Biocompatible Electrodes Research Articles

Electrochemical sensing of doxorubicin in unprocessed whole blood, cell lysate, and human plasma samples using thin film of poly-arginine modified glassy carbon electrode

A thin film of poly-arginine fabricated on glassy carbon electrode by one step electrodeposition method is applied for detection of doxorubicin hydrochloride in whole blood, cell lysate, and untreated-plasma samples. Cyclic voltammetry results indicated that the doxorubicin is oxidized via two electrons and two protons at physiological pH (pH=7.4) using poly-arginine thin film modified glassy carbon. More importantly, electrostatic repulsion takes place between the prepared polymer film-modified electrode and selected drug resulting in the signal amplification on oxidation of doxorubicin and lowering its over potential and thereby selective detection of doxorubicin in real samples. The apparent electron transfer rate constant and transfer coefficient were determined by cyclic voltammetry and were approximately 10.1s−1 and 0.82, respectively. Also, using differential-pulse voltammetric technique for sensitive detection of doxorubicin in whole blood and plasma samples, the lower limit of quantification was 69nM and 103nM, respectively. Also, application of this amino acid based biocompatible polymeric electrode was tested to the determination of doxorubicin in unprocessed whole blood and the results show that this sensor could be applied in online and real time monitoring of this anti-cancer drug in real samples which is important for clinical research.

A flexible and disposable battery powered by bacteria using eyeliner coated paper electrodes

Herein, an environment friendly paper-based biobattery is demonstrated that yields a power of 12.5W/m3. Whatman filter papers were used not only as support for electrode fabrication but also as separator of the biobattery. To provide electrical conductivity to the paper-based cathode and anode, commercially available eyeliner containing carbon nanoparticles and Fe3O4 was directly employed as conductive ink without any binder. With an instant start-up, the as-fabricated biocompatible electrodes could hold bacteria in an active form at the anode allowing chemical oxidation of organic fuel producing current. The facile process delineated here can be employed for the tailored electrode fabrication of various flexible energy harnessing devices.

Gold-modified indium tin oxide as a transparent window in optoelectronic diagnostics of electrochemically active biofilms

Microbial electrochemical technologies (METs) are one of the emerging green bioenergy domains that are utilizing microorganisms for wastewater treatment or electrosynthesis. Real-time monitoring of bioprocess during operation is a prerequisite for understanding and further improving bioenergy harvesting. Optical methods are powerful tools for this, but require transparent, highly conductive and biocompatible electrodes. Whereas indium tin oxide (ITO) is a well-known transparent conductive oxide, it is a non-ideal platform for biofilm growth. Here, a straightforward approach of surface modification of ITO anodes with gold (Au) is demonstrated, to enhance direct microbial biofilm cultivation on their surface and to improve the produced current densities. The trade-off between the electrode transmittance (critical for the underlying integrated sensors) and the enhanced growth of biofilms (crucial for direct monitoring) is studied. Au-modified ITO electrodes show a faster and reproducible biofilm growth with three times higher maximum current densities and about 6.9 times thicker biofilms compared to their unmodified ITO counterparts. The electrochemical analysis confirms the enhanced performance and the reversibility of the ITO/Au electrodes. The catalytic effect of Au on the ITO surface seems to be the key factor of the observed performance improvement since the changes in the electrode conductivity and their surface wettability are relatively small and in the range of ITO. An integrated platform for the ITO/Au transparent electrode with light-emitting diodes was fabricated and its feasibility for optical biofilm thickness monitoring is demonstrated. Such transparent electrodes with embedded catalytic metals can serve as multifunctional windows for biofilm diagnostic microchips.

Flexible and Highly Biocompatible Nanofiber-Based Electrodes for Neural Surface Interfacing.

Polyimide (PI)-based electrodes have been widely used as flexible biosensors in implantable device applications for recording biological signals. However, the long-term quality of neural signals obtained from PI-based nerve electrodes tends to decrease due to nerve damage by neural tissue compression, mechanical mismatch, and insufficient fluid exchange between the neural tissue and electrodes. Here, we resolve these problems with a developed PI nanofiber (NF)-based nerve electrode for stable neural signal recording, which can be fabricated via electrospinning and inkjet printing. We demonstrate an NF-based nerve electrode that can be simply fabricated and easily applied due to its high permeability, flexibility, and biocompatibility. Furthermore, the electrode can record stable neural signals for extended periods of time, resulting in decreased mechanical mismatch, neural compression, and contact area. NF-based electrodes with highly flexible and body-fluid-permeable properties could enable future neural interfacing applications.

A biocompatible implant electrode capable of operating in body fluids for energy storage devices

Implantable electronic medical devices (IEMDs) can potentially be used to solve various clinical problems including the monitoring of chronic diseases and electro-organ transplantation. Several recently introduced techniques based on implantable devices that exploit novel metal- or carbon-based hybrid materials are biocompatible owing to their encapsulation in nontoxic polymers. However, such techniques limit the correct functioning of implantable devices, resulting in frequent replacement, difficult miniaturization, and inflammatory side effects in the body. Here, we describe a new technique for application to IEMDs that is capable of providing energy storage using the natural ions of body fluids as electrolytes in a supercapacitor (or ultracapacitor). The system is constructed with a solar cell for energy harvesting and a supercapacitor for energy storage. We assembled IEMDs with two biocompatible electrodes, specifically, MnO2 nanoparticles affixed to multi-walled carbon nanotubes as the positive electrodes and phosphidated activated carbon as the negative electrodes. From the obtained result, this work can be further extended to the use of rats. This technique avoids the problems of performance degradation and toxicity that normally limits the reaction that is permissible in extracellular fluid. We present this concept schematically. The two biocompatible electrodes were successfully implanted into the subcutaneous layer of a rat's skin with both electrodes showing stable performance in use as parts of a supercapacitor. These findings establish a platform for potential biocompatible materials for implantable energy storage devices.

Biocompatible, optically transparent, patterned, and flexible electrodes and radio-frequency antennas prepared from silk protein and silver nanowire networks

We demonstrated biocompatible, optically transparent and flexible electrodes by embedding AgNWs just below the surface of the silk fibroin film.

Carbon nanoparticles of Chinese ink-wrapped natural loofah sponge: a low-cost three-dimensional electrode for high-performance microbial energy harvesting

A new highly conductive and biocompatible three-dimensional electrode with low-cost natural loofah sponge as the skeleton and Chinese ink as the conductive coating material is presented.

Fabrication challenges and perspectives on the use of carbon-electrode dielectrophoresis in sample preparation.

The focus of this review is to assess the current status of three-dimensional (3D) carbon-electrode dielectrophoresis (carbonDEP) and identify the challenges currently preventing it from its use in high-throughput applications such as sample preparation for diagnostics. The use of 3D electrodes over more traditional planar ones is emphasised here as a way to increase the throughput of DEP devices. Glass-like carbon electrodes are derived through the carbonisation of photoresist structures made using photolithography. These biocompatible carbon electrodes are not ideal electrical conductors but are more electrochemically stable than noble metals such as gold and platinum. They are also significantly less expensive than common electrode materials, both in terms of material cost and fabrication process. CarbonDEP has been demonstrated for the manipulation of microorganisms and biomolecules. This review is divided in three main sections: (i) carbonDEP fabrication process; (ii) applications using 3D carbonDEP; and (iii) challenges and perspectives on the use of carbonDEP for high-throughput applications.

A cost-effective fabrication of iridium oxide films as biocompatible electrostimulation electrodes for neural interface applications

Electrostimulation medical devices for neural diseases require electroactive and biocompatible interface materials to transmit signals from electrodes to targeting tissues. Iridium oxide is an attractive ceramic material for neurostimulation electrodes due to its desirable stability and biocompatibility. In this study, we developed a cost effective and thickness controllable process to fabricate iridium oxide film by chemical bath deposition (CIROF). Surface morphology, crystallinity, roughness, hydrophilicity, and charge storage capacity as well as biocompatibility of the CIROFs with different thicknesses were analyzed. Accordingly, the CIROFs present rough and hydrophilic surfaces for cell attachment and good biocompatibility for cell viability. In addition, the charge storage capacity (CSC) of the as-deposited and the annealed CIROFs were 78.29 mC/cm2 and 71.76 mC/cm2, respectively. Consequently, these results show advantages that make the CIROF a promising neurostimulation electrode material for implantable medical devices in neural systems.

Biocompatible ZrO2- reduced graphene oxide immobilized AChE biosensor for chlorpyrifos detection

Based on Acetylcholinestrase (AChE) inhibition, a novel biosensing electrode involving Reduced Graphene Oxide (RGO) supported Zirconium Oxide (ZrO2/RGO) nanoparticles is fabricated for Chlorpyrifos (pesticide) detection. AChE/ZrO2/RGO biosensor when used for pesticide detection, exhibited high sensitivity towards Chlorpyrifos. Typically AChE/ZrO2/RGO biosensing electrode is capable of detecting Chlorpyrifos concentration as low as 10−13M (with 28% enzyme inhibition). Furthermore the enzyme inhibition is remarkable high (>70%) in case of high Chlorpyrifos concentration (up to 10−4M). Our results indicate that AChE/ZrO2/RGO is an efficient and biocompatible electrode that can be used for Chlorpyrifos detection in ultra low concentrations. Electrochemical sensing response of AChE/ZrO2/RGO sensor revealed two different linear ranges of chlorpyrifos detection. The first linear response was observed from 10−13M to 10−9M whereas the second linear range was observed between 10−9M to 10−4M revealing complete saturation of enzyme active sites by Chlorpyrifos. Ameperometric response of AChE/ZrO2/RGO electrode demonstrates constant decrease in the current with respect to increase in the Chlorpyrifos concentration.

Metabolic Assay System Using Skeletal Muscle Cells Cultured with a Stretchable Fiber Electrode

In vitro bioassay systems with cultured living cells have been developed extensively as an alternative to animal experiments to quantify the physiological functions under simplified and controlled conditions. The bioassay systems integrated with an electrical stimulation system have enabled to control electrophysiological activities of the cells such as neural, cardiac, and skeletal muscle cells. Especially, the systems using skeletal muscle cells are one of the promising device to reveal the complex mechanisms of type 2 diabetes and obesity because these diseases are associated with a disorder of insulin- or contraction-induced glucose metabolism in a skeletal muscle cell in vivo. In addition, recent lines of evidence have suggested that the skeletal muscle functions as an endocrine organ that secretes a number of cytokines (myokines) in response to exercise in order to regulate the physiological activities of the whole body including glucose metabolism of the muscle itself. Three-dimensionally reconstructed skeletal muscle cells have been proven to exhibit in vivo-like structural and genetic characteristics, and therefore, various three dimensional culture technique has been developed. On the other hand, extracellular electrical stimulation using a pair of electrodes immersed in both sides of a culture medium still has technical problems concerning limitations on the current value, which can be applied without a faradic reaction causing perturbation of culture conditions such as pH value. Additionally, in the conventional electrode configuration, most of the applied current tends to pass only through the culture medium surrounding the insulative living cells, which cannot cause cell depolarization effectively. For reliable and reproducible bioassay, it is necessary to develop the low invasive electrical stimulation culture system in which the applied current can pass through the cells. In this study, we developed the in vitro bioassay systems with three dimensional skeletal muscle fiber enclosing a stretchable and biocompatible electrode wire composed of conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) and polyurethane (PU). The fibrous PEDOT has much capacity in its electrical double layer even in a composite form with PU that can apply current charge required for excitation of the surrounding skeletal muscle cells without any faradaic reaction. The electric current can pass through the cells surrounding the electrode wire, resulting in their quantitative depolarization, which was demonstrated by visualizing intracellular Ca2+ transients upon applied electrical stimulation with a Ca2+-sensitive fluorescent dye. PEDOT/PU wire was fabricated by twisting the PEDOT/PU strip (30 mm x 3 mm, 3 μm in thickness) cut out from the film. The PEDOT/PU film was prepared by spin-coating a precursor solution of EDOT monomer, pTSFe(III) dopant, and PU, followed by thermal polymerization of PEDOT on a glass substrate. Cyclic voltammetry measured in 0.1 M KCl solution suggested that maximum charge storing in an electric double layer of the PEDOT/PU wire was 75 μC. The wire was centrally set into the PDMS chamber pretreated with cell repulsive polymer solution. The C2C12 myoblast cells suspended in the mixture of collagen and Matrigel were poured into the PDMS chamber and incubated for 30min at 37 oC to facilitate gelation of the mixture. During three days of culture, the seeded cells self-assembled around the PEDOT/PU wire contracting the collagen/Matrigel matrix, resulting in a fiber form of myoblast cells/collagen/Matrigel matrix fiber around the PEDOT/PU wire. The cells were continuously cultured in the medium for additional seven days to induce differentiation of the myoblasts into the myotubes. Fluorescent Live/Dead imaging showed that almost all the myotubes around the PEDOT/PU electrode wire in alive suggesting non-citotoxity of the PEDOT/PU wire itself. The myotubes were aligned to longitudinal direction of the wire, which is similar structure as in vivo skeletal muscle tissue. Upon application of the constant current pulses to the PEDOT/PU electrode wire against a carbon electrode set outside of the myotubes/collagen/Matrigel matrix fiber, the cells exhibited twitch and tetanus contraction depending on the applied electric pulse frequency. The threshold current charge evaluated by visualizing intracellular Ca2+ transients upon applied electrical stimulation was 1.0 μC which value was much smaller than maximum charge derived from the electric double layer of PEDOT/PU wire, 75 μC. This suggested low invasive electric stimulation of the PEDOT/PU electrode even in close to the surrounding cells. Additional utility of embedding the electrode into the three dimensional skeletal muscle fiber was successfully demonstrated by selective electrical stimulation of the skeletal muscle fiber arrays in the same culture medium, that is beneficial for high-contrast comparison of the contraction effect on the skeletal muscle cellular functions such as contraction-dependent myokine secretion activity and contraction-dependent control of glucose metabolism in type 2 diabetes.

TiO2 nanotube array as biocompatible electrode in view of implantable supercapacitors

In this paper we propose the exploitation of TiO2 nanotube arrays as biocompatible electrodes for implantable supercapacitors. TiO2 nanotubes are obtained by anodic oxidation of titanium foil and the assembly of the whole energy storage device is conducted using only biocompatible materials: PDMS is selected as packaging material both for its biocompatibility and easy fabrication process, glass-fiber filter acts as separator and the Dulbecco’s Phosphate Buffered Saline solution as physiological electrolyte. Electrochemical characterizations of the proposed flexible device reveal promising performances of TiO2 nanotubes array for future implantable supercapacitors.

Effective area and charge density of dextran sulphate doped PEDOT modified electrodes

The performance of neural electrodes over chronic periods is poor with degrading signal-to-noise ratio and low biocompatibility. Consequently, electrodes require modification to improve their performance, biostability and biocompatibility. A large variety of doped conducting polymers have been proposed for optimising neural electrodes, but to date, none have achieved the required biostability and biocompatibility necessary for human application. Dextran sulfate is used as an antithrombotic and may be of use in improving neural electrode biocompatibility. Poly-3,4-ethylenedioxythiophene was successfully doped with dextran sulfate (PEDOT-DS) by electropolymerisation on neural electrode arrays. Deposited films increased the electrode area and displayed a rough morphology compared to uncoated electrodes. Electrode area and charge density were obtained using microscopy and reduction of Ru(NH3)63+. Deposition charge, geometrical and linear diffusion electroactive areas were strongly correlated with deposition time. The charge density calculated from the geometric area was greater on PEDOT-DS modified electrodes than unmodified and PEDOT-para-toluene sulfonate (PEDOT-pTs) modified electrodes. The charge density calculated from the linear diffusion electroactive area was smaller on PEDOT-DS modified electrodes than unmodified and PEDOT-pTs modified electrodes. The charge density of the PEDOT-DS modified electrodes was dependant on the electrode area.

Artificial photosynthesis steps up

Bioenergy Photosynthesis fixes CO2 from the air by using sunlight. Industrial mimics of photosynthesis seek to convert CO2 directly into biomass, fuels, or other useful products. Improving on a previous artificial photosynthesis design, Liu et al. combined the hydrogen-oxidizing bacterium Raistonia eutropha with a cobalt-phosphorus water-splitting catalyst. This biocompatible self-healing electrode circumvented the toxicity challenges of previous designs and allowed it to operate aerobically. When combined with solar photovoltaic cells, solar-to-chemical conversion rates should become nearly an order of magnitude more efficient than natural photosynthesis. Science , this issue p. [1210][1] [1]: /lookup/doi/10.1126/science.aaf5039

Water splitting-biosynthetic system with CO₂ reduction efficiencies exceeding photosynthesis.

Artificial photosynthetic systems can store solar energy and chemically reduce CO2 We developed a hybrid water splitting-biosynthetic system based on a biocompatible Earth-abundant inorganic catalyst system to split water into molecular hydrogen and oxygen (H2 and O2) at low driving voltages. When grown in contact with these catalysts, Ralstonia eutropha consumed the produced H2 to synthesize biomass and fuels or chemical products from low CO2 concentration in the presence of O2 This scalable system has a CO2 reduction energy efficiency of ~50% when producing bacterial biomass and liquid fusel alcohols, scrubbing 180 grams of CO2 per kilowatt-hour of electricity. Coupling this hybrid device to existing photovoltaic systems would yield a CO2 reduction energy efficiency of ~10%, exceeding that of natural photosynthetic systems.

Multifunctional hydrogel coatings on the surface of neural cuff electrode for improving electrode-nerve tissue interfaces

Recently, implantable neural electrodes have been developed for recording and stimulation of the nervous system. However, when the electrode is implanted onto the nerve trunk, the rigid polyimide has a risk of damaging the nerve and can also cause inflammation due to a mechanical mismatch between the stiff polyimide and the soft biological tissue. These processes can interrupt the transmission of nerve signaling. In this paper, we have developed a nerve electrode coated with PEG hydrogel that contains poly(lactic-co-glycolic) acid (PLGA) microspheres (MS) loaded with anti-inflammatory cyclosporin A (CsA). Micro-wells were introduced onto the electrode in order to increase their surface area. This allows for loading a high-dose of the drug. Additionally, chemically treating the surface with aminopropylmethacrylamide can improve the adhesive interface between the electrode and the hydrogel. The surface of the micro-well cuff electrode (MCE) coated with polyethylene glycol (PEG) hydrogel and drug loaded PLGA microspheres (MS) were characterized by SEM and optical microscopy. Additionally, the conductive polymers, poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT/PSS), were formed on the hydrogel layer for improving the nerve signal quality, and then characterized for their electrochemical properties. The loading efficiencies and release profiles were investigated by High Performance Liquid Chromatography (HPLC). The drug loaded electrode resulted in a sustained release of CsA. Moreover, the surface coated electrode with PEG hydrogel and CsA loaded MP showed a significantly decreased fibrous tissue deposition and increased axonal density in animal tests. We expect that the developed nerve electrode will minimize the tissue damage during regeneration of the nervous system. Statement of SignificanceThe nerve electrodes are used for interfacing with the central nervous system (CNS) or with the peripheral nervous system (PNS). The interface electrodes should facilitate a closed interconnection with the nerve tissue and provide for selective stimulation and recording from multiple, independent, neurons of the neural system. In this case, an extraneural electrodes such as cuff and perineural electrodes are widely investigated because they can completely cover the nerve trunk and provide for a wide interface area. In this study, we have designed and prepared a functionalized nerve cuff electrode coated with PEG hydrogel containing Poly lactic-co-glycol acid (PLGA) microspheres (MS) loaded with cyclosporine A (CsA). To our knowledge, our findings suggest that surface coating a soft-hydrogel along with an anti-inflammatory drug loaded MS can be a useful strategy for improving the long-term biocompatibility of electrodes.

Pyrolytic carbon-coated stainless steel felt as a high-performance anode for bioelectrochemical systems

Scale up of bioelectrochemical systems (BESs) requires highly conductive, biocompatible and stable electrodes. Here we present pyrolytic carbon-coated stainless steel felt (C-SS felt) as a high-performance and scalable anode. The electrode is created by generating a carbon layer on stainless steel felt (SS felt) via a multi-step deposition process involving α-d-glucose impregnation, caramelization, and pyrolysis. Physicochemical characterizations of the surface elucidate that a thin (20±5μm) and homogenous layer of polycrystalline graphitic carbon was obtained on SS felt surface after modification. The carbon coating significantly increases the biocompatibility, enabling robust electroactive biofilm formation. The C-SS felt electrodes reach current densities (jmax) of 3.65±0.14mA/cm2 within 7days of operation, which is 11 times higher than plain SS felt electrodes (0.30±0.04mA/cm2). The excellent biocompatibility, high specific surface area, high conductivity, good mechanical strength, and low cost make C-SS felt a promising electrode for BESs.

An ocular iontophoretic device using PEDOT electrode for local drug delivery

An ocular iontophoretic device using a biocompatible planar PEDOT electrode is reported. In vivo experiments on rabbit eyes demonstrated that the device can realize ocular iontophoresis effectively, simply, and conveniently. Compared with conventional eye cups, this device can be placed under the eyelid and deliver ions through a small area on the eyeball, reducing tissue damage during ion penetration. Devices were fabricated in different sizes for different cases. The efficiency was a function of the current, work time and solvent water content. The highest iontophoretic efficiency observed in the in vivo experiments was 396ng/mL, while the efficiency observed in the controlled experiments was only 2.69ng/mL. The temperature distribution was simulated and measured, and thermal injuries were not observed under an applied current of 1.5mA.

Orientation-Controlled Electrocatalytic Efficiency of an Adsorbed Oxygen-Tolerant Hydrogenase

Protein immobilization on electrodes is a key concept in exploiting enzymatic processes for bioelectronic devices. For optimum performance, an in-depth understanding of the enzyme-surface interactions is required. Here, we introduce an integral approach of experimental and theoretical methods that provides detailed insights into the adsorption of an oxygen-tolerant [NiFe] hydrogenase on a biocompatible gold electrode. Using atomic force microscopy, ellipsometry, surface-enhanced IR spectroscopy, and protein film voltammetry, we explore enzyme coverage, integrity, and activity, thereby probing both structure and catalytic H2 conversion of the enzyme. Electrocatalytic efficiencies can be correlated with the mode of protein adsorption on the electrode as estimated theoretically by molecular dynamics simulations. Our results reveal that pre-activation at low potentials results in increased current densities, which can be rationalized in terms of a potential-induced re-orientation of the immobilized enzyme.

Nanocarbon-Coated Porous Anodic Alumina for Bionic Devices.

A highly-stable and biocompatible nanoporous electrode is demonstrated herein. The electrode is based on a porous anodic alumina which is conformally coated with an ultra-thin layer of diamond-like carbon. The nanocarbon coating plays an essential role for the chemical stability and biocompatibility of the electrodes; thus, the coated electrodes are ideally suited for biomedical applications. The corrosion resistance of the proposed electrodes was tested under extreme chemical conditions, such as in boiling acidic/alkali environments. The nanostructured morphology and the surface chemistry of the electrodes were maintained after wet/dry chemical corrosion tests. The non-cytotoxicity of the electrodes was tested by standard toxicity tests using mouse fibroblasts and cortical neurons. Furthermore, the cell–electrode interaction of cortical neurons with nanocarbon coated nanoporous anodic alumina was studied in vitro. Cortical neurons were found to attach and spread to the nanocarbon coated electrodes without using additional biomolecules, whilst no cell attachment was observed on the surface of the bare anodic alumina. Neurite growth appeared to be sensitive to nanotopographical features of the electrodes. The proposed electrodes show a great promise for practical applications such as retinal prostheses and bionic implants in general.