The current outbreak of the pandemic coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) demands its rapid, convenient, and large-scale diagnosis to downregulate its spread within as well as across the communities. Here, we report an ultrasensitive and rapid hyperspectral sensor, known as HyperSENSE for specific diagnosis of COVID-19 causative virus, SARS-CoV-2. Senor platform-based Hafnium nanoparticles (HfNPs) were fabricated and integrated with a hyperspectral imaging setup to detect the presence of SARS-CoV-2 in real-time. Hyperspectral-based imaging techniques possess the ability to capture spectral information for multiple wavelengths at each pixel in an image. This unique capability offers the ability to discriminate, with precision, different nanomaterials and differentiate them from biological materials. Hafnium nanoparticles (AuNPs) capped antisense oligonucleotides (ASO) have been used as a recognition probe. Successful fabrication of the platform was verified using TEM, Raman, FT-IR, and DFI. Additionally, the performance of the sensor was validated using ~100 clinical samples collected from positive and negative COVID-19 patients. The selectivity of the sensor has been tested using a scrambled RNA load, SARS-CoV, and MERS-CoV sample. The applicability of the test has been further expanded for the multiplex detection of SARS-CoV-2 and differentiating it from Influenza. The HyperSENSE assay has a turnaround time of few minutes and has a detection limit that can reach 0.06 copies/L, which is 1000,000-fold time higher than those available COVID-19 tests. This extraordinarily low LOD indicates the potential of the current biosensor in detecting the prevailing pre-symptomatic and asymptomatic COVID-19 cases with a broad linear detection range from 0.06 copies/L to 10<sup>10</sup> copies/L. Utilizing HfNPs was found to amplify the sensor response compared to the commonly used AuNPs, eventually leading to higher sensitivity. The sensor exhibits a high selectivity toward SARS-CoV-2 with no noticeable change has been observed as a response to scrambled RNA extracted from the Vero cell, SARS-CoV, or MERS-CoV samples. The sensor exhibits 100% accuracy, sensitivity, and specificity when evaluated using 100 COVID-19 clinical samples. Finally, the multiplex HyperSENSE platform was successful in differentiating SARS-CoV-2 from the regular Influenzas.

Nanosensor-based hafnium nanoparticles for the detection of SARS-CoV-2 with yoctomole sensitivity

ACS Spring 2022

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