# Optopatch:high-throughput all-optical electrophysiology

> **NIH NIH R44** · Q-STATE BIOSCIENCES, INC. · 2020 · $724,571

## Abstract

Project summary
Neurological disorders remain a major unmet medical need in the US and worldwide, accounting
for significant societal burden and loss of healthy years of life. One barrier to discovery of effective
therapeutics is the challenge of establishing scalable neurological disease models that effectively
translate to clinical outcomes. Q-State has developed a platform that can execute phenotypic
screens for genetically defined neurological diseases. Patient-derived induced pluripotent stem
cells (iPSCs) are differentiated into a variety of neuronal types, and the activity of these cells is
measured using optogenetic methods to stimulate and record electrical activity with single-cell
resolution. The Firefly microscope, developed through Phase I and II efforts, enables widefield
optical electrophysiology recordings of 100s of cells per well in a 96-well format, providing a
~10,000-fold increase in throughput relative to manual patch clamp. The throughput makes it
practical to find genetically defined disease phenotypes in iPSC-derived neurons and to run
screens for candidate therapeutics that rescue the disease phenotype.
In the Phase IIB application, Q-State will adapt these technologies into an integrated high-
throughput screening platform through four Aims. 1) We will build a 384-well compatible Firefly
instrument that will both decrease cost by 4-fold and increase throughput by 4-fold. 2) We will
implement a liquid handling system for automated differentiation, plating, and feeding of human
iPSC-derived neurons in a 384-well plate format. 3) We will establish a human neuronal disease
model for the genetically defined neurological disorder caused by dominant negative mutations in
KCNQ2, which encodes a voltage-gated potassium channel. And 4) we will apply this platform to
drug discovery by running a 14,000-compound screen for molecules that reverse the disease
phenotype. At the conclusion of this Phase IIB work, the platform will be fully validated for
executing affordable phenotypic drug screens and may generate chemical hits that can be
developed for treating KCNQ2 encephalopathy patients.

## Key facts

- **NIH application ID:** 9939705
- **Project number:** 5R44MH112474-06
- **Recipient organization:** Q-STATE BIOSCIENCES, INC.
- **Principal Investigator:** Graham Thomas Dempsey
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $724,571
- **Award type:** 5
- **Project period:** 2014-04-01 → 2021-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9939705

## Citation

> US National Institutes of Health, RePORTER application 9939705, Optopatch:high-throughput all-optical electrophysiology (5R44MH112474-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9939705. Licensed CC0.

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