Microfabricated intracortical extracellular matrix-microelectrodes for improving neural interfaces

Abstract

Intracortical neural microelectrodes, which can directly interface with local neural microcircuits with high spatial and temporal resolution, are critical for neuroscience research, emerging clinical applications, and brain computer interfaces (BCI). However, clinical applications of these devices remain limited mostly by their inability to mitigate inflammatory reactions and support dense neuronal survival at their interfaces. Herein we report the development of microelectrodes primarily composed of extracellular matrix (ECM) proteins, which act as a bio-compatible and an electrochemical interface between the microelectrodes and physiological solution. These ECM-microelectrodes are batch fabricated using a novel combination of micro-transfer-molding and excimer laser micromachining to exhibit final dimensions comparable to those of commercial silicon-based microelectrodes. These are further integrated with a removable insertion stent which aids in intracortical implantation. Results from electrochemical models and in vivo recordings from the rat’s cortex indicate that ECM encapsulations have no significant effect on the electrochemical impedance characteristics of ECM-microelectrodes at neurologically relevant frequencies. ECM-microelectrodes are found to support a dense layer of neuronal somata and neurites on the electrode surface with high neuronal viability and exhibited markedly diminished neuroinflammation and glial scarring in early chronic experiments in rats.

Tissue Response to Neural Implants: The Use of Model Systems Toward New Design Solutions of Implantable Microelectrodes

“…The growing scientific interest in neural interfaces in the last decades is confirmed by the multitude of in vivo works focused on the testing of new and fully biocompatible coatings (Du et al, 2017; Spencer et al, 2017b; Shen et al, 2018; Vitale et al, 2018), less invasive implantation strategies (Tawakol et al, 2016; Shoffstall et al, 2018b) and new designs with improved electrical performance (Ferlauto et al, 2018; Xu et al, 2018) and with longer durability.…”

Simple Fabrication of Flexible Biosensor Arrays Using Direct Writing for Multianalyte Measurement from Human Astrocytes

“…Table 1 compares sensor performance parameters for biosensors calibrated in PBS to other enzyme-based biosensors in literature. 5,23,58–61 The upper limit of the linear range of lactate sensors on glass slides is low compared with similar lactate sensors on flexible laminate. Variation in enzyme functionalization may have been the cause.…”

“…Implanted (in vivo) enzymatic biosensors also suffer from biofouling. 41 Physical, 42–44 chemical, 45,46 and biological 47 approaches all have the potential to reduce biofouling and improve biosensor stability during chronic measurement in complex fluids.…”

Graphene Oxide–Based Nanomaterials: An Insight into Retinal Prosthesis

“…In human tissues, the extracellular matrix (ECM), mainly composed of collagen, elastin, and fibronectin, provides a favorable environment for the growth, repair, support, and connection of tissues [64]. In order to enhance tissue-chip integration, some studies have used conductive hydrogels that form a soft interface on the electrode surface that provides a medium for cellular attachment [65][66][67][68][69]. This modification, in addition to facilitating cellular attachment, overcomes electrode limitations in mechanical properties, charge transfer, and charge storage.…”