Can Nanofluidic Chemical Release Enable Fast, High Resolution Neurotransmitter-Based Neurostimulation?

Abstract

Artificial chemical stimulation could provide improvements over electrical neurostimulation. Physiological neurotransmission between neurons relies on the nanoscale release and propagation of specific chemical signals to spatially-localized receptors. Current knowledge of nanoscale fluid dynamics and nanofluidic technology allows us to envision artificial mechanisms to achieve fast, high resolution neurotransmitter release. Substantial technological development is required to reach this goal. Nanofluidic technology—rather than microfluidic—will be necessary; this should come as no surprise given the nanofluidic nature of neurotransmission. This perspective reviews the state of the art of high resolution electrical neuroprostheses and their anticipated limitations. Chemical release rates from nanopores are compared to rates achieved at synapses and with iontophoresis. A review of microfluidic technology justifies the analysis that microfluidic control of chemical release would be insufficient. Novel nanofluidic mechanisms are discussed, and we propose that hydrophobic gating may allow control of chemical release suitable for mimicking neurotransmission. The limited understanding of hydrophobic gating in artificial nanopores and the challenges of fabrication and large-scale integration of nanofluidic components are emphasized. Development of suitable nanofluidic technology will require dedicated, long-term efforts over many years.

A multimodal 3D neuro-microphysiological system with neurite-trapping microelectrodes

“…The structure was finally hard-baked in an oven at 170°C for 30 min (ramping up and down at 0.5°C/min) to complete cross-linking for chemical stability 41 and to prevent toxicity 42 .…”

Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design With Modulation, Coding, and Detection Techniques

“…Since there is a need for external pressure source, it is hard to design a practical stand-alone MC-Tx with this setup. Second, this solution does not completely eliminate the IM leakage; hence, Jones and Stelzle [77] suggest the utilization of porous membranes and electrical control of fluids to further improve MC-Tx against IM leakage. Nanoporous graphene membranes can provide molecule selectivity [78] by adjusting the pore size depending on the size of IM.…”

Pioneering medical advances through nanofluidic implantable technologies

“…Artificial brain stimulation has historically relied on electrical means rather than chemical. This has been attributed to the spatial imprecision of microfluidic delivery . However, there are inherent limitations to achieving precise and spatially selective electrical neurostimulation.…”

“…Physiological systems employ chemical neurotransmitter release through ~50 nm nanopores, implying nanofluidic technologies to be the solution. A recent review and commentary by Jones and Stelzle pitched nanofluidic implantables for high‐resolution neurostimulation via precision neurotransmitter release . Experiments and simulations showed rapid propagation (millisecond timeframe) of chemical impulses released from single nanopores.…”