Molecularly Imprinted Polymer Nanoparticles Enable Rapid, Reliable, and Robust Point-of-Care Thermal Detection of SARS-CoV-2

Rapid antigen tests are currently used for population screening of COVID-19. However, they lack sensitivityand utilize antibodies as receptors, which can only function innarrow temperature and pH ranges. Consequently, molecularlyimprinted polymer nanoparticles (nanoMIPs) are synthetized witha fast (2 h) and scalable process using merely a tiny SARS-CoV-2fragment (similar to 10 amino acids). The nanoMIPs rival the affinity ofSARS-CoV-2 antibodies under standard testing conditions andsurpass them at elevated temperatures or in acidic media. Therefore, nanoMIP sensors possess clear advantages over antibody-basedassays as they can function in various challenging media. A thermal assay is developed with nanoMIPs electrografted onto screen-printed electrodes to accurately quantify SARS-CoV-2 antigens. Heat transfer-based measurements demonstrate superior detectionlimits compared to commercial rapid antigen tests and most antigen tests from the literature for both the alpha (similar to 9.9 fg mL-1) anddelta (similar to 6.1 fg mL-1) variants of the spike protein. A prototype assay is developed, which can rapidly (similar to 15 min) validate clinicalpatient samples with excellent sensitivity and specificity. The straightforward epitope imprinting method and high robustness of nanoMIPs produce a SARS-CoV-2 sensor with significant commercial potential for population screening, in addition to the possibility of measurements in diagnostically challenging environments

Automated summary

Rapid antigen tests are commonly used for COVID-19 population screening, but they have low sensitivity and limited functionality in different conditions. This study presents a new approach using molecularly imprinted polymer nanoparticles (nanoMIPs) as receptors for SARS-CoV-2 antigens. The nanoMIPs exhibit high affinity and can function in challenging environments. A thermal assay with nanoMIPs is developed, which enables accurate measurement of SARS-CoV-2 antigens with low detection limits and rapid validation of clinical patient samples.