High‐Precision Viral Detection Using Electrochemical Kinetic Profiling of Aptamer‐Antigen Recognition in Clinical Samples and Machine Learning
Payel Sen, Zijie Zhang, Sadman Sakib, Jimmy Gu, Wantong Li, Bal Ram Adhikari, Ariel Motsenyat, Jonathan L'Heureux‐Hache, Jann C. Ang, Gurpreet Panesar, Bruno J. Salena, Debora Yamamura, Matthew S. Miller, Yingfu Li, Leyla Soleymani
Abstract
High-precision viral detection at point of need with clinical samples plays a pivotal role in the diagnosis of infectious diseases and the control of a global pandemic. However, the complexity of clinical samples that often contain very low viral concentrations makes it a huge challenge to develop simple diagnostic devices that do not require any sample processing and yet are capable of meeting performance metrics such as very high sensitivity and specificity. Herein we describe a new single-pot and single-step electrochemical method that uses real-time kinetic profiling of the interaction between a high-affinity aptamer and an antigen on a viral surface. This method generates many data points per sample, which when combined with machine learning, can deliver highly accurate test results in a short testing time. We demonstrate this concept using both SARS-CoV-2 and Influenza A viruses as model viruses with specifically engineered high-affinity aptamers. Utilizing this technique to diagnose COVID-19 with 37 real human saliva samples results in a sensitivity and specificity of both 100 % (27 true negatives and 10 true positives, with 0 false negative and 0 false positive), which showcases the superb diagnostic precision of this method.