8 ms·

Cheaper microscope could bring protein mapping technique to the masses

160 points by digital55 3y ago

KnuthIsGod 3y ago
"Russo wants a manufacturer to commercialize his team’s design, which he believes could be built and sold for $500,000" A microscope for the masses ? Hmm..
- ramraj07 3y ago
  Damn near every university microscope facility has a spinning disk confocal microscope that costs as much so yeah if it only costs half a mill instead of 10x itll be more widely available.
- deleted 3y ago
  [deleted]
onionisafruit 3y ago
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 3y ago
not to be that guy, but is protein mapping for the masses a potentially dangerous technology of mass destruction?
- COGlory 3y ago
  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 3y ago
  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 3y ago
Cheap SEMs are also useful for electron beam lithography, which has gotten some attention lately with Canons machine <10nm process.
aj7 3y ago
This and the precursor article in Science were very informative to this novice. Yet both articles seemed, by the halfway point, to devolve into marketing literature for Thermofisher.
mfragin 3y ago
This reminds me of https://www.bbc.com/news/technology-19343140 https://www.bbc.com/news/technology-19343140 I am totally unqualified to judge this current topic [except for a degree in Biology], but I'm just curious if the "foldiscope" was successful or not.
- ramraj07 3y ago
  It’s a fun project but the microscope is not the bottleneck in any place where you can do a research experiment.
- lofatdairy 3y ago
  I know Caltech did/does use it in their undergraduate core(?), and even has Dr. Prakash speak w/ the students. That said, I'm pretty sure field application of the device hasn't really panned out and runs into resolution problems. I'm honestly not sure if that was the intention, but checking a few literature review articles and recent pubs doesn't seem to show any major success stories, and mostly notes about resolution. My favorite invention from his lab is the Paperfuge[^1], though the device is probably too recent to know how useful it'll be. Considering that so much point-of-care diagnostics can be done with either a cheap lateral-flow kit or some Cepheid or Abbot microfluidic product though, a non-integrated centrifuge might be a bit tougher to justify. [^1]: https://www.nature.com/articles/s41551-016-0009 https://www.nature.com/articles/s41551-016-0009, the first author now leads his own lab at GaTech: https://bhamla.gatech.edu/people https://bhamla.gatech.edu/people
- aaron695 3y ago
  [dead]
CyberDildonics 3y ago
If there's one thing with mass appeal, it's protein mapping.
MichaelPayne 3y ago
[flagged]
COGlory 3y ago
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 Å 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 Å. 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 3y ago
  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.

160 points by digital55 3y ago

"Russo wants a manufacturer to commercialize his team’s design, which he believes could be built and sold for $500,000" A microscope for the masses ? Hmm..

ramraj07 3y ago
Damn near every university microscope facility has a spinning disk confocal microscope that costs as much so yeah if it only costs half a mill instead of 10x itll be more widely available.
deleted 3y ago
[deleted]

onionisafruit 3y ago

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 3y ago

not to be that guy, but is protein mapping for the masses a potentially dangerous technology of mass destruction?

COGlory 3y ago
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 3y ago
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 3y ago

Cheap SEMs are also useful for electron beam lithography, which has gotten some attention lately with Canons machine <10nm process.

aj7 3y ago

This and the precursor article in Science were very informative to this novice. Yet both articles seemed, by the halfway point, to devolve into marketing literature for Thermofisher.

mfragin 3y ago

This reminds me of https://www.bbc.com/news/technology-19343140 https://www.bbc.com/news/technology-19343140 I am totally unqualified to judge this current topic [except for a degree in Biology], but I'm just curious if the "foldiscope" was successful or not.

ramraj07 3y ago
It’s a fun project but the microscope is not the bottleneck in any place where you can do a research experiment.
lofatdairy 3y ago
I know Caltech did/does use it in their undergraduate core(?), and even has Dr. Prakash speak w/ the students. That said, I'm pretty sure field application of the device hasn't really panned out and runs into resolution problems. I'm honestly not sure if that was the intention, but checking a few literature review articles and recent pubs doesn't seem to show any major success stories, and mostly notes about resolution. My favorite invention from his lab is the Paperfuge[^1], though the device is probably too recent to know how useful it'll be. Considering that so much point-of-care diagnostics can be done with either a cheap lateral-flow kit or some Cepheid or Abbot microfluidic product though, a non-integrated centrifuge might be a bit tougher to justify. [^1]: https://www.nature.com/articles/s41551-016-0009 https://www.nature.com/articles/s41551-016-0009, the first author now leads his own lab at GaTech: https://bhamla.gatech.edu/people https://bhamla.gatech.edu/people
aaron695 3y ago
[dead]

CyberDildonics 3y ago

If there's one thing with mass appeal, it's protein mapping.

MichaelPayne 3y ago

[flagged]

COGlory 3y ago

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 Å 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 Å. 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 3y ago
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.