Implantable Biofuel Cells Operating In Vivo—Potential Power Sources for Bioelectronic Devices
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Implantable devices harvesting energy from biological sources and based on electrochemical transducers are currently receiving high attention. The energy collected from the body can be utilized to activate various microelectronic devices. This article is an overview of the recent research activity in the area of enzyme-based biofuel cells implanted in biological tissue and operating in vivo. The electrical power extracted from the biological sources presents use for activating microelectronic devices for biomedical applications. While some microelectronic devices can work within a fairly broad range of electrical operating conditions, others, such as pacemakers, require precise voltage levels and voltage regulation for correct operation. Thus, certain classes of electronic devices powered by implantable energy sources will require careful attention not only to energy and power considerations, but also to voltage scaling and regulation. This requires appropriate interfacing between the energy harvesting device and the energy consuming microelectronic device. The paper focuses on the problems in the present technology as well as offers their potential solutions. Lastly, perspectives and future applications of the implanted biofuel cells are also discussed. The considered examples include a pacemaker and a wireless signal transfer system powered by a implantable biofuel cell extracting electrical energy from biological sources.
Introduction: Bioelectronics and Implantable Electronics
The most challenging developments in bioelectronics are related to biomedical applications, particularly advancing the direct coupling of electronic devices/machines with living organisms, where electronics operate in a biological environment implanted within a living body. This technology is already highly advanced, at least in some medical applications such as implantable cardiostimulators (9,10) and various other implantable prosthetic devices (11,12), including vagus nerve stimulators (13,14) to treat rheumatoid arthritis (15). The most important issue in the biotechnological engineering of implantable devices is the interface between living tissues and artificial manmade implantable devices. Cardiac defibrillators/pacemakers, deep brain neurostimulators, spinal cord stimulators, gastric stimulators, foot drop implants, cochlear implants, insulin pumps, retinal implants, implantable neural electrodes, muscle implants and other implantable devices must perform their functions by directly interacting with the respective organs to improve their natural operation or substitute a missing function. The development of sophisticated implantable devices (for example, autonomously operating insulin pumps) (16) can improve the quality of life and contribute to the novel concept of personalized medicine (17). More sophisticated implantable devices, such as an artificial eye (18), currently are being designed and studied in research laboratories and will come to medical practice in the near future. Implantable medical devices also can restore function by integrating with non-damaged tissue within an organ. The artificially generated electrical and sometimes electromechanical activity in each of these cases must be engineered within the context of the physiological system and its biological characteristics. Long-term implants for different biomedical applications present specific engineering challenges related to the minimization of energy consumption, physical miniaturization and stable performance optimization. The successful integration of machines with biological systems requires energy sources harvesting power directly from physiological processes (19,20) to unify the energy supply for biological and electronic/mechanical parts of the integrated system.
Harvesting Power from Biological Sources—Implantable Biofuel Cells
Harvesting power from living species (21,22) including the human body (19,23, 24, 25) using a broad variety of physical and chemical methods (19,26) has recently attracted significant attention. Physical methods of energy harvesting from living species often employ transducers utilizing mechanical energy (27): muscle stretching (28), arm/leg swings (19), walking/running (19,29,30), heart beats (31,32), blood flow (26), gas flow due to respiration (19,31,33) and so on. Different thermoelectric (19), and piezoelectric (19) effects also can be used for energy harvesting from a living body. It should be noted, however, that all physical energy conversion methods are based on complex machinery and represent an engineering rather than a biological approach. They are highly dependent on the human/animal physical activity and conditions of the environment. Methods based on the internal physiological activity rather than physical/mechanical activity should be much more reliable for energy harvesting due to relatively stable physiological conditions in a living body. Implanted devices used for electrical power generation based on biological inspiration are the most biocompatible and promising. These systems include biological potential gradients (34) or interfacial electron transfer processes (that is, redox reactions) (35). Natural biological elements, usually enzymes, interfaced with electrodes in implantable bioelectrochemical systems, typically biofuel cells (36, 37, 38), have illustrated significant importance.
Interfacing Implanted Biofuel Cells with Biomedical Microelectronic Devices
Despite the fact that many papers demonstrated power release from biofuel cells, which may potentially be enough for activating electronic devices, real interfacing of electronics with implanted biofuel cells was limited to very few examples. The major problem is the low voltage produced by biofuel cells, which is thermodynamically limited by the redox potentials of the biological fuel (usually glucose) and oxygen. In most of the reported biofuel cells the open circuit voltage hardly exceeds 0.5 V being decreased upon consuming current from the cells (39, 40, 41); at best the voltage was measured as high as 0.78 V while operating under nonphysiological conditions (69). However, this voltage is still not enough for most electronic devices, which usually require several volts for their operation. Improving efficiency of biofuel cells includes mostly increasing their current production and results in a very little effect on the voltage, which is thermodynamically limited. It should be noted that most papers on biofuel cells do not discuss the problem of their interfacing with electronics, but remain concentrated on resolving internal problems of the biofuel cells, such as current efficiency, stability and so on. Two approaches have been applied to resolve the low voltage problem: (i) assembling biofuel cells in series electrically, thus increasing the total output voltage (59,70, 71, 72), and (ii) collecting produced electrical energy in capacitors/charge pumps for the burst release in short pulses (73, 74, 75, 76). The latter approach has already been applied for activating a wireless transmitting electronic device, however using nonimplantable enzyme-based (76,77) or microbial biofuel cells (73). These approaches, particularly as used with implantable enzyme-based biofuel cells, will be exemplified and discussed below.
The second approach based on electronic interface devices such as charge pumps and other forms of DC-DC convertors has already been applied for the activation of a wireless transmitting electronic device; however, using nonimplantable enzyme-based (76,77) or microbial biofuel cells (73). The application of an interface device to increase the voltage is rather well-known (78), however it should be remembered that the voltage increase is achieved at the expense of the current consumed by the charge pump, thus putting additional demand on the current output of the biofuel cell. Implantable microsize electrical energy generators connected to an electrical interface can be used effectively for activating microelectronic devices operating in the short-pulses regime, using the time between pulses for the accumulation of energy (34). However, an implantable biofuel cell connected to a charge pump and used for the continuous operation of implantable biomedical devices, for example, a pacemaker, requires constant current production sufficient to keep the device continuously running. To satisfy the high current demand for the operation of the charge pump, large biocatalytic electrodes (buckypaper with a geometric area of 6 cm2) modified with PQQ-GDH on the anode, and laccase on the cathode, were used in a biofuel cell filled with human serum solution and operating under conditions mimicking human physiological bloodflow (79). The biofuel cell was connected to a variable load resistance and polarization was measured, demonstrating the open circuitry voltage, Voc, ca. 470 mV and short circuitry current, Isc, ca. 5 mA. The biofuel cell mimicking an implantable device was connected to the charge pump and DC-DC converter interface circuit, which was further connected to a pacemaker (Figure 10c). To analyze the pacemaker performance, the pacemaker output leads were connected to an implantable loop recorder (ILR), a subcutaneous electrocardiographic (ECG) monitoring device. In the present setup, it was used as a medically relevant analyzer of the electrical pulses produced by the pacemaker receiving the power from the biofuel cell. The loop recorder output was read wirelessly by the sensor device of the Medtronic CareLink Programmer, Model 2090 (Medtronic, Minneapolis, MN, USA), typically used for the programming and maintenance of pacemakers and loop recorders after implantation (80). Two borderline indistinguishable functions were generated by the ILR upon registering the electrical pulses produced by the pacemaker: one from the pacemaker powered by a standard battery, and one from the pacemaker powered by the implantable biofuel cell. The profound similarities in these two results confirm the correct pacemaker operation while receiving power from the external biofuel cell through the charge pump and DC-DC converter interface circuit. This approach for powering the pacemaker using a single biofuel cell is already practically applicable for future biomedical applications. Still additional research and engineering are necessary to solve remaining major problems. The biocatalytic electrodes presently used in the fluidic system operating in vitro are too large to be implanted in a human body, thus current efficiency should be increased to allow for smaller electrodes.
Another important problem, which should be resolved prior to real biomedical applications of implantable biofuel cells, is the stability of such cells. The biofuel cells presently used for activating pacemakers can operate for hours, at best for several days, while the current batteries operating as electrical power supplies for pacemakers provide power for at least 10 years (9,10). Therefore, implanted biofuel cells will be competitive with the presently used batteries only if they can operate in vivo more than 10 years, which is not achievable at the present level of technology, at least using enzyme-based biocatalytic electrodes. On the other hand, there is an alternative approach to biofuel cells, where the catalytic electrodes are modified instead with inorganic materials. These biofuel cells are called “abiotic” (85, 86, 87, 88, 89, 90) and they demonstrated excellent performance (91, 92, 93, 94, 95), including operation in vivo (91,96), to allow their competition with the enzyme-based biofuel cells. Abiotic biofuel cells also were successfully applied for activation of biomedical devices, such as pacemakers (91,97,98). Abiotic biofuel cells can offer much better stability compared with the enzyme-based cells, at least when they operate in clean buffer solutions. However, this advantage is not obvious for their operation in biofluids, where the high concentration of biomolecules, particularly proteins, can result in rapid inactivation of the inorganic catalytic species due to the biomolecular adsorption. Also, the inorganic species do not have high selectivity for catalyzing redox reactions characteristic of enzymes. Thus, the anodic oxidation of glucose may interfere with the reduction of oxygen on the same electrode and vice versa, resulting in a decrease in the voltage generated by the cell.
Conclusions and Perspectives
The author declares he has no competing interests as defined by Bioelectronic Medicine, or other interests that might be perceived to influence the results and discussion reported in this paper.
This work at Clarkson University was supported by the NSF award # CBET-1066397
Notes: (a) Research on animals was approved by the appropriate institutional committees and complied with the Guide for the Care and Use of Laboratory Animals (103). Specific details were given in the cited papers. (b) The present paper includes materials originally published in recent reviews and books, particularly in references (1) and (38). The paper offers edited, extended and updated material comparing with the previous publications. Some figures and text fragments are reproduced with the permission. (c) Additional video materials illustrating the experiments described in the paper can be viewed here:
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