My present work is divided into at least four areas. All of my projects are aimed at using the techniques of physics to achieve a quantitative understanding of fundamental aspects of biological molecules and systems.

Sequence-dependent structure and rigidity of DNA and its influence on DNA-protein interactions: DNA is more than the simple repository of the triplet code for proteins, it is also a conformationally complex molecule where the physical aspects of the conformation play a major role in gene expression and control. We use a variety of probes, from optical techniques to differential scanning calorimetry to probe the ways that the structure of DNA is dependent on sequence. An recent example of this approach has been our studies of how homo dA tracts have a temperature dependent structure different from "normal" B-type DNA, how this temperature dependent structure alters the curvature and stiffness of the helix, and how it influences nucleosome reconstitution.

Studies of energy flow in biomolecules: Proteins are dynamic entities and it has long been our contention that the dynamics of proteins play a strong role in directing the activity of biomolecules. One of our main trusts recently has been using transient infrared spectroscopy to study the conformational dynamics of biomolecules. These experiments have ranged from monitoring the CO stretch line of carbon monoxide after flash photolysis to monitor the motion of the carbon monoxide molecule in a heme protein to using the intense Far-Infrared pulsed output of a Free Electron laser to pump collective modes in proteins and model compunds to observe the pathways of energy flow and the influence of collective modes on protein reactivity. This work is done at FELIX, a free electron laser in Holland.

Applications of microlithography to biology: We have realized that the optical lithography techniques of the semiconductor industry can be used to attack problems of biological interest. For example, we have constructed micron-sized "obstacle courses" on a silicon chip to mimic (and improve upon) the complex topology found in gels. We have shown that it is possible to image megabase long DNA molecules moving through these arrays and that the arrays can fractionate very long (chromosomal length) DNA molecules. We are pursuing this technology to sequence DNA. A s an extension of this work, we are also using microfluidics to isolate and fractionate the white blood cell components of the immune system.

Ultra-rapid mixing. The low Reynolds numbers of flow at the micron scale means that mixing of fluids occurs not by tubulenence but rather by diffusion. We have used this fact and applied the technology of hydrodynamic focusing to achieve ultra-rapid mixing (microseconds) of fluids that are moving at meters per second, allowing time resolution on the microsecond time scale. A further advantage of this work is the extremely low fluid consumption of the steady state mixer so that precious materials can be steading. We have recently shown that this technique can be used to do difficult experiments such as time-resolved small angle X-ray scattering.

• L. Richard Huang, Jonas O. Tegenfeldt, Jessica J. Kraeft, James C. Sturm, Robert H. Austin and Edward C. Cox (2002) A DNA prism: high speed continuous fractionation of large DNA molecules. Nature Biotechnology 20, 1048 - 1051
• Han Cao, Jonas O. Tegenfeldt, Robert H. Austin, Stephen Y. Chou (2002) Gradient nanostructures for interfacing microfluidics and nanofluidics, Applied Physics Letters 81:3058-3060
• Christelle Prinz, Jonas O. Tegenfeldt, Robert H. Austin, Edward C. Cox, James C. Sturm. (2002) Bacterial chromosome extraction and isolation, Lab on a Chip 2:207-212
• Lotien Richard Huang, Pascal Silberzan, Jonas O. Tegenfeldt, Edward C. Cox, James C. Sturm, Robert H. Austin, and Harold Craighead (2002) Role of Molecular Size in Ratchet Fractionation Phys. Rev. Lett. 89: 178301-4
• Matt Sullivan, Kun Zhao, Christopher Harrison, Robert H. Austin, Mischa Megens, Andrew Hollingsworth, William B Russel, Zhengdong Cheng, Thomas Mason and P M Chaikin (2003) Control of colloids with gravity, temperature gradients, and electric fields, J. Phys.: Condens. Matter 15: S11S18
• Mario Cabodi, Yi-Fan Chen, Stephen W. P. Turner, Harold G. Craighead, Robert H. Austin (2002) Continuous separation of biomolecules by the laterally asymmetric diffusion array with out-of-plane sample injection Electrophoresis 23:3496-3503
• Robert H. Austin, Aihua Xie, Lex van der Meer, Michelle Shinn, George Neil (2003) Self-trapped States in Proteins, Journal of Physics: Condensed Matter 15:S1693--S1698.
• Wanli Li, Jonas O Tegenfeldt, Lei Chen, Robert H Austin, Stephen Y Chou, Paul A Kohl, Jeff Krotine and James C Sturm, (2003) Sacrificial polymers for nanofluidic channels in biological applications Nanotechnology 14: 578-583
• Sungsu Park, Peter M. Wolanin, Emil A. Yuzbashyan, Jeffry B. Stock, Pascal Silberzan, Robert H. Austin (2003) Move for a Quorum, In Press, Science