CENTER FOR HIGH-THROUGHPUT MINIMALLY-INVASIVE DOSIMETRY

我们的总体主题是开发用于超高通量微创辐射生物剂量测定的产品。在发生大规模辐射事件后，需要在几天内评估数以万计的个人所受到的辐射剂量。相比之下，目前的“高通量”生物剂量学充其量只能评估几百个人/天。我们将开发实用的微创设备来满足这一需求，每天能够评估数万人。该联盟代表了辐射生物学家、辐射物理学家、辐射化学家、机械工程师、软件工程师、产品开发专家、该领域的商业公司和最终用户之间的多学科平衡。我们已经确定的三个最具高通量生物剂量学潜力的领域是细胞遗传学、功能基因组学和代谢组学；每个领域都有自己的项目，由生物信息学核心、功能基因组学核心、制造核心以及至关重要的产品开发核心支持。这三个项目在总体主题、核心资源的使用以及共同使用相同来源的人体样本--来自全身照射患者的血液/尿液/口腔细胞--方面是相互关联的： 项目1：基于机器人的自动化高通量辐射生物剂量测量-我们将开发一种高通量生物剂量测量设备，使用专门制造的机器人和先进的高速、自动图像采集。生产能力将达到每天30,000个样品，而目前的产能为每天几百个样品。可以使用几个终点(微核和γ-H_2AX灶)和几个组织(血液淋巴细胞、网状网眼和尿液脱落细胞)。 项目2：使用基因表达特征的全集成生物芯片的生物剂量学--暴露在电离辐射下，根据基因表达的变化产生明确的剂量依赖特征。我们的目标是使用这样一个签名，它将通过功能基因组核心建立，以血液指棒为基础，产生一个自给自足的辐射生物剂量计设备。 项目3：通过新陈代谢组学进行快速非侵入性辐射生物剂量测定--这里的总体目标是通过新陈代谢组学识别和利用辐射暴露的特征，以开发基于尿液、唾液或汗液的快速非侵入性生物剂量测定设备。 此外，该联盟的特点是广泛的放射学教学计划，既有面对面的，也有创新的电子研讨会方法，以及以新颖的两阶段审查程序为特色的大型试点研究计划。

Our overall theme is product development for very high throughput minimally-invasive radiation biodosimetry. After a large-scale radiological event, there will be a major need to assess, within a few days, the radiation doses received by tens of thousands of individuals. By contrast, current "high throughput" biodosimetry can, at best, assess a few hundred individuals / day. We will develop practical minimally-invasive devices to meet this need, capable of assessing tens of thousands of individuals per day. The Consortium represents a multidisciplinary balance between radiation biologists, radiation physicists, radiation chemists, mechanical engineers, software engineers, product development experts, commercial companies in the field, and end users. The three areas that we have identified as having the highest potential for high-throughput biodosimetry are cytogenetics, functional genomics, and metabolomics; each area has its own project, supported by a bioinformatics core, a functional genomics core, a fabrication core and, crucially, a product development core. The three projects are linked in terms of the overall theme, their use of the Core Resources, and also in terms of their shared use of the same sources of human samples - blood/urine/buccal cells from total-body irradiated patients: Project 1: Automated Robotically-Based High-Throughput Radiation Biodosimetry - We will develop a high-throughput biodosimetry device, using purpose-built robotics and advanced high speed, automated image acquisition. Throughput will reach 30,000 samples per day, compared with current throughputs of a few hundred samples per day. Several endpoints (micronuclei and y-H2AX foci) and several tissues (blood lymphocytes, reticuloctyes, and exfoliated cells from urine) can be used. Project 2: Biodosimetry with a Fully Integrated Biochip using Gene Expression Signatures - Exposure to ionizing radiation produces a well-defined dose-dependent signature in terms of changes in gene expression. Our goal is to use such a signature, which will be established through the Functional Genomics Core, to generate a self-contained radiation biodosimeter device, based on a blood finger stick. Project 3: Rapid Non-Invasive Radiation Biodosimetry through Metabolomics - Here the overall aim is to identify and utilize a signature of radiation exposure through metabolomics, in order to develop a very fast non-invasive biodosimetric device based on urine, saliva or sweat. In addition, this Consortium features an extensive radiological teaching program, both in person, and with an innovative E-seminars approach, and a large Pilot Research Program, featuring a novel two-phase review procedure.