Introduction Technology for electrical power generation using enzyme catalysts, established four decades ago, has recently received increased attention associated with demand for micro-scale and implantable power supplies. The main challenges, namely the fragility of enzyme molecules, characteristic low current density, and poor fundamental understanding of redox biocatalysis, are currently being addressed from a variety of research perspectives, to take advantage of enzyme selectivity, low temperature and moderate pH activity, and manufacturability in small-scale devices. Such an effort benefits from four decades of multidisciplinary research in biosensors and related bioelectrochemical fields. This review paper summarizes the current state of enzymatic biofuel cell research in the context of foreseeable applications and assesses the future prospects of the technology. Emphasis is placed on device performance and engineering aspects, with a view toward practical portable power devices based on enzymatic biofuel cells. Research in biocatalytically modified electrodes, particularly for sensor applications, has provided a significant technological underpinning for current biofuel cell development. There exists significant overlap in technical requirements between sensors and biofuel cells, including chemical and mechanical stability, selectivity, and cost of materials. However, these two technologies diverge in the areas of current density, cell potential and stability. There exists extensive review literature in the area of biological fuel cells. Notably, Palmore and Whitesides summarized biological fuel cell concepts and performance up until about 1992. More recently, Katz and Willner discussed recent progress in novel electrode chemistries for both microbial and enzymatic fuel cells. We do not duplicate these valuable contributions, but instead focus on the strengths and weaknesses of state-of-art materials in the context of specific classes of applications, and point to areas where additional knowledge is currently needed to exploit biological fuel cells. With some exceptions, we focus on contributions made after 1992. Biofuel cells have traditionally been classified according to whether the catalytic enzymes were located inside or outside of living cells. If living cells are involved the system is considered to be microbial, and if not it is considered enzymatic. Although microbial fuel cells posses unique features unmatched by enzymatic cells, such as long-term stability and fuel efficiency, the power densities associated with such devices are typically much lower owing to resistance to mass transfer across cell membranes. Thus, microbial fuel cells are expected to find limited application in smallscale electronic devices. This review will focus on enzymatic biofuel cells. While such cells typically demonstrate reduced stability due to the limited lifetime of extracellular enzymes, and are typically unable to fully oxidize fuels, they allow for substantial concentration of catalysts and removal of mass transfer barriers and provide higher current and power densities, approaching the range of applicability to microand mini-scale electronics applications. Applications and Requirements The range of possible applications for biofuel cells may be broken down into three main subclasses: 1. Implantable power, such as micro-scale cells implanted in human or animal tissue, or larger cells implanted in blood vessels. 2. Power derived from ambient fuels or oxidants, mainly plant saps and juices, but extending to sewage and other waste streams. 3. Power derived from conventional fuels including hydrogen, methanol or higher alcohols. Classes 1 and 2 are closely related. The fuels available for implantable power, such as blood borne glucose or lactate, are ambient in the sense that they are present in a physiological environment in the absence of a fuel cell device. One major distinction between these two classes is that the ambient-fueled cell need not be implanted, and focuses on plantor waste-derived fuels, whereas the implantable cell focuses on animal-derived fuels and is present within the physiological system. Class 3 is unique in that this class competes with well-established conventional fuel cell technology. To a greater or lesser extent, all three classes share the fundamental technical requirements of high power density and high activity.

Enzymatic biofuel cells for implantable and microscale devices.

A mediator-less microbial fuel cell using a metal reducing bacterium, Shewanella putrefaciens

https://blogs.epfl.ch/biofuelcells/documents/Biofuel%20cells%20and%20their%20development.pdf

Biofuel cells and their development

Flow Batteries: Current Status and Trends

The concept of a fuel cell dates back to 1839, from independent studies by Grove and Schoenbein. Like a battery, a fuel cell is a device for obtaining electrical energy directly from a chemical reaction, but unlike a battery, electrical power is sustained as long as the reacting chemicals are supplied to each electrode with the cathode receiving oxidant and the anode receiving reductant or “fuel”, hence “fuel cell”. There are environmental advantages over combustion because fuel cells avoid the high temperatures that cause NOx production, and they are usually reported as operating at a higher efficiency (typically 50-60%) than internal combustion engines (20-25%). Applications of fuel cells were largely neglected until the “space age” (1960s) when there became a need for reliable electrical power in challenging, niche situations. In addition to environmental driving forces, energy demands for niche applications continue to drive fuel cell development today. Fuel cells vary greatly in their power output, ranging from large-scale (kW) building-integrated systems, known as “combined heat and power” systems, to those that provide just enough power to operate electronics in special circumstances, such as an implantable device for sensing and controlling glucose levels in the body. As we outline below, the power output of a fuel cell can be limited by the electrochemical reactions occurring at either of the two electrodes, the anode for oxidizing fuel and the cathode for reducing oxidant, and so the electrodes are usually coated with electrocatalysts. An enzyme fuel cell uses an enzyme as the electrocatalyst, either at both cathode and anode, or at just one of the electrodes. The catalytic properties of redox enzymes offer some interesting advantages in fuel cell applications, although examples of devices exploiting enzyme electrocatalysis are almost exclusively at a “proof of concept” stage. Conventional low-temperature fuel cells are generally limited to H2 or primary alcohols as fuels; however, the use of an enzyme as the anode electrocatalyst means that any substance that is oxidized by an organism can become a useful fuel because it is obvious that enzymes for carrying out that specific task must exist. Not only are enzymes capable of very high activity (on a per mole basis), but they are usually highly selective for their substrates. This simplifies the design of a fuel cell because fuel and oxidant need not be separated by an ionically conducting membrane, and they can be introduced as a mixture, that is, mixed reactant fuel cells are possible. This also makes it possible to miniaturize the fuel cell to an extremely small scale. Enzymes are also renewable, meaning that their components are fully recycled using sunlight as an energy source. The main disadvantages of enzymes as electrocatalysts are as follows. First, they are usually very large molecules, so that although the active sites may be extremely active in comparison to the catalytic site of a conventional metal electrode, the catalytic (volume) density is low, and hence multilayers of enzyme are likely to be needed to provide sufficient current. Second, the catalytically active sites are usually buried, so that fast electron transfer to or from the electrode requires either use of an intrinsic electron relay system in the protein (such as a series of FeS clusters) or an extrinsic mediator that can penetrate sufficiently close to the active site. Third, enzymes are often unstable outside ambient / To whom correspondence should be addressed. E-mail: fraser.armstrong@ chem.ox.uk. Chem. Rev. 2008, 108, 2439–2461 2439

Enzymes as working or inspirational electrocatalysts for fuel cells and electrolysis.

A methanol/dioxygen biofuel cell that uses NAD+-dependent dehydrogenases as catalysts: application of an electro-enzymatic method to regenerate nicotinamide adenine dinucleotide at low overpotentials

Platinum black efficiently catalyzes the oxidation of methane by iron(III) to generate carbon dioxide and eight equivalents of iron(II) in solutions of sulfuric acid in water. The rate of oxidation increases over 4 hours to reach approximately 4.83 x 10(-2) moles of iron(II) per gram atom of surface platinum per second. A redox fuel cell was assembled that used this reaction in a liquid reformer to generate soluble reducing equivalents of iron(II) from methane, which was electrochemically oxidized to iron(III) in the cell. A vanadium(V)-(IV)-nitric acid-O(2) redox system catalyzed the electrochemical reduction of O(2). The open-circuit voltage of the cell was 0.48 volt, and the maximum power output of the cell was 8.1 milliwatts per cubic centimeter of graphite felt electrode.

https://science.sciencemag.org/content/sci/265/5177/1418.full.pdf

A redox fuel cell that operates with methane as fuel at 120°C

Platinum-catalyzed oxidations of organic compounds by ferric sulfate : use of a redox fuel cell to mediate complete oxidation of ethylene glycol by dioxygen at 80°C

Steven H. Bergens

Papers

A methanol/dioxygen biofuel cell that uses NAD+-dependent dehydrogenases as catalysts: application of an electro-enzymatic method to regenerate nicotinamide adenine dinucleotide at low overpotentials

A redox fuel cell that operates with methane as fuel at 120°C

Platinum-catalyzed oxidations of organic compounds by ferric sulfate : use of a redox fuel cell to mediate complete oxidation of ethylene glycol by dioxygen at 80°C