# HLS-Development of a cardiac ischemia model in an organ-on-a-chip platform

> **NIH NIH R44** · HESPEROS, LLC · 2023 · $854,765

## Abstract

Project Summary
Our overall strategy for Hesperos is to utilize microphysiological systems in combination with functional readouts
to establish platforms capable of sophisticated analysis of chemicals and drug candidates for toxicity and efficacy
during pre-clinical testing, with initial emphasis on predictive toxicity. This is a service based company and is
developing low-cost in vitro systems utilizing a novel “pumpless” microphysiological platform described in US
Patent 8,748,180B2. The commercialization potential of our system has been validated by the award of a Phase
IIB SBIR to apply advanced manufacturing techniques to increase output and lower cost of production. The
pumpless integrated system, using a rocking motion to pump the serum-free cellular medium, reduces the
complexity and cost of the fluidic circuit design and simplifies set-up and operation of the device. Hickman has
developed microelectrode arrays and cantilever systems that are integrated on chip for noninvasive electronic
and mechanical readouts. We have detailed an in vitro cardiac system where the two main components of
function, electrical conduction and muscle force, have been reproduced in vitro. The independent measurement
of these two key variables allows a detailed description of a compound’s effect on overall cardiac function and
is currently being used under contract by multiple companies. Because we can measure these functional outputs
independently, we can also use these readouts to give ideas on mechanism of action of a compound. We have
adapted this chip based system into a platform for testing cardiac ischemia and reperfusion as published in APL
Bioengineering that demonstrated an investigational compound effectively reduced ischemia/reperfusion
damage in vitro. The human iPSC cardiac cells used in this device were shown to reach some aspects of
functional maturation as primarily evidenced by patch clamp electrophysiological measurements indicating
resting membrane potentials of -85 mV or better. We will expand this system by integrating a hemodynamic
module of vascular smooth muscle cells and microvascular endothelial cells with the microfluidic system and
develop continuous monitoring instrumentation. This cardiac organ-on-a-chip platform will be validated by
screening compounds that act either directly on the cardiac cells or affect hemodynamics, and will be used to
screen investigational compounds from our pharma partners. A microphysiological system will be developed with
continuous readouts for smooth muscle cell contraction, cardiac electrical and mechanical function, fitted with
environmental sensors, and integrated with an environmental chamber for inducing ischemia. We will first
optimize and validate environmental conditions and protocols for inducing and measuring cardiac ischemic
damage, followed by validation with ischemia drugs with published in vivo and in vitro results. The uniqueness
will be the combination of Hickman’s functional modules w...

## Key facts

- **NIH application ID:** 10579914
- **Project number:** 5R44HL140920-03
- **Recipient organization:** HESPEROS, LLC
- **Principal Investigator:** James J Hickman
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $854,765
- **Award type:** 5
- **Project period:** 2018-09-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10579914

## Citation

> US National Institutes of Health, RePORTER application 10579914, HLS-Development of a cardiac ischemia model in an organ-on-a-chip platform (5R44HL140920-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10579914. Licensed CC0.

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