All polymer microfluidic chips—A fixed target sample delivery workhorse for serial crystallography

Abstract

The development of x-ray free electron laser (XFEL) light sources and serial crystallography methodologies has led to a revolution in protein crystallography, enabling the determination of previously unobtainable protein structures and near-atomic resolution of otherwise poorly diffracting protein crystals. However, to utilize XFEL sources efficiently demands the continuous, rapid delivery of a large number of difficult-to-handle microcrystals to the x-ray beam. A recently developed fixed-target system, in which crystals of interest are enclosed within a sample holder, which is rastered through the x-ray beam, is discussed in detail in this Perspective. The fixed target is easy to use, maintains sample hydration, and can be readily modified to allow a broad range of sample types and different beamline requirements. Recent innovations demonstrate the potential of such microfluidic-based fixed targets to be an all-around “workhorse” for serial crystallography measurements. This Perspective will summarize recent advancements in microfluidic fixed targets for serial crystallography, examine needs for future development, and guide users in designing, choosing, and utilizing a fixed-target sample delivery device for their system.

Advanced manufacturing provides tailor-made solutions for crystallography with x-ray free-electron lasers

“… 37,38 Beyond serial crystallography, ultrathin low-background sample environments, such as FT devices and liquid sheet jets, also offer exciting opportunities for (soft) x-ray spectroscopies (e.g., at ChemRIXS) and fluctuation and conventional solution scattering. 38,49,50 Owing to the continuously varying demands of the sample types, mixing times, and other challenges such as clogging and excessive sample consumption, 3D printed solutions have increasingly been integrated as components of the XFEL sample environment, either in the form of nozzles, mixing elements, 28 catchers, aerodynamics lenses, 51 or fixed-target support structures ( Fig. 1 ).…”

Fixed-Target Pink-Beam Serial Synchrotron Crystallography at Pohang Light Source II

“…However, sample delivery using a viscous material requires not only the selection of a delivery material that can stably store the crystal sample, but also technical efforts to provide a stable injection stream [16]. The fixed-target scanning method is widely applied for SX data collection at XFEL facilities or synchrotrons [19][20][21][22][23][24]. It can minimize sample consumption compared to injection systems and does not physically impact the crystal sample during data collection [25]; in the case of the injector method, pressure is applied to the crystal sample as it passes through the nozzle, which may have a physical effect on the crystal.…”