Biomedical Engineering Letters (2021) 11:107–115

https://doi.org/10.1007/s13534-021-00189-6

REVIEW ARTICLE

Recent advances in electrode development for biomedical

applications
Eun Kwang Lee1,2 · Ratul Kumar Baruah3 · Hansraj Bhamra4 · Young‑Joon Kim5 · Hocheon Yoo5

Received: 15 January 2021 / Revised: 27 March 2021 / Accepted: 10 April 2021 / Published online: 21 April 2021
© Korean Society of Medical and Biological Engineering 2021

Abstract
Elaborate electrodes that enable adhesion to the skin surface and effectively collect vital signs are necessitated. In recent
years, various electrode materials and novel structures have been developed, and they have garnered scientific attention due
to their higher sensing performances compared with those of conventional electrode-based sensors. This paper provides an
overview of recent advances in biomedical sensors, focusing on the development of novel electrodes. We comprehensively
review the different types of electrode materials in the context of efficient biosignal detection, with respect to material com-
position for flexible and wearable electrodes and novel electrode structures. Finally, we discuss recent packaging technologies
in biomedical applications using flexible and wearable electrodes.

Keywords Biosensors · Flexible electrodes · Packaging · Composite dry electrode · Electrical biosignals

1 Introduction future electronic medical devices, it is essential to strengthen

relationships with demanding institutions such as hospitals
Owing to the rapid development of information technology and medical services; furthermore, relevant and complemen-
(IT) based on computer and network technology, IT has tary cooperation with industries are expanding significantly
been applied in many fields, including the field of medical because of smarter electronic medical devices and their
devices in recent years. In particular, the field of small and association with software and content [1].
personal portable medical devices has become the central In addition, the trend in personal disease management has
point for incorporating IT in the medical field[1, 2]. For changed significantly. As the paradigm of medical treatment
shifts from treatment centered to prediction and prevention
Eun Kwang Lee and Ratul Kumar Baruah equally contributed to oriented, the importance of personal diagnostic technology
this work. is increasing [3]. According to the World Health Organi-
zation, the number of global cancer patients in 2018 was
* Young‑Joon Kim 18.1 million, of which one among five men and one among
youngkim@gachon.ac.kr
six women were diagnosed with cancer, and one among
* Hocheon Yoo eight men and one among 11 women were expected to die
hyoo@gachon.ac.kr
[4]. Although treatment methods for cancer are constantly
1
Weldon School of Biomedical Engineering, Purdue being developed, the mortality rate of cancer patients is still
University, West Lafayette, IN 47907, USA high owing to difficulties in the early detection of cancer
2
MLCC Development, 1 team, Samsung Electro‑Mechanics, and accurate diagnoses. To solve such difficulties, a next-
150, Maeyeong‑ro, Yeongtong‑gu, Suwon, Gyeonggi‑do, generation convergence diagnosis system that can accurately
Republic of Korea diagnose various diseases is being developed through the
3
Department of Electronics and Communication Engineering, combination of various technologies such as biotechnology,
Tezpur University, Assam 784028, India information communication technology, and conventional
4
Department of Electrical and Computer Engineering, Center diagnostic technologies [5].
for implantable devices, Purdue University, West Lafayette, Hence, to materialize a personalized and prediction-
IN 47907, USA
oriented disease diagnosis, the fabrication of high-perfor-
5
Department of Electronic Engineering, Gachon University, mance biosignal acquisition devices is essential. Biosignal
1342 Seongnam‑daero, Seongnam 13120, Republic of Korea

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108 Biomedical Engineering Letters (2021) 11:107–115

acquisition devices are categorized into electrocardiogram reaction occurs where charges are transferred at the inter-
(ECG), electroencephalogram (EEG), electromyogram face between an electrolyte without free electrons and an
(EMG), electrooculogram (EOG), skin conductivity (gal- electrode without ions. Owing to such a chemical reaction,
vanic skin response), skin temperature, and photoplethys- the neutral state of the interface between the electrode and
mography. Representative biosignals are shown in Table 1 electrolyte is compromised, and a potential difference from
[6]. that of the surrounding area appears. This potential differ-
The core technologies of biosignal acquisition devices ence is known as the “half-cell potential.” The lower the
are (1) sensor (detector and amplifier) technology to detect half-cell potential, the better is the performance because the
biosignals from a living body, (2) interfacial signal process- current passing through the interface between the electrode
ing analysis technology, (3) printer and display technology and electrolyte consumes less energy. Currently, silver/sil-
to output the analyzed result, and (4) circuit technology ver chloride (Ag/AgCl) electrodes are used widely in clini-
considering safety issues. Among the core technologies, cal practice owing to their ease of manufacture as well as
interfacial signal processing is one of the most crucial for safety for the human body owing to their low half-electrode
obtaining minute biosignals. Most biosignal losses during potential. However, regardless of the material, the wet elec-
its acquisition are from the interface condition between the trode presents several disadvantages owing to the attachment
electrode and the surface of the skin. Hence, soft and flexible method. First, to attach the wet electrode on the human skin,
electrodes that can offer intimate adhesion to the skin sur- dead skin cells at the desired location (skin abrasion) must
face and effectively collect biosignals should be developed. be peeled off. In addition, gel application, impedance tuning
Herein, we briefly overview the types of soft and flexible on a device level and cleaning after the biosignal measure-
electrode materials used in an efficient biosignal acquisition ment are required. In addition, as the electrolyte dries over
system. In Sect. 2, various electrode materials, including time, the impedance of the skin will increase, which is dis-
homogeneous and composite materials, are presented. The advantageous. Hence, it is not suitable for unprofessional
effective and novel structures of the electrodes are discussed persons to use wet electrodes in emergency cases.
in Sect. 3. In Sect. 4, packaging technologies for the con- Meanwhile, a dry electrode refers to an electrode that
struction of low-voltage circuitry are reviewed. In Sect. 5, does not contain an electrolyte. The development of dry
future opportunities for commercializing high-performance electrodes for the acquisition of biosignals have focused
soft and flexible electrodes in biosignal acquisition systems primarily on dry electrode materials, e.g., metals such as
are discussed. stainless steel, Ag/AgCl, and Ag. These electrodes can
be utilized for the emergency monitoring of critically ill
patients, brain–computer interfaces, etc. because they can
2  Materials be attached to the human skin surface quickly and easily. The
utilization of dry electrodes has been limited to EMG, ECG,
2.1 Homogeneous materials for soft and flexible and EOG, where biosignals are significant. The acquisition
electrodes of EEG signals using dry electrodes has not been extensively
investigated because of their small signal amplitude. Herein,
In clinical practice, a conductive paste or gel (electrolyte) we provide an overview of dry electrodes used in biosignal
is typically used to attach an electrode to the human skin. acquisition.
Conformal contact between electrodes and the human skin Wei et al. reported a metal dry bioelectrode using red
lowers the impedance of the skin, resulting in the efficient Cu (99.9 %), as shown in Fig. 1a [7]. The red Cu metal dry
acquisition of biosignals. Electrodes used in such a manner bioelectrodes were microstructured using laser microma-
are known as “wet electrodes.” In a wet electrode, a chemical chining technology. The synergistic effect of red Cu and the
microstructure provided an enhanced biosignal acquisition
Table 1  Typical amplitude and frequency ranges of electrical biosig- of ECG from patients. Baek et al. reported the fabrication of
nals Reprinted from Ref. [6] with permission Ti dry electrodes on a polydimethylsiloxane (PDMS) sub-
Electrical biosignals Amplitude (mV) Frequency range (Hz)
strate for the measurement of ECG signals [8]. Owing to the
utilization of PDMS, flexibility and biocompatibility were
Electromyogram (EMG) 0.5–5 2–500 achieved; the Ti/PDMS dry electrodes exhibited long-term
Electrooculogram (EOG) 1–10 0.05–100 reliability. Meng et al. described the fabrication of a micro-
Electrocardiogram (ECG) 5 × ­10− 4–5 Up to 100 dome array of Ni-based dry electrodes, as shown in Fig. 1b
Electroencephalogram 2 × ­10− 3–0.1 0.5–100 [9]. The performance of the Ni-based dry electrodes were
(EEG) comparable to that of a standard wet electrode (Ag/AgCl).
Evoked-potential/Even- 1 × ­10− 4–0.2 1–300 The Ni-based dry electrodes were encapsulated with PDMS
related potential (EP/RP)
to enhance their biocompatibility, and the structural benefit

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Biomedical Engineering Letters (2021) 11:107–115 109

Fig. 1  a Schematic diagram of

structure design of metal dry
bioelectrode. Reproduced from
Ref. [7] with permission. b
Illustration of dry microdome
electrode array. Reproduced
from Ref. [9] with permission.
c Schematic diagram showing
fabrication process of CNT/
PDMS composite electrodes.
Reproduced from Ref. [10]
with permission. d Chemical
structure of PEDOT/PSS

from the microdome design resulted in the acquisition of while in motion (e.g., sports) sweat secretions, etc. [12, 13].
high fidelity biosignals from patients. Jung et al. reported the Conventional Ag/AgCl wet gel electrodes cause inconven-
fabrication of a flexible dry electrode based on carbon nano- ience, instability, and infection to the skin and may be able
tubes (CNTs), as shown in Fig. 1c [10]. Commercially avail- to satisfy signal acquisition for wearable applications. In
able CNTs were mixed with PDMS (concentration range: addition to their exceptional electrical properties, CNTs offer
1–4.5 %). It is noteworthy that the concentration and diam- excellent mechanical properties; therefore, they are widely
eter of the CNT electrodes are important for the acquisition investigated as a promising candidate for a new generation
of ECG signals. In particular, CNT dry electrodes exhibited of composite resources. However, the greater the dispersion
long-term stability and high robustness during the monitor- and the weaker the interfacial bonding edge, the better is
ing of motion and sweat. the efficacy of CNTs for supporting polymeric media [12].
The use of an electrode coated with a conductive poly- Several techniques have been employed to improve adhesion
mer offers several advantages. For example, it is easy to at the interface. By adding 1 part per hundred resin (phr) of
increase the electrode surface area, control the hydrophilic- multiwall CNTs (MWCNTs) with styrene-butadiene copoly-
ity/hydrophobicity of the electrodes, and impregnate bio- mer, an increase in the modulus by 45 % and an increase in
molecules. The Kipke group at the University of Michigan, the tensile length by 70 % can be achieved. It was discovered
Ann Arbor, demonstrated that when poly(3,4-ethylenediox that the conductivity increased by five orders of magnitude
ythiophene):poly(styrene sulfonate) (PEDOT:PSS, chemi- for 2 and 4 phr, forming a percolating network. Therefore,
cal structure is shown in Fig. 1d) doped with a surfactant CNT-based elastomeric composites are suitable as a carbon-
(poly(oxyethylene) 10-oleyl ether) was electrochemically type supporting pitch for rubber constituents [12]. The ECG
coated on an Au electrode surface, the electrode indicated an signal intensity of a dry electrode using MWCNT/PDMS,
impedance that was 24 times lower than that of an unmodi- amalgamated as a conductive polymer, was discovered to be
fied electrode. In an in vivo insertion experiment, the imped- better than a marketable electrode with a wet Ag/AgCl layer
ance of the electrode modified with PEDOT increased by [13, 14]. Sanchez et al. fabricated a CNT/polysulfone com-
two to three times after 7 days of insertion; however, the posite, which was reported to demonstrate adequate poten-
impedance of the Au electrode increased by a factor of 0.5, tial in screen-printed disposable electrodes to exhibit high
indicating that the PEDOT-modified electrode had a signifi- electrochemical activity and mechanical stability in addi-
cantly lower impedance and better biocompatibility than the tion to allowing the incorporation of the HRP enzyme [15].
Au electrode [11]. According to the operating principle, three types of dry elec-
trodes were used: surface, invasive microneedle, and capaci-
2.2 Composite dry electrode for flexible tive electrodes. Among them, capacitive sensors, which do
and wearable biomedical applications not require any physical or conductive connection with the
skin surface, indicate a higher potential for the mainstream
Recently, researchers have employed printed/flexible/wear- market; however, data acquisition and fabrication techniques
able dry electrodes and, more specifically, composite dry must be improved [16]. Conduction in the CNT/poly epoxy
electrodes, for monitoring biomedical signals, e.g., ECG composite is primarily due to tunneling, and the insulating
signals, which does not require the application of wet gel polymer is vital to the transport mechanism [17]. The CNT
on the skin while providing conformal contact at the elec- content and interfacing orientation are crucial to the tem-
trode–skin interface, better impedance with skin, less noise perature and conduction dependencies. (Fig. 2)

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110 Biomedical Engineering Letters (2021) 11:107–115

Fig. 2  a Experiment setup for

skin impedance measurement.
b Setup for ECG measurements
using MWCNT/PDMS compos-
ite dry electrode. c Comparison
of dry and wet ECG signals
obtained from wet Ag/AgCl
electrode. Reprinted from Ref.
[13] with permission

Jung et al. fabricated a CNT–PDMS-based dry ECG and chemicals are dispersed, which may damage the CNT
electrode that can be easily applied to regularly used ECG interface [12].
devices to achieve optimum performance with different CNT In conclusion, composite dry electrodes have ample
orientations, thicknesses, and diameters [10]. The Gause fac- potential for achieving good conductivity, self-adhesiveness,
tor of a CNT/PDMS composite with 18 wt% is 12.4, indi- mechanical flexibility and stretchability, biocompatibility,
cating its excellent pressure sensitivity for biometric sen- low interfacial impedance of the skin electrode, and excel-
sors [18]. The advancement of novel stretchable conductors lent skin compliance. However, before CNT/PDMS dry
increases their potential to be applied in neuroscience as electrodes can be applied extensively and commercialized,
well as affects the development of new-generation wearable a few fundamental issues must be addressed: (i) their lower
and implantable biosensing platforms with solution-process- solubility and dispersion when combined with polymer res-
able and transportable energy substitutions [19]. Khan et al. ins; (ii) deprived CNT–polymer interfacial grip [23]. Using
established an MWCNT/PDMS composite layer on a thick different types of mechanical approaches, including ultra-
layer of polyethylene terephthalate (PET) flexible substrate sonics, stirring, shear mixing, ball milling, calendaring, and
for bendable applications. Resistance change was observed extrusion, a uniform dispersion may be achieved. Applicable
in the sensors at convex and concave angles [20]. Lee et al. methods and their fabrication processing conditions should
demonstrated a stretchable, elastomeric MWCNT/PDMS be optimized to minimize mechanical damage to CNTs.
composite fabricated via mixing and an electrical percola-
tion threshold method, which involved a significant decline
in resistance was observed at 0.6 wt% of MWCNT fillers 3 Electrode structure engineering
[21]. Using microcontact printing and casting mold tech-
niques, PDMS was implanted into a conductive elastomer, Electrode design is an important factor for improving sens-
whereas MWCNTs were extensively mixed into PDMS as ing characteristics. An improved readout current response
conductive fillers using toluene as the standard solvent. The can be achieved using a desirable electrode structure. Instead
fabrication process was easy and inexpensive [22]. of conventional flat-electrode deposition, periodic micro-
Two key methods, namely chemical and physical meth- or nanopatterned electrode structures have been proposed.
ods, are used to functionalize the fundamentally sluggish Herein, we present a compilation of recent studies pertain-
behavior exhibited by the CNT surface. A few chemical ing to novel electrode structures, including (1) micronee-
methods that can deliver covalent functional groups on top dles, (2) porous surfaces, (3) nanomeshes, and (3) atomic
of the CNT surface include fluorination, carbene and nitrene phase structure engineering for high-performance biosensing
addition, chlorination, hydrogenation, bromination, cycload- applications.
dition, and silanization. A microneedle-structured electrode penetrates the skin,
Polymer coating around CNTs, use of different ionic sur- forms a contact interface between the microneedle and
factants, and the endohedral method are physical approaches skin tissue, and removes the high impedance of the stra-
that enable CNTs to be dispersed and improve the inter- tum corneum. The dry electrode of a microneedle reduces
facial interactions between CNTs and the interface of the the motion artifact with a lower noise signal and accurately
polymer. In chemical functionalization techniques, acids records the vital signs (Fig. 3a) [24, 25]. Needle-shaped

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Biomedical Engineering Letters (2021) 11:107–115 111

Fig. 3  a Equivalent schematics of flexible dry electrode (FDE) and Reprinted from Ref. [44] with permission. d Measured electrochemi-
flexible microneedle array electrode (FMAE). Reprinted from Ref. cal characteristics curves of relative changes in current peak at fixed
[24] with permission. b Post-use dose-response curve for micronee- potential vs. concentration of DNA detected. Reprinted from Ref.
dle-based biosensor. Reprinted from Ref. [37] with permission. c [45] with permission
Illustration of fabrication process of graphene nanomesh structure.

electrodes have been fabricated using various processing nanometer-sized holes in graphene or TMDs, significantly
techniques, such as photolithography with overcut pho- enhanced sensing performances, such as a high biosens-
toresist [26–28], laser drilling, molding [29–31], and three- ing capability with a high surface-to-volume ratio, were
dimensional printing [32–35]. Using microneedle electrodes, achieved (Fig. 3c,d) [44, 45]. The most significant advan-
the detection of biomedical signals from EMG, ECG, and tage of the nanomesh structure is its easy-to-fabricate pat-
EEG were achieved [36]. Furthermore, a real-time β-lactam tern. As mentioned above, the self-assembled block copol-
sensing in vivo was conducted using a microneedle-based ymer offers elaborate hole patterns without additional or
electrode (Fig. 3b) [37] In order to record an efficient complex lithography processes. Although high surface-
biosignal, the form of invasive microneedle are fabricated. to-volume ratios have been achieved through nanomesh
However, the absence of reliable fabrication method for a or porous structures, it is still necessary to develop repro-
centimeter-scale microneedle array and an efficient protocol ducible and scalable manufacturing methods to implement
that describe the attachment of the microneedle array to the practical applications.
human skin surface must be investigated together. Instead of electrode structure modification, the atomic
To enhance the electrochemical sensing properties or to phase structure engineering of the material was attempted.
enlarge the active surface area, a novel porous structure Through a phase transition from 2 H (trigonal prismatic
has been presented [38, 39]. The porous structure of an coordination) to 1T (octahedral symmetry) of TMDs,
Fc-CS/SWNTs/GOD film provided highly sensitive elec- excellent capacitive behavior, electrocatalytic performance
trocatalytic properties for glucose detection limits with for the hydrogen evolution reaction, and biosensing with
excellent biocompatibility [40]. In addition, a porous high sensitivity have been achieved [46]. A 1T-phase W ­ S2
­Na2CO3/PDMS structure that resulted in a body moving exhibited a highly sensitive and selective H ­ 2O2 biosensor
sensor operation with self-powered energy harvesting with a wide range and low detection limits. Furthermore,
behavior has been proposed [41]. Recently, a nanomesh the detection of three types of hormones (i.e., T3, T4, and
structure platform using graphene or transition metal PTH) was successfully demonstrated using 1T-phase ­MoS2
dichalcogenides (TMDs) has been proposed [42, 43]. Per- on a polyimide-based flexible substrate [47]. Biosensing
forming photolithography using a block copolymer-based through atomic phase structure engineering has great
photoresist resulted in a nanomesh structure with periodic potential, but stable phase structure transformation and
holes of a few nanometers. Owing to accurately controlled stability thereof are still in the development level. (Fig. 4)

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112 Biomedical Engineering Letters (2021) 11:107–115

Fig. 4  Types of wearable device package technologies and signal ered with soft material. Reproduced from Ref. [57] with permission.
interconnections. a Fully soft package. Reproduced from Ref. [51] d Interconnection implemented using serpentine metal structures.
with permission. b Rigid components integrated on soft substrate. Reproduced from Ref. [54] with permission. e Kirigami structure.
Reproduced from Ref. [56] with permission. c Rigid substrate cov- Reproduced from Ref. [62] with permission

4 Packaging [54] have been investigated. However, a fully soft device is

limited in terms of circuitry integration, signal processing,
Packaging wearable sensor devices using mechanically flex- power delivery, and wireless communication. The second
ible materials is crucial for achieving a long device lifetime, approach, i.e., integrating rigid components on a soft sub-
reliable health signal acquisition, and comfortable patient strate material, can support simple integrated circuits (ICs)
experience. The outlying package material should be able with a certain degree of softness and flexibility [52, 55,
to support the integration of electronic elements. To achieve 56]. This method involves the integration of commercial
a comfortable, noninvasive wearable device for healthcare components or custom-designed ICs on stretchable metal
monitoring, the device should impose minimal restraint interconnections of soft, flexible substrates. Although this
on the natural motion of the body. An application-specific approach can only support simple ICs and basic routing
design approach should be considered, depending on the techniques, it provides more functionalities than a fully
functional requirements. soft device. As the third strategy, a highly integrated
Strategies to integrate flexible, stretchable, and soft printed circuit board is employed, where complex multi-
devices with electronic components can be primarily cat- functional ICs are packaged together with the electrodes
egorized into three types: fully soft, rigid components using a polymeric material [57, 58]. Even though the rigid
integrated on a soft substrate, and rigid substrates covered platform does not provide as much comfort as the epider-
with a soft material. A fully soft package is inspired by mal patch, it can support advanced circuit functions such
the epidermal patch-type device, which comprises stretch- as high resolution, multifunctional signal processing, and
able substrates with an elastic modulus similar to that of high-speed wireless communication with reliability.
skin and exhibit conformal contact [48–51]. In the first Additionally, metals that form a skin–electronic inter-
soft wearable device, silicone-based materials (PDMS, face and signal interconnection should be considered. Gold
Ecoflex, Solaris, etc.) were used as the substrate, and the and platinum are widely used as electrode contact materi-
electrodes for biomedical measurements were integrated als owing to their biocompatibility and chemical inertness
into the wearable device [48]. With the development of [48]. Copper is frequently used as a signal interconnect and
technology, other materials that can be used as a support- antenna material owing to its low cost and low electrical
ing material or passivation layer such as poly(vinyl alco- resistivity characteristics [59]. To support flexible and soft
hol) films [52], PET [53], parylene [49], and polyimide substrates, these metal materials are designed as meandered,

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Biomedical Engineering Letters (2021) 11:107–115 113

serpentine interconnects [60] as well as kirigami structures co-development approach of material, structure, and packag-
[61, 62] to endure mechanical stress. ing technology aspects lead to conformal contact between
electrodes and the human skin such that the impedance of
the skin can be reduced as well as offer new opportunities
5 Conclusions for realizing next-generation biomedical devices.

In summary, we presented a comprehensive review of recent Acknowledgements This work was supported by the National
Research Foundation of Korea (NRF) grant funded by the Korea gov-
research progress pertaining to electrode development, ernment (MSIT) (No.NRF-2020M3A9E4104385).
classified into three categories: (1) homogeneous and com-
posite materials, (2) structural aspects, and (3) packaging Declarations
technologies.
First, (1) regarding the electrode materials aspect, the Conflict of interest The authors declare that they have no conflict of
development of electrodes composed of homogeneous interest.
materials has been sufficiently progressed, in which has
Ethical approval This article does not contain any studies with human
categorized into dry and wet electrodes. However, there are participants or animals performed by the author.
pros and cons for each of the dry and wet electrodes. In the
case of the wet type, the electrode can be well-attached to
human skin by using a conductive paste or gel, but it shows
limitations in terms of biomedical aspects due to inconven-
ience of wetting on the body. On the other hand, the dry type References
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