Monday, August 11, 2025

SynchoSep-MS - Another top lab utilizing amazingly complicated HPLC!

 


Ummmmm.....okay.....so when I saw the first preprint with a similar concept, I thought something like "that's a weird idea that probably looks okay on paper but will absolutely never ever work in practice".

And....here is a bunch of top notch scientists like Dan frickin' Polasky, himself, demonstrating a very similar concept? 


Between the 2 studies there are 15 or so authors and I'm pretty sure that means 22 of them are smarter than me - so... 


...wait. That's upside down. 

Do we revisit this idea? It might be like the single ion mass spectrometry thing that I really couldn't figure out, that - to this day - still looks to me like you're just doing scan averaging of incredibly poor signa, but I have to accept that I'm not smart enough to understand why it's something else.

And that's totally fine as long as the science is good! 

Okay - so revist the idea? Here you inject 2 samples on an LCMS system but each one goes to a different nanoLC column so that peptide A for sample 1 and sample 2 come out at different times? 


If I'm anywhere close one getting this - you're operating under the assumption that your MS system is no longer as limiting in the number of ions/peptides/proteins that it can detect as your chromatography is....

Which is very confusing after a decade and a half (geez...longer...? wtf...?) of having way way way more peptides eluting than you can possibly detect - one blog post on the absolutely amazing paper that I was first aware that actually counted this discrepancy

If that is true then, this sorta makes sense....? The downsides in my mind that I noted when the similar preprint dropped that you're depending on two nanoLC columns (I'd rather not depend on one - two sounds like 4 times the trouble) still seem valid to me. Also, I'm going to add the concern that this is great for my proteins that exist at 20,000 copies or more, but probably really bad for the proteins in sample A or B that are only about 100 copies per cell.... However, if you're really truly desperate to get that throughput up without mutiplexing reagents, this appears to be an avenue you could explore. 

Let me know how it goes? I like my robust simple little HPLC system where my weak point (my column or emitter) is a single instance. 

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