Methods and apparatus for synthesizing labeled combinatorial chemistry libraries

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.

1. A labeled synthetic oligomer library comprising a plurality of different members each member comprising an oligomer linked to an identifier which is a microchip encoded with information identifying the structure of said oligomer. 
     
     
       2. The library of  claim 1  wherein said identifier tag is retained within a frame or housing and said oligomer is attached to a synthesis support, which synthesis support is also retained within said frame or housing. 
     
     
       3. The library of  claim 1  that has from about 100 to about 250,000 members. 
     
     
       4. The library of  claim 1 , wherein said oligomers are structurally related analogues having a common core structure. 
     
     
       5. The library of  claim 1  wherein said oligomers are selected from the group consisting of: benzodiazepine, β-lactam, hydantoin, quinone, hydroquinone, terpene, carbohydrate, polypeptide and polynucleotide. 
     
     
       6. The library of  claim 1  wherein said identifier tag relates information back to a detector when pulsed with electromagnetic radiation. 
     
     
       7. The library of  claim 6  wherein said identifier tag is selected from the group consisting of: encodable microchip and pre-encoded microchip. 
     
     
       8. The library of  claim 7  wherein said encodable microchip is a TIRIS™ and said pre-encoded microchip is an ELAM™. 
     
     
       9. The library of  claim 1  wherein:
 i. the library has from about 100 to about 250,000 members;  
 ii. said oligomers are structurally related analogues having a common core structure; and  
 iii. the identifier tag is selected from the group consisting of: pre-encoded microchip and encodable microchip.  
 
     
     
       10. A labeled synthetic oligomer library produced by synthesizing on each of a plurality of pre-encoded substrates, each of which has a unique identifier tag, which is a microchip encoded with information, a single oligomer structure obtained by a 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.  
 
     
     
       11. The library of  claim 10 , wherein said oligomer is attached to a synthesis support and said pre-encoded substrate comprises a frame or housing retaining said identifier tag which is a microchip encoded with information and said oligomer. 
     
     
       12. The library of  claim 10 , wherein at least one transformation event is a stepwise or concerted enzymatic or chemical addition of one or a plurality of monomers. 
     
     
       13. The library of  claim 10 , wherein said oligomers are structurally related analogues having a common core structure. 
     
     
       14. The library of  claim 10 , wherein said oligomers are selected from the group consisting of: benzodiazepine, β-lactam, hydantoin, quinone, hydroquinone, terpene, carbohydrate, polypeptide and polynucleotide. 
     
     
       15. The library of  claim 10 , wherein said oligomer is cleaved from said pre-encoded substrate after completion of oligomer synthesis. 
     
     
       16. A labeled synthetic oligomer library produced by synthesizing on each of a plurality of encodable substrates each of which contains a microchip encoded with information, a single oligomer structure obtained by a method comprising the steps of:
 a) apportioning said encodable substrates among a plurality of reaction vessels;  
 b) exposing said encodable substrates in each reaction vessel to one or a plurality of transformation events;  
 c) adding 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.  
 
     
     
       17. The library of  claim 16 , wherein said oligomer is attached to a synthesis support and said pre-encoded substrate comprises a frame or housing retaining said identifier tag and said oligomer. 
     
     
       18. The library of  claim 16 , wherein at least one transformation event is a stepwise or concerted enzymatic or chemical addition of one or a plurality of monomers. 
     
     
       19. The library of  claim 16 , wherein said oligomers are structurally related analogues having a common core structure. 
     
     
       20. The library of  claim 16 , wherein said oligomers are selected from the group consisting of: benzodiazepine, β-lactam, hydantoin, quinone, hydroquinone, terpene, carbohydrate, polypeptide and polynucleotide. 
     
     
       21. The library of  claim 16 , wherein said oligomer is cleaved from said pre-encoded substrate after completion of oligomer synthesis. 
     
     
       22. The library of  claim 16 , wherein said encodable substrate is blank prior to synthesis of a labeled oligomer library, and wherein each transformation event in a series of transformation events in the synthesis of a labeled oligomer library is recorded by adding identifier information to said encodable substrate in conjunction with each transformation event. 
     
     
       23. The library of  claim 16 , wherein said encodable substrate is encoded with a partial identifier information prior to synthesis, and wherein each transformation event in a series of transformation events in the synthesis of a labeled oligomer library is recorded by adding identifier information to said encodable substrate in conjunction with each transformation event. 
     
     
       24. A method of preparing a labelled  labeled synthetic oligomer library comprising a plurality of different members, each member comprising a pre-encoded substrate linked to a single oligomer structure and bearing a unique identifier tag which is a microchip encoded with information identifying said 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.  
 
     
     
       25. A method of preparing a labeled synthetic oligomer library comprising a plurality of different members, each member comprising an encodable substrate linked to a single oligomer structure and having a unique identifier tag which is a microchip encoded with information identifying said 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 vessel 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.  
 
     
     
       26. The method of  claim 24  wherein said encodable substrate is blank prior to synthesis of a labeled oligomer library, and wherein each transformation event in a series of transformation events in the synthesis of a labeled oligomer library is recorded by adding identifier information to said encodable substrate in conjunction with each transformation event. 
     
     
       27. The method of  claim 25 , wherein said encodable substrate is encoded with a partial identifier information prior to synthesis, and wherein each transformation event in a series of transformation events in the synthesis of a labeled oligomer library is recorded by adding identifier information to said encodable substrate in conjunction with each transformation event. 
     
     
       28. The method of  claim 25 , wherein said encodable substrate is an encodable microchip. 
     
     
       29. The method of  claim 24 , wherein said pre-encoded substrate is a pre-encoded microchip. 
     
     
       30. A labeled synthetic oligomer library produced by synthesizing on each of a plurality of pre-encoded substrates, each of which has a unique identifier tag which is a microchip encoded with information, a single oligomer structure obtained by a 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.  
 
     
     
       31. The library of  claim 30 , wherein said oligomer is attached to a synthesis support and said pre-encoded substrate comprises a frame or housing retaining said identifier tag and said oligomer. 
     
     
       32. The library of  claim 30 , wherein said oligomers are formed by the concerted addition of one or a plurality of monomers. 
     
     
       33. The library of  claim 30 , wherein said oligomers are structurally related analogues having a common core structure. 
     
     
       34. The library of  claim 30 , wherein said oligomers are selected from the group consisting of: benzodiazepine, β-lactam, hydantoin, quinone, hydroquinone, terpene, carbohydrate, polypeptide and polynucleotide. 
     
     
       35. The library of  claim 30 , wherein said oligomer is cleaved from said pre-encoded substrate after completion of oligomer synthesis. 
     
     
       36. A labeled synthetic oligomer library produced by synthesizing on each of a plurality of encodable substrates each of which has a unique identifier tag which is a microchip encodable with information, a single oligomer structure obtained by a method comprising the steps of:
 a) apportioning said encodable substrates among a plurality of reaction vessels;  
 b) exposing said encodable substrates in each reaction vessel to one or a plurality of monomers;  
 c) adding 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.  
 
     
     
       37. The library of  claim 36 , wherein said oligomer is attached to a synthesis support and said pre-encoded substrate comprises a frame or housing retaining said identifier tag and said oligomer. 
     
     
       38. The library of  claim 36 , wherein said oligomers are formed by the concerted addition of one or a plurality of monomers. 
     
     
       39. The library of  claim 36 , wherein said oligomers are structurally related analogues having a common core structure. 
     
     
       40. The library of  claim 36 , wherein said oligomers are selected from the group consisting of: benzodiazepine, β-lactam, hydantoin, quinone, hydroquinone, terpene, carbohydrate, polypeptide and polynucleotide. 
     
     
       41. The library of  claim 36 , wherein said oligomer is cleaved from said pre-encoded substrate after completion of oligomer synthesis. 
     
     
       42. The library of  claim 36 , wherein said encodable substrate is blank prior to synthesis of a labeled oligomer library, and wherein each step in a series of oligomer monomer additions in the synthesis of a labeled oligomer library is recorded by adding identifier information to said encodable substrate in conjunction with the addition of monomers. 
     
     
       43. The library of  claim 36 , wherein said encodable substrate is encoded with a partial identifier information prior to synthesis, and wherein each step in a series of oligomer monomer additions in the synthesis of a labeled oligomer library is recorded by adding identifier information to said encodable substrate in conjunction with the addition monomers. 
     
     
       44. A method of preparing a labelled  labeled synthetic oligomer library comprising a plurality of different members, each member comprising a pre-encoded substrate linked to a single oligomer structure and bearing a unique identifier tag which is a microchip encoded with information identifying said 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.  
 
     
     
       45. A method of preparing a labeled synthetic oligomer library comprising a plurality of different members, each member comprising an encodable substrate linked to a single oligomer structure and having a unique identifier tag which is a microchip encoded with information identifying said 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 vessel 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.  
 
     
     
       46. The method of  claim 45  wherein said encodable substrate is blank prior to synthesis of a labeled oligomer library, and wherein each step in a sequence of oligomer monomer additions in the synthesis of a labeled oligomer library is recorded by adding identifier information to said encodable substrate in conjunction with the addition of each monomer. 
     
     
       47. The method of  claim 45 , wherein said encodable substrate is encoded with a partial identifier information prior to synthesis, and wherein each step in a sequence of oligomer monomer additions in the synthesis of a labeled oligomer library is recorded by adding identifier information to said encodable substrate in conjunction with the addition of each monomer. 
     
     
       48. The method of  claim 44 , wherein said pre-encoded substrate is a pre-encoded microchip. 
     
     
       49. The method of  claim 45 , wherein said encodable substrate is an encodable microchip.