2026-06-11 カリフォルニア大学バークレー校（UCB）
A laser (purple) is powerfully amplified by highly polished mirrors and focused on the electron beam (blue) to shift its phase and increase the cryo-EM microscope’s contrast, allowing biologists to image smaller proteins and the crowded structures inside cells.
＜関連情報＞
- https://news.berkeley.edu/2026/06/11/a-breakthrough-in-electron-microscopy-delivers-sharper-images-of-our-bodys-tiniest-proteins/
- https://www.science.org/doi/10.1126/science.aeh0665
- https://www.biorxiv.org/content/10.64898/2026.06.05.730245v1
- https://www.nature.com/articles/s41467-026-74060-6
レーザー位相板はクライオ電子顕微鏡による小型タンパク質の構造決定を改善する Laser phase plate improves structure determination of small proteins by cryo-EM
Petar N. Petrov, Jessie T. Zhang, Jonathan Remis, Jeremy J. Axelrod, […] , and Holger Müller
Science Published:11 Jun 2026
DOI:https://doi.org/10.1126/science.aeh0665
Abstract
Phase plates can in principle overcome the poor image contrast in electron cryo–microscopy (cryo-EM) and the resulting limits on the structural reconstruction of small proteins. However, previous designs have been unstable and compromised the high-resolution signal. They have thus been unable to surpass results achieved by standard cryo-EM. Here, we show that the laser phase plate (LPP), installed in a custom, modern Titan Krios microscope, enhances the resolution in single-particle reconstruction of small proteins by improving specimen-motion correction, recovery of information from the early frames, as well as particle visualization, 3D classification, and alignment. These advances use standard defocus ranges and reconstruction procedures, but open the door to LPP-tailored protocols offering further improvements by leveraging the LPP demonstrated here.
クライオ電子顕微鏡用クロス型レーザー位相板 A Crossed Laser Phase Plate for CryoE
Yue Yu, Anchi Cheng, Elizabeth Montabana, Noeli Paz Soldán, Eric S. Cooper, Jessie T. Zhang, Jeremy J. Axelrod, Petar N. Petrov, Amir Torkaman, Dylan Roof, Matthew Derstine, Bart Buijsse, Wim Hagen, Dari Kimanius, Shawn Zheng, Mykhailo Kopylov, Mohammadreza Paraan, Deepan Balakrishnan, Joshua Hutchings, Hang Cheng, Jonathan Remis, Ashwin Singh, Lothar Maisenbacher, Clinton S. Potter, Holger Müller, Bridget Carragher, David Agard, Pavel K. Olshin
bioRxiv Posted: June 05, 2026
DOI:https://doi.org/10.64898/2026.06.05.730245
Abstract
The laser phase plate (LPP) enables phase-contrast imaging in cryogenic electron microscopy (cryoEM), enhancing image contrast without compromising high-resolution information. Here we report the implementation of a crossed laser phase plate (xLPP) comprising two optical cavities oriented orthogonally, installed in a ThermoFisher Scientific Krios G4 microscope equipped with a newly designed transfer lens module. We demonstrate the expected, strong contrast enhancement and stable, additive phase shifts of 90°, with a contrast transfer function (CTF) that closely matches theory. Single-particle analysis (SPA) of apoferritin, a standard benchmark sample, reached a resolution of 1.79 Å, demonstrating the system is capable of acquiring high-resolution cryoEM data. When imaging thick E. coli cells (∼350 nm), the xLPP enhances contrast and increases low-frequency template-matching signal. Together, these results establish the feasibility of the xLPP and highlight its potential for high-contrast, high-resolution cryoEM imaging of biological systems.
透過型電子顕微鏡用クロスレーザー位相板 Crossed laser phase plates for transmission electron microscopy
Petar N. Petrov,Jessie T. Zhang,Jeremy J. Axelrod,Pavel K. Olshin & Holger Müller
Nature Communications Published:05 June 2026
DOI:https://doi.org/10.1038/s41467-026-74060-6 Unedited version
Abstract
A phase plate has long been sought in transmission electron microscopy (TEM) to maximize the image contrast of weakly-scattering objects like biomolecules. The laser phase plate (LPP) has recently demonstrated that an amplified, focused laser standing wave reliably phase shifts the electron beam, achieving phase-contrast TEM. Building on the single-beam LPP, here we introduce the crossed laser phase plate (XLPP): two laser standing waves which intersect in the diffraction plane. We present a theoretical model for the XLPP inside the microscope and show that, relative to the original LPP, it increases information transfer at low spatial frequencies while suppressing ghost images formed by Kapitza-Dirac diffraction. We also present a simple acquisition scheme, enabled by the XLPP, which further suppresses ghosts. Finally, we discuss practical considerations of XLPP design and show experimental results from a prototype. The results of this study chart the course for future developments of LPP hardware.
集束連続波レーザーを用いた電子顕微鏡位相板の設計 Design of an electron microscope phase plate using a focused continuous-wave laser
H Müller, Jian Jin, R Danev, J Spence, H Padmore and R M Glaeser
New Journal of Physics Published: 12 July 2010
DOI:10.1088/1367-2630/12/7/073011
Abstract
We propose a Zernike phase contrast electron microscope that uses an intense laser focus to convert a phase image into a visible image. We present the relativistic quantum theory of the phase shift caused by the laser–electron interaction, study resonant cavities for enhancing the laser intensity and discuss applications in biology, soft-materials science and atomic and molecular physics.
