How much ion mobility would be necessary to replace the quadrupole?

 

Conflict of interest statement on this one - I'm both a compensated member of the Proteomics Advisory Board for Mobilion Systems and the first author of this preprint met weekly with me for 4 or 5 years while getting her PhD. I'm even more impressed by her work than by the quality of her education. ;)

Okay, but here is the real question and I know I've certainly wondered about this..... at what point would ion mobility and quadrupole isolation overlap? Or maybe this? Could you crank up your ion mobility resolution to a point you could widen your quadrupole and get equivalent data? Or if you had 1,000 resolving power ion mobility, would the quad just slow things down? 

Those are the questions tackled here. 

The short answers appear to be - absolutely, yes, and maybe. There is certainly a point where you can get enough ion mobility to get the same isolation you would get with a quadrupole alone. On the SLIM system the coisolation can be limited to about the coisolation of a quad running 5 Th windows. If you want the cleanest data you've ever seen, SLIM + 25 Th windows would get you there. And....yeah... in the world of wide window DIA or wide window DDA and now wide window PRM...these numbers are relevant. 

New Exploris confirmed! And...print cartridge LC columns....?

 

Just stealing Chris's post! 

Bonus, if you see Ian watch what he's eating and model your diet after it. He's at least 114 and he's out there on stage giving talks at 8 in the morning? 

Oh! Website went up on the Astral 2 "Zoomie"

270 Hz and the resolution to do TMT 32-plex (I thought it was 35? Does anyone know?) Big question should be - can it do the 32-plex at the highest acquisition rate? Or do you need to slow it down? 

We're going to see a lot of 300SPD proteomics on it, I guess. Probably with a 4cm column so everyone get excited to do label free quantification at 2 scans/peak! Still better than an aptamer! 

Informed DIA allows transcription factor quan in single cells? Also, new Astral?

 

If you've seen me talk about single cell proteomics, I like to point out the proteins I can see (50,000 copies and up) and I make a joke suggesting you come back in a decade if you're interested in transcription factors.

They turn on transcription at your DNA...you only have a couple copies of each gene. In many, most cases, we only expect a few copies of each of those proteins in each cell - certainly not tens of thousands! 

Yes this preprint demonstrates measuring them in global single cell data! 

How? Well...it's complicated. But basically it looks like we've got MS1 - DIA - and then what appears to be heavy isotope triggered wide window PRMs all in one cycle. I *think* the instrument sees the heavy spiked peptides and then moved a PRM window over to where the light should be. 

For you hardware nerds you may be interested in the fact this preprint seems to feature an Orbitrap Eclipse, and Orbitrap Asstral and something called an Orbitrap Astral Zoom, which might suggest we'll see an Asstral 2 at ASMS tomorrow? I guess we'll see! 

The first author will be presenting it as poster WP724 (Wednesday? Poster 724? I think!) if you're in Baltimore! 

pre-ASMS media drops - two new TIMSTOFs confirmed!

 

Hardware is already leaking to the media? Here is the first one - and a surprisingly well-written article with insight from a bunch of early adopters and/or beta testers. 

Oh crap, and my news feed was like "oh, so you like mass spectrometers? First I've ever heard you mention that... here's another! 

Looks like it's a top-down focused instrument with MSn(?) capabilities and some electron transfer thingamabobs, but I'm excited to see what it can do in the area of PTMs in bottom up as well. There area lot of PTMs that are just no fun at all to do with MS2 alone. 

I wonder if they had to get Disney's permission to use the same name or if it's so far from the meaning that there couldn't be confusion and trademarks wouldn't apply? 

 

pre-ASMS drops coming in! Seer system can prep 1,000 plasma proteomics samples/week!

 

Read more here! 

It sure makes the Illumina protein prep 384 samples/week seem even sillier.....

Electron capture increases protein stability by 60x - but you'll never get to use it!

 

Heading into ASMS shortly and there will be lots and lots of places where business and science interact. We'll see a load of vendor talks where the two things are clearly working together to make things better... but we'll also see... the other thing.

Case in point - 

An e-Mission EXD cell equipped after the quad on an Orbitrap UHMR can stablize the hell out of large proteins going into the Orbitrap for "single ion" detection (it's not really single ion, it's crappy signal measurements for deconvolution and enough combined to make it deconvolutable and since the mass accuracy is phenomenal it works AND it's way way way more sensitive than any other FTMS based intact protein measurement method - it's brilliant but the method name confuses people a lot). 

You know what it needs? Proteins to be 60x more stable!!! (It's not as much stability as charge reduction but that's enough nerd talk for now!) Want one? 

Too bad! E-mission was acquired! 

Man, they would still sell those products, though, right? 

Increase your multiplexing by adding the time dimension (and more nanoLC columns!)

 

My first thought when I saw this new preprint was something like "I've been working on these IRB documents for my clinical trial for waaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaay too many hours, cause I can't figure this out at all." 

I honestly might still not get it, so the less I type the better, but this is probably the best figure for driving the idea home in the preprint. 

I do think it is an interesting idea, and I'm all about getting extra throughput. Multiple samples running with time delays are demonstrated as being deconvolute-able using retention time re-alignments. 

From a practical standpoint - 

Since 2020 I think roughly 30% of my nanoLC columns have arrived in a completely non-functional state. The ones above just weren't glued at the ends so the capillaries just fall right out at the fittings. 

There is a vendor that produces nanoLC columns that have been famously reliable and successful over those few years, but - in my hands- the columns are amazing for about 2 weeks before they overpressure.

The thought of relying on 3 separate nanoLC columns performing properly chronologically seems just about as likely as me winning the big Powerball jackpot thing by buying 3 tickets. I've never gambled in my life, but I'm assured the odds aren't great of that happening. 

Spatial proteomics across laters of skins investigates psoriasis!

 

Okay - so who else was limited in their thoughs of how you could apply spatial proteomics in thinking of slicing being in 2 dimensions? 

This application find altered cholesterol metabolism in psoriasis patients compared to healthy matched controls at different layers of skin with the biggest differences being observed as you go down (?) 

LCM used a Leica 7 and LCMS was EasyNLC 1200 on a TIMSTOF. DIA and DDA(PASEF) were used and at least some of the data was analyzed in FragPipe. 

Really interesting stuff across the board. 

Last minute deadline for HLXMS Travel Awards to ASMS 2025!

 

Applications are still open - UNTIL TOMORROW! 

Chronic alcohol consumption alters acetylation in mice!

 

This is an extremely thorough analysis of the alterations that occur in the metabolome and proteome following chronic ethanol consumption.

On top of the proteomics - which involves both protein turnover analysis and acetylation enrichment multiple assays focus on absolute quantification of different panels of metabolite. Super solid work.