First experiences with semi-autonomous robotic harvesting of protein crystals

Viola, R.; Walsh, Jace; Melka, Alex; Womack, W C; Murphy, Sean; Riboldi-Tunnicliffe, A.; Rupp, Bernhard

doi:10.1007/s10969-011-9103-5

Cited by 14 publications

(16 citation statements)

References 22 publications

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“…To fully attain this goal, the automation of post-harvesting treatments, including cryoprotection, will be necessary. Methods for robotized crystal cryocooling, including hyper-quenching and dripcryoprotection, have already been described (Viola et al, 2011) and could be incorporated into a fully automated crystal-harvesting system. Alternative approaches that preclude the need to add cryoprotectant solutions have also been proposed and could be explored in this context (Kim et al, 2005;Pellegrini et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…However, the fact that in situ diffraction experiments are carried out at room temperature limits their use to well diffracting crystals. A different approach by Rupp and coworkers is based on the use of a six-axis industrial robot to harvest crystals from crystallization plates into standard crystallization cryoloops in a semi-automated manner (Viola et al, 2007(Viola et al, , 2011. Once harvested, the crystals are subjected to an automated cryoprotection treatment and used for cryogenic X-ray data collection (Viola et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

CrystalDirect: a new method for automated crystal harvesting based on laser-induced photoablation of thin films

Cipriani

Röwer

Landret

et al. 2012

Acta Crystallogr D Biol Crystallogr

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The use of automated systems for crystallization and X-ray data collection is now widespread. However, these two steps are separated by the need to transfer crystals from crystallization supports to X-ray data-collection supports, which is a difficult manual operation. Here, a new approach is proposed called CrystalDirect (CD) which enables full automation of the crystal-harvesting process. In this approach, crystals are grown on ultrathin films in a newly designed vapour-diffusion crystallization plate and are recovered by excision of the film through laser-induced photoablation. The film pieces containing crystals are then directly attached to a pin for X-ray data collection. This new method eliminates the delicate step of `crystal fishing', thereby enabling full automation of the crystal-mounting process. Additional advantages of this approach include the absence of mechanical stress and that it facilitates handling of microcrystals. The CD crystallization plates are also suitable for in situ crystal screening with minimal X-ray background. This method could enable the operational integration of highly automated crystallization and data-collection facilities, minimizing the delay between crystal identification and diffraction measurements. It can also contribute significantly to the advancement of challenging projects that require the systematic testing of large numbers of crystals.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

CrystalDirect: a new method for automated crystal harvesting based on laser-induced photoablation of thin films

Cipriani

Röwer

Landret

et al. 2012

Acta Crystallogr D Biol Crystallogr

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show abstract

“…Selected crystals could then be harvested with a dedicated robot tool, cryo-cooled, and exposed to the beam for DDC. Several examples of crystal harvesting involving robot arms already exist or are under development [79][80][81]. This is a picture that we can already draw if we consider the rapid progress of robotic systems in MX.…”

Section: Bmentioning

confidence: 99%

Recent progress in robot-based systems for crystallography and their contribution to drug discovery

Ferrer¹,

Larive²,

Bowler

et al. 2013

Expert Opinion on Drug Discovery

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The evolution in robot technology, together with progress in X-ray beam performance and software developments, contributes to a new era in macromolecular X-ray crystallography. Highly integrated experimental environments open new possibilities for crystallography experiments. It is likely that it will also change the way this technique will be used in the future, opening the field to a larger community.

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“…One strategy to eliminate the mounting bottleneck has been to avoid the need for transfer entirely, by developing in situ diffraction techniques (Bingel-Erlenmeyer et al, 2011;Michalska et al, 2015;Soliman, Warkentin, Apker, & Thorne, 2011). Other approaches to ex situ screening have tried to design human out of the process, via novel harvesting techniques, or by reproducing the human mounting technique with advanced robotics (Cipriani et al, 2012;Deller & Rupp, 2014;Viola et al, 2011;Viola, Carman, Walsh, Frankel, & Rupp, 2007). Nevertheless, no affordable and scalable solution to the overall bottleneck of crystal transfer has emerged, and the systematic inefficiency of the harvesting step remains.…”

Section: Introductionmentioning

confidence: 99%

The Low-Cost, Semi-Automated Shifter Microscope Stage Transforms Speed and Robustness of Manual Protein Crystal Harvesting

Wright

Collins

Talon

et al. 2019

Preprint

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Synopsis A motorised X/Y microscope stage is presented that combines human fine motor control with machine automation and automated experiment documentation, to transform productivity in protein crystal harvesting. AbstractDespite the tremendous success of x-ray cryocrystallography over recent decades, the transfer of crystals from the drops where they grow to diffractometer sample mounts, remains a manual process in almost all laboratories. Here we describe the Shifter, a semi-automated microscope stage that offers an accessible and scalable approach to crystal mounting that exploits on the strengths of both humans and machines. The Shifter control software manoeuvres sample drops beneath a hole in a clear protective cover, for human mounting under a microscope. By allowing complete removal of film seals the tedium of cutting or removing the seal is eliminated. The control software also automatically captures experimental annotations for uploading to the user's data repository, removing the overhead of manual documentation. The Shifter facilitates mounting rates of 100-240 crystals per hour, in a more controlled process than manual mounting, which greatly extends the lifetime of drops and thus allows for a dramatic increase in the number of crystals retrievable from any given drop, without loss of X-ray diffraction quality. In 2015 the first in a series of three Shifter devices was deployed as part of the XChem fragment screening facility at Diamond Light Source (DLS), where Acta Crystallographica Section D research papers 2 they have since facilitated the mounting of over 100,000 crystals. The Shifter was engineered to be simple, allowing for a low-cost device to be commercialised and thus potentially transformative as many research initiatives as possible.

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First experiences with semi-autonomous robotic harvesting of protein crystals

Cited by 14 publications

References 22 publications

CrystalDirect: a new method for automated crystal harvesting based on laser-induced photoablation of thin films

CrystalDirect: a new method for automated crystal harvesting based on laser-induced photoablation of thin films

Recent progress in robot-based systems for crystallography and their contribution to drug discovery

The Low-Cost, Semi-Automated Shifter Microscope Stage Transforms Speed and Robustness of Manual Protein Crystal Harvesting

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