# Ultra-high-throughput plate reader for drug discovery using all-optical electrophysiology

> **NIH NIH R44** · Q-STATE BIOSCIENCES, INC. · 2022 · $475,561

## Abstract

Project Summary:
Ultra-high-throughput plate reader for drug discovery using all-optical electrophysiology
Neurological disorders remain a major unmet medical need in the United States and worldwide, accounting for
more than 10% of the total years of healthy life lost in developed countries. Drug discovery for diseases of the
nervous system has been challenging in comparison with other disease areas. A major barrier to progress in
neuroscience drug discovery is the lack of translatable assays, models, and technologies that can be used to
predict human efficacy with both the information content and throughput needed for rapid identification and
optimization of therapeutic candidates. As such, there is a strong commercial need for scalable assay and
instrument platforms that can be leveraged throughout the CNS-based drug screening and discovery pipeline.
The Swarm microscope, developed through Phase I and Phase II efforts, leverages Q-State’s proprietary
Optopatch technology, enabling the recording of both voltage and calcium activity under optical stimulation from
24-objectives simultaneously. Our instrument has the potential to transform high-throughput screening (HTS) by
leveraging our advanced optogenetics tools in 96-, 384-, and 1536-well plate formats. The instrument was
successfully used to screen Q-State’s 200,000 internal compound library against Nav1.7, a genetically validated
target for pain, on our Spiking HEK cell assay demonstrating the utility of the Swarm for CNS-based therapeutic
discovery.
In this Phase IIB application, Q-State will leverage these technologies and expertise towards full
commercialization by building the next generation Swarm 2.0 platform with significantly improved functionality,
throughput, and stability. First, we will develop a camera-based Swarm 2.0 instrument with upgraded illumination,
stimulation, and detection subassemblies and pair these capabilities with new analysis tools. Next, we will
develop two differentiating Swarm 2.0 compatible optogenetic classes of assays: 1) target-based HEK cell
assays for voltage-gated Na channels, representing a major class of drug targets for CNS disorders, and 2)
intact, native cell assays in neurons, enabling critical bridging secondary assays for therapeutic discovery. After
the instrument is constructed and validated, we will optimize Nav1.8, a drug target for pain indications currently
pursued by the pharmaceutical industry, and secondary multiplexed spiking HEK assays for HTS compatibility
on the platform. Finally, we will perform a screening campaign using an in-house library of approximately 200,000
small molecules for inhibitors of Nav1.8 followed by the hit confirmation and selectivity counter-screens. At the
conclusion of this Phase IIB work, the Swarm 2.0 platform will be fully validated for commercialization, generating
chemical hits that can be optimized for pain therapeutics and more broadly by enabling execution of HTS
compound screens with the potential fo...

## Key facts

- **NIH application ID:** 10385256
- **Project number:** 9R44NS125689-04
- **Recipient organization:** Q-STATE BIOSCIENCES, INC.
- **Principal Investigator:** Graham Thomas Dempsey
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $475,561
- **Award type:** 9
- **Project period:** 2022-09-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10385256

## Citation

> US National Institutes of Health, RePORTER application 10385256, Ultra-high-throughput plate reader for drug discovery using all-optical electrophysiology (9R44NS125689-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10385256. Licensed CC0.

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