Analytical and Bioanalytical Chemistry

, Volume 409, Issue 1, pp 81–94 | Cite as

Enzyme-based logic gates and circuits—analytical applications and interfacing with electronics

Review

Abstract

The paper is an overview of enzyme-based logic gates and their short circuits, with specific examples of Boolean AND and OR gates, and concatenated logic gates composed of multi-step enzyme-biocatalyzed reactions. Noise formation in the biocatalytic reactions and its decrease by adding a “filter” system, converting convex to sigmoid response function, are discussed. Despite the fact that the enzyme-based logic gates are primarily considered as components of future biomolecular computing systems, their biosensing applications are promising for immediate practical use. Analytical use of the enzyme logic systems in biomedical and forensic applications is discussed and exemplified with the logic analysis of biomarkers of various injuries, e.g., liver injury, and with analysis of biomarkers characteristic of different ethnicity found in blood samples on a crime scene. Interfacing of enzyme logic systems with modified electrodes and semiconductor devices is discussed, giving particular attention to the interfaces functionalized with signal-responsive materials. Future perspectives in the design of the biomolecular logic systems and their applications are discussed in the conclusion.

Graphical Abstract

Various applications and signal-transduction methods are reviewed for enzyme-based logic systems

Keywords

Logic gate Enzymes Biosensors Biomedical application Forensic application Field-effect device 

Abbreviations

α-KTG

α-Ketoglutaric acid

Abs

Optical absorbance

ABTS

2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)

ABTSox

Oxidized ABTS (colored product)

AcCh

Acetylcholine

AcChE

Acetylcholinesterase (enzyme EC 3.1.1.7)

ADH

Alcohol dehydrogenase (enzyme EC 1.1.1.1)

ADP

Adenosine 5'-diphosphate

Ala

Alanine (amino acid)

ALT

Alanine transaminase (enzyme EC 2.6.1.2)

Asc

Ascorbic acid

ATP

Adenosine 5'-triphosphate

Be

Betaine (product of choline oxidation)

BuCh

Butyrylcholine

ChO

Choline oxidase (enzyme EC 1.1.3.17)

CK

Creatine kinase (enzyme EC 2.7.3.2)

Crt

Creatine

CrtP

Creatine phosphate

DHA

Dehydroascorbic acid (product of ascorbic acid oxidation)

EIS

Electrolyte–insulator–semiconductor

G6PDH

Glucose 6-phosphate dehydrogenase (enzyme EC 1.1.1.49)

GDH

Glucose dehydrogenase (enzyme EC 1.1.1.47)

Glc

Glucose

Glc6P

Glucose-6-phosphate

Glc6PA

Gluconate-6-phosphate acid (product of Glc6P oxidation)

GlcA

Gluconic acid

GOx

Glucose oxidase (enzyme EC 1.1.3.4)

Glu

Glutamate (amino acid, salt form)

HK

Hexokinase (enzyme EC 2.7.1.1)

HRP

Horseradish peroxidase (enzyme EC 1.11.1.7)

ITO

Indium tin oxide (electrode)

Lac

Lactate

LDH

Lactate dehydrogenase (enzyme EC 1.1.1.27)

MP-11

Microperoxidase-11

MPh

Maltose phosphorylase (enzyme EC 2.4.1.8)

NAD+

Nicotinamide adenine dinucleotide

NADH

Nicotinamide adenine dinucleotide reduced

P4VP

Poly(4-vinyl pyridine)

PEP

Phospho(enol)pyruvic acid

Pi

Inorganic phosphate

PK

Pyruvate kinase (enzyme EC 2.7.1.40)

PQQ

Pyrroloquinoline quinone

Pyr

Pyruvate

Va

Alternative voltage applied between the conducting support and reference electrode of the EIS device

Vbias

Constant (bias) voltage applied between the conducting support and reference electrode of the EIS device

VFB

Flat-band voltage of the EIS device

Notes

Acknowledgments

The research at Clarkson University (E.K.) was supported by the USA National Science Foundation, NSF (Awards CBET-1403208).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no potential conflict of interest.

References

  1. 1.
    Moore GE. Cramming more components onto integrated circuits. Proc IEEE. 1998;86:82–5.CrossRefGoogle Scholar
  2. 2.
    Calude CS, Costa JF, Dershowitz N, Freire E, Rozenberg G, editors. Unconventional computation. Lecture notes in computer science, vol. 5715. Berlin, Germany: Springer; 2009.Google Scholar
  3. 3.
    Mermin ND. Quantum computer science: an introduction. Cambridge, UK: Cambridge University Press; 2007.CrossRefGoogle Scholar
  4. 4.
    Katz E, editor. Biomolecular information processing - from logic systems to smart sensors and actuators. Weinheim, Germany: Wiley-VCH; 2012.Google Scholar
  5. 5.
    Katz E, editor. Molecular and supramolecular information processing—from molecular switches to unconventional computing. Weinheim, Germany: Willey-VCH; 2012.Google Scholar
  6. 6.
    Szacilowski K. Infochemistry. Chichester, UK: Wiley; 2012.CrossRefGoogle Scholar
  7. 7.
    de Silva AP. Molecular logic-based computation. Cambridge, UK: Royal Society of Chemistry; 2013.Google Scholar
  8. 8.
    de Silva AP. Molecular logic and computing. Nat Nanotechnol. 2007;2:399–410.CrossRefGoogle Scholar
  9. 9.
    Pischel U. Advanced molecular logic with memory function. Angew Chem Int Ed. 2010;49:1356–8.CrossRefGoogle Scholar
  10. 10.
    Szacilowski K. Digital information processing in molecular systems. Chem Rev. 2008;108:3481–548.CrossRefGoogle Scholar
  11. 11.
    Pischel U, Andreasson J, Gust D, Pais VF. Information processing with—Quo Vadis? ChemPhysChem. 2013;14:28–46.CrossRefGoogle Scholar
  12. 12.
    Benenson Y. Biomolecular computing systems: principles, progress and potential. Nat Rev Genet. 2012;13:455–68.CrossRefGoogle Scholar
  13. 13.
    Alon U. An introduction to systems biology: design principles of biological circuits. London, UK: Chapman and Hall/CRC Press; 2007.Google Scholar
  14. 14.
    Stojanovic MN, Stefanovic D, Rudchenko S. Exercises in molecular computing. Acc Chem Res. 2014;47:1845–52.CrossRefGoogle Scholar
  15. 15.
    Stojanovic MN, Stefanovic D. Chemistry at a higher level of abstraction. J Comput Theor Nanosci. 2011;8:434–40.CrossRefGoogle Scholar
  16. 16.
    Ezziane Z. DNA computing: applications and challenges. Nanotechnology. 2006;17:R27–39.CrossRefGoogle Scholar
  17. 17.
    Ashkenasy G, Dadon Z, Alesebi S, Wagner N, Ashkenasy N. Building logic into peptide networks: bottom-up and top-down. Israel J Chem. 2011;51:106–17.CrossRefGoogle Scholar
  18. 18.
    Unger R, Moult J. Towards computing with proteins. Proteins. 2006;63:53–64.CrossRefGoogle Scholar
  19. 19.
    Katz E, Privman V. Enzyme-based logic systems for information processing. Chem Soc Rev. 2010;39:1835–57.CrossRefGoogle Scholar
  20. 20.
    Katz E. Biocomputing—Tools, aims, perspectives. Curr Opin Biotechnol. 2015;34:202–8.CrossRefGoogle Scholar
  21. 21.
    Rinaudo K, Bleris L, Maddamsetti R, Subramanian S, Weiss R, Benenson Y. A universal RNAi-based logic evaluator that operates in mammalian cells. Nat Biotechnol. 2007;25:795–801.CrossRefGoogle Scholar
  22. 22.
    Arugula MA, Shroff N, Katz E, He Z. Molecular AND logic gate based on bacterial anaerobic respiration. Chem Commun. 2012;48:10174–6.CrossRefGoogle Scholar
  23. 23.
    Privman V, Katz E. Can bio-inspired information processing steps be realized as synthetic biochemical processes? Phys Status Solidi A. 2015;212:219–28.CrossRefGoogle Scholar
  24. 24.
    Kahan M, Gil B, Adar R, Shapiro E. Towards molecular computers that operate in a biological environment. Phys D. 2008;237:1165–72.CrossRefGoogle Scholar
  25. 25.
    Benenson Y. Biocomputers: from test tubes to live cells. Mol Biosyst. 2009;5:675–85.CrossRefGoogle Scholar
  26. 26.
    Adleman LM. Molecular computation of solutions to combinatorial problems. Science. 1994;266:1021–4.CrossRefGoogle Scholar
  27. 27.
    Katz E, Wang J, Privman M, Halámek J. Multi-analyte digital enzyme biosensors with built-in Boolean logic. Anal Chem. 2012;84:5463–9.CrossRefGoogle Scholar
  28. 28.
    Wang J, Katz E. Digital biosensors with built-in logic for biomedical applications. Israel J Chem. 2011;51:141–50.CrossRefGoogle Scholar
  29. 29.
    Wang J, Katz E. Digital biosensors with built-in logic for biomedical applications—Biosensors based on biocomputing concept. Anal Bioanal Chem. 2010;398:1591–603.CrossRefGoogle Scholar
  30. 30.
    Halámková L, Halámek J, Bocharova V, Wolf S, Mulier KE, Beilman G, et al. Analysis of biomarkers characteristic of porcine liver injury—from biomolecular logic gates to animal model. Analyst. 2012;137:1768–70.CrossRefGoogle Scholar
  31. 31.
    Zhou J, Halámek J, Bocharova V, Wang J, Katz E. Biologic analysis of injury biomarker patterns in human serum samples. Talanta. 2011;83:955–9.CrossRefGoogle Scholar
  32. 32.
    Halámek J, Windmiller JR, Zhou J, Chuang MC, Santhosh P, Strack G, et al. Multiplexing of injury codes for the parallel operation of enzyme logic gates. Analyst. 2010;135:2249–59.CrossRefGoogle Scholar
  33. 33.
    Manesh KM, Halámek J, Pita M, Zhou J, Tam TK, Santhosh P, et al. Enzyme logic gates for the digital analysis of physiological level upon injury. Biosens Bioelectron. 2009;24:3569–74.CrossRefGoogle Scholar
  34. 34.
    Yu X, Lian WJ, Zhang JN, Liu HY. Multi-input and -output logic circuits based on bioelectrocatalysis with horseradish peroxidase and glucose oxidase immobilized in multi responsive copolymer films on electrodes. Biosens Bioelectron. 2016;80:631–9.CrossRefGoogle Scholar
  35. 35.
    Gdor E, Shemesh S, Magdassi S, Mandler D. Multi-enzyme inkjet printed 2D arrays. ACS Appl Mater Interfaces. 2015;7:17985–92.CrossRefGoogle Scholar
  36. 36.
    Ayyub OB, Kofinas P. Enzyme induced stiffening of nanoparticle-hydrogel composites with structural color. ACS Nano. 2015;9:8004–11.CrossRefGoogle Scholar
  37. 37.
    Huang YY, Ran X, Lin YH, Ren JS, Qu XG. Enzyme-regulated the changes of pH values for assembling a colorimetric and multistage interconnection logic network with multiple readouts. Anal Chim Acta. 2015;870:92–8.CrossRefGoogle Scholar
  38. 38.
    Wang L, Lian WJ, Yao HQ, Liu HY. Multiple-stimuli responsive bioelectrocatalysis based on reduced graphene oxide/poly(N-isopropylacrylamide) composite films and its application in the fabrication of logic gates. ACS Appl Mater Interfaces. 2015;7:5168–76.CrossRefGoogle Scholar
  39. 39.
    Ma L, Diao AP. Design of enzyme-interfaced DNA logic operations (AND, OR, and INHIBIT) with an assaying application for single-base mismatch. Chem Commun. 2015;51:10233–5.CrossRefGoogle Scholar
  40. 40.
    Miyake T, Josberger EE, Keene S, Deng YX, Rolandi M, An enzyme logic bioprotonic transducer. APL Materials. 20153;Article Number: 014906.Google Scholar
  41. 41.
    Liu S, Wang L, Lian WJ, Liu HY, Li CZ. Logic gate system with three outputs and three inputs based on switchable electrocatalysis of glucose by glucose oxidase entrapped in chitosan films. Chem – Asian J. 2015;10:225–30.CrossRefGoogle Scholar
  42. 42.
    Ikeda M, Tanida T, Yoshii T, Kurotani K, Onogi S, Urayama K, et al. Installing logic-gate responses to a variety of biological substances in supramolecular hydrogel-enzyme hybrids. Nat Chem. 2014;6:511–8.CrossRefGoogle Scholar
  43. 43.
    Guo J, Zhuang JM, Wang F, Raghupathi KR, Thayumanavan S. Protein AND enzyme gated supramolecular disassembly. J Am Chem Soc. 2014;136:2220–3.CrossRefGoogle Scholar
  44. 44.
    Jia YM, Duan RX, Hong F, Wang BY, Liu NN, Xia F. Electrochemical biocomputing: a new class of molecular-electronic logic devices. Soft Matter. 2013;9:6571–7.CrossRefGoogle Scholar
  45. 45.
    Chen JH, Zeng LW. Enzyme-amplified electronic logic gates based on split/intact aptamers. Biosens Bioelectron. 2013;42:93–9.CrossRefGoogle Scholar
  46. 46.
    Liu WT, Wu LY, Yan SY, Huang R, Weng XC, Zhou X. Graphene oxide-based fluorescent detection of DNA and enzymes using Hoechst 33258 and its use for dual-output fluorescent logic gates. Anal Methods. 2013;5:3631–4.CrossRefGoogle Scholar
  47. 47.
    Radhakrishnan K, Tripathy J, Raichur AM. Dual enzyme responsive microcapsules simulating an "OR" logic gate for biologically triggered drug delivery applications. Chem Commun. 2013;49:5390–2.CrossRefGoogle Scholar
  48. 48.
    Domanskyi S, Privman V. Design of digital response in enzyme-based bioanalytical systems for information processing applications. J Phys Chem B. 2012;116:13690–5.CrossRefGoogle Scholar
  49. 49.
    Kim E, Liu Y, Bentley WE, Payne GF. Redox capacitor to establish bio-device redox-connectivity. Adv Funct Mater. 2012;22:1409–16.CrossRefGoogle Scholar
  50. 50.
    Zhou M, Wang J. Biofuel cells for self-powered electrochemical biosensing and logic biosensing. Electroanalysis. 2012;24:197–209.CrossRefGoogle Scholar
  51. 51.
    Rafael SP, Vallee-Belisle A, Fabregas E, Plaxco K, Palleschi G, Ricci F. Employing the metabolic "Branch Point Effect" to generate an all-or-none, digital-like response in enzymatic outputs and enzyme-based sensors. Anal Chem. 2012;84:1076–82.CrossRefGoogle Scholar
  52. 52.
    Tam TK. Switchable biocatalytic electrodes controlled by biomolecular computing systems. Int J Unconv Computing. 2012;8:367–81.Google Scholar
  53. 53.
    Pita M. Switchable biofuel cells controlled by biomolecular computing systems. Int J Unconv Comput. 2012;8:391–417.Google Scholar
  54. 54.
    Kim KW, Kim BC, Lee HJ, Kim J, Oh MK. Enzyme logic gates based on enzyme-coated carbon nanotubes. Electroanalysis. 2011;23:980–6.CrossRefGoogle Scholar
  55. 55.
    Zhou M, Wang FA, Dong SJ. Boolean logic gates based on oxygen-controlled biofuel cell in "one pot". Electrohim Acta. 2011;56:4112–8.CrossRefGoogle Scholar
  56. 56.
    Zhou M, Zheng XL, Wang J, Dong SJ. A self-powered and reusable biocomputing security keypad lock system based on biofuel cells. Chem – Eur J. 2010;16:7719–24.CrossRefGoogle Scholar
  57. 57.
    Richards E. Enzymes perform logic gate operations. J Mater Chem. 2006;16:C29.Google Scholar
  58. 58.
    Sivan S, Tuchman S, Lotan N. A biochemical logic gate using an enzyme and its inhibitor. Part II: The logic gate. Biosystems. 2003;70:21–33.CrossRefGoogle Scholar
  59. 59.
    Sivan S, Lotan N. A biochemical logic gate using an enzyme and its inhibitor. 1. The inhibitor as switching element. Biotech Prog. 1999;15:964–70.CrossRefGoogle Scholar
  60. 60.
    Arkin A, Ross J. Computational functions in biochemical reaction networks. Biophys J. 1994;67:560–78.CrossRefGoogle Scholar
  61. 61.
    Bakshi S, Zavalov O, Halámek J, Privman V, Katz E. Modularity of biochemical filtering for inducing sigmoid response in both inputs in an enzymatic AND gate. J Phys Chem B. 2013;117:9857–65.CrossRefGoogle Scholar
  62. 62.
    Privman V, Fratto BE, Zavalov O, Halámek J, Katz E. Enzymatic AND logic gate with sigmoid response induced by photochemically controlled oxidation of the output. J Phys Chem B. 2013;117:7559–68.CrossRefGoogle Scholar
  63. 63.
    Halámek J, Zavalov O, Halámková L, Korkmaz S, Privman V, Katz E. Enzyme-based logic analysis of biomarkers at physiological concentrations: AND gate with double-sigmoid “filter” response. J Phys Chem B. 2012;116:4457–64.CrossRefGoogle Scholar
  64. 64.
    Strack G, Pita M, Ornatska M, Katz E. Boolean logic gates using enzymes as input signals. ChemBioChem. 2008;9:1260–6.CrossRefGoogle Scholar
  65. 65.
    Baron R, Lioubashevski O, Katz E, Niazov T, Willner I. Logic gates and elementary computing by enzymes. J Phys Chem A. 2006;110:8548–53.CrossRefGoogle Scholar
  66. 66.
    Zavalov O, Bocharova V, Privman V, Katz E. Enzyme-based logic: OR gate with double-sigmoid filter response. J Phys Chem B. 2012;116:9683–9.CrossRefGoogle Scholar
  67. 67.
    Zhou J, Arugula MA, Halámek J, Pita M, Katz E. Enzyme-based NAND and NOR logic gates with modular design. J Phys Chem B. 2009;113:16065–70.CrossRefGoogle Scholar
  68. 68.
    Moseley F, Halámek J, Kramer F, Poghossian A, Schöning MJ, Katz E. Enzyme-based reversible CNOT logic gate realized in a flow system. Analyst. 2014;139:1839–42.CrossRefGoogle Scholar
  69. 69.
    Halámek J, Bocharova V, Arugula MA, Strack G, Privman V, Katz E. Realization and properties of biochemical-computing biocatalytic XOR gate based on enzyme inhibition by a substrate. J Phys Chem B. 2011;115:9838–45.CrossRefGoogle Scholar
  70. 70.
    Privman V, Zhou J, Halámek J, Katz E. Realization and properties of biochemical-computing biocatalytic XOR gate based on signal change. J Phys Chem B. 2010;114:13601–8.CrossRefGoogle Scholar
  71. 71.
    Privman V, Zavalov O, Halámková L, Moseley F, Halámek J, Katz E. Networked enzymatic logic gates with filtering: new theoretical modeling expressions and their experimental application. J Phys Chem B. 2013;117:14928–39.CrossRefGoogle Scholar
  72. 72.
    Strack G, Ornatska M, Pita M, Katz E. Biocomputing security system: Concatenated enzyme-based logic gates operating as a biomolecular keypad lock. J Am Chem Soc. 2008;130:4234–5.CrossRefGoogle Scholar
  73. 73.
    Niazov T, Baron R, Katz E, Lioubashevski O, Willner I. Concatenated logic gates using four coupled biocatalysts operating in series. Proc Natl Acad Sci U S A. 2006;103:17160–3.CrossRefGoogle Scholar
  74. 74.
    Privman V, Strack G, Solenov D, Pita M, Katz E. Optimization of enzymatic biochemical logic for noise reduction and scalability: How many biocomputing gates can be interconnected in a circuit? J Phys Chem B. 2008;112:11777–84.CrossRefGoogle Scholar
  75. 75.
    Mailloux S, Gerasimova YV, Guz N, Kolpashchikov DM, Katz E. Bridging the two worlds: a universal interface between enzymatic and DNA computing systems. Angew Chem Int Ed. 2015;54:6562–6.CrossRefGoogle Scholar
  76. 76.
    Jin Z, Güven G, Bocharova V, Halámek J, Tokarev I, Minko S, et al. Electrochemically controlled drug-mimicking protein release from iron-alginate thin-films associated with an electrode. ACS Appl Mater Interfaces. 2012;4:466–75.CrossRefGoogle Scholar
  77. 77.
    Guz N, Fedotova TA, Fratto BE, Schlesinger O, Alfonta L, Kolpashchikov D, et al. Bioelectronic interface connecting reversible logic gates based on enzyme and DNA reactions. ChemPhysChem. 2016;17:2247–55.CrossRefGoogle Scholar
  78. 78.
    Melnikov D, Strack G, Pita M, Privman V, Katz E. Analog noise reduction in enzymatic logic gates. J Phys Chem B. 2009;113:10472–9.CrossRefGoogle Scholar
  79. 79.
    Privman V, Domanskyi S, Mailloux S, Holade Y, Katz E. Kinetic model for a threshold filter in an enzymatic system for bioanalytical and biocomputing applications. J Phys Chem B. 2014;118:12435–43.CrossRefGoogle Scholar
  80. 80.
    Pita M, Privman V, Arugula MA, Melnikov D, Bocharova V, Katz E. Towards biochemical filter with sigmoidal response to pH changes: buffered biocatalytic signal transduction. Phys Chem Chem Phys. 2011;13:4507–13.CrossRefGoogle Scholar
  81. 81.
    Privman V, Halámek J, Arugula MA, Melnikov D, Bocharova V, Katz E. Biochemical filter with sigmoidal response: Increasing the complexity of biomolecular logic. J Phys Chem B. 2010;114:14103–9.CrossRefGoogle Scholar
  82. 82.
    Katz E, Halámek J, New approach in forensic analysis – Biomolecular computing based analysis of significant forensic biomarkers. Ann Forensic Res Anal. 2014; 1: Article Number 1002.Google Scholar
  83. 83.
    Bakshi S, Halámková L, Halámek J, Katz E. Biocatalytic analysis of biomarkers for forensic identification of gender. Analyst. 2014;139:559–63.CrossRefGoogle Scholar
  84. 84.
    Kramer F, Halámková L, Poghossian A, Schöning MJ, Katz E, Halámek J. Biocatalytic analysis of biomarkers for forensic identification of ethnicity between Caucasian and African American groups. Analyst. 2013;138:6251–7.CrossRefGoogle Scholar
  85. 85.
    Bocharova V, Halámek J, Zhou J, Strack G, Wang J, Katz E. Alert-type biological dosimeter based on enzyme logic system. Talanta. 2011;85:800–3.CrossRefGoogle Scholar
  86. 86.
    Mailloux S, Zavalov O, Guz N, Katz E, Bocharova V. Enzymatic filter for improved separation of output signals in enzyme logic systems towards ‘Sense and Treat’ medicine. Biomaterials Sci. 2014;2:184–91.CrossRefGoogle Scholar
  87. 87.
    Halámek J, Zhou J, Halámková L, Bocharova V, Privman V, Wang J, et al. Biomolecular filters for improved separation of output signals in enzyme logic systems applied to biomedical analysis. Anal Chem. 2011;83:8383–6.CrossRefGoogle Scholar
  88. 88.
    Guz N, Halámek J, Rusling JF, Katz E. A biocatalytic cascade with several output signals—towards biosensors with different levels of confidence. Anal Bioanal Chem. 2014;406:3365–70.CrossRefGoogle Scholar
  89. 89.
    Privman M, Tam TK, Pita M, Katz E. Switchable electrode controlled by enzyme logic network system: approaching physiologically regulated bioelectronics. J Am Chem Soc. 2009;131:1314–21.CrossRefGoogle Scholar
  90. 90.
    Tam TK, Ornatska M, Pita M, Minko S, Katz E. Polymer brush-modified electrode with switchable and tunable redox activity for bioelectronic applications. J Phys Chem C. 2008;112:8438–45.CrossRefGoogle Scholar
  91. 91.
    Tokarev I, Gopishetty V, Zhou J, Pita M, Motornov M, Katz E, et al. Stimuli-responsive hydrogel membranes coupled with biocatalytic processes. ACS Appl Mater Interfaces. 2009;1:532–6.CrossRefGoogle Scholar
  92. 92.
    Poghossian A, Katz E, Schöning MJ. Enzyme logic AND-Reset and OR-Reset gates based on a field-effect electronic transducer modified with multi-enzyme membrane. Chem Commun. 2015;51:6564–7.CrossRefGoogle Scholar
  93. 93.
    Poghossian A, Malzahn K, Abouzar MH, Mehndiratta P, Katz E, Schöning MJ. Integration of biomolecular logic gates with field-effect transducers. Electrochim Acta. 2011;56:9661–5.CrossRefGoogle Scholar
  94. 94.
    Poghossian A, Krämer M, Abouzar MH, Pita M, Katz E, Schöning MJ. Interfacing of biocomputing systems with silicon chips: enzyme logic gates based on field-effect devices. Procedia Chem. 2009;1:682–5.CrossRefGoogle Scholar
  95. 95.
    Krämer M, Pita M, Zhou J, Ornatska M, Poghossian A, Schöning MJ, et al. Coupling of biocomputing systems with electronic chips: electronic interface for transduction of biochemical information. J Phys Chem C. 2009;113:2573–9.CrossRefGoogle Scholar
  96. 96.
    Molinnus D, Sorich M, Bartz A, Siegert P, Willenberg HS, Lisdat F, et al. Towards an adrenaline biosensor based on substrate recycling amplification in combination with an enzyme logic gate. Sens Actuat B. 2016;237:190–5.CrossRefGoogle Scholar
  97. 97.
    Molinnus D, Bäcker M, Iken H, Poghossian A, Keusgen M, Schöning MJ. Concept for a biomolecular logic chip with an integrated sensor and actuator function. Phys Status Solidi A. 2015;212:1382–8.CrossRefGoogle Scholar
  98. 98.
    Tam TK, Pita M, Trotsenko O, Motornov M, Tokarev I, Halámek J, et al. Reversible “closing” of an electrode interface functionalized with a polymer brush by an electrochemical signal. Langmuir. 2010;26:4506–13.CrossRefGoogle Scholar
  99. 99.
    Motornov M, Sheparovych R, Katz E, Minko S. Chemical gating with nanostructured responsive polymer brushes: mixed brush versus homopolymer brush. ACS Nano. 2008;2:41–52.CrossRefGoogle Scholar
  100. 100.
    Poghossian AS. The super-Nernstian pH sensitivity of Ta2O5-gate ISFETs. Sens Actuat B. 1992;7:367–70.CrossRefGoogle Scholar
  101. 101.
    Siqueira JR, Abouzar MH, Bäcker M, Zucolotto V, Poghossian A, Oliveira ON, et al. Carbon nanotubes in nanostructured films: potential application as amperometric and potentiometric field-effect (bio-)chemical sensors. Phys Status Solidi A. 2009;206:462–7.CrossRefGoogle Scholar
  102. 102.
    Abouzar MH, Poghossian A, Cherstvy AG, Pedraza AM, Ingebrandt S, Schöning MJ. Label-free electrical detection of DNA by means of field-effect nanoplate capacitors: experiments and modeling. Phys Status Solidi A. 2012;209:925–34.CrossRefGoogle Scholar
  103. 103.
    Poghossian A, Weil M, Cherstvy AG, Schöning MJ. Electrical monitoring of polyelectrolyte multilayer formation by means of capacitive field-effect devices. Anal Bioanal Chem. 2013;405:6425–36.CrossRefGoogle Scholar
  104. 104.
    Poghossian A, Bäcker M, Mayer D, Schöning MJ. Gating capacitive field-effect sensors by the charge of nanoparticle/molecule hybrids. Nanoscale. 2015;7:1023–31.CrossRefGoogle Scholar
  105. 105.
    Albery WJ, O'Shea GJ, Smith AL. J Chem Soc Faraday Trans. 1996;92:4083–5.CrossRefGoogle Scholar
  106. 106.
    Lasia, A. Semiconductors and Mott-Schottky plots. In: Electrochemical impedance spectroscopy and its applications, Springer: New York;2014. Chap10, pp. 251–255.Google Scholar
  107. 107.
    Agliari E, Altavilla M, Barra A, Dello Schiavo L, Katz E. Notes on stochastic (bio)-logic gates: computing with allosteric cooperativity. Sci Rep. 2015; 5: Article Number 9415.Google Scholar
  108. 108.
    Mailloux S, Guz N, Zakharchenko A, Minko S, Katz E. Majority and minority gates realized in enzyme-biocatalyzed systems integrated with logic networks and interfaced with bioelectronic systems. J Phys Chem B. 2014;118:6775–84.CrossRefGoogle Scholar
  109. 109.
    Baron R, Lioubashevski O, Katz E, Niazov T, Willner I. Elementary arithmetic operations by enzymes: a model for metabolic pathway based computing. Angew Chem Int Ed. 2006;45:1572–6.CrossRefGoogle Scholar
  110. 110.
    Fratto BE, Lewer JM, Katz E. An enzyme-based half-adder and half-subtractor with a modular design. ChemPhysChem. 2016;17:2210–7.CrossRefGoogle Scholar
  111. 111.
    Fratto BE, Katz E. Reversible logic gates based on enzyme-biocatalyzed reactions and realized in flow cells—modular approach. ChemPhysChem. 2015;16:1405–15.CrossRefGoogle Scholar
  112. 112.
    Fratto BE, Katz E. Controlled logic gates—Switch gate and Fredkin gate based on enzyme-biocatalyzed reactions realized in flow cells. ChemPhysChem. 2016;17:1046–53.CrossRefGoogle Scholar
  113. 113.
    Craighead H. Future lab-on-a-chip technologies for interrogating individual molecules. Nature. 2006;442:387–93.CrossRefGoogle Scholar
  114. 114.
    Mailloux S, Katz E. The role of biomolecular logic systems in biosensors and bioactuators. Optical Eng. 2014; 53: Article Number 097107.Google Scholar
  115. 115.
    Zhou M, Zhou N, Kuralay F, Windmiller JR, Parkhomovsky S, Valdés-Ramírez G, et al. A self-powered “Sense-Act-Treat” system that is based on a biofuel cell and controlled by Boolean logic. Angew Chem Int Ed. 2012;51:2686–9.CrossRefGoogle Scholar
  116. 116.
    Pita M, Minko S, Katz E. Enzyme-based logic systems and their applications for novel multi-signal-responsive materials. J Mater Sci: Mater Med. 2009;20:457–62.Google Scholar
  117. 117.
    Katz E, Pingarrón JM, Mailloux S, Guz N, Gamella M, Melman G, et al. Substance release triggered by biomolecular signals in bioelectronic systems. J Phys Chem Lett. 2015;6:1340–7.CrossRefGoogle Scholar
  118. 118.
    Katz E, Bocharova V, Privman M. Electronic interfaces switchable by logically processed multiple biochemical and physiological signals. J Mater Chem. 2012;22:8171–8.CrossRefGoogle Scholar
  119. 119.
    Pita M, Katz E. Switchable electrodes: How can the system complexity be scaled up? Electroanalysis. 2009;21:252–60.CrossRefGoogle Scholar
  120. 120.
    Bocharova V, Katz E. Switchable electrode interfaces controlled by physical, chemical, and biological signals. Chem Rec. 2012;12:114–30.CrossRefGoogle Scholar
  121. 121.
    Katz E, Pita M. Biofuel cells controlled by logically processed biochemical signals: towards physiologically regulated bioelectronic devices. Chem Eur J. 2009;15:12554–64.CrossRefGoogle Scholar
  122. 122.
    Shapiro E. A mechanical Turing machine: blueprint for a biomolecular computer. Interface Focus. 2012;2:497–503.CrossRefGoogle Scholar
  123. 123.
    de Murieta IS, Miro-Bueno JM, Rodriguez-Paton A. Biomolecular computers. Curr Bioinformatics. 2011;6:173–84.CrossRefGoogle Scholar
  124. 124.
    Haller LA, Fels G. Chemistry and computer—biomolecular coupling. Nachrichten aus der Chemie. 2008;56:771–2.CrossRefGoogle Scholar
  125. 125.
    Yin YM, Lin XQ. Progress on molecular computer. Prog Chem. 2001;13:337–42.Google Scholar
  126. 126.
    Rambidi NG. Biomolecular computer: roots and promises. Biosystems. 1997;44:1–15.CrossRefGoogle Scholar
  127. 127.
    Rambidi NG, Maximychev AV. Towards a biomolecular computer. Information processing capabilities of biomolecular nonlinear dynamic media. Biosystems. 1997;41:195–211.CrossRefGoogle Scholar
  128. 128.
    Dirk SM, Price DW, Chanteau S, Kosynkin DV, Tour JM. Accoutrements of a molecular computer: switches, memory components, and alligator clips. Tetrahedron. 2001;57:5109–21.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Department of Chemistry and Biomolecular ScienceClarkson UniversityPotsdamUSA
  2. 2.Institute of Nano- and Biotechnologies, FH AachenAachen University of Applied SciencesJülichGermany
  3. 3.Peter Grünberg Institute (PGI-8)Research Centre Jülich GmbHJülichGermany

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