Nanocapillary feeds ions directly into vacuum for mass spectrometry

Compared with DNA’s four amino acids, differentiating between the 20 possible amino acids of proteins poses a significantly higher challenge for sequencing the complex molecules. An article in Review of Scientific Instruments presents a new mass spectrometer system with an elegant nanocapillary ion delivery mechanism that could lead to a refined approach to the problem.

Until a process called electrospray ionization (ESI) was introduced, there was no good way to transfer biological samples from liquid into the vacuum required by mass spectrometry. The electrospray technique employed gas molecules to collide with solvated samples and reduce charged droplet volumes via evaporation. Once the droplets reached a small enough size, the internal Coulomb forces of the droplets’ confined charges dominated, leading to an effective explosion, spraying molecular components outward. Only a fraction of these components could be detected and measured precisely.

These Coulomb explosions do not lend themselves well to maintaining the order of amino acids, as required for protein sequencing. Nanocapillary pores skip the need for evaporative steps to shrink the droplets containing whole molecules. With an opening of a few hundred nanometers or less, the nanopore delivers ions directly into a high vacuum — tested in this work with salt ions and DNA bases — without introducing enough solution to disturb vacuum equilibrium.

The hope is that in the future the instrument can be used with even smaller pores with openings that are only wide enough for a chemically denatured protein to pass through in a linear fashion. Amino acids would emerge ion-by-ion and the approach would deliver sequencing capabilities to mass spectrometry.

This nanopore mass spectrometer now provides a platform to explore optimal solvents and preparation methods for protein sequencing, notably without the need of background gas needed by standard ESI.

Source: “The nanopore mass spectrometer,” by Joseph Bush, William Maulbetsch, Mathilde Lepoitevin, Benjamin Wiener, Mirna Mihovilovic Skanata, Wooyoung Moon, Cole Pruitt, and Derek Stein, Review of Scientific Instruments (2017). The article can be accessed at https://doi.org/10.1063/1.4986043 .