2024 AIChE Annual Meeting
(4da) Scalable Manufacturing of X-Ray Compatible Microfluidics for High Throughput Structure Determination and Integrated Liquid Handling Strategies
Silicone-based elastomers, along with thermoplastics and paper, represent the most widely used materials for microfluidic devices. However, applications in structural biology require a level of X-ray transparency that is difficult to achieve with traditional materials. A key aspect of protein structure determination is the manual harvesting and freezing of protein crystals, which are analyzed by X-ray diffraction to resolve the final 3D structure. Here we demonstrate the use of UV-curable polymers that have good X-ray transparency, further allows automated sample loading into synchrotrons and remote X-ray data collection. We showcase continuous manufacturing of these devices to enable more cost-effective large-scale manufacturing, with manufacturing that is 80 times faster, thus reducing labor costs significantly.
We further developed microfluidic devices that allow on-chip crystallization and structure determination. This calls for the incorporation of a novel valving mechanism compatible with the UV-curable polymers. Our design incorporates advanced fluid handling systems, realized through both centrifugal and electrically actuated valves, departing from conventional pressure-driven systems typically associated with cumbersome equipment like pneumatic controllers and nitrogen cylinders. The developed device provides a one-step solution for structural biologists, from screening crystallization conditions to determining the protein structure. These capabilities in a microfluidic device would enable us to do amazing things from a structural biology standpoint, like ligand binding and time-resolved experiments, while bringing us one step closer to automating the entire process of crystallization and crystallography, which can be very intensive and requires hours of human labor.