A High-Throughput Screening Platform for Drug-Induced Physicochemical Perturbations in Multidimensional Model...

We developed a microfluidic high-throughput screening (HTS) platform for continuous, in situ physicochemical profiling of model lipid membranes, overcoming the limitations of traditional low-throughput methods. By integrating gradient mixing with in-line spectroscopy, the system enables dynamically programmable liposome synthesis across a broad landscape and simultaneous analysis of the membrane interfacial environment (GP₃₄₀) and hydrophobic core fluidity (r_DPH). We applied this platform to analyze model drug (bupivacaine hydrochloride)-induced perturbations in ternary model membranes. This approach generated 786 composition-resolved physicochemical data points within a single day, enabling high-density mapping of drug-induced membrane perturbations. Therefore, it enables lipid membrane analysis and high-resolution mapping and serves as a platform for composition-resolved analysis of physicochemical perturbations induced by membrane-active compounds.