ComplexEye: a multi-lens array microscope for high-throughput cell migration analysis

Autonomous migration is an essential immune cell function and has important roles in numerous diseases, for example, enabling neutrophils to access sites of infection. The ability to routinely measure or target immune cell migration would offer a wealth of clinical applications such as to predict adverse outcomes related to sepsis1 or the aggressiveness of human cancer2. Cell migration is most efficiently measured by time-lapse microscopy, but commercial video microscopes cannot generate enough videos to permit high-throughput analyses, making them unsuitable for clinical measurements. ComplexEye is a multi-lens array microscope that allows phenotypic high-throughput migration screens and routine migration analyses for clinical or experimental settings.

A key feature of ComplexEye is the ability to move the optics and lighting, by mounting them on a motorized XYZ stage, around a stationary well-plate holder. This enables imaging of 64 wells of a 384-well plate at one frame per 8 seconds, the minimum frame rate required to capture the rapid migration of human neutrophils in the presence of a bacterial trigger. To avoid focus drifts caused by uneven heating, the system is housed in a standard cell-culture-grade tempered cabinet, which allows us to closely regulate the temperature. The system is also energy efficient; it can simultaneously generate 64 videos using the same amount of energy that a conventional system uses to record 4 videos. With this system, we were able to screen 1,000 different substances in just 4 days and identified 12 compounds that strongly reduce the motility of human neutrophils in response to the chemotactic peptide N-formylmethionine-leucyl-phenylalanine. A conventional one-lens system would have taken 60 times longer.

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