Wednesday, May 22, 2019

Virtual lock masses!

Time Of Flight (TOF) instruments can be ridiculously fast. Compared to today's FTMS (mostly Orbitrap) instruments, they compare poorly in two pretty serious regards.

Is this new paper in biorXIV something that could finally lift one of these limitations?

My blogger-at-5:30AM interpretation is:

1) Sensitivity -- with the exception of TIMS, there is no way to accumulate signal before shooting the ions down a flight tube -- this is a generalization, but I expect around 100x less signal on a TOF compared to even the oldest Orbitrap systems (also keep in mind that more TOF resolution = less TOF signal since the ions are traveling farther in an imperfect vacuum system.)  This is even worse, considering that I sometimes acquire signal in C-traps prior to Orbitrap analysis for 1000ms (or more) when I want to prove that a QE can exceed even quadrupole LOD/LOQ

2) Accuracy -- again, more generalizations, but most TOFs without consistent lockmass are accurate to one decimal place, where Orbitraps are at least to the second decimal and almost always to the third. (TOFs are also massively affected by temperature in the room, with some needing calibrated many many times/day)

Aha! Okay -- so I haven't ran a TOF in a long-ish time now -- but -- I know consistent lockmass sprays are in use that improve #2, but could you mathematically drop in a virtual value and get improved accuracy all the time?  These authors sure think so.

I tell you what. I was seriously proud of my brain as far as page 5. For real. I probably didn't actually know what was going on, but some combination of espresso and birds chirping at 5:30 made me feel like I did. Go brain go! I had some random thought about "Vince Carter's coming back for one more year, maybe there is still hope for you down this senescence water slide, old brain!" ...then...

...maybe it's time to walk the dogs and look at flowers....

Importantly -- yes, this totally looks like it works, though my dummies interpretation is that you need a lot of spectra to get the maths to work out, but once you have that pile of spectra you can use learning machines to massively improve the quality of the TOFs data.

Now -- I know people often think that the mass accuracy off the Orbitraps is probably more than we need -- and just about no one uses MS/MS lockmass on their Tribrid systems, even though that capability is there -- but -- is it enough? Will future bioinformaGicians look back on our data and wonder "why on earth didn't they lockmass their MS/MS spectra -- I need it for this (insert undiscovered chemical modification here)!??!" I don't know, but it's nice to think that we could improve the data we already have!

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