Skin Insertion Mechanisms of Microneedle-based Dry Electrodes for Physiological Signal Monitoring

Conor O’Mahony1, Francesco Pini1,2, Liza Vereschagina1, Alan Blake1, Joe O’Brien1, Carlo Webster1, Paul Galvin1 and Kevin. G. McCarthy2

1Tyndall National Institute 2Dept. Electrical and Electronic Engineering

University College Cork, Cork, Ireland conor.omahony@tyndall.ie

Abstract—This paper assesses the skin penetration mechanisms and insertion forces of a microneedle-based dry electrode for physiological signal monitoring. Using force-displacement measurements, it is shown that these ultrasharp microneedles, fabricated using a bulk micromachining process and which have tip radii as low as 50 nm, penetrate in-vivo human skin smoothly and without a measurable rupturing action. Skin staining techniques have been used to demonstrate that 95% penetration is achieved at just 20 mN per needle. These very low penetration forces facilitate the design of safe microneedle arrays and remove the requirement for applicator devices. Wearable electrode prototypes have been assembled using these arrays, and electrocardiography (ECG) recordings have been carried out to verify the functionality of the technique.

I. INTRODUCTION Microneedle-based medical devices first emerged from

biomedical engineering laboratories in the late 1990s, and immediately demonstrated immense potential as a revolutionary method for the transdermal delivery of therapeutic agents in a painless and low-cost manner. Consisting of arrays of sharp protrusions generally measuring less than 1mm in length and made from a variety of microfabrication processes in materials such as silicon, plastics, metals and biodegradable polymers, microneedle patches can be used to penetrate the thin (10-20µm) but highly impermeable outer layer of the skin (known as the stratum corneum) and deliver drugs or vaccines to the viable epidemis immediately below [1].

In recent years, the use of microneedle-based electrodes for biopotential monitoring has also been explored. The stratum corneum presents not just a physical barrier to the passage of therapeutics, but also has very high electrical impedance and so can cause problems with the recording of

electrocardiography (ECG) signals for cardiac heath monitoring, electroencephalography (EEG) signals for brainwave activity analysis, and electromyography (EMG) for muscle activity detection. These signals are sensed using adhesive electrodes usually made of silver, silver-silver chloride or gold disks, and connected to external instrumentation via a snap-on connector on the rear of the electrode. To help reduce the impedance of the stratum corneum, the skin of the patient is often abraded and an electrolytic gel is applied between the skin and electrode, but this often causes issues with patient discomfort, clinical set-up time and with long-term degradation of the gel [2, 3].

In contrast to these ‘wet’ electrodes, microneedle-based dry electrodes require no gel or skin abrasion, but instead rely on painless perforation of the stratum corneum layer and direct electrical contact to the underlying epidermal layers, Fig. 1. This approach reduces the electrode-skin impedance and enhances measurement accuracy whilst eliminating the need for skin abrasion and/or gel application prior to electrode attachment.

Figure 1. Microneedle electrode-skin interconnection and equivalent electrical circuit.

The authors would like to thank the Tyndall National Institute’s Central Fabrication Facility for device processing. This work was partially supported by Enterprise Ireland under the Commercialisation Fund programme (CF 2012/2339), by Science Foundation Ireland through the ‘Embedded Digital Signal Processing for Mobile Digital Health’ Strategic Research Cluster, and by the Higher Education Authority through the PRTLI Programme.

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A key characteristic of microneedle-based devices is the force required to insert the needles into skin, i.e. beyond the stratum corneum barrier. This force should be low enough to allow painless, easy and repeatable skin penetration of the microneedles during electrode application, by hand, by untrained personnel. It also has a direct impact on the safety margin of the structure (i.e. the ratio of failure force to insertion force of the needle). Insertion force has been shown to be a function of microneedle sharpness and tip geometry [4], yet many designs do not appear to be sharp or narrow enough to fulfill the criteria pertaining to low insertion forces. Microneedle designs vary widely; some may require forces as high as several Newtons per needle for skin penetration, and usually break the skin barrier with a sharp rupturing action [5]. Arrays of such needles are unlikely to be capable of insertion by hand and may necessitate the use of a high-impact, electrical or spring-loaded applicator device to ensure safe and correct insertion [6].

This paper presents an analysis of the in-vivo human skin insertion forces and penetration mechanisms of silicon microneedle-based dry electrodes. It is shown that these ultrasharp microneedles smoothly penetrate untreated in-vivo human skin at very low forces of less than 20 mN per needle and 2 N per electrode, i.e. equivalent to that generated by very moderate finger pressure. An example of human, in-vivo ECG recording is also shown to demonstrate that the devices are clearly suitable for applicator-free use in a clinical setting.

II. ELECTRODE FABRICATION Microneedle-based dry electrodes were fabricated using a

novel double-etched silicon bulk micromachining process [7], during which a silicon wafer was simultaneously etched from both the front and back sides in a solution of potassium hydroxide (KOH). Using standard photolithographic techniques, square openings were first patterned in an oxide/nitride hard mask on the rear side of the wafer and square pads were patterned on the front (needle) side.

The wafer was then etched using hot aqueous potassium hydroxide (KOH). Microneedle formation is based on the anisotropic etch behaviour of monocrystalline silicon in KOH, where the mask pad on the front side of the wafer is gradually undercut until an octagonal needle is formed. A pyramidal pit is simultaneously formed from the back side of the wafer, which intersects with the front side etch to form a through-silicon via (TSV). The final needle is comprised of eight <263> planes, a base of <212> planes and has a height:base diameter aspect ratio of 3:2. Tip sharpness is a function of mask and crystal axis alignment accuracy, and tip radii are generally of the order of 50-100 nm.

In order to ensure electrical contact between the front (skin) side of the electrode and the rear (snap fastener) side of the electrode, a layer of 200 nm Ag was thermally evaporated onto both sides of the wafer, before the wafer was diced into individual electrode arrays. To create a wearable prototype, the electrolytic gel pad was removed from a standard commercial electrode (2239 Red Dot Monitoring Electrode, 3M Healthcare, Germany), and the microneedle arrays were affixed in its place using a conductive adhesive (Radionics, Ireland). This solution provides both an adhesive backing and

a metal snap fastener for connection to recording equipment. A scanning electron microscopy image of a needle is shown in Fig. 2; the TSV is visible at the base of the microneedle. Fig. 3 illustrates an assembled prototype electrode.

Figure 2. Scanning microscopy image of a 283µm silicon microneedle. Note the through-silicon via (TSV) at the base of the structure [7].

Figure 3. A prototype microneedle-based electrode (front). A traditional wet electrode is shown on the rear left of the image, and two unassembled

microneedle arrays are on the right [7].

III. SKIN INSERTION OF MICRONEEDLES

A. Insertion Mechanims Microneedle insertion tests were performed on a healthy

33-year-old Caucasian male, from whom informed consent was obtained prior to the study. The protocol was approved by the Clinical Research Ethics Committee of the Cork Teaching Hospitals. The subject was seated at a computer-controlled test station (Model 5565, Instron, Buckinghamshire, UK) and tests were carried out at locations on both the volar and dorsal forarm; in both cases, the subject’s skin was lightly shaved using a disposable safety razor 24 hours prior to the test. No other skin preparation or modification was carried out. Microneedle arrays were first sterilised by immersion in 70% ethanol for 30 minutes. The arrays used in this study consisted of a 9 x 9 arrangement of 280 µm tall needles located at a pitch of 1 mm on a 9.2 mm x 9.2 mm die, which was affixed to a custom-machined, 5 mm diameter aluminium rod using double-sided, adhesive tape (3M, Austin, Tx); this rod was then mounted on the load cell of the instrument.

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Tests were performed by placing the subject’s arm horizontally beneath the force-displacement tool and keeping the arm immobile during the procedure. The microneedle array was pressed against the subject’s arm at a rate of 1 mm/s until the desired maximum load was reached. A new skin site was used for each test, and a control device, consisting of a silicon plate of the same area as the microneedle array but without microneedles, was also analysed. The force-displacement station recorded time, array displacement and the force applied to the array with resolutions of 2 ms, 1 µm and 1 mN, respectively.

It is notable that a smooth force-displacement curve was almost always observed, even at relatively high application forces (up to 200 mN/needle) and for a range of needle array geometries. Representative data is shown in Fig.4 for maximum insertion forces corresponding to 100 mN per needle (8.1 N per array), together with the force-displacement curve of a control array. This is in contrast to previous works, which report that force-displacement curves measured during microneedle application show a discontinuity at the point of insertion which corresponds to skin rupture at penetration [4, 5]. Over the course of many tests, we have very rarely seen such a characteristic, and these isolated occurrences were furthermore usually attributable to movement of the subject.

Figure 4. Force-displacement curves for an 81-needle array; the maximum applie force is 8.1 N (100 mN per needle). Note that no skin rupture is

observed.

Since it is unlikely that the penetration force is below the resolution of the instrument, we postulate that in contrast to blunter needles where a sudden skin rupture take place, these ultrasharp tips do not suddenly rupture the skin; instead a smooth and gradual penetration occurs. These results and observations are similar to those made in [8], where ultrasharp dry-etched needles were assessed. Secondly, the nature of in-vivo measurements means that skin characteristics are very different to those encountered in commonly-reported ex-vivo experiments, where skin samples are typically stretched over a semi-rigid surface and where the subsequent tension of the skin sample may contribute to the rupturing effect.

This procedure has been repeated many times on a wide range of needle heights and array geometries. In some cases,

particularly for single needles greater than 700 µm in height, blood spots are occasionally visible and we are therefore confident that penetration has indeed taken place, despite the continuous nature of the force-displacement curve. While the experiment yields valuable information about the smooth nature of microneedle penetration, a conclusive identification of the point of skin penetration was not possible and so an alternative dye-staining method was used to measure insertion force.

B. Penetration Force Assessment In order to visually assess microneedle penetration

efficacy, insertion tests were carried out as described in Section III-A, above. Immediately after removal of the array, approximately 200 μl of 2% w/v methylene blue dye was applied to the test site and left for 5 minutes before excess dye was removed using a vigorous scrubbing action under cold running water. The site was then examined using a stereozoom microscope (SZX12, Olympus Inc., Center Valley, PA, USA) as shown in Fig. 5.

Methylene blue dye is used as a skin staining agent and has previously been used to indicate the site of microneedle penetration [13]. In this study, staining clearly indicated the presence of conduits formed as a result of microneedle insertion. For each test site, the number of conduits formed was recorded as a function of maximum application force per needle, and representative results are shown in Fig. 6 (averaged over four test sites). Over 40% of the needles have broken the stratum corneum barrier at forces as low as 5 mN per needle, and over 95% penetration is observed for forces of 20 mN (1.2 N per array). These figures are in close agreement with other work on ultrasharp microneedles [8]. 100% penetration has never been recorded; this is because at least one of the 81 needles on the array usually falls close to or on a hair follicle and this prevents insertion at that point. These dye marks are visible despite vigorous scrubbing under running water to remove surplus dye after the staining process, and remain visible after over 72 hours of normal daily living. We are therefore confident that the presence of these marks confirms skin penetration and is not due to residual surface marking or skin indentation.

Figure 5. Methylene blue-stained in-vivo human skin after array application at 50 mN per needle. The spacing between dots is 1 mm.

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Figure 6. Percentage of penetrated microneedles as a function of applied force per needle. There are 81 microneedle sper array.

IV. ECG RECORDING An evaluation board (AD7793 Evaluation Board, Analog

Devices) interfaced to a LabView GUI was used to record biopotential signals. The subject was a 27-year old Caucasian male who gave informed consent. Microneedle-based dry electrodes, incorporating a 5 x 5 array of 300 µm tall needles located at a pitch of 1.2 mm on a 7 mm x 7 mm die, were applied directly to the torso without prior skin preparation. The signal was read differentially through two electrodes located on the chest of the subject while a bias voltage was applied to the body through a third electrode located on the lower right torso of the subject [7].

Fig. 7 illustrates an unfiltered electrocardiograph obtained using the dry microneedle-based electrodes described in this work. The microneedle measurements show good results in terms of signal fidelity - the typical cardiac signatures of the P-wave, QRS-complex and T-wave are clearly visible, and the subject’s heart rate in this case is 60 beats per minute (bpm). This proves the ability of dry microneedle-based electrodes to detect and record biopotential signals.

Figure 7. Electrocardiograph recording obtained using a set of microneedle-based dry electrodes.

V. CONCLUSION It has been shown that dry electrodes based on arrays of

ultrasharp silicon microneedles, fabricated using bulk micromachining, can be easily and painlessly inserted in human subjects using very low forces. Force-displacement tests show that thesemicroneedles penetrate skin smoothly and easily, and, in contrast to previously published works, show no evidence of sudden skin rupture during stratum corneum penetration. Temporary skin staining dyes were used to show that that over 40% of needles have penetrated the skin at forces as low as 5 mN per needle, and over 95% penetration is observed for forces of 20 mN (1.62 N per array). Using handheld force gauges, we have estimated that typical finger pressure during electrode application is in the region of 8-12 N, i.e. much greater than that required for array penetration.

This very low penetration force allows easy and comfortable insertion of microneedle arrays containing a great many needles, and removes the need for an applicator device requiring high forces or velocities to insert the array. Furthermore, this design widens the safety margin between the insertion and failure forces of the microneedle, thereby facilitating the design of safe microneedle arrays which could be used for a wide range of applications including drug and vaccine delivery, electroporation and diagnostics.

ECG measurements show good results in terms of signal acquisition and fidelity, and prove the ability of dry microneedle electrodes to accurately record physiological signals without the use of advance skin preparation or electrolytic gel application. They are promising candidates for use in long-term continuous monitoring and diagnostics.

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