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Biosensors with built-in biomolecular logic gates for practical applications.

Lai YH, Sun SC, Chuang MC - Biosensors (Basel) (2014)

Bottom Line: These molecular computers are capable of receiving and integrating multiple stimuli of biochemical significance to generate a definitive output, opening a new research avenue to advanced diagnostics and therapeutics which demand handling of complex factors and precise control.In molecularly gated devices, Boolean logic computations can be activated by specific inputs and accurately processed via bio-recognition, bio-catalysis, and selective chemical reactions.In this review, we survey recent advances of the molecular logic approaches to practical applications of biosensors, including designs constructed with proteins, enzymes, nucleic acids, nanomaterials, and organic compounds, as well as the research avenues for future development of digitally operating "sense and act" schemes that logically process biochemical signals through networked circuits to implement intelligent control systems.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, Tunghai University, Taichung 40704, Taiwan; E-Mails: karenlai0222@gmail.com (Y.-H.L.); sandy79325@gmail.com (S.-C.S.).

ABSTRACT
Molecular logic gates, designs constructed with biological and chemical molecules, have emerged as an alternative computing approach to silicon-based logic operations. These molecular computers are capable of receiving and integrating multiple stimuli of biochemical significance to generate a definitive output, opening a new research avenue to advanced diagnostics and therapeutics which demand handling of complex factors and precise control. In molecularly gated devices, Boolean logic computations can be activated by specific inputs and accurately processed via bio-recognition, bio-catalysis, and selective chemical reactions. In this review, we survey recent advances of the molecular logic approaches to practical applications of biosensors, including designs constructed with proteins, enzymes, nucleic acids, nanomaterials, and organic compounds, as well as the research avenues for future development of digitally operating "sense and act" schemes that logically process biochemical signals through networked circuits to implement intelligent control systems.

No MeSH data available.


The design for simultaneous detection of H2O2 and caspase 8 activity through chemical reactions releasing Hydroxy-cyanobenzothiazole and D-cysteine and in situ formation of firefly luciferin. Reprinted with permission from [63]. Copyright © 2013, American Chemical Society.
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biosensors-04-00273-f010: The design for simultaneous detection of H2O2 and caspase 8 activity through chemical reactions releasing Hydroxy-cyanobenzothiazole and D-cysteine and in situ formation of firefly luciferin. Reprinted with permission from [63]. Copyright © 2013, American Chemical Society.

Mentions: In addition to nanoparticles, synthetic organic compounds are also excellent materials for creating computational modules based on their chemical reactivity towards specific biochemical species and special optical properties. For instance, the Chang group described an “AND” logic strategy (Figure 10) for dual-analyte detection in living animals [63]. They developed two organic molecules. One was Peroxy Caged Luciferin-2 (PCL-2), which would release 6-hydroxy-2-cyanobenzothiazole (HCBT) following the reaction with hydrogen peroxide. The other was a peptide-based probe, z-Ile-Glu-ThrAsp-D-Cys (IETDC), which could be hydrolyzed to produce D-cysteine by active caspase 8. The two released molecules HCBT and D-cysteine formed luciferin in situ, resulting in a bioluminescent signal if and only if both biochemical processes proceeded. By using the combination of the two organic probes, the authors successfully and selectively monitored the concomitant presence of H2O2 (reactive oxidative species, ROS) and active caspase 8 in living cells and animals to report the biological state of acute inflammation. This study offered a potential bio-imaging tool for in-situ monitoring of multiple analytes of physiological significance. In another communication published recently, Hettie et al. also described a three-input “AND” logic fluorescent molecular logical gate based on the coumarin-3-aldehyde scaffold for application in neuronal imaging [64]. This AND gate was responsive to glutamate, zinc, and pH through functional groups incorporated into the π-system of their designed fluorophore. The aldehyde at the coumarin 3-position reacted with glutamate to form imines, and thus created a binding pocket for coordination with zinc. Following the binding of the probe with glutamate and zinc, the hydroxyl group at the 7-position sensed the change in pH, turning on a fluorescence response. The authors believed that this sensor could serve as a prototype, which potentially offers significant insight into mechanisms of neuronal functions and diseases by imaging the co-release of neural transmitters.


Biosensors with built-in biomolecular logic gates for practical applications.

Lai YH, Sun SC, Chuang MC - Biosensors (Basel) (2014)

The design for simultaneous detection of H2O2 and caspase 8 activity through chemical reactions releasing Hydroxy-cyanobenzothiazole and D-cysteine and in situ formation of firefly luciferin. Reprinted with permission from [63]. Copyright © 2013, American Chemical Society.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4264359&req=5

biosensors-04-00273-f010: The design for simultaneous detection of H2O2 and caspase 8 activity through chemical reactions releasing Hydroxy-cyanobenzothiazole and D-cysteine and in situ formation of firefly luciferin. Reprinted with permission from [63]. Copyright © 2013, American Chemical Society.
Mentions: In addition to nanoparticles, synthetic organic compounds are also excellent materials for creating computational modules based on their chemical reactivity towards specific biochemical species and special optical properties. For instance, the Chang group described an “AND” logic strategy (Figure 10) for dual-analyte detection in living animals [63]. They developed two organic molecules. One was Peroxy Caged Luciferin-2 (PCL-2), which would release 6-hydroxy-2-cyanobenzothiazole (HCBT) following the reaction with hydrogen peroxide. The other was a peptide-based probe, z-Ile-Glu-ThrAsp-D-Cys (IETDC), which could be hydrolyzed to produce D-cysteine by active caspase 8. The two released molecules HCBT and D-cysteine formed luciferin in situ, resulting in a bioluminescent signal if and only if both biochemical processes proceeded. By using the combination of the two organic probes, the authors successfully and selectively monitored the concomitant presence of H2O2 (reactive oxidative species, ROS) and active caspase 8 in living cells and animals to report the biological state of acute inflammation. This study offered a potential bio-imaging tool for in-situ monitoring of multiple analytes of physiological significance. In another communication published recently, Hettie et al. also described a three-input “AND” logic fluorescent molecular logical gate based on the coumarin-3-aldehyde scaffold for application in neuronal imaging [64]. This AND gate was responsive to glutamate, zinc, and pH through functional groups incorporated into the π-system of their designed fluorophore. The aldehyde at the coumarin 3-position reacted with glutamate to form imines, and thus created a binding pocket for coordination with zinc. Following the binding of the probe with glutamate and zinc, the hydroxyl group at the 7-position sensed the change in pH, turning on a fluorescence response. The authors believed that this sensor could serve as a prototype, which potentially offers significant insight into mechanisms of neuronal functions and diseases by imaging the co-release of neural transmitters.

Bottom Line: These molecular computers are capable of receiving and integrating multiple stimuli of biochemical significance to generate a definitive output, opening a new research avenue to advanced diagnostics and therapeutics which demand handling of complex factors and precise control.In molecularly gated devices, Boolean logic computations can be activated by specific inputs and accurately processed via bio-recognition, bio-catalysis, and selective chemical reactions.In this review, we survey recent advances of the molecular logic approaches to practical applications of biosensors, including designs constructed with proteins, enzymes, nucleic acids, nanomaterials, and organic compounds, as well as the research avenues for future development of digitally operating "sense and act" schemes that logically process biochemical signals through networked circuits to implement intelligent control systems.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, Tunghai University, Taichung 40704, Taiwan; E-Mails: karenlai0222@gmail.com (Y.-H.L.); sandy79325@gmail.com (S.-C.S.).

ABSTRACT
Molecular logic gates, designs constructed with biological and chemical molecules, have emerged as an alternative computing approach to silicon-based logic operations. These molecular computers are capable of receiving and integrating multiple stimuli of biochemical significance to generate a definitive output, opening a new research avenue to advanced diagnostics and therapeutics which demand handling of complex factors and precise control. In molecularly gated devices, Boolean logic computations can be activated by specific inputs and accurately processed via bio-recognition, bio-catalysis, and selective chemical reactions. In this review, we survey recent advances of the molecular logic approaches to practical applications of biosensors, including designs constructed with proteins, enzymes, nucleic acids, nanomaterials, and organic compounds, as well as the research avenues for future development of digitally operating "sense and act" schemes that logically process biochemical signals through networked circuits to implement intelligent control systems.

No MeSH data available.