Towards 4D Spatial Omics in Organ-on-Chip platforms

Organ-on-chip systems are emerging as powerful models to study complex biological functions in physiologically relevant microenvironments. Recent advances have enabled continuous monitoring of tissue activity through integrated sensors to provide real-time information on cellular function. However, these platforms typically lack access to the underlying molecular programs that drive observed functional behavior. As a result, dynamic changes in gene expression, cellular state, and tissue heterogeneity remain largely hidden.

This PhD aims to establish a new generation of organ-on-chip platforms capable of 4D spatial genetic analysis, combining spatially resolved molecular information with continuous functional measurements in the same system. The research will investigate and develop multiple in situ molecular interrogation strategies compatible with micro-physiological systems. Potential approaches include localized electroextraction of intracellular RNA or high-content spatial transcriptomic methods following compartmentalized on-chip fixation. Additional molecular profiling approaches will be explored and benchmarked with respect to sensitivity, spatial resolution, invasiveness, and compatibility with long-term tissue culture.

A key objective is the integration of these molecular analysis techniques directly within the organ-on-chip environment, minimizing sample perturbation while preserving spatial context. This will enable the generation of temporally resolved molecular maps that can be correlated with simultaneous physiological and functional measurements obtained from integrated sensing platforms. Ultimately, this work seeks to establish a broadly applicable platform technology that bridges real-time monitoring and spatial genomics, opening new opportunities for advanced disease models, drug discovery, and next-generation organ-on-chip systems.