Hyperspectral Mapping for the Detection of SARS-CoV-2 Using Nanomolecular Probes with Yoctomole Sensitivity

Efficient monitoring of SARS-CoV-2 outbreak requires the use of a sensitive and rapid diagnostic test. Although SARS-CoV-2 RNA can be detected by RT-qPCR, the molecular-level quantification of the viral load is still challenging, time-consuming, and labor-intensive. Here, we report an ultrasensitive hyperspectral sensor (HyperSENSE) based on hafnium nanoparticles (HfNPs) for specific detection of COVID-19 causative virus, SARS-CoV-2. Density functional theoretical calculations reveal that HfNPs exhibit higher changes in their absorption wavelength and light scattering when bound to their target SARS-CoV-2 RNA sequence relative to the gold nanoparticles. The assay has a turnaround time of a few seconds and has a limit of detection in the yoctomolar range, which is 1 000 000-fold times higher than the currently available COVID-19 tests. We demonstrated in ∼100 COVID-19 clinical samples that the assay is highly sensitive and has a specificity of 100%. We also show that HyperSENSE can rapidly detect other viruses such as influenza A H1N1. The outstanding sensitivity indicates the potential of the current biosensor in detecting the prevailing presymptomatic and asymptomatic COVID-19 cases. Thus, integrating hyperspectral imaging with nanomaterials establishes a diagnostic platform for ultrasensitive detection of COVID-19 that can potentially be applied to any emerging infectious pathogen.