Bio-molecular Microscopy at Atomic Resolution

Chih-Yu Chao

《Chinese Journal of Physics》 45卷6_S1期 (2007/12) Pp. 557-578

並列摘要

The development of a molecular microscope for the direct observation of molecules at atomic resolution is important in the fields of physics, chemistry, biology, and medicine. However, it has been known for more than fifty years that intensive ionization radiation greatly limits the resolution in biological materials. In this paper, we propose a new technique, the cryo-specimen electrification (CSE) technique, which greatly reduces radiation damage to biological samples during electron beam irradiation. A unique cryo-charging specimen holder has been developed for CSE experiments. To uniformly electrify the cryo-specimen, we developed a method of doping a suitable amount of ions into the hydrated specimen, followed by rapid freezing. We demonstrated that after charging the ion doped vitrified ice layer can not only trap and store charge in equilibrium with the free and mobile charges, but also has a conductivity level comparable to that of metals. Hence it can promptly return electrons to ionized atoms and fragments in the frozen sample to efficiently repair the radiation damage that occurs under electron beam irradiation. Furthermore, our result represents the first development of a molecular microscope which enables the reconstruction of the 3D structure of biological molecules at atomic resolution.