Friday, April 23, 2021

WHAT? Single LIVE cell NATIVE intact protein mass spec??

I'm super impressed. All the pieces to do work like this already exist but you have to pull techniques from all over today's best analytical techniques to put it together. This team did

The single cell metabolomics people have live cell probes where they use a microscope and run a tiny object into the cell, pull out the cytoplasm and direct infuse it. It looks amazingly difficult to do right, but I know a lot of work is going into making it easier. The last couple talks I sat in on made it seem like something I probably couldn't do successfully rather than something there is no way in the world I could do successfully. I mean, you've got to get a cell and then stab it. 

How do you even find it? 

Super fancy microscopy or something. 

Not to put down the metabolomics people but small molecules are pretty easy to electrospray. You go to nanospray and you've got plenty of signal to work off of.

You know what isn't easy to ionize with electrospray? NATIVE INTACT PROTEINS. For native I like about 10 more protein than with reduced proteins. 

The fact that this group can resolve native hemoglobin from a single red blood cell is just nuts. Yes, there isn't much in an RBC but hemoglobin, but those cells are tiny. 

For the LCMS work you need to go to the supplemental where you really see how much optimization went into making this work. The instrument used was a Waters Synapt G2 HDMS. 

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