Prototype development of a novel bio-mimetic Lab-On-Chip for studying cancer metastasis in the breast ductal system.

Abstract

Breast cancer is the most common cancer and the second leading cause of mortality among women after lung cancer. Lab-on-a-chip (LOC) technology is shown to provide a structurally and functionally biomimetic environment that could be easily visualized in real-time. In this project, we designed a novel LOC model, which to our knowledge, is the first to mimic the full 3D ductal system of the human breast, with bio-mimetic structures, tissue types and matrix properties. Our system is composed of a thin porous circular cross-sectional duct, with the capability to assemble the proper extra cellular matrix (ECM) basal membrane, in addition to both the ductal epithelial tissue and the fibrous one on both sides of the duct. This work was carried out through performing several prototyping stages on the LOC model and testing it mechanically and biologically. Initially, several solutions were proposed, and a conceptual design was selected according to a set of needs and specifications. Then, an embodiment design was articulated through many modifications and experimental verification of the selected materials and design parameters. Finally, the detailed design was created after optimizing the manufacturing and assembling process through a large set of experimental iterations. The final design was then re-fabricated, tested mechanistically for leakage and precision, and assessed biologically for cellular viability and attachment. The next step will be optimizing the cellular ductal buildup and the experimental conditions for cancer migration testing. As a conclusion, this chip can be utilized by cancer researchers to study cancer invasion (extravasation and intravasation), metastasis, proliferation and even differentiation. It is designed in a way that can help investigate the prebuilt cellular structure for any specific physical, mechanical or molecular constituents inside and outside the duct in the fibrous tissue. Interestingly, our chip can be used on ductal systems other than breast such as lung, kidneys, glands, pancreas a