Responsive interface switchable by logically processed physiological signals: toward "smart" actuators for signal amplification and drug delivery.

Biomarkers characteristic of liver injury, alanine transaminase and lactate dehydrogenase, were processed by an enzyme-based system functioning as a logic AND gate. The NAD+ output signal produced by the system upon its activation in the presence of both biomarkers was then biocatalytically converted to a decrease in pH. The acidic pH value biocatalytically produced by the system as a response to the biomarkers triggered the restructuring of a polymer-modified electrode interface. This allowed a soluble redox species to approach the electrode surface, thus switching the electrochemical reaction ON. The redox transformations activated by the biochemical signals resulted in an amplification of signals. This system represents the first example of an integrated sensing-actuating chemical device with the implemented AND Boolean logic for processing natural biomarkers at their physiologically relevant concentrations.

[1]  Evgeny Katz,et al.  Biofuel cells controlled by logically processed biochemical signals: towards physiologically regulated bioelectronic devices. , 2009, Chemistry.

[2]  Vladimir Privman.  Biomolecular computing: learning through play. , 2010, Nature nanotechnology.

[3]  A. Credi.  Molecules that make decisions. , 2007, Angewandte Chemie.

[4]  Uwe Pischel,et al.  Smart molecules at work--mimicking advanced logic operations. , 2010, Chemical Society reviews.

[5]  E.E. May,et al.  Towards De Novo Design of Deoxyribozyme Biosensors for GMO Detection , 2008, IEEE Sensors Journal.

[6]  K. Szaciłowski.  Digital information processing in molecular systems. , 2008, Chemical reviews.

[7]  Itamar Willner,et al.  Concatenated logic gates using four coupled biocatalysts operating in series , 2006, Proceedings of the National Academy of Sciences.

[8]  I. Willner,et al.  Bioelectronics : from theory to applications , 2005 .

[9]  A. P. de Silva,et al.  Molecular logic and computing. , 2007, Nature nanotechnology.

[10]  Evgeny Katz,et al.  Digital biosensors with built-in logic for biomedical applications—biosensors based on a biocomputing concept , 2010, Analytical and bioanalytical chemistry.

[11]  Jian Zhou,et al.  Multiplexing of injury codes for the parallel operation of enzyme logic gates. , 2010, The Analyst.

[12]  M. Chiu,et al.  Hepatic enzymes have a role in the diagnosis of hepatic injury after blunt abdominal trauma. , 2009, Injury.

[13]  Jian Zhou,et al.  Bioelectrocatalytic system coupled with enzyme-based biocomputing ensembles performing boolean logic operations: approaching "smart" physiologically controlled biointerfaces. , 2009, ACS applied materials & interfaces.

[14]  A. P. Silva,et al.  A supramolecular chemistry basis for molecular logic and computation , 2007 .

[15]  Michael J Sailor,et al.  Nanoparticle self-assembly gated by logical proteolytic triggers. , 2007, Journal of the American Chemical Society.

[16]  Jan Halámek,et al.  Reversible gating controlled by enzymes at nanostructured interface. , 2010, Chemical communications.

[17]  Evgeny Katz,et al.  Switchable electrode controlled by enzyme logic network system: approaching physiologically regulated bioelectronics. , 2009, Journal of the American Chemical Society.

[18]  Jian Zhou,et al.  "Chemical transformers" from nanoparticle ensembles operated with logic. , 2008, Nano letters.

[19]  Andrew D. Hamilton,et al.  Digital analysis of protein properties by an ensemble of DNA quadruplexes. , 2009, Journal of the American Chemical Society.

[20]  E. Katz,et al.  Bio-logic analysis of injury biomarker patterns in human serum samples. , 2011, Talanta.

[21]  Jian Zhou,et al.  Boolean-format biocatalytic processing of enzyme biomarkers for the diagnosis of soft tissue injury , 2010 .

[22]  Uwe Pischel,et al.  Chemical approaches to molecular logic elements for addition and subtraction. , 2007, Angewandte Chemie.

[23]  Uwe Pischel,et al.  Digital Operations with Molecules ― Advances, Challenges, and Perspectives , 2010 .

[24]  Jian Zhou,et al.  An integrated multifunctional nanosystem from command nanoparticles and enzymes. , 2009, Small.

[25]  Vladimir Privman,et al.  Enzyme-based logic systems for information processing. , 2009, Chemical Society reviews.

[26]  Jian Zhou,et al.  Stimuli-responsive hydrogel membranes coupled with biocatalytic processes. , 2009, ACS applied materials & interfaces.

[27]  Jian Zhou,et al.  Multi-enzyme logic network architectures for assessing injuries: digital processing of biomarkers. , 2010, Molecular bioSystems.