Quantum dot-FRET systems for imaging of neuronal action potentials

Fluorescent semiconductor quantum dots (QDs) can act as energy donors or acceptors with a wide variety of environmentally-sensitive molecules. Conjugation of a single QD to a select number of the selected molecule can optimize the range of sensitivity for a given application, and the relatively large size of the QDs allows them to be tracked individually in cells. Using QDs as FRET acceptors, we have created first-generation sensors for membrane potential which shows good signal to noise and time resolution, but prohibitive toxicity. The challenges of delivery, calibration, and toxicity and plans for improvement of the sensors are presented, in the context of the eventual aim of monitoring membrane potential in a cultured motor neuron model of amyotrophic lateral sclerosis.