Rapid Detection and Monitoring of Biomarkers for Traumatic Brain Injury

描述(申请人提供)：美国每年有超过37万人因创伤性脑损伤(TBI)而住院。在美国，与脑损伤的治疗、住院和康复相关的费用估计为每年483亿美元。需要一种快速、简便、准确和有效的脑损伤测试来识别头部创伤并监测病情的进展。一旦发生与颅脑损伤相关的一次冲击，快速反应对于限制由于颅压升高和离子转运过程的异常改变而造成的二次损伤的影响至关重要。损伤患者的神经蛋白质组学变化是指示脑外伤的复杂分子事件的基础。对这些蛋白质组变化的快速和高度即刻的评估应该允许对脑损伤的特异性和敏感性的诊断和对病情的持续评估。辐射监测设备公司建议开发一种紧凑型、一次性微流控传感器，该传感器将从血液样本中快速检测一组多个脑损伤生物标志物。为了实现这一目标，我们将把基于硅基的CMOS(互补金属氧化物半导体)光子计数光学(GPD)探测器直接集成到微流控芯片中，该芯片将使用荧光标记的单抗以非常高的灵敏度检测目标蛋白质组分。这种高灵敏度是通过将光子探测器非常靠近微流控通道内的荧光信号源来实现的。在第一阶段，我们将对现有的微流控传感器进行改造，开发一个测试平台来演示光子计数检测器的集成，并测量模型样本中具有临床意义的TBI生物标志物浓度。在第二阶段，我们将优化微流控系统的设计，开发可在掌上电脑上运行的软件，用于数据分析和用户界面，并测量脑脊液中的脑损伤生物标志物。由此产生的设备将成为在一个单元中检测多个蛋白质的通用技术平台。 RMD建议开发一种紧凑型一次性传感器，可以快速检测创伤性脑损伤的生物标记物。该传感器将同时检测一组10到20个蛋白质生物标记物，用于诊断和监测脑损伤。该传感器基于RMDS专有的光子计数探测器阵列技术。

DESCRIPTION (provided by applicant): Over 370,000 people in the US are hospitalized for traumatic brain injury (TBI) each year. In the US, the cost associated with the treatment, hospitalization and rehabilitation of TBI are estimated to be $48.3 billion annually. A fast, easy, accurate and effective test for brain injury is required to identify head trauma and monitor the progression of the condition. Once the primary impact associated with TBI occurs, rapid response is critical to limit the impact of the secondary damage due to increased cranial pressure and abnormal changes in ion transport processes. Neuroproteomic changes in injured patients underlie the complex molecular events that are indicative of TBI. The high- speed and high-immediacy assessment of these proteomic changes should permit the specific and sensitive diagnosis of TBI and continued evaluation of the condition. Radiation Monitoring Devices proposes to develop a compact, disposable microfluidic sensor that will rapidly detect a panel of multiple TBI biomarkers from a blood sample. To accomplish this, we will integrate silicon-based CMOS (complementary metal oxide semiconductor) photon counting optical (GPD) detectors directly into a microfluidic chip which will detect target protein components with very high sensitivity using fluorescently label monoclonal antibodies. This high sensitivity is achieved by the placement of the photon detectors very close to the source of the fluorescent signal within the microfluidic channel. In Phase I, we will modify an existing microfluidic sensor to develop a test platform to demonstrate the integration of the photon-counting detector, and measure clinically significant concentrations of TBI biomarkers in model samples. In Phase II, we will optimize the design of the microfluidic system, develop software to run on a "palmtop" computer for data analysis and user interface, and measure TBI biomarkers in cerebral spinal fluid. The resulting device will be a general technology platform for the detection of multiple proteins in a single unit. RMD proposes to develop a compact disposable sensor that will rapidly detect biomarkers for traumatic brain injury. The sensor will simultaneously detect a panel of ten to twenty protein biomarkers that are used to diagnose and monitor brain injury. The sensor is based RMDs proprietary photon counting detector array technology.