Parallel reactor with sensing of internal properties

• US 7,288,229 B2
• Filed: 05/08/2001
• Issued: 10/30/2007
• Est. Priority Date: 08/13/1998
• Status: Expired due to Fees

• Current Assignee: Unchained Labs Inc.
• Original Assignee: Symyx Technologies Incorporated (Dassault Systemes SA)
• Inventors: Turner, Howard, Dales, G. Cameron, van Beek, Johannes A. M., VanErden, Lynn
• Primary Examiner(s): Soderquist; Arlen
• Application Number:
  US09/850,916
• Publication Number:
  US 20010034064A1
• Time in Patent Office: 2,366 Days
• Field of Search: 422/62, 422/93, 422/102, 422/104, 422130-131, 422196-197, 422/138, 422/109, 422/129, 436/37, 436/147, 436/159, 436/161, 436/164, 436172-173, 436/85, 436/43, 366/118, 366/198, 366272-274, 366213-214, 366244-254, 366297-298, 366282-283, 366291-292, 366/301
• US Class Current: 422/130
• 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

An apparatus and method for carrying out and monitoring the progress and properties of multiple reactions is 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.

Claims

1. Apparatus for parallel processing of reaction mixtures, comprising:

a plurality of vessels sealed against fluid communication with one another, adapted for holding reaction mixtures for processing, and adapted for pressurization of the vessels to pressures other than ambient pressure;

a stirring system for stirring the reaction mixtures in the vessels, said stirring system comprising stirrers at least partially contained in said vessels;

a drive mechanism positioned below the vessels and coupled to the stirrers for rotating the stirrers independently of one another within the vessels, said drive mechanism comprising a plurality of motors individually coupled to respective stirrers to rotate said stirrers;

a temperature control system operable to maintain the vessels at selected temperatures independent of one another whereby different vessels may simultaneously be maintained at different temperatures during said parallel processing; and

torque monitors for measuring torque exerted by the motors on the reaction mixtures, wherein the motors are rigidly attached to a motor support, and the torque monitors measure torque between the motor support and the motors.

2. Apparatus for parallel processing of reaction mixtures, comprising:

a plurality of vessels sealed against fluid communication with one another, adapted for holding reaction mixtures for processing, and adapted for pressurization of the vessels to pressures other than ambient pressure;

a stirring system for stirring the reaction mixtures in the vessels, said stirring system comprising stirrers at least partially contained in said vessels;

a drive mechanism positioned below the vessels and coupled to the stirrers for rotating the stirrers independently of one another within the vessels, said drive mechanism comprising a plurality of motors individually coupled to respective stirrers to rotate said stirrers;

a temperature control system operable to maintain the vessels at selected temperatures independent of one another whereby different vessels may simultaneously be maintained at different temperatures during said parallel processing; and

speed sensors for monitoring rotational speed of the stirrers.

3. Apparatus as set forth in claim 2 further comprising a processor in communication with the speed sensors, wherein the processor adjusts power supplied to each of the motors in response to signals received from the speed sensors to control the rotational speeds of the respective stirrers.

4. Apparatus as set forth in claim 3 wherein said processor adjusts the power supplied to each of the motors to maintain the rotational speeds of the respective stirrers at selected levels.

5. A method of processing reaction mixtures in parallel, comprising:

providing reaction mixtures in a plurality of vessels sealed against fluid communication with one another;

stirring the reaction mixtures in the vessels by rotating stirrers at least partially contained in the vessels at selected speeds independent of one another during said parallel processing using a drive mechanism positioned below the vessels and coupled to the stirrers;

maintaining the vessels at selected temperatures independent of one another during said parallel processing; and

monitoring the stirring speed of each stirrer.

6. A method as set forth in claim 5 further comprising monitoring the torque needed to rotate the stirrers.

7. A method as set forth in claim 6 wherein the torque is monitored by measuring a phase lag between the application of a driving force to the stirrers and the speed of the stirrers.

8. A method as set forth in claim 6 further comprising independently varying the torque of the stirrers.

9. A method of processing reaction mixtures in parallel comprising:

providing reaction mixtures in a plurality of vessels sealed against fluid communication with one another;

stirring the reaction mixtures in the vessels by rotating stirrers at least partially contained in the vessels using a drive mechanism positioned below the vessels and coupled to the stirrers and independently varying the speed, or torque, or speed and torque of the stirrers; and

maintaining the vessels at selected temperatures independent of one another during said parallel processing.

10. A method as set forth in claim 9 further comprising monitoring the power needed to rotate each of the stirrers.

11. A method as set forth in claim 10 further comprising adjusting the power supplied to each of the stirrers.