Circulating Tumor Cells

List of Contributors xv Foreword xxi Preface xxv PART I INTRODUCTION 1 1 Circulating Tumor Cells and Historic Perspectives 3 Jonathan W. Uhr 1.1 Early Studies on Cancer Dormancy Led to the Development of a Sensitive Assay for CTCs (1970-1998) 3 1.2 Modern Era for Counting CTCs: 1998-2007 6 1.3 Proof of Malignancy of CTCs 7 1.4 New Experiments Involving CTCs 7 1.5 Clinical Cancer Dormancy 8 1.6 Human Epidermal Growth Factor Receptor 2 (HER2) Gene Amplification can be Acquired as Breast Cancer Progresses 10 1.7 uPAR and HER2 Co-amplification 11 1.8 Epithelial-Mesenchymal Transition (EMT) 12 1.9 New Instruments to Capture CTCs 14 1.10 Genotypic Analyses 15 1.11 Conclusions 18 References 20 2 Introduction to Microfluidics 33 Kangfu Chen and Z. Hugh Fan 2.1 Introduction 33 2.2 Scaling Law 36 2.3 Device Fabrication 39 2.4 Functional Components in Microfluidic Devices 43 2.5 Concluding Remarks 46 References 47 PART II ISOLATION METHODS 51 3 Ensemble-decision Aliquot Ranking (eDAR) for CTC Isolation and Analysis 53 Mengxia Zhao, Perry G. Schiro, and Daniel T. Chiu 3.1 Overview of eDAR 53 3.2 Individual Components and Analytical Performance of eDAR 55 3.3 Application and Downstream Analyses of eDAR 69 3.4 Conclusion and Perspective 80 References 81 4 Sinusoidal Microchannels with High Aspect Ratios for CTC Selection and Analysis 85 Joshua M. Jackson, MaBgorzata A. Witek, and Steven A. Soper 4.1 Introduction 85 4.2 Parallel Arrays of High-Aspect-Ratio, Sinusoidal Microchannels for CTC Selection 90 4.3 Clinical Applications of Sinusoidal CTC Microchip 114 4.4 Conclusion 118 Acknowledgments 119 References 119 5 Cell Separation using Inertial Microfluidics 127 Nivedita Nivedita and Ian Papautsky 5.1 Introduction 127 5.2 Device Fabrication and System Setup 128 5.3 Inertial Focusing in Microfluidics 129 5.4 Cancer Cell Separation in Straight Microchannels 132 5.5 Cancer Cell Separation in Spiral Microchannels 136 5.6 Conclusions 142 References 142 6 Morphological Characteristics of CTCs and the Potential for Deformability-Based Separation 147 Simon P. Duffy and Hongshen Ma 6.1 Introduction 147 6.2 Limitations of Antibody-based CTC Separation Methods 148 6.3 Morphological and Biophysical Differences Between CTCs and Hematological Cells 149 6.4 Historical and Recent Methods in CTC Separation Based on Biophysical Properties 153 6.5 Microfluidic Ratchet for Deformability-Based Separation of CTCs 155 6.6 Resettable Cell Trap for Deformability-based Separation of CTCs 160 6.7 Summary 165 References 166 7 Microfabricated Filter Membranes for Capture and Characterization of Circulating Tumor Cells (CTCs) 173 Zheng Ao, Richard J. Cote, Ram H. Datar, and Anthony Williams 7.1 Introduction 173 7.2 Size-based Enrichment of Circulating Tumor Cells 174 7.3 Comparison Between Size-based CTC Isolation and Affinity-based Isolation 177 7.4 Characterization of CTCs Captured by Microfilters 178 7.5 Conclusion 180 References 181 8 Miniaturized Nuclear Magnetic Resonance Platform for Rare Cell Detection and Profiling 183 Sangmoo Jeong, Changwook Min, Huilin Shao, Cesar M. Castro, Ralph Weissleder, and Hakho Lee 8.1 Introduction 183 8.2 muNMR Technology 184 8.3 Clinical Application of muNMR for CTC Detection and Profiling 191 8.4 Conclusion 196 References 196 9 Nanovelcro Cell-Affinity Assay for Detecting and Characterizing Circulating Tumor Cells 201 Millicent Lin, Anna Fong, Sharon Chen, Yang Zhang, Jie-fu Chen, Paulina Do, Morgan Fong, Shang-Fu Chen, Pauline Yang, An-Jou Liang, Qingyu Li, Min Song, Shuang Hou, and Hsian-Rong Tseng 9.1 Introduction 202 9.2 Proof-of-Concept Demonstration of NanoVelcro Cell-Affinity Substrates 207 9.3 First-Generation NanoVelcro Chips for CTC Enumeration 209 9.4 Second-Generation NanoVelcro-LMD Technology for Single CTC Isolation 214 9.5 Third-Generation Thermoresponsive NanoVelcro Chips 219 9.6 Conclusions and Future Perspectives 220 Acknowledgment 221 References 221 10 Acoustophoresis in Tumor Cell Enrichment 227 Per Augustsson, Cecilia Magnusson, Hans Lilja, and Thomas Laurell 10.1 Introduction 227 10.2 Factors Determining Acoustophoresis Cell Separation 230 10.3 Acoustophoresis System for Separating Cells 234 10.4 Acoustophoresis Platform for Clinical Sample Processing 239 10.5 Unperturbed Cell Survival and Phenotype after Microchip Acoustophoresis 244 10.6 Summary 246 References 246 11 Photoacoustic Flow Cytometry for Detection and Capture of Circulating Melanoma Cells 249 John A. Viator, Benjamin S. Goldschmidt, Kiran Bhattacharyya, and Kyle Rood 11.1 Introduction 249 11.2 Current Methods for Detection and Capture of CMCs 254 11.3 Discussion 259 11.4 Future Work 261 References 262 12 Selectin-Mediated Targeting of Circulating Tumor Cells for Isolation and Treatment 267 Jocelyn R. Marshall and Michael R. King 12.1 Introduction 267 12.2 CTC Capture by E-selectin 271 12.3 Applications for E-selectin in Cancer Diagnosis and Treatment 273 12.4 Conclusions 278 References 279 13 Aptamer-Enabled Tumor Cell Isolation 287 Jinling Zhang and Z. Hugh Fan 13.1 Introduction 287 13.2 Aptamers and their Biomedical Applications 288 13.3 Aptamer-based Tumor Cell Isolation 290 13.4 Conclusion and Outlook 297 References 297 14 Depletion of Normal Cells for CTC Enrichment 301 Jeffrey J. Chalmers, Maryam B. Lustberg, Clayton Deighan, Kyoung-Joo Jenny Park, Yongqi Wu, and Peter Amaya 14.1 Introduction 301 14.2 Estimates of Number and Type of Cells in Blood 302 14.3 Summary of Examples of Negative Depletion 303 14.4 Types of Cells Observed After Depletion of Normal Cells 305 14.5 Incomplete Depletion of Normal Cells 305 14.6 Conclusion 310 References 311 PART III POST-ISOLATION ANALYSIS AND CLINICAL TRANSLATION 313 15 Tumor Heterogeneity and Single-cell Analysis of CTCs 315 Evelyn K. Sigal and Stefanie S. Jeffrey 15.1 Introduction 315 15.2 Tumor Heterogeneity 316 15.3 Single-Cell Analysis of CTCs and CTC Heterogeneity 318 15.4 Gene Expression Analysis 319 15.5 Mutational Analysis 321 15.6 Conclusion: Clinical Implications and Future Perspectives 323 References 324 16 Single-Cell Molecular Profiles and Biophysical Assessment of Circulating Tumor Cells 329 Devalingam Mahalingam, Pawel Osmulski, Chiou-Miin Wang, Aaron M. Horning, Anna D. Louie, Chun-Lin Lin, Maria E. Gaczynska, and Chun-Liang Chen 16.1 Introduction 329 16.2 Methods 331 16.3 CTC Applications 336 16.4 Conclusions 342 References 343 17 Directing Circulating Tumor Cell Technologies Into Clinical Practice 351 Benjamin P. Casavant, David Kosoff, and Joshua M. Lang 17.1 Introduction 351 17.2 Defining Biomarkers 352 17.3 The Technology 356 17.4 Translating Technology 357 17.5 Conclusions 360 References 361 PART IV COMMERCIALIZATION 365 18 DEPArray(TM) Technology for Single CTC Analysis 367 Farideh Z. Bischoff, Gianni Medoro, and Nicolo Manaresi 18.1 Challenges in Molecular Profiling of CTCs 367 18.2 DEPArray(TM) Technology Solution 368 18.3 DEPArray(TM) for Single Tumor Cell Analysis 369 18.4 Clinical Significance in Single CTC Profiling 373 18.5 Conclusion 374 References 374 19 CELLSEARCH(r) Instrument, Features, and Usage 377 Denis A. Smirnov, Brad W. Foulk, Mark C. Connelly, and Robert T. McCormack 19.1 Introduction 377 19.2 Principles of CELLSEARCH(r) 379 19.3 EpCAM Density and CTC Capture 380 19.4 Clinical Applications of CELLSEARCH(r) CTCs 383 19.5 Beyond EpCAM Capture 390 19.6 Discussion 391 References 394 PART V GLOSSARY 401 Circulating Tumor Cell Glossary 403 Jose I. Varillas and Z. Hugh Fan Index 423