# An integrated human organ-on-chip ultrasensitive miRNA detection platform for novel biomarker discovery

> **NIH NIH R01** · UNIVERSITY OF NOTRE DAME · 2020 · $385,733

## Abstract

Abstract
Circulating miRNAs have proposed as specific biomarkers of disease states, including some of the most
prevailing ones such as cardiovascular diseases and cancer. However using miRNAs as biomarkers is very
challenging despite recent advances in high-throughput miRNA profiling. Various detection technologies,
protocols, ligation and extraction/purification methods have led to varying miRNA profiling results of cells and
biofluids under different conditions. Most importantly, all require days long sample-to-answer assay times, thus
ruling them out for detection and monitoring of urgent, life threatening conditions such as myocardial infarction
(MI). A rapid real-time, PCR-free miRNA-profiling device would be exceedingly valuable for precision,
personalized medicine in years to come. However, it is very difficult to start even developing such a platform
because of the limitations in testing models. Animal models often fail to predict responses in humans; and studies
of human subjects do not readily allow for precise control over the disease events or temporal correlation of the
disease state and biomarker expression dynamics. To address this challenge, in this study, we will develop an
organ-on-a-chip device with an integrated attomolar (aM)-level miRNA sensing capability, which we will use for
optimizing real-time monitoring of fluctuations in multiple miRNAs for novel biomarker discovery. As an
immediate application, we will start with a human myocardium-on-chip (MoC) as a clinically relevant model and
imitate the course of a heart attack. We hypothesize that using the MoC with ultrasensitive miRNA detection, we
will discover a unique signature that indicates the onset of reperfusion injury during MI treatment. Finally, we will
test the sensor device and the miRNA signature using clinical blood samples. Our microfluidic organ-on-a-chip
platform will consist of four basic components: 1) the tissue engineered human MoC from human induced
pluripotent stem cells (hiPSCs), 2) the exosome lysing unit, 3) the concentration unit for the lysed RNAs and 4)
the detection unit for the miRNAs. In Aim 1, we will couple these components into a fully integrated microfluidic
platform. First we will validate the clinical relevance of the MoC model by comparing with human tissue and blood
samples. Then we will characterize and optimize the performance of a novel miRNA detection biosensor using
MoC and benchmark it against established miRNA analysis techniques. In Aim 2 we will focus on multiplexing
the sensing approach for the real-time detection of a panel of miRNAs, and 1) use the MoC to discover a miRNA
signature to be used as a novel biomarker that captures the RI onset, as well as 2) to optimize the multiplexed
sensor for faster clinical translation. In Aim 3 we will determine the diagnostic and prognostic capabilities of the
novel biosensor and miRNA biomarker signature we developed in Aims 1 and 2 using the MoC model, with
clinical samples from MI pat...

## Key facts

- **NIH application ID:** 9986885
- **Project number:** 5R01HL141909-03
- **Recipient organization:** UNIVERSITY OF NOTRE DAME
- **Principal Investigator:** Pinar Zorlutuna
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $385,733
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9986885

## Citation

> US National Institutes of Health, RePORTER application 9986885, An integrated human organ-on-chip ultrasensitive miRNA detection platform for novel biomarker discovery (5R01HL141909-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9986885. Licensed CC0.

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