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: 10596303
• 负责人: Richard Joseph Kowalski
• 金额: $ 10.15万
• 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/10596303
• 关键词: Acute; Address; Algorithms; 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; Goals; Hand; Health; Hematology; Hematopoietic; Hematopoietic System; Human; Immunoassay; Immunodiagnostics; Individual; Late Effects; Leukocytes; Measures; Medical; Methods; Microscopy; Microspheres; Morbidity - disease rate; National Institute of Allergy and Infectious Disease; Needs Assessment; Nuclear; Nuclear Accidents; Nuclear Radiology; Organ; Physical shape; Physiological; Plasma; Public Health; Radiation; Radiation Accidents; Radiation Dosage; Radiation Dose Unit; Radiation Injuries; Radiation Toxicity; Radiation exposure; Radiation induced damage; Risk; 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; base; biodosimetry; cell analyzer; clinically relevant; 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国保护公众健康的能力 通过开发单一移动护理点(POC)来应对大规模辐射/核事件 将填补我国目前辐射分类中三个已确定空白的诊断设备 评估能力。首先，它将区分那些忧心忡忡的人和暴露在 辐射剂量的阈值为2GY；其次，它将提供对造血的评估 急性辐射综合征(H-ARS)严重风险以及辐射剂量估计 2GY；第三，它将允许检测和定量可溶性(特定目标1，SA1)和 与细胞表面相关的(特异性目标2，SA2)血液和器官特异性辐射损伤 提供有关主要器官和生理系统的关键信息的生物标志物 损坏/故障。这项提议的主旨将是发展和展示 检测创新手持设备上的辐射损伤生物标记物。该设备包括 一种经过良好审查的POC血细胞分析仪，能够进行5部分白细胞区分 使用创新的无透镜显微镜技术在现场进行分析。该设备 使用全血的指棒，在8分钟内就能得出结果。在这里，我们将 进一步扩展这些能力，以实现基于免疫分析的血液/血浆分析 辐射损伤生物标志物。我们首先将演示检测和量化的能力 人体血液样本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，代表着 炎症、唾液腺损伤、骨髓祖细胞分布； 从而论证了该系统在多系统损伤评估中的实用性。我们的 可溶性生物标志物的免疫分析将使用高度敏感的微球-复合体形成 还允许多路传输功能的格式。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定辐射损伤的生物标记物。最后，我们 将在设备中集成两种特定于生物剂量学的算法，以允许将 将血细胞计数数据转化为辐射损伤、剂量暴露的指标，并预测 H-ARS的发展风险(特定目标3，SA3)。通过提供单一的便携式 能够解决NIAID在以下方面发现的许多差距的诊断设备 我们国家应对严重辐射事件的能力将大幅提升 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。