DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

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

Journal Article · · Biomicrofluidics
DOI: https://doi.org/10.1063/5.0167164 · OSTI ID:2203349

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. In conclusion, 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.

Research Organization:
Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)
Sponsoring Organization:
USDOE National Nuclear Security Administration (NNSA); USDOE Office of Science (SC), Basic Energy Sciences (BES); USDOE Office of Science (SC), Biological and Environmental Research (BER); National Science Foundation (NSF); National Institutes of Health (NIH)
Grant/Contract Number:
AC52-07NA27344; AC02-76SF00515
OSTI ID:
2203349
Report Number(s):
LLNL--JRNL-856310; 1085690
Journal Information:
Biomicrofluidics, Journal Name: Biomicrofluidics Journal Issue: 5 Vol. 17; ISSN 1932-1058
Publisher:
American Institute of Physics (AIP)Copyright Statement
Country of Publication:
United States
Language:
English

References (92)

Destruction-and-diffraction by X-ray free-electron laser: Diffraction-Before-Destruction or Destruction-and-Diffraction? journal June 2016
Oxygen additions in serial femtosecond crystallographic protein structures: Oxygen Additions in SFX Protein Structures journal July 2016
X-ray Free Electron Lasers book January 2018
Microfluidic sample delivery for serial crystallography using XFELs journal June 2019
Seeds to crystals journal April 2003
PEO–PPO–PEO-based poly(ether ester urethane)s as degradable reverse thermo-responsive multiblock copolymers journal March 2006
A Glimpse of Structural Biology through X-Ray Crystallography journal November 2014
Stability, flow alignment and a phase transition of the lipidic cubic phase during continuous flow injection journal April 2022
Fabrication of ultrathin suspended polymer membranes as supports for serial protein crystallography journal June 2020
A Bright Future for Serial Femtosecond Crystallography with XFELs journal September 2017
A sui generis whipping-instability-based self-sequencing multi-monodisperse 2D spray from an anisotropic microfluidic liquid jet device journal January 2023
Macromolecular room temperature crystallography journal January 2021
A Compact Disk-Like Centrifugal Microfluidic System for High-Throughput Nanoliter-Scale Protein Crystallization Screening journal May 2010
Influence of Alternating Electric Fields on Protein Crystallization in Microfluidic Devices with Patterned Electrodes in a Parallel-Plate Configuration journal May 2017
Real-Time Measurement of Protein Crystal Growth Rates within the Microfluidic Device to Understand the Microspace Effect journal July 2020
X-ray Transparent Microfluidic Chip for Mesophase-Based Crystallization of Membrane Proteins and On-Chip Structure Determination journal September 2014
Microfluidic Generation of Lipidic Mesophases for Membrane Protein Crystallization journal June 2009
Femtosecond X-ray protein nanocrystallography journal February 2011
Imaging live cell in micro-liquid enclosure by X-ray laser diffraction journal January 2014
Determination of damage-free crystal structure of an X-ray–sensitive protein using an XFEL journal May 2014
Concentric-flow electrokinetic injector enables serial crystallography of ribosome and photosystem II journal November 2015
Drop-on-demand sample delivery for studying biocatalysts in action at X-ray free-electron lasers journal February 2017
Protein crystallization: from purified protein to diffraction-quality crystal journal January 2008
Liquid explosions induced by X-ray laser pulses journal May 2016
Ultracompact 3D microfluidics for time-resolved structural biology journal January 2020
Growing and making nano- and microcrystals journal November 2022
Polyimide mesh-based sample holder with irregular crystal mounting holes for fixed-target serial crystallography journal June 2021
Serial femtosecond crystallography journal August 2022
Fixed-target protein serial microcrystallography with an x-ray free electron laser journal August 2014
A micro-patterned silicon chip as sample holder for macromolecular crystallography experiments with minimal background scattering journal May 2015
A microfluidic device for both on-chip dialysis protein crystallization and in situ X-ray diffraction journal January 2020
Room-temperature crystallography using a microfluidic protein crystal array device and its application to protein–ligand complex structure analysis journal January 2020
Plug-and-play polymer microfluidic chips for hydrated, room temperature, fixed-target serial crystallography journal January 2021
Polymer-based microfluidic device for on-chip counter-diffusive crystallization and in situ X-ray crystallography at room temperature journal January 2023
A chip-to-chip nanoliter microfluidic dispenser journal January 2009
Monte Carlo study for optimal conditions in single-shot imaging with femtosecond x-ray laser pulses journal December 2013
Microfluidic sorting of protein nanocrystals by size for X-ray free-electron laser diffraction journal July 2015
Fixed target matrix for femtosecond time-resolved and in situ serial micro-crystallography journal August 2015
Microfluidics: From crystallization to serial time-resolved crystallography journal May 2017
Microfluidic polyimide gas dynamic virtual nozzles for serial crystallography journal August 2020
Goniometer-based femtosecond crystallography with X-ray free electron lasers journal October 2014
A robust and scalable microfluidic metering method that allows protein crystal growth by free interface diffusion journal December 2002
Gas dynamic virtual nozzle for generation of microscopic droplet streams journal September 2008
X-ray lasers for structural and dynamic biology journal September 2012
The Protein Data Bank journal January 2000
Femtosecond crystallography of membrane proteins in the lipidic cubic phase journal July 2014
Microcrystallization techniques for serial femtosecond crystallography using photosystem II from Thermosynechococcus elongatus as a model system
  • Kupitz, Christopher; Grotjohann, Ingo; Conrad, Chelsie E.
  • Philosophical Transactions of the Royal Society B: Biological Sciences, Vol. 369, Issue 1647 https://doi.org/10.1098/rstb.2013.0316
journal July 2014
Liquid sample delivery techniques for serial femtosecond crystallography journal July 2014
Generation of high-intensity ultrasound through shock propagation in liquid jets journal April 2019
Observation of shock-induced protein crystal damage during megahertz serial femtosecond crystallography journal January 2021
Reproducible improvements in order and diffraction limit of crystals of bovine mitochondrial F1-ATPase by controlled dehydration journal August 2006
Improving diffraction by humidity control: a novel device compatible with X-ray beamlines journal November 2009
The minimum crystal size needed for a complete diffraction data set journal March 2010
Capture and X-ray diffraction studies of protein microcrystals in a microfluidic trap array journal March 2015
A high-transparency, micro-patternable chip for X-ray diffraction analysis of microcrystals under native growth conditions journal September 2015
Successful sample preparation for serial crystallography experiments journal November 2019
3D-printed holders forin meso in situfixed-target serial X-ray crystallography journal April 2020
The Macromolecular Femtosecond Crystallography Instrument at the Linac Coherent Light Source journal February 2019
Implementation of wedged-serial protein crystallography at PROXIMA-1 journal January 2022
Observations of phase changes in monoolein during high viscous injection journal March 2022
Microfluidic rotating-target device capable of three-degrees-of-freedom motion for efficient in situ serial synchrotron crystallography journal February 2023
Serial femtosecond crystallography of soluble proteins in lipidic cubic phase journal August 2015
Viscous hydrophilic injection matrices for serial crystallography journal May 2017
Fixed-target serial oscillation crystallography at room temperature journal February 2019
A simple and versatile microfluidic device for efficient biomacromolecule crystallization and structural analysis by serial crystallography journal April 2019
On-chip crystallization for serial crystallography experiments and on-chip ligand-binding studies journal June 2019
1 kHz fixed-target serial crystallography using a multilayer monochromator and an integrating pixel detector journal August 2019
A fixed-target platform for serial femtosecond crystallography in a hydrated environment journal January 2020
Rapid and efficient room-temperature serial synchrotron crystallography using the CFEL TapeDrive journal October 2022
JINXED: just in time crystallization for easy structure determination of biological macromolecules journal March 2023
Novel combined crystallization plate for high-throughput crystal screening and in situ data collection at a crystallography beamline journal August 2021
High-density grids for efficient data collection from multiple crystals journal January 2016
Low-dose fixed-target serial synchrotron crystallography journal March 2017
Sample delivery for serial crystallography at free-electron lasers and synchrotrons journal January 2019
Strategies for sample delivery for femtosecond crystallography journal February 2019
Attaining atomic resolution from in situ data collection at room temperature using counter-diffusion-based low-cost microchips journal July 2020
Homogeneous batch micro-crystallization of proteins from ammonium sulfate journal January 2021
Versatile microporous polymer-based supports for serial macromolecular crystallography journal August 2021
Best practices for time-resolved serial synchrotron crystallography journal January 2022
A user-friendly plug-and-play cyclic olefin copolymer-based microfluidic chip for room-temperature, fixed-target serial crystallography journal September 2023
A guide to sample delivery systems for serial crystallography journal August 2019
Serial Femtosecond Crystallography of G Protein-Coupled Receptors journal December 2013
Development of a Microfluidic Chip for Protein Crystallization by the Microbatch Method journal March 2019
Structure of the 30S ribosomal decoding complex at ambient temperature journal August 2018
Explosive vaporization of a large transparent droplet irradiated by a high intensity laser journal January 1987
Calculation of Photon Mass Energy-Transfer and Mass Energy-Absorption Coefficients journal November 1993
Towards an Optimal Sample Delivery Method for Serial Crystallography at XFEL journal March 2020
Increasing the X-ray Diffraction Power of Protein Crystals by Dehydration: The Case of Bovine Serum Albumin and a Survey of Literature Data journal March 2012
Sample Delivery Media for Serial Crystallography journal March 2019
Manufacturing of Ultra-Thin X-ray-Compatible COC Microfluidic Devices for Optimal In Situ Macromolecular Crystallography Experiments journal August 2022
Microfluidic Chips for In Situ Crystal X-ray Diffraction and In Situ Dynamic Light Scattering for Serial Crystallography journal April 2018
Fixed Target Serial Data Collection at Diamond Light Source journal February 2021