A Linkable, Polycarbonate Gut Microbiome-Distal Tumor Chip Platform for Interrogating Cancer Promoting Mechanisms

Abstract

Gut microbiome composition has been tied to diseases ranging from arthritis to cancer to depression. However, mechanisms of action are poorly understood, limiting development of relevant therapeutics. Organ-on-chip platforms, which model minimal functional units of tissues and can tightly control communication between them, are ideal platforms to study these relationships. Many gut microbiome models have been published to date but devices are typically fabricated using oxygen permeable PDMS, requiring interventions to support anaerobic bacteria. To address this challenge, a novel platform was developed where the chips were fabricated entirely from gas-impermeable polycarbonate without tapes or gaskets. These chips replicated polarized villus-like structures of the native tissue. Further, they enabled co-cultures of commensal anaerobic bacteria Blautia coccoides on the surface of gut epithelia for two days within a standard incubator. Another complication of PDMS devices is high ad-/absorption, limiting applications in high-resolution microscopy and biomolecule interaction studies. For future communication studies between gut microbiota and distal tumors, an additional polycarbonate chip design was developed to support hydrogel-embedded tissue culture. These chips enable high-resolution microscopy with all relevant processing done on-chip. Designed for facile linking, this platform will make a variety of mechanistic studies possible.