# High-Throughput Droplet-Scale Functional Screening of DNA-Encoded Combinatorial Libraries

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2020 · $301,422

## Abstract

Project Summary / Abstract
The NIH established the Molecular Libraries Program (MLP) and its network of high-throughput screening
(HTS) centers to discover probes – highly selective small molecules that modulate cellular function – within
the proteomes of humans and pathogens. Probes are not only tools for studying biological function to validate
new drug targets, but are also potential leads for new therapeutics. Though successful in its mission to provide
HTS resources to academia and having generated hundreds of probes, the MLP is sunsetting and its
operational screening centers face the logistic and financial issues that industrial HTS centers have battled for
decades (large facilities, costly robotic handling and optical screening equipment upkeep, static compound
libraries). Proteome-wide and pathogen-wide probe discovery remains a compelling goal well within reach
thanks to distributed and economical genome sequencing technology, which inspires this proposal to develop a
similarly distributable molecular screening platform. Combining droplet-scale microfluidic miniaturization
and automation with consumable DNA-encoded solid-phase compound libraries comprises a proposed bid to
reconstitute the operations of a HTS center in a single benchtop instrument. The device loads compound
library beads into picoliter-scale droplets of assay reagent, photochemically cleaves the compound from the
bead, incubates the dosed droplets, reads the fluorescence of the incubated droplets, and sorts droplets
exhibiting a desired assay fluorescence profile for collection and high-throughput sequencing. The instrument
will (1) screen a million compound library in ~6 h, (2) require several square feet of space, (3) consume ~100
µL of assay reagent, and (4) generate dose-response screening data, resulting in massively parallel pan-library
structure-activity relationship profiles. This technology will distribute molecular screening, moving it into
academic, industrial and government laboratories nationwide, and on a cost scale that will enable discovery of
thousands of probes annually.

## Key facts

- **NIH application ID:** 9850274
- **Project number:** 5R01GM120491-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Brian M Paegel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $301,422
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9850274

## Citation

> US National Institutes of Health, RePORTER application 9850274, High-Throughput Droplet-Scale Functional Screening of DNA-Encoded Combinatorial Libraries (5R01GM120491-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9850274. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*