# Functional drug fingerprinting with all-optical electrophysiology

> **NIH NIH R43** · Q-STATE BIOSCIENCES, INC. · 2020 · $434,945

## Abstract

Project Summary
Functional drug fingerprinting with all-optical electrophysiology
The Optopatch platform recently developed at Q-State Biosciences, which uses engineered
optogenetic proteins, custom microscopes, and software, makes it possible to simultaneously
stimulate (blue light) and record (red light) electrical activity from ~100 neurons with 1 millisecond
temporal resolution, single-cell spatial resolution and high signal-to-noise ratio. The Optopatch
assays can record hundreds of parameters characterizing intrinsic excitability and neuronal
function in both rodent and human induced pluripotent stem cell-derived neurons.
Using these tools, we propose to develop a “drug fingerprint” database, where we characterize
the impact of a library of drugs and tool compounds on neuronal excitability. The database will
capture the unique functional effects of each compound and represent them as vectors in a
reduced dimensionality fingerprinting space. The database can be leveraged in several ways in
both internal programs and with pharma partners:
 1) Identification of targets of hits from a phenotypic screen. – Phenotypic screening offers the
 advantage of testing compounds in a disease-relevant cell type or animal model but has the
 disadvantage of not knowing the target(s) of effect. Target ID is essential information for de-
 risking the drug discovery process and matching the hits’ functional effects to the drug
 fingerprint database can accelerate or augment standard target identification approaches.
 2) Rapid identification of therapies in personalized medicine. – Q-State is expanding capabilities
 to identify therapeutic approaches for patients with severe genetic disorders who have a short
 life expectancy. Optopatch has identified functional deficits in neurons derived from individual
 patients relative to healthy controls, and we hope the drug fingerprint database can be used
 to expedite and focus therapy selection to those with high potential to correct the problem.
 This obviates the need to screen and entire drug library in patient neurons; requiring only the
 most promising compounds to be tested and saving time for a patient where time is limited.
In this proposal, we first assemble the library and build the drug fingerprint database. We then
test the two applications. Fidelity of target identification is tested using compounds with known
targets, and the ability to identify phenotype-reversing drugs is tested using cell lines and
phenotypes already established at Q-State. The tools developed will be a permanent asset and
should catalyze the development of new therapeutics.

## Key facts

- **NIH application ID:** 10023196
- **Project number:** 5R43MH122052-02
- **Recipient organization:** Q-STATE BIOSCIENCES, INC.
- **Principal Investigator:** Nathaniel Delaney-Busch
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $434,945
- **Award type:** 5
- **Project period:** 2019-09-20 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10023196

## Citation

> US National Institutes of Health, RePORTER application 10023196, Functional drug fingerprinting with all-optical electrophysiology (5R43MH122052-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10023196. Licensed CC0.

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