Experiments in Fluids

, Volume 44, Issue 5, pp 675–689 | Cite as

Droplet streams for serial crystallography of proteins

  • U. Weierstall
  • R. B. Doak
  • J. C. H. Spence
  • D. Starodub
  • D. Shapiro
  • P. Kennedy
  • J. Warner
  • G. G. Hembree
  • P. Fromme
  • H. N. Chapman
Research Article

Abstract

Serial diffraction of proteins requires an injection method to deliver analyte molecules—preferably uncharged, fully hydrated, spatially oriented, and with high flux—into a focused probe beam of electrons or X-rays that is only a few tens of microns in diameter. This work examines conventional Rayleigh sources and electrospray-assisted Rayleigh sources as to their suitability for this task. A comparison is made and conclusions drawn on the basis of time-resolved optical images of the droplet streams produced by these sources. Straight-line periodic streams of monodisperse droplets were generated with both sources, achieving droplet diameters of 4 and 1 micrometer, respectively, for the conventional and electrospray-assisted versions. Shrinkage of droplets by evaporation is discussed and quantified. It is shown experimentally that proteins pass undamaged through a conventional Rayleigh droplet source.

References

  1. Aksyonov SA, Williams P (2001) Impact desolvation of electrosprayed microdroplets—a new ionization method for mass spectrometry of large biomolecules. Rapid Commun Mass Spectrom 15:2001–2006CrossRefGoogle Scholar
  2. Angert I, Burmester C, Dinges C, Rose H, Schröder RR (1996) Elastic and inelastic scattering cross-sections of amorphous layers of carbon and vitrified ice. Ultramicroscopy 63:181–192CrossRefGoogle Scholar
  3. Arakawa ET, Tuminello PS, Khare BN, Milham ME (1997) Optical properties of horseradish peroxidase from 0.13 to 2.5 mu m. Biospectroscopy 3:73–80CrossRefGoogle Scholar
  4. Arakawa ET, Tuminello PS, Khare BN, Milham ME (2001) Optical properties of ovalbumin in 0.130–2.50 mu m spectral region. Biopolymers 62:122–128CrossRefGoogle Scholar
  5. Bartell LS, Huang JF (1994) Supercooling of Water Below the Anomalous Range near 226 K. J Phys Chem 98:7455–7457CrossRefGoogle Scholar
  6. Benignos JAC (2005) Numerical simulation of a single emitter colloid thruster in pure droplet cone-jet mode. Ph.D. thesis, Department of Mechanical Engineering, MITGoogle Scholar
  7. Berglund M, Rymell L, Hertz HM (1996) Ultraviolet prepulse for enhanced X-ray emission and brightness from droplet-target laser plasmas. Appl Phys Lett 69:1683–1685CrossRefGoogle Scholar
  8. Berglund M, Rymell L, Hertz HM, Wilhein T (1998) Cryogenic liquid-jet target for debris-free laser-plasma soft X-ray generation. Rev Sci Instrum 69:2361–2364CrossRefGoogle Scholar
  9. Bras W, Diakun GP, Diaz JF, Maret G, Kramer H, Bordas J, Medrano FJ (1998) The susceptibility of pure tubulin to high magnetic fields: a magnetic birefringence and X-ray fiber diffraction study. Biophys J 74:1509–1521CrossRefGoogle Scholar
  10. Bruins AP, Covey TR, Henion JD (1987) Ion spray interface for combined liquid chromatography/atmospheric pressure ionization mass-spectrometry. Anal Chem 59:2642–2646CrossRefGoogle Scholar
  11. Cech NB, Enke CG (2001) Practical implications of some recent studies in electrospray ionization fundamentals. Mass Spectrom Rev 20:362–387CrossRefGoogle Scholar
  12. Chen DR, Pui DYH, Kaufman SL (1995) Electrospraying of conducting liquids for monodisperse aerosol generation in the 4 nm to 1.8 mu-m diameter range. J Aerosol Sci 26:963–977CrossRefGoogle Scholar
  13. Chudobiak MJ (1995) High-speed, medium voltage pulse-amplifier for diode reverse transient measurements. Rev Sci Instrum 66:5352–5354CrossRefGoogle Scholar
  14. Cloupeau M, Prunet-Foch B (1994) Electrohydrodynamic spraying functioning modes—a critical-review. J Aerosol Sci 25:1021–1036CrossRefGoogle Scholar
  15. Cole RB (1997) Electrospray ionization mass spectrometry: fundamentals, instrumentation, and applications. Wiley, New YorkGoogle Scholar
  16. Deponte D, Weierstall U, Starodub D, Warner J, Spence JCH, Doak RB (2007) Gas dynamic virtual nozzle for generation of microscopic droplet streams. submitted to J Appl PhysGoogle Scholar
  17. Dole M, Mack LL, Hines RL (1968) Molecular beams of macroions. J Chem Phys 49:2240–2249CrossRefGoogle Scholar
  18. Dunn RV, Daniel RM (2004) The use of gas-phase substrates to study enzyme catalysis at low hydration. Philos Trans R Soc Lond B Biol Sci 359:1309–1320CrossRefGoogle Scholar
  19. EPA: atmospheric concentrations of particulate matter of 10 micron or less (PM-10) and of 2.5 microns or less (PM 2.5) are available from the EPA. http://www.epa.gov/air/airtrends/aqtrnd95/pm10.html
  20. Faubel M, Kisters T (1989) Non-equilibrium molecular evaporation of carboxylic-acid dimers. Nature 339:527–529CrossRefGoogle Scholar
  21. Faubel M, Schlemmer S, Toennies JP (1988) A molecular-beam study of the evaporation of water from a liquid jet. Z Phys D-At Mol and Clus 10:269–277CrossRefGoogle Scholar
  22. Faubel M, Steiner B (1992) Strong bipolar electrokinetic charging of thin liquid jets emerging from 10 mu-m ptir nozzles. Ber Der Bunsen-Gesellschaft-Phys Chem Chem Phys 96:1167–1172Google Scholar
  23. Faubel M, Steiner B, Toennies JP (1998) Measurement of He I photoelectron spectra of liquid water, formamide and ethylene glycol in fast-flowing microjets. J Electron Spectrosc Rel Phenom 95:159–169CrossRefGoogle Scholar
  24. Faubel M, Steiner B, Toennies JP (1997a) Photoelectron spectroscopy of liquid water, some alcohols, and pure nonane in free micro jets. J Chem Phys 106:9013–9031CrossRefGoogle Scholar
  25. Faubel M, Steiner B, Toennies JP (1997b) The static and dynamic surface composition of formamide–benzyl alcohol and water–formamide liquid mixtures studied by means of HeI photoelectron spectroscopy. Mol Phys 90:327–344CrossRefGoogle Scholar
  26. Fenn JB, Mann M, Meng CK, Wong SF, Whitehouse CM (1989) Electrospray ionization for mass-spectrometry of large biomolecules. Science 246:64–71CrossRefGoogle Scholar
  27. Fienup JR (1982) Phase retrieval algorithms—a comparison. Applied Optics 21:2758–2769Google Scholar
  28. Fienup JR (1987) Reconstruction of a complex-valued object from the modulus of its fourier-transform using a support constraint. J Opt Soc Am A Opt Image Sci Vis 4:118–123Google Scholar
  29. Foster CA, Hendricks CD, Turnbull RJ (1975) Hollow hydrogen spheres for laser-fusion targets. Appl Phys Lett 26:580–581CrossRefGoogle Scholar
  30. Foster CA, Kim K, Turnbull RJ, Hendricks CD (1977) Apparatus for producing uniform solid spheres of hydrogen. Rev Sci Instrum 48:625–631CrossRefGoogle Scholar
  31. Frank J (2002) Single-particle imaging of macromolecules by cryo-electron microscopy. Annu Rev Biophys and Biomol Struct 31:303–319CrossRefGoogle Scholar
  32. French JB, Etkin B, Jong R (1994) Monodisperse dried microparticulate injector for analytical instrumentation. Anal Chem 66:685–691CrossRefGoogle Scholar
  33. Frohn A, Roth N (2000) Dynamics of droplets. Springer, BerlinMATHGoogle Scholar
  34. Fromme P, Yu HQ, DeRuyter YS, Jolley C, Chauhan DK, Melkozernov A, Grotjohann I (2006) Structure of photosystems I and II. C R Chimie 9:188–200Google Scholar
  35. Fuerstenau SD, Benner WH, Thomas JJ, Brugidou C, Bothner B, Siuzdak G (2001) Mass spectrometry of an intact virus. Angewandte Chemie-International Edition 40:542–544Google Scholar
  36. Gerchberg RW, Saxton WO (1971) Phase determination from image and diffraction plane pictures in electron-microscope. Optik 34:275–277Google Scholar
  37. Goff JA, Gratch S (1946) 52nd annual meeting of the American society of heating and ventilating engineers pp 95–122 (New York)Google Scholar
  38. Grisenti RE, Fraga RAC, Petridis N, Dorner R, Deppe J (2006) Cryogenic microjet for exploration of superfluidity in highly supercooled molecular hydrogen. Europhys Lett 73:540–546CrossRefGoogle Scholar
  39. Hager DB, Dovichi NJ (1994) Behavior of microscopic liquid droplets near a strong electrostatic-field—droplet electrospray. Anal Chem 66:1593–1594CrossRefGoogle Scholar
  40. Hager DB, Dovichi NJ, Klassen J, Kebarle P (1994) Droplet electrospray mass-spectrometry. Anal Chem 66:3944–3949CrossRefGoogle Scholar
  41. Hanson E (ed) (1999) Recent progress in ink jet technologies II. Society for imaging science and technology springfield, VAGoogle Scholar
  42. Hemberg O, Hansson BAM, Berglund M, Hertz HM (2000) Stability of droplet-target laser-plasma soft X-ray sources. J Appl Phys 88:5421–5425CrossRefGoogle Scholar
  43. Henderson R (2004) Realizing the potential of electron cryo-microscopy. Q Rev Biophys 37:3–13CrossRefGoogle Scholar
  44. Holstein WL, Hayes LJ, Robinson EMC, Laurence GS, Buntine MA (1999) Aspects of electrokinetic charging in liquid microjets. J Phys Chem B 103:3035–3042CrossRefGoogle Scholar
  45. Howard EI, Cachau RE (2002) Ink-jet printer heads for ultra-small-drop protein crystallography. Biotechniques 33:1302Google Scholar
  46. Iribarne JV, Thomson BA (1976) Evaporation of small ions from charged droplets. J Chem Phys 64:2287–2294CrossRefGoogle Scholar
  47. Keller W, Morgner H, Muller WA (1986) Probing the outermost layer of a free liquid surface—electron-spectroscopy of formamide under He(2(3)S) impact. Mol Phys 57:623–636CrossRefGoogle Scholar
  48. Koch MHJ, Dorrington E, Klaring R, Michon AM, Sayers Z, Marquet R, Houssier C (1988) Electric-field X-ray-scattering measurements on tobacco mosaic-virus. Science 240:194–196CrossRefGoogle Scholar
  49. Kondow T, Mafune F (2000) Structures and dynamics of molecules on liquid beam surfaces. Annu Rev Phys Chem 51:731–761CrossRefGoogle Scholar
  50. Kozhenkov VI, Kirsh AA, Fuks NA (1974) Investigation of monodisperse aerosol formation by electrostatic atomization of liquids. Colloid J USSR 36:1061–1063Google Scholar
  51. Kurkal V, Daniel RM, Finney JL, Tehei M, Dunn RV, Smith JC (2005) Enzyme activity and flexibility at very low hydration. Biophys J 89:1282–1287CrossRefGoogle Scholar
  52. Loo JA (1997) Studying noncovalent protein complexes by electrospray ionization mass spectrometry. Mass Spectrom Rev 16:1–23CrossRefGoogle Scholar
  53. Mafune F, Takeda Y, Nagata T, Kondow T (1992) Formation and ejection of cluster ions from a liquid beam of aniline ethanol solution by laser photoionization. Chem Phys Lett 199:615–620CrossRefGoogle Scholar
  54. Malmqvist L, Rymell L, Hertz HM (1996) Droplet-target laser-plasma source for proximity X-ray lithography. Appl Phys Lett 68:2627–2629CrossRefGoogle Scholar
  55. Middleman S (1998) An introduction to fluid dynamics. Wiley, New YorkGoogle Scholar
  56. Nishioka GM, Markey AA, Holloway CK (2004) Protein damage in drop-on-demand printers. J Am Chem Soc 126:16320–16321CrossRefGoogle Scholar
  57. Ohnesorge Wv (1936) Die bildung von tropfen an düsen und die auflösung flüssiger strahlen. Z Angew Mathematik und Mechanik 16:355–358Google Scholar
  58. Okamoto T, Suzuki T, Yamamoto N (2000) Microarray fabrication with covalent attachment of DNA using bubble jet technology. Nat Biotechnol 18:438–441CrossRefGoogle Scholar
  59. Oomens J, Polfer N, Moore DT, van der Meer L, Marshall AG, Eyler JR, Meijer G, von Helden G (2005) Charge-state resolved mid-infrared spectroscopy of a gas-phase protein. Phys Chem Chem Phys 7:1345–1348CrossRefGoogle Scholar
  60. Rayleigh L (1878) On the instability of jets. Proc London Math Soc 10:4–13CrossRefGoogle Scholar
  61. Ruotolo BT, Giles K, Campuzano I, Sandercock AM, Bateman RH, Robinson CV (2005) Evidence for macromolecular protein rings in the absence of bulk water. Science 310:1658–1661CrossRefGoogle Scholar
  62. Rymell L, Berglund M, Hertz HM (1995) Debris-Free Single-Line Laser-Plasma X-Ray Source for Microscopy. Appl Phys Lett 66:2625–2627CrossRefGoogle Scholar
  63. Rymell L, Hertz HM (1995) Debris elimination in a droplet-target laser-plasma soft-X-ray source. Rev Sci Instrum 66:4916–4920CrossRefGoogle Scholar
  64. Rymell L, Hertz HM (1993) Droplet target for low-debris laser-plasma soft-X-ray generation. Opt Commun 103:105–110CrossRefGoogle Scholar
  65. Siegbahn H, Siegbahn K (1973) ESCA applied to liquids. J Electron Spectr Rel Phenom 2:319–325CrossRefGoogle Scholar
  66. Simonson T (2003) Electrostatics and dynamics of proteins. Reports on Progress in Phys 66:737–787CrossRefGoogle Scholar
  67. Spence JCH, Doak RB (2004) Single molecule diffraction. Phys Rev Lett 92:198102CrossRefGoogle Scholar
  68. Starodub D, Doak RB, Schmidt K, Weierstall U, Wu JS, Spence JCH, Howells M, Marcus M, Shapiro D, Barty A, Chapman HN (2005) Damped and thermal motion of laser-aligned hydrated macromolecule beams for diffraction. J Chem Phys 123Google Scholar
  69. Taylor G (1964) Disintegration of water drops in electric field. Proc R Soc Lond A-Math Phys Sci 280:383–397MATHGoogle Scholar
  70. Trostell B (1995) Vacuum injection of hydrogen micro-sphere beams. Nucl Instrum Methods Phys Res A 362:41–52CrossRefGoogle Scholar
  71. Wilm M, Mann M (1996) Analytical properties of the nanoelectrospray ion source. Anal Chem 68:1–8CrossRefGoogle Scholar
  72. Wilson KR, Rude BS, Smith J, Cappa C, Co DT, Schaller RD, Larsson M, Catalano T, Saykally RJ (2004) Investigation of volatile liquid surfaces by synchrotron X-ray spectroscopy of liquid microjets. Rev Sci Instrum 75:725–736CrossRefGoogle Scholar
  73. Wu JS, Leinenweber K, Spence JCH, O’Keeffe M (2006) Ab initio phasing of X-ray powder diffraction patterns by charge flipping. Nat Mater 5:647–652CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • U. Weierstall
    • 1
  • R. B. Doak
    • 1
  • J. C. H. Spence
    • 1
  • D. Starodub
    • 1
  • D. Shapiro
    • 2
  • P. Kennedy
    • 1
  • J. Warner
    • 1
  • G. G. Hembree
    • 1
  • P. Fromme
    • 3
  • H. N. Chapman
    • 4
  1. 1.Department of PhysicsArizona State UniversityTempeUSA
  2. 2.Advanced Light Source Lawrence Berkeley National LaboratoryBerkeleyUSA
  3. 3.Department of Chemistry and BiochemistryArizona State UniversityTempeUSA
  4. 4.Lawrence Livermore National LaboratoryLivermoreUSA

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