Ki Yong Kwon

Opto-

Electrocorticogram (ECoG) recordings, taken from electrodes placed on the surface of the cortex, have been successfully implemented for control of brain machine interfaces (BMIs). Optogenetics, direct optical stimulation of neurons in brain tissue genetically modified to express channelrhodopsin-2 (ChR2), enables targeting of specific types of neurons with sub-millisecond temporal precision. In this work, we developed a BMI device, called an Opto- μECoG array, which combines ECoG recording and optogenetics-based stimulation to enable multichannel, bi-directional interactions with neurons. The Opto- μECoG array comprises two sub-arrays, each containing a 4 × 4 distribution of micro-epidural transparent electrodes (~200 μm diameter) and embedded light-emitting diodes (LEDs) for optical neural stimulation on a 2.5×2.5 mm2 footprint to match the bilateral hemispherical area of the visual cortex in a rat. The transparent electrodes were fabricated with indium tin oxide (ITO). Parylene-C served as the main structural and packaging material for flexibility and biocompatibility. Optical, electrical, and thermal characteristics of the fabricated device were investigated and in vivo experiments were performed to evaluate the efficacy of the device.

\mu{\rm ECoG}

A power-efficient wireless switched-capacitor based stimulating (SCS) system for electrical/optical deep brain stimulation (DBS) is presented. The SCS system efficiently charges storage capacitors directly from an inductive link and delivers accurately balanced charge to the tissue, improving the overall stimulator efficiency. In addition, the decaying exponential stimulus pulses generated by SCS can be more effective than conventional rectangular and ramp stimuli in activating neural tissue when consuming the same amount of energy, leading to higher stimulus efficacy. A 4-channel wireless SCS system in 0.35 μm CMOS process achieves stimulator efficiency of 80.4% with capacitor pairs charged to ±2V, while the decaying exponential stimulus requires equal or less stimulus energy and injected charge than other stimuli depending on pulse width to activate the same tissue area. The SCS system has also been utilized for power-efficient wireless optogenetic stimulation by periodically discharging capacitors into high-current micro-LED arrays. Results from acute in vivo experiments have verified the utility of the SCS system prototype in both electrical and optical stimulation.

Array: A Hybrid Neural Interface With Transparent

This paper presents a wireless-enabled, flexible optrode array with multichannel micro light-emitting diodes (μ-LEDs) for bi-directional wireless neural interface. The array integrates wirelessly addressable μ-LED chips with a slanted polymer optrode array for precise light delivery and neural recording at multiple cortical layers simultaneously. A droplet backside exposure (DBE) method was developed to monolithically fabricate varying-length optrodes on a single polymer platform. In vivo tests in rat brains demonstrated that the μ-LEDs were inductively powered and controlled using a wireless switched-capacitor stimulator (SCS), and light-induced neural activity was recorded with the optrode array concurrently.

\mu{\rm ECoG}

The recent development of optogenetics has created an increased demand for advancing engineering tools for optical modulation of neural circuitry. This paper details the design, fabrication, integration, and packaging procedures of a wirelessly-powered, light emitting diode (LED) coupled optrode neural interface for optogenetic studies. The LED-coupled optrode array employs microscale LED (μLED) chips and polymer-based microwaveguides to deliver light into multi-level cortical networks, coupled with microelectrodes to record spontaneous changes in neural activity. An integrated, implantable, switched-capacitor based stimulator (SCS) system provides high instantaneous power to the μLEDs through an inductive link to emit sufficient light and evoke neural activities. The presented system is mechanically flexible, biocompatible, miniaturized, and lightweight, suitable for chronic implantation in small freely behaving animals. The design of this system is scalable and its manufacturing is cost effective through batch fabrication using microelectromechanical systems (MEMS) technology. It can be adopted by other groups and customized for specific needs of individual experiments.

Electrode Array and Integrated LEDs for Optogenetics

This paper presents a three-dimensional (3-D) flexible micro light emitting diode (μ-LED) array for selective optical stimulation of cortical neurons. The array integrated individually addressable μ-LED chips with slanted polymer-based microneedle waveguides to allow precise light delivery to multiple cortical layers simultaneously. A droplet backside exposure method was developed to monolithically fabricate slanted microneedles on a single polymer platform. A wafer-level assembly technique was demonstrated, which permits large-scale, high-density system integration. The electrical, optical, thermal, and mechanical properties of the 3-D slanted microneedle-LED array were characterized experimentally.

24.2 A power-efficient switched-capacitor stimulating system for electrical/optical deep-brain stimulation

Analyzing the massive amounts of neural data collected using microelectrodes to extract biologically relevant information is a major challenge. Many scientific findings rest on the ability to overcome these challenges and to standardize experimental analysis across labs. This can be facilitated in part through comprehensive, efficient and practical software tools disseminated to the community at large. We have developed a comprehensive, MATLAB-based software package - entitled NeuroQuest - that bundles together a number of advanced neural signal processing algorithms in a user-friendly environment. Results demonstrate the efficiency and reliability of the software compared to other software packages, and versatility over a wide range of experimental conditions.

A wireless slanted optrode array with integrated micro leds for optogenetics

This paper presents a single-step backside ultraviolet lithography method, namely droplet backside exposure (DBE), for making slanted microneedle structures monolithically on a flexible polymer substrate. To demonstrate the feasibility of the DBE approach, SU-8 microneedle arrays were fabricated on polydimethylsiloxane substrates. The length of the microneedles was controlled by tuning the volume of the SU-8 droplet, utilizing the wetting barrier phenomenon at a liquid-vapor-hydrophilic surface-hydrophobic surface interface. The experimental results show excellent repeatability and controllability of the DBE method for microneedle fabrication. Analytical models and the finite element method were studied to predict the dimensions of the microneedles, which agreed with the experimental data. To verify the versatility of the proposed DBE method, different microneedle structures were implemented, including a slanted hollow microneedle array and a slanted microscale waveguide (μ-waveguide) array. Furthermore, an as-fabricated μ-waveguide array was coupled with a microlight-emitting diode array, which can potentially be utilized as an optical neural interface for applications in optogenetics-based neural stimulation.

Design, fabrication, and packaging of an integrated, wirelessly-powered optrode array for optogenetics application

This paper presents a three-dimensional (3-D) flexible micro light emitting diode (μ-LED) array for optogenetics. The array integrates individually addressable μ-LED chips with out-of-plane polymer-based microscale waveguides for deep brain optical stimulation. SU-8 waveguides were fabricated using a backside exposure method. A wafer-level assembly technique was demonstrated, which permits large scale, high-density system integration. The electrical, optical, and mechanical properties of the 3-D multi-LED array were characterized experimentally. This study lays the foundation to achieve a fully implantable optogenetics-based stimulator that enables high spatial resolution and precise stimulation of the target neurons.

Integrated slanted microneedle-LED array for optogenetics

This paper reports a hybrid optoelectronic neural interfacing probe, combining micro-scale light emitting diode (μLED) and microelectrodes on a polycrystalline diamond (PCD) substrate for optogenetic stimulation and electrical recording of neural activity. PCD has superior thermal conductivity (up to 1800 Wm-1K-1) [1], which allows rapid dissipation of localized LED heat to a larger area to improve heat exchange with surrounding perfused tissues, and thus significantly reduce the risk of thermal damage to nerve tissue. During repetitive stimulation with 100ms and 1Hz pulses, the maximum rise in surface temperature of the PCD probe is less than 1 °C, which is ~90% lower than that of a polymer-based probe. A PCD based probe with two stimulating sites and four recording sites was fabricated. The capacity of the probe for neural stimulation and recording has also been demonstrated in vivo by successfully observing light evoked action potentials.

NeuroQuest: A comprehensive analysis tool for extracellular neural ensemble recordings

This paper reports a method of making optical probes for optogenetics-based deep brain optical stimulation using SU-8, which effectively increases light coupling efficiency, has excellent mechanical stiffness, and reduces fabrication complexity. By mounting microscale LEDs (μLEDs) at the tip of a SU-8 probe and directly inserting the light source into deep brain regions, attenuation caused by light transmission in wave-guided structures such as optical fibers or optrodes can be minimized. Compared to silicon neural probes, SU-8 is more biocompatible and flexible, which can reduce brain damage. Parylene-C encapsulation can potentially improve the long-term biocompatibility and reliability of the device for chronic implantation. The functionality has been proven by clearly light-induced neural activity.