Fully flexible implantable neural probes for electrophysiology recording and controlled neurochemical modulation

Targeted delivery of neurochemicals and biomolecules for neuromodulation of brain activity is a powerful technique that,in addition to electrical recording and stimulation,enables a more thorough investigation of neural circuit dynamics.We have designed a novel,flexible,implantable neural probe capable of controlled,localized chemical stimulation and electrophysiology recording.The neural probe was implemented using planar micromachining processes on Parylene C,a mechanically flexible,biocompatible substrate.The probe shank features two large microelectrodes(chemical sites)for drug loading and sixteen small microelectrodes for electrophysiology recording to monitor neuronal response to drug release.To reduce the impedance while keeping the size of the microelectrodes small,poly(3,4-ethylenedioxythiophene)(PEDOT)was electrochemically coated on recording microelectrodes.In addition,PEDOT doped with mesoporous sulfonated silica nanoparticles(SNPs)was used on chemical sites to achieve controlled,electrically-actuated drug loading and releasing.Different neurotransmitters,including glutamate(Glu)and gamma-aminobutyric acid(GABA),were incorporated into the SNPs and electrically triggered to release repeatedly.An in vitro experiment was conducted to quantify the stimulated release profile by applying a sinusoidal voltage(0.5 V,2 Hz).The flexible neural probe was implanted in the barrel cortex of the wild-type Sprague Dawley rats.As expected,due to their excitatory and inhibitory effects,Glu and GABA release caused a significant increase and decrease in neural activity,respectively,which was recorded by the recording microelectrodes.This novel flexible neural probe technology,combining on-demand chemical release and high-resolution electrophysiology recording,is an important addition to the neuroscience toolset used to dissect neural circuitry and investigate neural network connectivity.

Ultrasonically sculpted virtual relay lens for in situ microimaging

We demonstrate in situ non-invasive relay imaging through a medium without inserting physical optical components.We show that a virtual optical graded-index(GRIN)lens can be sculpted in the medium using in situ reconfigurable ultrasonic interference patterns to relay images through the medium.Ultrasonic wave patterns change the local density of the medium to sculpt a graded refractive index pattern normal to the direction of light propagation,which modulates the phase front of light,causing it to focus within the medium and effectively creating a virtual relay lens.We demonstrate the in situ relay imaging and resolving of small features(22μm)through a turbid medium(optical thickness=5.7 times the scattering mean free path),which is normally opaque.The focal distance and the numerical aperture of the sculpted optical GRIN lens can be tuned by changing the ultrasonic wave parameters.As an example,we experimentally demonstrate that the axial focal distance can be continuously scanned over a depth of 5.4mm in the modulated medium and that the numerical aperture can be tuned up to 21.5%.The interaction of ultrasonic waves and light can be mediated through different physical media,including turbid media,such as biological tissue,in which the ultrasonically sculpted GRIN lens can be used for relaying images of the underlying structures through the turbid medium,thus providing a potential alternative to implanting invasive endoscopes.

Parylene photonics: a flexible, broadband optical waveguide platform with integrated micromirrors for biointerfaces

Targeted light delivery into biological tissue is needed in applications such as optogenetic stimulation of the brain and in vivo functional or structural imaging of tissue.These applications require very compact,soft,and flexible implants that minimize damage to the tissue.Here,we demonstrate a novel implantable photonic platform based on a high-density,flexible array of ultracompact(30μm×5μm),low-loss(3.2dB/cm at λ=680 nm,4.1 dB/cm at λ=633 nm,4.9 dB/cm at λ=532 nm,6.1 dB/cm at λ=450 nm)optical waveguides composed of biocompatible polymers Parylene C and polydimethylsiloxane(PDMS).This photonic platform features unique embedded input/output micromirrors that redirect light from the waveguides perpendicularly to the surface of the array for localized,patterned illumination in tissue.This architecture enables the design of a fully flexible,compact integrated photonic system for applications such as in vivo chronic optogenetic stimulation of brain activity.