Multi-pass microscopy – approaching Heisenberg limited sensitivity in optical and electron microscopy

Monday, May 1, 2017 - 4:00pm
Thomas Juffmann
Speaker's Institution: 
Stanford University

The number of biological macromolecules with a structure solved by cryogenic-electron microscopy (cryo-EM) increases dramatically each year. However, many small and weakly scattering protein structures remain out of reach, as electron dose induced specimen damage limits the achievable spatial resolution [1].

Improved sensitivity and spatial resolution can be obtained employing quantum measurement strategies. A quantum optimal approach to measuring small phase shifts, as induced by a thin protein, is to pass each probe particle through the specimen multiple times [2].
Employing self-imaging cavities, this idea can be applied to widefield microscopy [3]. We show post-selected optical birefringence and absorption measurements beyond the shot-noise limit and discuss the applicability of multi-pass microscopy to cryo-EM. Our EM simulations [4] show that multi-pass TEM allows for a tenfold damage reduction in imaging small proteins.

[1] Glaeser et al, Nat. Methods, 13, 1, 28-32 (2016).

[2] Giovannetti et al., Physical Review Letters 96, 10401 (2006).
[3] Juffmann et al, Nature Communications 7, 12858 (2016).
[4] Juffmann et al, arXiv:1612.04931 (2016).