A fundamental challenge for bioelectronics is to deliver power to miniature devices inside the body. Wires are common failure points and limit device placement. Wireless power by electromagnetic or ultrasound waves must overcome absorption by the body and impedance mismatches between air, bone, and tissue. Magnetic fields, on the other hand, suffer little absorption by the body or differences in impedance at interfaces between air, bone, and tissue. These advantages have led to magnetically-powered stimulators based on induction or magnetothermal effects. However, fundamental limitations in these power transfer technologies have prevented miniature magneticallypowered stimulators from applications in many therapies and disease models because they do not operate in clinical "high-frequency" ranges above 20 Hz. Here we show that magnetoelectric materials -applied for the first time in bioelectronics devices -enable miniature magnetically-powered neural stimulators that operate at clinically relevant high-frequencies. As an example, we show that ME neural stimulators can effectively treat the symptoms of a Parkinson's disease model in a freely behaving rodent. We also show that ME-powered devices can be miniaturized to sizes smaller than a grain of rice while maintaining effective stimulation voltages. These results suggest that ME materials are an excellent candidate for wireless power delivery that will enable miniature neural stimulators in both clinical and research applications. Wireless neural stimulators have the potential to provide less invasive, longer lasting interfaces to brain regions and peripheral nerves compared to batterypowered devices or wired stimulators. Indeed, wires are a common failure point for bioelectronic devices. Percutaneous wires present a pathway for infection 1 and implanted wires can also limit the ability of the stimulators to move with the tissue, leading to a foreign body response or loss of contact with the target tissue 2,3 . Additionally, chronic stress and strain on wires, particularly for devices in the periphery, can lead to failure in the wire itself or its connection to the stimulator 4 . In small animals like rats and mice, wires used to power neural stimulators can interfere with natural behavior, particularly when studying social interaction between multiple animals 5 .
Soft and conductive nanomaterials like carbon nanotubes, graphene, and nanowire scaffolds have expanded the family of ultraflexible 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. However, current methods to implant these highly flexible electrodes rely on temporary stiffening agents that temporarily increase the electrode size and stiffness thus aggravating neural damage during implantation, which can lead to cell loss and glial activation that persists even after the stiffening agents are removed or dissolve. A method to deliver thin, ultraflexible 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 ultraflexible 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) microelectrodes 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 implantation site during insertion and actuation. Overall, the fluidic microdrive technology provides a robust new method to implant and actuate ultraflexible neural electrodes.
A fundamental challenge for bioelectronics is to deliver power to miniature devices inside the body. Wires are common failure points and limit device placement. On the other hand, wireless power by electromagnetic or ultrasound waves must overcome absorption by the body and impedance mismatches between air, bone, and tissue. In contrast, magnetic fields suffer little absorption by the body or differences in impedance at interfaces between air, bone, and tissue. These advantages have led to magneticallypowered stimulators based on induction or magnetothermal effects. However, fundamental limitations in these power transfer technologies have prevented miniature magnetically-powered stimulators from applications in many therapies and disease models because they do not operate in clinical "highfrequency" ranges above 50 Hz. Here we show that magnetoelectric materials -applied in bioelectronic devices -enable miniature magnetically-powered neural stimulators that can operate up to clinically-relevant high-frequencies.As an example, we show that ME neural stimulators can effectively treat the symptoms of a hemi-Parkinson's disease model in freely behaving rodents. We further demonstrate that ME-powered devices can be miniaturized to mmsized devices, fully implanted, and wirelessly powered in freely behaving rodents. These results suggest that ME materials are an excellent candidate for wireless power delivery that will enable miniature bioelectronics for both clinical and research applications.
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.
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