Traumatic brain injury (TBI) is a substantial health care issue affecting both civilian and military populations. Although extremes of head injury are recognizable, mild to moderate TBI (mmTBI) is more difficult to diagnose leading to a need for the identification of circulating biomarkers of brain injury that may facilitate early identification. Using a rat model of TBI we identified a novel marker of neuronal injury, ubiquitinated visinin like protein 1 (ubVILIP-1) that is released into blood rapidly after injury. To facilitate rapid on-field point-of-care (POC) measurement of circulating ubVILIP-1, we developed a lateral flow device (LFD) that provides detection of the biomarker in less than 20 min from a single drop of blood from a finger stick. Although initial testing in human TBI patients in a small clinical trial in the Emergency Department of the University of Kentucky is promising, we have observed variability in the lab produced devices related to limited construction capacity that would likely limit further clinical trials. Therefore, there is a need for conversion of our lab produced devices to a commercial vendor for optimization of device architecture and production of analytically reproducible devices for future clinical trials.
The aim of the current Phase I STTR proposal is to work with DCN Diagnostics to optimize antibody conjugation and device architecture and to produce prototype devices for comparison to lab produced devices and evaluation of performance characteristics of DCN produced devices. Analytical performance characteristics for prototype devices to be evaluated include accuracy, precision, limit of detection (LOD), limit of quantification (LOQ), linearity of response, concentration range and device robustness. Results of the analytical validation will be compared to our lab produced devices particularly for LOD and LOQ. If successful, the proposed studies will verify that our lab produced device can transition to a commercial platform to allow analytically reproducible large scale production of devices necessary for larger clinical trials and pave the way for further commercialization.
Traumatic brain injury (TBI) is a substantial health care issue affecting both civilian and military populations and there remains substantial need for development of a point-of-care (POC) diagnostic tool that will allow rapid identification of patients with mild to moderate TBI (mmTBI). We recently developed a lateral flow device (LFD) that quantifies ubiquitinated visinin like protein 1 (ubVILIP-1), a post-translationally modified neuron specific Ca2+-sensor protein released into blood following TBI, that was effective in the identification of mmTBI patients from normal controls in a small clinical trial. Although our preliminary data are promising there is a need to transition our lab produced devices to a commercial platform for optimization and to compare analytical figures of merit for commercial devices relative to our lab produced devices paving the way for larger scale production of analytically reproducible devices necessary for further clinical trials and further commercialization.
