Apparatus and process for multiple chemical reactions

• US 6,274,091 B1
• Filed: 03/29/1999
• Issued: 08/14/2001
• Est. Priority Date: 09/22/1995
• Status: Expired due to Fees

• Current Assignee: Bayer Schering Pharma AG (Bayer AG)
• Original Assignee: Berlex Laboratories Incorporated (Bayer AG)
• Inventors: Martin, John T., Chitty, Andrew I., Mohan, Raju, Buckman, Brad O., Morrissey, Michael M.
• Primary Examiner(s): Le, Long V.
• Application Number:
  US09/277,724
• Time in Patent Office: 869 Days
• Field of Search: 422/63, 422/81, 422/100, 422/103, 422/104, 422/129, 422/131, 422/134, 422/138, 422/101, 436/43, 436/180, 436/183, 436/174, 436/177, 137/597, 137/637
• US Class Current: 422/537
• 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 2219/00308 interchangeably mounted in racks or blocks
• CPC Class Codes: B01J 2219/0031 the racks or blocks being mounted in stacked arrangements
• CPC Class Codes: B01J 2219/00335 Septa
• CPC Class Codes: B01J 2219/00394 in multiple arrangements
• CPC Class Codes: B01J 2219/00416 Vacuum
• CPC Class Codes: B01J 2219/00423 using filtration, e.g. through porous frits
• CPC Class Codes: B01J 2219/00454 by chemical cleavage from the solid support
• CPC Class Codes: B01J 2219/00484 by shaking, vibrating or oscillating of the reaction vessels
• CPC Class Codes: B01J 2219/00495 Means for heating or cooling the reaction vessels
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00547 Bar codes
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/0059 Sequential processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00686 Automatic
• CPC Class Codes: B01J 2219/0072 Organic compounds
• CPC Class Codes: C40B 50/14 Solid phase synthesis, i.e. wherein one or more library building blocks are bound to a solid support during library creation; Particular methods of cleavage from the solid support
• CPC Class Codes: C40B 60/14 for creating libraries
• CPC Class Codes: C40B 70/00 : Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or bar codes
• CPC Class Codes: Y10S 436/809 : Multifield plates or multicontainer arrays
• CPC Class Codes: Y10T 436/25 : including sample preparation
• CPC Class Codes: Y10T 436/25375 : Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]

Abstract

Multiple chemical reactions are performed in a plurality of reaction vessels mounted in inlets in a manifold valve block. The manifold valve block is connected to a channel block which is utilized in conjunction with a solvent delivery system as part of the reaction cycle. The solvent fluid is drained from the reaction vessels when valves in the manifold valve block are opened while applying a vacuum thereto. Optionally, a thermal block may be utilized in conjunction with the manifold valve block and the channel block to facilitate the reaction. Upon completion of the reactant cycle, the manifold valve block is disconnected from the channel block and connected to a cleavage block assembly which contains vials for collecting reaction products. The cleavage product is drained from the reaction vessels through the manifold valve block into the vials upon opening the valves in the manifold valve block and applying a vacuum to the channel block.

Claims

1. A manifold block assembly useful for supporting an array of reaction vessels, the manifold block comprising:

a block of resinous material having an upper surface, a lower surface and side surfaces;

an array of vertically extending first passages within and extending through the block from openings at the upper surface to openings at the lower surface, the openings being adapted to receive reaction vessels;

valve inserts extending through for allowing fluid from reaction vessels to flow through the first passages when open and for preventing fluid from flowing through the first passages when closed;

each valve having an upper end for receiving an outlet of a reaction vessel and a lower end for dispensing fluid from the reaction vessel;

an array of transverse second passages extending in a direction transverse to the first passages with and through the block, each transverse second passage intersecting the valve inserts in a plurality of first passages,

rods extending in the second passages and passing through the valve inserts for openig and closing valve inserts simultaneously, whereby the flow of fluid from a plurality of the reaction vessels out through the outlets in the lower surface of the block is controlled simultaneously.

2. The assembly of claim 1 and further comprising:

a capping assembly attached to the manifold block in spaced relation thereto, the capping assembly sealing inlets of the reaction vessels when the reaction vessels are mounted in the inlets of the manifold block.

3. The assembly of claim 1 further comprising:

a drainage block attachable to the lower surface of the manifold block, the drainage block having at least one cavity therein for receiving fluid from the reaction vessels when fluid in the reaction vessels flows from the outlets in the manifold block.

4. The assembly of claim 3, wherein drainage block has interconnected channels therein aligned with the outlets of the manifold block.

5. The assembly of claim 4 further including:

a capping assembly attached to the manifold block in spaced relation thereto, the capping assembly sealing inlets of the reaction vessels when the reaction vessels are mounted in the inlets of the manifold block.

6. The assembly comprising the manifold block of claim 1, wherein the upper end of each valve insert is a female Luer connection and the lower end of each valve insert is a male Luer connection.

7. The assembly of claim 6, wherein the rods each have a plurality of similarly oriented holes therethrough which when aligned with the female and male Luer connections allow the valve inserts to open.

8. The assembly of claim 7 further including a drainage block attachable to the lower surface of the manifold block, the drainage block having at least one cavity therein for receiving fluid from the reaction vessels when fluid in the reaction vessels flows from the outlets in the manifold block.

9. The assembly of claim 8, wherein drainage block has interconnected channels therein aligned with the outlets of the manifold block.

10. The assembly of claim 8 further comprising:

a capping assembly attached to the manifold block in spaced relation thereto, the capping assembly sealing inlets of the reaction vessels when the reaction vessels are mounted in the inlets of the manifold block.

11. The assembly comprising the manifold block of claim 1 and further comprising:

a thermal block held spaced from the manifold block for surrounding the reaction vessels when the reaction vessels are mounted in the inlets of the manifold for controlling the temperature of contents within the reaction vessels.

12. The assembly of claim 11 further including:

a drainage block attachable to the lower surface of the manifold block, the drainage block having at least one cavity therein for receiving fluid from the reaction vessels when fluid in the reaction vessels flows from the outlets in the manifold block.

13. The assembly of claim 7 further including:

a capping assembly attached to the manifold block in spaced relation thereto, the capping assembly sealing inlets of the reaction vessels when the reaction vessels are mounted in the inlets of the manifold block.

14. The assembly of claim 1 further comprising:

an agitation device for agitating the contents of the reaction vessels.

15. The assembly of claim 14, wherein the agitation device is a vortexer.

16. The assembly of claim 6 further comprising:

a vial retaining member for coupling to the lower surface of the manifold block and for holding a plurality of vials in alignment with the outlets of the manifold block.

17. The assembly of claim 16, wherein the vial retaining member is a cleavage block having a cavity therein in which the vials are received.

18. The assembly of claim 17 further comprising:

a capping assembly attached to the manifold block in spaced relation thereto, the capping assembly sealing inlets of the reaction vessels when the reaction vessels are mounted in the inlets of the manifold block.

19. The assembly of claim 17 further comprising:

a thermal block held spaced from the manifold block for surrounding the reaction vessels when the reaction vessels are mounted in the inlets of the manifold for controlling the temperature of contents within the reaction vessels.

20. The assembly of claim 19, wherein the valves are valve inserts in each of the first passages.

21. The assembly of claim 20, wherein the valve operators extending in each of the second passages simultaneously operate valve inserts in the first passages.

22. The assembly of claim 19 further comprising:

a capping assembly attached to the manifold block in spaced relation thereto, the capping assembly sealing inlets of the reaction vessels when the reaction vessels are mounted in the inlets of the manifold block.

23. The assembly of claim 22, wherein the valves are valve inserts in each of the first passages.

24. The assembly of claim 23, wherein the valve operators extending in each of the second passages simultaneously operate valve inserts in the first passages.