EAGER: Detection and Quantification of DNA and Brain-Specific Markers in Extracellar Vesicles for a Rapid Assessment of Neuroinjury in Liquid Biopsies

There is a critical need for the development of a simple, cost effective and reliable sensing platform for diagnosis and monitoring of brain trauma. Current developments in the fields of extracellular vesicles biology, molecular targeting, proteomics, optical biosensing and liquid biopsy technology offer a great opportunity for the development of novel optical based sensors that can detect and quantify the degree of brain injury based on the detection of biomarkers of brain injury present in biofluid samples that can be readily collected for non-invasive on-demand detection.

This approach has the potential of impacting the standard of care for managing brain injury by enabling rapid and inexpensive diagnosis of head trauma. In particular, the proposed optical biosensors have the potential of becoming a game-changer in early diagnosis and monitoring of brain trauma. The proposed sensors will yield quantitative results within minutes using established optical-based detection technology.

This technology will be inexpensive and is therefore very suited to be used in field and in resource challenged environments. The team of investigators will make an effort to recruit women and minority students for this R&D endeavor through well-established training programs at the University of Texas Medical Branch, thus facilitating the training of the next generation of scientists and engineers.

The current diagnosis of traumatic brain injury (TBI) patients includes a neurological exam and imaging tests; both are time consuming and require dedicated resources that are not readily available, particularly in resource-challenged environments such as emergency rooms, sports arenas and battlefields. Thus, there is an urgent need for the development of novel liquid biopsy technology for the early detection and quantitative monitoring of TBI severity, which is the ultimate goal of this project.

In this project the team aims to define DNA and protein content of brain-derived extracellular vesicles present in the circulation as a reliable biomarker for the assessment and prediction of severity of neuroinjury at the early post injury time point followed by monitoring long term TBI consequences as well as assessing the response to the potential therapeutic interventions. The aim is to develop a compact optical-based point-of-care device for detection and quantification of key biomarkers of brain injury including fluorescence-based sensing of circulating cell free (ccf)--DNA complemented with the detection of brain-specific biomarkers in blood that would enable engineering of a novel multi-sensing device that can be used for rapid, early and non-invasive assessment of TBI severity.

As part of the proposed development, the team will identify the key biomarkers of brain injury and their temporal distribution in the brain-derived extracellular vesicles collected from blood samples and then assemble, test, and validate novel optical biosensors that can be used to target these key markers for early and quantitative assessment of neuroinjury via readily available liquid biopsy. A multidisciplinary team of researchers with expertise in mitochondrial dysfunction, traumatic brain injury, biophotonics, medical device development, microfluidic technology, and bioengineering will be pursuing the stated goals of this project.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.