New spatial mass spectrometry technology alert - Tippy Tapping-Mode ESI!

Are you interested in getting into spatial mass spectrometry but all the super expensive commercial technologies aren't doing it for you? 

Why don't you...

..introducing Tappy-mode scanning ESI! 

What's that? Okay, they didn't invent it for this paper, but they explain it better than I can! 

Wait a minute. Is it just like this except really fast and with an electrospray plume in the middle? 

Close enough! 

Okay, but analogies aside, we can move tissues at incredibly absurdly high resolutions. Think about the stages they use for electron microscopy! Great imaging mass spec today is like 20 micron. Every vendor will sell you a "5 micron resolution"capable device, but have you ever seen a mass spec imaging ..image...at 5 micron without inflating it with diaper gel? I sure haven't. But EM stages can move in like sub micron easy. The limitations are things like our laser pixels. And when you start talking to people who do anything with piezos (which more the bird beak or capillary), those people are talking about things running at 10-100 kHz (10,000 to 100,000 vibrations/second!)  So...I'm totally talking out my nose, but these authors say they're doing 10 and 5 micron and while a healthy truckload of skepticism is always a good idea, this doesn't sound all that far fetched.....

They couple the device to a Waters TOF and then use multiple commercial software solutions from Waters and Shimadzu to convert and extract the data before going to LipidMaps to match the molecules they extracted. (They did lipids for this, I was leaving that part for the end) but why couldn't you pick up a little piezo capillary worth of intact proteins or digested peptides and do the exact same thing? Cool idea, right? 

iSCMS is in London October 6-8 plus an extra day for BMSS October 9!

 

iSCMS 2026 was just announced and it's SO cool. 

One of my favorite 2 day conferences - not just single cell proteomics, but all single cell mass spectrometry. At King's College in London! 

And if that's not cool enough it's a joint conference. You can stay an extra day for the British Mass Spectrometry Society Meeting! Alejandro Brenes and Felicia Green are the plenaries for the latter! 

Did you think that you had to be 90 years old to be a plenary speaker? Not here you don't! Psyched for both talks. 

You can come for BMSS or iSCMS or both and register here. 

Here are some completely and totally unrelated facts about that same week in London that are, in no way, affecting my personal travel plans because I'm a grown up professional. 

However, THE HAUNTED are playing October 8th. I've never seen them live, but I'd clearly be responsibly in my hotel that night and preparing for BMSS the next day. Not navigating the tubes with ringing in my ears. 

I probably can't find a way to justify staying extra days, unless - I dunno - someone out there invites me to speak at their university or come by their company headquarters to talk about cool stuff. However, if you happen to be there and have flexibility -

Metal Gods - 

Amon Amarth

Soilwork 

with ORBIT CULTURE??? 

play an early show on Saturday (!?!?! WHAT !?!?!) I have no idea what a pound is in real money but 62 of anything seems like a bargain to see those 3 shows. 

Boost ultra super low input proteomics with 2 micron nanoLC columns....?

 

...ummm....how do you make a 2 um inner diameter LC column....? 

 Leaving it here so I can think about it later.

Obviously required addition to this post...

Single cell proteomics by SDS-PAGE!

 

Okay, so what if you did proteomics on a sample and you were concerned that you'd homogenized too much tissue. Maybe you had an obvious phenotype and you just can't see anything differential in the proteome? And maybe you don't have a single cell sorter in your lab and a very very clean Astral, Exploris, Excedrin, 8600 or TIMSTOF sitting around. (For real, yo, I don't think we're past the requirements for very clean or almost dedicated instruments for single cells. This is from feedback from friends with Asstrals and 3 separate Ultra2s. Run 2 days of 50ng samples and that next 50 picogram single cell is garbage. Did I just come up with a smart community study idea right now? I think I did.)

Could you, with the help of a sorting core or with some quick dilution math, and some stuff you've definitely got sitting around, find out if you have single cell heterogeneity? 

Cue the skepticism, but I think this is absolutely worth trying. Good thing I've got a lab meeting in a couple of hours! 

They straight up do SDS-PAGE with single cells! The dye is something weird, and they're clearly doing some serious magnification on their gels, but its 1) A commercial gel and 2) It's the same ol' gel dock that you've got sitting around. There was a box in my lab bay with like 10 of them and the name of a professor who retired a while back! 

Here is the workflow in my mind, though. 

1) DIA proteomics

2) ...ummm....volcano plot with like nothing in it?? 

3) Repeat with DDA proteomics

4) Process with MetaMorpheus (or Bolt if you have that $20 a file) MSFragger open search would work if you have an Orbitrap or Astral probably. FDR shuts off if you have anything else. It still seems to work but not as well. 

5) ....ummmm....even with PTMs the proteomes look the same? 

6) Dilute cells (with membranes) down to statistically 1 cell per PCR tube (or have the FACs core do some sorting for you?) 

7) SDS-PAGE a bunch! 

8) Do you have clusters like this? 

9) You've got an over-homogenization issue! See if you can do some cell sorting and do single cell TYPE proteomics (cell sorted populations) OR

 10) Bite the bullet, clean the shit out of one of your instruments. Especially if you like literally study feces. Or talk to someone who does SCP through a core or collaboration. We do single cells at Pitt for like $50 internal for 40SPD. It's more unsubsidized, but we're trying to get that $ down with more hardware.

Convert protein sequences into text and use language models to reveal all their secrets!

 

Wow. I'm completely blown away by this one. If you've got VERY GOOD AD BLOCKERS INSTALLED, you can find the popsci article here. Don't click it if you don't. Hot dog, the little counter on the corner of my screen rang up 74 ads and trackers in just a second. And the banner at the top warned me of "consequences" of blocking those 74 ads. 

The article is sort of about this new PNAS paper! Click this instead. My school doesn't subscribe to PNAS? Weird. Maybe my ad blockers are too good. 

Okay, but here is the thing. What if you could convert protein sequences to text? For real, hear me out here. You could, in theory, assign each amino acid IN ORDER an alphabetical letter. Then you could take all the complexity of a protein sequences - even one with hundreds of amino acids! - and make it just a short paragraph! 

See where I'm going with this? I bet some of you super saavy scientists do. Good for you! Then you could use that text input into - you guessed it - these amazing LLM things! 

I suspect this group at the NIH did a far better job than me when I just tried it with the LLMs I have access to, but I swear I think I just found an interesting pattern in my proteomics data with a similar approach. I have this output I haven't ever seen before. 

Serine-Histidine-(Leucine, or Isoleucine, but likely the latter)-Threonine-Threonine-Tyrosine-Serine-Histidine-(Leucine, or Isoleucine, but likely the latter)-Threonine-Threonine-Tyrosine-Serine-Histidine-(Leucine, or Isoleucine, but likely the latter)-Threonine-Serine-Histidine-(Leucine, or Isoleucine, but likely the latter)-Threonine

Have I discovered an entirely new and obviously important protein motif? It seems worth investigating for potential phosphorylation sites alone! 

MSCards - An educational game to learn mass spectrometry hardware!

 

This is so clever! And I absolutely want a deck! (In English, probably, but I'd take the French ones for sure!)

If there is an opportunity missed in this EXCELLENT paper...

 (For real, this is such a great read from authors who understand both mass spectrometry and educational concepts. Neurons from my long ago training to be a teacher stood up and tried to do things when I read words like "pedagogy"). 

...I would have ABSOLUTELY, WITHOUT A DOUBT, cited a paper by Kenneth J. Rodgers first. 

It's a preprint, there is still time! Maybe this one? 

Scientist Exchange Program Award! Deadline September 11, 2026!

Are you a trainee of some kind in the US? 

Would you like to go to some US HUPO member lab and LEARN A NEW SKILL?

AND Win a fancy award for your CV? Check this shit out. 

I'm not saying this is what you should do, but here is a scenario. Imagine you wanted to do some single cell proteomics. You could totally come to Pittsburgh and get trained by my amazing team and do some badass single cell proteomics. And US HUPO would help pay for that experience and present you with an award or something.

You could obviously go to some other US HUPO lab and learn something else, but I'm just listing what I'd personally consider the coolest possible option. 

....

 

Optimize your low-load EvoSep loading!

 

Whoa. Okay, so someone else was wondering how to minimize low concentration sample prep to EvoTip loading. Turns out one of the culprits can be the lyophilization/speed vac'ing step! 

Worth checking out, for real.

Have an AI design your lab layout!

This weekend while watching too much stuff indoors because it was 40C (>100F) outside I kept seeing ads for using AI to "design your space".

We have a single lab bay not counting my office and the awesome open space for the TIMSTOF and EvoSep, but we do have to think hard when students rotate about where to put them. 

Maybe if I give an AI all the details of the lab and the dimensions it could......

....make me think this isn't the dumbest fad in all of human.....history....