Applied NanoBioscience Center and Medicine, University of Arizona, Phoenix, AZ 85004-2157, USA.
Health Phys. 2010 Feb;98(2):179-85. doi: 10.1097/01.HP.0000346706.44253.5c.
This paper reports the development of a biodosimetry device suitable for rapidly measuring expression levels of a low-density gene set that can define radiation exposure, dose and injury in a public health emergency. The platform comprises a set of 14 genes selected on the basis of their abundance and differential expression level in response to radiation from an expression profiling series measuring 41,000 transcripts. Gene expression is analyzed through direct signal amplification using a quantitative Nuclease Protection Assay (qNPA). This assay can be configured as either a high-throughput microplate assay or as a handheld detection device for individual point-of-care assays. Recently, we were able to successfully develop the qNPA platform to measure gene expression levels directly from human whole blood samples. The assay can be performed with volumes as small as 30 microL of whole blood, which is compatible with collection from a fingerstick. We analyzed in vitro irradiated blood samples with qNPA. The results revealed statistically significant discrimination between irradiated and non-irradiated samples. These results indicate that the qNPA platform combined with a gene profile based on a small number of genes is a valid test to measure biological radiation exposure. The scalability characteristics of the assay make it appropriate for population triage. This biodosimetry platform could also be used for personalized monitoring of radiotherapy treatments received by patients.
本文报告了一种适合快速测量低浓度基因集表达水平的生物剂量测定装置的开发,该基因集可在公共卫生紧急情况下定义辐射暴露、剂量和损伤。该平台由一组 14 个基因组成,这些基因是根据其在辐射响应中的丰度和差异表达水平选择的,这些基因是通过测量 41000 个转录本的表达谱系列得出的。通过使用定量核酸酶保护分析(qNPA)进行直接信号扩增来分析基因表达。该测定可以配置为高通量微孔板测定,也可以配置为用于个体即时护理测定的手持式检测装置。最近,我们成功地开发了 qNPA 平台,能够直接从人类全血样本中测量基因表达水平。该测定可以使用小至 30μL 的全血体积进行,这与从指尖采集兼容。我们用 qNPA 分析了体外辐照的血液样本。结果显示,辐照和未辐照样本之间存在统计学上显著的区分。这些结果表明,qNPA 平台与基于少数基因的基因谱相结合是测量生物辐射暴露的有效测试。该测定的可扩展性使其适合人群分类。该生物剂量测定平台还可用于监测患者接受的放射治疗。