In this critical review we review enzymatic systems which involve biocatalytic reactions utilized for information processing (biocomputing). Extensive ongoing research in biocomputing, mimicking Boolean logic gates has been motivated by potential applications in biotechnology and medicine. Furthermore, novel sensor concepts have been contemplated with multiple inputs processed biochemically before the final output is coupled to transducing “smart-material” electrodes and other systems. These applications have warranted recent emphasis on networking of biocomputing gates. First few-gate networks have been experimentally realized, including coupling, for instance, to signal-responsive electrodes for signal readout. In order to achieve scalable, stable network design and functioning, considerations of noise propagation and control have been initiated as a new research direction. Optimization of single enzyme-based gates for avoiding analog noise amplification has been explored, as were certain network-optimization concepts. We review and exemplify these developments, as well as offer an outlook for possible future research foci. The latter include design and uses of non-Boolean network elements, e.g., filters, as well as other developments motivated by potential novel sensor and biotechnology applications (136 references).

Enzyme-based biofuel cells implanted into living lobsters or designed as fluidic systems mimicking human blood circulation were used for powering electronic devices. Two lobsters with implanted biofuel cells connected in series were able to generate open circuit voltage (V_oc) up to 1.2 V and an electrical watch, selected as a model electronic device, was activated by the power extracted from the “living battery”. The fluidic system composed of five cells filled with human serum solution connected in series generated V_oc of ca. 3 V and was able to power a pacemaker. Sustainable operation of the pacemaker was achieved with the system closely mimicking human physiological conditions characteristic of normal and pathophysiological glucose concentrations with the fluidic rate typical for a blood circulation upon resting or performing physical exercises. While the “cyborg” lobsters demonstrate a model system with future possible military, homeland security and environmental monitoring applications, the system activating a pacemaker presents practicality for biomedical applications. The first demonstration of the pacemaker activated by the physiologically produced electrical energy shows promise for future electronic implantable medical devices powered by electricity harvested from the human body.

Biofuel cells implanted in living clams and producing sustainable electrical power in vivo were integrated in batteries. The “electrified” clams, being biotechnological living “devices”, were able to generate electrical power using physiologically produced glucose as the fuel. The activity of the living batteries was dependent on the environmental conditions which are affecting physiological processes in clams. The living batteries generated open circuitry voltage (V_oc), short circuitry current (I_sc) and maximum power (P_max) of ca. 800 mV, 25 μA, 5.2 μW and ca. 360 mV, 300 μA, 37 μW for the serial and parallel connections of 3 “electrified” clams, respectively. A clam-battery was connected to a capacitor which was charged up to 240 mV providing accumulation of electrical energy up to 28.8 mJ. Discharging the capacitor on an electrical motor resulted in the motor rotation. The “electrified” clams integrated in batteries demonstrated the possibility of activating electrical/electronic devices using energy produced in vivo.

This feature article is an overview of the recent research activity in the area of enzyme-based biofuel cells implanted and operating in vivo in living creatures (insects, mollusks, rats, rabbits, etc.). The electrical power extracted from these biological sources presents use for activating microelectronic devices for biomedical applications (e.g. pacemakers) or sensors/biosensors for environmental monitoring. The inequality of the voltage generated by the biofuel cell (which is thermodynamically limited by the redox potentials of the biomolecular fuel and oxygen) and the voltage demanded by the electronic devices requires special attention and can be resolved by specific interfacing with charge pumps and DC–DC converters. 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.

This review summarizes the fundamentals of the phenomenon of electron transfer (ET) reactions occurring in redox enzymes that were widely employed for the development of electroanalytical devices, like biosensors, and enzymatic fuel cells (EFCs). A brief introduction on the ET observed in proteins/enzymes and its paradigms (e.g., classification of ET mechanisms, maximal distance at which is observed direct electron transfer, etc.) are given. Moreover, the theoretical aspects related to direct electron transfer (DET) are resumed as a guideline for newcomers to the field. Snapshots on the ET theory formulated by Rudolph A. Marcus and on the mathematical model used to calculate the ET rate constant formulated by Laviron are provided. Particular attention is devoted to the case of glucose oxidase (GOx) that has been erroneously classified as an enzyme able to transfer electrons directly. Thereafter, all tools available to investigate ET issues are reported addressing the discussions toward the development of new methodology to tackle ET issues. In conclusion, the trends toward upcoming practical applications are suggested as well as some directions in fundamental studies of bioelectrochemistry.

Preparation, characterization and applications, particularly for signal-stimulated molecule release, of Fe ³⁺ -cross-linked alginate hydrogels are critically overviewed.