Integrating Simple Microfluidics Design/Fabrication with a Novel Ionization Source for Time-Resolved Chemical Reaction Studies by Mass Spectrometry

A 3D-printed herringbone mixing device has been coupled with high-efficiency capillary vibrating sharp-edge spray ionization (cVSSI) to perform time-resolved hydrogen-deuterium exchange (HDX) reactions. The microfluidics design consists of three inlet ports for reagent introduction and an efficient dual herringbone structure for efficient mixing. The outlet of the device is coupled to a variable-length fused-silica capillary that joins a cVSSI emitter tip for product molecule ionization and introduction into the mass spectrometer. The device design incorporates an omniphobic surface rendering to reduce chemical noise in the ionization process. The device is demonstrated to first show high-efficiency mixing of reagent streams across a wide range (>10-fold) of flow rates. Next, in conjunction with high-efficiency cVSSI-MS, the device is shown to be operable over a wide range of flow rates required for the study of time-dependent reactions. Using the model protein myoglobin, the reproducible performance of the combined approach is assessed using time-resolved HDX experiments monitored by mass spectrometry (MS). A simple deuterium uptake model is presented to demonstrate how this early-stage device can find utility.