At MDC, we have developed a multimodal advanced microscopy approach to combine high-resolution microscopy with complex cell model development. Using laser scanning confocal microscopy for 3D visualisation and high content spinning disk for drug screening, we have determined drug action, deconvoluted targets and further characterised cell models. Moreover, we have developed bespoke image analysis workflows for validation and quantification of drug response. The combination of these methods provides a powerful approach with multiple outputs to detail novel drug actions and cellular drug targets. 

 Here we show, characterisation of a triculture CNS model and a cardiac CMEF microtissue spheroid. Detailed 3D imaging has revealed ultrastructural arrangement of CNS tricultures containing a cell network of iPSC-derived neurons, astrocytes and microglia. Using 3D visualisation software, we could examine neuronal and microglia processes, allowing the measurement of morphological changes due to neuroinflammation, disease or drug treatments. Similarly, we have observed intra-spheroid formation of an endothelial component in the CMEF model alongside live visualisation of calcium and cellular displacement (nuclei and actin) during contraction. For both models, the increase in complexity and innovative imaging analysis may demonstrate their improved utility for drug screening or mechanism of action studies.