Fabrication and evaluation of conductive elastomer electrodes for neural stimulation

This study explored the feasibility of applying nanocomposites derived from conducting organic polymers and silicone elastomers to fabricate electrodes for neural stimulation. A novel combination of nanoparticulate polypyrrole polymerized within a processable elastomeric silicone host polymer was evaluated in vitro and in vivo. The electrical properties of the elastomeric conductors were strongly dependent on their composition, and mixtures were identified that provided high and stable conductivity. Methods were developed for incorporating conductive polymer-siloxane co-polymer nanocomposite and silicone insulating polymers into thin-layered structures for simple single-poled electrode fabrication. In vitro testing revealed that the materials were stable under continuous pulsing for at least 10 days. Single contact prototype nerve cuff electrodes were fabricated and device functionality was demonstrated in vivo following acute implantation. The results of this study demonstrate the feasibility of conductive elastomers for peripheral nerve stimulating electrodes. Matching the mechanical properties of cuff electrode to those of the underlying neural tissue is expected to improve the long-term tissue response to the presence of the electrode.     

Biocompatibility of platinum-metallized silicone rubber: in vivo and in vitro evaluation

Silicone rubber is commonly used for biomedical applications, including implanted cuff electrodes for both recording and stimulation of peripheral nerves. This study was undertaken to evaluate the consequences of a new platinum metallization method on the biocompatibility of silicone rubber cuff electrodes. This method was introduced in order to allow the manufacture of spiral nerve cuff electrodes with a large number of contacts. The metallization process, implying silicone coating with poly(methyl methacrylate) (PMMA), its activation by an excimer laser and subsequent electroless metal deposition, led to a new surface microtexture. The neutral red cytotoxicity assay procedure was first applied in vitro on BALB/c 3T3 fibroblasts in order to analyze the cellular response elicited by the studied material. An in vivo assay was then performed to investigate the tissue reaction after chronic subcutaneous implantation of the metallized material. Results demonstrate that silicone rubber biocompatibility is not altered by the new platinum metallization method.     

Hydrophilic interpenetrating polymer networks of poly(dimethyl siloxane) (PDMS) as biomaterial for cochlear implants

Poly(dimethyl siloxane) (PDMS) was bulk-modified to develop a new intra-cochlear electrode that can closely hug the inner wall of scala tympani (ST). The hydrophilicity of bulk and surface of PDMS was changed using a sequential method for preparation of interpenetrating polymer networks (IPNs). A series of IPNs, based on PDMS and poly(acrylic acid) (PAAc), was synthesized and characterized by means of attenuated total reflectance Fourier transform infrared spectroscopy, water contact-angle measurement, dynamic mechanical thermal analysis and peel strength tests. The performances of actual-sized fabricated electrodes were assessed inside a transparent model of ST, which was filled with saline. The cell behavior of L929 fibroblasts on materials was studied in vitro.     

Electrical characterization of conductive textile materials and its evaluation as electrodes for venous occlusion plethysmography

Abstract

The ambulatory monitoring of biosignals involves the use of sensors, electrodes, actuators, processing tools and wireless communication modules. When a garment includes these elements with the purpose of recording vital signs and responding to specific situations it is call a ‘Smart Wearable System’. Over the last years several authors have suggested that conductive textile material (e-textiles) could perform as electrode for these systems. This work aims at implementing an electrical characterization of e-textiles and an evaluation of their ability to act as textile electrodes for lower extremity venous occlusion plethysmography (LEVOP). The e-textile electrical characterization is carried out using two experimental set-ups (in vitro evaluation). Besides, LEVOP records are obtained from healthy volunteers (in vivo evaluation). Standard Ag/AgCl electrodes are used for comparison in all tests. Results shown that the proposed e-textiles are suitable for LEVOP recording and a good agreement between evaluations (in vivo and in vitro) is found.     

Comparison of neural damage induced by electrical stimulation with faradaic and capacitor electrodes

Arrays of platinum (faradaic) and anodized, sintered tantalum pentoxide (capacitor) electrodes were implanted bilaterally in the subdural space of the parietal cortex of the cat. Two weeks after implantation both types of electrodes were pulsed for seven hours with identical waveforms consisting of controlled-current, chargebalanced, symmetric, anodic-first pulse pairs, 400 μsec/phase and a charge density of 80–100 μC/cm² (microcoulombs per square cm) at 50 pps (pulses per second). One group of animals was sacrificed immediately following stimulation and a second smaller group one week after stimulation. Tissues beneath both types of pulsed electrodes were damaged, but the difference in damage for the two electrode types was not statistically significant. Tissue beneath unpulsed electrodes was normal. At the ultrastructural level, in animals killed immediately after stimulation, shrunken and hyperchromic neurons were intermixed with neurons showing early intracellular edema. Glial cells appeared essentially normal. In animals killed one week after stimulation most of the damaged neurons had recovered, but the presence of shrunken, vacuolated and degenerating neurons showed that some of the cells were damaged irreversibly. It is concluded that most of the neural damage from stimulations of the brain surface at the level used in this study derives from processes associated with passage of the stimulus current through tissue, such as neuronal hyperactivity rather than electrochemical reactions associated with current injection across the electrode-tissue interface, since such reactions occur only with the faradaic electrodes.     

Electrical characteristics of conductive yarns and textile electrodes for medical applications

Clothing with conductive textiles for health care applications has in the last decade been of an upcoming research interest. An advantage with the technique is its suitability in distributed and home health care. The present study investigates the electrical properties of conductive yarns and textile electrodes in contact with human skin, thus representing a real ECG-registration situation. The yarn measurements showed a pure resistive characteristic proportional to the length. The electrodes made of pure stainless steel (electrode A) and 20% stainless steel/80% polyester (electrode B) showed acceptable stability of electrode potentials, the stability of A was better than that of B. The electrode made of silver plated copper (electrode C) was less stable. The electrode impedance was lower for electrodes A and B than that for electrode C. From an electrical properties point of view we recommend to use electrodes of type A to be used in intelligent textile medical applications.     

Theory and design of capacitor electrodes for chronic stimulation

Conventional metal electrodes generate electrochemical byproducts during stimulation of nerve or muscle. These byproducts may cause tissue damage, especially with the long-term stimulation necessary with neural prosthetic devices. To prevent the possibility of such damage, completely insulated electrodes have been devised which deliver current pulses by capacitive charging of the electrode surface, not involving electrochemical reactions. Anodised discs of porous tantalum, 1·0 mm in diameter and 0·25 mm thick, can deliver 0·5 ms, 5 mA pulses. Such electrodes are available as components of commercial capacitors and are easily adapted for biological use. The design may be optimised by mathematical analysis of an equivalent electrical circuit.In vitro tests demonstrate a clear advantage of these electrodes over capacitively coupled platinum-iridium electrodes in preventing oxidation-reduction reactions. The electrodes are stable on chronic implantation and should provide a safer interface between neural prosthetic devices and human tissue.     

Fabrication and biocompatibility of polypyrrole implants suitable for neural prosthetics

Finding a conductive substrate that promotes neural interactions is an essential step for advancing neural interfaces. The biocompatibility and conductive properties of polypyrrole (PPy) make it an attractive substrate for neural scaffolds, electrodes, and devices. Stand-alone polymer implants also provide the additional advantages of flexibility and biodegradability. To examine PPy biocompatibility, dissociated primary cerebral cortical cells were cultured on PPy samples that had been doped with polystyrene-sulfonate (PSS) or sodium dodecylbenzenesulfonate (NaDBS). Various conditions were used for electrodeposition to produce different surface properties. Neural networks grew on all of the PPy surfaces. PPy implants, consisting of the same dopants and conditions, were surgically implanted in the cerebral cortex of the rat. The results were compared to stab wounds and Teflon implants of the same size. Quantification of the intensity and extent of gliosis at 3- and 6-week time points demonstrated that all versions of PPy were at least as biocompatible as Teflon and in fact performed better in most cases. In all of the PPy implant cases, neurons and glial cells enveloped the implant. In several cases, neural tissue was present in the lumen of the implants, allowing contact of the brain parenchyma through the implants.     

Co-culture of primary neural progenitor and endothelial cells in a macroporous gel promotes stable vascular networks in vivo

Most tissues cannot survive without microvascular networks. In many cases, the host cannot vascularize implanted tissues, motivating the need for implantable vascular networks for tissue engineered grafts. However, engineering microvascular networks that are stable and functional for long times has proven challenging. The co-culture of neural progenitor cells with endothelial cells may lead to long term, functional microvascular networks. Ideally, these networks should be made from primary cells to avoid the potential safety concerns associated with immortalized orgenetically-engineered cells. Thus, we have investigated and developed a paradigm for isolating and co-culturing primary rat endothelial cells and neural progenitor cells in biodegradable poly(ethylene glycol)/poly(L-lysine) macroporous hydrogels. The co-culture of these primary cells in the gels led to stabilization of vessels with no evidence of vessel regression even as far out as 6 weeks, the longest time point studied. Further more, the vessels contained host red blood cells, demonstrating they anastomosed with the host and were functional. Functional vessels were found throughout the implants, and no adverse effects such as clotting or thrombosis were observed. This work suggests that a co-culture of primary cells seeded in a macroporous hydrogel is a novel method to promote stable functional vascular networks which are critical for engineering complex tissues.     

Computer-aided design and evaluation of novel catheters for conductive interstitial hyperthermia

Conductive interstitial heating is a modality in which heating elements are implanted directly into the treated tissue. One implementation of such therapy employs electrically heated catheters that are implanted in staggered, parallel rows. To explore strategies for maximising the uniformity of tissue temperature distributions achieved with heated catheters, a two-dimensional computer model with cylindrical co-ordinates was used to evaluate radially and longitudinally the temperature distributions produced by a typical interior catheter surrounded by other similar catheters. Insights from the computer model led to new designs for catheters containing multiple heating elements that produced more uniform thermal distributions, eliminating previous ‘cold spots’ within the treatment volume located near the ends of the catheter. The new catheter designs also include compartments for the optional placement of radioactive seeds for simultaneous thermoradiotherapy.     

Fabrication and characterization of tunable polysaccharide hydrogel blends for neural repair

Hydrogels are an important class of biomaterials that have the potential to be used as three-dimensional tissue engineering scaffolds for regenerative medicine. This is especially true in the central nervous system, where neurons do not have the ability to regenerate due to the prohibitory local environment following injury. Hydrogels can fill an injury site, replacing the growth-prohibiting environment with a more growth-permissive one. In this study, dextran and chitosan were incorporated into a methylcellulose and agarose hydrogel blend. This created several thermally sensitive polysaccharide hydrogel blends that had tunable mechanical and surface charge properties. Cortical neurons were cultured on the hydrogels to determine the blend that had the greatest neuron compatibility. Our results show that softer, more positively charged polysaccharide hydrogel blends allow for greater neuron attachment and neurite extension, showing their promise as CNS regeneration scaffolds.     

Preparation and evaluation of a lubricious treated cartridge used for implantation of intraocular lenses

In the last decades, many surface modification technologies have been developed in an attempt to improve the function of medical device surfaces by adding or enhancing surface characteristics. These value-added processes included treatment to affect lubricity, hemocompatibility and drug delivery. A unique hydrophilic, lubricious coating was developed to treat hydrophobic polymer surfaces. The coating platforms described are composed of a polyelectrolyte molecular film containing hydrophilic, lubricant molecules. The molecular film is then further cross-linked with di-functional aldehyde molecules to form an interpenetrating network (IPN). The IPN entraps lubricant molecules in the matrix and provides for prolonged stability of the lubricity. This coating was applied to cartridges which were used to deliver intraocular lenses (IOLs) that replaced the cataractous crystalline lenses in patients In order to determine the safety and effectiveness of the coating, a rabbit in vivo study was designed to evaluate the ease of implantation and postoperative response to implantation of the foldable acrylic IOLs. The performance evaluation of the lubricious treated cartridges focused on the ease of insertion and post-IOL implantation response. It was found that the UNFOLDER^? Emerald Insertion System (Advanced Medical Optics) with lubricious treated cartridges generally required lower insertion forces than the standard UNFOLDER^? Emerald cartridges. The postoperative inflammatory response following lens extraction and posterior chamber implantation of low (6D), medium (20D) and high (30D) diopter foldable acrylic IOLs with both treated and standard cartridges was mild. Inflammation generally resolved by 3 weeks. Thus, in this animal study, the coating was shown to be effective in assisting the delivery of IOLs through cartridges, without causing any adverse effects.     

Fabrication and evaluation of a sequence-specific oligonucleotide miniarray for molecular genotyping

PURPOSE: Molecular genotyping relies on the identification of specific microbial DNA sequences. Accurate genotyping not only requires discrimination between low- and high-risk pathogens for effective diagnosis or disease management but also requires the identity of the specific strain or type of the microbe involved in pathogenesis. The majority of these assays require DNA amplification followed by genome identification either through sequencing or hybridization to specific oligonucleotide probes. We evaluated the use of a DNA microchip assay as a simple and easy-to-use procedure for genotyping. METHODS: Various methodological parameters were optimized for single-base mismatch discrimination on a DNA microarray. The fabrication procedures involved substrate chemistry for immobilization. The effect of various buffers and features associated with oligonucleotide sequences were standardized. The assay was evaluated on a low-density genotyping chip containing the sequences of various (Human Papilloma Virus) HPV subtypes. RESULTS: The specific subtype was identified with high specificity by hybridization in miniaturized condition. CONCLUSIONS: The DNA microchip provides a rapid and cost-effective genotyping procedure for microbial organisms and can be implemented easily in any laboratory.     

Fabrication and physical evaluation of a polymer-encapsulated paramagnetic probe for biomedical oximetry

Lithium octa-n-butoxynaphthalocyanine (LiNc-BuO) is a promising probe for biological electron paramagnetic resonance (EPR) oximetry and is being developed for clinical use. However, clinical applicability of LiNc-BuO may be hindered by potential limitations associated with biocompatibility, biodegradation, and migration of individual crystals in tissue. To overcome these limitations, we have encapsulated LiNc-BuO crystals in polydimethyl siloxane (PDMS), an oxygen-permeable and bioinert polymer, to fabricate conveniently implantable and retrievable oxygen-sensing chips. Encapsulation was performed by a simple cast-molding process, giving appreciable control over size, shape, thickness and spin density of chips. The in vitro oxygen response of the chip was linear, reproducible, and not significantly different from that of unencapsulated crystals. Cast-molding of the structurally-flexible PDMS enabled the fabrication of chips with tailored spin densities, and ensured non-exposure of embedded LiNc-BuO, mitigating potential biocompatibility/toxicological concerns. Our results establish PDMS-encapsulated LiNc-BuO as a promising candidate for further biological evaluation and potential clinical application.     

Electrical stimulation of sensory nerves with skin electrodes for research,diagnosis, communication and behavioral conditioning: A survey

When electrical current is passed through the body by means of electrodes applied to the skin, sensory nerves can be stimulated. This results in sensations that vary from barely perceivable to highly unpleasant. Such electrocutaneous stimulation of sensory nerves has been studied by engineers, neurologists, physiologists and psychologists, who have investigated the interrelationship between the physical parameters of the electrical stimulus and the psychological effect that it evokes, have used electrical stimulation to study the nervous system and its pathologies and have tried to use cutaneous stimulation as a communication medium. Despite a large number of publications reporting the results of this research, certain basic questions still remain unanswered.     

三维微小凹图式的制备及其与C17.2神经干细胞的复合

以紫外光光刻及氢氟酸湿法蚀刻加工硅阳模,采用基于聚二甲基硅氧烷(PDMS)的软光刻技术制备9种不同结构尺寸的聚乳酸-羟基乙酸共聚物(PLGA)和PMDS三维微小凹图式。PLGA及PDMS三维微小凹图式经等离子氧蚀刻和多聚赖氨酸裱衬处理后进行C17.2神经干细胞培养。随着在图式上培养时细胞的增殖,C17.2神经干细胞逐渐在微小凹中聚集,表现出明显的三维生长行为;通过羧基荧光素乙酰乙酸琥珀酰亚胺酯(CFDA-SE)染色后进行激光共聚焦显微扫描与三维重构,显示大部分细胞生长于微小凹中离底面30～90μm的区间内;免疫荧光结果显示C17.2神经干细胞在三维微结构中复合培养2d后呈现均一的巢蛋白(Nestin)阳性。结论:本文设计的微小凹图式适用于C17.2神经干细胞的三维培养及后续的分化研究,细胞于微小凹图式培养过程中可以保持均一的干细胞特性。     

The neural process of hazard perception and evaluation for warning signal words: Evidence from event-related potentials

Warning signs have been widely applied to industrial production. As an important component of warning signs, warning signal words were mostly studied by using questionnaire. This study used event-related potentials (ERPs) to explore neural temporal features during the processing of warning signal words in human brain, and found that there were two stages involved in processing warning signal words, providing an electrophysiological evidence for a previous warning information processing model, the Communication-Human Information Processing Model (C-HIP). Previous behavioral studies indicated that the subjective hazard perception of participants facilitates their attention to the warning sign, and people can get hazard information from warning words. Our results provided direct evidence for these conclusions. The present findings of significant differences in subjective hazard perception for warning words among individuals showed the importance and necessity of training for people to get the similar understanding of these words. Our results implicated that the warning words reflecting the same hazard level used in the warning sign should be somewhat changed, at the same time, convey equally or similarly hazardous information, to avoid desensitization and habituation due to overuse of them.     

Ca2+ measurement with ion selective electrodes. The French coordinated evaluation of seven analyzers, for a better clinical relevance and acceptance

The measurement of ionized calcium has evolved in the last decade, and can now be easily performed by clinical laboratories using direct potentiometric analyzers available from a number of manufacturers. An original protocol for a comparison of the analyzers was used through a parallel multicenter evaluation in France. Using newly developed aqueous buffered solutions, this study focused not only on the analytical performance and operational handling of analyzers, but also on possible interferences in biological samples and the clinical relevance of the measurement with respect to the techniques of sample collection. All the instruments exhibited good precision and linearity, and were easy to handle and robust for daily use. However, not all the models gave identical results on the same patient's specimen. The utility of some Ca2+ analyzers has been further enhanced by the ability to "correct" the results to pH 7.40, although care must be taken in the interpretation of these results. While there are a number of clear-cut situations in which Ca2+ measurement is more relevant than total calcium, it seems that chemical activity of Ca2+ in blood may sometimes be considered with great caution under pathological conditions. The role of Ca2+ measurement in routine will be discussed in relation to the potential benefits of the instruments in laboratories.     

Fabrication and characterization of medical grade polyurethane composite catheters for near-infrared imaging

Peripherally inserted central catheters (PICCs) are hollow polymeric tubes that transport nutrients, blood and medications to neonates. To determine proper PICC placement, frequent X-ray imaging of neonates is performed. Because X-rays pose severe health risks to neonates, safer alternatives are needed. We hypothesize that near infrared (NIR) polymer composites can be fabricated into catheters by incorporating a fluorescent dye (IRDye 800CW) and visualized using NIR imaging. To fabricate catheters, polymer and dye are dry mixed and pressed, sectioned, and extruded to produce hollow tubes. We analyzed surface roughness, stiffness, dye retention, NIR contrast intensity, and biocompatibility. The extrusion process did not significantly alter the mechanical properties of the polymer composites. Over a period of 23 days, only 6.35 ± 5.08% dye leached out of catheters. The addition of 0.025 wt% dye resulted in a 14-fold contrast enhancement producing clear PICC images at 1 cm under a tissue equivalent. The addition of IRDye 800CW did not alter the biocompatibility of the polymer and did not increase adhesion of cells to the surface. We successfully demonstrated that catheters can be imaged without the use of harmful radiation and still maintain the same properties as the unaltered medical grade equivalent.