Interview for Faculty Position

Conformational Sculpting of DNA:
Nanofluidics for Single Molecule DNA Analysis and Manipulation

W. Reisner

Physics Department, Brown University
DTU Nanotech - Dept. of Micro- and Nanotechnology, Technical University of Denmark
Department of Physics, Division of Solid State Physics, Lund University

My work uses sub micron nanofabrication tools like electron beam lithography to explore the fundamental physics of polymers in confinement and to develop nanotechnology approaches to key problems in biology. When a polymer is confined in a structure with dimension below the polymer's free solution gyration radius the confining geometry will alter the polymer equilibrium conformation. This fundamental result of statistical physics has a key technological implication: polymer conformation can be manipulated and controlled onchip by design of the nanofluidic confining geometry. This talk will consider two implications of this notion of ‘conformational sculpting’ for the field of single molecule DNA analysis. In a nanochannel, self-exclusion interactions within the polymer will create a linear unscrolling of the genome along the channel for analysis. Nanochannel based DNA stretching can serve as a platform for a new optical mapping technique based on measuring the pattern of partial melting along the extended molecules. We believe this melting mapping technology is the first optically based single molecule technique sensitive to genome wide sequence variation that does not require an additional enzymatic labeling or restriction scheme. In addition, by embedding sub micron nanotopographies in a slit-like nanochannel, we can create spatial variation in confinement across the slit. The confinement variation in turns varies a molecule's configurational freedom, or entropy. Consequently, by controlling device geometry, we can create a user-defined free energy landscape that allows us to ‘sculpt’ the equilibrium configuration of a molecule. Individual square depressions, or nanopits, can be used to trap DNA at specific points in the slit. Arrays of nanopits will lead to complex ‘digitized’ conformations with a single molecule linking a number of pits.