Developing and commercializing inorganic voltage sensing nanoparticles

This DAPPA SBIR proposal will develop a new class of voltage-sensing probes, type-II semiconductor nanorods with asymmetric band structure, to assay the bioelectrical states of human cells.Our previous study has demonstrated that nanorods can self-insert into the cell membrane and optically and non-invasively record action potentials (AP) at the single particle level. These nanoparticles, operating via the Quantum-Confined Stark Effect (QCSE), could offer unique advantages for AP recording, including: (1)much higher voltage sensitivity than conventional voltage-sensing dyes or fluorescent proteins; (2) exceptional brightness enabling single-molecule detection; (3) a large spectral shift as function of voltage; (4) a very fast (nanosecond) response; (5) do not bleach; (6) have very large Stokes shifts; (7) large two-photon cross sections; (8) excellent performance in the NIR; (9) superresolution imaging; and (10) able to be used at very low concentration.. In this phase II project, we will further optimize the structure of the voltage-sensing nanorod to achieve large QCSE; improve the surface coating of vsNRs for high efficient cell membrane insertion; and develop a voltage recording method.In our phase II option, we will study target-specific voltage sensing and finalize the voltage sensing probe and assay.