University of Twente Student Theses


Versatile microfluidic circulation to valuate tumor cross-talk using a multi-organ-on-chip approach

Schepop, L. van de (2021) Versatile microfluidic circulation to valuate tumor cross-talk using a multi-organ-on-chip approach.

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Abstract:Breast cancer is the most common cancer among women. Cancer metastases often determine the severity of the disease: rather than the primary tumor, cancer metastases account for 90% of cancer related death. Metastasis is a complex process depending on the primary tumor, the tumor microenvironment and secondary organs. Many distinct properties are required to establish successful dissemination. Rather than random distribution, tumor cells show organ preferential dissemination. This is partially explained by mechanical factors such as organ perfusability and shear stresses, but cellular and molecular processes, regarding both primary and secondary organ, play an important role as well. However, despite the evident clinical importance of metastasis research, knowledge on the biological processes involved in metastasis is limited. Current research focuses on mimicking the metastatic cascade in vitro. What is still missing, however, is a dynamic circulation that mimics all steps in the metastatic cascade and thus the complexity of tumor progression. Here, an automated circulation that is compatible with multiple organ-on-a-chip models is presented. The circulation can provide unidirectional flow and physiological shear stresses. By re-circulating medium, cross-talk between organs can be established. Sampling of the circulation can be performed on-demand for cellular and molecular analysis to eventually gain insight into the cross-organ communication processes. HEPES buffering is used to maintain culture conditions outside a conventional incubator. The efficiency and cytotoxicity of HEPES buffering is assessed first in 2D culture for all associated cell types. A vessel mimicking organ module is presented that is compatible with the circulation. The vessel module consists of a collagen hydrogel with a cylindrical lumen coated with endothelial cells. Viability and morphology is examined for both static vessel models and models subjected to shear corresponding to a flow of 30 µL/min. Morphological changes are observed for endothelium subjected to shear for 24 h, that are associated with better reproduction of the in vivo behavior of endothelium. Additionally, a future design aimed to recapitulate the breast tumor microenvironment, that is compatible with the circulation, is discussed. These results demonstrate the efficacy of the circulation as a promising tool to study cancer metastasis, but also display the versatility of the circulation to be used for a wide variety of conditions comprising organ cross-talk.
Item Type:Essay (Master)
Faculty:TNW: Science and Technology
Subject:30 exact sciences in general, 42 biology, 50 technical science in general
Programme:Biomedical Engineering MSc (66226)
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