Parallel reactor with internal sensing and method of using same

• US 6,787,112 B1
• Filed: 11/28/2000
• Issued: 09/07/2004
• Est. Priority Date: 08/13/1998
• Status: Expired due to Term

• Current Assignee: Freeslate Inc. (Unchained Labs Inc.)
• Original Assignee: Symyx Technologies Incorporated (Dassault Systemes SA)
• Inventors: VanErden, Lynn, Rust, William C., VanBeek, Johannes A. M., Turner, Howard, Dales, G. Cameron, Hajduk, Damian A., Nielsen, Ralph B.
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): Handy, Dwayne K.
• Application Number:
  US09/724,275
• Time in Patent Office: 1,379 Days
• Field of Search: 422/62, 422/63, 422/67, 422/93, 422/88, 422/99, 422/100, 422/102, 422/103, 422/129, 422/130, 422/131, 422/132, 422/138, 436/43, 436/50, 436/54, 436/34, 436/174, 436/181
• US Class Current: 422/130
• CPC Class Codes: B01F 33/452 using independent floating stirring elements
• CPC Class Codes: B01F 33/453 using supported or suspended stirring elements
• CPC Class Codes: B01F 35/212 of the driving system data, e.g. torque, speed or power data
• CPC Class Codes: B01F 35/213 of the properties of the mixtures, e.g. temperature, density or colour
• CPC Class Codes: B01F 35/2136 Viscosity
• CPC Class Codes: B01J 19/0006 Controlling or regulating processes controlling or regulating in general G05
• CPC Class Codes: B01J 19/0013 Controlling the temperature of the process
• CPC Class Codes: B01J 19/004 Multifunctional apparatus for automatic manufacturing of various chemical products sequential reactions B01J19/0046
• 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 2219/00029 Batch processes
• CPC Class Codes: B01J 2219/00162 controlling the pressure
• CPC Class Codes: B01J 2219/002 inside the reactor
• CPC Class Codes: B01J 2219/00283 Reactor vessels with top opening
• 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 2219/00333 Closures attached to the reactor vessels
• CPC Class Codes: B01J 2219/00335 Septa
• CPC Class Codes: B01J 2219/00351 Means for dispensing and evacuation of reagents
• CPC Class Codes: B01J 2219/00367 capillary
• CPC Class Codes: B01J 2219/00373 Hollow needles
• CPC Class Codes: B01J 2219/00389 : Feeding through valves
• CPC Class Codes: B01J 2219/00418 : using pressure
• CPC Class Codes: B01J 2219/00477 : Means for pressurising the reaction vessels
• CPC Class Codes: B01J 2219/00481 : by the use of moving stirrers within the reaction vessels
• CPC Class Codes: B01J 2219/00495 : Means for heating or cooling the reaction vessels
• 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 2219/00601 : High-pressure processes
• CPC Class Codes: B01J 2219/00686 : Automatic
• CPC Class Codes: B01J 2219/00689 : using computers
• CPC Class Codes: B01J 2219/00691 : using robots
• CPC Class Codes: B01J 2219/00695 : Synthesis control routines, e.g. using computer programs
• 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 2219/0072 : Organic compounds
• CPC Class Codes: B01J 2219/00722 : Nucleotides
• CPC Class Codes: B01J 2219/00736 : Non-biologic macromolecules, e.g. polymeric compounds
• CPC Class Codes: B01J 2219/00738 : Organic catalysts
• CPC Class Codes: B01J 2219/00745 : Inorganic compounds
• CPC Class Codes: B01L 2200/026 : Fluid interfacing between devices or objects, e.g. connectors, inlet details
• CPC Class Codes: B01L 2300/049 : Valves integrated in closure
• CPC Class Codes: B01L 2300/06 : Auxiliary integrated devices, integrated components
• CPC Class Codes: B01L 2300/0627 : Sensor or part of a sensor is integrated
• CPC Class Codes: B01L 2300/14 : Means for pressure control
• CPC Class Codes: B01L 2300/1805 : Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
• CPC Class Codes: B01L 3/50851 : specially adapted for heating or cooling samples laboratory heating apparatus B01L7/00; incubators C12M
• CPC Class Codes: B01L 3/50853 : with covers or lids
• CPC Class Codes: B01L 7/54 : using spatial temperature gradients
• CPC Class Codes: C40B 40/14 : Libraries containing macromolecular compounds and not covered by groups C40B40/06 - C40B40/12
• CPC Class Codes: C40B 40/18 : Libraries containing only inorganic compounds or inorganic materials
• CPC Class Codes: G01K 13/00 : Thermometers specially adapted for specific purposes
• CPC Class Codes: G01N 11/16 : by measuring damping effect upon oscillatory body
• CPC Class Codes: G01N 35/1079 : with means for piercing stoppers or septums
• CPC Class Codes: Y10T 436/11 : Automated chemical analysis
• CPC Class Codes: Y10T 436/115831 : Condition or time responsive
• CPC Class Codes: Y10T 436/119163 : with aspirator of claimed structure
• CPC Class Codes: Y10T 436/12 : Condition responsive control
• CPC Class Codes: Y10T 436/25 : including sample preparation
• CPC Class Codes: Y10T 436/25875 : Gaseous sample or with change of physical state

Abstract

Devices and methods for controlling and monitoring the progress and properties of multiple reactions are disclosed. The method and apparatus are especially useful for synthesizing, screening, and characterizing combinatorial libraries, but also offer significant advantages over conventional experimental reactors as well. The apparatus generally includes multiple vessels for containing reaction mixtures, and systems for controlling the stirring rate and temperature of individual reaction mixtures or groups of reaction mixtures. In addition, the apparatus may include provisions for independently controlling pressure in each vessel, and a system for injecting liquids into the vessels at a pressure different than ambient pressure. In situ monitoring of individual reaction mixtures provides feedback for process controllers, and also provides data for determining reaction rates, product yields, and various properties of the reaction products, including viscosity and molecular weight. Computer-based methods are disclosed for process monitoring and control, and for data display and analysis.

Claims

1. Apparatus for monitoring the consumption of a gas-phase reactant in a catalyzed liquid-phase reaction, the apparatus comprising

a vessel for containing a liquid-phase reaction mixture,

a vessel seal for permitting the vessel to be pressurized at pressures different from ambient pressure,

an injection system for injecting a catalytic liquid containing a catalyst for reacting the gas-phase reactant into the vessel, the catalytic liquid injection system being operable to inject the catalytic liquid into the vessel while the pressure within the vessel is different from ambient pressure, and

a pressure control system comprising:

a source of the gas-phase reactant maintained at a pressure in excess of the pressure within the vessel;

a gas delivery conduit providing a flow path for passing the gas-phase reactant from the source of the gas-phase reactant into the vessel;

a valve in the gas delivery conduit located between the source of the gas-phase reactant and the vessel such that when the valve is open, the gas-phase reactant passes from the source of the gas-phase reactant into the vessel and the pressure in the vessel is increased;

a valve controller communicating with the valve in the gas delivery conduit for opening and closing the valve;

a pressure sensor in fluid communication with the vessel for sensing the pressure in the vessel;

a processor communicating with the valve controller and the pressure sensor, the processor directing the valve controller to selectively open the valve in the gas delivery conduit when the pressure within the vessel decays to a predetermined lower pressure limit, P_L, as a result of consumption of the gas-phase reactant, and directing the valve controller to selectively close the valve in the gas delivery conduit when the pressure within the vessel increases to a predetermined upper pressure limit, P_H; and

a system for recording the pressure changes within the vessel.

2. Apparatus as set forth in claim 1 wherein the pressure control system is adapted to maintain the pressure in the vessel greater than about 10 psig and the injection system is operable to inject the catalytic liquid into the vessel while the vessel is pressurized to a pressure greater than about 10 psig.

3. Apparatus as set forth in claim 1 wherein the injection system comprises a movable fluid delivery probe for effecting the injection of the catalytic liquid into the vessel.

4. Apparatus as set forth in claim 3 wherein the injection system is operable for preventing leakage of fluid under pressure from the vessel during and after the injection of the catalytic liquid by the fluid delivery probe.

5. Apparatus as et forth in claim 1 further comprising a monitor for displaying the pressure sensed in the vessel.

6. Apparatus as set forth in claim 1 further comprising a data analysis module adapted to perform a calculation on the pressure data sensed in the vessel.

7. Apparatus as set forth in claim 6 further comprising a monitor for displaying the result of the calculation performed by the data analysis module on the pressure data sensed in the vessel.

8. An apparatus for parallel processing of a plurality of reaction mixtures and for monitoring the consumption or production of a gas-phase component of the reaction mixture, the apparatus comprising:

a plurality of vessels for containing the reaction mixtures,

a removable gas-tight closure for sealing the vessels against unintentional gas flow to or from the vessels, and

a pressure control system comprising;

a plurality of gas conduits, each gas conduit in fluid communication with one of the vessels and providing a flow path for passing the gas-phase component of the reaction mixture into or out of the vessel;

a valve in each of the gas conduits;

a valve controller communicating with each of the valves for opening and closing the valves in the gas conduits;

a plurality of pressure sensors each in fluid communication with one of the vessels for sensing the pressure in the vessel;

a processor communicating with the valve controller and the pressure sensors, the processor directing the valve controller to selectively open each of the valves in response to a signal received from the pressure sensor in the respective vessel and to selectively close each of the valves in response to a signal received from the pressure sensor in the respective vessel; and

a system for recording the pressure changes within each of the vessels.

9. Apparatus as set forth in claim 8 wherein the gas phase component of the reaction mixtures is a gas phase reactant and the apparatus monitors the consumption of the gas-phase reactant of the reaction mixtures, the apparatus further comprising a source of the gas-phase reactant in fluid communication with the gas conduits and maintained at a pressure in excess of the pressure within the vessels, the valve in each of the gas conduits being located between the source of the gas-phase reactant and the respective vessel such that when the valve is opened, gas-phase reactant is permitted to pass from the source into the vessel to cause an increase in the pressure in the vessel, and wherein the processor directs the valve controller to selectively open each valve when the pressure sensed within the respective vessel decreases to a predetermined lower pressure limit, P_L, as a result of consumption of the gas-phase reactant and the processor directs the valve controller to selectively close each valve when the pressure sensed within the respective vessel increases to a predetermined upper pressure limit, P_H.

10. Apparatus as set forth in claim 8 further comprising a plurality of temperature sensors, each temperature sensor in thermal contact with the reaction mixture in one of the vessels for sensing the temperature of the reaction mixture.

11. Apparatus as set forth in claim 10 wherein the temperature sensors communicate with the processor provide the processor with temperature data for determining pressure changes in the vessels resulting from variations in the temperature of the reaction mixtures.

12. Apparatus as set forth in claim 10 wherein each vessel contains a head space between the closure and condensed-phase components of the reaction mixture contained within the vessel, the pressure sensor is in fluid communication with the head space and the temperature sensor is in thermal contact with the reaction mixture in the head space.

13. Apparatus as set forth in claim 8 further comprising a temperature control system for regulating the temperature of the reaction mixtures.

14. Apparatus as set forth in claim 8 wherein the pressure control system is adapted to maintain the pressure in the vessels greater than about 10 psig.

15. Apparatus as set forth in claim 8 further comprising an injection system for injecting reaction materials into one or more of the vessels, the injection system being operable to inject the reaction material into the vessel while the pressure within the vessel is different from ambient pressure.

16. Apparatus as set forth in claim 15 wherein the injection system comprises a fluid delivery probe movable from one vessel to another vessel for effecting the injection of the reaction material into each of the vessels.

17. Apparatus as set forth in claim 16 wherein the injection system is operable for preventing leakage of fluid under pressure from each vessel during and after the injection by the fluid delivery probe.

18. Apparatus as set forth in claim 16 wherein the injection system further comprises

fill ports for receiving the fluid delivery probe, the probe being movable from one fill port to another to inject the reaction material into each of the vessels,

conduits connecting the fill ports and respective vessels, and

valves for opening and closing the conduits, each valve being operable to open and permit the injection of reaction material from the fluid delivery probe to a respective vessel at a pressure different from ambient pressure and to close after the injection.

19. Apparatus as set forth in claim 8 further comprising a data analysis module for processing the pressure data sensed in each of the vessels for use in screening the reaction mixtures.

20. Apparatus as set forth in claim 19 further comprising a monitor for displaying the pressure data sensed in each of the vessels during simultaneous reactions in the plurality of vessels.

21. Apparatus as set forth in claim 19 wherein the data analysis module is adapted to perform a calculation on the pressure data sensed in each of the vessels.

22. Apparatus as set forth in claim 21 further comprising a monitor for displaying the result of the calculation performed by the data analysis module on the pressure data sensed in each of the vessels.

23. Apparatus as set forth in claim 18 further comprising a reactor control system, the reactor control system adapted to control the injection system to inject a material into the vessels in response to the pressure sensed within the vessels.

24. Apparatus as set forth in claim 23 wherein the reactor control system is adapted to control the injection system to inject a quenching agent into the vessels and terminate the reaction in the vessels once a specified conversion target has been attained as determined from pressure changes within the vessels.