Enzyme logic gates for the digital analysis of physiological level upon injury

Manesh, Kalayil Manian; Halámek, Jan; Pita, Marcos; Zhou, Jian; Tam, Tsz Kin; Santhosh, P.; Chuang, Min‐Chieh; Windmiller, Joshua Ray; Abidin, Dewi; Katz, Evgeny; Wang, Joseph

doi:10.1016/j.bios.2009.05.019

Cited by 80 publications

(77 citation statements)

References 21 publications

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“…[23][24][25] We experimentally demonstrated, as well as identified by modeling considerations why is has been so challenging to accomplish, a key element for any "toolbox" for noise-tolerant networking for information processing: We realized a versatile biochemical filter. It is hoped that the results reported here will facilitate the development of the next-generation biomolecular logic systems of higher complexity, based not only on simple gates and their few-step concatenations, but also utilizing network element designs and other ideas form Si electronics, as well as from Nature.…”

Section: Resultsmentioning

confidence: 99%

“…[23][24][25] However, even for near-term applications, scalable and versatile networking paradigms are crucial. Recent studies suggest 8,58,59 that the level of noise in biochemical systems is quite high as compared to electronics.…”

Section: Introductionmentioning

confidence: 99%

“…The promise of biochemical computing has ranged from in situ decision making, 16,17 novel multi-input biosensors, [18][19][20][21][22] for instance, for signaling in cases of trauma/injury, [23][24][25] to bioelectronic devices [26][27][28] and actuators, 29 and ultimately to interfacing of living organisms with Si electronics. A key challenge has been…”

Section: Introductionmentioning

confidence: 99%

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Biochemical Filter with Sigmoidal Response: Increasing the Complexity of Biomolecular Logic

et al. 2010

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The first realization of a designed, rather than natural, biochemical filter process is reported and analyzed as a promising network component for increasing the complexity of biomolecular logic systems. Key challenge in biochemical logic research has been achieving scalability for complex network designs. Various logic gates have been realized, but a "toolbox" of analog elements for interconnectivity and signal processing has remained elusive. Filters are important as network elements that allow control of noise in signal transmission and conversion. We report a versatile biochemical filtering mechanism designed to have sigmoidal response in combination with signal-conversion process. Horseradish peroxidase-catalyzed oxidation of chromogenic electron donor by H 2 O 2 , was altered by adding ascorbate, allowing to selectively suppress the output signal, modifying the response from convex to sigmoidal. A kinetic model was developed for evaluation of the quality of filtering. The results offer improved capabilities for design of scalable biomolecular information processing systems.Web-link to future updates of this article: www.clarkson.edu/Privman/231.pdf 600-2 - IntroductionBiochemical processes, 1-8 and more generally, chemical kinetics, [9][10][11][12][13][14][15] Presently, biochemical information processing systems are not intended as a replacement of Si devices, but rather aim at offering additional functionalities in situations where direct wiring to computers and power sources is not practical such as in many biomedical applications. [23][24][25] However, even for near-term applications, scalable and versatile networking paradigms are crucial. Recent studies suggest 8,58,59 that the level of noise in biochemical systems is quite high as compared to electronics. This includes noise both the input/output signals and in the "gate machinery" chemical (e.g., enzyme) concentrations. Avoiding noise amplification by appropriate network design is therefore quite important even for small networks, similar to recent findings 60 for networking of neurons. Present estimates 8,61 suggest that, not only analog but also digital error correction will be required for networks involving more than order 10 processing steps.-3 -Considerations of scalability and control of noise have set the stage for new challenges.Large-scale interconnectivity and fault-tolerance cannot be achieved without the development of a "toolbox" of new network elements including filters, signal splitters, signal balancers, resetting functions, etc. These analog network elements for biochemical computing might not follow too closely the device components of Si electronics. In fact, concepts borrowed from natural systems, specifically, memory involving processes 62 have recently received attention in unconventional information processing studies. However, as a rule none of the standard elements for networking for (ultimately, digital) information processing has been experimentally realized to date in a setting demonstrating interconnectivity ...

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Biochemical Filter with Sigmoidal Response: Increasing the Complexity of Biomolecular Logic

et al. 2010

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“…18,19 Biomolecular computing systems in biochemical and biotechnological environments 20 promise design of novel biosensors capable of multiplexing and processing several biochemical signals in the binary format, 0 and 1, with the information processing carried out by (bio)chemical processes rather than electronics. 21,22 Specifically, biomolecular logic has been explored [23][24][25][26][27][28][29][30][31] for prospective biomedical/diagnostic applications aiming at analysis of biomarkers characteristic of various pathophysiological conditions of interest in diagnostics of diseases or injuries. respectively.…”

Section: Molecularmentioning

confidence: 99%

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

et al. 2012

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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.

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“…In order to determine the type and the extent of an injury, it is usually necessary to monitor several physiological parameters. A multiple biosensor device (enzymatic reactions) connected similarly to electronic circuits in computer logical gates can perform biocomputing and process various biochemical information received from body fluids to determine the injury type [24,25]. Various Boolean logic gates such as AND, OR, XOR, NOR, NAND, INHIB and XNOR were made using biomolecular switchable systems (proteins/enzymes, DNA, RNA, whole cells) [26][27][28][29].…”

Section: Enzyme Logical Gatesmentioning

confidence: 99%

Nanobiocatalysts for biofuel cells and biosensor systems

Prodanović¹,

Gavrović-Jankulović²,

Kovačević³

et al. 2011

Vojnotehnički glasnik

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Abstract:This overview summarizes the application of enzymes in the manufacture and design of biofuel cells and biosensors. The emphasis will be put on the protein engineering techniques used for improoving the properties of enzymes such as nanobiocatalysts, e.g. immobilization orientation, stability, activity and efficiency of electron transfer between immobilized enzymes and electrodes. Some possible applications in the military and some future designs of these electric devices will be discussed as well.

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Enzyme logic gates for the digital analysis of physiological level upon injury

Cited by 80 publications

References 21 publications

Biochemical Filter with Sigmoidal Response: Increasing the Complexity of Biomolecular Logic

Biochemical Filter with Sigmoidal Response: Increasing the Complexity of Biomolecular Logic

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

Nanobiocatalysts for biofuel cells and biosensor systems

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