US20020150942A1 - Probe carrier and method of manufacturing the same - Google Patents

Probe carrier and method of manufacturing the same Download PDF

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Publication number
US20020150942A1
US20020150942A1 US10/105,303 US10530302A US2002150942A1 US 20020150942 A1 US20020150942 A1 US 20020150942A1 US 10530302 A US10530302 A US 10530302A US 2002150942 A1 US2002150942 A1 US 2002150942A1
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United States
Prior art keywords
probe
filler
nucleic acid
ring bodies
carrier
Prior art date
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Abandoned
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US10/105,303
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English (en)
Inventor
Nobuko Yamamoto
Naoto Mihashi
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Canon Inc
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Individual
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Filing date
Publication date
Application filed by Individual filed Critical Individual
Assigned to CANON KABUSHIKI KAISHA reassignment CANON KABUSHIKI KAISHA ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: YAMAMOTO, NOBUKO, MIHASHI, NAOTO
Publication of US20020150942A1 publication Critical patent/US20020150942A1/en
Priority to US11/624,980 priority Critical patent/US7507576B2/en
Abandoned legal-status Critical Current

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    • 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
    • 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
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0046—Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00279—Features relating to reactor vessels
    • B01J2219/00306—Reactor vessels in a multiple arrangement
    • B01J2219/00313—Reactor vessels in a multiple arrangement the reactor vessels being formed by arrays of wells in blocks
    • B01J2219/00315—Microtiter plates
    • B01J2219/00317—Microwell devices, i.e. having large numbers of wells
    • 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
    • B01J2219/00351—Means for dispensing and evacuation of reagents
    • B01J2219/00421—Means for dispensing and evacuation of reagents using centrifugation
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B01J2219/00614—Delimitation of the attachment areas
    • B01J2219/00621—Delimitation of the attachment areas by physical means, e.g. trenches, raised areas
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00673—Slice arrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00677—Ex-situ synthesis followed by deposition on the substrate
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/0072—Organic compounds
    • B01J2219/00722—Nucleotides
    • 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
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B40/00—Libraries per se, e.g. arrays, mixtures
    • C40B40/04—Libraries containing only organic compounds
    • C40B40/06—Libraries containing nucleotides or polynucleotides, or derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B60/00—Apparatus specially adapted for use in combinatorial chemistry or with libraries
    • C40B60/14—Apparatus specially adapted for use in combinatorial chemistry or with libraries for creating libraries
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T156/00—Adhesive bonding and miscellaneous chemical manufacture
    • Y10T156/10—Methods of surface bonding and/or assembly therefor
    • Y10T156/1052—Methods of surface bonding and/or assembly therefor with cutting, punching, tearing or severing
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/14—Heterocyclic carbon compound [i.e., O, S, N, Se, Te, as only ring hetero atom]
    • Y10T436/142222—Hetero-O [e.g., ascorbic acid, etc.]
    • Y10T436/143333—Saccharide [e.g., DNA, etc.]

Definitions

  • This invention relates to a probe carrier carrying a probe rigidly secured thereto for detecting a target substance.
  • the present invention also relates to a method of manufacturing such a probe carrier.
  • such screening operations as described above that are conducted in parallel simultaneously consist in detecting an action or non-action or a response or non-response of each specimen to the known probes arranged in array, or probe array, provided as means for sorting the substances of specimens for evaluation under same conditions.
  • the action or response to be used with each probe is defined in advance and therefore substances of a same type are normally used as probe species that are mounted on a probe array.
  • the probe array may be that of DNA probes carrying a group of DNAs having different respective base sequences. DNAs, proteins and synthesized chemicals (drugs) are examples of substances that may be used for a group of probes.
  • probe array of a group of a plurality of probe species is used in many instances, a large number of identical DNAs having a same base sequence, identical proteins having a same amino acid sequence or identical chemical substances may be arranged in array. Such probes are mainly used for screening drugs.
  • the target substance is a nucleic acid
  • the probes may be formed by using a single stranded nucleic acid that shows a complementary sequence relative to all or part of the target nucleic acid and is adapted to a specific hybridization with the base sequence of the target nucleic acid.
  • a group of DNAs having different base sequences, a group of proteins having different amino acid sequences, a group of different chemical substances or the like are often arranged in array on a substrate according to a predetermined sequence of arrangement
  • DNA probe arrays are used for analyzing the base sequence of a gene DNA or conducting a gene diagnosis by analyzing a number of items simultaneously in order to raise the reliability of operation as pointed out above.
  • U.S. Pat. No. 5,424,186 describes a technique of preparing an array of DNA probes with DNAs having respective base sequences that are different from each other by means of a stepwise elongation reaction conducted on a carrier by utilizing photodecomposable protective groups and photolithography. With the proposed technique, it is possible to prepare a DNA probe array carrying DNAs of more than 10,000 different kinds that are different from each other in terms of base sequence per 1 cm 2 .
  • the process of synthesizing a DNA by means of a stepwise elongation reaction comprises a photolithography step in which dedicated photomasks are used respectively for the four different kinds of base (A, T, C, G) in order to selectively elongate any of the bases at a predetermined position of the array so that consequently DNAs of different species having desired respective base sequences are synthetically produced and arranged on a substrate in a predetermined order.
  • EP0703825B1 describes a technique of synthesizing DNAs of a plurality of different species having respective predetermined base sequences in a solid phase by supplying nucleotide monomers and activators by means of respective piezo jet nozzles for the purpose of solid phase synthesis of DNAs.
  • This supply (application) technique utilizing an ink-jet method is reliable in terms of reproducibility of supply rate if compared with a solution supply (application) technique utilizing capillaries and also provides advantages for realizing high density probe arrays because the nozzle structure of the ink-jet system can be miniaturized.
  • Patent Publication EP895082 discloses a technique of causing liquid containing a probe to adhere to a solid phase as liquid droplets by means of a bubble jet head and forming a spot containing a probe on the solid phase.
  • Patent Publication WO00/53736 discloses a method of manufacturing arrays by immobilizing nucleic acid in a hollow thread.
  • a flat plate-shaped probe carrier comprising a plurality of ring bodies having in the inside a region for fixing a probe adapted to be bonded specifically to a target substance and a filter filled among the ring bodies without any substantial space left therein.
  • a probe carrier comprising a plurality of ring bodies having in the inside a region for fixing a probe adapted to be bonded specifically to a target substance, the method comprising:
  • FIGS. 1A and 1B are schematic illustrations of a probe carrier according to the invention.
  • FIG. 2A is a schematic illustration of an apparatus for forming a region for fixing a probe in a hollow member.
  • FIG. 2B is a schematic illustration of a region for fixing a probe.
  • FIGS. 1A and 1B schematically illustrate a probe carrier according to the invention and having such a configuration.
  • FIG. 1A is a schematic plan view of the probe carrier, showing the surface thereof having opening sections 2 a of the ring bodies 2 .
  • FIG. 1B is a schematic cross sectional view of the probe carrier taken along line 1 B- 1 B in FIG. 1A.
  • the probe carrier 1 has a planar surface where the openings of the opening sections 2 a of the ring bodies 2 are arranged.
  • a probe is fixed to the surface of the inner surface 2 c of each opening section 2 a .
  • the region for fixing a probe of each ring body 2 is formed by the inner surface 2 c of the opening section 2 a .
  • the ring bodies 2 can be formed by using fiber, glass, resin or some other similar material.
  • each ring body has a pair of opposite surfaces produced by truncation and running substantially in parallel with each other in a direction perpendicular to the axial direction of the hollow members. At least one of the opposite surfaces can be used for arranging a region for fixing a probe of the carrier.
  • the operation of fixing a probe to the hollow area of each tubular member of the probe carrier may come before or after the operation of filling the outside space of the tubular members with a filler and solidifying it.
  • the external space of the ring bodies of the probe carrier is filled with a filler 3 to produce a layer 4 comprising the ring bodies as integral parts thereof. While the layer 4 is laid on a base member 5 supporting the former in the instance of FIGS. 1A and 1B, the base member 5 may be omitted if the layer 4 itself can provide a satisfactory mechanical strength.
  • the expression of “without any substantial space left therein” refers to a state where the space is filled with the filler to such an extent that cleansing or specimen solutions and various reagents would not permeate after washing the ring carrier.
  • a probe carrier as shown in FIGS. 1A and 1B can be manufactured by a method as described below.
  • each hollow member that may be a tubular member or a hollow thread is filled with a solution containing a probe and the probe is fixed to the inner wall of the hollow member.
  • the hollow member may be formed typically by extrusion molding of polypropylene film that is used for purification of water, artificial lung and artificial liver, polyethylene film or cupro-ammonia cellulose regenerated film.
  • the above fixing operation is conducted for each probe necessary for forming the probe carrier.
  • a reagent to be used for the purpose of fixation and/or a cleansing solution is supplied to the inside of the hollow member.
  • Any known appropriate technique can be used for the fixing operation.
  • liquid containing the probe may be poured into the hollow area of the hollow member to make the inner wall of the hollow member and the probe contact and react with each other.
  • the probe may be fixed to the inner wall of the hollow member by means of a chemical reaction utilizing any of various reaction groups and/or physical adsorption, which will be described hereinafter.
  • a hollow member carrying the probe fixed to the inner wall thereof is obtained by appropriately cleansing the hollow of the hollow member.
  • the hollow member now carrying the probe fixed to the inner wall thereof is closed at an end. Then, a necessary number of similar hollow members are arranged in a container to be used for a centrifugal process in parallel with each other along the axial direction thereof and bundled with the ends made flush with each other. Note that the hollow members are arranged and bundled in such a way that, when they are cut to show opposite surfaces, the region of each hollow member where the probe is fixed is located at a predetermined position on the corresponding surface.
  • FIG 2 A shows how the hollow members 7 are arranged in a container 6 that is to be used for a centrifugal process.
  • the container 6 is made to turn along a circular track having a given radius of gyration with the central axis of the container 6 located on a radius of gyration in order to generate centrifugal force that is directed toward the end of the bundle of the hollow members in the direction of the arrow shown in FIG. 2A.
  • a bonding material (potting material) that may typically be polyurethane is driven to move in the direction of the arrow and fill the external space of the hollow members 7 by the centrifugal force.
  • the mobilized bonding material As the application of the centrifugal force is suspended, the mobilized bonding material is solidified so that a fixed section 8 as shown in FIG. 2B is obtained. If the bonding material is in a gel state and subjected to centrifugal force, shearing force is generated in the bonding material to make it have a thixotropic property and turn into a sol state. As a result, the filler is mobilized and driven to move into the external space of the tubular members.
  • the ends of the hollow members where the fixed section 8 is formed is preferably closed by (filled with) resin if the lateral wall separating the hollow and the external space of each hollow member shows gas permeability. If the lateral wall of each hollow member does not show gas permeability, it is preferable to close the end where the fixed section 8 is formed in order to reliably prevent the bonding material (filler) from flowing into the hollow of the hollow member.
  • the gyration of the container 6 is terminated when the solidification of the bonding material is completed. Then, the hollow members 7 are cut into a short piece at predetermined positions of the fixed section 8 along a plane perpendicularly, for example, intersecting the axial direction of the hollow members that are arranged in parallel with and rigidly secured to each other.
  • the plane of arrangement of the hollow ring bodies 2 having respective openings is made to agree with one of the opposite surfaces of the short piece as shown in FIGS. 1A and 1B.
  • the ring bodies 2 illustrated in FIGS. 1A and 1B are formed by truncating the hollow members 7 to show a predetermined height
  • a probe carrier having regions for fixing probes that are arranged in a predetermined manner is obtained from the short piece.
  • the probes fixed to the probe carrier can be specifically bonded to a specific target substance.
  • the probes may contain oligonucleotide, polynucleotide and/or other polymers that can recognize a specific target.
  • the term of “probe” as used herein refers to a group of molecules that can operate as probe such as polynucleotide molecules or that of molecules such as polynucleotide molecules that are fixed to distributed respective positions of a surface to show a same and identical arrangement and includes molecules called ligands.
  • the probe and the target can often be exchangeable and also can he bonded or made to become bonded to each other as part of ligand-antiligant (or receptor) pairs.
  • a probe and a target can contain one or more than one natural bases and/or analogs.
  • Examples of probe that can be supported on a carrier include a substance having a bonding section that is to be bonded to the carrier in a part of the oligonucleotide thereof showing a base arrangement that can be hybridized with a target nucleic acid, said bonding section to be bonded to the carrier will show a structure linked to the surface of the carrier.
  • probes to be carried by a probe carrier manufactured by a method according to the invention may be appropriately selected depending on the application thereof, they are preferably selected from DNAs, RNAs, cDNAs (complementary DNAs), PNAs, oligonucleotides, polynucleotides and other nucleic acids, oligopeptides, polypeptides, proteins, enzymes, substrates relative to enzymes, antibodies, epitopes relative to antibodies, antigens, hormones, hormone receptors, ligands, ligand receptors, oligosaccharides and polysaccharides for the purpose of advantageously embodying the method of the present invention. If necessary, two or more than two of the above listed substances may be combined for use.
  • a probe carrier refers to an object realized by fixing a plurality of probe species in independent respective regions of the surface of the carrier (including the surface of the inner walls of hollow members or tubular carrier members) typically as dot-shaped spots, while a probe array is one where such respective regions are arranged at a predetermined interval.
  • each probe has a structure that makes it possible to be bonded to the surface of the carrier and preferably be bonded onto the carrier by way of the structure that makes it possible to be bonded to the surface thereof.
  • the structure of each probe that makes it possible to be bonded to the surface of the carrier is formed by means of a process of introducing an organic functional group such as an amino group, a mercapto group, a carboxyl group, a hydroxyl group, an acid halide (haloformyl group; —COX), a halide (—X), aziridine, a maleimide group, a succinimide group, isothiocyanate, a sulfonylchloride (—SO 2 Cl) group, an aldehyde group (formyl group, —CHO), hydrazine or acetamide iodide.
  • the surface of the carrier may be treated appropriately in a manner that depends on the structure necessary for bonding the

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  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Nanotechnology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Physics & Mathematics (AREA)
  • Composite Materials (AREA)
  • Condensed Matter Physics & Semiconductors (AREA)
  • General Physics & Mathematics (AREA)
  • Materials Engineering (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
US10/105,303 2001-03-28 2002-03-26 Probe carrier and method of manufacturing the same Abandoned US20020150942A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US11/624,980 US7507576B2 (en) 2001-03-28 2007-01-19 Method of manufacturing probe carrier

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP093268/2001(PAT) 2001-03-28
JP2001093268A JP3937742B2 (ja) 2001-03-28 2001-03-28 プローブ担体及びその製造方法

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US11/624,980 Expired - Fee Related US7507576B2 (en) 2001-03-28 2007-01-19 Method of manufacturing probe carrier

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Publication number Priority date Publication date Assignee Title
JP5295733B2 (ja) * 2007-11-30 2013-09-18 キヤノン株式会社 生体の保持方法、生体の試験方法、生体の成育方法、生体の保持用シートおよび生体の処理装置
JP5660468B2 (ja) * 2011-03-15 2015-01-28 三菱レイヨン株式会社 生体関連物質検出用ゲルマイクロアレイの製造方法

Citations (5)

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Publication number Priority date Publication date Assignee Title
US4983195A (en) * 1990-01-04 1991-01-08 Corning Incorporated Method of making fiber optic coupler with longitudinal protrusions
US5424186A (en) * 1989-06-07 1995-06-13 Affymax Technologies N.V. Very large scale immobilized polymer synthesis
US6037186A (en) * 1997-07-16 2000-03-14 Stimpson; Don Parallel production of high density arrays
US20020147330A1 (en) * 2001-03-28 2002-10-10 Nobuko Yamamoto Probe carrier, method of manufacturing the same and apparatus to be used for the method
US6887701B2 (en) * 1999-07-30 2005-05-03 Large Scale Proteomics Corporation Microarrays and their manufacture

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Publication number Priority date Publication date Assignee Title
US4786137A (en) * 1984-12-31 1988-11-22 Ericsson, Inc. Optical cable with filling compound and parallel fibers
DE4029433A1 (de) 1990-09-17 1992-03-19 Degussa Zeolithmembran
US5474796A (en) 1991-09-04 1995-12-12 Protogene Laboratories, Inc. Method and apparatus for conducting an array of chemical reactions on a support surface
JP2757772B2 (ja) 1994-03-30 1998-05-25 株式会社島津製作所 ゲル電気泳動法及びそれに用いる試薬
US5807522A (en) 1994-06-17 1998-09-15 The Board Of Trustees Of The Leland Stanford Junior University Methods for fabricating microarrays of biological samples
SE9404166D0 (sv) * 1994-11-30 1994-11-30 Pharmacia Biotech Ab Multifunctional surfaces
JP4313861B2 (ja) 1997-08-01 2009-08-12 キヤノン株式会社 プローブアレイの製造方法
ATE431848T1 (de) 1999-03-05 2009-06-15 Mitsubishi Rayon Co Microarray mit einer biologischen substanz

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5424186A (en) * 1989-06-07 1995-06-13 Affymax Technologies N.V. Very large scale immobilized polymer synthesis
US4983195A (en) * 1990-01-04 1991-01-08 Corning Incorporated Method of making fiber optic coupler with longitudinal protrusions
US6037186A (en) * 1997-07-16 2000-03-14 Stimpson; Don Parallel production of high density arrays
US6887701B2 (en) * 1999-07-30 2005-05-03 Large Scale Proteomics Corporation Microarrays and their manufacture
US20020147330A1 (en) * 2001-03-28 2002-10-10 Nobuko Yamamoto Probe carrier, method of manufacturing the same and apparatus to be used for the method

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JP3937742B2 (ja) 2007-06-27
JP2002286712A (ja) 2002-10-03
US20070117139A1 (en) 2007-05-24
US7507576B2 (en) 2009-03-24

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