Nanobioscience is a novel research field recently emerged out of the interests
from both nanotechnology and biology. Nanobioscience aims at utilizing
nanoscale analysis and measurement tools, that have remarkably progressed
for the last two decades in the Nanotechnolgy field, for studying biological
phenomena at a single molecular level. The direct information obtained
at a local nanoscale area should provide a better understanding of biological
systems, which in turn forms a basis for future development of nanoscale
functional devices in nanotechnology. In our research group, we develop
novel instruments and techniques of atomic force microscopy (AFM), which
is one of the most powerful nano-analysis tools, and thereby investigate
the biological phenomena at a single molecular level.
In AFM, a cantilever with a sharp tip at its end is used as a force sensor. The cantilever is brought close to the sample surface until the tip feels the interaction force. The interaction force is detected and kept constant by controlling the vertical tip position. This effectively regulates the tip-sample distance at a constant value. With this tip-sample distance regulation, the tip is raster-scanned over the surface, where the tip follows the surface corrugation. Therefore, the surface topographic image can be obtained by recording the vertical tip height with respect to the laterl tip position.
As described above, AFM is based on a simple operating principle yet is a powerful nano-analysis tool able to visualize atomic-scale structures in real space. However, atomic-resolution imaging techniques using AFM has been developed mainly for ultra high vacuum applications, which has prevented its applications to the research in nanobioscience. Recently, we have presented a way to overcome this limitation by developing an ultra low noise frequency modulation AFM (FM-AFM) and oscillating a cantilever with a very small amplitude. The novel method has made it possible to obtain true atomic resolution even in liquids. Furthermore, it has also enabled direct imaging of inidividual hydration layers and dynamics of mobiole ions weakly interacting with the lipid headgroups on a biological memebrane under physiological solution. The striking results have highlighted the capability of FM-AFM to visualize atomic-scale biological phenomena that has been inaccessible with conventional nanoanalysis tools.
In our reserach group, we have been working on further improvements of the high-resolution AFM technique for the practical biological applications. The improvements include the increase of imaging speed, enhancement of force sensitivity, implemention of extra functions. The developed instruments and methods are used for investigating biological phenomena at a molecular leve. The biological interests include the ordering of water molecules at the biological interface, nanoscale complexes consisting of multiple molecules in biological membrane and their interaction mediated through the surrounding physiological environment such as water molecules and ions.