Recent Advances in Enzymatic Biofuel Cells to Power Up Wearable and Implantable Biosensors

Abstract

Enzymatic biofuel cells (EBFCs) have emerged as a transformative solution in the quest for sustainable energy, offering a biocatalyst-driven alternative for powering wearable and implantable self-powered biosensors. These systems harness renewable enzyme activity under mild conditions, positioning them as ideal candidates for next-generation biosensing applications. Despite their promise, their practical deployment is limited by challenges such as low power density, restricted operational lifespan, and miniaturization complexities. This review provides an in-depth exploration of the evolving landscape of EBFC technology, beginning with fundamental principles and the latest developments in electron transfer mechanisms. A critical assessment of enzyme immobilization techniques, including physical adsorption, covalent binding, entrapment, and cross-linking, underscores the importance of optimizing enzyme stability and catalytic activity for enhanced bioelectrode performance. Additionally, we examine advanced bioelectrode materials, focusing on the role of nanostructures such as carbon-based nanomaterials, noble metals, conducting polymers, and metal-organic frameworks in improving electron transfer and boosting biosensor efficiency. Also, this review includes case studies of EBFCs in wearable self-powered biosensors, with particular attention to the real-time monitoring of neurotransmitters, glucose, lactate, and ethanol through sweat analysis, as well as their integration into implantable devices for continuous healthcare monitoring. Moreover, a dedicated discussion on challenges and trends highlights key limitations, including durability, power management, and scalability, while presenting innovative approaches to address these barriers. By addressing both technical and biological constraints, EBFCs hold the potential to revolutionize biomedical diagnostics and environmental monitoring, paving the way for highly efficient, autonomous biosensing platforms.

Keywords: energy sources; enzymatic biofuel cells; implantable sensors; remote sensing; self-powered biosensors; wearable devices.

Figure 7

Glucose SPB-Based EBFCs: (a) illustration of the assembly process for the 3D micropillar array platform, (b) FTIR spectra illustrating the immobilization stages, (c) SEM images depicting the morphology of the rGO/CNT/GOx-coated 3D carbon micropillar array, (d) amperometric response of the rGO/CNTs/GOx bioanode, with the inset showing the response to successive glucose. Reproduced with permission from [149], (e) key components of a screen-printed glucose BFC, emphasizing the vital redox reactions at both the bioanode and biocathode, (f) schematic diagram of the screen-printed biosensing electronic system, (g,h) amperometric response and calibration curves showing the current response for both the GOx/NQ/MWCNT-based bioanode and biocathode, respectively. Reproduced with permission from [153].

Figure 8

EBFCs based lactate SPB: (a) Diagram illustrating the flexible lactate biofuel cell and electrochemical reactions at the anode and cathode, (b) image of the flexible biofuel cell array printed on fabric for use as SPB in wearable socks, (c) photo of a volunteer wearing the sock-based biofuel cell array during exercise, (d) graph depicting power density versus potential for the stretchable glucose biofuel cell at various glucose concentration, (e) voltage output generated by the lactate SPB and a compact wireless device, (f) real-time monitoring of lactate levels during a cycling exercise test on the body. Reproduced with permission from [160], (g) Adaptable BFC device on a human arm with diagrams illustrating energy production via sweat lactate oxidation and O₂ reduction, (h) circuit schematic for using the flexible epidermal BFC patch to power an LED through a DC-DC converter, (i) resistance profile during a 20% stretch, with inset displaying resistance fluctuations, (j) current density output with inset showing current density fluctuations, (k) power density versus voltage graphs for various cycle counts in lactate, (l) percentage change in power density at 0.55 V across multiple stretching cycles. Reproduced with permission from [164].

Figure 1

Schematic representation of an EBFC, demonstrating mediator-assisted electron transfer at the bioanode (−) and direct electron transfer at the biocathode (+). The diagram also highlights proton (H⁺) movement across the electrolyte and the generation of voltage within the system.

Figure 2

Methods for enzyme immobilization encompass physical adsorption, covalent attachment, cross-linking, and encapsulation.

Figure 3

Applications of carbon nanomaterials in EBFC: (a) CNTs as a flexible substrate for GOx immobilization. Reproduced with permission from [95], (b) Combination of 3D graphene and CNT for GOD and laccase encapsulation. Reproduced with permission from [96], (c) hydrophobic CNT fiber as bioelectrode for BOx and laccase immobilization. Reproduced with permission from [97], (d) BP as bioelectrode for BOD electrografting. Reproduced with permission from [98].

Figure 4

Applications of noble metals in enzymatic biofuel cell: (a) AgNPs anchored ZnO based bioanode operation. Reproduced with permission from [114], (b) AuNPs-embedded nitrogen-doped graphene bioanode for formate dehydrogenase integration. Reproduced with permission from [115], (c) AuNPs entrapped PPCA shell used as bioanode. Reproduced with permission from [116]. (d) AuNPs@PtNPs-based cathode electrode supports oxygen reduction. Reproduced with permission from [117].

Figure 5

Applications of CPs in enzymatic biofuel cell: (a) Polyaniline as a flexible substrate for immobilization. Reproduced with permission from [121], (b) In situ growth of PPy for GOx encapsulation. Reproduced with permission from [122], (c) PEDOT integration in hybrid material for self-powered photoelectrochemical/visual sensing. Reproduced with permission from [123].

Figure 6

Applications of MOFs in enzymatic biofuel cell: (a) MIL-100(FeMOF) as immobilization matrix of laccase. Reproduced with permission from [135], (b) ZIF-8 as a host matrix for GOx. Reproduced with permission from [136], (c) ZIF-L as encapsulation matrix for GDH. Reproduced with permission from [137].

Figure 9

EBFCs based Ethanol SPB: (a) schematic illustrating the design of the bioanode and biocathode, along with the redox reactions at each electrode, (b) representative current density (blue) and power density (red) obtained for constant ethanol (0.5 M) and NAD⁺ (10 mM) concentrations, (c) calibration curves depict the power density at the BFC against ethanol concentration. Reproduced with permission from [89]. (d) Illustration of the 3D-NHCAs-based ethanol/oxygen BFC, (e) Real-time power density mapping of subject 1 across different skin regions during cycling, (f) correlation between peak power density and the initiation time of power generation for the epidermal ethanol BFC across various skin regions. Reproduced with permission from [168].

Figure 10

EBFCs-based implantable SPB: (a) schematic illustrating the electrical setup of the implanted GBFC in a Wistar rat coupled with enzyme reactions, (b) recovered GBFCs shown after 17 and 110 days of implantation in the rat brain. Reproduced with permission from [170], (c) Incorporation of BFC and ABS in a pigeon for wireless power management, (d) in vitro measurements, and (e) in vivo evaluations of BFC performance using a wireless power meter. Reproduced with permission from [171].