skip to main content


Title: A universal model of electrochemical safety limits in vivo for electrophysiological stimulation
Electrophysiological stimulation has been widely adopted for clinical diagnostic and therapeutic treatments for modulation of neuronal activity. Safety is a primary concern in an interventional design leveraging the effects of electrical charge injection into tissue in the proximity of target neurons. While modalities of tissue damage during stimulation have been extensively investigated for specific electrode geometries and stimulation paradigms, a comprehensive model that can predict the electrochemical safety limits in vivo doesn’t yet exist. Here we develop a model that accounts for the electrode geometry, inter-electrode separation, material, and stimulation paradigm in predicting safe current injection limits. We performed a parametric investigation of the stimulation limits in both benchtop and in vivo setups for flexible microelectrode arrays with low impedance, high geometric surface area platinum nanorods and PEDOT:PSS, and higher impedance, planar platinum contacts. We benchmark our findings against standard clinical electrocorticography and depth electrodes. Using four, three and two contact electrochemical impedance measurements and comprehensive circuit models derived from these measurements, we developed a more accurate, clinically relevant and predictive model for the electrochemical interface potential. For each electrode configuration, we experimentally determined the geometric correction factors that dictate geometry-enforced current spreading effects. We also determined the electrolysis window from cyclic-voltammetry measurements which allowed us to calculate stimulation current safety limits from voltage transient measurements. From parametric benchtop electrochemical measurements and analyses for different electrode types, we created a predictive equation for the cathodal excitation measured at the electrode interface as a function of the electrode dimensions, geometric factor, material and stimulation paradigm. We validated the accuracy of our equation in vivo and compared the experimentally determined safety limits to clinically used stimulation protocols. Our new model overcomes the design limitations of Shannon’s equation and applies to macro- and micro-electrodes at different density or separation of contacts, captures the breakdown of charge-density based approaches at long stimulation pulse widths, and invokes appropriate power exponents to current, pulse width, and material/electrode-dependent impedance.  more » « less
Award ID(s):
1728497
NSF-PAR ID:
10392408
Author(s) / Creator(s):
;
Date Published:
Journal Name:
Frontiers in Neuroscience
Volume:
16
ISSN:
1662-453X
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Abstract

    The efficacy of electrical brain stimulation in combatting neurodegenerative diseases and initiating function is expected to be significantly enhanced with the development of smaller scale microstimulation electrodes and refined stimulation protocols. These benefits cannot be realized without a thorough understanding of scaling effects on electrochemical charge injection characteristics. This study fabricates and characterizes the electrochemical stimulation capabilities of Au, Pt, poly(3,4‐ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS/Au), and PEDOT:PSS/Pt electrode arrays in the 20–2000 µm diameter range. This study observes substantial enhancement in charge injection capacity up to 9.5× for PEDOT:PSS microelectrodes compared to metal ones, and 88% lower required power for injecting the same charge density. These significant benefits are strongest for electrode diameters below 200 µm. Detailed quantitative analyses are provided, enabling optimization of charge injection capacity with potential bias and symmetric and asymmetric pulse width engineering for all diameters. These systematic analyses inform the optimal design for acute and potentially chronic implants in regards to safety and clinically effective stimulation protocols, ensure the longevity of the electrodes below critical electrochemical limits of stimulation, and demonstrate that the material choice and pulse design can lead to more energy efficiency stimulation protocols that are of critical importance for fully implanted devices.

     
    more » « less
  2. Ultrasmall microelectrode arrays have the potential to improve the spatial resolution of microstimulation. Carbon fiber (CF) microelectrodes with cross-sections of less than 8 μm have been demonstrated to penetrate cortical tissue and evoke minimal scarring in chronic implant tests. In this study, we investigate the stability and performance of neural stimulation electrodes comprised of electrodeposited platinum-iridium (PtIr) on carbon fibers. We conducted pulse testing and characterized charge injection in vitro and recorded voltage transients in vitro and in vivo. Standard electrochemical measurements (impedance spectroscopy and cyclic voltammetry) and visual inspection (scanning electron microscopy) were used to assess changes due to pulsing. Similar to other studies, the application of pulses caused a decrease in impedance and a reduction in voltage transients, but analysis of the impedance data suggests that these changes are due to surface modification and not permanent changes to the electrode. Comparison of scanning electron microscope images before and after pulse testing confirmed electrode stability. 
    more » « less
  3. Abstract

    Electrical microstimulation has enabled partial restoration of vision, hearing, movement, somatosensation, as well as improving organ functions by electrically modulating neural activities. However, chronic microstimulation is faced with numerous challenges. The implantation of an electrode array into the neural tissue triggers an inflammatory response, which can be exacerbated by the delivery of electrical currents. Meanwhile, prolonged stimulation may lead to electrode material degradation., which can be accelerated by the hostile inflammatory environment. Both material degradation and adverse tissue reactions can compromise stimulation performance over time. For stable chronic electrical stimulation, an ideal microelectrode must present 1) high charge injection limit, to efficiently deliver charge without exceeding safety limits for both tissue and electrodes, 2) small size, to gain high spatial selectivity, 3) excellent biocompatibility that ensures tissue health immediately next to the device, and 4) stable in vivo electrochemical properties over the application period. In this review, the challenges in chronic microstimulation are described in detail. To aid material scientists interested in neural stimulation research, the in vitro and in vivo testing methods are introduced for assessing stimulation functionality and longevity and a detailed overview of recent advances in electrode material research and device fabrication for improving chronic microstimulation performance is provided.

     
    more » « less
  4. ABSTRACT The ability to interface electronic materials with the peripheral nervous system is required for stimulation and monitoring of neural signals. Thus, the design and engineering of robust neural interfaces that maintain material-tissue contact in the presence of material or tissue micromotion offer the potential to conduct novel measurements and develop future therapies that require chronic interface with the peripheral nervous system. However, such remains an open challenge given the constraints of existing materials sets and manufacturing approaches for design and fabrication of neural interfaces. Here, we investigated the potential to leverage a rapid prototyping approach for the design and fabrication of nerve cuffs that contain supporting features to mechanically stabilize the interaction between cuff electrodes and peripheral nerve. A hybrid 3D printing and robotic-embedding (i.e., pick-and-place) system was used to design and fabricate silicone nerve cuffs (800 µm diameter) containing conforming platinum (Pt) electrodes. We demonstrate that the electrical impedance of the cuff electrodes can be reduced by deposition of the conducting polymer poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) on cuff electrodes via a post-processing electropolymerization technique. The computer-aided design and manufacturing approach was also used to design and integrate supporting features to the cuff that mechanically stabilize the interface between the cuff electrodes and the peripheral nerve. Both ‘self-locking’ and suture-assisted locking mechanisms are demonstrated based on the principle of making geometric alterations to the cuff opening via 3D printing. Ultimately, this work shows 3D printing offers considerable opportunity to integrate supporting features, and potentially even novel electronic materials, into nerve cuffs that can support the design and engineering of next generation neural interfaces. 
    more » « less
  5. Abstract

    Microelectrodes are widely used as a peripheral nerve interface (PNI) to connect the peripheral nerve to a computer for restoration of sensorimotor function and bionic device motion control. Materials used for implantable microelectrode are still facing the challenges from biocompatibility and bio‐fidelity in neural signal recording and nerve stimulating. In this study, we report that carbon multi‐electrode arrays (cMEAs) can be fabricated using carbon ink, micro resin dimethylsiloxane and 3D printing technology and ink for PNI. In vitro cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) demonstrated that the cMEAs have higher charge storage capacity (CSC) and less impedance than conventional platinum (Pt) electrode. In vivo studies using an animal model demonstrated that cMEAs are more effective in stimulating the nerve to elicit muscle contraction and recording compound muscle action potentials (CMAPs) than the Pt electrode. The cMEAs has lower stimulating threshold to elicit muscle activity, higher signal‐to‐noise (SNR) in CMAP. Our studies demonstrate that cMEAs can be an advanced healthcare materials in nerve signal nerve stimulation for PNI and muscle bioelectrical signal recording for peripheral muscle interface (PMI).

     
    more » « less