Topography and recognition imaging atomic force microscope and method of operation

摘要

A method of screening reagents (e.g. ligands) for binding to a particular target molecule comprises attaching the target molecule to the tip of a probe and scanning the surface of a sample containing at least one candidate reagent while oscillating said probe tip with a low mechanical Q factor (<20); using the extent of the downward displacement of said probe tip to control the height of the probe above the sample surface; and using the extent of the upward displacement of said probe tip to measure interactions between the target molecule and the candidate reagent. The tip displacement as a function of time may be used to determine the spatial location of recognition events by comparison to a predicted or recorded displacement pattern generated for the case when there is no recognition. Candidate reagents may be arranged in microtiter wells arrayed on a substrate. In this case, simultaneously recording both topographic images and the spatial location of interactions between the target molecule and the candidate reagents are recorded simultaneously such that recognition events are associated with specific wells.