Electrochemical Stimulation Research Articles

Electrochemical activation and inhibition of neuromuscular systems through modulation of ion concentrations with ion-selective membranes.

Conventional functional electrical stimulation aims to restore functional motor activity of patients with disabilities resulting from spinal cord injury or neurological disorders. However, intervention with functional electrical stimulation in neurological diseases lacks an effective implantable method that suppresses unwanted nerve signals. We have developed an electrochemical method to activate and inhibit a nerve by electrically modulating ion concentrations in situ along the nerve. Using ion-selective membranes to achieve different excitability states of the nerve, we observe either a reduction of the electrical threshold for stimulation by up to approximately 40%, or voluntary, reversible inhibition of nerve signal propagation. This low-threshold electrochemical stimulation method is applicable in current implantable neuroprosthetic devices, whereas the on-demand nerve-blocking mechanism could offer effective clinical intervention in disease states caused by uncontrolled nerve activation, such as epilepsy and chronic pain syndromes.

Combined Electro‐chemical Stimulation to Reduce the Required Current for Muscle Contraction

Facial nerve dysfunction and the subsequent inability to blink is a common complication caused by numerous medical problems, such as stroke. Denervation and dysfunction of the orbicularis oculi, the muscle responsible for eye blinks can result in corneal abrasions and breakdown. Direct electrical stimulation of the muscle is not a viable solution, as the required electrical stimulus needed to induce a blink in denervated muscle is 3 mA while the human pain threshold is 1 mA. The insufficiency of electrical stimulation alone in triggering painless muscle contraction in denervated orbicularis oculi muscles indicates a need to investigate other methods of stimulation. The aim of this study is to investigate the response of skeletal muscle to combined electrochemical stimulation by initiating the intricate cascade that leads to muscle contraction with the application of acetylcholine in order to reduce the required electrical stimulus. Muscle sheets are used as the model for the orbicularis oculi with electrical field stimulation being applied along with constant and intermittent application of chemical stimuli.

Computational design of mixers and pumps for microfluidic systems, based on electrochemically-active conducting polymers

We present a theoretical description of the propagation of composition waves along a strip of electrochemically-active conducting polymer, upon electrochemical stimulation. We develop an efficient solution of the electro-neutral Nernst-Plank equations in 2-D for electromigration and diffusional transport in the solution based on an extension of the methods of Scharfetter and Gummel [D. L. Scharfetter and H. K. Gummel, IEEE Trans. Electron Devices, 1969, ED16, 64-77.] and of Cohen and Cooley [H. Cohen and J. W. Cooley, Biophys. J., 1965, 5, 145-162.], and demonstrate important effects of the geometry of the cell. Under some circumstances, waves reflecting back from the end of the strip are predicted. We then demonstrate theoretically how such waves, associated as they are with expansion of the polymer, could be employed to enhance mixing or induce pumping in microfluidic systems.

A novel detection of hydrogen peroxide based on a luminescent polyoxometalate

In this paper, we attempt to construct a simple and sensitive detection method for hydrogen peroxide based on reversible colour change and luminescence switching modulated by the electrochemical stimulation and redox reaction of H(2)O(2) with electroreduced polyoxometalate. This method successfully combines the electrochromic and luminescent properties of the polyoxometalate to develop a novel detection method for H(2)O(2) with good reversibility, which displays high sensitivity, a wide linear range and a low detection limit to H(2)O(2).

Electroswitchable fluorescent thin film controlled by polyoxometalate

We have fabricated an organic/inorganic hybrid thin film based on a Dawson-type polyoxometalate P2W18O626− (P2W18) and a luminescent transition metal complex tris(2,2′-bipyridine)ruthenium [Ru(bpy)3]2+ (Rubpy) by using a layer-by-layer assembly technique, which functions as an electroswitchable fluorescent device operated by electrochemical stimulation.

Polyterthiophene as an electrostimulated controlled drug release material of therapeutic levels of dexamethasone

Polyterthiophene has been investigated as a substrate for the controlled release of dexamethasone, a synthetic glucocorticoid anti-inflammatory drug, which is widely used to help reduce inflammation in the central nervous system. Dexamethasone was incorporated into the polymer as an anionic dopant during electrochemical polymerisation from water–acetonitrile solutions. Optimal polymer synthesis conditions were established to yield reproducible dexamethasone release profiles into a simulated physiological receiving solution. A homogeneous morphology of the polyterthiophene substrate with minimal extraneous features was observed to be critical for achieving reproducibility of release. Release profiles were established using a range of electrochemical stimulation protocols over a 24 h time period. The amount of dexamethasone released from the polyterthiophene under all electrostimulation protocols was at therapeutically relevant levels, with a maximum release of ∼80 μg/cm 2 achieved when the polymer film was in a reduced state. The oxidation state of the polyterthiophene was found to be critical for controlled release of the dexamethasone. Polyterthiophene doped with dexamethasone was observed to auto-reduce when placed into the receiving solution. As a consequence, no significant difference was observed between the unstimulated (auto-reduced) polymer and the electrochemically reduced polyterthiophene. By electrochemically holding the polyterthiophene in the oxidised state, the rate of release of dexamethasone was significantly impeded with ∼40 μg/cm 2 released over a 24 h period.

An electroswitchable fluorescence thin-film based on a luminescent polyoxometalate cluster

We selected a Eu(3+)-containing tungstogermanate [(CH(3))(4)N](2.5)H(7.5)[Eu(GeW(11)O(39))(H(2)O)(2)](2)·4.5H(2)O (EuGeW) as a molecular dyad combining fluorescence and electroactivity components within the same framework and studied its electroswitchable fluorescence in solution and in the thin-film, which can be reversibly switched by electrochemical stimulation.

Probing Donor−Acceptor Interactions andCo-Conformational Changes in Redox Active Desymmetrized [2]Catenanes

We describe the synthesis and characterization of a series of desymmetrized donor-acceptor [2]catenanes where different donor and acceptor units are assembled within a confined catenated geometry. Remarkable translational selectivity is maintained in all cases, including two fully desymmetrized [2]catenanes where both donors and acceptors are different, as revealed by X-ray crystallography in the solid state, and by (1)H NMR spectroscopy and electrochemistry in solution. In all desymmetrized [2]catenanes the co-conformation is dominated by the strongest donor and acceptor pairs, whose charge-transfer interactions also determine the visible absorption properties. Voltammetric and spectroelectrochemical experiments show that the catenanes can be reversibly switched among as many as seven states, characterized by distinct electronic and optical properties, by electrochemical stimulation in a relatively narrow and easily accessible potential window. Moreover in some of these compounds the oxidation of the electron donor units or the reduction of the electron acceptor ones causes the circumrotation of one molecular ring with respect to the other. These features make these compounds appealing for the development of molecular electronic devices and mechanical machines.

Bioinspired Electrochemically Tunable Block Copolymer Full Color Pixels

By controlling absorption, reflection, and body surface texture cephalopods display an incredible ability to manage and manipulate light – a goal of modern display technology. With these and several other aquatic species, tunable, structural color plays a fundamental role in creating vivid and eye-catching color, which is produced in part by using and modulating 1D reflectors known as iridophores. The color change of the light reflected from these tunable Bragg reflectors is accomplished by the local introduction of chemical neurotransmitters that either change the spacing between high refractive index platelets or change the thickness (and possibly the refractive index) of the platelets themselves. Efficient, refined mechanisms of visual communication and disruptive coloration – such as iridophores are key to cephalopod survival. The next generation of display materials could benefit from the lessons learned over millions of years of evolution in order to produce inexpensive, robust, low-energy, high-contrast displays. Here we present a bioinspired, electrochemically tunable, full-color pixel based on a self-assembling block copolymer (BCP). Imitating cephalopod reflectin proteins, which form layered, highly reflective structures, the lamellar structure of these BCPs exhibits a periodic refractive index. Such structures are commonly known as 1D photonic crystals and yield photonic stop bands which reflect incident electromagnetic radiation of a wavelength range dependent on the angle of incidence of light, the index of refraction of the respective layers, and their periodicity. Partial color tunability has been demonstrated in numerous photonic crystal systems which have been intensely investigated due to their inherent passive structural color which negates the need for light-absorbing color filters and backlights common in emissive technologies. A number of types of photonic crystals based on cholesteric liquid crystals, synthetic opals, and diffraction gratings have attained full color tunability using direct or indirect electrical control. Tailored absorption using electrochromic materials has also achieved full color tunability in recent years. Electrical control is highly sought after for display applications because of the ease with which it can supply a local stimulus. Previously, BCPs have been used as photonic crystals but with limited tunability arising from changes in temperature and homopolymer or solvent concentration. Recently we reported a highly tunable, structural-color reflector based on a hydrophilic/hydrophobic block copolymer (polystyreneb-poly(2-vinylpyridine)PS-P2VP) that achieved substantial tunability (over 575%) of the primary stop band from ultraviolet (350 nm) to near infrared wavelengths (1600 nm) by changing the concentration of salt in the solvent. Here we employ the same block copolymer to create our biomimetic, full-color pixel. The lamellar structure of this block copolymer and the behavior of the electrically stimulated hydrophilic gel block mimic the type of optical response of the reflectin proteins found in certain cephalopod species. These cephalopods have the ability to change the iridescent colors reflected from their skin in real time by the secretion of the common neuromodulator acetylcholine, which alters the periodic spacing of the lamellar iridophore structure. In our work, we couple the structure-forming ability of a block copolymer with an electrically induced chemical tunability of the spacing and refractive index of the gel layers to obtain a tunable, reflectin-like structure. Polyelectrolyte polymer gels are well known for their stimuli responsiveness and have been shown to react to electric fields and changes in pH caused by electric fields. By selecting a diblock copolymer that incorporates a glassy domain (polystyrene) to limit the gel forming domain (poly 2-vinylpyridine) to expansion only in the direction normal to the layers, we control the swelling behavior of the gel andmagnify the response of the periodic dielectric stack to external stimuli. We use a modest molecular weight (102 kg/mol–97 kg/mol), PS-P2VP block copolymer in combination with a simple electrochemical cell to produce red, green, and blue color through electrochemical stimulation. Our biomimetic color pixel is based on a simple electrochemical cell in which the local chemical environment at the electrode/electrolyte interface can be changed by applying sufficient voltage to induce electrochemical oxidation or reduction. Because polymeric gels can undergo significant shape change in response to changes in their chemical environments, this chemical stimulus at the electrode can have major effects on the swelling behavior of the gel, as is the case in color changing iridophores in nature. Fish such as the blue damselfish, neon tetra, and paradise whiptail all employ 1D photonic crystals

The lack of effect of electrochemical stimulation of the hypothalamus and median eminence on the plasma corticosterone level after lesion of the paraventricular nuclei.

Electrochemical stimulation of the median eminence of intact rats causes a significant increase in plasma corticosterone level, while the same stimulation within the middle part of the medial basal hypothalamus outside the median eminence is ineffective. Partial removal of the paraventricular nuclei greatly reduces, while complete lesion abolishes the above effect of electrochemical stimulation of the median eminence upon plasma corticosterone level.

Optimization and Validation of a Multiplex, Electrochemiluminescence-Based Detection Assay for the Quantitation of Immunoglobulin G Serotype-Specific Antipneumococcal Antibodies in Human Serum

Pneumovax 23 consists of a mixture of highly purified capsular polysaccharides (Ps) from 23 of the most prevalent serotypes of Streptococcus pneumoniae. Testing of vaccine immunogenicity has been historically performed on the enzyme-linked immunosorbent assay (ELISA) platform, validated to measure immunoglobulin G (IgG) antibodies to all 23 serotypes included in Pneumovax 23. In order to significantly improve the throughput of this form of testing, we have developed and validated a direct binding electrochemiluminescence (ECL)-based multiplex assay that can measure the antibody response in human serum to eight serotypes within a single microtiter well. The pneumococcal (Pn) ECL assay is based on the Meso Scale Discovery (MSD) technology which utilizes a Sulfo-Tag-labeled anti-human IgG antibody that emits light upon electrochemical stimulation. The Pn ECL assay exhibits a wide dynamic range and provides the ability to read concentrations down to the minimum reported concentration in the Merck ELISA (0.1 microg/ml). Cross-reactivity assessment using type-specific monoclonal antibodies showed no cross talk between antigen spots within a well. By use of the WHO Pn sample reference panel, the results obtained with the Pn ECL assay were compared to the results obtained with the international Pn ELISA. The results for the Pn ECL assay satisfied the WHO-recommended acceptance criterion for concordance for all seven serotypes with published Pn ELISA values, and the overall correlation (r value) across the seven serotypes was 0.994. The MSD methodology has great potential to be extremely useful for simultaneously quantitating IgG responses to several Pn serotypes while conserving serum volumes and laboratory testing time.

Enhancement of Pseudo-capacitive Behaviors of Birnessite Type Manganese Dioxide by Electrolyte Additive

The birnessite type manganese dioxide electrode was prepared by the electrochemical stimulation as we recently described. It showed 190 F g-1 in a Na2SO4 aqueous solution between -0.1 and 0.9 V vs. Ag/AgCl at 1 A g-1. The specific capacitance of birnessite was decreased by the manganese dissolution when the reduction and oxidation were repeated. By adding small amounts of Na2HPO4 or NaHCO3 into the electrolyte, the capacitance increased to 200 - 230 F g-1 and the manganese dissolution was successfully suppressed. Thanks to the additives, the birnessite demonstrated the much improved cycleability over > 1800 cycles.

Enhanced supercapacitive behaviors of birnessite

The birnessite type manganese dioxide electrode was prepared by the electrochemical stimulation as we recently described. It showed 190 F g −1 in a Na 2SO 4 aqueous solution between −0.1 and 0.9 V versus Ag/AgCl at 1 A g −1. The specific capacitance of birnessite was decreased by the manganese dissolution when the reduction and oxidation were repeated. By adding small amounts of Na 2HPO 4 or NaHCO 3 into the electrolyte, the capacitance increased to 200–230 F g −1 and the manganese dissolution was successfully suppressed. Thanks to the additives, the birnessite demonstrated the much improved cycleability over >1800 cycles.

Molecular Clips with Extended Aromatic Sidewalls as Receptors for Electron-Acceptor Molecules. Synthesis and NMR, Photophysical, and Electrochemical Properties

We have synthesized molecular clips 1 comprising (i) two benzo[k]fluoranthene sidewalls and (ii) a dimethylene-connected benzene bridge that carries two acetoxy (1a), hydroxy (1b), or methoxy (1c) substituents in the para position. Their NMR spectra, single-crystal structures, and photophysical (fluorescence intensity, lifetime, depolarization) and electrochemical properties are discussed. For the purpose of comparison, similar compounds (2 and 3) containing only one benzo[k]fluoranthene unit have been prepared and studied. The strongly fluorescent clips 1 form stable complexes with electron-acceptor guests because of a highly negative electrostatic potential on the inner van der Waals surface of their cavity. The complexation constants in chloroform solution for a variety of guests, determined by NMR and fluorescence titration, are much larger than those of the corresponding anthracene and naphthalene clips (4 and 5), particularly in the case of extended aromatic guests. The effect of the substituents in the para position of the benzene spacer unit of clips 1 is discussed on the basis of the host-guest complex structures obtained by X-ray analysis and molecular mechanics simulations. In the case of 9-dicyanomethylene-2,4,7-trinitrofluorene (TNF) guest, complex formation with clip 1a causes dramatic changes in the photophysical and electrochemical properties: (i) a new charge-transfer band at 600 nm arises, (ii) a very efficient quenching of the strong benzo[k]fluoranthene fluorescence takes place, (iii) shifts of both the first oxidation (clip-centered) and reduction (TNF-centered) potentials are observed, and (iv) reversible disassembling of the complex can be obtained by electrochemical stimulation.

Generation of Aβ38 and Aβ42 Is Independently and Differentially Affected by Familial Alzheimer Disease-associated Presenilin Mutations and γ-Secretase Modulation

Alzheimer disease amyloid beta-peptide (Abeta) is generated via proteolytic processing of the beta-amyloid precursor protein by beta- and gamma-secretase. Gamma-secretase can be blocked by selective inhibitors but can also be modulated by a subset of non-steroidal anti-inflammatory drugs, including sulindac sulfide. These drugs selectively reduce the generation of the aggregation-prone 42-amino acid Abeta(42) and concomitantly increase the levels of the rather benign Abeta(38). Here we show that Abeta(42) and Abeta(38) generation occur independently from each other. The amount of Abeta(42) produced by cells expressing 10 different familial Alzheimer disease (FAD)-associated mutations in presenilin (PS) 1, the catalytic subunit of gamma-secretase, appeared to correlate with the respective age of onset in patients. However, Abeta(38) levels did not show a negative correlation with the age of onset. Modulation of gamma-secretase activity by sulindac sulfide reduced Abeta(42) in the case of wild type PS1 and two FAD-associated PS1 mutations (M146L and A285V). The remaining eight PS1 FAD mutants showed either no reduction of Abeta(42) or only rather subtle effects. Strikingly, even the mutations that showed no effect on Abeta(42) levels allowed a robust increase of Abeta(38) upon treatment with sulindac sulfide. Similar observations were made for fenofibrate, a compound known to increase Abeta(42) and to decrease Abeta(38). For mutants that predominantly produce Abeta(42), the ability of fenofibrate to further increase Abeta(42) levels became diminished, whereas Abeta(38) levels were altered to varying extents for all mutants analyzed. Thus, we conclude that Abeta(38) and Abeta(42) production do not depend on each other. Using an independent non-steroidal anti-inflammatory drug derivative, we obtained similar results for PS1 as well as for PS2. These in vitro results were confirmed by in vivo experiments in transgenic mice expressing the PS2 N141I FAD mutant. Our findings therefore have strong implications on the selection of transgenic mouse models used for screening of the Abeta(42)-lowering capacity of gamma-secretase modulators. Furthermore, human patients with certain PS mutations may not respond to gamma-secretase modulators.

Electrochemical Stimulation of Microbial Perchlorate Reduction

As part of our studies into the diversity of dissimilatory perchlorate reducing bacteria (DPRB) we investigated the reduction of perchlorate in the cathodic chamber of a bioelectrical reactor (BER). Our results demonstrated that washed cells of Dechloromonas and Azospira species readily reduced 90 mg L(-1) perchlorate in the BER with 2,6-anthraquinone disulfonate (AQDS) as a mediator. No perchlorate was reduced in the absence of cells or AQDS, or in an open-circuit control. Similar results were observed when a natural microbial community was inoculated into a fed-batch BER. After 70 days of operation, a novel DPRB, strain VDY, was isolated which readily reduced perchlorate in a mediatorless BER. Continuous up-flow BERs (UFBERs) were seeded with active cultures of strain VDY, and perchlorate at a volumetric loading of 60 mg L(-1) day(-1) was successfully removed. Gas phase analysis indicated that low levels of H2 produced at the cathode surface through electrolysis may mediate this metabolism. The results of these studies demonstrate that biological perchlorate remediation can be facilitated through the use of a cathode as the primary electron donor, and that continuous treatment in such a system approaches current industry standards. This has important implications for the continuous treatment of this critical contaminant in industrial waste streams and drinking water.

Optimising the incorporation and release of a neurotrophic factor using conducting polypyrrole

In this study, a neurotrophin delivery system based on an inherently conducting polymer (ICP) has been developed. Direct incorporation of neurotrophin-3 (NT-3) was investigated and controlled release was tested under various electrochemical conditions. The loading capacity and amount of NT-3 released from the polymer was determined using 125I-labelled NT-3. Electrochemical stimulation of polypyrrole by pulsed voltage, pulsed current or cyclic voltammetry promoted the release of NT-3 at a greater rate than natural diffusion of NT-3. NT-3 was released from polypyrrole as an initial burst in the first 24 h followed by prolonged release over a subsequent 6 days of sampling. The amount of NT-3 incorporated into the polymer could be controlled by varying the polymerisation time, with longer growth periods incorporating more NT-3. The NT-3 release results indicated that the polymers grown for longer released a lower percentage of the incorporated NT-3 compared to the polymers grown for shorter times. Polymer-based neurotrophin delivery systems have the potential to be incorporated into future treatments for nerve injuries to prevent nerve degradation and promote nerve protection.

Polarization Behavior of Powder Consolidated Zr Base Amorphous Alloy with Culturing Fibroblasts

Polarisation test and impedance measurement were performed on powder consolidated Zr-Al-Ni-Cu amorphous alloy with and without fibroblast L929 cells incubated in medium for 7 d. L929 cells show well extended morphology, indicating that the surface of the alloy dose not show toxicity. L929 does not influence the values of cathodic and passive current densities and pitting potential of the alloy. Also, impedance behaviour is not changed with L929 cells. Those results indicate that the corrosion resistance of the powder consolidated Zr base amorphous alloy is not influenced with L929 cells. However, the pitting potential varies in the wide potential range regardless of the existence of L929 cells. Significant uniform corrosion sometimes occurs under impedance measurement at open circuit potential. It is supposed that the alloy becomes sensitive to electrochemical stimulation during the immersion in solution probably due to the defects such as grain boundary between original amorphous alloy powders.

Host−Guest Complexes between an Aromatic Molecular Tweezer and Symmetric and Unsymmetric Dendrimers with a 4,4‘-Bipyridinium Core

We have investigated the spectroscopic and electrochemical behavior of symmetric and unsymmetric first-, second-, and third-generation dendrimers comprising an electron-acceptor 4,4'-bipyridinium core (viologen type) and electron-donor 1,3-dimethyleneoxybenzene (Fréchet-type) dendrons. The quite strong fluorescence of the symmetrically and unsymmetrically disubstituted 1,3-dimethyleneoxybenzene units of the dendrons is completely quenched as a result of donor-acceptor interactions that are also evidenced by a low-energy tail in the absorption spectrum. In dichloromethane solution, the 4,4'-bipyridinium cores of the investigated dendrimers are hosted by a molecular tweezer comprising a naphthalene and four benzene components bridged by four methylene units. Host-guest formation causes the quenching of the tweezer fluorescence. The association constants, as measured from fluorescence and (1)H NMR titration plots, (i) are of the order of 10(4) M(-1), (ii) decrease on increasing dendrimer generation, and (iii) are slightly larger for the unsymmetric than for the symmetric dendrimer of the same generation. The analysis of the complexation-induced shifts of the temperature-dependent (1)H NMR signals of the host and guest protons confirms that the bipyridinium core is positioned inside the tweezer cavity and allows the conclusions that (i) shuttling of the tweezer from one to the other pyridinium ring is fast (DeltaG < 10 kcal/mol), (ii) in the case of the unsymmetric dendrimers, the less substituted pyridinium ring is preferentially complexed in apolar solvents, and (iii) complexation of the 4,4'-bipyridinium core proceeds by clipping for the symmetric dendrimers and by threading in the case of unsymmetric ones. Host-guest formation causes a displacement of the first reduction wave of the 4,4'-bipyridinium unit toward more negative potential values, whereas the second reduction wave is unaffected. These results show that the host-guest complexes between the tweezer and the dendrimers are stabilized by electron donor-acceptor interactions and can be reversibly assembled/disassembled by electrochemical stimulation.

Effects of monomer and electrolyte concentrations on actuation of PPy(DBS) bilayers

Bilayers of gold-coated Kapton and polypyrrole doped with dodecylbenzenesulfonate PPy(DBS), were prepared electrochemically, and their bending movement was studied under electrochemical stimulation. The effects on actuation of monomer and electrolyte concentration during deposition, as well as electrolyte concentration during subsequent electrochemical cycling, are presented. Lowering the pyrrole concentration decreased hysteresis, somewhat increased actuator speed, and unexpectedly eliminated the so-called capacitive current above the oxidation peak. Neither pyrrole nor electrolyte concentration in the deposition solution affected the extent of movement, despite the fact that the former strongly impacted the cyclic voltammograms. The cyclic voltammograms were, therefore, not predictive of the extent of bending, and strain could not be significantly improved by altering the concentration of either monomer or salt in the deposition solution. Raising the deposition electrolyte concentration, and in particular raising it with respect to the pyrrole concentration, did increase the movement to charge ratio, making the actuators more efficient.