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

描述（由申请人提供）：拟定SBIR项目旨在开发一种快速床旁（POC）辅助测定装置，该装置可提供临床可操作数据，以预测重度创伤性脑损伤（sTBI）后高颅内压（HICP）的发生。HICP延迟发作是严重闭合性颅脑损伤后TBI导致患者预后不良的继发性损伤的表现。早期甚至先发制人的去骨瓣减压术可预防HICP发作，并显著改善重度TBI患者的预后。通常，缺乏临床上可操作的诊断信息严重性迫使临床医生 在治疗sTBI相关HICP发作方面，反应性治疗优于主动治疗。我们提出的SBIR研究和商业化计划是开发一种血液和CSF POC神经监测设备，以预测和识别将在以后发生延迟HICP发作的sTBI患者。POC装置基于微流控固相免疫测定（fSPIA）原理，由于测定通道内的大表面积与体积比，其允许快速动力学。我们设想，由此产生的预后数据将是可操作的临床医生在确定sTBI患者延迟HICP发作的高风险。基于近实时的信息，临床医生可以启动先发制人的去骨瓣减压术，并改善临床结果。我们已经确定了七个与人类sTBI相关的“铅”生物标志物蛋白。我们的初步研究还表明，它们在预测TBI诱导的HICP发作中的实用性。拟议的I期SBIR可行性研究将采用fSPIA POC平台来测量TBI大鼠血清中的四种候选TBI生物标志物。ELISA将是我们的“金标准”比较。我们将使用受控的皮质撞击诱导的严重TBI大鼠模型进行这些研究。将采用血清生物标志物的早期测量来预测重度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作为金标准，对七种TBI候选生物标志物中的每一种使用fSPIA POC方法。目标二：采用Δ fSPIA POC方法确定血清生物标志物水平的早期时间点变化，并将其与患有严重TBI的大鼠中在稍后时间点的脑水肿变化相关联。 公共卫生相关性：高颅内压延迟发作是严重创伤性脑损伤后继发性损伤的表现，导致患者预后不良。拟议的SBIR计划旨在开发一种快速的床旁诊断分析设备，该设备可在患者床边提供临床可操作的数据，以预测严重创伤性脑损伤后高颅内压的发生。这将有助于临床医生早期识别高颅内压患者的“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.