Additively Manufacturing High-Performance, Low-Cost Electrospray Ion Sources for Point-of-Care Mass Spectrometry

Abstract

Clinical mass spectrometry relies on ionization of liquid biological samples, often via electrospray. This work broadly leverages additive manufacturing for the development of electrospray emitters, doubling signal-to-clutter ratios relative to state-of-the-art. We demonstrate low-cost integration in clinically-relevant diagnostics protocols by designing emitters into surface mount devices, the first of their kind, that can be directly soldered to printed circuit boards with built-in digital microfluidics as part of automated device assembly. The benefits in terms of scalability of this solution are coupled with advantages gained from simultaneously tuning surface hydrophilicity, solvent evaporation, and geometry. Electrospray emitter efficiency is optimized, approaching the direct field ion evaporation limit. Several materials and additive manufacturing processes to make the electrospray emitters are evaluated; comparative testing is conducted with conventional paper spray and coated blade spray. Microstructure characterization with scanning electron microscopy shows reproducible microfabrication of bulk techniques and compatibility with additive manufacturing feedstock. Geometrically and electro-fluidically optimized electrospray emitters attain 130% higher steady-state currents than state-of-the-art emitters. The devices use novel extractor electrode designs, reducing corona discharge and air breakdown, enabling operation at ~24% larger bias voltages compared to conventional cylindrical inlets. MS data is presented for ZnONW-coated emitters, detecting therapeutically relevant targets at 1 µg/ml concentrations with a variety of solvents. In the case of Nicardipine, such emitters attain 99% higher signal-to-clutter ratios versus state-of-the-art, with far greater operative stability. This thesis bridges the gap between additive manufacturing and high-performance electrospray for mass spectrometry, unlocking industrial development of clinically relevant, next-generation point-of-care ion sources.