Emerging Roles of Microfluidics in Brain Research: From Cerebral Fluids Manipulation to Brain-on-a-Chip and Neuroelectronic Devices Engineering

Remarkable progress made in the past few decades in brain research enablesthe manipulation of neuronal activity in single neurons and neural circuits and thus allowsthe decipherment of relations between nervous systems and behavior. The discovery ofglymphatic and lymphatic systems in the brain and the recently unveiled tight relationsbetween the gastrointestinal (GI) tract and the central nervous system (CNS) furtherrevolutionize our understanding of brain structures and functions. Fundamental questionsabout 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 bloodvessels to regulate cerebral bloodflow (CBF) and cerebrospinalfluid (CSF) in health anddisease, however, remain. Microfluidics with unparalleled advantages in the control offluidsat microscale has emerged recently as an effective approach to address these criticalquestions in brain research. The dynamics of cerebralfluids (i.e., blood and CSF) and novelin vitrobrain-on-a-chip models and microfluidic-integrated multifunctional neuroelectronicdevices, for example, have been investigated. This review starts with a critical discussion of the current understanding of several keytopics in brain research such as neurovascular coupling (NVC), glymphatic pathway, and GBA and then interrogates a wide range ofmicrofluidic-based approaches that have been developed or can be improved to advance our fundamental understanding of brainfunctions. Last, emerging technologies for structuring microfluidic devices and their implications and future directions in brainresearch are discussed.

Automated summary

Remarkable progress has been made in brain research to decipher the relations between nervous systems and behavior. The discovery of glymphatic and lymphatic systems in the brain, as well as the connections between the gastrointestinal tract and the central nervous system, has revolutionized our understanding of brain structures and functions. Microfluidics has emerged as an effective approach to address fundamental questions in brain research, such as neurovascular coupling and the gut-brain axis, and has the potential to further advance our knowledge of brain functions.