Soft matter on-a-chip: Nanofluidics for single molecule DNA analysis and manipulation

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Nanofluidic devices are networks of fluid-filled channels etched on a chip with dimensions on order of 1-100nm. Devices with such small dimensions can have radically different properties than their macro world analogs, in particular the ability to manipulate and analyze single molecules. The core of the PI's research program-both pure and applied-is the use of nanofluidic devices for the manipulation and analysis of single molecules of DNA. DNA is of fundamental importance to biology, an important nanoscale structural material in its own right and a model system for understanding the physics of polyelectrolytes in confinement. The goal of the PI's fundamental research program is to create new knowledge (new scaling laws, explore new phenomena) while translating the basic science into new device concepts. The applied component makes use of nanofluidic technology to tackle immediate problems in biomedicine. When DNA is squeezed into a small 'nanopipe' (e.g. using high pressure) the molecule will stretch out, unscrolling the genome along the channel. The PI has developed a new 'melting mapping' approach for analyzing the unscrolled DNA. The extended DNA is partially melted via chemical and thermal denaturation, resulting in the co-existence of double stranded and single stranded regions along the molecule. This melting pattern is sequence dependent. By using dyes which unbind from melted regions, the local melting pattern can be observed optically as a "bar-code" of alternating dark and bright regions. The long term goal is to use this barcoding technology to create maps of entire genome to aid in sequencing, the study of large-scale structural variation and as a tool for single cell genomic analysis.