In situ continuous biomarker detection and controlled release for in-vitro microfluidic organ-on-chip application

Recent developments in in vitro microfluidic based disease models are opening new horizons to better our understanding of disease mechanisms such as cancer and develop new treatments. These so-called  “organ-on-chip” systems allow to recapitulate intricate cell-cell interactions under physiologically-relevant in vitro conditions and are set to replace in vivo animal testing. However, culturing and assessing tissue functionality in real time, continuously, over days to weeks, remains a challenge. Several groups have reported the integration of oxygen, pH or barrier integrity sensing capabilities with varying degrees of success, but sensitive in situ biomarker detection and quantification remains little explored which limits our understanding of tissue functionality and disease and treatment mechanisms.   

Focusing on cancer disease models, and leveraging recent insights on the secretome of cancer cells (such as glioblastoma multiforme, GBM), this project aims to leverage imec’s existing miniaturized biosensing technologies into a biodevice to capture and quantify in situ, in real time, continuously, the secreted GBM biomarkers of interest with high specificity and provide new insights in modelling disease progression. Furthermore, we envisage that such device could additionally be used to release the captured biomarkers and regulate the tumour microenvironment in a controllable fashion to perturbate cancer cell growth and tumour metastasis.

The student will explore and develop different biofunctionalization techniques and advanced surface chemistry for optimal biomolecule capture and controlled release. Sensing techniques, such as surface plasmon resonance, waveguide-based sensing and electrochemical techniques will be initially used for the assay development. The developed assays will then be demonstrated using 2D and 3D cell culture, with the goal to be further integrated within the wider organ-on-chip ambitions at imec.

The project is highly multidisciplinary, working at the intersection of biosensor development, microfluidic integration and bioengineering of 2D/3D cell constructs.

When required, other molecular biology techniques including quantification of cell growth, immunohistology, ELISA, gene expression analysis by qPCR, multi-omics (e.g. proteomics, lipidomics, sc/snRNA sequencing) and 3D confocal imaging will be employed to gain more insights into the biology of the cells and sensor performances.