Molecularly imprinted polymer nanoparticles enable rapid, reliable, and robust point-of-care thermal detection of SARS-CoV-2

McClements, J, Bar, L, Singla, P, Canfarotta, F, Thomson, A, Czulak, J, Johnson, RE, Crapnell, RD, Banks, CE, Payne, B, Seyedin, S, Losada-Pérez, P and Peeters, M (2022) Molecularly imprinted polymer nanoparticles enable rapid, reliable, and robust point-of-care thermal detection of SARS-CoV-2. ACS Sensors, 7 (4). pp. 1122-1131. ISSN 2379-3694

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Abstract

Rapid antigen tests are currently used for population screening of COVID-19. However, they lack sensitivity and utilize antibodies as receptors, which can only function in narrow temperature and pH ranges. Consequently, molecularly imprinted polymer nanoparticles (nanoMIPs) are synthetized with a fast (2 h) and scalable process using merely a tiny SARS-CoV-2 fragment (∼10 amino acids). The nanoMIPs rival the affinity of SARS-CoV-2 antibodies under standard testing conditions and surpass them at elevated temperatures or in acidic media. Therefore, nanoMIP sensors possess clear advantages over antibody-based assays 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 detection limits compared to commercial rapid antigen tests and most antigen tests from the literature for both the alpha (∼9.9 fg mL-1) and delta (∼6.1 fg mL-1) variants of the spike protein. A prototype assay is developed, which can rapidly (∼15 min) validate clinical patient 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.