Friday, May 22, 2015

Is nanopore separation coming to proteomics?

Hey! Do you guys know about this nanopore thing?  Its mostly new to me but its really cool.  Imagine this: you have a bead with a hole in it that is only a nanometer wide.  Then you apply a strong electric current to it to pull stuff to want to go through the hole.  But even single stranded DNA can only go through the hole one way.  Linear and straight through.  So it comes out the hole one nucleotide right after the other. Boom! Easy sequencing!

So...this has been going on for a couple years in genomics. And you can read a lot about it if you're interested. I stole the image above from this wikipedia article.  One of the cool things about this technology is how small it is...and how little power it requires.  You can literally power it off the 3.5V that comes out of your USB connection.  These are commercially available.  DNA sequencing wherever you are

They can make these this small because the detector is just the voltage shift caused by the charge of the very next thing through the pore.  Since there are only 4 bases in DNA a tiny little voltage shift is pretty easy to see (it can only be one of 4 things, right!).

Okay, so why am I rambling about this.  Well, for one I'm kinda drunk (its Friday!).  And for 2 the next thing? The thing that tons of big name people are working on?  Pulling proteins through these dumb little pores!  And you know what? It has worked some here and there!

Check out this paper from Christain Rosen et al., In this work this team pulled phosphoproteins through the nanopore.  Phosphos have a lot of charge!  So they could tell exactly when the phospho came out - BOOM - voltage shift!

The next trick, the one people are working on like crazy? Getting detectors sensitive enough that they can tell which amino acid is coming out at once.  Minor voltage shifts (and 26 of them!) but it doesn't sound like that big of a problem considering that we can measure the mass discrepancy of a single electron without trying all that hard.


  1. Actually in the current device 5 bases are in the pore at a time. So 1024 possible levels. For the protein detection they're looking for patterns rather than just a fixed level (see the tick down at the end in the figure, for example).

    At the recent conference for the MinIon sequencer this work was presented too:

    1. Awesome! Thanks for the additional info! Two close acquaintances have access to these and I really want to play with them.