Biodosimetry with a fully integrated biochip using gene expression signatures

使用基因表达特征通过完全集成的生物芯片进行生物剂量测定

基本信息

批准号：
7470135
负责人：
Frederic Zenhausern
金额：
$ 109.87万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/7470135
关键词：
3-Dimensional Affect Back Biological Biological Assay Blood Blood Volume Blood capillaries Blood specimen Cells Collaborations Collection Compatible Complex Cultured Cells Cytolysis DNA Microarray Chip DNA Microarray format Data Deposition Detection Development Devices Dimensions Dose Drops Drug Formulations Electronics Elements Ensure Enzymes Evaluation Event Exposure to Fingers Fluorescence Gel Gene Expression Gene Expression Profile Generations Genes Genetic Transcription Genomics Goals Housing Human Immobilization In Vitro Injury Ionizing radiation Kinetics Label Lasers Liquid substance Location Measures Methods Metric Microfluidics Oligonucleotide Microarrays Oligonucleotides Optics Paraffin Performance Phase Plastics Polymerase Chain Reaction Polymers Population Power Sources Preparation Procedures Process Production Protocols documentation Pump RNA RNA Processing RNA amplification RNA purification Radiation Radiation Monitoring Range Reaction Reader Reading Reagent Relative (related person)Reporting Reverse Transcription Running Sampling Screening procedure Sensitivity and Specificity Series Signal Transduction Site Skin Solutions Surface System Technology Testing Tube Vacuum Validation Whole Blood base biochip biodosimeter biodosimetry capillary concept cost design functional genomics high throughput screening imprint improved instrument instrumentation interest lithography magnetic beads micro-total analysis system nanochannel nanofluidic nanolitre nanoscale performance tests peripheral blood point of care prototype sample collection scale up sensor solution hybridization tissue culture

项目摘要

Exposure to ionizing radiation produces dose-dependent changes in the expression of many genes, potentially providing a means to assess both radiation exposure and dose. We have recently reported development of a completely self-contained biochip that consists of microfluidic mixers, valves, pumps, channels, chambers, heaters, and DNA microarray sensors to perform DMA analysis of complex biological sample solutions, such as blood. We propose to develop this device into a self-contained radiation biodosimeter suitable for large scale screening. The cartridge will contain its own power source, control electronics, functional microfluidic components and reagents. After assay completion, the cartridge is inserted into a reader where the signal is read out within seconds. The Specific Aims of this Project are to: 1. Develop a module for the collection of blood from a finger prick. 2. Fabricate and validate cyclo-olefinic co-polymer biochannel chips with integrated oligonucleotide arrays. 3. Develop and performance-test an integrated micro/nano fluidic cartridge for extraction and processing of RNA from whole blood. 4. Incorporate the radiation-related gene-expression signature identified by the Functional Genomics Core into customized microfluidic micro-arrays. 5. Integrate the blood sample collection device, the RNA extraction device and the hybridization microchannel device into a single self-contained biochip, and validate the performance of this biochip. 6. Integrate and evaluate reagent storage options for the self-contained cartridge. 7. Develop integrated control electronics, creating a portable instrument suitable for mass-production and application to high-throughput screening, and verification that this device meets product requirements. In summary, we will develop self-contained biochips capable of rapidly measuring expression levels of a hundred or more genes that will define radiation exposure, dose and injury. This approach will only require a drop of blood from a finger prick, and will be readily deployable for large-scale population screening in the event of a radiological incident.

暴露于电离辐射会导致许多基因的表达发生剂量依赖性变化，这可能提供一种评估辐射暴露和剂量的方法。我们最近报道了一种完全独立的生物芯片的开发，该芯片由微流体混合器、阀门、泵、通道、腔室、加热器和 DNA 微阵列传感器组成，用于对复杂的生物样品溶液（例如血液）进行 DMA 分析。我们建议将该设备开发成适合大规模筛查的独立辐射生物剂量计。该盒将包含自己的电源、控制电子设备、功能性微流体组件和试剂。测定完成后，将盒插入读取器中，在几秒钟内读出信号。该项目的具体目标是： 1. 开发一个用于从手指刺破处采集血液的模块。 2. 制造并验证具有集成寡核苷酸阵列的环烯共聚物生物通道芯片。 3. 开发并测试用于提取和处理的集成微/纳米流体盒来自全血的 RNA。 4. 纳入功能基因组核心识别的辐射相关基因表达特征定制的微流控微阵列。 5、集血样采集装置、RNA提取装置、杂交于一体将微通道装置集成到单个独立的生物芯片中，并验证该生物芯片的性能。 6. 集成并评估独立试剂盒的试剂存储选项。 7. 开发集成控制电子器件，打造适合批量生产和测量的便携式仪器应用到高通量筛选，并验证该设备满足产品要求。总之，我们将开发独立的生物芯片，能够快速测量一百个或更多基因的表达水平，这些基因将定义辐射暴露、剂量和损伤。这种方法只需要从手指上刺破一滴血，并且可以在发生放射性事件时轻松用于大规模人群筛查。