Development of spheroids and organoids on the microfluidic chip
- Publication Type:
- Thesis
- Issue Date:
- 2021
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Multicellular spheroids and organoids are typical in vitro models widely used in developmental biology, drug screening, precision medicine etc. Regulation and optimisation of these models and their residential microenvironments are crucial to maintaining their functions and behaviours. With the advances in microfabrication technology, microfluidic devices gradually become a useful tool for biomedical engineering of cultured spheroids and organoids. Building the complex multicellular systems on the microfluidic chips offers apparent advantages on these models (showcases in Chapter 1). The aim of this thesis is to implement a series of new designs of microfluidics devices and materials to improve the state-of-art cell co-culture and engineering of spheroids and organoids.
Multicellular spheroids are commonly used in vitro tumour models as they replicate the in vivo tumour. The size of spheroids plays a crucial role in cell responses during drug screening. Chapter 2 reports a method that can generate gradient-sized spheroids on a single chip with microwell arrays. As a liquid dome of cell suspension was formed on the chip, the size of spheroids can be regulated by the position of the microwells under the liquid dome.
Though tumour cells in the native microenvironment can be influenced by neighbouring stromal cells, the conventional co-culture cannot reveal the directional communications due to the random signal diffusion. In Chapter 3, a novel type of microfluidic chip was developed for the unidirectional communication between breast tumour spheroids and stromal cells.
The conventional culture of in vitro models lacks the mechanical cues, especially for the gastrointestinal organoids. In Chapter 4, a microfluidic chip that can mimic intestinal peristalsis was developed for human colon tumour organoids. The chip allows organoids’ high-throughput dynamic culture individually and parallelly in a microwell array.
The matrix that supports 3D cell growth poses another challenge that currently hinders the developments of organoid culture, due to the high cost and batch-to-batch variations. Chapter 5 found that the naturally-derived polymer, alginate, can be used for the mouse mammary tumour organoids, especially for the luminal organoids.
In summary, this thesis has developed a series of microfluidic designs and techniques for spheroids/organoids culture towards their applications in drug screening, cell biology and nanomedicine. This thesis advances the potential of on-chip technology, materials and devices for biomedical engineering.
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