# Cardiotoxicity Assays on an Integrated Platform of a Heart-on-a-Chip and an Optical Immunosensor

> **NIH NIH R01** · TERASAKI INSTITUTE FOR BIOMEDICAL INNOVATION · 2020 · $314,505

## Abstract

Abstract
Toxicity assays based on human organs-on-a-chip platforms have become increasingly important for drug
discovery and development, since they allow testing cytotoxic effects of pharmaceutical compounds on the
physiologically relevant human tissue models before moving forward to expensive animal testing or clinical
trials. Multiple physiological and biochemical parameters of the organ-on-a-chip models must be continually
monitored in order to assess the responses of these models to drug treatments. Although fluorescence
detection has been widely adopted for bioassays, it requires the addition of fluorophores to the samples,
which may disturb cellular activities and more seriously, it is practically impossible for real-time fluorescence
labeling of the biomarkers that are constantly secreted by the organ models during drug toxicity testing.
Thus, fluorescence detection is not a viable option here - direct detection, or “label-free” detection, is
required for monitoring the dynamic process of drug interactions with organoids to obtain detailed
information on transient as well as delayed or cumulative drug effects. The overarching goal of the proposed
research is thus to address these challenging issues of drug toxicity assays by using a human organ-on-a-
chip model monitored with an automated, label-free, optical biosensor system that allows for real-time, long-
term, sensitive, and kinetic analyses of human cardiac tissue models in response to various drugs in their
microenvironments.
To accomplish this goal, we propose a unique approach that is based on our patented label-free biosensor in
conjunction with advanced organ-on-a-chip technologies. The open-microcavity configuration of our
biosensor enables synergistic integration of the sensor chip with a heart-on-a-chip model through an
automated microfluidic platform, which has the built-in capability to regenerate the sensor surface for
continual kinetic studies over extended periods of time. The heart-on-a-chip model will be developed using
an innovative 3D bioprinting approach that produces functional biomimetic cardiac organoids using
cardiomyocytes derived from human induced pluripotent stem cells (iPSCs). A microfluidic perfusion
bioreactor with the built-in capacity for simultaneous electrical and mechanical stimulations will be
constructed to maintain long-term functionality of the organoids. On the other hand, the long-term stability of
the proposed biosensor system will be significantly enhanced using negative thermal expansion materials for
fabrication of the sensor chip. The cardiotoxicity of a panel of drugs will be evaluated in situ via quantification
of the biomarkers secreted by the human cardiac model. The technology developed from this project will be
highly transformative, which may be applied for other organs and lead to future personalized screening of
drug toxicities, efficacy, and pharmacokinetics for precision medicine.

## Key facts

- **NIH application ID:** 10249004
- **Project number:** 7R01GM126571-03
- **Recipient organization:** TERASAKI INSTITUTE FOR BIOMEDICAL INNOVATION
- **Principal Investigator:** Mehmet Remzi Dokmeci
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $314,505
- **Award type:** 7
- **Project period:** 2018-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10249004

## Citation

> US National Institutes of Health, RePORTER application 10249004, Cardiotoxicity Assays on an Integrated Platform of a Heart-on-a-Chip and an Optical Immunosensor (7R01GM126571-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10249004. Licensed CC0.

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