Rapid Assessment of Radiation Exposure

描述（由申请人提供）：大规模的灾害情况对现有的医疗基础设施以及地方政府和安全机构提出了相当大的要求。当电离辐射和人类接触这一额外因素成为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成为压倒性的问题。作为设计解决这一关键需求的方法和技术的一部分，本提案旨在开发和评估可从小容量血液样本中获得的两个辐射敏感端点。目标是创建一个分析平台，可以集成到移动响应单元中，在某些紧急分类情况下可以快速调查数千个主题。提供有用的剂量/暴露估计和足够快速的周转的关键是结合细胞富集通过免疫磁技术和高通量分析平台，采用多孔板，如384或1536孔。枚举循环淋巴细胞的超高通量方法将作为初始筛选，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，验证性测定将采用流式细胞术评估微核网状细胞作为辐射诱导的染色体损伤的标记。这种两阶段的方法将使第一次筛选能够迅速排除大多数受到最低或没有接触的个体，随后的分析将侧重于明确识别需要进一步医疗护理的受试者。通过快速有效地将担心健康的人送回家，资源和护理可以更有效地分配到最终需要的地方。这种方法对于确保对大规模紧急情况，如人口暴露于电离辐射所造成的紧急情况作出迅速和充分的反应至关重要。

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.