title: Biological applications of phase-contrast electron microscopy.
abstract: Here, I review the principles and applications of phase-contrast electron microscopy using phase plates. First, I develop the principle of phase contrast based on a minimal model of microscopy, introducing a double Fourier-transform process to mathematically formulate the image formation. Next, I explain four phase-contrast (PC) schemes, defocus PC, Zernike PC, Hilbert differential contrast, and schlieren optics, as image-filtering processes in the context of the minimal model, with particular emphases on the Zernike PC and corresponding Zernike phase plates. Finally, I review applications of Zernike PC cryo-electron microscopy to biological systems such as protein molecules, virus particles, and cells, including single-particle analysis to delineate three-dimensional (3D) structures of protein and virus particles and cryo-electron tomography to reconstruct 3D images of complex protein systems and cells.
authors.affiliation: National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Aichi, Japan.
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Nagayama
mesh_terms: D020285:Cryoelectron Microscopy / Q000379:methods*; D008858:Microscopy, Phase-Contrast / Q000379:methods*