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Microfluidic multiplexed cell chips

Final Report Summary - MULTICELL (Microfluidic multiplexed cell chips)

The primary aim of the "Multicell" project was to develop new microfluidic approaches for cellular biology. Starting from the observation that there were too few methods that provided both high-throughput and high-content information on cells, the desire was to build on the microfluidic devices we were developing to fill this gap. In order to reach its goals, the project required bringing together biologists with physicists, engineers, and chemists. This multi-disciplinary group structure allowed us to go beyond simple proof-of-concept ideas and to produce, in fine, a real technology that can be transfered outside our lab. The project advanced along three complementary paths.

1- First towards developing a deeper understanding of droplet and bubble dynamics in microfluidic devices, both on the fast time scales of the flowing drops and on the slow time scales that correspond to the exchange between the different immiscible phases. The results that emerged from this work allowed us to further develop microfluidic tools for producing and manipulating droplets in microchannels and to perform chemical reactions within them. More recent results also provided a fundamental understanding of the exchange between the droplets and their environment. These results will be important in devising ways to control these exchanges when they are unwanted.

2- Second, we invented new ways of obtaining quantitative measurements on cells that are cultured within the microfluidic droplets. The technologies that result from this work emerge directly from the physical insights that we have gained in the group. As such they leverage physical mechanisms that become dominant at microfluidic scales, which makes them robust, cost-effective, and easy to use. The new technologies are equally adaptable for microbiological applications (bacteria, yeast, etc.) and for mammalian cells (human or animal). They allow a new class of questions to be asked about the biological behavior, by combining precise quantification with large statistical significance and fine control of the culture conditions in space and time.

3- Third, we applied our microfluidics knowledge for developing a disruptive platform for three-dimensional (3D) cultures of mammalian cells in the form of cell spheroids. These cutting-edge methods of culturing cells have already been shown to represent cellular behavior in vivo to a much better extent than classical flask cultures. The platform that we have developed combines measurements having a single-cell resolution with large numbers never before obtained for 3D cultures. As such it allows "cytometry" (i.e. measurements on cells) on the scale of the individual cells, of the individual spheroid, as well as on the scale of the whole population, thus providing a global view of the behavior of the cells in their environment. These developments can now serve as a major step towards the "organ-on-a-chip" methods that aim to model the response to a stimulus on the scale of a whole organ, rather than on individual cells.

In summary the project has first advanced scientific knowledge on physical aspects of microfluidics. By doing so it provided new innovations for biological studies that have been demonstrated in several different contexts.