# High Throughput Screening of Pharmaceuticals Targeting Heart Cell Contractile Function

> **NIH NIH R44** · IONOPTIX, LLC · 2020 · $732,724

## Abstract

ABSTRACT
The overarching goal of this proposal is to produce a desktop instrument that will characterize the physiological state of
at least 10,000 cardiac myocytes per day. This represents roughly a 1,000-fold increase in cell throughput compared to
conventional technology. Substantial progress was made during Phase I of this project. We developed and have marketed
a platform that can routinely measure high temporal resolution sarcomere shortening under environmentally stable
conditions at over 1,000 cardiac myocytes per day. The major limitation of the current design developed in Phase I is that
cells are recorded sequentially, one at a time, plated on a single dish. In this Phase II proposal we aim to 1) substantially
increase cell throughput using rapid, parallel data acquisition and analysis of cells plated in a multi-well plate, 2) allow for
analysis of different tissue types, and 3) to automate robotic drug delivery and analyses that result in characterizing the
response of myocyte contractility, action potential and calcium regulation.
We will achieve a throughput goal of up to ~10,000 cells per day by recording from 3-5 cells simultaneously using video
imaging of both contractility and fluorescence, which indicates action potential or calcium regulation. The goal is to
characterize the physiological state of up to ~100 cells per well within each well of a 96 well plate in less than 4 hours.
Additionally, we aim to extend measurement tools to allow analysis of human induced pluripotent stem cell (hiPSC)-
derived cardiac myocytes in the form of monolayer preparations, embryonic bodies, and mechanically loaded
microtissues. The proposed Phase II system would be the first commercially available measuring the functional output of
these cell and tissue types in real time. This will help advance the field of personalized medicine and facilitate the use of
hiPSC-cardiomyocytes in disease modeling and drug testing.
Lastly, we propose to fully automate data collection and analyses. Sarcomeres within each cell will be automatically
identified and shortening-relaxation dynamics will be automatically characterized for physiological function. Similar
automated analyses would be performed for fluorescence, which would reflect action potential or calcium regulation
dynamics. These automated analyses will be more objective and more accurate than previously performed and will
eliminate potential experimenter bias.
Achieving these goals will greatly benefit efforts in: 1) basic research, enhancing our understanding of cardiac function as
population characteristics of cells can be described instead of relying on very small samples, 2) safety pharmacology,
allowing pre-clinical compounds to be more thoroughly tested before trials, and 3) most significantly, drug development,
enabling more compounds to be tested on both adult and hiPSC-cardiomyocytes during discovery.

## Key facts

- **NIH application ID:** 9996767
- **Project number:** 5R44HL137603-03
- **Recipient organization:** IONOPTIX, LLC
- **Principal Investigator:** BRADLEY M PALMER
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $732,724
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9996767

## Citation

> US National Institutes of Health, RePORTER application 9996767, High Throughput Screening of Pharmaceuticals Targeting Heart Cell Contractile Function (5R44HL137603-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9996767. Licensed CC0.

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