Advanced Optical Flow Cytometry: Methods and Disease Diagnoses

A detailed look at the latest research in non-invasive in vivo cytometry and its applications, with particular emphasis on novel biophotonic methods, disease diagnosis, and monitoring of disease treatment at single cell level in stationary and flow conditions. This book thus covers the spectrum ranging from fundamental interactions between light, cells, vascular tissue, and cell labeling particles, to strategies and opportunities for preclinical and clinical research. General topics include light scattering by cells, fast video microscopy, polarization, laser-scanning, fluorescence, Raman, multi-photon, photothermal, and photoacoustic methods for cellular diagnostics and monitoring of disease treatment in living organisms. Also presented are discussions of advanced methods and techniques of classical flow cytometry.

Table of Contents:
Preface XXI List of Contributors XXXI 1 Perspectives in Cytometry 1 Anja Mittag and Attila Tárnok 1.1 Background 1 1.2 Basics of Cytometry 2 1.3 Cytomics 4 1.4 Cytometry – State of the Art 5 1.5 Perspectives 7 1.6 Conclusion 16 References 16 2 Novel Concepts and Requirements in Cytometry 25 Herbert Schneckenburger, Michael Wagner, Petra Weber, and Thomas Bruns 2.1 Introduction 25 2.2 Fluorescence Microscopy 25 2.3 Fluorescence Reader Systems 27 2.4 Microfluidics Based on Optical Tweezers 30 2.5 Conclusion 30 Acknowledgment 31 References 31 3 Optical Imaging of Cells with Gold Nanoparticle Clusters as Light Scattering Contrast Agents: A Finite-Difference Time-Domain Approach to the Modeling of Flow Cytometry Configurations 35 Stoyan Tanev, Wenbo Sun, James Pond, Valery V. Tuchin, and Vladimir P. Zharov 3.1 Introduction 35 3.2 Fundamentals of the FDTD Method 37 3.3 FDTD Simulation Results of Light Scattering Patterns from Single Cells 45 3.4 FDTD OPCM Nanobioimaging Simulation Results 47 3.5 Conclusion 57 Acknowledgment 59 References 59 4 Optics of White Blood Cells: Optical Models, Simulations, and Experiments 63 Valeri P. Maltsev, Alfons G. Hoekstra, and Maxim A. Yurkin 4.1 Introduction 63 4.2 Optical Models of White Blood Cells 65 4.3 Direct and Inverse Light-Scattering Problems for White Blood Cells 69 4.4 Experimental Measurement of Light Scattering by White Blood Cells 78 4.5 Conclusion 89 Acknowledgments 90 References 90 5 Optical Properties of Flowing Blood Cells 95 Martina C. Meinke, Moritz Friebel, and Jürgen Helfmann 5.1 Introduction 95 5.2 Blood Physiology 96 5.3 Complex Refractive Index of Hemoglobin 100 5.4 Light Propagation in Turbid Media 102 5.5 Method for the Determination of Optical Properties of Turbid Media 104 5.6 Optical Properties of Red Blood Cells 109 5.7 Optical Properties of Plasma 122 5.8 Optical Properties of Platelets 126 5.9 Comparison of Optical Influences Induced by Physiological Blood Parameters 127 5.10 Summary 129 Acknowledgments 129 References 129 6 Laser Diffraction by the Erythrocytes and Deformability Measurements 133 Sergei Yu. Nikitin, Alexander V. Priezzhev, and Andrei E. Lugovtsov 6.1 Introduction 133 6.2 Parameters of the Erythrocytes 134 6.3 Parameters of the Ektacytometer 135 6.4 Light Scattering by a Large Optically Soft Particle 136 6.5 Fraunhofer Diffraction 138 6.6 Light Scattering by a Transparent Elliptical Disc 140 6.7 Light Scattering by an Elliptical Disc with Arbitrary Coordinates of the Disc Center 143 6.8 Light Diffraction by an Ensemble of Particles 144 6.9 Light Diffraction by Particles with Random Coordinates 145 6.10 Light Scattering by Particles with Regular Coordinates 146 6.11 Description of the Experimental Setup 147 6.12 Sample Preparation Procedure 149 6.13 Examples of Experimental Assessment of Erythrocyte Deformability in Norm and Pathology 150 6.14 Conclusion 153 References 153 7 Characterization of Red Blood Cells’ Rheological and Physiological State Using Optical Flicker Spectroscopy 155 Vadim L. Kononenko 7.1 Introduction 155 7.2 Cell State-Dependent Mechanical Properties of Red Blood Cells 156 7.3 Flicker in Erythrocytes 158 7.4 Experimental Techniques for Flicker Measurement in Blood Cells 173 7.5 The Measured Quantities in Flicker Spectroscopy and the Cell Parameters Monitored 187 7.6 Flicker Spectrum Influence by Factors of Various Nature 192 7.7 Membrane Flicker and Erythrocyte Functioning 201 7.8 Flicker in Other Cells 203 7.9 Conclusions 204 References 205 8 Digital Holographic Microscopy for Quantitative Live Cell Imaging and Cytometry 211 Björn Kemper and J¨urgen Schnekenburger 8.1 Introduction, Motivation, and Background 211 8.2 Principle of DHM 212 8.3 DHM in Cell Analysis 221 8.4 Conclusion 234 Acknowledgment 234 References 234 9 Comparison of Immunophenotyping and Rare Cell Detection by Slide-Based Imaging Cytometry and Flow Cytometry 239 József Bocsi, Anja Mittag, and Attila Tárnok 9.1 Introduction 239 9.2 Comparison of Four-Color CD4/CD8 Leukocyte Analysis by SFM and FCM Using Qdot Staining 247 9.3 Comparison of Leukocyte Subtyping by Multiparametric Analysis with LSC and FCM 250 9.4 Absolute and Relative Tumor Cell Frequency Determinations 256 9.5 Analysis of Drug-Induced Apoptosis in Leukocytes by Propidium Iodide 262 9.6 Conclusion 266 Acknowledgment 266 References 266 10 Microfluidic Flow Cytometry: Advancements toward Compact, Integrated Systems 273 Shawn O. Meade, Jessica Godin, Chun-Hao Chen, Sung Hwan Cho, Frank S. Tsai, Wen Qiao, and Yu-Hwa Lo 10.1 Introduction 273 10.2 On-Chip Flow Confinement 275 10.3 Optical Detection System 283 10.4 On-Chip Sorting 297 10.5 Conclusion 306 Acknowledgments 306 References 306 11 Label-Free Cell Classification with Diffraction Imaging Flow Cytometer 311 Xin-Hua Hu and Jun Q. Lu 11.1 Introduction 311 11.2 Modeling of Scattered Light 313 11.3 FDTD Simulation with 3D Cellular Structures 318 11.4 Simulation and Measurement of Diffraction Images 322 11.5 Summary 327 Acknowledgments 328 References 328 12 An Integrative Approach for Immune Monitoring of Human Health and Disease by Advanced Flow Cytometry Methods 333 Rabindra Tirouvanziam, Daisy Diaz, Yael Gernez, Julie Laval, Monique Crubezy, and Megha Makam 12.1 Introduction 333 12.2 Optimized Protocols for Advanced Flow Cytometric Analysis of Human Samples 335 12.3 Reagents for Advanced Flow Cytometric Analysis of Human Samples 341 12.4 Conclusion: The Future of Advanced Flow Cytometry in Human Research 355 Acknowledgments 359 Abbreviations 359 References 360 13 Optical Tweezers and Cytometry 363 Raktim Dasgupta and Pradeep Kumar Gupta 13.1 Introduction 363 13.2 Optical Tweezers: Manipulating Cells with Light 364 13.3 Use of Optical Tweezers for the Measurement of Viscoelastic Parameters of Cells 367 13.4 Cytometry with Raman Optical Tweezers 376 13.5 Cell Sorting 381 13.6 Summary 383 References 383 14 In vivo Image Flow Cytometry 387 Valery V. Tuchin, Ekaterina I. Galanzha, and Vladimir P. Zharov 14.1 Introduction 387 14.2 State of the Art of Intravital Microscopy 388 14.3 In vivo Lymph Flow Cytometry 401 14.4 High-Resolution Single-Cell Imaging in Lymphatics 415 14.5 In vivo Blood Flow Cytometry 418 14.6 Conclusion 424 Acknowledgments 424 References 425 15 Instrumentation for In vivo Flow Cytometry – a Sickle Cell Anemia Case Study 433 Stephen P. Morgan and Ian M. Stockford 15.1 Introduction 433 15.2 Clinical Need 434 15.3 Instrumentation 435 15.4 Image Processing 444 15.5 Modeling 447 15.6 Device Design – Sickle Cell Anemia Imaging System 453 15.7 Imaging Results – Sickle Cell Anemia Imaging System 455 15.8 Discussion and Future Directions 458 References 459 16 Advances in Fluorescence-Based In vivo Flow Cytometry for Cancer Applications 463 Cherry Greiner and Irene Georgakoudi 16.1 Introduction 463 16.2 Background: Cancer Metastasis 464 16.3 Clinical Relevance: Role of CTCs in Cancer Development and Response to Treatment 466 16.4 Current Methods 468 16.5 In vivo Flow Cytometry (IVFC) 474 16.6 Single-Photon IVFC (SPIVFC) 477 16.7 Multiphoton IVFC (MPIVFC) 485 16.8 Summary and Future Directions 492 Acknowledgments 495 References 495 17 In vivo Photothermal and Photoacoustic Flow Cytometry 501 Valery V. Tuchin, Ekaterina I. Galanzha, and Vladimir P. Zharov 17.1 Introduction 501 17.2 Photothermal and Photoacoustic Effects at Single-Cell Level 502 17.3 PT Technique 507 17.4 Integrated PTFC for In vivo Studies 518 17.5 Integrated PAFC for In vivo Studies 524 17.6 In vivo Lymph Flow Cytometery 539 17.7 In vivo Mapping of Sentinel Lymph Nodes (SLNs) 547 17.8 Concluding Remarks and Discussion 558 Acknowledgments 563 References 563 18 Optical Instrumentation for the Measurement of Blood Perfusion, Concentration, and Oxygenation in Living Microcirculation 573 Martin J. Leahy and Jim O’Doherty 18.1 Introduction 573 18.2 Xe Clearance 577 18.3 Nailfold Capillaroscopy 577 18.4 LDPM/LDPI 582 18.5 Laser Speckle Perfusion Imaging (LSPI) 583 18.6 TiVi 584 18.7 Comparison of TiVi, LSPI, and LDPI 586 18.8 Pulse Oximetry 592 18.9 Conclusions 597 Acknowledgments 598 References 599 19 Blood Flow Cytometry and Cell Aggregation Study with Laser Speckle 605 Qingming Luo, Jianjun Qiu, and Pengcheng Li 19.1 Introduction 605 19.2 Laser Speckle Contrast Imaging 605 19.3 Investigation of Optimum Imaging Conditions with Numerical Simulation 608 19.4 Spatio-Temporal Laser Speckle Contrast Analysis 614 19.5 Fast Blood Flow Visualization Using GPU 618 19.6 Detecting Aggregation of Red Blood Cells or Platelets Using Laser Speckle 621 19.7 Conclusion 623 Acknowledgments 624 References 624 20 Modifications of Optical Properties of Blood during Photodynamic Reactions In vitro and In vivo 627 Alexandre Douplik, Alexander Stratonnikov, Olga Zhernovaya, and Viktor Loshchenov 20.1 Introduction 627 20.2 Description and Brief History of PDT 627 20.3 PDT Mechanisms 628 20.4 Blood and PDT 632 20.5 Properties of Blood, Blood Cells, and Photosensitizers: Before Photodynamic Reaction 633 20.6 Photodynamic Reactions in Blood and Blood Cells, Blood Components, and Cells 651 20.7 Types of Photodynamic Reactions in Blood: In vitro versus In vivo 656 20.8 Blood Sample In vitro as a Model Studying Photodynamic Reaction 658 20.9 Monitoring of Oxygen Consumption and Photobleaching in Blood during PDT In vivo 677 20.10 Photodynamic Disinfection of Blood 679 20.11 Photodynamic Therapy of Blood Cell Cancer 682 20.12 Summary 685 Acknowledgments 686 Glossary 686 References 687 Index 699

About the Author :
Valery Tuchin is Head of Chair of Optics and Biomedical Physics and Director of Research-Educational Institute of Optics and Biophotonics at Saratov State University. He has authored more than 250 papers and books, including his latest, Tissue Optics. Light Scattering Methods and Instrumentation for Medical Diagnosis (SPIE Tutorial Texts in Optical Engineering, Vol. TT38, 2000; second edition, PM166, 2007), Handbook of Optical Biomedical Diagnostics (SPIE Press, Vol. PM107, 2002), Coherent-Domain Optical Methods for Biomedical Diagnostics, Environmental and Material Science, Kluwer Academic Publishers, Boston, USA, vols. 1 & 2, 2004, Optical Clearing of Tissues and Blood (SPIE Press, Vol. PM154, 2005), and Optical Polarization in Biomedical Applications (co-authors L. Wang and D.A. Zimnyakov; Springer, 2006). Some of the contributors: Martin Leahy, University of Limerick, Ireland Attila Tarnok, University of Leipzig, Germany Andreas O.H. Gerstner, University of Bonn, Germany Anja Mittag, University of Leipzig, Germany Megha Makam, Daisy Diaz, Rabindra Tirouvanziam, Stanford University School of Medicine, USA Steven Boutrus, Derrick Hwu & Cherry Greiner, Tufts University, MA, USA Michael Chan & Charlotte Kuperwasser, Tufts-New England Medical Center, MA, USA Charles P. Lin & Irene Georgakoudi, Harvard Medical School,MA, USA E.I. Galanzha, Saratov State University, Russia V.P. Zharov, Arkansas University of Medical Science, USA A.V. Priezzhev, A.G. Lugovtsov, S.Yu. Nikitin & Yu.I. Gurfinkel, Moscow State University, Russia Valeri P. Maltsev, Maxim A. Yurkin & Elena Eremina,Institute of Chemical Kinetics and Combustion, Novosibirsk, Russia Alfons G. Hoekstra & Thomas Wriedt,University of Amsterdam, The Neverlands Peter Nagy % Gyorgy Vereb, Janos Szollsi, University of Debrecen, Hungary