A MEMS ultrasound stimulation system for modulation of neural circuits with high spatial resolution in vitro

Neuromodulation by ultrasound has recently received attention due to its noninvasive stimulation capability for treating brain diseases.Although there have been several studies related to ultrasonic neuromodulation,these studies have suffered from poor spatial resolution of the ultrasound and low repeatability with a fixed condition caused by conventional and commercialized ultrasound transducers.In addition,the underlying physics and mechanisms of ultrasonic neuromodulation are still unknown.To determine these mechanisms and accurately modulate neural circuits,researchers must have a precisely controllable ultrasound transducer to conduct experiments at the cellular level.Herein,we introduce a new MEMS ultrasound stimulation system for modulating neurons or brain slices with high spatial resolution.The piezoelectric micromachined ultrasonic transducers(pMUTs)with small membranes(submm membranes)generate enough power to stimulate neurons and enable precise modulation of neural circuits.We designed the ultrasound transducer as an array structure to enable localized modulation in the target region.In addition,we integrated a cell culture chamber with the system to make it compatible with conventional cell-based experiments,such as in vitro cell cultures and brain slices.In this work,we successfully demonstrated the functionality of the system by showing that the number of responding cells is proportional to the acoustic intensity of the applied ultrasound.We also demonstrated localized stimulation capability with high spatial resolution by conducting experiments in which cocultured cells responded only around a working transducer.

A 3D flexible neural interface based on a microfluidic interconnection cable capable of chemical delivery

The demand for multifunctional neural interfaces has grown due to the need to provide a better understanding of biological mechanisms related to neurological diseases and neural networks.Direct intracerebral drug injection using microfluidic neural interfaces is an effective way to deliver drugs to the brain,and it expands the utility of drugs by bypassing the blood-brain barrier(BBB).In addition,uses of implantable neural interfacing devices have been challenging due to inevitable acute and chronic tissue responses around the electrodes,pointing to a critical issue still to be overcome.Although neural interfaces comprised of a collection of microneedles in an array have been used for various applications,it has been challenging to integrate microfluidic channels with them due to their characteristic three-dimensional structures,which differ from two-dimensionally fabricated shank-type neural probes.Here we present a method to provide such three-dimensional needle-type arrays with chemical delivery functionality.We fabricated a microfluidic interconnection cable(pFIC)and integrated it with a flexible penetrating microelectrode array(FPMA)that has a 3-dimensional structure comprised of silicon microneedle electrodes supported by a flexible array base.We successfully demonstrated chemical delivery through the developed device by recording neural signals acutely from in vivo brains before and after KCl injection.This suggests the potential of the developed microfluidic neural interface to contribute to neuroscience research by providing simultaneous signal recording and chemical delivery capabilities.