than 20 ⁇ m in their smallest dimension.
  • the ligands themselves may be randomly scattered or may be positioned in a controlled pattern.
  • the proportion of ligands "seeded" in the bilayer region may vary, but may be, for example, from up to 50% of the bilayer region of the substrate.
  • the lipids used in the membranes of the present invention may comprise any conventionally known lipids, for example, those described in International Patent Application No. WO 94/07593.
  • the ligand when the ligand is a fusogen it may comprise any conventionally known fusogen.
  • the fusogen may be a non-metallic fusogen, e.g. polyethylene glycol.
  • the fusogen may be a cation, plus a cation binding ligand, such as a carboxylic acid.
  • the cation may vary, but may be, for example, Ca 2+ , Mg 2+ , Al 3+ , etc.
  • the fusogen may comprise a cation and a phosphate moiety. It is within the scope of the present invention to use a mixture of fusogens, for example, a mixture of one or more carboxylic acids and one or more phosphate moieties.
  • the membranes of the invention may be manufactured using conventional processes known per se, for example by vesicle fusion.
  • the membranes of the invention are advantageous in that they may be useful, inter alia, in the manufacture of biosensors or in the field of drug discovery. Other uses not mentioned here can also be contemplated.
  • substrates may be used in the manufacture of the membranes of the invention.
  • substrates include, but shall not be limited to noble metals, such as gold, silver, platinum, or palladium; or other metals/metal derivatives, e.g. silicon, silicon oxide or silicon nitride.
  • noble metals such as gold, silver, platinum, or palladium
  • other metals/metal derivatives e.g. silicon, silicon oxide or silicon nitride.
  • non-metal substrates may be used, for example, a glass or a polymer substrate, such as a plastics substrate.
  • other substrates may be contemplated.
  • the substrate may be a coated substrate, e.g., a noble metal substrate coated with a photoresist, such as SU8.
  • the membrane material itself may comprise any conventionally known lipid, such lipids may be synthetic lipids or naturally occurring lipids. Examples as in claim (1) where the biomembrane is a bilayer, monolayer or hybrid monolayer/bilayer structure.
  • the membrane may, for example, comprise a fragment of a natural cell, h this case the cell may contain a channel or channel modulator, in some cases these components may be engineered to possess non-natural sequences or structures.
  • the membranes of the invention are advantageous in that, inter alia, the fabrication, stability, and performance of the membrane bilayer is improved over prior art membranes.
  • the membranes may be useful, inter alia, in the manufacture of electrodes and/or biosensors or in the field of drug discovery. Other uses not mentioned here can also be contemplated.
  • an electrode which comprises a membrane as hereinbefore described.
  • the device could be used to identify compounds which alter the function of the membrane (e.g. membrane potential, pore-forming agents, ion channel activity, systems engineered to report through ion channels, transport enzymes).
  • An array of pixels containing the membrane, with for example, an ion channel incorporated in the membrane could be fabricated to permit the high throughput exposure of the ion channel to many diverse compounds in a search to identify compounds which affect ion channel function.
  • Patterned membranes can be formed by creating wells, or corrals, out of resist or other materials. Membranes can then be formed at the bottom of the wells via vesicle rupture at the substrate surface. The patterning thus arises due to the barriers separating the neighbouring wells.
  • Such electrodes are especially advantageous in that they may be used in the manufacture of sensors, such as biosensors. Therefore, in a yet further aspect of the invention we provide a sensor, e.g. a biosensor, which comprises an electrode as hereinbefore described.
  • the sensor of the invention may comprise a means of detecting the amount of a species of interest in a sample and a membrane in accordance with the invention, the membrane providing both a barrier function and a biocompatible interface function between the detecting means and the sample.
  • the biosensor may comprise a reference electrode, e.g. a silver/silver chloride electrode.
  • a reference electrode e.g. a silver/silver chloride electrode.
  • the membrane When used as a sensor, the membrane may have incorporated in it one or more proteins, peptides, ionophores and/or other bioactive molecules.
  • the electrodes and/or sensors of the invention offer a reduced capacitance and/or increased resistance giving improved signal/noise ration in the detection of electronic events.
  • the electrodes and/or sensors may also provide enhanced -detection of ion- selectivity of ion channel proteins (or peptides/ionophores) wherein the activity of individual ion channel molecules can be recorded and/or other electronic events, such as pore formation, transport processes, changes in membrane potential etc. may be monitored.
  • a method of manufacturing a membrane of the invention which comprises generating a pattern by a method selected from the group, photolithography, e-beam lithography, microcontact printing, fluid flow, ink-jet printing and deposition of Langmuir Blodget films.
  • Figure 1 is a schematic representation of a solid supported bilayer
  • Figure 2 is a schematic representation of a bilayer supported on a patterned SAM
  • Figure 3 is an illustration of a lipid vesicle unrolling on a micropatterned SAM; and Figure 4 is a graph illustrating the variance of capacitance with bilayer diameter.
  • the substrate (1) is provided with anchor molecules (2) and the packing molecules (3), with hydrophilic portions (4 and 5).
  • the bilayer (6) comprises an inner leaflet (7) and an outer leaflet (8).
  • the hydrophilic portions (4 and 5) serve to provide an aqueous environment between the bilayer(6) and the solid support substrate (1).
  • the SAM was produced using microcontact printing.
  • a cholesterol was stamped on to a bare gold surface, the sample was then placed into a solution containing a short chain ethyleneoxy derivative.
  • a lipid monolayer was adsorbed on the hydrophobic surfaces (region 1) and a bilayer was formed on the hydrophilic areas (region 2).
  • Chromium-glass photo-lithography masks were constructed using electron beam lithography at the Rutherford-Appleton Laboratory, Didcot, UK.
  • the mask consists of seven separate patterns each being an array of circles spaced on a regular square lattice.
  • the circle diameters range from 0.1 ⁇ m to 16 ⁇ m.
  • the ratio of the circle area to surrounding area is kept constant.
  • the mask was used to create arrays of raised columns in SU18 photoresist (Chestech, rugby, UK) using standard lithographic techniques.
  • Poly-dimethylsiloxane (PDMS) was applied to the patterned photoresist and baked at 60° C for 1 hour. The baked PDMS was peeled off and examined under an optical microscope to ensure the pattern had been effectively reproduced in the stamp.
  • Each individual patterned stamp has gross dimensions of 7 x 7 mm.
  • the gold surfaces were cleaned in piranha solution (30% H 2 O 2 / 70% H 2 SO ) for 1 minute followed by washing in pure water.
  • the PDMS stamps were 'inked' with
  • Lipid vesicles were prepared by hydrating egg-phosphatidylcholine in 0.1M KC1 for 1 hour to give a lmg / ml dispersion, then extruding through 50 nm diameter polycarbonate membranes for 18 cycles. The resultant vesicle diameters were 60-70 nm. The vesicles were diluted to a working concentration of 0.2mg / ml with 0.1M KC1.
  • the vesicle solution was applied to the patterned surface and left for 90min followed by rinsing in 0.1M KC1.
  • Electrochemical impedance measurements were made on a Solartron 1260 frequency response analyser coupled to an EG&G 273A potentiostat.
  • the cell was operated in two electrode mode with a coiled platinum wire counter electrode.
  • a 12 mV r.m.s. AC potential was applied at the open circuit potential of the cell.
  • the applied AC frequency was swept between 50kHz and 300 MHz.
  • Measurements were first made on the bare SAM in 0.1 M KC1, then measurements made at regular intervals during the lipid deposition. Subsequently, the cell was rinsed with 0.1M KC1 and a final impedance measurement taken.
  • the high frequency part of the impedance spectrum pertains to the organic film whilst the low frequency impedance can be ascribed to the gold double layer capacitance. Fitting a simple RC series circuit to the data over the 50kHz - lMHz range gives a reasonable measure of the capacitance of the organic film (figure 4).
  • Vesicles incorporating gramicidin allowed to react with the patterned SAMs for 90min then washed with 0.1M KC1 to remove excess vesicles.
  • Ion channel activity measured by impedance methods. Measurements were carried out in different chloride salt solutions (KC1, NaCl, CsCl, BaCl 2 ) at 0.1M depending on the desired cation. The cell was thoroughly flushed between different electrolytes with Millipore water and four cell volumes of the desired electrolyte.
  • chloride salt solutions KC1, NaCl, CsCl, BaCl 2
  • Re Microcontact Printing of Lipophilic Self-assembled Monolayers for attachment of Biomimetic lipid Bilayers to surfaces A.T.A. Jenkins, N. Boden, RJ. Bushby, S.D. Evans*, P.F. Knowles, R.E.Miles, S.D. Ogier, H. Sch ⁇ nherr, G.J. Vancso J. Am. Chem. Soc. 1999 , 121, 521
  • Ion conductance and impedence spectroscopy measurements determine bilayer characteristics and ion channel activity. Single ion channel sensitivity results in A scale changes in current.
  • Fusogen consists of (a) the metal salt of a carboxylic acid functionalised SAM (20- 50mole%) or (b) polyethylene glycol functionalised thio derivatives (20-50mole%).

Abstract

Cette invention se rapporte à une membrane conçue pour être placée en support sur un substrat à motif, cette membrane se caractérisant en ce que ledit motif comprend des zones bicouches, dont la taille est inférieure à 20 νm dans au moins une dimension.
PCT/GB2002/005795 2001-12-19 2002-12-19 Membrane WO2003051506A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2002358214A AU2002358214A1 (en) 2001-12-19 2002-12-19 Membrane

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB0130318A GB0130318D0 (en) 2001-12-19 2001-12-19 Membrane
GB0130318.9 2001-12-19

Publications (1)

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WO2003051506A1 true WO2003051506A1 (fr) 2003-06-26

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GB (1) GB0130318D0 (fr)
WO (1) WO2003051506A1 (fr)

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1543317A2 (fr) * 2002-07-22 2005-06-22 Synamem Corporation Ensembles biodetecteurs et procedes y relatifs
EP1707636A1 (fr) * 2005-03-07 2006-10-04 Seiko Epson Corporation Substrat pour électrode, dispositif de détection et kit d'essai
EP1707635A1 (fr) * 2005-03-07 2006-10-04 Seiko Epson Corporation Substrat pour électrode, dispositif de détection et kit d'essai
WO2007084962A2 (fr) * 2006-01-18 2007-07-26 The Regents Of The University Of California Système de présentation de ligands basé sur une membrane fluide pour des essais biologiques sur cellules vivantes et pour le diagnostic de maladies
US8062491B1 (en) 2000-05-03 2011-11-22 The United States Of America As Represented By The Department Of The Navy Biological identification system with integrated sensor chip
EP2444464A1 (fr) * 2010-10-21 2012-04-25 Centre National de la Recherche Scientifique (CNRS) Nouveau (bio)matériau neutre
US8329010B2 (en) * 2000-05-03 2012-12-11 Kotura, Inc. Chip assay having improved efficiency
CN105738440A (zh) * 2016-01-29 2016-07-06 中国科学院合肥物质科学研究院 一种金纳米阵列电极及其制备的无酶过氧化氢传感器
US9708665B2 (en) 2008-07-21 2017-07-18 The Regents Of The University Of California Spatial biomarker of disease and detection of spatial organization of cellular receptors
CN110300630A (zh) * 2017-01-05 2019-10-01 国家科学研究中心 用于使用两亲性嵌段共聚物在固体支撑体上制造多层膜的方法
CN116337805A (zh) * 2023-05-22 2023-06-27 成都博瑞科传科技有限公司 基于阵列光谱和离子选择法的水中总磷检测方法及传感器

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5637201A (en) * 1992-10-01 1997-06-10 Australian Membrane And Biotechnology Research Ins. Sensor membranes
WO1998023948A1 (fr) * 1996-11-29 1998-06-04 The Board Of Trustees Of The Leland Stanford Junior University Agencements de membranes a bicouches fluidiques supportees, adressables independamment, et procedes d'utilisation correspondants
US5885613A (en) * 1994-09-30 1999-03-23 The University Of British Columbia Bilayer stabilizing components and their use in forming programmable fusogenic liposomes
US5942397A (en) * 1996-12-11 1999-08-24 Tarlov; Michael J. Surface immobilization of biopolymers
WO2001020330A1 (fr) * 1999-09-17 2001-03-22 The Texas A & M University System Agencements de bicouches lipidiques adressees et bicouches lipidiques avec compartiments aqueux confines adressables
WO2001026800A1 (fr) * 1999-10-08 2001-04-19 The Board Of Trustees Of The Leland Stanford Junior University Reseaux a double couche de lipides et procede de production et d'utilisation correspondant
US6329209B1 (en) * 1998-07-14 2001-12-11 Zyomyx, Incorporated Arrays of protein-capture agents and methods of use thereof

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5637201A (en) * 1992-10-01 1997-06-10 Australian Membrane And Biotechnology Research Ins. Sensor membranes
US5885613A (en) * 1994-09-30 1999-03-23 The University Of British Columbia Bilayer stabilizing components and their use in forming programmable fusogenic liposomes
WO1998023948A1 (fr) * 1996-11-29 1998-06-04 The Board Of Trustees Of The Leland Stanford Junior University Agencements de membranes a bicouches fluidiques supportees, adressables independamment, et procedes d'utilisation correspondants
US5942397A (en) * 1996-12-11 1999-08-24 Tarlov; Michael J. Surface immobilization of biopolymers
US6329209B1 (en) * 1998-07-14 2001-12-11 Zyomyx, Incorporated Arrays of protein-capture agents and methods of use thereof
WO2001020330A1 (fr) * 1999-09-17 2001-03-22 The Texas A & M University System Agencements de bicouches lipidiques adressees et bicouches lipidiques avec compartiments aqueux confines adressables
WO2001026800A1 (fr) * 1999-10-08 2001-04-19 The Board Of Trustees Of The Leland Stanford Junior University Reseaux a double couche de lipides et procede de production et d'utilisation correspondant

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8329010B2 (en) * 2000-05-03 2012-12-11 Kotura, Inc. Chip assay having improved efficiency
US8062491B1 (en) 2000-05-03 2011-11-22 The United States Of America As Represented By The Department Of The Navy Biological identification system with integrated sensor chip
EP1543317A4 (fr) * 2002-07-22 2006-10-04 Synamem Corp Ensembles biodetecteurs et procedes y relatifs
EP1543317A2 (fr) * 2002-07-22 2005-06-22 Synamem Corporation Ensembles biodetecteurs et procedes y relatifs
EP1707636A1 (fr) * 2005-03-07 2006-10-04 Seiko Epson Corporation Substrat pour électrode, dispositif de détection et kit d'essai
EP1707635A1 (fr) * 2005-03-07 2006-10-04 Seiko Epson Corporation Substrat pour électrode, dispositif de détection et kit d'essai
US8343333B2 (en) 2005-03-07 2013-01-01 Seiko Epson Corporation Electrode substrate, detection device equipped with electrode substrate, detection device kit and detection method using the kit
WO2007084962A2 (fr) * 2006-01-18 2007-07-26 The Regents Of The University Of California Système de présentation de ligands basé sur une membrane fluide pour des essais biologiques sur cellules vivantes et pour le diagnostic de maladies
WO2007084962A3 (fr) * 2006-01-18 2009-02-26 Univ California Système de présentation de ligands basé sur une membrane fluide pour des essais biologiques sur cellules vivantes et pour le diagnostic de maladies
US9708665B2 (en) 2008-07-21 2017-07-18 The Regents Of The University Of California Spatial biomarker of disease and detection of spatial organization of cellular receptors
WO2012052539A1 (fr) * 2010-10-21 2012-04-26 Centre National De La Recherche Scientifique (Cnrs) Nouveau (bio)matériau neutre
EP2444464A1 (fr) * 2010-10-21 2012-04-25 Centre National de la Recherche Scientifique (CNRS) Nouveau (bio)matériau neutre
CN105738440A (zh) * 2016-01-29 2016-07-06 中国科学院合肥物质科学研究院 一种金纳米阵列电极及其制备的无酶过氧化氢传感器
CN110300630A (zh) * 2017-01-05 2019-10-01 国家科学研究中心 用于使用两亲性嵌段共聚物在固体支撑体上制造多层膜的方法
CN116337805A (zh) * 2023-05-22 2023-06-27 成都博瑞科传科技有限公司 基于阵列光谱和离子选择法的水中总磷检测方法及传感器
CN116337805B (zh) * 2023-05-22 2023-07-21 成都博瑞科传科技有限公司 基于阵列光谱和离子选择法的水中总磷检测方法及传感器

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