Autonomous Uncertainty Quantification for Computational Point-of-Care Sensors.

Computational point-of-care (POC) sensors enable rapid, low-cost, and accessible diagnostics in emergency, remote, and resource-limited areas that lack access to centralized medical facilities. These systems can use neural network-based algorithms to accurately infer diagnoses from signals generated by rapid diagnostic tests or sensors. However, neural network-based diagnostic models are subject to hallucinations and can produce erroneous predictions, posing a risk of misdiagnosis and inaccurate clinical decisions. To address this challenge, here we present an autonomous uncertainty quantification technique developed for POC diagnostics. As our test bed, we used a paper-based, computational vertical flow assay (xVFA) platform developed for rapid POC diagnosis of Lyme disease, the most prevalent tick-borne disease globally. The xVFA platform integrates a disposable paper-based assay, a hand-held optical reader, and a neural network-based inference algorithm, providing rapid and cost-effective Lyme disease diagnostics in under 20 min using only 20 μL of patient serum. By incorporating a Monte Carlo dropout (MCDO)-based uncertainty quantification approach into the diagnostics pipeline with minimal computational and memory overhead, we identified and excluded erroneous predictions with high uncertainty, significantly improving the sensitivity and reliability of the xVFA in an autonomous manner, without access to the ground truth diagnostic information on patients. Blinded testing using new patient samples demonstrated an increase in diagnostic sensitivity from 88.2% to 95.7%, indicating the effectiveness of MCDO-based uncertainty quantification in enhancing the robustness of neural network-driven computational POC sensing systems.