Liver‐on‐a‐Chip Integrated with Label‐Free Optical Biosensors for Rapid and Continuous Monitoring of Drug‐Induced Toxicity

Abstract Drug toxicity assays using conventional 2D static cultures and animal studies have limitations preventing the translation of potential drugs to the clinic. The recent development of organs‐on‐a‐chip platforms provides promising alternatives for drug toxicity/screening assays. However, most studies conducted with these platforms only utilize single endpoint results, which do not provide real‐time/ near real‐time information. Here, a versatile technology is presented that integrates a 3D liver‐on‐a‐chip with a label‐free photonic crystal‐total internal reflection (PC‐TIR) biosensor for rapid and continuous monitoring of the status of cells. This technology can detect drug‐induced liver toxicity by continuously monitoring the secretion rates and levels of albumin and glutathione S‐transferase α (GST‐α) of a 3D liver on‐a‐chip model treated with Doxorubicin. The PC‐TIR biosensor is based on a one‐step antibody functionalization with high specificity and a detection range of 21.7 ng mL −1 to 7.83 x 10 3 ng mL −1 for albumin and 2.20 ng mL −1 to 7.94 x 10 2 ng mL −1 for GST‐α. This approach provides critical advantages for the early detection of drug toxicity and improved temporal resolution to capture transient drug effects. The proposed proof‐of‐concept study introduces a scalable and efficient plug‐in solution for organ‐on‐a‐chip technologies, advancing drug development and in vitro testing methods by enabling timely and accurate toxicity assessments.