Analytical Validation of Portable Devices for Detection of Traumatic Brain Injury Biomarkers

用于检测创伤性脑损伤生物标志物的便携式设备的分析验证

• 批准号: 10457242
• 负责人: Jane Grayson Wigginton
• 金额: $ 65.25万
• 依托单位: UNIVERSITY OF MASSACHUSETTS AMHERST
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10457242
• 关键词: Accident and Emergency department; American; Biological Assay; Biological Markers; Blood; Blood Tests; Blood specimen; Centers for Disease Control and Prevention (U.S.); Cessation of life; Characteristics; Clinical; Collection; Consumption; Data; Detection; Devices; Diagnosis; Diagnostic; Early Intervention; Enzyme-Linked Immunosorbent Assay; Fingers; Future; Glasgow Coma Scale; Glial Fibrillary Acidic Protein; Goals; Gold; Guidelines; Hospitalization; Hospitals; Hour; Image; In Vitro; Incentives; Individual; Laboratories; Lateral; Magnetic Resonance Imaging; Marketing; Measurement; Measures; NIH Program Announcements; Neurologic Examination; Neuron-Specific Enolase; Paper; Patients; Performance; Persons; Physicians; Plasma; Population; Pre-hospital setting; Procedures; Production; Quality Control; Radiation; Rapid diagnostics; Reproducibility; Research; Route; Sampling; Scanning; Sensitivity and Specificity; Signal Transduction; Specificity; Surface; Technology; Test Result; Testing; Time; Transducers; Traumatic Brain Injury; Triage; United States Food and Drug Administration; Validation; Work; X-Ray Computed Tomography; assault; base; clinical development; cost; cost effective; detection limit; detector; diagnostic tool; disability; falls; improved; in-vitro diagnostics; long-term sequelae; mild traumatic brain injury; minimally invasive; novel; point of care; point-of-care diagnostics; portability; protein biomarkers; prototype; quality assurance; rapid detection; response; screening; test strip; tool; trauma centers; ubiquitin C-terminal hydrolase; vehicular accident

POJECT SUMMARY Traumatic brain injury (TBI) causes a number of deaths and permanent disability. Today 5.3 million people live with disability caused by TBI in U.S. Typically, TBI is initially assed by the Glasgow Coma Scale on hospital admission and routine neurologic examination. Computed tomography (CT) scanning and magnetic resonance imaging (MRI) are used for confirmatory testing. However, CT and MRI are not always available for every visitor for initial screening at emergency department; and there is no CT and MRI in the pre-hospital settings. Measurement of biomarkers in blood can provide an alternative, cost- effective and rapid route to screen TBI. In 2018, the U.S. Food and Drug Administration (FDA) authorized marketing of blood testing of two diagnosis biomarkers, ubiquitin c-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP), to evaluate TBI. Also, neuron-specific enolase (NSE) has been extensively investigated as a diagnosis blood biomarker for TBI. But there is no any commercial portable in vitro diagnostic tool to rapidly measure these biomarkers in blood in the emergency department and prehospital settings. Recently the PI developed a point-of-care (POC) prototype device that is able to rapidly measure TBI biomarkers in plasma and blood. To bring this prototype POC device to the clinical use, it will require at least three steps: (i) analytical validation; (ii) clinical validation; and (iii) FDA approval and 510(k) clearance. Analytical validation of the prototype device is the first step, which has not been done yet, but it is necessary to accomplish prior to clinical validation. The objective of project is to perform analytical validation of the paper-based lateral flow strip (PLFS) for detection of TBI diagnosis biomarkers in blood, in which surface-enhanced Raman scattering (SERS) is utilized for sensing signal transduction. Three types of PLFS will be used to measure three most recognized TBI diagnosis biomarkers including NSE, UCH-L1 and GFAP with assistance of a portable Raman detector, respectively. Each TBI biomarker can be detected individually with a small volume (around 35 µL) of blood sample within 36 minutes. With establishment of appropriate quality control and improvement procedures, the performance of PLFS will be validated analytically in terms of accuracy, precision, analytical sensitivity, reportable range, and selectivity. This application is in response to the NIH Program Announcement of PAR-18-550 (analytical validation) instead of PAR-18- 548 (clinical validation). If successful, such an inexpensive and rapid diagnostic POC tool will change practice in TBI diagnosis in the emergency department and pre-hospital settings. It will reduce unnecessary CT scans, increase the accuracy of TBI diagnosis, save costs, and enable earlier intervention aimed at mitigating both short and long term sequelae.

产品概要 创伤性脑损伤（TBI）导致许多死亡和永久性残疾。今天530万 在美国，人们患有TBI引起的残疾。通常，TBI最初由格拉斯哥昏迷评估 入院及常规神经系统检查量表。计算机断层扫描（CT） 和磁共振成像（MRI）用于确认测试。然而，CT和MRI不是 急诊室始终为每位来访者提供初步筛查;没有CT， 在院前环境中进行MRI检查。测量血液中的生物标志物可以提供一种替代方案， 有效和快速筛查TBI途径。2018年，美国食品药品监督管理局（FDA）授权 销售两种诊断生物标志物的血液检测，泛素C末端水解酶-L1（UCH-L1）和 胶质细胞酸性蛋白（GFAP），以评估TBI。此外，神经元特异性烯醇化酶（NSE）已被 作为TBI的诊断血液生物标志物被广泛研究。但没有任何商业便携式 在急诊科快速测量血液中这些生物标志物的体外诊断工具， 院前环境。最近PI开发了一种即时护理（POC）原型设备，该设备能够 快速测量血浆和血液中的TBI生物标志物。为了将这一原型POC设备应用于临床， 使用时，它将需要至少三个步骤：（i）分析验证;（ii）临床验证;（iii）FDA 批准和510（k）许可。原型装置的分析验证是第一步， 尚未完成，但必须在临床验证之前完成。 该项目的目的是对纸基横向流条进行分析验证 用于检测血液中TBI诊断生物标志物的PLFS，其中表面增强拉曼散射 表面增强拉曼光谱（Sers）用于感测信号转导。三种类型的PLFS将用于测量三个 最公认的TBI诊断生物标志物包括NSE、UCH-L1和GFAP， 便携式拉曼检测器。每种TBI生物标志物都可以用小的 在36分钟内采集35微升左右的血液样本。建立适当的质量 控制和改进程序，PLFS的性能将在以下方面进行分析验证 准确度、精密度、分析灵敏度、可报告范围和选择性。该应用程序在 对NIH计划公告PAR-18-550（分析验证）而非PAR-18的响应- 548（临床验证）。 如果成功，这种廉价和快速的诊断POC工具将改变TBI的实践 在急诊室和院前环境中进行诊断。它将减少不必要的CT扫描， 提高TBI诊断的准确性，节省成本，并能够进行旨在减轻 短期和长期后遗症。