Systems and methods for rapidly identifying useful chemicals in liquid samples

• US 6,468,800 B1
• Filed: 04/21/1999
• Issued: 10/22/2002
• Est. Priority Date: 05/16/1997
• Status: Expired due to Term

• Current Assignee: Aurora Biotechnologies, Inc. (Azenta, Inc.)
• Original Assignee: Vertex Pharmaceuticals San Diego LLC (Vertex Pharmaceuticals Incorporated)
• Inventors: Beckey, Samuel S., Coassin, Peter J., Stylli, Chari, Shumate, Christopher Bentley
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): WRIGHT, PATRICIA KATHRYN
• Application Number:
  US09/296,436
• Time in Patent Office: 1,280 Days
• Field of Search: 422/63, 422/65, 422/67, 422/68.1, 422/82.05, 422/82.08, 422/100, 422/104, 436/43, 436/47, 436/48, 436/164, 436/180, 435/288.3, 435/288.7, 702/22
• US Class Current: 436/43
• CPC Class Codes: B01J 19/00 Chemical, physical or physico-chemical processes in general; Their relevant apparatus
• 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 2219/00011 Laboratory-scale plants
• CPC Class Codes: B01J 2219/00315 Microtiter plates
• CPC Class Codes: B01J 2219/00328 Movement by linear translation
• 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 2219/007 Simulation or vitual synthesis
• CPC Class Codes: B01J 2219/00702 Processes involving means for analysing and characterising the products
• CPC Class Codes: B01J 2219/00707 separated from the reactor apparatus
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2300/0893 having a very large number of wells, microfabricated wells
• CPC Class Codes: B01L 9/52 Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips
• CPC Class Codes: B01L 9/523 for multisample carriers, e.g. used for microtitration plates
• CPC Class Codes: C40B 60/14 for creating libraries
• CPC Class Codes: G01N 2035/00326 Analysers with modular structure
• CPC Class Codes: G01N 2035/042 moved independently, e.g. by fork manipulator
• CPC Class Codes: G01N 2035/0422 carried on a linear conveyor
• CPC Class Codes: G01N 2035/0425 Stacks, magazines or elevators for plates
• CPC Class Codes: G01N 35/0099 comprising robots or similar manipulators robots per se B25J
• CPC Class Codes: G01N 35/028 : having reaction cells in the form of microtitration plates
• CPC Class Codes: G01N 35/1002 : Reagent dispensers
• CPC Class Codes: G01N 35/1074 : arranged in a two-dimensional array
• CPC Class Codes: Y10T 436/11 : Automated chemical analysis
• CPC Class Codes: Y10T 436/110833 : Utilizing a moving indicator strip or tape
• CPC Class Codes: Y10T 436/113332 : with conveyance of sample along a test line in a container or rack
• CPC Class Codes: Y10T 436/114165 : with step of insertion or removal from test line
• CPC Class Codes: Y10T 436/114998 : with treatment or replacement of aspirator element [e.g., cleaning, etc.]
• CPC Class Codes: Y10T 436/25 : including sample preparation
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

The present invention provides for systems and methods that utilize automated and integratable workstations for identifying chemicals having useful activity. The present invention is also directed to chemical entities and information (e.g., chemical or biological activities of chemicals) generated or discovered by operation of workstations of the present invention. The present invention includes automated workstations that are programmably controlled to minimize processing times at each workstation and that can be integrated to minimize the processing time of the liquid samples from the start to finish of the process.

Claims

1. A database comprising chemical activity data for computational analysis of chemical structure and activity against targets, comprising data of the activity of discrete drug candidate compounds, said data stored on a computer readable storage media, and said data generated by using a method of screening drug candidate compounds for activity, said method comprising:

storing a set of drug candidate compounds in addressable wells;

programming a chemical storage and retrieval module containing said drug candidate compounds for the selection of a subset of said drug candidate compounds;

removing said subset of said addressable chemical wells from sad chemical storage module with an automated robotic retriever;

delivering said removed subset of addressable chemical wells to an automated transport pathway;

delivering said removed subset of addressable chemical wells to an automated liquid handler;

retrieving said programmed subset of drug candidate compounds with said liquid handler by retrieving compounds from less than all, of said removed subset of addressable chemical wells;

screening said selected subset of drug candidate compounds for activity; and

generating data related to the result of said screening.

2. The database of claim 1, said method additionally comprising returning said selected subset of chemical compounds to said addressable chemical storage and retrieval module via said automated transport pathway.

3. The database of claim 1, wherein said removing comprises retrieving said selected set of chemical compounds in a first order of selection, and wherein said step of delivering said selected subset of drug candidate compounds to said automated liquid handler comprises delivering said subset of drug candidate compounds in a second order of selection different from said first order of selection.

4. The database of claim 3, wherein said removing and delivering comprises retrieving and delivering multi-well plates containing said subset of chemical compounds.

5. The database of claim 4, said method additionally comprising stacking said multi-well plates prior to delivering said multi-well plates.

6. The database of claim 1, wherein said transport pathway comprises at least two parallel lanes;

and wherein at least one of said lanes is configured to provide bidirectional transport of said chemical compounds.

7. A method of making a database of chemical activity data comprising:

storing a set of drug candidate compounds in addressable wells;

programming a chemical storage and retrieval module containing said drug candidate compounds for the selection of a subset of said drug candidate compounds;

removing said subset of said addressable chemical wells from sad chemical storage module with an automated robotic retriever;

delivering said removed subset of addressable chemical wells to an automated transport pathway;

delivering said removed subset of addressable chemical wells to an automated liquid handler;

retrieving said programmed subset of drug candidate compounds with said liquid handler by retrieving compounds from less than all, of said removed subset of addressable chemical wells;

screening said selected subset of drug candidate compounds for activity;

generating data related to the result of said screening; and

storing said activity data collected by said reaction module on a computer readable storage medium.

8. The method of claim 7, wherein said transport pathway comprises at least two parallel lanes;

and wherein at least one of said lanes is configured to provide bidirectional transport of said chemical compounds.