High-throughput selective cell isolation based on imprinted microfluidics and fluorescence microscopy

Presentation on HEiKA Day 2018

Functional analysis of biological samples for diagnostic or research purposes often requires the isolation of small cell populations from heterogeneous mixtures. Traditionally, this is accomplished using either flow cytometry or microdissection/manipulation performed using microscopes. Flow cytometry-based cell sorters provide unparalleled throughput, but the information output is very limited when it comes to subcellular organization and cellular structures. This information can be collected through cell sorting using microscopy-based cell enrichment methods. However, these methods lack the required throughput for the analysis of large, complex samples and usually require expensive equipment.
In this interdisciplinary project, we aim to develop a fluorescence microscope with the ability to image and isolate highly parameterized subpopulations of phenotypic cell mixtures in real time. Cell imaging will be accomplished using roll-to-roll fabricated flexible microfluidic devices with an integrated cell immobilization mechanism for high throughput and high image resolution. The microfluidic chips will be designed, fabricated, and tested in house. Selective cell isolation will be achieved by directing a high energy laser beam onto cells exhibiting an unwanted phenotype, killing them, and thereby removing them from the pool. The remaining subpopulation of cells will be collected alive for further propagation and analysis. This process will be completely automated and repeated as many times as necessary using the same microfluidic device until the desired cell population has been isolated.
This cell isolation microscope will be developed and tested in the context of basic cell biology, but the impact of the successful development of such a system is expected to extend far beyond basic research into applications such as drug development and cancer research. 

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