Ultrasensitive and Selective Detection of SARS-CoV-2 Using Thermotropic Liquid Crystals and Image-Based Machine Learning

Rapid, robust virus-detection techniques with ultrahigh sensitivity and selectivity are required for the outbreak of the pandemic coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Here, we report that the femtomolar concentrations of single-stranded ribonucleic acid (ssRNA) of SARS-CoV-2 trigger ordering transitions in liquid crystal (LC) films decorated with cationic surfactant and complementary 15-mer single-stranded deoxyribonucleic acid (ssDNA) probe. More importantly, the sensitivity of the LC to the SARS ssRNA, with a 3-bp mismatch compared to the SARS-CoV-2 ssRNA, is measured to decrease by seven orders of magnitude, suggesting that the LC ordering transitions depend strongly on the targeted oligonucleotide sequence. Finally, we design a LC-based diagnostic kit and a smartphone-based application (app) to enable automatic detection of SARS-CoV-2 ssRNA, which could be used for reliable self-test of SARS-CoV-2 at home without the need for complex equipment or procedures.