# Development of an Ultrasensitive Point-of-Care Salivary Diagnostic for Mild Traumatic Brain Injury

> **NIH NIH F32** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $64,926

## Abstract

Project Summary: Mild traumatic brain injury (TBI), or concussion, is a growing public health concern, as large
populations of athletes, soldiers, and other young people are exposed to high risks of repetitive head injuries
and associated long-term risks of neurodegeneration. Early, accurate diagnosis of mild TBI is critical for effective
intervention and proper recovery, but remains an unmet clinical need. Current diagnoses are time-consuming
and rely on subjective clinical assessments and neuroimaging, which usually cannot show clear structural brain
damage in mild TBI. This work proposes to engineer an objective, ultrasensitive point-of-care diagnostic
tool that can rapidly determine the presence and severity of mild TBI at the point of injury, to enable
early treatment and sufficient recovery times. The proposed platform will utilize single molecule
detection to measure low abundance protein biomarkers for mild TBI in saliva, as a noninvasive test that
can easily be deployed in schools, military fields, and emergency rooms. Single Molecule Array (Simoa)
technology, developed by the Walt lab, is the current state of the art for ultrasensitive protein detection, using
digital enzyme-linked immunosorbent assay (ELISA) to isolate and count single molecules captured on beads in
femtoliter-sized microwells. Despite achieving 1000-fold higher sensitivity than conventional ELISA, the current
Simoa technology cannot be used in point-of-care applications due to its significant cost, size, and need for
specially trained personnel. The sensitivity of Simoa also remains insufficient for detecting brain-derived and
other potential protein biomarkers that exist at levels below its detection limit (~10-15 M), particularly in minimally
invasive biofluids such as plasma and saliva. To address these challenges, this work will design a simple, cost-
effective, and more sensitive Simoa platform, by dropcasting beads in a monolayer film for single molecule
counting, eliminating the need for costly microwells and bulky fluidics. Furthermore, this approach can greatly
improve sampling of rare molecules over the current Simoa technology, which will significantly enhance
sensitivity. This system will be integrated with a handheld reader as a point-of-care diagnostic tool and applied
for multiplexed detection of a salivary protein biomarker panel for mild TBI. The point-of-care platform will be
benchmarked against current Simoa assays for the biomarker panel and validated as a sensitive, specific
diagnostic tool for mild TBI, using saliva samples from concussed and healthy athletes. This project will also
provide rigorous scientific training for Dr. Connie Wu that will prepare her for a fully independent academic
research career. She will work closely with Dr. David Walt in a highly interdisciplinary, collaborative environment
at Brigham and Women’s Hospital and the Wyss Institute at Harvard University, and develop an extensive skillset
in analytical chemistry, diagnos...

## Key facts

- **NIH application ID:** 9990352
- **Project number:** 1F32EB029777-01
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Connie Wu
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $64,926
- **Award type:** 1
- **Project period:** 2020-04-02 → 2022-04-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9990352

## Citation

> US National Institutes of Health, RePORTER application 9990352, Development of an Ultrasensitive Point-of-Care Salivary Diagnostic for Mild Traumatic Brain Injury (1F32EB029777-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9990352. Licensed CC0.

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