The Material-Tissue Interface is Key to Bioelectronic Implant Performance

Neural interfaces form the material-tissue interface between electronic and biological circuits and systems. They must provide stable and reliable functional interfaces to the target structure in chronic implantations both in neuroscience experiments and especially in human clinical applications. Proper selection of substrate, insulation, and electrode materials is of paramount importance. In addition, aspects such as size, thickness, and shape contribute significantly to structural biocompatibility. To establish intimate contact with neural targets, minimize post-implantation foreign body reaction, and maintain functionality throughout the implantation period, a comprehensive set of design parameters must be considered. Our work focused on polyimide as the substrate and insulating material with integrated thin film metallization as the conductor in our flexible neural interface approach. Iridium oxide, carbon, and PEDOT serve as electrode coatings, depending on the intended electrode size and application. The scientific goal is not to compete for the smallest neural probes, but to balance size, stability, and usability for each individual animal model and neural target area. The results on the designs for epicortical and intracortical probes showed that the elastic modulus of a material is not the correct descriptor for predicting brain damage, but that the thickness of the probe relative to the brain curvature is a better parameter. The width of the probes in intracortical implants at a given thickness affects the foreign body response, but the size does not necessarily need to be miniaturized to its limits to minimize scarring. This trade-off increases robustness in handling and improves translation of developments to daily use in neuroscience laboratories and implementation in first-in-human studies to investigate new research hypotheses. Data from long-term aging studies and chronic experiments demonstrate the applicability and reliability of thin-film implants for stimulation and recording studies.<br/>Assembling systems and connecting microsystems with robust cables and connectors remains a major challenge in both chronic preclinical and clinical studies. The components from the probe to the input of the recording system are as important as the probe itself to ensure proper signal quality and avoid crosstalk and interference that distort the signal and impede data analysis. The results of a system analysis showed that the miniaturized probe was not the cause of the crosstalk, but the intermediate stages of the connection to the recording system.<br/>We present recordings of neuronal signals over months with high signal-to-noise ratios obtained for both local field potentials as well as for spikes and single unit activity. Stimulation in human clinical studies over a period of up to six months has demonstrated the stability of iridium oxide sites and the integrity of the metal-polymer multilayer film using silicon carbide as an adhesion promoter. The results are encouraging to continue the translational research path from basic studies to the first human clinical trials, which are necessary to prove that new materials, technologies and devices are applicable in clinical applications and can eventually be translated into an approved medical device.