Authors

K Paterson¹; J Beinarovica¹; A Sim²; M Zagnoni¹; 
¹ ScreenIn3D, UK;  ² AMSBIO-Oncoscreen, UK

Discussion

The need for physiologically relevant 3D, complex in vitro models is steadily increasing due to the emergence of drugs targeting the immune system and the tumour microenvironment. Further, an increasing interest in precision treatment of cancer patients has highlighted the need for microfluidic technologies capable of maximising generation of 3D tumour models from the small cell number contained in needle biopsies. We have developed ONCO-Chip3D, a versatile microfluidic platform for high quality and multiplexed screening assays on spheroids, organoids, co-cultures and primary tumour fragments (tumoroids). When using cell suspensions, hundreds of 3D models are created within 24-48 hours within a microfluidic cell culture array. When using tumoroids, these are seeded directly into the array according to their size. The platform is designed for self-generation of drug concentration gradients, lending itself to miniaturised drug combination studies using small amounts of patient’s tissue and creating cost-effective and fast immune-oncology assays. Readouts, such as the model volume, phenotype and viability, are generated from in house developed software prior to tissue retrieval, using brightfield and epifluorescence 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; 2) 3D co-cultures of several cell types were optimised in our platform to mechanistically study responses of the tumour microenvironment; 3) CAR-T cells were used to assess their target specificity and cytotoxicity in 3D co-cultures; 4) ovarian tumour tissue fragments were cultured for precision medicine purposes. These examples show the screening capabilities of the ONCO-Chip3D technology and especially its potential for extensive drug combination studies and precision medicine applications.