Introduction to Fluorescence Sensing: Volume 2: Target Recognition and Imaging

Preface
Contents
1 Principles Governing Molecular Recognition
	1.1 Multivalency: The Principle of Molecular Recognition
		1.1.1 Multivalent Pattern of Molecular Interactions
		1.1.2 Energetics and Kinetics in Molecular Recognition
		1.1.3 Reversibility in Molecular Interactions and Mass Action Law
	1.2 Lock-And-Key, Induced Fit, Conformation Selection and Induced-Assisted Folding Models
	1.3 Realization of Principles of Molecular Recognition in Fluorescence Sensing
		1.3.1 The Output Parameters Used in Fluorescence Sensors
		1.3.2 Different Strategies in Fluorescence Sensing
	1.4 Molecular Recognition of Different Strength and Specificity
		1.4.1 Sensors Providing Strong Highly Specific Binding
		1.4.2 Sensors Based on Competitive Target Binding
		1.4.3 Sensors Based on Reversible Specific Binding and Operating in a Large Volume
	1.5 Direct Reagent-Independent Sensing
	1.6 Simultaneous Analysis of Multiple Analytes
		1.6.1 Systems for Detection of Multiple Analytes
		1.6.2 Specific Target Recognition Versus Pattern Recognition Sensor Arrays
	1.7 Sensing and Thinking. Current Trends that Should Be Highlighted
	References
2 Basic Theoretical Description of Sensor-Target Binding
	2.1 Parameters that Need to Be Optimized in Every Sensor
		2.1.1 The Limit of Detection and Sensitivity
		2.1.2 Dynamic Range of Detectable Target Concentrations
		2.1.3 The Sensor Selectivity
		2.1.4 Multivalent Binding and Cooperativity
	2.2 Determination of Binding Constants
		2.2.1 Dynamic Association-Dissociation Equilibrium
		2.2.2 Determination of Kb by Titration
		2.2.3 Determination of Kb by Serial Dilutions
	2.3 Modeling the Analyte Binding Isotherms
		2.3.1 Receptors Free in Solution or Immobilized to a Surface
		2.3.2 Bivalent and Polyvalent Reversible Target Binding
		2.3.3 Reversible Binding of Analyte and Competitor
		2.3.4 Reversible Interactions in a Small Volume
	2.4 Kinetics of Target Binding
	2.5 Formats for Fluorescence Detection
		2.5.1 Linear Response Format
		2.5.2 Intensity-Weighted Format
	2.6 Sensing and Thinking. How to Provide the Optimal Quantitative Measure of Target Binding?
	References
3 Recognition Units Built of Small Macrocyclic Molecules
	3.1 Crown Ethers and Cryptands: Macrocyclic Hosts for Ions
	3.2 Cavity-Forming Compounds. Structures and Properties
		3.2.1 Cyclodextrins
		3.2.2 Calix[n]arenes
		3.2.3 Cucurbit[n]urils
		3.2.4 Pillar[n]arenes
		3.2.5 Comparison of Properties and Prospects of Supramolecular Macrocycles
	3.3 Porphyrins and Porphyrinoids. Unique Coupling of Recognition and Reporting
	3.4 Sensing and Thinking. The Recognition Properties of Parent Binders and of Their Derivatives
	References
4 Sensors Based on Peptides and Proteins as Recognition Units
	4.1 Designed and Randomly Synthesized Peptides
		4.1.1 The Development of Peptide Sensors
		4.1.2 Randomly Synthesized Peptides, Why They Do Not Fold?
		4.1.3 Template-Based Approach
		4.1.4 The Exploration of ‘Mini-Protein’ Concept
		4.1.5 Molecular Display Including Phage Display
		4.1.6 Peptide Binders for Protein Targets and the Prospects of Peptide Sensor Arrays
		4.1.7 Antimicrobial Peptides and Their Analogs
		4.1.8 Advantages of Peptide Technologies and Prospects for Their Development
	4.2 Sensors Based on Protein-Based Display Scaffolds
		4.2.1 Engineering the Binding Sites by Mutations
		4.2.2 Scaffolds Employing Proteins of Lipocalin Family
		4.2.3 Other Protein Scaffolds
	4.3 Natural Ligand-Binding Proteins and Their Modifications
		4.3.1 Bacterial Periplasmic Binding Protein (PBP) Scaffolds
		4.3.2 Engineering PBPs Binding Sites and Response of Environment-Sensitive Dyes
		4.3.3 Serum Albumins
	4.4 Antibodies and Their Recombinant Fragments
		4.4.1 Assay Formats Used for Immunosensing
		4.4.2 The Types of Antibodies and Their Fragments Used in Sensing
		4.4.3 Prospects for Antibody Technologies
	4.5 Sensing and Thinking. The Application Range and Benefit from Peptide and Protein Sensors
	References
5 Nucleic Acids as Scaffolds and Recognition Units
	5.1 DNA and RNA Fragments in Hybridization-Based Sensing
		5.1.1 The Types of Nucleic Acid Recognition Units
		5.1.2 Fluorescence Reporting in Hybridization Assays
	5.2 Nucleic Acid Aptamers
		5.2.1 Selection and Production of Aptamers
		5.2.2 Integration with Fluorescence-Responding Units
		5.2.3 Aptamer Applications and Comparison with Other Binders
	5.3 G-quadruplex-Based Analytical Sensing Platforms
		5.3.1 Production and Properties of G-quadruplexes
		5.3.2 Fluorescence Reporters for G-quadruplex Structures
		5.3.3 Applications of G-quadruplex Sensing Technology
	5.4 The DNA i-motif in Sensing
	5.5 Sensing and Thinking: The Versatile Recognizing Power of Nucleic Acids
	References
6 Self-assembled, Porous and Molecularly Imprinted Supramolecular Structures in Sensing
	6.1 Molecular Recognition on Supramolecular Scale
		6.1.1 Assembly of Organic and Inorganic Functionalities
		6.1.2 The Major Building Blocks
		6.1.3 Realization of Multiple Recognition Sites in Self-assembled Structures
	6.2 Formation and Operation of Supramolecular Fluorescent Sensors
	6.3 Fluorescence Sensing with Nanoporous and Mesoporous Materials
		6.3.1 Sensing Designed on the Basis of Mesoporous Silica
		6.3.2 The Hydrogel Layers in Sensor Technologies
		6.3.3 Porous Structures Formed of Organic Polymers
		6.3.4 Metal–Organic Frameworks
	6.4 Molecularly Imprinting in the Polymer Volume
		6.4.1 The Principle of Formation of Imprinted Polymers
		6.4.2 The Coupling of Molecular Recognition with Reporting Functionality
		6.4.3 Imprinted Polymers in the Form of Nanoparticles and Microspheres
		6.4.4 Exploration of Collective Properties of Fluorescent Dye Aggregates and Conjugated Polymers
		6.4.5 Nanomaterials with Molecularly Imprinted Sensing
		6.4.6 Formation of Nanocomposites with Molecular Imprinting Functionalities
	6.5 Sensing and Thinking: Extending the Fluorescence Sensing Possibilities with Designed and Spontaneously Formed Nano-ensembles
	References
7 Fluorescence Sensing Operating at Interfaces
	7.1 The Structural and Dynamic Properties of Surfaces and Interfaces
		7.1.1 Gas–Liquid Interfaces
		7.1.2 Liquid–Liquid Interfaces
		7.1.3 Solid–Liquid Interfaces
		7.1.4 Solid–Solid Interfaces
	7.2 The Self-assembled Functional Surfaces
		7.2.1 Formation of Functional Surfaces
		7.2.2 The Active Surfaces in Active Use
		7.2.3 Organic Dyes Forming Active Surfaces
		7.2.4 Supported Layers of Conjugated Polymers
	7.3 Preferential Location of Solutes in the Systems of Structural Heterogeneity and on Active Surfaces
	7.4 Binding Affinity at Interfaces
	7.5 Surface-Imprinted Sensors and Biosensors
		7.5.1 Surface Imprinting on Support
		7.5.2 Nanoparticle-Based Surface Imprinting
	7.6 Sensing and Thinking. The Strong Contribution of Surfaces and Interfaces to Sensor Technologies
	References
8 Fluorescence Sensing of Physical Parameters and Chemical Composition in Gases and Condensed Media
	8.1 Sensing the Physical Parameters of Environment: Temperature and Pressure
		8.1.1 Molecular Thermometry
		8.1.2 Luminescence for Pressure Measurement
	8.2 Fluorescence Studies in a Gas Phase
		8.2.1 Optimal Receptors for the Gas State Molecules
		8.2.2 Determining the Natural Gas Phase Composition
		8.2.3 Detection of Hydrocarbon Gasses
		8.2.4 Dangerous Compounds and Explosives
	8.3 Characterization of Solvents and Their Intermolecular Interactions
		8.3.1 Solvent Polarity Scaling
		8.3.2 Physical Modeling of Solvent Polarity Effects
		8.3.3 Wavelength-Ratiometric Response to Solvent Polarity
		8.3.4 Solvent Polarity and Hydrogen Bonding
		8.3.5 Preferential Solvation in Mixed Solvents
	8.4 Fluorescence Probing of Molecular Dynamics in Liquid State
		8.4.1 Rotating Sphere Approach
		8.4.2 Segmental Probe Rotations and Their Application
		8.4.3 Molecular Rotors Relaxing to TICT State
		8.4.4 Dyes Exhibiting the Excited-State Planarization
	8.5 Dynamics of Solvent Relaxations
		8.5.1 Solvation Dynamics Studied by Time-Resolved Spectroscopy
		8.5.2 Site-Selective Dynamics in Molecular Ensembles
	8.6 Detection of Traces of Water in Low-Polar Liquids
	8.7 Condensed-Phase Media of Special Interest: Supercritical Liquids, Ionic Liquids and Liquid Crystals
		8.7.1 Molecular Structure and Dynamics in Supercritical Fluids
		8.7.2 The Properties of Ionic Liquids
		8.7.3 Liquid Crystals
	8.8 The Structure and Dynamics in Polymers
		8.8.1 Monitoring the Polymerization Process
		8.8.2 Structures and Structural Transitions in Polymers
	8.9 Sensing and Thinking. The Value of Information on Correlation of Macroscopic and Microscopic Variables
	References
9 Quantitative Fluorescent Detection of Ions
	9.1 Fluorophore-Based Determination of pH
	9.2 Determination of Concentration of Cations
		9.2.1 Fluorescent Sensors for Alkali and Alkaline Earth Metal Cations
		9.2.2 Sensing the Transition Metal Ions
		9.2.3 Detection of Heavy Metal Ions
		9.2.4 Potential for λ-Ratiometric Sensing Based on Excited-State Intramolecular Proton Transfer
	9.3 Sensing the Anions
	9.4 Sensing and Thinking. Selecting the Ways to Apply the Principle of Wavelength-Ratiometry to Sensing Ions
	References
10 Detection and Imaging of Small Molecules of Biological Significance
	10.1 Gaseous Molecules of Physiological Signaling—Gasotransmitters
		10.1.1 Carbon Monoxide
		10.1.2 Nitric Oxide
		10.1.3 Hydrogen Sulfide
	10.2 Oxygen and Reactive Oxygen Species
		10.2.1 Determination of Oxygen Concentration
		10.2.2 Hydrogen Peroxide
		10.2.3 Hypochlorous Acid/Hypochlorite
	10.3 Detection of Biothiols (Cysteine, Homocysteine and Glutathione)
	10.4 Biologically Relevant Phosphate Anions
	10.5 Adenosine and Guanosine Triphosphates
	10.6 Redox Cofactors NADH/NAD+ and NAD(P)H/ NAD(P)+
	10.7 Sensing and Thinking. The Problem of Simultaneous Sensing and Imaging of Many Analytes
	References
11 Detection, Structure and Polymorphism of Nucleic Acids
	11.1 DNA Detection and Analysis of Its Conformation
		11.1.1 Double-Stranded DNA Structures
		11.1.2 Analysis of Single-Stranded DNA
		11.1.3 Identification of Non-canonical DNA Forms
	11.2 Recognition of Specific DNA Sequences by Hybridization
		11.2.1 The Microarray ‘DNA Chip’ Hybridization Techniques
		11.2.2 Sandwich Assays in DNA Hybridization
		11.2.3 Molecular Beacon Technique
		11.2.4 Specific DNA Sensing with the Aid of Conjugated Polymer
		11.2.5 DNA Structure Recognition with Peptide Nucleic Acids
		11.2.6 The Use of Nanomaterials in DNA Hybridization
	11.3 Probing on the Level of Single Nucleic Acid Bases
		11.3.1 Design of Local Site Responsive Sensors
		11.3.2 Operation with Parameters of Fluorescence Emission
		11.3.3 Probing the Single-Nucleotide Polymorphism
	11.4 RNA Detection, Analysis and Imaging
		11.4.1 RNA Detection in Cells
		11.4.2 RNA G-quadruplexes
	11.5 Sensing and Thinking. Increase of Sensitivity: Amplify the Target or the Detection System?
	References
12 Fluorescence Detection of Peptides, Proteins, Glycans
	12.1 Targeting Peptides
	12.2 Detection of Protein Targets
		12.2.1 Determination of Total Protein Content
		12.2.2 Labeling the Surface of Native Proteins
		12.2.3 The Recognition of Protein Surface by Small Molecules
		12.2.4 Protein Sensing with Peptide, Protein and Nucleic Acid Receptors
		12.2.5 Molecularly Imprinted Polymers in Protein Sensing
		12.2.6 Sensor Arrays and Machine Learning Algorithms
	12.3 Analysing Pathological β-Aggregated Forms of Proteins
		12.3.1 Organic Dyes as the Sensors for β-Sheets
		12.3.2 Following the Kinetics of Amyloid Formation
	12.4 Polysaccharides and Glycoproteins
	12.5 Sensing and Thinking. Precise Affinity Sensors or Chemical Noses?
	References
13 Detection of Harmful Microbes
	13.1 Detection and Identification of Vegetative Bacteria
		13.1.1 The Whole-Cell Detection
		13.1.2 Detection by Characteristic Features of Cell Surface
		13.1.3 Detection Based on Bacterial Genome Analysis
	13.2 Discovery and Recognition of Bacterial Spores
	13.3 Identification and Analysis of Biofilms
	13.4 Detection of Toxins
	13.5 Sensors for Viruses
		13.5.1 Nucleic Acid Based Detection
		13.5.2 Recognition of Viruses by Antibodies and Aptamers
	13.6 Sensing and Thinking. Future Trends in Pathogen Detection: Single-Particle Sensitivity Versus Signal Amplification
	References
14 Clinical Diagnostics Ex-Vivo Based on Fluorescence
	14.1 Biological Fluids Available for Sensing
	14.2 Detection of Disease Biomarkers
		14.2.1 Diagnostics of Cancer
		14.2.2 Diagnostics with Cardiac Biomarkers
		14.2.3 The Markers of Autoimmune Disorders
		14.2.4 Kidney-Related Diseases
		14.2.5 Neurodegenerative Diseases
	14.3 Glucose Sensing in Diagnosis and Treatment of Diabetes
	14.4 Uric Acid
	14.5 Cholesterol
	14.6 Sensing and Thinking. The Era of Digital Health is Approaching?
	References
15 Imaging and Sensing Inside the Living Cells. From Seeing to Believing
	15.1 Modern Fluorescence Microscopy
		15.1.1 Epi-Fluorescence Microscopy
		15.1.2 Total Internal Reflection Fluorescence Microscopy (TIRF)
		15.1.3 Confocal Fluorescence Microscopy
		15.1.4 Programmable Array Microscope
		15.1.5 Two-Photon and Three-Photon Microscopy
		15.1.6 Time-Resolved and Time-Gated Imaging
		15.1.7 Wavelength-Ratiometric Imaging
		15.1.8 Traditional Far-Field Fluorescence Microscopy: Advances and Limitations
	15.2 Far-Field Super-Resolution Microscopy
		15.2.1 Breaking the Diffraction Limit
		15.2.2 Stimulated Emission Depletion (STED) Microscopy
		15.2.3 Single Molecule Localization Microcopy
		15.2.4 Structured Illumination Microscopy (SIM)
		15.2.5 Correlative Light and Electron Microscopy
	15.3 Sensing and Imaging on a Single Molecule Level
		15.3.1 The Reason to Study Single Molecules
		15.3.2 Single-Molecular Studies in Solutions
		15.3.3 The Studies of Molecular Motions and Interactions
		15.3.4 Single Molecules Inside the Living Cells
	15.4 Site-Specific Intracellular Labeling and Genetic Encoding
		15.4.1 Attachment of Fluorescent Reporter to Any Cellular Protein
		15.4.2 Genetically Engineered Protein Labels
		15.4.3 Co-synthetic Incorporation of Fluorescence Dyes
	15.5 Advanced Nanosensors Inside the Cells
		15.5.1 Fluorescent Dye-Doped Nanoparticles
		15.5.2 The Quantum Dots Applications in Imaging
		15.5.3 Carbon Nanoparticles in Cell Research
	15.6 The Studies of Intracellular Motions
		15.6.1 Single-Particle Tracking
		15.6.2 Viscosimetry Inside the Living Cell
	15.7 Sensing Within the Cell Membrane
		15.7.1 Membrane Structure and Dynamics
		15.7.2 Lipid Asymmetry and Apoptosis
		15.7.3 Sensing the Membrane Potential
		15.7.4 Visualizing Membrane Receptors
	15.8 Sensing and Thinking. Intellectual and Technical Means to Go Deeper into Cellular Functions
	References
16 Fluorescent Imaging In Vivo
	16.1 Optical Properties of Biological Tissues
		16.1.1 Light Propagation Through Tissues
		16.1.2 Optical Windows in Near-Infrared
	16.2 Fluorescence Contrast Agents and Reporters
		16.2.1 Organic Dyes and Their Nanocomposites
		16.2.2 Nanomaterials
	16.3 Optimal Imaging Techniques
		16.3.1 Imaging and Microscopy in NIR-I Window
		16.3.2 Instrumentation for NIR-II Range
	16.4 The Studies on the Level of Tissue Imaging
		16.4.1 Contrasting the Blood Vessels and Lymph Nodes
		16.4.2 Monitoring Inflammatory Diseases and Response to Therapy
		16.4.3 Imaging Cancer Tissues
	16.5 Fluorescence Image-Guided Surgery
	16.6 Cell Tracking Inside the Living Body
		16.6.1 The Procedures for Cell Labeling
		16.6.2 Tracking Hematopoietic and Cancer Cells
		16.6.3 Tracing the Stem Cells
	16.7 Combination of Fluorescence with Photoacoustic Tomography
	16.8 Sensing and Thinking. Towards the Progress in Functional Bioimaging
	References
17 Phototheranostics: Combining Targeting, Imaging, Therapy
	17.1 Light in Theranostics Technologies
	17.2 Photothermal Therapy
		17.2.1 The Choice of Wavelengths
		17.2.2 The Choice of Materials
	17.3 Photodynamic Therapy
		17.3.1 The Factors Needed for Realizing Photodynamic Therapy
		17.3.2 The Mechanisms of Tumor Destruction
	17.4 Combining All Power of Phototheranostics
		17.4.1 Photoactivation of Prodrugs and Controlling the Drug Release
		17.4.2 Photoimmunotherapy with Near-Infrared Light
		17.4.3 Non-oncological Clinical Applications
		17.4.4 Photothermal and Photodynamic Inactivation of Harmful Microbes
	17.5 Sensing and Thinking. The Strategy of Controlling the Diagnostics and Treatment by Light
	References
18 Fluorescent Light Opening New Horizons
	18.1 Genomics, Proteomics and Other ‘Omics’
		18.1.1 Genomic and Gene Expression Analysis
		18.1.2 The Analysis of Proteome
		18.1.3 Addressing Interactome
		18.1.4 Outlook. Analysis on a Single-Cellular Level
	18.2 Unprecedented Scale of Complexity, How to Deal With It?
		18.2.1 Combinatorial Synthetic Approach on a New Level
		18.2.2 Advanced Sensors in Discovery of New Products
		18.2.3 Electronic (Photonic) Noses and Tongues
		18.2.4 Realizing the Pattern Recognition Principle
		18.2.5 Navigating Massive Datasets: Transforming Information into Knowledge
	18.3 New Level of Clinical Diagnostics
		18.3.1 The Progressing Sensor Developments
		18.3.2 The Sensing in Whole Blood
		18.3.3 Gene-Based Diagnostics
		18.3.4 Confronting the Global Virus Pandemic
	18.4 Sensors Promising to Change the Society
		18.4.1 Industrial Challenges and Safe Workplaces
		18.4.2 Biosensor-Based Lifestyle Management
		18.4.3 Wearable, Implantable and Digestible Miniature Sensors Are a Reality
		18.4.4 Living in a Safe Environment and Eating Safe Products
	18.5 Sensing and Thinking. Where Do We Stand and Where Should We Go?
	References
Epilogue
Index