Friday, June 18, 2021

ASMS 2021 Vendor Wrapup for Proteomics Stuff?

This post has been edited, because I realized later that some of this was me being kind of a jerk and I'm going to blame it on a really dumb injury I got being awesome that derailed my summer. 

Okay, this might take some time, because!! WOW!! what an ASMS hardware rollout! 

If I'm not covering your product, I apologize, its been a long year (and ASMS starts on Halloween!)

There were some seriously big vendor rollouts on the hardware front which got me to thinking ---

 From this Tweet, I learned a few thing. 

1) That there are people out there who didn't realize they were being eccentric with their low signal mediocre resolution data. 😇

2) It was kind of a tie between software and your relationship with your sales and support team. Which...probably doesn't bode well for Thermo since they recently got rid of their subject matter expert sales teams for their products in the US. If you weren't aware, they now sell by geography. So...your local rep who got her/his PhD from the famous proteomics lab? He/she might be selling ICP-OES systems now. Strategery from the company that can't seem to find a way to give up market share in proteomics fast enough to keep their executives happy! 


Bruker's launch was tied for the longest (3 days, thank goodness for how much time off we get in the USA) and was centered on the "TIMSTOF SCP"

This smaller TIMSTOF was the result of a close collaboration with Matthias Mann's lab and based around the preprint from last May. [Edited jerkness]

Another upside of this event was the TIMSTOF Pro X! This is a new instrument and/or field upgrade for TIMSTOF Pros! The price didn't seem absurd for current users and it's always cool to have a field upgrade for a 10 foot tall 2,000 pound box!

Legit, I think both of these things are totally cool, my job is to be a critic, I think 

ASMS Launch 2 and 2.5

The next week was coinciding launches by Waters and the first of 3 days of Thermo! 


I've been asked by multiple people "wow, you seem really pumped about this one" and I am from a theoretical standpoint. I'm extremely clear in my "mass spec physics taught by a dumb person" slide deck that you can't get above 70,000 resolution on a Time of Flight instrument. The vacuum on the flight tube just becomes far too long to make any sense at all.

Waters has a MALDI/DESI-TOF that can hit 200,000 resolution against the whole goshdarned mass range. Speed? About 10 scans/second. 

If you're thinking "my Orbitrap Fusion/Exploris/can get 480,000 resolution" let's stop for a second

1) How much time does that take? I don't feel like doing math, but it's probably about a second. (You can download my calculator here)

2) What about resolution degradation across a mass range? What? 

Okay, so there are a bunch of secret rules in mass spectrometry vendors that they must stick to. I can't tell you all of them, but:

1) The compounds that you are provided for calibration must be the stupidest thing they can come up with. A peptide that will only singly charge and will rapidly oxidize? PERFECT! A polymer that will stick in your system until the fucking end of goddamned time and will always affect your sensitivity? BINGO! 

2) Vendors can pick any one of these stupid inconvenient molecules and use that for the point where they provide their mass accuracy cutoff. As long as that molecule hurts the end user, it's fair game. 

On Orbitrap instruments, the resolution DECREASES as m/z INCREASES. Thermo, therefore specs their instruments on the lowest molecule they can get away with (which, to be fair, they use 200, if they really wanted to cheat, they'd go to 40 m/z where the resolutions is insane!) 

On TOF instruments they generally spec on that polymer you'll never ever get out of your system (acetone helps) and they aim for 1222 or maybe 922) and resolution slips (but not to the same level) as m/z decreases. 

For real, if you're doing stable isotope labeling (heavy glucose/glutamine incorporation, for example) on an Orbitrap) around 800 m/z you're out of luck. At max resolution (if you aren't running the 1M option) your heavy ATPs are all mixed up because your resolution has fallen off a cliff. You can't tell that heavy N from heavy C. That's a huge deal for metabolism researchers. 

So...200,000 resolution is a big deal to anyone in the medium mass molecule range who needs to resolve nitrogen from carbon isotopes. And 10Hz? That's fast. Yes, right now it's just MALDI and DESI, but how does DESI work? The last 3 letters are ESI! I'd be shocked if Waters doesn't have an LCMS super high resolution TOF out soon. I'd volunteer to test it! 

THERMO! due to the preprinting time of a really cool study from some ultra marathoning dude with who has great taste in high pressure turbochargers in the Seattle area, I think a lot of people were expecting somethig really super ultra cool for ASMS. 

What did we get? An ultra expensive metabolomics unit and a new FAIMS unit! 

(Again, my job is to be a critic. Who hired me, again? That's right! Nobody! Whassssuppp?)

Jokes aside, the FAIMS is super cool. 

It can do high flow without you having to hack it to do high flow yourself! And it's higher resolution or something. I don't have an instrument that it will go on right now, so I didn't pay attention. Again, anything that will add more capabilities to a currently existing instrument is awesome and there are tons of Thermo boxes out there with the next generation ion source that can get much cleaner data by tacking one of these awesome things on. 

And since this is the Proteomics blog and no one has discovered the hundreds of posts I've made on the Metabolomics blog, I'll move fast on this one. The ID-X (which I love) is a Fusion 1 that has been retarded (not in the insensitive way, in the way tractor trailers slow themselves in the Rockies way) do only do metabolomics, unless you've got 2 minutes and 15 seconds and a basic understanding of how to use a Windows computer to unlock it. The new instrument is based on the Eclipse and I bet it takes longer to release the brakes and make it an Eclipse. There is more intelligent acquisition software for both metabolomics and the small molecule biopharma community.  All of which does seem really impressive. 


You'd be fair if you said I've been "uncharitable" or "an absolute jerk" about SCIEX hardware over the years. For real, I have been. I started my career on ABI/SCIEX instruments and until I used a Q Exactive the 3200/4000 QTrap was my favorite instrument I'd ever used. I don't know what happened because from the 4000 QTrap onward all I ever saw was mediocre improvemetns on those instruments in difference colorss and medium resolution crazy expensive QTOFs and an overpaid marketing department (for real, why aren't they doing the NBA playoffs, not selling analytical instruments. As an aside, during this year's playoffs the NBA will interrupt the actual game to show a commercial about how you should be watching the NBA playoffs [for real, that's continuing to happen].) 

But this is something entirely different. The TIMSTOF is exciting because Bruker figured out how to accumulate ions prior to sending them into a TOF. Bruker has had a TOF for years that can hit QE level proteomic coverage, you just crank up your injections 10-fold. With the TIMS acquisition, you could get speed AND sensitivity. And this is where a ZenoTrap is similar. 

Actually, I think I covered this better in 140 (280?) characters during the event:

The new SCIEX instrument can acquire off the quadrupole (and the quad specs are legit. 0.4Da isolation in high res mode! they do know something about making good quads over there) and the ions can accumulate in the ZenoTrap before being fired into the TOF. Numbers from 4 really good speakers with real data? Looks like 5-20x more signal depending on the molecule.

In addition, there is a collision cell that is two 1 tesla magnets opposed. This (somehow! wtf?) induces a very democratic fragmentation similar to ETD and ECD...with very little decrease in scan speed! Birgit Schilling showed some great PTM fragment spectra to back this up. Think about how slow your ETD or ECD fragmentation is. You've got to inject your reagent and then allow the reaction to proceed, THEN scan your fragments. 50-100 ms reaction time is common. Not including the scan acquisition time, you're at tops 10-20 scans/second. Realistically about 5-10, max. This box can get around 100 EAD fragmentation scans.

I'm out of time so I'm going to just leave this here. I didn't catch the Agilent launch live and I will follow up on that one later, but I think it was small molecule IMS focused. And there were some other launches, but with this out of the way -- HALLOWEEN ASMS IN PHILLY should be just research focused, right?!??

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