The TriVersa NanoMate: Automation of Nano Electrospray Analyses

The evolution of nano‐electrospray ionization technology began in the mid‐1980s. At that time, no commercial vendors supplied the requisite electrospray emitters, which featured internal diameters of just a few microns. Tips were manually fabricated by pulling heated glass capillaries to create micron and sub‐micron inside diameter tips. High voltage was applied to a sample solution within the capillary body, and when placed close to a counter electrode of the atmospheric pressure ionization (API) mass spectrometer formed a sufficiently high electric field to produce an electrospray plume. Nano electrospray offered key advantages, including enhanced sensitivity and minimized matrix effects for chemical analysis due to better ionization efficiency and reduced contamination due to the lower mass transfer into the mass spectrometer orifice. By the late 1990s, Advion scientists utilized the Cornell Nanofabrication Facility equipment to create an array of nano‐electrospray emitters etched in a silicon wafer. Key to the success of this planar emitter array was the inclusion of a dielectric layer that enabled the formation of an electric field estimated to be equivalent to that of a pulled glass capillary emitter with dimensions near one micron, but with a 28 micron outside diameter emitter. This “ESI Chip” was commercialized along with a robot named NanoMate to enable automated, reproducible, and robust nano electrospray of 96 consecutive samples from the chip‐based array of micro‐fabricated emitters. This paper explores the development and commercialization story of the NanoMate and its use to expand scientific knowledge in the field of protein non‐covalent interactions, protein structure, lipidomics, drug metabolism, and a host of other applications.