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Introduction
Richard Feynman's statement that “there is plenty of room at the bottom” is as true today as it was more than 40 years ago. Nanotechnology has become a rapidly expanding research area which is truly interdisciplinary, ranging from electronics to biology. Scanning probe microscopes (SPM) such as the Atomic Force Microscope (AFM) are at the core of nanotechnology as they are the only tools for both manipulating and measuring matter down to the scale of single atoms or molecules. In addition, SPM is one of the most versatile techniques and is used in vacuum as well as in liquids measuring forces, currents or magnetic fields.
Forces are of fundamental importance in the understanding of physical processes at the nanoscale, be it short range atomic forces binding together a solid or the longer range forces associated with molecular ordering of water layers and protein folding. Despite their overwhelming importance, we know little about these forces by means of direct measurement. The AFM is ideally suited to address this problem. Unfortunately, commonly used AFM techniques suffer from problems such as mechanical instabilities, low force resolution, and difficulty in quantitative interpretation of results - all of which prevent the consistent measurement of molecular scale interactions. At the University of Oxford I was involved in the development and use of novel AFM techniques which avoid these problems and thus allow for the direct measurement of force gradients in a variety of situations. This research continues at Wayne State University (WSU) and by my colleagues at Trinity College in Dublin, Ireland, at Bilkent University in Ankara, Turkey and at Nanomagnetics Instruments.
At WSU, the new AFM technique is being further improved and used in a variety of nanotechnology related research situations. Two such instruments, one based in liquids and one based in ultra-high vacuum are the central focus of this laboratory. This new AFM technique relies on the use of sub-Angstrom oscillation amplitudes of the (stiff) measuring lever, a sub-resonance (quasi-static) operation and a extremely high sensitivity optical fiber interferometer deflection sensor. In the following I refer to it as '4S-AFM'. The four 'S' stand for Small amplitude, Sub-resonance, Stiff levers, and high Sensitivity. These features combine to allow for the direct measurement of any type of interaction in any environment. They also allow for high resolution imaging – our instrument routinely achieves atomic resolution in ultra-high vacuum (UHV).
In the UHV based AFM we are able to measure electrostatic fields, charges and magnetic fields in nanostructures, study forces in different adsorbate systems and ultimately measure the forces involved in room-temperature atomic manipulation in which single atoms are directly manipulated with the probe tip.
Using the liquid-based AFM we will focus on force measurements in biological liquid environments. We have already measured the stiffness variations associated with the molecular ordering of water in a confined geometry, a measurement that is impossible in a standard AFM setup. The structure of water is key to understanding the functionality and tertiary structure of biological macromolecules. It has long been postulated that the varying ‘hydrophobicity’ of constituent groups and the free energy associated with the surrounding solvent molecules is an important part of the primary – tertiary structure relationship of proteins. Now that we are able to directly measure these interactions in liquids we might be able to shed light on the range and functional form of solvent-mediated interactions in biological molecules.
The unique force control of our 4S-AFM will also make it possible to image fragile biological structures in situ and non-contact. There is promise to significantly improve the resolution of AFM using our technique, since unlike contact or tapping-mode AFM ours is a true non-contact technique and relies on a much more sensitive deflection sensor for its measurements. Ultimately, it will be possible to identify molecular constituents in biological structures and to measure force interactions and the water structure associated with them.