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

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Abstract

This 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.

Biochemical 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.

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Acknowledgements

This research was supported by the National Science Foundation (grants DMR-0706209, CCF-0726698), by ONR (grant N00014-08-1-1202), and by the Semiconductor Research Corporation (award 2008-RJ-1839G).

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Authors and Affiliations

  1. Department of NanoEngineering, University of California—San Diego, La Jolla, CA, 92093, USA

    Joseph Wang

  2. Department of Chemistry and Biomolecular Science, and NanoBio Laboratory (NABLAB), Clarkson University, Potsdam, NY, 13699-5810, USA

    Evgeny Katz

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Correspondence to Joseph Wang or Evgeny Katz.

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Wang, J., Katz, E. Digital biosensors with built-in logic for biomedical applications—biosensors based on a biocomputing concept. Anal Bioanal Chem 398, 1591–1603 (2010). https://doi.org/10.1007/s00216-010-3746-0

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  • DOI: https://doi.org/10.1007/s00216-010-3746-0

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