**2.2 Enzyme-based electrochemical power sources**

BFCs are energy-conversion devices that utilize biocatalysts to convert chemical energy into electricity. For wearable electronics, the need to anatomically power sources has attracted many research groups to develop a BFC, as a "green" energy-harvesting alternative, in order to extract energy from metabolites present in biofluids, such as perspiration. Since glucose, lactate, and oxygen are present in physiological fluids, in general, a majority of wearable enzymatic BFCs rely on (1) the generation of electrons from glucose or lactate biofuels and (2) the electron reduction by oxidants (such as oxygen). **Figure 1C** shows a typical example of a glucose/O2 BFC. In principle, a glucose BFC uses GOx, functionalized on the bioanode, to catalyze the glucose oxidation reaction to generate electrons. After this oxidation process, these harvested electrons are driven through an external circuit to the biocathode compartment where such electrons are accepted by oxidant molecule (commonly O2) and, eventually, generate complete electrical work. In addition to

*Wearable Devices - The Big Wave of Innovation*

Enzymatic biosensors are based on numerous mechanisms. The popular mechanism relies on the conversion of the analyte as an enzymatic substrate into a product, enabling the detection by using electrochemical transducer. Another way is to monitor the analyte (e.g., a toxic compound) that acts as an enzyme inhibitor. In addition, the enzyme can be used as a labeling transducer for bioaffinity recognition. Besides, a reverse approach can be designed to detect the enzyme level. In this case, the enzyme acts as an analyte, while the substrate is immobilized on the electrode surface. When the enzyme reaches the electrode sensor, it will generate

the signal, corresponding to the concentration level of the enzyme target.

In recent decades, enzymatic biosensors have been proven to be modern wearables to monitor numerous analytes, such as glucose, lactate, alcohol, and organophosphate nerve agents. Among several enzymes, oxidoreductase and hydrolase, such as glucose oxidase (GOx), lactate oxidase (LOx), alcohol oxidase (AOx), and organophosphorus hydrolase, are predominant for wearable biosensing applications. A temporary tattoo with the integration of transdermal enzymatic glucose biosensor has been introduced since glucose is a key biomarker for diabetes mellitus, which still affects hundreds of millions of patients globally (**Figure 2A**) [17]. The iontophoretic ISF extraction system was coupled with the amperometric

*Skin-worn enzyme-based electrochemical biosensors. (A) Transdermal tattoo-based glucose sensors, coupled with reversed iontophoresis [17]. Adapted with permission from ref [17]. Copyright 2015 American Chemical Society. (B) Tattoo-based alcohol biosensors, coupled with pilocarpine iontophoresis and wireless electronics [18]. Adapted with permission from ref [18]. Copyright 2016 American Chemical Society. (C) Biosensors integrated with a microfluidic patch for sweat collection and analysis [20]. Adapted with permission from ref [20]. Copyright 2017 American Chemical Society. (D) Microneedle-based β-lactam sensors [22]. Adapted with permission from ref [22]. Copyright 2019 American Chemical Society. (E) Integrated glucose/lactate enzymatic biosensors with electrolyte and temperature sensors. (F) Integrated sweat monitoring biosensing and* 

**34**

**Figure 2.**

*transdermal drug delivery system.*

Pt-based catalysts, multicopper oxidases such as laccase, bilirubin oxidase, and polyphenol oxidase are commonly used for electrocatalyzing oxygen-reduction reaction (ORR) in the BFC cathode [25].

Enzymatic BFCs represent an interesting alternative due to their unique advantages, such as outstanding selectivity and behaviors of enzymes. Unlike most traditional inorganic catalyst-based fuel cells, which require harsh conditions (such as acidic conditions or high temperatures ranging from 45°C to more than 100°C), the enzyme-based BFC can operate under mild conditions (20–40°C at neutral pH). Moreover, non-specific catalyst-based fuel cells require to separate anode and cathode chambers by a thin membrane. Unfortunately, this common use of separation membrane between the anode and the cathode compartments will be unsatisfactory for skin-worn miniaturized devices. Thanks to the nature of enzymes, utilizing high specificity of enzymatic catalysis can obviate this membrane requirement, facilitating the fabrication and applications [26]. In addition, enzyme-based BFCs can operate selectively in complex biofluids.

Interestingly, BFCs also offer opportunities to design self-powered biosensors (**Figure 1D**). For example, the power is proportional to the concentration of the fuel (also acting as analyte); self-powered output itself can determine the level of the target. This offers opportunities to eliminate external energy sources for powering potentiostat and signaling systems [9].

An initial concept integrating enzymatic BFCs with skin-worn technologies represented an exciting way to scavenge bioenergy available in human perspiration (**Figure 3A**). This demonstrated the first epidermal tattoo-based BFC that converted sweat lactate biofuel and oxygen into electricity [27]. The lactate oxidation by LOx electrocatalyzation was mediated by tetrathiafulvalene on the carbon nanotube (CNT)-based anode, while electroreduction on the oxygen-reduction cathode relies on Pt black catalyst. This system facilitates mediated oxidation of lactate at −0.1 V with a peak potential of 0.14 V (versus Ag/AgCl). This low anodic onset potential indicates the efficient electron-donor-acceptor TTF/CNT. The successful on-body test displayed a power up to 70 μW cm<sup>−</sup><sup>2</sup> . This idea was also established on fabrics and could power a light-emitting diode with an integrated DC-DC converter [28].

Mechanical stability has been the focus in the development of the next-generation of skin-worn BFCs due to the multiplex mechanical movements experienced *in vivo*. In order to minimize cracking of the device and maintain good electrochemical performance, screen-printable stretchable inks and judicious stretchable design have been engineered (**Figure 3B**) [29]. Combining additional degrees of stretchability with intrinsic mechanical resiliency of soft CNT/polyurethane (PU) composite offers the desirable stretchable platform. The BFC was then functionalized on the soft electrodes, allowing good mechanical stability. This holds promise applications for on-body bioenergy fields wherein resilience toward mechanical distortions is compulsory.

In addition to energy-conversion applications, BFCs can be applied further as another significant tool for wearable bioelectronics. Enzymatic BFC can serve as self-sustainable biosensors (without an extra powering device). In order to expand the spectrum of BFC applications for on-skin electroanalytical chemistry, the pioneering stretchable textile-based BFCs that can act as self-powered was demonstrated (**Figure 3C**) [30]. These biodevices can deliver two key functions: (1) harvesting electrical power from sweat glucose and lactate and (2) displaying signals of such metabolites. Extracted bioenergy from the wearer's sweat can directly indicate the metabolite levels. Sock-based biodevices were successfully demonstrated on human subjects, representing a promising concept for modern wearable self-powered biosensors.

**37**

**Figure 3.**

*Wearable Skin-Worn Enzyme-Based Electrochemical Devices: Biosensing, Energy Harvesting…*

Maximizing the loading amount of active enzyme, mediator, and conductive materials can improve the power performance of BFCs. The high amount of such active materials can be packed by a compress. However, this strategy will affect mechanical softness. Therefore, further engineering was to fabricate island-bridge assemblies merging the high enzyme loading packed islands with stretchable serpentine bridges [34]. This combination offered a soft bioelectronic

ficient to power a Bluetooth Low Energy (BLE) radio integrated with a DC-DC

Recently, additional efforts have been made to scavenge, improve, and store energy by hybridizing textile-based energy conversion with energy storage devices (BFCs and supercapacitors, respectively) (**Figure 3E**) [31]. The on-body demonstration showed that after perspiring, the supercapacitor could be charged by the

Furthermore, a photoelectric BFC was developed to convert external light andchemical energy from wearer's perspiration into electrical energy (**Figure 3D**) [32]. The anode relied on a LOx/Meldola's blue/buckypaper electrode, while the photocathode

*Skin-worn BFCs and self-powered sensors. (A) Epidermal tattoo-based lactate BFCs. (B) Stretchable glucose BFCs [29]. Adapted with permission from ref [29]. Copyright 2016 American Chemical Society. (C) Stretchable textile-based BFCs acting as self-powered biosensors [30]. Adapted with permission from ref [30]. Copyright 2016 The Royal Society of Chemistry. (D) Photoelectric BFCs. (E) Textile-based BFCsupercapacitor hybrid devices [31]. Adapted with permission from ref [31]. Copyright 2018 The Royal Society* 

*of Chemistry. (F) Built-in BFCs with transdermal iontophoresis patches.*

. This energy was suf-

*DOI: http://dx.doi.org/10.5772/intechopen.85459*

BFC energy and reach a stable 0.4 V output.

converter.

skin for harvesting a good power density of 1.2 mW cm<sup>−</sup><sup>2</sup>

*Wearable Skin-Worn Enzyme-Based Electrochemical Devices: Biosensing, Energy Harvesting… DOI: http://dx.doi.org/10.5772/intechopen.85459*

Maximizing the loading amount of active enzyme, mediator, and conductive materials can improve the power performance of BFCs. The high amount of such active materials can be packed by a compress. However, this strategy will affect mechanical softness. Therefore, further engineering was to fabricate island-bridge assemblies merging the high enzyme loading packed islands with stretchable serpentine bridges [34]. This combination offered a soft bioelectronic skin for harvesting a good power density of 1.2 mW cm<sup>−</sup><sup>2</sup> . This energy was sufficient to power a Bluetooth Low Energy (BLE) radio integrated with a DC-DC converter.

Recently, additional efforts have been made to scavenge, improve, and store energy by hybridizing textile-based energy conversion with energy storage devices (BFCs and supercapacitors, respectively) (**Figure 3E**) [31]. The on-body demonstration showed that after perspiring, the supercapacitor could be charged by the BFC energy and reach a stable 0.4 V output.

Furthermore, a photoelectric BFC was developed to convert external light andchemical energy from wearer's perspiration into electrical energy (**Figure 3D**) [32]. The anode relied on a LOx/Meldola's blue/buckypaper electrode, while the photocathode

#### **Figure 3.**

*Wearable Devices - The Big Wave of Innovation*

reaction (ORR) in the BFC cathode [25].

operate selectively in complex biofluids.

ing potentiostat and signaling systems [9].

DC-DC converter [28].

distortions is compulsory.

wearable self-powered biosensors.

successful on-body test displayed a power up to 70 μW cm<sup>−</sup><sup>2</sup>

Pt-based catalysts, multicopper oxidases such as laccase, bilirubin oxidase, and polyphenol oxidase are commonly used for electrocatalyzing oxygen-reduction

Enzymatic BFCs represent an interesting alternative due to their unique advantages, such as outstanding selectivity and behaviors of enzymes. Unlike most traditional inorganic catalyst-based fuel cells, which require harsh conditions (such as acidic conditions or high temperatures ranging from 45°C to more than 100°C), the enzyme-based BFC can operate under mild conditions (20–40°C at neutral pH). Moreover, non-specific catalyst-based fuel cells require to separate anode and cathode chambers by a thin membrane. Unfortunately, this common use of separation membrane between the anode and the cathode compartments will be unsatisfactory for skin-worn miniaturized devices. Thanks to the nature of enzymes, utilizing high specificity of enzymatic catalysis can obviate this membrane requirement, facilitating the fabrication and applications [26]. In addition, enzyme-based BFCs can

Interestingly, BFCs also offer opportunities to design self-powered biosensors (**Figure 1D**). For example, the power is proportional to the concentration of the fuel (also acting as analyte); self-powered output itself can determine the level of the target. This offers opportunities to eliminate external energy sources for power-

An initial concept integrating enzymatic BFCs with skin-worn technologies represented an exciting way to scavenge bioenergy available in human perspiration (**Figure 3A**). This demonstrated the first epidermal tattoo-based BFC that converted sweat lactate biofuel and oxygen into electricity [27]. The lactate oxidation by LOx electrocatalyzation was mediated by tetrathiafulvalene on the carbon nanotube (CNT)-based anode, while electroreduction on the oxygen-reduction cathode relies on Pt black catalyst. This system facilitates mediated oxidation of lactate at −0.1 V with a peak potential of 0.14 V (versus Ag/AgCl). This low anodic onset potential indicates the efficient electron-donor-acceptor TTF/CNT. The

established on fabrics and could power a light-emitting diode with an integrated

In addition to energy-conversion applications, BFCs can be applied further as another significant tool for wearable bioelectronics. Enzymatic BFC can serve as self-sustainable biosensors (without an extra powering device). In order to expand the spectrum of BFC applications for on-skin electroanalytical chemistry, the pioneering stretchable textile-based BFCs that can act as self-powered was demonstrated (**Figure 3C**) [30]. These biodevices can deliver two key functions: (1) harvesting electrical power from sweat glucose and lactate and (2) displaying signals of such metabolites. Extracted bioenergy from the wearer's sweat can directly indicate the metabolite levels. Sock-based biodevices were successfully demonstrated on human subjects, representing a promising concept for modern

Mechanical stability has been the focus in the development of the next-generation of skin-worn BFCs due to the multiplex mechanical movements experienced *in vivo*. In order to minimize cracking of the device and maintain good electrochemical performance, screen-printable stretchable inks and judicious stretchable design have been engineered (**Figure 3B**) [29]. Combining additional degrees of stretchability with intrinsic mechanical resiliency of soft CNT/polyurethane (PU) composite offers the desirable stretchable platform. The BFC was then functionalized on the soft electrodes, allowing good mechanical stability. This holds promise applications for on-body bioenergy fields wherein resilience toward mechanical

. This idea was also

**36**

*Skin-worn BFCs and self-powered sensors. (A) Epidermal tattoo-based lactate BFCs. (B) Stretchable glucose BFCs [29]. Adapted with permission from ref [29]. Copyright 2016 American Chemical Society. (C) Stretchable textile-based BFCs acting as self-powered biosensors [30]. Adapted with permission from ref [30]. Copyright 2016 The Royal Society of Chemistry. (D) Photoelectric BFCs. (E) Textile-based BFCsupercapacitor hybrid devices [31]. Adapted with permission from ref [31]. Copyright 2018 The Royal Society of Chemistry. (F) Built-in BFCs with transdermal iontophoresis patches.*

relied on an organic polyterthiophene semiconductor, which drove a reduction reaction under illumination (wavelengths of 350 nm to over 600 nm). This system presented an attractive example of on-skin autonomous power sources and sensors.

Additional efforts have been made to explore new biomedical applications of BFCs. **Figure 3F** shows an integrated fructose/O2 BFC patch that was conjugated with transdermal iontophoresis [33]. The current generated by the BFC was used to drive an osmotic flow from the anode to the cathode, resulting in the net ionic movement of small-molecule drug into the skin. The level of transdermal current to control the drug administration could be adjusted by connecting a thin poly(3,4-ethylenedioxythiophene)/PU resistor of a programmable resistance value.
