Modeling a Continuously Operating Electrospray Ionization Emitter Using Molecular Dynamics Simulations: From Bulk Solution to Gaseous Ions

Numerous analytical workflows involve electrospray ionization (ESI), a process that converts solution species into gaseous ions for detection by mass spectrometry (MS). Upon exposure of a solution-filled emitter capillary to an electric field, ESI proceeds via a liquid jet that forms at the apex of a Taylor cone. Breakup of this jet generates charged droplets that ultimately release analyte ions into the gas phase. Many facets of these events remain incompletely understood. Molecular dynamics (MD) simulations of ESI droplets have become an important tool for ESI mechanistic investigations. Here, we extend these modeling efforts to entire ESI emitter capillaries. Such simulations face significant challenges. Chief among these is the fact that experimental ESI emitters operate in steady-state mode, where ejected solution is constantly replenished from an upstream reservoir. Previous MD simulations employed capillaries with a finite amount of solution, resulting in only short bursts of sprayer operation. The current work develops an MD algorithm that combines trajectory stitching with "solution recycling". This algorithm periodically removes ejected droplets, while simultaneously replenishing the emitter inlet with fresh solution. For the first time, this approach provides continuous MD-based ESI operation, while keeping the instantaneous number of atoms (and hence computational cost) manageable. For a 50 ns simulation, we illustrate a reduction of wall clock time from an estimated 5000 days to 20 days. The ESI emitter MD simulations performed here are the most detailed to date, providing insights into the properties of the Taylor cone and the behavior of nascent ESI droplets. Focusing on aqueous NaCl solution, this work provides the first comprehensive perspective of the entire ESI process, from analyte solution in the emitter to MS-detectable gaseous ions.