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SU-8 microneedles based dry electrodes for Electroencephalogram G. Stavrinidis a, , K. Michelakis b , V. Kontomitrou a , G. Giannakakis c , M. Sevrisarianos d , G. Sevrisarianos d , N. Chaniotakis e , Y. Alifragis e , G. Konstantinidis a a Microelectronics Research Group, IESL-FORTH, Vassilika Vouton, Heraklion, Greece b Advanced Technology Institute, University of Surrey, Guildford, United Kingdom c Computational Medicine Laboratory, ICS-FORTH, Vassilika Vouton, Heraklion, Greece d Neurofeedback Institute Training, 49 Drakontopoulou Str., Heraklion, Greece e Laboratory of Analytical Chemistry, Department of Chemistry, University of Crete, Greece abstract article info Article history: Received 23 October 2015 Received in revised form 10 February 2016 Accepted 25 February 2016 Available online 3 March 2016 This work demonstrates a novel, simple method for the fabrication of dry Electroencephalogram (EEG) elec- trodes consisting of arrays of SU8 based microneedles. EEG electrodes fabricated this way will signicantly reduce the duration and complexity of the mounting procedure as they eliminate the need for skin preparation and the application of conductive paste. Arrays of polymer based microneedles were designed and then realized using a simple, low cost photolithographic technique. The polymer used for the microneedle fabrication is epoxy based SU-8 and the microneedle array is formed on a glass carrier. A single, back-sidephotolithographic exposure is applied for the formation of sharp and appropriately-sloped microneedles. The resulting needles are cone-shaped and 500 μm in height with a base of 100 μm in diameter and a tip smaller than 30 μm. The microneedles are sub- sequently covered conformally with a thin lm of biocompatible metal (Ag) rendering them suitable for human skin penetration. In addition, human skin penetration did not compromise the mechanical integrity of the microneedles. Initial electrical characterization results from a trial on a healthy human show that the fabricated electrodes provide excellent EEG signal strength presenting low resistivity contact. © 2016 Elsevier B.V. All rights reserved. Keywords: Electroencephalography (EEG) Dry electrodes Microneedles Biosensor Biocompatibility SU8-photoresist 1. Introduction State of the art: In all bio-signal recordings such as EEG, electrodes play a pivotal role in their acquisition and are the parts that are in con- stant contact with the body. No matter how advanced the rest of the EEG measuring system is, no quality signals will be picked up unless the electrodes meet specic requirements. EEG electrodes are usually made of metal. Silver chloride (AgCl) is preferred for common neurophysiologic applications. Because Ag is a slightly soluble salt, AgCl quickly saturates and comes to equilibrium. Therefore, Ag is a good metal for metallic skin-surface electrodes. Choosing the correct electrode as well as preparation of the skin before recording, critically affects the accuracy of the measure- ments [1]. One classication of EEG electrodes stems from their shape: there exist disc and cup shaped (EEG caps), sub-dermal needles (single-use needles that are placed under the skin) and implanted electrodes (to precisely pinpoint the origin of the seizure activity, for example). Needles are either available with permanently attached wire leads, where the whole assembly is discarded, or with sockets that are at- tached to lead wires with matching plugs. They are made of stainless steel or platinum. Some EEG electrodes can be used for special applica- tions. For example, implanted EEG electrodes also can be used to stimu- late the brain. A second classication of EEG electrodes describes them as either wet or dry, depending if an electrolytic gel or paste is used to facilitate electrical contact with the skin (wet electrodes), or if they actually pen- etrate the tissue, the uid of which is consequently acting as the electro- lyte (dry electrodes) [2]. In summary, only wet electrodes (Table 1) have reached the techno- logical maturity required in terms of performance, cost, reproducibility and patient comfort, to be universally acceptable for EEG recordings. However, dry electrodes (Table 2) present many advantages and, al- though not yet universally adopted, research outcomes suggest that they could be worthy candidates to consider. We propose a dry microneedle electrode with simple fabrication in- volving just a single lithography step without the use of sacricialsub- strates such as silicon. The resulting process is therefore simpler and of Microelectronic Engineering 159 (2016) 114120 Corresponding author at: Microelectronics Research Group (MRG), Institute of Electronic Structure and Laser (IESL), Foundation for Research and Technology-Hellas (FORTH), P.O. Box 1385, 71110 Heraklion, Crete, Greece. E-mail address: [email protected] (G. Stavrinidis). http://dx.doi.org/10.1016/j.mee.2016.02.062 0167-9317/© 2016 Elsevier B.V. All rights reserved. Contents lists available at ScienceDirect Microelectronic Engineering journal homepage: www.elsevier.com/locate/mee

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Page 1: SU-8 microneedles based dry electrodes for ...users.ics.forth.gr/~ggian/publications/journals/2016 Stavrinidis SU-8... · SU-8 microneedles based dry electrodes for Electroencephalogram

Microelectronic Engineering 159 (2016) 114–120

Contents lists available at ScienceDirect

Microelectronic Engineering

j ourna l homepage: www.e lsev ie r .com/ locate /mee

SU-8 microneedles based dry electrodes for Electroencephalogram

G. Stavrinidis a,⁎, K. Michelakis b, V. Kontomitrou a, G. Giannakakis c, M. Sevrisarianos d, G. Sevrisarianos d,N. Chaniotakis e, Y. Alifragis e, G. Konstantinidis a

a Microelectronics Research Group, IESL-FORTH, Vassilika Vouton, Heraklion, Greeceb Advanced Technology Institute, University of Surrey, Guildford, United Kingdomc Computational Medicine Laboratory, ICS-FORTH, Vassilika Vouton, Heraklion, Greeced Neurofeedback Institute Training, 49 Drakontopoulou Str., Heraklion, Greecee Laboratory of Analytical Chemistry, Department of Chemistry, University of Crete, Greece

⁎ Corresponding author at: Microelectronics ResearElectronic Structure and Laser (IESL), Foundation for Re(FORTH), P.O. Box 1385, 71110 Heraklion, Crete, Greece.

E-mail address: [email protected] (G. Stavrinidis).

http://dx.doi.org/10.1016/j.mee.2016.02.0620167-9317/© 2016 Elsevier B.V. All rights reserved.

a b s t r a c t

a r t i c l e i n f o

Article history:Received 23 October 2015Received in revised form 10 February 2016Accepted 25 February 2016Available online 3 March 2016

This work demonstrates a novel, simple method for the fabrication of dry Electroencephalogram (EEG) elec-trodes consisting of arrays of SU8 basedmicroneedles. EEG electrodes fabricated thiswaywill significantly reducethe duration and complexity of the mounting procedure as they eliminate the need for skin preparation and theapplication of conductive paste. Arrays of polymer based microneedles were designed and then realized using asimple, low cost photolithographic technique. The polymer used for the microneedle fabrication is epoxy basedSU-8 and the microneedle array is formed on a glass carrier. A single, “back-side” photolithographic exposure isapplied for the formation of sharp and appropriately-slopedmicroneedles. The resulting needles are cone-shapedand 500 μm in height with a base of 100 μm in diameter and a tip smaller than 30 μm. The microneedles are sub-sequently covered conformally with a thin film of biocompatible metal (Ag) rendering them suitable for humanskin penetration. In addition, human skin penetration did not compromise the mechanical integrity of themicroneedles. Initial electrical characterization results from a trial on a healthy human show that the fabricatedelectrodes provide excellent EEG signal strength presenting low resistivity contact.

© 2016 Elsevier B.V. All rights reserved.

Keywords:Electroencephalography (EEG)Dry electrodesMicroneedlesBiosensorBiocompatibilitySU8-photoresist

1. Introduction

State of the art: In all bio-signal recordings such as EEG, electrodesplay a pivotal role in their acquisition and are the parts that are in con-stant contact with the body. No matter how advanced the rest of theEEG measuring system is, no quality signals will be picked up unlessthe electrodes meet specific requirements.

EEG electrodes are usually made of metal. Silver chloride (AgCl)is preferred for common neurophysiologic applications. BecauseAg is a slightly soluble salt, AgCl quickly saturates and comes toequilibrium. Therefore, Ag is a good metal for metallic skin-surfaceelectrodes. Choosing the correct electrode as well as preparation ofthe skin before recording, critically affects the accuracy of the measure-ments [1].

One classification of EEG electrodes stems from their shape: thereexist disc and cup shaped (EEG caps), sub-dermal needles (single-use

ch Group (MRG), Institute ofsearch and Technology-Hellas

needles that are placed under the skin) and implanted electrodes(to precisely pinpoint the origin of the seizure activity, for example).

Needles are either available with permanently attached wire leads,where the whole assembly is discarded, or with sockets that are at-tached to lead wires with matching plugs. They are made of stainlesssteel or platinum. Some EEG electrodes can be used for special applica-tions. For example, implanted EEG electrodes also can be used to stimu-late the brain.

A second classification of EEG electrodes describes them as eitherwet or dry, depending if an electrolytic gel or paste is used to facilitateelectrical contact with the skin (wet electrodes), or if they actually pen-etrate the tissue, thefluid ofwhich is consequently acting as the electro-lyte (dry electrodes) [2].

In summary, onlywet electrodes (Table 1) have reached the techno-logical maturity required in terms of performance, cost, reproducibilityand patient comfort, to be universally acceptable for EEG recordings.However, dry electrodes (Table 2) present many advantages and, al-though not yet universally adopted, research outcomes suggest thatthey could be worthy candidates to consider.

We propose a dry microneedle electrode with simple fabrication in-volving just a single lithography stepwithout the use of “sacrificial” sub-strates such as silicon. The resulting process is therefore simpler and of

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Table 1Conventional electrodes (usually wet electrodes).

Metal disc and cup electrodesDisc and cup electrodes are generally made of high purity tin, silver, gold or evensurgical steel.They usually have a diameter that is within 4–10 mm [3].

Needle electrodesNeedle electrodes are sterilized, single-use needles placed under the skin. Theseelectrodes are typically made of surgical grade steel and are inserted into thescalp after thorough disinfection of the insertion site (painful).

Nasopharyngeal electrodesThese electrodes are made of a wire that are embedded into a rigid plastic. Thetip is an uninsulated 2–5 mm diameter metal ball. These electrodes are insertedthrough the nostril and maneuvered to place it against the roof of thenasopharynx and close to the skull.

Table 2Micro-spike electrodes (dry electrodes).

Micro-spike EEG electrodesThese dry electrodes consist of many micro-spikes, with each micro-spike beingbuilt on a pillar with a big shoulder [4].

CNT EEG electrodesThis design was to eliminate skin preparation and gel application requirementsin order to reduce noise while improving wearability [5].

Si microneedle electrodesRecently, some successful attempts of EEG recording have been performed withspiked electrodes (microneedle arrays) made by silicon micromachining [6].

Polymer microneedle electrodesPolymer microneedle electrodes covered with a nanoporous parylene film thatcan serve as flexible electrodes for a brain–machine interface [7].

Microneedle array electrodesMicroneedle array electrodes for EEG significantly reduce the mounting time,particularly by circumvention of the need for skin preparation by scrubbing [8].

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lower cost. The microneedle array can be also formed on a flexible sub-strate (Polyimide) which has the capability to compensate for skinmovement.

2. Fabrication method

2.1. Dry electrode design

Three different designs were realized. In the first one, the micro-needles were 300 μm in height, had a base of 100 μm in diameter andthe tip was smaller than 30 μm in size, as shown in Fig. 1. The pitch be-tween microneedles was 650 μm and 10 × 10 arrays were formed.

In the second design, the height was increased to 500 μm, the basediameter remained at 100 μm and the tip was smaller than 30 μm, asshown in Fig. 2.

The pitch between the microneedles was kept at 650 μm but therewas a single, extended array, covering all the available electrode surface,for increased sensitivity. Hence, the active area in this design is largerand also the total number of the microneedles is drastically increasedwith respect to the first design.

Finally, the third microneedle array design is the same as the firstone, but the final structure rests onto a flexible polyimide organiclayer, to provide improved mounting application on the skin. Theresulting electrode can follow the curvature of the skin, and this helpsmaintaining better contact, leading to increased signal strength and ac-quisition efficiency. This flexibility is shown in Fig. 3. As mentionedabove, all these microneedle electrodes were coated with Ag, as is thecase with conventional electrodes.

2.2. Fabrication process

The electrodes were fabricated on 100 μm thick glass substrates.First, the glasses were cleaned using a standard degreasing processwith organic solvents and were subsequently dehydrated by baking at140 °C. Then, application of a 50 μm thick SU-8-50 negative photoresistlayer was performed by spin coating. This layer, which acts as a base

for the microneedles, was cured by flood exposure using the UV light(i-line) of a standard contact lithography mask aligner followed bypost-baking. In the final fabrication step, SU-8-100 is applied with spincoating to form the layer that is to be used for rendering the actual ar-rays ofmicroneedles. Various spin speedswere tested, in order to obtainthe desired film thickness, which ultimately defines the microneedleheight. Following the SU-8 soft bake, the microneedle array photomaskis brought into contact with the backside of the glass and the UV expo-sure is made from the backside on the mask aligner [9]. Following stan-dard post-exposure bake, a subsequent development reveals themicroneedle array. The only difference between the three designs isthat, during the third process, a uniform polyimide layer was appliedbefore the first SU-8 50 layer. Following the full fabrication procedure,this layer can be then easily unmounted from the carrier substrate by

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Fig. 1. The 1st design of microneedle. (a) Design of the electrode, (b) electrode, (c) SEM close-up.

116 G. Stavrinidis et al. / Microelectronic Engineering 159 (2016) 114–120

pilling-off, giving the possibility of having the microneedle arraysformed on flexible substrates. For all designs, following the formationof the polymer microneedle arrays, the samples are covered with athin layer of silver by electron-gun evaporator, utilizing a rotating sam-ple holder in order to aid conformal deposition.

3. In vivo experiments and results

The microneedle electrodes were initially tested with a commercialEEG system from the University General Hospital of Heraklion inCrete, through human trials with volunteers.

3.1. Test 1

We tested the first electrode design without any skin preparation orconductive paste, as required for the conventional electrodes. The re-sults were compared to those obtained with a commercial one. Duringthedata recording from the EEG system, the commercial electrode resis-tivity was lower than our microneedle electrode. More specifically, the

Fig. 2. The 2nd design of microneedles. (a) Design o

results were as follows: Microneedle electrode R= 4.2 kΩ; Commercialelectrode R = 2.7 kΩ. Typical results are shown in Fig. 4. Point Fp1 cor-responds to the microneedle electrode while Fp2 corresponds to thecommercial electrode.

3.2. Test 2

The same measurements were performed once more, however,this time both electrodes were located at the same point Fp1 alsoperforming skin preparation and applying conductive paste to themicroneedle electrode. Typical results are shown in Fig. 5. This timethe commercial electrode resistivity was higher than the microneedleone: Commercial electrode at Fp1, R = 2.9 kΩ; Microneedle electrodeat Fp1, R = 1.7 kΩ.

3.3. Test 3

We used two electrodes to test the second electrode design withoutany skin preparation or conductive paste for the microneedle electrode

f the electrode, (b) electrode, (c) SEM close-up.

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Fig. 3. The 3rd design of microneedles. (a) Design of the flexible electrode, (b) flexible electrode, (c) SEM close-up.

Fig. 4. EEG data recording. (a) Electrode placement, (b) EEG recording from test 1.

117G. Stavrinidis et al. / Microelectronic Engineering 159 (2016) 114–120

(dry electrode). The results were compared to two commercial ones.During the data recording from the EEG system, the commercial elec-trode resistivity was higher this time compared to the microneedle

Fig. 5. EEG data recording. (a) Electrode pla

electrodes: Microneedle electrodes, RFp1 = 3 kΩ and RCz = 2.7 kΩ;Commercial electrodes, RFp1 = 6.4 kΩ and RCz = 3.2 kΩ. Typical resultsare shown in Fig. 7. Point Fp1 corresponds to both electrodes, as does Cz,

cement, (b) EEG recording from test 2.

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Fig. 6. Electrode placement for test 3.

Fig. 7. EEG signals located at Fp1 and Cz (Fig. 6) for

118 G. Stavrinidis et al. / Microelectronic Engineering 159 (2016) 114–120

as shown in Fig. 6. After electrode removal there were noticeable smallspots on the skin confirming minimal penetration. Observing the EEGrecordings following an eyebrow movement (between 25 and 30 s),the microneedle electrode seems to bemore resistant to the signal arti-facts thus offering lower noise levels (Fig. 7.1 and 2). For this test weperformed additional analysis of the EEG signals in order to determinethe power spectral densities (PSDs). From Fig. 8 we observe that theconventional andmicroneedle electrodes display quite similar temporaland spectral properties in the EEG signal power densities. Alpha rhythm(8–13 Hz) from both electrodes appears similar although from Fig. 8.1and 2 it is evident that the microneedle electrode at Fp1 producesmore μV/cm, thus promises higher sensitivity. The PSDs do not containhigh values of beta rhythms (14–30 Hz) which is though expectedsince high beta rhythm is associated with alertness.

3.4. Test 4

From electrochemistry it is known that by using different metals aselectrodes and appropriate biasing, gases like O2 or ions like hydrogencan be detected. We therefore investigated the potential of themicroneedles as candidates for chemical sensing targeting chemicalspecies like oxygen and pH. The ultimate aim is to investigate the poten-tial of the microneedles for simultaneous recording of chemical param-eters during EEG for cross correlation analysis. Effective potentiometryrequires two electrodes (working and reference) with as low resistanceas possible between them. We tested the resistance between a Pt flat

both conventional and microneedle electrodes.

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Fig. 8. EEG power spectral densities corresponding to EEG signals reported in Fig. 7.

Fig. 9. pH detection with oxidized Ir spikes.

119G. Stavrinidis et al. / Microelectronic Engineering 159 (2016) 114–120

electrode as reference and an Irworking electrode, either flat or coveredmicroneedle arrays, attached to human tissue. Both of the electrodes arein equal distance from the reference. The resistance of the flat electrodewas 15 MΩwhile the resistance of the microneedle one was 7 MΩ.

Ir covered microneedles were oxidized by cyclic voltammetry in0.5 M sulfuric acid, using 200 cycles from 0 to 1 V oxidative potentialsat a scan rate of 100mV/s in order tomake itmore sensitive in the inves-tigation of H+ cation for pH detection. The pH calibration curve was de-veloped by using standard solutions and the initial results are presentedin Fig. 9. It is evident that the pH behavior of the oxidized Irmicroneedles presents a theoretical slope of −68.75.

Experimental results also indicated that the microneedle electrodesdid not move during the trial since attached to the skin and deliveredstable readings, in contrast to the flat ones that exhibited significantreading variations.

4. Conclusions

A novel, single lithographic step fabrication protocol, without “sacri-ficial” substrates, for the realization of SU8 based microneedle arrayshas beendeveloped. These arrays are subsequently conformally coveredwith thin layers of biocompatiblemetals such as Ag, rendering the arraydrymicroneedles based electrodes aimed atmaking EEG recordings.Wedeveloped two versions, one on thin glass substrates and one on thin

polyimide flexible substrates. The first (on glass) was tested in realhuman conditions yielding very promising initial results as a true dryelectrode, as compared to commercial wet electrodes both in terms of

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lower resistivity and improved PSD at least for the alpha rhythm. Thenext steps in this research involve, initially, a full EEG recording with aset of themicroneedle arrays, and direct comparison to the correspond-ing EEG with a set of commercial electrodes. In parallel, we will fullycharacterize the flexible version. We have already fabricated a set ofelectrodes that will be dedicated to biocompatibility analysis for longerexposures of human tissue to the electrodes. Furthermore, we plan torealize an analytical array platform involving microneedle arrays cov-ered with different metals with the aim to try to correlate EEG readingsto chemical species like oxygen and pH.

Acknowledgments

Thisworkwas supported by Predictes (Predicting epileptic seizures)11ΣΥΝ-10-998 ΑΠ.2140/18-9-13 funded from GSRT within the frame-work of the call “Synergasia 2011”.

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