Transmission electron microscopy (TEM) of rapidly frozen biological specimens, or cryo-EM, would benefit from the development of a phase plate for in-focus phase contrast imaging. Several types of phase plates have been investigated, but rapid electrostatic charging of all such devices has hindered these efforts. Here, we demonstrate electron phase manipulation with a high-intensity continuous-wave laser beam, and utilize it as a phase plate for TEM. We demonstrate the laser phase plate by imaging an amorphous carbon film. The laser phase plate provides a stable and tunable phase shift without charging or unwanted electron scattering. These results suggest the possibility for dose-efficient imaging of unstained biological macromolecules and cells.

Transmission electron microscopy (TEM) of vitrified biological macromolecules (cryo-EM) is limited by the weak phase contrast signal that is available from such samples. Using a phase plate would thus substantially improve the signal-to-noise ratio. We have previously demonstrated the use of a high-power Fabry–Perot cavity as a phase plate for TEM. We now report improvements to our laser cavity that allow us to achieve record continuous wave intensities of over 450 GW/cm 2 , sufficient to produce the optimal 90° phase shift for 300 keV electrons. In addition, we have performed the first cryo-EM reconstruction using a laser phase plate, demonstrating that the stability of this laser phase plate is sufficient for use during standard cryo-EM data collection.

Manipulating free-space electron wave functions with laser fields can bring about new electron-optical elements for transmission electron microscopy (TEM). In particular, a Zernike phase plate would enable high-contrast TEM imaging of soft matter, leading to new opportunities in structural biology and materials science. A Zernike phase plate can be implemented using a tight, intense continuous laser focus that shifts the phase of the electron wave by the ponderomotive potential. Here, we use a near-concentric cavity to focus 7.5 kW of continuous-wave circulating laser power at 1064 nm into a 7 µm mode waist, achieving a record continuous laser intensity of 40 GW/cm. Such parameters are sufficient to impart a phase shift of 1 rad to a 10 keV electron beam, or 0.16 rad to a 300 keV beam. Our numerical simulations confirm that the standing-wave phase shift profile imprinted on the electron wave by the intra-cavity field can serve as a nearly ideal Zernike phase plate.