Micro- and Nanomanipulation Tools

Combining robotics with nanotechnology, this ready reference summarizes the fundamentals and emerging applications in this fascinating research field. This is the first book to introduce tools specifically designed and made for manipulating micro- and nanometer-sized objects, and presents such examples as semiconductor packaging and clinical diagnostics as well as surgery. The first part discusses various topics of on-chip and device-based micro- and nanomanipulation, including the use of acoustic, magnetic, optical or dielectrophoretic fields, while surface-driven and high-speed microfluidic manipulation for biophysical applications are also covered. In the second part of the book, the main focus is on microrobotic tools. Alongside magnetic micromanipulators, bacteria and untethered, chapters also discuss silicon nano- and integrated optical tweezers. The book closes with a number of chapters on nanomanipulation using AFM and nanocoils under optical and electron microscopes. Exciting images from the tiniest robotic systems at the nano-level are used to illustrate the examples throughout the work. A must-have book for readers with a background ranging from engineering to nanotechnology.

Table of Contents:
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