This is the Guest Editorial to the First Virtual Issue of Fuel Cells – From Fundamentals to Systems on Microbial and Enzymatic Fuel Cells. Browse here http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1615-6854/homepage/2293_vi_bio_fuelcells.html to access all articles compiled in the Virtual Issue. Increased economic growth and development are leading to a large gap between energy demands and the availability of fossil fuels. The concerns for the environment and climate change urge the innovation for new technologies for waste treatment and resource recovery. The development of bioelectrochemical systems (BES) represents a new approach for harvesting electricity from waste and biomass 1. The development of biological fuel cells using biocatalysts, i.e., electrogenic microorganisms and purified enzymes, has attracted numerous interests resulted in large quantity of research projects and publications in the area in the past decade. Enzymatic fuel cells using purified redox enzymes as the catalysts are attractive for biomedical applications 2. Electrogenic reactors based on microbial fuel cells (MFCs) represent a new approach for harvesting electricity from waste and biomass 1. Bioelectrochemical systems (BES) mainly include microbial fuel cells (MFCs) and microbial electrolysis cells (MECs). Microbial fuel cell (MFC) technology combines the developments in the biotechnology and fuel cell technology. The major difference between MFC and other types of fuel cells is the catalyst used. Instead of expensive noble metal or other chemical catalysts, microorganisms, such as bacteria and yeasts, are used. About a century ago in 1911, M. C. Potter first discovered the concept of electricity production from bacteria decomposing organic compounds by generating electricity with E. coli 3. Figure 1 compares the two biological fuel cell systems: enzymatic fuel cells and microbial fuel cells. As biocatalysts, enzymes catalyze specific reactions, while living microorganisms in MFCs are more roburst. Schematic diagrams of enzymatic and microbial fuel cells. As a potential power source for implantable medical devices, enzymatic fuel cells posses particular advantages over other types of fuel cells, due to high specificity of catalytic activity of enzymes. It is possible to design and manufacture simple structured and membraneless reactors using nontoxic and highly biocompatible materials. A review by Willner et al., summarized methods used to enhance electrical communication between the enzymes and the electrodes: (i)reconstitution of apoenzymes on relay-cofactor monolayers; immobilization of enzymes in redox-active hydrogels; the use of nanomaterials, such as carbon nanotubes (CNT) 2. A glucose/oxygen enzymatic fuel cell operated in physiological buffer and conditions (pH 7.4, 37 °C and 0.15 M NaCl in phosphate buffer) using two different Osmium redox polymers as mediators with redox potential tailored for glucose oxidase (anode) and laccase (cathode). High outputs of 52 μW cm−2 at 0.21 V and 17 μW cm−2 at 0.34 V were obtained. However, in the long term, due to the toxicity of Os and danger of leaching out, it might be better to use something non-toxic and robust 4. Also, it is possible to use various physiological fluids as fuels, such as sweat or saliva, which makes it possible to have a versatile non-invasive system. Apart from glucose oxidase, which is most studied enzyme for enzymatic fuel cells, other types enzymes, have also been studied. Cellobiose dehydrogenase (CDH) was studied by Shleev's group as the anode biocatalyst for carbonhydrate/oxygen enzymaticl fuel cells. Bilirubin oxidase was used for the cathode oxygen reduction catalyst. Open circuit voltages in the range of 0.62–0.67 V were obtained in phosphate buffer solutions with glucose or lactose 5, and (OCVs) were slightly lower as 0.56–0.58 V in physiological fluids of sweat, saliva 6 and serum 7. Direct electron transfer (DET) between CDH was achieved by modifying Au nanoparticles with a positively charged thiol N-(6-mercapto) hexylpyridinium (MHP) 5. Highest power density was obtained from 10mM lactose in air-saturated phosphate buffer as 8.64 μW cm−2, and for 5mM glucose, it was 4.77 μW cm−2 at cell voltage of 0.5 V 5. The power density was only slightly lower in serum as 4 μW cm−2 at the cell voltage of 0.19V 7. However, the power density was much lower in sweat and saliva, in the range of 0.1–0.26 μW cm−2 at 0.5 V 6. Efforts were also made to increase number of electrons produced from carbonhydrate oxidation using multiple enzyme cascades. Matsumoto et al. investigated a two-stage oxidation of glucose with three co-immobilised enzymes: NAD-dependent glucose dehydrogenase (GDH), NAD(P)(+)-dependent gluconate-5-dehydrogenase (Ga5DH), and diaphorase (DI) 8. Four electrons instead of two electrons were obtained from glucose oxidation due to two electrons achieved by oxidation of gluconate at the C5 carbon to 5-keto-glueonate by Ga5DH. 10.51 μW cm−2 was achieved. Arechederra and Minteer explored oxidation of glycerol, which is a by-product of biodiesel production with high energy density, with a three-enzyme cascade using PQQ-dependent alcohol dehydrogenase (PQQ-ADH), PQQ-dependent aldellyde dehydrogenase (PQQ-AldDH), and oxalate oxidase immobilized within a tetrabutylammonium-modified Nafion membrane 9. The power densities of up to 1.32 mW cm−2 were achieved. How to design a combination of enzymes to harvest maximum electrons produced from organic substrate oxidation, is the way to achieve high power output for enzymatic fuel cells. Microbial fuel cells (MFC) as a technology combining waste treatment and energy harvesting have been developed rapidly in the past decade 10, 11. There have been almost 7,000 research papers on microbial fuel cells published. The number of papers published per year increased from around 70 in 2004 to more than 800 in 2014. As a multidisciplinary research area, research on MFC and other BES covers a wide range of topics across different disciplines. In an MFC, bacteria immobilized on the anode oxidize organic matters from wastewaters and produce electrons and protons. The most common cathode reaction is the oxygen reduction reaction (ORR) with oxygen from air reduced by the electrons transferred from anode, which is similar to conventional chemical fuel cells. Electrical energy generation in MFCs largely depends on electrochemical active microorganism community, which are able to transfer electrons from bacteria to the electrode. Research on understanding the mechanisms of extracellular electron transfer from bacteria to electrode surface has been carried out by several groups. Both membrane-associated direct electron transfer (DET) by physical contact or electronically conducting pili, or mediator-associated electron transfer (MET) have been discovered for different microorganism species 12. Studies, using single species of microorganism or a mixed culture as biocatalysts in MFCs, have been carried out. Shewanella putrefaciens, Pseudomonas aeruginosa, Geobacter sp., and Rhodoferax ferrireducens have been used as the anode catalysts in MFCs 13. Compared to conventional fuel cells, the power outputs from MFCs are low. The maximum power outputs from the best prototype MFCs are between 1–5 Wm−2. Therefore, the material used for MFCs is the main factor limiting their commercialization potentials, and also affects power output. Low cost but high performance materials are desirable. For the MFC anode, materials with good electronic conductivity, biocompatibility and chemical stability, as well as high surface area are essential as the substrate for biofilm to grow, and for electron transfer. Carbon materials with high surface area, such as carbon felt and carbon brush, are commonly used. Stainless steel has also been used for MFCs 14. Further modifications of the anode with ammonia treatment 15, and nano carbon materials (graphene and carbon nanotubes) 16 have also been examined to increase electrode surface charge and enhance electron transfer, as well as reduce internal resistance, which result in improvement on MFC power outputs. Membrane separators are used in most MFCs to separate anode and cathode chambers and keep anaerobic conditions at anode. Nafion was used in the earlier MFC research, however, due to high cost of Nafion, alternative lower cost materials, such as anion exchange membranes polymers 17, battery separator 18, ceramics 19, have been widely investigated. For MFC cathode oxygen reduction reaction, Pt is not an option due to its high cost. Low cost non-Pt catalysts, such as iron phthalocyanine, have shown comparable or even higher power output from MFCs 20. Research on using bacteria as the biocatalysts for ORR to develop an aerobic bio-cathode has been reported 21, 22. This can be a more sustainable and low cost solution for MFCs. The papers (already published in Fuel Cells – From Fundamental to Systems) in this virtual issue, although not in large number, cover a range of topics and reflect the research and development in MFC community. From materials aspect, Frainwan et al. examined six different materials, including three-dimensional carbon nanomaterials and gold micro- and nanofibers, and two-dimensional planar gold and carbon paper, for MFC anode in micro-sized MFCs. This study provided understanding of interactions between micro-/nano-structure of the anode and active biofilm, which is important for material development and selection for MFCs 23. The same group also looked at a performance with a micro-fabricated microscale MFC testing effects of anode structure and flowrate to the cell performance 24. This method can be applied to fabricating enzymatic fuel cells as well. Modified carbon anode by MWCNTs/PANI used in marine sediment MFCs was reported by Fu et al., showing the maximum power density of the modified SMFC reached 527.0 mW m−2, 4 times higher than that of the unmodified one 25. This indicated MWCNTs/PANI being a promising approach to enhance power output of MFC. In contrast to the effort to scale up MFCs, microscale MFC could be for different applications, and used as a tool for examining various factors affecting MFC performance. Novel size-selective separators were evaluated by Moon et al. 26. The textile fabrics of polyphenylene sulfide and sulfonated polyphenylene sulfide and the nonwoven fabrics of plypropylene 80 and 100 were tested and found to exhibit higher power output than Nafion. These separators also showed better biofouling resistance than Nafion after long period of operation suggesting these materials can be good alternative separators for MFCs 26. Studies on yeast-based MFCs were also presented here. Both study developed model and simulations to investigate anode reaction kinetics with mediators 27 and operational characteristics 28 to identify the factors affecting the cell performance the most. Another manuscript by He and Ma used a stochastic simulation based multi-objective genetic algorithm approach to study robust optimal operation of a two-chamber MFC under uncertainty, to understand the mechanism of uncertainty propagation 29. It is a promising tool for optimal design and operation of fuel cells. A review paper on hemoproteins by Ramanavicius 30 suggested possible use of heme-c containing enzymes enabling direct electron transfer (DET) as a synthetic biological tool for a designed MFC or enzymatic fuel cells. Instead of chemical catalyst, You et al. examined an aerobic biocathode using graphite fiber brush as cathode material 31. The bacteria catalyzed MFC generated power density of 68.4 W m–3 suggesting a promising sustainable electricity recovery approach from wastewater. With a wide range of applications from biomedical engineering with enzymatic fuel cells to wastewater treatment and resource recovery by microbial fuel cells, biological fuel cells (BFC) reveal a promising technology on power generation using biocatalysts. Challenges are to be tackled to make the technology a more practical for real applications. Efforts on applying enzymatic fuel cells in real animal physiological conditions using clams, locusts and rat have taken place 32-34. These studies proved the feasibility of enzymatic fuel cells as a power source for implantable medical devices. For enzymatic fuel cells, the most significant challenges are: long term stability of the enzyme electrodes; efficient electron transfer between enzymes and electrode surfaces; improved enzyme bio-catalytic activity. These areas are crucial for pushing forward the technology 35: (i) Protein engineering of native enzyme molecules with desired properties tailored for specific applications; (ii) Novel immobilization methods and biomaterials to improve the stability of enzymes; (iii) Nano-materials integrated in the enzyme electrode structure to enhance the electron transfer and enzyme catalytic activity; (iv) Optimized fuel cell design configurations to increase the cell voltage and power output. The main interest for MFCs is combining wastewater treatment and energy harvesting in the form of electricity or hydrogen. To make MFC a viable technology, scale-up to practical dimensions is to way forward, and extremely challenging. Several pilot scale MFCs have been constructed. The first large-scale test of MFCs was conducted at Foster's brewery in Yatala, Queensland in 2009. The tubular shaped MFC contained 12 modules with a total volume approximately 1 m3. The performance of the MFC was not known but the current generation was low due to low conductivity of the brewery wastewater 36. Microbial electrolysis cell (MEC) for hydrogen production was set up at the Napa Wine Company, USA, also in 2009. Another pilot scale MEC for hydrogen production was conducted in a wastewater treatment plant by researchers from Newcastle University, UK. The MEC produced hydrogen 0.015 L day−1 for more than 12 months 36. More recently, a stackable domestic wastewater MFC was demonstrated in Harbin, China. The MFC generated 0.116 W for electrolyte volume of 250 L from brewery wastewater, and it was had a COD removal rate of 0.2 kg COD m−3 day−1, attaining a volumetric power density of 8.5 W m−3 37. The concept of MFCs using energy from wastewater can apply to bioremediation and biosynthesis. Compared to the conventional fuel cells, the energy generation from MFCs is limited. Therefore, more and more attention has been directed to reducing energy demand for wastewater treatment, and using cathode reactions, anoxic or aerobic, for recovering resources from waste. H2 production from MEC, metal recovery by electrodeposition of metals (or metal compounds) 38, 39 and microbial electrosynthesis of organic compounds has been investigated for the production of acetate and other hydrocarbon compounds from CO2 40, 41. Figure 2 depicts a schematic diagram of MFC and MEC for different applications. Schematic diagraph of integrated bioelectrochemical system combining wastewater treatment with different cathode applications. Microbial electrochemical system combining waste treatment and extracting energy and recovering resources from waste is a promising technology for sustainable chemical and fuel production, and will have positive impact on the environment and society. In Fuel Cells – from Fundamental to Systems, we will encourage and continue to publish the research on novel materials for biological fuel cells understanding fundamentals of reaction kinetics and electron transfer mechanisms between biocatalysts and electrodes, identifying and characterizing factors for biological fuel cell operation and optimising system design, and advances in bio-anodes and bio-cathodes. We will also catch the latest development and research perspectives of the bioelectrochemical systems with critical reviews on the technology. New technological developments with the element of using energy from waste for resource recovery and carbon dioxide utilization will be in the scope. Scale-up/down of the system and studies on developing pilot scale reactor will also be of our interests to cover the full spectra of the technology development. We hope Fuel Cells – from Fundamental to Systems becoming a platform and showcase to inspire the advances of the technology.