Networked Enzymatic Logic Gates with Filtering: New Theoretical Modeling Expressions and Their Experimental Application

We report the first study of a network of connected enzyme-catalyzed reactions, with added chemical and enzymatic processes that incorporate the recently developed biochemical filtering steps into the functioning of this biocatalytic cascade. New theoretical expressions are derived to allow simple, few-parameter modeling of network components concatenated in such cascades, both with and without filtering. The derived expressions are tested against experimental data obtained for the realized networks responses, measured optically, to variations of its input chemicals concentrations with and without filtering processes. We also describe how the present modeling approach captures and explains several observations and features identified in earlier studies of enzymatic processes when they were considered as potential network components for multi-step information/signal processing systems.

Enzymatic AND Logic Gate with Sigmoid Response Induced by Photochemically Controlled Oxidation of the Output

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 to make the gates response 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.

Modularity of Biochemical Filtering for Inducing Sigmoid Response in Both Inputs in an Enzymatic AND Gate

We report the first systematic study of designed two-input biochemical systems as information processing gates with favorable noise-transmission properties accomplished by modifying the gates response from convex shape to sigmoid in both inputs. This is realized by an added chemical filter process which recycles some of the output back into one of the inputs. We study a system involving the biocatalytic function of the enzyme horseradish peroxidase, functioning as an AND gate. We consider modularity properties, such as the use of three different input chromogens that, when oxidized yield signal-detection outputs for various ranges of the primary input, hydrogen peroxide. We also examine possible uses of different filter-effect chemicals (reducing agents) to induce the sigmoid-response. A modeling approach is developed and applied to our data, allowing us to describe the enzymatic kinetics in the framework of a formulation suitable for evaluating the noise-handling properties of the studied systems as logic gates for information processing steps.

Two-Input Enzymatic Logic Gates Made Sigmoid by Modifications of the Biocatalytic Reaction Cascades

Computing based on biochemical processes is a newest rapidly developing field of unconventional information and signal processing. In this paper we present results of our research in the field of biochemical computing and summarize the obtained numerical and experimental data for implementations of the standard two-input OR and AND gates with double-sigmoid shape of the output signal. This form of response was obtained as a function of the two inputs in each of the realized biochemical systems. The enzymatic gate processes in the first system were activated with two chemical inputs and resulted in optically detected chromogen oxidation, which happens when either one or both of the inputs are present. In this case, the biochemical system is functioning as the OR gate. We demonstrate that the addition of a filtering biocatalytic process leads to a considerable reduction of the noise transmission factor and the resulting gate response has sigmoid shape in both inputs. The second system was developed for functioning as an AND gate, where the output signal was activated only by a simultaneous action of two enzymatic biomarkers. This response can be used as an indicator of liver damage, but only if both of these of the inputs are present at their elevated, pathophysiological values of concentrations. A kinetic numerical model was developed and used to estimate the range of parameters for which the experimentally realized logic gate is close to optimal. We also analyzed the system to evaluate its noise-handling properties.

Extended Linear Response for Bioanalytical Applications Using Multiple Enzymes

We develop a framework for optimizing a novel approach to extending the linear range of bioanalytical systems and biosensors by utilizing two enzymes with different kinetic responses to the input chemical as their substrate. Data for the flow-injection amperometric system devised for detection of lysine based on the function of L-Lysine-alpha-Oxidase and Lysine-2-monooxygenase are analyzed. Lysine is a homotropic substrate for the latter enzyme. We elucidate the mechanism for extending the linear response range and develop optimization techniques for future applications of such systems.

Enzyme-Based Logic: OR Gate with Double-Sigmoid Filter Response

The first realization of a biomolecular OR gate function with double-sigmoid response (sigmoid in both inputs) is reported. Two chemical inputs activate the enzymatic gate processes resulting in the output signal: chromogen oxidation, which occurs when either one of the inputs or both are present (corresponding to the OR binary function), and can be optically detected. High-quality gate functioning in handling of sources of noise is enabled by filtering involving pH control with an added buffer. The resulting gate response is sigmoid in both inputs when proper system parameters are chosen, and the gate properties are theoretically analyzed within a model devised to evaluate its noise-handling properties.

Enzyme-Based Logic Analysis of Biomarkers at Physiological Concentrations: AND Gate with Double-Sigmoid Filter Response

We report the first realization of a biomolecular AND gate function with double-sigmoid response (sigmoid in both inputs). Two enzyme biomarker inputs activate the gate output signal which can then be used as indicating liver injury, but only when both of these inputs have elevated pathophysiological concentrations, effectively corresponding to logic-1 of the binary gate functioning. At lower, normal physiological concentrations, defined as logic-0 inputs, the liver-injury output levels are not obtained. High-quality gate functioning in handling of various sources of noise, on time scales of relevance to potential applications is enabled by utilizing filtering effected by a simple added biocatalytic process. The resulting gate response is sigmoid in both inputs when proper system parameters are chosen, and the gate properties are theoretically analyzed within a model devised to evaluate its noise-handling properties.

Morphology of Nanoclusters and Nanopillars Formed in Nonequilibrium Surface Growth for Catalysis Applications

We consider growth of nanoclusters and nanopillars in a model of surface deposition and restructuring yielding morphologies of interest in designing catalysis applications. Kinetic Monte Carlo numerical modeling yields examples of the emergence of FCC-symmetry surface features, allowing evaluation of the fraction of the resulting active sites with desirable properties, such as (111)-like coordination, as well as suggesting the optimal growth regimes.