Development and Validation of Handheld Dried-Plasma Biosampling Lateral Flow (LF) Technology for TBI Protein and Metabolites Diagnostics
Abstract
Our proposal addresses Focus Area 2, Prevent as our proposed research will address the prevention or progression of TBI or psychological health conditions through population, selective, and indicated prevention approaches and its Subarea 2a, Identification and validation of biomarkers or other objective markers for diagnosis, prognosis, or monitoring of psychological health conditions/brain injuries. Traumatic brain injury (TBI) complex pathophysiological events involving neurodegeneration and cognitive decline has been associated with abnormalities in biofluid molecular analyte biomarker signature coupled with neurobehavioral and imaging modalities reflecting these TBI-associated pathologies. These biomarkers are derived from an intravenous (IV) blood draw that is considered semi-invasive and shown to be challenging from a biosampling standpoint. This is especially relevant due to the recent COVID-19 pandemic that significantly impacts in-person and clinical activities, as well as clinical trials where invasive procedures and diagnostic evaluation require patient-clinician contact. Thus, based on these evolving obstacles, our proposal aims to develop and validate minimally invasive dried plasma biosampling lateral flow (DPB-LF) platform device compatible with pan-analyte biofluid biomarkers (protein, metabolites, miRNAs). Our main concept is that the development of a minimally invasive (DPB-LF) device will facilitate detecting TBI biomarkers and represent an innovative and a paradigm shift in the area of biomarker diagnostic/prognostic field. The successful development of this novel handheld dried plasma biosampling lateral flow technology that has a direct impact on (1) reducing biosampling burden relative to imaging and other more expensive and/or more invasive measures (e.g., CSF and IV blood-based biomarkers), (2) facilitating clinical and longitudinal studies impacted by substantial recruitment bias and loss to follow-up, and (3) enabling scalable, cost-effective use with the potential at-home sample collection at-home or during prolonged field care (PFC). The revolutionary technology represents an urgent unmet need for devices, biomarkers, or analyses to detect TBI sequelae. Our proposed project has the following main tasks: (1) optimize the DPB-LF device and conduct method development, characterization/optimization, and validation of the performance of the DPB-LF platform-design, condition of dry plasma rehydration/recovery, analyte compatibility for biomarker subtypes (proteins, metabolites, and miRNAs), and ruggedness (stability at different storage condition (up to 7 days at varied temperatures (4, 25, 40 ), atmospheric humidity, and storage; (2) leverage archived TRACK TBI (TBI and normal control wet plasma to be used in the ‘method development set on clinical samples. The objective is to compare and contrast the wet plasma and dry plasma samples (subsequently renatured) for different analyte levels (proteins, autoantibodies, microRNAs, and global proteomic profiling); and (3) involve a small- scale, prospective, clinical, emergency medicine-based TBI study (GCS 3-14) that collects serial wet plasma and dry DPM-LF dry plasma samples (N=35 TBI and N=15 healthy controls ) that will be testing the effectiveness and utilities of the DPM-LF platform DPB-LF dry plasma samples compared to wet sample assessment to achieve validated performance. This proposal aims to design a no-cost and non-invasive handheld DPB-LF device platform that will provide a minimally invasive dry biosample collection for TBI-related key biomarkers (e.g., protein, autoantibodies, miRNA, metabolites). Successful implementation of this work can be translated into other research areas and other diseases and disorders. It will have a direct impact on the civilian, geriatrics military, and Veteran population, enabling design of appropriately powered clinical trials that provide timely diagnosis and sound clinical trials.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210740
Entities
People
- Kevin G. Wang
Organizations
- Morehouse School of Medicine
- United States Army