Teaching an old dog new tricks: a lipid membrane-based electric immunosensor for real-time probing of the spike S1 protein subunit from SARS-CoV-2.

Asandei, Alina; Mereuta, Loredana; Schiopu, Irina; Park, Yoonkyung; Luchian, Tudor

Fast, cheap and easy to implement point-of-care testing for various pathogens constituted a game changer in past years due to its potential for early disease diagnosis. Herein, we report on the proof-of-concept of a simple method enabling in-vitro detection of a structural spike protein subunit from the SARS-CoV-2 (S1 ) in aqueous samples. At the core of this discovery lies the well-known paradigm of monitoring the capacitive current across a reconstituted zwitterionic lipid membrane subjected to a periodic transmembrane potential, followed by the real-time spectral analysis enabling the extraction of the second harmonic of the capacitive current. Subsequent changes in the amplitude of this harmonic recorded during lipid membrane-S1 interactions were correlated with alterations induced in the inner membrane potential profile by the S1 protein subunit adsorption, and were shown to be augmented by ionic strength, the presence of a specific monoclonal antibody designed against the S1 subunit and the angiotensin-converting enzyme 2 protein receptor (ACE2), and uninhibited by the presence of other human serum proteins. This article is protected by copyright. All rights reserved.