Dynamic Tracking Biosensors: Unconstrained Detection and Performance Limits

TL;DR

This paper introduces a novel dynamic tracking biosensor scheme that improves detection limits in molecular sensing by eliminating the need for prior reaction constant knowledge, supported by theoretical and simulation analyses.

Contribution

The work proposes an unconstrained detection method for DT biosensors, enabling easier parameter extraction and demonstrating significant performance improvements over traditional EP biosensors.

Findings

DT sensors outperform EP biosensors by several orders of magnitude

The scheme allows extraction of critical sensor parameters without prior knowledge

Theoretical and simulation results validate the performance gains

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.