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Review
. 2023 Dec 18;23(24):9911.
doi: 10.3390/s23249911.

Recent Advancements in Graphene-Based Implantable Electrodes for Neural Recording/Stimulation

Md Eshrat E Alahi  1 , Mubdiul Islam Rizu  2 , Fahmida Wazed Tina  3 , Zhaoling Huang  4 , Anindya Nag  5   6 , Nasrin Afsarimanesh  7
Affiliations
Review

Recent Advancements in Graphene-Based Implantable Electrodes for Neural Recording/Stimulation

Md Eshrat E Alahi et al. Sensors (Basel). .

Abstract

Implantable electrodes represent a groundbreaking advancement in nervous system research, providing a pivotal tool for recording and stimulating human neural activity. This capability is integral for unraveling the intricacies of the nervous system's functionality and for devising innovative treatments for various neurological disorders. Implantable electrodes offer distinct advantages compared to conventional recording and stimulating neural activity methods. They deliver heightened precision, fewer associated side effects, and the ability to gather data from diverse neural sources. Crucially, the development of implantable electrodes necessitates key attributes: flexibility, stability, and high resolution. Graphene emerges as a highly promising material for fabricating such electrodes due to its exceptional properties. It boasts remarkable flexibility, ensuring seamless integration with the complex and contoured surfaces of neural tissues. Additionally, graphene exhibits low electrical resistance, enabling efficient transmission of neural signals. Its transparency further extends its utility, facilitating compatibility with various imaging techniques and optogenetics. This paper showcases noteworthy endeavors in utilizing graphene in its pure form and as composites to create and deploy implantable devices tailored for neural recordings and stimulations. It underscores the potential for significant advancements in this field. Furthermore, this paper delves into prospective avenues for refining existing graphene-based electrodes, enhancing their suitability for neural recording applications in in vitro and in vivo settings. These future steps promise to revolutionize further our capacity to understand and interact with the neural research landscape.

Keywords: GFET recording; graphene; implantable electrode; neural recording/stimulation.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 9
Figure 9
In vitro neural recording by graphene transistor arrays. (a) Microscopic image of a dense neuronal network cultured over a GMEA array; (b) a time-series recording of spiking–bursting activity propagating through different network channels [reprinted with permission from [146]]; (c) the design layout of 32 arrays in GFET chip for in vitro recording of neuronal signals; (d) time track recording of an intrinsic neuronal bursting activity displays the alternative burst periods at high frequency and spikes at low frequency and the average AP (red) obtained from 77 individual APs (grey) [reprinted with permission from [151]]; (e) a 3D self-rolled biosensor array fabricated on a sacrificial layer; insets D and S are the drain and source of GFET, respectively; (f) a 3D confocal microscopic image of this biosensor array, scale bar 50 µm; (g) recording of the FPs where Ca2+ fluorescence intensity was continuously recorded as a function of time and average FP peak (red) calculated from 100 peaks (gray) [reprinted with the permission from [154]].
Figure 10
Figure 10
GFET devices were utilized for in vivo electrophysiological mapping. Panel (a) displays a pictorial representation of the SG-GFET array featuring various components. In panel (b), a synchronous LFP (local field potential) was recorded from the cerebral cortex of WAG rats, exhibiting a frequency range of 3–4 Hz [reprinted with the permission from [155]]. (c,d) Optical photographs of the crumpled GFET arrays taken before and after positioning them over the left cortical surface of the rat’s brain. (e) Live monitoring of induced epilepsy activities featuring three distinct phases; the penicillin injection time is marked by the black arrow [reprinted with the permission from [162]]. (f) The experimental configuration depicting the interfacing of the SG-GFET array with the brain, coupled with a custom-built front-end amplifier. (g) Captured recording illustrating a CSD propagating front using a single SG-GFET. Activity within the 1–50 Hz frequency range is depicted in blue (left axis), while wide-band activity (0.001−50 Hz) is represented in black (right axis), alongside the corresponding spectrogram within the 1−50 Hz band. [Reprinted with the permission from [159]]. (h) Array of SG-GFET positioned on the rat cortex. (i) Illustration outlining the SG-GFET prototype for conducting in vivo biocompatibility assessments. (j) The evaluation of discrimination ratio was conducted using the novel object recognition test on various days following the implantation. [Reprinted with the permission from [160]].
Figure 1
Figure 1
Extensive utilization of graphene-based materials in regenerative medicine and tissue engineering. [Reproduced with permission from [71]].
Figure 2
Figure 2
Graphene microelectrodes are utilized for in vitro recording of neural activity. (a) Illustration of the experimental arrangement featuring transparent graphene electrodes seamlessly integrated with an inverted microscope. (b) Images from fluorescence microscopy demonstrate well-established cultured neurons flourishing on the surface of graphene field-effect transistors. [Adapted from [58]. Copyright (2017), with permission from Frontiers].
Figure 3
Figure 3
The porous graphene electrode array is being made. The diagrams below show the steps involved in making the porous graphene electrode array: a photograph showing the finished 64-electrode array is displayed, a tilted scanning electron microscopy (SEM) image of the 64-spot porous graphene array is shown, and impedance measurements of the 64 electrodes were carried out at 1 kHz. (a) Using laser pyrolysis to pattern the graphene; (b) establishing metal interconnects; (c) applying SU-8 encapsulation; (d) Image capturing a created 64-electrode array; (e) Tilted scanning electron microscopy (SEM) depiction of a 64-spot array composed of porous graphene. The inset showcases an SEM view of an individual spot; and (f) Evaluation of impedance for all 64 electrodes at 1 kHz. [Reprinted with the permission of [105]].
Figure 4
Figure 4
Manufacturing and visualizing LCGO brush electrodes. (a) The electrodes are connected to copper wires and insulated with polytetrafluoroethylene, and possess an approximate diameter of 1 mm. This bonding is achieved using a conductive epoxy containing silver. (b) After this bonding, a layer of Parylene C is applied as a protective coating. (c) A laser operating at 250 mW is utilized for ablation. This step opens up the end of the electrode, resulting in the formation of a distinctive ‘brush’ electrode. (d) The application of laser treatment leads to the formation of an amorphous electrode, characterized by an exceptionally high degree of surface irregularities and porosity [reprinted with the permission from [106]].
Figure 5
Figure 5
It illustrates the clear micro-ECoG device, highlighting key fabrication steps. (a) Initial metal patterning on a Parylene C-coated silicon wafer substrate for traces and pads. (b) Sequential stacking of four graphene monolayers. (c) Precise graphene patterning to form electrode locations. [Reprinted with the permission from [88]].
Figure 6
Figure 6
This figure illustrates a multielectrode ERG recording employing a soft and transparent graphene electrode array. The construction of the array involves layered structures (a). The top section displays the array’s optical transparency when positioned over printed paper, with recording sites arranged linearly (b). The bottom part offers an optical microscopy view, emphasizing graphene electrode sites and traces, including an insulated electrode (c). A stripped graphene electrode array is also shown over a dilated rabbit eye (d). The schematic showcases the distribution of recording channels on the rabbit eye, from the temporal area to the nasal periphery (d). [This figure has been adapted from [117]].
Figure 7
Figure 7
In vivo cortical vasculature images were captured using the CLEAR device. Panels (a,c) present the bright-field image of the graphene electrode on the cerebral cortex beneath a cranial window. Correspondingly, panels (b,d) showcase the fluorescence images of the same device as shown in (a,c). The cortical vasculature was visible through the graphene electrode in panels (e,f). A schematic illustrating optical stimulation by blue light with a 473 nm wavelength on the cerebral cortex is provided in panel (g), demonstrating its compatibility with a transparent graphene MEA. Lastly, panel (h) displays the recording of neural signals evoked by blue light via the transparent graphene MEA. (Reproduced with permission from [88]).
Figure 8
Figure 8
The neuronal signals were captured using a TGVH device. Panel (a) exhibits optical images of a custom-designed electrode array composed of patterned graphene. This array comprises 35 distinct graphene electrodes, each with 1 × 1 mm dimensions, accompanied by an internal ground electrode spanning 2.9 mm2, all positioned on a Cr/Pt base electrode. The inset provides a closer view of a single-channel graphene electrode. In panel (b), a topographical AFM image reveals a two-layer graphene electrode, with the inset indicating the thickness of the marked line. Panel (c) displays the finalized TGVH device. Panels (d,e) show FE-SEM images, respectively, of the multielectrode array constructed from vertically aligned carbon nanotubes (VACNT) in its original state and a single VACNT electrode. Finally, panel (f) presents a schematic representation of the TGVH device. [Reprinted with the permission of [132]].
Figure 11
Figure 11
(a) This schematic illustrates the equivalent circuit representing the interface between the probe and neural tissue locations. Only the neural recording process is depicted to simplify the representation, with neurons acting as a voltage source (Ve). However, it is important to note that an analogous neural stimulation circuit can be characterized as well. (b) Depicted here is the scenario of an implantable neural device failure, along with its corresponding equivalent circuit.
Figure 12
Figure 12
(a) Illustration depicting the process of graphene electrode fabrication. (b) Electrocardiogram (ECG) of a zebrafish heart. (Reprinted with the permission from [171]). The adhesion of graphene on the electrode has been enhanced, a crucial factor for ensuring long-term implantation. (Reproduced with permission from [171]).
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