Okay...if you've visited this blog much at all you've heard my soapbox proclamations that if you need ultimate sensitivity you need to use the Orbitrap. I'm very biased. But...maybe this new paper might convince you that --for absolute sensitivity you don't go to the triple quad -- you go to the Orbitrap!
Let's start out with this clip taken from WikiPedia, just so we see how amazing what we're going to see in this study is.
You could argue a yoctomol of a substance isn't very much of that substance. In fact, WikiPedia doesn't currently have a lower prefix listed. In fact, the world gave us...
DJ Jazzy Jeff getting thrown out a door by Uncle Phil for over a year(!) before the yocto- metric prefix was even coined!
This is a really small amount of material AND these guys would like you to know that you can measure this amount of material with this generation's Orbitraps!
The paper hasn't been published yet, but it is a solid piece of work on exploring the ultimate sensitivity that you can get with mass spectrometry.
They mess with a lot of features, but to get sensitivity levels I've never heard of -- they do 2D nanofractionation and PRM. Interestingly, they achieve such levels here that they don't find that increasing their maximum injection time increase their sensitivity. This might be a more powerful feature in a more complex mixture (but that is just speculation on my part!).
Random mass spec nerd note (that is really smart!):
They drop their nanospray voltage throughout their reversed phase gradient (less voltage as acetonitrile goes up!)
The only way I can think of setting up that would be time consuming, but it makes a lot of sense in terms of spray stability!