Ultracompact 3D microfluidics for time-resolved structural biology

Knoška, Juraj; Adriano, Luigi; Awel, Salah; Beyerlein, Kenneth R.; Yefanov, Oleksandr; Oberthuer, Dominik; Peña Murillo, Gisel E.; Roth, Nils; Sarrou, Iosifina; Villanueva-Perez, Pablo; Wiedorn, Max O.; Wilde, Fabian; Bajt, Saša; Chapman, Henry N.; Heymann, Michael

doi:10.1038/s41467-020-14434-6

Title: Ultracompact 3D microfluidics for time-resolved structural biology

Journal Article · 30 January 2020 · Nature Communications

DOI: https://doi.org/10.1038/s41467-020-14434-6 · OSTI ID:1624244

^[1]; Adriano, Luigi ^[2]; Awel, Salah ^[3];

^[2]; Yefanov, Oleksandr ^[2]; Oberthuer, Dominik ^[2];

^[3]; Roth, Nils ^[3]; Sarrou, Iosifina ^[2]; Villanueva-Perez, Pablo ^[2]; Wiedorn, Max O. ^[3];

^[4];

^[2];

^[3];

^[5]

Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Univ. of Hamburg (Germany); DOE/OSTI
Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)
Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Univ. of Hamburg (Germany)
Helmholtz-Zentrum Geesthacht (Germany)
Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Univ. of Stuttgart (Germany)

To advance microfluidic integration, we present the use of two-photon additive manufacturing to fold 2D channel layouts into compact free-form 3D fluidic circuits with nanometer precision. We demonstrate this technique by tailoring microfluidic nozzles and mixers for time-resolved structural biology at X-ray free-electron lasers (XFELs). We achieve submicron jets with speeds exceeding 160 ms^-1, which allows for the use of megahertz XFEL repetition rates. By integrating an additional orifice, we implement a low consumption flow-focusing nozzle, which is validated by solving a hemoglobin structure. Also, aberration-free in operando X-ray microtomography is introduced to study efficient equivolumetric millisecond mixing in channels with 3D features integrated into the nozzle. Such devices can be printed in minutes by locally adjusting print resolution during fabrication. This technology has the potential to permit ultracompact devices and performance improvements through 3D flow optimization in all fields of microfluidic engineering.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: SLAC National Accelerator Laboratory, Menlo Park, CA (United States). Linac Coherent Light Source (LCLS)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: AC02-76SF00515

OSTI ID:: 1624244

Journal Information:: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 11; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

References (164)

Tailored 3D Mechanical Metamaterials Made by Dip-in Direct-Laser-Writing Optical Lithography Bückmann, Tiemo; Stenger, Nicolas; Kadic, Muamer Advanced Materials, Vol. 24, Issue 20 https://doi.org/10.1002/adma.201200584	journal	April 2012
3D-Printed Microfluidics Au, Anthony K.; Huynh, Wilson; Horowitz, Lisa F. Angewandte Chemie International Edition, Vol. 55, Issue 12 https://doi.org/10.1002/anie.201504382	journal	February 2016
Liquid Capillary Micro/Nanojets in Free-Jet Expansion Gañán-Calvo, Alfonso M.; DePonte, Daniel P.; Herrada, Miguel A. Small, Vol. 6, Issue 7 https://doi.org/10.1002/smll.200901786	journal	April 2010
iLIF: illumination by Laser-Induced Fluorescence for single flash imaging on a nanoseconds timescale van der Bos, Arjan; Zijlstra, Aaldert; Gelderblom, Erik Experiments in Fluids, Vol. 51, Issue 5 https://doi.org/10.1007/s00348-011-1146-7	journal	June 2011
Mapping ligand binding using microfluidics-enabled millisecond timescale hydrogen-deuterium exchange Resetca, Diana; Wilson, Derek J. International Journal of Mass Spectrometry, Vol. 420 https://doi.org/10.1016/j.ijms.2017.06.002	journal	September 2017
Serpentine microfluidic mixer made in LTCC Malecha, Karol; Golonka, Leszek J.; Bałdyga, Jerzy Sensors and Actuators B: Chemical, Vol. 143, Issue 1 https://doi.org/10.1016/j.snb.2009.08.010	journal	December 2009
The Kenics static mixer: a three-dimensional chaotic flow Hobbs, D. M.; Muzzio, F. J. Chemical Engineering Journal, Vol. 67, Issue 3 https://doi.org/10.1016/s1385-8947(97)00013-2	journal	June 1997
The Diffusion Coefficients of Sodium and Potassium Iodides in Aqueous Solution at 25° ¹ Dunlop, P. J.; Stokes, R. H. Journal of the American Chemical Society, Vol. 73, Issue 11 https://doi.org/10.1021/ja01155a520	journal	November 1951
Structure of Hæmoglobin: A Three-Dimensional Fourier Synthesis at 5.5-Å. Resolution, Obtained by X-Ray Analysis Perutz, M. F.; Rossmann, M. G.; Cullis, Ann F. Nature, Vol. 185, Issue 4711 https://doi.org/10.1038/185416a0	journal	February 1960
Potential for biomolecular imaging with femtosecond X-ray pulses Neutze, Richard; Wouts, Remco; van der Spoel, David Nature, Vol. 406, Issue 6797 https://doi.org/10.1038/35021099	journal	August 2000
Digitally tunable physicochemical coding of material composition and topography in continuous microfibres Kang, Edward; Jeong, Gi Seok; Choi, Yoon Young Nature Materials, Vol. 10, Issue 11 https://doi.org/10.1038/nmat3108	journal	September 2011
Integrative, dynamic structural biology at atomic resolution—it's about time van den Bedem, Henry; Fraser, James S. Nature Methods, Vol. 12, Issue 4 https://doi.org/10.1038/nmeth.3324	journal	March 2015
Liquid explosions induced by X-ray laser pulses Stan, Claudiu A.; Milathianaki, Despina; Laksmono, Hartawan Nature Physics, Vol. 12, Issue 10 https://doi.org/10.1038/nphys3779	journal	May 2016
Time-lapse X-ray phase-contrast microtomography for in vivo imaging and analysis of morphogenesis Moosmann, Julian; Ershov, Alexey; Weinhardt, Venera Nature Protocols, Vol. 9, Issue 2 https://doi.org/10.1038/nprot.2014.033	journal	January 2014
Structural absorption by barbule microstructures of super black bird of paradise feathers McCoy, Dakota E.; Feo, Teresa; Harvey, Todd Alan Nature Communications, Vol. 9, Issue 1 https://doi.org/10.1038/s41467-017-02088-w	journal	January 2018
Serial femtosecond crystallography datasets from G protein-coupled receptors White, Thomas A.; Barty, Anton; Liu, Wei Scientific Data, Vol. 3, Issue 1 https://doi.org/10.1038/sdata.2016.57	journal	August 2016
Three-dimensionally crossing manifold micro-mixer for fast mixing in a short channel length Lim, Tae Woo; Son, Yong; Jeong, Yu Jin Lab Chip, Vol. 11, Issue 1 https://doi.org/10.1039/c005325m	journal	January 2011
Global and local instability of flow focusing: The influence of the geometry Vega, Emilio J.; Montanero, José M.; Herrada, Miguel A. Physics of Fluids, Vol. 22, Issue 6 https://doi.org/10.1063/1.3450321	journal	June 2010
Ceramic micro-injection molded nozzles for serial femtosecond crystallography sample delivery Beyerlein, K. R.; Adriano, L.; Heymann, M. Review of Scientific Instruments, Vol. 86, Issue 12 https://doi.org/10.1063/1.4936843	journal	December 2015
Mixing injector enables time-resolved crystallography with high hit rate at X-ray free electron lasers Calvey, George D.; Katz, Andrea M.; Schaffer, Chris B. Structural Dynamics, Vol. 3, Issue 5 https://doi.org/10.1063/1.4961971	journal	August 2016
Structural enzymology using X-ray free electron lasers Kupitz, Christopher; Olmos, Jose L.; Holl, Mark Structural Dynamics, Vol. 4, Issue 4 https://doi.org/10.1063/1.4972069	journal	December 2016
Discrete elements for 3D microfluidics Bhargava, Krisna C.; Thompson, Bryant; Malmstadt, Noah Proceedings of the National Academy of Sciences, Vol. 111, Issue 42 https://doi.org/10.1073/pnas.1414764111	journal	September 2014
Atomic structure of granulin determined from native nanocrystalline granulovirus using an X-ray free-electron laser Gati, Cornelius; Oberthuer, Dominik; Yefanov, Oleksandr Proceedings of the National Academy of Sciences, Vol. 114, Issue 9 https://doi.org/10.1073/pnas.1609243114	journal	February 2017
The New Macromolecular Femtosecond Crystallography (MFX) Instrument at LCLS Boutet, Sébastien; Cohen, Aina E.; Wakatsuki, Soichi Synchrotron Radiation News, Vol. 29, Issue 1 https://doi.org/10.1080/08940886.2016.1124681	journal	January 2016
Generation of Steady Liquid Microthreads and Micron-Sized Monodisperse Sprays in Gas Streams Gañán-Calvo, Alfonso M. Physical Review Letters, Vol. 80, Issue 2 https://doi.org/10.1103/physrevlett.80.285	journal	January 1998
Phaser crystallographic software McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D. Journal of Applied Crystallography, Vol. 40, Issue 4 https://doi.org/10.1107/s0021889807021206	journal	July 2007
Indexing in single-crystal diffractometry with an obstinate list of reflections Duisenberg, A. J. M. Journal of Applied Crystallography, Vol. 25, Issue 2 https://doi.org/10.1107/s0021889891010634	journal	April 1992
Structures of riboswitch RNA reaction states by mix-and-inject XFEL serial crystallography Stagno, J. R.; Liu, Y.; Bhandari, Y. R. Acta Crystallographica Section A Foundations and Advances, Vol. 73, Issue a1 https://doi.org/10.1107/s0108767317099081	journal	May 2017
Crystallographic model quality at a glance Urzhumtseva, Ludmila; Afonine, Pavel V.; Adams, Paul D. Acta Crystallographica Section D Biological Crystallography, Vol. 65, Issue 3 https://doi.org/10.1107/s0907444908044296	journal	February 2009
Features and development of Coot Emsley, P.; Lohkamp, B.; Scott, W. G. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4 https://doi.org/10.1107/s0907444910007493	journal	March 2010
Overview of the CCP 4 suite and current developments Winn, Martyn D.; Ballard, Charles C.; Cowtan, Kevin D. Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4 https://doi.org/10.1107/s0907444910045749	journal	March 2011
iMOSFLM : a new graphical interface for diffraction-image processing with MOSFLM Battye, T. Geoff G.; Kontogiannis, Luke; Johnson, Owen Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4 https://doi.org/10.1107/s0907444910048675	journal	March 2011
Towards automated crystallographic structure refinement with phenix.refine Afonine, Pavel V.; Grosse-Kunstleve, Ralf W.; Echols, Nathaniel Acta Crystallographica Section D Biological Crystallography, Vol. 68, Issue 4 https://doi.org/10.1107/s0907444912001308	journal	March 2012
OnDA : online data analysis and feedback for serial X-ray imaging Mariani, Valerio; Morgan, Andrew; Yoon, Chun Hong Journal of Applied Crystallography, Vol. 49, Issue 3 https://doi.org/10.1107/s1600576716007469	journal	May 2016
Lipidic cubic phase serial millisecond crystallography using synchrotron radiation Nogly, Przemyslaw; James, Daniel; Wang, Dingjie IUCrJ, Vol. 2, Issue 2, p. 168-176 https://doi.org/10.1107/s2052252514026487	journal	March 2015
Experimental strategies for imaging bioparticles with femtosecond hard X-ray pulses. Corrigendum Daurer, Benedikt J.; Okamoto, Kenta; Bielecki, Johan IUCrJ, Vol. 6, Issue 3 https://doi.org/10.1107/s2052252519004317	journal	April 2019
Watching a Protein as it Functions with 150-ps Time-Resolved X-ray Crystallography Schotte, F. Science, Vol. 300, Issue 5627 https://doi.org/10.1126/science.1078797	journal	June 2003
Direct observation of ultrafast collective motions in CO myoglobin upon ligand dissociation Barends, T. R. M.; Foucar, L.; Ardevol, A. Science, Vol. 350, Issue 6259 https://doi.org/10.1126/science.aac5492	journal	September 2015
Retinal isomerization in bacteriorhodopsin captured by a femtosecond x-ray laser Nogly, Przemyslaw; Weinert, Tobias; James, Daniel Science https://doi.org/10.1126/science.aat0094	journal	June 2018
Enzyme intermediates captured “on the fly” by mix-and-inject serial crystallography Olmos, Jose L.; Pandey, Suraj; Martin-Garcia, Jose M. BMC Biology, Vol. 16, Issue 1 https://doi.org/10.1186/s12915-018-0524-5	journal	May 2018
Accurate determination of segmented X-ray detector geometry Yefanov, Oleksandr; Mariani, Valerio; Gati, Cornelius Optics Express, Vol. 23, Issue 22 https://doi.org/10.1364/oe.23.028459	journal	January 2015
Three-dimensional-printed gas dynamic virtual nozzles for x-ray laser sample delivery Nelson, Garrett; Kirian, Richard A.; Weierstall, Uwe Optics Express, Vol. 24, Issue 11 https://doi.org/10.1364/oe.24.011515	journal	January 2016
PHENIX: a comprehensive Python-based system for macromolecular structure solution. Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Apollo - University of Cambridge Repository https://doi.org/10.17863/cam.45787	text	January 2010
Jet delivery system for Raman scattering on bio-inorganic compounds Wetzel, Alina; Biebl, F.; Beyerlein, K. R. Deutsches Elektronen-Synchrotron, DESY, Hamburg https://doi.org/10.3204/pubdb-2016-06119	text	January 2016
Flow-aligned, single-shot fiber diffraction using a femtosecond X-ray free-electron laser Popp, David; Loh, N. Duane; Zorgati, Habiba Deutsches Elektronen-Synchrotron, DESY, Hamburg https://doi.org/10.3204/pubdb-2017-11811	text	January 2017
Megahertz Data Collection from Protein Microcrystals at an X-Ray Free-Electron Laser Grünbein, Marie Luise; Bielecki, Johan; Gorel, Alexander Deutsches Elektronen-Synchrotron, DESY, Hamburg https://doi.org/10.3204/pubdb-2018-03217	text	January 2018
3D printed nozzles on a silicon fluidic chip Chapman, Henry N.; Trieu, Hoc Khiem; Bajt, Sasa Deutsches Elektronen-Synchrotron, DESY, Hamburg https://doi.org/10.3204/pubdb-2019-01297	text	January 2019
Gas Dynamic Virtual Nozzle for Generation of Microscopic Droplet Streams DePonte, D. P.; Weierstall, U.; Starodub, D. arXiv https://doi.org/10.48550/arxiv.0803.4181	text	January 2008
Visualizing aerosol-particle injection for diffractive-imaging experiments Awel, Salah; Kirian, Richard A.; Eckerskorn, Niko arXiv https://doi.org/10.48550/arxiv.1512.06231	text	January 2015
Femtosecond x-ray diffraction from an aerosolized beam of protein nanocrystals Awel, Salah; Kirian, Richard A.; Wiedorn, Max O. arXiv https://doi.org/10.48550/arxiv.1702.04014	text	January 2017
Droplet beams for serial crystallography of proteins Weierstall, U.; Doak, R. B.; Spence, J. C. H. arXiv https://doi.org/10.48550/arxiv.physics/0701129	text	January 2007
Multimaterial 3D laser microprinting using an integrated microfluidic system Mayer, Frederik; Richter, Stefan; Westhauser, Johann American Association for the Advancement of Science (AAAS) https://doi.org/10.5445/ir/1000090939	text	January 2019
Tailored 3D Mechanical Metamaterials Made by Dip-in Direct-Laser-Writing Optical Lithography Bückmann, Tiemo; Stenger, Nicolas; Kadic, Muamer Advanced Materials, Vol. 24, Issue 20 https://doi.org/10.1002/adma.201200584	journal	April 2012
3D-Printed Microfluidics Au, Anthony K.; Huynh, Wilson; Horowitz, Lisa F. Angewandte Chemie International Edition, Vol. 55, Issue 12 https://doi.org/10.1002/anie.201504382	journal	February 2016
Flow-aligned, single-shot fiber diffraction using a femtosecond X-ray free-electron laser Popp, David; Loh, N. Duane; Zorgati, Habiba Cytoskeleton, Vol. 74, Issue 12 https://doi.org/10.1002/cm.21378	journal	June 2017
Understanding and Optimizing the SMX Static Mixer Singh, Mrityunjay K.; Anderson, Patrick D.; Meijer, Han E. H. Macromolecular Rapid Communications, Vol. 30, Issue 4-5 https://doi.org/10.1002/marc.200800710	journal	February 2009
Liquid Capillary Micro/Nanojets in Free-Jet Expansion Gañán-Calvo, Alfonso M.; DePonte, Daniel P.; Herrada, Miguel A. Small, Vol. 6, Issue 7 https://doi.org/10.1002/smll.200901786	journal	April 2010
Droplet streams for serial crystallography of proteins Weierstall, U.; Doak, R. B.; Spence, J. C. H. Experiments in Fluids, Vol. 44, Issue 5 https://doi.org/10.1007/s00348-007-0426-8	journal	November 2007
iLIF: illumination by Laser-Induced Fluorescence for single flash imaging on a nanoseconds timescale van der Bos, Arjan; Zijlstra, Aaldert; Gelderblom, Erik Experiments in Fluids, Vol. 51, Issue 5 https://doi.org/10.1007/s00348-011-1146-7	journal	June 2011
Exploring the gas access routes in a [NiFeSe] hydrogenase using crystals pressurized with krypton and oxygen Zacarias, Sónia; Temporão, Adriana; Carpentier, Philippe JBIC Journal of Biological Inorganic Chemistry, Vol. 25, Issue 6 https://doi.org/10.1007/s00775-020-01814-y	journal	August 2020
The Kenics static mixer: a three-dimensional chaotic flow Hobbs, D. M.; Muzzio, F. J. Chemical Engineering Journal, Vol. 67, Issue 3 https://doi.org/10.1016/S1385-8947(97)00013-2	journal	June 1997
Mapping ligand binding using microfluidics-enabled millisecond timescale hydrogen-deuterium exchange Resetca, Diana; Wilson, Derek J. International Journal of Mass Spectrometry, Vol. 420 https://doi.org/10.1016/j.ijms.2017.06.002	journal	September 2017
Serpentine microfluidic mixer made in LTCC Malecha, Karol; Golonka, Leszek J.; Bałdyga, Jerzy Sensors and Actuators B: Chemical, Vol. 143, Issue 1 https://doi.org/10.1016/j.snb.2009.08.010	journal	December 2009
The Diffusion Coefficients of Sodium and Potassium Iodides in Aqueous Solution at 25° ¹ Dunlop, P. J.; Stokes, R. H. Journal of the American Chemical Society, Vol. 73, Issue 11 https://doi.org/10.1021/ja01155a520	journal	November 1951
Structure of Hæmoglobin: A Three-Dimensional Fourier Synthesis at 5.5-Å. Resolution, Obtained by X-Ray Analysis Perutz, M. F.; Rossmann, M. G.; Cullis, Ann F. Nature, Vol. 185, Issue 4711 https://doi.org/10.1038/185416a0	journal	February 1960
Potential for biomolecular imaging with femtosecond X-ray pulses Neutze, Richard; Wouts, Remco; van der Spoel, David Nature, Vol. 406, Issue 6797 https://doi.org/10.1038/35021099	journal	August 2000
Femtosecond X-ray protein nanocrystallography Chapman, Henry N.; Fromme, Petra; Barty, Anton Nature, Vol. 470, Issue 7332, p. 73-77 https://doi.org/10.1038/nature09750	journal	February 2011
Structures of riboswitch RNA reaction states by mix-and-inject XFEL serial crystallography Stagno, J. R.; Liu, Y.; Bhandari, Y. R. Nature, Vol. 541, Issue 7636 https://doi.org/10.1038/nature20599	journal	November 2016
Single-cell genome sequencing at ultra-high-throughput with microfluidic droplet barcoding Lan, Freeman; Demaree, Benjamin; Ahmed, Noorsher Nature Biotechnology, Vol. 35, Issue 7 https://doi.org/10.1038/nbt.3880	journal	May 2017
Sub-micrometre accurate free-form optics by three-dimensional printing on single-mode fibres Gissibl, Timo; Thiele, Simon; Herkommer, Alois Nature Communications, Vol. 7, Issue 1 https://doi.org/10.1038/ncomms11763	journal	June 2016
Lipidic cubic phase injector facilitates membrane protein serial femtosecond crystallography Weierstall, Uwe; James, Daniel; Wang, Chong Nature Communications, Vol. 5, Issue 1 https://doi.org/10.1038/ncomms4309	journal	February 2014
Digitally tunable physicochemical coding of material composition and topography in continuous microfibres Kang, Edward; Jeong, Gi Seok; Choi, Yoon Young Nature Materials, Vol. 10, Issue 11 https://doi.org/10.1038/nmat3108	journal	September 2011
Integrative, dynamic structural biology at atomic resolution—it's about time van den Bedem, Henry; Fraser, James S. Nature Methods, Vol. 12, Issue 4 https://doi.org/10.1038/nmeth.3324	journal	March 2015
High-speed fixed-target serial virus crystallography Roedig, Philip; Ginn, Helen M.; Pakendorf, Tim Nature Methods, Vol. 14, Issue 8 https://doi.org/10.1038/nmeth.4335	journal	June 2017
Liquid explosions induced by X-ray laser pulses Stan, Claudiu A.; Milathianaki, Despina; Laksmono, Hartawan Nature Physics, Vol. 12, Issue 10 https://doi.org/10.1038/nphys3779	journal	May 2016
Time-lapse X-ray phase-contrast microtomography for in vivo imaging and analysis of morphogenesis Moosmann, Julian; Ershov, Alexey; Weinhardt, Venera Nature Protocols, Vol. 9, Issue 2 https://doi.org/10.1038/nprot.2014.033	journal	January 2014
Pink-beam serial crystallography Meents, A.; Wiedorn, M. O.; Srajer, V. Nature Communications, Vol. 8, Issue 1 https://doi.org/10.1038/s41467-017-01417-3	journal	November 2017
Structural absorption by barbule microstructures of super black bird of paradise feathers McCoy, Dakota E.; Feo, Teresa; Harvey, Todd Alan Nature Communications, Vol. 9, Issue 1 https://doi.org/10.1038/s41467-017-02088-w	journal	January 2018
Megahertz data collection from protein microcrystals at an X-ray free-electron laser Grünbein, Marie Luise; Bielecki, Johan; Gorel, Alexander Nature Communications, Vol. 9, Issue 1 https://doi.org/10.1038/s41467-018-05953-4	journal	August 2018
Megahertz serial crystallography Wiedorn, Max O.; Oberthür, Dominik; Bean, Richard Nature Communications, Vol. 9, Issue 1 https://doi.org/10.1038/s41467-018-06156-7	journal	October 2018
PARP1 exhibits enhanced association and catalytic efficiency with γH2A.X-nucleosome Sharma, Deepti; De Falco, Louis; Padavattan, Sivaraman Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-13641-0	journal	December 2019
Cavin1 intrinsically disordered domains are essential for fuzzy electrostatic interactions and caveola formation Tillu, Vikas A.; Rae, James; Gao, Ya Nature Communications, Vol. 12, Issue 1 https://doi.org/10.1038/s41467-021-21035-4	journal	February 2021
Late steps in bacterial translation initiation visualized using time-resolved cryo-EM Kaledhonkar, Sandip; Fu, Ziao; Caban, Kelvin Nature, Vol. 570, Issue 7761 https://doi.org/10.1038/s41586-019-1249-5	journal	May 2019
Abseq: Ultrahigh-throughput single cell protein profiling with droplet microfluidic barcoding Shahi, Payam; Kim, Samuel C.; Haliburton, John R. Scientific Reports, Vol. 7, Issue 1 https://doi.org/10.1038/srep44447	journal	March 2017
Double-flow focused liquid injector for efficient serial femtosecond crystallography Oberthuer, Dominik; Knoška, Juraj; Wiedorn, Max O. Scientific Reports, Vol. 7, Issue 1 https://doi.org/10.1038/srep44628	journal	March 2017
Three-dimensionally crossing manifold micro-mixer for fast mixing in a short channel length Lim, Tae Woo; Son, Yong; Jeong, Yu Jin Lab Chip, Vol. 11, Issue 1 https://doi.org/10.1039/C005325M	journal	January 2011
Microfluidic liquid jet system with compatibility for atmospheric and high-vacuum conditions Trebbin, Martin; Krüger, Kilian; DePonte, Daniel Lab Chip, Vol. 14, Issue 10 https://doi.org/10.1039/C3LC51363G	journal	January 2014
Tandem emulsification for high-throughput production of double emulsions Eggersdorfer, M. L.; Zheng, W.; Nawar, S. Lab on a Chip, Vol. 17, Issue 5 https://doi.org/10.1039/C6LC01553K	journal	January 2017
Global and local instability of flow focusing: The influence of the geometry Vega, Emilio J.; Montanero, José M.; Herrada, Miguel A. Physics of Fluids, Vol. 22, Issue 6 https://doi.org/10.1063/1.3450321	journal	June 2010
Injector for scattering measurements on fully solvated biospecies Weierstall, U.; Spence, J. C. H.; Doak, R. B. Review of Scientific Instruments, Vol. 83, Issue 3 https://doi.org/10.1063/1.3693040	journal	March 2012
Ceramic micro-injection molded nozzles for serial femtosecond crystallography sample delivery Beyerlein, K. R.; Adriano, L.; Heymann, M. Review of Scientific Instruments, Vol. 86, Issue 12 https://doi.org/10.1063/1.4936843	journal	December 2015
Micro-CT at the imaging beamline P05 at PETRA III Wilde, Fabian; Ogurreck, Malte; Greving, Imke PROCEEDINGS OF THE 12TH INTERNATIONAL CONFERENCE ON SYNCHROTRON RADIATION INSTRUMENTATION – SRI2015, AIP Conference Proceedings https://doi.org/10.1063/1.4952858	conference	January 2016
A liquid jet setup for x-ray scattering experiments on complex liquids at free-electron laser sources Steinke, I.; Walther, M.; Lehmkühler, F. Review of Scientific Instruments, Vol. 87, Issue 6 https://doi.org/10.1063/1.4953921	journal	June 2016
Mixing injector enables time-resolved crystallography with high hit rate at X-ray free electron lasers Calvey, George D.; Katz, Andrea M.; Schaffer, Chris B. Structural Dynamics, Vol. 3, Issue 5 https://doi.org/10.1063/1.4961971	journal	August 2016
Jet delivery system for Raman scattering on bio-inorganic compounds Wetzel, A.; Biebl, F.; Beyerlein, K. R. Applied Physics Letters, Vol. 109, Issue 21 https://doi.org/10.1063/1.4967476	journal	November 2016
Structural enzymology using X-ray free electron lasers Kupitz, Christopher; Olmos, Jose L.; Holl, Mark Structural Dynamics, Vol. 4, Issue 4 https://doi.org/10.1063/1.4972069	journal	December 2016
3D printed nozzles on a silicon fluidic chip Bohne, Sven; Heymann, Michael; Chapman, Henry N. Review of Scientific Instruments, Vol. 90, Issue 3 https://doi.org/10.1063/1.5080428	journal	March 2019
Continuous inertial focusing, ordering, and separation of particles in microchannels Di Carlo, D.; Irimia, D.; Tompkins, R. G. Proceedings of the National Academy of Sciences, Vol. 104, Issue 48, p. 18892-18897 https://doi.org/10.1073/pnas.0704958104	journal	November 2007
Discrete elements for 3D microfluidics Bhargava, Krisna C.; Thompson, Bryant; Malmstadt, Noah Proceedings of the National Academy of Sciences, Vol. 111, Issue 42 https://doi.org/10.1073/pnas.1414764111	journal	September 2014
Atomic structure of granulin determined from native nanocrystalline granulovirus using an X-ray free-electron laser Gati, Cornelius; Oberthuer, Dominik; Yefanov, Oleksandr Proceedings of the National Academy of Sciences, Vol. 114, Issue 9 https://doi.org/10.1073/pnas.1609243114	journal	February 2017
The New Macromolecular Femtosecond Crystallography (MFX) Instrument at LCLS Boutet, Sébastien; Cohen, Aina E.; Wakatsuki, Soichi Synchrotron Radiation News, Vol. 29, Issue 1 https://doi.org/10.1080/08940886.2016.1124681	journal	January 2016
Gas dynamic virtual nozzle for generation of microscopic droplet streams DePonte, D. P.; Weierstall, U.; Schmidt, K. Journal of Physics D: Applied Physics, Vol. 41, Issue 19, Article No. 195505 https://doi.org/10.1088/0022-3727/41/19/195505	journal	September 2008
A new flow focusing technique to produce very thin jets Acero, A. J.; Rebollo-Muñoz, N.; Montanero, J. M. Journal of Micromechanics and Microengineering, Vol. 23, Issue 6 https://doi.org/10.1088/0960-1317/23/6/065009	journal	April 2013
Generation of Steady Liquid Microthreads and Micron-Sized Monodisperse Sprays in Gas Streams Gañán-Calvo, Alfonso M. Physical Review Letters, Vol. 80, Issue 2 https://doi.org/10.1103/PhysRevLett.80.285	journal	January 1998
Phaser crystallographic software McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D. Journal of Applied Crystallography, Vol. 40, Issue 4 https://doi.org/10.1107/S0021889807021206	journal	July 2007
CrystFEL : a software suite for snapshot serial crystallography White, Thomas A.; Kirian, Richard A.; Martin, Andrew V. Journal of Applied Crystallography, Vol. 45, Issue 2 https://doi.org/10.1107/S0021889812002312	journal	March 2012
Indexing in single-crystal diffractometry with an obstinate list of reflections Duisenberg, A. J. M. Journal of Applied Crystallography, Vol. 25, Issue 2 https://doi.org/10.1107/S0021889891010634	journal	April 1992
Crystallographic model quality at a glance Urzhumtseva, Ludmila; Afonine, Pavel V.; Adams, Paul D. Acta Crystallographica Section D Biological Crystallography, Vol. 65, Issue 3 https://doi.org/10.1107/S0907444908044296	journal	February 2009
MolProbity : all-atom structure validation for macromolecular crystallography Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1 https://doi.org/10.1107/S0907444909042073	journal	December 2009
PHENIX: a comprehensive Python-based system for macromolecular structure solution Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221 https://doi.org/10.1107/S0907444909052925	journal	January 2010
Features and development of Coot Emsley, P.; Lohkamp, B.; Scott, W. G. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4 https://doi.org/10.1107/S0907444910007493	journal	March 2010
Overview of the CCP 4 suite and current developments Winn, Martyn D.; Ballard, Charles C.; Cowtan, Kevin D. Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4 https://doi.org/10.1107/S0907444910045749	journal	March 2011
iMOSFLM : a new graphical interface for diffraction-image processing with MOSFLM Battye, T. Geoff G.; Kontogiannis, Luke; Johnson, Owen Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4 https://doi.org/10.1107/S0907444910048675	journal	March 2011
Towards automated crystallographic structure refinement with phenix.refine Afonine, Pavel V.; Grosse-Kunstleve, Ralf W.; Echols, Nathaniel Acta Crystallographica Section D Biological Crystallography, Vol. 68, Issue 4 https://doi.org/10.1107/S0907444912001308	journal	March 2012
Cheetah : software for high-throughput reduction and analysis of serial femtosecond X-ray diffraction data Barty, Anton; Kirian, Richard A.; Maia, Filipe R. N. C. Journal of Applied Crystallography, Vol. 47, Issue 3 https://doi.org/10.1107/S1600576714007626	journal	May 2014
Recent developments in CrystFEL White, Thomas A.; Mariani, Valerio; Brehm, Wolfgang Journal of Applied Crystallography, Vol. 49, Issue 2 https://doi.org/10.1107/S1600576716004751	journal	March 2016
OnDA : online data analysis and feedback for serial X-ray imaging Mariani, Valerio; Morgan, Andrew; Yoon, Chun Hong Journal of Applied Crystallography, Vol. 49, Issue 3 https://doi.org/10.1107/S1600576716007469	journal	May 2016
Femtosecond X-ray diffraction from an aerosolized beam of protein nanocrystals Awel, Salah; Kirian, Richard A.; Wiedorn, Max O. Journal of Applied Crystallography, Vol. 51, Issue 1 https://doi.org/10.1107/S1600576717018131	journal	February 2018
Double-focusing mixing jet for XFEL study of chemical kinetics Wang, Dingjie; Weierstall, Uwe; Pollack, Lois Journal of Synchrotron Radiation, Vol. 21, Issue 6 https://doi.org/10.1107/S160057751401858X	journal	October 2014
Lipidic cubic phase serial millisecond crystallography using synchrotron radiation Nogly, Przemyslaw; James, Daniel; Wang, Dingjie IUCrJ, Vol. 2, Issue 2, p. 168-176 https://doi.org/10.1107/S2052252514026487	journal	March 2015
Experimental strategies for imaging bioparticles with femtosecond hard X-ray pulses Daurer, Benedikt J.; Okamoto, Kenta; Bielecki, Johan IUCrJ, Vol. 4, Issue 3, p. 251-262 https://doi.org/10.1107/S2052252517003591	journal	April 2017
Mix-and-diffuse serial synchrotron crystallography Beyerlein, Kenneth R.; Dierksmeyer, Dennis; Mariani, Valerio IUCrJ, Vol. 4, Issue 6 https://doi.org/10.1107/S2052252517013124	journal	October 2017
Analysis of XFEL serial diffraction data from individual crystalline fibrils Wojtas, David H.; Ayyer, Kartik; Liang, Mengning IUCrJ, Vol. 4, Issue 6 https://doi.org/10.1107/S2052252517014324	journal	October 2017
Rapid sample delivery for megahertz serial crystallography at X-ray FELs Wiedorn, Max O.; Awel, Salah; Morgan, Andrew J. IUCrJ, Vol. 5, Issue 5 https://doi.org/10.1107/S2052252518008369	journal	July 2018
Structures of riboswitch RNA reaction states by mix-and-inject XFEL serial crystallography Stagno, J. R.; Liu, Y.; Bhandari, Y. R. Acta Crystallographica Section A Foundations and Advances, Vol. 73, Issue a1 https://doi.org/10.1107/s0108767317099081	journal	May 2017
Trends in synchrotron-based tomographic imaging: the SLS experience Stampanoni, M.; Groso, A.; Isenegger, A. SPIE Optics + Photonics, SPIE Proceedings https://doi.org/10.1117/12.679497	conference	August 2006
The CSPAD megapixel x-ray camera at LCLS Hart, Philip; Boutet, Sébastien; Carini, Gabriella SPIE Optical Engineering + Applications, SPIE Proceedings https://doi.org/10.1117/12.930924	conference	October 2012
3D-printed eagle eye: Compound microlens system for foveated imaging Thiele, Simon; Arzenbacher, Kathrin; Gissibl, Timo Science Advances, Vol. 3, Issue 2 https://doi.org/10.1126/sciadv.1602655	journal	February 2017
Multimaterial 3D laser microprinting using an integrated microfluidic system Mayer, Frederik; Richter, Stefan; Westhauser, Johann Science Advances, Vol. 5, Issue 2 https://doi.org/10.1126/sciadv.aau9160	journal	February 2019
Electrospray sample injection for single-particle imaging with x-ray lasers Bielecki, Johan; Hantke, Max F.; Daurer, Benedikt J. Science Advances, Vol. 5, Issue 5 https://doi.org/10.1126/sciadv.aav8801	journal	May 2019
Watching a Protein as it Functions with 150-ps Time-Resolved X-ray Crystallography Schotte, F. Science, Vol. 300, Issue 5627 https://doi.org/10.1126/science.1078797	journal	June 2003
Time-resolved serial crystallography captures high-resolution intermediates of photoactive yellow protein Tenboer, Jason; Basu, Shibom; Zatsepin, Nadia Science, Vol. 346, Issue 6214 https://doi.org/10.1126/science.1259357	journal	December 2014
Direct observation of ultrafast collective motions in CO myoglobin upon ligand dissociation Barends, T. R. M.; Foucar, L.; Ardevol, A. Science, Vol. 350, Issue 6259 https://doi.org/10.1126/science.aac5492	journal	September 2015
Production of amorphous nanoparticles by supersonic spray-drying with a microfluidic nebulator Amstad, E.; Gopinadhan, M.; Holtze, C. Science, Vol. 349, Issue 6251 https://doi.org/10.1126/science.aac9582	journal	August 2015
Retinal isomerization in bacteriorhodopsin captured by a femtosecond x-ray laser Nogly, Przemyslaw; Weinert, Tobias; James, Daniel Science https://doi.org/10.1126/science.aat0094	journal	June 2018
3D Printed Microfluidics Nielsen, Anna V.; Beauchamp, Michael J.; Nordin, Gregory P. Annual Review of Analytical Chemistry, Vol. 13, Issue 1 https://doi.org/10.1146/annurev-anchem-091619-102649	journal	June 2020
Mix and Inject: Reaction Initiation by Diffusion for Time-Resolved Macromolecular Crystallography Schmidt, Marius Advances in Condensed Matter Physics, Vol. 2013 https://doi.org/10.1155/2013/167276	journal	January 2013
Enzyme intermediates captured “on the fly” by mix-and-inject serial crystallography Olmos, Jose L.; Pandey, Suraj; Martin-Garcia, Jose M. BMC Biology, Vol. 16, Issue 1 https://doi.org/10.1186/s12915-018-0524-5	journal	May 2018
Accurate determination of segmented X-ray detector geometry Yefanov, Oleksandr; Mariani, Valerio; Gati, Cornelius Optics Express, Vol. 23, Issue 22 https://doi.org/10.1364/OE.23.028459	journal	January 2015
Visualizing aerosol-particle injection for diffractive-imaging experiments Awel, Salah; Kirian, Richard A.; Eckerskorn, Niko Optics Express, Vol. 24, Issue 6 https://doi.org/10.1364/OE.24.006507	journal	January 2016
Three-dimensional-printed gas dynamic virtual nozzles for x-ray laser sample delivery Nelson, Garrett; Kirian, Richard A.; Weierstall, Uwe Optics Express, Vol. 24, Issue 11 https://doi.org/10.1364/OE.24.011515	journal	January 2016
Velocimetry of fast microscopic liquid jets by nanosecond dual-pulse laser illumination for megahertz X-ray free-electron lasers Grünbein, Marie Luise; Shoeman, Robert L.; Doak, R. Bruce Optics Express, Vol. 26, Issue 6 https://doi.org/10.1364/OE.26.007190	journal	January 2018
3D printed nozzles on a silicon fluidic chip Bohne, Sven; Heymann, Michael; Chapman, Henry N. American Institute of Physics https://doi.org/10.15480/882.2171	text	January 2019
Megahertz serial crystallography Wiedorn, Max Oliver; Oberthür, Dominik; Bean, Richard Nature Publishing Group UK https://doi.org/10.15480/882.2175	text	January 2018
Rapid sample delivery for megahertz serial crystallography at X-ray FELs Wiedorn, Max Oliver; Awel, Salah; Morgan, Andrew J. TUHH Universitätsbibliothek https://doi.org/10.15480/882.2221	text	January 2018
PHENIX: a comprehensive Python-based system for macromolecular structure solution. Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Apollo - University of Cambridge Repository https://doi.org/10.17863/cam.45787	text	January 2010
Overview of the CCP4 suite and current developments. Winn, Martyn D.; Ballard, Charles C.; Cowtan, Kevin D. Apollo - University of Cambridge Repository https://doi.org/10.17863/cam.52322	text	January 2011
Accurate determination of segmented X-ray detector geometry Yefanov, Oleksandr; Mariani, Valerio; Gati, Cornelius Deutsches Elektronen-Synchrotron, DESY, Hamburg https://doi.org/10.3204/pubdb-2015-04830	text	January 2015
Visualizing aerosol-particle injection for diffractive-imaging experiments Awel, Salah; Kirian, Richard A.; Eckerskorn, Niko Deutsches Elektronen-Synchrotron, DESY, Hamburg https://doi.org/10.3204/pubdb-2015-06272	text	January 2016
Structures of riboswitch RNA reaction states by mix-and-inject XFEL serial crystallography Stagno, J. R.; Liu, Y.; Bhandari, Y. R. Deutsches Elektronen-Synchrotron, DESY, Hamburg https://doi.org/10.3204/pubdb-2016-05392	text	January 2016
Jet delivery system for Raman scattering on bio-inorganic compounds Wetzel, Alina; Biebl, F.; Beyerlein, K. R. Deutsches Elektronen-Synchrotron, DESY, Hamburg https://doi.org/10.3204/pubdb-2016-06119	text	January 2016
Structural enzymology using X-ray free electron lasers Kupitz, Christopher; Olmos, Jose L.; Holl, Mark Deutsches Elektronen-Synchrotron, DESY, Hamburg https://doi.org/10.3204/pubdb-2016-06266	text	January 2017
Mix-and-diffuse serial synchrotron crystallography Beyerlein, Kenneth R.; Dierksmeyer, Dennis; Mariani, Valerio Deutsches Elektronen-Synchrotron, DESY, Hamburg https://doi.org/10.3204/pubdb-2017-10745	text	January 2017
Analysis of XFEL serial diffraction data from individual crystalline fibrils Wojtas, David H.; Ayyer, Kartik; Liang, Mengning Deutsches Elektronen-Synchrotron, DESY, Hamburg https://doi.org/10.3204/pubdb-2017-11523	text	January 2017
Flow-aligned, single-shot fiber diffraction using a femtosecond X-ray free-electron laser Popp, David; Loh, N. Duane; Zorgati, Habiba Deutsches Elektronen-Synchrotron, DESY, Hamburg https://doi.org/10.3204/pubdb-2017-11811	text	January 2017
Femtosecond X-ray diffraction from an aerosolized beam of protein nanocrystals Awel, Salah; Kirian, Richard A.; Wiedorn, Max O. Deutsches Elektronen-Synchrotron, DESY, Hamburg https://doi.org/10.3204/pubdb-2018-01024	text	January 2018
Rapid Sample Delivery for Megahertz Serial Crystallography at X-ray FELs Wiedorn, Max O.; Awel, Salah; Morgan, Andrew J. Deutsches Elektronen-Synchrotron, DESY, Hamburg https://doi.org/10.3204/pubdb-2018-02209	text	January 2018
Megahertz Data Collection from Protein Microcrystals at an X-Ray Free-Electron Laser Grünbein, Marie Luise; Bielecki, Johan; Gorel, Alexander Deutsches Elektronen-Synchrotron, DESY, Hamburg https://doi.org/10.3204/pubdb-2018-03217	text	January 2018
Megahertz serial crystallography Wiedorn, Max O.; Oberthür, Dominik; Bean, Richard Deutsches Elektronen-Synchrotron, DESY, Hamburg https://doi.org/10.3204/pubdb-2018-03705	text	January 2018
Retinal isomerization in bacteriorhodopsin captured by a femtosecond x-ray laser Nogly, Przemyslaw; Weinert, Tobias; James, Daniel Deutsches Elektronen-Synchrotron, DESY, Hamburg https://doi.org/10.3204/pubdb-2018-05837	text	January 2018
A Review on Mixing in Microfluidics Suh, Yong Kweon; Kang, Sangmo Micromachines, Vol. 1, Issue 3 https://doi.org/10.3390/mi1030082	journal	September 2010
Lipidic cubic phase serial millisecond crystallography using synchrotron radiation Nogly, Przemyslaw; James, Daniel; Wang, Dingjie ETH Zurich https://doi.org/10.3929/ethz-b-000102380	text	January 2015
Visualizing aerosol-particle injection for diffractive-imaging experiments Awel, Salah; Kirian, Richard A.; Eckerskorn, Niko arXiv https://doi.org/10.48550/arxiv.1512.06231	text	January 2015
Multimaterial 3D laser microprinting using an integrated microfluidic system Mayer, Frederik; Richter, Stefan; Westhauser, Johann American Association for the Advancement of Science (AAAS) https://doi.org/10.5445/ir/1000090939	text	January 2019

Cited By (2)

Ultracompact 3D microfluidics for time-resolved structural biology Knoška, J. Coherent X-ray Imaging Data Bank (Lawrence Berkeley National Laboratory); CFEL, DESY, Stuttgart University https://doi.org/10.11577/1601629	dataset	January 2019
Ultracompact 3D microfluidics for time-resolved structural biology Knoška, J. Coherent X-ray Imaging Data Bank (Lawrence Berkeley National Laboratory); CFEL, DESY, Stuttgart University https://doi.org/10.11577/1601629	dataset	January 2019

Similar Records

Packaging of electro-microfluidic devices

Patent · 2003 · OSTI ID:921326

Benavides, Gilbert L; Galambos, Paul C; Emerson, John A; +4 more

Packaging of electro-microfluidic devices

Patent · 2001 · OSTI ID:874697

Benavides, Gilbert L; Galambos, Paul C; Emerson, John A; +3 more

Method Of Packaging And Assembling Electro-Microfluidic Devices

Patent · 2004 · OSTI ID:879946

Benavides, Gilbert L; Galambos, Paul C; Emerson, John A; +4 more

Related Subjects

3-D reconstruction
73 NUCLEAR PHYSICS AND RADIATION PHYSICS
Imaging
Lab-on-a-chip
X-ray crystallography
X-ray tomography

Title: Ultracompact 3D microfluidics for time-resolved structural biology

Citation Formats

References (164)

Cited By (2)

Similar Records

Related Subjects