Inorganic Voltage Nanosensors

We have been developing targetable voltage sensing inorganic nanoparticles (vsNPs) that are designed to self-insert into the cell membrane and non-invasively optically record, via the quantum confined Stark effect, action potential on the single-particle level, at multi-sites and in a large field-of-view. We synthesized a library of vsNPs with different compositions and developed a high-throughput screen for optimization of their performance. We have explored several strategies for imparting these vsNPs with membrane-protein-like properties, including functionalization with libraries of peptides, lipids, and nanodiscs. We have developed screening assays for improving the efficiency of vsNPs’ membrane insertion and for their voltage sensitivity once embedded in the membrane. We have demonstrated membrane voltage sensing by membrane-inserted vsNPs in WT HEK cells using valinomycin and modulated concentration of potassium ions in a microfluidic chamber, and by patch-clamped in primary cultured cortical neurons. These novel voltage nansensors hold great promise for electrophysiological investigations of the nervous system.