Graphene-Based Microfluidics for Serial Microcrystallography

The idea of coupling microfluidic technology with advanced protein crystallography techniques for in situ analysis is an area where significant advances can be made. Microfluidic platforms have the benefit of not only enabling experiments at small volumes, but also create an environment free of inertial or convective effects while providing exquisite control over local conditions and gradients. A significant problem of microfluidic-based crystallography is the background noise caused by device materials, which may obscure the signal from weakly diffracting micro-crystals. Graphene is a single-atom-thick material that has a negligible scattering effect on X-ray and should be the best option available to solve this problem. Also its remarkable mechanical strength and impermeability to gas make it suitable to be integrated into microfluidic devices.

We have successfully validated the feasibility of graphene as a component in an ultra-thin microfluidic chip, demonstrating a significant reduction in background noise and a subsequent enhancement in the quality of the observed diffraction signal. Furthermore, graphene acts as a diffusion barrier within our microfluidic devices, creating a sample environment that is stable over the course of weeks. We are currently utilizing these platforms for the structure determination of caspase7, a member of the cysteine-aspartate family of proteases that are implicated in cellular apoptosis, and halorhodopsin, a light-sensitive membrane protein commonly utilized in optogenetics. Our goals include the collection of radiation-damage free structural data and the time-resolved structural analysis of key reaction intermediates for these targets.