Neural Interface Enables Capacitive Stimulation
by Warren Grill, senior technical editor
Establishing one-to-one links between electrodes and neurons—in other words, an exceedingly high-density neural interface—is one of the broad, long-term objectives in neurotechnology. The size of stimulating electrodes is limited by their ability to pass charge from the electronic charge carriers in metal electrodes to ionic charge carriers in the tissue, which is related to the surface area of the electrode.
Exceeding the limits on the charge per unit area of the electrode can lead to damage to the electrode through dissolution (corrosion) or damage to the tissue by generation of chemical species as a result of reduction or oxidation reactions (redox or Faradaic reactions) at the electrode-tissue interface. In a recent issue of the Journal of Neurophysiology Ingmar Schoen and Peter Fromherz, from the Max Plank Institute for Biochemistry in Martinsried/Munich, Germany, describe an approach to stimulate neurons using purely capacitive (non-Faradaic) charge injection.
The objective was to stimulate neurons with capacitive currents by coating the conductive (doped silicon) electrode with titanium dioxide, an effective dielectric that avoids electron transfer and thus redox reactions at the interface. Guyton and Hambrecht, who in 1973 introduced the tantalum pentoxide capacitor electrode in their publication in Science, pioneered such an approach. Subsequent in vivo testing by McCreery and colleagues, reported in the Annals of Biomedical Engineering in 1988, suggested that rather than electrochemical reactions, which were avoided under the tantalum electrodes, neuronal damage was caused by some other source—later attributed to the synchronous activation of large numbers of neurons. More recently, the BION device exploited the biocompatibility and charge storage capacity of tantalum pentoxide as one of its bipolar pair of electrodes.
Schoen and Fromherz demonstrated the feasibility of their approach using neurons cultured atop the dielectric layer, and the surrounding electrolyte served as the other “plate” in a classic parallel plate capacitor. Voltage-dependent sodium channels normally found in muscle cells were expressed in human embryonic kidney cells (HEK293) as a “model” of mammalian neurons. Sawtooth voltage waveforms were applied to the doped silicon “plate” of the capacitor. Recall that capacitor current is proportional to the time derivative of the capacitor voltage. Thus, this generated a biphasic, rectangular current pulse.
Measurements of the voltage across the membrane of the cultured cells showed that this approach indeed generated changes in the transmembrane potential of the HEK cells. Further, there was a residual change in transmembrane potential that persisted after the sawtooth, which was attributable to activation of voltage-dependent sodium channels and the resulting inward ionic currents. More important, a train of such sawtooth waveforms generated a steadily increasing change in transmembrane potential that eventually led to an action-potential-like response. Both the residual change in transmembrane potential and the action potential were eliminated by application of tetrodotoxin, which blocks the sodium channels. The results were replicated in cultured neurons from rat hippocampus.
These results demonstrate that weak capacitive stimuli were able to generate neuronal stimulation without passing charge through Faradaic electrochemical reactions. Such reactions may lead to either degradation of the electrode or damage to the neurons.
This advance serves as a glimpse of the potential of complementary metal oxide semiconductor (CMOS) technology with the biological electrolytic conductor taking the place of the metal gate as a means of high-density neural stimulation and recording.