Evgeny Katz

Biocomputing Security System: Concatenated Enzyme-Based Logic Gates Operating as a Biomolecular Keypad Lock

A biomolecular security system mimicking a keypad lock device was developed using enzyme-based concatenated AND logic gates resulting in the implication logic network.

From “cyborg” lobsters to a pacemaker powered by implantable biofuel cells

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 (Voc) 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 Voc 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.

Digital biosensors with built-in logic for biomedical applications—biosensors based on a biocomputing concept

AbstractThis article reviews biomolecular logic systems for bioanalytical applications, specifically concentrating on the prospects and fundamental and practical challenges of designing digitally operating biosensors logically processing multiple biochemical signals. Such digitally processed information produces a final output in the form of a yes/no response through Boolean logic networks composed of biomolecular systems, and hence leads to a high-fidelity biosensing compared with traditional single (or parallel) sensing devices. It also allows direct coupling of the signal processing with chemical actuators to produce integrated “smart” “sense/act” (biosensor-bioactuator) systems. Unlike common biosensing devices based on a single input (analyte), devices based on biochemical logic systems require a fundamentally new approach for the sensor design and operation and careful attention to the interface of biocomputing systems and electronic transducers. As common in conventional biosensors, the success of the enzyme logic biosensor would depend, in part, on the immobilization of the biocomputing reagent layer. Such surface confinement provides a contact between the biocomputing layer and the transducing surface and combines efficiently the individual logic-gate elements. Particular attention should thus be given to the composition, preparation, and immobilization of the biocomputing surface layer, to the role of the system scalability, and to the efficient transduction of the output signals. By processing complex patterns of multiple physiological markers, such multisignal digital biosensors should have a profound impact upon the rapid diagnosis and treatment of diseases, and particularly upon the timely detection and alert of medical emergencies (along with immediate therapeutic intervention). Other fields ranging from biotechnology to homeland security would benefit from these advances in new biocomputing biosensors and the corresponding closed-loop “add/act” operation. FigureBiochemical computing and logic-gate systems based on biomolecules have the potential to revolutionize the field of biosensors. This article reviews the prospects, fundamental and practical challenges of designing digitally operating biosensors logically processing multiple biochemical signals.

Biofuel Cell Controlled by Enzyme Logic Systems

An enzyme-based biofuel cell with a pH-switchable oxygen electrode, controlled by enzyme logic operations processing in situ biochemical input signals, has been developed. Two Boolean logic gates (AND/OR) were assembled from enzyme systems to process biochemical signals and to convert them logically into pH-changes of the solution. The cathode used in the biofuel cell was modified with a polymer-brush functionalized with Os-complex redox species operating as relay units to mediate electron transport between the conductive support and soluble laccase biocatalyzing oxygen reduction. The electrochemical activity of the modified electrode was switchable by alteration of the solution pH value. The electrode was electrochemically mute at pH > 5.5, and it was activated for the bioelectrocatalytic oxygen reduction at pH < 4.5. The sharp transition between the inactive and active states was used to control the electrode activity by external enzymatic systems operating as logic switches in the system. The enzyme logic systems were decreasing the pH value upon appropriate combinations of the biochemical signals corresponding to the AND/OR Boolean logic. Then the pH-switchable electrode was activated for the oxygen reduction, and the entire biofuel cell was switched ON. The biofuel cell was also switched OFF by another biochemical signal which resets the pH value to the original neutral value. The present biofuel cell is the first prototype of a future implantable biofuel cell controlled by complex biochemical reactions to deliver power on-demand responding in a logical way to the physiological needs.

Chemical Gating with Nanostructured Responsive Polymer Brushes: Mixed Brush versus Homopolymer Brush

In this report, we describe a novel approach to create an electrochemical gating system using mixed polymer brushes grafted to an electrode surface, and we explore the switchable properties of these mixed polymer brushes. The morphological transitions in the mixed polymer brushes associated with the electrode surface result in the opening, closing, or precise tuning of their permeability for ion transport through the channels formed in the nanostructured thin film in response to an external stimulus (pH change). The gating mechanism was studied by atomic force microscopy, ellipsometry, contact angle measurements, force-distance measurements, and electrochemical impedance spectroscopy. In comparison to a homopolymer brush system, the mixed brush demonstrates much broader variation of ion transport through the thin film. We suggest that this approach could find important applications in electrochemical sensors and devices with tunable/switchable access to the electrode surface.

Living battery - biofuel cells operating in vivo in clams.

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 (Voc), short circuitry current (Isc) and maximum power (Pmax) 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.

Implanted biofuel cells operating in vivo – methods, applications and perspectives – feature article

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.

Biochemically controlled bioelectrocatalytic interface.

A switchable bioelectrocatalytic system for glucose oxidation controlled by external biochemical signals exemplifies interfacing between bioelectronic and biochemical ensembles.

Boolean logic gates that use enzymes as input signals.

Biochemical systems that demonstrate the Boolean logic operations AND, OR, XOR, and InhibA were developed by using soluble compounds, which represent the chemical “devices”, and the enzymes glucose oxidase (GOx), glucose dehydrogenase (GDH), alcohol dehydrogenase (AlcDH), and microperoxidase‐11 (MP‐11), which operated as the input signals that activated the logic gates. The enzymes were used as soluble materials and as immobilized biocatalysts. The studied systems are proposed to be a step towards the construction of “smart” signal‐responsive materials with built‐in Boolean logic.

Multianalyte digital enzyme biosensors with built-in Boolean logic.

Novel biosensors based on the biocomputing concept digitally process multiple biochemical signals through Boolean logic networks of coupled biomolecular reactions and produce output in the form of a YES/NO response. Compared to traditional single-analyte sensing devices, biocomputing approach enables a high-fidelity multianalyte biosensing, particularly beneficial for biomedical applications.