PhD candidate The George Washington University Arlington, Virginia, United States
Introduction:: Bioelectronic platforms that can combine electrophysiological and optophysiological techniques are urgently needed to enable multi-functional electrical and optical operations for studies at high resolution. Transparent and soft microelectrodes have shown great potential in multi-functional optical and electrical bio-interfaces, which allows the integration with soft tissue systems for biomedical and biological applications. However, conventional opaque electrodes can hardly bridge these two technologies because it requires a balance between transparency, flexibility, biocompatibility, and good electrical and electrochemical performance. Therefore, new materials and fabrication strategies are urgently needed. Here, we provide three solutions to meet the needs, one is the use of hybrid-structure flexible microelectrodes/interconnects using indium tin oxide (ITO) and metal grid, the second is silver nanowires (Ag NWs)-based flexible microelectrode arrays (MEAs), and the third is gold (Au)-electroplated Ag NWs stretchable MEAs. Ex vivo demonstrations are applied to validate their feasibility. In vivo histology studies reveal their compatibility.
Materials and Methods:: For the hybrid-structure microelectrodes, the metals Cr/Au (5 nm/80 nm) or Cr/Cu (5 nm/80 nm) were deposited by sputter and patterned into grids by photolithography on ITO-coated polyethylene terephthalate (PET) substrate. For the Ag NWs-based MEAs, the Ag NWs were spin coated and patterned on PET substrates with SU-8 adhesive layers by photolithography. For the Au-coated Ag NWs, A 6 nm Au layer was electroplated on the unencapsulated Ag NW surface using a sulfite-based solution under agitation at a current density of 0.1 mA cm−2. The mouse hearts with channelrhodopsin-2 (ChR2) were used for the optogenetic study. A rat heart was used for the optical mapping. The histology was analyzed by implanting the devices onto rat hearts for four weeks.
Results, Conclusions, and Discussions:: The hybrid structure using ITO and metal grid (Fig. 1a) possesses high transparency (59-81%), electrochemical impedance (5.4-18.4 Ω cm2) and sheet resistance (Rs) (5.6-14.1 Ω sq-1). Furthermore, the prepared microelectrodes and interconnects show great improvement on mechanical stability (5000 bending cycles at 5 mm radius), compared to brittle pristine ITO. The microelectrode demonstrates high-fidelity recording of a ChR2 mouse heart under co-localized optogenetic stimulation (Fig. 1b).
The Ag NWs network exhibits high transparency > 90.0% at 550 nm and mechanical stability up to 100,000 bending cycles at 5 mm radius. The nanowires solution of different concentrations enables tunable electrochemical (impedance: 3.4-15 Ω cm2) and electrical (Rs: 4.1-25 Ω sq-1) performance. The solution-processing fabrication enables large-area structure (Fig. 1c). The Ag NWs MEAs demonstrates the capability to record high-fidelity electrogram signals during optical mapping (Fig. 1d,e) and co-localized optogenetic pacing. In vivo histology study reveals that both the ITO/metal grids and Ag NWs MEAs are biocompatible.
Electroplating of an ultrathin Au layer on Ag NW surface simultaneously improves the chemical stability and electrochemical performance without significantly sacrificing optical transparency (Fig. 1f,g). The resulting Au-Ag NW microelectrodes exhibit excellent optical transparency >80%, low electrochemical impedance of 0.80–8.6 kΩ at 1 kHz, superior oxidation resistance under oxygen plasma treatment for 5 min, and chronic stability under a soak test in a PBS for >1 month, and durable mechanical performance under cyclic stretching of 600 cycles at 20% tensile strain. Successful proof-of-concept demonstrations in cardiac electrophysiology experiments demonstrate that the Au-Ag NW MEAs enable high-fidelity colocalized extracellular electrical and action potential/calcium transient optical mapping of excised perfused hearts during sinus rhythm and pacing (Fig. 1h).
Our results greatly expand the landscape for MEA technologies and present high-performance soft transparent MEA platforms as promising tools to interrogate soft biological systems via multimodal measurement.