Remarkable progress made in the past few decades in brain research enables the manipulation of neuronal activity in single neurons and neural circuits and thus allows the decipherment of relations between nervous systems and behavior. The discovery of glymphatic and lymphatic systems in the brain and the recently unveiled tight relations between the gastrointestinal (GI) tract and the central nervous system (CNS) further revolutionize our understanding of brain structures and functions. Fundamental questions about how neurons conduct two-way communications with the gut to establish the gut–brain axis (GBA) and interact with essential brain components such as glial cells and blood vessels to regulate cerebral blood flow (CBF) and cerebrospinal fluid (CSF) in health and disease, however, remain. Microfluidics with unparalleled advantages in the control of fluids at microscale has emerged recently as an effective approach to address these critical questions in brain research. The dynamics of cerebral fluids (i.e., blood and CSF) and novel in vitro brain-on-a-chip models and microfluidic-integrated multifunctional neuroelectronic devices, for example, have been investigated. This review starts with a critical discussion of the current understanding of several key topics in brain research such as neurovascular coupling (NVC), glymphatic pathway, and GBA and then interrogates a wide range of microfluidic-based approaches that have been developed or can be improved to advance our fundamental understanding of brain functions. Last, emerging technologies for structuring microfluidic devices and their implications and future directions in brain research are discussed.
Microfluidic technology has established itself as a powerful tool to enable highly precise spatiotemporal control over fluid streams for mixing, separations, biochemical reactions, and material synthesis. 3D printing technologies such as extrusion-based printing, inkjet, and stereolithography share similar length scales and fundamentals of fluid handling with microfluidics. The advanced fluidic manipulation capabilities afforded by microfluidics can thus be potentially leveraged to enhance the performance of existing 3D printing technologies or even develop new approaches to additive manufacturing. This review discusses recent developments in integrating microfluidic elements with several well-established 3D printing technologies, highlighting the trend of using microfluidic approaches to achieve functional and multimaterial 3D printing as well as to identify potential future research directions in this emergent area.
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