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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!



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


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.


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.


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.


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.


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


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.


In the US, this is already handled by prior authorization.

/s


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.


A good MRI machine is way more than $500k!


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


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.


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?


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…


Aren't there are also operating cost ? What you said is just depreciating cost of the machine.


Indeed. Let’s add electricity and maybe double the costs ? Note some of the costs will be shared anyway with the bacteria culture anyway ( you need folks to interpret the results, real estate , etc ). Still at 4 usd/ analysis, it looks reasonable to me.


It could be very useful for Oncohematology patients. Cultures take a long time, relatively, for them, who often are severely immunosuppressed due to treatment.


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).


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.




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