Emerging micro and nanotechnologies in neuroscience: Devices, fabrication methods, and implementation in monitoring of neural activity and drug delivery

Abstract

Neural activity that occur during motor movement, speech, thought, and various other events can be observed in the form of brainwaves composed of synchronized electrical pulses emitted from adjoining communicative neurons. Observations of these brainwaves have been made possible through neurodevices, which can detect changes in electrical and/or mechanical parameters. For decades, the field of neuroscience has been enriched by the utilization of neurotechnologies at the microscale, which has begun to gain further enhancement with the introduction of nanotechnology. For example, microelectrodes were initially used for only extracellular measurements, but over the past decade, developments have been made to also record intracellular signals. Likewise, nanoknives, which gained popularity due to their versatility, can now be used for both fabricating bio-Micro-Electro-Mechanical Systems (MEMS) and also as a neurosurgery tool. Thus, considerable efforts have been made over the years to make micro- and nanosystems reliable, accurate, and sensitive to neural activity. In the late 20th century, several sophisticated technologies, including magnetic resonance imaging (MRI), computed tomography (CT), and intracranial pressure (ICP) monitoring have been integrated with MEMS. Furthermore, existing biotechnologies are being miniaturized at both the system and component level. For example, there is a remarkable interest in the field of neuroscience to utilize microfluidic technology as a diagnostic tool using specimens such as cerebrospinal fluid (CSF). Microfluidic devices are also employed as biocompatible drug delivery systems to target cells, tissues, and organs. This paper summarizes the recent developments in micro- and nano-scale neurotechnologies, including devices, fabrication processes, detection methods, their implementation challenges, in neural stimulation, monitoring, and drug delivery. This review discusses recent developments in micro and nanotechnologies, fabrication methods, and their implementation in neuroimaging, neurostimulation, monitoring of neural activities, and neural drug delivery.

Alternative Brain Slice-on-a-Chip for Organotypic Culture and Effective Fluorescence Injection Testing

“…Specific reagents, such as pharmacological agents or fluorescent dyes, can be dissolved in the reservoir fluid, either by not reaching their optimal concentration or by constantly exposing brain slices to these stimulations. There are brain-on-a-chip devices [ 29 , 30 , 31 ] focused on localized drug application for brain-on-a-chip, but the alternatives for this application in brain slice-on-a-chip cultures are minimal [ 28 , 32 ]. For this reason, it is necessary to develop alternative methodologies for local delivery in fluidic chips for brain slice evaluation without depending on a flow.…”

A Novel PDMS-Based Microfeature-Size Fabrication Method for Biocompatible and Flexible Devices

“…PDMS can be made in different shapes to fit biological tissues. Moreover, its mechanical impedance matching property to soft tissues such as the spinal cord and the oxygen-permeability make it one of the best MEA/neural tissue interfaces [13][14][15]. Other flexible substrate options include parylene-c [16,17], Ecoflex 00-30 [18], silicon elastomers like RTV-2 [19], and so on.…”

Interfacing Neurons with Nanostructured Electrodes Modulates Synaptic Circuit Features

“…[2][3][4] By means of nano-and micro-technologies, the benefits of substrate-integrated extracellular electrode arrays are being combined with those of intracellular electrodes to improve the quality and performance of neural interfaces. [1,5] Importantly, nanotechnology allows for an improved design of lower impedance and a more intimate interface with individual neurons by better mimicking the native extracellular environment. [6] Early studies reported the ability of high-density silicon nanowire (NW) transistor arrays to record signals from up to 50 different spatial points in a single axon.…”

“…[17] Aiming to biomedical applications, the flexibility of the electrodes becomes an essential factor to minimize the mechanical mismatch at the interface and guarantee an effective coupling. [5] In this line, a series of flexible electrodes have been proposed, [18][19][20] but only a few combine flexibility with nanostructure. [21,22,23] For instance, Rogers and colleagues described a bio-interfaced system based on ultrathin electronics supported by bioresorbable substrates of silk fibroin, [18] which assures minimal stresses on the tissue and highly conformal coverage.…”