MRC-LMB Crystallisation Facility: Technology Overview

Initial screening

The high number of initial crystallisation conditions is key for samples recalcitrant to crystallise and minimise the difficulties observed later during optimisation and screening of crystals. Fabrice Gorrec has investigated a multitude of atypical reagents and generated innovative screen formulations to complement the screens commercially available. The corresponding 96-condition screens were commercialised through MRCT (Morpheus-I, 2009; Pi-minimal and Pi-PEG, 2012; Morpheus-II, 2015; LMB sparse matrix, 2016). Subsequently, there are now 2,016 initial conditions available (i.e. 21 x 96-well plates).

To facilitate high-throughput, a collaboration was established with Hamilton Robotics (2011) to develop a fully automated system that set-up 1-20 crystallisation plates. The system is based on the LabStar liquid-handler, it integrates a Mosquito nanoliter drop dispenser and a plate-sealer (Brandel).

The Labstar can also be used to produced custom-made Pi screens (once they have been formulated with the corresponding applet).

Optimisation

A collaboration was established with the Technology Transfer Parternship Labtech (TTP LT) in 2013 for the development of the liquid-handler ‘Dragonfly’. This innovative robot has a small footprint, user-friendly software and makes optimisation screens faster and more precisely than traditional liquid-handlers. We proceed according to the 4-corner method. We also developed an applet to formulate 6 grid screen across 96 conditions (‘DELTA sampling‘) on the Dragonfly.

To complement the optimisation, we developed additive screens and the corresponding protocols on the LabStar.

Data analysis

The ‘LMB screen DB‘ web-based interface for basic data analysis over results with initial screening has been developed in collaboration with Paul Hart (IT Manager, LMB). Notably, multiple searches of condition formulations can be done at the same time.

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