Microfluidic Multielectrode Arrays for Spatially Localized Drug Delivery and Electrical Recordings of Primary Neuronal Cultures

Abstract

Neuropathological models and neurological disease progression and treatments have always been of great interest in biomedical research because of their impact on society. The application of in vitro microfluidic devices to neuroscience-related disciplines provided several advancements in therapeutics or neuronal modeling thanks to the ability to control the cellular microenvironment at spatiotemporal level. Recently, the introduction of three-dimensional nanostructures has allowed high performance in both in vitro recording of electrogenic cells and drug delivery using minimally invasive devices. Independently, both delivery and recording have let to pioneering solutions in neurobiology. However, their combination on a single chip would provide further fundamental improvements in drug screening systems and would offer comprehensive insights into pathologies and diseases progression. Therefore, it is crucial to develop platforms able to monitor progressive changes in electrophysiological behavior in the electrogenic cellular network, induced by spatially localized injection of biochemical agents. In this work, we show the application of a microfluidic multielectrode array (MEA) platform to record spontaneous and chemically stimulated activity in primary neuronal networks. By means of spatially localized caffeine injection via microfluidic nanochannels, the device demonstrated its capability of combined localized drug delivery and cell signaling recording. The platform could detect activity of the neural network at multiple sites while delivering molecules into just a few selected cells, thereby examining the effect of biochemical agents on the desired portion of cell culture.

Intravitreous delivery of melatonin affects the retinal neuron survival and visual signal transmission: in vivo and ex vivo study

“…It is also applied to study the spontaneous activity of neuronal and cardiac cell populations (Andrew et al., 2010 ). This system can simultaneously record the extracellular signals from multiple sites of circuits in real time, increasing spatial detection and thereby providing a robust evaluation of network function (Bruno et al., 2020 ). The key advantage of this technique is the potency to detect and excite large populations of neurons, without causing adverse effects to the tissue.…”

Electrophysiology Read-Out Tools for Brain-on-Chip Biotechnology

“…These devices have also been demonstrated to be suitable for integration of microelectrodes for electrophysiological measurements with single neuron resolution [ 193 ]. More recently, microfluidic MEAs have been developed, which allow simultaneous electrical recording and localized drug delivery [ 194 ] ( Figure 7 C), thanks to which it is possible to address the effect of biochemical modulation of small neuronal ensembles on the overall network activity.…”

“…Along with electrical read-out, BoC platforms should enable probing and modulation of the tissue input/output features. This can be attained by electrical stimulation, by optogenetic approaches (see §5.3) or by localized delivery of specific molecules, e.g., via microfluidics MEAs [ 194 ]. A step further would be implementing closed-loop paradigms to these probing strategies: being based on real-time feed-back from the electrical activity generated by the bioengineered brain tissue, closed-loop paradigms would offer vast possibilities to dynamically interact with the tissue at all levels (molecular, sub-cellular, cellular, sub-network, or network-wide).…”

Microfluidics for core–shell drug carrier particles – a review

“…46 The development of appropriate drug carriers in biomedical applications to reduce the side effects is desirable and has benecial therapeutic effects. [47][48][49] Nanoparticles are essential as drug carriers because of their ability to transport various types of drugs to different parts of the body and release them at the right time. 50,51 Drug delivery is the mechanism or process of delivering a pharmaceutical substance that involves releasing a bioactive agent at the optimal and required rate.…”