Feynman once asked physicists to build better electron microscopes to be able to watch biology at work. While electron microscopes can now provide atomic resolution, electron beam induced specimen damage precludes high resolution imaging of sensitive materials, such as single proteins or polymers. Here, we use simulations to show that an electron microscope based on a multi-pass measurement protocol enables imaging of single proteins, without averaging structures over multiple images. While we demonstrate the method for particular imaging targets, the approach is broadly applicable and is expected to improve resolution and sensitivity for a range of electron microscopy imaging modalities, including, for example, scanning and spectroscopic techniques. The approach implements a quantum mechanically optimal strategy which under idealized conditions can be considered interaction-free.
Multi-pass transmission electron microscopy (MPTEM) has been proposed as a way to reduce damage to radiation-sensitive materials. For the field of cryo-electron microscopy (cryo-EM), this would significantly reduce the number of projections needed to create a 3D model and would allow the imaging of lower-contrast, more heterogeneous samples. We have designed a 10 keV proof-of-concept MPTEM. The column features fast-switching gated electron mirrors which cause each electron to interrogate the sample multiple times. A linear approximation for the multi-pass contrast transfer function (CTF) is developed to explain how the resolution depends on the number of passes through the sample.
The classical nonlinear dynamics of a dilute gas of rubidium atoms in an optical lattice is studied for a range of polarizations of the laser beams forming the lattice. The dynamics ranges from integrable to chaotic, and mechanisms leading to the onset of chaos in the lattice are described.
With the introduction of hardware aberration correction, direct electron detectors, ultra-bright electron sources and highly precise spectrometers, it seems like we are approaching the pinnacle of transmission electron microscopy (TEM) imaging and spectroscopy. However, the field of electron microscopy is still far from the ultimate signal-to-noise and efficiency limits imposed by electron scattering physics. Current TEM experiments where images are measured with high quantum efficiency detectors can approach the shot noise (or Poisson noise) limits, but the true upper bound for signal-to-noise for any electron imaging measurement is the Heisenburg limit [1]. Some initially proposed methods for approaching this measurement limit were quantum techniques such as highly-entangled measurement particles, which are impractical to use in a large-scale imaging experiments using photons. Entangling large numbers of electrons is even more difficult and seems unlikely to be achieved with existing technology. However, there is an alternative method to approach the Heisenburg limit: allowing the electron probe to interact with the sample many times before the image intensity measurement [2], as in the recently proposed design for a multipass transmission electron microscope [3,4].In this talk, we will describe a multipass TEM instrument designed using the principles of quantum metrology. A simplified schematic of the experimental geometry is shown in Figure 1. A multipass TEM is very similar to a conventional TEM, except for the addition of two electron mirrors and the use of a pulsed electron source. The biasing of these electron mirrors can be reduced to allow the pulsed electron beam to enter the center portion of the instrument. The central portion is composed of two mirror-image configurations of a TEM instrument with mirrors on each end. The electron beam can therefore be passed through the sample multiple times. After a set number of passes, the electron beam can be passed out through the second mirror shown in the Figure 1 schematic. Finally, the electron pulse can be imaged using a standard electron detector, either after using a phase plate or applying a defocus to generate a phase contrast image. We assume that the mirrors and lenses can compensate for each other's aberrations in this configuration.The advantage of using a multipass instrument is demonstrated in Figure 2. In this example, we have used multislice simulations to show how a multipass instrument could transform a low-dose imaging experiment of an isolated, small protein sample that is representative of cryo-EM experiments, the hexameric unit of the immature HIV-1 Gag CTD-SP1 lattice [5]. The structure and projected potential of this protein sample is shown in two different orientations in Figures 2a and b. Simulated TEM images at different electron doses for different numbers of passes are plotted in Figure 2c. The reported dose is the total dose seen by the specimen, which is approximately equal to one divided by the number of passes. These simulation...
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