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Principal Investigator: Corey Acker
Organization: POTENTIOMETRIC PROBES, LLC
Fiscal Year: 2024
Award: $282,266
Funding agency: National Heart Lung and Blood Institute
PROJECT SUMMARY/ABSTRACT POTENTIOMETRIC PROBES
The overall goal of this Phase I SBIR project is to expand the capabilities of tools, invented by the founders of
Potentiometric Probe, LLC, for high-fidelity optical recording of electrical activity in cardiac cells, tissues, and
whole hearts. Potentiometric Probes develops organic voltage-sensitive dyes (VSDs) that convert the changes
in voltage across cell membranes to visible changes in fluorescence. Instead of individual electrodes, this
technology enables the use of sensitive high-speed cameras, where each pixel can be considered an
electrode, for massively parallel high throughput screening, or for high-resolution spatiotemporal maps of
electrical signal propagation. Importantly, our VSDs are unique in enabling dual-wavelength ratiometric
recording of electrical activity; this is particularly important for cardiac studies because it eliminates
contraction-induced motion artifacts, permitting high-fidelity records of the action potential waveform. Human
stem cell-derived cardiomyocytes (hiPSC-CMs) are human skin or other cells that are “reprogrammed” to be
beating heart cells in a dish. These human cells and the tissues derived from them are increasingly being used
for research and development purposes, including screening new drugs for cardiotoxicity, and in the future may
be used for “personalized medicine” and the analysis of patient-derived cells. We believe high throughput
recording of accurate action potential waveforms from hiPSC-CMs and tissues will be a major market for the
proposed technology. While these cells beat spontaneously, pacing or stimulating these cells to beat at specific
frequencies is a critical part of screening protocols because electrical activity and the contribution of specific
ion channels is highly dependent on beat frequency. This external stimulation can be applied using light and
researchers have incorporated light-dependent channel rhodopsins to conveniently achieve the desired pacing.
However, it is crucial to separate the spectra of light used for optical voltage imaging and stimulation.
Preliminary work shows that a new chromophore developed at our company can extend the wavelength of our
VSDs to the near-infrared and allow them to be used to their full potential, including ratiometric imaging, in
concert with channel rhodopsins for pacing. In this proposal, Potentiometric Probes will synthesize a set of
near-infrared VSDs and will characterize their performance in cells including hiPSC-CMs. Ultimately, the
technology may allow much greater flexibility to researchers, enable multiplexed imaging experiments not
previously possible, and in the future may also be applied clinically for high-resolution imaging of action
potential propagation in the heart.
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