Finally got around to reading the "Ballistic Microscopy" paper, and it is really incredible. The paper opens with a compelling idea; one I hadn’t explicitly thought about before: “Light and electron microscopy utilizes interactions of either photons or electrons with matter to create images…” In other words, we see small objects by literally hurling things at them. Particles bounce off the object and reflect back into a lens, or scatter into a detector, which we then use to "see." The question asked in this paper, then, is thus: Can we hurl even larger things at cells to image them? The answer is yes. The gist of ballistic microscopy is that you first "bombard living cells with millions of nanoparticles traveling at ~1000 m/s." Each particle rips through the cell, picks up a tiny amount of cytoplasm, and comes out the other side. If you place a hydrogel film underneath the sample, the nanoparticles will crash into it and get stuck there; just like shooting a bullet into a ballistics dummy. Finally, you take out these nanoparticles and study the molecules they carry, like by using mass spectrometry or really anything else. This method preserves spatial information. The "nano-bullets" rip through the cell in a straight line, meaning that the pattern in the hydrogel corresponds with the nano-bullet's path through the cell. Nano-bullets embedded in the left side of the hydrogel will be carrying proteins, metabolites, and other "pieces" from the same side of the cell. So TL;DR, you're getting SPATIAL and MOLECULAR information, without having to label cells with anything. "This is akin to a 'physical image' being captures on a hydrogel 'film'," the authors write, "with physical material captured on these nano-bullets." Each bullet is between 50 to 1,000 nanometers in diameter. This is small but not exceptionally small. A typical E. coli bacterium measures about 2 micrometers long and 1 micrometer wide. Human cells are quite a bit larger. The next step will be to increase the resolution of this method, perhaps by using smaller nanoparticles. But then there is a tradeoff; if the nanoparticles are TOO small, they need to be accelerated at much higher speeds or they won't penetrate cleanly, or their path of travel will get deflected and mess up the spatial information. This first paper is just a proof-of-concept, of course. It reminds me a bit of Expansion Microscopy, at least in the narrow sense that it's a super creative, original solution to solving a problem. In expansion microscopy, you use a swellable polymer gel to physically ENLARGE a biospecimen, rather than try to make a microscope that can see smaller objects. It's an inverse solution to the microscopy resolution problem. In the original expansion microscopy paper (from 2015), samples were only expanded ~4.5x in each dimension. More recent papers have upped this to ~20x in each dimension; a huge improvement. I expect similar improvements for ballistic microscopy.