Apparatus for multi-well microscale synthesis

• US 6,054,100 A
• Filed: 11/18/1997
• Issued: 04/25/2000
• Est. Priority Date: 11/18/1996
• Status: Expired due to Fees

• Current Assignee: Robbins Scientific Corporation
• Original Assignee: Robbins Scientific Corporation
• Inventors: Wright, David J., Robbins, Paul B., Stanchfield, James E., Bailey, Chris N.
• Primary Examiner(s): Gulakowski, Randy
• Assistant Examiner(s): Markoff, Alexander
• Application Number:
  US08/972,996
• Time in Patent Office: 889 Days
• Field of Search: 422/99, 422/102, 422/101, 422/104, 435/305.3, 435/288.4
• US Class Current: 422/534
• 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 2219/00286 Reactor vessels with top and bottom openings
• CPC Class Codes: B01J 2219/00313 the reactor vessels being formed by arrays of wells in blocks
• CPC Class Codes: B01J 2219/00319 the blocks being mounted in stacked arrangements
• CPC Class Codes: B01J 2219/00335 Septa
• CPC Class Codes: B01J 2219/00416 Vacuum
• CPC Class Codes: B01J 2219/00423 using filtration, e.g. through porous frits
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• 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

Abstract

A multi-well synthesis and filtration apparatus (10) dimensionally arrayed in a standard multi-well format for performing multiple chemical reactions includes a deep-well synthesis block (12) with flowthrough wells (24) fitted with filter disks (48), an upper cover (14), and a lower cover (16). First and second sheet gaskets (18 and 20) seal inlet portions (38) and outlet spouts (40) of the wells (24). An optional skirt (26) provides a site for the independently releasable attachment of the upper and lower covers (14 and 16) to the block (12) while maintaining the seal on the unreleased cover. An alternative synthesis apparatus (310) additionally includes a reinforcement assembly (372) to improve the clamping action of the covers (14 and 16) upon the synthesis block (12). A rotating carrier apparatus (200) and a modified oven assembly (202) are provided to enable agitation and heating of multiple synthesis blocks (12) simultaneously.

Claims

1. An apparatus for multiple, simultaneous synthesis, comprising:

a synthesis block, said synthesis block including a plurality of reaction wells integrally formed within said block and arranged in ordered array, each well having an inlet portion and an outlet spout, said synthesis block further having a periphery;

a first sheet gasket sealable upon the inlet portions;

a second sheet gasket sealable upon the outlet spouts;

an upper cover for pressured engagement with said first sheet gasket;

a lower cover for pressured engagement with said second sheet gasket;

attachment means for releasably and independently attaching each one of said upper and lower covers to said periphery, said attachment means including said synthesis block having at least one protruding structure located on the periphery for attachment of said upper and lower covers; and

said attachment means further includes a reinforcement assembly having an upper collar and a lower collar for opposable sandwiching of the at least one protruding structure, each of said upper and lower covers attached to one of said upper and lower collars.

2. The apparatus of claim 1 wherein:

each well further includes a well bottom in fluid communication with the outlet spouts, and a filter element, the filter element seated upon the well bottom.

3. The apparatus of claim 1 wherein:

said upper cover includes a plurality of apertures in axial alignment with the wells.

4. The apparatus of claim 1 wherein:

there is one such protruding structure in the nature of a laterally extending skirt, the skirt being continuous about the periphery.

5. The apparatus of claim 1 wherein:

said attachment means further includes each of said upper and lower covers having a plurality of clips for latching onto the at least one protruding structure.

6. The apparatus of claim 1 wherein:

the reinforcement assembly further includes holding means for removably holding the upper and lower collars upon the at least one protruding structure.

7. The apparatus of claim 6 wherein:

the holding means includes a plurality of finger screws.

9. The apparatus of claim 1 further including:

agitation means for agitating at least one synthesis block with said upper and lower covers attached.

14. The apparatus of claim 1 wherein:

said synthesis block has block body of a generally rectangular shape, said block body having an upper surface, a lower surface, and side surfaces;

each of said plurality of wells of said synthesis block including a tube bore, each of said tube bores extending between said upper and lower surfaces;

said outlet spouts depending from said lower surface, each outlet spout in fluid communication with a said tube bore; and

said inlet portions extending upwardly from the upper surface, each inlet portion in axial alignment with a said tube bore.

15. The apparatus of claim 1 wherein:

each inlet portion includes a distinctly raised, thin-walled well rim.

16. The apparatus of claim 1 wherein:

said inlet portions are separated by rifts.

17. The apparatus of claim 1 wherein:

said wells are arrayed in a standard 96-well format.

18. The apparatus of claim 1 wherein:

said outlet spouts have a tapered Luer-tip shape.

19. The apparatus of claim 14 wherein:

said tube bores have a cross-sectional shape selected from the group of shapes consisting of round and rounded square, each outlet spout in general axial alignment with each tube bore.

20. The apparatus of claim 14 wherein:

said tube bores have a cross-sectional shape selected from the group of shapes consisting of generally rectangular and oval, each outlet spout axially offset with respect to each tube bore to provide alignment of said outlet spouts with the odd-numbered columns of wells of a multi-well collection plate in a first orientation of said block, and alignment with the even-numbered columns of wells of the collection plate in a second orientation in which said block is turned 180 degrees from the first orientation.

21. The apparatus of claim 20 wherein:

each tube bore has an inclined bottom surface portion, the lower aspect of which is in the direction of said outlet spouts.

22. The apparatus of claim 1 wherein:

said upper cover attaches to said upper collar; and

said lower cover attaches to said lower collar.

23. The apparatus of claim 1 wherein:

said upper collar attaches to said lower collar; and

said lower cover attaches to said upper collar.

8. An apparatus for multiple, simultaneous synthesis, comprising:

a synthesis block, said synthesis block including a plurality of reaction wells integrally formed within said block and arranged in ordered array, each well having an inlet portion and an outlet spout, said synthesis block further having a periphery;

a first sheet gasket sealable upon the inlet portions;

a second sheet gasket sealable upon the outlet spouts;

an upper cover for pressured engagement with said first sheet gasket;

a lower cover for pressured engagement with said second sheet gasket; and

attachment means for releasably and independently attaching each one of said upper and lower covers to said periphery, said attachment means including said synthesis block having at least one protruding structure located on the periphery for attachment of said upper and lower covers; and

a manifold apparatus and said synthesis block further having a block body lower surface, the manifold apparatus including a base, a removable lid, a first gasket, a second gasket, and means for securing the lid to the base, the base having an open chamber sized to receive a collection plate, a top surface, and an outlet for applying a reduced pressure to the chamber, the lid having an open area bounded by a shelf, the first and second gaskets having a generally rectangular band shape, the first gasket interposable between the base top surface and the lid, the second gasket interposable between the shelf and the block body lower surface.

11. An apparatus for multiple, simultaneous synthesis, comprising:

a synthesis block, said synthesis block including a plurality of wells arranged in ordered array, each well having an inlet portion and an outlet spout, said synthesis block further having a periphery and upper and lower synthesis block surfaces;

a first sheet gasket sealable upon the inlet portions;

a second sheet gasket sealable upon the outlet spouts;

an upper cover for pressured engagement with said first sheet gasket;

a lower cover for pressured engagement with said second sheet gasket;

a first collar and a second collar, said first and second collars opposably located about the periphery;

first attachment means for removably attaching the collars about the periphery;

second attachment means for releasably and independently attaching each of said upper and lower covers to one of said first and second collars.

10. The apparatus of claim 11 wherein:

said agitation means includes a carrier apparatus, the carrier apparatus including a platform, the platform sized to receive at least one covered synthesis block with upper and lower covers attached, retaining means for retaining the at least one covered synthesis block upon the platform, at least one shaft affixed to the platform and extending planarly therefrom, and rotational drive means for turning the shaft.

12. The apparatus of claim 11 wherein:

said first attachment means includes a plurality of threaded rods.

13. The apparatus of claim 11 wherein:

said upper and lower covers have a dimensional footprint which corresponds to that of a standard microplate.

24. The apparatus of claim 11 wherein:

said first collar is an upper collar;

said second collar is a lower collar;

said upper cover attaches to said first collar; and

said lower cover attaches to said second collar.

25. The apparatus of claim 11 wherein:

said first collar is an upper collar;

said second collar is a lower collar;

said upper cover attaches to said second collar; and

said lower cover attaches to said first collar.

26. An apparatus as in claim 11 wherein:

said first attachment means includes opposably sandwiching a portion of said synthesis block between said upper and lower collars.

27. The apparatus of claim 26 wherein:

said synthesis block portion which is sandwiched by said upper and lower collars includes said upper and lower synthesis block surfaces.

28. The apparatus of claim 26 wherein;

said synthesis block portion which is sandwiched by said upper and lower collars includes at least one protruding structure located on the periphery of said synthesis block.

29. The apparatus of claim 28 wherein:

said protruding structure is a laterally extending skirt, said skirt being continuous about the periphery of said synthesis block.

30. The apparatus of claim 11 wherein:

said first attachment means include fasteners which attach said first and second collars directly to said synthesis block periphery.

31. The apparatus of claim 11 further including:

a manifold apparatus and said synthesis block further having a block body lower surface, the manifold apparatus including a base, a removable lid, a first gasket, a second gasket, and means for securing the lid to the base, the base having an open chamber sized to receive a collection plate, a top surface, and an outlet for applying a reduced pressure to the chamber, the lid having an open area bounded by a shelf, the first and second gaskets having a generally rectangular band shape, the first gasket interposable between the base top surface and the lid, the second gasket interposable between the shelf and the block body lower surface.

32. The apparatus of claim 11 further including:

agitation means for agitating at least one said synthesis block with said upper and lower covers attached.

33. The apparatus of claim 11 wherein:

said agitation means includes a carrier apparatus, the carrier apparatus including a platform, the platform sized to receive at least one covered synthesis block with upper and lower covers attached, retaining means for retaining the at least one covered synthesis block upon the platform, at least one shaft affixed to the platform and extending planarly therefrom, and rotational drive means for turning the shaft.

34. The apparatus of claim 11 wherein:

each of said plurality of wells of said synthesis block includes a tube bore, each of said tube bores extending between said upper and lower synthesis block surfaces, said tube bores having a cross-sectional shape selected from the group of shapes consisting of generally rectangular and oval, each outlet spout axially offset with respect to each tube bore to provide alignment of said outlet spouts with the odd-numbered columns of wells of a multi-well collection plate in a first orientation of said block, and alignment with the even-numbered columns of wells of the collection plate in a second orientation in which said block is turned 180 degrees from the first orientation.

35. An apparatus for multiple, simultaneous synthesis, comprising:

a synthesis block, said synthesis block including a plurality of reaction wells integrally formed within said block and arranged in ordered array, each well having an inlet portion and an outlet spout, said synthesis block further having a periphery;

a first sheet gasket sealable upon the inlet portions;

a second sheet gasket sealable upon the outlet spouts;

an upper cover for pressured engagement with said first sheet gasket;

a lower cover for pressured engagement with said second sheet gasket;

attachment means for releasably and independently attaching each one of said upper and lower covers to said periphery, said attachment means including said synthesis block having at least one protruding structure located on the periphery for attachment of said upper and lower covers; and

said outlet spouts have a tapered Luer-tip shape.

36. An apparatus for multiple, simultaneous synthesis, comprising:

a synthesis block, said synthesis block including a plurality of reaction wells integrally formed within said block and arranged in ordered array, each well having an inlet portion and an outlet spout, said synthesis block further having a periphery;

a first sheet gasket sealable upon the inlet portions;

a second sheet gasket sealable upon the outlet spouts;

an upper cover for pressured engagement with said first sheet gasket;

a lower cover for pressured engagement with said second sheet gasket;

attachment means for releasably and independently attaching each one of said upper and lower covers to said periphery, said attachment means including said synthesis block having at least one protruding structure located on the periphery for attachment of said upper and lower covers;

said synthesis block has block body of a generally rectangular shape, said block body having an upper surface, a lower surface, and side surfaces;

each of said plurality of wells of said synthesis block including a tube bore, each of said tube bores extending between said upper and lower surfaces;

said outlet spouts depending from said lower surface, each outlet spout in fluid communication with a said tube bore;

said inlet portions extending upwardly from the upper surface, each inlet portion in axial alignment with a said tube bore;

said tube bore have a cross-sectional shape selected from the group of shapes consisting of generally rectangular and oval, each outlet spout axially offset with respect to each tube bore to provide alignment of said outlet spouts with the odd-numbered columns of wells of a multi-well collection plate in a first orientation of said block, and alignment with the even-numbered columns of wells of the collection plate in a second orientation in which said block is turned 180 degrees from the first orientation.

37. The apparatus of claim 36 wherein:

each tube has an inclined bottom surface portion, the lower aspect of which is in the direction of said outlet spouts.