Method and apparatus for producing position addressable combinatorial libraries
OwnerPeter J. Dehlingerinventor
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Abstract
Method and apparatus for producing combinatorial position-addressable libraries of different-sequence oligomers or different-substituent small molecule compounds are disclosed. The method employs massive parallel synthesis by stepwise subunit addition or substituent addition in a dense capillary-tube array. The libraries allow high throughput screening of library compounds in either solid phase or solution phase, and position-related identification of active library compounds.
Claims12
A method of producing a position-addressable combinatorial library of different-sequence oligomer or different-substitiuent small molecule compounds, comprising the steps of:
- (i) identifying, in an array of capillary tubes, a selected subset of tubes into which a selected one of a plurality of different chemical reagents in a reagent solution is to be introduced, and a complementary subset of remaining tubes in the array,
- (ii) selectively plugging a tube end of each capillary tube in said complementary subset,
- (iii) placing ends of the tubes in said array in contact with said solution, under conditions effective to draw solution into the unplugged tubes only,
- (iv) allowing the solution in the tubes in the selected subset to react with a wall portion of each tube on which a library compound is being formed,
- (v) unplugging the plugged tubes, and
- (vi) repeating steps (i)-(v) for different subsets of tubes and reagent solutions until said library is produced in said tubes.
Apparatus for producing a position-addressable combinatorial library of different-sequence oligomer or different-substituent small molecule compounds in an array of capillary tubes, comprising
- (i) means for selectively plugging each tube end in a subset of tubes which is complementary to a selected subset of tubes in said array,
- (ii) means for drawing a selected reagent solution into unplugged tubes in the selected subset of tubes in the array, thereby to effect a compound-addition reaction directly on the inner surface of tubes in the selected subset;
- (iii) means for removing the reagent solution from the tubes in the selected subset after said reaction, and for unplugging the tubes in the complementary subset, and
- (iv) means for repeating the steps performed by elements (i)-(iii) until a desired library of compounds, one library compound in each tube, is produced.
Dependencies are inferred from the claim text.