Greg Randall

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Recent advances in gene therapy and crime investigation have spurred a demand for rapid gene mapping of large (kbp-Mbp) DNA molecules. Because current electrophoresis technologies are inadequate for large DNA, several promising MEMS designs for DNA mapping have been recently proposed that require either 1) a DNA molecule negotiating an obstacle course in a microchannel or 2) stretching a DNA coil for linear analysis. The goal of our research is to experimentally probe the fundamental physics that underlie these DNA mapping designs. In general, the governing physics is complex due to the confinement of the microchannel, the coiled-nature of long DNA molecules, and the induced electric field gradients from obstacles and changes in channel dimensions.

With single molecule microscopy, we have demonstrated many of the governing physical mechanisms at play in these gene mapping microfluidic devices [1-3]. For example, we have shown the experimental scaling for the diffusion coefficient of DNA in a confined channel (Figure 1a) and the probability distribution for the collision time of a DNA molecule unhooking from a small obstacle (Figure 1c). In addition, we have thoroughly investigated DNA stretching in electric field gradients created by a contraction and an obstacle (Figure 2). Just as a flow gradient stretches a polymer, an electric field gradient can stretch a charged polymer like DNA. Because electric field gradients have no local rotational components, a charged polymer will experience purely extensional deformation. These findings will aid the design of DNA separation devices that contain many obstacles and contractions and they also offer an attractive way to completely stretch DNA for linear analysis.