This paper reports the development of flexible, neural electrode arrays made from liquid crystal polymer (LCP) and a polynorbornene (PNB) known by its trade name AvatrelTM. Each array consists of a single flexible, polymeric structure composed of an 8 mm-wide pad supporting eight Pt contacts connected to an ASIC mounting pad by a 5 cm-long, 2 mm-wide shaft carrying eight, 50 μm-wide Pt interconnect lines. The Pt conductors sit atop a 50 μm-thick base layer and are isolated from the environment except at the contacts by a capping layer of the same material as the base. In both cases, the devices were fabricated using conventional microfabrication techniques adapted for the particular polymeric material. In the case of LCP, the base structure was fabricated on 50 μm-thick sheets that were laminated and etched into the final structure. In contrast to LCP, PNB is spin castable and photodefinable, which enabled conventional photolithographic patterning techniques to be employed in a straightforward manner. The PNB-based devices could readily be fabricated, however issues related to LCP etching necessitated the development of a multi-step etch process to form the vias that expose the contacts. Electrodes made from both polymers could support electrical loads typical of stimulation applications without failing. A simple cell culture test suggests that Avatrel™ may be biocompatible, at least for short term applications.

We have developed flexible, polymer-based electrodes for potential medical applications including neural recording and stimulation. Using various combinations of liquid crystal polymer (LCP) substrates, implantable grade silicone and polyimide, we have developed and tested several prototype multi-layer polymer electrodes. We report here on two specific electrodes. In the first case, a multilayer electrode consisting of high-melt temperature liquid crystal polymer (LCP) material with patterned electrodes of sputter deposited and plated gold, laminated together with a lower-melt temperature LCP was produced. Iridium oxide was deposited on the exposed electrode sites to facilitate effective charge transfer for neural stimulation. The electrode was designed for acute implantation in a cat cochlea and contained 12 contacts, with a pitch of 200 microns. The small contact spacing allowed testing of electric field focusing techniques both in vitro and in vivo. We subjected the electrodes to electrical and mechanical tests to assess potential suitability as a long-term biomedical implant. Chronic electrical leakage testing indicated higher than desired ionic permeability of the low and high temperature LCP interface. In a second case we produced a mock circuit using high-melt LCP and medical grade low durometer silicone in place of the low-melt LCP as the interlayer adhesive. Mechanical and electrical testing of the hybrid design indicated the potential to fabricate cochlear electrodes containing up to 72 contacts with a footprint and mechanical performance similar or better than current commercially available cochlear implant arrays (containing up to 24 elements). Multi-layer polymer electrode technology offers the opportunity to create new electrodes with higher numbers of channels, offering improved performance in neural stimulation applications including cochlear implants, retinal arrays, deep brain stimulators and paraplegic remobilization devices.

This paper presents the use of a-Si:H electrolyte-gate thin film transistors (EG-TFTs) for the pH sensing and the detection of DNA and proteins (horseradish peroxidase, HRP). The sensing layer used was SiNx or SiO2. The devices show linear sensitivity to pH above the point of zero charge and respond to the adsorption of oligonuleotides and HRP with typical Langmuir adsorption behavior. DNA immobilization and hybridization detection is demonstrated. Surface control and reproducibility issues are addressed by the measurement of surface contact angles.

Intracortical microelectrodes currently have the greatest potential for achieving a functional neural prosthesis in patients with neurodegenerative diseases or spinal cord injury. Device efficacy is lacking in long-term performance as seen in both chronological histology and biopotential recording studies.

Some researchers have shown that small single polymer fibers (less than 7-μm diameter) do not induce an encapsulation layer in the rat subcutis so we have extended this concept to neural probe design. In this experiment we investigated the brain-tissue response of polymer probes with 4-μm feature sizes that are capable of withstanding insertion forces when penetrating the rat neocortex. This polymer probe has both a stiff penetrating shank (70-μm by 42-μm) and fine polymer structures (4-μm by 5-μm) that extend laterally from the shank. Our testing verifies that despite a flexible substrate and small dimensions, these devices are mechanically robust and practical as neural probes. We developed a microfabrication process using SU-8 and parylene to create the relatively thick probe shank and thin lateral arms.

In vivo testing was conducted on seven Sprague-Dawley rats. These parylene devices were chronically implanted in the motor cortex for 4-weeks and then imaged using fluorescence microscopy. Cellular encapsulation and neuronal loss were assessed using a Hoechst counterstain and the immunomarker NeuN (neuronal nuclei).

The tissue reactivity immediately around the fine-feature structures is greatly reduced, showing mild cell encapsulation (90±68% increase) relative to the probe shank (460±320% increase). Neuronal loss was only (21±25%) out to 25-μm relative to significant loss around the probe shank (47±19%). Additionally, laminin+, fibronectin+, and Ox42+ tissue often showed greater intensity and thickness at the shank, indicating that the dense scar formation typical of cortical implants was mitigated around the fine lateral structure.

These results suggest that using MEMS-based microfabrication to create sub-cellular structures will significantly reduce encapsulation, which should extend the longevity of neural probes. We also believe this concept could be beneficial to any implantable sensor capable of scaled geometries.

We use a photo-patternable silicone polymer to fabricate an elastically deformable encapsulation film on stretchable gold lines that electrically conduct while stretched to >50% strain. To detect bioelectrical signals, these stretchable gold lines are patterned as leads and micro-electrodes. They need to be encapsulated with a material that is electrically insulating, as stretchable as the elastomeric substrate, and that can be readily patterned to define recording sites. First, we evaluate the biocompatibility of the elastic encapsulation polymer by assessing the viability of the organotypic hippocampal slices cultured on it. Then, to test the electrical performance of the encapsulation film under large mechanical stress, we measure the dielectric strength of the encapsulation film to 50% tensile strain. Our findings indicate that the photo-patternable silicone material is a suitable interface to in vitro living tissue, and is a reliable stretchable insulator for soft and conformable electronic devices.

We describe highly sensitive, non–invasive, label-free, electrical detection of protein biomarkers using nanoporous alumina membrane based electrochemical conductance based devices. The principle of operation of these sensors are based on electrochemical conductance varitions associated with the binding of antibody-antigen complexes to a metallic substrate.In these devices distinct pore clusters are selectively surface functionalized with specific antibodies, that are in turn are incorporated into micro scale arrays. Protein markers were routinely detected at nanomolar concentrations. This opens the potential for developing highly sensitive and selective biomarker detection assays in clinically relevant samples for diagnosis of complex disease state like vulnerable coronary plaque rupture that results in poor post surgical outcomes and other complex diseases.

Electrical interfaces between technical system and the biological system differs with respect to material and shape depending on their intended application. Although there are different approaches using silicon as basic material for sieve or needle like electrodes interfacing the nerve tissue. This abstract will focus on polymer-based flexible implantable electrodes.

Mechanical interaction between the electrode and tender nerve tissues can induce adverse body reaction such as fibrous tissue encapsulation. Using flexible materials to design the electro-biological interface might reduce this effect. Different designs of such flexible electrodes were proposed for contacting the nerve or as platform for sensors. For example, Cuff like electrodes can be elastically wrapped around the nerve for recording or stimulation of neural signals. Using microtechnology for the structuring of polymer substrates new fiber like electrodes with multiple electrode sites were developed that can be sewed into the nerve. Thereby the possibility of selective nerve recording and stimulation was improved. One major problem of these tiny and flexible electrodes is the connection to recording and stimulation system. Incorporating electronics such as multiplexer or amplifier directly on the flexible substrate could reduce the number of connection lines or improve the sensor capabilities. Further, the integration of flexible organic electronics on the implant allows the design of more flexible and intelligent electrodes. Additionally the electrodes and sensors can be designed using conductive polymers to create a new generation of “All Polymer” active implants. Not only the chemical and mechanical properties of the materials employed can influence the biocompatibility of an implant but also the surface topography in the nanometer range plays a key role such as the growth of cells on the implants. Selective adhesion of different type of cells to different parts of the implant is a challenge for the interdisciplinary research. Finally the combination of surface nanostructuring, for example the interference laser beam structuring, and organic electronics with microstructured polymer implants offers interesting potentials for new active implants of the next decades

An MID (Moulded Interconnect Device) technology was developed for the production of elastic electronic interconnections. The stretchability is obtained using tortuous horseshoe shaped metallic wiring, embedded in a matrix of PDMS (poly dimethyl siloxane). In this way stretchable interconnects have been realized, consisting of 4 micron thick gold wires, embedded in 250 − 500 μm thick silicone material. . Stretchable interconnections, realised with this technology, have a maximum stretchability above 100%, with a stable resistivity of about 1.5 Ω per running cm for a track width of 100μm. A first simple operating stretchable electronic circuit has been fabricated, consisting of a blue LED driven by stretchable wiring. The technology is under development for use in biomedical applications in the first place, but has potential to be extended for various other applications like smart textiles, robotic skins, etc.

Foster-Miller, Inc., in conjunction with InnerSea Technology, NanoTechLabs and Dr. Lois Robblee, has demonstrated a simple, low cost process for the fabrication of high capacitance, low impedance, and high surface area carbon nanotube (CNT) electrodes for use as implantable microelectrodes. Implantable microelectrodes for electrical stimulation of neurons and recording neuronal responses are essential tools for neurophysiologists studying the behavior of neurons in the brain, spinal cord and peripheral nerve. Critical properties of an electrode interface should include: low noise, low impedance, biocompatibility, electrical stability during chronic use, and high charge capacity. Iridium oxide has all of these properties and thus has been utilized for significant developments in the neural prostheses area. However, these electrodes have several shortcomings, including: high material cost, labor-intensive processing, and deterioration of long term stability.

The results of electrochemical testing of the CNT electrodes show high capacitance and low impedance. Preliminary testing indicates that the CNT felt electrodes have advantages over state of the art iridium oxide electrodes in that their highest charge capacity is distributed within the cathodic portion of the water window, exactly where iridium oxide charge capacity is lowest. When the integration of the cathodic part of a CV is done in the potential window from 0.3 V (open circuit) to −0.7 V, at which the electrode will be used, we obtain a value of 38 μc-cm−2. Similar integration for an iridium oxide electrode gives a value of 15 mC cm−2. The high charge capacity of the CNT felt electrode over the cathodic potential range below 0.0 V is advantageous for electrical stimulation with cathodal current pulses. This is a feature lacking in Iridium oxide electrodes for which most of the charge capacity is accessed over anodic potentials above 0.0 V. In order for Iridium oxide electrodes to utilize their charge capacity during cathodal pulses, it is necessary to apply an anodic bias to the stimulation electrode between stimulus pulses. This leads to increased complexity of stimulation circuitry and the possibility of the intermittent occurrence of low dc current, both of which will be avoided with the CNT felt electrodes.

Traumatic brain injury (TBI) can be caused by motor vehicle accidents, falls and firearms. Approximately 2% of the US population lives with disabilities cause by TBI. To discover mechanisms of functional deficits underlying TBI, as well as to develop strategies to restore lost function with neural interfaces, we developed a stretchable microelectrode array (SMEA), which can be used for continuous recording of neuronal function, pre-, during, and post-stretch injury. The SMEAs were fabricated on elastomeric substrates, consisting of stretchable 100μm wide, 25nm thick gold electrodes patterned on a polydimethylsiloxane (PDMS) substrate, and encapsulated with a 10-20μm thick, photo-patternable silicone (WL-5150, Dow Corning) insulation layer. Finally, the SMEA was packaged between two printed circuit boards and mounted in a commercial Multi Channel Systems amplifier. Combining with our TBI model, which can generate precise and reproducible injury of hippocampal cultures, SMEAs were able to monitor the extracellular field potentials of neuronal populations within the cultures grown on SMEAs and injured by bi-axialy stretching the stretchable membranes. Previous biocompatibility tests showed no overt necrosis or cell death caused by the SMEAs after 2 weeks in culture [2]. The electrical performance of the SMEAs was tested in electrophysiological saline solution before, during and after biaxial stretching. The initial electrode impedance at 1kHz was ∼2kΩ. The SMEA was stretched to 8.5% biaxial strain. The microelectrode impedance increased with the strain to reach 800kΩ at 8.5% strain. Upon relaxation, the impedance recovered to 10kΩ. The working noise level of the sMEA remained below 20 ΩVpp during the whole process. New methodologies for improving the design of microelectrode arrays structure, the choice of materials and the new technology of fabrication were tested on gold microelectrode arrays supported on glass. By using the prototype arrays, population spikes were able to be recorded from organotypic hippocampal slice cultures of brain tissue. Our results demonstrate that the prototype arrays have good electrical performance compatible with existing multielectrode array systems. Moreover, the results indicate the ability of the prototype arrays to record neuronal activity from hippocampal slices. This novel technology of SMEAs will enable new studies to understand injury mechanisms leading to post-traumatic neuronal dysfunction.

We have fabricated micro-probes consisting of gold microelectrode sites (500 μm long and 12 μm wide) modified with conductive polymers and carbon nanotubes to achieve intimate contact with the nervous system. The fabrication process includes photolithography, electroplating and micromachining techniques. In order to obtain a high quality neural contact, we have investigated the preparation and characterization of neural interface materials. Electrochemical polymerization using potentiostatic and galvanostatic methods was used to optimize the surface of the metal electrode sites. Scanning electron microscopy (SEM), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS) were used to study the surface morphology, electrochemical properties, and stability of electrodeposited polymers. Cytotoxicity tests using fibroblasts and Schwann cells were performed to evaluate the biocompatibility of the micro-probes and neural interface materials. Dorsal root ganglion (DRG) in vitro preparation was used to evaluate neuronal cell cell adhesion to the electrode. Polypyrrole (PPy) and poly(3,4-ethylendioxythiophene) (EDOT) with various thicknesses and dopants were deposited onto microelectrode sites from aqueous solution. Our results demonstrate that we can control the morphology, size and electrical properties of PPy and PEDOT by changing the polymerization conditions and adding dopant structures, such as chloride and carbon nanotubes (CNT). It was observed that the addition of carbon nanotubes favors the formation of nodules and increases the surface roughness. Also, electrochemical impedance spectroscopy revealed that conductive polymer composites lower the impedance of gold microelectrodes by three orders of magnitude. We found that PPy and PEDOT carbon nanotubes composite coated electrodes maintain intimate contact with axons. Using these conductive polymer composites, high quality nerve spike signals can be detected and electrical stimulation of axons can be achieved.

This paper is devoted to the laser irradiated joints between glass and polyimide. To facilitate bonding between them, a thin titanium film with a thickness of approximately 0.2 μm was deposited on glass wafers using the physical vapor deposition (PVD) process. Two sets of samples were fabricated where the bonds were created using diode and fiber lasers. The samples were subjected to tension using a microtester for bond strength measurements. The failure strengths of the bonds generated using fiber laser are quite consistent, while a wide variation of failure strengths are observed for the bonds generated with diode laser. Few untested samples were sectioned and the microstructures near the bond areas were studied using an optical microscope. The images revealed the presence of a sharp crack in the glass substrate near the bond generated with the diode laser. However, no such crack was observed in the samples made using fiber laser. To investigate further the reasons behind such discrepancy in bond quality, three-dimensional uncoupled finite element analysis (FEA) was conducted for both types of samples. The transient heat diffusion-based FEA model utilizes the laser power intensity distribution as a time dependent heat source to calculate the temperature distribution within the substrates as a function of time.

Parylene neurocages are biocompatible and very robust, making them ideally suited for studying neural networks. We present a design and fabrication process for building parylene neurocages for in vitro studies of neural networks. The fabrication process, on either silicon or glass substrates, incorporates electrodes into the neurocages to allow for stimulation and recording of action potentials. The resulting neurocages have a long-term cell survival rate of ∼50% and have proven to be 99% effective in trapping neurons.

We have encapsulated lipid bilayer membranes within a polyethylene glycol dimethacrylate hydrogel (PEG-DMA). These hydrogel encapsulated membranes (HEMs) are significantly longer-lived and more mechanically stable than traditional lipid membranes. Over 50 attempts, HEMs usually remained intact for over 48 hours, and some lasted up to 5 days. The electrical characteristics of the HEMs were consistently stable over this period of time. The approximate thickness of the HEM was measured to be 4.7±0.5 nm (n=25), consistent with a lipid bilayer. The resistance of the HEM remained over 10 GΩ over the period of electrical measurement. Simultaneous electrical and optical measurements showed that HEMs have unusual mechanical stability, whereas free-standing lipid membranes are typically susceptible to mechanical perturbation. The HEMs could withstand much greater applied pressures than unsupported membranes. In situ electrical and optical monitoring of the HEMs showed that the gel made intimate contact with the membrane, suggesting that direct mechanical support of the bilayer is the mechanism of membrane stabilization. Single channels of alpha-hemolysin, were incorporated into HEMs and continuously measured for over 4 days. Finally, combination of the HEM with an automated membrane microfluidic formation process is proposed as a prototype platform for high throughput drug screening or small molecule sensing.

This paper will present ongoing work in the development of a thin, flexible, photolithographically-defined polymer-based electrode array based on Liquid Crystal Polymer (LCP) films and substrates. The goal of the effort is to develop and qualify a new platform technology that would allow accurate positioning of large numbers of electrode contacts in neural tissue for chronic applications. LCP films are a far greater match to the density of neural tissue than the competing wire and silicon arrays and thus will match the bending and flexing as the neural tissues change dimension. This flexibility would cause less neural damage and will maintain a more constant relationship with local neurons. Technology development activities include thin film metallization, interconnect insulation and device microfabrication.