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I don't do much experimentation, but I am pretty sure that you can very easily distinguish individual atoms with electron beam microscopy, and get pretty close

I don't do much experimentation, but I am pretty sure that you can very easily distinguish individual atoms with electron beam microscopy, and get pretty close using atomic force microscopy. And I am not sure what exactly is the resolving power of synchrotron radiation, but I expect if to be pretty high. However, the breakthrough here seems being able to do so using a low-energy electron beam. All the methods I quoted above are probably impractical or damaging with biological samples.

natechols 6y ago
With hard xrays you can visualize interatomic densities and lone pairs. I know there are structures down to 0.5Å resolution now but that must have required careful setup. I've seen diffraction out to 0.75Å but I could never collect complete data at that resolution.
- thechao 6y ago
  I’m imagining a collector plate the size of my dining room table, with a staff of crazy-haired scrawny physicists clambering around some sort of neo-Victorian rube-Goldbergesque X-ray source — like a wine-barrel-sized copper anode and a small nuclear power plant for the arc.
  - natechols 6y ago
    This is not far from the truth, except the detectors are actually relatively small (and very expensive), there's more aluminum foil than the Victorians used, and we have slightly better hair on average. The last time I used one of these facilities, it looked like this (and still does): https://lcls.slac.stanford.edu/sites/lcls.slac.stanford.edu/files/styles/basic_page_large_image/public/cxi-banner01.jpg https://lcls.slac.stanford.edu/sites/lcls.slac.stanford.edu/... Compared to this electron microscopy is downright boring - and a couple of orders of magnitude cheaper to set up.
jtaillon 6y ago
That's pretty much correct. Single-atom imaging is possible using aberration-corrected scanning TEM, but the beam doses used will typically obliterate anything organic through radiolysis or ionization damage (although there are emerging ways around that using some interesting compressive sensing techniques). Most "atomic resolution" EM images you see are actually images of columns of atoms, since the imaging mode is transmission, so necessarily the image is summed through the plane of the sample (so atomic resolution is only in the perpendicular plane). The techniques used in this paper get around the dose issue by taking many images of very many presumably identical proteins (called dose fractionation) at very low dose. Computer algorithms are then used to stitch together a 3D model based on the low-dose individual images. Making it really cold also helps things from breaking down under the beam.

natechols 6y ago

With hard xrays you can visualize interatomic densities and lone pairs. I know there are structures down to 0.5Å resolution now but that must have required careful setup. I've seen diffraction out to 0.75Å but I could never collect complete data at that resolution.

thechao 6y ago
I’m imagining a collector plate the size of my dining room table, with a staff of crazy-haired scrawny physicists clambering around some sort of neo-Victorian rube-Goldbergesque X-ray source — like a wine-barrel-sized copper anode and a small nuclear power plant for the arc.
- natechols 6y ago
  This is not far from the truth, except the detectors are actually relatively small (and very expensive), there's more aluminum foil than the Victorians used, and we have slightly better hair on average. The last time I used one of these facilities, it looked like this (and still does): https://lcls.slac.stanford.edu/sites/lcls.slac.stanford.edu/files/styles/basic_page_large_image/public/cxi-banner01.jpg https://lcls.slac.stanford.edu/sites/lcls.slac.stanford.edu/... Compared to this electron microscopy is downright boring - and a couple of orders of magnitude cheaper to set up.

jtaillon 6y ago

That's pretty much correct. Single-atom imaging is possible using aberration-corrected scanning TEM, but the beam doses used will typically obliterate anything organic through radiolysis or ionization damage (although there are emerging ways around that using some interesting compressive sensing techniques). Most "atomic resolution" EM images you see are actually images of columns of atoms, since the imaging mode is transmission, so necessarily the image is summed through the plane of the sample (so atomic resolution is only in the perpendicular plane). The techniques used in this paper get around the dose issue by taking many images of very many presumably identical proteins (called dose fractionation) at very low dose. Computer algorithms are then used to stitch together a 3D model based on the low-dose individual images. Making it really cold also helps things from breaking down under the beam.