CA2339163A1 - Thermal and fluidic cycling device for nucleic acid hybridization - Google Patents
Thermal and fluidic cycling device for nucleic acid hybridization Download PDFInfo
- 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
- Authority
- 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
Links
- 230000001351 cycling effect Effects 0.000 title 1
- 238000007899 nucleic acid hybridization Methods 0.000 title 1
- 239000012530 fluid Substances 0.000 claims abstract 37
- 239000007787 solid Substances 0.000 claims abstract 28
- 239000000758 substrate Substances 0.000 claims abstract 28
- 238000009396 hybridization Methods 0.000 claims abstract 6
- 239000002699 waste material Substances 0.000 claims 14
- 239000007788 liquid Substances 0.000 claims 11
- 238000000018 DNA microarray Methods 0.000 claims 10
- 238000009792 diffusion process Methods 0.000 claims 9
- 230000000712 assembly Effects 0.000 claims 4
- 238000000429 assembly Methods 0.000 claims 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 2
- 229910002804 graphite Inorganic materials 0.000 claims 2
- 239000010439 graphite Substances 0.000 claims 2
- 229920006169 Perfluoroelastomer Polymers 0.000 claims 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims 1
- 238000013178 mathematical model Methods 0.000 claims 1
- 229920002492 poly(sulfone) Polymers 0.000 claims 1
- 229910001220 stainless steel Inorganic materials 0.000 claims 1
- 239000010935 stainless steel Substances 0.000 claims 1
- 238000000034 method Methods 0.000 abstract 2
- 230000008569 process Effects 0.000 abstract 2
- 239000011521 glass Substances 0.000 abstract 1
- 150000007523 nucleic acids Chemical class 0.000 abstract 1
- 102000039446 nucleic acids Human genes 0.000 abstract 1
- 108020004707 nucleic acids Proteins 0.000 abstract 1
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)
- WHAT IS CLAIMED IS:
- 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. The apparatus of claim 2, wherein the apparatus includes at least two assemblies for securing solid substrates during hybridization.
- 4. The apparatus of claim 3, wherein the apparatus includes at least two thermal management modules.
- 5. The apparatus of claim 4, wherein each of the thermal management modules thermally contact different assemblies.
- 6. The apparatus of claim 2, wherein the apparatus includes at least six assemblies for securing solid substrates during hybridization.
- 7. The apparatus of claim 6, wherein the apparatus includes at least six thermal management modules.
- 8. The apparatus of claim 7, wherein each of the thermal management modules thermally contact different assemblies.
- 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. 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. 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. The apparatus of claim 11, wherein the o-ring is fabricated from a perfluoroelastomer.
- 13. The apparatus of claim 2, wherein the removable cover is fabricated from a high-temperature plastic.
- 14. The apparatus of claim 13, wherein the high temperature plastic is polysulfone.
- 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. 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. The apparatus of claim 15, wherein the first and second diffusion channels provide for fluid flow into and out of the cavity.
- 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. The apparatus of claim 15, further comprising a port located in the removable cover for manually injecting liquids directly into the cavity.
- 20. The apparatus of claim 19, wherein the port is tapered.
- 21. The apparatus of claim 19, wherein the port is dimensioned to receive a pipette.
- 22. The apparatus of claim 19, wherein the port is in fluid communication with the second diffusion channel.
- 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. 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. The apparatus of claim 2, wherein the carrier includes tabs for reducing lateral movement of the solid substrate.
- 26. The apparatus of claim 2, wherein the Garner is fabricated from stainless steel.
- 27. The apparatus of claim 2, wherein the removable. cover and the carrier are adapted to secure at least two solid substrates.
- 28. The apparatus of claim 2, wherein the fluid manifold comprises multiple layers of acrylic.
- 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. The apparatus of claim 29, wherein the valves are zero dead volume valves.
- 31. The apparatus of claim 2, wherein the fluid control module includes at least two waste containers.
- 32. The apparatus of claim 2, wherein the vacuum source is a vacuum pump.
- 33 The apparatus of claim 2, wherein the thermal management module includes at least one Peltier device in thermal contact with the assembly.
- 34. The apparatus of claim 33, wherein the thermal management module includes a thermal plate disposed between the assembly and the Peltier device.
- 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. The apparatus of claim 35, wherein the thermal management module includes a thermal plate disposed between the assembly and the graphite-loaded pad.
- 37. The apparatus of claim 2, wherein the thermal management module includes at least four Pettier devices in thermal contact with the assembly.
- 38. The apparatus of claim 2, wherein the thermal management module includes at least one temperature sensor located adjacent the carrier.
- 39. The apparatus of claim 2, wherein the thermal management module is capable of temperature ramp rates of about one °C per second.
- 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. The apparatus of claim 2, further comprising an embedded personal computer communicating with the fluid control module.
- 42. The apparatus of claim 2, further comprising an embedded personal computer communicating with the thermal management module.
- 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. The apparatus of claim 2, further comprising a power supply module providing electrical current to the fluid control module and thermal management module.
- 45. The apparatus of claim 44, wherein the power supply module uses intelligent energy scheduling.
- 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. 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.
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 |
Family
ID=22255392
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)
Country | Link |
---|---|
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) |
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AU5553299A (en) | 2000-03-06 |
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