Fabrication of Biomedical Electrodes Using Printing Approaches
Fabrication of Biomedical Electrodes Using Printing Approaches
Fabrication of Biomedical Electrodes Using Printing Approaches
https://doi.org/10.1007/s44174-024-00176-2
REVIEW
Abstract
In this review, we focus on the fabrication of electrodes, using printing techniques. Generally speaking, electrodes are
comprised of a metal conductor with a metal lead (sometimes the same material) for the conduction of electrical current.
Different inorganic and organic materials including metal, polymers, carbon, as well as their composites thereof, have
been used for electrodes on different substrates. While material-dependent characteristics, including conductivity, optical
transparency, corrosion resistance and biocompatibility, determine the choice of material, printing, as the manufacturing
method, offers precise control over the geometry and scale of electrodes for selective and sensitive performance. Both 2D-
and 3D-printed electrodes have been widely used as sensors for electrochemical applications as well as quantification of
biological compounds, establishing contact with biological surfaces and systems, finding application in medical diagnosis,
therapy and treatment of various conditions. Costa et al. (Energy Storage Mater 28:216–234, 2020), Mensing et al. (Sustain
Mater Technol 25:e00190, 2020) depict the difference between the 2D and 3D printing techniques which can be used for
fabrication of 2D and 3D electrodes. The 3D structure of the electrode provides advantages over the 2d electrodes in terms
of its catalytic properties through enhancement in its mass transfer process, adsorption efficiency and active exposure sites
(Mensing et al. in Sustain Mater Technol 25:e00190, 2020).
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Biomedical Materials & Devices
examples include vagus nerve stimulation for epilepsy [10], used, both organic and inorganic material may be chosen as
occipital nerve stimulation for occipital neuralgia [11] and the ink precursor material. In this review, we study the fun-
stimulation of motor neurons to restore lost motor function damental properties of medical electrodes and explore the
[12]. Recording electrodes, on the other hand, are used for printing methods for potential fabrication while reviewing
sensing applications, particularly as wearable devices, for the ink formulation for making electrodes.
health-monitoring purposes and have been incorporated into
clothing and other accessories [13]. The application of these
wearable devices for the monitoring of neural signals such as Applications
in the collection of electroencephalograms (EEG) [14], elec-
trocardiograms (ECoG) [15] and electromyograms (EMG) Electrodes may be placed on the skin surface or be surgically
[16] has also been demonstrated. implanted within the body in order to measure biological
Academic research today is largely focused more on signals (Fig. 1) [29]. On the surface, epidermal electrodes
improving the existing electrodes structure and potential are generally non-invasive and used for wearable applica-
through the use of novel materials and fabrication strategies. tions. They include sensors for simple recording and have
Depending on the application and materials involved, drop found application in health monitoring. These electrodes can
casting [17], spin coating [18] and electrochemical deposi- be seen in electrical devices including smartphones, smart-
tion [19] have been some of the simplest ways of depositing watches and smartbands, being configured to measure sim-
materials for fabricating electrodes. Fabrication techniques ple physiological signals (including motion, respiration rate,
such as sputter coating [20, 21], thermal evaporation [22] pressure) and neural signals (such as in EEG, ECoG, EMG).
and chemical vapor deposition processes [23] are also used Smart textiles, including sensor laden clothing and footwear
for uniformity control in electrodes. For more controlled and sensor-disguised tattoos, are also available [30–33].
feature sizes and geometry, lithographic methods (electron Some specific sensors can also measure biochemical ana-
beam [24], nanoimprint [24] and x-ray [25]) and laser abla- lytes from bodily fluids (e.g., glucose from sweat and blood)
tion [26] have also been used. Electrodes can be manufac- sending signals to mobile devices. These signals, obtained
tured by printing through the synthesis and formulation of from the electrodes, can also be used to provide remote
conducting inks. Printing has already been established for feedback to medical practitioners, through protocols such
fabricating various active and passive electronic components as bluetooth, Wi-Fi, 3G, 4G and/or 5G, taking advantage of
including thin-film transistors (TFT)-based display devices, the internet of things (IoT). Electrodes for wearable health
memory devices and sensors [27]. Printing is preferred for monitoring have been summarized and reviewed recently
the ease of rapid prototyping and scalability [28]. The print- by Ha et al. [34]. Implantable electrodes on the other hand
ing process generally involves deposition of functional inks are invasive, requiring surgical procedures. These implant-
possessing conducting, semi-conducting and dielectric prop- able electrodes are typically comparatively small in size and
erties on flexible polymer-based substrates for the fabrica- designed to be more sensitive, selective and biocompatible.
tion of electronic components. Structures with minimum fea- Deep brain stimulators, cochlear implants and cardiac pace-
ture sizes in the micron scale can be made using the process makers, are examples of implants with electrodes for tar-
of printing. Depending on application and printing method get organ stimulation. Implants and implant electrodes in
Biomedical Materials & Devices
general are usually expected to last for the lifetime of the they may be classified as stimulating or recording types.
patient and are used for treating chronic illnesses. As such Electrodes used for electrical stimulation of neural tissues
the materials chosen should be rather robust, but at the same may be categorized either as microelectrodes or as mac-
time, patient compatible for long-term use preventing the roelectrodes depending on their size. Microelectrodes have
need for re-surgery and complications. geometric surface area (GSA), i.e., length times breadth
Gao et al. reported a flexible printed circuit board (FPCB) for a rectangular electrode, less than 10,000 μm2, whereas
with an integrated sweat sensor array, which selectively macroelectrodes are larger than 100,000 μm2. Electrodes in
and quantitatively analyzes multiple metabolites (glucose between 10,000 and 100,000 μm2 are called mesoelectrodes
and lactate), electrolytes (sodium and potassium ions) skin or intermediate-sized electrodes [41]. In case of stimulation
temperature and wireless data communication module [35]. electrodes, larger area of stimulating electrodes has advan-
Mannoor et al. reported a tooth sensor for breath and saliva tages of high current delivery through the larger surface
analysis for monitoring of pathogenic bacteria where the area. However, a higher signal amplitude is also required
electrode consists of graphene nano-sensors, printed onto with large area electrodes to activate neurons at farther dis-
silk substrates, and incorporated with a resonant coil for tances. For most cases, smaller area stimulating electrodes
wireless connection [36]. Meanwhile Kim et al. reported are preferred over larger area size for localized modulation
a wearable tattoo consisting of multifunctional sensors for and clinical merit [42, 43]. For recording electrodes, elec-
temperature, strain and electrophysiological measurements trodes with larger area can record low-frequency signals for
[37]. Similar to wearables, recording electrodes for neural the neuronal area covered. The smaller recording electrodes
prostheses measure the electric potential generated by the detect local field potentials (LPFs) and other high-frequency
flow of ions across the membrane of an electrically excit- signals. Microelectrodes have greater selectively and spatial
able cell (Fig. 1). Branner et al. reported a Utah electrode resolution, with the ability to stimulate small and specific
array, used for stimulation and recording of sciatic nerve volumes of tissue [44]. Table 1 shows the different types of
in the peripheral region in cats. The array consists of 25 electrodes used as neural interfaces [42].
1-mm-long electrodes fabricated on a 2 × 2-mm base with The schematic diagram for an electrode-tissue interface
electrodes spaced at 400 μm. The electrode array demon- showing different charge injection mechanisms is shown
strated recording and stimulation stability for up to 60 h [38] in Fig. 2a. As the charge is transferred from electrode to
Similarly, Lu et al. reported a minimally invasive porous the tissue, it changes its form from an electron to an ion.
graphene-based 64-electrode array fabricated on a polyim- Charge injection mechanism in stimulating electrodes can
ide substrate using laser pyrolysis and additional supporting be capacitive (non-Faradic), Faradic or both with generation
metal interconnects. In vivo cortical stimulation and sens- of adsorbable species. In capacitive charging, Coulombic
ing were conducted on anesthetized rats using the fabricated forces redistribute equal and opposite charges on the tissue
electrode array. Electrodes show high endurance with no surface, whereas in Faradaic charging electrons are trans-
sign of delamination and degradation, even after 1 million ferred between electrode and tissue via redox reactions [44].
biphasic stimulation cycles [39]. Capacitive charging reactions can be electrostatic or electro-
lytic involving charging and discharging of electrode–elec-
Electrode Conduction Mechanics trolyte layer, while Faradaic charging is based on electro-
chemical redox reactions between the surrounding media
By controlling the direction of flow of electric current, and the electrode. Metals and metal-like compounds, such
electrodes can be designed to deliver and receive electri- as titanium nitride, tantalum and platinum, inject charge
cal charge to stimulate biological surfaces and/or monitor through the capacitive route [45]. These materials are chem-
their condition [40]. Depending on the mode of operation, ically inert during the reaction process with no chemical
Fig. 2 a Schematic diagram of an electrode-tissue interface show- if Biomedical Engineering. c Amplitude vs frequency distribution of
ing different charge injection mechanism for stimulating electrodes. bioelectric signals that can be recorded through applying non-inva-
Reprinted from [51] Copyright (2015), with permission from Else- sive on-surface electrodes. Reprinted from [52] Copyright (2019),
vier. b Biphasic symmetric current waveform applied to the stimulat- with permission from Elsevier
ing electrodes. Reprinted from [45], Copyright 2008 Annual Review
species being consumed even with high bias voltage (> 4 V) anodal phases. Biphasic current waveforms are charge
and are generally regarded as safe in biological systems. balanced and the electrode potential maintained in a
Capacitive electrodes also have naturally large reversible range to prevent any irreversible reactions from occur-
charge storage capacities (RCSC), which prevents induc- ring, such as electrolysis of water, gas formation, pH
tion of irreversible reaction at the electrode-tissue interface changes, corrosion and electrode dissolution that might
during the charge transfer. There are however limitations to alter the electrode performance during the charge injec-
charge injection and therefore limitations with respect to tion (either directly or by unaccounted alterations to the
electrode miniaturization [46]. Rough and porous materials, local environment). In 2008 penetrating microelectrodes
including those with high dielectric coatings, can improve with GSA ≤ 2000 μm 2, where charge/phase thresholds
the charge injection capacity—as this increased roughness are in the range of ~ 1 nC∙ph−1, were used by McCreery
and porosity in the material increases the electrochemical for safe excitation in feline cochlea and cerebral cortex.
surface area (ESA) with respect to the GSA [45]. Feline cochlear nuclei have been shown to have same cell
Most neural applications employ a series of bipha- types as that of the human cochlear nuclei. This study
sic current pulses for electrical stimulation. Figure 2b was conducted to determine the feasibility of multichan-
shows a symmetric biphasic current waveform where the nel auditory prostheses and safe excitation levels within
flow of electrons takes place from electrode to the tis- human ventral cortex through experimentation on young
sue during the cathodal phase and in the opposite direc- adult cats [45, 47]. Stimulating electrodes are generally
tion for the anodal phase. The charge delivered (q) at designed to have low impedance and supply low voltage
the cathode is given by the product of constant current applied, corresponding to the charge applied for stimula-
magnitude (i c) and corresponding pulse width (t c), i.e., tion, as high current input to the target tissue is known to
q = i c × t c, with analogous behavior at the anode, i.e., induce tissue damage. An in vitro charge injection capac-
q = i a × t a. The system maintains a net zero charge bal- ity of 0.9 mC∙cm−2, with a 0.5 ms pulse-width, has been
ance with an equal number of charges in the cathodal and reported for an array of 4000 μm2 porous TiN electrodes.
Biomedical Materials & Devices
TiN is interesting material with a columnar structure, tissue trauma that in any way may degrade the electrode
where the electrodes fabricated with this material have performance.
a resulting high effective area. As such, more electrical
charge can be transferred from metal to tissue for stimula- Tissue Interaction
tion with a small electrode size [48]. Materials including
iridium oxide ( IrO 2), Pt and PtIr alloy conduct through Biocompatibility and Corrosion Resistance
the aforementioned Faradaic route. Activated IrO 2
film (AIROF) has reportedly shown intrinsic injection Medical devices implanted underneath the skin or placed
capacities of ~ 1–4 mC∙cm−2 [49]. Recently, intrinsically on the epidermis to monitor, record and/or stimulate, are
conducting polymers, including polypyrrole (PPy) and susceptible to the intermediate tissue response that arises
poly(ethylenedioxythiophene) (PEDOT), as well as car- from the direct or interfacial contact between the electrode
bon nanotubes, have emerged as alternatives, which allow and the biological environment. Biocompatible materials
chemical surface modification to enhance functionality of are characterized by their non-toxic, non-inflammatory and
the electrodes. PEDOT-modified electrodes have shown non-allergenic effects when in contact with biological sys-
to exhibit charge injection of up to ~ 15 mC∙cm−2 [50]. tems. Often noble metals including gold, platinum, iridium
Recording electrodes measure small signals, often in and tantalum, are used as conducting material for electrodes
the range of millivolts and below. Action potentials are due to their biocompatible nature. For on-surface epidermal
nerve signals generated and conducted by neurons to trans- electrodes, the use of non-biocompatible materials as the
mit information to target tissues, and voltage amplitudes primary material or as an applied decorative finish, increases
for such central nervous system (CNS) action potentials the potential for reaction at the skin–electrode interface and
are typically measured to be in the order of 100 μV. These causes skin irritability. In the case of invasive implant elec-
recorded signals are also often subject to noise. Intrinsic trodes, biocompatibility issues are normally more severe.
noise can be attributed to the motion of charge carriers The surgical implantation procedure inflames the tissue
and extrinsic noise to atmospheric disturbances including around the implant leading to the formation of an encap-
electromagnetic fields from sources such as power lines. sulation sheath around the foreign body, the direct effects
Additional sources also include physical disturbances due of which includes a decrease in the SNR and increase in
to physiological processes including respiratory, cardiac electrical impedance at the electrode-tissue interface. This
processes and muscle contraction along with movement of foreign body response may be immediate, occurring within
tissue and electrode relative to each other. As such, record- hours of coming in contact with the device or long term
ing electrodes are designed so as to minimize all forms that can take from days to months to develop progressively
of noise so that signals can be recorded with high signal from the initial response [53]. Chronic responses developed
to noise ratio (SNR). These electrodes are also generally over time have also led to the migration of implant [54].
designed to operate with low current density and as such The schematic in Fig. 3a shows the foreign body response
have low impedance. This prevents irreversible reactions for a typical subcutaneous implant, beginning with protein
at the electrode-tissue interface leading to electrode corro- adsorption on the implant surface, followed by adhesion and
sion [44]. Typical impedance of recording electrodes var- differentiation of neutrophils and monocytes, which have
ies between 50 kΩ and 1 MΩ, measured at 1 kHz, which emigrated from the vasculature resulting in the formation of
is larger than the impedance of the tissues into which they a collagenous fibrous capsule around the implant. Similarly,
are embedded [45]. High impedance of a recording elec- Fig. 3b shows foreign body response for an intravascular
trode, in addition to the network’s distributed capacitance
and amplifier, can affect its high-frequency response. The
amplitude and corresponding frequency range of some
of the bioelectric signals measured by non-invasive elec-
trodes on the surface of the body are shown in Fig. 2c.
There is a limitation for spatial resolution and operation
frequency band. However, it should be noted that higher
electrical impedance does not itself contribute to the noise
in the system. Comparatively speaking, implanted elec-
trodes have better-signal reception; however, they typically
develop problems in the long run and have risks involv-
ing tissue damage. Thus, electrode design for implant-
Fig. 3 Foreign body response (a) of a subcutaneous implant (b) of
able electrodes should accommodate potential risks of a intravascular implant. Reprinted from [79] Copyright (2015), with
permission from Elsevier
Biomedical Materials & Devices
implant beginning with protein adsorption, followed by [57, 67]. Metals, among the extensively used materials to
adhesion of platelets and leucocytes, generating clotting fabricate electrodes, are likely to corrode owing to forma-
factors like thrombin. Thrombin converts soluble fibrino- tion of galvanic cells, with redox electrochemical reactions
gen protein into insoluble fibrin that entraps other platelets, occurring at the metal/tissue interface [63, 65]. As such cor-
blood cells and plasma in contact. According to the Interna- rosion limits the biocompatibility of a material by inducing
tional Organization for Standardization 109993-5, there are host reactions through the release of allergenic and toxic
three different types of tests, namely extract, direct contact species and products during the corrosion process.
and indirect contact used for quantifying the biocompat- Several approaches, both chemical and biological, can be
ibility or checking the cytotoxicity of electrode materials used to improve biocompatibility of electrodes and modu-
and medical devices [55]. The MMT or the 3-(4,5-dimethyl- late tissue responses. Electrode surfaces and/or electrode-
2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (methyl tissue interface sites can be modified with self-assembling
thiazolyl tetrazolium assay) is a rapid test for measuring cell monolayers in order to repel protein adsorption, through
metabolism, growth and toxicity through cell proliferation. the construction of defined surface structures [68] and cell
In the direct contact method, electrodes are placed in direct adhesive peptides to promote selective cell adhesion [69].
contact of the cells in vitro and observed for the changes in Alternatively, hydrogel coatings have also shown to improve
cell number and other morphological changes. Indirect con- biocompatibility [70]. Implanted electrodes can also be con-
tact tests include molecular filtration and agar overlay assay. figured to release therapeutic substances in vivo to prevent
The molecular filtration method is suitable for mildly toxic the foreign body response from occurring [71–74]. Her-
devices, whereas the agar overlay assay is suitable for small metic sealing with barrier coatings which are simultane-
molecular weight and water-soluble particles [55]. ously biocompatible in composition, defect free, long-life,
Corrosion of an electrode refers to the degradation of the highly insulating, have low thermal conductivity and mass,
physical and mechanical properties of electrode materials high transparency (in the case of an optically responsive
in response to the harsh body environment that it is exposed electrode), have low mass density, are highly flexible and
to. This is a common issue related to both non-invasive on- can resist bio-dissolution can be used [75]. However, care-
surface and implanted electrodes, owing to the ionic com- ful consideration must be taken as the selection and use of
positions of various body fluids [56, 57]. With on-surface hermetic coatings into the system as coatings may lead to
applications, wearable electrode materials are subject to bio- increase in weight, inflexibility and manufacturing chal-
fluids for sensing. These biofluids such as saliva, tears and lenges [76]. Electrodeposition of conducting polymers like
sweat are often corrosive in nature and may change electrode PEDOT with dopants of suitable molecular weight, which
properties through irreversible chemical reactions and acid may be further oxidized, can also be incorporated in order
attacks. Non-invasive wearable sweat sensors have been used to minimize corrosion as well as to improve conductivity
to detect different body analytes like sodium, ammonium and [77]; however, it is to be noted that thin polymer coatings
calcium. The electric current applied in the process of detec- are often brittle [78]. Polymer and CNT composites can
tion however makes these sweat sensors prone to galvanic also prevent deposition of species for polarized electrodes
corrosion [58–60]. For invasive applications, complications through controlled charge injection. This can also be accom-
can be more severe with the potential risk of the implant plished through application of an AC signal in the electrode
loosening leading to failure. Long-term cytotoxicity in plati- for the release of the encapsulated species. Other problems
num electrodes due to corrosion has been observed in coch- including metal dissolution, deposition and ion migration,
lear implants [61]. Corrosion of gold-plated tungsten wire in common to heterogeneous alloy surfaces, can be prevented
phosphate buffer saline (PBS) solutions, impacting electrical by constructing electrodes with homogeneous alloys having
properties and generating toxic tungsten metal ions, has been transition metals with higher atomic weight.
observed [62, 63]. Similarly, significantly elevated metal
concentrations in blood, with presence in serum and urine, Flexibility and Mechanical Strength
have been reported in total joint replacement patients [64].
Metal ions including cobalt, nickel and chromium in com- The mechanical robustness of an electrode, that is, its ability
bination with protein available in skin, blood and connec- to withstand abrasion and tearing, as well as stretching, is a
tive tissues have potential to trigger immune responses [65]. key feature for reliable performance in an electrode. An elec-
Accumulation of metal ions has also been reported to result trode should be mechanically robust to continuously transmit
from the production of digestive enzymes that degrade the signals allowing deformations including bending, twisting,
extracellular matrix including cells, morphological change compression and stretching. It should also be flexible enough
in organs and implant loosening [66]. Dissolved salts and to avoid substantial mechanical strain on the tissues it is in
halide ions in the body promote corrosion reactions of inva- contact with [80, 81]. Skin tissue has an elastic bilayer struc-
sive electrodes in conjunction with pH and body temperature ture consisting of outer epidermis with a Young’s modulus
Biomedical Materials & Devices
140–600 kPa and inner dermis with Young’s modulus of compromises their intrinsic strength respective to the geo-
2–80 kPa [82–84]. Similarly, tissues such as bone, including metrical design. As such, elastomeric substrates with a low
skeletal muscles, exhibit high elastic moduli in the range modulus of between 50 and 100 kPa have been employed
of 2–4 GPa. In comparison mechanically static tissues like for the fabrication of devices with metal conductors. An
heart or breast and compliant tissues like the lungs exhibit advantage of using elastomers for wearables is the ability
low elastic moduli of < 1 kPa [85]. to have conformal and intimate integration with the epi-
The chart from Ashby in Fig. 4 shows the modulus of a dermis, which helps to avoid errors introduced by small
material against stress at failure. Such charts provide a good air gaps or artifacts associated with relative motion that
starting point to guide materials selection in the fabrica- affect their performance significantly. Incorporating elec-
tion of electrodes specific to target tissues, as well as the tronic components like silicon (Young’s modulus of 160
incorporation of materials together in a composite struc- GPa) with elastomers, comes with the risk of mechani-
tures for said electrode fabrication [86]. Heavy transition cal strain on the low elastic modulus material affected by
group metals like gold, platinum, iridium including alloys, the high elastic modulus material due to their difference
carbon-based materials like SWCNT and graphene display in mechanical properties [89]. As such, effective moduli
good conducting properties; however, they are fairly stiff should be maintained within 100–150 kPa to prevent inter-
and strong materials. The rigidity of implanted electrodes facial cracking and delamination [37].
may induce micro-motion-related mechanical strain in tissue Together with individual material properties of the
such as brain tissues and result in inflammation and tissue electrode, such as the conducting material, the underly-
injury, leading, among other things, to device failure [87]. ing substrate can improve the collective ability to endure
Similarly, the migration of microglia from softer to stiffer mechanical strain as well as avoid mechanical mismatch
areas of the electrode has also been observed [88]. of electrode subcomponents and geometry. For weara-
For their implementation in implants, electrodes need bles, placed on the skin surface, the effective moduli of
to be small in size as well as flexible, such that they the device in contact should be low. High moduli devices
can be selective for stimulation and recording purpose. can lead to interfacial cracks, impedance increase and sig-
The smaller and compact size also addresses the issue nal loss leading to device failure. Polymers offer tunable
of mechanical mismatch at the abiotic–biotic interface; conductive and mechanical properties through controlled
however, controlling the feature size of the material particle loading [90]. Thus, depending on the placement of
an electrode in the body, the flexibility and stretchability
of the electrode can (and must) be designed for matching applications [89]. Adding a layer of coating such as a
in order to provide reliable performance. hydrogel onto these materials has however been shown
to facilitate improved biocompatibility, rendering them
compatible for bioelectronics interfacing [94]. On the
Types of (Semi) Conductors other hand, signal transduction across the abiotic–biotic
surface face problems due to increase in impedance at the
Materials may be classified as conductors, semiconduc- point of contact. This is an underlying problem common
tors or insulators, depending on their ability to conduct to inorganic materials interfacing with the biological sys-
electricity. Insulators (wide band gap materials, with high tems that limit efficient charge transfer. Conjugated poly-
dielectric constants) are poor conductors of electricity, mer composites, as a class of semiconductor, are often
and as such mostly find application as dielectric compo- used as coating materials on these inorganic electrodes, in
nents in electronic devices [91]. For example, implanted order to decrease the impedance of the electrode structure.
devices typically use materials with high dielectric con- Polymers also have unique ionic charge transport capa-
stants, such as silicone and Parylene for hermetic sealing bilities, similar to the conduction process in biological
of the implant [92]. systems. As such polymer materials are favored for bio-
Metal conductors, with their ordered atom arrangement, electronics application and interfacing as electrodes and
are the most widely used electrode materials attributed to coating materials for inorganic electrodes. In contrast to
property of wire drawing in older electrode preparation inorganic metals and non-metallic elemental solids such
processes. Conductors have an energy overlap between as silicon, polymers can also be flexible in nature and
their conduction and valence band, meaning charges can thus are sometimes referred to as ‘soft organic materi-
migrate without needing to be excited first. Gold and plati- als’ [95]. Although polymers are intrinsically insulating,
num are some of the most common metals to be used as they can be made fairly conducting by addition of dopants,
electrodes for interacting with biological systems. which lead to the creation of free charge carriers. N-type
Semiconductors, as the name suggests, are mid-way dopants partially oxidize the conjugated network, while
between conductors and insulators. They have a narrow p-type dopants partially reduce it [96]. A number of bio-
band gap between their conduction and valence band. molecules and therapeutic agents can function as dopants.
This band gap energy is the minimum required to excite a Furthermore, these may be functionalized into conducting
charge carrier to a state in which it can participate in the polymers themselves during the polymerization process
conduction process. The application of voltage, as well [97–99]. The building blocks of polymers are covalently
as rise in temperature, can trigger electron flow bridging bonded atoms. These blocks form chains, connected to
the narrow energy gap resulting in their high conductiv- one another through Van-der Waals force and electrostatic
ity. Silicon is the archetypal semiconductor and is widely forces. In contrast to the covalently bonded silicon atoms,
used in electronic applications. Silicon has a network of these bonds can be easily broken, allowing for tunable
covalently bonded atoms, where each neighbor shares four functionality and opportunities for application-specific
valence electrons. Pure semiconductors are called intrinsic
semiconductors. Conduction in such types of semiconduc-
tors occurs through the movement of both holes and elec-
trons. As such, total current is equal to the sum of electron
current and hole current. The conductivity of semiconduc-
tors can be increased by the addition of impurities and the
process is called doping, creating what is known as an
extrinsic semiconductor. In the case of silicon, addition of
pentavalent impurities, with 5 electrons in their outermost
shell, like arsenic or bismuth, increases the electron charge
carriers. These semiconductors with excess electrons due
to doping are called N-type semiconductors. The addition
of trivalent impurities with 3 electrons in their outermost
shell, like boron and aluminum, increases the hole charge
carriers. Due to the excess of positive hole carriers, these
semiconductors are called P-type semiconductors [93].
For the interfacing of bioelectronics however, silicon Fig. 5 Comparing the structural organization of inorganic silicon
with organic PEDOT:PSS electrode along with their responses in a
tends to have poor suitability in terms of biocompatibility biological environment. Reprinted (adapted) with permission from
or flexibility and are likely to underperform in in vitro [100]. Copyright 2014 American Chemical Society
Biomedical Materials & Devices
materials engineering. A schematic comparing the inter- highlighted with an evaluation of electrical properties. Inks
action of inorganic silicon and organic PEDOT:PSS elec- can be used singularly for making simple passive structures
trode with the biological system is given in Fig. 5 [100]. like resistors, or in combination for constructing active
In the case of a silicon electrode, the formation of silicon structures such as thin-film transistors, depending on how
oxide on the silicon surface causes ion accumulation at the they are applied. Table 2, adapted from Fukuda et al., pro-
electrolyte/ion interface, which affects its doping state due vides general specifications of different printing methods
to field-effect mechanism. As such, conduction is limited for the fabrication of printed thin-film transistors [27]. Dif-
on the surface of the electrode, increasing the impedance ferent printing methods are listed in the table with required
of the structure. Organic polymer electrodes on the other ink viscosity, attainable line resolution (specified through
hand employ ionic charge transport and utilize the entirety physical dimensions of the print including line width and
of its material volume for conduction. Other advantages thickness) and printing speed, based on the printing method
of using polymers for electrodes include low-temperature selected. Considerations regarding the proper choice of ink,
processing, oxide-free interfacing and facile modification substrate and design of patterned structure determine print-
process with tunable functionalities. ing method selection. The results being the yield, quality
and production cost for the entire operation. Metals includ-
ing Ag, Au, Cu, ceramics oxides, carbon-based graphene,
Printing Techniques nanotubes and organic polymers including poly(3,4-ethyl-
enedioxythiophene) polystyrene sulfonate (PEDOT/PSS)
Conventional practices of electrode fabrication range from compounds, have been used as conducting pigments in con-
simple methods like drop casting [17], spin coating [18] ducting inks for printing interconnects and electrode pads.
and electrodeposition [19]; to more complicated methods Interconnects are the connecting wire or conducting line in
including lithography [24, 25] and laser ablation [101, 102]. a circuit. Among the conducting materials, metals feature
Depending upon the material choice and application, these comparatively higher conductivity and low resistance than
methods can yield high resolution with controlled geometry their polymer and ceramic counterparts.
and feature sizes. However, the main interest and advantage
of printing as an alternative to conventional practices lies Metals
in the ease of prototyping and scalability [28]. The print-
ing process involves deposition of functional materials or Metals are normally the first choice when it comes to fabri-
pigments with conducting, non-conducting dielectric and cating conducting electrodes. Metals have high conductivity
semi-conducting properties, fashioned into electronic inks due to the overlap of their conduction and valence bands.
through the incorporation of appropriate solvents, binder For applications in the biomedical field, heavy transition
polymers, surfactants and/or stabilizers. Suganuma et al. noble metals including iridium, platinum, gold, tungsten,
provide an insightful introduction to the field of printed tantalum are generally preferred on account of their bio-
electronics and should be referred to as a starting point for compatibility, mechanical strength and corrosion resistance
newcomers [103]. In the present work, we review different [104, 105]. In some cases, more inexpensive options, such as
printed organic and inorganic electrodes and their potential copper and silver, have also been used [106, 107]. Generally,
use in biological sensing and stimulation. The construction one-dimensional high aspect ratio nanoparticles, nanorods
of these electrodes through different printing techniques is and nanofibers of metals are attractive for ink formulations,
Table 2 Comparison of Printing method Ink viscosity (mN∙m−1) Line width (um) Line thickness (μm) Speed (m∙min−1)
different printing methods.
Reprinted from [27] Copyright Inkjet 1–100 30–50 0.1–1 1–500
2017 Wiley Advanced Materials
E-jet 1–10,000 1 0.001–0.1 <1
Dispense 1000–1,000,000 10–1000 50–100 Single stroke
Offset 100–100,000 10 1–10 1000
Gravure 100–1000 10–50 0.1–1 1000
Flexo 50–500 45–100 <1 500
Screen 500–100,000 30–50 5–100 50–150
Gravure-offset 5000–50,000 5–20 1–3 1–10
Reverse-offset 1–5 1–10 0.05–1 0.01–1
Transfer printing – 0.1 1 Slow
Nanoimprint – 0.01 0.1 Slow
Biomedical Materials & Devices
given their advanced electrochemical performance, electrical Post-deposition heat treatment of the printed structures can
and heat conductivity [108, 109]. Metal nanoparticles, with help decompose and remove these organic binder materi-
dimensions between 1 and 100 nm, can be easily suspended als, in addition to performing the role of sintering the metal
in solvents such as short-chain alcohols (ethanol, isopropyl particles [125]. Inorganic inks that utilize polymeric layers
alcohol), glycols, water or toluene in order to form low- for ink formulation, however, may require very high-temper-
viscosity inks, without significant sedimentation over the ature treatment to improve conductivity, restricting the use
timeframes required. Such low-viscosity inks can be used of many flexible plastic substrates which may degrade and/
in inkjet, flexo and offset gravure printing. Nanoparticles or distort at such temperatures. Metal–organic decomposi-
exhibit high surface energy due to the small particle size, tion (MOD) inks are another approach to printing of metallic
which facilitates post-printing annealing/sintering of neigh- structures, which utilize metal precursors like metal salts
boring individual particles can be accomplished to create a dissolved in solvent. The ink itself is free from nanoparti-
solid, continuous product after printing [110]. cles and typically transparent or translucent in nature. The
Nanoparticles are generally synthesized through chemi- molecular nature of the compound allows for low-temper-
cal routes by the reduction of organometallic compounds ature processing of the printed pattern, in favor of plastic
in wet-chemical environments [111]. Other methods also substrates. β-Ketocarboxylate Ag MOD ink decomposes at
include mechanical machining, aided with high energy 100 °C, giving Ag metal features with a resistance of 10−6
sources like ultrasound and laser ablation. The chemi- Ω at 120 °C [126]. Cu- [127], Au- [128] and Pt [129]-based
cal synthesis route is normally preferred as it offers bet- MOD inks have also been used.
ter control over the final morphology and higher yields of Various printing methods, including high-resolution
the metal nanoparticles. Solvents including polyols [112, inkjet, gravure, offset printing and screen printing, as well
113], octyl ether [114], octylamine [115] and toluene [116] as less conventional ‘advanced manufacturing processes’
have been used for such synthesis procedures. Among the such as transfer and 3D printing, have been used to print
organic solvents used for nanoparticle synthesis, ethylene metal nanoparticle-based inks. Depending on the printing
glycol is the most widely reported [112, 117] and is itself a method used, ink viscosity can be tuned to match the rheo-
mild reducing agent, assisting the creation of nanoparticles logical requirement of the printer. Generally, metal loadings
from electropositive metal salts, including those of silver, of 20–60 wt% are required to obtain high conductivity in an
gold, palladium and platinum [112]. During the reaction, inkjet-printed pattern. Alternatively, inks with high vapor
control of particle growth is facilitated by addition of appro- pressure may be used to afford a high density of the metal
priate surfactants, which further helps prevent nanoparticle particles without unwanted organic materials.
agglomeration. Surfactants should have good affinity to the In terms of conductivity, Ag nanoparticle-based metal
metal nanoparticles to provide electrostatic and steric stabi- inks are the leaders and widely researched, with resistivi-
lization of particles in the solvent, avoiding agglomeration ties of just a few μΩ∙cm [130, 131], comparable to bulk Ag,
and/or uncontrolled growth of the particles. Sulfur-enriched which has a resistivity 1.59 μΩ∙cm. Grau et al. reported a
thiol molecules have been widely used to stabilize gold high-resolution Ag nanoparticle-based source–drain elec-
nanoparticles [118, 119]. It has also been observed that the trode for TFT application fabricated using a gravure printing
concentration of alkanethiol used as stabilizing agent also process, which is shown in Fig. 6a. The source–drain elec-
affects the particle size of the metal [119, 120]. trodes are printed at 5 µm distances, called channel lengths
Poly(N-vinyl-2-pyrrolidone) (PVP) is a common steric for a transistor, with each individual electrode having a 5 µm
stabilizing agent used for Ag- and Cu-based inks[117, 121], width. The source–drain electrodes are overlaid with differ-
with other stabilizers including carboxylic acids [114, 116], ent viscosity semiconductor ink for assessing performance
cetyltrimethylammonium bromide (CTAB) [112], poly [132]. Kang et al. reported comparable results using gra-
(acrylic acid) salts [122] and poly(ethyleneimine) [123]. vure printing with a line spacing of 10 μm in a TFT, with
Besides the use of stabilizing surfactants, materials like optimized ink viscosity and print speed [133]. Meanwhile,
copper may also require to be processed in anaerobic envi- Shen et al. have reported inkjet-printed Ag nanoparticle-
ronments, as they are prone to oxidation. Furthermore, poly- based electrodes, shown in Fig. 6b with a width of ~ 526 µm,
mer binders may also be added for good ink adhesion to the fabricated on paper substrates. The usefulness of these elec-
substrate. Organic surfactants including ligand molecules trodes was demonstrated with them being used as conductive
and polymer binders can also be added in the later stage tracks to supply an LED in a circuit [134].
during the ink formulation for metal nanoparticles synthe- With a focus toward biological applications, Ali et al.
sized without the stabilizers. These organic layers, however, reported that an interdigitated Ag nanoparticle-based elec-
can cause several types of defects, including the formation trode, produced using inkjet printing, is shown in Fig. 6c.
of an insulating energy barrier that inhibits charge injec- This was successfully used for pathogen detection, with
tion and/or altering the work function of the metal [124]. Salmonella typhimurium, and the Escherichia coli strains
Biomedical Materials & Devices
Fig. 6 a High-resolution gravure-printed Ag nanoparticle-based matic cross section of the OTFT. (ii) Optical images of OTFT chan-
source–drain electrodes with equal channel length and electrode nel length L = 1, 2 and 5 µm. (iii) Atomic force microscopy (AFM)
width of 5 µm, overlaid with semiconductor inks of different viscosi- of OTFT with 5-µm channel length. Reprinted from [136] Copyright
ties for TFT application. Reprinted from [132] Copyright 2016 Wiley 2008 National Academy of Sciences, USA. e Inkjet-printed gold
Advanced Electronic Materials. b Optical image of inkjet-printed sil- 31-electrode array with minimum feature size of 62 µm for bioel-
ver tracks with (i) different line widths, (ii) a “1.0pt” printing width ectronics interfacing. Reprinted from [146] Copyright 2016 Wiley
of 562 µm. Reprinted from [134] Copyright 2014 Nanoscale. c Inkjet- Advanced Functional Materials. f Inkjet-printed Au-based MEAs in
printed Ag nanoparticle-based disposable electrodes for pathogen a 64-electrode configuration with 200 µm pitch and individual elec-
detection. Reprinted from [135] Copyright 2016 Scientific Reports. trode measuring ~ 31 µm. Reprinted from [147] Copyright 2017 Flex-
d High-resolution line spacing/channel of 1um demonstrated for ible and Printed Electronics
pentacene-based OTFTs with inkjet-printed Ag electrodes. (i) Sche-
JM109 and DH5-α all identified using this biosensor and accurately aligned patterns. Recent studies, however,
[135]. The direct write inkjet printing method has been have shown Ag to be less biocompatible and rather toxic
demonstrated to achieve high-resolution line spacing/chan- with migration effects for in vivo applications [137, 138].
nel length of 1 μm between the drain and source electrodes Similar to silver, copper nanoparticle-based inks are
for organic TFTs, with sub-femtoliter droplets of a Ag attractive due to their low cost and high conductivity.
nanoparticle-based ink and a low sintering temperature of Norita et al. have reported printed Cu nanoparticle ink-
130 °C (see Fig. 6d). For comparison, channel lengths 1, based electrodes with resistivities as low as 7 μΩ.cm after
2 and 5 µm were also reported for pentacene-based OTFTs photonic sintering using a Xenon (Xe) flash lamp [139].
[136]. The low-viscosity inks utilized by these printing In the case of copper, the particles themselves are prone to
methods are often aqueous-based dispersions. Ink viscos- surface oxidation, resulting in the printed structures often
ity, metal particle size, wettability and adhesion of the ink having much higher resistance. As such, higher sintering
to the substrate need to be considered for high resolution temperatures in inert atmospheres and/or more severe
Biomedical Materials & Devices
reducing conditions are required to provide good conduc- application, graphene of different qualities can be obtained
tivity [140]. Recently, the biomedical prospects of copper using mechanical or chemical splitting of graphite and car-
oxide nanoparticles have also been investigated, with a bon nanotubes, liquid phase exfoliation, chemical vapor
few reports on printed electrochemical sensors [106, 141]. deposition (CVD), plasma-enhanced CVD, solvothermal
Platinum is another attractive metal for biomedical appli- synthesis from organic compounds and/or thermal decom-
cations, due to its high conductivity, stability and inertness, position of SiC [159]. Graphene-based printing inks can be
radiopacity, durability and mechanical strength attributed formulated by dispersing graphene flakes in solvents such
its high atomic weight [142]. Platinum nanoparticle inks for as water [160, 161], ethanol [162, 163], terpineol [164],
inkjetting have been developed and the resultant metal pat- N-methylpyrrolidone (NMP) [165, 166] and o-dichlo-
terns have been used as base electrode for applications such robenzene [166]. Additionally, stabilizing agents such as
as pH sensing [143] and electrodes for dye-sensitized solar poly cyclic aromatic hydrocarbons, surfactants including
cells [144]. Similarly, platinum ink has also been screen sodium dodecyl sulfate (SDS) [167], sodium dodecylb-
printed for electroanalytical applications [145]. enzene sulfonate (NaDDBS) [161], sodium deoxycholate
Inkjet-printed gold nanoparticle-based electrode arrays, [166], sodium cholate [168] and CTAB [169], as well as
shown in Fig. 6e, consisting of 31 electrodes with features polymeric PVP [170], PVA [171] and ethyl cellulose [163]
as small as 62 μm, spaced at between 2 and 7 mm and with a have also been used for maintaining stable dispersions.
conductivity of 5 × 106 S∙m−1, have been realized on a poly- Figure 7a shows a schematic representation of processing
ethylene naphthalate (PEN) substrate and used to map the steps for the preparation of graphene-based inks as used in
impedance of conformal surfaces at 15 kHz for bioelectronic inkjet printing. Formulated at room temperature, this ink
interfacing purposes [146]. Similarly, Fig. 6f shows MEAs uses ethanol as a solvent and ethyl cellulose as a surfactant.
with 64 electrodes, which were fabricated using an inkjet First, the precursor graphite powder is exfoliated in a solu-
printing method on Kapton sheets, and were used for extra- tion of ethanol with ethyl cellulose by probe ultrasonication
cellular recording of cardiomyocytes. These MEAs had a process. Ethyl cellulose acts as the stabilizing agent for the
200 μm pitch, with individual electrodes measuring ~ 31 μm exfoliated graphene. The exfoliated ethyl cellulose-encapsu-
in width [147]. Gold nanoparticle-based screen-printed sen- lated graphene is then subjected to sedimentation centrifuga-
sor electrodes were also produced for use in DNA detec- tion for removal of larger particles. Then, an aqueous solu-
tion [148, 149], while high-precision screen-printed gold tion of NaCl is added to the mixture, in order to flocculate
nanoparticle-based source–drain electrodes produced with the graphene and ethyl cellulose. The obtained solid is then
a 90-μm line spacing/channel and conductivity of 1.0 × 105 washed, dried and finally dispersed in a variety of solvents
S∙cm−1 for OTFTs have also been demonstrated [150]. to prepare ink for printing [163].
Aside from dispersions of graphene itself, graphene oxide
Carbon Nanomaterials (GO) and its chemical derivative (reduced graphene oxide
(rGO)) may also be used to prepare inks. Reduction of GO
Carbon nanomaterials have become a popular choices for after printing is required in order to improve conductivity
electrodes and sensor applications given their low cost, to a useful range. Compared to pristine graphene flakes,
environmentally sustainable nature due to their associated the hydroxyl, carbonyl and carboxylic groups in GO enable
processing steps and excellent electrochemical performances easy dispersion without the need for stabilizing agents. GO
[151]. Carbon materials including graphene, carbon nano- has been dispersed in water [165] and other polar organic
tubes (CNT), carbon dots, carbon nanofibers, nanodiamonds solvents including NMP, N, N-dimethylformamide (DMF),
and fullerenes exhibit large surface-to-volume ratios, high tetrahydrofuran (THF) and ethylene glycol [172]. Gener-
conductivity and electron mobility, chemical inertness and ally, particle loading for low-viscosity graphene-based
higher sensitivity for electrochemical analysis resulting in inks is in the range 0.002–1 wt% [166] and GO-based inks
their widespread application. Among them, CNTs and gra- are 0.1–1 wt%, requiring multiple layer prints in order to
phene have become the most attractive materials for printed attain reasonable conductivities. Viscous graphene inks can
electronic applications, with fabrication of TFTs [152, 153], be prepared by increasing particle concentration [173] or
RFID tags [154], electrochemical and bio-sensing electrodes by gelation of graphene dispersions [174]. Apart from the
[155, 156] all being reported. Other larger carbon materials wet-chemical synthesis methods, porous graphene has also
including fibers and particles are also used as resistors and been prepared by direct laser writing on carbon materials
electrodes. using CO2 lasers in an ambient environment [175]. Figure 7b
Graphene is a two-dimensional carbon allotrope with shows a 64-electrode array fabricated from graphene, pro-
sheet thickness of 0.34 nm and sp2-hybridized carbon units duced by direct laser ablation of a polyimide substrate [39].
[157]. The ideal sheet resistance of graphene is Rs ~ 62.4/N CNTs are one-dimensional allotropes of carbon having
Ω∙cm, where N is the number of layers [158]. Depending on cylindrical structure with hexagonal honeycomb lattices
Biomedical Materials & Devices
Fig. 7 a Schematic representation of graphene ink preparation with sistor (EGT) with a channel length of 90 µm and width of 900 µm;
graphene flakes and stabilizing polymer; (i) probe sonication exfolia- (iii) schematic illustration of EGT with screen-printed graphene elec-
tion of graphite powder and simultaneous isolation in ethanol/EC; (ii) trodes. Reprinted from [173] Copyright 2015 Wiley Advanced Mate-
removal of residual graphite flakes by sedimentation; (iii) graphene/ rials. d Screen-printed graphene: (i) rheology characterization of ink
EC flocculation with salt; (iv) ink with graphene/EC dispersed in through viscosity measurement for 52 mg∙mL−1 concentration ink in
85:15 cyclohexane/terpineol; (v) photograph of the prepared gra- dipropylene glycol; (ii) graphene paste on spatula; (iii) screen-printed
phene ink. Reprinted (adapted) with permission from [163] Copyright graphene on PET and folded. Reprinted from [174] Copyright 2016
2013 American Chemical Society. b Porous graphene-based 64-elec- Advanced Functional Materials. (e) Screen printed: (i) graphene
trode array fabricated on polyimide substrate for cortical stimulation oxide ink-based circuit; (ii) reduced graphene oxide showing printed
and sensing. Reprinted from [39] Copyright 2016 Scientific Reports. circuit. Reprinted from [180] Copyright 2017 Wiley Advanced Mate-
c Screen-printed graphene electrode: (i) single 40-µm-wide track; (ii) rials Technologies
implemented as source–drain electrodes for electrolyte-gated tran-
built by sp2 carbon units. CNTs have been used for different their metallic configurations, SWCNT and MWCNT are
electrochemical and biosensing applications [176, 177]. Two still less conductive than most metals used as electrodes at
structural groups including single-walled carbon nanotubes 10−6 Ω∙cm and 3.10−5 Ω∙cm, respectively, although they
(SWNTs) and multi-walled carbon nanotubes (MWNTs) do exhibit superior mechanical strength [178]. For use as a
have been identified for CNTs. SWCNTs consists of a hollow conducting element, separation of semiconducting CNTs is
rolled up individual graphite sheet with possible diameters an essential requirement. Electric arc discharge, laser abla-
between 1 and 2 nm, whereas MWNTs are nested graphite tion and chemical vapor deposition (CVD) are some of the
cylinders with diameters between 2 and 25 nm with spacing methods used for synthesis of CNTs.
between tubes of 0.34 nm [176]. Thin films composed of Similar to graphene, CNT-based printing ink can be
randomly distributed CNT can also be flexible and stretcha- formulated by dispersing CNTs in organic solvents.
ble, making them very useful for flexible devices. CNTs may Ultrasonication and high-pressure homogenization are
have either metallic or semiconducting properties depend- used for dissociating agglomerates and preparing homog-
ing on the chirality or lattice symmetry along the sheet. In enous dispersions. Additional stabilizing agents including
Biomedical Materials & Devices
surfactants with anionic, cationic and non-ionic groups plastic substrates using inkjet printing technology, a sheet
or polymers may also be used in the process. Reported resistance of ~ 40,000 Ω∙sq−1 was demonstrated [185].
surfactants for stabilizing CNTs include Triton X-100, Among screen-printed MWNT inks, sheet resistances of
SDS, Tween 20, Tween 80, sodium cholate, CTAB, dode- 0.5–13 Ω∙sq−1 have been achieved for 3 successive layers
cyl trimethylammonium bromide (DTAB) and NaDDBS of print [186].
[179]. In the case of dispersion in water-based media or
other hydrophilic solvent, surface modification may be Polymers
needed since CNTs generally have hydrophobic nature.
CNT-based inks generally have low particle concentra- Conducting polymers are organic compounds composed
tions, ranging from 0.01 to 10 g∙L−1. of repeating units, linked together by alternating single
A variety of printing techniques including inkjet [163], and double bonds [187]. Despite having lower conductiv-
gravure [181], screen [174] and flexographic method have ity than metals, conducting polymers have advantages of
been used for printing graphene and CNT-based elec- being inexpensive [188] and mechanically more flexible
trodes. Graphene lines with resolution ~ 30 µm have been and elastic with lower Young’s moduli than metals [189].
gravure printed for large area flexible electronics [181]. Polyaniline (PANI) [190], polypyrrole (PPy) [191] and
High-resolution prints have also been reported with sili- poly (ethylene dioxythiophene) (PEDOT) [192] are some
con stencil-based screen-printed graphene demonstrating of the first reported and most commonly used biocompat-
line width of ~ 40 μm, high conductivity of ~ 1.86 × 1 04 ible polymers. Conducting polymers are compatible with a
S∙m−1 with a particle concentration of ~ 80 mg∙mL−1. The wide variety of aqueous solvents making them an attractive
optical image for the printed line is shown in Fig. 7c.i. material for printing and ink formulation, often by disper-
This ink was subsequently used for the fabrication of an sion. Conducting polymers have been printed using several
electrolyte-gated transistor having a channel length 90 µm printing methods including inkjet [193], gravure [194],
and channel width 900 µm, as shown in Fig. 7c.ii. A sche- screen printing [195] and 3D printing [196], for applications
matic of the full fabricated device is shown in Fig. 7c. including flexible electronics and energy storage applica-
iii [173]. Similarly, a highly concentrated (52 mg.mL−1) tions [197]. These polymers tend to have narrow bandgaps,
graphene paste was screen printed to give lines with 40 μm allowing easy transfer of electrons from valence band to the
width and 25 μm thickness, exhibiting a sheet resistance conduction band. Most polymers intrinsically lack charge
of 30 Ω.sq−1 after being dried at 100 °C. The rheologi- carriers for conduction despite having narrow bandgaps. As
cal characterization of the ink, shown in Fig. 7d.i, shows such, dopants are required to increase the carrier mobility
shear thinning behavior with high viscosity suitable for and improve conductivity. Dopants are agents that either
screen printing. For screen printing, ink viscosity needs partially oxidize or partially reduce the polymer and are
to be high 500–100,000 m∙Nm −1 (as given in Table 1). typically added during the synthesis process. Depending on
The viscous ink in a spatula is shown in the photographic the added dopant, polymers can, similar to inorganic semi-
image in Fig. 7d.ii. This ink was used to prepare a flexible conductors, be n-doped or p-doped through the addition and
screen-printed circuit on PET substrate, shown in Fig. 7d. removal of electrons. Within the polymer backbone, elec-
iii [174]. A reasonable resistance of 327 Ω∙sq−1 was also trons can move along the π-bonded network in conjugated
achieved using screen-printed water-based graphene molecules to conduct current; however, electron hopping
oxide ink, as demonstrated by the as a conductive circuit is observed between localized conjugated molecules of the
shown in Fig. 7e.i. The same circuit was also printed using non-conjugated bonds. Conducting polymers can be synthe-
rGO-based ink, screen printed as shown in Fig. 7e.ii. In sized generally via chemical and electrochemical processes
this case GO was reduced with 1:1 mixture of trifluoro- [198, 199]. Chemical synthesis generally involves mixing
acetic acid and hydroiodic acid, at 80 °C [180]. A slightly the monomer solution with the oxidizing agent, forming bulk
lower sheet resistance of 250 Ω∙sq−1 was achieved using powder or thick polymer film. On the other hand, electro-
an inkjet printer, with a graphene oxide concentration of chemical polymerization involves application of electrical
3.2 mg∙mL−1 in the ink [182]. Similarly, at a concentration current to a solution containing a monomer, usually with
of 3.4 mg∙mL −1, a low resistance of just 4 mΩ∙cm was a dopant resulting in deposition of thin polymer films on
achieved for 20-μm thick inkjet-printed graphene samples another conducting (usually metal) electrode. Electrochemi-
[163]. Aside from graphene, inkjet-printed MWNT elec- cally synthesized polymers have superior properties includ-
trodes have also been reported to achieve a conductivity ing higher electrical conductivity and enhanced redox activ-
up to 30 S∙cm−1 without post-treatment [183]. Similarly, ity compared to their chemically synthesized counterparts,
inkjet-printed SWCNT on stretchable substrates with 1- but the process is time-consuming and has low yield. For
and 5- layers showed respective sheet resistances of 170 commercial applications and printing, chemically synthe-
and 19 Ω∙sq−1 [184]. For SWNT printed onto paper and sized polymeric nanoparticles are generally preferred.
Biomedical Materials & Devices
Fig. 8 a 3D printed PEDOT: PSS-based conducting polymer devices: OTFT: (i) schematic structure; (ii) photograph of the OTFT with an
(i) photographs for high-density circuits fabricated by using conduct- inset microscopic image of the fabricated OTFT. Reprinted (adapted)
ing polymer; (ii) LED lit using the fabricated high-density circuit pat- with permission from [215] Copyright 2017, American Chemical
tern; (iii) bending test for the fabricated high-density circuit; (iv) pho- Society. c PEDOT: PSS-based μ-needle electrode array construc-
tograph for 9-channel 3D printed neural probe; (v) magnified image tion for bioelectronics application using a combination of inkjet and
of soft neural probe from figure (iv). Reprinted from [196] Copyright aerosol-jet printing. Reprinted (adapted) with permission from [220]
2020 Nature Communications. b All inkjet-printed TIPS pentacene Copyright 2019 American Chemical Society
Biomedical Materials & Devices
Biomedical Materials & Devices
◂Fig. 9 a A generalized method for synthesis of pure and doped TCOs. using PEDOT:PSS and MWNT to create a composite.
(i) Schematic illustration of reaction process; (ii) TCO nanocrystal- The micro-needles had diameters of 10 ± 2 μm and were
based inks dispersed in toluene solvent; (iii) UV–Vis spectra of TCO
nanocrystal films on glass substrates; (iv) sheet resistance measure-
33 ± 4 μm tall, with demonstrated conductivity of 323 ± 75
ment against dopant concentration; (v) study of integrated transmit- S∙m−1. The constructed micro-needles performed stably in
tance against sheet resistance of TCO nanocrystal films. Reprinted an aqueous electrolyte and were used to record extracellular
from [229] Copyright 2015 Wiley Angewandte Chemie International signals from cardiomyocyte-like HL-1 cells [220]. Along
Edition. b Inkjet-printed ITO film results: (i) FE-SEM of printed film;
(ii) sheet resistance and resistivity of printed ITO film measured by
with PEDOT, PANI is another printable polymer that is
Hall measurement corresponding to annealing temperature; (iii) environmentally stable. PANI can be tuned to achieve high
transmittance graph of the printed film. Reprinted from [230] Copy- conductivity through protonic doping using appropriate
right 2011, with permission from Elsevier. c (i) organic light-emitting dopant [221]. Inkjet-printed PANI nanoparticle inks, doped
diode (OLED) fabricated with ITO anode (ii) SEM of gravure-printed
ITO film on PET substrate. (iii) Optical characterization of fabricated
with dodecylbenzenesulfonic acid (DBSA), have been used
OLED. Reprinted from [231] Copyright 2008, with permission from in both chemical [203] and biosensing [222] applications. In
Elsevier fact, the printed device showed comparable conductive and
electrochemical properties to its electrochemically deposited
counterpart, with ink stability demonstrated over several
Ink formulations for printing polymers may be either months. An ammonia gas sensor fabricated using the inkjet-
include organic solutions [200–202] or dispersions of pol- printed PANI nano-dispersion showed good sensitivity and
ymer nanoparticles [203, 204] obtained through various rapid response to ammonia (t = 15 s) [223]. High-viscosity
chemical synthesis routes. These synthesis routes include PANI nanocomposite inks have also been screen printed to
deposition of monomer followed by reaction or polymer produce pH sensors [224]. Similarly, inkjet-printed PPy has
growth during the deposition process like chemical vapor been used as vapor sensor [225], whereas screen-printed PPy
deposition (CVD). Among the conducting polymers, poly electrode has been used as a carbon dioxide gas sensor [226]
(ethylene dioxythiophene) (PEDOT), doped with oxidative
polystyrene sulfonate (PSS) to give PEDOT:PSS, has dem- Metal Oxides
onstrated conductivities as high as 1 03 S∙cm−1 [200] and
is widely commercially available. Both electrochemically Metal oxides and other ceramics may also be utilized in
and environmentally stable, this polymer exhibits excellent the fabrication of conducting electrodes, particularly those
biocompatibility and has been used as electromyography heavily doped (termed degenerate semiconductors). Indium
(EMG) electrodes [205], electrocorticography (ECoG) elec- tin oxide (ITO), fluorine-doped tin oxide (FTO), Al- and
trodes [206, 207], neural electrodes [208, 209] and coatings Ga-doped zinc oxide (AZO and GZO), antimony-doped tin
[210], nerve grafts and heart patches [211–213]. Different oxide (ATO), CdO, G a2O3 and I n2O3 are some commonly
printing methods including inkjet [214–216], aerosol [217], used conducting oxides. Degenerate semiconductors are
roll-to-roll gravure [218] and 3D printing have been used of particular interest as electronic conduction and optical
to fabricate PEDOT:PSS-based electrodes. Recently, inkjet- absorption may be decoupled, allowing them to be applied in
printed PEDOT:PSS interconnects on elastic substrates hav- opto-electronic devices including thin-film solar cells, touch
ing high conductivity of 700 S∙cm−1 and low sheet resist- screens, light-emitting devices, display devices along with
ance 75 Ω∙sq−1 have been reported [219]. PEDOT:PSS-based opto-electronic interfaces. Among these, ITO, with demon-
inks have also been 3D printed to realize conducting polymer strated resistivities as low as 1 0−4 Ω.cm−1, with transpar-
devices as shown in Fig. 8a. This ink was used to construct ency > 80% in visible range, is the industry standard with
high-density flexible circuits patterned using this method, recorded $6.99 billion in revenue and 97.6% market share
shown in Fig. 8a.i. This circuit was used for lighting an LED, in transparent conductive film in 2010 [227]. Typically pro-
(Fig. 8a.ii). The circuit is bendable and flexible, shown in duced with 90% I n2O3 and 10% S nO2, polycrystalline or
Fig. 8a.iii and a.iv. A 9-channel soft neural probe using the amorphous ITO can be deposited using various thin-film
same construction with magnification is shown in Fig. 8a.iv. technologies including ion-assisted plasma evaporation,
The constructed 3D printed PEDOT:PSS soft neural probe high-power pulsed magnetron sputtering, radio frequency
was implanted in mouse dorsal hippocampus and used for (RF) magnetron sputtering, electron beam evaporation,
neural recording [196]. Using inkjet printing, a TIPS penta- thermal evaporation, pulsed layer deposition and printing.
cene-based OTFT was reported with PEDOT:PSS electrodes. The conductivity of transparent conducting oxides (TCO)
Figure 8b.i shows the schematic of the TFT with channel is highly dependent upon the dopant levels in the oxides.
length 60 µm and channel width of 1050 µm. A photographic Gravure-printed ITO films compared to sputter-coated ITO
image with inset microscopic details of the fabricated OTFT films show comparable performance in addition to mechanical
is shown in Fig. 8b.ii. Similarly, Fig. 8c shows a fully printed flexibility [228]. These printed films can endure small bending
micro-needle electrode array, based on an ink formulated radii and retain their electrical characteristics [228]. Printed
Biomedical Materials & Devices
metal oxides are thus potential candidates for fabricating 1.52 × 10−2 Ω∙cm−1 have also been reported earlier [234].
flexible electrodes. For implementation in printed electron- ITO nanoparticle-based inks have also been gravure printed,
ics, decomposition of inorganic metal complexes in a wet- exhibiting sheet resistances of 3 to 10 kΩ∙sq−1, for thick-
chemical environment has been the generally favored route to nesses of solid areas ranging between 300 and 100 nm. This
synthesize ITO and other TCO nanocrystal inks. Song et al. ink was UV curable and resulted in a film of 88% transpar-
reported a generalized batch method for synthesizing differ- ency [235]. Another ITO nanoparticle-based ink was gra-
ent forms of pure and doped TCO nanocrystal ink with yields vure printed onto either PET or PEN substrates and applied
of up to 10 g. The method is illustrated in Fig. 9a.i, where as an anode for an organic light-emitting diode (OLED, see
the process involves two key reactions: the ester elimination Fig. 9c.i.). These ITO films demonstrated a sheet resistance
reaction and the condensation reaction. First, one or more of 400 Ω∙sq−1 at thickness from 0.2 to > 1 μm. SEM image
metal precursor molecules react with 1-dodecanol (DDL) to of the fabricated ITO film is given in Fig. 9c.ii, showing
produce a metal hydroxide M–OH species through the release connected nanoparticles. Similarly, Fig. 9c.iii shows the
of ester by-products. The M–OH species then condense form- optical characterization of the fabricated device with > 80%
ing M–O–M1–OH where M and M1 represent two metal spe- transmittance [231]. Similar works on gravure printing
cies. These eventually form the doped TCOs. The resultant ITO-based electrodes for transparent electrode applica-
nanocrystals exhibit high crystallinity, uniform morphology, tions yielded sheet resistances of 23.5 kΩ∙sq−1 for a film
high ink stability with resultant electrodes having sheet resist- thickness of 600 nm, on a PET substrate. This is compared
ances of 110 Ω∙sq−1 and transmittance of 88%. Figure 9a.ii to sputtered ITO coatings, with a sheet resistance of 80
shows the various TCO nanocrystal-based inks dispersed in kΩ∙sq−1 for 100 nm thickness. Although the sheet resistance
toluene solvent. The ink may vary from transparent to colored, of printed ITO film is 6 times larger than sputter-coated
depending on the identity and concentration of dopants such film, printed films have higher transparency of 95% in the
as Al, Ga, In or Sn. The above-reported ink dispersions are visible light region, with electrical performance retained
said to be stable for more than a year. Figure 9a.iii shows the even after bending at small radii of curvature [228]. Water-
UV–Vis spectra of the TCO nanocrystal-based films on glass based ITO nanoparticle inks have also been inkjet printed
substrate. The films show > 80% transmittance, only slightly for fabrication of toluene vapor sensors [236].
lower than the reference glass. Similarly, Fig. 9a.iv shows the The limited availability of indium in the earth’s crust
measurement of sheet resistance against dopant concentra- and expense of manufacturing serve as major drawbacks
tion used. In a test to measure the dependence of conductivity for expansion of the flexible electronics market for ITO.
against dopant concentration, optimal doping ratios for lowest As such, alternative materials including AZO and indium-
obtained resistance were 1% for AZO, 3% for GZO, 5% for doped CdO with low indium content are being investi-
IZO and 5% for ITO, respectively. With a thickness of 300 nm gated. In a similar context, aluminum-doped cadmium
IZO and ITO, sheet resistances of 350 and 110 Ω∙sq−1 were (ACO) ink was inkjet printed as source–drain electrodes
obtained. Figure 9a.v shows the transmittance corresponding of transistors with sheet resistances of 600 Ω∙sq −1 to
to the sheet resistance of the TCO nanocrystal-based films. 2 kΩ∙sq−1 [237].
The films meet the requirements for electrodes in applications
including resistive touch panels, windows and displays with
high transparency and resistance < 400 Ω∙sq−1 [229].
Traditional methods including shadow masks [232] and Summary and Conclusion
sputter deposition [233] have been used significantly for
the deposition of TCOs. Various printing methods have In this review, printing as a manufacturing method for fab-
also been used for fabricating TCO-based opto-electronic ricating electrodes for applications in medical diagnostics
and display devices, with inkjet printing being the most and therapy has been discussed. Depending upon their
common of these. ITO nanoparticle-based inks have been surface area and geometry, printed electrodes of different
inkjet printed. Figure 9b.i shows the FE-SEM of the inkjet- sizes can be constructed for both recording and stimula-
printed ITO film after microwave annealing at 400 °C with tion in vivo and quantification of biological compounds
presence of connected nanoparticles. Figure 9b.ii shows in vitro. The main advantage of printed electronics is that
the electrical measurements of the printed device, whereas it is a rapid prototyping platform that can easily be inte-
Fig. 9b.iii shows the optical characterization of the device. grated for mass scale production. The diversity of materi-
The inkjet-printed ITO nanoparticle ink demonstrated sheet als like metals, transparent conducting oxides, carbon and
resistance of 517 Ω∙sq−1 and 3.0 × 10−2 Ω∙cm−1 at a thick- polymers used and their tailored ink formulation has over-
ness of ~ 580 nm. The printed film had > 87% transmittance come challenges relating to device performance, geom-
irrespective of the annealing temperature [230]. Similar etry and resolution, reliability and fabrication throughput.
results sheet resistance of 202.7 Ω∙sq−1 and resistivity of
Biomedical Materials & Devices
Additive manufacturing and the printing process in general shows exciting results and opportunities for fabricating
electrodes for integration and biological application.
Acknowledgements This work was supported by ARC Industrial Data Availability The authors would like to state that no data set was
Transformation Training Center (ITTC) in Additive Biomanufactur- analyzed or generated for this review work and all depicted knowledge
ing. The authors would like to acknowledge ARC Centre of Excellence is taken from published work cited in the references.
for Electromaterials Science (ACES).
Open Access This article is licensed under a Creative Commons Attri-
Funding Open Access funding enabled and organized by CAUL and bution 4.0 International License, which permits use, sharing, adapta-
its Member Institutions. tion, distribution and reproduction in any medium or format, as long
as you give appropriate credit to the original author(s) and the source,
provide a link to the Creative Commons licence, and indicate if changes
were made. The images or other third party material in this article are
Biomedical Materials & Devices
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