Lumina-Chip - a tubular lumen-based microfluidic approach for enhanced physiological relevance in modeling cancer metastasis

Organ-on-Chip (OoC) systems are advanced in vitro models containing compartments and microchannels in which the in vivo characteristics of the microenvironment of human organs are emulated to enhance physiological relevance. OoC models often include microchannel-based vessels and ducts with rectangular cross-sections, and therefore these lack the geometry and morphology found in tubular structures in vivo. Channels with round cross sections can better mimic the physiology and cellular behavior of tubular structures, such as (micro)vessels and breast ducts, via providing a more in vivo-like geometry and a uniform wall shear stress under physiological flow conditions. Here, we utilize femtosecond laser machining to integrate tubular lumens in an Organ-on-Chip device; our "Lumina-Chip" contains two tubular lumens, both connected to a central channel along their entire length. This versatile fabrication technique enables us to obtain a medium-throughput version of the device including nine Lumina-Chips. Compared with rectangular channels, culture of endothelial cells in our tubular channels results in better cell coverage along the entire channel cross section and therefore better integrity of the endothelium, as well as in different cell morphology and alignment due to the channel curvature. Permeability analysis shows that the vessel wall in the Lumina-Chip has good barrier functionality. We demonstrate the we can use the Lumina-Chip to mimic and observe breast cancer invasion from a breast duct (formed in the first lumen, lined with normal epithelial cells), into extracellular matrix (formed by collagen I in the central channel), and subsequent intravasation into a vessel (formed in the second lumen, lined with endothelial cells). Two types of cancer cells (invasive and non-invasive) show distinctly different behavior throughout this process. We demonstrate our model with cancer metastasis, but it also can be useful for other biological applications in which epithelial ducts and vessels are essential components.