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Neuromodulation technologies hold significant promise for treating neurological disorders and advancing cognition research. However, traditional approaches like electrical stimulation and optogenetics face various technical and biological challenges, limiting their efficacy in both therapeutic and research applications. A novel alternative, photoelectric neurostimulation, utilizes near-infrared light to generate electrical pulses, enabling neuronal stimulation without requiring genetic modifications.Our research explores innovative design strategies to enhance photoelectric stimulation using minimally invasive, ultra-small, untethered carbon electrodes. These electrodes, activated by a multiphoton laser source, are evaluated both in benchtop experiments and in vivo studies using Thy1-GCaMP6s mice. Our findings reveal that high duty-cycle laser scanning and photovoltaic polymer interfaces significantly improve photo-stimulated voltage in implanted electrodes.Additionally, we demonstrate the potential of carbon-based diamond electrodes for photoelectric stimulation and their application in precise chemical delivery. By loading mesoporous silica nanoparticles co-deposited with polyethylenedioxythiophene (PEDOT), we achieve targeted drug delivery, further enhancing the therapeutic potential of this technology.This project is poised to advance the next generation of neurostimulation technology by combining photoelectric stimulation with cutting-edge diamond-based materials. These innovations offer improved spatial and temporal resolution, paving the way for more precise and effective neuromodulation strategies in both clinical and research settings.
The outcomes of this project are also likely to establish new biologically inspired paradigms for creating long-lasting, high-fidelity neural interfaces with biomimetic materials. This project will impact both the neuroscience research community, and clinical communities (neurosurgeons, neurologists, and patients) that use and benefit from neuroprosthetic- and neurostimulation-based treatments interventions. The public health relevance of this project is to improve neural prosthetic and neural stimulation devices for treatment of neurological diseases or injury.
When the opportunity arises, we capitalize on opportunistic engineering. By understanding the fundamental science behind brain injury and downstream consequences to neuronal activity, it becomes abundantly clear which of the competing design parameters need to be prioritized1. It is this philosophy that led to the design of the chronically implantable carbon fiber ultra-microelectrodes, which was ultimately published in Nature Materials2. Similarly, we discovered that it was much more difficult to eliminate the two-photon photoelectric effect on carbon fiber electrodes during simultaneous electrophysiology and two-photon imaging experiments, which we discussed in detail in the Journal of Material Chemistry B3. We instead used this “bug” as a “feature” to drive wireless electrical stimulation in free-floating carbon fiber electrodes in the brain, which was recently published in IEEE TBME4. While it is difficult to predict when basic science research exposes opportunities for innovative engineering, we demonstrate that we have the capability to capitalize on these opportunities. Our research program is taking a more "long-ranged view" in building fundamental knowledge and filling in basic science gaps. By understanding and uncovering the underlying scientific principles, we build foundational knowledge that can more readily apply to new conditions.
1 Wellman, S. M. et al. A Materials Roadmap to Functional Neural Interface Design. Advanced Functional Materials 28, 201701269, doi:10.1002/adfm.201701269 (2018).
2 Kozai, T. D. Y. et al. Ultrasmall implantable composite microelectrodes with bioactive surfaces for chronic neural interfaces. Nat Mater 11, 1065-1073, doi:10.1038/nmat3468 (2012).
3 Kozai, T. D. Y. & Vazquez, A. L. Photoelectric artefact from optogenetics and imaging on microelectrodes and bioelectronics: New Challenges and Opportunities. Journal of Materials Chemistry B 3, 4965-4978 (2015).
4 Stocking, K. C., Vazquez, A. L. & Kozai, T. D. Y. Intracortical neural stimulation with untethered, ultrasmall carbon fiber electrodes mediated by the photoelectric effect. Ieee T Bio-Med Eng (2019).
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