Yoon-Kyu Song

Listening to Brain Microcircuits for Interfacing With External World—Progress in Wireless Implantable Microelectronic Neuroengineering Devices

Acquiring neural signals at high spatial and temporal resolution directly from brain microcircuits and decoding their activity to interpret commands and/or prior planning activity, such as motion of an arm or a leg, is a prime goal of modern neurotechnology. Its practical aims include assistive devices for subjects whose normal neural information pathways are not functioning due to physical damage or disease. On the fundamental side, researchers are striving to decipher the code of multiple neural microcircuits which collectively make up natures amazing computing machine, the brain. By implanting biocompatible neural sensor probes directly into the brain, in the form of microelectrode arrays, it is now possible to extract information from interacting populations of neural cells with spatial and temporal resolution at the single cell level. With parallel advances in application of statistical and mathematical techniques tools for deciphering the neural code, extracted populations or correlated neurons, significant understanding has been achieved of those brain commands that control, e.g., the motion of an arm in a primate (monkey or a human subject). These developments are accelerating the work on neural prosthetics where brain derived signals may be employed to bypass, e.g., an injured spinal cord. One key element in achieving the goals for practical and versatile neural prostheses is the development of fully implantable wireless microelectronic ¿brain-interfaces¿ within the body, a point of special emphasis of this paper.

290 and 340 nm UV LED arrays for fluorescence detection from single airborne particles

We demonstrate a compact system, incorporating a 32-element linear array of ultraviolet (290 nm and 340 nm) light-emitting diodes (LEDs) and a multi-anode photomultiplier tube, to the in-flight fluorescence detection of aerosolized particles, here containing the biological molecules tryptophan and NADH. This system illustrates substantial advances in the growth and fabrication of new semiconductor UV light emitting devices and an evolution in packaging details for LEDs tailored to the bio-aerosol warning problem. Optical engineering strategies are employed which take advantage of the size and versatility of light-emitting diodes to develop a truly compact fluorescence detector.

A Brain Implantable Microsystem with Hybrid RF/IR Telemetry for Advanced Neuroengineering Applications

A prototype cortical neural interface microsystem has been developed for brain implantable neuroengineering applications, featuring hybrid RF (radio- frequency) inductive and IR (infrared) optical telemetries. The system is aimed at neural recording from primates by converting cortical signals to a digital stream of IR light pulses, while acquiring clock signal and electrical power through RF induction. The implantable unit employs a flexible LCP (liquid crystal polymer) substrate for integration of analog, digital, and optoelectronic components, while adapting to the anatomical and physiological constraints of the environment. An ultra-low power analog CMOS chip, which includes preamplifier and multiplexing circuitry, is directly flip-chip bonded to the microelectrode array to form the immediate cortical neuroprobe device. A 16-channel version of the probe has been tested in various in-vivo animal experiments, including measurements of neural activity in somatosensory cortex of a rat.

Origin of complex behaviour of spatially discordant alternans in a transgenic rabbit model of type 2 long QT syndrome

Enhanced dispersion of repolarization has been proposed as an important mechanism in long QT related arrhythmias. Dispersion can be dynamic and can be augmented with the occurrence of spatially out‐of‐phase action potential duration (APD) alternans (discordant alternans; DA). We investigated the role of tissue heterogeneity in generating DA using a novel transgenic rabbit model of type 2 long QT syndrome (LQT2). Littermate control (LMC) and LQT2 rabbit hearts (n= 5 for each) were retrogradely perfused and action potentials were mapped from the epicardial surface using di‐4‐ANEPPS and a high speed CMOS camera. Spatial dispersion (ΔAPD and Δslope of APD restitution) were both increased in LQT2 compared to LMC (ΔAPD: 34 ± 7 ms vs. 23 ± 6 ms; Δslope:1.14 ± 0.23 vs. 0.59 ± 0.19). Onset of DA under a ramp stimulation protocol was seen at longer pacing cycle length (CL) in LQT2 compared to LMC hearts (206 ± 24 ms vs. 156 ± 5 ms). Nodal lines between regions with APD alternans out of phase from each other were correlated with conduction velocity (CV) alternation in LMC but not in LQT2 hearts. In LQT2 hearts, larger APD dispersion was associated with onset of DA at longer pacing CL. At shorter CLs, closer to ventricular fibrillation induction (VF), nodal lines in LQT2 (n= 2 out of 5) showed persistent complex beat‐to‐beat changes in nodal line formation of DA associated with competing contribution from CV restitution and tissue spatial heterogeneity, increasing vulnerability to conduction block. In conclusion, tissue heterogeneity plays a significant role in providing substrate for ventricular arrhythmia in LQT2 rabbits by facilitating DA onset and contributing to unstable nodal lines prone to reentry formation.

Wireless, high-bandwidth recordings from non-human primate motor cortex using a scalable 16-Ch implantable microsystem

A multitude of neuroengineering challenges exist today in creating practical, chronic multichannel neural recording systems for primate research and human clinical application. Specifically, a) the persistent wired connections limit patient mobility from the recording system, b) the transfer of high bandwidth signals to external (even distant) electronics normally forces premature data reduction, and c) the chronic susceptibility to infection due to the percutaneous nature of the implants all severely hinder the success of neural prosthetic systems. Here we detail one approach to overcome these limitations: an entirely implantable, wirelessly communicating, integrated neural recording microsystem, dubbed the Brain Implantable Chip (BIC).

Spectroscopic Sorting of Aerosols by a Compact Sensor Employing UV LEDs

A compact sensor for physically sorting bioaerosols based on fluorescence spectra from single particles excited using arrays of ultraviolet light emitting diodes (UV LEDs) is presented. The optical system integrates electronics for real-time processing of spectral data and a miniaturized aerodynamic deflector for particle separation. Fluorescent polystyrene latex spheres are used to demonstrate fluorescence collection on-the-fly, operation of a real-time spectral algorithm, and physical separation of individual particles. This sensor illustrates the utility of recently developed UV LEDs, in conjunction with novel optical design and custom electronics, to shrink the size of aerosol fluorescence detection systems.

A microscale photovoltaic neurostimulator for fiber optic delivery of functional electrical stimulation

Recent advances in functional electrical stimulation (FES) show significant promise for restoring voluntary movement in patients with paralysis or other severe motor impairments. Current approaches for implantable FES systems involve multisite stimulation, posing research issues related to their physical size, power and signal delivery, surgical and safety challenges. To explore a different means for delivering the stimulus to a distant muscle nerve site, we have elicited in vitro FES response using a high efficiency microcrystal photovoltaic device as a neurostimulator, integrated with a biocompatible glass optical fiber which forms a lossless, interference-free lightwave conduit for signal and energy transport. As a proof of concept demonstration, a sciatic nerve of a frog is stimulated by the microcrystal device connected to a multimode optical fiber (core diameter of 62.5 microm), which converts optical activation pulses ( approximately 100 micros) from an infrared semiconductor laser source (at 852 nm wavelength) into an FES signal.

High Performance AlGaInN Ultraviolet Light-Emitting Diode at the 340 nm Wavelength

We report on high output power from the quaternary AlGaInN multiple quantum well (MQW) ultraviolet light emitting diodes (UV LEDs) in the 340 nm wavelength range. The output power up to 1.5 mW from a 100 µm diameter device with bare-chip configuration was measured under room temperature cw operation. The internal quantum efficiency was estimated to be between 7 and 10%. In addition, the output power and external quantum efficiency for fully packaged 1×1 mm2 large area device were as high as 54.6 mW and 1.45%, respectively, at the injection current of 200 A/cm2 under pulsed operation. The devices were incorporated into prototype system for fluorescence based bio-sensing as excitation source.

A compact aerosol sensor and spectroscopic sorting with UV LEDs

We demonstrate a compact system incorporating a 32-element linear array of ultraviolet (UV) light-emitting diodes (LEDs) to the in-flight fluorescence detection of aerosolized particles. Custom electronics manage a standalone system and enable real-time processing of spectral data, which is used to cue a miniaturized aerodynamic deflector for physical particle separation. This front-end system improves the prospects for many second-stage analysis methods by reducing the background particle burden and providing a suspicious-particle enriched sample. The performance of UV LED arrays as an excitation source is established by the ability to detect emission from NADH and tryptophan in aerosol samples. On-the-fly fluorescence collection, operation of a real-time spectral algorithm, and aerosol concentration is demonstrated by separating particles that exhibit a specific spectral feature from a background of otherwise fluorescing particles.

Optical control of neural activity by waveguide delivery in genetically targeted brain tissue

Genetically targeted neurons in brain expressing light sensitive channel Channelrhodopsin can be stimulated optically. We report a novel optical waveguide probe for simultaneous optical stimulation and electrical recording of neurons to modulate neural network behavior.