Micro- and Milli-fluidic Systems for X-Ray Scattering Analysis of Crystallization Processes

X-ray diffraction is one of the oldest, most popular, and also most powerful techniques for the study of crystals, and microfluidic devices provide some of the cleanest and most controlled environments for crystal growth. However, it is extremely rare to see these two tools combined for the study of crystallization processes in situ. This is in part due to the difficulty of building X-ray “transparent” sample environments and the low performance of most diffractometers, which requires the use of specialized synchrotron radiation facilities for analysis. This thesis presents the development of Xray compatible microfluidic and millifluidic devices and the required data collection and processing strategies to begin to address this deficiency in the study of crystal nucleation and growth. After a thorough review of crystallization theory, microfluidic devices, and previous efforts at building flow systems for time-resolved X-ray scattering analysis, the initial results chapters are focused on the characterization and optimization of a versatile polymer insert-based microfluidic platform. A range of experiments in continuous and segmented flow were conducted with the device, and the effects of these different flow configurations on device performance and data collection are discussed. Wellsegmented flow is shown to effectively isolate reactions from the channel walls, enabling crystallization to be studied as a function of the residence time of individual droplets along the microchannel in steady flow operation. Here termed, “Droplet Microfluidics-Coupled X-ray Diffraction” or DMC-XRD, this type of analysis allows the collection of serial powder diffraction patterns that reveal the average crystal structure present at each time-point along the flow. Then as a demonstration, this technique is utilized to help identify effective nucleating agents for calcium carbonate and quantitatively and qualitatively compare their efficiency. The remainder of the thesis explores the possibility of conducting similar types of experiments at larger length-scales and with different X-ray sources. First, a mesoscale flow crystallizer is demonstrated to be suitable for the millifluidic equivalent of DMCXRD. Next, the successful trial of a very different continuous stirred-tank reactor (CSTR)-type system for inline X-ray analysis is reported. Finally, this thesis presents a series of microfluidic and millifluidic experiments that were conducted with two different state-of-the-art commercial diffractometers. Preliminary results obtained with these systems suggest that there is enormous potential for performing flow-based X-ray analysis of crystallization processes in the home laboratory, as long as X-ray source optics and detectors are tuned to provide comparable beamsizes and exposure frame rates to those employed at the synchrotron.