Lipid Membrane-Coated Nanopipettes for Enhanced Resistive Pulse Sensing of Exosomes

We report the use of lipid membrane-coated quartz nanopipettes to enhance exosome detection via resistive pulse sensing. By exploiting the self-assembly and compositional versatility of lipid molecules, nanopipettes were functionalized with lipid membranes comprising neutral and cationic lipids, with or without cholesterol, to modulate surface charge and membrane viscosity. Using bovine milk-derived exosomes as a model system, we demonstrate a marked improvement in capture rate and a reduction in nonspecific adsorption. This improvement further enabled statistical analysis of translocation times and signal amplitudes, providing significant insights into the interactions between exosomes and lipid membranes during nanopore passage under an applied electric field.