Extraction of restrained liquid from wells

• US 9,447,925 B2
• Filed: 11/08/2013
• Issued: 09/20/2016
• Est. Priority Date: 11/08/2012
• Status: Active Grant

• Current Assignee: Takara Bio Usa, Inc. (Ningbo Junsheng Investment Group Co., Ltd.)
• Original Assignee: WaferGen, Inc.
• Inventors: Griswold, Bradley L., Husain, Syed A., Moti, Robert, Dong, Wesley B., Kotturi, GoPaul, Dunne, Jude, Lin, Philip
• Primary Examiner(s): Hixson, Christopher A
• Assistant Examiner(s): BERKELEY, EMILY R
• Application Number:
  US14/075,631
• Publication Number:
  US 20140130885A1
• Time in Patent Office: 1,047 Days
• Field of Search: 436/45
• US Class Current: 1/1
• CPC Class Codes: B01L 2300/0609 Holders integrated in container to position an object
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 2300/0893 having a very large number of wells, microfabricated wells
• CPC Class Codes: B01L 2300/0896 Nanoscaled
• CPC Class Codes: B01L 2300/126 Paper
• CPC Class Codes: B01L 2400/0409 centrifugal forces
• CPC Class Codes: B01L 2400/049 vacuum
• CPC Class Codes: B01L 3/5025 for parallel transport of multiple samples
• CPC Class Codes: B01L 3/50857 using arrays or bundles of open capillaries for holding samples
• CPC Class Codes: C12Q 1/6806 Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay C12Q1/6804 takes precedence
• CPC Class Codes: F17D 1/08 for liquids or viscous products water-main or service pipe systems E03B7/04; domestic hot-water supply systems F24D17/00
• CPC Class Codes: G01N 1/28 Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Qmounting specimens on microscopic slides G02B21/34; means for supporting the objects or the materials to be analysed in electron microscopes H01J37/20 ; laboratory gas handling apparatus B01L5/00
• CPC Class Codes: Y10T 137/0391 Affecting flow by the addition of material or energy
• CPC Class Codes: Y10T 137/8593 Systems
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

The present invention provides methods, systems, assemblies, and articles for extracting restrained liquid (e.g., surface tension-restrained liquid) from open wells in a chip, where the restrained liquid does not flow out of the wells due to gravity when the wells are held upside down. For example, the present invention provides extraction fixtures that may be attached to, and/or held adjacent to, a chip such that any restrained liquid that is forced out of the open wells is collected by, or flows through, the extraction fixtures. Also for example, the present invention provides assemblies composed of a extraction fixture attached to, and/or held adjacent to, a chip, and methods of subjecting such assemblies to a force such that at least a portion of the restrained liquid in the open wells is forced out and collected by, or flows through, the extraction fixture.

Claims

1. A method of removing restrained liquid from at least one open well in a chip comprising:

a) providing an assembly comprising at least one extraction fixture enclosing a chip,

i) wherein said chip comprises a substrate and a plurality of open wells formed in said substrate, wherein said plurality of open wells contain restrained liquid,

ii) wherein said at least one extraction fixture comprises an extraction fixture base and an extraction fixture top plate,

wherein said extraction fixture base comprises a pocket component dimensioned to hold said chip,

wherein said extraction fixture top plate is attached to said extraction fixture base enclosing said chip and comprises a sample cup configured to allow a sample to be dispensed through said fixture top plate, and

wherein said at least one extraction fixture encloses said chip such that any of said restrained liquid that is forced out of said plurality of open wells is collected by said at least one extraction fixture; and

b) subjecting said assembly to a force such that at least a portion of said restrained liquid becomes released liquid that flows out of at least one of said plurality of open wells and is held by, or flows through, said at least one extraction fixture.

2. The method of claim 1, wherein said force is selected from the group consisting of centripetal force, centrifugal force, vacuum force, and a sudden stop of motion.

3. The method of claim 1, where said force is generated by a centrifuge.

4. The method of claim 1, wherein said extraction fixture base comprises a conical section dimensioned to collect fluid.

5. The method of claim 1, wherein said extraction fixture base further comprises:

a conical section dimensioned to collect fluid, and a gasket track dimensioned to hold a gasket.

6. The method of claim 1, wherein said assembly further comprises a paper gasket configured to fit between said chip and said extraction fixture top plate.

7. The method of claim 1, wherein said liquid that flows out of at least one of said plurality of open wells is held by said at least one extraction fixture.

8. The method of claim 1, further providing a base holding component, wherein said base holding component is dimensioned to hold said at least one extraction fixture adjacent to said chip.

9. The method of claim 8, further comprising at least one collection tube mounted in said base holding component, wherein said liquid that flows out of at least one of said plurality of open wells flows through said at least one extraction fixture into said at least one collection tube.

10. The method of claim 1, wherein said at least one extraction fixture is attached to said chip.

11. The method of claim 1, wherein at least 35% of said restrained liquid becomes said released liquid and flows out of said plurality of open wells and is collected by said extraction fixture.

12. The method of claim 1, wherein said restrained liquid is surface tension-restrained liquid.

13. The method of claim 1, wherein said at least one extraction fixture comprises at least two extraction fixtures.

14. The method of claim 1, wherein said at least one extraction fixture comprises at least nine extraction fixtures.

15. The method of claim 1, wherein each of said plurality of open wells has a volume between 0.1 nanoliters and 500 nanoliters.

16. The method of claim 1, wherein said plurality of open wells comprises at least 3 open wells.

17. The method of claim 1, wherein said plurality of open wells comprises at least 1000 open wells.

18. The method of claim 1, wherein said restrained liquid comprises PCR reagents and/or amplified nucleic acid.