Method and apparatus for transferring and combining distinct chemical compositions with reagents

• US 6,054,325 A
• Filed: 07/02/1997
• Issued: 04/25/2000
• Est. Priority Date: 12/02/1996
• Status: Expired due to Fees

• Current Assignee: Glaxo Wellcome Incorporated (GlaxoSmithKline PLC)
• Original Assignee: Glaxo Wellcome Incorporated (GlaxoSmithKline PLC)
• Inventors: Binnie, Alastair A., Barrett, Ronald W., Sugarman, Jeffrey H., Kedar, Haim
• Primary Examiner(s): Soderquist, Arlen
• Application Number:
  US08/887,141
• Time in Patent Office: 1,028 Days
• Field of Search: 422/99, 422/100, 422/101, 422/102, 422/103, 422/104, 422/56, 422/58, 422/70, 436/94, 436/180, 436/501, 436/508, 436/178, 435/6, 435/91
• US Class Current: 436/178
• 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 2200/021 Adjust spacings in an array of wells, pipettes or holders, format transfer between arrays of different size or geometry
• CPC Class Codes: B01L 2300/069 Absorbents; Gels to retain a fluid
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0409 centrifugal forces
• CPC Class Codes: B01L 2400/0688 surface tension valves, capillary stop, capillary break
• 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 one exemplary embodiment, the invention provides a fluid transfer system which comprises a donor member having a plurality of separate regions. At least some of the regions contain at least one chemical composition, with each chemical composition being distinct from any other chemical composition in the donor member. An acceptor member is also provided and includes a plurality of defined locations which are each adapted to receive a liquid medium. A transfer mechanism is provided to systematically transfer at least some of the chemical compositions from the donor member regions to at least some of the acceptor member locations such that the locale of each transferred chemical composition within the acceptor member is known. Further, each of the acceptor member locations has a volume that is less than about 500 μl. In this way, a large number of acceptor member locations may be provided within a single system to efficiently transfer, in parallel fashion, large numbers of chemical compositions from the donor member to the acceptor member where evaluation or further processing of the chemical compositions may proceed.

Claims

1. A method for combining distinct chemical compositions with reagents, the method comprising:

providing a plurality of solid supports having the chemical compositions thereon;

organizing the solid supports having the chemical compositions thereon into separate regions of a donor member so that each region includes a distinct chemical composition, wherein the donor member regions each include a liquid medium, wherein the donor member regions each have a bottom end with a hole extending therethrough, and wherein the bottom ends slope toward the holes;

releasing at least some of the chemical compositions from their solid supports and into the liquid medium while within the donor member regions;

applying centrifugation to the donor member to systematically transfer at least some of the liquid medium containing the released chemical compositions through the holes and into individual locations within an acceptor member such that the locale of each transferred chemical composition within the acceptor member is known, and wherein the individual locations define a volume that is less than about 500 μ

l; and

introducing a reagent to each location having one of the chemical compositions.

2. A method as in claim 1, further comprising maintaining the solid supports within the donor member regions while transferring the released chemical compositions to the acceptor member locations.

3. A method as in claim 1, wherein the same reagent is delivered to each location.

4. A method as in claim 1, wherein the acceptor ember includes at least four locations per square centimeter.

5. A method as in claim 1, wherein the donor member regions each have a volume that is less than about 500 μ

l.

6. A method as in claim 1, wherein the donor member regions and the acceptor member regions are organized into two dimensions arrays.

7. A method as in claim 6, further comprising aligning the donor member regions with the acceptor member regions before transferring the chemical compositions.

8. A method as in claim 7, wherein more than one donor member region is aligned with a single acceptor member location.

9. A method for combining distinct chemical compositions with reagents, the method comprising:

providing a plurality of solid supports, with each solid support having a chemical composition thereon;

organizing the solid supports into separate donor chambers that are included within a housing so that each donor chamber includes a distinct chemical composition, wherein at least some of the donor chambers include a hole and are sloped toward the hole;

releasing at least some of the chemical compositions from their solid supports into a liquid medium held within the donor chambers;

systematically transferring at least some of the liquid medium containing the released chemical compositions to acceptor chambers that are included within a housing such that the locale of each transferred chemical composition within the acceptor member is known, wherein the transferring step comprises spinning the housings containing the donor chambers and the acceptor chambers to move the liquid medium containing the released chemical compositions through the holes of the donor chambers and into the acceptor chambers, and wherein the acceptor chambers define a volume that is less than about 500 μ

l; and

introducing a reagent to each acceptor chamber having one of the chemical compositions.

10. A method as in claim 9, further comprising transferring reagents from an acceptor chamber into another acceptor chamber or one of the donor chambers.