Toward guiding principles for the design of biologically-integrated electrodes for the central nervous system

Abstract

Innovation in electrode design has produced a myriad of new and creative strategies for interfacing the nervous system with softer, less invasive, more broadly distributed sites with high spatial resolution. However, despite rapid growth in the use of implanted electrode arrays in research and clinical applications, there are no broadly accepted guiding principles for the design of biocompatible chronic recording interfaces in the central nervous system (CNS). Studies suggest that the architecture and flexibility of devices play important roles in determining effective tissue integration: device feature dimensions (varying from ‘sub’- to ‘supra’-cellular scales, <10 µm to >100 µm), Young’s modulus, and bending modulus have all been identified as key features of design. However, critical knowledge gaps remain in the field with respect to the underlying motivation for these designs: (1) a systematic study of the relationship between device design features (materials, architecture, flexibility), biointegration, and signal quality needs to be performed, including controls for interaction effects between design features, (2) benchmarks for success need to be determined (biological integration, recording performance, longevity, stability), and (3) user results, particularly those that champion a specific design or electrode modification, need to be replicated across laboratories. Finally, the ancillary effects of factors such as tethering, site impedance and insertion method need to be considered. Here, we briefly review observations to-date of device design effects on tissue integration and performance, and then highlight the need for comprehensive and systematic testing of these effects moving forward.

Immunohistological and Ultrastructural Study of the Inflammatory Response to Perforated Polyimide Cortical Implants: Mechanisms Underlying Deterioration of Electrophysiological Recording Quality

“…Simultaneous recordings of electrophysiological signals from many individual neurons and their stimulation in freely behaving subjects over timespans of months and years are critical to progress in basic and clinically oriented brain research ( Lebedev and Nicolelis, 2017 ; Thompson et al, 2020 ). Most currently available in vivo multi-electrode array (MEA) implants suffer from a number of drawbacks ( Jorfi et al, 2015 ; Seymour et al, 2017 ; Campbell and Wu, 2018 ; Wellman et al, 2018 ; Hong and Lieber, 2019 ).…”

Next-Generation Diamond Electrodes for Neurochemical Sensing: Challenges and Opportunities

“…Biofouling is a key determinant of sensitivity, and both protein and cellular adhesion have the potential to interrupt the performance of implanted sensors. Glial scarring and neuronal loss can contribute to noise and effectively isolate the sensor from target electrical and neurochemical signals [ 155 , 156 ]. The glial encapsulation can extend up to several hundred microns from the implant center [ 157 ], which is typically ~10–100× the electrode size.…”

“…Fabrication of an electrode implant with small dimensions, which improves mechanical flexibility through reduced bending stiffness, is one solution to minimize the inflammatory response and prolong the functional lifetime of the device. In neural sensing applications, subcellular dimensions have been shown to facilitate a reduced tissue response to implanted electrode arrays [ 156 ]. Carbon-based electrodes with small feature sizes (7 micron diameter) have demonstrated minimal observable gliotic scarring and improved integration into surrounding brain tissue in comparison to traditional, silicon-based electrodes [ 162 ].…”

Flexible, diamond-based microelectrodes fabricated using the diamond growth side for neural sensing

“…While the underlying mechanism has yet to be determined, it is possible that the topographical cues presented by the granular MCD surface may promote neuronal maturation and neurite elongation 50,51 . However, the underlying mechanism has yet to be determined in future studies, and it is possible that the surface chemistry, material stiffness, and/or conductivity also play a role in this result 52,53 . Overall, the MCD and Parylene C substrates performed as expected in vitro and supported neuronal growth and maturation similarly to the control conditions.…”