Biodosimetry with a fully integrated biochip using gene expression signatures

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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.