2012
DOI: 10.1021/jp300447w
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Enzyme-Based Logic Analysis of Biomarkers at Physiological Concentrations: AND Gate with Double-Sigmoid “Filter” Response

Abstract: 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-… Show more

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Cited by 47 publications
(93 citation statements)
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“…[30][31][32]37,44 Applying this approach to the majority gate, we assembled a biocatalytic cascade partially consuming the produced NADH (Scheme 1C). Malate dehydrogenase (MDH) oxidized NADH produced by the reactions included in the majority gate with the concomitant reduction of oxaloacetate (Oxacet) to malate.…”
Section: ■ Results and Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…[30][31][32]37,44 Applying this approach to the majority gate, we assembled a biocatalytic cascade partially consuming the produced NADH (Scheme 1C). Malate dehydrogenase (MDH) oxidized NADH produced by the reactions included in the majority gate with the concomitant reduction of oxaloacetate (Oxacet) to malate.…”
Section: ■ Results and Discussionmentioning
confidence: 99%
“…While computational applications of biomolecular systems 14−16 competing with modern electronics are rather futuristic, their use in low scale information processing for biosensing 17−19 and bioactuating, 20−22 particularly aiming at medical use 23−26 and operation in a biological environment, 27,28 is already feasible at the present level of technology. Rapid progress in enzyme-based information processing systems resulted in the design of biocatalytic cascades mimicking various Boolean logic gates, 1 including AND, [29][30][31][32][33][34][35][36]34,36,37 NAND,38,39 NOR,36,39 CNOT, 40 XOR,34,36,41,42 INHIBIT,34,36 Identity, 36 and Inverter 36 gates. Assembling enzyme logic gates in complex networks composed of several concatenated gates resulted in an increased complexity of the information processing systems.…”
mentioning
confidence: 99%
“…Rapid progress in enzyme-based information processing systems has resulted in the design of biocatalytic cascades mimicking various Boolean logic gates [19 ], including AND [30][31][32][33][34], OR [33,35], NAND [36], NOR [34,36], CNOT [37], XOR [33,34,38,39], INHIBIT [33,34], Identity [34] and Inverter [34] gates. In order to digitalize chemical processes the reacting species considered as logic input signals were applied at two levels of their concentrations: their physical absence (zero concentration) was defined as logic 0 input, while logic 1 input was defined as experimentally optimized and conveniently high concentration, thus allowing significant separation in the produced output signals when inputs 0 or 1 were applied in different combinations.…”
Section: Logic Gates Based On Enzyme Reactionsmentioning
confidence: 99%
“…The enabled AND function with the recycling step, Figure 4d, bars 'b', allowed good separation between the output signals produced in the presence of low and high concentration of the input signals, thus allowing conclusion on the LI only when both biomarkers appeared at their pathophysiological elevated concentrations (1,1 input signals). This approach with a recycling step (called a 'filter' by analogy with its electronic counterpart) was successfully applied to improve logic performance of other gates by converting convex response function to sigmoidal dependence, thus allowing sharp transition from 0 to 1 logic output [30][31][32].…”
Section: Quest For Novel Applicationsmentioning
confidence: 99%
“…The goal for the simplest single input transduction is to have the resulting sigmoid response as symmetric and steep as possible, preserving the saturation regime at large inputs, and without losing too much of the overall signal intensity. Most of the reported designs and realizations 31,[53][54][55][56][57][58][59][60][61][62][63][64][65] of such "biochemical filtering" involved modifying the response at low inputs to a practically zero-slope, while largely preserving the saturation regime. These approaches, including generalizations to two-input processes, typically involve "intensity filtering" whereby the input or output is efficiently diverted (chemically consumed), but only up to a limited quantity.…”
Section: Introductionmentioning
confidence: 99%