High-stringency screening of target-binding partners using a microfluidic device

摘要

The invention provides a method of screening a library of candidate agents by contacting the library with a target in a reaction mixture under a condition of high stringency, wherein the target includes a tag that responds to a controllable force applied to the tag, and passing the members of the library through a microfluidic device in a manner that exposes the library members to the controllable force, thereby displacing members of the library that are bound to the target relative to their unbound counterparts. Kits and systems for use with the methods of the invention are also provided.

主权项

1. A method of screening a library, the method comprising:
contacting a library of candidate agents with a target in a reaction mixture under a condition of high stringency, wherein the condition of high stringency includes providing in the reaction mixture a total number of target molecules that is at least three orders of magnitude less than the total number of library members, wherein said library of candidate agents comprises at least 1,000 chemically distinct species, and wherein said target comprises a magnetic tag that responds to a controllable magnetic field applied to said magnetic tag; and passing the members of the library through a microfluidic device in a manner that exposes said members to said controllable magnetic field, wherein members of the library of candidate agents that are bound to the target are displaced relative to their unbound counterparts, and wherein the application of the controllable magnetic field provides for a partition efficiency which is greater than 106.