Dynamic Tracking Biosensors: Unconstrained Detection and Performance Limits

Abstract

Accurate detection of target molecules at low concentrations in the presence of a high concentration of undesired molecules is a major challenge for End Point (EP) assays. Non-specific binding of undesired molecules to receptors limits the minimum detectable concentration of the target significantly. Dynamic tracking (DT) of binding and unbinding events allows us to overcome this challenge and provides a remarkable improvement in the minimum detectable target concentration, as demonstrated recently. In this manuscript, we propose a novel unconstrained detection scheme which does not rely on a priori knowledge of the reaction constants. This scheme allows facile back extraction of various critical sensor parameters as well. Further, through a combination of theoretical analysis and detailed statistical simulations, we show that DT sensors could be several orders of magnitude better than $EP$ biosensors. This work identifies and establishes the functional dependence of critical parameters on the performance of DT sensors and hence could be of broad interest to the community towards further optimization.