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Microfluidic sample delivery for serial crystallography using XFELs

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Abstract

Serial femtosecond crystallography (SFX) with X-ray free electron lasers (XFELs) is an emerging field for structural biology. One of its major impacts lies in the ability to reveal the structure of complex proteins previously inaccessible with synchrotron-based crystallography techniques and allowing time-resolved studies from femtoseconds to seconds. The nature of this serial technique requires new approaches for crystallization, data analysis, and sample delivery. With continued advancements in microfabrication techniques, various developments have been reported in the past decade for innovative and efficient microfluidic sample delivery for crystallography experiments using XFELs. This article summarizes the recent developments in microfluidic sample delivery with liquid injection and fixed-target approaches, which allow exciting new research with XFELs.

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References

  1. Chapman HN, Fromme P, Barty A, White TA, Kirian RA, Aquila A, et al. Femtosecond X-ray protein nanocrystallography. Nature. 2011;470(7332):73–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Schlichting I. Serial femtosecond crystallography: the first five years. IUCrJ. 2015;2(2):246–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Chapman HN. X-ray free-electron lasers for the structure and dynamics of macromolecules. Annu Rev Biochem. 2019;88(1).

  4. Neutze R, Wouts R, van der Spoel D, Weckert E, Hajdu J. Potential for biomolecular imaging with femtosecond X-ray pulses. Nature. 2000;406(6797):752–7.

    Article  CAS  PubMed  Google Scholar 

  5. Barty A, Kirian RA, Maia FR, Hantke M, Yoon CH, White TA, et al. Cheetah: software for high-throughput reduction and analysis of serial femtosecond X-ray diffraction data. J Appl Crystallogr. 2014;47(3):1118–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. White TA, Kirian RA, Martin AV, Aquila A, Nass K, Barty A, et al. CrystFEL: a software suite for snapshot serial crystallography. J Appl Crystallogr. 2012;45(2):335–41.

    Article  CAS  Google Scholar 

  7. White TA. Processing serial crystallography data with CrystFEL: a step-by-step guide. Acta Crystallogr D Struct Biol. 2019;75(2):219–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Spence JC, Doak RB. Single molecule diffraction. Phys Rev Lett. 2004;92(19):198102.

    Article  CAS  PubMed  Google Scholar 

  9. Bogan MJ, Benner WH, Boutet S, Rohner U, Frank M, Barty A, et al. Single particle X-ray diffractive imaging. Nano Lett. 2008;8(1):310–6.

    Article  CAS  PubMed  Google Scholar 

  10. Johansson LC, Stauch B, Ishchenko A, Cherezov V. A bright future for serial femtosecond crystallography with XFELs. Trends Biochem Sci. 2017;42(9):749–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Barty A, Kupper J, Chapman HN. Molecular imaging using X-ray free-electron lasers. Annu Rev Phys Chem. 2013;64(1):415–35.

    Article  CAS  PubMed  Google Scholar 

  12. Boutet S, Lomb L, Williams GJ, Barends TR, Aquila A, Doak RB, et al. High-resolution protein structure determination by serial femtosecond crystallography. Science. 2012;337(6092):362–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Hunter MS, Segelke B, Messerschmidt M, Williams GJ, Zatsepin NA, Barty A, et al. Fixed-target protein serial microcrystallography with an x-ray free electron laser. Sci Rep. 2014;4(1):6026.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Lee J-H, Zatsepin NA, Kim KH. Time-resolved serial femtosecond X-ray crystallography. BioDesign. 2018;6(1):15–22.

    CAS  Google Scholar 

  15. Altarelli M, Mancuso AP. Structural biology at the European X-ray free-electron laser facility. Philos Trans R Soc Lond Ser B Biol Sci. 2014;369(1647):20130311.

    Article  Google Scholar 

  16. Wiedorn MO, Oberthur D, Bean R, Schubert R, Werner N, Abbey B, et al. Megahertz serial crystallography. Nat Commun. 2018;9(1):4025.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Martiel I, Muller-Werkmeister HM, Cohen AE. Strategies for sample delivery for femtosecond crystallography. Acta Crystallogr D Struct Biol. 2019;75(2):160–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Weierstall U. Liquid sample delivery techniques for serial femtosecond crystallography. Philos Trans R Soc Lond Ser B Biol Sci. 2014;369(1647):20130337.

    Article  Google Scholar 

  19. DePonte DP, Weierstall U, Schmidt K, Warner J, Starodub D, Spence JCH, et al. Gas dynamic virtual nozzle for generation of microscopic droplet streams. J Phys D Appl Phys. 2008;41(19):195505.

    Article  CAS  Google Scholar 

  20. Weierstall U, Spence JC, Doak RB. Injector for scattering measurements on fully solvated biospecies. Rev Sci Instrum. 2012;83(3):035108.

    Article  CAS  PubMed  Google Scholar 

  21. Oberthuer D, Knoška J, Wiedorn MO, Beyerlein KR, Bushnell DA, Kovaleva EG, et al. Double-flow focused liquid injector for efficient serial femtosecond crystallography. Sci Rep. 2017;7(1):44628.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Calvey GD, Katz AM, Schaffer CB, Pollack L. Mixing injector enables time-resolved crystallography with high hit rate at X-ray free electron lasers. Struct Dyn. 2016;3(5):054301.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Lomb L, Steinbrener J, Bari S, Beisel D, Berndt D, Kieser C, et al. An anti-settling sample delivery instrument for serial femtosecond crystallography. J Appl Crystallogr. 2012;45(4):674–8.

    Article  CAS  Google Scholar 

  24. Hutchison CDM, Cordon-Preciado V, Morgan RML, Nakane T, Ferreira J, Dorlhiac G, et al. X-ray free electron laser determination of crystal structures of dark and light states of a reversibly photoswitching fluorescent protein at room temperature. Int J Mol Sci. 2017;18(9):1918.

  25. Beyerlein KR, Adriano L, Heymann M, Kirian R, Knoska J, Wilde F, et al. Ceramic micro-injection molded nozzles for serial femtosecond crystallography sample delivery. Rev Sci Instrum. 2015;86(12):125104.

    Article  CAS  PubMed  Google Scholar 

  26. Wojtas DH, Ayyer K, Liang M, Mossou E, Romoli F, Seuring C, et al. Analysis of XFEL serial diffraction data from individual crystalline fibrils. IUCrJ. 2017;4(6):795–811.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Piotter V, Klein A, Plewa K, Beyerlein KR, Chapman HN, Bajt S. Development of a ceramic injection molding process for liquid jet nozzles to be applied for X-ray free-electron lasers. Microsyst Technol. 2018;24(2):1247–52.

    Article  Google Scholar 

  28. Trebbin M, Kruger K, DePonte D, Roth SV, Chapman HN, Forster S. Microfluidic liquid jet system with compatibility for atmospheric and high-vacuum conditions. Lab Chip. 2014;14(10):1733–45.

    Article  CAS  PubMed  Google Scholar 

  29. Sia SK, Whitesides GM. Microfluidic devices fabricated in poly (dimethylsiloxane) for biological studies. Electrophoresis. 2003;24(21):3563–76.

    Article  CAS  PubMed  Google Scholar 

  30. Nguyen NT, Hejazian M, Ooi CH, Kashaninejad N. Recent advances and future perspectives on microfluidic liquid handling. Micromachines. 2017;8(6):186.

  31. Nelson G, Kirian RA, Weierstall U, Zatsepin NA, Farago T, Baumbach T, et al. Three-dimensional-printed gas dynamic virtual nozzles for x-ray laser sample delivery. Opt Express. 2016;24(11):11515–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Bohne S, Heymann M, Chapman HN, Trieu HK, Bajt S. 3D printed nozzles on a silicon fluidic chip. Rev Sci Instrum. 2019;90(3):035108.

    Article  PubMed  CAS  Google Scholar 

  33. Stagno JR, Liu Y, Bhandari YR, Conrad CE, Panja S, Swain M, et al. Structures of riboswitch RNA reaction states by mix-and-inject XFEL serial crystallography. Nature. 2017;541(7636):242–6.

    Article  CAS  PubMed  Google Scholar 

  34. Kupitz C, Olmos JL Jr, Holl M, Tremblay L, Pande K, Pandey S, et al. Structural enzymology using X-ray free electron lasers. Struct Dyn. 2017;4(4):044003.

    Article  PubMed  CAS  Google Scholar 

  35. Wang D, Weierstall U, Pollack L, Spence J. Double-focusing mixing jet for XFEL study of chemical kinetics. J Synchrotron Radiat. 2014;21(6):1364–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Olmos JL Jr, Pandey S, Martin-Garcia JM, Calvey G, Katz A, Knoska J, et al. Enzyme intermediates captured "on the fly" by mix-and-inject serial crystallography. BMC Biol. 2018;16(1):59.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Ishigami I, Lewis-Ballester A, Echelmeier A, Brehm G, Zatsepin NA, Grant TD, et al. Snapshot of an oxygen intermediate in the catalytic reaction of cytochrome c oxidase. Proc Natl Acad Sci U S A. 2019;116(9):3572–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Kim D, Echelmeier A, Villarreal JC, Gandhi S, Quintana S, Egatz-Gomez A et al. Electric triggering for enhanced control of droplet generation. Anal Chem. 2019, submitted.

  39. Mafune F, Miyajima K, Tono K, Takeda Y, Kohno JY, Miyauchi N, et al. Microcrystal delivery by pulsed liquid droplet for serial femtosecond crystallography. Acta Crystallogr D Struct Biol. 2016;72(4):520–3.

    Article  CAS  PubMed  Google Scholar 

  40. Roessler CG, Agarwal R, Allaire M, Alonso-Mori R, Andi B, Bachega JFR, et al. Acoustic injectors for drop-on-demand serial femtosecond crystallography. Structure. 2016;24(4):631–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Fuller FD, Gul S, Chatterjee R, Burgie ES, Young ID, Lebrette H, et al. Drop-on-demand sample delivery for studying biocatalysts in action at X-ray free-electron lasers. Nat Methods. 2017;14(4):443–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Weierstall U, James D, Wang C, White TA, Wang D, Liu W, et al. Lipidic cubic phase injector facilitates membrane protein serial femtosecond crystallography. Nat Commun. 2014;5(1):3309.

    Article  PubMed  CAS  Google Scholar 

  43. Echelmeier A, Nelson G, Abdallah BG, James D, Roy-Chowdhury S, Tolstikova A, et al. Biphasic droplet-based sample delivery of protein crystals for serial femtosecond crystallography with an x-ray free electron laser. MicroTAS - Int Conf Miniaturized Syst Chem Life Sci. 2015;19:1374–6.

    Google Scholar 

  44. Kubo M, Nango E, Tono K, Kimura T, Owada S, Song C, et al. Nanosecond pump-probe device for time-resolved serial femtosecond crystallography developed at SACLA. J Synchrotron Radiat. 2017;24(5):1086–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Sierra RG, Gati C, Laksmono H, Dao EH, Gul S, Fuller F, et al. Concentric-flow electrokinetic injector enables serial crystallography of ribosome and photosystem II. Nat Methods. 2016;13(1):59–62.

    Article  CAS  PubMed  Google Scholar 

  46. Young ID, Ibrahim M, Chatterjee R, Gul S, Fuller F, Koroidov S, et al. Structure of photosystem II and substrate binding at room temperature. Nature. 2016;540(7633):453–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Ganan-Calvo AM, Montanero JM. Revision of capillary cone-jet physics: electrospray and flow focusing. Phys Rev E Stat Nonlinear Soft Matter Phys. 2009;79(6):066305.

    Article  CAS  Google Scholar 

  48. Sierra RG, Laksmono H, Kern J, Tran R, Hattne J, Alonso-Mori R, et al. Nanoflow electrospinning serial femtosecond crystallography. Acta Crystallogr D Biol Crystallogr. 2012;68(11):1584–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Dao EH, Poitevin F, Sierra RG, Gati C, Rao Y, Ciftci HI, et al. Structure of the 30S ribosomal decoding complex at ambient temperature. Rna. 2018;24(12):1667–76.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. O'Sullivan ME, Poitevin F, Sierra RG, Gati C, Dao EH, Rao Y, et al. Aminoglycoside ribosome interactions reveal novel conformational states at ambient temperature. Nucleic Acids Res. 2018;46(18):9793–804.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Kern J, Alonso-Mori R, Tran R, Hattne J, Gildea RJ, Echols N, et al. Simultaneous femtosecond X-ray spectroscopy and diffraction of photosystem II at room temperature. Science. 2013;340(6131):491–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Landau EM, Rosenbusch JP. Lipidic cubic phases: a novel concept for the crystallization of membrane proteins. Proc Natl Acad Sci U S A. 1996;93(25):14532–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Cherezov V. Lipidic cubic phase technologies for membrane protein structural studies. Curr Opin Struct Biol. 2011;21(4):559–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Stauch B, Cherezov V. Serial femtosecond crystallography of G protein-coupled receptors. Annu Rev Biophys. 2018;47(1):377–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Ishchenko A, Gati C, Cherezov V. Structural biology of G protein-coupled receptors: new opportunities from XFELs and cryoEM. Curr Opin Struct Biol. 2018;51:44–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Sugahara M, Mizohata E, Nango E, Suzuki M, Tanaka T, Masuda T, et al. Grease matrix as a versatile carrier of proteins for serial crystallography. Nat Methods. 2015;12(1):61.

    Article  CAS  PubMed  Google Scholar 

  57. Sugahara M, Song C, Suzuki M, Masuda T, Inoue S, Nakane T, et al. Oil-free hyaluronic acid matrix for serial femtosecond crystallography. Sci Rep. 2016;6(1):24484.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Conrad CE, Basu S, James D, Wang D, Schaffer A, Roy-Chowdhury S, et al. A novel inert crystal delivery medium for serial femtosecond crystallography. IUCrJ. 2015;2(4):421–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Park J, Park S, Kim J, Park G, Cho Y, Nam KH. Polyacrylamide injection matrix for serial femtosecond crystallography. Sci Rep. 2019;9(1):2525.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Nogly P, Panneels V, Nelson G, Gati C, Kimura T, Milne C, et al. Lipidic cubic phase injector is a viable crystal delivery system for time-resolved serial crystallography. Nat Commun. 2016;7(1):12314.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Nango E, Royant A, Kubo M, Nakane T, Wickstrand C, Kimura T, et al. A three-dimensional movie of structural changes in bacteriorhodopsin. Science. 2016;354(6319):1552–7.

    Article  CAS  PubMed  Google Scholar 

  62. Nogly P, Weinert T, James D, Carbajo S, Ozerov D, Furrer A, et al. Retinal isomerization in bacteriorhodopsin captured by a femtosecond x-ray laser. Science. 2018;361(6398):eaat0094.

    Article  PubMed  CAS  Google Scholar 

  63. Suga M, Akita F, Sugahara M, Kubo M, Nakajima Y, Nakane T, et al. Light-induced structural changes and the site of O=O bond formation in PSII caught by XFEL. Nature. 2017;543(7643):131–5.

    Article  CAS  PubMed  Google Scholar 

  64. Tosha T, Nomura T, Nishida T, Saeki N, Okubayashi K, Yamagiwa R, et al. Capturing an initial intermediate during the P450nor enzymatic reaction using time-resolved XFEL crystallography and caged-substrate. Nat Commun. 2017;8(1):1585.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Seibert MM, Ekeberg T, Maia FR, Svenda M, Andreasson J, Jonsson O, et al. Single mimivirus particles intercepted and imaged with an X-ray laser. Nature. 2011;470(7332):78–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Chavas LM, Gumprecht L, Chapman HN. Possibilities for serial femtosecond crystallography sample delivery at future light sources. Struct Dyn. 2015;2(4):041709.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Hantke MF, Hasse D, Maia FRNC, Ekeberg T, John K, Svenda M, et al. High-throughput imaging of heterogeneous cell organelles with an X-ray laser. Nat Photonics. 2014;8(12):943–9.

    Article  CAS  Google Scholar 

  68. Hantke MF, Hasse D, Ekeberg T, John K, Svenda M, Loh D, et al. A data set from flash X-ray imaging of carboxysomes. Sci Data. 2016;3(1):160061.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Kirian RA, Awel S, Eckerskorn N, Fleckenstein H, Wiedorn M, Adriano L, et al. Simple convergent-nozzle aerosol injector for single-particle diffractive imaging with X-ray free-electron lasers. Struct Dyn. 2015;2(4):041717.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Awel S, Kirian RA, Wiedorn MO, Beyerlein KR, Roth N, Horke DA, et al. Femtosecond X-ray diffraction from an aerosolized beam of protein nanocrystals. J Appl Crystallogr. 2018;51(1):133–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Schulz EC, Kaub J, Busse F, Mehrabi P, Muller-Werkmeister HM, Pai EF, et al. Protein crystals IR laser ablated from aqueous solution at high speed retain their diffractive properties: applications in high-speed serial crystallography. J Appl Crystallogr. 2017;50(6):1773–81.

    Article  CAS  Google Scholar 

  72. Grunbein ML, Nass Kovacs G. Sample delivery for serial crystallography at free-electron lasers and synchrotrons. Acta Crystallogr D Struct Biol. 2019;75(2):178–91.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Ghazal A, Lafleur JP, Mortensen K, Kutter JP, Arleth L, Jensen GV. Recent advances in X-ray compatible microfluidics for applications in soft materials and life sciences. Lab Chip. 2016;16(22):4263–95.

    Article  CAS  PubMed  Google Scholar 

  74. Murray TD, Lyubimov AY, Ogata CM, Vo H, Uervirojnangkoorn M, Brunger AT, et al. A high-transparency, micro-patternable chip for X-ray diffraction analysis of microcrystals under native growth conditions. Acta Crystallogr D Biol Crystallogr. 2015;71(10):1987–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Mueller C, Marx A, Epp SW, Zhong Y, Kuo A, Balo AR, et al. Fixed target matrix for femtosecond time-resolved and in situ serial micro-crystallography. Struct Dyn. 2015;2(5):054302.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Roedig P, Ginn HM, Pakendorf T, Sutton G, Harlos K, Walter TS, et al. High-speed fixed-target serial virus crystallography. Nat Methods. 2017;14(8):805–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Lyubimov AY, Murray TD, Koehl A, Araci IE, Uervirojnangkoorn M, Zeldin OB, et al. Capture and X-ray diffraction studies of protein microcrystals in a microfluidic trap array. Acta Crystallogr D Biol Crystallogr. 2015;71(4):928–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Mathews II, Allison K, Robbins T, Lyubimov AY, Uervirojnangkoorn M, Brunger AT, et al. The conformational flexibility of the acyltransferase from the disorazole polyketide synthase is revealed by an X-ray free-electron laser using a room-temperature sample delivery method for serial crystallography. Biochemistry. 2017;56(36):4751–6.

    Article  CAS  PubMed  Google Scholar 

  79. Oghbaey S, Sarracini A, Ginn HM, Pare-Labrosse O, Kuo A, Marx A, et al. Fixed target combined with spectral mapping: approaching 100% hit rates for serial crystallography. Acta Crystallogr Sect D. 2016;72(8):944–55.

    Article  CAS  Google Scholar 

  80. Daewoong N, Chan K, Yoonhee K, Tomio E, Marcus G-J, Jaehyun P, et al. Fixed target single-shot imaging of nanostructures using thin solid membranes at SACLA. J Phys B Atomic Mol Phys. 2016;49(3):034008.

    Article  CAS  Google Scholar 

  81. Górzny MŁ, Opara NL, Guzenko VA, Cadarso VJ, Schift H, Li XD, et al. Microfabricated silicon chip as lipid membrane sample holder for serial protein crystallography. Micro and Nano Eng. 2019;3:31–6.

    Article  Google Scholar 

  82. Schieferstein JM, Pawate AS, Varel MJ, Guha S, Astrauskaite I, Gennis RB, et al. X-ray transparent microfluidic platforms for membrane protein crystallization with microseeds. Lab Chip. 2018;18(6):944–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Denz M, Brehm G, Hemonnot CYJ, Spears H, Wittmeier A, Cassini C, et al. Cyclic olefin copolymer as an X-ray compatible material for microfluidic devices. Lab Chip. 2017;18(1):171–8.

    Article  PubMed  Google Scholar 

  84. Doak RB, Nass Kovacs G, Gorel A, Foucar L, Barends TRM, Grunbein ML, et al. Crystallography on a chip - without the chip: sheet-on-sheet sandwich. Acta Crystallogr D Struct Biol. 2018;74(10):1000–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

Financial support from the STC Program of the National Science Foundation through BioXFEL under Agreement No. 1231306 and the National Institutes of Health Award No. R01GM095583 is gratefully acknowledged.

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Authors and Affiliations

  1. School of Molecular Sciences, Arizona State University, Box 871604, Tempe, AZ, 85287-1604, USA

    Austin Echelmeier, Mukul Sonker & Alexandra Ros

  2. Center for Applied Structural Discovery, The Biodesign Institute, Arizona State University, Box 875001, Tempe, AZ, 85287-7401, USA

    Austin Echelmeier, Mukul Sonker & Alexandra Ros

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Echelmeier, A., Sonker, M. & Ros, A. Microfluidic sample delivery for serial crystallography using XFELs. Anal Bioanal Chem 411, 6535–6547 (2019). https://doi.org/10.1007/s00216-019-01977-x

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