Rapid Assessment of Radiation Exposure

描述(申请人提供)：大规模的灾难情况对现有的医疗基础设施以及地方管理和安全机构提出了相当大的要求。当电离辐射和人体暴露的额外因素是紧急情况的一部分时，缺乏有效的评估工具和管理战略很容易变得不堪重负。作为设计满足这一关键需求的方法和技术的努力的一部分，这项提议旨在开发和评估可以从少量血液样本中获得的两个辐射敏感终点。其目标是创建一个分析平台，可以集成到移动响应单元中，可以快速调查在某些紧急分流情况下预计会有数千名受试者。以足够快的速度提供有用的剂量/暴露估计的关键是将通过免疫磁性技术进行的细胞浓缩与采用多孔板(例如384或1536井)的高通量分析平台相结合。一种超高通量的循环淋巴细胞计数方法将作为初始筛查，可以快速调查和标记受试者以进行进一步分析。使用相同的血液样本，验证性试验将使用流式细胞术评估微核网织红细胞作为辐射诱发的染色体损伤的标志。这种分两个阶段进行的方法将使第一次筛查能够迅速排除大多数已经接受最小到没有接触的个体，而随后的检测将专注于最终确定需要进一步医疗护理的受试者。通过快速有效地将忧心忡忡的人送回家，可以将资源和护理更有效地分配到最终需要的地方。这种办法对于确保立即和充分地应对大规模紧急情况至关重要，这些紧急情况是人口暴露在电离辐射下造成的。 公共卫生相关性：人类意外或故意暴露在电离辐射中，不仅将直接影响公众健康，还将影响世界各地的经济、政治和社会。制定评估和减轻这些影响的工具和战略具有至关重要的国家和全球重要性。这项提议寻求产生一种快速、高通量的方法，使用两个已建立的辐射损害生物标记物来确定个人在护理点分类设置中的暴露情况。

DESCRIPTION (provided by applicant): Large-scale disaster situations put considerable demands on existing medical infrastructure, as well as local governing and safety agencies. When the additional factor of ionizing radiation and exposure of humans is part of the emergency, the lack of effective assessment tools and management strategies can easily become overwhelming. As part of efforts to devise methods and technologies that will address this critical need, this proposal is designed to develop and evaluate two radiation- sensitive endpoints that can be obtained from a small volume blood sample. The goal is to create an analytical platform that could be integrated into mobile response units that can quickly survey the thousands of subjects expected in certain emergency triage situations. The key to delivering useful dose/exposure estimation with a sufficiently rapid turnaround is the combination of cell enrichment via immunomagnetic technologies with high throughput analytical platforms that employ multi-well plates, e.g. 384 or 1536 well. An ultra-high throughput method that enumerates circulating lymphocytes will serve as an initial screen that can rapidly survey and flag subjects for further analysis. Using the same blood sample, the confirmatory assay will employ flow cytometric assessment of micronucleated reticulocytes as a marker of radiation-induced chromosome damage. This two-stage approach will enable the first screen to quickly dismiss the majority of individuals that have received minimal-to-no exposure and the subsequent assay will focus on definitive identification of subjects that will require further medical care. By quickly and efficiently sending the worried-well home, more effective allocation of resources and care can be directed where it is ultimately needed. Such an approach is critical to ensuring an immediate and sufficient response to large-scale emergencies such as those presented by exposure of human populations to ionizing radiation. PUBLIC HEALTH RELEVANCE: Accidental or intentional exposure of human populations to ionizing radiation will not only directly impact public health, but will also affect economics, politics and societies worldwide. The development of tools and strategies to assess and mitigate these impacts are of critical national and global importance. This proposal seeks to generate a rapid high throughput approach using two established biomarkers of radiation damage to determine exposure of individual humans in point-of-care triage settings.