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

描述(由申请人提供)：建议的SBIR计划旨在开发一种快速的护理点(POC)预测分析设备，提供临床上可操作的数据，以预测严重创伤性脑损伤(STBI)后高颅内压(HICP)的发生。重型闭合性颅脑损伤后继发性脑损伤的一种表现为HICP发病延迟，导致患者预后不良。早期甚至先发制人的开颅去骨瓣减压术可以预防HICP的发生，并显著改善重型颅脑损伤患者的预后。通常，临床上可操作的预测性信息的缺乏迫使临床医生 在治疗sTBI相关的HICP发病方面，反应性多于主动性。我们建议的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，以预测和识别将经历延迟HICP发病的sTBI患者。POC设备基于微流控固相免疫分析(FSPIA)原理，由于分析通道内的大表面积与体积比，该原理允许快速动力学。我们预见，由此产生的预后数据将可用于临床医生识别具有延迟HICP发病的高风险的sTBI患者。根据近乎实时的信息，临床医生可以启动先发制人的去骨瓣减压术，改善临床结果。我们已经确定了七种与人类sTBI相关的“铅”生物标志物蛋白。我们的初步研究也表明，它们在预测颅脑损伤诱导的HICP发病方面是有用的。拟议的第一阶段SBIR可行性研究将使用fSPIA POC平台来测量我们在脑损伤大鼠血清中的四个候选脑损伤生物标志物。酶联免疫吸附试验将成为我们的“黄金标准”。我们将使用受控皮质撞击诱导的严重脑外伤大鼠模型进行这些研究。血清生物标记物的早期测量将用于预测重型颅脑损伤后第3天的水肿。我们的目标是：目标1：以传统的酶联免疫吸附试验为金标准，开发和验证七种脑损伤候选生物标志物的fSPIA POC方法。目的：用fSPIA POC方法测定重型颅脑损伤大鼠早期时间点血清生物标志物水平的变化，并将其与后期脑水肿的变化相关联。 公共卫生相关性：严重颅脑损伤后，延迟出现高颅压是继发性损伤的一种表现，导致患者预后不良。建议的SBIR计划旨在开发一种快速护理点预测分析设备，通过患者床边提供临床可操作的数据，以预测严重颅脑损伤后高颅压的发生。这将有助于临床医生及早识别患者的高颅压风险，并采取积极的神经外科方法来改善患者的预后。

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.