Fig. 4: Clinical performance validation.

Clinical samples include COVID-19 patients (n = 42) and healthy controls (n = 20). We included low-viral patient samples (Ct ≥ 30, n = 20: 48%) to observe the enhancement in the case of low viral load. We performed the clinical test for each patient once (n = 1). a–f Sensitivity enhancement with BEETLES² using (a) NP/OP samples, (b) saliva samples, (c) Delta variants, d Omicron variants, (e) samples from asymptomatic individuals, and (f) healthy controls. g–i Diagnostic accuracy of BEETLES², including all the samples of NP/OP, saliva, asymptomatic, and various variants, shows that the overall sensitivity of BEETLES² is significantly higher (88.1%) (P < 0.0001) than those using commercial LFA (14.29%) (P = 0.0041). Two-sided unpaired t-test was used for analysis and adjustments were not made for multiple comparisons. j Cross-reactivity using different respiratory viruses showing no cross-reactivity. k RT-qPCR with enrichment with AAO only and BEETLES², showing that BEETLES² can enhance molecular diagnostics even with VTM. l–n The feasibility of daily monitoring of COVID-19 represents the ability of frequent tests with significantly higher accuracy. With BEETLES², we measured the Ct value over 37. Error bars represent standard deviation from the mean. VTM viral transport medium, BEETLES² bioengineered enrichment tools for the LFA with enhanced sensitivity and specificity, AAO anodic aluminum oxide, LFA lateral flow assay, NP/OP nasopharyngeal/oropharyngeal.