Accuracy and Precision Limits of Concentration Sensing Using Nanopore Biosensors

Developing novel diagnostic methods with a deep understanding of their physical limitations can greatly improve the early detection of diseases like cancer. Nanopore-based single-molecule sensors are making rapid advances toward the development of novel diagnostic applications. In this study, the accuracy and precision of nanopore sensors are systematically evaluated by extending previous work on the sensing limits of single receptors in biological cells. A mathematical model is developed to evaluate the effect of measurement noise on the precision and accuracy of nanopore sensors. Two approaches are proposed for estimating concentrations from noisy nanopore data demonstrating an accuracy-precision trade-off that underscores a challenge in optimizing practical sensor performance. A surprising and counter-intuitive regime is also identified where even extensive signal averaging over long durations does not improve the concentration sensing accuracy. The insights from this study will be helpful in guiding nanopore-based quantitative biosensing applications.