Toward Personalized Immunotherapeutic Drug Monitoring with Multiplexed Extended‐Gate Field‐Effect‐Transistor Biosensors

The selection and optimization of therapies for cancer patients urgently need personalization. Portable point-of-care electronic biosensors emerge as a groundbreaking solution contributing to better decision-making in precision oncology. In this study, the innovative use of extended-gate field-effect-transistor (EG-FET) biosensors is showcased for monitoring the concentration and pharmacokinetics of immunotherapeutic drugs in vivo. Complementary positron emission tomography and radioactivity biodistribution studies in mice validate the EG-FET measurements. Herein, a novel indirect assay format is also introduced for detecting target modules (TMs) in an adapter chimeric antigen receptor T-cell therapy model, effectively addressing the current limitations of potentiometric measurements. In pharmacokinetic evaluations, the EG-FET biosensor performance aligns with standard radioactivity measurements, revealing the distinct lifespans of small-sized single-chain-fragment-variable-derived TMs (15 min) and larger IgG4-derived TMs (14 h). Advantageously, the EG-FET sensors exhibit exceptional sensitivity and fulfill the requirements for immunotherapeutic drug monitoring without complex radioactive labeling, which is indispensable. In these promising findings, the exploration of next-generation electronic biosensors as therapeutic monitoring tools is advocated for. With their cost, size, and response time advantages, these biosensors hold immense potential for advancing personalized oncology, transcending the conventional diagnostic roles typically highlighted in the literature.