光学显微及其在生命科学中的应用.pdf

光学显微及其在生命科学中的应用 Light-microscopy and its life science applications 毕国强（gqbi@) 1. Microscopy – a historical sketch 2. Basic principles and techniques in light microscopy 3. Advanced fluorescence microscopy 1 A historical sketch of microscopy and imaging technology th th • 16 -17 Century – Invention of microscope • 1878 – Ernst Abbe formulates a mathematical theory of resolution limit (分辨率极限) due to the wavelength of light. • 1932 – Frits Zernike, phase-contrast microscope (相衬显微 镜，1953 Nobel Prize in Physics) • 1938 – Ernst Ruska, electron microscope ( 电子显微镜， 1986 Nobel Prize in Physics) • 1961-2000’s – Martin Chalfie, Osamu Shimura Roger Tsien, Green fluorescent protein (绿色荧光蛋白，2008 Nobel Prize in Chemistry) • 21st century – CryoEM （冷冻电镜）, Super-resolution optical microscopy （超高分辨光学显微） Micrographia Robert Hooke, 1667 100 m 10 m 1 m 100 nm 10 nm 1 nm 1 Å Length scales of biological imaging techniques 1 Å 1 nm 10 nm 100 nm 1 m 10 m 100 m 1 mm 10 mm 100 mm 1 m MEG PET MRI CT Light microscopy Soft x-ray E