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.

暴露于电离辐射会在许多基因的表达中产生剂量依赖性变化，这可能提供了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发展，该生物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，以对复杂生物样品溶液（例如血液）进行DMA分析。我们建议将该设备开发为适合大规模筛选的独立辐射生物轴测指体。该墨盒将包含其自身的电源，控制电子，功能性微流体成分和试剂。测定完成后，将墨盒插入读取器中，该读取器在几秒钟内读出信号。该项目的具体目的是： 1。开发一个用于从手指刺收集血液的模块。 2。制造和验证具有集成寡核苷酸阵列的环链共聚合物生物渠道芯片。 3。开发和性能测试一个集成的微/纳米流体墨盒，用于提取和处理全血的RNA。 4。结合了由功能基因组核心鉴定的辐射相关基因表达特征进入定制的微流体微阵列。 5。整合血液样品收集装置，RNA提取装置和杂交微通道设备进入单个独立的生物芯片，并验证该生物芯片的性能。 6。整合和评估自包含墨盒的试剂存储选项。 7。开发集成的控制电子设备，创建适合批量生产和的便携式仪器应用于高通量筛选，并验证该设备满足产品要求。总而言之，我们将开发能够快速测量一百个或多个基因的表达水平的独立生物芯片，以定义辐射暴露，剂量和损伤。这种方法只需要从手指刺中滴一滴血，并且在放射线事件发生的情况下很容易部署以进行大规模的人口筛查。