Project 4: nanoManipulator

The nanoManipulator System integrates haptic force feedback control of a nanoscale probe tip with imaging in a fluorescence optical microscope. It has been used for virus, chromosome, cell and clot manipulation experiments. Beyond developments in instrumentation and software, CISMM develops methodologies for force measurements. Through our work with our Thrombosis collaborators on fibrin fiber mechanics, we have developed methods of fabricating “structured surfaces” (SS). These engineered surfaces enable stretching experiments in which biological fiber samples are suspended across channels and there for free of the confounding mechanical influence underlying surfaces. We will be developing integrated in-plane uniaxial and biaxial strain capabilities that will greatly expand the host of mechanical interrogations our collaborators can perform.

At right is (A) side view of experimental set up. Inverted optical microscope objective images the fibrin manipulation through the coverslip with structured channel-ridge surface. Suspended fibrin fibers are labeled with fluorescent beads and then stretched with the afm tip. Perspective view (b,d) of afm tip, and fibrin fiber suspended across channel. Fluorescence images of suspended fiber before being stretched (c) after and stretched to ~200% strain by the afm tip (e).

Falvo, M. R., D. Millard, et al. (2008). “Length of tandem repeats in fibrin’s alphaC region correlates with fiber extensibility.” J Thromb Haemost.

Falvo, M. R., S. Washburn, et al. (1997). “Manipulation of individual viruses: Friction and mechanical properties.” Biophysical Journal 72(3): 1396-1403.

Guthold, M., M. R. Falvo, et al. (2000). “Controlled Manipulation of Molecular Samples with the nanoManipulator.” IEEE/ASME Transactions on Mechatronics 5(2): 189-198.

Guthold, M., W. Liu, et al. (2004). “Visualization and Mechanical Manipulations of Individual Fibrin Fibers.” Biophys. J. 87(6): 4226-4236.

Guthold, M., G. Matthews, et al. (1999). “Quantitative Manipulation of DNA and Viruses with the nanoManipulator Scanning Force Microscope.” Surf. Interf. Analysis 27: 437-443.

Guthold, M., R. Superfine, et al. (2001). “The rules are changing: Force measurements on single molecules and how they relate to bulk reaction kinetics and energies.” Biomedical Microdevices 3(1): 9-18.

Guthold, M., J. Mullin, et al. (2001). Investigating the mechanical properties of individual fibrin fibers with the nanomanipulator AFM. Biophysical J. 80: 1274.