Human induced pluripotent stem (hiPS) cell-based organoids have recently emerged as a promising model system to recapitulate the structure and function of actual biological tissues and organs. These 3D self-organized multi-cellular tissue systems bridge the gap from cell to tissue/organ levels, providing bio-relevant model systems with foreseeable utility in drug discovery, regenerative medicine, and the study of disease pathogenesis, but the increased complexity and unique attributes of each system introduces new challenges in cell culture and experimental reproducibility. While organoids offer profound potential for applications in biological and biomedical research, their scientific value is limited by how closely they mimic the in vivo tissue systems they are intended to model. To achieve a successful organoid-based predictive model system, it is crucial to have a quantitative biochemical and structural analysis technique for single cells and organoids.
In UltraRamanomics, I will develop a robust quantitatively-calibrated bioanalytical platform for high content phenotypic profiling of individual stem cells and hiPS cell-derived organoids, to allow direct structural and quantitative compositional comparison of organoid models in absolute biochemical measurements, thereby addressing the currently unmet analytical need. The platform will be based on micro-Raman spectroscopy – enabling direct measurements of the absolute biochemical composition of single-cells and tissue organoids with unprecedented spatial resolution – to provide a novel analytical solution to the existing gap in stem cell organoid research. This proposal takes full advantage of recent advances in ultraquantitative micro-calibration technology I developed during my PhD, quantitative volumetric Raman imaging (qVRI) methodology developed by the Stevens Group, and the organoid-on-a-chip platform in development at the Centre of Excellence Hybrid Technology Hub with the Krauss Group (Secondment).
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