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

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 103 ng mL-1 for albumin and 2.20 ng mL-1 to 7.94 x 102 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.

Characterizing Conformational Change of a Thermoresponsive Polymeric Nanoparticle with Raman Spectroscopy.

Molecular conformational changes in the collapsing and reswelling processes occurring during the phase transition at the lower critical solution temperature (LCST) of the polymer are not well understood. In this study, we characterized the conformational change of Poly(oligo(Ethylene Glycol) Methyl Ether Methacrylate)-144 (POEGMA-144) synthesized on silica nanoparticles using Raman spectroscopy and zeta potential measurements. Changes in distinct Raman peaks associated with the oligo(Ethylene Glycol) (OEG) side chains (1023, 1320, and 1499 cm-1) with respect to the methyl methacrylate (MMA) backbone (1608 cm-1) were observed and investigated under increasing and decreasing temperature profiles (34 °C to 50 °C) to evaluate the polymer collapse and reswelling around its LCST (42 °C). In contrast to the zeta potential measurements that monitor the change in surface charges as a whole during the phase transition, Raman spectroscopy provided more detailed information on vibrational modes of individual molecular moieties of the polymer in responding to the conformational change.