Electrodes for high-definition transcutaneous DC stimulation for applications in drug delivery and electrotherapy, including tDCS

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Abstract

Transcutaneous electrical stimulation is applied in a range of biomedical applications including transcranial direct current stimulation (tDCS). tDCS is a non-invasive procedure where a weak direct current (<2 mA) is applied across the scalp to modulate brain function. High-definition tDCS (HD-tDCS) is a technique used to increase the spatial focality of tDCS by passing current across the scalp using <12 mm diameter electrodes.

The purpose of this study was to design and optimize “high-definition” electrode–gel parameters for electrode durability, skin safety and subjective pain. Anode and cathode electrode potential, temperature, pH and subjective sensation over time were assessed during application of 2 mA direct current, for up to 22 min on agar gel or subject forearms. A selection of five types of solid-conductors (Ag pellet, Ag/AgCl pellet, rubber pellet, Ag/AgCl ring and Ag/AgCl disc) and seven conductive gels (Signa, Spectra, Tensive, Redux, BioGel, Lectron and CCNY-4) were investigated.

The Ag/AgCl ring in combination with CCNY-4 gel resulted in the most favorable outcomes. Under anode stimulations, electrode potential and temperature rises were generally observed in all electrode–gel combinations except for Ag/AgCl ring and disc electrodes. pH remained constant for all solid-conductors except for both Ag and rubber pellet electrodes with Signa and CCNY-4 gels. Sensation ratings were independent of stimulation polarity. Ag/AgCl ring electrodes were found to be the most comfortable followed by Ag, rubber and Ag/AgCl pellet electrodes across all gels.

Introduction

The goal of this study was to evaluate reduced contact area electrode configurations for safe and innocuous DC stimulation across the skin for biomedical applications including enhanced drug delivery (Prausnitz et al., 1993) and electrotherapy. We especially considered the electrotherapy application, transcranial direct current stimulation (tDCS) which involves the passage of a constant direct current (generally 260 μA–2 mA) through the brain. The spatial focality (targeting) of DC stimulation is considered pivotal for efficacy and safety in many biomedical applications, including tDCS. Focality is limited, in part, by the electrode size used. Traditional tDCS designs include sponge based electrodes, saturated with water, saline, electrode paste and/or gel (e.g. fatty electrode gels) connected to the stimulator via conductive rubber mesh electrodes, rubber bands or standard alligator clips. Decreasing electrode–skin contact area can improve spatial focality; however, for a given electrode current, the current density at the skin surface concomitantly increases (Nitsche et al., 2007, Bikson et al., 2008, Datta et al., 2008, Miranda et al., 2008). Further incentives to reduce electrode size include device compactness, portability and a potentially increased overall safety profile.

All applications involving transdermal DC stimulation share common safety concerns related to skin irritation. However, distinct safety concerns related to actions on deeper tissue also exist. For example, from the perspective of tDCS safety, it is important to independently consider: (1) pruritic, painful or injurious effects of electrical currents on the skin (Ledger, 1992, Prausnitz, 1996, Dundas et al., 2007) and (2) potential injurious effects of electrical currents on the brain (Yuen et al., 1981, Agnew and McCreery, 1987, Merrill et al., 2005, Nitsche et al., 2008, Gilad et al., 2007, Poreisz et al., 2007, Miranda et al., 2008, Liebetanz et al., 2009, Roth, 2009). The relationship between effects on the skin and any effects on the brain is complex, independent of the electrode montage; from an electrode design perspective these effects should be considered independent of one another (Datta et al., 2009a). Stimulation causing changes at the skin may not have any effect on brain function and vice versa (Swartz, 1989a, Swartz, 1989b, Bikson et al., 2009a, Liebetanz et al., 2009). The focus of this study is the optimization of electrode parameters to minimize skin irritation and pain, with a specific goal to engineer small (<12 mm) surface electrode configurations for focal stimulation with DC currents. Such DC stimulation electrodes may be ultimately integrated into stimulation arrays, analogous to high-definition EEG and are thus termed here “high-definition” DC stimulation electrodes (Datta et al., 2009a, Datta et al., 2009b).

Chemical and physical conditions at the electrode solid-conductor site may indicate potential skin hazards during DC stimulation; temperature, pH, voltage and resistance serve as global measures of the changes occurring at the electrode. For wet surface electrodes, three main “phases” (solid-conductor, gel, skin) and thus two interfaces (solid–gel, gel–skin) are considered. Within each material and across each interface, chemical (oxidation/reduction) and/or physical (e.g. heating) processes may occur (Merrill et al., 2005). In addition, through conduction and diffusion, changes in one region may affect another. In designing electrodes, the key solid-conductor parameters include its materials, size and shape; gel parameters include chemical composition, shape and volume (e.g. as determined by the design of a holder).

Several previous studies have considered the safety and comfort level of transcutaneous DC electrical stimulation using specific stimulation protocols (durations, intensities, …) and electrode configurations, including metal directly on skin (Molitor and Fernandez, 1939, Prausnitz, 1996, Dundas et al., 2007). The safety and comfort level of “conventional” tDCS which employ large sponge electrodes have also been considered (Prausnitz, 1996, Nitsche et al., 2003, Dundas et al., 2007). In this paper, smaller “high-definition” gel based electrodes suitable for transdermal DC stimulation were evaluated (Datta et al., 2009a, Datta et al., 2009b). Since temperature, acid/base and other chemical burns have been suggested to account for DC irritation/damage (Prausnitz, 1996, Merrill et al., 2005), changes in temperature, pH, as well as electrode over-potential (measured on agar gel) and self-reported sensation levels over time were examined. Initial electrode potential experiments screened seven gels (Signa, Spectra, Tensive, Redux, BioGel, Lectron and CCNY-4) and five solid-conductors (Ag pellet, Ag/AgCl pellet, rubber pellet, Ag/AgCl ring and Ag/AgCl disc). A subset of gels (Signa, Lectron, CCNY-4) and solid-conductors (Ag pellet, Ag/AgCl sintered pellet, conductive rubber pellet and Ag/AgCl sintered ring) were selected for additional tests including subject sensation experiments. Here, we describe how 2 mA of direct current may be applied for up to 22 min with minimal skin irritation and discomfort using appropriately designed 12 mm diameter Ag/AgCl ring electrodes and CCNY-4 gel. The safety and advantages of high-definition DC transdermal stimulation is discussed in broader context.

Section snippets

Electrode configurations: materials and geometry

Five types of solid-conductors were tested in this study: (1) “Ag pellet” (2117-Silver Wire; Surepure Chemetals, Florham Park, NJ, USA); (2)“Ag/AgCl sintered pellet” (550015-pellet electrode; A–M Systems Inc., Carlsborg, WA, USA); (3) “rubber pellet” (116A-GSR-5, rubber electrode; Austin Medical equipment, Westchester, TX, USA; all pellets were 2 mm(D) × 4 mm(L) resulting in ∼28 ± 2.5 mm2 solid-conductor–gel contact area); (4) “Ag/AgCl sintered ring” (EL-TP-RNG Sintered; Stens Biofeedback Inc., San

Electrode potential

Electrode potential across conductive agar was recorded during 2 mA DC stimulation. During clinical stimulation it is desirable to minimize electrode potential for several reasons including: (1) voltage limits on constant current stimulators and (2) increased risk for skin injury including through electrochemical reactions (limited by electrode over-potential; the difference between the electrode's potential and it's equilibrium potential (both measured with respect to some reference electrode) (

Transcutaneous DC stimulation at increasing current densities

This study was motivated by the need to develop smaller electrodes for transcutaneous DC stimulation; the most common current applications being transdermal drug delivery (Ledger, 1992, Prausnitz, 1996, Dundas et al., 2007) and electrotherapies including transcranial DC stimulation (Prausnitz, 1996; Datta et al., 2009a, Nitsche et al., 2007). The most evident advantage of smaller electrodes is increased therapy focality (as the tissue targeted focality is presumably limited by electrode contact

Summary: toward high-definition DC stimulation, potential for increased safety

Though fundamental questions remain about the causes of pruritic sensation during transcutaneous DC stimulation, and the role of associated phenomena such as erythema, the initial approach taken in this study indicate that incremental change in electrode design can fundamentally improve stimulation comfort. The observed interface electrochemistry of DC stimulation is explained largely by considering existing theories (Merrill et al., 2005), though the description of a detergible “chemical”

Acknowledgments

The authors are grateful for the technical assistance and overall expertise provided by Thomas Radman of the City College of New York. This work was supported in part by the Wallace H Coulter Foundation, a P.S.C. CUNY Grant, The Andy Grove Foundation and NIH–NCI.

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