SBIR Phase I: Microfluidic Technology for Single Cell Multi-Omic Sample Preparation

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project is to commercialize an automatable microfluidic technology capable of disrupting the existing sample preparation market. This market, projected to surpass $5.32 billion USD by 2025, is driven by the development of new and automatable technology platforms. These technology platforms not only facilitate the development of precision medicine, but also our understanding of the fundamental mechanisms behind cellular behavior. Here, automated sample preparation platforms are favored for their ease of use and integration potential with both upstream cell capture technologies (e.g. single cell selection, rare cell enrichment) as well as downstream analysis technologies (e.g. DNA/RNA sequencing, mass spectrometry). Rather than requiring scientists to reproduce complex in-house protocols developed by different academic laboratories, automated platforms would allow users the freedom of simply loading a sample and walking away. However, existing platforms in this market are limited by their fundamental single-compartment design, making the processing of complex systems highly challenging. This Small Business Innovation Research (SBIR) Phase I project proposes to demonstrate the feasibility of a fundamentally different approach to multi-omic single cell processing. Instead of relying on a single-compartment design (e.g. droplet microfluidics, microwell technologies, valved and chambered microchannels, tube-based kits, etc.) for cell processing, this project will use novel micropillar-based microfluidic technology for high efficiency separation and isolation of single cell omes. Here, micropillar arrays within our microfluidic channels serve to physically size-separate genomic DNA from proteins and RNA during cell lysis in a manner compatible with existing analysis methods. In Phase I, we will build upon our preliminary results by demonstrating bi-omic isolation of the genome and transcriptome from the same cell along with the ability to amplify and sequence the genomic DNA before and after bisulfite treatment for tri-omic isolation of the genome, transcriptome, and methylome. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.