# Streamlined and comprehensive circulating brain-derived exosome profiling by microfluidic arrayed nanoplasmonic sensors and actuators

> **NIH NIH R01** · UNIVERSITY OF HOUSTON · 2022 · $247,033

## Abstract

PROJECT SUMMARY
Despite keen interests in early diagnosis of Alzheimer’s disease & its related dementias (AD/ADRD), which faces
a multitude of underlying nuanced and mixed pathologies, the progress has been hampered by insufficient
sensitivity and low specificity to the pathology. New molecular assays include cerebrospinal fluid measurements
and brain amyloid plaque imaging through positron emission tomography (PET). However, these techniques
face limitations as they either require lumbar punctures, have insufficient sensitivity for early detection, or are
too expensive for wider adoption. As a result, there is an unmet need in timely and cost-effective AD diagnostics.
 Detection of disease biomarkers in the blood, known as “liquid biopsy”, can in principle improve the accuracy
of measuring nearly invisible diseases. Exosomes are cell-excreted extracellular vesicles that contain surface
proteins and genetic materials (DNA and RNA) that reflect the characteristics and make-up of the parental cells.
Analyzing brain-derived exosomes (BDE) would therefore provide direct insight into the state of the parental cells
of neuronal and glial origins. For Alzheimer’s disease & related dementias (AD/ADRD) diagnostics in particular,
recent evidences have shown that several pathological surface proteins and cargo micro-RNAs are differentially
expressed in BDE in AD/ADRD. Therefore, unlocking the wealth of information in circulating BDE can potentially
cause a paradigm shift. However, current limitations for profiling BDE are the following: (1) significant blood
volume is needed; (2) sophisticated protocols; (3) label-free sizing/counting lacks molecular specificity; (4)
provide highly averaged results with high background from normal exosomes, thus leading to poor sensitivity.
(5) provide “partial” information: either surface antigen or cargo DNA/RNA, but not both. All of the above has
hampered the development of further understanding of circulating BDE associated with AD/ADRD and a potential
blood test for AD/ADRD diagnostics. In this Administrative Supplement, we propose to extend the microfluidic
arrayed nanoplasmonic sensor & actuator (MANSA) platform in the original R01 to single BDE profiling. The
MANSA platform will enable: (1) streamlined operation from capturing to profiling. (2) improved sensitivity by
digital counting via dynamic imaging. (3) improved specificity by profiling multiple surface proteins and cargo
microRNA associated with AD pathologies. A high-resolution, exosome array with multiplex surface protein and
cargo microRNA profiles will facilitate high dynamic range enumeration and boost sensitivity in blood-based AD
diagnostics and accentuate high-value circulating AD biomarkers. The proposed technology would lead to a
cost-effective, point-of-care-friendly, translational platform.

## Key facts

- **NIH application ID:** 10499572
- **Project number:** 3R01EB030623-02S1
- **Recipient organization:** UNIVERSITY OF HOUSTON
- **Principal Investigator:** Wei-Chuan Shih
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $247,033
- **Award type:** 3
- **Project period:** 2021-06-15 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10499572

## Citation

> US National Institutes of Health, RePORTER application 10499572, Streamlined and comprehensive circulating brain-derived exosome profiling by microfluidic arrayed nanoplasmonic sensors and actuators (3R01EB030623-02S1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10499572. Licensed CC0.

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