This Major Research Instrumentation award funds the development of a novel Zernike laser phase plate for cryo-TEM at University of California-Berkeley. In Zernike phase contrast microscopy, a quarter-wave plate in the focal plane of the object lens shifts the phase of the undiffracted part of the beam to provide optimal conversion of phase modulations into image contrast. The new laser phase plate will allow researchers to operate TEMs in an optimal phase-contrast mode for indefinite periods of time. Compared with defocused bright field method, the contrast in the imaging of biological macromolecules and supramolecular structures could be as much as ten times greater. Moreover, the possibility to make a tiny focus and the possibility to tune it optically makes it possible to image lower spatial frequencies and offers greater flexibility than with microfabricated phase plates. This new phase contrast system will be used to investigate problems in molecular and cell biology that are out of the reach of existing techniques in electron microscopy, x-ray crystallography, or multi-dimensional NMR spectroscopy. Finally, we anticipate additional applications in fundamental physics, e.g., developing an optical dipole trap for atoms and molecules of almost any species, with the ability to trap even room-temperature samples. The results of the development effort will be broadly disseminated through abstracts and peer reviewed publications, as well as by active participation of students and faculty at professional meetings.
