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Microfluidics Flow Control for on-Chip 3D Vascularized Micro Tissues

Creative Commons 'BY' version 4.0 license

The bottleneck for drug discovery and drug screening has prompted the recent surge for organ-on-a-chip 3D in vitro models that recapitulate physiological and disease mechanisms. Among those models, it is critical to incorporate the vascular capillary networks into micro tissue to better recapitulate the in vivo microenvironment. Microfluidics technology has become an important tool to provide better control of mass transport in the microenvironment for nutrient supply and waste removal. However, the current models only mimic certain aspects of in vivo situations. As in vitro models continue to be developed, more complex on-chip vascularized tissues are necessary to provide more precise physiological systems towards the ultimate goal of ‘human-on-a-chip’.

In this dissertation, a series of microfluidic platforms are developed to enable the culturing of large scale vascularized micro tissues. The system is built on a high throughput format integrated with 96-well plate that contains multiple units for parallelization of experiments. The microfluidics channel design of each unit in this system allows co-culture of multiple types of tissue. Here, complex tissues are formed by retaining certain types of tissue in designated regions, and the interaction of different tissue types can be studied by controlling the tissue formation and mass transport of each region. In this dissertation, a novel 3D hydrogel/medium interface and a siphon-based passive pump are developed to overcome these difficulties. Furthermore, oxygen, one of the important factors affecting tissue growth, is controlled to be at a more physiological level. Various physiological or disease models can be built by selecting and combining these microfluidics components, such as compartmentalized micro tumors co-cultured with vasculature, hereditary hemorrhagic telangiectasia induced by high shear stress, vascularized liver model with in vivo liver structure and oxygen gradient, etc.

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