A new high-density (25 electrodes/mm²) penetrating microelectrode array for recording and stimulating sub-millimeter neuroanatomical structures.

OBJECTIVE: Among the currently available neural interface devices, there has been a need for a penetrating electrode array with a high electrode-count and high electrode-density (the number of electrodes/mm(2)) that can be used for electrophysiological studies of sub-millimeter neuroanatomical structures. We have developed such a penetrating microelectrode array with both a high electrode-density (25 electrodes/mm(2)) and high electrode-count (up to 96 electrodes) for small nervous system structures, based on the existing Utah Slanted Electrode Array (USEA). Such high electrode-density arrays are expected to provide greater access to nerve fibers than the conventionally spaced USEA especially in small diameter nerves. APPROACH: One concern for such high density microelectrode arrays is that they may cause a nerve crush-type injury upon implantation. We evaluated this possibility during acute (<10 h) in vivo experiments with electrode arrays implanted into small diameter peripheral nerves of anesthetized rats (sciatic nerve) and cats (pudendal nerve). MAIN RESULTS: Successful intrafascicular implantation and viable nerve function was demonstrated via microstimulation, single-unit recordings and histological analysis. Measurements of the electrode impedances and quantified electrode dimensions demonstrated fabrication quality. The results of these experiments show that such high density neural interfaces can be implanted acutely into neural tissue without causing a complete nerve crush injury, while mediating intrafascicular access to fibers in small diameter peripheral nerves. SIGNIFICANCE: This new penetrating microelectrode array has characteristics un-matched by other neural interface devices currently available for peripheral nervous system neurophysiological research.

A 3D glass optrode array for optical neural stimulation.

This paper presents optical characterization of a first-generation SiO(2) optrode array as a set of penetrating waveguides for both optogenetic and infrared (IR) neural stimulation. Fused silica and quartz discs of 3-mm thickness and 50-mm diameter were micromachined to yield 10 × 10 arrays of up to 2-mm long optrodes at a 400-µm pitch; array size, length and spacing may be varied along with the width and tip angle. Light delivery and loss mechanisms through these glass optrodes were characterized. Light in-coupling techniques include using optical fibers and collimated beams. Losses involve Fresnel reflection, coupling, scattering and total internal reflection in the tips. Transmission efficiency was constant in the visible and near-IR range, with the highest value measured as 71% using a 50-µm multi-mode in-coupling fiber butt-coupled to the backplane of the device. Transmittance and output beam profiles of optrodes with different geometries was investigated. Length and tip angle do not affect the amount of output power, but optrode width and tip angle influence the beam size and divergence independently. Finally, array insertion in tissue was performed to demonstrate its robustness for optical access in deep tissue.

Characterization of a 3D optrode array for infrared neural stimulation.

This paper characterizes the Utah Slant Optrode Array (USOA) as a means to deliver infrared light deep into tissue. An undoped crystalline silicon (100) substrate was used to fabricate 10 × 10 arrays of optrodes with rows of varying lengths from 0.5 mm to 1.5 mm on a 400-µm pitch. Light delivery from optical fibers and loss mechanisms through these Si optrodes were characterized, with the primary loss mechanisms being Fresnel reflection, coupling, radiation losses from the tapered shank and total internal reflection in the tips. Transmission at the optrode tips with different optical fiber core diameters and light in-coupling interfaces was investigated. At λ = 1.55µm, the highest optrode transmittance of 34.7%, relative to the optical fiber output power, was obtained with a 50-µm multi-mode fiber butt-coupled to the optrode through an intervening medium of index n = 1.66. Maximum power is directed into the optrodes when using fibers with core diameters of 200 µm or less. In addition, the output power varied with the optrode length/taper such that longer and less tapered optrodes exhibited higher light transmission efficiency. Output beam profiles and potential impacts on physiological tests were also examined. Future work is expected to improve USOA efficiency to greater than 64%.

Evaluation of the packaging and encapsulation reliability in fully integrated, fully wireless 100 channel Utah Slant Electrode Array (USEA): Implications for long term functionality.

The encapsulation and packaging reliability in fully integrated, fully wireless 100 channel Utah Slant Electrode Array (USEA)/integrated neural interface-recording version 5 (INI-R5) has been evaluated by monitoring the extended long term in-vitro functional stability and recording longevity. The INI encapsulated with 6-µm Parylene-C was immersed in phosphate buffer saline (PBS) at room temperature for a period of over 12 months. The USEA/INI-R5, while being soaked was powered and configured wirelessly through 2.765 MHz inductive link and the transmitted frequency shift keying (FSK) modulated radio-frequency (RF) (900 MHz Industrial, scientific, medical-ISM band) signal was also recorded wirelessly as a function of soak time. In order to test the long term recording ability, in-vitro wireless recording was performed in agarose for few channels. The full functionality and the ability of the electrodes to record artificial neural signals even after 12 months of PBS soak provides a measure of encapsulation reliability, the functional and recording stability in fully integrated wireless neural interface and potential usefulness for future chronic implants.

Thermodynamic Analysis of the Selectivity Enhancement Obtained by Using Smart Hydrogels That Are Zwitterionic When Detecting Glucose With Boronic Acid Moieties.

Because the boronic acid moiety reversibly binds to sugar molecules and has low cytotoxicity, boronic acid-containing hydrogels are being used in a variety of implantable glucose sensors under development, including sensors based on optical, fluorescence, and swelling pressure measurements. However, some method of glucose selectivity enhancement is often necessary, because isolated boronic acid molecules have a binding constant with glucose that is some forty times smaller than their binding constant with fructose, the second most abundant sugar in the human body. In many cases, glucose selectivity enhancement is obtained by incorporating pendant tertiary amines into the hydrogel network, thereby giving rise to a hydrogel that is zwitterionic at physiological pH. However, the mechanism by which incorporation of tertiary amines confers selectivity enhancement is poorly understood. In order to clarify this mechanism, we use the osmotic deswelling technique to compare the thermodynamic interactions of glucose and fructose with a zwitterionic smart hydrogel containing boronic acid moieties. We also investigate the change in the structure of the hydrogel that occurs when it binds to glucose or to fructose using the technique of small angle neutron scattering.

A Wafer-Scale Etching Technique for High Aspect Ratio Implantable MEMS Structures.

Microsystem technology is well suited to batch fabricate microelectrode arrays, such as the Utah electrode array (UEA), intended for recording and stimulating neural tissue. Fabrication of the UEA is primarily based on the use of dicing and wet etching to achieve high aspect ratio (15:1) penetrating electrodes. An important step in the array fabrication is the etching of electrodes to produce needle-shape electrodes with sharp tips. Traditional etching processes are performed on a single array, and the etching conditions are not optimized. As a result, the process leads to variable geometries of electrodes within an array. Furthermore, the process is not only time consuming but also labor-intensive. This report presents a wafer-scale etching method for the UEA. The method offers several advantages, such as substantial reduction in the processing time, higher throughput and lower cost. More importantly, the method increases the geometrical uniformity from electrode to electrode within an array (1.5 ± 0.5 % non-uniformity), and from array to array within a wafer (2 ± 0.3 % non-uniformity). Also, the etching rate of silicon columns, produced by dicing, are studied as a function of temperature, etching time and stirring rate in a nitric acid rich HF-HNO(3) solution. These parameters were found to be related to the etching rates over the ranges studied and more-importantly affect the uniformity of the etched silicon columns. An optimum etching condition was established to achieve uniform shape electrode arrays on wafer-scale.

Development, Fabrication, and Characterization of Hydrogel Based Piezoresistive Pressure Sensors with Perforated Diaphragms.

Hydrogels have been demonstrated to swell in response to a number of external stimuli including pH, CO(2), glucose, and ionic strength making them useful for detection of metabolic analytes. To measure hydrogel swelling pressure, we have fabricated and tested novel perforated diaphragm piezoresistive pressure sensor arrays that couple the pressure sensing diaphragm with a perforated semi-permeable membrane. The 2×2 arrays measure approximately 3 × 5 mm(2) and consist of four square sensing diaphragms with widths of 1.0, 1.25, and 1.5 mm used to measure full scale pressures of 50, 25, and 5 kPa, respectively. An optimized geometry of micro pores was etched in silicon diaphragm to allow analyte diffusion into the sensor cavity where the hydrogel material is located. The 14-step front side wafer process was carried out by a commercial foundry service (MSF, Frankfurt (Oder), Germany) and diaphragm pores were created using combination of potassium hydroxide (KOH) etching and deep reactive ion etching (DRIE).Sensor characterization was performed (without the use of hydrogels) using a custom bulge testing apparatus that simultaneously measured deflection, pressure, and electrical output. Test results are used to quantify the sensor sensitivity and demonstrate proof-of-concept. Simulations showed that the sensitivity was slightly improved for the perforated diaphragm designs while empirical electrical characterization showed that the perforated diaphragm sensors were slightly less sensitive than solid diaphragm sensors. This discrepancy is believed to be due to the influence of compressive stress found within passivation layers and poor etching uniformity. The new perforated diaphragm sensors were fully functional with sensitivities ranging from 23 to 252 µV/V-kPa (FSO= 5 to 80mV), and show a higher nonlinearity at elevated pressures than identical sensors with solid diaphragms. Sensors (1.5×1.5 mm(2)) with perforated diaphragms (pores=40 µm) have a nonlinearity of approximately 10% while for the identical solid diaphragm sensor it was roughly 3 % over the entire 200 kPa range. This is the first time piezoresistive pressure sensors with integrated diffusion pores for detection of hydrogel swelling pressure have been fabricated and tested.

High speed wafer scale bulge testing for the determination of thin film mechanical properties.

A wafer scale bulge testing system has been constructed to study the mechanical properties of thin films and microstructures. The custom built test stage was coupled with a pressure regulation system and optical profilometer which gives high accuracy three-dimensional topographic images collected on the time scale of seconds. Membrane deflection measurements can be made on the wafer scale (50-150 mm) with up to nanometer-scale vertical resolution. Gauge pressures up to 689 kPa (100 psi) are controlled using an electronic regulator with and accuracy of approximately 0.344 kPa (0.05 psi). Initial testing was performed on square diaphragms 350, 550, and 1200 microm in width comprised of 720+/-10 nm thick low pressure chemical vapor deposited silicon nitride with approximately 20 nm of e-beam evaporated aluminum. These initial experiments were focused on measuring the system limitations and used to determine what range of deflections and pressures can be accurately measured and controlled. Gauge pressures from 0 to approximately 8.3 kPa (1.2 psi) were initially applied to the bottom side of the diaphragms and their deflection was subsequently measured. The overall pressure resolution of the system is good (approximately 350 Pa) but small fluctuations existed at pressures below 5 kPa leading to a larger standard deviation between deflection measurements. Analytical calculations and computed finite element analysis deflections closely matched those empirically measured. Using an analytical solution that relates pressure deflection data for the square diaphragms the Young's modulus was estimated for the films assuming a Poisson's ratio of v=0.25. Calculations to determine Young's modulus for the smaller diaphragms proved difficult because the pressure deflection relationship remained in the linear regime over the tested pressure range. Hence, the calculations result in large error when used to estimate the Young's modulus for the smaller membranes. The deflection measurements of three 1200 x 1200 microm(2) Si(3)N(4-x) membranes were taken at increased pressures (>25 kPa) to increase nonlinearity and better determine Young's modulus. This pressure-deflection data were fit to an analytical solution and Young's modulus estimated to be 257+/-3 GPa, close to those previously reported in literature.

In vitro comparison of sputtered iridium oxide and platinum-coated neural implantable microelectrode arrays.

Neural interfaces connect signal processing electronics to the nervous system via implanted microelectrode arrays such as the Utah electrode array (UEA). The active sites of the UEA are coated with thin films of either platinum (Pt) or iridium oxide (IrOx). Pt and IrOx have attracted attention as a stimulating or recording material due to their ability to transfer between ionic and electronic current and to resist corrosion. The physical, mechanical, chemical, electrical and optical properties of thin films depend on the method and deposition parameters used to deposit the films. In this work, surface morphology, impedance and charge capacity of Pt and sputtered iridium oxide film (SIROF) were investigated and compared with each other. UEAs with similar electrode area and shape were employed in this study. DC sputtering was used to deposit Pt films and pulsed-dc reactive sputtering was used to deposit SIROF. The electrodes coated with SIROF and Pt were characterized by scanning electron microscopy, cyclic voltammetry, electrochemical impedance spectroscopy and potential transient measurements to measure charge injection capacity (CIC). SIROF and Pt selectively deposited on the electrode tip had dendrite and granular microstructure, respectively. The CIC of unbiased SIROF and Pt was 2 and 0.3 mC cm(-2), respectively. The average impedance at 1 kHz, of SIROF and Pt electrodes, was 6 kOmega and 125 kOmega, respectively. Low impedance and high CIC make SIROF promising stimulation/recording material for neural prosthetic applications.

Hydrogel based sensor arrays (2 × 2) with perforated piezoresistive diaphragms for metabolic monitoring (in vitro).

This report details the first experimental results from novel hydrogel sensor array (2 × 2) which incorporates analyte diffusion pores into a piezoresistive diaphragm for the detection of hydrogel swelling pressures and hence chemical concentrations. The sensor assembly was comprised of three components, the active four sensors, HPMA/DMA/TEGDMA (hydroxypropyl methacrylate (HPMA), N,N-dimethylaminoethyl methacrylate (DMA) and crosslinker tetra-ethyleneglycol dimethacrylate (TEGDMA)) hydrogel, and backing plate. Each of the individual sensors of the array can be used with various hydrogels used to measure the presence of a number of stimuli including pH, ionic strength, and glucose concentrations. Ideally, in the future, these sensors will be used for continuous metabolic monitoring applications and implanted subcutaneously. In this paper and to properly characterize the sensor assembly, hydrogels sensitive to changes ionic strength were synthesized using hydroxypropyl methacrylate (HPMA), N,N-dimethylaminoethyl methacrylate (DMA) and crosslinker tetra-ethyleneglycol dimethacrylate (TEGDMA) and inserted into the sensor assembly. This hydrogel quickly and reversibly swells when placed environments of physiological buffer solutions (PBS) with ionic strengths ranging from 0.025 to 0.15 M, making it ideal for proof-of-concept testing and initial characterization. The assembly was wire bonded to a printed circuit board and coated with 3 ± 0.5 µm of Parylene-C using chemical vapor deposition (CVD) to protect the sensor and electrical connections during ionic strength wet testing. Two versions of sensors were fabricated for comparison, the first incorporated diffusion pores into the diaphragm, and the second used a solid diaphragm with perforated backing plate. This new design (perforated diaphragm) was shown to have slightly higher sensitivity than solid diaphragm sensors with separate diffuse backing plates when coupled with the hydrogel. The sensitivities for the 1 mm × 1 mm, 1.25 mm × 1.25 mm, 1.5 mm × 1.5 mm perforated diaphragm sensors were 53.3 ± 6.5, 171.7 ± 8.8, and 271.47 ± 27.53 mV/V-M, respectively. These results show that perforations in the diaphragm can be used not only to allow the diffusion of analyte into the cavity but to increase mechanical stress in the piezoresistive diaphragm, thereby increasing sensor output signal. The time constants for swelling (τswelling) and contracting (τcontracting) were calculated by fitting the sensor output half cycles to an exponential growth function. We found that the sensors' response was initially retarded during the preliminary hydrogel conditioning period then improved after 3-5 cycles with values of approximately 9 and 7 min for τswelling and τcontracting. For all sensors tested τswelling > τcontracting. This may be due to the increased loading on the hydrogel from the diaphragm during the swelling process. During contraction the diaphragm aids the hydrogel by reversibly applying mechanical pressure and therefore reducing τcontracting. Long term stability testing showed the sensors remained functional for upwards of 2 weeks in the test phosphate buffer solution (PBS).

Integrated wireless neural interface based on the Utah electrode array.

This report presents results from research towards a fully integrated, wireless neural interface consisting of a 100-channel microelectrode array, a custom-designed signal processing and telemetry IC, an inductive power receiving coil, and SMD capacitors. An integration concept for such a device was developed, and the materials and methods used to implement this concept were investigated. We developed a multi-level hybrid assembly process that used the Utah Electrode Array (UEA) as a circuit board. The signal processing IC was flip-chip bonded to the UEA using Au/Sn reflow soldering, and included amplifiers for up to 100 channels, signal processing units, an RF transmitter, and a power receiving and clock recovery module. An under bump metallization (UBM) using potentially biocompatible materials was developed and optimized, which consisted of a sputter deposited Ti/Pt/Au thin film stack with layer thicknesses of 50/150/150 nm, respectively. After flip-chip bonding, an underfiller was applied between the IC and the UEA to improve mechanical stability and prevent fluid ingress in in vivo conditions. A planar power receiving coil fabricated by patterning electroplated gold films on polyimide substrates was connected to the IC by using a custom metallized ceramic spacer and SnCu reflow soldering. The SnCu soldering was also used to assemble SMD capacitors on the UEA. The mechanical properties and stability of the optimized interconnections between the UEA and the IC and SMD components were measured. Measurements included the tape tests to evaluate UBM adhesion, shear testing between the Au/Sn solder bumps and the substrate, and accelerated lifetime testing of the long-term stability for the underfiller material coated with a a-SiC(x):H by PECVD, which was intended as a device encapsulation layer. The materials and processes used to generate the integrated neural interface device were found to yield a robust and reliable integrated package.

A Novel Method of Fabricating Convoluted Shaped Electrode Arrays for Neural and Retinal Prostheses.

A novel fabrication technique has been developed for creating high density (6.25 electrodes/mm(2)), out of plane, high aspect ratio silicon-based convoluted microelectrode arrays for neural and retinal prostheses. The convoluted shape of the surface defined by the tips of the electrodes could compliment the curved surfaces of peripheral nerves and the cortex, and in the case of retina, its spherical geometry. The geometry of these electrode arrays has the potential to facilitate implantation in the nerve fascicles and to physically stabilize it against displacement after insertion. This report presents a unique combination of variable depth dicing and wet isotropic etching for the fabrication of a variety of convoluted neural array geometries. Also, a method of deinsulating the electrode tips using photoresist as a mask and the limitations of this technique on uniformity are discussed.

The occupational health service. Staffing, facilities, and equipment.

An occupational health service can be an integral part of any company. It is incumbent on the industry to conduct a thorough assessment of the need for such a service and then support the service from a financial and resource perspective. Consequently, staffing and equipping an occupational health service adequately are dependent on the services to be delivered and the type of professional staff hired. All occupational health programs can be conducted in a cost effective manner when the goals and mission are in alignment with company goals, management supports appropriate funding, and space supports the delivery of quality health care.

Integrated disability management: taking a coordinated approach to managing employee disabilities.

1. Disability management provides opportunities to control costs and improve employee benefits through three levels of prevention: primary prevention of disabilities (work and non-work related); secondary minimization of disability costs; and tertiary facilitation of rehabilitation and early return to work. 2. A totally integrated disability management program has many components, all of which must be effectively coordinated. Management of these components will result in lower disability related costs, increased employee productivity and job satisfaction, and less employee turnover. 3. All employees receive individualized services designed to assist them in returning to work and emphasizing their contributions to the company's overall dedication to global leadership, continuous growth, and success.