# High Throughput Digital Droplet Assays for Ultrasensitive Multimodal (DNA, RNA, and Protein) Diagnostics

> **NIH NIH R33** · UNIVERSITY OF PENNSYLVANIA · 2024 · $389,746

## Abstract

Abstract
Digital assays — in which ultra-sensitive molecular measurements are made by performing
millions of parallel experiments in picoliter droplets — have generated much recent enthusiasm
due to their single molecule resolution of RNA, DNA, and proteins, and their robustness to
reaction conditions. These assays have enormous potential for the diagnosis of difficult to
diagnose diseases, such as pancreatic cancer, but are currently confined to laboratory settings
due to the cumbersome instrumentation necessary to generate, control, and measure tens of
millions of independent droplets. To overcome this challenge, we are developing a hybrid
microelectronic / microfluidic chip to ‘unlock’ droplet-based assays for clinical use. Our
microdroplet megascale detector (µMD) can generate and detect the fluorescence of millions of
droplets per second (1000× faster than existing digital approaches), while achieving a 1000x
greater sensitivity than conventional ELISA or ddPCR, using only a conventional cell phone
camera. The key innovation of our approach is borrowed from the telecommunications industry,
wherein we modulate the excitation light with a pseudorandom sequence that enables individual
droplets to be resolved that would otherwise overlap due to the limited frame rate of digital
cameras. Building on the success of our R21, we propose to develop a platform technology to
ultrasensitively quantify proteins, ctDNA, and single EVs in an integrated device, directly in
patient blood, to address critical issues in multimodal diagnostics. In collaboration with the
Abramson Cancer Center and building on prior work together on multi-modal diagnostics, we
focus our attention on Pancreatic ductal adenocarcinoma-the third leading cause of cancer-
related death in the United States with an overall 5-year survival of only 9%.

## Key facts

- **NIH application ID:** 10798798
- **Project number:** 1R33CA287135-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** David Aaron Issadore
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $389,746
- **Award type:** 1
- **Project period:** 2024-03-07 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10798798

## Citation

> US National Institutes of Health, RePORTER application 10798798, High Throughput Digital Droplet Assays for Ultrasensitive Multimodal (DNA, RNA, and Protein) Diagnostics (1R33CA287135-01). Retrieved via AI Analytics 2026-05-31 from https://api.ai-analytics.org/grant/nih/10798798. Licensed CC0.

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