28 Jun Exploring the Intersection of Microfluidics and Neural Modulation: Advancing Precision in Neuroscience Research

In the ever-evolving realm of neuroscience, understanding and manipulating neural activity is at the forefront of groundbreaking research. Advancements in microfluidic technology for neural modulation have opened up new frontiers in understanding the intricacies of the brain. Enter NeuroStack, an innovative microfluidic-based hardware and software system that is revolutionizing neural modulation studies.

In this recent study published in Nature Biotechnology, researchers have developed a new type of microfluidic chip that can be used to wirelessly modulate neural circuits in the brain and gut. The interface is made up of an integrated microfluidic device which includes polymer fibers that are embedded with solid-state microelectronic components. These components can be used for a variety of purposes, including optogenetics, precision thermometry, electrophysiology, and drug and gene delivery. With its advanced microfluidic fabrication techniques, NeuroStack offers researchers unprecedented opportunities to delve into the mysteries of the brain.

“Our approach uses meters-long continuous fibers that can integrate light sources, electrodes, thermal sensors and microfluidic channels in a miniature footprint. Paired with custom-fabricated control modules, the fibers wirelessly deliver light for optogenetics and transfer data for physiological recording. We validate this technology by modulating the mesolimbic reward pathway in the mouse brain. “, the authors explained. 

The NeuroStack module boasts a custom printed circuit board (PCB) equipped with a wireless microcontroller and optional modules integrated with a microfluidic device for controlling optical intensity. Its seamless connectivity to implanted probes facilitates seamless interaction with brain or gut regions in animal subjects. Powered by rechargeable lithium batteries, the system provides extensive operation time on a single charge.

At the heart of NeuroStack lies a custom printed circuit board (PCB) housing a wireless microcontroller, the MDBT42V, which enables seamless communication with the central system. The circular board features a male header pin for easy connection to implanted microfluidic probes and vertical header pins for attaching optional microfluidic modules. These optional modules provide precise control of fluid flow rates and microscale fluid manipulation, enhancing the versatility of NeuroStack in experimental setups. The integration of µLEDs with microfluidic channels enables stimulation with precise spatiotemporal control, ensuring optimal delivery of biochemical agents or electrical stimuli.

Simplicity meets sophistication in the NeuroStack user interface. Designed with researchers in mind, the user-friendly graphical interface, developed in MATLAB, allows real-time stimulation updates, functionality customization, and comprehensive data recording and analysis. The firmware embedded in the neuromodulation board ensures smooth communication and control between the hardware and user interface.

To validate its efficacy, NeuroStack has undergone rigorous testing in compliance with regulatory committees. Both wild-type mice and transgenic mice have been utilized in a range of experiments involving surgical implantation of microelectronics fibers and microfluidic devices. This integration of microfluidic technology enables precise recording and stimulation of neural activity, facilitating a deeper understanding of brain function and gut dynamics.

NeuroStack has yielded exceptional results in various neural modulation experiments. From electrophysiology and opto-electrophysiology to temperature measurements and feeding studies, the system, enhanced by microfluidic devices and chips, has provided invaluable insights into brain and gut functionality. By manipulating neural activity and observing resultant behavioral changes, researchers have unlocked novel perspectives and potential therapeutic avenues.

“a, High-throughput, monolithic fabrication of multifunctional polymer fibers using thermal drawing yields several tens of meters of continuous fibers (~1,000 rodent-scale probes) with tunable mechanics and solid-state microelectronic components. b, Such fibers can host multiple independently addressable µLEDs for optogenetics, microelectrodes for extracellular electrophysiology, microfluidics for gene/chemical payload delivery and thermal sensors for tissue thermometry—all in a miniature footprint. c, NeuroStack, a custom designed modular wireless control circuit, enables real-time programmable optical stimulation and data transfer for recording of tissue temperature. d, The multifunctional microelectronic fibers together with NeuroStack allow for wireless modulation of neural circuits in the deep-brain and in the small intestine of awake behaving mice.” Reproduced from Sahasrabudhe, A., Rupprecht, L.E., Orguc, S. et al. Multifunctional microelectronic fibers enable wireless modulation of gut and brain neural circuits. Nat Biotechnol (2023). under Creative Commons Attribution 4.0 International License.

NeuroStack stands as a cutting-edge microfluidic technology that empowers researchers in the field of neural modulation research. Its advanced hardware, wireless connectivity, and intuitive user interface provide unparalleled control and precision, enabling a deeper understanding of neural circuits and their functional implications. With its versatile applications and potential impact on neuroscience, NeuroStack opens up new possibilities for unraveling the complexities of the brain and holds promise for future therapeutic interventions.

“We anticipate that with the ever-increasing repertoire of transgenic animals, multifunctional wireless fiber-based tools will provide key insights into the roles of specific cells in bidirectional communication between the peripheral organs and the brain. These tools will empower the study of the enigmatic interoceptive networks in health and disease. “, the authors explained.

Figures are reproduced from Sahasrabudhe, A., Rupprecht, L.E., Orguc, S. et al. Multifunctional microelectronic fibers enable wireless modulation of gut and brain neural circuits. Nat Biotechnol (2023).  under Creative Commons Attribution 4.0 International License.

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