(490d) Liquid Handling Strategies for X-Ray Compatible Microfluidics

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. Here we use UV curable polymers that have good X-ray transparency and are used to make multi-layer devices via photolithography and thermal imprinting. The combination of these two techniques allows for the fabrication of hollow channels and chambers, which is impossible with traditional photolithography. Our device designs incorporate fluid handling capabilities that take advantage of surface forces, rather than requiring bulky ancillaries (e.g., pressure controllers, pumps, etc.). Our microfluidic devices allow for the fluid flow control and metering necessary for protein crystallization, and in-situ crystallography. In particular, the diffusion dominated mixing in these microfluidic devices allows for more reproducible growth of higher quality crystals, and the use of X-ray transparent materials allows for direct analysis of the crystals without the need for harvesting from the device. Hence in a nutshell, the three key aspects of our devices are: (i) the use of X-ray transparent materials, (ii) the fabrication of hollow channel structures using advanced manufacturing strategies, and (iii) the use of an integrated fluid manipulation system that can easily be adapted for use across a range of situations. 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.