Sino-Swiss cooperation project

Nano-structured Bio-chip Development for Stem Cells Monitoring

Project Leader:
Giovanni De Micheli, Professor and Director, EPFL-IC-LSI

Partners:

Sandro Carrara, Lecturer and Senior Scientist, EPFL-IC-LSI
(Biomedical circuits and systems)

Cristina Boero, PhD Student, EPFL-IC-LSI
(Biomedical circuits and systems)

Christine Nardini, CAS-MPG Partner Institute for Computational Biology, Shangai, China
(genetic and genomics by using gene network reverse engineering approaches and systemic approaches)

Laura Calzà, Medicine and Veterinary Department, University of Bologna, Italy
(nervous system following experimental investigation also using stem cells)

Presentation:

The aim of this project is to develop a bio-chip for metabolic detection in stem cell culture medium with the purpose of on-line monitoring stem cells differentiation. The final device will appear as an automatic system able to detect metabolic compounds released into the cell medium during the cell differentiation with a parallelism, sensitivity and velocity improved with respect to the present state-of-the-art in cell monitoring biosensors.

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Statistical-Computational Techniques for Extraction of Functional Genomic Units from Microarray Experiments. Stems cells research involves an incredible amount of unknowns, and the complexity of the fundamental activity of differentiations require the use of powerful strategies to shrink down the important pathways involved in this function. For this reason, sensors able to identify the state of such cells cannot preclude from investigating the best target and the final products involved in the process. To identify such best targets, un/differentiated stem cells activity will be observed with microarrays able to measure in one single screen the activity of thousands of coding and non coding transcripts (mRNAs, miRNAs).

Special focus will be given to the bio-chip sensitivity improvement thanks to nanostructures such as carbon nanotubes (CNT). We propose nano-electrodes for stem cell monitoring of the differentiation based on the functionalization of CNT by mean of oxidases and/or reductases and/or esterases and/or cytochromes in order to monitor the cell’s secretoma with an improved sensitivity with respect to the present state-of-the-art in cell monitoring biosensors. CNT are suggested for biosensor improvement because they are a good candidate for promoting heterogeneous electron-transfer to non covalently bound proteins.

Since the actual knowledge on metabolic properties of Pluripotent Embryonic Stem Cells (ESCs) is very poor, in order to test the Bio-chip array, we will use a well known cellular system, e.g. a neural cell lines (SN56) that differentiates in the presence of retinoic acid. Neural cells have a simplified metabolic system, which is based on glucose utilization, only. According to this, glucose deprivation in the culture media produces quite reproducible metabolic changes. This cellular system will be used for testing of the bio-chip.