Engineering localized injury: a 3D microfluidic platform approach for ex vivo tissue interrogation

Over the years, interrogating and replicating biological events ex vivo and in vitro has proven to provide a breadth of knowledge into various mechanisms of diseases; however, there remains a challenge in understanding the onset of disease within tonic, localized environments over time. Microfluidics provides an alternative approach that can be coupled with many methods to better replicate specific localized and prolonged biological events. In this work, we introduce a novel 3D-printed device that significantly improves upon previous microfluidic approaches aimed at maintaining high spatial resolution and sustainment of delivery, ultimately enabling us to examine localized injuries within an ex vivo model with higher precision and control. This work focuses on focal ischemia; however, it should be noted that the device is applicable to any event that needs high spatial resolution and sustained fluidic delivery. We demonstrate that tissue remains viable on this platform and that we are capable of achieving exquisite fluidic control, not affordable from standard lithographic techniques. Additionally, we incorporate real-time neurochemical monitoring to demonstrate rapid and robust changes in dopamine signaling at the site of focal ischemia, further validating our platform for localized injury studies. This device fills a critical gap in the existing literature by significantly improving upon the capabilities of localized tissue stimulation and further enhances our understanding of local physiological changes during ischemic events, providing a critical advance in biomedical tools for measuring at localized regions within tissue.