# Solid-state nanopores for translational analysis of hyaluronan abundance and size distribution

> **NIH NIH R01** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2020 · $312,723

## Abstract

Project Summary
Hyaluronan (or hyaluronic acid, HA) is a ubiquitous biomolecule in vivo, with diverse roles ranging from
regulating key immunomodulatory functions to serving as the primary lubricating component of synovial fluid
(SF) in joints. Consequently, the accurate and comprehensive characterization of the molecule is critical to
improving our understanding of a broad range of biological processes and disease states, and may have
potential downstream applications in translational diagnostics. However, current technologies for assessing HA
have significant limitations. For example, techniques like the enzyme-linked immunosorbent assay (ELISA) are
adept at quantifying HA but ignore the critical structure-function relationship that makes HA molecular weight
(MW) a defining characteristic of its role. Approaches that are able to resolve HA MW have challenges that
include limited dynamic range (mass spectrometry) and large sample mass requirement (gel electrophoresis),
and generally lack the ability to determine concentration, necessitating multiple techniques for complete
assessment. To address this gap, we propose to employ solid-state (SS-) nanopores for robust molecular
analysis. In a SS-nanopore measurement, charged biomolecules are transported electrically through a
synthetic, nanometer-scale aperture. A current signature, or `event', is produced with each individual
translocation that can be measured and interpreted to denote characteristics about the threading molecule,
including MW. In addition, the overall rate of these events scales with molecular concentration, providing a
means by which to quantify analytes in solution. As a result, the platform is uniquely positioned to probe HA. In
Aim 1 of this project, we will first optimize SS-nanopore device performance for HA analysis by investigating
key experimental parameters systematically and expand our isolation protocols to also target inflammation-
marked HA specifically. Then, we will take advantage of the high sensitivity of our system to analyze HA in
biofluids that are conventionally challenging to probe. This will be accomplished by performing measurements
in the context of two disease states where HA is thought to have particular relevance: urinary HA in kidney
cancer (Aim 2) and plasma and urinary HA in rheumatoid arthritis (Aim 3). We hypothesize that the increased
sensitivity and quantitation offered by our SS-nanopore approach will enable correlations between HA
abundance/size distribution and disease progression to be identified and used for minimally- or non-invasive
diagnostics. This project will be conducted by a team of researchers that is positioned uniquely to succeed,
with expertise in SS-nanopore analysis, molecular diagnostics, glycobiology, statistical methods, urological
oncology, and rheumatology. The resulting technology will address the challenges of current analytical
methods, widening consideration of HA and its varied functions in basic biology and disease.

## Key facts

- **NIH application ID:** 9973615
- **Project number:** 1R01GM134226-01A1
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Adam Roger Hall
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $312,723
- **Award type:** 1
- **Project period:** 2020-09-05 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9973615

## Citation

> US National Institutes of Health, RePORTER application 9973615, Solid-state nanopores for translational analysis of hyaluronan abundance and size distribution (1R01GM134226-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9973615. Licensed CC0.

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