This Small Business Innovation Research (SBIR) Phase I project aims to develop a commercial nanofluidic chip for the rapid identification of epigenetic marks on individual molecules. The instrument will dramatically improve existing methods of epigenomic analysis by removing two major limitations of the current technology. The proposed device will enable automated quantification of multiple epigenetic marks simultaneously using minute inputs of chromatin and high throughput single molecule observations. The approach involves measuring distinct fluorescent signals from antibodies bound specifically to epigenetic marks on individual chromatin fragments that are electrophoretically transported through lasers focused within a nanoscale fluidic channel. The objectives of this proposal are to transform this laboratory setup into a prototype commercial product by increasing the throughput using parallel fluidic channels and transforming to a free space optical system. It is anticipated that this Phase I proposal will result in the fabrication of devices containing 96 parallel nanofluidic channels and the design of the free space optical system that will facilitate this transformation. The broader impact/commercial potential of this project is that it will result in commercially available products that overcome two key limitations of current epigenomic technology. Current technology requires an abundant amount of input material and can query only one epigenetic mark at a time. The proposed single molecule analytical methods can overcome both of these limitations. It is anticipated that this effort will yield a new disruptive epigenomics technology to serve commercial, academic, and clinical needs. By developing an automated instrument that can interrogate multiple epigenetic marks simultaneously on single chromatin molecules extracted from very small inputs of cells, this technology will enable epigenomic analyses that are far more information rich and lower in cost than is currently possible.
