Electrical and Label-Free Detection of T-Cell Activation Against COVID-19: A Method Towards Point-of-Care Monitoring of Immune System

Abstract

Despite great progress in biotechnology, COVID19 has revealed the inadequacy of current healthcare technologies to contain an infectious outbreak, specifically in rapid infection recognition to facilitate containment. Wide deployment of testing methods such as viral RNA (antigen) PCR and antibody detection have provided some relief in this regard; however, current technologies still require many hours to provide results. Thus, there remains a critical need for fast, sensitive, low-cost point-of-care (POC) biosensing assays to report on the infection status and immunity of patients. Emerging data on the importance of T-cell responses in generating long-term immunity against COVID19 has highlighted T-cell activation detection as a potential way for real-time monitoring native and acquired immunity. However, current approaches for T-cell stimulation monitoring are complex, laborious, time-consuming, and costly.Here we provide proof-of-principle experiments which indicate that an electrical and label-free detection method based on CMOS-compatible silicon nanowire ion-selective field-effect transistors (SNW-ISFET) can act as a fast, sensitive, reliable, and low-cost approach to monitor T-cell response to pathogens such COVID-19. This technology enables direct detection of COVID-19-specific T-cells directly from patient blood, with potential utility as a POC diagnostic device. Detection of antigen-specific T-cell activation from clonal human T-cells lines utilizing CD8-restricted peptide-MHC complexes has been demonstrated using SNW-ISFET devices. The cell concentration was varied to achieve a clear understanding about the device sensitivity, detection limit, and reliability (Figure 1). SNW-ISFET structures were applied to detect T-cell activation in clonal T-cell lines and whole peripheral blood mononuclear cell (PBMC) with multiple cell concentrations (Figure 2). Reference experiments were applied to ensure the device reliability and sensing mechanism (Figure 3). These findings show that SNW-FETs platform are promising candidates for antigen-specific T-cell activation detection from whole blood. Figure 1