Title Details

About the Editors XVII

Series Editors Preface XIX

Preface XXI

List of Contributors XXV

1 High-Speed Microfluidic Manipulation of Cells 1
Aram J. Chung and Soojung Claire Hur

1.1 Introduction 1

1.2 Direct Cell Manipulation 3

1.2.1 Electrical Cell Manipulation 3

1.2.2 Magnetic Cell Manipulation 4

1.2.3 Optical Cell Manipulation 4

1.2.4 Mechanical Cell Manipulation 5

1.2.4.1 Constriction-Based Cell Manipulation 5

1.2.4.2 Shear-Induced Cell Manipulation 7

1.3 Indirect Cell Manipulation 9

1.3.1 Cell Separation 9

1.3.1.1 Hydrodynamic (Passive) Cell Separation 13

1.3.1.2 Nonhydrodynamic (Active) Particle Separation 18

1.3.2 Cell Alignment (Focusing) 25

1.3.2.1 Cell Alignment (Focusing) for Flow Cytometry 28

1.3.2.2 Cell Solution Exchange 29

1.4 Summary 31

Acknowledgments 31

References 31

2 Micro and Nano Manipulation and Assembly by Optically Induced Electrokinetics 41
Fei Fei Wang, Sam Lai, Lianqing Liu, Gwo-Bin Lee, and Wen Jung Li

2.1 Introduction 41

2.2 Optically Induced Electrokinetic (OEK) Forces 45

2.2.1 Classical Electrokinetic Forces 45

2.2.1.1 Dielectrophoresis (DEP) 45

2.2.1.2 AC Electroosmosis (ACEO) 46

2.2.1.3 Electrothermal Effects (ET) 47

2.2.1.4 Buoyancy Effects 47

2.2.1.5 Brownian Motion 47

2.2.2 Optically Induced Electrokinetic Forces 48

2.2.2.1 OEK Chip: Operational Principle and Design 48

2.2.2.2 Spectrum-Dependent ODEP Force 53

2.2.2.3 Waveform-Dependent ODEP Force 54

2.3 OEK-Based Manipulation and Assembly 55

2.3.1 Manipulation and Assembly of Nonbiological Materials 55

2.3.2 Biological Entities: Cells and Molecules 60

2.3.3 Manipulation of Fluidic Thin Films 63

2.4 Summary 65

References 67

3 Manipulation of DNA by Complex Confinement Using Nanofluidic Slits 75
Elizabeth A. Strychalski and Samuel M. Stavis

3.1 Introduction 75

3.2 Slitlike Confinement of DNA 78

3.3 Differential Slitlike Confinement of DNA 82

3.4 Experimental Studies 83

3.5 Design of Complex Slitlike Devices 86

3.6 Fabrication of Complex Slitlike Devices 88

3.7 Experimental Conditions 90

3.8 Conclusion 92

Disclaimer 93

References 93

4 Microfluidic Approaches for Manipulation and Assembly of One-Dimensional Nanomaterials 97
Shaolin Zhou, Qiuquan Guo, and Jun Yang

4.1 Introduction 97

4.2 Microfluidic Assembly 99

4.2.1 Hydrodynamic Focusing 100

4.2.1.1 Concept and Mechanism 100

4.2.1.2 2D and 3D Hierarchy 101

4.2.1.3 Symmetrical and Asymmetrical Behavior 103

4.2.2 HF-Based NWAssembly 104

4.2.2.1 The Principle 104

4.2.2.2 Device Design and Fabrication 105

4.2.2.3 NWAssembly by Symmetrical Hydrodynamic Focusing 107

4.2.2.4 NWAssembly by Asymmetrical Hydrodynamic Focusing 108

4.3 Summary 112

References 113

5 Optically Assisted and Dielectrophoretical Manipulation of Cells and Molecules on Microfluidic Platforms 119
Yen-Heng Lin and Gwo-Bin Lee

5.1 Introduction 119

5.2 Operating Principle and Fundamental Physics of the ODEP Platform 122

5.2.1 ODEP Force 122

5.2.2 Optically Induced ACEO Flow 123

5.2.3 Electrothermal (ET) Force 125

5.2.4 Experimental Setup of an ODEP Platform 126

5.2.4.1 Light Source 126

5.2.4.2 Materials of the Photoconductive Layer 127

5.3 Applications of the ODEP Platform 129

5.3.1 Cell Manipulation 129

5.3.2 Cell Separation 130

5.3.3 Cell Rotation 130

5.3.4 Cell Electroporation 131

5.3.5 Cell Lysis 131

5.3.6 Manipulation of Micro- or Nanoscale Objects 132

5.3.7 Manipulation of Molecules 134

5.3.8 Droplet Manipulation 135

5.4 Conclusion 136

References 137

6 On-Chip Microrobot Driven by Permanent Magnets for Biomedical Applications 141
Masaya Hagiwara, Tomohiro Kawahara, and Fumihito Arai

6.1 On-Chip Microrobot 141

6.2 Characteristics of Microrobot Actuated by Permanent Magnet 142

6.3 Friction Reduction for On-Chip Robot 144

6.3.1 Friction Reduction by Drive Unit 144

6.3.2 Friction Reduction by Ultrasonic Vibrations 146

6.3.3 Experimental Evaluations of MMT 146

6.3.3.1 Positioning Accuracy Evaluation 146

6.3.3.2 Output Force Evaluation 149

6.4 Fluid Friction Reduction for On-Chip Robot 150

6.4.1 Fluid Friction Reduction by Riblet Surface 150

6.4.2 Principle of Fluid Friction Reduction Using Riblet Surface 150

6.4.3 Optimal Design of Riblet to Minimize the Fluid Friction 152

6.4.4 Fluid Force Analysis on MMT with Riblet Surface 153

6.4.5 Fabrication Process of MMT with Riblet Surface Using Si–Ni Composite Structure 156

6.4.6 Evaluation of Si–Ni Composite MMT with Optimal Riblet 158

6.5 Applications of On-Chip Robot to Cell Manipulations 160

6.5.1 Oocyte Enucleation 160

6.5.2 Multichannel Sorting 162

6.5.3 Evaluation of Effect of Mechanical Stimulation on Microorganisms 162

6.6 Summary 165

References 166

7 Silicon Nanotweezers for Molecules and Cells Manipulation and Characterization 169
Dominique Collard, Nicolas Lafitte, Hervé Guillou, Momoko Kumemura, Laurent Jalabert, and Hiroyuki Fujita

7.1 Introduction 169

7.2 SNT Operation and Design 170

7.2.1 Design 170

7.2.1.1 Electrostatic Actuation 171

7.2.1.2 Mechanical Structure 171

7.2.1.3 Capacitive Sensor 173

7.2.2 Operation 174

7.2.2.1 Instrumentation 174

7.2.2.2 Characterization 175

7.2.2.3 Modeling 176

7.3 SNT Process 177

7.3.1 MEMS Fabrication versus the Design Constrains and User Applications 177

7.3.2 Sharp Tip Single Actuator SNT Process Flow 178

7.3.2.1 Nitride Deposition 178

7.3.2.2 Defining Crystallographic Alignment Structures 178

7.3.2.3 Photolithography (Level 1) – Nitride Patterning for LOCOS 179

7.3.2.4 Photolithography (Level 2) – Sensors and Actuators 179

7.3.2.5 DRIE Front Side 180

7.3.2.6 Sharp Tip Fabrication and Gap Control 181

7.3.2.7 Photolithography (Level 3) and Rearside DRIE 182

7.3.2.8 Releasing in Vapor HF 182

7.3.3 Concluding Remarks on the Silicon Nanotweezers Microfabrication 183

7.4 DNA Trapping and Enzymatic Reaction Monitoring 183

7.5 Cell Trapping and Characterization 186

7.5.1 Introducing Remarks 186

7.5.2 Specific Issues 187

7.5.3 Design of SNT 187

7.5.4 Instrumentation 189

7.5.5 Experimental Platform 190

7.5.6 Cells in Suspension 190

7.5.7 Spread Cells 192

7.5.8 Cell Differentiation 193

7.5.9 Concluding Remarks for Cell Characterization with SNT 194

7.6 General Concluding Remarks and Perspectives 194

Acknowledgments 196

References 196

8 Miniaturized Untethered Tools for Surgery 201
Evin Gultepe, Qianru Jin, Andrew Choi, Alex Abramson, and David H. Gracias

8.1 Introduction 201

8.2 Macroscale Untethered Surgical Tools 203

8.2.1 Localization and Locomotion without Tethers 204

8.2.1.1 Localization 204

8.2.1.2 Locomotion 206

8.2.2 Powering and Activating a Small Machine 207

8.2.2.1 Stored Chemical Energy 207

8.2.2.2 Stored Mechanical Energy 208

8.2.2.3 External Magnetic Field 208

8.2.2.4 Other Sources of Energy 209

8.3 Microscale Untethered Surgical Tools 210

8.3.1 Applications 210

8.3.1.1 Angioplasty 210

8.3.1.2 SurgicalWound Closure 212

8.3.1.3 Biopsy 213

8.3.1.4 Micromanipulation 214

8.3.2 Locomotion 214

8.3.2.1 Magnetic Force 215

8.3.2.2 Electromechanical 217

8.3.2.3 Optical Tweezers 218

8.3.2.4 Biologic Tissue Powered 219

8.4 Nanoscale Untethered Surgical Tools 219

8.4.1 Fuel-Driven Motion 222

8.4.2 Magnetic Field-Driven Motion 223

8.4.3 AcousticWave-Driven Motion 225

8.4.4 Light-Driven Motion 226

8.4.5 Nano-Bio Hybrid Systems 227

8.4.6 Artificial Molecular Machines 227

8.5 Conclusion 228

Acknowledgments 229

References 229

9 Single-Chip Scanning ProbeMicroscopes 235
Neil Sarkar and Raafat R. Mansour

9.1 Scanning Probe Microscopy 237

9.2 The Role of MEMS in SPM 239

9.3 CMOS–MEMS Manufacturing Processes Applied to sc-SPMs 240

9.4 Modeling and Design of sc-SPMs 242

9.4.1 Electrothermal Model of Self-Heated Resistor 245

9.4.2 Electrothermal Model of Vertical Actuator 247

9.4.3 Electro-Thermo-Mechanical Model 248

9.5 Imaging Results 250

9.6 Conclusion 254

References 254

10 Untethered Magnetic Micromanipulation 259
Eric Diller and Metin Sitti

10.1 Physics of Micromanipulation 260

10.2 Sliding Friction and Surface Adhesion 260

10.2.1 Adhesion 260

10.2.1.1 van der Waals Forces 262

10.2.2 Sliding Friction 263

10.3 Fluid Dynamics Effects 264

10.3.1 Viscous Drag on a Sphere 265

10.4 Magnetic Microrobot Actuation 266

10.5 Locomotion Techniques 266

10.5.1 Motion in Two Dimensions 267

10.5.2 Motion in Three Dimensions 267

10.5.3 Magnetic Actuation Systems 268

10.5.4 Special Coil Arrangements 269

10.6 Manipulation Techniques 271

10.6.1 Contact Micromanipulation 271

10.6.1.1 Direct Pushing 271

10.6.1.2 Grasping Manipulation 274

10.6.2 Noncontact Manipulation 275

10.6.2.1 Translation 276

10.6.2.2 Rotation 277

10.6.2.3 Parallel Manipulation 279

10.6.3 Mobile Microrobotics Competition 279

10.7 Conclusions and Prospects 280

References 281

11 Microrobotic Tools for Plant Biology 283
Dimitrios Felekis, Hannes Vogler, Ueli Grossniklaus, and Bradley J. Nelson

11.1 Why Do We Need a Mechanical Understanding of the Plant Growth Mechanism? 283

11.2 Microrobotic Platforms for Plant Mechanics 285

11.2.1 The Cellular Force Microscope 286

11.2.1.1 Force Sensing Technology 286

11.2.1.2 Positioning System 288

11.2.1.3 Imaging System and Interface 289

11.2.2 Real-Time CFM 290

11.2.2.1 Positioning System 290

11.2.2.2 Data Acquisition 291

11.2.2.3 Automated Cell Selection and Positioning 292

11.3 Biomechanical and Morphological Characterization of Living Cells 294

11.3.1 Cell Wall Apparent Stiffness 295

11.3.2 3D Stiffness and Topography Maps 299

11.3.3 Real-Time Intracellular Imaging During Mechanical Stimulation 301

11.4 Conclusions 302

References 303

12 Magnetotactic Bacteria for the Manipulation and Transport of Micro and Nanometer-Sized Objects 307
Sylvain Martel

12.1 Introduction 307

12.2 Magnetotactic Bacteria 308

12.3 Component Sizes and Related Manipulation Approaches 310

12.3.1 Transport and Manipulation of MS Components 311

12.3.2 Transport and Manipulation of AE Components 314

12.3.3 Transport and Manipulation of ML Components 314

12.4 Conclusions and Discussion 317

References 318

13 Stiffness and Kinematic Analysis of a Novel Compliant Parallel Micromanipulator for Biomedical Manipulation 319
Xiao Xiao and Yangmin Li

13.1 Introduction 319

13.2 Design of the Micromanipulator 320

13.3 Stiffness Modeling of the Micromanipulator 322

13.3.1 Stiffness Matrix of the Flexure Element 323

13.3.2 Stiffness Modeling of the Compliant P Module 324

13.3.3 Stiffness Modeling of the Compliant 4S Module 325

13.3.4 Stiffness Modeling of the Compliant P(4S) Chain 327

13.3.5 Stiffness Modeling of the Complete Mechanism 327

13.3.6 Model Validation Based on FEA 329

13.4 Kinematics Modeling of the Micromanipulator 333

13.5 Conclusion 336

References 337

14 Robotic Micromanipulation of Cells and Small Organisms 339
Xianke Dong,Wes Johnson, Yu Sun, and Xinyu Liu

14.1 Introduction 339

14.2 Robotic Microinjection of Cells and Small Organisms 340

14.2.1 Robotic Cell Injection 340

14.2.1.1 Cell Immobilization Methods 343

14.2.1.2 Image Processing and Computer Vision Techniques 344

14.2.1.3 Control System Design 345

14.2.1.4 Force Sensing and Control 347

14.2.1.5 Experimental Validation of Injection Success and Survival Rates 349

14.2.1.6 Parallel Cell Injection 350

14.2.2 Robotic Injection of Caenorhabditis elegans 350

14.3 Robotic Transfer of Biosamples 351

14.3.1 Pipette-Based Cell Transfer 351

14.3.2 Microgripper/Microhand-Based Cell Transfer 352

14.3.3 Microrobot-Based Cell Transfer 354

14.3.4 Laser Trapping-Based Cell Transfer 355

14.4 Robot-Assisted Mechanical Characterization of Cells 357

14.4.1 MEMS-Based Cell Characterization 357

14.4.2 Laser Trapping-Based Cell Characterization 358

14.4.3 Atomic Force Microscopy (AFM)-Based Cell Characterization 359

14.4.4 Micropipette Aspiration 359

14.5 Conclusion 360

References 361

15 Industrial Tools for Micromanipulation 369
Michaël Gauthier, Cédric Clévy, David Hériban, and Pasi Kallio

15.1 Introduction 369

15.2 Microrobotics for Scientific Instrumentation 371

15.2.1 MEMS Mechanical Testing 371

15.2.2 Mechanical Testing of Fibrous Micro- and NanoScale Materials 372

15.2.3 Mobile Microrobots for Testing 375

15.3 Microrobotics for Microassembly 376

15.3.1 Microassembly of Micromechanisms 377

15.3.1.1 Microgrippers 379

15.3.1.2 High-Resolution Vision System 380

15.3.1.3 Integrated Assembly Platform 381

15.3.2 Microassembly in MEMS and MOEMS Industries 382

15.3.2.1 Thin Die Packaging 383

15.3.2.2 Flexible MOEMS Extreme Assembly 384

15.4 Future Challenges 387

15.4.1 Current Opportunities 387

15.4.2 Future Opportunity 388

15.4.3 Barriers to Market 388

15.4.4 Key Market Data 389

References 389

16 Robot-Aided Micromanipulation of Biological Cells with Integrated Optical Tweezers and Microfluidic Chip 393
Xiaolin Wang, Shuxun Chen, and Dong Sun

16.1 Introduction 393

16.2 Cell Micromanipulation System with Optical Tweezers and Microfluidic Chip 395

16.3 Enhanced Cell Sorting Strategy 396

16.3.1 Operation Principle 396

16.3.2 Microfluidic Chip Design 397

16.3.3 Cell Transportation by Optical Tweezers 398

16.3.4 Experimental Results and Discussion 400

16.3.4.1 Isolation of Yeast Cells 400

16.3.4.2 Isolation of hESCs 402

16.3.4.3 Discussion 403

16.4 Novel Cell Manipulation Tool 404

16.4.1 Operation Principle 404

16.4.2 Microwell Array-Based Microfluidic Chip Design 405

16.4.3 Chip Preparation and Fluid Operation 406

16.4.4 Experimental Results and Discussion 407

16.4.4.1 Cell Levitation from Microwell 407

16.4.4.2 Cell Assembly by Multiple Optical Traps 408

16.4.4.3 Automated Cell Transportation and Deposition 408

16.4.4.4 Isolation and Deposition on hESCs and Yeast Cells 410

16.4.4.5 Quantification of the Experimental Results 411

16.4.4.6 Discussion 413

16.5 Conclusion 414

References 415

17 Investigating the Molecular Specific Interactions on Cell Surface Using Atomic Force Microscopy 417
Mi Li, Lianqing Liu, Ning Xi, and Yuechao Wang

17.1 Background 417

17.2 Single-Molecule Force Spectroscopy 420

17.3 Force Spectroscopy of Molecular Interactions on Tumor Cells from Patients 423

17.4 Mapping the Distribution of Membrane Proteins on Tumor Cells 430

17.5 Summary 435

Acknowledgments 436

References 436

18 Flexible Robotic AFM-Based Systemfor Manipulation and Characterization of Micro- and Nano-Objects 441
Hui Xie and Stéphane Régnier

18.1 AFM-Based Flexible Robotic System for Micro- or Nanomanipulation 444

18.1.1 The AFM-Based Flexible Robotic System 444

18.1.1.1 The Flexible Robotic Setup 444

18.1.1.2 Force Sensing during Pick-and-Place 444

18.1.2 Experimental Results 446

18.1.2.1 3D Micromanipulation Robotic System 446

18.1.2.2 3D Nanomanipulation Robotic System 449

18.1.3 Conclusion 453

18.2 In situ Peeling of 1D Nanostructures Using a Dual-Probe Nanotweezer 453

18.2.1 Methods 453

18.2.2 Results and Discussion 457

18.2.3 Conclusion 457

18.3 In situ Quantification of Living Cell Adhesion Forces: Single-Cell Force Spectroscopy with a Nanotweezer 459

18.3.1 Materials and Methods 459

18.3.1.1 Nanotweezer Setup 459

18.3.1.2 Cell Cultivation and Sample Preparation 461

18.3.1.3 Nanotweezer Preparation 461

18.3.2 Protocol of the Adhesion Force Measurement 462

18.3.3 Clamping Detection during Cell Grasping 464

18.3.3.1 Cell Release 466

18.3.4 Experimental Results 466

18.3.4.1 Cell–Substrate Adhesion Force Measurement 466

18.3.4.2 Cell–Cell Adhesion Force Measurement 469

18.3.5 Discussion 470

18.3.6 Conclusion 471

18.4 Conclusion and Future Directions 471

References 472

19 Nanorobotic Manipulation of Helical Nanostructures 477
Lixin Dong, Li Zhang, Miao Yu, and Bradley J. Nelson

19.1 Introduction 477

19.2 Nanorobotic Manipulation Tools and Processes 479

19.2.1 Nanomanipulators and Tools 479

19.2.2 Nanorobotic Manipulation Processes 480

19.3 Characterization of Helical Nanobelts 482

19.3.1 Axial Pulling of Rolled-Up Helical Nanostructures 483

19.3.2 Lateral Bending and Local Buckling of a Rolled-Up SiGe/Si Microtube 483

19.3.3 Axial Buckling of Rolled-Up SiGe/Si Microtubes 485

19.3.4 Tangential Unrolling of a Rolled-Up Si/Cr Ring 488

19.3.5 Radial Stretching of a Si/Cr Nanoring 489

19.4 Applications 492

19.4.1 Typical Configurations of NEMS 492

19.4.2 Motion Converters 492

19.4.2.1 Design of Motion Converters 494

19.4.2.2 Displacement Conversion 495

19.4.2.3 Load Conversion 497

19.4.2.4 Application in 3D Microscopy 498

19.5 Summary 500

References 501

20 Automated Micro- and Nanohandling Inside the Scanning Electron Microscope 505
Malte Bartenwerfer, Sören Zimmermann, Tobias Tiemerding, Manuel Mikczinski, and Sergej Fatikow

20.1 Introduction and Motivation 505

20.1.1 SEM-Based Manipulation 506

20.2 State of the Art 508

20.2.1 The Scanning Electron Microscope as Fundamental Tool 508

20.2.2 Conditions for Automation on the Micro- and Nanoscales 509

20.3 Automation Environment 511

20.3.1 Robotic Setup 511

20.3.1.1 Dedicated Setups 511

20.3.1.2 Modular Setups 512

20.3.2 Control Environment 514

20.3.2.1 OFFIS Automation Framework 514

20.4 Case Studies 517

20.4.1 Manipulation and Automation Overview 517

20.4.1.1 High-Speed Object Tracking Inside the SEM 519

20.4.2 Assembly of Building Blocks: NanoBits 521

20.4.2.1 Assembly Environment and Tools 521

20.4.3 Handling of Colloidal Nanoparticles 524

20.4.4 Measuring the Transverse Fiber Compression 526

20.5 Outlook 530

20.5.1 Future Developments 530

20.5.2 Software and Automation 530

Acknowledgments 531

References 531

21 Manipulation of Biological Cells under ESEM and Microfluidic Systems 537
Toshio Fukuda, Masahiro Nakajima, Masaru Takeuchi, and Mohd Ridzuan Ahmad

21.1 Introduction 537

21.2 ESEM-Nanomanipulation System 538

21.3 ESEM Observation of Single Cells 540

21.4 Manipulation of Biological Cells under ESEM 541

21.4.1 Cell Viability Detection Using Dual Nanoprobe 541

21.4.2 Preparation of Dead Cell Colonies ofW303 Cells 543

21.4.3 Fabrication of the Dual Nanoprobe 544

21.4.4 Electrical Measurement Setup 545

21.4.5 Experimental Results and Discussions 546

21.4.5.1 Single-Cell Viability Assessment by Electrical Measurement under HVMode 547

21.4.5.2 Single-Cell Viability Assessment by Electrical Measurement under ESEMMode 548

21.5 Manipulation of Biological Cells under Microfluidics 549

21.5.1 Nanoliters Discharge/Suction by Thermoresponsive Polymer Actuated Probe 549

21.5.2 Fabrication of TPA Probe 550

21.5.3 Solution Discharge by TPA Probe 552

21.5.4 Suction and Discharge of Micro-Object by TPA Probe Inside Semiclosed Microchip 553

21.5.4.1 Semiclosed Microchip 553

21.5.4.2 Suction and Discharge of Microbead by TPA Probe Inside Semiclosed Microchip 554

21.5.4.3 Cell Suction by TPA Probe Inside Semiclosed Microchip 556

21.6 Conclusion 556

References 557

Index 559