Advertisement

First experiences with semi-autonomous robotic harvesting of protein crystals

  • Robert Viola
  • Jace Walsh
  • Alex Melka
  • Wesley Womack
  • Sean Murphy
  • Alan Riboldi-Tunnicliffe
  • Bernhard Rupp
Article

Abstract

The demonstration unit of the Universal Micromanipulation Robot (UMR) capable of semi-autonomous protein crystal harvesting has been tested and evaluated by independent users. We report the status and capabilities of the present unit scheduled for deployment in a high-throughput protein crystallization center. We discuss operational aspects as well as novel features such as micro-crystal handling and drip-cryoprotection, and we extrapolate towards the design of a fully autonomous, integrated system capable of reliable crystal harvesting. The positive to enthusiastic feedback from the participants in an evaluation workshop indicates that genuine demand exists and the effort and resources to develop autonomous protein crystal harvesting robotics are justified.

Keywords

Protein crystallography Protein crystals Protein crystal harvesting Cryo-protection Flash-cooling Autonomous robotics High throughput crystallography Robotic harvesting Structural biology 

Notes

Acknowledgments

We gratefully acknowledge sponsorship by the NIH National Institute of General Medicine under STTR Phase II Grant No. R42 GM073278-02A1 and supplement. The project was supported by additional contributions from Square One Systems Design, WY, q.e.d. life science discoveries, CA, and k.-k. Hofkristallamt, CA. Additional information and movies can be downloaded from http://www.ruppweb.org/robot/.

References

  1. 1.
    Anderson WF (2009) Structural genomics and drug discovery for infectious diseases. Infect Disord Drug Targets 9:507–517PubMedCrossRefGoogle Scholar
  2. 2.
    Beteva A, Cipriani F, Cusack S, Delageniere S, Gabadinho J, Gordon EJ, Guijarro M, Hall DR, Larsen S, Launer L, Lavault CB, Leonard GA, Mairs T, McCarthy A, McCarthy J, Meyer J, Mitchell E, Monaco S, Nurizzo D, Pernot P, Pieritz R, Ravelli RG, Rey V, Shepard W, Spruce D, Stuart DI, Svensson O, Theveneau P, Thibault X, Turkenburg J, Walsh M, McSweeney SM (2006) High-throughput sample handling and data collection at synchrotrons: embedding the ESRF into the high-throughput gene-to-structure pipeline. Acta Crystallogr D62:1162–1169Google Scholar
  3. 3.
    Bochkarev A, Tempel W (2008) High throughput crystallography at SGC Toronto: an overview. Methods Mol Biol 426:515–521PubMedCrossRefGoogle Scholar
  4. 4.
    Chen W, Peddi A, Zheng YF, Caffrey M (2004) Automating crystal harvesting and mounting for high-Throughput macromolecular crystallography. Intelligent Control and Automation, Proc. 5th World Congress, Hangzhou, P.R. China, 4650–4655Google Scholar
  5. 5.
    Congreve M, Murray CW, Blundell TL (2005) Structural biology and drug discovery. Drug Disc Today 10:895–907CrossRefGoogle Scholar
  6. 6.
    Elsliger M-A, Deacon AM, Godzik A, Lesley SA, Wooley J, Wuthrich K, Wilson IA (2010) The JCSG high-throughput structural biology pipeline. Acta Crystallographica Sect F 66:1137–1142CrossRefGoogle Scholar
  7. 7.
    Garman EF, Pearson AR, Vonrhein C (2010) Experimental phasing and radiation Damage—Proceedings of the CCP4 study weekend. Acta Crystallogr D66:325–501Google Scholar
  8. 8.
    Gittleman MM, Hunter RC, Smith NL, Johnston AP (1999) Robotic harvesting of solids from fluids: US Patent 6,417,007Google Scholar
  9. 9.
    Hiraki M, Kato R, Yamada Y, Matsugaki N, Igarashi N, Wakatsuki S (2005) High-throughput protein crystallography. Acta Crystallogr A61:C149–C150Google Scholar
  10. 10.
    Joachimiak A (2009) High-throughput crystallography for structural genomics. Curr Opin Struct Biol 19:573–584PubMedCrossRefGoogle Scholar
  11. 11.
    Karain WI, Bourenkov GP, Blume H, Bartunik HD (2002) Automated mounting, centering and screening of crystals for high-throughput protein crystallography. Acta Crystallogr D58:1519–1522Google Scholar
  12. 12.
    Kitatani T, Sugiyama S, Matsumura H, Adachi H, Yoshikawa HY, Maki S, Murakami S, Inoue T, Mori Y, Takano K (2008) New technique of manipulating a protein crystal using adhesive material. Appl Phys Express 1:37002CrossRefGoogle Scholar
  13. 13.
    Mallett C, Mickley M, Mosko R, Robbins D, Sterling C, Vondran T, Willis M, Xu J (2007) CrystalMation: capacity, reproducibility and efficiency of a fully integrated automatic high throughput crystallization platform. Acta Crystallogr A63:s117Google Scholar
  14. 14.
    Markley JL, Aceti DJ, Bingman CA, Fox BG, Frederick RO, Makino S, Nichols KW, Phillips GN Jr, Primm JG, Sahu SC, Vojtik FC, Volkman BF, Wrobel RL, Zolnai Z (2009) The center for eukaryotic structural genomics. J Struct Funct Genomics 10:165–179PubMedCrossRefGoogle Scholar
  15. 15.
    Montelione GT, Szyperski T (2010) Advances in protein NMR provided by the NIGMS protein structure initiative: impact on drug discovery. Curr Opin Drug Discov Devel 13:335–349PubMedGoogle Scholar
  16. 16.
    Pflugrath JW (2004) Macromolecular cryocrystallography-methods for cooling and mounting protein crystals at cryogenic temperatures. Methods 34:415–423PubMedCrossRefGoogle Scholar
  17. 17.
    Rees DC, Congreve M, Murray CW, Carr R (2004) Fragment-based lead discovery. Nat Rev Drug Discov 3:660–672PubMedCrossRefGoogle Scholar
  18. 18.
    Rosenbaum G, Alkire R, Evans G, Rotella FJ, Lazarski K, Zhang R, Ginell SL, Duke N, Naday I, Lazarz J, Molitsky MJ, Keefe J, Gonczy J, Rock L, Sanishvili R, Walsh MA, Westbrook E, Joachimiak A (2006) The Structural biology center 19ID undulator beamline: facility specifications and protein crystallographic results. J Synchr Rad 13:30–45CrossRefGoogle Scholar
  19. 19.
    Sauder MJ, Rutter ME, Bain K, Rooney I, Gheyi T, Atwell S, Thompson DA, Emtage S, Burley SK (2008) High throughput protein production and crystallization at NYSGXRC. Methods Mol Biol 426:561–575PubMedCrossRefGoogle Scholar
  20. 20.
    Snell G, Cork C, Nordmeyer R, Cornell E, Meigs G, Yegian D, Jaklevic J, Jin J, Stevens RC, Earnest TE (2004) Automatic sample mounting and alignment system for biological crystallography at a synchrotron source. Structure 12:1–12CrossRefGoogle Scholar
  21. 21.
    Sugahara M, Asada Y, Shimizu K, Yamamoto H, Lokanath NK, Mizutani H, Bagautdinov B, Matsuura Y, Taketa M, Kageyama Y, Ono N, Morikawa Y, Tanaka Y, Shimada H, Nakamoto T, Yamamoto M, Kunishima N (2008) High-throughput crystallization-to-structure pipeline at RIKEN SPring-8 center. J Struct Funct Genomics 9:21–28PubMedCrossRefGoogle Scholar
  22. 22.
    Thorne RE, Stum Z, Kmetko J, O’Neill K, Gillilan R (2003) Microfabricated mounts for high-throughput macromolecular cryocrystallography. J Appl Crystallogr 36:1455–1460CrossRefGoogle Scholar
  23. 23.
    Viola R, Carman P, Walsh J, Frankel D, Rupp B (2007) Automated robotic harvesting of protein crystals—addressing a critical bottleneck or instrumentation overkill? J Struct Funct Genomics 8:145–152PubMedCrossRefGoogle Scholar
  24. 24.
    Viola R, Carman P, Walsh J, Miller E, Benning M, Frankel D, McPherson A, Cudney B, Rupp B (2007) Operator-assisted harvesting of protein crystals using a universal micromanipulation robot. J Appl Cryst 40:539–545CrossRefGoogle Scholar
  25. 25.
    Wang BC, Adams MW, Dailey H, DeLucas L, Luo M, Rose J, Bunzel R, Dailey T, Habel J, Horanyi P, Jenney FE Jr, Kataeva I, Lee HS, Li S, Li T, Lin D, Liu ZJ, Luan CH, Mayer M, Nagy L, Newton MG, Ng J, Poole FL 2nd, Shah A, Shah C, Sugar FJ, Xu H (2005) Protein production and crystallization at SECSG–an overview. J Struct Funct Genomics 6:233–243PubMedCrossRefGoogle Scholar
  26. 26.
    Warkentin M, Berejnov V, Husseini NS, Thorne RE (2006) Hyperquenching for protein cryocrystallography. J Appl Crystallogr 39:805–811PubMedCrossRefGoogle Scholar
  27. 27.
    Warkentin M, Thorne RE (2007) A general method for hyperquenching protein crystals. J Struct Funct Genomics 8:141–144PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Robert Viola
    • 1
  • Jace Walsh
    • 1
  • Alex Melka
    • 1
  • Wesley Womack
    • 1
  • Sean Murphy
    • 2
  • Alan Riboldi-Tunnicliffe
    • 3
  • Bernhard Rupp
    • 4
  1. 1.Square One Systems DesignJacksonUSA
  2. 2.The Johns Hopkins University Applied Physics LaboratoryLaurelUSA
  3. 3.Australian SynchrotronClaytonAustralia
  4. 4.k.-k. HofkristallamtLivermoreUSA

Personalised recommendations