Interferometry for electron microscopy

Transmission electron microscopy (TEM) holds the potential to resolve many questions in life science by providing a close view of the molecular machinery of the cell. However, biological matter is mostly transparent to electron beams, making for poor image contrast. Although biological macromolecules are almost invisible in TEM, their structure is imprinted in the transmitted electron beam as small variations in the phase of the electron wave function.

Both electron microscopy and light microscopy face the problem of visualizing weak phase variations. In optical imaging, this has been solved by the introduction of Zernike phase contrast. In this method, a spatially selective phase retarder is inserted in the beam path to induce a 90o phase shift in the weak scattered wave relative to the strong directly transmitted wave. The interference between the phase-shifted scattered wave and the transmitted wave creates amplitude modulations, giving rise to a visible image.

Phase contrast imaging with an electron microscope requires creating an analogous phase retarder for electron waves, which has proven difficult due to rapid deterioration experienced by any retardation element exposed to the high energy electron beam.

We are working on a radical solution to this problem, using a laser field configuration as a transparent, indestructible, controllable electron wave retarder. Realization of a reliable phase contrast TEM is likely to bring about many discoveries in structural microbiology, and could lead to further applications for laser-based coherent control of the electron wave function.

Team members

Osip Schwartz

Sara Campbell

Jeremy Axelrod

Carter Turnbaugh


  1. Laser phase plate for transmission electron microscopy. Osip Schwartz, Jeremy J. Axelrod, Sara L. Campbell, Carter Turnbaugh, Robert M. Glaeser, and Holger Müller. Nat. Methods 16, 1016-1020 (2019) and arXiv:1812.04596 (2018).

  2. Near-concentric Fabry-Pérot cavity for continuous-wave laser control of electron waves. Osip Schwartz, Jeremy J. Axelrod, Daniel R. Tuthill, Philipp Haslinger, Colin Ophus, Robert M. Glaeser, and Holger Müller. Opt. Express 25, 14453-14462 (2017) and arXiv:1610.08493.

  3. Design of an electron microscope phase plate using a focused continuous-wave laser. Holger Müller, Jian Jin, Radostin Danev, John Spence, Howard Padmore, and Robert Glaeser, New J. of Physics 12, 073011 (2010) and arXiv:1002.4237.