Handbook of Cell Biosensors

Preface
Contents
About the Editor-in-Chief
Section Editors
Contributors
Part I: Introduction
	1 Introduction to Cell Biosensors Through 55 Years of Scientific Production
		Introduction
		What Is a Cell Biosensor?
		Evolution of the Research Topics from 1965 to 2020
		The ``Ideal´´ Bibliography
		Conclusions and Future Directions
		References
			References Related to Fig. 3
			1965-1990
			1991-2000
			2001-2010
			2011-2020
Part II: Fundamentals and Genetics for Cell Biosensors Applications
	2 Stress Response-Based Whole-Cell Biosensor Development: Sentinels, Serendipity, and Circuitry
		Introduction
		Foundation
		Precedents
			Baltimore
			New Haven
			Palo Alto
		Wilmington, DE
			Other Technologies Were also Advancing
			Serendipity Intervened in the Form of the Sulfonylurea Herbicides
			The Heat Shock Response
			Environmental Biotechnology
				State of the Art
					The Ames Test (Ames et al. 1973)
					Microtox (Blaise et al. 1994)
					Metal-Detecting Biosensors
					Stress Response Induction
			Conceptual Protection of Wastewater Treatment Plant Bacterial Flora
				Concept Validation
			Expanding the Paradigm at DuPont
				Parallel Efforts
				Advantages of lux-Based Whole-Cell Biosensors
			Screening for Stress-Responsive Promoters
			An Ordered Array of E. coli Promoter::lux Whole-Cell Biosensors
			Comparison of Whole-Cell Biosensor and Nucleic Acid Hybridization Measures of Gene Expression
		Coda
		References
	3 Engineering Autobioluminescent Eukaryotic Cells as Tools for Environmental and Biomedical Surveillance
		Introduction
		Whole-Cell Bioluminescent Bioreporters
		The Transition from Bioluminescence to Autobioluminescence
		Environmental Surveillance Using Autobioluminescent Yeast Bioreporters
		Biomedical Surveillance Using Autobioluminescent Human Cell Lines
		Conclusions and Future Directions
		References
	4 Biosensors of the Well-being of Cell Cultures
		Introduction
		Current Paradigms for Measurement in Bioproduction
		Sensor Architectures
		Cell Stress Signaling
			I Am Well Generally
			Stress from the External Environment
			Stress from Internal Processes
		Biosensors of Metabolites
		Conclusions and Future Directions
		References
	5 Systematic Design of a Quorum Sensing-Based Biosensor for the Detection of Metal Ions in Escherichia coli
		Introduction
		The Basic Principles of Quorum Sensing
		Design Example of QS-Based Metal Ion Biosensor
			Construction of QS-Based Metal Ion Biosensor
			Mathematical Model of QS-Based Metal Ion Biosensor
			Design Specifications for QS-Based Metal Ion Biosensor
			Design Procedure for the QS-Based Metal Ion Biosensor
		Experimental Results
		Conclusion
		Appendix
			Component Libraries
		References
	6 Riboswitches as Sensor Entities
		Introduction
		Development of Riboswitches Responsive to Small Molecule Analytes
			Aptamer Selection
			Riboswitch Selection In Vivo
			Reengineering Natural Riboswitches
			Riboswitch Selection In Vitro
			Rational and Computational Design of Synthetic Riboswitches
		Riboswitch Detection Systems
			Monitoring Functionality of Synthetic Riboswitches
			Coupling Synthetic Riboswitches with New Reporter Systems
		Riboswitch Optimization toward Sensing Requirements
			Selectivity, but at a Cost
			Biological Circuits
			Riboswitch Circuitry
			Corollary Advantages of Signal Amplification
			Tandem Riboswitches
		Applications of Synthetic Riboswitches
		Conclusions
		References
	7 Integration of Sensor Cells into Hardware Platforms
		Introduction
		Hardware Platforms for Sensor Cells
			Platform Substrate Material
			Platform Fabrication Approach
			Platform Architecture and Geometry
		Sensor Cells Immobilization onto Hardware Platforms
			Sensor Cells Immobilization Method
				Covalent Attachment
				Cross-Linking
				Affinity Binding
				Electrostatic, Van der Waals, Hydrophobic, and Ionic Interactions
				Entrapment
			Immobilization Method Biocompatibility
		Sensor Cells Bio-response Transduction to Bioelectronic Signals
			Electrochemical Transducers
				Potentiometric Transducers
				Amperometric Transducers
				Impedometric Transducers
			Optical Transducers
				Colorimetric Transducers
				Chemiluminescent Transducers
				Fluorescent Transducers
				Bioluminescent Transducers
			Mechanical Transducers
		Sensor Cells-Integrated Platform Modeling
			Sensor Cell Biological Response
			Bioelectronic Interface and Physicochemical Transducer Responses
		Conclusions and Future Directions
		References
	8 Whole-Cell-Based Fiber-Optic Biosensors
		Introduction
		Whole-Cell-Based Fiber-Optic Biosensors
			Biosensors as Analytical Tools
			Fiber-Optic Transducers
			Whole-Cell Bioreporters
			Immobilization Approaches
		Biosensors for Toxicity Monitoring
			Determining Chemicals in Water
			Determining Chemicals in Soil
			Determining Chemicals in Air
		Conclusions and Future Directions
		References
	9 Optical Approaches to Visualization of Cellular Activity
		Introduction
			Biosensors and Whole-Cell Biosensors
			Bioreporters Utilizing Natural Whole Cells
			Bioreporters Utilizing Genetically Modified Whole Cells
			Optical Detectors
		Commonly Used Reporter Genes
			Fluorescent Proteins
			Bacterial Luciferase (Lux)
			Firefly Luciferase (luc)
			β-galactosidase (lacZ)
			Multiple Reporter Proteins Within a Bioreporter Cell
		Optical Detector for Monitoring Bioreporters
			Photomultiplier Tube (PMT)
			Charge-Coupled Device (CCD) or Complementary Metal-Oxide-Semiconductor (CMOS)
		Conclusions and Future Prospects
		References
	10 Digital and Analogue Approaches to Whole-Cell Sensor Design
		Introduction
		Digital Computing
		Analog Circuits
		Mixed Signals
		Conclusions and Future Directions
		References
	11 Engineering of Sensory Proteins with New Ligand-Binding Capacities
		Introduction: What Are Bioreporters
		Sensor Elements for Bioreporters
		Strategies for Obtaining New Sensory Proteins
		Mutagenesis and Selection of Mutant Transcription Activators
		Periplasmic Binding Proteins and Selection
		Bacterial Bioreporters Based on Methylaccepting Chemotaxis Proteins
		Conclusions
		References
	12 Cell-Free Biosensors: Synthetic Biology Without Borders
		Introduction
		Background
		Accessibility of Biosensor Infrastructure
			Storage and Distribution
			Companion Devices
			Rapid Prototyping and Sensor Programmability
		Definition of Cell-Free Biosensing
		Isothermal Amplification-Based Diagnostics
			Nucleic Acid Sequence-Based Amplification (NASBA)
			Loop-Mediated Isothermal Amplification (LAMP)
			Recombinase Polymerase Amplification (RPA)
			Drawbacks of Using Isothermal Amplification Strategies for Sensing
		CFPE-Based Biosensors
		Recognition Components in Biosensors
			Riboregulators, Riboswitches, and Fluorogenic Aptamers
				Riboswitches for Nucleic Acid Sensing
				Riboswitches for Small Molecule and Protein Sensing
				Fluorogenic Aptamers and Sensor Systems
			CRISPR-Enabled Nucleic Acid Detection
			Functional DNA Molecules for Biosensing
				Functional DNA Molecules for Nucleic Acid and Protein Detection
				Amplification and Polymorphism Detection Using Dynamic DNA Nanotechnology
				DNA/Antibody Hybrid Systems for Protein and Small Molecule Detection
				Light-Sensitive Transcription Factors and Promoters
		Conclusion and Future Directions
		References
	13 Engineering Prokaryote Synthetic Biology Biosensors
		Introduction
		Synthetic Biology as an Enabling Platform for Rapid Construction and Optimization of Prokaryotic Biosensors
			A Streamlined Approach to Developing Novel Prokaryotic Biosensors
			Efficient Sensor Optimization by Standardized and Modularized Genetic Parts
			Biosensor Improvement by Directed Evolution
			Development of New Sensing Modules
				Part Mining
				Antibody-Derived Domains as Universal Sensing Modules
		Tools and Strategies from Synthetic Biology for Optimizing Biosensor Performance
			Properties of a Biosensor
			Strategies for Enhancing Selectivity
			Strategies for Lowering the Limit of Detection (LOD)
				LOD Improvement by Tuning Receptor Densities
				LOD Improvement by Tuning Intracellular Ligand Densities
			Strategies for Increasing Output Dynamic Range
			Strategies for Reducing Leakiness
				Managing Leakiness on a Transcriptional Level
					Receptor and Promoter Engineering
					Antisense Transcription
				Managing Leakiness on a Translational Level
				Managing Leakiness on a Post-translational Level
		Functional Expansion of Biosensors by Synthetic Biology
			Memory Devices
				Toggle Switches
				Recombinase-Based Memory Devices
				CRISPR/Cas-Based Memory Devices
				Other Notable Memory Devices
			Computation Modules to Integrate Signals
			Modules to Reshape Response Function
			Reporter Modules for Interfacing with Different Detection Platforms
			Biosafety Enhancing Modules
		Conclusions and Future Directions
		References
	14 Cell-Free Synthetic Biology Biosensors
		Introduction
		Cell-Free Protein Expression Platforms
			E. coli Cell-Free Systems
			Variety of Available Platforms
		Sensing Methods
			Protein-Based Sensing
			Nucleotide-Based Sensing
		Regulation with Synthetic Gene Networks
		Output
		Deployment
			Sample Processing
			Stability
			Encapsulation
		Conclusions and Future Directions
		References
	15 Genetic Circuit Design Principles
		Introduction
			Biosensors and Their Applications
			Biosensing Parameters
			Molecule-Based and Cell-Based Biosensors
			Sensing Architectures in Cell-Based Biosensors
			Advantages and Challenges of Cell-Based Biosensors
			Synthetic Biology and the Rational Design of Cell-Based Biosensors
		Principles in Design and Construction of Genetic Circuits
			Choice of Host Chassis
			Insights into the Basic Components of Genetic Circuits
			Plasmid Design and Construction
			Primer Design
			DNA Assembly
			Experimental Design Tools
		Model-Driven Approach Toward Rational Design
			Modelling Framework
			Tuning Steady-State Response Curves
			Deterministic Kinetic Modelling
			Design and Modelling Tools
			A Rational Design Optimization Workflow
		Tuning Circuit Performance
			Failure Modes and Engineering Solutions
		Conclusions and Future Perspectives
		References
	16 Fundamental Building Blocks of Whole-Cell Biosensor Design
		Introduction
		Sensing Mechanisms
			Transcriptional
			Translational
			Posttranslational
		Design Considerations
			Inputs
			Output
			Chassis
		Optimizing Biosensor Performance
			Tuning Design Parameters
			Enhancing Sensing Mechanisms
			Environmental Compatibility
		Conclusions and Future Directions
		References
	17 Mammalian Cell-Based Biosensors
		Introduction
		Reporter Gene Constructs and Optical Detection
		Electric Cell-substrate Impedance Sensing
		Quartz Microbalance Sensing
		Three-Dimensional Cell-Based Biosensors Based on Synthetic Scaffolds
		References
	18 Mammalian Synbio Sensors
		Introduction
		Transcriptional Biosensors´ Architecture
		Input Sensing Coupled to Synthetic Transcriptional Systems
		Biosensors with Endogenous Transcription Factors Coupled to Synthetic Promoters
		Other Sensors That Connect to a Transcriptional Response
		Biosensors That Respond to Light
		Post-transcriptional Sensors
		Riboswitches and Aptazymes-Based Biosensors
			RNAi-Based Biosensors
		Post-translational Control
		Conclusion and Future Perspective
		References
	19 Environmental Biosensors: A Microbiological View
		Introduction
		Environmental Biosensors: Why Use Microorganisms?
		Metal(loid) Biosensors
			Bacteria-Based Metal(loid) Biosensors
			Bacterial-WCBs Based on Riboswitches
			Eukaryotic Microorganism-Based Metal(loid) Biosensors
		Xenobiotic Biosensors
			Bacteria-Based Xenobiotic Biosensors
		Conclusions and Future Perspectives
		References
Part III: Transducers, Materials, and Systems
	20 Live Cell Immobilization
		Introduction
		Covalent Attachment
		Adsorption
			Encapsulation
			Entrapment
		Cell Immobilization on 3D-Printed Matrices
		Whole-Cell Biosensors Based on Immobilized Microbial Cells
		Whole-Cell Biosensors Based on Immobilized Mammalian Cells
		Conclusion
		References
	21 Sol-Gel Process, Structure, and Properties
		Introduction
		The Chemistry of the Sol-Gel Process
			Inorganic Polymerization: The Example of Silica
			Controlling Inorganic Polymerization: The Alkoxide Precursors
			Organically Modified Metal Oxides
		Structural Properties of Sol-Gel Materials
			Structural Evolution upon Aging
			From Gels to Ceramics
			Controlling Porous Structures
		Properties of Sol-Gel Materials
			Chemical Properties
				Chemical Composition
				Chemical Stability
				Surface Reactivity
				Compatibility with Processing Techniques
			Physical Properties
				Optical and Mechanical Properties
				Specific Properties
			Biological Properties
				Cytocompatibility
				Biocompatibility
		Conclusions and Future Directions
		References
	22 Acoustic Transducer and Its Applications in Biosensors
		Introduction
		Acoustic Transducer
		Acoustic Wave Devices
			Quartz Crystal Microbalance
			Film Bulk Acoustic Resonator
			Rayleigh Wave
			Shear-Horizontal Surface Acoustic Wave
			Surface Transverse Wave
			Love Wave
			Shear-Horizontal Acoustic Plate Mode
			Flexural Plate Wave
		Conclusions and Future Directions
		References
	23 Acoustic Biosensors for Cell Research
		Introduction
		Overview of Acoustic Wave Biosensors
			Basic Parts of Acoustic Wave Biosensors
			Fundamentals and Categories of Acoustic Wave Biosensors
				Bulk Acoustic Wave (BAW) Sensors
					Quartz Crystal Microbalance (QCM)
						Bulk Acoustic Wave (BAW) Sensors
					Shear Horizontal Acoustic Plate Mode (SH-APM)
				Surface Acoustic Wave (SAW) Sensors
		Assembly of Puzzle Pieces to Design Biosensor Architectures
		Applications of Acoustic Biosensors
			Acoustic Biosensors for Cell Mimicry: Lipid Membrane-Based Biosensor
			Acoustic Biosensors for Cell Behavior: Whole Cell-Based Biosensors
			Acoustic Biosensors for Cell Detection
			Cells as Sensors
		Conclusion
		References
	24 Electrodes for Cell Sensors Interfacing
		Introduction
		Electrode Materials
			Electrode Nanomaterials
			Electrode Classification
		Substrate
			Architecture
			Patterning
		Electrode Patterning by Subtractive Processes
		Electrode Patterning by Additive Processes
			Nonplanar Electrodes
		Electrode Shape Modification Using 3D Structures
		Electrode Material and Texture Modification
			3D Printed Electrodes
			Three-Dimensional Polymeric Sensors
			Metal Nanoparticle Electrodes
			The Electrode Mounting Problem
		ZnO Nanoparticle Electrodes
		Summary and Conclusions
		References
	25 New Materials for the Construction of Electrochemical Cell-Based Biosensors
		Introduction
		Generalities
			Electrochemical Approach
			Cell Viability Strategies
			Improvement in the Properties of the Whole-Cells Biosensors
		Carbon-Based Nanomaterials as Platform for Cell Biosensors
			Carbon Nanotubes
			Graphene
			Other Carbon-Based Materials
		Metallic-Based Nanomaterial as Platform for Cell Biosensors
		Wearable Sensing Devices Future Trends
			New Materials for Flexible Wearable Sensors
			New Materials for Stretchable Wearable Sensors
			New Materials for Self-healing Wearable Sensors
		Conclusions
		References
	26 Biosensors and Bioelectronics on Smartphone
		Introduction
		Smartphone-Based Electrochemistry System
			Amperometry Sensing
			Potentiometry Sensing
			Impedimetry Sensing
		Smartphone-Based Spectroscopy System
			Optical Sensing
			Electrochemical-LSPR Sensing
			Electrochemiluminescence Sensing
		NFC on Smartphone for Biosensing
			NFC-Based Wearable Devices
			NFC-Based Implanted Devices
			NFC-Based Gas Sensing Tags
		Conclusion and Future Direction
		References
Part IV: Biosensor, Market, and Innovation
	27 Business Models for Biosensors in the Food Industry
		The Food Industry
		Innovation in the Food Industry
		Technological Innovations: Product and Process
		Non-technological Innovations: Marketing and Networking
		Business Model and Business Model Innovations: What Do They Mean?
		Business Model Innovation in the Food Industry
		New Trends and Future Challenges in Food Industry
		Business Model Innovation Enabled by Biosensors
		Conclusions
		References
	28 Biosensors: Ethical, Regulatory, and Legal Issues
		Introduction
		Biosensor: Definition, Emergence, and Applications
		Biosensors: Ethics, Regulation, and Law
			Ethical Issues
				Access to Health Care, Nondiscrimination, and Equal Opportunities for all
				Animal Testing and Medical Research with Human Being
				Informed Consent
				Privacy and Personal Data Protection Issues
				Citizen´s Right to Information
			Legal Regulations: An Overview
			Legal Issues
				Medical Device
				Informed Consent
				Consumer Protection
				Product Liability
				Personal Information Protection
				Cybersecurity
				Environmental Law Principles
		Biosensors, Ethical, Legal, and Regulatory Responses: An Evaluation
		Last Few Words
		References
	29 University-Industry Relationships for the Development and Commercialization of Biosensors
		The Biosensor Innovation Hub and the Role of Industry
		Methodology
		Established University Clusters in Cell-Based Biosensing
			The Scientific Frame and the Orientation of the Research
			The Collaborative Framework
		The Innovation Environment and the Role of Industry
		Concluding Remarks on Current Aspects and Future Trends
		References
Part V: Applications of Cells Biosensors
	30 International Organization of Standards for Measurement Validation: Food Analysis
		Introduction
			Analytical Method Quality Assurance: Where Does Method Validation Fit in
		Finding One´s Way Around the Maze of Standards and Guidelines
		What Is Involved in Validating a Method
			Different Approaches to Method Validation
			The Key Stages of a Criteria-Based Approach to Method Validation
			Method Performance Criteria
				Accuracy (Trueness and Precision)
				Measurement Bias, Recovery
				Repeatability, Intermediate Precision, Reproducibility
				Working Range (Limits of Detection, Limits of Quantification, Linearity)
				Ruggedness/Robustness
				Selectivity
		Validating a Method for Analytes with Regulatory or Action Limits
		Validating an Alternative or Proprietary Method Against a Reference Method
		Validating a Qualitative or Semi-Quantitative Screening Method
		Further Requirements for Internal Quality Control and Laboratory Accreditation
			Internal Quality Control (IQC)
			Proficiency Testing (PT) Schemes
			Laboratory Accreditation
		Conclusions and Future Directions
		References
	31 Nutrient Detection with Whole-Cell Biosensors
		Introduction
			Whole-Cell Biosensors for Carbohydrate Detection
			Whole-Cell Biosensors for Amino Acid Assays
			Whole-Cell Biosensors for Vitamins Analysis
			Whole-Cell Biosensors for Determination of Glycolysis Products
			Whole-Cell Biosensors for Other Nutrients Analytes
		Typical Technologies Involved in the Applications of Whole-Cell Biosensors
			Whole-Cell Biosensors Based on Nanotechnology
			Immobilization of Biomaterials for Biosensor Applications
			Molecular Biology Technology in Whole-Cell Biosensor
		Conclusions and Perspectives of Whole-Cell Biosensors in Nutrient Detection
		References
	32 Luminescent Microbial Bioassays and Microalgal Biosensors as Tools for Environmental Toxicity Evaluation
		Introduction
		Naturally Bioluminescent Microorganisms for Environmental Toxicity Evaluation
		Recombinant Optical Microbial Bioreporter Assays and their Application in Toxicity Evaluation
			Turn-Off Bioreporters
			Oxidative Stress Bioreporters
		Microalgal-Based Biosensors
			Electrochemical Microalgal Biosensors
			Optical Microalgal Biosensors
		Conclusions and Future Directions
		References
	33 Detection and Effects of Metal and Organometallic Compounds with Microbial Bioluminescence and Raman Spectroscopy
		Introduction
		Metals and Organometallic Compounds
			Definition
			Toxic Effects and Regulations
		Measurement by Microbial Bioluminescence
			Toxicity Assessment
				Overall Effect
				Specific Effects
			Bioavailable/Bioaccessible Fraction Assessment
			Field Application: Biosensor Development
			Advantages, Limits, and Perspectives
		Evaluation of Toxicity by Raman Spectroscopy
			Principle of Raman Spectroscopy
			Non-targeted Approach for Measuring the Toxicity of Heavy Metals by Raman Spectroscopy
			Advantages, Limits, and Perspectives
		References
	34 Microbial Biosensors for the Detection of Organic Pollutants
		Introduction
		Naphthalene
		Benzene, Toluene, Ethylbenzene and Xylene (BTEX)
		Aliphatic Hydrocarbons
		Nitroaromatic Explosives
		Pharmaceuticals
			Hormones and Endocrine-Disrupting Compounds
			Antibiotics
		Pesticides and Other Agrochemicals
		Halogenated Organic Pollutants
		Conclusions and Future Outlook
		References
	35 Microbial Fuel Cells, Concept, and Applications
		Introduction
		History
		Bioelectrochemical Systems and Microbial Fuel Cells
		A Range of Organics to be Degraded
		Microbial Fuel Cell Main Components
			Anode Materials and Development
			Cathode Materials and Development
			Membrane and Separator Materials
		MFC Designs
		Scaling-Up for Energy Production
		Microbial Fuel Cell for Wastewater Treatment
		Microbial Fuel Cell and Practical Applications
		Microbial Fuel Cell as Biosensor
			Sensors for BOD Monitoring
			Sensors for Toxicity Assessment
			Sensors for Microbial Activity Monitoring
			Microbial Fuel Cells (MFCs) for Monitoring Bio-Corrosion
			Other Sensor Applications
		References
	36 Organic Matter BOD Biosensor Monitoring
		Introduction
		Appearance of Microbial BOD Biosensor
		Progress in Microbial BOD Biosensor
		Microbial Fuel Cell (MFC)-Based BOD Biosensors
		Selection of Microorganisms for BOD Biosensor
		Immobilization Technique for Microorganisms
		Autonomous Microbial BOD Biosensor
		Conclusions and Future Directions
		References
	37 Cell-Based Biosensor for Rapid Screening of Pathogens and Toxins
		Introduction
		Cell-Based Biosensor
			Microbes as Biosensor
			Mammalian Cells as Biosensor
			B Cell
			Vero Cell
			Mast Cell
			Neuron
		Conclusions
		References
	38 Application of Bacterial Whole-Cell Biosensors in Health
		Introduction
		WCB for Cancer Diagnosis and Treatment
		WCB for Antibiotic Discovery and Identification
		WCB for In Vitro Assessment of Health Risk
		Conclusions and Future Perspectives
		References
	39 Smartphone-Based Cell Detection
		Introduction
		Smartphone Camera as Light Detector
		Smartphone-Based Fluorescence Platforms
		Smartphone-Based Bioluminescence Platforms
		Smartphone-Based Colorimetric Platforms
		Smartphone-Based Electrochemical Platforms
		Turning Smartphones into Microscopes
		Conclusion
		References
Index