The primary goal of bioprocess cell line development is to obtain high product yields from robustly growing and well-defined clonal cell lines in timelines measured in weeks rather than months. Likewise, high-throughput screening of B cells and hybridomas is required for most cell line engineering workflows. A substantial bottleneck in these processes is detecting and isolating rare clonal cells with the required characteristics. Traditionally, this was achieved by the resource-intensive method of limiting dilution cloning, and more recently aided by semiautomated technologies such as cell sorting (e.g., fluorescence-activated cell sorting) and colony picking. In this paper we report on our novel Cyto-Mine Single Cell Analysis and Monoclonality Assurance System, which overcomes the limitations of current technologies by screening hundreds of thousands of individual cells for secreted target proteins, and then isolating and dispensing the highest producers into microtiter plate wells (MTP). The Cyto-Mine system performs this workflow using a fully integrated, microfluidic Cyto-Cartridge. Critically, all reagents and Cyto-Cartridges used are animal component-free (ACF) and sterile, thus allowing fast, robust, and safe isolation of desired cells.

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Although CCD X-ray detectors can be faster to use, their large-area versions can be much more expensive than similarly sized photographic plate detectors. When indexing X-ray diffraction patterns, large-area detectors can prove very advantageous as they provide more spots, which makes fitting an orientation easier. On the other hand, when looking for single crystals in a polycrystalline sample, the speed of CCD detectors is more useful. A new setup is described here which overcomes some of the limitations of limited-range CCD detectors to make them more useful for indexing, whilst at the same time making it much quicker to find single crystals within a larger polycrystalline structure. This was done by combining a CCD detector with a six-axis goniometer, allowing the compilation of images from different angles into a wide-angled image. Automated scans along the sample were coupled with image processing techniques to produce grain maps, which can then be used to provide a strategy to extract single crystals from a polycrystal.

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