Bipolar electrochemical growth of conductive microwires for cancer spheroid integration: a step forward in conductive biological circuitry.

The field of bioelectronics is developing exponentially. There is now a drive to interface electronics with biology for the development of new technologies to improve our understanding of electrical forces in biology. This builds on our recently published work in which we show wireless electrochemistry could be used to grow bioelectronic functional circuitry in 2D cell layers. To date our ability to merge electronics with in situ with biology is 3D limited. In this study, we aimed to further develop the wireless electrochemical approach for the self-assembly of microwires in situ with custom-designed and fabricated 3D cancer spheroids. Unlike traditional electrochemical methods that rely on direct electrical connections to induce currents, our technique utilises bipolar electrodes that operate independently of physical wired connections. These electrodes enable redox reactions through the application of an external electric field. Specifically, feeder electrodes connected to a power supply generate an electric field, while the bipolar electrodes, not physically connected to the feeder electrodes, facilitate the reduction of silver ions from the solution. This process occurs upon applying a voltage across the feeder electrodes, resulting in the formation of self-assembled microwires between the cancer spheroids.Thereby, creating interlinked bioelectronic circuitry with cancer spheroids. We demonstrate that a direct current was needed to stimulate the growth of conductive microwires in the presence of cell spheroids. Microwire growth was successful when using 50 V (0.5 kV/cm) of DC applied to a single spheroid of approximately 800 µm in diameter but could not be achieved with alternating currents. This represents the first proof of the concept of using wireless electrochemistry to grow conductive structures with 3D mammalian cell spheroids.

Impedimetric Characterization of Bipolar Nanoelectrodes with Cancer Cells.

Merging of electronics with biology, defined as bioelectronics, at the nanoscale holds considerable promise for sensing and modulating cellular behavior. Advancing our understanding of nanobioelectronics will facilitate development and enable applications in biosensing, tissue engineering, and bioelectronic medicine. However, studies investigating the electrical effects when merging wireless conductive nanoelectrodes with biology are lacking. Consequently, a tool is required to develop a greater understanding of merging conductive nanoparticles with cells. Herein, this challenge is addressed by developing an impedimetric method to evaluate bipolar electrode (BPE) systems that could report on electrical input. A theoretical framework is provided, using impedance to determine if conductive nanoparticles can be polarized and used to drive current. It is then demonstrated that 125 nm of gold nanoparticle (AuNP) bipolar electrodes (BPEs) could be sensed in the presence of cells when incorporated intracellularly at 500 µg/mL using water and phosphate-buffered saline (PBS) as electrolytes. These results highlight how nanoscale BPEs act within biological systems. This research will impact the rational design of using BPE systems in cells for both sensing and actuating applications.