{"title":"Electrical stimulation of neuroretinas with 3D pyrolytic carbon electrodes","authors":"Pratik Kusumanchi, Jesper Guldsmed Madsen, Toke Bek, Stephan Sylvest Keller, Rasmus Schmidt Davidsen","doi":"10.1007/s10544-024-00729-8","DOIUrl":null,"url":null,"abstract":"<div><p>Retinal prosthesis has been one of the medical strategies aimed at restoring some degree of vision for patients affected by retinal degenerative diseases, such as Retinitis Pigmentosa (RP) and age-related macular degeneration (AMD), which are leading causes of irreversible visual loss. In retinal prosthesis, electrical pulses are typically delivered to the retinal neurons via electrodes on the surface of the implant. In this work, we fabricated 3D carbon pillar electrodes by pyrolysis of SU-8 structures defined photolithographically on Si wafers. We then measured compound action potentials induced in porcine neuroretinas stimulated with electrical pulses. The recorded spikes were validated to be biological in origin by adding the voltage-gated sodium-channel blocking agent tetrodotoxin. The minimum threshold voltage needed to effectively stimulate retinal cells, such as retinal ganglion cells, with 3D electrodes was analyzed through systematic investigation of the spike rate and amplitudes as a function of stimulation voltage. 3D electrodes significantly increased spike rate and amplitudes above spontaneous activity in the tissue during stimulation and outperformed the 2D counterpart, both in terms of spike rate and amplitude. Our results indicate a threshold voltage range of 500-600 mV for 1 ms pulses at a frequency of 10 Hz above which a significant increase in spike count was observed. Furthermore, we report an order of magnitude increase in peak-to-peak amplitude for evoked spikes (> 3 mV), compared to spontaneous spikes (∼ 200 µV). Based on numerical integration, we estimate the area under the curve to be ~14 times larger in evoked compound action potentials compared to spontaneous activity. This indicates the relative increase in number of contributing cells to the compound action potential. At a stimulation voltage of 600 mV the spike rate for 3D electrodes was above 10 spikes/channel/s. We hypothesize that the significant difference between 2D and 3D electrodes is not only caused by the higher active electrode surface area of the 3D micropillar electrodes, but also by more intricate contact and interaction with the inner cell layers of the retinal tissue. Our findings indicate that 3D carbon micropillar electrodes are promising for electrical stimulation of the retina.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"27 1","pages":""},"PeriodicalIF":3.0000,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10544-024-00729-8.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomedical Microdevices","FirstCategoryId":"5","ListUrlMain":"https://link.springer.com/article/10.1007/s10544-024-00729-8","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}
引用次数: 0
Abstract
Retinal prosthesis has been one of the medical strategies aimed at restoring some degree of vision for patients affected by retinal degenerative diseases, such as Retinitis Pigmentosa (RP) and age-related macular degeneration (AMD), which are leading causes of irreversible visual loss. In retinal prosthesis, electrical pulses are typically delivered to the retinal neurons via electrodes on the surface of the implant. In this work, we fabricated 3D carbon pillar electrodes by pyrolysis of SU-8 structures defined photolithographically on Si wafers. We then measured compound action potentials induced in porcine neuroretinas stimulated with electrical pulses. The recorded spikes were validated to be biological in origin by adding the voltage-gated sodium-channel blocking agent tetrodotoxin. The minimum threshold voltage needed to effectively stimulate retinal cells, such as retinal ganglion cells, with 3D electrodes was analyzed through systematic investigation of the spike rate and amplitudes as a function of stimulation voltage. 3D electrodes significantly increased spike rate and amplitudes above spontaneous activity in the tissue during stimulation and outperformed the 2D counterpart, both in terms of spike rate and amplitude. Our results indicate a threshold voltage range of 500-600 mV for 1 ms pulses at a frequency of 10 Hz above which a significant increase in spike count was observed. Furthermore, we report an order of magnitude increase in peak-to-peak amplitude for evoked spikes (> 3 mV), compared to spontaneous spikes (∼ 200 µV). Based on numerical integration, we estimate the area under the curve to be ~14 times larger in evoked compound action potentials compared to spontaneous activity. This indicates the relative increase in number of contributing cells to the compound action potential. At a stimulation voltage of 600 mV the spike rate for 3D electrodes was above 10 spikes/channel/s. We hypothesize that the significant difference between 2D and 3D electrodes is not only caused by the higher active electrode surface area of the 3D micropillar electrodes, but also by more intricate contact and interaction with the inner cell layers of the retinal tissue. Our findings indicate that 3D carbon micropillar electrodes are promising for electrical stimulation of the retina.
期刊介绍:
Biomedical Microdevices: BioMEMS and Biomedical Nanotechnology is an interdisciplinary periodical devoted to all aspects of research in the medical diagnostic and therapeutic applications of Micro-Electro-Mechanical Systems (BioMEMS) and nanotechnology for medicine and biology.
General subjects of interest include the design, characterization, testing, modeling and clinical validation of microfabricated systems, and their integration on-chip and in larger functional units. The specific interests of the Journal include systems for neural stimulation and recording, bioseparation technologies such as nanofilters and electrophoretic equipment, miniaturized analytic and DNA identification systems, biosensors, and micro/nanotechnologies for cell and tissue research, tissue engineering, cell transplantation, and the controlled release of drugs and biological molecules.
Contributions reporting on fundamental and applied investigations of the material science, biochemistry, and physics of biomedical microdevices and nanotechnology are encouraged. A non-exhaustive list of fields of interest includes: nanoparticle synthesis, characterization, and validation of therapeutic or imaging efficacy in animal models; biocompatibility; biochemical modification of microfabricated devices, with reference to non-specific protein adsorption, and the active immobilization and patterning of proteins on micro/nanofabricated surfaces; the dynamics of fluids in micro-and-nano-fabricated channels; the electromechanical and structural response of micro/nanofabricated systems; the interactions of microdevices with cells and tissues, including biocompatibility and biodegradation studies; variations in the characteristics of the systems as a function of the micro/nanofabrication parameters.