Tether particle biosensor with different capture molecules for detection of switching events

摘要

A method for biosensing a target substance (110) uses a group of particles (104) connected to a surface (100) by tether particles (102). The first capture molecule (106) is bound to the particle (104) or tether molecule. The second capture molecule (108) is bound to a surface or tether molecule. The first capture molecule binds to the target substance (110) and is selected to have a first off-rate, and the second capture molecule binds to the target substance and has a first off-rate rate. Have been selected to have a second target off-rate that is at least three times different. A time series of the spatial coordinate parameters of the particles is detected, and a time series of individual binding / dissociation events of the target substance with the capture molecule is identified in the detected time series. Each event corresponds to a change between the binding state of the first capture molecule to the target substance and the binding state of the second capture molecule. The concentration of the target substance is determined from the identified time series of each event. [Selection diagram] FIG. 1A