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by iheartmemcache 3206 days ago
The size of a red blood cell is ~100 um. The size of a nucleus of a cell is ~6um in a mammal (so says wikipedia at least, I know less than a 9th grader re: biology). You can get that resolution with < 10k worth of name-brand optics gear (Zeiss, Nikkor JP, whatever) off eBay.

Pair that to a x,y stepper and some Python OpenCV script and you have a ready to go "cell counter", which this paper espouses as one of its uses. Not only that but they only get 20nm with shadow imaging techniques which (I'd imagine[2])are inherently awful for actual examination of features.

Here's[3] a paper that uses wet-methods (i.e. good for biology, where you can add florescence/dyes/stains to your culture; not nearly good enough for modern chip fabrication) that gets you down to the 20nm range. And at that point your lab already has a microscope to hit those lengths.

Basically this lowers the price of this use-case: "oh at t(0) we have 30 blurry units we can sorta-kinda safely assume as eukaryotic; t(1hr) = 600 blurry features". I can see this being a market opportunity for having in-house cancer biopsy diagnostics.

From a research point of view, you're doing at the lower level (protein folding, crystallography, whatever), you're already equipped with the proper mass-specs/NMR/SEMs/TEMs you picked up from Waters or Agilent at half a million. I mean that's got the potential to save a lot of lives, which is awesome, but I probably sound disappointed because I was really hoping for an actual advancement in lens-less microscopy.

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[1] en.wikipedia.org/wiki/Diffraction-limited_system ~200 nm under ideal conditions, no pedantry please on apertures or practical things like chromatic/spherical abberation issues, etc. I realize these limits exist, we're just talking orders of rough orders of magnitude. [2] Not in the field, just remarking based on conversations with people who have had to setup labs at universities with limited NIH/NSF budgets. [3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2645564/ There are a boatload of other papers out there, but this is the one I had off hand.

2 comments

> The size of a red blood cell is ~100 um.

~10 um actually. You might like the "How to remember sizes" section of http://www.clarifyscience.info/part/Atoms . If you imagine zooming 1 millimeter to arms-sized (1000x), then a grain of salt looks like a cardboard box. And a red blood cell, looks like a red M&M candy. Finger-nail sized in this 1000x micro view. So ~10 micrometers. Once you care about a factor of 2, M&M Minis are better match than regular M&M's, as rbc's are a bit under 10 um.

Building a science grade microscope that can be used to produce research-grade results is not a trivial problem. Sure you can strap a few lenses and steppers to a frame and make a microscope but that's a very long distance from being able to produce quantitative results of other scientists care about.
I think you misunderstood me when I said "name-brand". I don't mean some 30 dollar microscope with $20 glass lapped with 2 passes of alumina 35 micron by a 12 year old in a Chinese sweatshop. Those brands I mentioned were (and apparently still are) more than good enough to get you into industry primer publications. This[1] is literally a random paper I picked off of Nature Medicine. I intentionally chose the first DOI from Nature Medicine I saw to get it as 'random' as possible. (Nikkor is the trademark Nikon used to use to indicate their high-end domestically manufactured equipment.)

Hmm, Nikon, check. Agilent, check. Zeiss, check. Hell, everything in that paper, from the Sigma-Aldrich sourced chemicals to the BioGen PCR sequencer is 100% bog standard. Go pick up this months copy of any journal of medicine (hard medicine, not like, psychiatry -- JAMA, NE Journal of Medicine, Cell, whatever) and see what hit-rate you have with those 5 brands. "Research quality science equipment" is bog standard.

In fact, I was curious to see what equipment the CRISPR-Cas9 guys were using, because I mean cleaving nt's is about as low-level as anyone with an MD/PhD is going to get. (It also meets your "research-grade" criteria, cause, you know, its CRISPR-CAS9.)[2] Same brands, more sensitive equipment, still pretty bog standard. Again, semi-conductor equipment from the mid 2000s still has it beat for requirements re: sterile conditions for SiO seed -> ingot growth, re: resolution by an order of magnitude (at least) for making chip masks, re: chemical purity when CVD'ing your poly/metals, and for resolution re: SEM/FIB'ing for inspecting your wafers.

[1] https://i.imgur.com/IC56Nxj.png [2] https://i.imgur.com/EAQo77W.png

you're talking $50-100K of investment to buy that Nikon scope.