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

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.

Magnetite Nanoparticles in Magnetic Hyperthermia and Cancer Therapies: Challenges and Perspectives

“…Currently nanoparticles are tested in various fields such as catalysis [ 16 , 17 ], energy storage [ 18 ], energy conversion [ 19 , 20 ], and optoelectronic, for example, as light-emitting diodes [ 21 ]. In the case of the biomedical applications, NPs are tested not only as anticancer agents, which will be discussed later in this paper but also as antibacterial agents (for example in form of the layers on medical implants) [ 22 , 23 ], and sensitive tests to detect various diseases [ 24 , 25 ]. Generally, this wide application range is related to their unique properties and highly reactive surface.…”

Ultra-Fast and Sensitive Screening for Antibodies against the SARS-CoV-2 S1 Spike Antigen with a Portable Bioelectric Biosensor

“…In addition, it should be said tools become available as portable or handheld devices tailor-made for home testing, a considerable milestone would be achieved in supporting individual strategies and decisions regarding social distancing and revaccination. Novel materials such as molecularly imprinted polymer nanoparticles can be utilized to increase test sensitivity and the ability to withstand harsh environmental conditions [47].…”

A Molecularly Imprinted Polymer-Based Thermal Sensor for the Selective Detection of Melamine in Milk Samples

“…To develop viable sensors, MIPs need to be combined with a readout technology that is capable of converting binding events at the receptor surface into a quantifiable signal, while operating in complex media. The heat-transfer method (HTM) [ 31 ] can detect temperature changes across a solid–liquid interface, allowing for various targets, ranging from small molecules to bacteria, and, more recently, viral antigens for COVID-19 diagnosis [ 32 , 33 , 34 , 35 , 36 ]. In short, when the target solution is introduced into the flow cell, MIP particles bind to the analyte, resulting in a thermal change at the interface.…”