RT Journal Article SR Electronic T1 Fluidic microactuation of flexible electrodes for neural recording JF bioRxiv FD Cold Spring Harbor Laboratory SP 155937 DO 10.1101/155937 A1 Flavia Vitale A1 Daniel G. Vercosa A1 Alexander V. Rodriguez A1 Sushma Sri Pamulapati A1 Frederik Seibt A1 Eric Lewis A1 J. Stephen Yan A1 Krishna Badhiwala A1 Mohammed Adnan A1 Gianni Royer-Carfagni A1 Michael Beierlein A1 Caleb Kemere A1 Matteo Pasquali A1 Jacob T. Robinson YR 2017 UL http://biorxiv.org/content/early/2017/06/26/155937.abstract AB Ultra-flexible microelectrodes that can bend and flex with the natural movement of the brain reduce the inflammatory response and improve the stability of long-term neural recordings.1-5 However, current methods to implant these highly flexible electrodes rely on temporary stiffening agents that increase the electrode size6-10 thus aggravating neural damage during implantation, which leads to cell loss and glial activation that persists even after the stiffening agents are removed or dissolve.11-13 A method to deliver thin, ultra-flexible electrodes deep into neural tissue without increasing the stiffness or size of the electrodes will enable minimally invasive electrical recordings from within the brain. Here we show that specially designed microfluidic devices can apply a tension force to ultra-flexible electrodes that prevents buckling without increasing the thickness or stiffness of the electrode during implantation. Additionally, these “fluidic microdrives” allow us to precisely actuate the electrode position with micron-scale accuracy. To demonstrate the efficacy of our fluidic microdrives, we used them to actuate highly flexible carbon nanotube fiber (CNTf) microelectrodes11,14 for electrophysiology. We used this approach in three proof-of-concept experiments. First, we recorded compound action potentials in a soft model organism, the small cnidarian Hydra. Second, we targeted electrodes precisely to the thalamic reticular nucleus in brain slices and recorded spontaneous and optogenetically-evoked extracellular action potentials. Finally, we inserted electrodes more than 4 mm deep into the brain of rats and detected spontaneous individual unit activity in both cortical and subcortical regions. Compared to syringe injection, fluidic microdrives do not penetrate the brain and prevent changes in intracranial pressure by diverting fluid away from the injection site during insertion and actuation. Overall, the fluidic microdrive technology provides a robust new method to implant and actuate ultra-flexible neural electrodes.