Enzyme-Based Computing Systems

Evgeny Katz received his Ph.D. in Chemistry from Frumkin Institute of Electrochemistry (Moscow), Russian Academy of Sciences, in 1983. He was a senior researcher in the Institute of Photosynthesis (Pushchino), Russian Academy of Sciences, in 1983-1991. In 1992-1993 he performed research at München Technische Universität (Germany) as a Humboldt fellow. Later, in 1993-2006, Dr. Katz was a Research Associate Professor at the Hebrew University of Jerusalem. Since 2006 he is Milton Kerker Chaired Professor at the Department of Chemistry and Biomolecular Science, Clarkson University, NY (USA). His scientific interests are in the broad areas of bioelectronics, biosensors, biofuel cells, biomolecular information processing and recently in forensic science.

• Preface xvAcknowledgment xviiList of Abbreviations xxiii1 Introduction 11.1 Motivation and Applications 11.2 Enzyme-Based Logic Gates and Short Logic Circuits 3References 52 Boolean Logic Gates Realized with Enzyme-Catalyzed Reactions: Unusual Look at Usual Chemical Reactions 92.1 General Introduction and Definitions 92.2 Fundamental Boolean Logic Operations Mimicked with Enzyme-Catalyzed Reactions 112.2.1 Identity (YES) Gate 112.2.2 Inverted Identity (NOT) Gate 122.2.3 OR Gate 132.2.4 NOR Gate 152.2.5 XOR Gate 152.2.6 NXOR Gate 182.2.7 AND Gate 202.2.8 NAND Gate 212.2.9 INHIB Gate 222.2.10 Summary on the Basic Boolean Gates Realized with Enzyme Systems 232.3 Modular Design of NOR and NAND Logic Gates 242.4 Majority and Minority Logic Gates 282.5 Reconfigurable Logic Gates 342.5.1 3-Input Logic Gates Switchable Between AND–OR Logic Functions Operating in a Solution 342.5.2 Enzyme-Based Logic Gates Switchable Between OR, NXOR, and NAND Boolean Operations Realized in a Flow System 352.6 Conclusions and Perspectives 40References 413 Optimization of Enzyme-Based Logic Gates for Reducing Noise in the Signal Transduction Process 473.1 Introduction 473.2 Signal Transduction Function in the Enzyme-Based Logic Systems: Filters Producing Sigmoid Response Functions 483.2.1 Identity (YES) Logic Gate Optimization 503.2.2 AND Logic Gate Optimization 523.2.3 OR Logic Gate Optimization 553.2.4 XOR Logic Gate Optimization 563.3 Summary 59References 594 Enzyme-Based Short Logic Networks Composed of Concatenated Logic Gates 634.1 Introduction: Problems in Assembling of Multistep Logic Networks 634.2 Logic Network Composed of Concatenated Gates: An Example System 644.3 Logic Networks with Suppressed Noise in the Presence of Filter Systems 664.4 Logic Circuits Activated with Biomolecular Signals and Magnetic Field Applied 684.4.1 Biocatalytic Reactions Proceeding with Bulk Diffusion of Intermediate Substrates/Products and with Their Channeling 684.4.2 Magneto-Controlled Biocatalytic Cascade Switchable Between Substrate Diffusion and Substrate Channeling Modes of Operation 694.4.3 Logic Signal Processing with the Switchable Biocatalytic System 724.5 The Summary: Step Forward from Single Logic Gates to Complex Logic Circuits 74References 755 Sophisticated Reversible Logic Systems 795.1 Introduction 795.1.1 Reversible Logic Gates and Their Features 795.1.2 Logic Reversibility vs. Physical Reversibility 805.1.3 Integration of Reversible Logic Gates into Biomolecular Computing Systems 815.1.4 Spatial Separation of Enzyme Logic Operation: The Use of Flow Devices 815.2 Feynman Gate: Controlled NOT (CNOT) Gate 825.3 Double Feynman Gate (DFG) Operation 865.4 Toffoli Gate Operation 905.5 Peres Gate Operation 945.6 Gates Redirecting Output Signals 995.6.1 Controlled-Switch Gate 995.6.2 Fredkin (Controlled-Swap) Gate 1025.7 Advantages and Disadvantages of the Developed Approach 1075.7.1 Advantages 1075.7.2 Disadvantages 1085.8 Conclusions and Perspectives 109References 1096 Transduction of Signals Generated by Enzyme Logic Gates 1136.1 Optical Analysis of Output Signals Generated by Enzyme-Based Logic Systems 1136.1.1 Optical Absorbance Measurements for Transduction of Output Signals Produced by Enzyme-Based Logic Gates 1146.1.2 Bioluminescence Measurements for Transduction of Output Signals Produced by Enzyme-Based Logic Gates 1206.1.3 Surface Plasmon Resonance (SPR) Measurements for Transduction of Output Signals Produced by Enzyme-Based Logic Gates 1216.2 Electrochemical Analysis of Output Signals Generated by Enzyme-Based Logic Systems 1226.2.1 Chronoamperometric Transduction of Chemical Output Signals Produced by Enzyme-Based Logic Systems 1236.2.2 Potentiometric Transduction of Chemical Output Signals Produced by Enzyme-Based Logic Systems 1246.2.3 pH Measurements as a Tool for Transduction of Chemical Output Signals Produced by Enzyme-Based Logic Systems 1266.2.4 Indirect Electrochemical Analysis of Output Signals Generated by Enzyme-Based Logic Systems Using Electrodes Functionalized with pH-Switchable Polymers 1276.2.5 ConductivityMeasurements as a Tool for Transduction of Chemical Output Signals Produced by Enzyme-Based Logic Systems 1306.2.6 Transduction of Chemical Output Signals Produced by Enzyme-Based Logic Systems Using Semiconductor Devices 1326.3 Macro/Micro/Nano-mechanical Transduction of Chemical Output Signals Produced by Enzyme-Based Logic Systems 1346.3.1 Mechanical Bending of a Cantilever Used for Transduction of Chemical Output Signals Produced by Enzyme-Based Logic Systems 1356.3.2 Quartz Crystal Microbalance (QCM) Transduction of Chemical Output Signals Produced by Enzyme-Based Logic Systems 1376.3.3 Atomic Force Microscopy (AFM) Transduction of Chemical Output Signals Produced by Enzyme-Based Logic Systems 1386.4 Conclusions and Perspectives 142References 1437 Circuit Elements Based on Enzyme Systems 1517.1 Enzyme-Based Multiplexer and Demultiplexer 1517.1.1 General Definition of the Multiplexer and Demultiplexer Functions 1517.1.2 2-to-1 DigitalMultiplexer Based on the Enzyme-Catalyzed Reactions 1537.1.3 1-to-2 Digital Demultiplexer Based on the Enzyme-Catalyzed Reactions 1557.1.4 1-to-2 Digital Demultiplexer Interfaced with an Electrochemical Actuator 1587.2 Biomolecular Signal Amplifier Based on Enzyme-Catalyzed Reactions 1647.3 Biomolecular Signal Converter Based on Enzyme-Catalyzed Reactions 1667.4 Utilization of a Fluidic Infrastructure for the Realization of Enzyme-Based Boolean Logic Circuits 1677.5 Other Circuit Elements Required for the Networking of Enzyme Logic Systems and General Conclusions 169References 1708 Enzyme-Based Memory Systems 1758.1 Introduction 1758.2 Enzyme-Based Flip-Flop Memory Elements 1758.2.1 Set/Reset (SR) Flip-Flop Memory Based on Enzyme-Catalyzed Reactions 1768.2.2 Delay (D) Flip-Flop Memory Based on Enzyme-Catalyzed Reactions 1828.2.3 Toggle (T) Flip-Flop Memory Based on Enzyme-Catalyzed Reactions 1858.2.4 Enzyme-Based Flip-Flop Memory Systems: Conclusions and Perspectives 1868.3 Memristor Based on Enzyme Biocatalytic Reactions 1888.3.1 Memristors: From Semiconductor Devices to Soft Matter and Biomolecular Materials 1888.3.2 The Memristor Device Based on a Biofuel Cell 1898.3.3 The Memristor Device Controlled by Logically Processed Biomolecular Signals 1968.3.4 Enzyme-Based Memristors: Conclusions and Perspectives 1988.4 Enzyme-Based Associative Memory Systems 1988.4.1 Associative Memory: Biological Origin and Function 1998.4.2 Realization of the Associative Memory with a Multienzyme Biocatalytic Cascade 2018.4.3 Enzyme-Based Associative Memory: Challenges and Perspectives 2038.5 Enzyme-Based Memory Systems: Challenges, Perspectives, and Limitations 204References 2069 Arithmetic Functions Realized with Enzyme-Catalyzed Reactions 2119.1 Molecular and Biomolecular Arithmetic Systems: Introduction and Motivation 2119.2 Half-Adder 2129.3 Half-Subtractor 2169.4 Conclusions and Perspectives 219References 21910 Information Security Applications Based on Enzyme Logic Systems 22310.1 Keypad Lock Devices as Examples of Electronic Information Security Systems 22310.2 Keypad Lock Systems Based on Biocatalytic Cascades 22410.3 Other Biomolecular Information Security Systems 22910.3.1 Steganography and EncryptionMethods Based on Bioaffinity Complex Formation Followed by a Biocatalytic Reaction 22910.3.2 Barcodes Produced by Bioelectrocatalytic Reactions 23110.4 Summary 233References 23311 Enzyme Logic Digital Biosensors for Biomedical, Forensic, and Security Applications 23511.1 Introduction: Short Overview 23511.2 From Traditional Analog Biosensors to Novel Binary Biosensors Based on the Biocomputing Concept 23511.3 How Binary Operating Biosensors Can Benefit Biomedical Analysis: Requirements, Challenges, and First Applications 23811.4 Binary (YES/NO) Analysis of Liver Injury Biomarkers: From Test Tube Probes to Animal Research 24011.5 Further Examples of Injury Biomarker Analysis Using AND/NAND Logic Gates 24511.5.1 Soft Tissue Injury (STI) Logic Analysis 24611.5.2 Traumatic Brain Injury (TBI) Logic Analysis 24711.5.3 Abdominal Trauma (ABT) Logic Analysis 25011.5.4 Hemorrhagic Shock (HS) Logic Analysis 25111.5.5 Oxidative Stress (OS) Logic Analysis 25411.5.6 Radiation Injury (RI) Logic Analysis 25811.6 Multienzyme Logic Network Architectures for Assessing Injuries: Aiming at the Increased Complexity of the Biocomputing–Bioanalytic Systems 26111.6.1 The System Structure Based on the Complex Biocatalytic Cascade 26111.6.2 STI Operation Mode of the Logic Network 26411.6.3 TBI Operation Mode of the Logic Network 26511.6.4 Switching Between the STI and TBI Modes and General Comments on the System 26711.7 New Approach in Forensic Analysis: Biomolecular Computing-Based Analysis of Forensic Biomarkers 26811.8 Logic Analysis of Security Threats (Explosives and Nerve Agents) Based on Biocatalytic Cascades 27011.9 Integration of Biocatalytic Cascades with Microelectronics and Wearable Sensors 27211.10 Conclusions and Perspectives 276References 27612 Release of Molecular Species Stimulated by Logically Processed Biomolecule Signals 28312.1 Motivation and Experimental Background 28312.2 Fe3+-Cross-Linked Alginate Hydrogel is a Good Example of Matrix for Signal-Stimulated Release 28412.3 DNA Release as an Example of Signal-Stimulated Biomolecule Release 28712.4 Bioelectrochemical Systems with Sensing and Releasing Electrodes 28712.4.1 Sensing Electrodes Activated with Single Input Identity Gate 28812.4.2 Sensing Electrodes Activated with Multi-input Logic Networks 28812.4.3 Releasing Electrodes: Various Released Species for Different Applications 29112.5 Fe3+-Cross-Linked Alginate Hydrogel Decomposition and Entrapped Molecule Release Triggered by Enzymatically Produced H2O2 29412.5.1 DNA Release from Fe3+-Cross-Linked Alginate Hydrogel Stimulated by Signals Processed through OR, AND, and INHIB Logic Gates 29412.5.2 DNA Release from Fe3+-Cross-Linked Alginate Hydrogel Stimulated by Signals Processed Through Multi-gate Network Composed of Concatenated AND Gates 30412.6 Conclusions and Perspectives 307References 30713 Biofuel Cells Controlled by Biocomputing Systems 31313.1 Introduction: Biofuel Cells,Their Applications, and Motivation for Designing Adaptive, Signal-Controlled Devices 31313.2 Biofuel Cells Controlled by Logically Processed Biochemical Signals 31513.3 Biofuel Cells Controlled by Biomolecular Keypad Lock Systems 32613.4 Conclusions and Perspectives 328References 33014 Bioelectronic Interface Between Enzyme-Based and DNA-Based Computing Systems 33514.1 Introduction: Interfacing Enzyme-Based and DNA-Based Computing Systems Is a Challenging Goal 33514.2 Bioelectronic Interface Transducing Logically Processed Signals from an Enzymatic System to a DNA System 33614.3 The Bioelectronic Interface Connecting Enzyme-Based Reversible Logic Gates and DNA-Based Reversible Logic Gates: Realization in a Flow Device 34414.3.1 Enzyme-Based Fredkin Gate Processing Biomolecular Signals Prior to the Bioelectronic Interface 34514.3.2 Reversible DNA-Based Feynman Gate Activated by Signals Produced by the Enzyme-Based Fredkin Gate 34814.4 Conclusions and Perspectives 351References 35215 What Is Next? Mimicking Natural Biological Information Processes 35715.1 Motivation and Goals 35715.2 Example and Discussion of Feed Forward Loops 35815.3 Enzymatic Feed-Forward Loops 36015.4 Process Design and Kinetic Modeling 36415.5 Simpler Biocatalytic Systems: Not a Feed-Forward Loop Yet 36615.6 Conclusion 367References 36816 Conclusions and Perspectives: Where Are We Going? 37116.1 Conclusions 37116.2 Perspectives 37316.2.1 Information Processing Through Complex Biological Pathways in Cells 37416.2.2 Signal-Controlled Bioelectronic Devices and Signal-Triggered Molecular Release 37516.2.3 Allosteric and Hybrid Enzymes 37516.2.4 Enzyme System Controlled by Various Chemical and Physical Signals 37716.2.5 Molecular and Nanomachines for Self-Propulsion and Logic Operation 37816.3 Final Comments 379References 380Index 383