[HN Gopher] Mass spectrometry method identifies pathogens within...
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       Mass spectrometry method identifies pathogens within minutes
       instead of days
        
       Author : pseudolus
       Score  : 124 points
       Date   : 2025-05-06 15:13 UTC (2 days ago)
        
 (HTM) web link (phys.org)
 (TXT) w3m dump (phys.org)
        
       | timetobuild wrote:
       | Super interesting! But mass spectrometry is an old method, why
       | just now?
        
         | prox wrote:
         | "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 wrote:
         | 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 wrote:
         | Checking out the actual article
         | (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 wrote:
           | 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 wrote:
         | 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 wrote:
           | 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.
        
       | pbmonster wrote:
       | 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 wrote:
         | 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_ wrote:
           | 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 wrote:
             | 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 wrote:
           | 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.
        
           | analog31 wrote:
           | In the US, this is already handled by prior authorization.
           | 
           | /s
        
           | Ey7NFZ3P0nzAe wrote:
           | Soon resident here: not really super critical to know the
           | exact pathogen. There are classes of antibiotics and
           | depending on many factors we can have a good estimate of what
           | will work so the first try usually helps. What's usually done
           | (at least in france) is:
           | 
           | 1. Take some blood to send to the labs to grow bacterias
           | 
           | 2. Only then IV of antibiotics
           | 
           | 3. Adjust at day 3 when you get the results.
           | 
           | And what if it looks super severe en urgent? Then 1. we do
           | that too because it's often impossible to know what the
           | pathogen was once you IVed all the antibiotics. And 2. we
           | start by wide spectrum super strong high dose antibiotics.
           | 
           | Example: purpura fulminans: 1g of 3rd gen cephalosporins.
           | 
           | Ymmv in other countries, especially the USA because IIRC you
           | have selected tons of emergent pathogens.
        
             | darth_avocado wrote:
             | This. Literally last week, I had to go to the ER and they
             | ran a PCR test to identify the infection. But they also
             | started broad spectrum antibiotics immediately. But since
             | it was a Thursday and the lab only works weekdays, I
             | couldn't get the results back until Tuesday. They adjusted
             | the antibiotics to a more targeted one once the results
             | were back.
        
               | Ey7NFZ3P0nzAe wrote:
               | Pretty usual stuff I'd say. And I'm willing to bet that
               | the 2nd sets of antibiotic had a lower spectrum of action
               | than the 1sr because we had some guess about the initial
               | strain.
               | 
               | Also because you're still with us so it probably worked.
               | 
               | In any case I'm glad you're better and sorry you had to
               | go through this.
        
         | Agingcoder wrote:
         | Do you know how cheap culturing bacteria is ( I really have no
         | idea )?
         | 
         | At 1 million/year ( worst case ), that's roughly 3k/day so 40
         | dollars / analysis using your numbers . Assuming the machine
         | lasts a bit longer ( say 5 years ) that's 8 dollars/analysis,
         | assuming 20min/sample. Make it a bit faster (5 minutes) and
         | you're down to two dollars which doesn't look super expensive
         | to me.
        
           | 5123125 wrote:
           | Aren't there are also operating cost ? What you said is just
           | depreciating cost of the machine.
        
           | aziaziazi wrote:
           | That's assuming the machine works 24/7 matching marching
           | perfectly the demand. I'm not a doctor but I guess it's a
           | seasonal "business" with more demand when cold winter starts,
           | back to school September, epidemic episodes...
        
           | mapt wrote:
           | I would also wonder whether cultures are compatible with mass
           | spec, and what the bottleneck is on measurement.
           | 
           | Culturing for optical microscopy seems like you need 1-10
           | DAYS before you get enough of a colony going to identify
           | things, assuming you can successfully culture them at all.
           | What if you plopped your culture down on the fermenter and
           | gave it three hours (very cheap! Parallelizable!), then threw
           | it in the mass spec? Would that shorten mass spec measurement
           | time?
        
         | davikr wrote:
         | It could be very useful for Oncohematology patients. Cultures
         | take a long time, relatively, for them, who often are severely
         | immunosuppressed due to treatment.
        
         | vondur wrote:
         | I wonder if it needs the high resolution models for this
         | technique? The models we used in undergrad were far cheaper
         | (probably $250k and up).
        
         | stonemetal12 wrote:
         | MRI machines cost up to 0.5 million, and take more than minutes
         | for a scan. So this is in the upper realm of reasonable. At
         | this point it is an engineering problem to get costs down.
        
           | mattkrause wrote:
           | A good MRI machine is way more than $500k!
        
           | westurner wrote:
           | There are 0.05 Tesla MRI machines that almost work with a
           | normal 15A 110V outlet now FWIU;
           | https://news.ycombinator.com/item?id=40965068 :
           | 
           | > _" Whole-body magnetic resonance imaging at 0.05 Tesla"
           | [1800W] https://www.science.org/doi/10.1126/science.adm7168
           | .. https://news.ycombinator.com/item?id=40335170 _
           | 
           | Other emerging developments in __ spectroscopy:
           | 
           | /?hnlog Spectro:
           | 
           | NIRS;
           | 
           | > _Are there implied molecular structures that can be
           | inferred from low-cost {NIRS, Light field, [...]} sensor
           | data?_
           | 
           | NIRS would be low cost, but the wavelength compared to the
           | sample size.
           | 
           | From https://news.ycombinator.com/item?id=38528844 :
           | 
           | > _" Reversible optical data storage below the diffraction
           | limit (2023)" [at cryogenic temperatures]
           | https://news.ycombinator.com/item?id=38528844 :_
           | 
           | > [...] _have successfully demonstrated that a beam of light
           | can not only be confined to a spot that is 50 times smaller
           | than its own wavelength but also "in a first of its kind" the
           | spot can be moved by minuscule amounts at the point where the
           | light is confined._
           | 
           | "Eye-safe laser technology to diagnose traumatic brain injury
           | in minutes" https://news.ycombinator.com/item?id=38510092 :
           | 
           | > _" Window into the mind: Advanced handheld spectroscopic
           | eye-safe technology for point-of-care neurodiagnostic" (2023)
           | https://www.science.org/doi/10.1126/sciadv.adg5431 _
           | 
           | > multiplex resonance Raman spectroscopy
           | 
           | Holotomographic imaging is yet another imaging method that
           | could be less costly than MRI;
           | https://news.ycombinator.com/item?id=40819864
           | 
           | "Quantum microscopy study makes electrons visible in slow
           | motion" https://news.ycombinator.com/item?id=40981054 :
           | 
           | > _" Terahertz spectroscopy of collective charge density wave
           | dynamics at the atomic scale" (2024)
           | https://www.nature.com/articles/s41567-024-02552-7 _
        
         | 0cf8612b2e1e wrote:
         | If they are just looking for a few signature metabolites, you
         | can easily do that on a single quadrupole for <$100k.
         | Realistically, I would expect something more precise for
         | medical purposes. Say a QExactive orbitrap -gives you
         | phenomenal performance (<5ppm accuracy) and can be had for
         | $500k.
         | 
         | The only mass specs I think of costing multiple millions of
         | dollars are accelerator mass spectrometers (AMS) which are
         | meant for isotopic analysis.
        
       | rurban wrote:
       | 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 wrote:
         | 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 wrote:
         | 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 wrote:
           | 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 wrote:
             | >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
             | [1] https://www.cdc.gov/healthcare-associated-
             | infections/php/dat...
        
           | cma wrote:
           | It could be used for disease control and not necessarily
           | personal health care. You could use something like the plant
           | thing if it worked for people by photographing an entire
           | stadium of people and finding infected people, airport entry
           | lines, etc.
        
           | rurban wrote:
           | > B/W cameras and AI.
           | 
           | You forgot multi-spectral. That means single hires images for
           | a lot of frequency ranges, which is better than a single
           | color image, which merges together all frequencies at once.
           | 
           | In the end the accuracy of detections, false-positives,
           | false-negatives wins. And this not comparable to this certain
           | car company which refuses to use proper sensors. we also do
           | infrared, 3d pointclouds to get the angle at each pixel, and
           | thermal imaging.
           | 
           | another neighbor of us is doing real-time imaging for face
           | detection, which is the industry leader world-wide. They can
           | install a lot of cheap cams in football stadiums and give you
           | a list of all 80.000 people, when they have access to the
           | government passport/driver license photo database. they have.
           | but they cannot detect virus infections as we can do. nor
           | bacterial infections. only if they do something illegal. who
           | threw a bengal fire or started a fight.
        
             | JoshTko wrote:
             | This. Mass Spectrometry should portably only be used to
             | confirm/train AI vision models. Once a large enough data
             | set has been created for a particular pathogen, incremental
             | diagnostic cost would be effectively 0.
        
             | caseyy wrote:
             | You're right, I didn't notice the multi-spectral part. My
             | point still stands, I wouldn't want human diagnostic
             | standards to slip but it is exciting technology. Thanks for
             | sharing.
        
           | anarticle wrote:
           | A reason for bw cam is sensitivity. No bayer filter means you
           | capture all the photons. There are cameras that are sensitive
           | enough to count photons as well. When I was in the lab we
           | used EMCCD cameras (electron multiplier ccd) that we used to
           | detect very low signals from cells (we wanted to be nice to
           | them, if you hit them with UV light they don't like that).
           | 
           | There are all kinds of really great hacks to eke out an extra
           | couple % at this level, if you consider you're counting
           | photons. Back thinned, reverse mounting, high bandwidth
           | multichannel readouts. Most of those trade offs are a thing
           | of the past, but in the 2000s we were hacking the beans off
           | those cameras to get them to do stunts for us.
           | 
           | Things are fast good AND cheap now though!
        
         | meindnoch wrote:
         | >Normal hires B/W cameras. 10 days before visible symptoms.
         | 
         | *visible to the human eye
        
       | JR1427 wrote:
       | 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/ , and this
       | company that is commercialising it https://microbira.com/
        
       | snalty wrote:
       | This is cool, but I still see sequencing and metagenomics as
       | being the gold standard going forward.
        
         | davikr wrote:
         | Metagenomics can do hard diagnoses. We achieved the first truly
         | confirmed diagnosis of neurohistoplasmosis in our region using
         | that technique.
        
         | michaelbarton wrote:
         | Yes specifically mcfDNA which also has the advantage of only
         | needing a blood draw
        
       | Inuit wrote:
       | I wonder how much resolution they need for diagnosis...
        
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