# Understanding the Heterogeneity of Nanoscale Extracellular Vesicles, Exomeres, and Supermeres using Next Generation Optical Nanotweezers

> **NIH NIH R35** · VANDERBILT UNIVERSITY · 2024 · $382,734

## Abstract

Project Summary
Nanosized extracellular vesicles and particles (EVPs) have been identified as an important means for cells to
communicate with neighboring and distant cells. EVPs are actively investigated to understand their roles in
cancer, non-invasive disease diagnosis, and therapeutics. One of the most significant urgent challenges to
overcome in EVP research is understanding the heterogeneity of EVPs. EVPs are heterogeneous in their size
and molecular cargo contents. As a result, single EVP analysis has been identified as crucial to deciphering the
heterogeneity of individual EVPs and understanding their biological roles in diverse diseases. As an example,
an ongoing scientific question concerns whether the newly discovered extracellular particles called exomeres
and supermeres are monolithic nanoparticles enriched with multiple makers such as proteins, RNA and lipids or
if they are a distribution of different functionally-active nanoparticles (such as proteins, nucleic acid and lipids)
co-isolated together. The widely used analysis techniques such as mass spectrometry are incapable of analyzing
individual EVPs and hence these assays mask the impact of the heterogeneity of EVPs, which has made it
impossible to address this question and other open questions to date. To select individual EVs for analysis in a
non-destructive manner, it is imperative to develop methods for trapping them in solution. Optical tweezers
recently recognized with a 2018 Nobel Prize in Physics have been demonstrated as effective approaches for
trapping single cells and larger EVs. Unfortunately, the diffraction limit of light precludes their use for the trapping
of single nanosized EVs, and the recently discovered exomeres, and supermeres that are only 35 nm and 25
nm in diameter, respectively. This MIRA research program is comprised of a collection of projects designed to
develop new optical nanotweezer technologies for high throughput parallelized trapping of single nanosized
EVPs combined with enhanced Raman analysis to provide unique information on the global biomolecular
composition of individual nanosized EVs, exomeres and supermeres. Subsequently, we will investigate the use
of these tools to address ongoing controversies in EV research.
First, we will develop a novel optical nanotweezer approach based on nanoplasmonic structures that will enable:
(i) parallelized trapping of thousands of single EVPs within seconds; (ii) enhancement and acquisition of Raman
signals from single trapped EVPs nondestructively while they are trapped in solution near nanoplasmonic
cavities; and (iii) biomolecular component analysis to determine the global biomolecular composition of individual
trapped EVPs. Secondly, we will utilize the developed technologies to address ongoing questions in EVP
research including whether the newly discovered exomeres and supermeres are monolithic or comprise a
diverse distribution of functionally active nanoparticles. The pertinent findings to be ob...

## Key facts

- **NIH application ID:** 10895559
- **Project number:** 5R35GM150572-02
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Justus Chukwunonso Ndukaife
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $382,734
- **Award type:** 5
- **Project period:** 2023-08-01 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10895559

## Citation

> US National Institutes of Health, RePORTER application 10895559, Understanding the Heterogeneity of Nanoscale Extracellular Vesicles, Exomeres, and Supermeres using Next Generation Optical Nanotweezers (5R35GM150572-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10895559. Licensed CC0.

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