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

Abstract

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.

Sensors-integrated organ-on-a-chip for biomedical applications

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Human mini-brains for reconstituting central nervous system disorders

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The future is here: Mind control and torture in the digital era

“…Neural implants have multiple applications in medicine, especially related to neurostimulation in motor and sensory disorders, but also epilepsy, and they are in early experimentation stage in depressive and obsessive-compulsive disorders (Costa e Silva & Steffen, 2017). This is a rapidly progressing research area in which biochips and implants are built in new and better materials that produce no tissue rejection, incorporating nanotechnologies to diminish the size and with more powerful software to control and interact with the neural system (Dabbour et al, 2021;Salari et al, 2022;Wan et al, 2021) while, again, there is no international regulation of its use (McGee & Maguire, 2007). The most important concern regarding the use of neuroimplants -not in the near future, for now -is represented by the possibility of controlling an individual's mental functions via wireless waves interacting with the electric activity of the brain.…”