Integration of pre-aligned liquid metal electrodes for neural stimulation within a user-friendly microfluidic platform

Electrical stimulation of nervous tissue is used clinically for the treatment of multiple neurological disorders and experimentally for basic research. With the increase of optical probes to record neuronal activity, simple and user-friendly methods are desired to stimulate neurons and their subcellular compartments for biological experimentation. Here we describe the novel integration of liquid metal electrodes with microfluidic culture platforms to accomplish this goal. We integrated electrode and cell channels into a single poly(dimethylsiloxane) (PDMS) chip, eliminating entirely the need to align electrodes with microchannels. We designed the electrode channels such that the metal can be injected by hand and when the device is non-covalently bound to glass. We demonstrated the biocompatibility of the electrodes for long-term cultures (12 days) using hippocampal neurons. We demonstrated the use of these electrodes to depolarize neurons and recorded neuronal activity using the calcium indicator dye, Fluo-4. We established optimal stimulation parameters that induce neuronal spiking without inducing damage. We showed that the liquid metal electrode evoked larger calcium responses in somata than bath electrodes using the same stimulus parameters. Lastly we demonstrated the use of these liquid metal electrodes to target and depolarize axons. In summary, the integration of liquid metal electrodes with neuronal culture platforms provides a user-friendly and targeted method to stimulate neurons and their subcellular compartments, thus providing a novel tool for future biological investigations.