[HN Gopher] Cheaper microscope could bring protein mapping techn...
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Cheaper microscope could bring protein mapping technique to the
masses
Author : digital55
Score : 36 points
Date : 2023-11-27 20:45 UTC (2 hours ago)
(HTM) web link (www.science.org)
(TXT) w3m dump (www.science.org)
| COGlory wrote:
| Not my submission, but I am a cryo-electron microscopist if
| anyone has any questions about what's in the article, or more
| general. (and have worked with some of the people in the
| article).
|
| I will comment that the major expensive most facilities face is
| the cost of the service contracts, which are partially parts, but
| also partially the need to pay multiple talented service
| engineers to be available to fly in on a moment's notice, and
| troubleshoot and fix the microscopes. Electron microscopes break
| constantly, and most users are not skilled enough to even
| troubleshoot, let alone fix them.
|
| I will also point out that this part of the article:
|
| >Levels of 100 kiloelectronvolts (KeV)--one-third as high--
| suffice to reveal molecular structure, and they reduce costs by
| eliminating the need for a regulated gas, sulfur hexafluoride, to
| snuff out sparks
|
| Is wildly inaccurate. Relative to the cost of a microscope, SF6,
| and a high tension tank are absolutely pennies. Frankly, the cost
| savings are primarily in two areas:
|
| 1) The fact that Thermo Fisher isn't involved (the Tundra is a
| joke and a move for market monopolization)
|
| 2) Going from 300 kV (or even 200 kV) drastically reduces the
| needed tolerances for parts. 100 kV microscopes have been around
| forever, though, and almost none are going to the resolutions of
| 200 and 300 kV microscopes, although like Russo and Henderson, I
| agree that's a solvable problem. It's worth noting that the
| resolutions they are describing, while encouraging, are not
| great. 2.6 A on Apoferritin, which is a best case scenario never
| seen in the "real-world" is quite a ways behind even the cheaper
| 200 kV scopes that have gotten down to 1.6 A. This is still
| firmly in "screening and learning" territory for most flexible
| samples, which is not without value, but not the answer to the 5
| million dollar Krios that we all so desperately want.
|
| Re: the national centers in the article, it depends which one you
| go to. NCCAT is fantastic, in my experience, but S2C2 is in the
| costly bay area and they just can't afford to pay their staff
| scientists enough. So what happens if you get tossed in with a
| fresh PhD that is underpaid and uninterested in your project.
| I've seen, in general, a lack of caring by the staff there, and
| no desire to understand specific problems each user is trying to
| solve. That results in lots of wasted iterations, especially if
| you are starting from scratch with no experience.
| onionisafruit wrote:
| I would think that the "need to pay multiple talented service
| engineers to be available to fly in on a moment's notice" is
| reduced when you are talking about a $500k capital expense
| sitting idle vs $5M. If you are willing to risk let it sit a
| few days then you can spread the technician cost among a larger
| pool.
| COGlory wrote:
| While that's true, it'd be exacerbated by a few things (in
| theory):
|
| 1) These instruments would still need to generate income to
| cover service costs.
|
| 2) Income generated per microscope would be reduced because
| of increased competition lowering beam time prices
| dramatically, so downtime is still very bad for microscope
| facilities.
|
| 3) More microscopes spread out over a wider geographical area
| means more service engineers needed (something I've
| experienced first-hand being in a state with only 3
| microscopes, Thermo has been entirely unwilling to place a
| service engineer here because they can't cover the costs with
| just 3 microscopes, despite making probably ~1 million/year
| in service contracts).
|
| In general, I think reduced costs and increased accessibility
| are a very good thing, but when VPRs go to do the math on
| these, I think they still don't make a lot of sense.
| dekhn wrote:
| Never, ever be surprised by the ability of people with large
| amounts of money to buy expensive toys (err, tools) and then
| go cheap on all the supporting infrastructure. Like, $1M on a
| scope, which then runs at about 1/10th capacity because the
| network is too slow to drain the SSD.
|
| I call this the "You bought a Ferrari to drive on 101 at
| 10MPH when you really needed a fleet of trucks" problem
| fabian2k wrote:
| I wonder how much potential there is to make them a lot more
| reliable and easier to use. Other kinds of instruments in the
| lab have gotten much more reliable and much easier to use over
| time, though this is not a particularly quick process. But I
| suspect this depends a lot on how well you can isolate the
| fragile parts of the equipment from the users.
|
| Regarding the last paragraph, it's incredibly frustrating if
| you see time on expensive instruments wasted because there
| aren't enough experts around and people have to try and figure
| out stuff for themselves. But it seems that it's almost always
| easier to buy another expensive instrument compared to hiring
| an expert on a permanent position.
| COGlory wrote:
| > I wonder how much potential there is to make them a lot
| more reliable and easier to use. Other kinds of instruments
| in the lab have gotten much more reliable and much easier to
| use over time, though this is not a particularly quick
| process. But I suspect this depends a lot on how well you can
| isolate the fragile parts of the equipment from the users.
|
| Going to 100 kV makes everything a little more forgiving in
| theory. SEMs that operate in the 10 kV range can be had for a
| full order of magnitude cheaper, although that price probably
| scales a bit with achievable resolution. But for an example,
| the 200 kV/300 kV microscopes can't change temperature by +-
| 1degF over a 24 hour period without the lenses going out of
| alignment (presumably because of the resistance change in the
| electromagnets).
|
| >Regarding the last paragraph, it's incredibly frustrating if
| you see time on expensive instruments wasted because there
| aren't enough experts around and people have to try and
| figure out stuff for themselves. But it seems that it's
| almost always easier to buy another expensive instrument
| compared to hiring an expert on a permanent position.
|
| The NIH and NSF have been quite willing to provide money to
| purchase microscopes. They are far less willing to provide
| money to cover annual operational expenses.
| passwordoops wrote:
| >The NIH and NSF have been quite willing to provide money
| to purchase microscopes. They are far less willing to
| provide money to cover annual operational expenses.
|
| This is a fundamental issue worldwide. I completed grad
| school in Canada, post-doc in the US setting up both labs
| with various GC-MS systems, then worked in the EU with
| laser spectroscopy and mass spec companies... Everyone had
| the same lament. Plenty of money for new toys, pennies for
| operations. Heck even now, after a decade away I decided to
| go back and the Prof had to apologize because in spite of
| nearly $10M for new equipment over the past four years,
| they only have $60K annually for an expert to run them.
| They're lucky I made bank and my wife is paid pretty well
| so I'm taking the plunge, but frack...
| nwiswell wrote:
| > Relative to the cost of a microscope, SF6, and a high tension
| tank are absolutely pennies.
|
| While I don't doubt this is true, it's worth mentioning that
| the 100-year GHG potential of SF6 is the single highest of ANY
| industrially used gas -- worse even than HFCs, PFCs, and NF3.
|
| So it's nice in general to avoid using it (maybe the cost
| SHOULD be higher!)
|
| (The 100 year GHG warming potential of 1 ton SF6 is
| approximately 23,500 tons of CO2)
| onionisafruit wrote:
| This looks like the biologist equivalent of not having to mail
| your punch cards and wait for the results. You still won't be
| able to afford one of your own, but your lab probably can.
| SubiculumCode wrote:
| not to be that guy, but is protein mapping for the masses a
| potentially dangerous technology of mass destruction?
| COGlory wrote:
| Probably not. Plenty of toxic proteins have a published
| structure and are quite easy to grow in a lab (i.e. an
| undergraduate could do it). The problem with using proteins to
| do evil things is that they tend to have short half-lives,
| aren't easily transmissible, etc. There are some exceptions to
| this, of course, but there's far more practical ways to do evil
| things.
| dekhn wrote:
| It seems implausible, and weighed against the probability of
| positive scientific discoveries made with the technology, it
| seems reasonable to proceed with caution.
|
| Back when I was a maker i talked with the FBI and they said
| they knew it was OK/legal to work on viruses in your garage,
| "but just be sure to let us know if you see somebody doing
| something dangerous"
| marktangotango wrote:
| Cheap SEMs are also useful for electron beam lithography, which
| has gotten some attention lately with Canons machine <10nm
| process.
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