Open-Space Microfluidics: Concepts, Implementations, Applications

Summarizing the latest trends and the current state of this research field, this up-to-date book discusses in detail techniques to perform localized alterations on surfaces with great flexibility, including microfluidic probes, multifunctional nanopipettes and various surface patterning techniques, such as dip pen nanolithography. These techniques are also put in perspective in terms of applications and how they can be transformative of numerous (bio)chemical processes involving surfaces. The editors are from IBM Zurich, the pioneers and pacesetters in the field at the forefront of research in this new and rapidly expanding area.

Table of Contents:
Foreword xv Preface xvii Part I Hydrodynamic Flow Confinement (HFC) 1 1 Hydrodynamic Flow Confinement Using a Microfluidic Probe 3 Emmanuel Delamarche, Robert D. Lovchik, Julien F. Cors, and Govind V. Kaigala 1.1 Introduction 3 1.2 HFC Principle 4 1.3 MFP Heads 7 1.4 Vertical MFP 8 1.5 Advanced MFP Heads and Holders 9 1.6 Surface Processing Using an MFP 11 1.7 MFP Components 15 1.8 Outlook 16 Acknowledgments 17 References 17 2 Hierarchical Hydrodynamic Flow Confinement (hHFC) and Recirculation for Performing Microscale Chemistry on Surfaces 21 Julien F. Cors, Julien Autebert, Aditya Kashyap, David P. Taylor, Robert D. Lovchik, Emmanuel Delamarche, and Govind V. Kaigala 2.1 Introduction 21 2.2 Hierarchical HFC 22 2.2.1 Minimal Dilution of the Processing Liquid 22 2.2.2 Numerical Simulations of Hierarchical HFC 22 2.2.3 Dilution Measurement of hHFC 25 2.2.4 Microscale Chemistry Using hHFC 26 2.3 Recirculation 28 2.3.1 Recirculation of Small Volumes of Liquids within an MFP Head 28 2.3.2 AnalyticalModel: Diffusive Transport between Two Laminar Flows in hHFC 30 2.4 Microscale Deposition 33 2.4.1 Patterning Proteins on Surfaces 33 2.4.2 Protein Deposition Using hHFC and Recirculation 35 2.4.3 AnalyticalModel: Convective Transport between Two Laminar Flows in hHFC 39 2.4.4 Conclusion and Outlook 42 Acknowledgments 43 References 43 3 Design of Hydrodynamically ConfinedMicroflow Devices with Numerical Modeling: Controlling Flow Envelope, Pressure, and Shear Stress 47 Choongbae Park, Kevin V. Christ, and Kevin T. Turner 3.1 Introduction 47 3.2 Theory 48 3.2.1 Pressure, Velocity Distribution, and Nondimensional Quantities 48 3.2.2 Shear Stress 50 3.3 Device and ExperimentalMethods for CFD Validation 50 3.4 Numerical Modeling of HCM devices 52 3.5 Envelope Size and Pressure Drop Across HCMs 54 3.6 Hydrodynamic Loads Generated by HCM Devices 58 3.7 Concluding Remarks 60 References 60 4 Hele-Shaw Flow Theory in the Context of Open Microfluidics: From Dipoles to Quadrupoles 63 Étienne Boulais and Thomas Gervais 4.1 Introduction 63 4.2 Fundamentals of Hele-Shaw Flows 64 4.2.1 Derivation of Hele-Shaw Equation from the Navier–Stokes Equation 64 4.2.2 Hele-Shaw Point Sources, Round Monopoles, and Square Monopoles 68 4.3 Applications to Microfluidic Dipoles and Quadrupoles 69 4.3.1 Velocity Potentials for Dipoles and Quadrupoles 70 4.3.2 Deriving Key Operation Characteristics for Dipoles and Quadrupoles 71 4.3.2.1 Stagnation Points and the Hydrodynamic Flow Confinement Zone 71 4.3.3 Numerical Investigation of Model Accuracy 74 4.4 Diffusion in Hele-Shaw Flows 76 4.4.1 Advection–Diffusion Transport Equations 76 4.4.2 High Péclet Number Asymptotic Solutions Near Stagnation Points 77 4.4.2.1 Floating Gradient Along the Central Line in a Microfluidic Quadrupole 78 4.4.2.2 Diffusion Broadening in the HFC Envelope for Dipoles and Quadrupoles 80 4.4.3 Numerical Investigation of Model Accuracy 80 4.5 Conclusion 81 References 82 5 Implementation and Applications of Microfluidic Quadrupoles 83 Ayoola T. Brimmo andMohammad A. Qasaimeh 5.1 Introduction 83 5.2 Principles and Configurations of MQs 85 5.3 Implementation of MQs 87 5.4 MQ Analysis and Characterization 88 5.4.1 Stagnation Point Visualization 88 5.4.2 Hydrodynamic Flow Confinement 90 5.4.3 Concentration Gradient Measurement 91 5.4.4 Stagnation Point Hydrodynamic Manipulation 92 5.5 Application of MQs in Biology and Life Sciences 94 5.5.1 MQs for Biochemical Concentration Gradient Assays 94 5.5.2 Studying Neutrophil Chemotaxis Using the Lateral MQ 95 5.6 Summary and Outlook 95 References 98 6 Hydrodynamic Flow Confinement-Assisted Immunohistochemistry from Micrometer to Millimeter Scale 101 Robert D. Lovchik, David P. Taylor, Emmanuel Delamarche, And Govind V. Kaigala 6.1 Immunohistochemical Analysis of Tissue Sections 101 6.2 Probe Heads for Multiscale Surface Interactions 102 6.2.1 Probe Design and Operating Conditions for Millimeter-Scale HFCs 103 6.2.2 Slit-Aperture Probes 105 6.2.3 Aperture-Array Probes 105 6.3 Immunohistochemistry with Microfluidic Probes 107 6.4 Micro-IHC on Human Tissue Sections 108 6.4.1 Micro-IHC on Tissue Microarrays 109 6.5 Millimeter-Scale Immunohistochemistry 109 6.6 Outlook 112 Acknowledgments 113 References 113 7 Local Nucleic Acid Analysis of Adherent Cells 115 Aditya Kashyap, Deborah Huber, Julien Autebert, and Govind V. Kaigala 7.1 Introduction 115 7.1.1 Heterogeneity in Cells and Their Microenvironments 115 7.1.2 State of the Art: Microfluidic Devices for Nucleic Acid Analysis 116 7.1.3 Microfluidic Probe for Spatial Probing of Standard Biological Substrates 119 7.2 Methods 121 7.2.1 MFP Platform, Head, and Handling 121 7.2.2 Cell Handling 122 7.2.3 μFISH Protocol 123 7.2.4 Local Lysis and Sample Retrieval Protocol 123 7.2.5 DNA and RNA Quantification 124 7.3 Results 124 7.3.1 Genomic Analysis 126 7.3.1.1 Study of Chromosomal Characteristics of Adherent Cells Using μFISH 124 7.3.1.2 Operational Parameterization for μFISH 126 7.3.1.3 Improved Probe Incubation and Consumption Using μFISH 126 7.3.1.4 μFISH Allows for SpatialMultiplexing of Probes 127 7.3.1.5 Selective Local Lysis for DNA Analysis Using the MFP (Spatialyse) 127 7.3.1.6 Operational Parameterization and Liquid Handling for Spatialyse 127 7.3.1.7 Quantitation of DNA in Local Lysate 129 7.3.2 Transcriptomic Analysis 130 7.3.2.1 Spatially Resolved Probing of Gene Expression in Adherent Cocultures 130 7.4 Discussion 131 7.5 Concluding Remarks 133 Acknowledgments 134 References 134 8 Microfluidic Probe for Neural Organotypic Brain Tissue and Cell Perfusion 139 Donald MacNearney, Mohammad A. Qasaimeh, and David Juncker 8.1 Introduction 139 8.2 Microperfusion of Organotypic Brain Slices Using the Microfluidic Probe 141 8.2.1 Design of Perfusion Chamber for Organotypic Brain Slice Culture 141 8.2.2 Design of PDMS MFP 143 8.2.3 Microscope Setup 147 8.2.4 Microperfusion of Organotypic Brain Slices 148 8.3 Microperfusion of Live Dissociated Neural Cell Cultures Using the Microfluidic Probe 148 8.4 Conclusion 152 Acknowledgments 153 References 153 9 The Multifunctional Pipette 155 Aldo Jesorka and Irep Gözen 9.1 Introduction 155 9.2 Open Volume Probes 157 9.3 Detailed View on the Multifunctional Pipette 159 9.3.1 Chip Concept 159 9.3.2 Device Design and Function 161 9.3.3 Fabrication 165 9.4 Integrated Functions 167 9.4.1 Valveless Switching 168 9.4.2 Control Schematics 169 9.4.3 Operation 170 9.5 Functional Extensions and Applications 172 9.5.1 In-Channel Electrodes 172 9.5.2 Single-Cell Superfusion 173 9.5.3 Optofluidic Thermometer 173 9.5.4 Multiprobe Operation 175 9.5.5 Lab-on-a-Membrane 176 9.6 Future Technology 178 9.6.1 Materials and Fabrication 179 9.6.2 Collection and Integration of Assays and Sensors 181 9.6.3 Automation 182 Acknowledgments 183 References 183 10 Single-Cell Analysis with the BioPen 187 Irep Gözen, Gavin Jeffries, Tatsiana Lobovkina, Emanuele Celauro, Mehrnaz Shaali, Baharan Ali Doosti, and Aldo Jesorka 10.1 Introduction 187 10.2 The Single-Cell Challenge 189 10.2.1 Single-Cell Analysis 189 10.2.2 Technology Overview 190 10.2.3 Adherent Cells 191 10.3 Superfusion Techniques 192 10.3.1 Hydrodynamic Confinement 192 10.4 The BioPen 193 10.5 Application Areas 194 10.5.1 Cell Zeiosis and Ion Channel Activation 194 10.5.2 Single Cell Enzymology 196 10.5.3 Local Temperature Adjustment and Measurement in a Single-Cell Environment 199 10.5.4 Intercellular Communication 202 10.5.5 Single-Cell Viability Test 203 10.5.6 Single Muscle Fiber Physiology 205 10.5.7 Single-Cell Electroporation 208 10.5.8 Local Superfusion of Tissue Slices 210 10.6 Future Technology 213 Acknowledgments 215 References 215 11 Microfluidic Probes for Single-Cell Proteomic Analysis 221 Aniruddh Sarkar, LidanWu, and Jongyoon Han 11.1 Introduction 221 11.2 Technical Requirements of Single-Cell Proteomic Analysis 223 11.3 Methods for Single-Cell Proteomic Analysis 225 11.4 Microfluidics Enabling Next-Generation Single-Cell Proteomics 229 11.5 Open-Ended Microwells for Proteomic and Multiparameter Single-Cell Studies 231 11.6 Microfluidic Probes in In Situ Single-Cell Proteomic Measurement 231 11.7 Outlook for FutureWork with Microfluidic Single-Cell Proteomic Assay 236 11.7.1 Sensitivity 236 11.7.2 Throughput 238 11.7.3 Porting Other Assays to the Microfluidic Probe 240 11.7.4 Applications in Single-Cell Biology 241 11.8 Conclusion 242 References 242 Part II Localized Chemistry 249 12 Aqueous Two-Phase Systems for Micropatterning of Cells and Biomolecules 251 Stephanie L. Ham and Hossein Tavana 12.1 Introduction 251 12.2 Small Molecules Applications 253 12.2.1 Bioreagent Patterning 253 12.2.2 Antibody Assays 253 12.2.3 Collagen Microgels 256 12.3 Cell Patterning 258 12.3.1 Bacterial Cells 258 12.3.2 Mammalian Cells 260 12.3.2.1 Cell Exclusion and Cell Island Patterning 260 12.3.2.2 Cell Co-Culturing 262 12.3.2.3 Heterocellular Stem Cell Niche Engineering 264 12.3.2.4 Skin Tissue Engineering 265 12.3.2.5 Three-Dimensional Cellular Models 266 12.4 Conclusions 269 Acknowledgments 269 References 269 13 Development of Pipettes as Mobile Nanofluidic Devices for Mass Spectrometric Analysis 273 Anumita Saha-Shah and Lane A. Baker 13.1 Introduction 273 13.2 Segmented Flow Analysis 275 13.3 Utility of Nano- and Micropipettes in Mass Spectrometry 276 13.4 Development of Nanopipette Probes for Local Sampling 276 13.5 MALDI-MS Analysis of Analyte Post-Nanopipette Sampling 278 13.5.1 Single Allium cepa Cell Analysis 279 13.5.2 Lipid Analysis in Mouse Brain 280 13.6 Development of Segmented Flow Sampling 282 13.7 Study of Intercellular Heterogeneity 286 13.8 Conclusion and Outlook 288 Acknowledgments 290 References 290 14 FluidFM: Development of the Instrument as well as Its Applications for 2D and 3D Lithography 295 Tomaso Zambelli, Mathias J. Aebersold, Pascal Behr, Hana Han, Luca Hirt, VincentMartinez, Orane Guillaume-Gentil, and János Vörös 14.1 Microchanneled AFM Cantilevers 296 14.1.1 Silicon-Based Hollow Probes 296 14.1.2 Polymer-Based Hollow Probes 297 14.2 Development of the FluidFM 300 14.3 Calibration of Hollow Probes: Stiffness and Flow 303 14.3.1 Stiffness 303 14.3.2 Flow 305 14.4 FluidFM as Lithography Tool in Liquid 308 14.4.1 Patterning Nanoparticles 308 14.4.2 Electrochemical 2D Patterning and 3D Printing 312 14.5 Conclusions and Outlook 316 Acknowledgments 317 References 317 15 FluidFM Applications in Single-Cell Biology 325 Orane Guillaume-Gentil,MaximilianMittelviefhaus, Livie Dorwling-Carter, Tomaso Zambelli and Julia A. Vorholt 15.1 Introduction 325 15.2 Nondestructive Cell Manipulations 326 15.3 Spatial Cell Manipulation 327 15.3.1 Substrate Micropatterning 327 15.3.2 Pick and Place 329 15.3.3 Cell Dispensing/Removal 330 15.4 Controlled Fluid Delivery 331 15.4.1 Extracellular Fluid Delivery 332 15.4.2 Intracellular Fluid Delivery 333 15.5 Mechanical Measurements 335 15.5.1 Quantification of Cell Elasticity 336 15.5.2 Quantification of Single-Cell Adhesion Forces 337 15.6 Ionic Current Measurements 341 15.6.1 Adaptation of the FluidFM Setup for Picoampere Current Measurements 342 15.6.2 Force-Controlled Patch Clamp with the FluidFM 343 15.6.3 Scanning Ion Conductance Microscopy with the FluidFM 346 15.7 Molecular Analyses 348 15.8 Conclusion and Future Perspectives 349 References 350 16 Soft Probes for Scanning ElectrochemicalMicroscopy 355 Tzu-En Lin, Andreas Lesch, Alexandra Bondarenko, Fernando Cortés-Salazar, and Hubert H. Girault 16.1 Introduction 355 16.2 Principles of Scanning Electrochemical Microscopy (SECM) 356 16.2.1 SECM Feedback Mode 356 16.2.2 SECM Generation/Collection Modes 358 16.3 Soft Probes for SECM 358 16.3.1 Fabrication and Characterization 359 16.3.2 Operation Principles 360 16.4 Applications of Soft SECM Probes 360 16.4.1 Reactivity Imaging of Extended Three-Dimensional Samples 362 16.4.2 High-Throughput Patterning and Imaging of Delicate Surfaces 362 16.4.3 Detection of Cancer Biomarkers in Skin Biopsy Sections 364 16.5 Conclusions and Future Perspectives 368 References 368 17 Microfluidic Probes for Scanning Electrochemical Microscopy 373 Alexandra Bondarenko, Fernando Cortés-Salazar, Tzu-En Lin, Andreas Lesch, and Hubert H. Girault 17.1 Introduction 373 17.2 Combining Microfluidics with SECM 374 17.2.1 Fountain Pen Probe 374 17.2.2 Electrochemical Push–Pull Probes 375 17.3 Electrochemical Characterization 377 17.3.1 Cyclic Voltammetry 377 17.3.2 SECM Experiments 378 17.4 Applications 382 17.4.1 SECM Imaging of Human Fingerprints Contaminated with Explosive Traces 382 17.4.2 Monitoring Enzymatic Reactions 384 17.4.3 Local Manipulation of Adherent Live Cell Microenvironments 385 17.5 Conclusions and Outlook 389 References 389 18 Chemistrode for High Temporal- and Spatial-Resolution Chemical Analysis 391 Alexander J. Donovan and Ying Liu 18.1 Introduction 391 18.2 Chemistrode Design and Operation 394 18.2.1 Chemistrode Design and Fabrication 394 18.2.2 Chemistrode Operation 394 18.3 Physical Principles Governing the Transport Processes 395 18.3.1 Non-dimensional Groups 395 18.3.2 Coalescence Dynamics of Incoming Plugs with the Hydrophilic Substrate 396 18.3.3 Mass Transfer at the Hydrophilic Substrate 398 18.4 Multiform Chemical Analysis Independent in Space and Time from Data Acquisition 400 18.4.1 Online Analysis 400 18.4.2 Parallel Offline Analysis 401 18.5 Applicability for Stimuli–Response Surfaces 403 18.5.1 Single Islet Cell Stimulation and Response Analysis 403 18.5.2 Isolation and Incubation of Individual Cells from Multispecies Mixtures 405 18.6 Challenges and Future Directions 406 Acknowledgments 407 References 407 Index 411