Lumen-based microfluidics for cancer-on-chip devices

INTRODUCTION:Most breast cancer related deaths are not caused directly by primary tumor, but by secondary tumors formedthrough metastasis to other organs [1]. Metastasis is a complex cascade that we still poorly understand due to the limitations ofcurrent in-vitro models. Hence, we focus on modeling cancer metastasis on a chip, via introducing the relevant physiologicalfactors in the tumor microenvironment. To obtain such a model, we exploit our 3D sugar-printing technology to create luminalchannels with circular cross section to mimic (micro) vasculature and breast duct in ductal carcinoma.METHODS:We use 3D sugar printing technology [2] to create sugar glass structures that subsequently form perfusable lumens.These carbohydrate glass structures can be cast either in Extra Cellular Matrix (ECM), or synthetic polymers; after the ECMmaterial or synthetic polymer is cross-linked and the sugar glass is selectively dissolved, hollow perfusable lumens are obtained.When the lumens are seeded with endothelial cells, they form the (micro) vasculature. Combined with either a neighboring lumenfor cancer cell culture, the process of cancer invasion, migration through ECM, and intravasation can be studied. Furthermore,neighboring lumens can be filled with different types of hydrogels or cell types to mimic the pre-invasive and invasive cancermicroenvironment.RESULTS:We have developed a vessel and duct with 3D luminal geometry where cell-cell tight junctions are present, as a basisfor further study to recapitulate metastatic cascade.DISCUSSION & CONCLUSIONS:Cancer-on-Chip devices enable us to mimic key biophysical characteristics of the breast cancermicroenvironment. We use 3D sugar printing to create lumens directly in the ECM which enables us to study the invasion andsubsequent intravasation. This way, we avoid using synthetic materials which often have drawbacks for cellular experiments.However, casting lumens or other circular structures in synthetic polymers, is still a feasible option. Lumen channels with roundcross section provide more biophysical-alike perfusion. ECM structure and properties are expected to play a role in breast cancerinvasion, and our model composed of multiple cell types and different concentrations of hydrogels can potentially lead to betterunderstanding of pre-invasive and invasive breast cancer. Our model has also the capability to add more components of the in vivocancer microenvironment, such as immune cells or oxygen gradients