WO2001032934A2 - Station d"hybridation - Google Patents

Station d"hybridation Download PDF

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Publication number
WO2001032934A2
WO2001032934A2 PCT/US2000/041899 US0041899W WO0132934A2 WO 2001032934 A2 WO2001032934 A2 WO 2001032934A2 US 0041899 W US0041899 W US 0041899W WO 0132934 A2 WO0132934 A2 WO 0132934A2
Authority
WO
WIPO (PCT)
Prior art keywords
carrier
chamber
station
raised portion
fluid
Prior art date
Application number
PCT/US2000/041899
Other languages
English (en)
Other versions
WO2001032934A3 (fr
Inventor
Thomas M. Baer
Bruce J. Richardson
Chris T. Kitazawa
Darren Berns
Keith E. Moravick
Bruce A. Johnson
Alan L. Schenck
Craig S. Barker
Original Assignee
Arcturus Engineering, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Arcturus Engineering, Inc. filed Critical Arcturus Engineering, Inc.
Priority to AU37927/01A priority Critical patent/AU3792701A/en
Publication of WO2001032934A2 publication Critical patent/WO2001032934A2/fr
Publication of WO2001032934A3 publication Critical patent/WO2001032934A3/fr

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/30—Staining; Impregnating ; Fixation; Dehydration; Multistep processes for preparing samples of tissue, cell or nucleic acid material and the like for analysis
    • G01N1/31—Apparatus therefor
    • G01N1/312—Apparatus therefor for samples mounted on planar substrates
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • 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
    • B01L2200/02—Adapting objects or devices to another
    • B01L2200/026—Fluid interfacing between devices or objects, e.g. connectors, inlet details
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • B01L2300/0636—Integrated biosensor, microarrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0822—Slides
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0877—Flow chambers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • 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
    • 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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L9/00—Supporting devices; Holding devices
    • B01L9/52—Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips
    • 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
    • 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
    • G01N35/1004—Cleaning sample transfer devices

Definitions

  • the present invention relates to a hybridization station and, more particularly, to a hybridization station having a hybridization chamber for rapidly performing repeated hybridizations.
  • Nucleic acid hybridizations generally utilize arrays of oligonucleotide sequences immobilized on solid supports to detect complementary nucleic acid sequences in an assayed sample.
  • the arrays can be used to determine the complete sequence of the assayed nucleic acid and to detect the presence of a nucleic acid with a specific nucleotide sequence.
  • a wide variety of applications are possible including sequencing-by- hybridization techniques and diagnostic methods for monitoring differential gene expression and detecting genetic and other disorders.
  • hybridization rate and stringency can be affected by a variety of conditions.
  • One such condition is the temperature of the hybridization reaction.
  • Hybridizations occur at a fixed and very critical temperature. During the hybridization process, it is required that hybridization solution be introduced to the hybridization chamber at a specific temperature.
  • Conventional hybridization chambers do not allow for introducing hybridization solution into the chamber while incubated at a specific temperature. Such conventional chambers often require that the chamber be removed from the heat source, hybridized and then returned to the heat source. Therefore, conventional hybridization chambers can often result in significant temperature differences within the chamber during the hybridization process. These temperature differences can be problematic. In addition, the above-mentioned factors also apply to rather elaborate wash procedures that follow hybridization.
  • hybridization rate includes the concentration of the target nucleic acid in the sample, the composition of the hybridization solution, and the level of mixing of the target nucleic acid during the hybridization. Insufficient mixing can result in slower binding rates of probe to target. Given these numerous conditions that affect the rate of the hybridization reaction it is desirable to provide integrated devices that are capable of optimizing a number of the specific conditions of these hybridization reactions.
  • a hybridization station that is capable of rapidly and repeatedly delivering a sample onto an array, mixing the sample during hybridization, maintaining the sample at an optimal temperature for hybridization, removing the sample from the chamber following hybridization, and washing the array is desirable.
  • a chamber for performing hybridization reactions includes an examination surface and a chamber element.
  • the chamber element has an inner surface and a raised portion defining an interior. The raised portion extends from the inner surface.
  • the chamber is formed by the chamber element contacting the examination surface such that the raised portion engages the examination surface.
  • the chamber is defined by the examination surface and the interior wherein the inner surface of the interior is spaced from the examination surface.
  • a carrier includes at least one chamber.
  • the chamber is formed by a chamber element contacting an examination surface.
  • the chamber element has an inner surface and a raised portion extending from the inner surface.
  • a hybridization method includes providing a hybridization station having a carrier and a wash station.
  • the carrier is removably insertable into the wash station.
  • At least one slide having sample coupled to an examination surface is loaded into the carrier.
  • a chamber element is provided.
  • the chamber element is disposed in the carrier and the chamber element has an inner surface and a raised portion extending from the inner surface.
  • the chamber element has at least one orifice.
  • the at least one chamber element is located over the at least one slide to form a chamber such that the raised portion contacts the slide and the inner surface, that is encompassed by the raised portion, is spaced from the examination surface.
  • the raised portion contacts the slide such that fluid does not cross the raised portion.
  • the carrier is loaded into the wash station and fluid is injected into the chamber through the at least one orifice.
  • a method in accordance with another aspect of the invention, includes inserting at least one first carrier into a hybridization station.
  • the at least one first carrier has at least one chamber.
  • a solution is injected into the at least one chamber of the first carrier.
  • the at least one first carrier is removed from the hybridization station to free the hybridization station for receiving at least one second carrier.
  • the at least one second carrier has at least one chamber.
  • the at least one second carrier is inserted into the hybridization station.
  • a carrier removably insertable into a hybridization station.
  • the carrier includes at least one chamber.
  • the chamber has a first surface and a second surface.
  • the second surface has a side wall extending from the second surface.
  • the side wall of the second surface contacts the first surface and encompasses sample coupled to the first surface. A portion of the second surface that is encompassed by the side wall being spaced from the first surface.
  • a hybridization station in accordance with another aspect of the invention, there is provided a hybridization station.
  • the hybridization station includes at least one wash station assembly and a fluid delivery system coupled to the wash station assembly.
  • the hybridization station further includes a sample delivery system adapted for fluid communication with the wash station assembly.
  • a temperature control system in thermal communication with the wash station assembly is also included.
  • a controller is coupled to the fluid delivery system.
  • FIG. 3 is an exploded view of the wash station assembly of the present invention
  • FIG. 4 is a perspective view of the carrier assembly of the present invention
  • FIG. 5 is an exploded view of the carrier assembly of the present invention
  • FIG. 6 is a perspective view of the carrier base assembly of the present invention
  • FIG. 7 is a perspective view of the carrier base of the present invention
  • FIG. 8 is a top view of the ca ⁇ ier base of the present invention
  • FIG. 9 is a cross-section view along line 9-9 of FIG. 8 of the carrier base of the present invention.
  • FIG. 10 is a side elevational view of a latch pin of the present invention
  • FIG. 11 is a top view of the lower pad of the present invention
  • FIG. 12 is a top view of the slide locator of the present invention
  • FIG. 13 is a perspective view of the carrier top assembly of the present invention
  • FIG. 14 is a perspective view of the ca ⁇ ier top of the present invention
  • FIG. 15 is a bottom view of the carrier top of the present invention
  • FIG. 16 is a partial sectional view along line 16-16 of FIG. 14 of the carrier top of the present invention
  • FIG. 17 is a detailed view of the partial cross section of FIG 16 of the carrier top of the present invention.
  • FIG. 18 is a top view of the top pad of the present invention.
  • FIG. 19 is a top view of the chamber element of the present invention.
  • FIG. 20 is a side elevational end view of the chamber element of the present invention.
  • FIG. 21 is a bottom view of the chamber element of the present invention
  • FIG. 22 is a cross-sectional view along line 22-22 of FIG. 21 of the chamber element of the present invention
  • FIG. 23 is a detailed view of the cross-section of FIG. 22 of the chamber element of the present invention.
  • FIG. 24 is perspective view of the carrier clamp assembly of the present invention.
  • FIG. 25 is a perspective view of the first hook assembly of the present invention.
  • FIG.26 is a perspective view of the wash station assembly of the present invention with the carrier assembly removed;
  • FIG. 27 is a perspective view of the needle assembly of the present invention;
  • FIG. 28 is a perspective view of the needle frame of the present invention.
  • FIG. 29 is a cross-sectional view of the needle tube of the present invention.
  • FIG. 30 is a perspective view of the guide pin of the present invention.
  • FIG. 31 is a cross-sectional view of the guide pin of the present invention.
  • FIG. 32 is an exploded view of the needle system of the present invention.
  • FIG. 33 is a perspective view of a needle system of the present invention.
  • FIG. 34 is a perspective view of the needle assembly and a portion of the frame structure of the present invention.
  • FIG. 35 is a schematic of the fluid delivery system and the sample delivery system of the present invention.
  • hybridization is a process well known to those of ordinary skill in the art.
  • the hybridization station 10 is generally used for performing hybridization reactions such as hybridizing a sample of nucleic acids to an array of nucleic acid probes; however, it is understood by those skilled in the art from this disclosure that the hybridization station 10 could be used for other purposes such as staining a tissue sample, washing a hybridization a ⁇ ay or a stained slide, recovering sample from a hybridization array, recovering stain from a stained slide, and the like without departing from the spirit and scope of the invention.
  • the hybridization station 10 includes at least one wash station assembly 12, a fluid delivery system 14, a sample delivery system 16, a temperature control system 18, and a process controller 20.
  • the hybridization station 10 of FIG. 1 illustrates two wash station assemblies 12, the invention is not so limited. Because the wash station assemblies 12 are substantially identical only one wash station assembly 12 will now be described.
  • a wash station assembly 12 is shown in FIG. 2 and an exploded view of the wash station assembly 12 is shown in FIG. 3.
  • the wash station assembly 12 includes a carrier assembly 22, a needle assembly 24, and a frame structure 26.
  • the carrier assembly 22 or cassette includes a carrier base assembly 28, a carrier top assembly 30, and a carrier clamp assembly 32.
  • the carrier base assembly 28 and the carrier top assembly 30 are removably joined via the carrier clamp assembly 32.
  • the carrier base assembly 28 is shown in FIG. 6.
  • the carrier base assembly 28 includes a carrier base 34, a lower pad 36, and a slide locator 38.
  • the carrier base 34 is substantially a rectangular block comprising stainless steel or any other suitable material.
  • the carrier base 34 is approximately 9.0 inches in length, approximately 4.0 inches in width and approximately 0.4 inches in thickness.
  • the carrier base 34 includes a top 40, a bottom 42, a first side wall 44, a second side wall 46, a first end wall 48 and a second end wall 50.
  • the first and second side walls 44, 46 and the first and second end walls 48, 50 extend upwardly from the bottom 42 towards the top 40.
  • a plurality of slide apertures 52 are defined in the carrier base 34.
  • the slide apertures 52 are dimensioned slightly smaller than a standard slide 53.
  • slide apertures 52 are approximately 0.80 inches wide and approximately 2.20 inches in length; whereas, a standard slide is approximately 1.0 inches in width and approximately 3.0 inches in length.
  • carrier base 34 is shown with six slide apertures 52, the invention is not so limited and any number of slide apertures 52 are within the scope of the invention.
  • a plurality of locator bores 54 are defined in the top 40 of the carrier base 34.
  • two male-member bores 56 each for receiving a male member 58, as shown in FIG. 6, are defined in the top 40 of the carrier base 34.
  • two female-member bores 60 are defined in the top 40 of the carrier base 34.
  • a recess 64 is defined in the bottom 42 of the carrier base 34 for easily accessing the slide apertures 52.
  • a first side cut 66 is defined in the first end wall 48 of the carrier base 34.
  • the first end wall 48 of the carrier base 34 includes a first latch pin bore 68 for receiving a latch pin 70.
  • the first latch pin bore 68 is defined in a location of the first side cut 66.
  • a second side cut 72 is defined in the second end wall 50 of the carrier base 34.
  • the second end wall 50 of the carrier base 34 includes a second latch pin bore 74 for receiving a latch pin 70.
  • the second latch pin bore 74 is defined in a location of the second side cut 72.
  • a latch pin 70 is shown in FIG. 10.
  • the latch pin is generally cylindrical and defines a groove 76.
  • Latch pins 70 are insertable into the latch pin bores 68, 74 of the first and second end walls 48, 50 such that the groove 76 of the latch pin 70 is exposed and directed away from the top 40 and towards the bottom 42 of the carrier base 34.
  • FIG. 11 there is shown a lower pad 36.
  • the lower pad 36 is made of resilient silicone material for cushioning the slides 53, however, any suitable material may be employed for the lower pad 36 to achieve the same effect.
  • the lower pad 36 is generally rectangular in shape having a length of approximately 7.5 inches, a width of approximately 4.0 inches and a thickness of approximately 0.031 inches.
  • a plurality of slide apertures 80 are defined in the lower pad 36. The slide apertures 80 of the lower pad
  • the slide apertures 80 of the lower pad 36 are approximately 0.800 inches wide and approximately 2.20 inches in length; whereas, a standard slide 53 is approximately 1.00 inches in width and approximately 3.00 inches in length.
  • a standard slide 53 is approximately 1.00 inches in width and approximately 3.00 inches in length.
  • a plurality openings 82 are defined in the lower pad 36 adjacent to the slide apertures 80.
  • a plurality of locator apertures 84 are defined in the lower pad 36.
  • the slide locator 38 is a generally rectangular sheet approximately 7.50 inches in length, approximately 4.00 inches in width and approximately 0.02 inches in thickness.
  • the slide locator 38 is made of stainless steel; however, any suitable material may be employed.
  • a plurality of slide apertures 86 are defined in the slide locator 38.
  • Each of the slide apertures 86 of the slide locator 38 are dimensioned to have substantially the same size as a standard slide 53.
  • the slide apertures 86 of the slide locator 38 are approximately 1.0 inches wide and approximately 3.0 inches in length.
  • the slide locator 38 is shown with six slide apertures 86, the invention is not so limited and any number of slide apertures
  • the slide apertures 86 in the slide locator 38 serve to position each slide 53 in a desired location on the carrier base 34.
  • a plurality of locator apertures 88 are defined in the slide locator 38.
  • the slide apertures 52 of the carrier base 34, the slide apertures 80 of the lower pad 36, and the slide apertures 86 of the slide locator 38 are all aligned. Also, locator apertures 84 of the lower pad 36 and the locator apertures 88 of the slide locator 38 are aligned with the locator bores 54 of the carrier base 34. Locator fasteners 90, as shown in FIGs. 5 and 6, are passed through the locator apertures 84 in the lower pad 36, the locator apertures 88 in the slide locator 38 and threaded into the locator bores 54 of the ca ⁇ ier base 34 to secure the slide locator 38 and lower pad 36 to the carrier base 34.
  • latch pins 70 are inserted into the latch pin bores 68, 74 of the first and second end walls 48, 50 such that the groove 76 of each latch pin 70 is exposed and directed away from the top 40 and towards the bottom 42 of the ca ⁇ ier base 34.
  • the carrier top assembly 30 includes a carrier top 92, a top pad 94, chamber element 96, and a carrier clamp assembly 32 as shown in FIG. 13.
  • a carrier top 92 is illustrated in FIGs. 14-17.
  • the ca ⁇ ier top 92 is substantially a rectangular block comprising aluminum or any other suitable material.
  • the carrier top 92 is approximately
  • the carrier top 92 includes a top 98, a bottom 100, a first side wall 102, a second side wall 104, a first end wall 106, and a second end wall 108.
  • the first and second side walls 102, 104 and the first and second end walls 106, 108 extend upwardly from the bottom 100 of the ca ⁇ ier top 92 towards the top 98 of the carrier top 92.
  • the top 98 includes a recess 110 and mounting features 111 for receiving a clamp assembly 32.
  • a first side cut 112 is defined in the first end wall 106 of the carrier top 92.
  • a second side cut 114 is defined in the second end wall 108 of the ca ⁇ ier top 92.
  • a plurality of flow apertures 116 are defined in the carrier top 92.
  • twelve flow apertures 116 are defined in the carrier top 92; however, the invention is not so limited and any optimal number of flow apertures 116 are within the scope of the invention.
  • the flow apertures 116 are generally cylindrical in shape. As shown in FIG. 16 and 17, the flow apertures 116 have a tapered end 118 such that the diameter of a flow aperture 116 at the bottom 100 of the carrier top 92 is approximately 0.125 inches and the diameter of the flow aperture 116 at the top 98 of the carrier top 92 is approximately 0.179 inches.
  • a chamber locator bore 120 Adjacent to each flow aperture 116, a chamber locator bore 120 is defined.
  • the chamber locator bore 120 is designed for receiving a chamber pin (not shown) for securing the chamber element 96 to the carrier top 92.
  • a plurality of pad locator bores 122 are defined in the bottom 100 of the ca ⁇ ier top 92.
  • two female-member bores 126, each for receiving a female member 128, as shown in FIG. 13, are defined in the bottom 100 of the carrier top 92.
  • a top pad 94 is illustrated in FIG. 18.
  • the top pad 94 is made of urethane foam for cushioning the slides, however, any suitable material may be employed for the top pad 94.
  • the top pad 94 is substantially rectangular in shape having a length of approximately 8.25 inches, a width of approximately 2.765 inches, and a thickness of approximately 0.64 inches.
  • a plurality of slide apertures 132 are defined in the top pad 94.
  • the slide apertures 132 of the top pad 94 are dimensioned slightly smaller than a standard slide 53.
  • the top pad 94 further includes a plurality of pad locator apertures 134.
  • a plurality of flow apertures 136 are also defined in the top pad 94 adjacent to the slide apertures 132.
  • a pair of flow apertures 136 are positioned adjacent to each slide aperture 132 of the top pad 94.
  • the flow apertures 136 of the top pad 94 are substantially coincident with the flow apertures 116 of the carrier top 92.
  • a plurality of chamber locator apertures 138 are formed in the top pad 94. Adjacent to each flow aperture 136, a chamber locator aperture 138 is defined in the top pad 94.
  • the chamber locator aperture 138 is designed for receiving a fastener (not shown) for securing the chamber element 96 to the carrier top 92.
  • the chamber element 96 is substantially rectangular in shape having a length of approximately 2.5 inches, a width of approximately 1.0 inch, and a thickness of approximately 0.1 inches.
  • the chamber element 96 is made from an elastomer, such as Multi-Flex TPE D 4210, or any suitable material.
  • the surface of the chamber element can be treated by siliconizing or silanizing the surface to increase its hydrophilic properties.
  • the chamber element 96 is disposable after each operation.
  • the chamber element includes an inner surface 140, an outer surface 142, a first side 144, a second side 146, a first end 148, a second end 150, a first orifice 152, a second orifice 154, a first chamber locator aperture 156, a second chamber locator aperture 158, a raised portion 160, a plurality of ridges 162, and a ledge
  • the first orifice 152 is located proximately to the first end 148 of the chamber element 96.
  • the second orifice 154 is located proximately to the second end 150 of the chamber element 96. Illustrated in FIG. 23, there is shown a detailed view of the first orifice 152. Since the geometry of the first and second orifices 152, 154 are the substantially the same, only the first orifice 152 will be described.
  • the first orifice 152 includes a first taper 166 wherein the diameter of the orifice is approximately 0.08 inches at the inner surface 140 and approximately 0.045 inches at a location interior to the chamber element 96.
  • the first taper 166 has a radius of curvature of approximately 0.15 inches. The first taper 166 helps control fluid flow towards the inner surface 140.
  • the first taper 166 helps control fluid flow towards the inner surface 140.
  • the 166 is integral with a second taper 168 that is located within the chamber element 96.
  • the second taper 168 has a radius of curvature of approximately 0.05 inches.
  • the second taper 168 provides an interface for sealing with the needle assembly.
  • the needle assembly will be described in more detail below.
  • An annular portion 170 of the first orifice 152 is located adjacent to the second taper 168.
  • the annular portion 170 has a diameter of approximately
  • the first orifice 152 further includes a third taper 172 located adjacent to the annular portion 170.
  • the third taper 172 is linear wherein the diameter of the third taper is approximately 0.065 at a location adjacent to the annular portion 170 and approximately 0.085 at the outer surface 142.
  • the third taper 172 helps guide the needle assembly into the first orifice 152 such that if the needle assembly is not exactly aligned with the first orifice 152, the third taper 172 will direct the needle assembly into the first orifice 152.
  • the first and second orifices 152, 154 are shown having three tapers 166, 168, 172 and a single annular portion 170, the invention is not so limited.
  • the first and second orifices 152, 154 serve as inlet and/or outlet ports for fluids. As seen in FIG. 23, the first orifice 152 projects outwardly from the outer surface 142 by a distance of approximately 0.03 inches.
  • the first and second chamber locator apertures 156, 158 are formed in the chamber element 96.
  • the first chamber locator aperture 156 is substantially circular and is located between the first orifice 152 and the first end 148.
  • the second chamber locator aperture 158 is slightly elongated in shape so as to form a slot and is located between the second orifice 154 and the second end 150.
  • the first chamber locator aperture 156 serves to locate the chamber element 96 on the carrier top 92 and the second chamber locator aperture 158 provides some tolerance accommodation to allow the chamber element 96 to locate on the carrier top 92.
  • the chamber element 96 further includes a raised portion 160 extending from the inner surface 140.
  • the raised portion 160 of the inner surface 140 defines an interior 174.
  • the interior 174 is defined by the raised portion 160, and a portion of the inner surface 140 of the chamber element 96 that is encompassed by the raised portion 160.
  • the raised portion 160 is a continuous rib 176 integrally formed with the inner surface 140.
  • FIG. 19 illustrates one continuous rib 176, the invention is not so limited such that at least one rib 176 may be formed and, furthermore, the raised portion need not define a rib 176.
  • the rib 176 is raised and projects outwardly from the inner surface 140 a distance of approximately 0.005 inches.
  • the rib 176 of the chamber element 96 forms a continuous chamber wall.
  • the inner surface 140 of the chamber element 96 that is encompassed by the rib 176 forms a top of a chamber and the surface of the slide 53 that is encompassed by the rib 176 forms the bottom of the chamber.
  • the rib 176 itself forming the side wall of the chamber.
  • the rib 176 includes two opposing substantially parallel sides—a first side 178 and a second side 180.
  • the rib 176 also includes two opposing substantially parallel ends— a first end 182 and a second end 184.
  • the first and second sides 178, 180 and the first and second ends 182, 184 are interconnected at curved corners 186.
  • the first end 182 of the rib 176 is proximate to the first end 148 of the chamber element 96 and the second end 184 of the rib 176 is proximate to the second end 150 of the chamber element 96.
  • the continuous rib 176 encompasses both the first and second orifices 152, 154 such that the first end 182 of the rib 176 encompasses the first orifice 152 and the second end 184 of the rib 176 encompasses the second orifice 154.
  • the first end 182 of the rib 176 encompasses the first orifice 152 and the second end 184 of the rib 176 encompasses the second orifice 154.
  • the 182 of the rib 176 includes a first jog region 188 wherein the first orifice 152 is positioned so as to be seated in the first jog region 188.
  • the second end 184 of the rib 176 includes a second jog region 190 wherein the second orifice 154 is positioned so as to be seated in the second jog region 190.
  • the first and second orifices 152, 154 may be partially seated in the first and second jog regions 188, 190, respectively.
  • ridges 162 are formed on the inner surface 140 of the chamber element 96 and are integrally formed therewith. Two of the ridges 162 are located between the first end 182 of the rib 176 and the first end 148 of the chamber element 96 and two of the ridges 162 are located between the second end 184 of the rib 176 and the second end 150 of the chamber element 96. However, any number of ridges 162 may be employed. The ridges 162 serve as stops to limit the downward travel of the chamber element 96 when force is applied to sealingly engage the rib 172 to the slide 53.
  • a ledge 164 is defined adjacent to the first end 148 of the chamber element 96.
  • the ledge 164 is a recessed portion of the chamber element 96.
  • the ledge 164 is designed to clear a bar code label (not shown) that is usually placed on the end of the slide 53.
  • the carrier clamp assembly 32 is placed in the recess 110 of the carrier top 92. Fasteners are used to secure the carrier clamp assembly 32 and the carrier top 92.
  • the carrier clamp assembly 32 includes a block 194, a first hook assembly 196, and a second hook assembly 198.
  • the block 194 is dimensioned such that it fits into the recess 110 of the carrier top 92.
  • the block 194 includes fastener features 113, a first pair of bores 200 for securing the first hook assembly 196 to the block 194 and a second pair of bores 202 for securing the second hook assembly 198.
  • the block 194 is secured to the carrier top 92 via fastener features 113 in block 194 and fastener features 111 in the carrier top.
  • the first hook assembly 196 includes a base element 204, a linkage 206, a pivot 208, a hook 210, and a lever 212.
  • the base element 204 is inserted into the block 194 and secured thereto with fasteners 214 passed through the first pair of bores 200.
  • the base element 204 is rotatably coupled to the linkage 206 and the lever 212 is connected to the linkage 206.
  • the pivot 208 is pivotally coupled to the linkage 206 and the hook 210 is connected to the pivot 208.
  • the top pad 94 is placed on the carrier top 92 and into the pad recess 130 such that the pad locator apertures 134 of the top pad 94 are aligned with the pad locator bores 122 of the carrier top 92.
  • Fasteners 192 are passed through the pad locator apertures 134 and into the pad locator bores 122 to secure the top pad 94 to the ca ⁇ ier top 92.
  • the flow apertures 136 of the top pad 94 and the flow apertures 116 of the carrier top 92 will be in alignment, and the chamber locator bores pins and the chamber locator apertures 138 of the top pad 94 will be in alignment.
  • the chamber elements 96 are pressed onto the pins.
  • Female members 128 are inserted into the female-member bores 126 of the carrier top 92.
  • FIGs. 4 and 5 An assembled ca ⁇ ier 22 assembly is shown in FIGs. 4 and 5. Assembly of the carrier assembly 22 will now be discussed. Slides 53 are inserted into the slide apertures 86 of the slide locator 38. The carrier assembly 30 and the carrier base assembly 28 are joined such that the male members 58 of the ca ⁇ ier base 28 are mated with the female members 128 of the carrier top assembly 30.
  • the hooks 210 of the first and second hook assemblies 196, 198 are latched over the latch pins 70 of the carrier base assembly 28 and then the levers 212 are rotated to join the carrier top assembly 30 and the carrier base assembly 28 together.
  • the raised portion 160 of the chamber element 96 engages the examination surface or slide 53 such that a chamber is formed.
  • a seal is formed between the chamber element 96 and the slide 53 as a result of the pressure applied on the slide 53 by the chamber element 96 such that liquid may not escape across the interface between the chamber element 96 and slide 53.
  • a pressure seal is disclosed, a seal employing adhesive may also be employed.
  • the chamber that is formed is defined by the raised portion 160, the inner surface 140 of the chamber element 96 that is encompassed by the raised portion 160, and the surface area of the slide 53 that is encompassed by the raised portion 160.
  • the raised portion 160 or rib 176 forms the side wall of the chamber.
  • the inner surface 140 of the chamber element that is encompassed by the raised portion 160 forms a top of the chamber.
  • the surface area of the slide 53 that is encompassed by the rib 176 or raised portion 160 forms a base of the chamber.
  • the ridges 162 of the chamber element 96 may also engage the examination surface or slide 53 to serve as a stop to prevent further travel of the chamber element 96 towards the slide 53 so as to prevent collapse of the chamber.
  • the inner surface 140 of the chamber element 96 that is encompassed by rib 176 or raised portion 160 is spaced from the slide surface by a distance of approximately 0.0034 inches and the resulting chamber volume is approximately 125 ⁇ l.
  • the wash station assembly 12 with the carrier assembly 22 removed is depicted in FIG. 26. After the carrier assembly 22 is assembled, it is ready to be inserted into the wash station assembly 12.
  • the needle assembly 24 is shown in FIG. 27.
  • the needle assembly 24 includes a needle frame 216, a plurality of needle systems 218, and at least one cover plate 220.
  • the needle frame 216 includes at least one horizontal travel slide (not shown), a plurality of needle apertures 224, needle cover supports 226, and a plurality of needle cover apertures 228.
  • the horizontal travel slide 222 is mounted to the frame structure 26 so as to permit horizontal movement of the needle frame 216.
  • each of the needle systems 218 depicted in FIG. 27 includes a guide pin 230, a guide pin spring 231 , a wash needle spring 232, and a needle tube 234.
  • the needle tube 234 is substantially cylindrical in shape and includes a first end 236 that is tapered and a second end 238.
  • a fluid passage 240 is defined within the needle tube 234.
  • the needle tube 234 also includes a tube stop 242.
  • the guide pin 230 is generally cylindrical having a passage 244 dimensioned for receiving the needle tube 234.
  • the guide pin 230 includes a first end 246, a second end 248, a first portion 250, and a second portion 252.
  • the first portion 250 has a diameter that is smaller relative to the diameter of the second portion 252 of the guide pin 230.
  • the first end 246 is tapered and a recess 254 dimensioned for receiving the guide pin spring 231.
  • Each of the needle systems 218 is assembled by inserting the needle tube 234 into the passage 244 of the guide pin 230 such that the needle tube stop 242 abuts the recess 254 of the guide pin 230.
  • the needle systems 218 are then inserted into the needle apertures 224 of the needle frame 216.
  • the wash needle spring 232 is then added over the needle tube 234 and abuts the needle tube stop 242.
  • the guide pin spring 231 is then generally placed around the needle tube 234.
  • the cover plate 220 is substantially a rectangular plate having a plurality of needle apertures 256 and at least one cover plate aperture 258.
  • the cover plate 220 is placed over the needle systems 218 such that the needle tubes 234 pass through the needle apertures 256 in the cover plate 220.
  • the cover plate 220 is attached to the needle frame 216 with fasteners. Although two cover plates 220 are shown in FIG. 27, the invention is not so limited.
  • the frame structure 26 is seen in FIGs. 3 and 34.
  • the frame structure 26 includes a horizontal travel rail 260, a vertical travel rail 262, a base frame 264, a handle 266, and a shield 268.
  • the shield 268 and handle 266 are connected to the horizontal travel rail 260.
  • the horizontal travel rail 260 is connected to the vertical travel rail 262 which is connected to the base frame 264.
  • the base frame 264 includes a heating/cooling platform 270, a carrier assembly platform 272, a wash tip drain 274, a carrier assembly lock 276, and a wash assembly lock 278.
  • the needle frame 216 is mounted to the frame structure 26 such that the horizontal travel slide (not shown) of the needle frame 216 engages the horizontal travel rail 260 such that the needle frame 216 can be moved horizontally along the horizontal travel rail 260.
  • Rail 260 attached to the vertical travel rail 262 allows vertical travel of assembly.
  • the carrier assembly 22 is located on the carrier assembly platform 272 and may be locked in position with the carrier assembly lock 276. This position has the ca ⁇ ier assembly 22 down and in contact with the heating/cooling platform 270.
  • the needle assembly 24 is moved along the horizontal rail 260 to a position wherein the guide pins 230 of the needle assembly 24 are substantially aligned with the flow apertures 116 of the carrier top 92.
  • the needle assembly 24 is then moved vertically down towards the carrier assembly 22. As the needle assembly 22 is lowered, the guide pins 230 contact the carrier top 92.
  • the guides pins 230 direct the position of the needle tubes 234 relative to the carrier top 92.
  • the needle tubes 234 enter the orifices 152, 154 of the chamber elements 96 and the needle tubes 234 seal against the orifices 152, 154 of the chamber elements 96.
  • the wash station assembly 12 is locked into position with the wash assembly lock 278.
  • the wash assembly lock 278 is disengaged and the needle assembly 24 is moved upwards along the vertical rail 262 and then horizontally along the horizontal rail 260.
  • the needle tubes 234 are free to drip fluid into the wash tip drain 274. If the carrier assembly lock 276 is disengaged, the carrier assembly 22 may be removed from the wash station if desired.
  • FIGs. 1 and 35 there is shown one variation of a fluid delivery system 14 that can be employed with the wash station assembly 12 of the present invention.
  • the fluid delivery system 14 delivers various fluids such as a wash fluid and a sample containing fluid, to and from the carrier assembly 22.
  • a schematic of the fluid delivery system 14 is shown in FIG. 35.
  • the fluid delivery system 14 includes a plurality of fluid reservoirs 280, at least one pump 282 for moving fluid, a valve system 284, needle system 218, a waste manifold 286, and a waste reservoir 288.
  • the fluid reservoirs 280 or fluid sources are fluidly connected to a valve system 284.
  • the valve system includes one or more valves 292 and a manifold 290 for directing one or more different fluids to the chamber.
  • the valve system 284 may be coupled to a controller and the valves 292 may be adjusted manually or automatically.
  • the valve system 284 allows for selectively connecting one or more fluid reservoirs 280.
  • a selected valve 292 may be opened to provide a fluid connection.
  • multiple independent valves 292 in combination with a manifold are illustrated in FIG. 35, multi-port distribution valves may be employed.
  • Fluid from the fluid reservoirs 280 passes via tubing into a manifold 290. From the manifold 290, fluid is directed to a first set of pumps 296 and to a second set of pumps 298.
  • Each of the first and second set of pumps 282 is shown to have six pumps 282; however, the invention is not so limited and any number of pumps 282 may be employed. Fluid from the first set of pumps 296 is directed via tubing 294 to the needle assembly 24 of the first wash station assembly 12.
  • Fluid from the second set of pumps 298 is directed via tubing to the needle assembly 24 of the second wash station assembly 12.
  • syringe pumps such as the Cavro model XP 3000 syringe pump
  • peristaltic pumps and diaphragm pumps may be used to deliver fluids to the chamber.
  • fluid from the needle assembly 24 enters each chamber via the first orifice 152 and exits the chamber via the second orifice 154. Fluid from the chamber enters a waste manifold 286 via tubing and is directed towards a waste reservoir 288 via a first waste pump 300. Although a diaphragm pump is illustrated, a number of different pump types may be employed.
  • a sample delivery system 16 includes a microwell plate 302, a sample pump 304, a sample tip 306, a sample tip wash station 308, and an automated arm 310. Sample to be delivered to the chamber is located in each microwell
  • Sample from the microwell plate 302 is drawn by the sample tip 306.
  • the sample tip 306 is in fluid communication with the sample pump 304.
  • a syringe pump is used, however, any suitable pump may be employed.
  • the sample pump 304 may be fluidly connected to one or more fluid reservoirs 280 via a valve 314.
  • the sample tip 306 is automatically directed to and from the microwell plate 302 as well as to and from the sample tip wash station 308 by the automated arm 310.
  • the automated arm 310 is controlled by a controller (not shown) such as a process controller 20 to draw sample from appropriate microwells 312 and deliver sample to one or more chambers.
  • the automated arm 310 is automated to move the sample tip 306 vertically and horizontally as directed by the controller.
  • a sample tip wash station 308 wherein the sample tip 306 can be substantially flushed clean.
  • the sample tip wash station 308 is fluidly connected to a waste reservoir 288 via a pump 316.
  • the hybridization station 10 includes a temperature control system 18.
  • the temperature control system 18 operates to maintain the temperature within the hybridization chamber 10 at optimized levels according to a preselected temperature profile.
  • the temperature control system 18 generally monitors and controls the temperature of the various fluids delivered to the chamber.
  • the temperature of sample in the microwell plate 302 is controlled by the temperature control system 18.
  • a desired temperature is maintained within the microwell plate 302 by thermal exchange across the microwell plate 302 and a temperature control block 318 against which the microwell plate 302 is placed as shown in FIG. 35.
  • Adjacent to the temperature control block 318 is at least one Peltier heater/cooler 320 and a fan-cooled heat sink 322. These Peltier heater/coolers 320 are in thermal communication with the sample in the microwell plate 302.
  • the temperature of the chamber is maintained at a desired temperature by the temperature control system 18 via a heating/cooling assembly 324 that is located on the heating/cooling assembly platform 270 adjacent to the carrier assembly 22.
  • the heating/cooling assembly 324 includes a temperature control block 326, a Peltier heater/cooler 328, and a heat sink 330, as shown in FIGs. 2, 3, and 26.
  • a desired temperature is maintained within the chamber by thermal exchange across the ca ⁇ ier assembly 22 and the temperature control block 326.
  • the Peltier heater/cooler 328 is shown to be adjacent to a fan-cooled heat sink 330 and is in thermal communication with the chamber.
  • the fluid delivery system 14 also includes temperature control elements 322 controlled by the temperature control system 18 for maintaining a desired temperature of the fluids delivered to the chamber of the carrier assembly 22.
  • the temperature of the fluid can be controlled in different ways.
  • temperature control elements 322 such as fluid heaters, are located adjacent to tubing at a location just prior to the carrier assembly 22. Any number of fluid heaters/coolers, controlled by the temperature control system 18, may be employed along and in thermal communication with the fluid path to maintain the desired fluid temperature.
  • at least one precision temperature sensor (not shown) is embedded close to the chamber or other locations to provide accurate temperature control.
  • the hybridization station 10 also includes a process controller 20 for automatically carrying out the various steps involved in hybridization.
  • the process controller 20 generally controls and monitors the hybridization station 10 including the fluid delivery system 14, the sample delivery system 16, and the temperature control system 18 according to a preprogrammed set of instructions. This generally involves delivering sample and or wash fluids to the hybridization chamber at selected times during a hybridization operation and controlling the temperature of the hybridization chamber according to a selected temperature profile.
  • Process control is generally ca ⁇ ied out by an onboard processor contained within the hybridization station 10 itself.
  • the onboard processor is typically appropriately programmed to operate the above described systems according to an input set of process parameters.
  • the processor operates to provide appropriate instructions to each of the elements of the hybridization station 10 according to a pre-selected time/temperature/mixing profile/flow rate selected by the user including pump or valve operation, temperature control system operation, etc.
  • the process parameters may be input by the user into a computer that is connected to the hybridization station. Custom software controls allow modifications of the mixing protocol.
  • the hybridization station is operated to deliver reagents, samples, buffer and wash solutions to the hybridization chamber, and to maintain optimal reaction conditions, e.g., temperature and mixing, within the hybridization chamber for a preselected time or number of cycles. Operation of the hybridization chamber begins with the insertion of at least one micro-arrayed slide into the slide locator 38 of the ca ⁇ ier base assembly 28. The ca ⁇ ier top assembly 30 and carrier base assembly 28 are joined, as previously described, and the carrier assembly 22 is positioned atop the carrier assembly platform 272. Positioning the carrier assembly 22 onto the carrier platform 272 automatically aligns the carrier assembly
  • a solution containing a target nucleic acid is automatically delivered from the microwell plate 302 to the hybridization chambers with the sample tip 306 being directed by the automated arm
  • the solution containing target nucleic acid incorporates a fluorescent label for subsequent detection.
  • the process controller 20 can be pre-programmed to follow any number of wash protocols. If, for example, the first solution to be delivered to the chamber after hybridization is a buffer solution, the needle assembly 24 is lowered along the vertical rail
  • the rate at which fluid is pumped into and out of the chamber is controlled to avoid the formation of air bubbles within the chamber.
  • the rate at which fluid is pumped into the chamber is approximately 25 ⁇ l/second. This rate can vary between approximately 6 ⁇ l/second to approximately 100 ⁇ l/second.
  • the rate at which fluid is pumped from the chamber can vary between 6 ⁇ l/second to approximately 100 ⁇ l/second.
  • the chamber is filled for a set time period.
  • the carrier assemblies 22 may be removed from the hybridization station 10 to be placed in a humidity controlled incubator at a temperature of approximately 40° C. Alternatively, the carrier assemblies may remain in the hybridization station 10 while the chambers are incubated on the hybridization station 10, or the entire station 10 could be incubated. Once the ca ⁇ ier assemblies 22 are removed from the hybridization station 10, the hybridization station is free for inserting additional carrier assemblies 23. This method of removing at least one ca ⁇ ier assembly 22 from the hybridization station 10 and then inserting at least one other ca ⁇ ier assembly 22 greatly expedites the hybridization process and is made possible by the removable carrier assembly 22. Although the station 10 is refe ⁇ ed to as a hybridization station 10, it is not so limited, that is, actual hybridization does not necessarily have to take place within the station 10.
  • the hybridization station 10 of the instant invention may be interchangeably and equally appropriately called a fluidics station. Whether the station 10 is called a hybridization station 10 or a fluidics station is not limiting with respect to whether hybridization actually takes place within the station 10.
  • the carrier assembly 22 is maintained at an appropriate temperature and time period for the particular hybridization reaction.
  • Appropriate time periods can vary widely depending on the hybridization protocol and are generally long periods of time typically in excess of twelve hours.
  • Appropriate temperatures are generally in the range of acceptable biological temperatures such as approximately 30° C to approximately 40° C, but will often vary from this range, depending upon the reaction being performed, or the nature of the species involved in the hybridization.
  • mixing can be provided in a variety of ways including mechanical mixing, rocking mixing, and push-pull mixing.
  • a "drain and fill” operation can also be performed. This operation involves repeated draining and filling of the hybridization chamber with the sample. In operation, once the chamber is initially filled, the "drain and fill” operation involves the reversal of the pump which draws the sample out of the hybridization chamber. During this operation, the sample is either being returned to its reservoir or is retained in the volume of the tubing.
  • Mixing can also be provided by push and pull mixing wherein the chamber is pushed in a horizontal direction and then pulled back in the opposite but horizontal direction.
  • the carrier assembly 22 is returned to the hybridization station 10 for a wash process.
  • the needle assembly 24 is lowered such that the needle systems 218 engage and seal against the chamber element.
  • the hybridization station 10 will typically deliver a wash solution, and/or buffer to the hybridization chamber, to rinse substantially all of the solution containing sample from the chamber.
  • Pumps 282 are activated and wash and/or buffer is delivered from the appropriate valved reservoirs 280 into the hybridization chamber via first orifices
  • washing the hybridization chamber avoids any difficulty associated with background fluorescence that can impede clear and accurate determinations of hybridization. Wash steps will typically be repeated as desired, to sufficiently reduce or eliminate any remaining, unhybridized target. Typically, the wash steps will be repeated from two to ten times.
  • the carrier assembly 22 is removed from the hybridization station 10 and opened by removing the ca ⁇ ier top.
  • the slides 53 are also removed.
  • the slides 53 may be dipped in a final water bath, dried and transfe ⁇ ed to a reader/scanner device to identify the locations on the array to which the target hybridized.
  • the hybridization station 10 can be utilized to load sample-containing solution into the chambers, incubate the slide arrays, perform limited mixing if necessary, and wash the slide arrays without removal of the carrier assembly from the hybridization station 10.
  • the hybridization station 10 can be utilized to load sample-containing solution into the chambers and perform all of the functions except incubation in the hybridization station 10 wherein the carrier assembly would be removed from the hybridization station 10 for the incubation process. After incubation, the carrier assembly 22 would be returned to the hybridization station 10 for washing the slides 53.
  • Significant cost savings and greater throughput can be realized with the above variation in comparison with prior art devices.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Physics & Mathematics (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Engineering & Computer Science (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

La présente invention concerne une station permettant de préparer rapidement des lames disposées en jeux ordonnés en vue de leur hybridation. A cet effet, on insère au moins une lame de micro-arrangements dans un support. Un élément de chambre en contact avec la lame forme une chambre d"hybridation. Le support peut être inséré dans la station de manière amovible en vue de la réalisation de plusieurs étapes associées aux processus de pré-hybridation et de post-hybridation. La station comprend généralement au moins un ensemble station de lavage, un système d"apport de fluide, un système d"apport des échantillons ainsi qu"un système de régulation de la température.
PCT/US2000/041899 1999-11-04 2000-11-03 Station d"hybridation WO2001032934A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU37927/01A AU3792701A (en) 1999-11-04 2000-11-03 Hybridization station

Applications Claiming Priority (2)

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US16363499P 1999-11-04 1999-11-04
US60/163,634 1999-11-04

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WO2001032934A3 WO2001032934A3 (fr) 2002-09-12

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Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100408167B1 (ko) * 2001-05-21 2003-12-03 (주)지노믹트리 디엔에이 마이크로 어레이 시스템용 하이브리다이제이션챔버
KR100419003B1 (ko) * 2001-05-11 2004-02-14 (주)로봇앤드디자인 디엔에이/프로테인 어레이어의 가습조절 장치
US6913931B2 (en) 2002-10-03 2005-07-05 3M Innovative Properties Company Devices, methods and systems for low volume microarray processing
DE102004046724B3 (de) * 2004-09-27 2006-02-02 Zell-Kontakt Gmbh Reaktionsgefäß und Verfahren zur Behandlung biologischen Materials
EP1724564A1 (fr) * 2005-05-18 2006-11-22 Miltenyi Biotec GmbH Chambre améliorée d'échantillonnage pour un dispositif d'analyse.
US7517498B2 (en) 2003-08-19 2009-04-14 Agilent Technologies, Inc. Apparatus for substrate handling
EP2169383A1 (fr) 2001-06-15 2010-03-31 Bayer Technology Services GmbH Organe pour l'écoulement à travers des cuvettes et son utilisation
CN105044371A (zh) * 2015-04-14 2015-11-11 广州安必平医药科技股份有限公司 样品反应仓

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993019207A1 (fr) * 1992-03-23 1993-09-30 Gene Tec Corporation Appareil permettant de confiner des specimens biologiques devant subir un traitement thermique
EP0611598A2 (fr) * 1993-02-16 1994-08-24 The Perkin-Elmer Corporation Procédé d'amplification PCR in situ

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993019207A1 (fr) * 1992-03-23 1993-09-30 Gene Tec Corporation Appareil permettant de confiner des specimens biologiques devant subir un traitement thermique
EP0611598A2 (fr) * 1993-02-16 1994-08-24 The Perkin-Elmer Corporation Procédé d'amplification PCR in situ

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100419003B1 (ko) * 2001-05-11 2004-02-14 (주)로봇앤드디자인 디엔에이/프로테인 어레이어의 가습조절 장치
KR100408167B1 (ko) * 2001-05-21 2003-12-03 (주)지노믹트리 디엔에이 마이크로 어레이 시스템용 하이브리다이제이션챔버
EP2169383A1 (fr) 2001-06-15 2010-03-31 Bayer Technology Services GmbH Organe pour l'écoulement à travers des cuvettes et son utilisation
US6913931B2 (en) 2002-10-03 2005-07-05 3M Innovative Properties Company Devices, methods and systems for low volume microarray processing
US7517498B2 (en) 2003-08-19 2009-04-14 Agilent Technologies, Inc. Apparatus for substrate handling
DE102004046724B3 (de) * 2004-09-27 2006-02-02 Zell-Kontakt Gmbh Reaktionsgefäß und Verfahren zur Behandlung biologischen Materials
EP1724564A1 (fr) * 2005-05-18 2006-11-22 Miltenyi Biotec GmbH Chambre améliorée d'échantillonnage pour un dispositif d'analyse.
WO2006122968A1 (fr) * 2005-05-18 2006-11-23 Miltenyi Biotec Gmbh Enceinte d'echantillonnage amelioree pour un dispositif d'analyse
CN105044371A (zh) * 2015-04-14 2015-11-11 广州安必平医药科技股份有限公司 样品反应仓

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AU3792701A (en) 2001-05-14
WO2001032934A3 (fr) 2002-09-12

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