We report a study of a system which involves an enzymatic cascade realizing an AND logic gate, with an added photochemical processing of the output, allowing the gate's response to be made sigmoid in both inputs. New functional forms are developed for quantifying the kinetics of such systems, specifically designed to model their response in terms of signal and information processing. These theoretical expressions are tested for the studied system, which also allows us to consider aspects of biochemical information processing such as noise transmission properties and control of timing of the chemical and physical steps.

Reversible logic gates, such as the double Feynman gate, Toffoli gate and Peres gate, with 3‐input/3‐output channels are realized using reactions biocatalyzed with enzymes and performed in flow systems. The flow devices are constructed using a modular approach, where each flow cell is modified with one enzyme that biocatalyzes one chemical reaction. The multi‐step processes mimicking the reversible logic gates are organized by combining the biocatalytic cells in different networks. This work emphasizes logical but not physical reversibility of the constructed systems. Their advantages and disadvantages are discussed and potential use in biosensing systems, rather than in computing devices, is suggested.

Controlled logic gates, where the logic operations on the Data inputs are performed in the way determined by the Control signal, were designed in a chemical fashion. Specifically, the systems where the Data output signals directed to various output channels depending on the logic value of the Control input signal have been designed based on enzyme biocatalyzed reactions performed in a multi-cell flow system. In the Switch gate one Data signal was directed to one of two possible output channels depending on the logic value of the Control input signal. In the reversible Fredkin gate the routing of two Data signals between two output channels is controlled by the third Control signal. The flow devices were created using a network of flow cells, each modified with one enzyme that biocatalyzed one chemical reaction. The enzymatic cascade was realized by moving the solution from one reacting cell to another which were organized in a specific network. The modular design of the enzyme-based systems realized in the flow device allowed easy reconfiguration of the logic system, thus allowing simple extension of the logic operation from the 2-input/3-output channels in the Switch gate to the 3-input/3-output channels in the Fredkin gate. Further increase of the system complexity for realization of various logic processes is feasible with the use of the flow cell modular design.

It is believed that connecting biomolecular computation elements in complex networks of communicating molecules may eventually lead to a biocomputer that can be used for diagnostics and/or the cure of physiological and genetic disorders. Here, a bioelectronic interface based on biomolecule-modified electrodes has been designed to bridge reversible enzymatic logic gates with reversible DNA-based logic gates. The enzyme-based Fredkin gate with three input and three output signals was connected to the DNA-based Feynman gate with two input and two output signals-both representing logically reversible computing elements. In the reversible Fredkin gate, the routing of two data signals between two output channels was controlled by the control signal (third channel). The two data output signals generated by the Fredkin gate were directed toward two electrochemical flow cells, responding to the output signals by releasing DNA molecules that serve as the input signals for the next Feynman logic gate based on the DNA reacting cascade, producing, in turn, two final output signals. The Feynman gate operated as the controlled NOT gate (CNOT), where one of the input channels controlled a NOT operation on another channel. Both logic gates represented a highly sophisticated combination of input-controlled signal-routing logic operations, resulting in redirecting chemical signals in different channels and performing orchestrated computing processes. The biomolecular reaction cascade responsible for the signal processing was realized by moving the solution from one reacting cell to another, including the reacting flow cells and electrochemical flow cells, which were organized in a specific network mimicking electronic computing circuitries. The designed system represents the first example of high complexity biocomputing processes integrating enzyme and DNA reactions and performing logically reversible signal processing.

A half-adder and a half-subtractor have been realized using enzymatic reaction cascades performed in a flow cell device. The individual cells were modified with different enzymes and assembled in complex networks to perform logic operations and arithmetic functions. The modular design of the logic devices allowed for easy re-configuration, enabling them to perform various functions. The final output signals, represented by redox species [Fe(CN)6 ](3-/4-) or NADH/NAD(+) , were analyzed optically to derive the calculation results. These output signals might be applicable in the future for actuation processes, for example, substance release activated by logically processed signals.