6 ms·

Mass spectrometry method identifies pathogens within minutes instead of days

136 points by pseudolus 2y ago

timetobuild 2y ago
Super interesting! But mass spectrometry is an old method, why just now?
- prox 2y ago
  "Our innovative approach is not to look directly for the pathogenic bacteria, but only for their metabolic products. This allows us to detect them indirectly, but much more quickly."
- pbmonster 2y ago
  Often, stuff like that is a compliance thing. Very possible they're doing the research now, because one of the mass spectrometer companies has gotten ISO 13485 certified and can now offer the spectrometer for diagnostics in humans as a medical device manufacturer.
- WJW 2y ago
  Checking out the actual article (https://www.nature.com/articles/s41467-024-55457-7 https://www.nature.com/articles/s41467-024-55457-7) the authors write that: "In recent years, matrix-assisted laser desorption/ionisation-mass spectrometry (MALDI-MS) has been rapidly adopted in clinical practice to identify bacteria based on unique protein profiles6,7. However, while the identification process itself is faster, MALDI-MS-based analysis suffers from the same time-consuming isolation step as traditional approaches. Time, however, is a decisive factor in the successful treatment of several infection scenarios such as sepsis4,8. Consequently, the ideal scenario of microbial diagnosis is to identify bacteria directly from the clinical sample. Using MALDI, so far only a small number of applications could be implemented due to the high protein background in most clinical samples9." While mass spectrometry is an old(-ish) method, only recently has it become good and fast enough for clinical use. They also needed to make their own database of bacterial byproduct signatures to look for, as that did not exist yet. As to "why just now": not everything has been invented yet, even things that might seem relatively straightforward.
  - w10-1 2y ago
    glossing... Article mentions existing tools e.g., MasSpec Pen, which detect signals of interest in samples with minimal processing (i.e., avoiding the hard part of processing/cleaning bio samples). But those were specific cancer signals that stood out from the general protein noise. (See also the cancer knife, that burns to cut and analyzes the smoke to see if you have enough margin). Problem with bacteria is (a) wide diversity and (b) previous work was mostly on lipids, not small molecules. For small molecule metabolites of bacteria, previous article reported a medium-size proof of concept (hundreds of target), and this is doing more (thousands), where they identify a few hundred unique patterns and then demonstrate their detection. At 90%, it's likely this would be used for pre-screening to identify possible candidates, though it might reinforce initial clinical suspicion and preliminary antibiotics.
- shakna 2y ago
  Old does not really mean widely available. These machines can run into the hundreds of millions of dollars. Having one spare for research is not the norm, any more than having one is.
  - 0cf8612b2e1e 2y ago
    Incredibly capable mass spectrometers can be had for half a million. Plenty of undergrad labs have access to one. A student quality single quad is <$100k.
    - shakna 2y ago
      Sure, but those aren't high resolution - like this technique requires.
      - 0cf8612b2e1e 2y ago
        A QE is an absolutely fantastic instrument for half a million and more capable than the baseline Exactive used here.
pbmonster 2y ago
Would be interesting how much resolution they need for the diagnosis to be reliable. Because high resolution mass spectrometers cost millions of dollars, and "minutes" for a diagnosis can mean that one spectrometer can only run 3 samples per hour - or 72 per day. And while a research university can afford a million dollar spectrometer (and the grad students that run it), even a small hospital will create 72 bacterial swaps per hour - while absolutely not having the money to get 10 spectrometers with the corresponding technicians. And the incumbent/competitor - standard bacterial cultures - is cheap!
- californical 2y ago
  But couldn’t a hospital use it only for the critical cases? Where it is immediately important to know what infection someone may have, at imminent risk of death? Who cares if they need to charge $30k per patient to use it if that fast knowledge saves the patient’s life. It doesn’t need to fully replace the existing methods, but could be a useful supplement when a patient is in critical condition
  - Cthulhu_ 2y ago
    Sure, but then they'd have a million(s) dollar machine (plus the people trained to operate it) waiting for these critical cases. It's a cost / benefit tradeoff, just like whether to use an MRI or CAT scan vs x-rays or an echo.
    - passwordoops 2y ago
      Plus high-res mass specs can't just be turned on, they need to be kept on standby which isn't cheap when you cost it out over a year
  - mapt 2y ago
    This is a false dichotomy. It doesn't have to be used for every patient, and it doesn't have to be kept around waiting for Doctor House's third act. There is nothing stopping you from a middle ground.
  - 2y ago
rurban 2y ago
Mass spectromity is a bit expensive. My company can detect a common plant virus reliable with multi-spectral imaging only. Normal hires B/W cameras. 10 days before visible symptoms. SpexAI.com Only vision scales. We did mass spectromity in Formula 1 because we had the money and it doesn't need to scale.
- amelius 2y ago
  Sounds like this is exploiting a correlation between the virus and how the plant reacts to it. That's very specific. The nice thing about mass-spec is that you can use it as a dragnet detection method.
- caseyy 2y ago
  Such approaches are cool for plants and maybe animal healthcare, where the other reasonably priced alternative is nothing. I don't know how I'd feel about reliable precision tools in human healthcare being substituted with B/W cameras and AI. It reminds me of a certain car company, where the human lives lost aspect wasn't so liked, even if they saved some money.
  - ptsneves 2y ago
    This is doing correctly what the car company did wrong. They start with a system that does not have a fatal incident upon failure. Meaning that even 1% or 10% failure rate is totally fine and possibly positive in terms of ROI. On the other hand, even 0.01% is not acceptable when the system is responsible for human lives. I also believe that cameras and visible spectrum are scalable and sufficient, and there is evidence it is so. The most reliable system driving cars is the homo sapiens and apart from a bit of proprioceptive, vehicles are operated based on vision sensors(eyes). To conclude, I find it a clever move to start refining the technology in a field where ROI is in dollar terms and not in lives saved. To the found: Good luck, i am jealous.
    - sfilmeyer 2y ago
      >On the other hand, even 0.01% is not acceptable when the system is responsible for human lives. I've got bad news for you about a whole lot of medical tests and interventions if 0.01% is unacceptable for you. I get your point that the stakes might be higher with medical technology than in some other fields, but you're still setting the bar too high. The first pathogen I saw mentioned by name while skimming through the linked article was H. Pylori, where the false-positive and false-negative rates for various currently used tests are several dozen times worse than that at about 0.30-0.90% [0]. Even just being hospitalized in and of itself has failure rates. Just eyeballing some of the numbers at [1] and elsewhere, I suspect that at least 0.01% of hospitalizations result in a death attributable to a hospital acquired infection. [0] https://www.aafp.org/pubs/afp/issues/2019/0701/p16.html https://www.aafp.org/pubs/afp/issues/2019/0701/p16.html [1] https://www.cdc.gov/healthcare-associated-infections/php/data/index.html https://www.cdc.gov/healthcare-associated-infections/php/dat...
JR1427 2y ago
You can identify quite a few pathogens with Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy. I think the machines for that are smaller and cheaper than mass spec machines. see https://pmc.ncbi.nlm.nih.gov/articles/PMC5631018/ https://pmc.ncbi.nlm.nih.gov/articles/PMC5631018/ , and this company that is commercialising it https://microbira.com/ https://microbira.com/
snalty 2y ago
This is cool, but I still see sequencing and metagenomics as being the gold standard going forward.
- davikr 2y ago
  Metagenomics can do hard diagnoses. We achieved the first truly confirmed diagnosis of neurohistoplasmosis in our region using that technique.
- michaelbarton 2y ago
  Yes specifically mcfDNA which also has the advantage of only needing a blood draw
Inuit 2y ago
I wonder how much resolution they need for diagnosis...

136 points by pseudolus 2y ago

timetobuild 2y ago

Super interesting! But mass spectrometry is an old method, why just now?

prox 2y ago
"Our innovative approach is not to look directly for the pathogenic bacteria, but only for their metabolic products. This allows us to detect them indirectly, but much more quickly."
pbmonster 2y ago
Often, stuff like that is a compliance thing. Very possible they're doing the research now, because one of the mass spectrometer companies has gotten ISO 13485 certified and can now offer the spectrometer for diagnostics in humans as a medical device manufacturer.
WJW 2y ago
Checking out the actual article (https://www.nature.com/articles/s41467-024-55457-7 https://www.nature.com/articles/s41467-024-55457-7) the authors write that: "In recent years, matrix-assisted laser desorption/ionisation-mass spectrometry (MALDI-MS) has been rapidly adopted in clinical practice to identify bacteria based on unique protein profiles6,7. However, while the identification process itself is faster, MALDI-MS-based analysis suffers from the same time-consuming isolation step as traditional approaches. Time, however, is a decisive factor in the successful treatment of several infection scenarios such as sepsis4,8. Consequently, the ideal scenario of microbial diagnosis is to identify bacteria directly from the clinical sample. Using MALDI, so far only a small number of applications could be implemented due to the high protein background in most clinical samples9." While mass spectrometry is an old(-ish) method, only recently has it become good and fast enough for clinical use. They also needed to make their own database of bacterial byproduct signatures to look for, as that did not exist yet. As to "why just now": not everything has been invented yet, even things that might seem relatively straightforward.
- w10-1 2y ago
  glossing... Article mentions existing tools e.g., MasSpec Pen, which detect signals of interest in samples with minimal processing (i.e., avoiding the hard part of processing/cleaning bio samples). But those were specific cancer signals that stood out from the general protein noise. (See also the cancer knife, that burns to cut and analyzes the smoke to see if you have enough margin). Problem with bacteria is (a) wide diversity and (b) previous work was mostly on lipids, not small molecules. For small molecule metabolites of bacteria, previous article reported a medium-size proof of concept (hundreds of target), and this is doing more (thousands), where they identify a few hundred unique patterns and then demonstrate their detection. At 90%, it's likely this would be used for pre-screening to identify possible candidates, though it might reinforce initial clinical suspicion and preliminary antibiotics.
shakna 2y ago
Old does not really mean widely available. These machines can run into the hundreds of millions of dollars. Having one spare for research is not the norm, any more than having one is.
- 0cf8612b2e1e 2y ago
  Incredibly capable mass spectrometers can be had for half a million. Plenty of undergrad labs have access to one. A student quality single quad is <$100k.
  - shakna 2y ago
    Sure, but those aren't high resolution - like this technique requires.
    - 0cf8612b2e1e 2y ago
      A QE is an absolutely fantastic instrument for half a million and more capable than the baseline Exactive used here.

pbmonster 2y ago

Would be interesting how much resolution they need for the diagnosis to be reliable. Because high resolution mass spectrometers cost millions of dollars, and "minutes" for a diagnosis can mean that one spectrometer can only run 3 samples per hour - or 72 per day. And while a research university can afford a million dollar spectrometer (and the grad students that run it), even a small hospital will create 72 bacterial swaps per hour - while absolutely not having the money to get 10 spectrometers with the corresponding technicians. And the incumbent/competitor - standard bacterial cultures - is cheap!

californical 2y ago
But couldn’t a hospital use it only for the critical cases? Where it is immediately important to know what infection someone may have, at imminent risk of death? Who cares if they need to charge $30k per patient to use it if that fast knowledge saves the patient’s life. It doesn’t need to fully replace the existing methods, but could be a useful supplement when a patient is in critical condition
- Cthulhu_ 2y ago
  Sure, but then they'd have a million(s) dollar machine (plus the people trained to operate it) waiting for these critical cases. It's a cost / benefit tradeoff, just like whether to use an MRI or CAT scan vs x-rays or an echo.
  - passwordoops 2y ago
    Plus high-res mass specs can't just be turned on, they need to be kept on standby which isn't cheap when you cost it out over a year
- mapt 2y ago
  This is a false dichotomy. It doesn't have to be used for every patient, and it doesn't have to be kept around waiting for Doctor House's third act. There is nothing stopping you from a middle ground.
- 2y ago

rurban 2y ago

Mass spectromity is a bit expensive. My company can detect a common plant virus reliable with multi-spectral imaging only. Normal hires B/W cameras. 10 days before visible symptoms. SpexAI.com Only vision scales. We did mass spectromity in Formula 1 because we had the money and it doesn't need to scale.

amelius 2y ago
Sounds like this is exploiting a correlation between the virus and how the plant reacts to it. That's very specific. The nice thing about mass-spec is that you can use it as a dragnet detection method.
caseyy 2y ago
Such approaches are cool for plants and maybe animal healthcare, where the other reasonably priced alternative is nothing. I don't know how I'd feel about reliable precision tools in human healthcare being substituted with B/W cameras and AI. It reminds me of a certain car company, where the human lives lost aspect wasn't so liked, even if they saved some money.
- ptsneves 2y ago
  This is doing correctly what the car company did wrong. They start with a system that does not have a fatal incident upon failure. Meaning that even 1% or 10% failure rate is totally fine and possibly positive in terms of ROI. On the other hand, even 0.01% is not acceptable when the system is responsible for human lives. I also believe that cameras and visible spectrum are scalable and sufficient, and there is evidence it is so. The most reliable system driving cars is the homo sapiens and apart from a bit of proprioceptive, vehicles are operated based on vision sensors(eyes). To conclude, I find it a clever move to start refining the technology in a field where ROI is in dollar terms and not in lives saved. To the found: Good luck, i am jealous.
  - sfilmeyer 2y ago
    >On the other hand, even 0.01% is not acceptable when the system is responsible for human lives. I've got bad news for you about a whole lot of medical tests and interventions if 0.01% is unacceptable for you. I get your point that the stakes might be higher with medical technology than in some other fields, but you're still setting the bar too high. The first pathogen I saw mentioned by name while skimming through the linked article was H. Pylori, where the false-positive and false-negative rates for various currently used tests are several dozen times worse than that at about 0.30-0.90% [0]. Even just being hospitalized in and of itself has failure rates. Just eyeballing some of the numbers at [1] and elsewhere, I suspect that at least 0.01% of hospitalizations result in a death attributable to a hospital acquired infection. [0] https://www.aafp.org/pubs/afp/issues/2019/0701/p16.html https://www.aafp.org/pubs/afp/issues/2019/0701/p16.html [1] https://www.cdc.gov/healthcare-associated-infections/php/data/index.html https://www.cdc.gov/healthcare-associated-infections/php/dat...

JR1427 2y ago

You can identify quite a few pathogens with Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy. I think the machines for that are smaller and cheaper than mass spec machines. see https://pmc.ncbi.nlm.nih.gov/articles/PMC5631018/ https://pmc.ncbi.nlm.nih.gov/articles/PMC5631018/ , and this company that is commercialising it https://microbira.com/ https://microbira.com/

snalty 2y ago

This is cool, but I still see sequencing and metagenomics as being the gold standard going forward.

davikr 2y ago
Metagenomics can do hard diagnoses. We achieved the first truly confirmed diagnosis of neurohistoplasmosis in our region using that technique.
michaelbarton 2y ago
Yes specifically mcfDNA which also has the advantage of only needing a blood draw

Inuit 2y ago

I wonder how much resolution they need for diagnosis...