The observation of spectroscopic signals in response to mechanically induced changes in biological macromolecules can be enabled at an unprecedented level of resolution by coupling single-molecule manipulation/sensing using carbon nanotubes with single-molecule fluorescence imaging. Proteins, DNA and other biomolecules can be attached to nanotubes to give highly specific single-molecule probes for the investigation of intermolecular dynamics, the assembly of hybrid biological and nanoscale materials and the development of molecular electronics. Recent advances in nanotube fabrication and Atomic Force Microscope (AFM) imaging with nanotube tips have demonstrated the potential of these tools to achieve high-resolution images of single molecules. In addition, proof-of-principle demonstrations of nanotube functionalization and attachment of single molecules to these probes have been successfully made. Improved techniques for the growth and attachment of single wall carbon nanotubes as robust and well-characterized tools for AFM imaging are being developed. This work serves as a foundation toward development of single-molecule sensors and manipulators on nanotube AFM tips for a hybrid atomic force microscope that also has single-molecule fluorescence imaging capability. An individual single wall carbon nanotube (SWNT) attached to an AFM tip can function as a structural scaffold for nanoscale device fabrication on a scanning probe. Such a probe can have a novel role, to trigger specific biochemical reactions or conformational changes in a biological system with nanometer precision. The consequences of these perturbations can be read out in real time by single-molecule fluorescence and/or AFM sensing. Of particular interest is the possibility of electrical wiring of single redox enzymes to carbon nanotube scanning probes, which will allow for observation and electrochemical control of single enzymatic reactions, by monitoring fluorescence from a redox-active cofactor or the formation of fluorescent products. Enzymes """"""""nanowired"""""""" to carbon nanotube tips may enable extremely sensitive probing of biological stimulus-response with high spatial resolution, including product-induced signal transduction. ? ?
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