**3. Challenges and possible solutions**

#### **3.1 Mechanical properties**

Young's modulus of the human skin is in a range of 10–500 kPa [35, 36], while the moduli of common electronic materials, such as silicon and gold, are much higher (high GPa), indicating significant mechanical mismatch when integrating with the skin. Therefore, functionalities of non-stretchable electrodes will deteriorate after multiplex deformations commonly experienced by daily life activities. Furthermore, such rigidity and bulkiness of traditional devices also restrict the wearability and comfortability [14]. Non-compliant electrochemical devices will limit continuous long-term functions due to cracking and increasing of material resistance. This increasing of resistivity, which opposes the current flow in bioelectronics, causes poor electron communication at the enzyme-electrode interface.

This major challenge of skin-integrated electronics can be addressed by exploring stretchable materials which display mechanical properties in a similar range of skin's modulus. One approach is using polymers due to their low mechanical toughness. For example, conducting materials with high moduli can be blended with soft polydimethylsiloxane or Ecoflex materials (Young's moduli of 0.4–3.5 MPa and 125 kPa, respectively) in order to tune the mechanical properties while keeping good electrochemical functions [37]. CNT-based materials, which are powerful for electrochemical devices [38], are used to combine with soft elastomers, such as PU and styrene-butadiene-styrene (SBS) [29, 39]. PU and SBS composites have moduli of ~700–800 kPa. As shown in **Figure 3C**, CNT filler (with the highaspect ratio ∼1300) was combined with PU [30], achieving stretchable conductive electrode materials. The percolation of dispersed CNTs can facilitate the electric flow in stretchable bioelectronics. Combining the intrinsic stretchability of this engineered inks with the structural stretchability of the serpentine design allows the device to tolerate strains as high as 500% with a small effect on its electrochemical performance [29]. This concept can be expanded by adding new functionalities into electrodes. For example, platinum-decorated graphite was mixed with PU to obtain stretchable electrocatalytic materials, allowing the fabrication of stretchable electrodes for glucose biosensors [40].

#### **3.2 Powering wearable devices**

Growing demand of wearable technologies has stimulated the need of the development of viable energy sources. The lack of anatomically power sources becomes a key bottleneck for the progress in wearable bioelectronics. Skin-worn bioelectronics mandates the compliant and efficient energy sources to supply multitasks, including

**39**

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

sensing and data communication. In addition to developing low-power-consuming electronic microelectronics [9, 41], there is an increasing interest in advancing bioenergy-harvesting devices. Enzymatic BFCs are attractive self-sustainable energy devices to meet this growing energy demand. For example, 0.3-V complementary metal-oxide-semiconductor (CMOS) wireless glucose or lactate biosensing systems, which consumed power of ~1.2 μW, could be powered by BFCs [9]. Nevertheless, several applications of enzymatic BFCs still have some challenges, such as lowpower output. The major challenge in enzymatic BFC is faced by the electrical "wiring" of enzymes with electrodes. The difficulty of electrical wiring, referring to

electron transfer, and their possible solutions will be detailed in Section 3.3.

Compared with traditional fuel cells, enzymatic BFCs are challenging due to their multicomponent including redox potentials of enzyme, cofactor, and mediator. This results in the typical unwanted deviation of open-circuit voltages (OCV) from their theoretical maximum values, referring to "cell voltage losses." The redox potential for electrocatalytic oxidation at the bioanode required to be higher than that of the biocathode for reduction reaction in order to deliver a sufficient electromotive force for electron transfer between enzyme active site and mediator. The voltage difference between the formal redox potentials (E°′) of redox enzyme cofactors in the active sites, in the anode and cathode, will govern the maximum cell voltage. Parameters, including redox potential of mediator and cofactor redox potential in the enzyme, can influence the resulting potential output of BFCs. Therefore, the mediator should be carefully chosen. For example, ferrocene derivatives coimmobilized with GOx at a graphite electrode can be used for glucose sensors [42]. Nevertheless, ferrocene derivatives display high redox potentials (0.1–0.4 V versus SCE); these will cause cell voltage losses in the GOx-based BFC if they are used as anode mediators. It should be noted that the difference between the redox potentials of the enzymes wired at the anode and the cathode determines the cell voltage. An example of a successful anode mediator used in skin-worn BFCs is 1,4-naphthoquinone [30]. This quinone compound is also almost insoluble in cold water, preventing leaching during on-body operations. One challenge of using GOx on the anode is the O2 competition with a mediator, decreasing the oxidation current on the bioanode. Moreover, O2 competitive reaction on the anode can produce H2O2. This by-product can inhibit GOx activity and decrease the overall BFC performance. Therefore, catalase should be cofunctionalized to the bioanode

A single-enzyme BFC can usually convert only a partial portion of biochemical energy, resulting in low current output. For instance, wearable BFCs, such as for harvesting energy from lactate sweat, commonly employ a single enzyme-based bioanode, catalyzing the oxidation of lactate to pyruvate, which only harvests two electrons. In other words, they utilize only a portion of the biofuel energy and leave most of the energy in the oxidized product. Therefore, it is interesting to harvest the total of 12 electrons in order to maximize the energy-conversion efficiency. A potential solution is to design an enzyme cascade system for complete oxidation of lactate fuel. For example, the bioinspired multienzyme catalytic cascade could complete the metabolic cycle, successfully enhancing net BFC power [44].

Furthermore, in order to optimize the current output, diffusion and enzyme loading should be enhanced. The engineering of specific enzyme activity and three-

The selection of enzymes is a primary subject which should be discussed. Enzymes must be selected by considering their particular reactions to target

dimensional structure of enzymatic electrodes should be explored.

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

to diminish the undesirable H2O2 [43].

**3.3 Enzyme-related aspects**

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

sensing and data communication. In addition to developing low-power-consuming electronic microelectronics [9, 41], there is an increasing interest in advancing bioenergy-harvesting devices. Enzymatic BFCs are attractive self-sustainable energy devices to meet this growing energy demand. For example, 0.3-V complementary metal-oxide-semiconductor (CMOS) wireless glucose or lactate biosensing systems, which consumed power of ~1.2 μW, could be powered by BFCs [9]. Nevertheless, several applications of enzymatic BFCs still have some challenges, such as lowpower output. The major challenge in enzymatic BFC is faced by the electrical "wiring" of enzymes with electrodes. The difficulty of electrical wiring, referring to electron transfer, and their possible solutions will be detailed in Section 3.3.

Compared with traditional fuel cells, enzymatic BFCs are challenging due to their multicomponent including redox potentials of enzyme, cofactor, and mediator. This results in the typical unwanted deviation of open-circuit voltages (OCV) from their theoretical maximum values, referring to "cell voltage losses." The redox potential for electrocatalytic oxidation at the bioanode required to be higher than that of the biocathode for reduction reaction in order to deliver a sufficient electromotive force for electron transfer between enzyme active site and mediator. The voltage difference between the formal redox potentials (E°′) of redox enzyme cofactors in the active sites, in the anode and cathode, will govern the maximum cell voltage. Parameters, including redox potential of mediator and cofactor redox potential in the enzyme, can influence the resulting potential output of BFCs. Therefore, the mediator should be carefully chosen. For example, ferrocene derivatives coimmobilized with GOx at a graphite electrode can be used for glucose sensors [42]. Nevertheless, ferrocene derivatives display high redox potentials (0.1–0.4 V versus SCE); these will cause cell voltage losses in the GOx-based BFC if they are used as anode mediators. It should be noted that the difference between the redox potentials of the enzymes wired at the anode and the cathode determines the cell voltage. An example of a successful anode mediator used in skin-worn BFCs is 1,4-naphthoquinone [30]. This quinone compound is also almost insoluble in cold water, preventing leaching during on-body operations. One challenge of using GOx on the anode is the O2 competition with a mediator, decreasing the oxidation current on the bioanode. Moreover, O2 competitive reaction on the anode can produce H2O2. This by-product can inhibit GOx activity and decrease the overall BFC performance. Therefore, catalase should be cofunctionalized to the bioanode to diminish the undesirable H2O2 [43].

A single-enzyme BFC can usually convert only a partial portion of biochemical energy, resulting in low current output. For instance, wearable BFCs, such as for harvesting energy from lactate sweat, commonly employ a single enzyme-based bioanode, catalyzing the oxidation of lactate to pyruvate, which only harvests two electrons. In other words, they utilize only a portion of the biofuel energy and leave most of the energy in the oxidized product. Therefore, it is interesting to harvest the total of 12 electrons in order to maximize the energy-conversion efficiency. A potential solution is to design an enzyme cascade system for complete oxidation of lactate fuel. For example, the bioinspired multienzyme catalytic cascade could complete the metabolic cycle, successfully enhancing net BFC power [44].

Furthermore, in order to optimize the current output, diffusion and enzyme loading should be enhanced. The engineering of specific enzyme activity and threedimensional structure of enzymatic electrodes should be explored.
