Methods and apparatus for synthesizing labeled combinatorial chemistry libraries

• US 6,417,010 B1
• Filed: 03/03/1999
• Issued: 07/09/2002
• Est. Priority Date: 07/16/1993
• Status: Expired

• Current Assignee: NEXUS Biosystems, Inc. (Azenta, Inc.)
• Original Assignee: Discovery Partners International, Inc. (Infinity Pharmaceuticals, Inc.)
• Inventors: Cargill, John, Armstrong, Robert W.
• Primary Examiner(s): Ponnaluri, Padmashri
• Application Number:
  US09/261,718
• Time in Patent Office: 1,224 Days
• Field of Search: 436/518, 436/524, 436/523, 436/525, 436/526, 436/527, 436/528, 530/334, 530/335, 435/6, 435/7.1, 435/7.2, 435/DIG.2, 435/DIG.9, 435/DIG.14, 435/DIG.21, 435/DIG.49, 435/DIG.29, 435/DIG.34, 536/24.33, 536/24.37, 235/439, 340/572.1, 340/825.72, 455/92, 343/720
• US Class Current: 506/31
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• 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 2219/00281 Individual reactor vessels
• CPC Class Codes: B01J 2219/00308 interchangeably mounted in racks or blocks
• CPC Class Codes: B01J 2219/00351 Means for dispensing and evacuation of reagents
• CPC Class Codes: B01J 2219/00463 Directed sorting
• CPC Class Codes: B01J 2219/00497 Features relating to the solid phase supports
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00502 Particles of irregular geometry
• CPC Class Codes: B01J 2219/00504 Pins
• CPC Class Codes: B01J 2219/0054 Means for coding or tagging the apparatus or the reagents
• CPC Class Codes: B01J 2219/00545 Colours
• CPC Class Codes: B01J 2219/00547 Bar codes
• CPC Class Codes: B01J 2219/00549 2-dimensional
• CPC Class Codes: B01J 2219/00554 Physical means
• CPC Class Codes: B01J 2219/00563 Magnetic means
• CPC Class Codes: B01J 2219/00565 Electromagnetic means
• CPC Class Codes: B01J 2219/00567 Transponder chips
• CPC Class Codes: B01J 2219/00572 Chemical means
• CPC Class Codes: B01J 2219/00585 : Parallel processes
• CPC Class Codes: B01J 2219/0059 : Sequential processes
• CPC Class Codes: B01J 2219/00592 : Split-and-pool, mix-and-divide processes
• CPC Class Codes: B01J 2219/00596 : Solid-phase processes
• CPC Class Codes: B01J 2219/00659 : Two-dimensional arrays
• CPC Class Codes: B01J 2219/00686 : Automatic
• CPC Class Codes: B01J 2219/00689 : using computers
• CPC Class Codes: B01J 2219/0072 : Organic compounds
• CPC Class Codes: B01J 2219/00722 : Nucleotides
• CPC Class Codes: B01J 2219/00725 : Peptides
• CPC Class Codes: B01J 2219/00731 : Saccharides
• CPC Class Codes: C07B 43/06 : of amide groups
• CPC Class Codes: C07K 1/047 : Simultaneous synthesis of different peptide species; Peptide libraries
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 40/10 : Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: C40B 40/12 : Libraries containing saccharides or polysaccharides, or derivatives thereof
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: C40B 70/00 : Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or bar codes
• CPC Class Codes: G01N 33/532 : Production of labelled immunochemicals
• CPC Class Codes: G01N 33/54373 : involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: G01N 33/552 : Glass or silica
• CPC Class Codes: G01N 33/553 : Metal or metal coated

Abstract

The present invention provides labeled synthetic libraries of random oligomers and methods and apparatus for generating labeled synthetic oligomer libraries. Each member of such a library is labeled with a unique identifier tag that specifies the structure or sequence of the oligomer. In a preferred embodiment of the present invention the identifier tag is a microchip that is pre-encoded or encodable with information that is related back to a detector when the identifier tag is pulsed with electromagnetic radiation.

Claims

1. A device for tracking synthesis of a library member of a combinatorial library, the device comprising:

a synthesis support having a surface adapted for linking to a first monomer;

an identifier tag disposed within or linked to the synthesis support, the identifier tag comprising encoded information readable by a radiofrequency scanner or barcode scanner that is unique to the synthesis support and means for scanning the identifier tag, wherein, when a first monomer is linked to the synthesis support, the first monomer and any oligomer synthesized using the first monomer is identified.

2. The device of claim 1 wherein the identifier tag comprises a microchip having an electronic memory within which is stored unique electronic information.

3. The device of claim 2 wherein the microchip comprises means for receiving and transmitting a radiofrequency signal.

4. The device of claim 2, wherein the microchip is encodable for recording synthesis information during synthesis of the library member.

5. The device of claim 4, wherein the synthesis information comprises descriptions of synthesis steps.

6. The device of claim 2, wherein the microchip is pre-encoded with an identification of the synthesis support.

7. The device of claim 2, wherein the microchip is encased in a glass or polymeric material.

8. The device of claim 7, wherein the polymeric material is derivatized with a functional group or linker.

9. The device of claim 8, wherein the polymeric material is selected from the group consisting of polystyrene-divinyl benzene, polyethylene-grafted polystyrene, polyacrylamide kieselguhr composite, and controlled pore glass.

10. The device of claim 8, wherein the linker is cleavable by a reaction selected from the group consisting of thermal, photochemical, electrochemical, oxidative, and reductive reactions.

11. The device of claim 3, wherein the microchip is powered by the radiofrequency signal.

12. The device of claim 2, wherein the unique electronic information is digitally encoded.

13. The device of claim 2, wherein the synthesis support is in a form selected from the group consisting of pellets, disks, capillaries, hollow fibers, solid fibers, cellulose beads, pore-glass beads, silica gels, polystyrene beads, grafted co-poly beads, poly-acrylimide beads, latex beads, dimethylacrylamide beads, and glass particles.

14. The device of claim 2, wherein the first monomer is linked to the synthesis support by a linker comprising a spacer residue.

15. The device of claim 1, wherein the identifier tag comprises a bar code having unique information.

16. The device of claim 15, wherein the bar code is capable of receiving sequential synthesis information.

17. The device in claim 16, wherein the synthesis information comprises descriptions of synthesis steps.

18. The device of claim 15, wherein the barcode is pre-encoded with the identity of the synthesis support.

19. The device of claim 15, wherein the barcode is encased in a glass or polymeric material.

20. The device of claim 19, wherein the polymeric material is derivatized with a functional group or linker.

21. The device of claim 20, wherein the polymeric material is selected from the group consisting of polystyrene-divinyl benzene, polyethelene-grafted polystyrene, polyacrylamide kieselguhr composite, and controlled pore glass.

22. The device of claim 20, wherein the linker is cleavable by a reaction selected from the group consisting of thermal, photochemical, electrochemical, oxidative, and reductive reactions.