Analysis and control of parallel chemical reactions

• US 6,727,096 B1
• Filed: 11/28/2000
• Issued: 04/27/2004
• Est. Priority Date: 08/13/1998
• Status: Expired due to Term

• Current Assignee: Unchained Labs Inc.
• Original Assignee: Symyx Technologies Incorporated (Dassault Systemes SA)
• Inventors: Wang, Pei, Dales, G. Cameron
• Primary Examiner(s): Soderquist, Arlen
• Application Number:
  US09/723,720
• Time in Patent Office: 1,246 Days
• Field of Search: 422/62, 422/102, 422/104, 422/93, 422/196-197, 422/105, 422/107, 422/108, 422/112, 422/130, 436/34, 436/37, 436/43, 436/50, 436/55, 436/85, 436/147, 436/159, 436/161, 436/164, 436/173, 700/266, 700/268, 700/269
• US Class Current: 436/37
• CPC Class Codes: B01F 33/45 Magnetic mixers; Mixers with magnetically driven stirrers
• CPC Class Codes: B01F 33/71 working at super-atmospheric pressure, e.g. in pressurised vessels
• CPC Class Codes: B01F 35/213 of the properties of the mixtures, e.g. temperature, density or colour
• CPC Class Codes: B01F 35/2213 Pressure
• CPC Class Codes: B01F 35/2215 Temperature
• CPC Class Codes: B01F 35/3231 Driving several stirrer shafts, e.g. about the same axis
• 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 2219/00745 : 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: F28F 27/00 : Control arrangements or safety devices specially adapted for heat-exchange or heat-transfer apparatus control arrangements in general G05
• CPC Class Codes: G01K 13/00 : Thermometers specially adapted for specific purposes
• CPC Class Codes: G01N 21/253 : for batch operation, i.e. multisample apparatus analytical automats G01N35/00
• 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 436/12 : Condition responsive control

Abstract

Computer programs and computer-implemented methods for monitoring the progress and properties of parallel chemical reactions. The invention repeatedly receives a measured value or values associated with the contents of each of a plurality of reactor vessels and displays the measured over the course of a combinatorial chemical reaction. Reaction parameters associated with individual reactor vessels are changed in response to the value measured during the reaction. Reaction parameters include temperature, pressure, stirring speed. The reaction occurring in one or more reactor vessels is quenched in response to values measured during the reaction. The measured values are used to calculate experimental results including temperature change, pressure change, percent conversion of starting material, and viscosity. The measured values and experimental results are displayed. In another aspect, the invention features a method for controlling a combinatorial chemical reactor. The method includes receiving set points for properties associated with the reaction environment in multiple reactor vessels, measuring experimental values associated with each reactor vessel, displaying the experimental values, and changing the vessels'"'"' reaction environment in response to input set points and changing experimental values. In another aspect, the invention features a reactor control system for monitoring and controlling a parallel chemical reaction. The system includes modules for providing control signals to a parallel chemical reactor, receiving measured values from the parallel chemical reactor and calculating experimental results from the measured values, and for receiving reaction parameters from the user and displaying the set of measured values and the calculated values.

Claims

1. A method for monitoring a combinatorial chemistry experiment during which a plurality of reactions are simultaneously occurring substantially independent of each other in a plurality of reactor vessels, respectively, each of the plurality of vessels having one or more sensors associated therewith providing measured values relating to the reaction in the reactor vessels, said method comprising:

(a) receiving the measured value associated with each of the plurality of reactor vessels;

(b) storing the measured values in a memory;

(c) repeating steps (a) and (b) multiple times during the course of the combinatorial chemical reactions;

(d) processing experimental data comprising at least one of the stored measured values or comprising an experimental value calculated from at least one of the measured values; and

(e) screening at least one of the reactions or at least one of the materials used in the reactions with respect to said experimental data of another of the reactions.

2. The method of claim 1, wherein said screening occurs during the course of the combinatorial chemical reactions.

3. The method of claim 1 wherein said screening comprises ranking said at least one of the reactions or at least one of the materials used in the reactions with respect to said experimental data of another of the reactions.

4. The method of claim 1, wherein processing experimental data comprises calculating process variables from the stored measured values and/or calculating product variables from the stored measured values.

5. The method of claim 1 wherein processing experimental data comprises processing the stored measured values.

6. The method of claim 1 wherein the experimental data comprises at least one selected from the following group:

temperature, pressure, torque, power, mixing variables, stirring rate, motor speed, viscosity, reaction kinetics, reaction conversion, polymer concentration, polymer conversion, monomer conversion, percent conversion, molecular conversion, rate of conversion, rate of reaction, molecular weight, particle size, stability and catalyst related parameters.

7. The method of claim 6 wherein the experimental data comprises viscosity measurements to screen or characterize dilute suspensions of insoluble particles.

8. The method of claim 1, wherein receiving the measured value comprises receiving a set of values corresponding to reaction conditions associated with the plurality of reactor vessels.

9. The method of claim 1, wherein parameters of the vessels are controlled in response to control parameters and further comprising:

changing at least one of the control parameters associated with the plurality of reactor vessels in response to the measured values.

10. The method of claim 9, wherein the changing step maintains the reactor vessel at a predetermined set point, and wherein the control parameters comprise at least one parameter selected from the following group:

temperature, pressure, viscosity and motor speed.

11. The method of claim 1 further comprising displaying in graphical form the experimental data.

12. The method of claim 1, wherein step (c) is performed at a predetermined sampling rate.

13. The method of claim 1, further comprising:

quenching a catalyst in at least one of the plurality of reactor vessels in response to the experimental data associated with the contents of the reactor vessel.

14. The method of claim 1, further comprising:

using the experimental data to calculate an experimental value for at least one of the plurality of reactor vessels.

15. The method of claim 14, wherein the experimental value comprises at least one value selected from the following group:

temperature change, pressure change, percent conversion of starting material and viscosity.

16. The method of claim 14, further comprising displaying the experimental value.

17. A computer program on a computer-readable medium for monitoring a combinatorial chemistry experiment during which a plurality of reactions are simultaneously occurring substantially independent of each other in a plurality of reactor vessels, respectively, each of the plurality of vessels having one or more sensors associated therewith providing measured values relating to the reaction in the reactor vessels, the program comprising instructions to:

(a) receive a measured value associated with each of a plurality of reactor vessels;

(b) store the measured values in a memory;

(c) repeat steps (a) and (b) multiple times during the course of the combinatorial chemical reactions;

(d) process experimental data comprising at least one of the stored measured values or comprising an experimental value calculated from at least one of the stored measured values; and

(e) screen at least one of the reactions or at least one of the materials used in the reactions with respect to said experimental data of another of the reactions.

18. The computer program of claim 17, wherein the instructions to screen execute screening during the course of the combinatorial chemical reactions.

19. The computer program of claim 17, wherein the instructions to screen comprise instructions to rank said at least one of the reactions or at least one of the materials used in the reactions with respect to said experimental data of another of the reactions.

20. The computer program of claim 17, wherein the instructions to process experimental data comprise instructions to calculate process variables from the stored measured values and/or to calculate product variables from the stored measured values.

21. The computer program of claim 17 wherein the experimental data comprises at least one selected from the following group:

temperature, pressure, torque, power, mixing variables, stirring rate, motor speed, viscosity, reaction kinetics, reaction conversion, polymer concentration, polymer conversion, monomer conversion, percent conversion, molecular conversion, rate of conversion, rate of reaction, molecular weight, particle size, stability and catalyst related parameters.

22. The computer program of claim 17 wherein the experimental data comprises viscosity measurements to screen or characterize dilute suspensions of insoluble particles.

23. The computer program of claim 17 further comprising instructions to store in a memory experimental values calculated from the measured values.

24. The computer program of claim 17 further comprising instructions to display the measured values or experimental values calculated from the measured values on a user interface module.

25. A system which monitors a combinatorial chemistry experiment during which a plurality of reactions are simultaneously occurring substantially independent of each other in a plurality of reactor vessels, respectively, each of the plurality of vessels having one or more sensors associated therewith providing measured values relating to the reaction in the reactor vessels, said system comprising:

(a) a receiver for receiving the measured value associated with the contents of each of the plurality of reactor vessels during the course of the combinatorial chemical reaction;

(b) a graphical display for simultaneously displaying during the course of the combinatorial chemical reaction the received measured values or experimental values calculated from the measured values; and

(c) a data analysis module for processing experimental data comprising at least one of the measured values or comprising an experimental value calculated from at least one of the measured values for use in screening at least one of the reactions or at least one of the materials used in the reactions with respect to said experimental data of another of the reactions.

26. The system of claim 25, wherein the data analysis module screens during the course of the combinatorial chemical reactions.

27. The system of claim 25, wherein said screening by the data analysis module comprises ranking said at least one of the reactions or at least one of the materials used in the reactions with respect to said experimental data of another of the reactions.

28. The system of claim 25, wherein the data analysis module calculates process variables from the stored measured values and/or calculates product variables from the stored measured values.

29. The system of claim 25 wherein the experimental data comprises at least one selected from the following group:

temperature, pressure, torque, power, mixing variables, stirring rate, motor speed, viscosity, reaction kinetics, reaction conversion, polymer concentration, polymer conversion, monomer conversion, percent conversion, molecular conversion, rate of conversion, rate of reaction, molecular weight, particle size, stability and catalyst related parameters.

30. The system of claim 25 wherein the experimental data comprises viscosity measurements to screen or characterize dilute suspensions of insoluble particles.

31. The system of claim 25 further comprising a control controlling parameters of the reactor vessels and changing the parameters in response to the received measured values received by the receiver.

32. The system of claim 25 wherein the display displays a tabular representation of the received measured values, and wherein the tabular array and the graphical representation are simultaneously displayed.

33. A system which monitors a combinatorial chemistry experiment during which a plurality of reactions are simultaneously occurring substantially independent of each other in a plurality of reactor vessels, respectively, each of the plurality of vessels having one or more sensors associated therewith providing measured values relating to the reaction in the reactor vessels, said system comprising:

(a) a receiver for receiving the measured value associated with the contents of each of the plurality of reactor vessels during the course of the combinatorial chemical reaction;

(b) a storage media for storing during the course of the combinatorial chemical reaction the received measured values or experimental values calculated from the measured values; and

(c) a data analysis module for processing experimental data comprising at least one of the stored measured values or comprising an experimental value calculated from at least one of the measured values for use in screening at least one of the reactions or at least one of the materials used in the reactions with respect to said experimental data of another of the reactions.

34. The system of claim 33, wherein the data analysis module screens during the course of the combinatorial chemical reactions.

35. The system of claim 33, wherein said screening by the data analysis module comprises ranking said at least one of the reactions or at least one of the materials used in the reactions with respect to said experimental data of another of the reactions.

36. The system of claim 33, wherein the data analysis module calculates process variables from the stored measured values and/or calculates product variables from the stored measured values.

37. The system of claim 33 wherein the experimental data comprises at least one selected from the following group:

temperature, pressure, torque, power, mixing variables, stirring rate, motor speed, viscosity, reaction kinetics, reaction conversion, polymer concentration, polymer conversion, monomer conversion, percent conversion, molecular conversion, rate of conversion, rate of reaction, molecular weight particle size, stability and catalyst related parameters.

38. The system of claim 33 wherein the experimental data comprises viscosity measurements to screen or characterize dilute suspensions of insoluble particles.

39. The system of claim 33 further comprising a control controlling parameters of the reactor vessels and changing the parameters in response to the received measured values received by the receiver.

40. The system of claim 33 wherein the display displays a tabular representation of the received measured values, and wherein the tabular array and the graphical representation are simultaneously displayed.

41. A method of monitoring a combinatorial chemistry experiment during which a plurality of reactions are simultaneously occurring substantially independent of each other in a plurality of reactor vessels, respectively, each of the plurality of vessels having one or more sensors associated therewith providing measured values relating to the reaction in the reactor vessels, said method comprising:

(a) receiving the measured value associated with each of the plurality of reactor vessels during the course of the combinatorial chemical reaction;

(b) displaying or storing the received measured values or experimental values calculated from the measured values, and

(c) screening the reactions or materials used in the reactions by processing experimental data comprising the measured values or experimental values calculated from the measured values for use in screening at least one of the reactions or at least one of the materials used in the reactions with respect to said experimental data of another of the reactions.

42. The method of claim 41 wherein said screening occurs during the course of the combinatorial chemical reactions.

43. The method of claim 41 wherein said screening comprises ranking said at least one of the reactions or at least one of the materials used in the reactions with respect to said experimental data of another of the reactions.

44. The method of claim 41, wherein processing experimental data comprises calculating process variables from the stored measured values and/or calculating product variables from the stored measured values.

45. The method of claim 41, wherein the experimental data comprises at least one selected from the following group:

temperature, pressure, torque, power, mixing variables, stirring rate, motor speed, viscosity, reaction kinetics, reaction conversion, polymer concentration, polymer conversion, monomer conversion, percent conversion, molecular conversion, rate of conversion, rate of reaction, molecular weight, particle size, stability and catalyst related parameters.

46. The method of claim 41 wherein the experimental data comprises viscosity measurements to screen or characterize dilute suspensions of insoluble particles.