Helium-Electrospray: an improved sample delivery system for single-particle imaging with X-ray lasers

Imaging the structure and observing the dynamics of isolated proteins using single-particle X-ray diffractive imaging (SPI) is one of the potential applications of X-ray free-electron lasers (XFELs). Currently, SPI experiments on isolated proteins are limited by three factors: low signal strength, limited data and high background from gas scattering. The last two factors are largely due to the shortcomings of the aerosol sample delivery methods in use. Here we present our modified electrospray ionization (ESI) source, which we dubbed Helium-ESI (He-ESI). With it, we increased particle delivery into the interaction region by a factor of 10, for 26 nm-sized biological particles, and decreased the gas load in the interaction chamber corresponding to an 80% reduction in gas scattering when compared to the original ESI. These improvements will lead to a significant increase in the quality and quantity of SPI diffraction patterns in future experiments using He-ESI, resulting in higher-resolution structures.