Methods for screening catalysts in a parallel fixed-bed reactor

• US 6,869,799 B1
• Filed: 06/29/2000
• Issued: 03/22/2005
• Est. Priority Date: 06/09/1998
• Status: Expired due to Term

• Current Assignee: Symyx Solutions, Inc.
• Original Assignee: Symyx Technologies Incorporated (Dassault Systemes SA)
• Inventors: Guan, Shenheng, Haushalter, Robert C., Van Erden, Lynn, Zhou, Xiao Ping, Wang, Xuejun Jason, Srinivasan, Ravi
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): Handy, Dwayne K
• Application Number:
  US09/607,535
• Time in Patent Office: 1,727 Days
• Field of Search: 422 80- 81, 422/83, 422/131, 422/89, 422/211, 422/213, 422/129, 422/130, 436/43, 436/174, 436/180, 436/161, 436/37, 436/159, 436/172, 436/173, 436/147, 436/177
• US Class Current: 436/37
• 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 2219/00306 Reactor vessels in a multiple arrangement
• 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 2219/00353 Pumps
• CPC Class Codes: B01J 2219/00391 Rotary valves
• CPC Class Codes: B01J 2219/00394 in multiple arrangements
• CPC Class Codes: B01J 2219/00409 Solenoids in combination with valves
• 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: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00689 using computers
• CPC Class Codes: B01J 2219/00698 Measurement and control of process parameters
• CPC Class Codes: B01J 2219/00702 Processes involving means for analysing and characterising the products
• CPC Class Codes: B01J 2219/00704 integrated with the reactor apparatus
• CPC Class Codes: B01J 2219/00745 Inorganic compounds
• CPC Class Codes: B01J 2219/00747 Catalysts
• CPC Class Codes: C40B 30/08 by measuring catalytic activity
• CPC Class Codes: C40B 40/18 : Libraries containing only inorganic compounds or inorganic materials
• CPC Class Codes: G01N 31/10 : using catalysis
• CPC Class Codes: Y10T 436/11 : Automated chemical analysis
• CPC Class Codes: Y10T 436/25 : including sample preparation
• CPC Class Codes: Y10T 436/25625 : Dilution
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

The present invention discloses an apparatus and method for rapid analysis of members of a combinatorial library. The apparatus includes a plurality of vessels for containing individual library members and a fluid handling system that apportions a test fluid about equally between each of the vessels. This allows for simultaneous screening of library members by detecting changes in test fluid following contact with individual library members. Fluid flow through each of the vessels is controlled using passive flow restrictors or active flow controllers to ensure that each library member contacts approximately the same amount of test fluid per unit time. The disclosed apparatus is especially useful for screening library members based on their ability to catalyze the conversion of fluid reactants.

Claims

1. A method for screening catalysts for a reaction of interest, the method comprising

feeding one or more reactants through one or more distribution valves to six or more reaction vessels, the one or more reactants being fed simultaneously to at least two of the reaction vessels, each of the six or more vessels comprising an inlet in fluid communication with an entrance control volume, an outlet in fluid communication with an exit control volume, and a different candidate catalyst in the reaction vessel, the one or more distribution valves providing selective fluid communication between the entrance control volume and the six or more reaction vessels,

contacting the six or more different candidate catalysts with the one or more reactants in the six or more reaction vessels under reaction conditions for the reaction of interest, at least two different candidate catalysts being contacted simultaneously with the one or more reactants in the at least two reaction vessels into which the one or more reactants are fed simultaneously,

discharging reaction products and unreacted reactants, if any, from the six or more reaction vessels, through one or more selection valves to one or more detectors, the one or more selection valves providing selective fluid communication between the six or more reaction vessels and the one or more detectors, reaction products or unreacted reactants being discharged simultaneously from the at least two reaction vessels into which the one or more reactants are fed simultaneously,

controlling the contact time to be about the same for each of the six or more candidate catalysts by synchronized operation of one or more distribution valves and the one or more selection valves, and

detecting resulting reaction products or unreacted reactants to determine the efficacy of the six or more catalyst candidates, the resulting reaction products or unreacted reactants discharged simultaneously from the at least two vessels being detected simultaneously.

2. The method of claim 1 further comprising controlling the flowrate of the one or more reactants to be about the same in the six or more reaction vessels.

3. The method of claim 1 further comprising controlling the flowrate of the one or more reactants to be about the same in the six or more reaction vessels by flowing the one or more reactants through six or more flow restrictors, each of six or more flow restrictors providing fluid communication between one of the six or more vessels and (i) the one or more distribution valves, or alternatively, (ii) the one or more selection valves.

4. The method of claim 3 wherein the resistance to fluid flow within a given flow channel is greatest in the flow restrictor, and the resistance to flow in each of the six or more flow restrictors is approximately the same, such that maintaining a higher pressure in the entrance control volume than in the exit control volume results in fluid flow through the at least six vessels that is apportioned approximately equally between each of the at least six vessels.

5. The method of claim 3 wherein each of the six or more flow restrictors provide fluid communication between one of the six or more reaction vessels and the one or more distribution valves.

6. The method of claim 1 further comprising controlling the flowrate of the one or more reactants to be about the same in the six or more reaction vessels by flowing the one or more reactants through one or more flow regulators.

7. A method for screening catalysts for a reaction of interest, the method comprising

simultaneously feeding one or more reactants through six or more reaction vessels, each of the six or more vessels comprising an inlet in fluid communication with an entrance control volume, an outlet in fluid communication with an exit control volume, and a different candidate catalyst in the reaction vessel,

simultaneously flowing the one or more reactants through six or more flow restrictors, each of the six or more flow restrictors providing fluid communication between one of the six or more vessels and the entrance control volume, the resistance to fluid flow being greatest and approximately the same in each of the six or more flow restrictors so that the flowrate of the one or more reactants through each of the six or more reaction vessels is approximately the same,

contacting the six or more different candidate catalysts with the one or more reactants in the six or more reaction vessels under reaction conditions for the reaction of interest, and

detecting the reaction products or unreacted reactants to determine the efficacy of the six or more catalyst candidates.

8. A method for screening members of a combinatorial library, the method comprising

simultaneously flowing a test fluid through six or more vessels, each of the six or more vessels comprising a member of the combinatorial library,

simultaneously flowing the test fluid through six or more flow restrictors, each of the six or more flow restrictors providing fluid communication between one of the six or more vessels and (i) an entrance control volume, or alternatively, (ii) an exit control volume, the resistance to fluid flow being greatest and approximately the same in each of the six or more flow restrictors so that the flowrate of the test fluid through each of the six or more vessels is approximately the same,

simultaneously contacting at least six of the six or more library members with the test fluid in the six or more vessels,

simultaneously detecting changes in the test fluid following contact with each of the six or more library members, and

correlating the changes in the test fluid to a property of each of the six or more library members.

10. The method of claim 8 or 9 wherein each of the six or more flow restrictors provide fluid communication between one of the six or more reaction vessels and an entrance control volume.

11. The method of claim 8 wherein the time from initial contact of a library member with the test fluid to detection of changes in the test fluid is approximately the same for each of the six or more library members.

12. The method of claim 8 wherein the detecting step determines changes in the composition of the test fluid.

13. The method of claim 8 wherein the detecting step determines changes in the composition of the test fluid using gas chromatography, mass spectrometry, visible spectrometry, ultraviolet spectrometry, ultraviolet spectrometry or infrared spectrometry.

14. The method of claim 8 wherein the six or more library members are at least forty-eight library members.

15. The method of claim 8 wherein the total time to screen the six or more library members is less than about six minutes.

16. The method of claim 8 wherein the total time to screen the six or more library members is less than about three minutes.

17. The method of claim 8 wherein the six or more library members are at least forty-eight library members and the total time to screen the at least forty-eight library members is less than about forty-eight minutes.

18. The method of claim 8 wherein the six or more library members are at least forty-eight library members and the total time to screen the at least forty-eight library members is less than about twenty-four minutes.

19. The method of claim 8 wherein the six or more library members are exposed to a uniform temperature or a temperature gradient during the test.

20. The method of claim 8 wherein about the same amount of each of the six or more library members are present in the respective vessels.

21. The method of claim 8 wherein the test fluid is a gaseous test fluid.

22. The method of claim 8 wherein the test fluid is a liquid test fluid.

23. The method of claim 8 wherein the library member is a solid.

24. The method of claim 8 wherein the library member is a liquid.

25. The method of claim 8 wherein the test fluid is a gaseous test fluid and the library member is a solid.

26. The method of claim 8 wherein the test fluid is a gaseous test fluid and the library member is a liquid.

9. A method for screening catalysts for a reaction of interest, the method comprising

simultaneously feeding one or more reactants through six or more reaction vessels, each of the six or more vessels comprising a different candidate catalyst,

simultaneously flowing the one or more reactants through six or more flow restrictors, each of the six or more flow restrictors providing fluid communication between one of the six or more reaction vessels and (i) an entrance control volume, or alternatively, (ii) an exit control volume, the resistance to fluid flow being greatest and approximately the same in each of the six or more flow restrictors so that the flowrate of the one or more reactants through each of the six or more reaction vessels is approximately the same,

simultaneously contacting the candidate catalysts with the one or more reactants in the six or more reaction vessels under reaction conditions for the reaction of interest, and

simultaneously detecting resulting reaction products or unreacted reactants to determine the efficacy of the six or more catalyst candidates.

27. A method for screening catalysts for a reaction of interest, the method comprising

simultaneously feeding one or more reactants through six or more reaction vessels, each of the six or more vessels comprising a different candidate catalyst,

simultaneously flowing the one or more reactants through six or more flow restrictors, the flow restrictors being capillary tubes or micromachined channels, each of the six or more flow restrictors providing fluid communication between one of the six or more reaction vessels and (i) an entrance control volume, or alternatively, (ii) an exit control volume, the resistance to fluid flow being greatest and approximately the same in each of the six or more flow restrictors so that the flowrate of the one or more reactants through each of the six or more reaction vessels is approximately the same,

contacting the candidate catalysts with the one or more reactants in the six or more reaction vessels under reaction conditions for the reaction of interest, and

detecting resulting reaction products or unreacted reactants to determine the efficacy of the six or more catalyst candidates.

28. The method of claim 7 or 27 further comprising

discharging reaction products and unreacted reactants, if any, from the six or more reaction vessels, and

sampling the discharged reaction products or unreacted reactants with a sampling probe, the sampling probe being in fluid communication with one or more detectors.

29. The method of claim 9, 7 or 27 wherein the time from initial contact of a catalyst with the one or more reactants to detection of the reaction products or unreacted reactants is approximately the same for each of the six or more catalysts.

30. The method of claim 9, 7 or 27 wherein the detecting step determines the reaction products or unreacted reactants using gas chromatography, mass spectrometry, visible spectrometry, ultraviolet spectrometry, ultraviolet spectrometry or infrared spectrometry.

31. The method of claim 9, 7 or 27 wherein the six or more catalysts are exposed to a uniform temperature or a temperature gradient.

32. The method of claim 9, 7 or 27 wherein the six or more catalysts are confined in the reaction vessels in the form of fixed beds.

33. The method of claim 7 or 27 wherein the fluid handling system comprises

a selection valve providing selective fluid communication between a selected vessel and the detector, such that the reaction products or unreacted reactants can be sequentially directed from the selected vessel to the detector, and

a fluid distribution valve providing selective fluid communication between the entrance control volume and the inlet of a selected vessel, such that the one or more reactants can be directed into the selected vessel,

the method further comprising synchronizing the fluid distribution valve and the selection valve such that a time interval between the initial contact of the one or more reactants with one of the six or more catalysts and detection of reaction products or unreacted reactants is approximately the same for each of the six or more catalysts.