WO2007140294A2 - Dispositif d'analyse - Google Patents

Dispositif d'analyse Download PDF

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Publication number
WO2007140294A2
WO2007140294A2 PCT/US2007/069731 US2007069731W WO2007140294A2 WO 2007140294 A2 WO2007140294 A2 WO 2007140294A2 US 2007069731 W US2007069731 W US 2007069731W WO 2007140294 A2 WO2007140294 A2 WO 2007140294A2
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WO
WIPO (PCT)
Prior art keywords
support
analysis device
coating
polymer coating
polymer
Prior art date
Application number
PCT/US2007/069731
Other languages
English (en)
Other versions
WO2007140294A3 (fr
Inventor
Amarnauth Singh
Andrew Sitterer
Jeffrey B. Burns
Original Assignee
Pall 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 Pall Corporation filed Critical Pall Corporation
Publication of WO2007140294A2 publication Critical patent/WO2007140294A2/fr
Publication of WO2007140294A3 publication Critical patent/WO2007140294A3/fr

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5088—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above confining liquids at a location by surface tension, e.g. virtual wells on plates, wires
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00009—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with a sample supporting tape, e.g. with absorbent zones
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/12—Specific details about manufacturing devices
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/069—Absorbents; Gels to retain a fluid
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0822—Slides
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0832—Geometry, shape and general structure cylindrical, tube shaped
    • B01L2300/0845—Filaments, strings, fibres, i.e. not hollow
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates

Definitions

  • This invention pertains to analysis devices for binding biomolecules such as nucleic acids and proteins, and methods for binding, and more preferably, detecting, the biomolecules.
  • Many techniques for analyzing biomolecules include placing a sample containing the biomolecules on a solid surface such as a supported membrane, or a non-porous glass or polymeric slide, and placing a binding agent, such as a complementary nucleic acid probe or antibody that will specifically bind to the biomolecule, in contact with the biomolecules and forming a complex between the biomolecule and binding agent.
  • a binding agent can be immobilized on the solid surface and the biomolecule in the sample can be placed in contact with the binding agent to form a complex.
  • a binding agent may be labeled before use and/or one or more labels may be added to the complex.
  • binding agents e.g., nucleic acid probes or anti-antibodies
  • labeling reagents can also be utilized.
  • the label that is bound to the complex is subsequently detected, thus indicating the presence of the biomolecules of interest.
  • Analysis devices have been developed wherein small volumes of fluid e.g., containing the sample or a binding agent are deposited (typically by printing or ink jetting) at predetermined locations on the solid surface, and the other member(s) to be part of the complex are subsequently added to the location in a similar manner so the complex can be formed.
  • Some devices allow the binding agent to be synthesized on the surface before the sample is added.
  • These devices having material deposited in a microarray pattern, allow numerous samples to be analyzed simultaneously, and are particularly suitable for automated analysis.
  • analysis devices have suffered from a number of drawbacks. For example, some solid surfaces have exhibited insufficient and/or inconsistent binding capacity or binding efficiency. Additionally or alternatively, some devices, e.g., including membranes attached to glass supports via adhes ⁇ ves, have been labor intensive to produce, difficult to handle and/or are not particularly suitable for automated analysis.
  • the invention provides an analysis device comprising a cord-shaped support comprising a filament, the support having a porous surface; and a polymer coating.
  • the coating surrounds the porous surface and adheres to the surface.
  • the analysis device has a microporous surface.
  • the polymer coating comprises the rnicroporous surface of the analysis device.
  • the analysis device can have a charged or uncharged microporous surface.
  • the surface of the analysis device has a critical wetting surface tension (CWST) of at least about 60 dynes/cm (about 60 x 10 "5 N/cm).
  • CWST critical wetting surface tension
  • the support includes a core and a porous layer surrounding the core, and the porous layer has a thickness in the range of from about 2 microns to about 25 microns, wherein the layer is bounded by the core and the porous surface of the support.
  • the analysis device is suitable for binding biomolecules such as nucleic acids, proteins, and antibodies, and the analysis device has a variety of applications, especially in hybridization assays and immunoassays.
  • Embodiments of the invention are particularly useful as microarray devices, e.g., wherein samples containing nucleic acids to be tested or evaluated, and nucleic acids containing nucleotide sequences complementary to those of the nucleic acids to be tested or evaluated, are deposited in a microarray pattern on the microporous of the analysis device, and complexes formed between the complementary sequences are detected.
  • the microarray devices can be used in automated protocols, e.g., they are compatible with conventional scanning and analysis equipment.
  • a method of making an analysis device comprises obtaining a cord-shaped support comprising a filament, the support having a porous surface, and, coating the support with a coating composition to provide a polymer coating.
  • the method includes treating the support at least once, preferably by etching, to provide the porous surface before coating the support with the coating composition.
  • coating the support comprises providing a charged coating.
  • An embodiment of a method for detecting biomolecules according to the invention comprises depositing on the microporous surface of an embodiment of the analysis device (a) one or more samples containing one or more biomolecules of interest, the biomolecules of interest having nucleic acid sequences, and (b) at least one binding agent comprising one or more probe nucleic acids having nucleotide sequences complementary to a nucleotide sequence of one or more biomolecules of interest.
  • One or more immobilized complexes are formed between at least one biomolecule of interest and at least one binding agent comprising at least one probe nucleic acid having a nucleotide sequence complementary to a nucleotide sequence of at least one biomolecule of interest, and, one or more of the immobilized complexes are detected.
  • a method for detecting biomolecules comprising providing at least one binding agent comprising one or more probe nucleic acids having nucleotide sequences on a microporous surface of an analysis device such that the probe nucleic acids are immobilized.
  • the probe nucleic acid nucleotide sequences are complementary to a nucleotide sequence of one or more biomolecules of interest in a sample.
  • the microporous surface of the analysis device is suitable for receiving the probe nucleic acids and one or more samples containing the biomolecule(s).
  • the method includes depositing the sample(s) onto the microporous surface of the analysis device such that the biomolecule(s) contact the probe nucleic acid(s) and one or more complexes are formed, the formed complexes comprising a probe nucleic acid nucleotide sequence bound to the complementary nucleotide sequence of the biomolecule; and, detecting the complexes.
  • Figure 1 shows an exemplary apparatus for preparing an embodiment of a support and/or an analysis device according to the present invention.
  • Figure 2 provides scanning electron micrographs (SEMs) of surface and cross- sectional views of a support of an analysis device according to an embodiment of the present invention, the support having a porous surface.
  • Figure 2A shows a surface view of the porous surface of the support
  • Figure 2B shows a cross-section of the support showing the core and the porous layer
  • Figure 2 C shows a partial cross-sectional view of the porous layer of the support bounded by the core and the porous surface of the support.
  • Figure 3 provides SEMs of surface and cross-sectional views of an analysis device according to an embodiment of the present invention.
  • FIG. 3 A shows a microporous polymer coating surface
  • Figure 3B shows a cross-sectional view of the core, porous layer, and polymer coating
  • Figure 3 C shows a cross- section of a portion of an analysis device, showing an enlarged view of the support core and porous layer (labeled as the "porous middle region"), as well as the polymer coating (labeled as the "coated layer").
  • Figure 4 shows another exemplary apparatus for preparing an embodiment of a support and/or an analysis device according to the present invention.
  • Figure 4 A shows a front view
  • Figure 4B shows a side view of the first bath of the apparatus.
  • an analysis device comprising a cord-shaped support comprising a filament, the support having a porous surface; and a polymer coating, the coating surrounding the porous surface and adhering thereto, wherein the analysis device has a microporous surface.
  • the polymer coating comprises the microporous surface of the analysis device.
  • the analysis device can have a charged or uncharged microporous surface.
  • the surface of the analysis device has a critical wetting surface tension (CWST) of at least about 60 dynes/cm.
  • the support includes a core and a porous layer surrounding the core, the porous layer having a thickness in the range of from about 2 microns to about 25 microns, wherein the layer is bounded by the core and the porous surface of the support.
  • Embodiments of the invention also include systems and/or kits for analysis comprising the analysis device, wherein the kit and/or system further comprises, for example, at least one container containing a buffer.
  • the kit and/or system can comprise a spool or reel, wherein an embodiment of the analysis device is wrapped around the spool or reel.
  • a method of making an analysis device comprises obtaining a cord-shaped support comprising a filament, the support having a porous surface, and, coating the support with a polymer coating.
  • the method includes treating the support at least once, preferably by etching, to provide the porous surface.
  • treating the support to provide the porous surface includes drawing the support through a thimble containing an etching solution therein.
  • coating the support includes drawing the support through a thimble containing a coating composition comprising a polymer solution.
  • coating the support comprises providing a charged coating.
  • An embodiment of a method for detecting biomolecules comprises depositing on the microporous surface of an embodiment of the analysis device (a) one or more samples containing one or more biomolecules of interest, the biomolecules of interest having nucleic acid sequences, and (b) at least one binding agent comprising one or more probe nucleic acids having nucleotide sequences complementary to a nucleotide sequence of one or more biomolecules of interest; forming one or more immobilized complexes between at least one biomolecule of interest and at least one binding agent comprising at least one probe nucleic acid having a nucleotide sequence complementary to a nucleotide sequence of at least one biomolecule of interest; and, detecting the one or more immobilized complexes.
  • a method for detecting biomolecules comprising providing at least one binding agent comprising one or more probe nucleic acids having nucleotide sequences on a microporous surface of an analysis device such that the probe nucleic acids are immobilized, the probe nucleic acid nucleotide sequences being complementary to a nucleotide sequence of one or more biomolecules of interest, the analysis device comprising a cord-shaped support comprising a filament, the support having a porous surface and a polymer coating, the coating surrounding the porous surface and adhering thereto, and the microporous surface; the microporous surface being suitable for receiving the probe nucleic acids and one or more samples containing the biomolecule(s); depositing the sample(s) onto the microporous surface of the analysis device such that the b ⁇ omolecule(s) contact the probe nucleic acid(s) and one or more complexes are formed, each formed complex comprising a probe nucleic acid nucleotide
  • the at least one sample containing the at least one biomolecule of interest is initially placed on the microporous surface of the analysis device and immobilized, and one or more probes are subsequently deposited on the analysis device such that one or more complexes are formed, and subsequently detected.
  • inventions include, for example, immunoassays, e.g., wherein a binding agent comprising at least one antibody is initially deposited on the microporous surface, and at least one sample is subsequently deposited to form a complex, or wherein at least one sample is initially deposited, and a binding agent comprising an antibody is subsequently deposited to form a complex.
  • a binding agent comprising at least one antibody is initially deposited on the microporous surface, and at least one sample is subsequently deposited to form a complex
  • a binding agent comprising an antibody is subsequently deposited to form a complex.
  • a plurality of biomolecules and binding agents are deposited, and a plurality of complexes are formed and subsequently detected.
  • additional reagents e.g., one or more binding agents (including, for example, anti-antibodies and/or specific binding agents), or labels
  • binding agents including, for example, anti-antibodies and/or specific binding agents
  • labels can be utilized, e.g., to form a complex, or to label a complex.
  • labels e.g., radioactive, fluorescent, or chemiluminescent
  • a variety of labels including a plurality of distinguishable labels when two or more labels are used in an assay, can be utilized as is known in the art.
  • the analysis device can be easily manipulated for use with a variety of systems without adversely affecting the coating.
  • the analysis device can be, for example, wrapped around a rectangular or circular block, reel, or spool, and it will still be suitable for sequencing applications.
  • the analysis device can easily be optimized for different applications, e.g., the device can have any desired characteristics, e.g., a desired porosity, critical wetting surface tension (CWST) and/or surface charge.
  • CWST critical wetting surface tension
  • the support is preferably in the form of a cord or string.
  • the support has a core that is non-porous, and a surface that is porous, in some embodiments, microporous.
  • the support has a porous layer surrounding the core, wherein the outer portion (i.e., the portion farthest from the core) of the layer provides the porous surface of the support.
  • the porous layer has a thickness in the range of from about 2 microns to about 25 microns, wherein the layer is bounded by the core and the porous surface of the support.
  • the porous layer has a thickness in the range of from about 5 to about 10 microns.
  • the support is treated or processed to provide the porous surface (and porous layer, if present) and/or to modify the porous surface (and porous layer, if present).
  • the support can be surface etched one or more times, e.g., by chemical etching, to provide the porous surface, and, if desired, the porous layer.
  • the porous surface results in enhanced adhesion of the polymer coating, allowing for a more uniform coating of the support and/or reducing the possibility of delamination or peeling of the coating from the support.
  • the support can be treated or processed to provide the porous surface and/or to modify the porous surface by a variety of techniques, e.g., by immersing the support in an etching solution.
  • the support is drawn through a container having etching solution therein, wherein the bottom of the container (sometimes referred to as a "thimble") has an opening (e.g., with a diameter approximating that of the support) through which the support can be drawn.
  • the support comprises a polymer.
  • suitable polymers include polyaromatics, polysulfones, polyarylsufones, polyphenol sulfones, polyamides, polyimides, polyolefins, polystyrenes, polycarbonates, cellulosic polymers such as cellulose acetates and cellulose nitrates, fluoropolymers, and PEEK.
  • a support Commercially available materials suitable for use as a support include, for example, polymeric filaments such as a p-nylon monofilament (Sauders Tread Co., Gastonia, NC).
  • the support comprises a monofilament.
  • the support comprises an optical fiber.
  • a variety of treatment fluids can be used to provide the porous surface of the support and/or the modified porous surface of the support.
  • Illustrative etching fluids include one or more acids, preferably, the etching fluid includes at least one inorganic acid solution,
  • the support is coated with a coating composition to provide a polymer coating on the porous surface of the support, more typically, to provide the microporous surface of the analysis device.
  • the polymer coating can be used to provide desired surface characteristics of the analysis device, e.g., to provide one or more of the following: a desired CWST, a surface that is charged or uncharged, attached functional groups at the surface, and a desired porosity of the surface.
  • surface characteristics of the analysis device can be modified (e.g., to affect the CWST, to include a surface charge, e.g., a positive or negative charge, and/or to alter the polarity or hydrophilicity of the surface) by wet or dry oxidation, by coating or depositing another polymer on the surface of the polymer coating, or by a grafting reaction.
  • Modifications include, e.g., irradiation, a polar or charged monomer, coating and/or curing the polymer coating surface with a charged polymer, and carrying out chemical modification to attach functional groups on the polymer coating surface.
  • Grafting reactions may be activated by exposure to an energy source such as gas plasma, heat, a Van der Graff generator, ultraviolet light, electron beam, or to various other forms of radiation, or by surface etching or deposition using a plasma treatment.
  • coating composition can be prepared as is known in the art.
  • the coating composition can further comprise, for example, a crosslinker and, in some embodiments, an initiator.
  • the polymer coating can include any suitable polymer, e.g., a polymer that has affinity for a biomaterial.
  • the polymer coating can include, for example, a hydrophilic polymer, a polar polymer, or a charged polymer.
  • Hydrophilic polymers include those having an affinity for water or water based solutions or a critical wetting surface tension greater than about 0.37 (+0.005) erg/sq. mm, for example, from about 0.37 to about 1 erg/sq. mm or more, and in some embodiments, from about 0.38 to about 0.73 erg/sq. mm.
  • Polar polymers include those having a solubility parameter greater than about 10.0 ( ⁇ 0.2) [cal/cm 3 ] 1 - 4 , for example, from about 10 to about 20 [cal/cm 3 ]'' 4 or more, illustratively, 10 to about 16 [cal/cm 3 ] /2 .
  • Charged polymers include those containing positive, negative, or amphoteric polymers.
  • suitable polymers include a polyamide, polysulfone, polyarylsufones, polyphenol sulfones, polyolefin, polyhalogenated olefin, polystyrene, polyol, polyamine, polyimine, polyester, an acrylic polymer, polyacrylic acid, polyacrylic ester, polyhydroxyalkyl acrylate, polyacrylic amide, polyacrylonitrile, polyvinyl heterocyclic, poly heterocyclic, polycarbonate, polyimide, polyamide-imide, polylactide, polyglycolide, polyglycolide/lactide, polypeptide, polysiloxane, polysilane, polyacetylene, polyphosphazene, polysaccharide, polyether, epoxy resin, polyacetal, polyurethane, polyurea, urea-formaldehyde resin, polyphenol, phenol-formaldehyde resin, alkyd resin, melamine-formaldehyde
  • polyhalogenated olefin is polyvinylidene fluoride.
  • blends of two or more of the above polymers can be employed, and copolymers comprising monomer segments of one or more of these polymers can be employed.
  • cellulose derivatives include ethyl cellulose, hydroxyethyl cellulose, and hydroxypropyl cellulose.
  • cellulose esters include the nitrates, acetates, propionates, and butyrates of cellulose.
  • the polymer coating can be prepared from a mix of two or more polymers such as, for example, a mix of at least one high molecular weight polyamide and at least one low molecular weight polyamide.
  • Examples of charged polymers include a polyamide, polyamine, polyimine, polyacrylic amide, polyvinyl heterocyclic, polyheterocyclic, polyimide, polyamide-imide, polypeptide, polyurethane, polyurea, urea-formaldehyde resin, melamine-formaldehyde resin, a dendrimer, and cellulose derivatives.
  • hydrophilic polymers include a polyamide, polyol, polyamine, polyimine, polyester, polyarylsufones, polyphenol sulfones, an acrylic polymer, polyacrylic acid, polyacrylic ester, polyhydroxyalkyl acrylate, polyacrylic amide, polyacrylic nitrile, polyvinyl heterocyclic, polyheterocyclic, polyimide, polyamide-imide, polylactide, polypeptide, polysaccharide, polyether, epoxy resin, polyacetal, polyurethane, polyurea, urea-formaldehyde resin, polyphenol, phenol-formaldehyde resin, alkyd resin, melamine- formaldehyde resin, a dendrimer, a spiro polymer, polysulfide, polyketone, polyaldehyde, cellulose, cellulose ester, or cellulose derivative; a polysulfone, polyolefin, polyhalogenated ole
  • polar polymers include a polyamide, polysulfone , polyarylsufones, polyphenol sulfones, polyol, polyamine, polyimine, polyester, an acrylic polymer, polyacrylic acid, polyacrylic ester, polyhydroxyalkyl acrylate, polyacrylic amide, polyacrylic nitrile, polyvinyl heterocyclic, polyheterocycHc, polycarbonate, polyimide, polyamide-imide, polylactide, polypeptide, polysaccharide, polyether, epoxy resin, polyacetal, polyurethane, polyurea, urea-formaldehyde resin, polyphenol, phenol- formaldehyde resin, alkyd resin, melamine-formaldehyde resin, a dendrimer, a spiro polymer, polyaryleneoxide, polysulfide, polyketone, polyetherketone, polyetheretherketone, polyaromatic, polyaldehy
  • any suitable method can be used, e.g., oxidation, reduction, sulfonation, nitration, amidation, carbonylation, hydroxylation, carboxylation, phosphorylation, treatment with surfactants, and/or grafting of polar monomers or polymers.
  • the polymer coating comprises one or more of nylon, polyvinylidene fluoride (PVDF), nitrocellulose, cellulose actetate, and sulfone.
  • the polymer coating is selected from the group consisting of nylon, polyvinylidene fluoride (PVDF), nitrocellulose, cellulose actetate, and sulfone.
  • the polymer coating includes a polyamide, copolyamide, polysulfone, or polyvinylidene fluoride.
  • polyamides and copolyamides include nylons, e.g., nylon 4, nylon 45, nylon 6, nylon 66, nylon 1 1, nylon 610, nylon 612, and nylon 6T.
  • Nylon 66 is a further preferred polyamide.
  • polysulfone include bisphenol A polysulfone, polyethersulfone, and polyarylsulfone. Polyethersulfone is a further preferred polysulfone.
  • One or more polymers described above can be cast, coated, or applied to the porous surface of the support.
  • one or more polymers can be combined with a modifying polymer and cast, coated, or applied to the porous surface.
  • the modifying polymer may be associated by any number of mechanisms, e.g., covalent, ionic, coordinate, hydrogen bonding, or van der waals interactions or bonding, with the porous polymer such that it imparts hydroph ⁇ icity, charge, or polarity to the polymer coating.
  • the modifying polymer or monomer can have a variety of functional groups, e.g., hydroxyl, carboxyl, amine, pyridyl, sulfonic, sulflxydryl, thiocarbonyl, phosphlne, phosphoryl, and imine.
  • suitable modifying polymers include polyethyleneimine, polyvinyl alcohol, polyacrylic acid, hydrolyzed copolymer of maleic anhydride/methylvinyl ether, polystyrene sulfonic acid or a salt thereof, polyvinyl sulfonic acid or a salt thereof, as described in, e.g., U.S. Patent 4,707,266; hydroxyl containing polymers such as polyhydroxyacrylates, as described in, e.g., U.S.
  • the coating can be applied to the support by a variety of techniques.
  • the support is drawn through a container having a coating composition therein, wherein the bottom of the container (sometimes referred to as a "thimble") has an opening (e.g., with a diameter approximating that of the support) through which the support can be drawn.
  • the resultant polymer coating can have any desired critical wetting surface tension (CWST, as defined in, for example, U.S. Patent No. 4,925,572).
  • CWST critical wetting surface tension
  • the polymer coating has a CWST of at least about 40 dynes/cm (about 40 x 10 "5 N/cm), more typically, a CWST of at least about 60 dynes/cm (about 60 x 10 *5 N/cm), and more preferably, a CWST of at least about 70 dynes/cm (about 70 x 10 '5 N/cm).
  • the polymer coating can have a CWST of about 74 dynes/cm (about 74 x 10 "5 N/cm) or more.
  • the resultant polymer coating may have a CWST in the range from about 74 dynes/cm to about 115 dynes/cm (about 74 x 10 "5 N/cm to about 115 x 10 "5 N/cm), e.g., in the range of about 80 to about 100 dynes/cm (about 80 to about 100 x 10 "5 N/cm).
  • the polymer coating has a CWST of about 85 dynes/cm (85 x 10 "5 N/cm), or greater, e.g., in the range from about 90 to about 105 dynes/cm (about 90 to about 105 x 10 "5 N/cm), or in the range from about 85 dynes/cm to about 98 dynes/cm (about 85 to 98 x 10 "5 N/cm).
  • the resultant polymer coating can have any desired thickness. If desired, the thickness can be optimized, e.g., to reduce background autofluorescence. For example, in some embodiments of devices, including some embodiments wherein the device includes a polyamide coating, the thickness of the coating can be reduced, providing a reduced surface area, further minimizing background autofluorescence.
  • the resultant polymer coating can be further processed, e.g., dyed, to, for example, reduce background autofluorescence.
  • the dye can provide a darker background, providing more absorbance than reflectance, increasing the signal-to-noise ratio.
  • Suitable dyes include, for example, Irgalan Black, sometimes referred to as acid black 107 or acid black 132.
  • the resultant polymer coating can have any desired porosity.
  • the resultant polymer coating is microporous, for example, having a pore size of about 4 microns ( ⁇ m) or less, in some embodiments, about 2 microns or less.
  • the pore size is at least about 0.5 microns.
  • the pore size is in the range of about 1 to about 3 microns.
  • the pore size can be less than about 1 microns or more than about 4 microns.
  • a polymer coating can be prepared at an increased temperature to provide a coating with larger pores, and prepared at a decreased temperature to provide a coating with smaller pores.
  • the resultant polymer coating on the support can have a neutral charge, or be charged, e.g., positively or negatively charged.
  • the polymer coating can include a combination of charged groups, e.g., positively and negatively charged groups.
  • a positively charged polymer coating can include, for example, a quaternary ammonium group.
  • a negatively charged polymer coating can include, for example, a sulfonic or carboxylic group.
  • the polymer coating can include a polar group.
  • the coating composition can be prepared by a variety of methods known in the art.
  • the coating composition can be prepared by dissolving at least one polymer, e.g., polyam ⁇ ne, in a suitable solvent.
  • Preferred solvents include, for example, water, formic acid, hydrochloric acid, phosphoric acid, low boiling alcohols such as methanol, ethanol, and propanol, and combinations thereof.
  • the solvent can be present in an amount of, for example, from about 40% to about 99%, and preferably in an amount of from about 90% to about 99% by weight of the coating composition.
  • the polymer(s), e.g., polyamine can be present in an amount of, for example, from about 1% to about 15%, and preferably in an amount of from about 1% to about 2.5% by weight of the coating composition.
  • the coating composition of certain embodiments can be prepared by, for example, combining and polymerizing monomers, a crosslinking agent, and an initiator.
  • the polymerization can be carried out in a solvent, preferably in water or water/methanol solution.
  • the polymerization is preferably stopped prior to the formation of a gel or excessive crosslinking.
  • the viscosity of the polymerization solution can be monitored to control the degree of polymerization.
  • the polymerization is carried out for any suitable length of time, e.g., for about 4 hours or more. According to certain embodiments, the polymerization is carried out for a period of from about 4 hours to about 5 hours. According to certain other embodiments, the polymerization is carried out for a period of from about 16 hours to about 24 hours.
  • the viscosity of the solution is typically below about 2000 cps, e.g., from about 50 cps to about 500 cps, preferably from about 50 cps to about 500 cps, and more preferably from about 100 cps to about 500 cps. According to certain embodiments, the viscosity is from about 100 cps to about 250 cps.
  • the resulting coated support can be cured to effect the curing or crosslinking of the coating composition as is known in the art.
  • the coated support can be cured at a temperature of below 130 0 C, e.g., from about 5O 0 C to about 130 0 C, and preferably at a temperature of from about 70 0 C to about 130 0 C, for a suitable period of time, which can range from, for example, about 5 minutes to about 60 minutes, and preferably from about 10 minutes to about 30 minutes.
  • the resulting device can be washed to leach out any extractables in the membrane.
  • the device can be leached in hot deionized water, e.g., in water held above 73 0 C.
  • the resulting device can then dried in air or in an oven to remove the water.
  • the coated support is immersed in a non-solvent bath to coagulate the polymer coating.
  • non-solvents include water, alcohol, and mixtures containing one or more of water, formamide, formic acid, and alcohol
  • the resulting analysis is typically dried to remove some or all of the non-solvent associated with the coating.
  • Analysis devices according to the present invention are simple to manufacture and can be especially suited to automated fabrication.
  • the formed devices can be packaged, e.g., individually, or in packs of multiple devices.
  • the analysis devices include bar-coding, e.g., for ease in data tracking.
  • samples e.g., containing one or more biomolecules of interest
  • reagents e.g., binding agents and labels
  • various assays can be performed, as is known in the art.
  • Embodiments of analysis devices according to the invention have a variety of applications, especially in hybridization assays and immunoassays, including, but not limited to, dots and blots, as well as arrays (e.g., microaxrays).
  • arrays e.g., microaxrays
  • Embodiments of the invention are compatible with automated and semi-automated protocols, as well as high throughput applications, and are especially suitable for bioinformatics applications, e.g., for data mining and data visualization.
  • the analysis device can be used in accordance with the devices and methods disclosed in U.S. published patent application no. US 2004/0037750 Al.
  • any suitable hybridization condition can be employed, e.g., highly stringent, moderately stringent, or low stringent, conditions.
  • low stringency hybridization conditions may be at 5O 0 C and 6X SSC (0.9 M sodium chloride/0.09 M sodium citrate) while hybridization under stringent conditions may be at 5O 0 C or higher and 0.1 X SSC (15 mM sodium chloride/1.5 mM sodium citrate).
  • the excess probe molecules are typically removed, and the microarray is analyzed for a signal such as fluorescence.
  • any suitable binding agent such as a probe can be employed, for example, the nucleic acid probe comprises a nucleic acid and, if the probe is to be hybridized with an immobilized complementary sequence, the probe can comprise a nucleic acid and a label such as a fluorescent label.
  • at least one binding agent is preferably a specific binding agent.
  • Suitable labels include fluorescein, rhodamine, BODIPY, cyanine dyes such as Cy 5 and the like, and radioactive isotopes, such as, e.g., 33 S, 32 P 5 and 3 H. Multiple probes and multiple labels can be utilized in accordance with embodiments of the invention.
  • a hybridization method for analyzing biomolecules comprises providing (e.g., depositing) a binding agent comprising one or more probe nucleic acids having nucleotide sequences on the surface of an embodiment of the analysis device such that the one or more probe nucleic acids are immobilized, the probe nucleic acid nucleotide sequences being complementary to a nucleotide sequence of at least one biomolecule of interest, the polymer coating having a surface for receiving the probe nucleic acids and a sample containing the biomolecule; depositing the sample containing the biomolecule onto the surface of the device such that the biomolecule contacts the probe nucleic acid and a complex is formed between the probe nucleic acid nucleotide sequence and the complementary nucleotide sequence of the biomolecule; and, detecting the complex.
  • the sample containing the at least one biomolecule of interest is initially placed on the surface of the analysis device and immobilized, and one or more probes are subsequently deposited on the device such that one or more complexes are formed, and subsequently detected.
  • the analysis device can be flexible, the analysis device is wrapped around a spool or reel and the complexes formed on the device are detected while the device is wrapped around the spool or reel.
  • hybridization assays according to the invention that can include, for example, monitoring levels of gene expression, or determining the presence or absence of known or new mutations in gene sequences
  • numerous probes and samples are deposited in a microarray pattern on a single analysis device, and the complexes are subsequently detected, e.g., via automated analytical protocols.
  • inventions include, for example, immunoassays, e.g., wherein a binding agent comprising at least one antibody is initially deposited on the surface, and a sample is subsequently deposited to form a complex, or wherein a sample is initially deposited, and a binding agent comprising an antibody is subsequently deposited to form a complex.
  • immunoassays e.g., wherein a binding agent comprising at least one antibody is initially deposited on the surface, and a sample is subsequently deposited to form a complex, or wherein a sample is initially deposited, and a binding agent comprising an antibody is subsequently deposited to form a complex.
  • additional reagents e.g., PCR products, PCR reagents and/or one or more binding agents (including, for example, anti-antibodies and/or specific binding agents), or labels
  • binding agents including, for example, anti-antibodies and/or specific binding agents
  • labels can be utilized, e.g., to form a complex, or to label a complex.
  • labels e.g., radioactive, fluorescent, or chemiluminescent
  • biomolecules includes, but is not limited to, nucleic acid sequences, e.g., natural or synthetic DNA (for example, cDNA obtained after transcribing mRNA), RNA (including mRNA, tRNA, and rRNA); PNA (peptide nucleic acids); mixtures and/or hybrids thereof, as well as oligonucleotides, modified nucleic acids, fragments and/or derivatives of nucleic acids), antigens, proteins (including antibodies, and some antigens), peptides, bacteria, viruses, protozoans (as well as components of bacteria, viruses, and protozoans), and one or more analytes of interest (e.g., recombinant nucleic acid products and/or byproducts, drugs, pollutants, and poisons).
  • nucleic acid sequences e.g., natural or synthetic DNA (for example, cDNA obtained after transcribing mRNA), RNA (including mRNA, tRNA, and rRNA); PNA (peptid
  • the biomolecu ⁇ es can be obtained from a variety of sources.
  • a sample containing the biomolecules can comprise one or more cells, or an aqueous or aqueous miscible solution that is obtained directly from a liquid source or as a wash from a solid material, a growth medium or buffer solution in which biomolecules are present or have been introduced.
  • the sample is obtained from a biological fluid, including separated or unfiltered fluids such as blood or blood components, urine, cerebrospinal fluid, lymph fluids, tissue homogenate, cell extracts, saliva, sputum, stool, or physiological secretions.
  • the sample can be obtained from an environmental source, e.g., a waste stream, a water source, a supply line, or a production lot.
  • Industrial sources include fermentation media, such as from a biological reactor or food fermentation process such as brewing, or foodstuffs, such as meat, produce, or dairy products.
  • binding agent includes, but is not limited to, one or more ligands and receptors, e.g., nucleic acid probes and/or antibodies (including a monoclonal antibodies, polyclonal antibodies, and anti-antibodies).
  • at least one binding agent e.g., the binding agent that is capable of binding to the biomolecules of interest, is a specific binding agent.
  • the specific binding agent has at least about 30% (more preferably, at least about 50%) complementarity with a region in the biomolecules of interest.
  • the desired specificity can vary, depending on the particular nature of the biomolecules to be detected, the information desired about the nature of the sample, and the like.
  • the first binding agent is capable of binding to the biomolecules
  • the second binding agent is capable of binding to either the first binding agent (e.g., as in a double antibody assay), or to the biomolecules (e.g., as in a sandwich assay).
  • detecting the biomolecules can include confirming the presence of the biomolecules, as well as (if desired) identifying the v biomolecules, analyzing the biomolecules, and/or quantifying the biomolecules.
  • Biomolecules can be detected as part of an on-going or monitoring process, e.g., as part of a quality control system, and/or to monitor the appearance/removal (or rate of appearance/removal) of the biomolecules in the sample, in the material of interest and/or in the product or process fluid being produced.
  • the complex(es) are analyzed utilizing automated equipment.
  • the illustrated apparatus also includes a tension reel 50, idler reels 51a-51h, and a wind up reel 51, wherein wind up reel 51 is rotated by a motor (not shown).
  • the first chamber 10 includes an acid solution, and the precipitation bath 10 and rinsing bath 20 are filled with deionized (DI) water.
  • DI deionized water
  • a commercially available nylon monofilament is obtained (p-nylon monofilament, Saunders Tread Co., Gastonia, NC) and washed with isopropyl alcohol to remove the protective coating.
  • the washed monofilament 1 is threaded into the apparatus via reels 50, 51a-51h, and 52, and the speed is set on the wind-up motor driving the wind-up reel 52.
  • a vacuum of about 0.5 inches of mercury is applied to the chamber via vacuum port 11 to prevent dripping of the acid solution into the precipitation bath 101.
  • the treated support is then precipitated in deionized (DI) water in the precipitation bath 101 (about 60-80 seconds), followed by rinsing in DI water in the rinsing bath 102 (about 60-80 seconds), drying in the drying chamber 20 (6O 0 C; about 30-40 seconds) and winding onto a reel.
  • DI deionized
  • the etched support has a porous layer surrounding the core, wherein the outer portion (i.e., the portion farthest from the core) of the layer provides the porous surface of the support.
  • the etched support has a thickness of about 135 microns + 5 microns, and a tensile strength of between about 45000-60000 psi (tension at maximum load) with about
  • the etched support has a low background fluorescence of less than about 500
  • TMs example demonstrates the preparation of an embodiment of an analysis device with a polymer coating in accordance with the invention, wherein the polymer coating has a symmetric microporous structure.
  • first chamber 10 includes the polymer coating solution.
  • the dried etched support is wound onto the apparatus, as described in Example 1.
  • a polyamide polymer coating solution is prepared as follows. 14.5% of a high molecular weight nylon 6,6 resin, commercially available as E55 (weight average molecular weight of about 125,000), is dissolved in 77% formic acid and 8.5% water at 35 0 C for 4 hours. The coating solution is degassed, and placed in the first chamber 10.
  • the speed is set on the wind-up motor driving the wind-up reel 52, and the dried etched support is drawn through the polymer coating solution in the first chamber 10 (6 seconds residence time).
  • the polymer coating solution is cast on the support as the support exits the base of chamber 10.
  • the coated support is drawn into the precipitation bath 101 containing 52% formic acid such that the support is drawn into the aqueous formic acid bath perpendicular to the liquid surface.
  • the support is then rinsed upon drawing the coated support into the DI water filled rinse bath 102 for about 30-40 seconds, followed by drying in the drying chamber 20 (6O 0 C) for about 15-20 seconds, and winding onto the wind-up reel.
  • the CWST of the coating is about 72-76 dynes/cm (about 7.2-7.6 x 10 "s N/cm).
  • the coating that has a thickness of about 5-7 microns, has a symmetric microporous structure having an average pore size of about 0.5 microns.
  • the porous layer of the support that has a thickness of about 5-7 microns, has a symmetric microporous structure having an average pore size of about 0.5 microns.
  • the etched portion of the support has a thickness of about 7-10 microns.
  • Figures 3B and 3C show illustrative cross-sectional views of an analysis device, showing an etched support, with a porous layer surrounding the core, and a polymer coating surrounding the porous layer.
  • This example demonstrates the preparation of an embodiment of an analysis device with a polymer coating to provide a positively charged surface in accordance with the invention.
  • a polyamide polymer coating solution is prepared as follows.
  • the CWST of the coating is about 72-76 dynes/cm (about 72-76 x 10 "s N/cm).
  • the coating that has a thickness of about 5-7 microns, has a symmetric microporous structure having an average pore size of about 0.5 microns.
  • the porous layer of the support that has a thickness of about 5-7 microns, has a symmetric microporous structure having an average pore size of about 0.5 microns.
  • the etched portion of the support has a thickness of about 7-10 microns.
  • a solution containing Ponceau S (a negatively charged dye) is placed in contact with the surface of the device, and the excess is washed off. After washing, the surface of the device is a pinkish-reddish color, as dye remains bound to the surface, showing that the negatively bound dye is adsorbed to the positively charged polymer coating.
  • EXAMPLE 4 (0108] This example demonstrates the preparation of an embodiment of an analysis device with a polymer coating to provide a negatively charged surface in accordance with the invention.
  • a polyamide polymer coating solution is prepared as follows. 13.5% of a high molecular weight nylon 6,6 resin, commercially available as E55 (weight average molecular weight of about 125,000) and 1% Gantrez, is dissolved in 77% formic acid and 8.5% water at 35 0 C for 4 hours. The coating solution is degassed, and placed in the first chamber 10. [011OJ An etched support is coated with the polymer solution as generally described in Example 2.
  • the CWST of the coating is about 72-76 dynes/cm (about 72-76 x 10 "5 N/cm).
  • the coating that has a thickness of about 5-7 microns, has a symmetric microporous structure having an average pore size of about 0.5 microns.
  • the porous layer of the support (the etched portion of the support) has a thickness of about 7-10 microns.
  • a solution containing Toluidine Blue (a positively charged dye) is placed in contact with the surface of the device, and the excess is washed off. After washing, the surface of the device has a bluish color, as dye remains bound to the surface, showing that the positively bound dye is adsorbed to the negatively charged polymer coating.
  • a polymer coating solution is prepared as follows. A polymer solution containing 9% nitrocellulose is dissolved in 91% dimethyl ammonium chloride (DMAC) at
  • the coating solution is degassed, and placed in the first chamber 10.
  • the CWST of the coating is about 72-76 dynes/cm (about 72-76 x IO "5 N/cm).
  • the coating that has a thickness of about 5-7 microns, has a symmetric microporous structure having a pore size of about 0.5 microns.
  • the porous layer of the support (the etched portion of the support) has a thickness of about 7-10 microns.
  • a solution containing Ponceau S is placed in contact with the surface of the device, and the excess is washed off. After washing, the surface of the device has show dye remains bound to the surface, showing that the negatively bound dye is adsorbed to the positively charged polymer coating.
  • This example demonstrates an embodiment of an analysis device is hydrophilic and has good wettability.
  • spots of dye are readily absorbed by the strand, and spread laterally (along the axis of the device), rather than beading up and rolling off the device. This shows the device is hydrophilic with good wettability.
  • a polyamide polymer solution is prepared as follows.
  • a high molecular weight nylon 6,6 resin commercially available as E55 (weight average molecular weight of about 125,000) is mixed with a low molecular weight nylon 6,6 resin, commercially available as E53 (weight average molecular weight of about 110,000) wherein the mixture has 50% high molecular weight resin and 50% low molecular weight resin.
  • the resultant mixture having 7.5% high molecular weight resin solids and 7.5% low molecular weight resin solids, is dissolved in formic acid and water wherein the 15% resin solids mixture is combined with 73% formic acid and 12% water at 25 0 C for 4 hours.
  • the polymer solution is degassed and poured into the first chamber 10.
  • the CWST of the coating is about 72-76 dynes/cm (about 72-76 x 10 ⁇ 5 N/cm).
  • the coating that has a thickness- of about 5-7 microns, has a symmetric microporous structure having an average pore size of about 0.7 microns.
  • the porous layer of the support (the etched portion of the support) has a thickness of about 7-10 microns.
  • EXAMPLE 8 [0125] This example demonstrates the preparation of an embodiment of an analysis device with a polymer coating in accordance with the invention, wherein the polymer coating has an asymmetric microporous structure.
  • the first chamber 10 includes the polymer coating solution.
  • the dried etched support is threaded into the apparatus.
  • a polyamide polymer coating solution is prepared as follows. 14.5% of a high molecular weight nylon 6,6 resin, commercially available as E55 (weight average molecular weight of about 125,000), is dissolved in 77% formic acid and 8.5% water at 35 0 C for 4 hours. The coating solution is degassed, and placed in the first chamber 10.
  • the speed is set on the wind-up motor driving the wind-up reel, and the dried etched support is drawn through the polymer coating solution in the first chamber 10 (6 seconds residence time).
  • the polymer coating solution is cast on the support as the support exits the base of the first chamber 10.
  • the coated support is drawn into the precipitation bath 101 containing 100% DI water such that the support is drawn into the aqueous bath perpendicular to the liquid surface.
  • the support is then rinsed upon drawing the coated support into the DI water filled rinse bath 102 for about 30-40 seconds, followed by drying in the drying chamber 20 (6O 0 C) for about 15-20 seconds, and winding onto the wind-up reel.
  • the CWST of the coating is about 72-76 dynes/cm (about 72-76 x 10 "5 N/cm).
  • the coating that has a thickness of about 5-7 microns, has an asymmetric microporous structure.
  • the porous layer of the support (the etched portion of the support) has a thickness of about 7-10 microns.
  • This example demonstrates an analysis device can be used in the detection of biomolecules in a hybridization assay.
  • the diluent is TE buffer, and each solution contains 10% glycerol.
  • spots are applied to an analysis device using a solid pin (Telchem).
  • the first spot is a blank, TE buffer only.
  • Each subsequent spot is an unlabeled oligonucleotide serial dilution, applied sequentially in increasing order of unlabeled DNA per spot, i.e., 30000x, 1000Ox, 3000x, and so on to 3Ox.
  • a spot of 1% BPB in T AE/ 10% glycerol is applied near the end of the device as a marker.
  • the unlabeled oligonucleotides are fixed to the devices by baking at 8O 0 C for 30 minutes and exposure to UV for 1 minute, followed by prewetting in 2x SSC, prehybridization using 50 mM sodium phosphate (pH 7.2), 0.5% w/v hammersten grade casein, 10% SDS, at room temperature, draining the prehybridization solution, hybridization with Cy3-DNA or CyS-DNA complementary to the unlabeled nucleotides, washing (twice) in Ix SSCj 0,1% SDS, at room temperature for 15 minutes, rinsing in 2x SSC, and air drying.
  • a glass cover slip is taped on top of each slide to ensure the analysis devices are flat and on the same place.
  • the slides are scanned using a Mirai scanner (model CRBIOIIe) and the signal is optimized for each slide.
  • This example demonstrates the preparation of an embodiment of an analysis device with a polymer coating in accordance with the invention, wherein the polymer coating has a reduced thickness compared to the coating described in Example 2.
  • the etched support prepared according to Example 1 is coated with a polymer solution utilizing the apparatus as shown in Figure 1 as follows.
  • first chamber 10 includes the polymer coating solution.
  • the dried etched support is wound onto the apparatus, as described in Example 1.
  • a polyamide polymer coating solution is prepared as follows. 5% of a high molecular weight nylon 6,6 resin, commercially available as E55 (weight average molecular weight of about 125,000), is dissolved in 80% formic acid and 15% water at 35 0 C for 4 hours. The coating solution is degassed, and placed in the first chamber 10. [0143] The speed is set on the wind-up motor driving the wind-up reel 52, and the dried etched support is drawn through the polymer coating solution in the first chamber 10 (6 seconds residence time). The polymer coating solution is cast on the support as the support exits the base of chamber 10. The coated support is drawn into the precipitation bath 101 containing 52% formic acid such that the support is drawn into the aqueous formic acid bath perpendicular to the liquid surface.
  • the support is then rinsed upon drawing the coated support into the DI water filled rinse bath 102 for about 30-40 seconds, followed by drying in the drying chamber 20 (6O 0 C) for about 15-20 seconds, and winding onto the wind-up reel.
  • the CWST of the coating is about 72-76 dynes/cm (about 7.2-7.6 x 10 "3 N/cm).
  • the coating that has a thickness of about 1-3 microns, has a symmetric microporous structure having an average pore size of about 0.5 microns.
  • the porous layer of the support (the etched portion of the support) has a thickness of about 7-10 microns.
  • This example demonstrates the preparation of an embodiment of an analysis device with a polymer coating in accordance with the invention, wherein the polymer coating is coated with a black dye to reduce background autofluorescence.
  • the etched support prepared according to Example 1 is coated with a polymer solution as described in Example 2.
  • the analysis device comprising an etched support and a polymer coating is coated with a black dye utilizing the apparatus as shown in Figures 4A and 4B as follows.
  • an apparatus 1000 as shown in Figure 4 A including a first bath 101 (hereinafter referred to as the "dye bath"), a second bath 102 (hereinafter referred to as the "rinsing bath”), and a second chamber 20 (hereinafter referred to as the “drying chamber”), is used.
  • the illustrated apparatus also includes a tension reel 50, idler reels 5 Ia- 5 Ih, and a wind up reel 51, wherein wind up reel 51 is rotated by a motor (not shown).
  • the apparatus shown in Figure 4 A does not include a first chamber 10.
  • the polymer coated strand in the dye bath is wound to form a double loop, whereas the strand is wound in a single loop in the precipitation bath in Examples 1-10.
  • the analysis device comprising the etched support having a polymer coating is wound onto the apparatus.
  • the dye bath includes the dye coating solution.
  • a dye coating solution is prepared as follows. 0.0002% of Irgalan black (acid black 132) is dissolved in 2% aqueous acetic acid solution and placed in the dye bath.
  • the speed is set on the wind-up motor driving the wind-up reel 52, and the polymer coated support is drawn through the dye solution in the dye bath 101 (about 2 minutes residence time), wherein the dye is adsorbed to the polymer coated surface, to provide a dye coating on the polymer coated device (hereinafter referred to as the "dye coated strand").
  • the dye coated strand is then rinsed upon drawing the strand into the DI water filled rinse bath 102 for about 30-40 seconds, followed by drying in the drying chamber 20 (6O 0 C) for about 15-20 seconds, and winding onto the wind-up reel.

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Abstract

La présente invention concerne un dispositif d'analyse comportant un support présentant une surface poreuse revêtue d'un polymère pour fournir un dispositif d'analyse avec une surface microporeuse.
PCT/US2007/069731 2006-05-30 2007-05-25 Dispositif d'analyse WO2007140294A2 (fr)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015126522A1 (fr) * 2014-02-21 2015-08-27 Clontech Laboratories, Inc. Dispositifs de dosage comprenant une membrane poly(acide), et procédés les utilisant
US9895665B2 (en) 2014-02-21 2018-02-20 Takara Bio Usa, Inc. Spin columns comprising poly(acid) membrane separation matrices, and methods of making and using the same
US10351846B2 (en) 2014-09-17 2019-07-16 Illumina Cambridge Limited Flexible tape-based chemistry apparatus

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Publication number Priority date Publication date Assignee Title
WO1999013313A1 (fr) * 1997-09-11 1999-03-18 Genovations, Inc. Procede de production de reseaux a haute densite
EP1162262A1 (fr) * 1999-03-05 2001-12-12 Mitsubishi Rayon Co., Ltd. Fibres contenant des acides nucleiques immobilises, alignement de fibres contenant des acides nucleiques immobilises et coupe transversale de telles fibres
EP1249702A1 (fr) * 2000-01-17 2002-10-16 Unitec Co., Ltd. Support integre, micro-recipient integre et membrane permeable, et procede de production et d'utilisation correspondants

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999013313A1 (fr) * 1997-09-11 1999-03-18 Genovations, Inc. Procede de production de reseaux a haute densite
EP1162262A1 (fr) * 1999-03-05 2001-12-12 Mitsubishi Rayon Co., Ltd. Fibres contenant des acides nucleiques immobilises, alignement de fibres contenant des acides nucleiques immobilises et coupe transversale de telles fibres
EP1249702A1 (fr) * 2000-01-17 2002-10-16 Unitec Co., Ltd. Support integre, micro-recipient integre et membrane permeable, et procede de production et d'utilisation correspondants

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015126522A1 (fr) * 2014-02-21 2015-08-27 Clontech Laboratories, Inc. Dispositifs de dosage comprenant une membrane poly(acide), et procédés les utilisant
US9895665B2 (en) 2014-02-21 2018-02-20 Takara Bio Usa, Inc. Spin columns comprising poly(acid) membrane separation matrices, and methods of making and using the same
US10195569B2 (en) 2014-02-21 2019-02-05 Takara Bio Usa, Inc. Spin columns comprising poly(acid) membrane separation matrices, and methods of making and using the same
US11103831B2 (en) 2014-02-21 2021-08-31 Takara Bio Usa, Inc. Spin columns comprising poly(acid) membrane separation matrices, and methods of making and using the same
US10351846B2 (en) 2014-09-17 2019-07-16 Illumina Cambridge Limited Flexible tape-based chemistry apparatus

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