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, noncytotoxic, 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] Index Terms-3D printed MEMS, bioMEMS, cytotoxicity, microfluidics, stereolithography, tumor trap. I. INTRODUCTION M ICROFLUIDICS enable precise manipulation of small volumes of fluid for the investigation and analysis of microscopic physical, chemical, and biological phenomena. Device miniaturization and batch fabrication have traditionally translated into reductions in cost, materials, and time required for experimental execution [1]. These attributes render microfluidic devices promising platforms for clinical investigations, which demand judicious and economical analysis methods-as procurement of biological samples often comes at the expense of a patient's physical and financial well-being.

Presented is the first demonstration of real‐time monitoring of the response of resident lymphocyte populations in biopsied tumor tissue to immunotherapeutic agents in a perfused tumor microenvironment. This technology comprises a microfluidic tumor trapping device constructed from a novel 3D‐printed, transparent, noncytotoxic substrate. The 3D‐printed device sustains viability of biopsied tissue fragments under dynamic perfusion for at least 72 h while enabling simultaneous administration of various drug treatments, illustrating a useful tool for drug development and precision medicine for immunotherapy. Confocal microscopy of the tumor tissue and resident lymphocytes in the presence of fluorescent tracers provides real‐time monitoring of tumor response to various immunotherapies. Devices are additively manufactured in Pro3dure GR‐10 (i.e., a relatively new, high‐resolution stereolithographic resin with properties suitable for biomedical applications), allowing integration of a set of finely featured functional components into a monolithically constructed platform. The presented platform comprises a new methodology for modeling and analyzing tumor response for the improved prediction of patient‐specific immunotherapy efficacy. It is acknowledged that this is the first report of human tumor fragments cultured in a dynamic perfusion system capable of testing the effect of circulating immune checkpoint inhibitors on resident tumor‐infiltrating lymphocytes.

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