Pedro P. Irazoqui

Toward a comparison of microelectrodes for acute and chronic recordings.

Several variations of microelectrode arrays are used to record and stimulate intracortical neuronal activity. Bypassing the immune response to maintain a stable recording interface remains a challenge. Companies and researchers are continuously altering the material compositions and geometries of the arrays in order to discover a combination that allows for a chronic and stable electrode-tissue interface. From this interface, they wish to obtain consistent quality recordings and a stable, low impedance pathway for charge injection over extended periods of time. Despite numerous efforts, no microelectrode array design has managed to evade the host immune response and remain fully functional. This study is an initial effort comparing several microelectrode arrays with fundamentally different configurations for use in an implantable epilepsy prosthesis. Specifically, NeuroNexus (Michigan) probes, Cyberkinetics (Utah) Silicon and Iridium Oxide arrays, ceramic-based thin-film microelectrode arrays (Drexel), and Tucker-Davis Technologies (TDT) microwire arrays are evaluated over a 31-day period in an animal model. Microelectrodes are compared in implanted rats through impedance, charge capacity, signal-to-noise ratio, recording stability, and elicited immune response. Results suggest significant variability within and between microelectrode types with no clear superior array. Some applications for the microelectrode arrays are suggested based on data collected throughout the longitudinal study. Additionally, specific limitations of assaying biological phenomena and comparing fundamentally different microelectrode arrays in a highly variable system are discussed with suggestions on how to improve the reliability of observed results and steps needed to develop a more standardized microelectrode design.

Fully Wireless Implantable Cardiovascular Pressure Monitor Integrated with a Medical Stent

This paper presents a fully wireless cardiac pressure sensing system. Food and Drug Administration (FDA) approved medical stents are explored as radiating structures to support simultaneous transcutaneous wireless telemetry and powering. An application-specific integrated circuit (ASIC), designed and fabricated using the Texas Instruments 130-nm CMOS process, enables wireless telemetry, remote powering, voltage regulation, and processing of pressure measurements from a microelectromechanical systems (MEMS) capacitive sensor. This paper demonstrates fully wireless-pressure-sensing functionality with an external 35-dB·m RF powering source across a distance of 10 cm. Measurements in a regulated pressure chamber demonstrate the ability of the cardiac system to achieve pressure resolutions of 0.5 mmHg over a range of 0-50 mmHg using a channel data-rate of 42.2 kb/s.

A Miniature-Implantable RF-Wireless Active Glaucoma Intraocular Pressure Monitor

Glaucoma is a detrimental disease that causes blindness in millions of people worldwide. There are numerous treatments to slow the condition but none are totally effective and all have significant side effects. Currently, a continuous monitoring device is not available, but its development may open up new avenues for treatment. This work focuses on the design and fabrication of an active glaucoma intraocular pressure (IOP) monitor that is fully wireless and implantable. Major benefits of an active IOP monitoring device include the potential to operate independently from an external device for extended periods of time and the possibility of developing a closed-loop monitoring and treatment system. The fully wireless operation is based off using gigahertz-frequency electromagnetic wave propagation, which allows for an orientation independent transfer of power and data over reasonable distances. Our system is comprised of a micro-electromechanical systems (MEMS) pressure sensor, a capacitive power storage array, an application-specific integrated circuit designed on the Texas Instruments (TI) 130 nm process, and a monopole antenna all assembled into a biocompatible liquid-crystal polymer-based tadpole-shaped package.

Evaluation of Cardiovascular Stents as Antennas for Implantable Wireless Applications

In this study, we explore the use of stents as radiating structures to support transcutaneous wireless telemetry for data transfer of internal measurements from within the circulatory system. The implant location is chosen for the specific application of heart failure detection by monitoring internal pressure measurements of the pulmonary artery. The radiative properties of the single stent are quantified in free space within an anechoic chamber and compared with measurements taken while implanted in a live porcine subject. The in vivo studies of our 2.4-GHz stent-based transmitter, implanted at a depth of 3.5 cm within the chest, showed a 32-35-dB power reduction at a receive distance of 10 cm for both co- and cross-polarizations. The approximate far-field H-plane antenna pattern is quantified at a distance of 50 cm both in free space within an anechoic chamber and while implanted within a porcine chest. These results are used to explore the accuracy of a high-fidelity simulation model developed using Ansofts High Frequency Structural Simulator and components of their Human Body Model to provide a model that is validated with empirical data. This study provides insight into the effects of tissue on high-frequency electromagnetic transcutaneous transmission and develops a high-fidelity model that can be used for further design and optimization.

The design and hardware implementation of a low-power real-time seizure detection algorithm

Epilepsy affects more than 1% of the worlds population. Responsive neurostimulation is emerging as an alternative therapy for the 30% of the epileptic patient population that does not benefit from pharmacological treatment. Efficient seizure detection algorithms will enable closed-loop epilepsy prostheses by stimulating the epileptogenic focus within an early onset window. Critically, this is expected to reduce neuronal desensitization over time and lead to longer-term device efficacy. This work presents a novel event-based seizure detection algorithm along with a low-power digital circuit implementation. Hippocampal depth-electrode recordings from six kainate-treated rats are used to validate the algorithm and hardware performance in this preliminary study. The design process illustrates crucial trade-offs in translating mathematical models into hardware implementations and validates statistical optimizations made with empirical data analyses on results obtained using a real-time functioning hardware prototype. Using quantitatively predicted thresholds from the depth-electrode recordings, the auto-updating algorithm performs with an average sensitivity and selectivity of 95.3 +/- 0.02% and 88.9 +/- 0.01% (mean +/- SE(alpha = 0.05)), respectively, on untrained data with a detection delay of 8.5 s [5.97, 11.04] from electrographic onset. The hardware implementation is shown feasible using CMOS circuits consuming under 350 nW of power from a 250 mV supply voltage from simulations on the MIT 180 nm SOI process.

Mixed-signal integrated circuits for self-contained sub-cubic millimeter biomedical implants

Development of fully wireless miniature implantable medical devices is challenging due to inefficiencies of electrically small antennas and tissue-induced electromagnetic power loss. Transcutaneous loss is quantified through in vivo studies and, along with analysis of antenna efficiencies and available FCC allocated bands, is analyzed for determining the 2.4GHz operating frequency. Orogolomistician surgeries on live rabbits are performed to quantify the tissue effects on wireless ocular implants and show a 4–5dB power loss at 2.4GHz [1]. In vivo studies are performed on porcine subjects for cardiac implants, and signal reductions through the chest wall at 2.4GHz are measured to be 33-35dB [2].

Implantable Wireless Telemetry Boards for In Vivo Transocular Transmission

We report live animal studies that verify and quantify successful transocular transmission of data from a miniature low-power implant. To minimize damage, implantation within layers of the eye requires an ultrasmall device on a scale of just a few millimeters on each side and less than 500 mum in thickness. A high-frequency transmitter integrated circuit (IC) was designed, fabricated, and bonded onto a board containing an antenna, matching network components, and interconnects. The transmitter must achieve sufficient efficiency to draw minimal power from the limited onboard storage array while outputting a sufficiently large signal to overcome tissue-induced attenuation. Two different versions of the system were developed, one using a low-temperature co-fired ceramic material for the substrate and the other using silicon. Animal studies performed using live rabbits followed by empirical measurements verified the feasibility of a wireless telemetry scheme for a low-power miniature ocular implant.

Wireless Powering and the Study of RF Propagation Through Ocular Tissue for Development of Implantable Sensors

This paper evaluates RF powering techniques, and corresponding propagation through tissue, to supply wireless-energy for miniature implantable devices used to monitor physical-conditions in real-time. To improve efficiencies an impulsive powering technique is used with short duty-cycle high instantaneous-power-bursts, which biases the rectifier in its nonlinear regime while maintaining low average input-powers. The RF rectifier consists of a modified two-stage voltage multiplier which produces the necessary turn-on voltage for standard low-power CMOS systems while supplying the required current levels. The rectifier, fabricated on the TI 130 nm CMOS process, measures 215 μm × 265 μm, and is integrated with an antenna to quantify wireless performance of the power transfer. In-vivo studies performed on New Zealand white rabbits demonstrate the ability of implanted CMOS RF rectifiers to produce 1 V across a 27 kΩ load at a distance of 5 cm with a transmit-power of just over 1.5 W. Using a pulsed-powering technique, the circuit generates just under 0.9 V output with an average transmit-power of 300 mW. The effects of implantation on the propagation of RF powering waves are quantified and demonstrated to be surmountable, allowing for the ability to supply a low-power wireless sensor through a miniature rectifier IC.

Implantable RF Medical Devices: The Benefits of High-Speed Communication and Much Greater Communication Distances in Biomedical Applications

In the early ages of implantable devices, radio frequency (RF) technologies were not commonplace due to the challenges stemming from the inherent nature of biological tissue boundaries. As technology improved and our understanding matured, the benefit of RF in biomedical applications surpassed the implementation challenges and is thus becoming more widespread. The fundamental challenge is due to the significant electromagnetic (EM) effects of the body at high frequencies. The EM absorption and impedance boundaries of biological tissue result in significant reduction of power and signal integrity for transcutaneous propagation of RF fields. Furthermore, the dielectric properties of the body tissue surrounding the implant must be accounted for in the design of its RF components, such as antennas and inductors, and the tissue is often heterogeneous and the properties are highly variable. Additional challenges for implantable applications include the need for miniaturization, power minimization, and often accounting for a conductive casing due to biocompatibility and hermeticity requirements [1]?[3]. Today, wireless technologies are essentially a must have in most electrical implants due to the need to communicate with the device and even transfer usable energy to the implant [4], [5]. Low-frequency wireless technologies face fewer challenges in this implantable setting than its higher frequency, or RF, counterpart, but are limited to much lower communication speeds and typically have a very limited operating distance. The benefits of high-speed communication and much greater communication distances in biomedical applications have spawned numerous wireless standards committees, and the U.S. Federal Communications Commission (FCC) has allocated numerous frequency bands for medical telemetry as well as those to specifically target implantable applications. The development of analytical models, advanced EM simulation software, and representative RF human phantom recipes has significantly facilitated design and optimization of RF components for implantable applications.

EFFECT OF STIMULUS PARAMETERS IN THE TREATMENT OF SEIZURES BY ELECTRICAL STIMULATION IN THE KAINATE ANIMAL MODEL

Preliminary results from animal and clinical studies demonstrate that electrical stimulation of brain structures can reduce seizure frequency in patients with refractory epilepsy. Since most researchers derive stimulation parameters by trial and error, it is unclear what stimulation frequency, amplitude and duration constitutes a set of optimal stimulation parameters for aborting seizure activity in a given patient. In this investigation, we begin to quantify the independent effects of stimulation parameters on electrographic seizures, such that they could be used to develop an efficient closed-loop prosthesis that intervenes before the clinical onset of a seizure and seizure generalization. Biphasic stimulation is manually delivered to the hippocampus in response to a visually detected electrographic seizure. Such focal, responsive stimulation allows for anti-seizure treatment delivery with improved temporal and spatial specificity over conventional open-loop stimulation paradigms, with the possibility of avoiding tissue damage stemming from excessive exposure to electrical stimulation. We retrospectively examine the effects of stimulation frequency (low, medium and high), pulse-width (low and high) and amplitude (low and high) in seizures recorded from 23 kainic acid treated rats. We also consider the effects of total charge delivered and the rate of charge delivery, and identify stimulation parameter sets that induce after-discharges or more seizures. Among the stimulation parameters evaluated, we note 2 major findings. First, stimulation frequency is a key parameter for inhibiting seizure activity; the anti-seizure effect cannot be attributed to only the charge delivered per phase. Second, an after-discharge curve shows that as the frequency and pulse-width of stimulation increases, smaller pulse amplitudes are capable of eliciting an after-discharge. It is expected that stimulation parameter optimization will lead to devices with enhanced treatment efficacies and reduced side-effect profiles, especially when used in conjunction with seizure prediction or detection algorithms in a closed-loop control application.