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The advent at 3rd generation synchrotron sources of extremely brilliant beamlines for macromolecular crystallography (MX) has meant that for systems which produce only small crystals, the practice of multi-crystal data collection, in which partial data sets collected from a series of crystals of the same target are merged to produce a final, complete data set, is enjoying a renaissance. In principle such experiments are straightforward. All that is needed is to mount all the crystals required on the sample support, to collect the partial data sets in series and then to merge them to produce the final data set. However, multi-crystal data collection is actually fraught with difficultly. The positions of the crystals on the sample support must be determined; individual partial data sets should be collected without inducing too much radiation damage; and the correct choice of partial data sets to merge in order to produce the best final data set must be made. Here, we describe an automatic pipeline, Mesh&Collect, which facilitates multi-crystal experiments, present newer developments designed to improve the quality of the final data sets obtained, give examples of the successes that can be obtained and describe the pitfalls to be avoided in such experiments.

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