Charge Injection Capacity Research Articles

Corrosion Study of Implanted Tin Electrodes Using Excessive Electrical Stimulation in Minipigs

(1) Background: Titanium nitride (TiN) electrodes have been used for implantable stimulation and sensing electrodes for decades. Nevertheless, there still is a discrepancy between the in vitro and in vivo determined safe charge injection limits. This study investigated the consequences of pulsing implanted electrodes beyond the in vivo safe charge injection limits. (2) Methods: The electrodes were implanted for a month and then pulsed at 20 mA and 50 mA and 200 Hz and 400 Hz. Afterwards, the electrodes were investigated using electrochemical and analytical methods to evaluate whether electrode degradation had occurred. (3) Results: Electrochemical tests showed that electrodes that pulsed at 20 mA and 200 Hz (lowest electrical dose) had a significantly lower charge injection capacity and higher impedance than the other used and unused electrodes. (4) Conclusions: The electrodes pulsed at the lowest electrical dose, for which no tissue damage was found, appeared to have degraded. Electrodes pulsed at higher electrical doses for which tissue damage did occur, on the other hand, show no significant degradation in electrochemical tests compared to unused implanted and not implanted electrodes. It is thus clear that the tissue surrounding the electrode has an influence on the charge injection properties of the electrodes and vice versa.

High-Performance Graphene-Fiber-Based Neural Recording Microelectrodes.

Fabrication of flexible and free-standing graphene-fiber- (GF-) based microelectrode arrays with a thin platinum coating, acting as a current collector, results in a structure with low impedance, high surface area, and excellent electrochemical properties. This modification results in a strong synergistic effect between these two constituents leading to a robust and superior hybrid material with better performance than either graphene electrodes or Pt electrodes. The low impedance and porous structure of the GF results in an unrivalled charge injection capacity of 10.34 mC cm-2 with the ability to record and detect neuronal activity. Furthermore, the thin Pt layer transfers the collected signals along the microelectrode efficiently. In vivo studies show that microelectrodes implanted in the rat cerebral cortex can detect neuronal activity with remarkably high signal-to-noise ratio (SNR) of 9.2 dB in an area as small as an individual neuron.

Electrodeposited poly(3,4-ethylenedioxypyrrole) films as neural interfaces: Cytocompatibility and electrochemical studies

Conducting polymers have been extensively reported as promising coating materials for applications involving interactions with electrically excitable tissues. Specifically, metal electrodes functionalized with conducting polymer coatings have been employed as biointerfaces presenting tailored properties to promote electrode integration as well as chronic functionality. Currently, polypyrrole (PPy) and poly(3,4-ethylenedioxythiophene) (PEDOT) represent the most extensively studied conducting polymers, exhibiting favourable electrochemical properties and biocompatibility. In this paper, we study electrodeposited poly(3,4-ethylenedioxypyrrole) (PEDOP), a conducting polymer which is structurally related to both PEDOT and PPy, and is expected to outperform its “parent” polymers in terms of electrochemical properties and biocompatibility. The performance of PEDOP doped with chloride/phosphate, p-toluenesulfonate or polystyrene sulfonate was subsequently investigated to assess the efficacy of these ionic dopants in promoting electrochemical stability and neural cytocompatibility. Electrodeposited PEDOP films exhibited a high charge storage capacity (50.07 ± 6.96 mC cm−2), charge injection capacity (203 ± 24 μC cm−2) and substantial stability (performance loss of 0.49 ± 0.06% after 100 000 stimulation pulses). Furthermore, PEDOP films promoted enhanced neuron outgrowth and viability relative to control substrates. In particular, PEDOP/PTS was shown to increase the average neurite length by a factor of three when compared with cells cultured on bare Pt control substrates. Consequently, due to its favourable electrochemical characteristics together with high neural cytocompatibility, PEDOP can be indicated as a promising alternative to PPy and PEDOT in the field of neural science.

Electrochemical Characterization of Graphene Microelectrodes for Biological Applications

AbstractGraphene is a promising material both as a coating for existing neural electrodes as well as for transparent electrodes made exclusively from graphene. We studied graphene‐based microelectrodes by investigating their recording and stimulation properties in order to evaluate their suitability for neuronal implants. In this work, we compare three different electrode material compositions. Microelectrode arrays (MEA) with an electrode size of about 700 μm2 were prepared of gold, graphene on gold, and plain graphene on glass substrate. In order to reduce polymer contamination during graphene transfer, we employed a polymer‐free transfer and lift‐off process. Impedance studies revealed a value of 2.3 MΩ at 1 kHz for plain, and 0.88 MΩ for graphene on gold. Neuronal recording experiments showed a sufficient SNR for both graphene‐based materials and a stable impedance, unaffected by surface degradation metal electrodes are known for. Stimulation measurements yielded a charge injection capacity of 0.15 mC/cm2 using biphasic pulses of 1 ms and 1 μA transparent graphene electrodes. Cyclic voltammetry revealed a large voltage range of −1.4 V to +1.6 V before water electrolysis occurs. Graphene‐coated gold microelectrodes show enhanced recording properties, whereas plain graphene electrodes might be better suited for stimulation applications.

A Measurement Setup and Automated Calculation Method to Determine the Charge Injection Capacity of Implantable Microelectrodes.

The design of safe stimulation protocols for functional electrostimulation requires knowledge of the “maximum reversible charge injection capacity” of the implantable microelectrodes. One of the main difficulties encountered in characterizing such microelectrodes is the calculation of the access voltage Va. This paper proposes a method to calculate Va that does not require prior knowledge of the overpotential terms and of the electrolyte (or excitable tissue) resistance, which is an advantage for in vivo electrochemical characterization of microelectrodes. To validate this method, we compare the calculated results with those obtained from conventional methods for characterizing three flexible platinum microelectrodes by cyclic voltammetry and voltage transient measurements. This paper presents the experimental setup, the required instrumentation, and the signal processing.

Diamond/Porous Titanium Nitride Electrodes With Superior Electrochemical Performance for Neural Interfacing.

Robust devices for chronic neural stimulation demand electrode materials which exhibit high charge injection (Qinj) capacity and long-term stability. Boron-doped diamond (BDD) electrodes have shown promise for neural stimulation applications, but their practical applications remain limited due to the poor charge transfer capability of diamond. In this work, we present an attractive approach to produce BDD electrodes with exceptionally high surface area using porous titanium nitride (TiN) as interlayer template. The TiN deposition parameters were systematically varied to fabricate a range of porous electrodes, which were subsequently coated by a BDD thin-film. The electrodes were investigated by surface analysis methods and electrochemical techniques before and after BDD deposition. Cyclic voltammetry (CV) measurements showed a wide potential window in saline solution (between −1.3 and 1.2 V vs. Ag/AgCl). Electrodes with the highest thickness and porosity exhibited the lowest impedance magnitude and a charge storage capacity (CSC) of 253 mC/cm2, which largely exceeds the values previously reported for porous BDD electrodes. Electrodes with relatively thinner and less porous coatings displayed the highest pulsing capacitances (Cpulse), which would be more favorable for stimulation applications. Although BDD/TiN electrodes displayed a higher impedance magnitude and a lower Cpulse as compared to the bare TiN electrodes, the wider potential window likely allows for higher Qinj without reaching unsafe potentials. The remarkable reduction in the impedance and improvement in the charge transfer capacity, together with the known properties of BDD films, makes this type of coating as an ideal candidate for development of reliable devices for chronic neural interfacing.

Self-supporting carbon nanotube films as flexible neural interfaces

Advances in neural interface technologies have sought to identify electroactive materials that are able to translate neural depolarisation events into digital signals or modulate neural firing through ionic or electrical stimulation with greater efficiency. An ideal material for neural recording and/or stimulation should possess low electrical impedance coupled with a high cathodic charge storage capacity (CSCC), charge injection capacity (CIC) and electroactive surface area (ESA), as well as optimal mechanical biomimicry. In this study, we present the robustness of self-supporting CNT films as neural interfaces, combining advantageous electrical and mechanical properties with high cytocompatibility. Films were observed to possess a high CSCC (29.95 ± 0.91 mC cm−2), CIC (352 ± 5 μC V−1 cm−2) and ESA (0.908 ± 0.053 cm2), low impedance (110 Ω at 1 kHz), low resistance (75 ± 13 Ω) and high capacitance (378 ± 9 μF cm−2), and outperformed Pt control electrodes. Self-supporting CNT films were also found to facilitate neuron growth and decrease the presence of reactive astrocytes in a mixed neural cell population. Self-standing CNT films were shown to be promising materials for the design of flexible and cytocompatible neural interfaces.

In vitro electrochemical assessment of electrodes for neurostimulation in roach biobots.

Biobotics investigates the use of live insects as biological robots whose locomotion can be controlled by neurostimulation through implanted electrodes. Inactivity in the biobots (biological robots) can sometimes be noticed following extended neurostimulation, partly owing to incompatibility of implanted electrodes with the biobotic application or gradual degradation of the tissue-electrode interface. Implanted electrodes need to sufficiently exhibit consistent, reliable, and stable performance during stimulation experiments, have low tissue-electrode impedance, facilitate good charge injection capacity, and be compact in size or shape. Towards the goal of finding such electrodes suitable for biobotic applications, we compare electrochemical performances of five different types of electrodes in vitro with a saline based electrolytic medium. These include stainless steel wire electrodes, microfabricated flexible gold electrodes coated with PEDOT:PSS conductive polymer, eutectic gallium indium (EGaIn) in a tube, and “hybrid” stainless steel electrodes coated with EGaIn. We also performed accelerated aging of the electrodes to help estimate their longitudinal performance. Based on our experimentation, microfabricated electrodes with PEDOT:PSS and stainless steel electrodes coated with EGaIn performed remarkably well. This is the first time conductive polymer and liquid metal electrodes were studied comparatively for neurostimulation applications. These in vitro comparison results will be used in the future to provide a benchmark for subsequent in vivo tests with implanted electrodes in cockroach biobots.

PEDOT: PSS coating on gold microelectrodes with excellent stability and high charge injection capacity for chronic neural interfaces

PEDOT: PSS has become one of the best choices as coating material of neural interfaces electrodes for its excellent biocompatibility, chemical steadiness and extremely inhomogeneous topography that facilitate reversible faradaic charge injection. However, chronic application of this material is still a matter of challenge for its poor adhesion to metallic electrodes. This study presents two new methods that increases stability and stimulation capacity of PEDOT: PSS (poly(3,4-ethylenedioxythiophene): poly(styrene sulfonate)) coated neural interfaces electrodes. These improvements in the characteristics make PEDOT: PSS as a promising coating material for the long-term stable bidirectional neural application. The first process ensures long-term stability of PEDOT: PSS coating. The stability improvement is done by creating a rough and porous surface with selective iodine etching of Au electrodes. The pores act as anchors and increases mechanical bonding between PEDOT: PSS coating and electrode surface, hence the stability of the coating increases. PEDOT: PSS coating on iodine etched gold electrode showed 100% stability under strong ultrasonic stability test compared to non-etched electrodes. Long-term in vitro continuous stimulation for 7 days was performed to evaluate the stability of the coating. 1 μm thick PEDOT:PSS coating on iodine etched Au electrode completely survived under 604 million continuous current pulses that was evaluated by SEM image and electrochemical impedance spectroscopy (EIS). The second process improves the characteristics of PEDOT: PSS coated electrodes in terms of stimulation capacity. This is done by electrochemical modification of PEDOT: PSS coating surface by applying a cyclic voltammetry method. A perfect and effective method is developed by comparative analysis and optimizing the parameters of cyclic voltammetry. The PEDOT: PSS coating presented here (1 μm thick) reduces the impedance of bare Au electrode by around 99%. This electrochemical modification method further reduces the impedance of this PEDOT: PSS coated electrode by 33%. Moreover, this method reduces electrode polarization under stimulation by 30.5%. Reduced electrode impedance and polarization under stimulation are beneficial for increasing safe charge injection limit of the electrode for stimulation. Both processes facilitate the use of PEDOT: PSS coating as a true long-term stable and promising material on gold microelectrodes of neural interfaces.

Buffer-modified C60/pentacene as organic charge generation layer based on Al and MoO3

We demonstrate tandem organic light-emitting diodes (TOLEDs) with excellent performance using Al and MoO3 buffer-modified C60/pentacene as charge generation layer (CGL). Al and MoO3 were used as the electron and hole injection layers of C60/pentacene CGL, respectively. Green phosphorescence TOLEDs with the structure of ITO/NPB/mCP:Ir(ppy)3/TPBi/Al/C60/pentacene/MoO3/NPB/mCP:Ir(ppy)3/TPBi/Cs2CO3/Al were fabricated. The results show that the inserted Al and MoO3 can effectively increase the charge injection capacity of organic CGL, resulting the improvement of luminance and current efficiency of TOLEDs. The turn-on voltage of TOLEDs is much lower than that of single-unit device, and the current efficiency is more than 2 times larger than that of the single-unit device. TOLEDs can exhibit excellent photoelectric performance when the thicknesses of Al, C60, pentacene and MoO3 are 3 nm, 15 nm, 25 nm and 1 nm, respectively. The maximum luminance and current efficiency are 7 920.0 cd/m2 and 16.4 cd/A, respectively. This work is significant to build new CGL structures for realizing high-performance TOLEDs.

Feasibility of Nitrogen Doped Ultrananocrystalline Diamond Microelectrodes for Electrophysiological Recording From Neural Tissue.

Neural prostheses that can monitor the physiological state of a subject are becoming clinically viable through improvements in the capacity to record from neural tissue. However, a significant limitation of current devices is that it is difficult to fabricate electrode arrays that have both high channel counts and the appropriate electrical properties required for neural recordings. In earlier work, we demonstrated nitrogen doped ultrananocrystalline diamond (N-UNCD) can provide efficacious electrical stimulation of neural tissue, with high charge injection capacity, surface stability and biocompatibility. In this work, we expand on this functionality to show that N-UNCD electrodes can also record from neural tissue owing to its low electrochemical impedance. We show that N-UNCD electrodes are highly flexible in their application, with successful recordings of action potentials from single neurons in an in vitro retina preparation, as well as local field potential responses from in vivo visual cortex tissue. Key properties of N-UNCD films, combined with scalability of electrode array fabrication with custom sizes for recording or stimulation along with integration through vertical interconnects to silicon based integrated circuits, may in future form the basis for the fabrication of versatile closed-loop neural prostheses that can both record and stimulate.

Measuring the effective area and charge density of platinum electrodes for bionic devices

Objective. Neural stimulation is usually performed with fairly large platinum electrodes. Smaller electrodes increase the applied charge density, potentially damaging the electrode. Greater understanding of the charge injection mechanism is required for safe neural stimulation. Approach. The charge injection mechanism and charge injection capacity were measured by cyclic voltammetry. Electrodes were cleaned mechanically or by potential cycling in acidic solutions. The effective electrode area was measured by hydrogen adsorption or reduction of . Main results. The water window and safe potential window were affected by changes to electrolyte, electrode size, polishing method and oxygen concentration. Capacitance and Faradaic current contribute to the charge injection capacity. Varying voltammetric scan rate (measurement time), electrode size, polishing method, potential window, electrolyte and oxygen concentration affected the charge injection capacity and ratio of oxidation to reduction charge. Hydrogen adsorption in acidic solutions provided an inaccurate effective electrode area. Reduction of a solution phase redox species with a linear or radial diffusion profile could provide an effective electrode area. The charge density (charge injection capacity divided by electrode area) of a platinum electrode is dependent on the charge injection capacity and electrode area measurement technique. By varying cyclic voltammetric conditions, the charge density of platinum ranged from 0.15 to 5.57 mC cm−2. Significance. The safe potential window, charge injection mechanism, charge injection capacity and charge density of platinum depends on electrolyte, size of the electrode, oxygen concentration and differences in electrode polishing method. The oxidation and reduction charge injection capacities are not equal. Careful control of a platinum electrodes surface may allow larger charge densities and safe use of smaller electrodes. New electrode materials and geometries should be tested in a consistent manner to allow comparison of potential suitability for neural stimulation.

Electrochemical Evaluations of Fractal Microelectrodes for Energy Efficient Neurostimulation

Advancements in microfabrication has enabled manufacturing of microscopic neurostimulation electrodes with smaller footprint than ever possible. The smaller electrodes can potentially reduce tissue damage and allow better spatial resolution for neural stimulation. Although electrodes of any shape can easily be fabricated, substantial effort have been focused on identification and characterization of new materials and surface morphology for efficient charge injection, while maintaining simple circular or rectangular Euclidean electrode geometries. In this work we provide a systematic electrochemical evaluation of charge injection capacities of serpentine and fractal-shaped platinum microelectrodes and compare their performance with traditional circular microelectrodes. Our findings indicate that the increase in electrode perimeter leads to an increase in maximum charge injection capacity. Furthermore, we found that the electrode geometry can have even more significant impact on electrode performance than having a larger perimeter for a given surface area. The fractal-shaped microelectrodes, despite having smaller perimeter than other designs, demonstrated superior charge injection capacity. Our results suggest that electrode design can significantly affect both Faradaic and non-Faradaic electrochemical processes, which may be optimized to enable a more energy efficient design for neurostimulation.

Carbon fiber on polyimide ultra-microelectrodes

Objective. Most preparations for making neural recordings degrade over time and eventually fail due to insertion trauma and reactive tissue response. The magnitudes of these responses are thought to be related to the electrode size (specifically, the cross-sectional area), the relative stiffness of the electrode, and the degree of tissue tolerance for the material. Flexible carbon fiber ultra-microelectrodes have a much smaller cross-section than traditional electrodes and low tissue reactivity, and thus may enable improved longevity of neural recordings in the central and peripheral nervous systems. Only two carbon fiber array designs have been described previously, each with limited channel densities due to limitations of the fabrication processes or interconnect strategies. Here, we describe a method for assembling carbon fiber electrodes on a flexible polyimide substrate that is expected to facilitate the construction of high-density recording and stimulating arrays. Approach. Individual carbon fibers were aligned using an alignment tool that was 3D-printed with sub-micron resolution using direct laser writing. Indium deposition on the carbon fibers, followed by low-temperature microsoldering, provided a robust and reliable method of electrical connection to the polyimide interconnect. Main results. Spontaneous multiunit activity and stimulation-evoked compound responses with SNR >10 and >120, respectively, were recorded from a small (125 µm) peripheral nerve. We also improved the typically poor charge injection capacity of small diameter carbon fibers by electrodepositing 100 nm-thick iridium oxide films, making the carbon fiber arrays usable for electrical stimulation as well as recording. Significance. Our innovations in fabrication technique pave the way for further miniaturization of carbon fiber ultra-microelectrode arrays. We believe these advances to be key steps to enable a shift from labor intensive, manual assembly to a more automated manufacturing process.

Amorphous silicon carbide ultramicroelectrode arrays for neural stimulation and recording

Objective. Foreign body response to indwelling cortical microelectrodes limits the reliability of neural stimulation and recording, particularly for extended chronic applications in behaving animals. The extent to which this response compromises the chronic stability of neural devices depends on many factors including the materials used in the electrode construction, the size, and geometry of the indwelling structure. Here, we report on the development of microelectrode arrays (MEAs) based on amorphous silicon carbide (a-SiC). Approach. This technology utilizes a-SiC for its chronic stability and employs semiconductor manufacturing processes to create MEAs with small shank dimensions. The a-SiC films were deposited by plasma enhanced chemical vapor deposition and patterned by thin-film photolithographic techniques. To improve stimulation and recording capabilities with small contact areas, we investigated low impedance coatings on the electrode sites. The assembled devices were characterized in phosphate buffered saline for their electrochemical properties. Main results. MEAs utilizing a-SiC as both the primary structural element and encapsulation were fabricated successfully. These a-SiC MEAs had 16 penetrating shanks. Each shank has a cross-sectional area less than 60 µm2 and electrode sites with a geometric surface area varying from 20 to 200 µm2. Electrode coatings of TiN and SIROF reduced 1 kHz electrode impedance to less than 100 kΩ from ~2.8 MΩ for 100 µm2 Au electrode sites and increased the charge injection capacities to values greater than 3 mC cm−2. Finally, we demonstrated functionality by recording neural activity from basal ganglia nucleus of Zebra Finches and motor cortex of rat. Significance. The a-SiC MEAs provide a significant advancement in the development of microelectrodes that over the years has relied on silicon platforms for device manufacture. These flexible a-SiC MEAs have the potential for decreased tissue damage and reduced foreign body response. The technique is promising and has potential for clinical translation and large scale manufacturing.

Electrodeposited Iridium Oxide on Carbon Fiber Ultramicroelectrodes for Neural Recording and Stimulation

Host encapsulation decreases the ability of chronically implanted microelectrodes to record or stimulate neural activity. The degree of foreign body response is thought to depend strongly on the cross-sectional dimensions of the electrode shaft penetrating neural tissue. Microelectrodes with cellular or sub-cellular scale shaft cross-sectional dimensions, such as carbon fiber ultramicroelectrodes have been previously demonstrated to elicit minimal tissue response, but their small geometric surface area results in high electrode impedances for neural recording, and reduced charge injection capacity during current pulsing for neural stimulation. We investigated electrodeposited iridium oxide films (EIROF) on carbon fiber ultramicroelectrodes as a means of enhancing the charge injection capacity and reducing electrode impedance. EIROF coatings reduced the electrode impedance measured at 1 kHz by a factor of 10 and improved charge storage and charge injection capacities. The maximum charge injection capacity was also strongly dependent on the interpulse bias and pulse width, and reflected a potential-dependent EIROF impedance. The charge injection capacity of the EIROF-coated carbon fiber ultramicroelectrodes measured in an inorganic buffered saline model of interstitial fluid exceeded 17 mC/cm2 with appropriate biasing, allowing charge-injection at levels well above reported charge/phase thresholds for intraneural microstimulation.

Graphene – Coated Microelectrode Arrays

Graphene – Coated Microelectrode Arrays

Charge injection based electrical stimulation on polypyrrole planar electrodes to regulate cellular osteogenic differentiation.

In this study, polypyrrole (Ppy) electrodes were prepared to support an electrical stimulation to MC3T3-E1 cells for regulating their osteogenic differentiation. The charge injection capacity (CQ) of the Ppy electrodes could be adjusted by the Ppy thickness, and a higher CQ could make the electrode able to produce a higher charge injection quantity (Qinj) at applied voltage. The Qinj onto electrode could be considered as the intensity of the stimulation pulse to cells, and the pulse frequency means the number of electric stimulation with Qinj at one second. Hence, we conducted the present work in the view of Qinj. When the cells were electrically stimulated for 1 hour per day, the electrodes with Qinj ranged in 0.08–0.15 μQ had an obvious role in enhancing cellular osteogenic differentiation whereas Qinj of lower than 0.03 μQ or more than 0.30 μQ gave the stimulations with no or negative effects. And the stimulation with 1 or 25 Hz showed to enhance the differentiation, whereas the stimulation with 50 Hz gave an inhibiting effect. We further found the osteogenic differentiation potential triggered by electrical simulation was related to cell growth stage, and the stimulation carried out at early stage (day 2–5) during 8 days cell culture showed more contribution to enhancing osteogenic differentiation than that at later stage (day 6–8). It is proposed that the desired stimulation effects require that an appropriate voltage-gated calcium ion channel and efficient intracellular calcium ion oscillation are well activated. This work therefore reveals Qinj as an important electrode parameter to decide effective simulations and provides an insight into understanding of the role of electrode material characters in regulating cellular osteogenic differentiation during stimulation.

Electrochemical Roughening of Thin-Film Platinum for Neural Probe Arrays and Biosensing Applications

We report a method for electrochemical roughening of thin-film platinum (Pt) electrodes that increases active surface area, decreases electrode impedance, increases charge injection capacity, increases sensitivity of biosensors and improves adhesion of electrochemically deposited films. First, a well-established technique for electrochemical roughening of thick Pt electrodes (wires and foils) by oxidation-reduction pulses was modified for use on thin-film Pt. Optimal roughening of thin-film Pt electrodes with this established protocol in a sulfuric acid solution was found to occur at about four times lower frequency than that typically used for thick Pt. This modification in established procedure created a 21x surface area increase but showed nanoscale cracks from inter-grain Pt dissolution that compromised film integrity. A crack free surface with Pt nanocrystal re-deposition (20–30 nm in size) and higher enhancement in surface area (44x) was obtained when the electrolyte was switched to a non-adsorbing perchloric acid solution. These electrochemically roughened electrodes have charge injection limits comparable to titanium nitride and just below carbon nanotube-based materials. Roughened microelectrodes showed a 2.8x increase in sensitivity to hydrogen peroxide detection, indicative of improved enzymatic biosensor performance. Platinum iridium and iridium oxide coatings on these roughened surfaces showed an improvement in adhesion.

(Invited) Scaling Effects on the Electrophysiological Stimulation Capabilities of PEDOT:PSS, Pt, and Au

Recent clinical successes of neuromodulator devices such as cochlear implants, deep brain stimulation (DBS) and spinal cord stimulation have generated a wide interest in exploiting emerging state-of-the-art biomaterials for therapeutic electrical stimulation of neurological diseases and disorders. Some of these applications require localized stimulation using microelectrodes with a charge injection density beyond 0.5 mC/cm2 that exceeds Pt and Pt alloys charge injection limits (0.3 mC/cm2). This is where IrOx, TiN and conducting polymers (CPs) emerge as potential candidates as materials for next generation microelectrodes. Here, we present a systematic in-vitro charge injection study to benchmark stimulation performance of PEDOT:PSS on Au, PEDOT:PSS on Pt, and reference Au and Pt electrodes across 20μm to 2000μm electrode diameters. In our study, higher charge injection capacity was measured for PEDOT:PSS/Pt microelectrodes (20 µm to 150 µm diameter size) which was ~3.4 time larger than Pt and ~9 time larger than Au microelectrodes. However, macroscale PEDOT:PSS/Au electrodes (200 µm to 2000 µm diameter size) displayed higher charge injection capacity compare to other electrode materials. Optimal OCP bias voltage was presented at 0.4 V for both PEDOT:PSS/Au and Pt micro/macro electrodes. Particularly, CICs of microelectrodes experienced ~55% and ~135% enhancement compare to zero bias voltage, resulted in maximum 1.88 mC/cm2 and 0.8 mC/cm2 CIC for PEDOT:PSS/Au and Pt microelectrodes respectively. CICs of PEDOT:PSS/Au micro/macro electrodes boosted ~ 13-14% further at 0.5 V OCP bias voltage by pulse engineering (asymmetric pulse injection). Charge injection capacity introduced as frequency-dependent parameter whereas PEDOT:PSS/Au microdots and macrodots demonstrated 40% and 21% larger CIC by pulse width expansion from 200 µs to 2 ms duration; which highlights the importance of accurate regulation of stimulation methodology parameters such as pulse width to make proper balance between safe (higher CIC) and initiative neural stimulation (higher current and frequency). Finally, Charge storage capacity (CSC) evaluation revealed the largest CSC for Pt micro/macro electrodes compare to other electrode materials, whereas PEDOT:PSS/Au micro/macro electrodes offered higher capability to convert those available stored charges into injected electrical pulse (higher CIC/ CSC ratio). We believe that these results could pave the way toward establishing safe and efficient clinically-relevant stimulation protocol for PEDOT:PSS microelectrodes.