A simple goniometer-compatible flow cell for serial synchrotron X-ray crystallography

J Appl Crystallogr. 2023 Mar 9;56(Pt 2):449-460. doi: 10.1107/S1600576723001036. eCollection 2023 Apr 1.

Abstract

Serial femtosecond crystallography was initially developed for room-temperature X-ray diffraction studies of macromolecules at X-ray free electron lasers. When combined with tools that initiate biological reactions within microcrystals, time-resolved serial crystallography allows the study of structural changes that occur during an enzyme catalytic reaction. Serial synchrotron X-ray crystallography (SSX), which extends serial crystallography methods to synchrotron radiation sources, is expanding the scientific community using serial diffraction methods. This report presents a simple flow cell that can be used to deliver microcrystals across an X-ray beam during SSX studies. This device consists of an X-ray transparent glass capillary mounted on a goniometer-compatible 3D-printed support and is connected to a syringe pump via light-weight tubing. This flow cell is easily mounted and aligned, and it is disposable so can be rapidly replaced when blocked. This system was demonstrated by collecting SSX data at MAX IV Laboratory from microcrystals of the integral membrane protein cytochrome c oxidase from Thermus thermophilus, from which an X-ray structure was determined to 2.12 Å resolution. This simple SSX platform may help to lower entry barriers for non-expert users of SSX.

Keywords: cytochrome c oxidase; goniometer-compatible flow cells; macromolecular crystallography; serial synchrotron X-ray crystallography.

Grants and funding

RN acknowledges financial support from the European Union’s Horizon 2020 research and innovation programme (grant Nos. 789030; 963936), H2020 European Research Council (grant Nos. 789030 and 963936 awarded to RN) and the Swedish Research Council (grant No. 2015–00560 awarded to RN). GB acknowledges financial support from the Swedish Foundation for Strategic Research (grant No. 17–0060) and the Swedish Research Council (grant Nos. 2017–06734; 2021–05662). RN, GB, SG and PD have been granted a Swedish patent (SE 544493C2) covering the magnetically mounted 3D flow cell described here (publication No. WO 2021/246936A1, PCT pending). A spin-off company (Serial X AB) has been founded which aims to make this device available to other users of synchrotron radiation. Serial crystallography data collection was performed at the BioMAX beamline at MAX IV Laboratory, Sweden (proposal Nos. 20190465; 20220186).