3 ms·

where can I buy one ;) Seriously though, this would be great for getting microscopes in tightly-integrated platforms.

marcosdumay 9y ago
The first three methods shouldn't be very expensive. There's no special purpose components, no moving parts. As soon as patents expire you will probably be able to buy one at the corner store.
- iheartmemcache 9y 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. -- [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/ 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.
  - dekhn 9y ago
    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.
    - iheartmemcache 9y ago
      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 https://i.imgur.com/IC56Nxj.png [2] https://i.imgur.com/EAQo77W.png https://i.imgur.com/EAQo77W.png
      - dekhn 9y ago
        you're talking $50-100K of investment to buy that Nikon scope.

The first three methods shouldn't be very expensive. There's no special purpose components, no moving parts. As soon as patents expire you will probably be able to buy one at the corner store.

iheartmemcache 9y 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. -- [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/ 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.
- dekhn 9y ago
  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.
  - iheartmemcache 9y ago
    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 https://i.imgur.com/IC56Nxj.png [2] https://i.imgur.com/EAQo77W.png https://i.imgur.com/EAQo77W.png
    - dekhn 9y ago
      you're talking $50-100K of investment to buy that Nikon scope.