Label-Free FET Based Biosensor for Detection of Engineered CAR T-Cells at Single Cell Resolution

Abstract

Immunotherapy has revolutionized cancer treatment, with Chimeric Antigen Receptor (CAR) T-cell therapy emerging as a highly effective approach for, e.g., hematological malignancies. However, the complexity of this living drug necessitates efficient methods to ensure the identity of the engineered cells during manufacturing and post-infusion therapy monitoring. In this study, a proof-of-concept is presented using a silicon nanowire field-effect transistor (SiNW FET) nanosensing platform capable of label-free, real-time identification and quantification of CAR T-cells at single-cell resolution. The nanosensor's functionalized surface mimics tumor antigens, enabling selective interaction with CAR-expressing cells. This platform demonstrates exceptional specificity by distinguishing CAR T-cells from wild-type T-cells and quantifying cell populations with ultrasensitivity. These results establish the SiNW FET nanosensing platform as a promising tool for streamlining CAR T-cell manufacturing and post-treatment monitoring, improving quality assurance, and advancing clinical applications in immunotherapy.