Increasing the throughput of crystallization condition screens: Challenges and pitfalls of acoustic dispensing systems

Advances in contactless acoustic liquid transfer technologies have unlocked opportunities to substantially increase the throughput of crystallization screens and decrease the consumption of reagents and consumables. Acoustic energy transfer enables crystallization experiments to be set up precisely and rapidly on a nanoliter scale. Nonetheless, adapting acoustic transfer methods to a diverse range of crystallization conditions and their physicochemical idiosyncrasies remains a major bottleneck for true universality of this technique. Even though the reagent limitations still remain an issue, we present a straightforward protocol for setting up crystallization experiments by acoustic transfer using a Labcyte Echo 550 instrument, with a focus on the technical limitations of this method, including reagent compatibilities, spatial resolution and downscaling limits. • Set up crystallization screens in a small scale with reliable drop volumes as low as 50 nl; • Overview of commonly used crystallographic screen compatibility with acoustic dispensing; • Comparison of instrument calibrations and settings and its effects on error rate and screen reproducibility.