Research and Development of a Hand-held, Rapid, Point-of-Care Radiation Biodosimetry Triage Device and Integration of Soluble and Cell-surface Radiation Injury Biomarker Assays

NIH-NIAID RFA-A1-18-045 项目概要/摘要 该项目的总体目标是提高我们国家保护公众健康的能力， 通过开发单个移动的监护点（POC）， 一种诊断设备，将填补我国目前辐射分类中的三个空白 评估能力。首先，它将区分担心的人和暴露在危险中的人。 辐射剂量在2Gy的阈值;第二，它将提供造血评估 急性辐射综合征（H-ARS）的严重风险，以及辐射剂量估计超过 第三，它将允许检测和定量可溶性（特异性目标1，SA 1）和 细胞表面相关（特异性目标2，SA 2）血液和器官特异性辐射损伤 生物标志物提供关于主要器官和生理系统的关键信息 损坏/故障。本提案的主旨是发展和展示以下能力： 在创新的手持设备上检测辐射损伤生物标志物。该装置包括： 经过严格审查的POC血细胞分析仪能够进行5部分白细胞分类 使用创新的无透镜显微镜技术进行现场分析。设备 使用手指针刺全血，并在8分钟内提供结果。在这里，我们将 进一步扩展这些能力，以允许基于免疫测定的血液/血浆分析 辐射损伤生物标志物。我们最初将展示检测和量化 人血液样品中辐射损伤的三种可溶性生物标志物;血清淀粉样蛋白-A， 唾液α-淀粉酶和Fms相关酪氨酸激酶3配体，代表 炎症、唾液腺损伤和骨髓祖细胞分布; 从而证明了该系统用于多系统损伤评估的实用性。我们 可溶性生物标志物免疫测定将使用高度敏感的微球复合物形成 格式，也允许多路复用能力。此外，我们还将展示以下能力： 在我们的设备上检测许多细胞表面特异性辐射损伤生物标志物。最后我们 将在设备中集成两种生物剂量学特定算法， 将血细胞计数数据转化为辐射损伤、剂量暴露和 H-ARS（Specific Aim 3，SA 3）的风险。通过提供单个便携式 诊断设备能够解决许多差距，已确定的NIAID在 我们将大大提高我国应对严重辐射事故的能力， 辐射分流公共卫生反应能力，以及提供革命性的潜力， POC免疫诊断。

NIH-NIAID RFA-A1-18-045 Project Summary/Abstract The overall goal of this project is to advance our nation's ability to protect public health in the event of a large-scale, radiation/nuclear event by developing a single mobile point of care (POC) diagnostic device that will fill three identified gaps in our country's current radiation triage assessment capabilities. First, it will distinguish the worried-well from individuals exposed to radiation doses at a threshold of 2Gy; second, it will provide an assessment of hematopoietic acute radiation syndrome (H-ARS) severity risk, as well as a radiation dose estimate beyond 2Gy; and third, it will allow the detection and quantification of soluble (Specific Aim 1, SA1) and cell-surface associated (Specific Aim 2, SA2) blood- and organ-specific radiation damage biomarkers to provide critical information about major organ and physiological system damage/failure. The thrust of this proposal will be on developing and demonstrating the ability to detect radiation damage biomarkers on an innovative handheld device. The device is comprised of a well-vetted POC blood cell analyzer capable of performing a 5-part leukocyte differential analysis in field-settings using an innovative lensless microscopy technology. The device utilizes a fingerstick of whole blood and provides results in under 8 minutes. Here, we will further expand these capabilities to allow for the immunoassay-based analysis of blood/plasma radiation damage biomarkers. We initially will demonstrate the ability to detect and quantify three soluble biomarkers of radiation damage in human blood samples; serum amyloid-A, salivary α-amylase, and Fms-related tyrosine kinase 3 ligand, representing markers of inflammation, salivary gland damage, and bone marrow progenitor cell distribution, respectively; thereby demonstrating the utility of the system for multiple systems damage assessment. Our immunoassay for soluble biomarkers will use a highly sensitive microsphere-complex formation format that also allows for multiplex capabilities. In addition, we will demonstrate the ability to detect a number of cell surface specific radiation damage biomarkers on our device. Lastly, we will integrate into the device two biodosimetry-specific algorithms to allow the conversion of blood cell enumeration data into indicators of radiation injury, dose exposure, and a prediction of the risk of development of H-ARS (Specific Aim 3, SA3). By providing a single portable diagnostic device capable of addressing many of the gaps that have been identified by NIAID in our country's ability to respond to severe radiation incidents we will significantly advance radiation triage public health responsiveness, as well as provide for the potential to revolutionize POC immunodiagnostics.