A phase plate can provide optimum image contrast for weak-phase objects in transmission electron microscopy, but approaches toward realizing a phase plate have suffered from instabilities. We have developed a phase plate that is based on coherently phase-shifting the electron wave function by a laser beam, which is built up to a record-high intensity of ~400 GW/cm^2 by resonance in a Fabry-Perot cavity. We have demonstrated contrast enhancement with the laser phase plate (LPP) and shown the long-term stability of the device, as well as generated a high-resolution map of 20S proteasome particles using a standard single-particle cryo-electron microscopy (cryo-EM) workflow. This talk will focus on our recent work to move beyond proof-of-concept, as well as the computational opportunities that lie ahead. To demonstrate the benefits of the LPP to cryo-EM
as well as cryo-electron tomography, we will soon begin working with a state-of-the-art
microscope equipped with a spherical aberration corrector, gun monochromator, and postcolumn energy filter. We will explore improvements to the phase plate design and pursue new strategies for image acquisition and processing, such as high-resolution two-dimensional template matching.