WO2004071665A1 - Sample tray heater module - Google Patents

Sample tray heater module Download PDF

Info

Publication number
WO2004071665A1
WO2004071665A1 PCT/US2004/002811 US2004002811W WO2004071665A1 WO 2004071665 A1 WO2004071665 A1 WO 2004071665A1 US 2004002811 W US2004002811 W US 2004002811W WO 2004071665 A1 WO2004071665 A1 WO 2004071665A1
Authority
WO
WIPO (PCT)
Prior art keywords
heater module
distribution plate
tray
heat distribution
purification
Prior art date
Application number
PCT/US2004/002811
Other languages
French (fr)
Inventor
Todd A. Weinfield
Gary Lim
Donald R. Sandell
Kevin S. Bodner
Mark Borodkin
Mark Oldham
Jon Hoshizaki
Original Assignee
Applera 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 Applera Corporation filed Critical Applera Corporation
Priority to EP04707411A priority Critical patent/EP1599288B1/en
Priority to DE602004022259T priority patent/DE602004022259D1/en
Priority to AT04707411T priority patent/ATE437698T1/en
Publication of WO2004071665A1 publication Critical patent/WO2004071665A1/en

Links

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
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5025—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures for parallel transport of multiple samples
    • B01L3/50255—Multi-well filtration
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D61/00—Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
    • B01D61/14—Ultrafiltration; Microfiltration
    • B01D61/18—Apparatus therefor
    • 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
    • G01N35/0099—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor comprising robots or similar manipulators
    • 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
    • B01J2219/00281—Individual reactor vessels
    • B01J2219/00286—Reactor vessels with top and bottom openings
    • B01J2219/00288—Reactor vessels with top and bottom openings in the shape of syringes
    • 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
    • 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
    • B01J2219/00319—Reactor vessels in a multiple arrangement the reactor vessels being formed by arrays of wells in blocks the blocks being mounted in stacked arrangements
    • 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
    • B01J2219/00331—Details of the reactor vessels
    • B01J2219/00333—Closures attached to the reactor vessels
    • B01J2219/00335—Septa
    • 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
    • B01J2219/00414—Means for dispensing and evacuation of reagents using suction
    • B01J2219/00416—Vacuum
    • 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
    • B01J2219/00418—Means for dispensing and evacuation of reagents using pressure
    • 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
    • B01J2219/00423—Means for dispensing and evacuation of reagents using filtration, e.g. through porous frits
    • 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
    • B01L2200/02—Adapting objects or devices to another
    • B01L2200/025—Align devices or objects to ensure defined positions relative to each other
    • 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
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0631—Purification arrangements, e.g. solid phase extraction [SPE]
    • 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
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0689—Sealing
    • 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
    • B01L2200/14—Process control and prevention of errors
    • B01L2200/141—Preventing contamination, tampering
    • 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
    • B01L2300/0829—Multi-well plates; Microtitration plates
    • 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
    • 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
    • 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
    • G01N1/40—Concentrating samples
    • G01N1/4077—Concentrating samples by other techniques involving separation of suspended solids
    • 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
    • G01N2035/00465—Separating and mixing arrangements
    • G01N2035/00475—Filters
    • G01N2035/00485—Filters combined with sample carriers
    • 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
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
    • G01N35/1016—Control of the volume dispensed or introduced
    • G01N2035/102—Preventing or detecting loss of fluid by dripping
    • 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
    • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/028—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations having reaction cells in the form of microtitration plates
    • 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
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1065—Multiple transfer devices
    • G01N35/1074—Multiple transfer devices arranged in a two-dimensional array
    • 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
    • Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
    • Y10T436/25375—Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]

Definitions

  • the present invention relates to a multi-well microfiltration apparatus and methods for processing a plurality of fluid samples simultaneously at a desired temperature.
  • microtitration wells have assumed an important role in many biological and biochemical applications, such as sample preparation, genome sequencing, and drug discovery programs.
  • a variety of multi-well arrangements, constructed according to standardized formats, are now popular. Methods of heating samples in such multi-well arrangements, such as those described in U.S. Patent No. 5,459,300 and U.S. Patent No.
  • a sample tray heater module that can be used on an automated or manual sample preparation station is described.
  • the sample tray heater module can include a heat distribution plate and a heat source.
  • the sample tray heater module can further include a heating tray.
  • a system including a sample tray heater module wherein the temperature of the sample tray heater module can be monitored and controlled during heating.
  • the heater module is capable of heating a sample to a temperature in a range of from about 5° C to about 100° C. In other embodiments, the heater module is capable of heating a sample to a temperature in a range of from about 20° C to about 70° C. According to various embodiments, the heater module is capable of heating a sample at a rate of greater than or equal to about 1° C per minute.
  • a system wherein a sample tray heater module can be fitted with a sample purification tray, and/or a receiving well array, prior to processing samples.
  • a sample tray heater module includes a plurality of protrusions capable of interacting with a sample purification tray for proper positioning thereof relative to the heater module.
  • the plurality of protrusions can provide uniform heating to a plurality of discharge columns of a sample purification tray according to various embodiments.
  • a sample tray heater module is provided that is inexpensive and reliable.
  • the sample tray heater module can be disposable.
  • the heat distribution plate, heat source, and optional heating tray of the heater module can each be made from a thermally conductive material such as a metal, metal alloy, or polymeric material, such as a thermoplastic, or a combination thereof
  • a purification apparatus including a heater module for heating of a sample passing therethrough is described according to various embodiments.
  • a method for purifying a sample wherein the sample is heated during purification.
  • a sample tray heater module includes a heat distribution plate and a heat source.
  • the heat distribution plate can include a bottom portion and one or more protrusions extending away from the bottom portion
  • the heat source can be in contact with an underside of the bottom portion of the heat distribution plate.
  • One or more electrical contacts can be in electrical communication with the heat source.
  • the heater module can include a heating tray adapted to receive the heat source and the heat distribution plate.
  • Fig. 1 is a perspective view of a sample purification tray and a heater module.
  • Fig. 2 is atop view of a heat distribution plate according to various embodiments.
  • Fig. 3 is a sectional side view taken along line 3-3 in Fig. 2.
  • Fig. 4 is a front view of a heater module according to various embodiments.
  • Fig. 5 is a back view of the heater module shown in Fig. 4.
  • Fig. 6 is a bottom view of the heater module shown in Figs. 4 and 5.
  • Fig. 7 is a cut-away top view of a heater module according to various embodiments taken along various cut-aways.
  • Fig. 8 is a perspective view of a purification apparatus having a sample purification tray, a heater module, and a sample well tray, wherein the heater module comprises a heat distribution plate, a heat source, and a heating tray.
  • Fig. 9 is a side-sectional view of a heater module having a heating tray, a heat source, and a heat distribution plate.
  • Fig. 10 is a perspective view of a purification apparatus including a sample tray, a heater module, and a carriage.
  • Fig. 11 is a graph illustrating the temperature rate increase of water using a heater module according to various embodiments.
  • a sample tray heater module is provided, for example, for a purification apparatus.
  • the heater module can be used in or with an apparatus useful for purification, filtration, and or separation of biological and/or chemical samples, such as DNA.
  • the purification apparatus can include a sample purification tray having a plurality of discharge columns, each with a distal end, wherein each discharge column is adapted to receive or includes a filter medium.
  • the sample purification tray can be, for example, a discharge conduit array, a sample purification array, or other device capable of receiving and allowing passage therethrough of a sample.
  • the sample purification tray can be disposed in a purification apparatus and held aligned with and in fluid communication with a receiving well array, for example, a sample well array, sample well tray, sample tray, array of receiving wells, or other device capable of receiving and containing, restraining, or holding a sample therein.
  • the distal end of each discharge column of the sample purification tray can be in fluid communication with a respective receiving well of the receiving well array.
  • the sample tray heater module can be disposed between the sample purification tray and the receiving well array.
  • the purification apparatus can be located in a carriage such that the sample purification tray is capable of horizontal and/or vertical movement with respect to the heating device and/or the receiving well array. Further details regarding exemplary sample purification trays, receiving well arrays, and purification apparatuses, and methods for the use thereof, are described in co-pending U.S. Patent Application No. 10/104,335, filed March 22, 2002.
  • a sample tray heater module can include a heat distribution plate having a plurality of protrusions, and a heat source.
  • the heat source can be in contact with a side of a bottom portion of the heat distribution plate.
  • the sample tray heater module can include a plurality of through holes for nozzle tips passing through the heat distribution plate and the heat source.
  • the sample tray heater module can include a heating tray for holding the heat source and the heat distribution plate.
  • the heating tray can be capable of receiving and aligning the heat source and heat distribution plate, and can include a plurality of through holes for nozzle tips corresponding to the through holes for nozzle tips in the heat distribution plate and the heat source.
  • the heater module can be constructed from a thermally conductive material, for example, a metal such as aluminum or stainless steel, a thermally conductive polymer, or a combination thereof.
  • the heater module 10 can comprise a heat distribution plate 20 having a bottom portion 22 having a first side and a second opposing side, and from which sidewalls 24 extend substantially perpendicularly or perpendicularly from the first side of bottom portion 22. Also extending from the first side of bottom portion 22 can be a plurality of protrusions 26. As used herein, “protrusion” refers to a projection, extension, elongation, or other raised feature extending out of a plane of bottom portion 22. The sidewalls 24 and each of the plurality of protrusions 26 can be the same height.
  • the plurality of protrusions 26 and sidewalls 24 define a plurality of discharge column receptacles 28, for example, to accommodate a plurality of discharge conduits or columns from a discharge conduit array, for example, a sample purification tray 80.
  • Each discharge column receptacle 28 can have a respective through hole 30 for a nozzle tip through which a discharge column nozzle tip can extend.
  • the heat distribution plate 20 can include screw-through holes 32 as shown, tap holes, clips, or other devices useful for fastening the heater module together.
  • a heat source 40 can be in contact with the second side of the bottom portion of the heat distribution plate 20.
  • the heat source 40 can be a substantially flat material.
  • the heat source 40 can include a bottom layer 44 in which can be disposed heating wires 50 for carrying power to a wire layout 48.
  • the wire layout 48 can be attached to temperature sensor wires or contact wires 52.
  • the temperature probes 52 and/or the wires 50 can extend through through holes 94 of sample purification tray 80 to secure the sample purification tray 80 to the heater module 10.
  • the temperature sensor can be a thermistor or a thermocouple, or the heating wires themselves can act as temperature sensors as, for example, measured based on resistivity through the wires.
  • the bottom layer 44 of heat source 40 having the wire layout 48 disposed therein can be covered by cover layer 46 to protect the wires.
  • the heat source 40 can have through holes 54 for nozzle tips to extend therethrough.
  • the through holes 54 for nozzle tips can correspond to through holes 30 for nozzle tips of a heat distribution plate 10 and, optionally, can correspond to through holes 66 for nozzle tips of a tray 60.
  • the power wires 50 can be connected to a controller 57 or connection module 56 as shown in Figs. 7 and 8.
  • the controller 57 can be connected to a power source to provide energy for heating the wires.
  • the controller can include computer controls, thermal cut-offs, and/or PID controllers, or other controllers that can modify the current flowing through the heating elements and/or heating wires.
  • the heat source 40 can be attached to or separate from the heat distribution plate 20. According to various embodiments, the heat source 40 can be incorporated in the heat distribution plate, for example, by integral molding therewith. The heat source 40 can be in contact with the first side of the bottom portion 22 of the heat distribution plate 20, wherein the first side of the bottom portion 22 includes the surfaces of the plurality of protrusions 26.
  • the heater module 10 can further comprise a tray 60 having an inwardly facing bottom portion 62 from a first side of which sidewalls 64 extend substantially perpendicularly or perpendicularly.
  • the tray 60 can be adapted to receive the heat source 40 and the heat distribution plate 20 within the area defined by sidewalls 64 and bottom portion 62.
  • the tray 60 can have through holes 66 for nozzle tips corresponding to through holes 54 for nozzle tips of the heat source 40 and through holes 30 for nozzle tips of the heat distribution plate 20.
  • Tray 60 can also comprise screw holes 68 for fastening together the heater module by screws, bolts, or other attachment devices passing through at least one screw-through hole 32 and at least one screw hole 68.
  • the heat distribution plate 20 can be capable of receiving a discharge conduit array, for example, a sample purification tray 80, as shown in Figs. 1 and 8.
  • Sample purification tray 80 can include a top plate 82 from a side of which sidewalls 84 extend substantially perpendicularly or pe endicularly.
  • Sample purification tray 80 can have openings 86 in top plate 82, which openings lead into discharge columns 88.
  • the discharge columns 88 can include more than one section, for example, a first portion 90 and a second portion 92, as shown in Figs. 1 and 8.
  • the discharge column 88 can terminate in a nozzle tip having a discharge opening 96 which is capable of fluid communication with a respective opening 106 in corresponding sample well tray or receiving well array 100, as shown in Fig. 8.
  • At least the nozzle tips of discharge columns 88 can pass through respective through holes 30 for nozzle tips of the heat distribution plate, respective through holes 54 for nozzle tips of the heat source, and, optionally, respective through holes 66 for nozzle tips of the tray 60, to extend below heater module 10.
  • the sample purification tray 80 can also have openings 94 to receive temperature probe 52 and/or power wires 50 from heat source 40.
  • the portions 90, 92 of the discharge columns 88 of the sample purification tray 80 can be formed separately and joined together by any suitable method, such as heat welding or adhesive bond, or they can be integrally formed such as by molding.
  • suitable method such as heat welding or adhesive bond
  • the sample purification tray can be formed from a plastic material, a metal, or any other suitable material or combination of materials as known to those skilled in the art.
  • the sample purification tray can be formed of a material which does not interact or react with the sample to be purified. Examples of suitable materials include polypropylene, polyethylene, polycarbonate, and mixtures thereof.
  • the sample purification tray 80 can be adapted to receive one or more filters in one or more of the discharge columns 88.
  • Various sample purification trays and details regarding the size, shape, material, and manufacture of sample purification trays, discharge conduit arrays, and filters for use therein, can be found in co-pending U.S. Patent Application 10/104,335, U.S. Patent No. 6,419,827 Bl, and U.S Patent No. 6,159,368, all of which are herein incorporated in their entireties by reference.
  • the sample purification tray can fit snuggly into heat distribution plate 20 such that discharge columns 88 are in good, snug, thermal contact with the protrusions of heat distribution plate 20.
  • the regions between adjacent projections are referred to herein as discharge column receptacles 28.
  • a portion of at least one of the plurality of protrusions 26 separates each discharge column 88 from the next discharge column 88.
  • at least a portion of a discharge column 88 can be located between one of the plurality of protrusions 26 and a sidewall 24.
  • the sample purification tray and heater module can be held in housing assembly 120 by carriage frame 122 having receiving area 124, as shown in Fig. 10.
  • a vent plate can be located between the heater module 10 and the receiving well array 100.
  • the vent plate can have a plurality of though holes for nozzle tips corresponding to the though holes for nozzle tips in the heater module, and corresponding to the wells in the receiving well array, to allow fluid communication from the sample purification tray through the heater module and vent plate to the receiving well array.
  • Apertures or vents can extend through the vent plate. At least one aperture can be located adjacent each through hole for a nozzle tip in the vent plate. The apertures permit fluid communication between the regions above and below the vent plate. By this construction, a vacuum drawn from beneath the vent plate will extend to the regions above the vent plate.
  • the vent plate material can be the same as the material used to form the heater module.
  • an aerosol guard or other cross-flow restrictor as described, for example, in U.S. Patent Application 09/182,946, filed October 29, 1998, issued as U.S. Patent No. 6,159,368, can be located between heater module 10 and vent plate 70, or between heater module 10 and sample well tray 100.
  • the aerosol guard can prevent aerosols from each of sample wells 108 from cross-contaminating other sample wells.
  • the aerosol guard can allow the passage of gases, but not aerosols, therethrough.
  • the aerosol guard can be placed immediately adjacent and below heat source 40 of heater module 10 or, if tray 60 is used, immediately adjacent and below tray 60 of heater module 10. According to various embodiments, the aerosol guard can be placed immediately adjacent and below a vent plate.
  • the aerosol guard can include a plurality of through holes for nozzle tips positioned substantially in alignment with one or more of through holes 54 for nozzle tips of heat source 40, through holes 66 for nozzle tips of tray 60, and through holes 72 for nozzle tips of heat plate 70, and also substantially in alignment with openings 106 in top plate 102 of sample well tray 100. At least the nozzle tips of discharge columns 88 can pass through the through holes for nozzle tips of the aerosol guard and can be in fluid communication with sample wells 108 through openings 106 of the sample well tray 100.
  • the aerosol guard can be made of a flexible or non-flexible material and the material can be capable of withstanding the temperatures associated with use of heater module 10.
  • the aerosol guard material can be substantially non-reactive with the chemicals and/or biological components of the sample.
  • the aerosol guard can be made from foam-like material.
  • the aerosol guard can be a porous, hydrophilic polymer material, such as, for example, ethyl vinyl acetate. Other suitable materials for the aerosol guard are apparent to those of ordinary skill in the art.
  • vent plate and aerosol guard can be found in related co-pending U.S. Patent Application No. 10/104,335, U.S. Patent No. 6,419,827 Bl, and U.S. Patent No. 6,159,368, all of which are incorporated herein in their entireties by reference. As shown, for example, in Fig.
  • any sample placed in sample purification tray 80 through an opening 86 into a discharge column 88 can flow through the discharge column 88 and can emerge from respective discharge opening 96 into respective opening 106 of the top plate 102 of the sample well tray 100, and can proceed through opening 106 into respective sample well 108.
  • the number of discharge columns 88, discharge openings 96, through holes 30, 54 and 66 for nozzle tips, and openings 106 in sample well tray 100 are equivalent. According to various embodiments, the number of openings 106 in sample well tray 100 can be less than the number of discharge columns 88, discharge openings 96, and through holes 30, 54, and 66 for nozzle tips, such that multiple adjacent discharge columns 88 and corresponding discharge openings 96 are in fluid communication with a single opening 106 of sample well tray 100.
  • Heater module 10 is capable of providing heat to sample purification tray 80 such that samples can be heated before and/or during passage through discharge columns 88 of sample purification tray 80.
  • Heater module 10 can be, for example, capable of mamtaining a temperature or raising a temperature of samples in the respective plurality of discharge columns 88 of sample purification tray 80 during the period of time it takes for the samples to pass through the discharge columns 88.
  • heater module 10 is capable of heating at a rate sufficient to heat 1 ml of water at 1°C per minute or greater, when the water disposed in a thermally conductive polymeric receptacle having an area of about three cm 2 in thermal contact with the heater module. For example, as shown in Fig.
  • the heater module 10 can raise the temperature of 1 ml of water in a 0.25 inch diameter column of a sample purification tray 80 fitted into the heater module 10, from about 23°C to about 65°C in 20 minutes or less.
  • the heater module 10 can be capable of providing heat sufficient to heat samples to a temperature in a range of from about 5°C to about 100°C.
  • the heater module 10 can be capable of providing heat sufficient to heat samples to a temperature in a range of from about 20°C to about 70°C.
  • One or more of the heat distribution plate 20, heat source 40, and tray 60 of the heater module 10 can be constructed from a thermoconductive material. According to various embodiments, each of the heat distribution plate 20, heat source 40, and tray 60 are made from a thermoconductive material.
  • the thermoconductive material can be a metallic thermoconductive material, such as du inum, iron, tantalum, titanium, copper, or alloys thereof.
  • the thermoconductive material can be a thermoconductive polymeric material capable of withstanding temperatures in the range or from about 5°C to about 100°C without deforming, cracking or melting.
  • the polymeric material can include a thermoconductive filler material.
  • the filler material can be one or more different fillers selected from a carbon material, boron nitride, and metallic materials, for example, aluminum, alumina, copper, magnesium, and brass, or a combination thereof.
  • heat distribution plate 20 can be constructed of a substantially rigid, thermoconductive material.
  • the plurality of protrusions 26 can be made of the same material as sidewalls 24.
  • the heat distribution plate 20, including bottom portion 22, sidewalls 24, and the plurality of protrusions 26, can be made of a substantially unitary construction.
  • the heat distribution plate 20 can be molded or machined to include the plurality of protrusions 26 and the sidewalls 24.
  • the plurality of protrusions 26 can be formed separately from bottom portion 22 and bonded thereto or otherwise attached.
  • the sidewalls 24 can be formed separately from bottom portion 22 and bonded or otherwise attached thereto.
  • Bonding of the plurality of protrusions 26 or sidewalls 24 to bottom portion 22 can be done by any known process, for example, bonding by epoxy or by a welding process such as heat welding or ultrasonic bonding or welding.
  • the thermoconductive material of the heat distribution plate 20 is a polymer
  • the material can be a mixture of one or more polymers, one or more monomers, or of one or more polymers with at least one thermoconductive filler material.
  • the polymer can be a liquid crystal polymer.
  • the filler material can be one or more different fillers selected from a carbon material, boron nitride, and metallic materials, for example, aluminum, alumina, copper, magnesium, and brass, or a combination thereof.
  • a thermally conductive composite materials are described, for example, in U.S. Patent No. 6,048,919.
  • Exemplary thermally conductive liquid crystalline polymers (LCP) can be obtained from Cool-Polymers, Inc.
  • the tray 60 can be made of or include any thermoconductive material as described herein.
  • the tray 60 can be made from the same material as the heat distribution plate 20, for example, the same thermoconductive material.
  • the heating tray can be a non-conductive material.
  • the heating tray can be made of glass, ceramic, a polymeric material, a metal, an alloy, or a combination thereof.
  • the heat 40 source can be located against bottom portion 62 of tray 60 in a space defined by bottom portion 62 and sidewall 64.
  • the heat source 40 can be bonded to or placed against bottom portion 62 of tray 60.
  • the heat source 40 can be bonded or otherwise attached to a side of the bottom portion 22 of heat distribution plate 20, which can be set into tray 60 in a space defined by bottom portion 62 and sidewall 64.
  • both a heat distribution plate 20 and a tray 60 can be used in a heater module 10 wherein both the heat distribution plate 20 and tray 60 can be made of or include aluminum
  • the heater module 10 can contain both a heat distribution plate 20 and a tray 60, wherein the heat distribution plate 20 and tray 60 can both be made of or include a thermoplastic material.
  • the heat distribution plate 20 and tray 60 can be bonded together. Heat distribution plate 20 and tray 60 can be bonded together after, for example, placing a heat source 40 between the heat distribution plate 20 and tray 60.
  • the heat distribution plate 20 and tray 60 can be attached mechanically such that the heater module 10 comprising the heat distribution plate 20 and tray 60 with or without a heat source 40 therebetween can be moved as a single unit.
  • the heat source 40 can include any heating system known to those skilled in the art to provide uniform distribution of heat.
  • the heat source 40 can be attached to the heat distribution plate 20, attached to the tray 60, attached to both the heat distribution plate 20 and tray 60, or set between the heat distribution plate 20 and tray 60.
  • the heat source 40 can be made from a flexible material and can comprise a film or sheet, for example, a polyimide sheet material such as KAPTON, available from DuPont High Performance Materials, Circleville, Ohio.
  • the heat source 40 can be a printed resistor circuit on a side of bottom portion 22 of heat distribution plate 20 or can be a printed resistor circuit on the bottom portion 62 of tray 60, wherein the printed resistor circuit is capable of generating heat.
  • the wire layout 48 can be made from any conductive material capable of producing a predetermined, minimum, and/or maximum amount of heat.
  • the wire layout can be made from various metals or metal alloys, including gold, silver, aluminum, copper, titanium, alloys thereof, and other metals and metal alloys as known to those of ordinary skill in the art.
  • the wire layout 48 can be set forth in a bottom layer 44 capable of accepting and holding in place the wire layout.
  • the bottom layer 44 can be made from a flexible or non-flexible material.
  • the bottom layer 44 can be made from silicone, a polymeric material, glass, or any other material known to those of ordinary skill in the art, including composite materials.
  • the cover layer 46 can be made of or include any material capable of encapsulating wire layout 48 and bottom layer 44, wherein the cover layer material is capable of transferring heat from the wire layout 48 to the heat distribution plate 20. According to various embodiments, the cover layer 46 can be the same material as the bottom layer 44. According to various embodiments, the cover layer 46 can be a polymeric material. Other suitable materials are apparent to those of ordinary skill in the art.
  • the heat source 40 comprising the bottom layer 44, wire layout 48, and cover layer 46, can be capable of generating a predetermined amount of heat dependent upon the resistance and current input of the wire layout 48.
  • the amount of heat capable of being generated can be changed by changing the resistance of wire layout 48, or by lowering or raising the amount of current passing through wire layout 48.
  • Electrical current is provided to wire layout 48 through wires 50, which are connected to controller 57 by connector 56. Controller 57 can control the amount of current that passes through wires 50 to wire layout 48, and therefore the amount of heat generated by wire layout 48 and heat source 40.
  • heat source 40 can be formed integrally with tray 60 or heat distribution plate 20.
  • the heat source 40 can be formed integrally with tray 60 such that bottom layer 44 of heat source 40 corresponds to bottom portion 62 of tray 60.
  • the heat source 40 can be formed integrally with heat distribution plate 20 such that cover layer 46 of heat source 40 corresponds to bottom portion 22 of heat distribution plate 20.
  • a heat source can be incorporated into heat distribution plate 20.
  • heat distribution plate 20 with the incorporated heat source can be used as an alternative to or in addition to heat source 40.
  • Wires, a wire layout, and/or a printed resistor circuit can be molded or otherwise formed within the heat distribution plate 20 having an incorporated heat source.
  • the wires, wire layout, and/or printed resistor circuit can be molded or otherwise formed within at least one of the bottom portion 22, the sidewalls 24, and the plurality of protrusions 26.
  • the heat distribution plate 20 with the incorporated heat source can be formed similar to the way that a steel- reinforced concrete slab is formed by pouring concrete into a mold containing a network or a grid pattern of steel rebar.
  • a network of resistors, wires, a wire layout, resistive heat elements, and or a printed resistor circuit can be placed into a mold and a thermoconductive material that is in a molten state can be poured into the mold.
  • a thermoconductive material that is in a molten state can be poured into the mold.
  • the hardened object forms the heat distribution plate 20 with the incorporated heat source.
  • the resistors, wires, wire layout, resistive heat elements, and/or printed resistor circuit can be affixed to, inserted in, and/or embedded into the at least one of the bottom portion 22, the sidewalls 24, and the plurality of protrusions 26.
  • the resistors, wires, wire layout, resistive heat elements, and/or printed resistor circuit can be made of various metals or metal alloys, including gold, silver, aluminum, copper, titanium, alloys thereof, and other metals and metal alloys as known to those of ordinary skill in the art.
  • the heat distribution plate 20 with the incorporated heat source can be capable of generating a predetermined amount of heat dependent upon the resistance and current input of the wires and/or wire layout.
  • a controller can provide current to the wires and/or wire layout via a connector.
  • the heat distribution plate 20 with the incorporated heat source can perform in the same manner as the heat source 20 without the incorporated heat source and heat source 40.
  • the temperature of the sample tray heater module 10 can be monitored.
  • the heat source 40 can include one or more heat sensor or temperature probe 52 such as a thermistor, a thermostat, a thermal protection tube, or a non-contact sensor such as an infrared sensor.
  • the heat sensor or temperature probe 52 can be positioned such that it contacts the bottom portion 22 of heat distribution plate 20.
  • the heat generated by heat source 40 can be controlled based upon the temperature detected or temperature readings obtained from the heat sensor or temperature probe 52.
  • Other suitable heat sensors or temperature probe designs as known to those of ordinary skill in the art can be used with heat source 40.
  • the heat sensor or temperature probe can be located above sample purification tray 80 in order to determine the temperature of the samples inside discharge columns 88.
  • a heat sensor or temperature probe can be located inside one or more of the discharge columns 88.
  • heater module 10 is designed to interact with and complement sample purification tray 80.
  • the sidewalls 24 of heat distribution plate 20 of heater module 10 extend substantially perpendicularly or perpendicularly from a side of bottom portion 22 such that when mated with a sample purification tray 80, the sidewalls 24 of heat distribution plate 20 substantially cover discharge columns 88 of sample purification tray 80 from view.
  • the sidewalls 24 of heat distribution plate 20 can touch a side of top plate 82 of the sample purification tray 80.
  • the sidewalls 24 of heat distribution plate 20 can be in contact with one or more discharge columns 88 of sample purification tray 80.
  • the sidewalls 24 can be in contact with one or more portion of discharge column 88, for example, the second portion 92 or the first portion 90 of discharge column 88. According to various other embodiments, the sidewalls 24 of heat distribution plate 20 can be in contact with the sidewalls 84 of the sample purification tray 80.
  • the plurality of protrusions 26 of heat distribution plate 20 can be in contact with a side of top plate 82 of the sample purification tray 80. According to various embodiments, the plurality of protrusions 26 of heat distribution plate 20 extend from heat distribution plate 20 and are located between discharge columns 88 of the sample purification tray 80. According to various embodiments, each of the plurality of protrusions 26 is in contact with one or more of the discharge columns 88.
  • one or more of the plurality of protrusions 26 can be in contact with a second portion 92, a first portion 90, or both a second portion 92 and a first portion 90, of a discharge column 88 of sample purification tray 80. At least a portion of one or more of the discharge columns 88 can substantially fit between two or more of the plurality of protrusions 26, or between one or more of the plurality of protrusions 26 and sidewall 24 of the heat distribution plate 20.
  • the plurality of protrusions 26 of the heat distribution plate 20 can function as a heat sink to dissipate heat by heating discharge columns 88 of the sample purification tray 80.
  • a fan can be positioned to promote heat distribution between the plurality of protrusions 26 and heat absorption by the discharge columns 88.
  • one or more of through hole 30 for a nozzle tip of heat distribution plate 20, through hole 54 for a nozzle tip of heat source 40, and optionally through hole 66 for a nozzle tip of tray 60 can be sized so as to closely fit the profile of discharge column 88 of sample purification tray 80.
  • One or more through hole 30, 54, or 66 for a nozzle tip can be sized to closely mate with a corresponding discharge column 88 so that bending of the discharge column 88 can be niinimized.
  • the spacing of one or more through hole 30, 54, or 66 for a nozzle tip can assist in maintaining equal spacing between the discharge columns 88.
  • a purification apparatus comprising a sample purification tray 80, a heater module 10, a sample well tray 100, optionally a vent plate, and optionally an aerosol guard, can be formed using the components described herein.
  • the purification apparatus can be placed under vacuum conditions to create a pressure differential.
  • openings and seams in the purification apparatus, and between the purification apparatus and a housing assembly 120 can be sealed using any sealant capable of maintaining vacuum conditions as known to those of ordinary skill in the art.
  • An exemplary sealant can be made from organopolysiloxane materials.
  • a purification apparatus as described herein can be used for filtering samples, such as biological materials, and directing the filtered samples into a plurality of respective sample wells in a sample well tray or receiving well array. Any procedure known to those of ordinary skill in the art can be used to filter the samples. For example, purification of a nucleic acid such as RNA for polymerase chain reaction (PCR) analysis can be performed using the purification apparatus set forth herein. Besides RNA purification, other processes such as, but not limited to, purification of DNA, extraction and/or purification of RNA or DNA from blood, and extraction and/or purification of proteins, can be performed using the purification apparatus described herein.
  • PCR polymerase chain reaction
  • the purification apparatus can be used for purifying specific sequences of DNA or RNA by varying, for example, the filter element of the sample purification tray, the chemistries used to react with the sequences, and/or reagents.
  • the purification apparatus can be used for processing biological or chemical samples, such as by filtration, separation, species immobilization, or other chemical or physical action or reaction of two or more chemical or biological substances.
  • Various purification, filtration, separation, immobilization, or reaction processes can be enhanced by heating during processing.
  • the purification apparatus as described herein can be heated during processing of samples. The ability to heat a sample tray of a purification apparatus as described herein allows the apparatus to be used for a wide range of processes.
  • Heating can increase the kinetic energy of the samples in the discharge columns of the sample purification tray, which can result in a decrease in the amount of time required for reaction, facilitate a more thorough mixing of the sample, catalyze a reaction, and/or lower viscosity to facilitate discharge of the sample through the filtering medium
  • Maintaining the temperature of a sample during filtering, purification, separation, immobilization, or reaction can improve or maintain viability of the sample, and/or decrease reaction times of later process steps.
  • the use of a heater module as described herein in a purification apparatus can avoid or eliminate compatibility issues of biological samples, such as PCR material, by indirectly heating the samples of such materials and not directly heating the samples themselves.
  • the purification apparatus described herein can be used to maintain a constant temperature, or to fluctuate the temperature of a sample during processing.
  • the purification apparatus as described herein can be used, for example, in manual or automated workstations for sample preparations.
  • one or more of the sample purification tray, heater module and sample well tray of various embodiments can be used in the ABI PRISM 6700 Automated Nucleic Acid Workstation or the ABI PRISM 6100 Workstation, both of which are manufactured by Applied Biosystems.
  • One or more of the sample purification tray, heater module, and sample well tray can also be suitable for use with a wide variety of available automated or manual sample preparation workstations, which workstations are known to those of ordinary skill in the art.
  • the heater module described herein can be used to heat a sample purification tray while the sample purification tray is being installed in a housing assembly.
  • one or more samples can be placed in one or more of the plurality of discharge columns 88 of a sample purification tray 80 such that the samples pass through the discharge columns 88, through respective discharge openings 96, and into respective openings 106 of sample wells 108 of a sample well tray 100.
  • the samples can be heated by heater module 10 while they are passed through discharge columns 88.
  • the heat distribution plate 20 of heater module 10 can surround and provide constant and uniform heating to each of the plurality of the discharge columns 88 and thereby uniformly heat the sample or samples passing through the discharge columns 88.
  • the heater module 10 can be used to preheat the sample purification tray 80, to heat the sample purification tray 80 while a sample passes therethrough, or to preheat and heat the sample purification tray 80 during use.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Health & Medical Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Water Supply & Treatment (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Hematology (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Robotics (AREA)
  • Molecular Biology (AREA)
  • Devices For Use In Laboratory Experiments (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Investigating Or Analyzing Materials Using Thermal Means (AREA)

Abstract

A heater module is described that includes a heat distribution plate including a bottom portion having first and second sides and a plurality of projections extending away from one of the sides. A heat source is provided for heating the heat distribution plate, and, optionally, a heating tray can be used to receive the heat source and heat distribution plate. The heater module is adapted to engage a sample purification tray having a plurality of purification and/or discharge columns which can extend through openings in the heater module and direct a sample into a sample receiving tray. Methods of heating samples using the heater module are also described.

Description

SAMPLE TRAY HEATER MODULE CROSS REFERENCE TO RELATED APPLICATIONS
This application claims the priority benefit of U.S. Patent Application No.
10/359,665, filed February 5, 2003, which is a continuation-in-part application of U.S. Patent Application No. 10/104,335, filed March 22, 2002, which is a continuation-in-part of U.S. Patent Application No. 09/552,301, filed April 18, 2000, now U.S. Patent No.
6,419,827 Bl, issued July 16, 2002, which is a continuation-in-part of U.S. Patent
Application No. 09/182,946, filed October 29, 1998, now U.S. Patent No. 6,159,368, issued December 12, 2000. Cross reference is made to the following related applications which are divisional applications of U.S. Patent Application No. 09/182,946, filed
October 29, 1998, now U.S. Patent No. 6,159,368, issued December 12, 2000: U.S. Patent
Application No. 09/565,673, filed May 4, 2000, now U.S. Patent No. 6,451,261 Bl, issued
September 17, 2002; U.S. Patent Application No. 09/565,202, filed May 4, 2000, now U.S.
Patent No. 6,506,343 Bl, issued January 14, 2003; and 09/565,566, filed May 4, 2000, now U.S. Patent No. 6,338,802 Bl, issued January 15, 2002. All references cited herein are incorporated in their entireties by reference.
FIELD
The present invention relates to a multi-well microfiltration apparatus and methods for processing a plurality of fluid samples simultaneously at a desired temperature. BACKGROUND
In recent years, microtitration wells have assumed an important role in many biological and biochemical applications, such as sample preparation, genome sequencing, and drug discovery programs. A variety of multi-well arrangements, constructed according to standardized formats, are now popular. Methods of heating samples in such multi-well arrangements, such as those described in U.S. Patent No. 5,459,300 and U.S. Patent No.
5,681,492, are known in the art, but do not perform consistent, uniform heating of all samples in a multi-sample array.
It is desirable to provide an apparatus for consistently and uniformly mamtaining, raising, or lowering the temperature of a plurality of samples, to facilitate processing such as purification.
SUMMARY
According to various embodiments, a sample tray heater module that can be used on an automated or manual sample preparation station is described. According to various embodiments, the sample tray heater module can include a heat distribution plate and a heat source. According to various other embodiments, the sample tray heater module can further include a heating tray.
According to various embodiments, a system including a sample tray heater module is provided wherein the temperature of the sample tray heater module can be monitored and controlled during heating. According to various embodiments, the heater module is capable of heating a sample to a temperature in a range of from about 5° C to about 100° C. In other embodiments, the heater module is capable of heating a sample to a temperature in a range of from about 20° C to about 70° C. According to various embodiments, the heater module is capable of heating a sample at a rate of greater than or equal to about 1° C per minute.
According to various embodiments, a system is provided wherein a sample tray heater module can be fitted with a sample purification tray, and/or a receiving well array, prior to processing samples.
According to various embodiments, a sample tray heater module is provided that includes a plurality of protrusions capable of interacting with a sample purification tray for proper positioning thereof relative to the heater module. The plurality of protrusions can provide uniform heating to a plurality of discharge columns of a sample purification tray according to various embodiments.
According to various embodiments, a sample tray heater module is provided that is inexpensive and reliable. According to various embodiments, the sample tray heater module can be disposable. According to various embodiments, the heat distribution plate, heat source, and optional heating tray of the heater module can each be made from a thermally conductive material such as a metal, metal alloy, or polymeric material, such as a thermoplastic, or a combination thereof A purification apparatus including a heater module for heating of a sample passing therethrough is described according to various embodiments.
According to various embodiments, a method is provided for purifying a sample wherein the sample is heated during purification.
Additional features and advantages of the heater module and its use will be set forth in part in the description that follows, and in part will be apparent from the description and drawings, or may be learned by practice. Objectives and other advantages of the heater module and methods of making and using the heater module will be realized and obtained by means of the elements and combinations described in the written description herein and the appended claims.
To achieve these and other advantages, a sample tray heater module is provided that includes a heat distribution plate and a heat source. The heat distribution plate can include a bottom portion and one or more protrusions extending away from the bottom portion The heat source can be in contact with an underside of the bottom portion of the heat distribution plate. One or more electrical contacts can be in electrical communication with the heat source. ptionaUy, the heater module can include a heating tray adapted to receive the heat source and the heat distribution plate. BRIEF DESCRIPTION OF THE DRAWINGS
Fig. 1 is a perspective view of a sample purification tray and a heater module.
Fig. 2 is atop view of a heat distribution plate according to various embodiments.
Fig. 3 is a sectional side view taken along line 3-3 in Fig. 2.
Fig. 4 is a front view of a heater module according to various embodiments. Fig. 5 is a back view of the heater module shown in Fig. 4.
Fig. 6 is a bottom view of the heater module shown in Figs. 4 and 5.
Fig. 7 is a cut-away top view of a heater module according to various embodiments taken along various cut-aways.
Fig. 8 is a perspective view of a purification apparatus having a sample purification tray, a heater module, and a sample well tray, wherein the heater module comprises a heat distribution plate, a heat source, and a heating tray.
Fig. 9 is a side-sectional view of a heater module having a heating tray, a heat source, and a heat distribution plate.
Fig. 10 is a perspective view of a purification apparatus including a sample tray, a heater module, and a carriage.
Fig. 11 is a graph illustrating the temperature rate increase of water using a heater module according to various embodiments.
Other various embodiments of the present invention will be apparent to those skilled in the art from consideration of the specification and practice of the invention described herein. It is intended that the specification and examples be considered as exemplary only, and that the true scope and spirit of the invention include those other various embodiments. DESCRIPTION OF CERTAIN EMBODIMENTS
According to various embodiments, a sample tray heater module is provided, for example, for a purification apparatus. The heater module can be used in or with an apparatus useful for purification, filtration, and or separation of biological and/or chemical samples, such as DNA. The purification apparatus can include a sample purification tray having a plurality of discharge columns, each with a distal end, wherein each discharge column is adapted to receive or includes a filter medium. The sample purification tray can be, for example, a discharge conduit array, a sample purification array, or other device capable of receiving and allowing passage therethrough of a sample. The sample purification tray can be disposed in a purification apparatus and held aligned with and in fluid communication with a receiving well array, for example, a sample well array, sample well tray, sample tray, array of receiving wells, or other device capable of receiving and containing, restraining, or holding a sample therein. The distal end of each discharge column of the sample purification tray can be in fluid communication with a respective receiving well of the receiving well array. The sample tray heater module, according to various embodiments, can be disposed between the sample purification tray and the receiving well array. The purification apparatus can be located in a carriage such that the sample purification tray is capable of horizontal and/or vertical movement with respect to the heating device and/or the receiving well array. Further details regarding exemplary sample purification trays, receiving well arrays, and purification apparatuses, and methods for the use thereof, are described in co-pending U.S. Patent Application No. 10/104,335, filed March 22, 2002.
According to various embodiments, a sample tray heater module is provided that can include a heat distribution plate having a plurality of protrusions, and a heat source. The heat source can be in contact with a side of a bottom portion of the heat distribution plate. The sample tray heater module can include a plurality of through holes for nozzle tips passing through the heat distribution plate and the heat source.
The sample tray heater module can include a heating tray for holding the heat source and the heat distribution plate. The heating tray can be capable of receiving and aligning the heat source and heat distribution plate, and can include a plurality of through holes for nozzle tips corresponding to the through holes for nozzle tips in the heat distribution plate and the heat source. The heater module can be constructed from a thermally conductive material, for example, a metal such as aluminum or stainless steel, a thermally conductive polymer, or a combination thereof.
According to various embodiments, and as shown in Figs. 1-3, the heater module 10 can comprise a heat distribution plate 20 having a bottom portion 22 having a first side and a second opposing side, and from which sidewalls 24 extend substantially perpendicularly or perpendicularly from the first side of bottom portion 22. Also extending from the first side of bottom portion 22 can be a plurality of protrusions 26. As used herein, "protrusion" refers to a projection, extension, elongation, or other raised feature extending out of a plane of bottom portion 22. The sidewalls 24 and each of the plurality of protrusions 26 can be the same height. The plurality of protrusions 26 and sidewalls 24 define a plurality of discharge column receptacles 28, for example, to accommodate a plurality of discharge conduits or columns from a discharge conduit array, for example, a sample purification tray 80. Each discharge column receptacle 28 can have a respective through hole 30 for a nozzle tip through which a discharge column nozzle tip can extend. The heat distribution plate 20 can include screw-through holes 32 as shown, tap holes, clips, or other devices useful for fastening the heater module together.
As shown in Figs. 1 and 4-7, a heat source 40 can be in contact with the second side of the bottom portion of the heat distribution plate 20. According to various embodiments, the heat source 40 can be a substantially flat material. The heat source 40 can include a bottom layer 44 in which can be disposed heating wires 50 for carrying power to a wire layout 48. The wire layout 48 can be attached to temperature sensor wires or contact wires 52. According to various embodiments, and as shown in Fig. 1, the temperature probes 52 and/or the wires 50 can extend through through holes 94 of sample purification tray 80 to secure the sample purification tray 80 to the heater module 10. For example, the temperature sensor can be a thermistor or a thermocouple, or the heating wires themselves can act as temperature sensors as, for example, measured based on resistivity through the wires. The bottom layer 44 of heat source 40 having the wire layout 48 disposed therein can be covered by cover layer 46 to protect the wires. The heat source 40 can have through holes 54 for nozzle tips to extend therethrough. The through holes 54 for nozzle tips can correspond to through holes 30 for nozzle tips of a heat distribution plate 10 and, optionally, can correspond to through holes 66 for nozzle tips of a tray 60. The power wires 50 can be connected to a controller 57 or connection module 56 as shown in Figs. 7 and 8. The controller 57 can be connected to a power source to provide energy for heating the wires. The controller can include computer controls, thermal cut-offs, and/or PID controllers, or other controllers that can modify the current flowing through the heating elements and/or heating wires. The heat source 40 can be attached to or separate from the heat distribution plate 20. According to various embodiments, the heat source 40 can be incorporated in the heat distribution plate, for example, by integral molding therewith. The heat source 40 can be in contact with the first side of the bottom portion 22 of the heat distribution plate 20, wherein the first side of the bottom portion 22 includes the surfaces of the plurality of protrusions 26.
As shown in Figs. 7, 8, and 9, the heater module 10 can further comprise a tray 60 having an inwardly facing bottom portion 62 from a first side of which sidewalls 64 extend substantially perpendicularly or perpendicularly. The tray 60 can be adapted to receive the heat source 40 and the heat distribution plate 20 within the area defined by sidewalls 64 and bottom portion 62. The tray 60 can have through holes 66 for nozzle tips corresponding to through holes 54 for nozzle tips of the heat source 40 and through holes 30 for nozzle tips of the heat distribution plate 20. Tray 60 can also comprise screw holes 68 for fastening together the heater module by screws, bolts, or other attachment devices passing through at least one screw-through hole 32 and at least one screw hole 68.
The heat distribution plate 20 can be capable of receiving a discharge conduit array, for example, a sample purification tray 80, as shown in Figs. 1 and 8. Sample purification tray 80 can include a top plate 82 from a side of which sidewalls 84 extend substantially perpendicularly or pe endicularly. Sample purification tray 80 can have openings 86 in top plate 82, which openings lead into discharge columns 88. The discharge columns 88 can include more than one section, for example, a first portion 90 and a second portion 92, as shown in Figs. 1 and 8. The discharge column 88 can terminate in a nozzle tip having a discharge opening 96 which is capable of fluid communication with a respective opening 106 in corresponding sample well tray or receiving well array 100, as shown in Fig. 8. At least the nozzle tips of discharge columns 88 can pass through respective through holes 30 for nozzle tips of the heat distribution plate, respective through holes 54 for nozzle tips of the heat source, and, optionally, respective through holes 66 for nozzle tips of the tray 60, to extend below heater module 10. The sample purification tray 80 can also have openings 94 to receive temperature probe 52 and/or power wires 50 from heat source 40.
The portions 90, 92 of the discharge columns 88 of the sample purification tray 80 can be formed separately and joined together by any suitable method, such as heat welding or adhesive bond, or they can be integrally formed such as by molding. Various methods of forming the sample purification tray will be apparent to those skilled in the art. The sample purification tray can be formed from a plastic material, a metal, or any other suitable material or combination of materials as known to those skilled in the art. The sample purification tray can be formed of a material which does not interact or react with the sample to be purified. Examples of suitable materials include polypropylene, polyethylene, polycarbonate, and mixtures thereof.
The sample purification tray 80 can be adapted to receive one or more filters in one or more of the discharge columns 88. Various sample purification trays and details regarding the size, shape, material, and manufacture of sample purification trays, discharge conduit arrays, and filters for use therein, can be found in co-pending U.S. Patent Application 10/104,335, U.S. Patent No. 6,419,827 Bl, and U.S Patent No. 6,159,368, all of which are herein incorporated in their entireties by reference.
The sample purification tray can fit snuggly into heat distribution plate 20 such that discharge columns 88 are in good, snug, thermal contact with the protrusions of heat distribution plate 20. The regions between adjacent projections are referred to herein as discharge column receptacles 28. According to various embodiments, a portion of at least one of the plurality of protrusions 26 separates each discharge column 88 from the next discharge column 88. According to various embodiments, at least a portion of a discharge column 88 can be located between one of the plurality of protrusions 26 and a sidewall 24. The sample purification tray and heater module can be held in housing assembly 120 by carriage frame 122 having receiving area 124, as shown in Fig. 10.
According to various embodiments, and as shown and described in U.S. Patent Application 09/552,301, filed April 18, 2000, and issued as U.S. Patent No. 6,419,827 Bl, which is incorporated herein in its entirety by reference, a vent plate can be located between the heater module 10 and the receiving well array 100. The vent plate can have a plurality of though holes for nozzle tips corresponding to the though holes for nozzle tips in the heater module, and corresponding to the wells in the receiving well array, to allow fluid communication from the sample purification tray through the heater module and vent plate to the receiving well array. Apertures or vents can extend through the vent plate. At least one aperture can be located adjacent each through hole for a nozzle tip in the vent plate. The apertures permit fluid communication between the regions above and below the vent plate. By this construction, a vacuum drawn from beneath the vent plate will extend to the regions above the vent plate. The vent plate material can be the same as the material used to form the heater module.
According to various embodiments, an aerosol guard or other cross-flow restrictor, as described, for example, in U.S. Patent Application 09/182,946, filed October 29, 1998, issued as U.S. Patent No. 6,159,368, can be located between heater module 10 and vent plate 70, or between heater module 10 and sample well tray 100. The aerosol guard can prevent aerosols from each of sample wells 108 from cross-contaminating other sample wells. The aerosol guard can allow the passage of gases, but not aerosols, therethrough. The aerosol guard can be placed immediately adjacent and below heat source 40 of heater module 10 or, if tray 60 is used, immediately adjacent and below tray 60 of heater module 10. According to various embodiments, the aerosol guard can be placed immediately adjacent and below a vent plate. The aerosol guard can include a plurality of through holes for nozzle tips positioned substantially in alignment with one or more of through holes 54 for nozzle tips of heat source 40, through holes 66 for nozzle tips of tray 60, and through holes 72 for nozzle tips of heat plate 70, and also substantially in alignment with openings 106 in top plate 102 of sample well tray 100. At least the nozzle tips of discharge columns 88 can pass through the through holes for nozzle tips of the aerosol guard and can be in fluid communication with sample wells 108 through openings 106 of the sample well tray 100. The aerosol guard can be made of a flexible or non-flexible material and the material can be capable of withstanding the temperatures associated with use of heater module 10. The aerosol guard material can be substantially non-reactive with the chemicals and/or biological components of the sample. The aerosol guard can be made from foam-like material. The aerosol guard can be a porous, hydrophilic polymer material, such as, for example, ethyl vinyl acetate. Other suitable materials for the aerosol guard are apparent to those of ordinary skill in the art.
Various embodiments and details of the vent plate and aerosol guard can be found in related co-pending U.S. Patent Application No. 10/104,335, U.S. Patent No. 6,419,827 Bl, and U.S. Patent No. 6,159,368, all of which are incorporated herein in their entireties by reference. As shown, for example, in Fig. 8, when the sample purification tray 80 is fitted with heater module 10, at least the nozzle tips of the discharge columns 88 can protrude through discharge column receptacles 28 and through holes 30 for nozzle tips in heat distribution plate 20, through through holes 54 for nozzle tips in heat source 40, and, optionally, if tray 60 is used, through through holes 66 for nozzle tips in tray 60, to extend below tray 60 or heat source 40 and be in fluid communication with sample well tray 100. According to various embodiments, any sample placed in sample purification tray 80 through an opening 86 into a discharge column 88 can flow through the discharge column 88 and can emerge from respective discharge opening 96 into respective opening 106 of the top plate 102 of the sample well tray 100, and can proceed through opening 106 into respective sample well 108. According to various embodiments, the number of discharge columns 88, discharge openings 96, through holes 30, 54 and 66 for nozzle tips, and openings 106 in sample well tray 100 are equivalent. According to various embodiments, the number of openings 106 in sample well tray 100 can be less than the number of discharge columns 88, discharge openings 96, and through holes 30, 54, and 66 for nozzle tips, such that multiple adjacent discharge columns 88 and corresponding discharge openings 96 are in fluid communication with a single opening 106 of sample well tray 100.
Heater module 10 is capable of providing heat to sample purification tray 80 such that samples can be heated before and/or during passage through discharge columns 88 of sample purification tray 80. Heater module 10 can be, for example, capable of mamtaining a temperature or raising a temperature of samples in the respective plurality of discharge columns 88 of sample purification tray 80 during the period of time it takes for the samples to pass through the discharge columns 88. According to various embodiments, heater module 10 is capable of heating at a rate sufficient to heat 1 ml of water at 1°C per minute or greater, when the water disposed in a thermally conductive polymeric receptacle having an area of about three cm2 in thermal contact with the heater module. For example, as shown in Fig. 11, the heater module 10 can raise the temperature of 1 ml of water in a 0.25 inch diameter column of a sample purification tray 80 fitted into the heater module 10, from about 23°C to about 65°C in 20 minutes or less. The heater module 10 can be capable of providing heat sufficient to heat samples to a temperature in a range of from about 5°C to about 100°C. The heater module 10 can be capable of providing heat sufficient to heat samples to a temperature in a range of from about 20°C to about 70°C. One or more of the heat distribution plate 20, heat source 40, and tray 60 of the heater module 10 can be constructed from a thermoconductive material. According to various embodiments, each of the heat distribution plate 20, heat source 40, and tray 60 are made from a thermoconductive material. The thermoconductive material can be a metallic thermoconductive material, such as du inum, iron, tantalum, titanium, copper, or alloys thereof. The thermoconductive material can be a thermoconductive polymeric material capable of withstanding temperatures in the range or from about 5°C to about 100°C without deforming, cracking or melting. The polymeric material can include a thermoconductive filler material. The filler material can be one or more different fillers selected from a carbon material, boron nitride, and metallic materials, for example, aluminum, alumina, copper, magnesium, and brass, or a combination thereof.
According to various embodiments, heat distribution plate 20 can be constructed of a substantially rigid, thermoconductive material. According to various embodiments, the plurality of protrusions 26 can be made of the same material as sidewalls 24. The heat distribution plate 20, including bottom portion 22, sidewalls 24, and the plurality of protrusions 26, can be made of a substantially unitary construction. For example, the heat distribution plate 20 can be molded or machined to include the plurality of protrusions 26 and the sidewalls 24. According to various embodiments, the plurality of protrusions 26 can be formed separately from bottom portion 22 and bonded thereto or otherwise attached. The sidewalls 24 can be formed separately from bottom portion 22 and bonded or otherwise attached thereto. Bonding of the plurality of protrusions 26 or sidewalls 24 to bottom portion 22 can be done by any known process, for example, bonding by epoxy or by a welding process such as heat welding or ultrasonic bonding or welding. According to various embodiments, wherein the thermoconductive material of the heat distribution plate 20 is a polymer, the material can be a mixture of one or more polymers, one or more monomers, or of one or more polymers with at least one thermoconductive filler material. According to various embodiments, the polymer can be a liquid crystal polymer. According to various embodiments wherein a thermally conductive filler material is used, the filler material can be one or more different fillers selected from a carbon material, boron nitride, and metallic materials, for example, aluminum, alumina, copper, magnesium, and brass, or a combination thereof. Various examples of thermally conductive composite materials are described, for example, in U.S. Patent No. 6,048,919. Exemplary thermally conductive liquid crystalline polymers (LCP) can be obtained from Cool-Polymers, Inc. under the trademarks Cool-Poly® E200, Cool-Poly® RB018, Cool- Poly® RB019, Cool-Poly® RB020, Cool-Poly® RS008, Cool-Poly® D2, Cool-Poly® RS007, and Cool-Poly® RS012. According to various embodiments wherein a tray 60 is part of the heater module 10, the tray 60 can be made of or include any thermoconductive material as described herein. According to various embodiments, the tray 60 can be made from the same material as the heat distribution plate 20, for example, the same thermoconductive material. According to various embodiments, the heating tray can be a non-conductive material. The heating tray can be made of glass, ceramic, a polymeric material, a metal, an alloy, or a combination thereof. According to various embodiments wherein a tray 60 is included, the heat 40 source can be located against bottom portion 62 of tray 60 in a space defined by bottom portion 62 and sidewall 64. The heat source 40 can be bonded to or placed against bottom portion 62 of tray 60. The heat source 40 can be bonded or otherwise attached to a side of the bottom portion 22 of heat distribution plate 20, which can be set into tray 60 in a space defined by bottom portion 62 and sidewall 64. According to various embodiments, both a heat distribution plate 20 and a tray 60 can be used in a heater module 10 wherein both the heat distribution plate 20 and tray 60 can be made of or include aluminum The heater module 10 can contain both a heat distribution plate 20 and a tray 60, wherein the heat distribution plate 20 and tray 60 can both be made of or include a thermoplastic material. According to various embodiments wherein the heat distribution plate 20 and tray 60 are both made from or include thermoplastic material, the heat distribution plate 20 and tray 60 can be bonded together. Heat distribution plate 20 and tray 60 can be bonded together after, for example, placing a heat source 40 between the heat distribution plate 20 and tray 60. Such bonding can be achieved by any method known to those skilled in the art, such as by the use of epoxy, thermoconductive epoxy, or thermal bonding. According to various other embodiments, the heat distribution plate 20 and tray 60 can be attached mechanically such that the heater module 10 comprising the heat distribution plate 20 and tray 60 with or without a heat source 40 therebetween can be moved as a single unit.
According to various embodiments, the heat source 40 can include any heating system known to those skilled in the art to provide uniform distribution of heat. The heat source 40 can be attached to the heat distribution plate 20, attached to the tray 60, attached to both the heat distribution plate 20 and tray 60, or set between the heat distribution plate 20 and tray 60. The heat source 40 can be made from a flexible material and can comprise a film or sheet, for example, a polyimide sheet material such as KAPTON, available from DuPont High Performance Materials, Circleville, Ohio. The heat source 40 can be a printed resistor circuit on a side of bottom portion 22 of heat distribution plate 20 or can be a printed resistor circuit on the bottom portion 62 of tray 60, wherein the printed resistor circuit is capable of generating heat. According to various embodiments wherein the heat source 40 comprises a printed resistor circuit in the form of wire layout 48, the wire layout 48 can be made from any conductive material capable of producing a predetermined, minimum, and/or maximum amount of heat. For example, the wire layout can be made from various metals or metal alloys, including gold, silver, aluminum, copper, titanium, alloys thereof, and other metals and metal alloys as known to those of ordinary skill in the art. The wire layout 48 can be set forth in a bottom layer 44 capable of accepting and holding in place the wire layout. The bottom layer 44 can be made from a flexible or non-flexible material. The bottom layer 44 can be made from silicone, a polymeric material, glass, or any other material known to those of ordinary skill in the art, including composite materials. The cover layer 46 can be made of or include any material capable of encapsulating wire layout 48 and bottom layer 44, wherein the cover layer material is capable of transferring heat from the wire layout 48 to the heat distribution plate 20. According to various embodiments, the cover layer 46 can be the same material as the bottom layer 44. According to various embodiments, the cover layer 46 can be a polymeric material. Other suitable materials are apparent to those of ordinary skill in the art.
The heat source 40 comprising the bottom layer 44, wire layout 48, and cover layer 46, can be capable of generating a predetermined amount of heat dependent upon the resistance and current input of the wire layout 48. The amount of heat capable of being generated can be changed by changing the resistance of wire layout 48, or by lowering or raising the amount of current passing through wire layout 48. Electrical current is provided to wire layout 48 through wires 50, which are connected to controller 57 by connector 56. Controller 57 can control the amount of current that passes through wires 50 to wire layout 48, and therefore the amount of heat generated by wire layout 48 and heat source 40.
According to various embodiments, heat source 40 can be formed integrally with tray 60 or heat distribution plate 20. The heat source 40 can be formed integrally with tray 60 such that bottom layer 44 of heat source 40 corresponds to bottom portion 62 of tray 60. The heat source 40 can be formed integrally with heat distribution plate 20 such that cover layer 46 of heat source 40 corresponds to bottom portion 22 of heat distribution plate 20.
According to various embodiments, a heat source can be incorporated into heat distribution plate 20. In such embodiments, heat distribution plate 20 with the incorporated heat source can be used as an alternative to or in addition to heat source 40. Wires, a wire layout, and/or a printed resistor circuit can be molded or otherwise formed within the heat distribution plate 20 having an incorporated heat source. The wires, wire layout, and/or printed resistor circuit can be molded or otherwise formed within at least one of the bottom portion 22, the sidewalls 24, and the plurality of protrusions 26. The heat distribution plate 20 with the incorporated heat source can be formed similar to the way that a steel- reinforced concrete slab is formed by pouring concrete into a mold containing a network or a grid pattern of steel rebar. For example, at least part of a network of resistors, wires, a wire layout, resistive heat elements, and or a printed resistor circuit can be placed into a mold and a thermoconductive material that is in a molten state can be poured into the mold. When the thermoconductive material hardens, the hardened object forms the heat distribution plate 20 with the incorporated heat source. The resistors, wires, wire layout, resistive heat elements, and/or printed resistor circuit can be affixed to, inserted in, and/or embedded into the at least one of the bottom portion 22, the sidewalls 24, and the plurality of protrusions 26. The resistors, wires, wire layout, resistive heat elements, and/or printed resistor circuit can be made of various metals or metal alloys, including gold, silver, aluminum, copper, titanium, alloys thereof, and other metals and metal alloys as known to those of ordinary skill in the art. The heat distribution plate 20 with the incorporated heat source can be capable of generating a predetermined amount of heat dependent upon the resistance and current input of the wires and/or wire layout. A controller can provide current to the wires and/or wire layout via a connector. The heat distribution plate 20 with the incorporated heat source can perform in the same manner as the heat source 20 without the incorporated heat source and heat source 40.
According to various embodiments, the temperature of the sample tray heater module 10 can be monitored. The heat source 40 can include one or more heat sensor or temperature probe 52 such as a thermistor, a thermostat, a thermal protection tube, or a non-contact sensor such as an infrared sensor. The heat sensor or temperature probe 52 can be positioned such that it contacts the bottom portion 22 of heat distribution plate 20. The heat generated by heat source 40 can be controlled based upon the temperature detected or temperature readings obtained from the heat sensor or temperature probe 52. Other suitable heat sensors or temperature probe designs as known to those of ordinary skill in the art can be used with heat source 40. For example, the heat sensor or temperature probe can be located above sample purification tray 80 in order to determine the temperature of the samples inside discharge columns 88. According to various embodiments, a heat sensor or temperature probe can be located inside one or more of the discharge columns 88.
According to various embodiments, and as shown in Fig. 1, heater module 10 is designed to interact with and complement sample purification tray 80. The sidewalls 24 of heat distribution plate 20 of heater module 10 extend substantially perpendicularly or perpendicularly from a side of bottom portion 22 such that when mated with a sample purification tray 80, the sidewalls 24 of heat distribution plate 20 substantially cover discharge columns 88 of sample purification tray 80 from view. According to various embodiments, the sidewalls 24 of heat distribution plate 20 can touch a side of top plate 82 of the sample purification tray 80. According to various other embodiments, the sidewalls 24 of heat distribution plate 20 can be in contact with one or more discharge columns 88 of sample purification tray 80. The sidewalls 24 can be in contact with one or more portion of discharge column 88, for example, the second portion 92 or the first portion 90 of discharge column 88. According to various other embodiments, the sidewalls 24 of heat distribution plate 20 can be in contact with the sidewalls 84 of the sample purification tray 80. The plurality of protrusions 26 of heat distribution plate 20 can be in contact with a side of top plate 82 of the sample purification tray 80. According to various embodiments, the plurality of protrusions 26 of heat distribution plate 20 extend from heat distribution plate 20 and are located between discharge columns 88 of the sample purification tray 80. According to various embodiments, each of the plurality of protrusions 26 is in contact with one or more of the discharge columns 88. For example, one or more of the plurality of protrusions 26 can be in contact with a second portion 92, a first portion 90, or both a second portion 92 and a first portion 90, of a discharge column 88 of sample purification tray 80. At least a portion of one or more of the discharge columns 88 can substantially fit between two or more of the plurality of protrusions 26, or between one or more of the plurality of protrusions 26 and sidewall 24 of the heat distribution plate 20.
According to various embodiments, the plurality of protrusions 26 of the heat distribution plate 20 can function as a heat sink to dissipate heat by heating discharge columns 88 of the sample purification tray 80. A fan can be positioned to promote heat distribution between the plurality of protrusions 26 and heat absorption by the discharge columns 88.
According to various embodiments, one or more of through hole 30 for a nozzle tip of heat distribution plate 20, through hole 54 for a nozzle tip of heat source 40, and optionally through hole 66 for a nozzle tip of tray 60, can be sized so as to closely fit the profile of discharge column 88 of sample purification tray 80. One or more through hole 30, 54, or 66 for a nozzle tip can be sized to closely mate with a corresponding discharge column 88 so that bending of the discharge column 88 can be niinimized. According to various embodiments, the spacing of one or more through hole 30, 54, or 66 for a nozzle tip, can assist in maintaining equal spacing between the discharge columns 88.
According to various embodiments, a purification apparatus comprising a sample purification tray 80, a heater module 10, a sample well tray 100, optionally a vent plate, and optionally an aerosol guard, can be formed using the components described herein. For purification of a sample, the purification apparatus can be placed under vacuum conditions to create a pressure differential. According to various embodiments wherein a vacuum condition will be endured, openings and seams in the purification apparatus, and between the purification apparatus and a housing assembly 120, can be sealed using any sealant capable of maintaining vacuum conditions as known to those of ordinary skill in the art. An exemplary sealant can be made from organopolysiloxane materials. Other suitable sealants as known to those of ordinary skill in the art can be used such as those described, for example, in U.S. Patents Nos. 5,929,138; 5,079,300; 5,037,667; 4,950,546; 4,777,063; 4,680,233; and 4,595,635.
A purification apparatus as described herein can be used for filtering samples, such as biological materials, and directing the filtered samples into a plurality of respective sample wells in a sample well tray or receiving well array. Any procedure known to those of ordinary skill in the art can be used to filter the samples. For example, purification of a nucleic acid such as RNA for polymerase chain reaction (PCR) analysis can be performed using the purification apparatus set forth herein. Besides RNA purification, other processes such as, but not limited to, purification of DNA, extraction and/or purification of RNA or DNA from blood, and extraction and/or purification of proteins, can be performed using the purification apparatus described herein. The purification apparatus can be used for purifying specific sequences of DNA or RNA by varying, for example, the filter element of the sample purification tray, the chemistries used to react with the sequences, and/or reagents. The purification apparatus can be used for processing biological or chemical samples, such as by filtration, separation, species immobilization, or other chemical or physical action or reaction of two or more chemical or biological substances. Various purification, filtration, separation, immobilization, or reaction processes can be enhanced by heating during processing. The purification apparatus as described herein can be heated during processing of samples. The ability to heat a sample tray of a purification apparatus as described herein allows the apparatus to be used for a wide range of processes. Heating can increase the kinetic energy of the samples in the discharge columns of the sample purification tray, which can result in a decrease in the amount of time required for reaction, facilitate a more thorough mixing of the sample, catalyze a reaction, and/or lower viscosity to facilitate discharge of the sample through the filtering medium Maintaining the temperature of a sample during filtering, purification, separation, immobilization, or reaction can improve or maintain viability of the sample, and/or decrease reaction times of later process steps. According to various embodiments, the use of a heater module as described herein in a purification apparatus can avoid or eliminate compatibility issues of biological samples, such as PCR material, by indirectly heating the samples of such materials and not directly heating the samples themselves. The purification apparatus described herein can be used to maintain a constant temperature, or to fluctuate the temperature of a sample during processing.
The purification apparatus as described herein can be used, for example, in manual or automated workstations for sample preparations. For example, one or more of the sample purification tray, heater module and sample well tray of various embodiments can be used in the ABI PRISM 6700 Automated Nucleic Acid Workstation or the ABI PRISM 6100 Workstation, both of which are manufactured by Applied Biosystems. One or more of the sample purification tray, heater module, and sample well tray can also be suitable for use with a wide variety of available automated or manual sample preparation workstations, which workstations are known to those of ordinary skill in the art. According to various embodiments, the heater module described herein can be used to heat a sample purification tray while the sample purification tray is being installed in a housing assembly. Interrelation of a sample purification tray and carriage frame of a housing assembly is set forth, for example, in U.S. Patent No. 6,419,827 Bl, incorporated herein in its entirety by reference. According to various embodiments, one or more samples can be placed in one or more of the plurality of discharge columns 88 of a sample purification tray 80 such that the samples pass through the discharge columns 88, through respective discharge openings 96, and into respective openings 106 of sample wells 108 of a sample well tray 100. The samples can be heated by heater module 10 while they are passed through discharge columns 88. The heat distribution plate 20 of heater module 10 can surround and provide constant and uniform heating to each of the plurality of the discharge columns 88 and thereby uniformly heat the sample or samples passing through the discharge columns 88. The heater module 10 can be used to preheat the sample purification tray 80, to heat the sample purification tray 80 while a sample passes therethrough, or to preheat and heat the sample purification tray 80 during use.
Various examples of the components described herein are further set forth and described, for example, in co-pending related U.S. Patent Application No. 10/104,335, U.S. Patent No. 6,419,827 Bl, and U.S. Patent No. 6,159,368. All pubhcations cited herein are incorporated by reference in their entireties.
Those skilled in the art can appreciate from the foregoing description that the broad teachings of the present invention can be implemented in a variety of forms. Therefore, while this invention has been described in connection with certain embodiments and examples thereof, the true scope of the invention should not be so limited. Various changes and modifications can be made without departing from the scope or spirit of the invention, as defined by the appended claims.

Claims

WHAT IS CLAIMED IS:
1. A heater module comprising: a heat distribution plate comprising a bottom portion having a first side and an opposite second side, a plurality of protrusions spaced from one another and extending away from the first side, and a plurality of through holes passing through the heat distribution plate; and a heat source in thermal contact with the heat distribution plate and comprising a thermally conductive material capable of providing uniform heating across the heat distribution plate, the heat source including a plurality of through holes; wherein the plurality of through holes through the heat distribution plate are aligned with the plurality of through holes through the heat source.
2. The heater module of claim 1, wherein the heat distribution plate further comprises sidewalls extending away from the first side.
3. The heater module of claim 2, wherein each of the plurality of protrusions has a distal tip and a height equal to the distance the distal tip extends away from the first side of the heat distribution plate, and wherein the sidewalls each have a height equal to the distance the sidewalls extends away from the first side of the heat distribution plate, and wherein the height of the protrusions are equal to the height of the sidewalls.
4. The heater module of claim 1, wherein the heat source is incorporated in the heat distribution plate.
5. The heater module of claim 1, wherein the heat source comprises a first side.
6. The heater module of claim 5, wherein the first side of the heat source is in contact with the first side of the heat distribution plate.
7. The heater module of claim 5, wherein the first side of the heat source is in contact with the second side of the heat distribution plate.
8. The heater module of claim 1, further comprising a heating tray including an inwardly facing bottom surface and sidewalls extending away from the bottom surface, wherein the heating tray is adapted to receive both the heat distribution plate and the heat source.
9. The heater module of claim 8, wherein the heating tray further comprises a plurality of through holes capable of being aligned with the pluralities of through holes through the heat distribution plate and through the heat source.
10. The heater module of claim 8, wherein the heat distribution plate is disposed within the heating tray, and the heat source is disposed within the heating tray between the bottom surface of the heating tray and the heat distribution plate.
11. The heater module of claim 1, wherein the heat source further comprises a temperature sensor.
12. The heater module of claim 1, wherein the heat distribution plate comprises a polymeric material.
13. The heater module of claim 1, wherein the heat distribution plate comprises a metallic material.
14. The heater module of claim 13, wherein the metallic material is selected from aluminum, copper, titanium, tantalum, iron, alloys thereof and combinations thereof
15. The heater module of claim 8, wherein the heating tray comprises a metallic material.
16. The heater module of claim 15, wherein the metallic material is selected from aluminum, copper, titanium, tantalum, iron, alloys thereof, and combinations thereof
17. The heater module of claim 8, wherein the heating tray comprises a polymeric material.
18. The heater module of claim 8, wherein the heating tray comprises a thermoconductive material.
19. The heater module of claim 8, wherein the heating tray comprises a non- thermoconductive material.
20. The heater module of claim 1, wherein at least some of the through holes are surrounded by two or more of the protrusions.
21. A sample purification apparatus comprising: a heater module of claim 1; and a sample purification tray comprising a first surface, a second surface opposing the first surface, and a plurality of purification columns extending away from the second surface, each purification column including a distal tip portion including an outlet opening through which sample liquid in the purification column can be discharged from the purification column, wherein the plurality of purification columns are spaced from one another in an array having a configuration adapted such that the purification columns can be positioned among the plurality of protrusions of the heat distribution plate so that at least some of the plurality of discharge columns are each surrounded by two or more respective protrusions of the plurality of protrusions, and such that the outlet openings of the plurality of purification columns are capable of being aligned with the plurality of through holes through the heat distribution plate.
22. The purification apparatus of claim 21, wherein the heater module further comprises sidewalls extending away from the first surface.
23. The purification apparatus of claim 21, wherein the sample purification tray engages the heater module such that at least one of the protrusions of the heat distribution plate is surrounded by four purification columns.
24. The purification apparatus of claim 21, wherein the sample purification tray engages the heater module such that at least one of the purification columns of the sample purification tray is surrounded by four of the protrusions of the heat distribution plate.
25. The purification apparatus of claim 21, wherein the sample purification tray is in mating engagement with the heater module such that the plurality of purification columns abut the plurality of protrusions.
26. A purification method comprising: providing the sample purification apparatus of claim 17; disposing a plurality of respective samples in the purification columns of the sample purification tray; activating the heat source of the heater module to provide heat to the heat distribution plate; and passing the samples through the purification columns and out the respective outlet openings while the heat distribution plate heats the samples.
27. The method of claim 26, comprising heating the respective samples to a temperature of from about 20°C to about 70°C.
28. The method of claim 26, comprising heating the respective samples at a rate of about 1°C per minute or greater.
29. The method of claim 26, wherein the heat source of the heater module is activated before the plurality of respective samples is disposed in the purification columns of the sample purification tray.
PCT/US2004/002811 2003-02-06 2004-02-02 Sample tray heater module WO2004071665A1 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP04707411A EP1599288B1 (en) 2003-02-06 2004-02-02 Sample tray heater module
DE602004022259T DE602004022259D1 (en) 2003-02-06 2004-02-02 HEATING MODULE FOR SAMPLE CARRIER
AT04707411T ATE437698T1 (en) 2003-02-06 2004-02-02 HEATING MODULE FOR SAMPLE CARRIER

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US10/359,665 2003-02-06
US10/359,665 US6906292B2 (en) 1998-10-29 2003-02-06 Sample tray heater module

Publications (1)

Publication Number Publication Date
WO2004071665A1 true WO2004071665A1 (en) 2004-08-26

Family

ID=32867926

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2004/002811 WO2004071665A1 (en) 2003-02-06 2004-02-02 Sample tray heater module

Country Status (5)

Country Link
US (3) US6906292B2 (en)
EP (1) EP1599288B1 (en)
AT (1) ATE437698T1 (en)
DE (1) DE602004022259D1 (en)
WO (1) WO2004071665A1 (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018147029A1 (en) * 2017-02-07 2018-08-16 株式会社 日立ハイテクノロジーズ Automatic analysis device
US11434462B2 (en) 2016-12-01 2022-09-06 Berkeley Lights, Inc. Well-plate incubator
US11492584B2 (en) 2015-10-01 2022-11-08 Berkeley Lights, Inc. Well plate incubator

Families Citing this family (57)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6906292B2 (en) * 1998-10-29 2005-06-14 Applera Corporation Sample tray heater module
US6657169B2 (en) * 1999-07-30 2003-12-02 Stratagene Apparatus for thermally cycling samples of biological material with substantial temperature uniformity
EP1322421A2 (en) * 2000-09-29 2003-07-02 Avantium International B.V. Assembly of an integrated vessel transporter and at least one reaction vessel for transporting a chemical substance
WO2004008108A1 (en) * 2002-07-15 2004-01-22 Avantium International B.V. A system for the preparation of multiple solid state samples, in particular for spectroscopic and microscopic analysis
CN1817421B (en) * 2002-07-25 2012-07-04 大日本印刷株式会社 Thin film supporting substrate used in filter for hydrogen production and method for manufacturing filter for hydrogen production
US7763833B2 (en) * 2004-03-12 2010-07-27 Goodrich Corp. Foil heating element for an electrothermal deicer
WO2006015012A1 (en) * 2004-07-27 2006-02-09 Protedyne Corporation Method and apparatus for applying pressure diferential to multi-well plate
US7799283B2 (en) * 2004-11-12 2010-09-21 Ortho-Clinical Diagnostics, Inc. Heating and cooling multiple containers or multi-chamber containers
DE102005016755B3 (en) * 2005-04-11 2006-11-30 Eppendorf Ag Apparatus, system comprising such apparatus and method for drying cavities in microtiter filter plates and filters disposed therein
US20070116444A1 (en) * 2005-06-16 2007-05-24 Sratagene California Heat blocks and heating
JP4617209B2 (en) * 2005-07-07 2011-01-19 株式会社豊田自動織機 Heat dissipation device
US7923668B2 (en) * 2006-02-24 2011-04-12 Rohr, Inc. Acoustic nacelle inlet lip having composite construction and an integral electric ice protection heater disposed therein
EP2023056A1 (en) * 2007-07-30 2009-02-11 Chia-Hsiung Wu Binding process for an air heater and structure thereof
US20090098593A1 (en) * 2007-10-15 2009-04-16 Biocision, Inc. Laboratory plate thermal vault
US8460621B2 (en) * 2007-10-15 2013-06-11 Biocision, Llc Temperature transfer stand
WO2009100933A1 (en) * 2008-02-15 2009-08-20 Eppendorf Ag Thermal device
JP2013513470A (en) * 2009-12-10 2013-04-22 ネフロス，インク． Means for checking filter integrity in liquid purification systems
US9170028B1 (en) * 2010-10-06 2015-10-27 Lawrence Livermore National Security, Llc Methods and compositions for rapid thermal cycling
US10883100B2 (en) 2011-03-29 2021-01-05 Phynexus, Inc Devices and methods for plasmid purification
US10597652B2 (en) 2011-03-29 2020-03-24 Phynexus, Inc. Methods and devices for nucleic acid purification
US20150119563A1 (en) * 2011-03-29 2015-04-30 Chris Suh Methods and devices for nucleic acid purification
US11274292B2 (en) 2011-03-29 2022-03-15 Phynexus, Inc. Devices and methods for plasmid purification
US20130017132A1 (en) * 2011-07-12 2013-01-17 Biocision, Inc. Reagent reservoir and thermoconductive adaptor
GB201118774D0 (en) * 2011-10-31 2011-12-14 British American Tobacco Co Fluid distribution in an exposure device
TWM441823U (en) * 2012-04-13 2012-11-21 Taiwan Advanced Nanotech Inc Reagent trough, sample carrier, and combined tray for biochemical inspection
EP2864761B1 (en) * 2012-06-22 2020-12-16 Bio-Rad Laboratories, Inc. Two station sample and washing system
AU2013202808B2 (en) 2012-07-31 2014-11-13 Gen-Probe Incorporated System and method for performing multiplex thermal melt analysis
US9573128B1 (en) * 2012-09-06 2017-02-21 SciKon Innovation, Inc. Fluidics device allowing fluid flow between a plurality of wells
USD735881S1 (en) * 2012-10-22 2015-08-04 Qiagen Gaithersburg, Inc. Tube strip holder for automated processing systems
US9180461B2 (en) 2012-10-22 2015-11-10 Qiagen Gaithersburg, Inc. Condensation-reducing incubation cover
US20140112829A1 (en) * 2012-10-22 2014-04-24 Qiagen Gaithersburg, Inc. Tube strip handling and heating apparatus
US20150316457A1 (en) * 2012-12-12 2015-11-05 Hitachi Chemical Company, Ltd. Cancer cell isolation device and cancer cell isolation method
DE102013101176B4 (en) * 2013-02-06 2018-04-05 Cybio Ag Cooling box with a rack equipped with tube-shaped vessels for automatic filling with a pipetting machine
US10285564B2 (en) 2013-04-30 2019-05-14 Grenova, Inc. Pipette tip washing device
EP2991776B8 (en) 2013-04-30 2020-04-22 Grenova, Inc. Pipette tip washing device
US9744570B2 (en) 2013-04-30 2017-08-29 Grenova, Llc Pipette tip washing device
US9976993B2 (en) * 2014-05-20 2018-05-22 Tecan Sp, Inc. Sample extraction apparatus with micro elution bed design
EP3177258A4 (en) 2014-08-08 2018-09-12 Fremon Scientific, Inc. Smart bag used in sensing physiological and/or physical parameters of bags containing biological substance
US10035145B2 (en) 2014-12-02 2018-07-31 SciKon Innovation, Inc. Piston assembly and related systems for use with a fluidics device
GB201501429D0 (en) * 2015-01-28 2015-03-11 British American Tobacco Co Apparatus for heating aerosol generating material
EP3274711A4 (en) 2015-03-23 2019-01-16 Scikon Innovation Inc. A method and related systems for use with a fluidics device
CN108138116A (en) * 2015-08-25 2018-06-08 通用电气公司 In biological manufacturing equipment and it is related to its improvement
WO2017139262A1 (en) * 2016-02-12 2017-08-17 Grenova, Llc Pipette tip washing device
GB201700812D0 (en) 2017-01-17 2017-03-01 British American Tobacco Investments Ltd Apparatus for heating smokable material
US10736817B2 (en) * 2017-06-16 2020-08-11 Biofridge Inc. Thermally isolated blood carrier tray
US10399048B2 (en) 2017-08-03 2019-09-03 Agilent Technologies, Inc. Sample processing apparatus with integrated heater, shaker and magnet
US10816446B2 (en) 2018-05-07 2020-10-27 Fremon Scientific, Inc. Thawing biological substances
EP3837344A4 (en) * 2018-08-17 2022-01-26 Sierra Biosystems, Inc. Row-independent oligonucleotide synthesis
FR3093651A1 (en) * 2019-03-15 2020-09-18 Seigniory Chemical Products Ltd. - Produits Chimiques Seigneurie Ltee SYSTEM AND METHOD FOR FILTERING SAMPLES FROM CONTAINERS
GB201911386D0 (en) 2019-08-09 2019-09-25 Stratec Se Calibration tool for planar chip applications
USD914231S1 (en) 2019-11-20 2021-03-23 Agilent Technologies, Inc. Sample processing apparatus
USD917063S1 (en) 2019-11-20 2021-04-20 Agilent Technologies, Inc. Sample processing apparatus
WO2022167617A1 (en) * 2021-02-05 2022-08-11 Synhelix Improved thermocycled multistep reactions device
EP4288205A1 (en) * 2021-02-05 2023-12-13 Quantoom Biosciences France SAS Device for thermocycled multistep reactions
US20240181461A1 (en) * 2021-03-17 2024-06-06 Dh Technologies Development Pte. Ltd. Heated well plate
CN118541608A (en) * 2021-12-29 2024-08-23 帝肯基因组学公司 Dispensing unit
LU103082B1 (en) 2023-03-01 2024-09-02 Stratec Se Calibration and monitoring tool for thermocycler

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4022792A1 (en) * 1990-07-18 1992-02-06 Max Planck Gesellschaft PLATE WITH AT LEAST ONE RECESS FOR RECEIVING CHEMICAL AND / OR BIOCHEMICAL AND / OR MICROBIOLOGICAL SUBSTANCES AND METHOD FOR PRODUCING THE PLATE
JPH06210189A (en) * 1993-01-14 1994-08-02 Ngk Spark Plug Co Ltd Heater block
US6451261B1 (en) * 1998-10-29 2002-09-17 Applera Corporation Multi-well microfiltration apparatus

Family Cites Families (85)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US582665A (en) * 1897-05-18 Electric-arc lamp
US3463322A (en) * 1967-07-28 1969-08-26 Horace W Gerarde Pressure filtration device
US3721364A (en) * 1970-11-17 1973-03-20 Wolfen Filmfab Veb Plastic magazine for photosensitive sheet materials
US4167875A (en) * 1976-08-05 1979-09-18 Meakin John C Filtration method and apparatus
EP0009320B1 (en) * 1978-08-31 1982-04-21 National Research Development Corporation Apparatus and method for harvesting material from micro-culture plates
US4246339A (en) * 1978-11-01 1981-01-20 Millipore Corporation Test device
US4279342A (en) * 1980-03-24 1981-07-21 Robert Van Pelt Lunch box employing a built-in radio receiver
US4346339A (en) * 1980-10-29 1982-08-24 Sperry Corporation Apparatus for automatic regulation of AC power
US4422151A (en) * 1981-06-01 1983-12-20 Gilson Robert E Liquid handling apparatus
US4734192A (en) * 1982-07-01 1988-03-29 Millipore Corporation Multiwell membrane filtration apparatus
US4704255A (en) 1983-07-15 1987-11-03 Pandex Laboratories, Inc. Assay cartridge
US4950546A (en) 1985-05-02 1990-08-21 Raychem Corporation Radiation grafting of organopolysiloxanes
US4680233A (en) 1985-05-02 1987-07-14 Raychem Corporation Sealing material
US5037667A (en) 1985-05-02 1991-08-06 Raychem Corporation Radiation grafting of organopolysiloxanes
US4595635A (en) 1985-05-02 1986-06-17 Raychem Corporation Organopolysiloxane materials having decreased surface tack
US4777063A (en) 1985-05-02 1988-10-11 Raychem Corporation Curable organopolysiloxane composition
US4948442A (en) * 1985-06-18 1990-08-14 Polyfiltronics, Inc. Method of making a multiwell test plate
US5047215A (en) * 1985-06-18 1991-09-10 Polyfiltronics, Inc. Multiwell test plate
US5108703A (en) * 1986-03-26 1992-04-28 Beckman Instruments, Inc. Automated multi-purpose analytical chemistry processing center and laboratory work station
USD297602S (en) 1986-10-28 1988-09-13 Metrokane Imports, Inc. Lunchbox
US4948564A (en) * 1986-10-28 1990-08-14 Costar Corporation Multi-well filter strip and composite assemblies
US5110556A (en) * 1986-10-28 1992-05-05 Costar Corporation Multi-well test plate
SE454771B (en) * 1986-11-19 1988-05-30 Sprinter System Ab DEVICE FOR CLOSING A FLANGE SUPPLY, FILLED CARTRIDGE
WO1989001966A1 (en) * 1987-08-27 1989-03-09 Polyfiltronics Limited Filter units for biological sample preparation
US4902481A (en) * 1987-12-11 1990-02-20 Millipore Corporation Multi-well filtration test apparatus
US5108704A (en) * 1988-09-16 1992-04-28 W. R. Grace & Co.-Conn. Microfiltration apparatus with radially spaced nozzles
US5002889A (en) * 1988-10-21 1991-03-26 Genetic Systems Corporation Reaction well shape for a microwell tray
US4927604A (en) * 1988-12-05 1990-05-22 Costar Corporation Multiwell filter plate vacuum manifold assembly
CA2049019A1 (en) 1989-03-01 1990-09-02 Robert S. Dubrow Method of curing organopolysiloxane compositions and compositions and articles therefrom
US5352086A (en) * 1990-01-27 1994-10-04 Georg Speiss Gmbh Apparatus for lifting sheets from a stack
US5114681A (en) * 1990-03-09 1992-05-19 Biomedical Research And Development Laboratories, Inc. Superfusion apparatus
US5582665A (en) * 1990-07-18 1996-12-10 Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. Process for sealing at least one well out of a number of wells provided in a plate for receiving chemical and/or biochemical and/or microbiological substances, and installation for carrying out the process
US5141719A (en) * 1990-07-18 1992-08-25 Bio-Rad Laboratories, Inc. Multi-sample filtration plate assembly
US5227290A (en) * 1990-08-29 1993-07-13 Pocock Douglas A Method for conducting diagnostic assays
US5409832A (en) * 1990-08-29 1995-04-25 Stratecon Diagnostics International Membrane holder for use in an assay device
KR100236506B1 (en) * 1990-11-29 2000-01-15 퍼킨-엘머시터스인스트루먼츠 Apparatus for polymerase chain reaction
US5282543A (en) * 1990-11-29 1994-02-01 The Perkin Elmer Corporation Cover for array of reaction tubes
US5525302A (en) * 1991-02-01 1996-06-11 Astle; Thomas W. Method and device for simultaneously transferring plural samples
DE4107262A1 (en) * 1991-03-07 1992-09-10 Eppendorf Geraetebau Netheler SUCTION DEVICE FOR MEMBRANE MICROTITER PLATES
US5116496A (en) * 1991-03-19 1992-05-26 Minnesota Mining And Manufacturing Company Membrane-containing wells for microtitration and microfiltration
US5264184A (en) * 1991-03-19 1993-11-23 Minnesota Mining And Manufacturing Company Device and a method for separating liquid samples
US5227137A (en) * 1991-04-04 1993-07-13 Nicholson Precision Instruments Inc. Vacuum clamped multi-sample filtration apparatus
US5650323A (en) * 1991-06-26 1997-07-22 Costar Corporation System for growing and manipulating tissue cultures using 96-well format equipment
US5205989A (en) * 1991-09-18 1993-04-27 Minnesota Mining And Manufacturing Company Multi-well filtration apparatus
US5384024A (en) * 1992-03-13 1995-01-24 Applied Biosystems, Inc. Capillary electrophoresis
AU683413B2 (en) 1992-04-13 1997-11-13 Dana-Farber Cancer Institute, Inc. Antibodies specific for carcinoma-associated antigens
US5326533A (en) * 1992-11-04 1994-07-05 Millipore Corporation Multiwell test apparatus
US5380437A (en) * 1993-02-02 1995-01-10 Biomedical Research And Development Laboratories, Inc. Multifunctional filtration apparatus
US5459300A (en) * 1993-03-03 1995-10-17 Kasman; David H. Microplate heater for providing uniform heating regardless of the geometry of the microplates
US5342581A (en) * 1993-04-19 1994-08-30 Sanadi Ashok R Apparatus for preventing cross-contamination of multi-well test plates
US6258325B1 (en) * 1993-04-19 2001-07-10 Ashok Ramesh Sanadi Method and apparatus for preventing cross-contamination of multi-well test plates
GB9311276D0 (en) 1993-06-01 1993-07-21 Whatman Scient Limited Well inserts for use in tissue culture
US5368729A (en) * 1993-07-23 1994-11-29 Whatman, Inc. Solid phase extraction device
US5961926A (en) 1993-09-27 1999-10-05 Packard Instrument Co., Inc. Microplate assembly and method of preparing samples for analysis in a microplate assembly
US5427265A (en) * 1993-10-22 1995-06-27 Dart Industries Inc. Lunchbox with safety lock
DE4412286A1 (en) 1994-04-09 1995-10-12 Boehringer Mannheim Gmbh System for contamination-free processing of reaction processes
EP0706649B1 (en) 1994-04-29 2001-01-03 Perkin-Elmer Corporation Method and apparatus for real time detection of nucleic acid amplification products
US5721136A (en) * 1994-11-09 1998-02-24 Mj Research, Inc. Sealing device for thermal cycling vessels
JPH08196299A (en) * 1995-01-26 1996-08-06 Tosoh Corp Thermal cycling reaction apparatus and reaction vessel therefor
US5846493A (en) * 1995-02-14 1998-12-08 Promega Corporation System for analyzing a substance from a solution following filtering of the substance from the solution
BE1010984A3 (en) * 1995-02-17 1999-03-02 Praet Peter Van INCUBATOR FOR microtiter plate.
US5603900A (en) * 1995-05-19 1997-02-18 Millipore Investment Holdings Limited Vacuum filter device
US5604130A (en) * 1995-05-31 1997-02-18 Chiron Corporation Releasable multiwell plate cover
US5679310A (en) * 1995-07-11 1997-10-21 Polyfiltronics, Inc. High surface area multiwell test plate
US5792430A (en) * 1996-08-12 1998-08-11 Monsanto Company Solid phase organic synthesis device with pressure-regulated manifold
US5665247A (en) 1996-09-16 1997-09-09 Whatman Inc. Process for sealing microplates utilizing a thin polymeric film
US5929138A (en) 1996-11-05 1999-07-27 Raychem Corporation Highly thermally conductive yet highly comformable alumina filled composition and method of making the same
DE19652327C2 (en) 1996-12-16 2002-04-04 Europ Lab Molekularbiolog Method and device for carrying out chemical reaction sequences
US5961925A (en) 1997-09-22 1999-10-05 Bristol-Myers Squibb Company Apparatus for synthesis of multiple organic compounds with pinch valve block
DE59711973D1 (en) 1997-12-17 2004-11-04 Europ Lab Molekularbiolog Device for carrying out chemical reaction sequences
DE29722473U1 (en) 1997-12-19 1998-02-19 Macherey, Nagel GmbH & Co. Handelsgesellschaft, 52355 Düren Separation device for the separation of substances
FR2772639B1 (en) 1997-12-24 2000-02-04 Hospal Ind USE OF A NEUTRAL OR CATIONIC POLYMER TO PREVENT ACTIVATION OF THE CONTACT PHASE OF BLOOD OR PLASMA IN CONTACT WITH A SEMI-PERMEABLE MEMBRANE
US6251343B1 (en) * 1998-02-24 2001-06-26 Caliper Technologies Corp. Microfluidic devices and systems incorporating cover layers
US6896849B2 (en) * 1998-10-29 2005-05-24 Applera Corporation Manually-operable multi-well microfiltration apparatus and method
US6906292B2 (en) * 1998-10-29 2005-06-14 Applera Corporation Sample tray heater module
US6419827B1 (en) * 1998-10-29 2002-07-16 Applera Corporation Purification apparatus and method
US6048919A (en) 1999-01-29 2000-04-11 Chip Coolers, Inc. Thermally conductive composite material
US7169355B1 (en) * 2000-02-02 2007-01-30 Applera Corporation Apparatus and method for ejecting sample well trays
US6520663B1 (en) * 2000-03-23 2003-02-18 Henkel Loctite Corporation UV curing lamp assembly
US6503457B1 (en) 2000-04-14 2003-01-07 Discovery Partners International, Inc. Container and method for high volume treatment of samples on solid supports
US6572033B1 (en) * 2000-05-15 2003-06-03 Nordson Corporation Module for dispensing controlled patterns of liquid material and a nozzle having an asymmetric liquid discharge orifice
US6435425B1 (en) * 2000-05-15 2002-08-20 Nordson Corporation Module and nozzle for dispensing controlled patterns of liquid material
US6260583B1 (en) * 2000-05-24 2001-07-17 Illinois Tool Works Inc. Segmented stackable head design
US6581492B1 (en) * 2002-01-28 2003-06-24 Far Great Plastics Industrial Co., Ltd. Handle folding structure for a foldable bicycle
US6730883B2 (en) * 2002-10-02 2004-05-04 Stratagene Flexible heating cover assembly for thermal cycling of samples of biological material

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4022792A1 (en) * 1990-07-18 1992-02-06 Max Planck Gesellschaft PLATE WITH AT LEAST ONE RECESS FOR RECEIVING CHEMICAL AND / OR BIOCHEMICAL AND / OR MICROBIOLOGICAL SUBSTANCES AND METHOD FOR PRODUCING THE PLATE
JPH06210189A (en) * 1993-01-14 1994-08-02 Ngk Spark Plug Co Ltd Heater block
US6451261B1 (en) * 1998-10-29 2002-09-17 Applera Corporation Multi-well microfiltration apparatus

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
PATENT ABSTRACTS OF JAPAN vol. 018, no. 575 (C - 1268) 4 November 1994 (1994-11-04) *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11492584B2 (en) 2015-10-01 2022-11-08 Berkeley Lights, Inc. Well plate incubator
US11434462B2 (en) 2016-12-01 2022-09-06 Berkeley Lights, Inc. Well-plate incubator
WO2018147029A1 (en) * 2017-02-07 2018-08-16 株式会社 日立ハイテクノロジーズ Automatic analysis device
US11300488B2 (en) 2017-02-07 2022-04-12 Hitachi High-Tech Corporation Automatic analysis device

Also Published As

Publication number Publication date
US20060191893A1 (en) 2006-08-31
EP1599288A1 (en) 2005-11-30
US6906292B2 (en) 2005-06-14
EP1599288B1 (en) 2009-07-29
US20050194371A1 (en) 2005-09-08
DE602004022259D1 (en) 2009-09-10
US20040033619A1 (en) 2004-02-19
US7019267B2 (en) 2006-03-28
ATE437698T1 (en) 2009-08-15
US7452510B2 (en) 2008-11-18

Similar Documents

Publication Publication Date Title
US6906292B2 (en) Sample tray heater module
EP1192006B1 (en) Devices for the performance of miniaturised in vitro amplification assays
EP0632839A1 (en) Apparatus for containing and thermal processing of biological specimens
US9023639B2 (en) Apparatus for amplifying nucleic acids
CA2134475C (en) Polynucleotide amplification analysis using a microfabricated device
US5587128A (en) Mesoscale polynucleotide amplification devices
EP1735458B1 (en) Nucleic acid amplification with continuous flow emulsion
EP1123739B1 (en) Integrated device for microfluid thermoregulation, and manufacturing process thereof
EP0545736B1 (en) Method and apparatus for temperature control of multiple samples
WO2008098094A1 (en) Devices and methods for the performance of miniaturized in vitro assays
US7332326B1 (en) Centripetally-motivated microfluidics system for performing in vitro hybridization and amplification of nucleic acids
CA2312102C (en) Integrated fluid manipulation cartridge
US20030008286A1 (en) Miniaturized multi-chamber thermal cycler for independent thermal multiplexing
EP1878501A1 (en) Instrument for heating and cooling
US20050233440A1 (en) Apparatus for biochemical analysis
US20100311616A1 (en) Reaction chip and method of manufacturing the same
WO2007044917A2 (en) Polynucleotide sample preparation device
WO2000069560A1 (en) A centripetally-motivated microfluidics system for performing in vitro hybridization and amplification of nucleic acids
US9919314B2 (en) Air cooling systems and methods for microfluidic devices
KR101513273B1 (en) A rotary type PCR machine and a PCR chip
WO2002016652A2 (en) Device for rapid dna sample processing with integrated liquid handling, thermocycling, and purification
Felbel et al. Technical Concept of a Flow‐through Microreactor for In‐situ RT‐PCR
Fuchs et al. A silicon lab-on-chip for integrated sample preparation by PCR and DNA analysis by hybridization
US7398015B2 (en) Apparatus for controlling fluid-heating using polymer disk
WO2007142604A1 (en) Micro thermal cycler with selective heat isolation

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NA NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): BW GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 2004707411

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 2004707411

Country of ref document: EP