Assessment of neurovascular dynamics during transient ischemic attack by the novel integration of micro-electrocorticography electrode array with functional photoacoustic microscopy.

This study developed a novel system combining a 16-channel micro-electrocorticography (µECoG) electrode array and functional photoacoustic microscopy (fPAM) to examine changes in neurovascular functions following transient ischemic attack (TIA) in rats. To mimic the pathophysiology of TIA, a modified photothrombotic ischemic model was developed by using 3 min illumination of 5 mW continuous-wave (CW) green laser light focusing on a distal branch of the middle cerebral artery (MCA). Cerebral blood volume (CBV), hemoglobin oxygen saturation (SO2), somatosensory evoked potentials (SSEPs) and alpha-to-delta ratio (ADR) were measured pre- and post-ischemia over a focal cortical region (i.e., 1.5×1.5 mm(2)). Unexpectedly, the SO2, peak-to-peak amplitude (PPA) of SSEPs and ADR recovered and achieved levels greater than the baseline values at the 4th hour post-ischemia induction without any intervention, whereas the CBV value only partially recovered. In other words, transient ischemia led to increased neural activity when the relative CBV was reduced, which may further compromise neural integrity or lead to subsequent vascular disease. This novel µECoG-fPAM system complements currently available imaging techniques and represents a promising technology for studying neurovascular coupling in animal models.

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

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.

An implantable, miniaturized SU-8 optical probe for optogenetics-based deep brain stimulation.

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.

A wireless implantable switched-capacitor based optogenetic stimulating system.

This paper presents a power-efficient implantable optogenetic interface using a wireless switched-capacitor based stimulating (SCS) system. The SCS efficiently charges storage capacitors directly from an inductive link and periodically discharges them into an array of micro-LEDs, providing high instantaneous power without affecting wireless link and system supply voltage. A custom-designed computer interface in LabVIEW environment wirelessly controls stimulation parameters through the inductive link, and an optrode array enables simultaneous neural recording along with optical stimulation. The 4-channel SCS system prototype has been implemented in a 0.35-µm CMOS process and combined with the optrode array. In vivo experiments involving light-induced local field potentials verified the efficacy of the SCS system. An implantable version of the SCS system with flexible hermetic sealing is under development for chronic experiments.

Integrated slanted microneedle-LED array 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.

Droplet backside exposure for making slanted SU-8 microneedles.

This paper presented a droplet backside exposure (DBE) method for making slanted microneedle structures on a flexible polymer substrate. To demonstrate the feasibility of the DBE approach, SU-8 microneedle arrays were fabricated on polydimethylsiloxane (PDMS) 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 showed excellent repeatability and controllability of the DBE method for microneedle fabrication. Analytical models were also studied to predict the dimensions of the microneedles, which agreed with the experimental data.

Opto- µECoG array: a hybrid neural interface with transparent µECoG electrode array and integrated LEDs for optogenetics.

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.

NeuroQuest: a comprehensive analysis tool for extracellular neural ensemble recordings.

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.

Evaluation of a closed loop inductive power transmission system on an awake behaving animal subject.

This paper presents in vivo experimental results for a closed loop wireless power transmission system to implantable devices on an awake behaving animal subject. In this system, wireless power transmission takes place across an inductive link, controlled by a commercial off-the-shelf (COTS) radio frequency identification (RFID) transceiver (TRF7960) operating at 13.56 MHz. Induced voltage on the implantable secondary coil is rectified, digitized by a 10-bit analog to digital converter, and transmitted back to the primary via back telemetry. Transmitter (Tx) and receiver (Rx) circuitry were mounted on the back of an adult rat with a nominal distance of ~7 mm between their coils. Our experiments showed that the closed loop system was able to maintain the Rx supply voltage at the designated 3.8 V despite changes in the coils' relative distance and alignment due to animal movements. The Tx power consumption changed between 410 ~ 560 mW in order to deliver 27 mW to the receiver. The open loop system, on the other hand, showed undesired changes in the Rx supply voltage while the Tx power consumption was constant at 660 mW.