Monolithic, 3D-Printed microfluidic platform for recapitulation of dynamic tumor microenvironments

Abstract

We report the development of an entirely 3D-printed, monolithic microfluidic platform that provides a dynamic microenvironment for perfusing and sustaining tumor fragments from a biopsy sample. The finely featured, non-cytotoxic, and transparent tumor trap is integrated with threaded connectors for rapid, leak-proof fluid interfacing, an in-line trap for removal of bubbles arising from oxygenated media flow or tumor loading procedures, and a network of microchannels for supplying media (and potentially immune cells) to the trapped tumor fragment. The devices were additively manufactured in Pro3dure GR-10-a relatively new, high-resolution stereolithographic resin with properties suitable for biomedical applications requiring interrogation via fluorescence microscopy. Overlaid bright-field and fluorescence microscopy images demonstrate trapping of human tumor fragments by the printed microfluidic device, as well as visualization of individual cells within the fragment. A multi-day trapping experiment evidences the ability to sustain a live tumor fragment under dynamic perfusion within the device-a configuration capable of modeling of interactions between tumors and various drug treatments in the presence of circulating immune cells, e.g., for assessment of the efficacy of chemotherapy and immunotherapy treatments. [2018-0048]