Method and apparatus for transferring and combining reagents

• US 6,083,761 A
• Filed: 12/01/1997
• Issued: 07/04/2000
• Est. Priority Date: 12/02/1996
• Status: Expired due to Fees

• Current Assignee: Smithkline Beecham Corporation (GSK plc)
• Original Assignee: Glaxo Wellcome Incorporated (GSK plc)
• Inventors: Martin, Edith Lo, Barrett, Ronald W., Chan, Sam, Sugarman, Jeffrey H., Kedar, Haim, Binnie, Alastair A.
• Primary Examiner(s): Soderquist, Arlen
• Application Number:
  US08/982,068
• Time in Patent Office: 946 Days
• Field of Search: 422/99-104, 422/56, 422/58, 436/94, 436/180, 436/501, 436/508, 436/178, 435/6, 435/91
• US Class Current: 506/30
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00315 Microtiter plates
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00319 the blocks being mounted in stacked arrangements
• CPC Class Codes: B01J 2219/00369 in multiple or parallel arrangements
• CPC Class Codes: B01J 2219/00421 using centrifugation
• CPC Class Codes: B01J 2219/00468 by manipulation of individual beads
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 3/5025 for parallel transport of multiple samples
• CPC Class Codes: B01L 3/50255 Multi-well filtration
• CPC Class Codes: C40B 60/14 for creating libraries
• CPC Class Codes: Y10T 436/143333 Saccharide [e.g., DNA, etc.]
• CPC Class Codes: Y10T 436/255 including use of a solid sorbent, semipermeable membrane, or liquid extraction
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

The invention provides exemplary systems, methods, and apparatus for distinctly allocating liquids containing chemical compositions or compounds to known locations in an organized manner so that assays may be performed on the compositions, or so that the chemical compositions may be combined with other distinct chemical compositions or reagents prior to evaluation. In an exemplary embodiment, the invention includes a multiwell plate for handling articles such as resin beads suspended in a liquid. The plate comprises a plurality of wells. The wells in turn have a capillary hole that is adapted to (i) retain articles in the well, and (ii) retain liquid in the well while the liquid is not subjected to extrinsic forces, such as centrifugation or vacuum.

Claims

1. A multiwell plate system for handling articles suspended in a liquid, comprising:

a plate body;

a plurality of wells, with each well having a bottom end;

a liquid retained in at least some of the wells;

at least one generally spherical article in at least some of the wells that have the retained liquid; and

a capillary hole having a non-circular profile in at least some wells of said plurality that have the retained liquid and the generally spherical article, the capillary hole extending through the plate body and being adapted to (i) retain said generally spherical article in the well having said hole, (ii) retain said liquid in said well while said liquid is not subjected to extrinsic forces, and (iii) permit said liquid in said well to flow around said generally spherical article and out of said hole when said liquid is subjected to an extrinsic force produced by centrifugation;

wherein the capillary holes are disposed in the bottom ends of said wells, and wherein said bottom ends are sloped toward said capillary holes.

2. A plate system as in claim 1, wherein the bottom end is tapered to an apex.

3. A plate system as in claim 1, wherein the capillary hole has a triangular profile.

4. A plate system as in claim 1, wherein said well includes only a single hole.

5. A plate system as in claim 1, wherein the capillary hole has a limiting dimension that is between about 5 μ

m and about 500 μ

m.

6. A plate system as in claim 5, wherein the capillary hole has a limiting dimension that is between about 10 μ

m and about 300 μ

m.

7. A plate system as in claim 1, wherein liquid is retained in said well, in absence of extrinsic forces, by capillary forces.

8. A plate system as in claim 1, wherein the hole is biased closed in absence of extrinsic forces.

9. A plate system as in claim 1, wherein the plate contains 96 wells.

10. A plate system as in claim 1, wherein the plate contains 864 wells.

11. A system for handling articles, the system comprising:

a multiwell plate system of claim 1; and

a bottom plate having a plurality of holding vessels;

wherein the number of wells equals or exceeds the number of holding vessels such that when the multiwell plate is positioned above the bottom plate, each well is aligned with at least one holding vessel, wherein said liquid from wells having said capillary hole may be transferred into a corresponding holding vessel by application of an extrinsic force.

12. A system as in claim 11, further comprising a centrifuge, and wherein the extrinsic force is provided by centrifuging the plates using the centrifuge.

13. A system as in claim 11, wherein each well is aligned with a separate holding vessel.

14. A system as in claim 11, wherein multiple wells are aligned with a single holding vessel.

15. A method for identifying compounds, the method comprising:

providing a multiwell plate comprising a plate body having a plurality of wells that each have a bottom end, and a capillary hole having a non-circular profile in at least some wells of said plurality, with the capillary hole extending through the plate body, and wherein the bottom end is sloped toward the hole;

providing a bottom plate having a plurality of holding vessels;

introducing a liquid and at least one generally spherical article into at least some of the wells, with the article having a compound included thereon, wherein the liquid is retained in said well while said liquid is not subjected to extrinsic forces;

releasing the compound from each of the articles;

transferring at least a portion of the released compounds through the capillary holes and into at least one of the holding vessels of the bottom plate by centrifuging the plates to cause the liquid in the wells to flow around said generally spherical articles and out of said holes; and

performing assays on the compounds transferred from the wells to assess activity of the compounds.

16. A method as in claim 15, wherein the article is a solid support useful for performing solid-phase chemical or oligomer synthesis.

17. A method as in claim 15, wherein only a portion of the released compound is transferred into a holding vessel.

18. A method as in claim 15, wherein the assays are performed in the holding vessels.

19. A multiwell plate adapted for handling articles suspended in a liquid, comprising:

a plate body;

a plurality of wells formed in the plate body, with each well having a bottom end and a capillary hole formed in at least some wells of said plurality, wherein the bottom end is sloped toward the capillary hole, and wherein the capillary hole extends through the plate body and is adapted to (i) retain a generally spherical article in the well having said hole, (ii) retain a liquid in said well while said liquid is not subjected to extrinsic forces, and (iii) permit said liquid in said well to flow around said generally spherical article and out of said hole when said liquid is subjected to an extrinsic force created by centrifugation.