3 ms·

I recently wondered if you can take your saliva, or blood, and get a diffraction scan of it. Kind of like a spectrograph. You’d feed this into a machine learni

I recently wondered if you can take your saliva, or blood, and get a diffraction scan of it. Kind of like a spectrograph. You’d feed this into a machine learning system, and it would match up your pattern against a known dataset. This might allow for faster identification and recognition, of known viruses and diseases. Especially if the technology can identify the virus from just your spit.

umvi 6y ago
Sounds suspiciously like Theranos
- blackrock 6y ago
  Hah! I didn’t think of that. What kind of fraudulent product was she selling anyways?
  - sergiotapia 6y ago
    spit in = diseases.json out
azureus 6y ago
We're working on this, its fun, and already possible at lab scale. Check out Surface Enhanced Raman Spectroscopy (SERS). And we've got a huge shot in the arm with covid. At consumer scale the hard problem is skipping any kind of sample prep. Requires unrealistically high sensitivity - we're trying to work around this with different no-prep based amplification techniques. There is actually a lot of interesting work happening in this space. Further, currently the substrates use gold to enhance the raman scattering of the incident light. As you can imagine, this can get pretty expensive. There has been some success in using low cost paper/inkjet, textile/dye based approaches to introduce gold nanoparticles onto more familiar and easily mass produced substrate to achieve the same effect. SERS is pretty cool, hasn't got its due and I think its going to be one of the underdogs in the diagnostic/detection market in the coming years. Whats especially cool about it is - it doesn't restrict you to one thing - only genomes, only proteins etc. You may need a different strategy for different pathogens, detecting the a gene or cell wall for one, a synthesised protein for another, or even the waste product / metabolite to check if a reaction took place - its not a hammer looking for a nail.
koeng 6y ago
Current methods can pretty easily identify the virus from just your spit (in fact, that's a protocol that is pretty widely used for different applications). The biggest problem is that normally you need to concentrate the virus in order to get detectable range for earlier days of infection. Seems like the range is approximately ~2 days earlier with concentrating vs spit only, which is actually significant. All diseases (other than prions) are just nucleic acid, so that's already possible. Nanopore sequencing is the future and will eat most other technologies lunch.
- azureus 6y ago
  We're a nanopore sequencing shop. Couldn't agree with you more that nanopore generally is the future, not just for sequencing. Can't wait for ONT's solid state nanopore flow cells - you may get flowcells that go 2/3 times as long then. But then for most things .. the problem is the prep, not just because the whole portability thing goes for a toss. Yay, great the sequencer is the size of a USB drive, but the rest of the lab isn't :/ More worryingly the biggest and most stubborn cost is now the prep, not the sequencing. As you correctly pointed out - need to find a way around amplification - then both of these problems above go away if you can do direct PCR free sequencing. The other less mentioned problem related to the above is also the need for parallelisation - some of those ultra low costs you read about can only be realised when you sufficiently multiplex your samples. For instance, its about 100 USD per reaction for ligation (last step of prep before the sequencing starts), you generally wait till you're sequencing atleast 12 samples in the same reaction so that you're paying <10$ per sample, not 100$ per sample, which is obviously insane.
  - koeng 6y ago
    The key is to do barcoding at the PCR amplification step. That way, you can get away with barcoding hundreds of samples in a single tube. Really the prep screws it any other way. Is ONT coming out with solid state? Got a reference?
    - azureus 6y ago
      Solid state nanopores: still in research: https://nanoporetech.com/how-it-works/types-of-nanopores https://nanoporetech.com/how-it-works/types-of-nanopores I'm pretty sure they will come out with it. The protein nanopores were the first wave of nanopore research - its tried tested and stable now so they stick with it. A few years after they launched, the first solid state nanopores were being demonstrated in the lab. Commercialising solid state nanopores seems to be easier if anything than protein nanopores because they slot right into silicon fabrication. On PCR/barcoding .. Yeah, thats right - do it right in the PCR step .. sometimes we avoid it, if we are not yet sure about the protocol. I think what I meant to say is that the full promise of nanopore sequencing for me is achieved only when you can skip having to amplify/multiplex/barcode - just extract dna, wash, add sequencing adaptors and go - for almost anything. I think the way they are talked about people generally come in expecting that TODAY .. they think they can literally stick a single sample with no prep and get 1gb of sequencing done for 10$ in an hour. I've seen quite a lot of that. (even from people with PhD's :) ) So yeah its more that the minute you go PCR, you're in for a minimum 20$ per sample, often its the highest cost line item in your whole process. If you're doing things like 16S metagenomics, you get sequencing at 2-3$ and prep at 10 times that, starts to feel "wrong" after a while, if you get what I mean. Why're trying everything we can to make sure we're running at full capacity so that we can always give low prices even if its single samples. Also seeing if we can reduce prep cost with microfluidics/mems - they have voltrax for this, but there are a few other vendors in the market. That has the positive knock-on effect of also reducing labour cost.

umvi 6y ago

Sounds suspiciously like Theranos

blackrock 6y ago
Hah! I didn’t think of that. What kind of fraudulent product was she selling anyways?
- sergiotapia 6y ago
  spit in = diseases.json out

azureus 6y ago

We're working on this, its fun, and already possible at lab scale. Check out Surface Enhanced Raman Spectroscopy (SERS). And we've got a huge shot in the arm with covid. At consumer scale the hard problem is skipping any kind of sample prep. Requires unrealistically high sensitivity - we're trying to work around this with different no-prep based amplification techniques. There is actually a lot of interesting work happening in this space. Further, currently the substrates use gold to enhance the raman scattering of the incident light. As you can imagine, this can get pretty expensive. There has been some success in using low cost paper/inkjet, textile/dye based approaches to introduce gold nanoparticles onto more familiar and easily mass produced substrate to achieve the same effect. SERS is pretty cool, hasn't got its due and I think its going to be one of the underdogs in the diagnostic/detection market in the coming years. Whats especially cool about it is - it doesn't restrict you to one thing - only genomes, only proteins etc. You may need a different strategy for different pathogens, detecting the a gene or cell wall for one, a synthesised protein for another, or even the waste product / metabolite to check if a reaction took place - its not a hammer looking for a nail.

koeng 6y ago

Current methods can pretty easily identify the virus from just your spit (in fact, that's a protocol that is pretty widely used for different applications). The biggest problem is that normally you need to concentrate the virus in order to get detectable range for earlier days of infection. Seems like the range is approximately ~2 days earlier with concentrating vs spit only, which is actually significant. All diseases (other than prions) are just nucleic acid, so that's already possible. Nanopore sequencing is the future and will eat most other technologies lunch.

azureus 6y ago
We're a nanopore sequencing shop. Couldn't agree with you more that nanopore generally is the future, not just for sequencing. Can't wait for ONT's solid state nanopore flow cells - you may get flowcells that go 2/3 times as long then. But then for most things .. the problem is the prep, not just because the whole portability thing goes for a toss. Yay, great the sequencer is the size of a USB drive, but the rest of the lab isn't :/ More worryingly the biggest and most stubborn cost is now the prep, not the sequencing. As you correctly pointed out - need to find a way around amplification - then both of these problems above go away if you can do direct PCR free sequencing. The other less mentioned problem related to the above is also the need for parallelisation - some of those ultra low costs you read about can only be realised when you sufficiently multiplex your samples. For instance, its about 100 USD per reaction for ligation (last step of prep before the sequencing starts), you generally wait till you're sequencing atleast 12 samples in the same reaction so that you're paying <10$ per sample, not 100$ per sample, which is obviously insane.
- koeng 6y ago
  The key is to do barcoding at the PCR amplification step. That way, you can get away with barcoding hundreds of samples in a single tube. Really the prep screws it any other way. Is ONT coming out with solid state? Got a reference?
  - azureus 6y ago
    Solid state nanopores: still in research: https://nanoporetech.com/how-it-works/types-of-nanopores https://nanoporetech.com/how-it-works/types-of-nanopores I'm pretty sure they will come out with it. The protein nanopores were the first wave of nanopore research - its tried tested and stable now so they stick with it. A few years after they launched, the first solid state nanopores were being demonstrated in the lab. Commercialising solid state nanopores seems to be easier if anything than protein nanopores because they slot right into silicon fabrication. On PCR/barcoding .. Yeah, thats right - do it right in the PCR step .. sometimes we avoid it, if we are not yet sure about the protocol. I think what I meant to say is that the full promise of nanopore sequencing for me is achieved only when you can skip having to amplify/multiplex/barcode - just extract dna, wash, add sequencing adaptors and go - for almost anything. I think the way they are talked about people generally come in expecting that TODAY .. they think they can literally stick a single sample with no prep and get 1gb of sequencing done for 10$ in an hour. I've seen quite a lot of that. (even from people with PhD's :) ) So yeah its more that the minute you go PCR, you're in for a minimum 20$ per sample, often its the highest cost line item in your whole process. If you're doing things like 16S metagenomics, you get sequencing at 2-3$ and prep at 10 times that, starts to feel "wrong" after a while, if you get what I mean. Why're trying everything we can to make sure we're running at full capacity so that we can always give low prices even if its single samples. Also seeing if we can reduce prep cost with microfluidics/mems - they have voltrax for this, but there are a few other vendors in the market. That has the positive knock-on effect of also reducing labour cost.