Fast and uniform microfluidic mixing to follow chemical reaction in time
Keywords: Mechanical Engineering.

Structural biology is a rapidly growing field which seeks to understand the atomic structure of biomolecules. Applications of this field include drug discovery and determination of basic biomolecular functions. Time-resolved X-ray methods are a key tool for structural biology as they offer atomic-scale measurements of protein structure and conformational changes. Sample handling, mixing, and reactions required for X-ray studies benefit from new and improved microfluidic mixers which can be used to initiate and control biological processes with spatial and temporal accuracy. The main theme of this dissertation is the design, development, and evaluation of microfluidic mixers applicable to time-resolved X-ray methods. These devices mix aqueous solutions (containing reactants) to drive changes in chemical potential and thereby initiate chemical reactions in order micron diameter streams with high temporal precision. These reactant and product flow streams are then interrogated using line-of-sight integrating X-ray detection. In this dissertation, we develop and characterize novel microfluidic mixers for time-resolved X-ray studies. The majority of this dissertation focuses on reactions performed and interrogated within internal flow streams. Internal flow streams are challenging since molecules moving near walls move more slowly than those away from walls. These velocity gradients cause large disparities in residence time and therefore in the estimated reaction time. To address this challenge, we develop a coaxial capillary-based three-dimensional (3D) hydrodynamic focusing device which rapidly mixes a high flow rate (annular) sheath stream with (and into) a centered, low flow rate sample stream. We develop experimentally validated numerical and semi-analytical models to explore trade-offs between mixing rate and residence time uniformity. We next design, evaluate, and model a novel 3D hydrodynamic focusing device which is microfabricated from a monolithic block of fused silica. The chip format of the latter device affords facile interfacing with current X-ray beamline device holders and reproducible fabrication. We supplement our commercially reproducible chip with convection-diffusion-reaction models to predict product formation as a function of the Lagrangian time history of reactant and product species. This model, importantly, is validated with experimental confocal microscopy and XAS/XES measurements of a millisecond timescale reaction. We subsequently turn to microfluidic jet-based sample delivery applications for X-ray emission spectroscopy and photoelectron spectroscopy. To that end, we present a new device fabricated from commercially available theta glass capillaries. These theta glass capillaries refer to structures created using two sintered glass capillaries that are subsequently pulled to create a single, two-area nozzle where each is supplied by an independent inlet channel. The device enables a novel jetting and mixing modality wherein a thin (very low flow rate) sample jet is mixed with and laminated above a thicker, high flow rate "carrier" jet. The principal benefit of this architecture is that sample reactant species are found very near the jet surface. This contrasts with most microfluidic mixers wherein sample reactant is typically flanked on two (or all) sides by a second reactant stream. This dissertation presents the fabrication and experimental characterization of the theta device. We find that this device enables mixing on the order of microseconds