Characterization tools and paradigms for understanding the neural electrode-tissue interface

Intracortical microelectrode arrays record and stimulate neurons; however, the chronic performance of these devices is still significantly limited by tissue integration and material failures. We seek to understand the changes at the tissue-device interface that contribute to the foreign body response to implanted probes and the degradation of electrode materials. This requires multimodal analysis including:

• in vivo 2-photon imaging
• post-mortem histology
• electrophysiology
• electrochemical characterization
• in vitro aging
• explant analysis such as scanning electron microscopy

These analyses allow us to develop and evaluate new strategies for improving the long-term performance of neural interfaces including:

• Bioactive coatings (carbohydrates and protein)
• Drug-loaded nanoparticles
• Anti-fouling zwitterionic polymer coatings
• Microfabrication of flexible microelectrode arrays
• Electrode site modifications (PEDOT/PSS, PEDOT/CNT, Nano-platinum)

SEM analysis of metal trace degradation on an explanted silicon probe.

Michelson et al 2019

2-Photon imaging of calcium activity (Thy1-GCaMP6) following probe insertion.

Eles et al 2018

Evaluating the tissue response to a superoxide-scavenging (iSODm) coating using histology.

Zheng et al 2019

Single unit waveforms recorded from a PEDOT/CNT flexible microelectrode array.

Wu et al 2024

Example publications include:

• Kevin Woeppel, Vaishnavi Dhawan, Delin Shi, Xinyan Tracy Cui. Nanotopography-enhanced biomimetic coating maintains bioactivity after weeks of dry storage and improves chronic neural recording. September 2023. Biomaterials. [Link]
• Daniela Krahe, Kevin M. Woeppel, Qianru Yang, Neetu Kushwah, and Xinyan Tracy Cui. Melatonin Decreases Acute Inflammatory Response to Neural Probe Insertion. Antioxidants 11, no. 8: 1628. 2022. [Link]
• Neetu Kushwah, Kevin Woeppel, Vaishnavi Dhawan, Delin Shi, Xinyan Tracy Cui. Effects of neuronal cell adhesion molecule L1 and nanoparticle surface modifcation on microglia. Acta Biomaterialia. 2022. [Link]
• Kevin Woeppel, Christopher Hughes, Angelica J Herrera, James R Eles, Elizabeth C Tyler-Kabara, Robert A Gaunt, Jennifer L Collinger, Xinyan Tracy Cui, Explant analysis of Utah electrode arrays implanted in human cortex for brain-computer-interfaces. Frontiers in Bioengineering and Biotechnology, 07 December 2021 
• Qianru Yang, Alberto Vazquez, Xinyan Tracy Cui. Long-term in vivo Two-Photon Imaging of the Neuroinflammatory Response to Intracortical Implants and Micro-vessel Disruptions in Awake Mice. Biomaterials. 2021. [Link]
• Kevin Woeppel, Xinyan Tracy Cui. Nanoparticle and Biomolecule Surface Modification Synergistically Increases Neural Electrode Recording Yield and Minimizes Inflammatory Host Response. Advanced Healthcare Materials. 2021. [Link]
• X Sally Zheng, Noah R Snyder, Kevin Woeppel, Jenna Hanner, Xia Li, James Eles, Christi L Kolarcik, X Tracy Cui, A Superoxide Scavenging Coating for Improving Tissue Response to Neural Implants. Acta Biomateriala. 2019 [Link]
• Asiyeh Golabchi, Bingchen Wu, Xia Lia, Diane L. Carlisle, Takashi D. Y. Kozai, Robert M. Friedlander, Xinyan Tracy Cui, Melatonin improves quality and longevity of chronic neural recording, Biomaterials [Link]
• James Eles, Alberto Vazquez, TK Kozai, X. Tracy Cui, In vivo imaging of neuronal calcium during electrode implantation: spatial and temporal mapping of damage and recovery, Biomaterials, 2018, 174: 79-94. [Link]
• Michelson NJ, Vazquez AL, Eles JR, Salatino JW, Purcell EK, Williams JJ, Cui XT, Kozai TDY. Multi-scale, multi-modal analysis uncovers complex relationship at the brain tissue-implant neural interface: New Emphasis on the Biological Interface. J Neural Engineering. 2017 Nov 28. [Link]
• Kozai, TDY, Vazquez AL, Weaver CL, Kim SG, Cui XT. In vivo two photon microscopy reveals immediate microglial reaction to implantation of microelectrode through extension of processes. J Neural Eng. 2012. 9. 066001. [Link]
• Takashi DY Kozai, Zhanhong Du, Zhannetta V Gugel, Matthew A Smith, Steven M Chase, Lance M Bodily, Ellen M Caparosa, Robert M Friedlander, X Tracy Cui, Comprehensive chronic laminar single-unit, multi-unit, and local field potential recording performance with planar single shank electrode arrays, J. Neuroscience Methods, 2015, 242, 15-40. [Link]
• Du ZJ, Luo X, Weaver C, Cui XT. Poly (3, 4-ethylenedioxythiophene)-ionic liquid coating improves neural recording and stimulation functionality of MEAs. Journal of Material Chemistry C. 2015. [in press] [Link]
• Kozai TDY, Eles JR, Vazquez AL, Cui XT. Two-photon imaging of chronically implanted neural electrodes: Sealant Methods and new insights. Journal of Neuroscience Methods. 2015, 258(30) 46-55. [Link]