Additive manufacturing of microfluidics for evaluation of immunotherapy efficacy

Abstract

This thesis presents the development of an entirely 3D-printed, monolithic microfluidic platform for evaluating the efficacy of immunotherapy treatments. The platform provides a dynamic microenvironment for perfusing and sustaining tumor samples extracted from a biopsy. 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 immunotherapies to a retained tumor fragment. The device configuration is capable of modelling interactions between tumors and various drug treatments. Tested devices were additively manufactured in Pro3dure GR-10 -a relatively new, high-resolution stereolithographic resin with properties suitable for biomedical applications. Retention of human tumor fragments within the printed microfluidic device is confirmed through overlaid bright-field and fluorescence micrographs, which permit visualization of individual tumor cells within the biological sample. Under dynamic perfusion of media, live tumor fragments can be sustained for a period of at least 72 hours. Confocal microscopy confirmed that sustained tumors and the resident lymphocytes exhibited a response to perfused immunotherapy treatments compared to an untreated control. With further validation, the proposed platform may be capable of providing critical predictive insight into an individual's response to selected immunotherapies.