An electronic interface for recording and stimulating nerves that innervate the bladder helps to restore normal bladder function in rats with spinal cord injury.

Reliably interfacing a nerve with an electrode array is one of the approaches to restore motor and sensory functions after an injury to the peripheral nerve. Accomplishing this with current technologies is challenging as the electrode-neuron interface often degrades over time, and surrounding myoelectric signals contaminate the neuro-signals in awake, moving animals. The purpose of this study was to evaluate the potential of microchannel electrode implants to monitor over time and in freely moving animals, neural activity from regenerating nerves. We designed and fabricated implants with silicone rubber and elastic thin-film metallization. Each implant carries an eight-by-twelve matrix of parallel microchannels (of 120 × 110 μm2 cross-section and 4 mm length) and gold thin-film electrodes embedded in the floor of ten of the microchannels. After sterilization, the soft, multi-lumen electrode implant is sutured between the stumps of the sciatic nerve. Over a period of three months and in four rats, the microchannel electrodes recorded spike activity from the regenerating sciatic nerve. Histology indicates mini-nerves formed of axons and supporting cells regenerate robustly in the implants. Analysis of the recorded spikes and gait kinematics over the ten-week period suggests firing patterns collected with the microchannel electrode implant can be associated with different phases of gait.

This work demonstrates the design, fabrication, packaging, characterization, and functionality of an electrically and fluidically active three-dimensional micro-electrode array (3D MEA) for use with neuronal cell cultures. The successful function of the device implies that this basic concept-construction of a 3D array with a layered approach-can be utilized as the basis for a new family of neural electrode arrays. The 3D MEA prototype consists of a stack of individually patterned thin films that form a cell chamber conducive to maintaining and recording the electrical activity of a long-term three-dimensional network of rat cortical neurons. Silicon electrode layers contain a polymer grid for neural branching, growth, and network formation. Along the walls of these electrode layers lie exposed gold electrodes which permit recording and stimulation of the neuronal electrical activity. Silicone elastomer microfluidic layers provide a means for loading dissociated neurons into the structure and serve as the artificial vasculature for nutrient supply and aeration. The fluidic layers also serve as insulation for the micro-electrodes. Cells have been shown to survive in the 3D MEA for up to 28 days, with spontaneous and evoked electrical recordings performed in that time. The micro-fluidic capability was demonstrated by flowing in the drug tetrotodoxin to influence the activity of the culture. IntroductionPlanar multi-electrode arrays (MEAs) have been developed for neural applications including brain slice recording [1,2] and dissociated cultures [3,4], to the point where commercial devices are readily available for the study of two-dimensional (2D) or monolayer networks of neurons. There is growing interest in developing three-dimensional (3D) systems that add greater fidelity to these models of the brain. In fact, many cell types have been cultured in both 2D and 3D, and significant differences in behavior have been observed [5][6][7]. In vitro micro-cavity impedance studies have been performed on 3D multi-cellular spheroids [8]. Compared to monolayer cultures, the spheroids better approximate the in vivo cell-cell and cellextracellular matrix contacts that impact cell growth, differentiation, and programmed cell death [9]. The guiding hypotheses of this work are that neuronal culture systems are more realistic in 3D, inferences drawn from 3D cultures are more likely to be valid in vivo, and the development of 3D MEAs would enable advances in this science.The state-of-the-art in 3D arrays for in vivo use includes microwire arrays [10] and silicon multi-electrode probes (e.g., arrays from Michigan [11] and Utah [12]). One group has reported a design for dual-side and double-layer electrode arrays that have been successfully tested in brain tissue samples [13]. It is possible, but sub-optimal, to insert these probes into a 3D in vitro sample. These devices do not include the capability for fluid exchange that is required by in vitro samples and do not have adequate surface area for culturing cells in a liquid media.Pr...

Here we present a novel idea for a replaceable insulator, and thus advance toward the goal of a single-use planar microelectrode array (MEA) for the study of electrogenic tissues. The concept of a replaceable insulator is motivated by insulator degradation after repeated usage of an MEA. Instead of fabricating a more durable insulator for repeated MEA usage, we propose replacing the insulator and effectively producing a fresh MEA for each experiment. We chose a polydimethylsiloxane (PDMS) microstencil as a candidate for the replaceable insulator as it is biocompatible, shows reversible adhesion to surfaces, and can be easily and controllably fabricated. As a proof-of-concept, we demonstrate two applications using microstencils: the rejuvenation of an old MEA and the fabrication of a single-use MEA. These MEAs were tested with dissociated neural cell cultures and neural recordings were performed at 14 days in vitro. Inexpensive and quick supply of insulators with micrometer-sized holes provides a way of constructing an MEA that can be treated as a disposable component in high throughput cell-based biosensor applications.

BackgroundA serious complication with drug-eluting coronary stents is late thrombosis, caused by exposed stent struts not covered by endothelial cells in the healing process. Real-time detection of this healing process could guide physicians for more individualized anti-platelet therapy. Here we present work towards developing a sensor to detect this healing process. Sensors on several stent struts could give information about the heterogeneity of healing across the stent.MethodsA piezoelectric microcantilever was insulated with parylene and demonstrated as an endothelialization detector for incorporation within an active coronary stent. After initial characterization, endothelial cells were plated onto the cantilever surface. After they attached to the surface, they caused an increase in mass, and thus a decrease in the resonant frequencies of the cantilever. This shift was then detected electrically with an LCR meter. The self-sensing, self-actuating cantilever does not require an external, optical detection system, thus allowing for implanted applications.ResultsA cell density of 1300 cells/mm2 on the cantilever surface is detected.ConclusionsWe have developed a self-actuating, self-sensing device for detecting the presence of endothelial cells on a surface. The device is biocompatible and functions reliably in ionic liquids, making it appropriate for implantable applications. This sensor can be placed along the struts of a coronary stent to detect when the struts have been covered with a layer of endothelial cells and are no longer available surfaces for clot formation. Anti-platelet therapy can be adjusted in real-time with respect to a patient's level of healing and hemorrhaging risks.