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

手持式快速护理点辐射生物剂量测定分类装置的研究和开发以及可溶性和细胞表面辐射损伤生物标志物测定的集成

• 批准号: 10574613
• 负责人: Richard Joseph Kowalski
• 金额: $ 37.13万
• 依托单位: ASELL, LLC
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10574613
• 关键词: Acute; Address; Algorithms; Authorization documentation; Biological Assay; Biological Markers; Blood; Blood Cells; Blood specimen; Bone Marrow; Cell surface; Cells; Cellular Morphology; Complete Blood Count; Complex; Country; Data; Detection; Development; Devices; Diagnostic; Diagnostic Equipment; Discrimination; Dose; Emergency Situation; Emergency response; Event; Exposure to; FLT3 ligand; Failure; Fingers; Goals; Health; Hematology; Hematopoietic; Hematopoietic System; Human; Immunoassay; Immunodiagnostics; Individual; Late Effects; Leukocytes; Measures; Medical; Microscopy; Microspheres; Morbidity - disease rate; National Institute of Allergy and Infectious Disease; Needs Assessment; Nuclear; Nuclear Accidents; Organ; Physical shape; Physiological; Plasma; Public Health; Radiation; Radiation Accidents; Radiation Dosage; Radiation Dose Unit; Radiation Injuries; Radiation Toxicity; Radiation exposure; Radiation induced damage; Radiology Specialty; Risk; Risk Assessment; Safety; Salivary; Salivary Glands; Serum amyloid A protein; Severities; System; Technology; Testing; Time; Tissues; Triage; United States; United States National Institutes of Health; Whole Blood; alpha-amylase; authority; biodosimetry; cell analyzer; clinically relevant; detection method; first responder; handheld equipment; improved; indexing; inflammatory marker; innovation; instrument; irradiation; mass casualty; medical countermeasure; minimally invasive; mobile application; mobile computing; mortality; novel; point of care; point-of-care diagnostics; portability; predictive marker; public health emergency; radiation effect; research and development; risk prediction; stem cells; tissue injury

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.

NIH-NIAID RFA-A1-18-045 项目摘要/摘要 该项目的总体目标是提高我们国家保护公共卫生的能力 通过开发单个移动护理点（POC），发生大规模辐射/核事件的事件 诊断设备将填补我国当前辐射分类中的三个确定空白 评估功能。首先，它将区分忧虑孔和暴露的人 辐射剂量在2Gy的阈值；其次，它将提供造血的评估 急性辐射综合征（HARS）严重程度风险，以及辐射剂量估算 2gy;第三，它将允许检测和量化固体（特定目标1，SA1）和 细胞表面相关（特定AIM 2，SA2）血液和器官特异性辐射损伤 生物标志物提供有关主要器官和生理系统的关键信息 伤害/失败。该提案的主旨将是发展并证明能力 检测创新的手持设备上的辐射损伤生物标志物。该设备已完成 能够执行5部分白细胞差异的良好vet的POC血细胞分析仪 使用创新的无透镜显微镜技术进行现场分析的分析。设备 利用全血的指尖，并在不到8分钟的时间内提供结果。在这里，我们会的 进一步扩展这些功能，以允许基于免疫测定的血液/等离子体分析 辐射损害生物标志物。我们最初将证明检测和量化的能力 人类血液样本中辐射损伤的三种固体生物标志物；血清淀粉样蛋白A， 唾液α-淀粉酶和与FMS相关的酪氨酸激酶3配体，代表标记 炎症，唾液腺损伤和骨髓祖细胞分布； 从而证明了系统对多个系统损害评估的实用性。我们的 固体生物标志物的免疫测定将使用高度敏感的微粒形成 格式也允许多路复用功能。此外，我们将证明 检测我们设备上的许多细胞表面特异性辐射损伤生物标志物。最后，我们 将集成到设备中两个生物测量特异性算法，以允许转换 血细胞枚举数据中的辐射损伤指标，剂量暴露和预测 H-ARS发展的风险（特定目标3，SA3）。通过提供一个便携式 诊断设备能够解决NIAID在 我国应对严重辐射事件的能力，我们将大大提高 辐射分类公共卫生的响应能力，并提供了革新的潜力 POC免疫诊断。