Internalized Liquid Crystal Microcapsules for pH Sensing in Living Single Cells

Liquid crystal (LC) materials provide a unique sensing platform because their long-range molecular order is highly sensitive to interfacial physicochemical changes. However, most LC-based systems operate at extracellular interfaces, limiting their applicability for intracellular analysis in living cells. Here, we report cell-internalized liquid crystal microcapsules for configuration-based monitoring of local intracellular pH-responsive changes. The sensing platform, denoted M-E7PBA, consists of an E7 liquid crystal core doped with pentyl biphenyl carboxylic acid (PBA) and encapsulated within a polyelectrolyte shell via layer-by-layer self-assembly. Protonation of PBA modulates interfacial anchoring, inducing a reversible radial-bipolar transition of the LC director that can be directly visualized under polarized optical microscopy. This interfacial transduction mechanism enables optical detection of pH variations over a physiologically relevant range (5.8-7.8) with a resolution of 0.1 pH units. Importantly, microfluidic control enables efficient and reproducible internalization of the LC microcapsules, allowing intracellular LC optical measurements at the single-cell level. Using this platform, vincristine-induced intracellular acidification in HeLa cells was monitored in real time. These results establish a microfluidic-enabled LC-based analytical strategy for probing intracellular biochemical dynamics in living cells.