Direct clone analysis and selection technology

摘要

The present invention describes a spatial addressing technique that uses a very high-density micro-pore array for high-throughput screening of biological interactions. The therapeutic, diagnostic and drug-discovery implications of being able to identify, select and characterize specific protein-protein, protein-DNA and/or protein-carbohydrate interactions from heterogeneous populations of millions (to billions) of cells is discussed. Importantly, this technique possesses the screening and selection capacity of current display-based screening systems (i.e., millions-billions) but with greater efficiency and shorter time.

主权项

1. A method for identifying a sub-population of at least one biological cell from a heterogeneous population of biological cells, said method comprising:
a) contacting the heterogeneous population of biological cells with a solid substrate attached to at least one binding partner such that a sub-population comprising at least one of said biological cells settles into at least one micro-pores of an array of micro-pores, the array comprising a plurality of longitudinally fused fibers each having opposed openings and an internal diameter in a range of between approximately 1.0 micrometers and 500 micrometers, the fibers being reversibly attached to the solid substrate; b) incubating said array under conditions to promote the secretion of molecules from said biological cells; c) detecting desired secreted molecules in association with said at least one binding partner on the solid substrate; and d) sealing a polymeric film to the longitudinally fused fibers and positioning at least one hole in the film over at least one longitudinally fused fiber containing the sub-population of at least one cell secreting desired molecules, and removing the longitudinally fused fiber array from the solid substrate, to thereby identify said sub-population of at least one cell.