FIGURE 6 (A) A alternating-current nanogenerator based on a single piezoelectric fine nanowire harvesting mechanical energy from the breath and heartbeat of a live rat. Reproduced with permission.[104]Copyright 2010, Wiley-VCH GmbH. (B) A self-powered cardiac pacemaker by biocompatible polymer-based PENG on the heart of an adult dog. Reproduced with permission.[29] Copyright 2021, Elsevier. (C) In vivo simultaneously ECG signals recorded by flexible PENG attached to a porcine heart harvesting energy from rhythmical cardiac contraction and relaxation. Reproduced with permission.[106]Copyright 2017, Wiley-VCH GmbH. (D) Implantable thin film PENG powered in vivo blood pressure monitoring. Reproduced with permission.[107] Copyright 2016, Elsevier. (E) Self-powered cardiac pacemaker with breath-driven implanted TENG in vivo. Reproduced with permission.[30] Copyright 2014, Wiley-VCH GmbH. (F) VNS device for effective weight control powered by TENG harvesting mechanical energy from gastric peristalsis. Reproduced with permission.[112] Copyright 2018, Springer Nature.
3.2.2. Biofuel cell
The source ingredients for biofuel cells are abundantly available in our bodies including blood, sweat and tear. Due to the self-restorative body fluid, the reactant glucose for biofuel cells is abundant enough for long-term electricity generation. During the oxidation reaction, glucose can generate 12 electrons per molecule and provide energy up to 16 kWh g-1.[66] By inserting two biofuel electrodes with enzymatic catalysts into the tissue, the biofuel cell can convert chemical energy from glucose oxidization and dioxygen reduction to electricity, and the product gluconolactone will be then absorbed by organisms. It has been reported that biofuel cells have been fabricated and implanted into various organisms (snail, clam, lobster, slug, rat), and the power densities generated by biofuel cells range from 2 μW to 97 μW.[102] Since 2012, sustainable generation of electrical power from a snail was achieved for the first time, and it has been proved that biofuel cells implanted in small animals can operate for several months.[115] The reversible decay in the electrical power generation can be observed in Figure 7A , it was reported that the local depletion of glucose at the electrode surface led to the current decay, but the electrical output was restored after feeding the snail followed by slow metabolic processes and glucose diffusion. It is worthy of notice that small species have limited amounts of glucose for biofuel mass transport, which is different from the process in a mammal. To investigate the influence of the implanted glucose biofuel cell on the habits and fitness of the host, researchers investigated the weight of the rat and the food consumption when a biofuel cell based on carbon nanotube/enzyme electrodes was implanted.[116] It was implanted into the abdominal cavity and generated an average open-circuit voltage of 0.57 V and a power output of 38.7 μW, which is enough to power a light-emitting diode, and as a result, no immunological rejection happens in the rat after the implantation of the biofuel cells for 110 days, as shown in Figure 7B . It shows a promising prospect of the implantation of biofuel cells in a mammal’s body fluids for the biomedical electronic power source. To further decrease the dimension of the biofuel cell, a modified flexible carbon fibre microelectrode as intravenous implantable biofuel cell was developed and implanted in the thoracic region of living rats through a catheter.[31] An open circuit voltage of approximately 0.125 V was obtained and maximum output power of 95 μW cm-2 at 80 mV in a living rat was achieved (Figure7C ). However, the significant limitations of biofuel cells lay in the limited output voltage (less than 1 V) due to the limited oxidation-reduction potential, which means the biofuel cells can only drive electronics with a low voltage range. There are some improvement methods for the limited output voltage of biofuel cells, such as using a direct current to direct current (DC-DC) converter and connecting several biofuel cells in series.[117-118] But the DC-DC converter will consume current while connecting several enzymatic electrodes biofuel cells in series will bring more problems such as the expanded volume and implantation difficulty. Also, inflammatory reactions can also occur around the electrode surfaces and phagocytosis of the enzyme coatings of the biofuel cell will shorten the lifespan of the device, so developing a new biocompatible material to protect the electrodes is necessary.[31] At the same time, the oxidation reaction of glucose on the enzymatic electrodes will generate by-products (hydrogen peroxide) which may cause harm to the living body and therefore cause problems during long-term applications in vivo.[102] In this case, the development of new biocompatible materials to protect the enzyme coatings from phagocytosis should be considered for the advancement of this novel long-term applicable power electronics as a promising sustainable power source for the miniaturised IMEs.