CA2339163A1 - Thermal and fluidic cycling device for nucleic acid hybridization - Google Patents

Thermal and fluidic cycling device for nucleic acid hybridization Download PDF

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Publication number
CA2339163A1
CA2339163A1 CA002339163A CA2339163A CA2339163A1 CA 2339163 A1 CA2339163 A1 CA 2339163A1 CA 002339163 A CA002339163 A CA 002339163A CA 2339163 A CA2339163 A CA 2339163A CA 2339163 A1 CA2339163 A1 CA 2339163A1
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CA
Canada
Prior art keywords
solid substrate
thermal management
fluid
cavity
management module
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CA002339163A
Other languages
French (fr)
Other versions
CA2339163C (en
Inventor
Aaron Custance
Jonathan Iam Parker
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
DIGILAB Inc
Original Assignee
Genomic Solutions, Inc.
Aaron Custance
Jonathan Iam Parker
Digilab, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Genomic Solutions, Inc., Aaron Custance, Jonathan Iam Parker, Digilab, Inc. filed Critical Genomic Solutions, Inc.
Publication of CA2339163A1 publication Critical patent/CA2339163A1/en
Application granted granted Critical
Publication of CA2339163C publication Critical patent/CA2339163C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/30—Staining; Impregnating ; Fixation; Dehydration; Multistep processes for preparing samples of tissue, cell or nucleic acid material and the like for analysis
    • G01N1/31—Apparatus therefor
    • G01N1/312—Apparatus therefor for samples mounted on planar substrates
    • 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
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • B01L7/52—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples
    • 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
    • G01N35/00029—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 flat sample substrates, e.g. 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
    • B01L2300/04—Closures and closing means
    • B01L2300/041—Connecting closures to device or container
    • B01L2300/045—Connecting closures to device or container whereby the whole cover is slidable
    • 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
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • B01L2300/0636—Integrated biosensor, microarrays
    • 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
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0877—Flow chambers
    • 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
    • B01L2300/18—Means for temperature control
    • B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
    • B01L2300/1822—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks using Peltier elements
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
    • B01L2400/049—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics vacuum
    • 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
    • G01N35/00029—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 flat sample substrates, e.g. slides
    • G01N2035/00099—Characterised by type of test elements
    • G01N2035/00158—Elements containing microarrays, i.e. "biochip"
    • 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
    • G01N2035/00346—Heating or cooling arrangements
    • G01N2035/00356—Holding samples at elevated temperature (incubation)
    • G01N2035/00366—Several different temperatures used

Abstract

An apparatus (100) for automatically hybridizing nucleic acid samples is disclosed. The apparatus includes a fluid control module (108) and a temperature control (104) for precisely controlling fluid contacting and temperature of a plurality of DNA samples. The DNA samples are typically arrayed on solid substrates (glass microscope slides) (106), and the disclos ed apparatus can process up to twelve slides at one time on a master unit; satellite units can be added to increase the number of slides. All slides ca n be processed in parallel, or may be addressed individually to undergo different hybridization protocols. Thermal control is typically by slide pairs, such that slide pair undergoes the same temperature profile. Processe s are carried out under software control by an embedded PC (personal computer) (122). User input is by touchscreen (124) or floppy disk drive (126).</SDOAB >

Claims (47)

  1. WHAT IS CLAIMED IS:
  2. 2. An apparatus for automatically hybridizing a DNA microarray immobilized on a surface of a solid substrate, the apparatus comprising:
    at least one assembly for securing the solid substrate during hybridization, the assembly comprising a Garner and a removable cover having a surface facing the carrier, the carrier and the removable cover dimensioned to receive the solid substrate between the carrier and the surface of the removable cover so that the surfaces of the removable cover and the solid substrate define a cavity;
    a fluid control module comprising a fluid manifold, at least one liquid reservoir, at least one waste container, and a vacuum source in fluid communication with the waste container, the fluid manifold providing fluid communication between the liquid reservoir and the cavity and between the cavity and the waste container, and the vacuum source providing a pressure drop between the liquid reservoir and the waste container, wherein the pressure drop drives fluid flow throughout the fluid control module;
    at least one thermal management module for controlling temperature of the DNA
    microarray immobilized on the surface of the solid substrate, the thermal management module thermally contacting the assembly.
  3. 3. The apparatus of claim 2, wherein the apparatus includes at least two assemblies for securing solid substrates during hybridization.
  4. 4. The apparatus of claim 3, wherein the apparatus includes at least two thermal management modules.
  5. 5. The apparatus of claim 4, wherein each of the thermal management modules thermally contact different assemblies.
  6. 6. The apparatus of claim 2, wherein the apparatus includes at least six assemblies for securing solid substrates during hybridization.
  7. 7. The apparatus of claim 6, wherein the apparatus includes at least six thermal management modules.
  8. 8. The apparatus of claim 7, wherein each of the thermal management modules thermally contact different assemblies.
  9. 9. The apparatus of claim 2, further comprising a shim removably disposed between the surface of the solid substrate and the removable cower, the shim defining a standoff between the surface of the removable cover and the surface of the solid substrate.
  10. 10. The apparatus of claim 9, wherein the shim has a cut-out demarcating an inner periphery, the inner periphery of the shim encompassing a smaller area than the surface of the solid substrate.
  11. 11. The apparatus of claim 10, further comprising an o-ring contained in a groove on the surface of the removable cover, the grove located adjacent the inner periphery of the shim.
  12. 12. The apparatus of claim 11, wherein the o-ring is fabricated from a perfluoroelastomer.
  13. 13. The apparatus of claim 2, wherein the removable cover is fabricated from a high-temperature plastic.
  14. 14. The apparatus of claim 13, wherein the high temperature plastic is polysulfone.
  15. 15. The apparatus of claim 2, wherein the removable cover has first and second diffusion channels opening into the cavity, the first and second diffusion channels in fluid communication with the fluid manifold.
  16. 16. The apparatus of claim 15, wherein the fluid control module includes a pulse valve in fluid communication with the first diffusion channel for agitating fluid within the cavity.
  17. 17. The apparatus of claim 15, wherein the first and second diffusion channels provide for fluid flow into and out of the cavity.
  18. 18. The apparatus of claim 17, wherein the first and second diffusion channels are spaced apart so that fluid entering and exiting the cavity via the first and second diffusion channels flows across the DNA microarray immobilized on the surface of the solid substrate.
  19. 19. The apparatus of claim 15, further comprising a port located in the removable cover for manually injecting liquids directly into the cavity.
  20. 20. The apparatus of claim 19, wherein the port is tapered.
  21. 21. The apparatus of claim 19, wherein the port is dimensioned to receive a pipette.
  22. 22. The apparatus of claim 19, wherein the port is in fluid communication with the second diffusion channel.
  23. 23. The apparatus of claim 22, wherein the assembly for containing the solid substrate is tilted upward from the second diffusion channel towards the first diffusion channel.
  24. 24. The apparatus of claim 2, wherein the removable. cover includes thermal breaks for reducing distortion resulting from thermal gradients in a direction parallel to the surface of the solid substrate.
  25. 25. The apparatus of claim 2, wherein the carrier includes tabs for reducing lateral movement of the solid substrate.
  26. 26. The apparatus of claim 2, wherein the Garner is fabricated from stainless steel.
  27. 27. The apparatus of claim 2, wherein the removable. cover and the carrier are adapted to secure at least two solid substrates.
  28. 28. The apparatus of claim 2, wherein the fluid manifold comprises multiple layers of acrylic.
  29. 29. The apparatus of claim 2, wherein the fluid control module includes valves providing selective fluid communication between the liquid reservoir and the cavity and between the cavity and the waste container.
  30. 30. The apparatus of claim 29, wherein the valves are zero dead volume valves.
  31. 31. The apparatus of claim 2, wherein the fluid control module includes at least two waste containers.
  32. 32. The apparatus of claim 2, wherein the vacuum source is a vacuum pump.
  33. 33 The apparatus of claim 2, wherein the thermal management module includes at least one Peltier device in thermal contact with the assembly.
  34. 34. The apparatus of claim 33, wherein the thermal management module includes a thermal plate disposed between the assembly and the Peltier device.
  35. 35. The apparatus of claim 33, wherein the thermal management module includes a graphite-loaded pad disposed between the assembly and the Pettier device.
  36. 36. The apparatus of claim 35, wherein the thermal management module includes a thermal plate disposed between the assembly and the graphite-loaded pad.
  37. 37. The apparatus of claim 2, wherein the thermal management module includes at least four Pettier devices in thermal contact with the assembly.
  38. 38. The apparatus of claim 2, wherein the thermal management module includes at least one temperature sensor located adjacent the carrier.
  39. 39. The apparatus of claim 2, wherein the thermal management module is capable of temperature ramp rates of about one °C per second.
  40. 40. The apparatus of claim 2, wherein the thermal management module is capable of controlling the temperature of the DNA microarray between about one °C and about one hundred °C.
  41. 41. The apparatus of claim 2, further comprising an embedded personal computer communicating with the fluid control module.
  42. 42. The apparatus of claim 2, further comprising an embedded personal computer communicating with the thermal management module.
  43. 43. The apparatus of claim 42, further comprising software running on the embedded personal computer, the software controlling the thermal management module using a mathematical model that approximates thermal characteristics of the thermal management module.
  44. 44. The apparatus of claim 2, further comprising a power supply module providing electrical current to the fluid control module and thermal management module.
  45. 45. The apparatus of claim 44, wherein the power supply module uses intelligent energy scheduling.
  46. 46. An apparatus for automatically hybridizing a DNA microarray immobilized on a surface of a solid substrate, the apparatus comprising:
    at least one assembly for securing the solid substrate during hybridization, the assembly comprising a carrier and a removable cover having a surface facing the carrier, the carrier and the removable cover dimensioned to receive the solid substrate between the carrier and the surface of the removable cover so that the surfaces of the removable cover and the solid substrate define a cavity;
    a fluid control module comprising a fluid manifold, at least one liquid reservoir, at least one waste container, and a vacuum source in fluid communication with the waste container, the fluid manifold providing fluid communication between the liquid reservoir and the cavity and between the cavity and the waste container, and the vacuum source providing a pressure drop between the liquid reservoir and the waste container, wherein the pressure drop drives fluid flow throughout the fluid control module;
    at least one thermal management module for controlling temperature of the DNA
    microarray immobilized on the surface of the solid substrate, the thermal management module thermally contacting the DNA microarray through the earner and the solid substrate.
  47. 47. An apparatus for automatically hybridizing DNA microarrays, the apparatus comprising:
    a solid substrate having a DNA microarray immobilized. on a surface of the solid substrate;
    at least one assembly for securing the solid substrate doting hybridization, the assembly comprising a carrier and a removable cover having a surface facing the carrier, the carrier and the removable cover dimensioned to receive the solid substrate between the carrier and the surface of the removable cover so that the surfaces of the removable cover and the solid substrate define a cavity;
    a fluid control module comprising a fluid manifold, at least one liquid reservoir, at least one waste container, and a vacuum source in fluid communication with the waste container, the fluid manifold providing fluid communication between the liquid reservoir and the cavity and between the cavity and the waste container, and the vacuum source providing a pressure drop between the liquid reservoir and the waste container, wherein the pressure drop drives fluid flow throughout the fluid control module;
    at least one thermal management module for controlling temperature of the DNA
    microarray immobilized on the surface of the solid substrate, the thermal management module thermally contacting the assembly.
CA002339163A 1998-08-10 1999-08-10 Thermal and fluidic cycling device for nucleic acid hybridization Expired - Fee Related CA2339163C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US9610998P 1998-08-10 1998-08-10
US60/096,109 1998-08-10
PCT/US1999/018122 WO2000009650A1 (en) 1998-08-10 1999-08-10 A thermal/fluidic cycling device for the purpose of nucleic acid hybridization

Publications (2)

Publication Number Publication Date
CA2339163A1 true CA2339163A1 (en) 2000-02-24
CA2339163C CA2339163C (en) 2010-01-12

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Family Applications (1)

Application Number Title Priority Date Filing Date
CA002339163A Expired - Fee Related CA2339163C (en) 1998-08-10 1999-08-10 Thermal and fluidic cycling device for nucleic acid hybridization

Country Status (7)

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US (2) US6238910B1 (en)
EP (1) EP1105458B1 (en)
JP (1) JP2002522065A (en)
AU (2) AU772769B2 (en)
CA (1) CA2339163C (en)
DE (1) DE69935230T2 (en)
WO (1) WO2000009650A1 (en)

Families Citing this family (109)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030017081A1 (en) * 1994-02-10 2003-01-23 Affymetrix, Inc. Method and apparatus for imaging a sample on a device
DE69527585T2 (en) * 1994-06-08 2003-04-03 Affymetrix Inc Method and device for packaging chips
US6287850B1 (en) * 1995-06-07 2001-09-11 Affymetrix, Inc. Bioarray chip reaction apparatus and its manufacture
US6410275B1 (en) 1997-05-02 2002-06-25 Biomerieux, Inc. Disposable test devices for performing nucleic acid amplification reactions
US6429007B1 (en) 1997-05-02 2002-08-06 BIOMéRIEUX, INC. Nucleic acid amplification reaction station for disposable test devices
DE69935230T2 (en) * 1998-08-10 2007-12-20 Genomic Solutions, Inc., Ann Arbor DEVICE FOR THERMAL AND LIQUID CIRCULATION FOR HYBRIDIZING NUCLEIC ACIDS
US6673620B1 (en) 1999-04-20 2004-01-06 Cytologix Corporation Fluid exchange in a chamber on a microscope slide
US6773676B2 (en) * 1999-04-27 2004-08-10 Agilent Technologies, Inc. Devices for performing array hybridization assays and methods of using the same
EP1279020B1 (en) * 2000-04-26 2016-03-16 Life Technologies Corporation Laser capture microdissection (lcm) extraction device and device carrier and method for post-lcm fluid processing
EP1188840A3 (en) * 2000-07-26 2003-04-23 Agilent Technologies, Inc. (a Delaware corporation) Chemical reaction method and apparatus
ES2593683T3 (en) * 2001-03-09 2016-12-12 Trovagene, Inc. Conjugated probes and optical analyte detection
JP4148778B2 (en) 2001-03-09 2008-09-10 バイオミクロ システムズ インコーポレイティッド Microfluidic interface equipment with arrays
US20020192806A1 (en) * 2001-05-14 2002-12-19 Genomic Solutions, Inc. Thermal and fluidic cycling device for nucleic acid hybridization
US9157875B2 (en) * 2001-05-16 2015-10-13 Benjamin P. Warner Drug development and manufacturing
US20080220441A1 (en) 2001-05-16 2008-09-11 Birnbaum Eva R Advanced drug development and manufacturing
DE50202157D1 (en) 2001-05-25 2005-03-10 Tecan Trading Ag Maennedorf System with a processing unit for hybridizing nucleic acid samples, proteins and tissue sections
US7294478B1 (en) 2001-06-06 2007-11-13 Rosetta Inpharmatics Llc Microarray reaction cartridge
US6485918B1 (en) 2001-07-02 2002-11-26 Packard Bioscience Corporation Method and apparatus for incubation of a liquid reagent and target spots on a microarray substrate
EP1439910A2 (en) * 2001-07-26 2004-07-28 Motorola, Inc. System and methods for mixing within a microfluidic device
US6881579B2 (en) * 2001-07-30 2005-04-19 Agilent Technologies, Inc. Sample processing apparatus and methods
US7008788B2 (en) 2001-07-30 2006-03-07 Agilent Technologies, Inc. Containers for supports comprising biopolymers
US7413859B2 (en) * 2001-11-14 2008-08-19 Siemens Aktiengesellschaft Method and biosensors for detecting macromolecular biopolymers
US20030152934A1 (en) * 2002-02-11 2003-08-14 Industrial Technology Research Institute High performance nucleic acid hybridization device and process
US20030162283A1 (en) * 2002-02-22 2003-08-28 Hitachi, Ltd. Circulating type biochemical reaction apparatus
US20030177380A1 (en) * 2002-03-18 2003-09-18 Woods Stanley P. Devices for storing array data and methods of using the same
US20030208936A1 (en) * 2002-05-09 2003-11-13 Lee Charles Hee Method for manufacturing embroidery decorated cards and envelopes
US7452712B2 (en) 2002-07-30 2008-11-18 Applied Biosystems Inc. Sample block apparatus and method of maintaining a microcard on a sample block
US7148057B2 (en) * 2002-08-13 2006-12-12 Gongin Precision Industries, Co., Ltd Array biochip workstation
US20040120861A1 (en) * 2002-10-11 2004-06-24 Affymetrix, Inc. System and method for high-throughput processing of biological probe arrays
US20040157336A1 (en) * 2002-11-14 2004-08-12 Affymetrix, Inc. Automated fluid control system and process
US20040259111A1 (en) * 2002-12-10 2004-12-23 Rosetta Inpharmatics Llc Automated system and method for preparing an assay ready biological sample
US7648678B2 (en) * 2002-12-20 2010-01-19 Dako Denmark A/S Method and system for pretreatment of tissue slides
EP2390352A1 (en) 2003-03-18 2011-11-30 Quantum Genetics Ireland Limited Systems and methods for improving protein and milk production of dairy herds
WO2004083824A1 (en) * 2003-03-20 2004-09-30 Dakocytomation Denmark A/S System for establishing a sample cover on a substrate
TW579430B (en) * 2003-05-02 2004-03-11 Dr Chip Biotechnology Inc Automatic micro-fluid hybridization chip platform
US7501283B2 (en) * 2003-08-11 2009-03-10 Sakura Finetek U.S.A., Inc. Fluid dispensing apparatus
US9518899B2 (en) 2003-08-11 2016-12-13 Sakura Finetek U.S.A., Inc. Automated reagent dispensing system and method of operation
US7767152B2 (en) * 2003-08-11 2010-08-03 Sakura Finetek U.S.A., Inc. Reagent container and slide reaction retaining tray, and method of operation
US7744817B2 (en) * 2003-08-11 2010-06-29 Sakura Finetek U.S.A., Inc. Manifold assembly
US20050226779A1 (en) 2003-09-19 2005-10-13 Oldham Mark F Vacuum assist for a microplate
US20050221358A1 (en) * 2003-09-19 2005-10-06 Carrillo Albert L Pressure chamber clamp mechanism
US9492820B2 (en) 2003-09-19 2016-11-15 Applied Biosystems, Llc High density plate filler
US7998435B2 (en) 2003-09-19 2011-08-16 Life Technologies Corporation High density plate filler
US7407630B2 (en) * 2003-09-19 2008-08-05 Applera Corporation High density plate filler
US7695688B2 (en) * 2003-09-19 2010-04-13 Applied Biosystems, Llc High density plate filler
US8277760B2 (en) * 2003-09-19 2012-10-02 Applied Biosystems, Llc High density plate filler
US20070015289A1 (en) * 2003-09-19 2007-01-18 Kao H P Dispenser array spotting
US20050226782A1 (en) * 2003-09-19 2005-10-13 Reed Mark T High density plate filler
US20050233472A1 (en) * 2003-09-19 2005-10-20 Kao H P Spotting high density plate using a banded format
US20060233671A1 (en) * 2003-09-19 2006-10-19 Beard Nigel P High density plate filler
US20050226771A1 (en) * 2003-09-19 2005-10-13 Lehto Dennis A High speed microplate transfer
US20050220675A1 (en) * 2003-09-19 2005-10-06 Reed Mark T High density plate filler
US20060272738A1 (en) * 2003-09-19 2006-12-07 Gary Lim High density plate filler
DK2322278T3 (en) * 2003-10-24 2017-04-10 Aushon Biosystems Inc Apparatus and method for dispensing liquid, semi-solid and solid samples
US20050170361A1 (en) * 2004-02-02 2005-08-04 Chih-Wei Ho Method of preparing reaction regions for biochips
NZ549384A (en) 2004-02-19 2008-08-29 Univ Alberta Leptin promoter polymorphisms and uses thereof
WO2005113834A2 (en) 2004-05-20 2005-12-01 Quest Diagnostics Investments Incorporated Single label comparative hybridization
US20050274395A1 (en) * 2004-06-14 2005-12-15 Applera Corporation Microarray wash tray
US7615370B2 (en) * 2004-07-08 2009-11-10 Tecan Trading Ag System having device for preventing air bubbles in a hybridization chamber and corresponding method
AU2005271688B2 (en) * 2004-08-03 2011-10-06 Becton, Dickinson And Company Use of magnetic material to direct isolation of compounds and fractionation of multipart samples
DE102004037848B4 (en) * 2004-08-04 2007-03-29 Advalytix Ag Sample carrier washing container, sample carrier washing station, system for washing sample carriers and method for washing sample carriers
JP2006153785A (en) * 2004-12-01 2006-06-15 Hitachi Ltd Solution stirring device and analyzing system
KR100612880B1 (en) * 2004-12-06 2006-08-14 삼성전자주식회사 Packing device for the sample loading hole of a chamber
KR100612879B1 (en) 2004-12-06 2006-08-14 삼성전자주식회사 Hybridization device using the control of pump and valves in closed system
WO2006081353A2 (en) 2005-01-27 2006-08-03 Quest Diagnostics Investments Incorporated Rapid comparative genome hybridization
US20060246576A1 (en) * 2005-04-06 2006-11-02 Affymetrix, Inc. Fluidic system and method for processing biological microarrays in personal instrumentation
EP2255880B1 (en) 2005-06-21 2014-05-28 Tecan Trading AG System and method to prevent air bubbles in a hybridization chamber
US8076074B2 (en) 2005-11-29 2011-12-13 Quest Diagnostics Investments Incorporated Balanced translocation in comparative hybridization
JP4721425B2 (en) * 2005-12-01 2011-07-13 キヤノン株式会社 Fluid moving method and fluid moving device
US7818092B2 (en) * 2006-01-20 2010-10-19 Fisher Controls International Llc In situ emission measurement for process control equipment
JP2007209236A (en) * 2006-02-08 2007-08-23 Canon Inc Method and device of hybridization
US20100200021A1 (en) * 2006-02-17 2010-08-12 Nils Adey Slide Conditioning Systems and Methods
AU2007227202B2 (en) * 2006-03-21 2013-08-22 Amylin Pharmaceuticals, Llc Peptide-peptidase inhibitor conjugates and methods of using same
US8459509B2 (en) 2006-05-25 2013-06-11 Sakura Finetek U.S.A., Inc. Fluid dispensing apparatus
JP4939910B2 (en) * 2006-11-29 2012-05-30 株式会社東芝 Micro chemical analysis system and micro chemical analysis device
US7807359B2 (en) 2006-12-01 2010-10-05 Quest Diagnostics Investments Incorporated Methods of detecting TPMT mutations
KR20080060661A (en) * 2006-12-27 2008-07-02 삼성전자주식회사 Device for providing hybridization chambers whose structure prevents air bubbles and hybridization device comprising the same device
US20090061497A1 (en) * 2007-06-29 2009-03-05 Becton, Dickinson And Company Methods for Extraction and Purification of Components of Biological Samples
US7507539B2 (en) 2007-07-30 2009-03-24 Quest Diagnostics Investments Incorporated Substractive single label comparative hybridization
AU2008291469A1 (en) * 2007-08-29 2009-03-05 Dako Denmark A/S On-site liquid production
US7842238B2 (en) * 2007-10-30 2010-11-30 Industrial Technology Research Institute Fully automated microarray processing system
US8093063B2 (en) 2007-11-29 2012-01-10 Quest Diagnostics Investments Incorporated Assay for detecting genetic abnormalities in genomic nucleic acids
US20110190153A1 (en) * 2008-06-09 2011-08-04 Nils Adey System and method for hybridization slide processing
US20100167943A1 (en) * 2008-06-09 2010-07-01 Nils Adey System and Method for Hybridization Slide Processing
WO2010033844A2 (en) * 2008-09-22 2010-03-25 Biomicro, Inc. Selective processing of biological material on a microarray substrate
US8501115B2 (en) 2008-10-24 2013-08-06 Statspin, Inc. Modular system for performing laboratory protocols and associated methods
CH699853A1 (en) * 2008-11-13 2010-05-14 Tecan Trading Ag Meter and method for determining provided by a laboratory fluid system parameters.
US8622072B2 (en) * 2008-12-05 2014-01-07 Fisher Controls International, Llc Apparatus to control fluid flow
US8039794B2 (en) 2008-12-16 2011-10-18 Quest Diagnostics Investments Incorporated Mass spectrometry assay for thiopurine-S-methyl transferase activity and products generated thereby
CN102630250A (en) 2009-09-25 2012-08-08 基因诊断测试公司 Multiplex (+/-) stranded arrays and assays for detecting chromosomal abnormalities associated with cancer and other diseases
EP2367058A1 (en) 2010-03-17 2011-09-21 Université Jean-Monnet Fabrication method of cylindrical gratings
WO2011117275A1 (en) * 2010-03-25 2011-09-29 Endress+Hauser Conducta Gesellschaft Für Mess- Und Regeltechnik Mbh+Co. Kg System for treating liquids
US10697990B2 (en) 2010-04-29 2020-06-30 Leica Biosystems Richmond, Inc. Analytical system for performing laboratory protocols and associated methods
US20110303197A1 (en) 2010-06-09 2011-12-15 Honda Motor Co., Ltd. Microcondenser device
US8752732B2 (en) 2011-02-01 2014-06-17 Sakura Finetek U.S.A., Inc. Fluid dispensing system
US8580568B2 (en) 2011-09-21 2013-11-12 Sakura Finetek U.S.A., Inc. Traceability for automated staining system
US8932543B2 (en) 2011-09-21 2015-01-13 Sakura Finetek U.S.A., Inc. Automated staining system and reaction chamber
USD753311S1 (en) 2011-10-12 2016-04-05 Alere Switzerland Gmbh Isothermal nucleic acid amplification meter
CA2866854C (en) 2012-03-09 2020-08-18 Leica Biosystems Richmond, Inc. Device and method for controlling the temperature in a moving fluid in a laboratory sample processing system
US10876936B2 (en) 2012-12-03 2020-12-29 Leica Biosystems Melbourne Pty Ltd Thermal module for a sample processing assembly
US9410977B2 (en) * 2013-08-08 2016-08-09 Illumina, Inc. Fluidic system for reagent delivery to a flow cell
US10876937B2 (en) * 2013-10-04 2020-12-29 Biogenex Laboratories, Inc. Assembly for forming microchamber for inverted substrate
AU2015222944A1 (en) 2014-02-27 2016-09-08 Massachusetts Institute Of Technology T cell balance gene expression, compositions of matters and methods of use thereof
WO2016085876A1 (en) 2014-11-25 2016-06-02 The Broad Institute Inc. Clonal haematopoiesis
WO2016086197A1 (en) 2014-11-25 2016-06-02 The Brigham And Women's Hospital, Inc. Method of identifying and treating a person having a predisposition to or afflicted with a cardiometabolic disease
EP3262193A2 (en) 2015-02-26 2018-01-03 The Broad Institute Inc. T cell balance gene expression, compositions of matters and methods of use thereof
RU2699612C2 (en) * 2015-05-29 2019-09-06 Иллюмина, Инк. Sample cassette and analytical system for carrying out certain reactions
WO2017131951A1 (en) * 2016-01-28 2017-08-03 Becton, Dickinson And Company Enhanced composite liquid cell (clc) devices, and methods for using the same
WO2018200489A1 (en) 2017-04-25 2018-11-01 The Brigham And Women’S Hospital, Inc. Il-8, il-6, il-1b and tet2 and dnmt3a in atherosclerosis

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4753775A (en) * 1985-04-12 1988-06-28 E. I. Du Pont De Nemours And Company Rapid assay processor
GB2200210B (en) * 1986-12-04 1991-07-24 Univ Leicester Apparatus for reactions with liquids
US4847208A (en) * 1987-07-29 1989-07-11 Bogen Steven A Apparatus for immunohistochemical staining and method of rinsing a plurality of slides
US5188963A (en) * 1989-11-17 1993-02-23 Gene Tec Corporation Device for processing biological specimens for analysis of nucleic acids
US5346672A (en) * 1989-11-17 1994-09-13 Gene Tec Corporation Devices for containing biological specimens for thermal processing
US5273905A (en) * 1991-02-22 1993-12-28 Amoco Corporation Processing of slide mounted material
US5849486A (en) * 1993-11-01 1998-12-15 Nanogen, Inc. Methods for hybridization analysis utilizing electrically controlled hybridization
US5364790A (en) * 1993-02-16 1994-11-15 The Perkin-Elmer Corporation In situ PCR amplification system
NZ276860A (en) * 1993-11-02 1997-09-22 Affymax Tech Nv Apparatus and its use for synthesising diverse molecular products on substrates
CA2214263A1 (en) * 1995-03-07 1996-09-12 Biomolecular Assays, Inc. Pressure cycling reactor
GB9506312D0 (en) * 1995-03-28 1995-05-17 Medical Res Council Improvements in or relating to sample processing
US5589136A (en) * 1995-06-20 1996-12-31 Regents Of The University Of California Silicon-based sleeve devices for chemical reactions
US5804384A (en) * 1996-12-06 1998-09-08 Vysis, Inc. Devices and methods for detecting multiple analytes in samples
DE69935230T2 (en) * 1998-08-10 2007-12-20 Genomic Solutions, Inc., Ann Arbor DEVICE FOR THERMAL AND LIQUID CIRCULATION FOR HYBRIDIZING NUCLEIC ACIDS

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US6238910B1 (en) 2001-05-29
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AU772769B2 (en) 2004-05-06
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JP2002522065A (en) 2002-07-23
DE69935230T2 (en) 2007-12-20

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