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MEMSforLife Report Summary

Project ID: 320404
Funded under: FP7-IDEAS-ERC
Country: Switzerland

Final Report Summary - MEMSFORLIFE (Microfluidic systems for the study of living roundworms (Caenorhabditis elegans) and tissues)

The MEMSforLife project was situated at the interface of microengineering and the biomedical field. It aimed at developing microfluidic devices for studying living roundworms (Caenorhabditis elegans), ex vivo cultured liver tissue slices obtained from mice, and formaldehyde/paraffin-fixed human breast cancer tissue slices and tumors. Microfluidic chips, specifically designed for each type of application, form the central component of a computer-controlled platform for accurate dosing of reagents, advanced microscopic observation or other types of detection. Our approach allowed addressing major unsolved problems in biology and medicine.

In particular, semi-automated multi-functional microfluidic platforms have been developed for C. elegans lifespan, development, behavioral and drug studies. Studies were conducted at all worm development stages, starting from the embryonic level, to provide clues to understand the aging process and age-related diseases, for instance. As an example, we analyzed in vivo protein aggregation in a C. elegans model for amyotrophic lateral sclerosis (ALS). Other approaches enabled microfluidic assays for studying signaling via diffusive secreted compounds in C. elegans populations, or high-resolution timelapse imaging of early embryogenesis in conjunction with small molecule cellular division inhibitors. An important achievement was the realization of a highly sensitive nanocalorimetric platform designed for direct on-chip metabolic heat measurements of C. elegans. In this way, we could assess the impact of on-chip worm treatment with specific compounds on the metabolic activity at different larval stages. Furthermore, we were seeking for a more general understanding of particle interactions with different surfaces, including worm cuticles. In the frame of this subproject, we also used arrays of immobilized high-refractive index microspheres as in situ microlenses for optical nanoscopic imaging, and achieved super-resolution imaging of nanostructures with sub-diffraction feature sizes, including subcellular structures.

Living ex vivo cltured tissue slices promise real-time on-chip monitoring of the glucose synthesis process in the liver, a process of primary metabolic importance. In view of the development of living tissue culture chips, we focused on the on-chip implementation of electrochemical detection to quantify uptake or release of compounds from cells-on-paper constructs. This strategy is cheap, versatile (many different cell types can be used) and does not require animal models. For instance, myoblasts were studied as model cells and glucose uptake upon insulin stimulation was observed. Some of our data also showed that molecular motors may be involved in the surface expression of glucose transporters, and therefore in the regulation of glucose levels. Furthermore, a multiscale study of the role of dynamin in the regulation of glucose uptake was performed.

In the field of rapid cancer diagnosis, we focused on fluorescent in-situ hybridization (FISH), which is the gold standard in clinical detection of cancer. We took advantage of a microfluidic tissue processor for applying reagents to breast tissue samples. We demonstrated the advantage of microfluidic protocols with respect to the conventional method. In particular, the incubation time could be shortened to tens of minutes for cell line and human tissue samples corresponding to a reduction by more than a half of the duration of the corresponding step in the classical FISH protocol. We found a good correlation between on-chip experiments and the clinical evaluation results on tissue slides, as provided in a blinded fashion by a pathologist. It is therefore expected that this approach will have a significant impact in future clinical sample management.

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