A rapid microfluidic P.O.C CNS biomarker platform to predict delayed HICP onset.

一种快速微流体 P.O.C CNS 生物标志物平台，用于预测延迟 HICP 发作。

• 批准号: 8312928
• 负责人: SOMASUNDAR PRASAD GABBITA
• 金额: $ 34.87万
• 依托单位: P2D, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8312928
• 关键词: Animals; Area; Biological Assay; Biological Markers; Blood; Brain; Brain Edema; Brain Injuries; Calibration; Cessation of life; Cleaved cell; Clinical; Closed head injuries; Data; Devices; Edema; Enzyme-Linked Immunosorbent Assay; Feasibility Studies; Gold; Human; Hydrolase; IL8 gene; Immunoassay; Indwelling Catheter; Injury; Interleukin-6; Intracranial Pressure; Kinetics; Laboratories; Lead; Legal patent; Measurement; Measures; Methods; Microfluidics; Modeling; Monitor; Morbidity - disease rate; Neurofilament-H; Neuron-Specific Enolase; Neurosurgical Procedures; Outcome; Patient Selection; Patients; Phase; Procedures; Proteins; Rattus; Receiver Operator Characteristics; Regression Analysis; Research; Rights; Risk; Sampling; Selection Criteria; Serum; Severities; Small Business Innovation Research Grant; Solid; Study models; Surface; TBI Patients; Technology; Time; Traumatic Brain Injury; Ubiquitin; Ventriculostomy; X-Ray Computed Tomography; base; commercialization; controlled cortical impact; disability; evidence base; experience; high risk; improved; indexing; point of care; prevent; prognostic; programs; sham surgery; standard of care; success; tau Proteins; tool

DESCRIPTION (provided by applicant): The proposed SBIR program aims to develop a rapid point-of-care (POC) prognosticative assay device that provides clinically actionable data to predict onset of high intracranial pressure (HICP) after a severe traumatic brain injury (sTBI). Delayed onset of HICP is a manifestation of secondary injury leading to poor patient outcome following TBI after a severe closed head injury. Early and even preemptive decompressive craniectomy prevents HICP onset and significantly improves outcome in severe TBI patients. Often, a lack of clinically actionable prognosticative information severity forces clinicians to be reactive than proactive in treating sTBI-associated HICP onset. Our proposed SBIR research and commercialization program is to develop a blood and CSF POC neuromonitoring device to predict and identify sTBI patients who will experience delayed HICP onset later. The POC device is based on microfluidic solid phase immunoassay (¿fSPIA) principles, which permit rapid kinetics due to large surface area to volume ratios within the assay channels. We envision that resulting prognostic data will be actionable for clinicians in identifying sTBI patients at strong risk of delayed HICP onset. Based on the near-real time information clinicians can initiate a preemptive decompressive craniectomy and improve clinical outcomes. We have identified seven "lead "biomarker proteins that are associated with sTBI in humans. Our Preliminary Studies also indicate their utility in predicting TBI-induced HICP onset. The proposed Phase I SBIR feasibility study will employ the ¿fSPIA POC platform to measure our four candidate TBI biomarkers in serum from TBI rats. ELISA will be our "gold standard" comparator. We will use the controlled cortical impact-induced severe TBI rat model for these studies. Early measures of serum biomarkers will be employed to predict edema by Day 3 after severe TBI. Our Aims are: Aim 1: Develop and validate the ¿fSPIA POC method for each of the seven TBI candidate biomarkers employing a traditional ELISA as the gold standard. Aim 2: Determine early time point changes in serum biomarker levels employing the ¿fSPIA POC method and correlate it to changes in brain edema at later time point in rats with severe TBI. PUBLIC HEALTH RELEVANCE: Delayed onset of high intracranial pressure is a manifestation of secondary injury leading to poor patient outcome after a severe traumatic brain injury. The proposed SBIR program aims to develop a rapid point-of-care prognosticative assay device that provides clinically actionable data by the patient bedside to predict onset of high intracranial pressure after a severe traumatic brain injury. This will assist clinicians to identify patients "a risk" for high intracranial pressure early and take proactive neurosurgical approaches to improve patient outcome.

描述（由申请人提供）：拟议的 SBIR 计划旨在开发一种快速护理点 (POC) 预后测定装置，该装置提供临床上可操作的数据，以预测严重创伤性脑损伤 (sTBI) 后高颅压 (HICP) 的发生HICP 的延迟发作是继发性损伤的一种表现，导致严重闭合性颅脑损伤后 TBI 后患者预后不良。通常，由于缺乏临床上可操作的预后信息，严重性迫使 HICP 发生并显着改善其预后。 我们提出的 SBIR 研究和商业化计划是开发一种血液和脑脊液 POC 神经监测设备，以预测和识别稍后会经历延迟性 HICP 发作的 sTBI 患者。相免疫分析 (¿fSPIA) 原理，由于分析通道内的表面积与体积之比较大，因此可以实现快速动力学，我们预计由此产生的预后数据将可用于操作。 sTBI 患者在识别具有延迟性 HICP 发作高风险的 sTBI 患者时，基于近乎实时的信息，群体可以启动先发性去骨瓣减压术并改善临床结果，我们已经确定了与人类 sTBI 相关的七种“主要”生物标志物蛋白。我们的初步研究还表明它们在预测 TBI 引起的 HICP 发作方面的效用，拟议的第一阶段 SBIR 可行性研究将采用 ¿用于测量 TBI 大鼠血清中四种候选 TBI 生物标志物的 fSPIA POC 平台将是我们的“黄金标准”比较器，我们将使用受控皮质冲击诱导的严重 TBI 大鼠模型来进行血清生物标志物的早期测量。用于预测严重 TBI 后第 3 天的水肿 我们的目标是： 目标 1：开发并验证 ¿使用传统 ELISA 作为黄金标准，对七种 TBI 生物标志物候选物进行 fSPIA POC 方法 目标 2：使用 ¿ 确定血清生物标志物水平的早期时间点变化。 fSPIA POC 方法并将其与严重 TBI 大鼠稍后时间点的脑水肿变化相关联。 公共健康相关性：高颅压延迟发作是继发性损伤的一种表现，导致严重创伤性脑损伤后患者预后不良。拟议的 SBIR 计划旨在开发一种快速护理点预后检测装置，提供临床上可行的数据。在患者床边预测严重创伤性脑损伤后高颅压的发生，这将有助于早期识别患者出现高颅压的“风险”并采取积极主动的措施。改善患者预后的神经外科方法。