Shifting the crystallography bottleneck with miniaturization and automation

In this article, Chris Waddling, head of our North American FAS Team, writes about his experience managing a core facility for crystallography prior to joining SPT Labtech and the benefits of automated and miniaturized workflows.

Miniaturizing crystallization experiments 

In my previous life as a manager of a crystallography core facility, one of my duties was to find the latest equipment that would remove hurdles in the way of my users' progress toward their scientific goals. In 2005, after decades of pipetting by hand, we acquired our first piece of automation: the cutting-edge, five-position mosquito® crystal. Miniaturizing our crystallization experiments saved on reagents and gave us 10x more screen conditions out of every protein prep.

These were early days for automated crystal drop-setting equipment, and, without doubt, the mosquito crystal was the best fit for our growing multi-user facility. As we explored more crystallization conditions, we discovered our workflow bottleneck shifted from protein preparation and crystal drop setup to viewing drops on a consistent basis.

Being accustomed to using a stereomicroscope to examine 1-2µL drops in 24-well plates, we didn't appreciate how much more effort was required to view and score 200nL drops in our 96-well plates. We quickly found ourselves spending more time at the microscope or missing days of crystal growth because we had so many drops to look at.

As we grew from 7 to well over 30 research groups using the facility, our need increased for robust, automated imaging of our crystal trays. We needed a solution that would allow us to track crystal growth remotely and give us the ability to score drops in an electronic notebook database.

The expansion of our instrumentation in 2014 to include a mosquito LCP and, in 2015, a dragonfly® crystal and MXOne mixer increased our capabilities, but also our output and need for automated imaging. To address this need, we added two imaging hotels to the lab's compliment of instrumentation. At its peak, the users of the facility were setting around 30K crystallization drops per month, and we were easily keeping up with demand.

A complete solution for crystallography

As with the imagers in my former lab, the fully automated Jansi UVEX PS-256 and PS-640 hotel systems, the manual UVEX-M and the automated UVEX-P standalone imagers (all now offered through SPT Labtech in North America), relieve the crystal viewing, tracking, and scoring bottleneck for every crystallography lab.

The UVEX imagers all have arguably the best visible and UV images in crystallography work seamlessly with the dragonfly crystal, and each come with CrystalDetect software that is intuitive and easy to learn and use. All without a cumbersome and costly annual software service agreement.

The University of Washington was one of our customers who were early adopters of the Jansi imagers. The Jansi PS-600 allows them to monitor 860 plates (~240000 drops) that have been set up using their mosquito LCP. From there, they can optimize potential hits with the dragonfly crystal. According to Alex Kang, the main user of the crystallography lab:

"The combination of these instruments has simplified the workflow and dramatically improved the pace at which we can go from initial screening to structure determination. Particularly during this time of COVID, but even prior, the ability to monitor our plates remotely has been enormously helpful and allowed us to continue to track crystal development when not able to work on site." 

Alex Kang | Research Engineer | Baker Lab at University of Washington-Seattle

The c2005 mosquito crystal in my former lab is still in use, having seen more than 3 million tips pass through it over the past fifteen years. The first-generation humidity chamber that we used is still there too, as is the mosquito® LCP and its active humidity chamber.

If I were setting up the lab today, I'd include the purpose-built mosquito® Xtal3 and mosquito® LCP each fitted with the all-new precise humidity chamber that raises that bar on humidification. The dragonfly would be there too, of course, as would its indispensable little brother the MXOne mixer. To round it all out would be one Peltier-cooled Jansi UVEX PS-640 at 4C and one at room temperature. This complete crystallography lab would be well suited to generate structures for decades to come.

Want to automate your crystallography workflow?

If you'd like to learn more about streamlining your workflows and fully automating your laboratory's protein crystallization screening, take a look at our proven miniaturization solutions. For a tailored discussion of your requirements, get in touch with us by clicking the link below. We'd love to hear from you.

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