CSEM CellFactor: Automated Preprocessing of Large Microbiological Entities

CSEM CellFactor

CSEM has developed a modular cell-handling system, CellFactor, to provide automated, high volume processing of large biological entities such as oocytes, fish larvae, cell clusters, tissue samples, and pollen. The system works by combining microfluidics with robotics and generic vision algorithms to achieve automated storage, inspection, sorting, dosing, and microinjection. The system’s automation significantly reduces error rate and enhances throughput by factors compared to today’s manual approach.

In pharmaceutical research or toxicity testing, large single cells, cell clusters, or small single organisms such as Xenopus oocytes or fertilized Zebrafish eggs are becoming new standards. Such biological entities can replace ethically questionable animal testing, while still providing biologically relevant information. As a result, the demand for automated solutions for cell sample preparation is increasing. Currently, the main bottlenecks for widespread usage of large microbiological entities in life science applications are (i) ensuring quality, and (ii) the high costs of manual handling.

Our automatic cell-handling system resolves these two problems: saving time and money and allowing researchers to concentrate on the characterization phase of their experiments. Thanks to our modular system – consisting of three main modules, the CellSorter, the MicroInjector, and the PlateFeeder – single biological entities are delivered-on-demand, making the cost-efficient CellSorter module ideally suited for integration into an automated process.

In one application, named ZebraFactor, the CellSorter is combined with the PlateFeeder to sort wild type and transgenic fertilized Zebrafish eggs, with and without chorion, into 96 multi-well plates. This is accomplished in less than 7 minutes (around 4 seconds per embryo) with a survival rate comparable to manual control (6.6% control, 7.6% cell sorter). Sorting can be based on size alone or, if a more complex self-learning vision algorithm is used, on a multitude of specific characteristics of the fertilized eggs, which normally would require an experienced lab technician to identify.

In another application, named XenoFactor, the CellSorter is combined with the MicroInjector to automatically sort individual Xenopus oocytes based on their quality, and dose the viable ones into a dedicated microinjection carousel where the oocytes are immobilized, microinjected, and finally collected in containers or, again, multi-well plates. The cycle time for one oocyte is about 10 seconds compared to the manual cycle time of 2 minutes (average for quality control, sorting, injecting, and collecting).

Besides offering the technology as it stands for biological entities such as Xenopus oocytes or Zebrafish eggs, CSEM is also interested in working with partners to develop the technology further for other applications and for smaller entities such as cell clusters or single cells.

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