I received some questions about my longer term impressions of the amazingly sensitive and somewhat fast TIMSTOF Ultra2.
It's been a year already? Yikes. I guess I'll reference my earlier TIMSTOF reviews.
Great stuff!
1) The sensitivity of this thing is still absolutely unreal. Multiple people are writing up papers on single cells ran on it with DIA label free and the numbers are cell type specific and amazing.
Even with a high loss, but very inexpensive and very fast sample prep, most cancer cell check in at well above 2,000 protein groups per cell and human hepatocytes are around 2,500. Throw in a big cohort and actual spectral libraries (non-predicted) and you can add 50% to those numbers. Most studies of >100 cells will have 5,000+ protein groups across the study. Some big cells like cultured human neurons will come in >7,000 on their own. Crazy.
Some small blood cells <10 microns have been a challenge, but if you've only got 80 pg of protein and we know our fast sample prep loses about 50pg, that's...involved..... someone FACs isolated 12 different cell types from patient blood and we struggled with getting 500 protein groups in 2 of the cell types. It's tough to tell what's going on from those levels of sample.
Not so great stuf!
1) Compass data analysis is still the only way you can do things like extract an XIC. Looking for a weird peptide? Good luck. As an aside, Biognosys sells a targeted quan package that we had for several months because I thought it would do that part for us. It will if you're doing prmPASEF, but it won't help you find a peptide in DIA or DDA data. It also doesn't help you predict the IMS so you basically have to identify your peptide to target it. So we traded that software back for more months of SpectroNaut.
2) We've went through more internal electrical components in the last 6 months than HPLC columns. That's not an exaggeration. This board, that board, that other board, the second board's power supply, the TIMS cartridge, etc., etc.,. This is rough because I knew we didn't have a very local FSE here. They have to come in from DC or Jersey or fly in from Bremen or California. So the downtime can be on the long side when they go down. I thought going into 2026 we basically had a brand new instrument thanks to the sleigh load of electric components we got over the holidays so I wasn't super stressed about a short lapse between warranty and service plan starting up but - there went another pile of electronics.....whoops. To be fair they are building one of the biggest hospitals in the country next door to us and we've had a couple of power outages. But...you start to wonder if they're getting these circuit boards from Alibaba....
3) There appear to be even less support people in the field today. This one is a real surprise given the fact that it looks like the company has been doing really well and the prices of some instruments have increased more than 200%. You'd think that would equal a higher number of apps scientists and engineers in the field, but it appears to be just the opposite. The ones we have are INCREDIBLE. But you get the impression that they never sleep or get a day off because there are two of them for planet earth.
4) Look, I'm going to complain about absolutely everything. And I have absolutely zero regret for this fit-for-my-lab purpose instrument. It's an incredible precision instrument for what it does. We locked down a full workflow 8 months ago and we just do biological discovery on this thing. Same prep, same column, same method and the papers in preparation are a million times better than anything I've ever done. It's nice to have time to write because your one instrument is down, but there is a point where you have to look back at 50-ish weeks of ownership and start counting the weeks that the front of the instrument has been bright red doom and panic a little.
5) I did a lot of searching as well, and unlike other instruments there still appears to be no second party field apps support. That's a bummer because in some places you can go to a second party like ZefSci and get superior field apps support than what the vendor offers for a lot less money. If you know of someone who services these things PLEASE LET ME KNOW! I'd switch in a heartbeat.
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