Methods and apparatus for synthesizing labeled combinatorial chemistrylibraries

• US 5,770,455 A
• Filed: 06/07/1995
• Issued: 06/23/1998
• Est. Priority Date: 07/19/1993
• Status: Expired

• Current Assignee: NEXUS Biosystems, Inc. (Azenta, Inc.)
• Original Assignee: Ontogen Corporation (Infinity Pharmaceuticals, Inc.)
• Inventors: Cargill, John, Armstrong, Robert W.
• Primary Examiner(s): ACHUTAMURTHY, PONNATHAPURA N
• Application Number:
  US08/480,438
• Time in Patent Office: 1,112 Days
• Field of Search: 436/518, 436/523, 436/524, 436/525, 436/526, 436/527, 436/528, 530/334, 530/335
• US Class Current: 506/20
• 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 pre-encoded substrate useful for being linked to a single oligomer structure whereby said pre-encoded substrate bears a unique identifier, said tag being a pre-encoded microchip identifying said oligomer structure.

3. One or a plurality of the pre-encoded substrate of claim 1 useful for in a method of preparing a labeled synthetic oligomer library comprising a plurality of different members, each member comprising a distinct pre-encoded substrate whereby said one or plurality of pre-encoded substrate is linked to a oligomer structure said method comprising the steps of:

a) apportioning said pre-encoded substrates among a plurality of reaction vessels;

b) exposing said pre-encoded substrates in each reaction vessel to one or a plurality of transformation events;

c) detecting and recording identifier information for each of said identifier tags in each of said reaction vessels;

d) apportioning said pre-encoded substrates among a plurality of reaction vessels; and

e) repeating steps a) through c) from at least one to about twenty times wherein said preencoded substrate being a pre-encoded microchip.

5. One or a plurality of the pre-encoded substrate of claim 1 useful in a method of preparing a labeled synthetic oligomer library comprising a plurality of different members, each member comprising a distinct pre-encoded substrate whereby said one or plurality of pre-encoded substrate is linked to a oligomer structure said method comprising the steps of:

a) apportioning said pre-encoded substrates among a plurality of reaction vessels;

b) exposing said pre-encoded substrates in each reaction vessel to one or a plurality of monomers;

c) detecting and recording identifier information for each of said identifier tags in each of said reaction vessels;

d) apportioning said pre-encoded substrates among a plurality of reaction vessels; and

e) repeating steps a) through c) from at least one to about twenty times wherein said pre-encoded substrate being a pre-encoded microchip.

2. An encodable substrate useful for being linked to a single oligomer structure whereby said encodable substrate has a unique identifier, said tag being a encodable microchip identifying said oligomer structure.

4. One or a plurality of the encodable substrate of claim 2 useful in a method of preparing a labeled synthetic oligomer library comprising a plurality of different members, each member comprising a distinct encodable substrate whereby said one or plurality of pre-encoded substrate a oligomer structure is linked to a oligomer structure said method comprising the steps of:

a) apportioning said encodable substrates among a plurality of reaction vessels;

b) exposing said encodable substrates in each reaction vessels to one or a plurality of transformation events;

c) adding first identifier information to said encodable substrates;

d) apportioning said encodable substrates among a plurality of reaction vessels; and

e) repeating steps a) through c) from at least one to about twenty times wherein said encodable substrate being a encodable microchip.

6. One or a plurality of the encodable substrate of claim 2 useful in a method of preparing a labeled synthetic oligomer library comprising a plurality of different members, each member comprising a distinct encodable substrate whereby said one or plurality of pre-encoded substrate a oligomer structure is linked to a oligomer structure said method comprising the steps of:

a) apportioning said encodable substrates among a plurality of reaction vessels;

b) exposing said encodable substrates in each reaction vessels to one or a plurality of monomers;

c) adding first identifier information to said encodable substrates;

d) apportioning said encodable substrates among a plurality of reaction vessels; and

e) repeating steps a) through c) from at least one to about twenty times wherein said encodable substrate being a encodable microchip.