Introduction to Fluorescence Sensing

Transcription

1 Alexander P. Demchenko Introduction to Fluorescence Sensing Springei

2 Contents Preface Introduction v xxi 1 Basic Principles Overview of Strategies in Molecular Sensing Basic Definitions: Sensors and Assays, Homogeneous and Heterogeneous Principles of Sensor Operation Label-Free, General Approaches Label-Free, System-Specific Approaches Label-Based Approaches Labeled Targets in Fluorescence Assays Arrays for DNA Hybridization Labeling in Protein-Protein and Protein-Nucleic Acid Interactions Micro-Array Immunosensors Advantages and Limitations of the Approach Based on Pool Labeling Competitor Displacement Assay Unlabeled Sensor and Labeled Competitor in Homogeneous Assays Labeling of Both Receptor and Competitor Competition Involving Two Binding Sites Advantages and Limitations of the Approach Sandwich Assays Sensing the Antigens and Antibodies Ultrasensitive DNA Detection Hybridization Assays Advantages and Limitations of the Approach Catalytic Biosensors Enzymes as Sensors Ribozymes and Deoxyribozymes Sensors Labeling with Catalytic Amplification 26 vii

3 viii Contents Advantages and Limitations of the Approach Direct Reagent-Independent Sensing The Principle of Direct 'Mix-and-Read' Sensing Contact and Remote Sensors Advantages and Limitations of the Approach 31 Sensing and Thinking 1: How to Make the Sensor? Comparison of Basic Principles 32 Questions and Problems 32 References 34 2 Theoretical Aspects Parameters that Need to Be Optimized in Every Sensor The Limit of Detection and Sensitivity Dynamic Range of Detectable Target Concentrations Selectivity Determination of Binding Constants Dynamic Association-Dissociation Equilibrium Determination of K b by Titration Determination of К ъ by Serial Dilutions Modeling the Ligand Binding Isotherm Receptors Free in Solution or Immobilized to a Surface Bivalent and Polyvalent Reversible Target Binding Reversible Binding of Ligand and Competitor Interactions in a Small Volume Kinetics of Target Binding Formats for Fluorescence Detection Linear Format Intensity-Weighted Format 59 Sensing and Thinking 2: How to Provide the Optimal Quantitative Measure of Target Binding 61 Questions and Problems 62 References 63 3 Fluorescence Detection Techniques Intensity-Based Sensing Peculiarities of Fluorescence Intensity Measurements How to Make Use of Quenching Effects Quenching: Static and Dynamic Non-linearity Effects Internal Calibration in Intensity Sensing Intensity Response as a Choice for Fluorescence Sensing Anisotropy-Based Sensing and Polarization Assays Background of the Method 77

4 3.2.2 Practical Considerations Applications Comparisons with Other Methods of Fluorescence Detection Lifetime-Based Fluorescence Response Physical Background Technique Time-Resolved Anisotropy Applications Extension to Reporter Response Based on Phosphorescence Comparison with Other Fluorescence Detection Methods Excimer and Exciplex Formation Application in Sensing Technologies Comparison with Other Fluorescence Reporter Techniques Förster Resonance Energy Transfer (FRET) Physical Background of the Method FRET Modulated by Light Applications of FRET Technology FRET to Non-fluorescent Acceptor Comparison with Other Detection Methods Wavelength-Shift Sensing The Phy sic al В ackground В ehind the Wavelength Shifts The Measurements of Wavelength Shifts in Excitation and Emission Wavelength-Ratiometric Measurements Application in Sensing Comparison with Other Fluorescence Reporting Methods Two-Band Wavelength-Ratiometric Sensing with a Single Dye Generation of a Two-Band Ratiometric Response by Ground-State Isoforms Excited-State Reactions Generating a Two-Band Response in Emission Excited-State Intramolecular Proton Transfer (ESIPT) Prospects for Two-Band Ratiometric Recording Ill Sensing and Thinking 3: The Choice of Fluorescence Detection Technique and Optimization of Response 112 Questions and Problems 112 References 114 ix

5 x Contents 4 Design and Properties of Fluorescence Reporters Organic Dyes General Properties of Fluorescence Reporter Dyes Dyes for Labeling The Dyes Providing Fluorescence Response The Environment-Sensitive (Solvatochromic) Dyes Hydrogen Bond Responsive Dyes Electric Field Sensitive (Electrochromic) Dyes Supersensitive Multicolor Ratiometric Dyes The Optimal FRET Pairs Phosphorescent Dyes and the Dyes with Delayed Fluorescence Combinatorial Discovery and Improvement of Fluorescent Dyes Prospects Luminescent Metal Complexes Structure and Spectroscopy of Complexes of Lanthanide Ions Lanthanide Chelates as Labels and Reference Emitters Dissociation-Enhanced Lanthanide Fluoroimmunoassay (DELFIA) Switchable Lanthanide Chelates Transition Metal Complexes that Exhibit Phosphorescence Metal-Chelating Porphyrins Prospects Dye-Doped Nanoparticles and Dendrimers The Dye Concentration and Confinement Effects Nanoparticles Made of Organic Polymer Silica-Based Nanoparticles Dendrimers Applications of Dye-Doped Nanoparticles in Sensing Summary and Prospects Semiconductor Quantum Dots and Other Nanocrystals The Properties of Quantum Dots Stabilization and Functionalization of Quantum Dots Applications of Quantum Dots in Sensing Nanobeads with Quantum Dot Cores Porous Silicon and Silicon Nanoparticles Other Fluorescent Nanocrystal Structures Prospects Noble Metal Nanoparticles and Molecular Clusters Light Absorption and Emission by Noble Metal Nanoparticles 172

6 Contents xi Preparation and Stabilization Gold and Silver Nanoparticles as Fluorescence Quenchers Nanoparticles and Molecular Clusters as Emitters Metal Nanoclusters Prospects Fluorescent Conjugated Polymers Structure and Spectroscopic Properties Possibilities for Fluorescence Reporting in Sensor Design Nanocomposites Based on Conjugated Polymers Prospects Visible Fluorescent Proteins Green Fluorescent Protein (GFP) and Its Colored Variants Labeling and Sensing Applications of Fluorescent Proteins Other Fluorescent Proteins Finding Simple Analogs of Fluorescent Proteins Prospects 185 Sensing and Thinking 4: Which Reporter to Choose for Particular Needs? 185 Questions and Problems 186 References Recognition Units Recognition Units Built of Small Molecules Crown Ethers, Cryptands, Polyhydroxilic and Boronic Acid Derivatives Cyclodextrins Calixarenes Porphyrins Dendrimers Prospects Antibodies and Their Recombinant Fragments The Types of Antibodies Used in Sensing The Assay Formats Used for Immunoassays Prospects for Antibody Technologies Ligand-Binding Proteins and Protein-Based Display Scaffolds Engineering the Binding Sites by Mutations Bacterial Periplasmic Binding Protein (PBP) Scaffolds Engineering PBPs Binding Sites and the Response of Environment-Sensitive Dyes Scaffolds Based on Proteins of the Lipocalin Family 217

7 xii Contents Other Protein Scaffolds Prospects Designed and Randomly Synthesized Peptides Randomly Synthesized Peptides, Why They Do Not Fold? Template-Based Approach The Exploration of the 'Mini-Protein' Concept Molecular Display Including Phage Display Antimicrobial Peptides and Their Analoges Advantages of Peptide Technologies and Prospects for Their Development Nucleic Acid Aptamers Selection and Production of Aptamers Attachment of Fluorescence Reporter, Before or After Aptamer Selection? Obtaining a Fluorescence Response and Integration into Sensor Devices Aptamer Applications Comparison with Other Binders: Prospects Peptide Nucleic Acids Structure and Properties DNA Recognition with Peptide Nucleic Acids Molecularly Imprinted Polymers The Principle of the Formation of an Imprinted Polymer The Coupling with Reporting Functionality Applications 238 Sensing and Thinking 5: Selecting the Tool for Optimal Target Recognition 238 Questions and Problems 239 References Mechanisms of Signal Transduction Basic Photophysical Signal Transduction Mechanisms Photoinduced Electron Transfer (PET) Intramolecular Charge Transfer (ICT) Excited-State Proton Transfer Prospects Signal Transduction via Excited-State Energy Transfer Directed Excited-State Energy Transfer in Multi-fluorophore Systems Light-Harvesting (Antenna) Effect Peculiarities of FRET with and Between Nanoparticles 266

8 Contents xiii The Optimal Choice of FRET Donors Lanthanides as FRET Donors Quantum Dots as FRET Donors The Optimal Choice of FRET Acceptors Prospects Signal Transduction via Conformational Changes Excited-State Isomerism in the Reporter Dyes and Small Molecules Conformational Changes in Conjugated Polymers Conformational Changes in Peptide Sensors and Aptamers Molecular Beacons Proteins Exhibiting Conformational Changes Prospects Signal Transduction via Association and Aggregation Phenomena Association of Nanoparticles on Binding a Polyvalent Target Association-Induced FRET and Quenching Integration of Molecular and Digital Worlds The Direct Recording of Digital Information from Molecular Sensors Hybrid Molecular-Digital Systems Logical Operations with Fluorescent Dyes Prospects 289 Sensing and Thinking 6: Coupling Recognition and Reporting Functionalities 289 Questions and Problems 290 References Supramolecular Structures and Interfaces for Sensing Building Blocks for Supramolecular Sensors Carbon Nanotubes Core-Shell Compositions Polynucleotide Scaffolds Peptide Scaffolds Self-Assembled Supramolecular Systems Affinity Coupling Self-Assembly Two-Dimensional Self-Assembly of S-Layer Proteins Template-Assisted Assembly Micelles: The Simplest Self-Assembled Sensors Prospects Conjugation, Labeling and Cross-linking 312

9 7.3.1 Conjugation and Labeling Co-synthetic Modifications Chemical and Photochemical Cross-linking Supporting and Transducing Surfaces Surfaces with a Passive Role: Covalent Attachments Self-Assembled Monolayers Langmuir-Blodgett Films Layer-by-Layer Approach Prospects Functional Lipid Bilayers Liposomes as Integrated Sensors Stabilized Phospholipid Bilayers Polymersomes Formation of Protein Layers over Lipid Bilayers Prospects 327 Sensing and Thinking 7: Extended Sensing Possibilities with Smart Nano-ensembles 327 Questions and Problems 328 References 329 Non-Conventional Generation and Transformation of Response Chemiluminescence and Electrochemiluminescence Chemiluminescence Enhanced Chemiluminescence Electrochemiluminescence Cathodic Luminescence Solid-State Electroluminescence Essentials of the Techniques and Their Prospects Bioluminescence The Origin of Bioluminescence Genetic Manipulations with Luciferase Bioluminescence Resonance Energy Transfer Prospects Two-Photon Excitation, Up-Conversion and Stimulated Emission Two-Photon and Multi-Photon Fluorescence Up-Conversion Technique with Nanocrystals Possessing Lanthanine Guests Sensors as Lasers and Lasers as Sensors Direct Generation of the Electrical Response Signal Light-Addressable Potentiometrie Sensors (LAPS) Photocells as Sensors Evanescent-Wave Fluorescence Sensors 354

10 Contents xv Excitation by the Evanescent Field Applications in Sensing Plasmonic Enhancement of Emission Response Surface Plasmon-Field Enhanced Fluorescence Enhancement of Dye Fluorescence Near Metal Nanoparticles Application of Metal-Nanoparticle Enhancement Microwave Acceleration of Metal-Enhanced Emission Prospects 365 Sensing and Thinking 8: Eliminating Light Sources and Photodetectors: What Remains? 366 Questions and Problems 366 References The Sensing Devices Instrumentation for Fluorescence Spectroscopy Standard Spectrofluorimeter Light Sources Light Detectors Passive Optical Elements Integrated Systems Prospects Optical Waveguides, Optodes and Surface-Sensitive Detection Optical Fiber Sensors with Optode Tips Evanescent-Field Waveguides Multi-Analyte Sensor Chips and Microarrays Fabrication Problems with Microarray Performance Read-Out and Data Analysis Applications of Microarrays Prospects Microsphere-Based Arrays Barcodes for Microsphere Suspension Arrays Reading the Information from Microparticles Prospects Microfluidic Devices Fabrication and Operation of a Lab-on-a-Chip Microfluidic Devices as Microscale Reactors and Analytical Tools Fluorescence Detection in Microfluidic Devices Prospects Devices Incorporating Whole Living Cells Cellular Microorganisms or Human Cultured Cell Lines? 396

11 xvi Contents Living and Fixed Cells Single Cells in Microfluidic Devices Bacterial Cells with Genetically Incorporated Sensors The Cultured Human Cells Whole Cell Arrays Prospects 400 Sensing and Thinking 9: Optimizing Convenience, Sensitivity and Precision to Obtain the Proper Sensor Response 401 Questions and Problems 401 References Focusing on Targets Temperature, Pressure and Gas Sensing Molecular Thermometry Molecular Barometry Sensors for Gas Phase Composition Probing the Properties of Condensed Matter Polarity Probing in Liquids and Liquid Mixtures Viscosity and Molecular Mobility Sensing Probing Ionic Liquids The Properties of Supercritical Fluids The Structure and Dynamics in Polymers Fluorescence Probing the Interfaces Detection of Small Molecules and Ions ph Sensing Oxygen Heavy Metals Glucose Cholesterol Nucleic Acid Detection and Sequence Identification Detection of Total Double-Stranded DNA Detection of Single-Stranded DNA and RNA Sequence-Specific DNA Recognition 'DNA Chip' Hybridization Techniques Sandwich Assays in DNA Hybridization Molecular Beacon Technique DNA Sensing Based on Conjugated Polymers Concluding Remarks and Prospects Recognition of Protein Targets Total Protein Content Specific Protein Recognition Protein Arrays Polysaccharides, Glycolipids and Glycoproteins Detection of Harmful Microbes 442

12 xvii Detection and Identification of Bacteria Bacterial Spores Detection of Toxins Sensors for Viruses Conclusions and Prospects 445 Sensing and Thinking 10: Adaptation of Sensor Units for a Multi-scale and Hierarchical Range of Targets 445 Questions and Problems 446 References 447 Sensing Inside Living Cells and Tissues Modern Fluorescence Microscopy Epi-fluorescence Microscopy Total Internal Reflection Microscopy Confocal Microscopy Two-Photon and Three-Photon Microscopy Time-Gated and Time-Resolved Imaging Breaking the Diffraction Limit: Near-Field Microscopy Stimulated Emission Depletion Microscopy in Breaking the Diffraction Limit Considerations on the Problem of Photobleaching Critical Comparison of the Techniques Sensing on a Single Molecule Level Single Molecules in Sensing Detection of Single Molecules Inside the Living Cells Fluorescence Correlation Spectroscopy and Microscopy Additional Comments Site-Specific Intracellular Labeling and Genetic Encoding Attachment of a Fluorescent Reporter to Any Cellular Protein Genetically Engineered Protein Labels The Co-synthetic Incorporation of Fluorescence Dyes Concluding Remarks Advanced Nanosensors Inside the Cells Fluorescent Dye-Doped Nanoparticles in Cell Imaging Quantum Dots Applications in Imaging Self-Illuminating Quantum Dots Extending the Range of Detection Methods Sensing the Cell Membrane Lipid Asymmetry and Apoptosis 486

13 xviii Contents Sensing the Membrane Potential Membrane Receptors Future Directions Molecular Recognitions in the Cell's Interior Ion Sensing Tracking Cellular Signaling Location of Metabolites and Tracking Metabolic Events In Situ Hybridization Looking Forward Sensing the Whole Body Optimal Emitters for the Human Body Contrasting the Blood Vessels Imaging Cancer Tissues Surgical Operations Under the Control of Fluorescence Image: Fantasy or Close Reality? 498 Sensing and Thinking 11: Intellectual and Technical Means to Address Systems of Great Complexity 499 Questions and Problems 499 References Opening New Horizons Genomics, Proteomics and Other 'Omics' Gene Expression Analysis The Analysis of Proteomes Addressing Interactome Outlook Sensors to Any Target and to an Immense Number of Targets The Combinatorial Approach on a New Level Toxic Agents and Pollutants Inconvenient for Detection The Problem of Coding and Two Strategies for Its Solution Prospects New Level of Clinical Diagnostics The Need for Speed Whole-Blood Sensing Testing Non-invasive Biological Fluids Gene-Based Diagnostics Protein Disease Biomarkers Prospects Advanced Sensors in Drug Discovery High-Throughput Screening Screening for Anti-cancer Drugs Future Directions 528

14 Contents xix 12.5 Towards a Sensor that Reproduces Human Senses Electronic Nose Electronic Tongue Olfactory and Taste Cells on Chips and Whole-Animal Sensing Lessons Obtained for Sensing Sensors Promising to Change Society Industrial Challenges and Safe Workplaces Biosensor-Based Lifestyle Management Living in a Safe Environment and Eating Safe Products Implantable and Digestible Miniature Sensors Are a Reality Prospects 538 Sensing and Thinking 12: Where Do We Stand and Where Should We Go? 539 Questions and Problems 540 References 541 Epilogue 545 Appendix Glossary of Terms Used in Fluorescence/Luminescence Sensing 549 Index 561 Color Plates 571