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Updated: Jan 28, 2026

Preparation and Delivery of Protein Microcrystals in Lipidic Cubic Phase for Serial Femtosecond Crystallography
Published on: September 20, 2016
Sample delivery for serial crystallography at free-electron lasers and synchrotrons
Marie Luise Grünbein1, Gabriela Nass Kovacs1
1Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany.
High-brilliance X-ray lasers enable new experiments. Review covers serial femtosecond crystallography sample delivery techniques, crucial for X-ray free-electron laser (XFEL) and synchrotron sources, especially for time-resolved studies.
Area of Science:
- Structural biology
- Biophysics
- Crystallography
Background:
- X-ray free-electron lasers (XFELs) offer high peak brilliance and femtosecond pulse durations, opening new avenues in physics, chemistry, and biology.
- Serial femtosecond crystallography (SFX) is a key application in structural biology, leveraging XFELs' capabilities.
- Intense XFEL pulses destroy microcrystals, necessitating serial data collection and high-throughput sample delivery.
Purpose of the Study:
- To review current sample delivery techniques for X-ray free-electron lasers (XFELs) and synchrotron sources.
- To emphasize liquid injection and high-viscosity extrusion methods for serial femtosecond crystallography.
- To discuss the application of these techniques in time-resolved experiments and challenges for megahertz XFELs.
Main Methods:
- Review of existing literature and techniques for sample delivery in serial femtosecond crystallography.
- Focus on liquid injection and high-viscosity extrusion methods.
- Consideration of sample delivery for both XFEL and synchrotron radiation sources.
Main Results:
- Several high-throughput sample delivery techniques have been developed for SFX.
- Techniques like liquid injection and high-viscosity extrusion are effective for XFEL and synchrotron sources.
- These methods facilitate low-dose, room-temperature data collection and are applicable to time-resolved studies.
Conclusions:
- Advanced sample delivery is critical for maximizing the potential of XFELs and synchrotrons in structural biology.
- Liquid injection and high-viscosity extrusion are promising techniques for serial femtosecond crystallography.
- Further development is needed to address challenges, particularly for future megahertz repetition-rate XFEL facilities.
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