A microfluidic platform to upscale screening of patient-derived 3D models

The need for physiologically relevant 3D, complex in vitro models of disease is steadily increasing due to the emergence of drugs targeting the immune system and their microenvironment. Further, an increasing interest in precision treatment of cancer patients has highlighted the need for microfluidic technologies capable of maximising generation and screening of 3D patient-derived models from the small cell number contained in biopsies. We have developed a versatile microfluidic platform for high quality and multiplexed screening assays on spheroid co-cultures, organoids and tissue micro-explants. When using cell suspensions, hundreds of 3D models are created within 24-48 hours within a microfluidic cell culture array. When using explants of preformed organoids, these are seeded directly into the array according to their size. The platform is designed for self-generation of multiple drug concentration gradients, offering a unique system to miniaturize drug combination studies using patient tissue and, at the same time, creating cost-effective and fast immune-oncology assays. Readouts, such as the model volume, phenotype and viability, are generated from platform-specific image analysis software, using epifluorescence or confocal microscopy images. The technology has been validated using a variety of cell sources. As examples of diverse and customisable screens: 1) human prostate biopsies were grown for the screening of clinical therapies on thousands of 3D multicellular structures1; 2) 3D co-cultures of several cell types were optimised in our platform to mechanistically study responses of the tumour microenvironment2; 3) CAR-T cells were used to assess their target specificity and cytotoxicity in 3D co-cultures3; 4) organoids from fresh and frozen tissue were cultured for precision medicine purposes, accelerating time to results. These examples show the screening capabilities of our microfluidic platform and especially its potential for extensive drug combination studies and precision medicine applications. Ultimately, the power of miniaturising combination studies on patient derived models has significant opportunities to produce faster and better preclinical data. References 1) T. Mulholland et al., Sci. Rep., 2018, 8, 14672. 2) E. Kay et l., Nature Metabolism, 2022, 4 (6), 693-710. 3) K. Paterson et al., IEEE OJEMB, 2022, 3, 86-95.

Michele Zagnoni, Ph.D.

Chief Scientific Officer

ScreenIn3D

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A microfluidic platform to upscale screening of patient-derived 3D models
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Open to view video.  |   Closed captions available The need for physiologically relevant 3D, complex in vitro models of disease is steadily increasing due to the emergence of drugs targeting the immune system and their microenvironment. Further, an increasing interest in precision treatment of cancer patients has highlighted the need for microfluidic technologies capable of maximising generation and screening of 3D patient-derived models from the small cell number contained in biopsies. We have developed a versatile microfluidic platform for high quality and multiplexed screening assays on spheroid co-cultures, organoids and tissue micro-explants. When using cell suspensions, hundreds of 3D models are created within 24-48 hours within a microfluidic cell culture array. When using explants of preformed organoids, these are seeded directly into the array according to their size. The platform is designed for self-generation of multiple drug concentration gradients, offering a unique system to miniaturize drug combination studies using patient tissue and, at the same time, creating cost-effective and fast immune-oncology assays. Readouts, such as the model volume, phenotype and viability, are generated from platform-specific image analysis software, using epifluorescence or confocal microscopy images. The technology has been validated using a variety of cell sources. As examples of diverse and customisable screens: 1) human prostate biopsies were grown for the screening of clinical therapies on thousands of 3D multicellular structures [1]; 2) 3D co-cultures of several cell types were optimised in our platform to mechanistically study responses of the tumour microenvironment [2]; 3) CAR-T cells were used to assess their target specificity and cytotoxicity in 3D co-cultures [3]; 4) organoids from fresh and frozen tissue were cultured for precision medicine purposes, accelerating time to results. These examples show the screening capabilities of our microfluidic platform and especially its potential for extensive drug combination studies and precision medicine applications. Ultimately, the power of miniaturising combination studies on patient derived models has significant opportunities to produce faster and better preclinical data.