Non-PCR Ultrasensitive Detection of Viral RNA by a Nanoprobe-Coupling Strategy: SARS-CoV-2 as an Example

Developing efficient and highly sensitive diagnostic techniques for early detections of pathogenic viruses such as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is vitally important for preventing its widespread. However, the conventional polymerase chain reaction (PCR)-based detection features high complexity, excessive time-consumption, and labor-intensiveness, while viral protein-based detections suffer from moderate sensitivity and specificity. Here, a non-PCR but ultrasensitive viral RNA detection strategy is reported based on a facile nanoprobe-coupling strategy without enzymatic amplification, wherein PCR-induced bias and other shortcomings are successfully circumvented. This approach endows the viral RNA detection with ultra-low background to maximum signal ratio in the linear signal amplification by using Au nanoparticles as reporters. The present strategy exhibits 100% specificity toward SARS-CoV-2 N gene, and ultrasensitive detection of as low as 52 cp mL⁻¹ of SARS-CoV-2 N gene without pre-PCR amplification. This approach presents a novel ultrasensitive tool for viral RNA detections for fighting against COVID-19 and other types of pathogenic virus-caused diseases.