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

Note: Pizza served at 11:30 AM
Speaker: Walter Reisner, Brown University

When: April 10, 2009 (Fri), 12:00PM to 01:00PM (add to my calendar)
Location: SCI 352
Hosted by: Ophelia Tsui

This event is part of the Biophysics/Condensed Matter Seminar Series.

Abstract:
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 nanofludic 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.