Introduces the reader to Circulating Tumor Cells (CTCs), their isolation method and analysis, and commercially available platforms

* Presents the historical perspective and the overview of the field of circulating tumor cells (CTCs)

* Discusses the state-of-art methods for CTC isolation, ranging from the macro- to micro-scale, from positive concentration to negative depletion, and from biological-property-enabled to physical-property-based approaches

* Details commercially available CTC platforms

* Describes post-isolation analysis and clinical translation

* Provides a glossary of scientific terms related to CTCs

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 (19701998) 3

1.2 Modern Era for Counting CTCs: 19982007 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 EpithelialMesenchymal 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, Magorzata 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 NMR Technology 184

8.3 Clinical Application of NMR for CTC Det...