Exactive plus EMR. Is the last excuse for buying a TOF gone?

The title sounds kind of arrogant, really, until you think about it.  Q-TOFs are neat instruments.  They were a revelation when they first appeared way back when.  Speed of a quadrupole plus the mass accuracy of a TOF, right?

Except it is always a compromise.  You don't really get the quad speed because you can't load the ions into the flight path of the TOF that fast.  And if you try to run at quadrupole-like speeds then the mass accuracy of the TOF is compromised.  And you have the drawback that the only real way to improve the resolution is to lengthen the flight path, and then your sensitivity takes a hit.  But they are good for a lot of things.

Sure I'm biased, but every year the Orbitrap starts to kill the reasons you might want a Q-TOF.  First came resolution and it is now a very clear fact that no TOF can compete with an Orbi in resolution. Sensitivity?  In TOF resolution is the inverse of sensitivity, you can never have both.   The next argument for the Q-TOFs was the price, but then the Q Exactive hit the market and that argument was gone. (And you can make a pretty strong case that the QE took away the speed argument as well).

The last and final argument standing?   TOFs are so good  intact analysis.  Orbis are good too, I've done 150kDa antibodies on a QE before (I should post that).  But I kept hearing that the Q-TOFs are better.

Enter the Exactive plus EMR.  I just got 3 days on one.  Imagine that you took an Orbi, ran the m/z mass range to 20,000, changed the vacuum to result in the preservation of intact proteins, added HCD cell trapping (to also help the sensitive intact proteins)...oh, and DOUBLED THE SPEED OF THE ORBITRAP relative to that of our speedy friend the Q Exactive and you have the Exactive plus EMR.  There are special solvation functions so that you don't even have to reduce your protein.  Just run it native.  And it works.  Beautifully.

I had to steal this screenshot.  But I have personally done this experiment.  I've got the RAW data right here but I'm just learning the new Protein Deconvolution 2.0 necessary to process that data.  I'll have it up soon.  If you follow my blog, you know that intact analysis isn't my strongest area. My strength is in shotgun proteomics and bioinformatics.  So when I tell you that when the first EMR got into the country and 12 or so of us flew out to get time on it and I generated gorgeous data on it when everyone else went to lunch, I want that to have it's full weight.

Intact analysis is hard.  It was hard when I did my first on in grad school and it has always been that way.  And I don't care what instrument you have been using.  If you can take an intact protein and get it to charge up enough so you can see it via mass spectrometry, you have always had my enduring respect.

The Exactive plus EMR takes away a little tiny bit of that respect.  Cause it isn't anywhere near as hard to get extremely nice and accurate information on the intact mass of a big protein as it used to be.

Real data from my lunch break on the instrument will follow once I get a handle on the new software.