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.