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LABS CHIP
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LABS CHIP
Principles, Design, and Technology
on
Eugenio Iannone
D i anax s.r.l. CEO and Founder, Milano, Ita l y
Boca Raton London New York
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This book is dedicated to my wife, Flavia, and to my children,
Emanuele, Maria Grazia, and Gabriele. I simply would not be
who I am without my family, and this book would not have been
possible without their continuous encouragement and support.

Contents
Preface............................................................................................................................................xxv
Acknowledgment..........................................................................................................................xxvii
Author............................................................................................................................................xxix
Introduction....................................................................................................................................xxxi
Section I Biological Chemistry
Chapter 1 Elements of Organic Chemistry....................................................................................3

1.1 Introduction........................................................................................................3
1.2 Thermodynamic and Chemical Properties of Solutions....................................3
1.2.1 Thermodynamic State Functions..........................................................3
1.2.1.1 Enthalpy.................................................................................5
1.2.1.2 Gibbs Free Energy.................................................................6
1.2.1.3 Chemical Potential.................................................................8
1.2.1.4 Quasi-Equilibrium State and Local Thermodynamic
State Functions......................................................................9
1.2.2 Chemical Properties of Solutions........................................................ 11
1.2.2.1 Solution Concentration........................................................ 11
1.2.2.2 Solvability............................................................................ 14
1.2.2.3 Solution Colligative Properties............................................ 17
1.2.3 Chemical Equilibrium in Reactions among Solutes........................... 17
1.2.3.1 Simple Reaction Equilibrium and the Law of Mass
Action................................................................................. 17
1.2.3.2 Simultaneous Equilibrium of Several Reactions.................20
1.2.4 Reaction Kinetics................................................................................ 23
1.2.5 Catalysis..............................................................................................28
1.2.6 Solvability in a Polar Solvent.............................................................. 29
1.2.6.1 Solutions of Gases in Liquids.............................................. 32
1.2.6.2 Solutions of Liquids in Liquids............................................ 32
1.2.6.3 Solutions of Solids in Liquids.............................................. 33
1.3 Organic Chemistry Building Blocks................................................................34
1.3.1 Hydrocarbons: Types and Structure.................................................... 35
1.3.1.1 Alkanes................................................................................ 35
1.3.1.2 Alkyl Groups....................................................................... 37
1.3.1.3 Alkenes................................................................................ 38
1.3.1.4 Alkynes................................................................................ 39
1.3.1.5 Stereoscopic Structure of Hydrocarbons............................. 39
1.3.1.6 Aromatic Hydrocarbons......................................................40
1.3.2 Functional Groups............................................................................... 41
1.3.2.1 Allogeneic Functional Group.............................................. 41
1.3.2.2 Alcoholic Functional Group................................................ 42
1.3.2.3 Ester Functional Group........................................................44
1.3.2.4 Ether Functional Group....................................................... 45
1.3.2.5 Aldehyde Functional Group................................................46
xi

xii Contents
1.3.2.6 Ketone Functional Group.................................................... 48

1.3.2.7 Acid Functional Group........................................................ 50
1.3.2.8 Amino Functional Group..................................................... 52
1.3.2.9 Amide Functional Group..................................................... 55
1.4 Polymers........................................................................................................... 56
1.4.1 Polymerization and Polymer Types..................................................... 57
1.4.2 Polymeric Materials Structure............................................................60
1.4.3 Polymers for Microfabrication Main Properties................................. 65
1.5 Microscopic Models of Macromolecule Solutions........................................... 72
1.5.1 Implicit Solvent Models for Solution in Equilibrium.......................... 73
1.5.1.1 Cavity Free Solvation Energy.............................................. 75
1.5.1.2 Electromagnetic Free Solvation Energy.............................. 77
1.5.1.3 van der Waals Free Solvation Energy.................................. 79
1.5.1.4 Implicit Solvent Models and Explicit Solvent Simulations.....79
1.5.2 Chemical Reactions between Macromolecules: The Perfect
Gas of Macromolecules....................................................................... 82
1.5.3 Collisions and Reaction Kinetics........................................................84
References................................................................................................................... 91
Chapter 2 Elements of Biochemistry........................................................................................... 95

2.1 Introduction...................................................................................................... 95
2.2 Structural Organization of Biochemical Macromolecules...............................96
2.2.1 General Properties of Macromolecules...............................................99
2.2.1.1 van der Waals Forces...........................................................99
2.2.1.2 Hydrogen Bonds................................................................ 100
2.2.1.3 Ionic Interactions............................................................... 102
2.2.1.4 Biological Macromolecule Complementarity.................... 102
2.2.1.5 Enzymatic Catalysis.......................................................... 103
2.2.2 Organization and Structure of the Cell............................................. 104
2.2.2.1 Cell Structural Organization............................................. 105
2.2.3 Viruses............................................................................................... 107
2.2.4 Classes of Biological Macromolecules.............................................. 108
2.3 Protein Structure and Chemistry.................................................................... 108
2.3.1 Protein Chemical Structure............................................................... 108
2.3.1.1 Acid–Base Reactions of Amino Acids.............................. 109
2.3.1.2 Protein General Chemical Composition............................ 110
2.3.1.3 Protein Primary Structure................................................. 111
2.3.2 Protein Stereography: Secondary Structure...................................... 112
2.3.2.1 The Protein Helixes........................................................... 113
2.3.2.2 The Protein β-Sheets......................................................... 116
2.3.3 Protein Stereography: Tertiary Structure.......................................... 118
2.3.4 Role of Proteins in Biochemistry...................................................... 122
2.3.4.1 Contractile Proteins........................................................... 122
2.3.4.2 Enzymatic Proteins............................................................ 125
2.3.4.3 Hormones........................................................................... 125
2.3.4.4 Structural Proteins............................................................. 128
2.3.4.5 Storage Proteins................................................................. 128
2.3.4.6 Transport Proteins............................................................. 128
2.4 Immunoglobulin............................................................................................. 130
2.4.1 Immunoglobulin G Structure............................................................ 131

Contents xiii
2.4.2 Classification of Human Immunoglobulin........................................ 135

2.5 Enzymatic Catalysis....................................................................................... 138
2.5.1 The Basic Principle of Enzymes Working........................................ 138
2.5.2 Kinetics of Enzyme-Catalyzed Reactions........................................ 139
2.5.2.1 The Michaelis–Menten Kinetic Model.............................. 141
2.5.3 Dependency of Enzyme Kinetics on Enzyme Type and
Environment...................................................................................... 146
2.5.3.1 Allosteric Enzymes............................................................ 146
2.5.3.2 Effect of pH on Enzymatic Activity.................................. 147
2.5.3.3 Effect of Temperature on Enzymatic Activity................... 148
2.5.4 Enzyme Inhibition............................................................................. 149
2.5.4.1 Competitive Inhibition....................................................... 150
2.5.5 Enzymatic Catalysis Thermodynamics............................................. 151
2.5.5.1 ES Binding Energy............................................................ 152
2.5.5.2 Entropy Loss and Destabilization of the ES Complex...... 152
2.6 Nucleic Acids.................................................................................................. 153
2.6.1 Deoxyribonucleic Acid...................................................................... 155
2.6.1.1 DNA General Structure..................................................... 155
2.6.1.2 DNA Supercoiling............................................................. 157
2.6.1.3 Genetic Code for Proteins Synthesis................................. 158
2.6.1.4 DNA Replication............................................................... 160
2.6.1.5 DNA Interactions with Proteins........................................ 160
2.6.2 Ribonucleic Acid Structure............................................................... 161
2.6.3 RNA Types and Roles....................................................................... 162
2.6.3.1 RNA Role in Translation................................................... 163
2.6.3.2 Regulatory RNAs.............................................................. 164
2.7 Lipids.............................................................................................................. 164
2.7.1 Free Fatty Acids................................................................................ 164
2.7.2 Triacylglycerols................................................................................. 166
2.7.3 Membrane Lipids.............................................................................. 166
2.7.4 Steroids.............................................................................................. 169
2.8 Carbohydrates................................................................................................. 169
2.8.1 Monosaccharides............................................................................... 170
2.8.2 Oligosaccharides............................................................................... 175
2.8.3 Glycoproteins.................................................................................... 176
References................................................................................................................. 178
Chapter 3 Biochemical Assays and Sequencing Techniques..................................................... 183

3.1 Introduction.................................................................................................... 183
3.2 Assay Procedure and Preparation.................................................................. 183
3.2.1 Cells Lysis Techniques...................................................................... 185
3.2.1.1 Mild Lysis (Osmotic Lysis)................................................ 185
3.2.1.2 Enzymatic Lysis Method................................................... 186
3.2.1.3 Bead Lysis Method............................................................ 186
3.2.1.4 Sonication Lysis................................................................. 187
3.2.1.5 Detergent Lysis Method..................................................... 187
3.2.1.6 Thermal Lysis Method....................................................... 188
3.2.2 Nucleic Acid Extraction from Cell Lysates....................................... 188
3.2.2.1 Guanidinium Thiocyanate–Phenol–Chloroform
Extraction........................................................................... 188

xiv Contents
3.2.2.2 Spin Column-Based Nucleic Acid Extraction................... 189

3.2.2.3 Magnetic Bead-Based Nucleic Acid Extraction................ 190
3.2.2.4 Anion-Exchange-Based Nucleic Acid Extraction............. 190
3.2.3 Protein Extraction from Cell Lysates................................................ 191
3.2.3.1 Ammonium Sulfate Precipitation...................................... 191
3.2.4 Protein Hydrolysis............................................................................. 192
3.3 DNA Amplification by Polymerase Chain Reaction...................................... 193
3.3.1 PCR Efficiency.................................................................................. 194
3.3.2 PCR Alternative Procedures............................................................. 197
3.3.2.1 Real-Time PCR.................................................................. 198
3.3.2.2 Reverse Transcriptase-Polymerase Chain Reaction.......... 199
3.3.2.3 PCR Variations..................................................................200
3.4 Enzymatic Assays........................................................................................... 201
3.4.1 Detection Methods in Enzymatic Assays.......................................... 201
3.4.1.1 Continuous Detection........................................................202
3.4.1.2 Discontinuous Detection....................................................205
3.5 Chromatography.............................................................................................206
3.5.1 Liquid Column Chromatography......................................................206
3.5.2 High-Performance Liquid Chromatography..................................... 211
3.5.3 Alternatives to Adsorption Liquid-Phase Chromatography.............. 212
3.5.3.1 Ions-Exchange Liquid-Phase Chromatography................. 212
3.5.3.2 Size-Exclusion Chromatography....................................... 213
3.5.3.3 Gas Chromatography......................................................... 215
3.6 Electrophoresis............................................................................................... 219
3.6.1 Electrophoresis Gel Types................................................................. 221
3.6.1.1 Agarose.............................................................................. 221
3.6.1.2 Polyacrylamide.................................................................. 222
3.6.1.3 Starch................................................................................. 222
3.6.2 Protein Electrophoresis..................................................................... 222
3.6.3 Nucleic Acid Electrophoresis............................................................224
3.7 Immunoassays................................................................................................ 228
3.7.1 Structure and Thermodynamic of Antigen–Antibody
Neutralization.................................................................................... 228
3.7.2 Kinetic of Antigen–Antibody Neutralization.................................... 232
3.7.3 Immunoassay Processes.................................................................... 236
3.7.4 Western Blot or Immunoelectrophoresis........................................... 239
3.7.4.1 Tissue Preparation............................................................. 239
3.7.4.2 Gel Electrophoresis............................................................ 241
3.7.4.3 Transfer.............................................................................. 241
3.7.4.4 Blocking............................................................................. 241
3.7.4.5 Detection............................................................................ 241
3.7.4.6 Analysis............................................................................. 242
3.7.5 Enzyme-Linked Immunosorbent Assay............................................ 242
3.7.5.1 Indirect ELISA..................................................................244
3.7.5.2 Sandwich ELISA...............................................................244
3.7.5.3 Competitive ELISA........................................................... 245
3.7.6 Flow Cytometry Assay......................................................................246
3.7.6.1 Particle Labeling in Flow Cytometry................................246
3.7.6.2 Flow Cytometer Structure.................................................248
3.7.6.3 List of Measurable Parameters.......................................... 249

Contents xv
3.8 Nucleic Acid Sequencing................................................................................ 249

3.8.1 First-Generation Fragment Sequencing............................................ 252
3.8.1.1 Chain Termination Method (Sanger Method)................... 252
3.8.1.2 Maxam–Gilbert Sequencing Method................................ 254
3.8.2 Second-Generation Fragment Sequencing........................................ 256
3.8.2.1 Polony Sequencing............................................................. 256
3.8.2.2 Pyrosequencing.................................................................. 258
3.8.2.3 Other Second-Generation Sequencing Methods............... 262
3.8.3 Third-Generation Fragment Sequencing........................................... 263
3.8.3.1 Sequencing by Hybridization............................................264
3.8.3.2 Microscopy-Based Techniques..........................................264
3.8.3.3 RNAP Sequencing.............................................................264
3.8.4 Fragmenting and Assembly Methods................................................264
3.8.4.1 Primer Walking (Chromosome Walking).........................264
3.8.4.2 Shotgun Sequencing.......................................................... 265
3.9 Protein Sequencing and Structural Assessment.............................................266
3.9.1 Protein Sequencing............................................................................266
3.9.1.1 Sequencing through Edman Degradation.......................... 267
3.9.1.2 Protein N-Terminus Identification..................................... 267
3.9.2 Protein Structure Assessment........................................................... 269
References................................................................................................................. 269
Section II Lab on Chip Technology
Chapter 4 Planar Technology..................................................................................................... 279

4.1 Introduction.................................................................................................... 279
4.2 Planar Process Flow of a Lab on Chip...........................................................280
4.2.1 Front-End Process Flow.................................................................... 281
4.2.2 Back-End Process Flow..................................................................... 289
4.2.3 Production Testing Techniques......................................................... 292
4.2.3.1 On-Wafer Testing............................................................... 292
4.2.3.2 Back-End Testing............................................................... 294
4.2.3.3 Fault Simulation................................................................. 294
4.2.3.4 Design for Testing.............................................................. 296
4.2.4 In-Field Testing................................................................................. 297
4.3 Micro- and Nano-Fabrication Fabs................................................................ 297
4.3.1 Clean Rooms..................................................................................... 298
4.3.1.1 Clean Room Classification................................................ 298
4.3.1.2 Clean Room Structure and Procedures............................. 299
4.3.2 Fabrication Materials: Silicon, Silica on Silicon and Pure
Silica Wafers.....................................................................................304
4.3.2.1 Standard Silicon Wafers.................................................... 305
4.3.2.2 Glass Wafers......................................................................307
4.3.2.3 Number of Chips on a Wafer.............................................308
4.4 Planar Technology Cost Model......................................................................308
4.4.1 Industrial Cost Models...................................................................... 310
4.4.1.1 General Expression of the Cost of Produced Goods......... 310
4.4.1.2 Different Cost Models....................................................... 311

xvi Contents
4.4.2 Industrial Cost Estimation for Microfluidic-Based Labs

on Chip.............................................................................................. 312
4.4.2.1 Industrial Cost Parameters................................................ 312
4.5 Photolithography............................................................................................ 316
4.5.1 Wafer Cleaning.................................................................................. 317
4.5.2 Photoresist Deposition....................................................................... 317
4.5.2.1 Photoresist Spin Coating Deposition................................. 317
4.5.2.2 Alternative Photoresist Deposition Processes................... 319
4.5.2.3 Photoresist Types............................................................... 322
4.5.2.4 Permanent Resists.............................................................. 324
4.5.3 Mask Alignment................................................................................ 325
4.5.3.1 Types of Masks for Planar Lithography............................ 325
4.5.3.2 Three-Dimensional Photolithography Masks.................... 329
4.5.4 Photoresist Exposure......................................................................... 330
4.5.5 Post-Exposure Processes................................................................... 334
4.5.5.1 Post-Exposure Bake........................................................... 334
4.5.5.2 Development...................................................................... 334
4.5.5.3 Postbake............................................................................. 335
4.5.5.4 Pattern Transfer................................................................. 336
4.5.5.5 Photoresist Stripping.......................................................... 336
4.5.6 Photolithography Definition.............................................................. 336
4.6 Electron Beam Lithography........................................................................... 339
4.7 Etching............................................................................................................ 341
4.7.1 Wet Etching Techniques.................................................................... 342
4.7.1.1 Wet Etching Characteristics.............................................. 342
4.7.1.2 Wet Etching Equipments................................................... 345
4.7.2 Plasma Characteristics and Plasma Generation for Planar
Processes........................................................................................... 347
4.7.2.1 Plasma Characteristics and Generation............................. 347
4.7.2.2 DC Glow Plasma Generation............................................. 349
4.7.2.3 RF Plasma Generation....................................................... 351
4.7.3 Dry Etching Techniques.................................................................... 354
4.7.3.1 Sputtering Etching (Ion Milling)....................................... 355
4.7.3.2 Reactive Ion Etching: Plasma Etching.............................. 358
4.7.3.3 Reactive Ion Etching: Physical plus Chemical Etching...... 360
4.7.3.4 Deep Reactive Ion Etching................................................ 363
4.8 Deposition.......................................................................................................364
4.8.1 Chemical Vapor Deposition.............................................................. 365
4.8.1.1 CVD Process Types and CVD Reactors........................... 365
4.8.1.2 CVD Deposition of Different Materials............................ 369
4.8.2 Physical Vapor Deposition................................................................ 372
4.8.2.1 Thermal PVD.................................................................... 373
4.8.2.2 Electron-Beam PVD.......................................................... 373
4.8.2.3 Other PVD Techniques...................................................... 374
4.8.3 Other Physical Deposition Techniques.............................................. 375
4.8.3.1 Physical Plasma Deposition (Sputtering)........................... 375
4.8.3.2 Molecular Beam Epitaxy................................................... 377
4.9 Wafer Bonding................................................................................................ 379
4.9.1 Planarization..................................................................................... 379
4.9.2 Adhesive Wafer Bonding................................................................... 381
4.9.2.1 Adhesive Wafer Bonding Principle................................... 381

Contents xvii
4.9.2.2 Bond Quality of Adhesive Wafer Bonding........................ 382

4.9.2.3 Adhesive Wafer Bonding Process and Reactor
Structure......................................................................... 384
4.9.3 Direct Wafer Bonding....................................................................... 386
4.9.3.1 Direct Wafer Bonding Principle........................................ 386
4.9.3.2 Thermal Direct Wafer Bonding......................................... 389
4.9.3.3 Electrically Enhanced Thermal Wafer Bonding
(Anodic Bonding).............................................................. 390
4.9.3.4 Plasma-Enhanced Direct Wafer Bonding.......................... 391
4.9.4 Wafer Alignment............................................................................... 392
4.9.4.1 Optical Microscopy Alignment Method............................ 393
4.9.4.2 Backside Alignment with Digitalized Image.................... 394
4.9.4.3 Smart View Alignment Method........................................ 394
References................................................................................................................. 394
Chapter 5 Polymer Technology.................................................................................................. 401

5.1 Introduction.................................................................................................... 401
5.2 Soft Lithography.............................................................................................402
5.2.1 Micro-Contact Printing.....................................................................403
5.2.1.1 Self-Assembled Monolayer Inks for Micro-Contact
Printing..............................................................................404
5.2.1.2 Micro-Contact Printing Properties....................................406
5.2.2 Micro-Transfer Molding....................................................................407
5.2.3 Micro-Molding in Capillaries and Micro-Replica Molding.............408
5.3 Deposition Techniques................................................................................... 410
5.3.1 Polymer Film Deposition through Spray Coating............................. 411
5.3.1.1 Plasma Spray Coating........................................................ 411
5.3.1.2 Polymers for Spray Deposition.......................................... 413
5.3.2 Polymer Knife Coating..................................................................... 413
5.3.3 Plasma-Enhanced Polymerization..................................................... 414
5.3.4 Langmuir–Blodgett Deposition......................................................... 418
5.4 Patterning Techniques.................................................................................... 421
5.4.1 Inkjet Printing................................................................................... 422
5.4.2 Micro-Stereo-Lithography................................................................ 423
5.5 Micro-Molding............................................................................................... 427
5.5.1 Thin Wall Injection Molding............................................................. 429
5.5.2 Hot Embossing.................................................................................. 430
5.6 Lithographie, Galvanik und Abformung........................................................ 432
5.6.1 Deep X-Ray Lithography for LIGA.................................................. 434
5.6.1.1 Fabrication of an Intermediate Mask................................. 434
5.6.1.2 Fabrication of a Working Mask......................................... 436
5.6.1.3 Deep X-Ray Lithography................................................... 437
5.6.1.4 Electroforming of Metal Mold: Hot Embossing................ 437
5.6.2 X-Ray Lithography............................................................................ 437
5.6.2.1 X-Ray Source..................................................................... 439
5.6.2.2 X-Ray Resists..................................................................... 441
5.6.3 Electroplating.................................................................................... 443
5.7 Laser Ablation................................................................................................444
5.7.1 Laser Ablation Basics and Mechanism.............................................444
5.7.2 Parameters of Laser Ablation............................................................446

xviii Contents
5.7.2.1 Substrate Absorption and Reflection of the Laser

Wavelength........................................................................446
5.7.2.2 Laser Spot Size..................................................................448
5.7.2.3 Depth of Focus................................................................... 450
5.7.2.4 Laser Pulse Repetition Rate and Pulse Length................. 450
5.7.3 Laser Ablation Alternative Processes............................................... 452
References................................................................................................................. 453
Chapter 6 Back-End Technologies............................................................................................. 457

6.1 Introduction.................................................................................................... 457
6.2 Back-End Requirements and Process Flow.................................................... 458
6.3 Hybrid Integration.......................................................................................... 462
6.3.1 Chip-on-Chip Integration.................................................................. 462
6.3.2 Multi-Chip Packaging....................................................................... 467
6.3.2.1 Multi-Chip Packaging for Electronic Integration..............468
6.3.2.2 Flip-Chip Electronic Connection between Chips..............469
6.4 Bonding Techniques in Micro-Fabrication..................................................... 470
6.4.1 Gluing................................................................................................ 470
6.4.2 Laser Welding................................................................................... 473
6.4.3 Soldering........................................................................................... 479
6.4.4 Eutectic Bonding............................................................................... 481
6.5 Back-End Processes........................................................................................ 482
6.5.1 Wafer Dicing and Die Attach............................................................ 482
6.5.2 Electronic Interface Fabrication........................................................ 485
6.5.2.1 Wire Bonding.................................................................... 485
6.5.3 Microfluidic Interface Fabrication.................................................... 488
6.5.3.1 Microfluidic Vertical Inlet................................................. 490
6.5.3.2 Microfluidic Horizontal Inlet/Outlet................................. 494
6.5.3.3 Chip Charging with Reactants........................................... 495
6.5.4 Optical Interface Fabrication............................................................ 496
6.5.4.1 Chip Multi-Mode Fiber Interface...................................... 497
6.5.4.2 Si-SiO2 Chip: Single-Mode Fiber Interface.......................500
6.5.4.3 Optical Interfaces without Fiber Optics............................ 503
6.6 Temperature Control.......................................................................................506
6.6.1 Heaters and Thermistors...................................................................506
6.6.2 Temperature Stabilization by Peltier Elements................................. 508
6.6.3 Heating Micro-Systems..................................................................... 511
References................................................................................................................. 514
Section III Lab on Chip Design
Chapter 7 Fluid Dynamics in Microfluidic Circuits.................................................................. 521

7.1 Introduction.................................................................................................... 521
7.2 Kinematic of Fluid Motion............................................................................. 522
7.2.1 The Continuous Fluid Model............................................................ 522
7.2.2 Fluid Motion Description.................................................................. 523
7.2.3 Continuity Equation.......................................................................... 529

Contents xix
7.3 Fluid Dynamics.............................................................................................. 530

7.3.1 The Momentum Evolution Equation................................................. 530
7.3.1.1 Change of Momentum Due to Fluid Motion..................... 531
7.3.1.2 Stress Tensor in the Fluid, Pressure, and Viscosity........... 532
7.3.1.3 Change of Momentum Due to Pressure and Viscous
Forces................................................................................. 533
7.3.1.4 Change of Momentum Due to Body Forces...................... 536
7.3.1.5 The General Equation of Motion and Newtonian Fluids......536
7.3.2 The Energy Evolution Equation........................................................ 539
7.3.3 Newtonian Liquids Flow in Lab-on-Chip Ducts: Simplified Model....543
7.3.3.1 State Equation: Incompressibility Hypothesis................... 543
7.3.3.2 Low Reynolds Number and Temperature Fluctuations.....544
7.3.3.3 No-Slip Boundary Condition............................................. 545
7.3.4 The Liquid Flow in a Microfluidic Duct: Poiseuille Flow................ 545
7.3.4.1 Energy Aspects of the Poiseuille Flow.............................. 550
7.3.4.2 Hydrodynamic Circuit Theory.......................................... 550
7.3.4.3 Poiseuille Flow in Ducts with a Simple Geometry........... 552
7.3.4.4 Transition Region at the Duct Input/Output...................... 557
7.3.4.5 Temporal Transient at the Start/End of a Poiseuille Flow....560
7.3.5 Interfaces Phenomena and Droplets.................................................. 561
7.3.5.1 Pressure on a Curved Interface.........................................564
7.3.5.2 Contact Angle and Wetting Capacity of a Liquid.............. 567
7.3.5.3 Capillary Effect................................................................. 571
7.3.5.4 Droplet Generation............................................................ 574
7.3.6 Non-Newtonian Fluids...................................................................... 578
7.3.6.1 Time-Independent Non-Newtonian Fluids........................ 580
7.3.6.2 Time-Dependent Non-Newtonian Fluids.......................... 582
7.3.6.3 Visco-Elastic Non-Newtonian Fluids................................ 583
7.4 Solutions Dynamics: Diffusion...................................................................... 584
7.4.1 Diffusion Models............................................................................... 584
7.4.2 The Diffusion Coefficient................................................................. 587
7.4.3 Diffusion Equation Basic Solutions: Free Diffusion......................... 591
7.4.3.1 Green Function and Free Diffusion from an Initial
Distribution........................................................................ 592
7.4.3.2 Source and Flux-Driven Free Diffusion............................ 593
7.4.4 Diffusion Equation Basic Solutions: Diffusion in Limited
Volumes............................................................................................. 597
7.4.5 The Chemical–Diffusion Model: Examples.....................................600
7.4.6 Diffusion–Convection Model: Examples..........................................604
7.5 Electro-Hydrodynamics.................................................................................608
7.5.1 Ions Electrophoresis.......................................................................... 610
7.5.2 Stern and Debye Layers.................................................................... 611
7.5.3 Protein and Nucleic Acids Electrophoresis....................................... 616
7.5.4 Electroosmosis.................................................................................. 617
7.5.5 Electrophoresis of Neutral Particles (Dielectrophoresis).................. 620
7.5.6 Electrowetting................................................................................... 624
7.6 Magneto-Hydrodynamics............................................................................... 626
7.6.1 Magnetostatic Basics......................................................................... 626
7.6.2 Magnetophoresis............................................................................... 629
7.6.3 Bead Concentration Evolution........................................................... 631
References................................................................................................................. 633

xx Contents
Chapter 8 Microfluidic Building Blocks.................................................................................... 637

8.1 Introduction.................................................................................................... 637
8.2 Fluid Flow Control: Microvalves................................................................... 637
8.2.1 Control Microvalves.......................................................................... 637
8.2.2 Active Microvalves............................................................................ 641
8.2.2.1 Electrostatic and Electromagnetic Microvalves................ 642
8.2.2.2 Pneumatic and Thermopneumatic Microvalves................646
8.2.2.3 Thermomechanical Microvalves....................................... 650
8.2.2.4 Shape Memory Alloy Microvalves.................................... 653
8.2.2.5 Piezoelectric Microvalves.................................................. 656
8.2.2.6 Electrochemical and Chemical Microvalves..................... 658
8.2.3 Microvalve Design Considerations...................................................664
8.2.3.1 Valve Equivalent Spring and Bistable Valves
(Latching Valves)...............................................................664
8.2.3.2 Valve Seat.......................................................................... 667
8.2.3.3 Fluid Flux through the Valve............................................. 667
8.2.4 Microvalve Performance Comparison.............................................. 669
8.3 Fluid Flow Generation: Micropumps............................................................. 673
8.3.1 Mechanical Micropumps................................................................... 675
8.3.2 Capillary Micropumps...................................................................... 679
8.3.2.1 Passive Capillary Micropumps..........................................680
8.3.2.2 Transpiration Micropumps................................................ 685
8.3.3 Electromagnetic Micropumps........................................................... 687
8.3.3.1 Electrostatic Micropumps.................................................. 688
8.3.4 Comparison among Different Micropump Architectures................. 693
8.4 Sample Preparation: Micromixers.................................................................. 696
8.4.1 Lamination Mixers............................................................................ 697
8.4.1.1 Basic Lamination Mixer Structures.................................. 697
8.4.1.2 Parallel, Sequential and Other Lamination Mixer
Structures...........................................................................700
8.4.1.3 Lamination Mixing by Stream Focusing........................... 706
8.4.2 Chaotic Advection Micromixers....................................................... 712
8.4.2.1 Chaotic Advection Micromixers in a High Reynolds
Number Regime................................................................. 713
8.4.2.2 Chaotic Advection Micromixers in an Intermediate
Reynolds Number Regime................................................. 714
8.4.2.3 Chaotic Advection Micromixers in a Low Reynolds
Number Regime................................................................. 715
8.4.3 Active Micromixers........................................................................... 716
8.4.4 Comparison among Different Micromixer Architectures................ 717
8.5 Sample Purification: Filters............................................................................ 718
8.5.1 Hydrodynamic Filters........................................................................ 720
8.5.1.1 Pure Hydrodynamic Filters............................................... 723
8.5.1.2 Pinched Flow Fractionation Filters.................................... 724
8.5.1.3 Diffusion-Based Filters...................................................... 728
8.5.1.4 On-Chip Chromatography................................................. 731
8.5.2 Electrophoresis Filters....................................................................... 731
8.5.2.1 Free-Flow Electrophoresis................................................. 736
8.5.2.2 Capillary Electrophoresis.................................................. 738
8.5.3 Membrane Filters.............................................................................. 741

Contents xxi
8.5.3.1 Size-Exclusion Membrane Filters...................................... 741

8.5.3.2 Microdialysis Filters.......................................................... 743
8.6 Microdroplets in Microfluidic Circuits.......................................................... 750
8.6.1 Droplet Stability and Breaking Down............................................... 750
8.6.2 Microdroplet Break........................................................................... 754
8.6.2.1 T Junction.......................................................................... 754
8.6.2.2 Droplets Break-Up by Stream Focusing............................ 756
8.6.2.3 λ Junction........................................................................... 760
8.7 Droplet Generation......................................................................................... 760
8.7.1 T Junction Droplet Generator............................................................ 761
8.7.2 Stream Focus Droplet Generator....................................................... 765
8.8 Micropumps for Droplet Flow........................................................................ 768
8.8.1 Thermocapillary Micropumps.......................................................... 769
8.8.2 Electrowetting Micropumps.............................................................. 775
References................................................................................................................. 777
Chapter 9 Surface Functionalization......................................................................................... 785

9.1 Introduction.................................................................................................... 785
9.2 Surface Activation for Labs on Chip.............................................................. 786
9.2.1 Noncovalent Chemical Surface Activation....................................... 787
9.2.2 Covalent Chemical Surface Activation............................................. 788
9.2.2.1 Covalent Activation by Zero-Length Crosslinkers............ 788
9.2.2.2 Bifunctional Crosslinker.................................................... 789
9.3 Activation of Different Substrates.................................................................. 791
9.3.1 Glass Surface Activation................................................................... 791
9.3.2 Polymer Surface Activation.............................................................. 793
9.3.3 Metal Layer Activation...................................................................... 797
9.3.4 Nanoparticle Activation and Functionalization................................800
9.4 Surface Activation Using Carbon Nanotubes.................................................802
9.4.1 Carbon Nanotube Nature and Growth..............................................802
9.4.2 Carbon Nanotube Functionalization.................................................804
9.5 Antibody and Aptamer Surface Functionalization........................................807
9.5.1 Antibody Monolayers on Activated Surfaces....................................807
9.5.2 Aptamer Monolayers on Functionalized Surfaces............................808
9.6 Stability of Functionalized Surfaces for Labs on Chip.................................. 810
9.7 On-Chip Cells Immobilization....................................................................... 812
9.7.1 Immobilization through Adhesion Molecules................................... 813
9.7.1.1 Adhesion Molecule Families............................................. 813
9.7.1.2 Adhesion Molecule-Based Cell Immobilizations.............. 815
9.7.2 Immobilization in Gel....................................................................... 817
9.7.2.1 Gel Entrapment by Ionic Network Formation................... 818
9.7.2.2 Gel Entrapment by Precipitation....................................... 818
9.7.2.3 Gel Entrapment by Polymerization................................... 818
9.7.3 Immobilization in Artificial Structures............................................ 819
References................................................................................................................. 820
Chapter 10 Electronic Detection.................................................................................................. 825

10.1 Introduction.................................................................................................... 825
10.2 Detection System Parameters......................................................................... 826

xxii Contents
10.3 Impedance Detection...................................................................................... 828

10.3.1 Non-Faradaic Impedance Detection................................................. 831
10.3.1.1 Impedance of an Electrolytic Cell..................................... 832
10.3.1.2 Non-Faradaic Impedance Affinity Detection.................... 835
10.3.2 Faradaic Impedance Detection......................................................... 838
10.3.2.1 Reaction Rate Influence on Faradaic Impedance
Detection............................................................................ 839
10.3.2.2 Mass Transport Influence on Faradaic Impedance
Detection............................................................................ 842
10.3.2.3 Faradaic Impedance Detection in Lab on Chip.................844
10.3.3 Impedance-Based Cell Detection and Cell Activity Analysis..........846
10.3.4 Impedance Measurement Techniques............................................... 851
10.4 Voltammetry Detection.................................................................................. 854
10.4.1 Step Voltammetry or Chronoamperometry...................................... 856
10.4.2 Variable Potential Voltammetry........................................................860
10.4.2.1 Variable Potential Voltammetry Theory...........................860
10.4.2.2 Linear Voltammetry.......................................................... 867
10.4.2.3 Cyclic Voltammetry........................................................... 869
10.4.3 Electrodes for Voltammetry Detection............................................. 873
10.4.3.1 Carbon Electrodes for Lab on Chip................................... 873
10.4.3.2 Noble Metal Electrodes for Lab on Chip........................... 875
10.5 Amperometry Detection................................................................................. 876
10.5.1 Amperometry Enzymatic Detection................................................. 876
10.5.1.1 Amperometry Enzymatic Detector Analysis.................... 877
10.5.1.2 Mediator Selection............................................................. 882
10.5.2 Amperometry Detection with Integrated Capillary
Electrophoresis................................................................................ 885
10.5.3 Alternate On-Chip Amperometry Methods...................................... 888
10.5.3.1 Pulsed Amperometry......................................................... 889
10.5.3.2 Amperometry Detection Using Electrode Arrays............. 890
10.6 Mechanical Detection Based on Microcantilevers......................................... 891
10.6.1 Static Cantilever-Based Detection..................................................... 892
10.6.2 Dynamic Cantilever-Based Detection............................................... 894
10.6.3 Piezo-Resistive Cantilever Displacement Measure........................... 897
10.7 Calorimetric Detection................................................................................... 899
10.7.1 Enzymatic Dynamic Calorimeter Detection.....................................900
10.7.2 On-Chip Calorimeters....................................................................... 901
10.7.2.1 Thermopile-Based Microcalorimeters.............................. 901
10.7.2.2 Calorimeter Implementation..............................................904
References.................................................................................................................907
Chapter 11 Optical Detection...................................................................................................... 917

11.1 Introduction.................................................................................................... 917
11.2 Elements of Optics.......................................................................................... 918
11.2.1 Light Description by Waves and Photons......................................... 919
11.2.2 Classical Description of Interaction of Light with Matter................926
11.2.2.1 Light Propagation in a Nonconducting Material...............926
11.2.2.2 Light Propagation in an Electrolyte Solution.................... 931
11.2.3 Quantum Description of Interaction of Light with Matter................ 933

Contents xxiii
11.2.4 Light Detection..................................................................................940

11.2.4.1 Structure of an Optical Detector.......................................940
11.2.4.2 Optical Detector Performances.........................................944
11.2.5 Integrated Optical Circuits................................................................948
11.2.5.1 Optical Propagation in Integrated Dielectric
Waveguides...................................................................... 949
11.2.5.2 Optical Dielectric Waveguide Attenuation........................ 954
11.2.5.3 Integrated Optics Components.......................................... 958
11.3 Lab-on-Chip Spectroscopy............................................................................. 968
11.3.1 Absorption Spectroscopy.................................................................. 968
11.3.1.1 Absorption Spectroscopy Theory...................................... 968
11.3.1.2 Absorption Spectroscopy Implementation in Lab
on Chip.............................................................................. 970
11.3.2 Fluorescence Spectroscopy............................................................... 976
11.3.2.1 Fluorescence Spectroscopy Theory................................... 977
11.3.2.2 Fluorescence Spectroscopy Implementation in Lab
on Chip.............................................................................. 983
11.4 Surface Plasmon Resonance........................................................................... 988
11.4.1 Plasmons: Definition and Properties................................................. 988
11.4.1.1 Bulk Plasmons................................................................... 988
11.4.1.2 Surface Plasmons............................................................... 989
11.4.1.3 Surface Plasmon Excitation............................................... 993
11.4.2 Surface Plasmon Immunoassay Detection........................................997
11.4.3 Localized Plasmon Resonance Detection....................................... 1001
11.4.3.1 Localized Plasmons and Scattering from Nanoparticles....1001
11.4.3.2 Detection through Localized Plasma Resonance
Measurement.................................................................... 1003
11.5 Lab-on-Chip Interferometry......................................................................... 1009
References............................................................................................................... 1013
Chapter 12 Building Blocks for Genetics.................................................................................. 1021

12.1 Introduction.................................................................................................. 1021
12.2 On-Chip DNA Purification.......................................................................... 1022
12.2.1 Cell Lysis......................................................................................... 1022
12.2.1.1 Mechanical Lysis............................................................. 1023
12.2.1.2 Thermal lysis................................................................... 1025
12.2.1.3 Chemical Lysis................................................................ 1025
12.2.1.4 Electrical Lysis................................................................ 1027
12.2.1.5 Comparison of On-Chip Lysis Techniques...................... 1029
12.2.2 Nucleic Acid Extraction.................................................................. 1030
12.2.2.1 Silica-Based Surface Affinity Extraction........................ 1030
12.2.2.2 Electrostatic Interaction-Based Extraction...................... 1031
12.2.2.3 Nanoporous Membrane Filtration-Based Extraction....... 1032
12.2.2.4 Functionalized Microparticle-Based Extraction............. 1032
12.2.2.5 Comparison among On-Chip DNA Extraction Methods.1033
12.2.2.6 RNA Extraction............................................................... 1033
12.3 On-Chip PCR Amplification........................................................................ 1034
12.3.1 Stationary PCR Amplification........................................................ 1034
12.3.1.1 On-Chip PCR Temperature Control................................ 1035

xxiv Contents
12.3.1.2 Bubble Formation and Evaporation Prevention............... 1037

12.3.1.3 PCR Chamber Fabrication Material................................ 1038
12.3.2 Continuous-Flow and Droplet-Based PCR Amplification.............. 1038
12.3.2.1 Continuous-Flow PCR Amplification............................. 1039
12.3.2.2 On-Chip Droplet-Based PCR.......................................... 1041
12.4 On-Chip Nucleic Acid Assays...................................................................... 1041
12.4.1 Complete Sequencing Integration................................................... 1042
12.4.2 Lab-on-Chip Integrating Sequencing Subsystems.......................... 1045
References............................................................................................................... 1046
Appendix 1: Convention for Organic Formulas and Molecules Stereographic

Representation............................................................................................................................. 1051
Appendix 2: Building Blocks of Proteins.................................................................................. 1063
Appendix 3: Conventions for Mathematical Notations........................................................... 1071
Appendix 4: Time-Scale Separation Method........................................................................... 1079
Appendix 5: Elements of Bio-Electrochemistry....................................................................... 1083
Appendix 6: Detection Requirements of Selected Clinical Blood Tests................................ 1093
Index............................................................................................................................................. 1099

Preface
I discovered the impressive potentiality of miniaturization and integration very early in my career.
In 1984, when I concluded my university studies, IBM on one side and Olivetti on the other side
were struggling to reduce computer dimensions. The dream was to shrink into a tabletop machine a
system occupying several great closets.
That dream now seems quite old: we hold in our hands electronic devices much more power-
ful, easier to use, and functionally richer than 1984 computers. Integrated electronics has radically
changed our way of living: neither the Internet nor mobile communications would have been pos-
sible without it.
Miniaturization has been applied to many fields since the first revolutionary successes: miniatur-
ized optical components, mechanical, chemical and optical sensors, and micro-actuators are present
in huge numbers in our homes, in our cars, and even on our person.
Currently, a new revolution seems near the edge, with the potential to change the lifestyle itself
all over the world—miniaturized biochemical analysis performed via small, electronic-like chips,
called lab on chip.
A lab-on-chip device, also known as a micro-total-analysis system (μTAS), is a device that can
integrate miniaturized laboratory functions on a single microprocessor-like chip, such as separation
and analysis of components of a mixture. It uses extremely small fluid volumes, nanoliters or even
picoliters, thus eliminating the need for large samples.
Integration also promises huge cost reduction, strong resilience, and ease of use, up to conceiving
systems that can be used with no training whatsoever.
From the beginning, the first application predicted for this technology was monitoring of human
health, even if huge application opportunities also exist in the fields of environmental control, food
industry, security, and more.
Extended and inexpensive prevention and screening could be introduced using labs on chip while
reducing the need for centralized structures. In-field diagnosis in emergencies can dramatically
change the possibility of a correct intervention and save a huge number of human lives. Home moni-
toring of chronic patients can improve their quality of life while increasing their general health.
In advanced countries, a lab on chip could give a substantial contribution to the required decrease
of healthcare expenses while improving the quality of the service. In developing countries, labs on
chip can be key in allowing an effective, in-field prevention strategy without the need for expensive
structures. An effective prevention and an early solution to small problems can be a way to reduce
the number of critical patients in developing countries, allowing the development of a sustainable
healthcare system.
The huge potential of the lab-on-chip idea fascinated me ever since I started working in this field
several years ago. A huge research effort was made in the past two decades to discover and refine
microfluidic systems, biochemistry miniaturization, and new technology processes. Nevertheless,
about 20 years were required to arrive at the edge of a widespread introduction of a lab on chip, and
a huge scientific, industrial, and engineering research study is still required.
The mere nature of a lab on chip as the synthesis of microfluidic systems, biochemical sensors,
and miniaturized technologies is one of the causes of this long struggle. It is practically impossible
to collect specific competencies and experiences in all these fields in a single person, and integration
between researchers and engineers with different attitudes and skills is a key to succeed in this field.
Such an integration is frequently difficult in universities and industries due to the strongly special-
ized education of technical people and the sectorial structure of many organizations.
xxv

xxvi Preface
This book is meant to be an instrument for such an integration, presenting a global view of the
lab-on-chip field. The treatment of each specific subject is intended to provide a path starting with a
recap of basic elements and progressing toward advanced concepts typical of a labs-on-chip study.
This structure allows the different parts of the book to be useful both for specialists of the sector
and for professionals coming from different specializations.
I hope this will be a small but useful contribution to the way of labs-on-chip diffusion causing a
widespread, low-cost availability of effective diagnostic and prevention systems to all humankind.

Acknowledgment
I would like to acknowledge Dr. Maurizio Moroni, R&D director of Dianax s.r.l. His experience and
passion were invaluable in organizing, refining, and reviewing the biochemical part of this book.
I would also like to thank Dr. Giusy Nocca for his help in reviewing selected parts of Chapters 2
and 3.
Finally, I thank the whole Dianax R&D team for the continuous discussions and support.
xxvii

Author
Eugenio Iannone earned the Italian Laurea degree in engineering (classical version) from Rome
University “La Sapienza,” Rome, Italy, in 1984.
He was a researcher in Fondazione Ugo Bordoni until 1997, and was engaged in developing new
fields in optical communications to which he made relevant contributions. From 1997 to 2009 he
joined Pirelli and subsequently worked at Cisco as a research leader in optical communications and
as a product management leader.
Since 2009, his main interest has been in the field of industrial research, especially labs on chip.
In 2011 he founded the Dianax Study Group, an independent research group active in the lab-on-
chip field. Since the end of 2013, he has been the CEO of Dianax s.r.l., a start-up company operating
in the same field.
Dr. Iannone is the author of three books on optical communication, among them
Telecommunication Networks (CRC Press), which was published in 2011. He is also an author of
more than 100 papers in peer-reviewed journals. Dr. Iannone is a member of IEEE-Engineering in
Medicine and Biology Society and the American Chemical Society.
xxix

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Under the act of July 17, 1862.
August 4, 1862—The President ordered a draft of three hundred
thousand militia, for nine months unless sooner discharged; and
directed that if any State shall not, by the 15th of August, furnish its
quota of the additional 300,000 authorized by law, the deficiency of
volunteers in that State will also be made up by special draft from the
militia. Wednesday, September 3, was subsequently fixed for the
draft.
May 8, 1863—Proclamation issued, defining the relations of aliens
to the conscription act, holding all aliens who have declared on oath
their intention to become citizens and may be in the country within
sixty-five days from date, and all who have declared their intention to
become citizens and have voted.
June 15, 1863—One hundred thousand men, for six months, called
to repel the invasion of Maryland, West Virginia, Ohio, and
Pennsylvania.
October 17, 1863—A proclamation was issued for 300,000
volunteers, to serve for three years or the war, not, however,
exceeding three years, to fill the places of those whose terms expire
“during the coming year,” these being in addition to the men raised
by the present draft. In States in default under this call, January 5,
1864, a draft shall be made on that day.
February 1, 1864—Draft for 500,000 men for three years or during
the war, ordered for March 10, 1864.
March 14, 1864—Draft for 200,000 additional for the army, navy
and marine corps, ordered for April 15, 1864, to supply the force
required for the navy and to provide an adequate reserve force for all
contingencies.
April 23, 1864—85,000 one hundred day men accepted, tendered
by the Governors of Ohio, Indiana, Illinois, Iowa, and Wisconsin;
30,000, 20,000, 20,000, 10,000 and 5,000 being tendered
respectively.
UNION MILITARY LEGISLATION.

1861, July 22—The President was authorized to accept the services
of volunteers, not exceeding five hundred thousand, for a period not
exceeding three years. July 27, this authority was duplicated.
1861, July 27—Nine regiments of infantry, one of cavalry, and one
of artillery, added to the regular army.
1861 August 5—Passed bill approving and legalizing the orders of
the President respecting the army and navy, issued from 4th of
March to that date.
1862, July 17—Authorized the President, when calling forth the
militia of the States, to specify the period of such service, not
exceeding nine months; and if by reason of defects in existing laws or
in the execution of them, it shall be found necessary to provide for
enrolling the militia, the President was authorized to make all
necessary regulations, the enrollment to include all able-bodied male
citizens between eighteen and forty-five, and to be apportioned
according to representative population. He was authorized, in
addition to the volunteers now authorized, to accept 100,000
infantry, for nine months; also, for twelve months, to fill up old
regiments, as many as may be presented for the purpose.
1863, February 7—Authorized the Governor of Kentucky, by the
consent and under the direction of the President, to raise twenty
thousand volunteers, for twelve months, for service within the limits
of the State, for repelling invasion, suppressing insurrection, and
guarding and protecting the public property—two regiments to be
mounted riflemen. With the consent of the President, these troops
may be attached to, and become a part of, the body of three years’
volunteers.
1863, March 3—The conscription act passed. It included as a part
of the national forces, all able-bodied male citizens of the United
States, and persons of foreign birth who shall have declared on oath
their intention to become citizens under and in pursuance of the laws
thereof, between the ages of twenty-one and forty-five years, except
such as are rejected as physically or mentally unfit for the service;
also, the Vice-President, the judges of the various courts of the
United States, the heads of the various executive departments of the
Government, and the Governors of the several States; also, the only
son liable to military service, of a widow dependent upon his labor
for support; also, the only son of aged or infirm parent or parents,
dependent upon his labor for support; also, where there are two or
more sons of aged or infirm parents, subject to draft, the father, or if
he be dead, the mother, may elect which son shall be exempt; also,
the only brother of children not twelve years old, having neither
father nor mother, dependent upon his labor for support; also, the
father of motherless children under twelve years of age, dependent
upon his labor for support; also, where there are a father and sons in
the same family and household, and two of them are in military
service of the United States as non-commissioned officers,
musicians, or privates, the residue of such family; provided that no
person who has been convicted of any felony shall be enrolled or
permitted to serve in said forces. It divided the forces into two
classes: 1st, those between twenty and thirty-five and all unmarried
persons above thirty-five and under forty-five; 2d, all others liable to
military duty. It divided the country into districts, in each of which
an enrollment board was established. The persons enrolled were
made subject to be called into the military service for two years from
July 1, 1863, and continue in service for three years. A drafted person
was allowed to furnish an acceptable substitute, or pay $300, and be
discharged from further liability under that draft. Persons failing to
report, to be considered deserters. All persons drafted shall be
assigned by the President to military duty in such corps, regiments,
or branches of the service as the exigencies of the service may
require.
1864, Feb. 24—Provided for equalizing the draft by calculating the
quota of each district or precinct and counting the number
previously furnished by it. Any person enrolled may furnish an
acceptable substitute who is not liable to draft, nor, at any time, in
the military or naval service of the United States; and such person so
furnishing a substitute shall be exempt from draft during the time for
which such substitute shall not be liable to draft, not exceeding the
time for which such substitute shall have been accepted. If such
substitute is liable to draft, the name of the person furnishing him
shall again be placed on the roll and shall be liable to draft in future
calls, but not until the present enrollment shall be exhausted. The
exemptions are limited to such as are rejected as physically or
mentally unfit for the service; to persons actually in the military or
naval service of the Government, and all persons who have served in
the military or naval service two years during the present war and
been honorably discharged therefrom.
The separate enrollment of classes is repealed and the two classes
consolidated.
Members of religious denominations, who shall by oath or
affirmation declare that they are conscientiously opposed to the
bearing of arms, and who are prohibited from doing so by the rules
and articles of faith and practice of said religious denomination, shall
when drafted, be considered non-combatants, and be assigned to
duty in the hospitals, or the care of freedmen, or shall pay $300 to
the benefit of sick and wounded soldiers, if they give proof that their
deportment has been uniformly consistent with their declaration.
No alien who has voted in county, State or Territory shall, because
of alienage, be exempt from draft.
“All able-bodied male colored persons between the ages of twenty
and forty-five years, resident in the United States, shall be enrolled
according to the provisions of this act, and of the act to which this is
an amendment, and form part of the national forces; and when a
slave of a loyal master shall be drafted and mustered into the service
of the United States, his master shall have a certificate thereof; and
thereupon such slave shall be free, and the bounty of one hundred
dollars, now payable by law for each drafted man, shall be paid to the
person to whom such drafted person was owing service or labor at
the time of his muster into the service of the United States. The
Secretary of War shall appoint a commission in each of the slave
States represented in Congress, charged to award to each loyal
person to whom a colored volunteer may owe service a just
compensation, not exceeding three hundred dollars, for each such
colored volunteer, payable out of the fund derived from
commutations, and every such colored volunteer on being mustered
into the service shall be free. And in all cases where men of color
have been enlisted, or have volunteered in the military service of the
United States, all the provisions of this act so far as the payment of
bounty and compensation are provided, shall be equally applicable,
as to those who may be hereafter recruited. But men of color, drafted
or enlisted, or who may volunteer into the military service, while
they shall be credited on the quotas of the several States, or sub-
divisions of States, wherein they are respectively drafted, enlisted, or
shall volunteer, shall not be assigned as State troops, but shall be
mustered into regiments or companies as United States colored
troops.”
1864, Feb. 29—Bill passed reviving the grade of Lieutenant-
General in the army, and Major General Ulysses S. Grant was
appointed March 2d.
1864, June 15—All persons of color shall receive the same pay and
emoluments, except bounty, as other soldiers of the regular or
volunteer army from and after Jan. 1, 1864, the President to fix the
bounty for those hereafter mustered, not exceeding $100.
1864, June 20—The monthly pay of privates and non-
commissioned officers was fixed as follows, on and after May 1:
Sergeant majors, twenty-six dollars; quartermaster and
commissary sergeants of Cavalry, artillery, and infantry, twenty-two
dollars; first sergeants of cavalry, artillery, and infantry, twenty-four
dollars; sergeants of cavalry, artillery, and infantry, twenty dollars;
sergeants of ordnance, sappers and miners, and pontoniers, thirty-
four dollars; corporals of ordnance, sappers and miners, and
pontoniers, twenty dollars; privates of engineers and ordnance of the
first class, eighteen dollars, and of the second class, sixteen dollars;
corporals of cavalry, artillery, and infantry, eighteen dollars; chief
buglers of cavalry, twenty-three dollars; buglers, sixteen dollars;
farriers and blacksmiths, of cavalry, and artificers of artillery,
eighteen dollars; privates of cavalry, artillery and infantry, sixteen
dollars; principal musicians of artillery and infantry, twenty-two
dollars; leaders of brigade and regimental bands, seventy-five
dollars; musicians, sixteen dollars; hospital stewards of the first
class, thirty-three dollars; hospital stewards of the second class,
twenty-five dollars; hospital stewards of the third class, twenty-three
dollars.
July 4—This bill became a law:
Be it enacted, &c. That the President of the United States may, at
his discretion, at any time hereafter call for any number of men as
volunteers for the respective terms of one, two, and three years for
military service; and any such volunteer, or, in case of draft, as
hereinafter provided, any substitute, shall be credited to the town,
township, ward of a city, precinct, or election district, or of a county
not so subdivided towards the quota of which he may have
volunteered or engaged as a substitute; and every volunteer who is
accepted and mustered into the service for a term of one year, unless
sooner discharged, shall receive, and be paid by the United States, a
bounty of one hundred dollars; and if for a term of two years, unless
sooner discharged, a bounty of two hundred dollars; and if for a term
of three years, unless sooner discharged, a bounty of three hundred
dollars; one third of which bounty shall be paid to the soldier at the
time of his being mustered into the service, one-third at the
expiration of one-half of his term of service, and one-third at the
expiration of his term of service. And in case of his death while in
service, the residue of his bounty unpaid shall be paid to his widow,
if he shall have left a widow; if not, to his children; or if there be
none, to his mother, if she be a widow.
Sec. 8. That all persons in the naval service of the United States,
who have entered said service during the present rebellion, who have
not been credited to the quota of any town, district, ward, or State, by
reason of their being in said service and not enrolled prior to
February twenty-four, eighteen hundred and sixty-four, shall be
enrolled and credited to the quotas of the town, ward, district, or
State, in which they respectively reside, upon satisfactory proof of
their residence made to the Secretary of War.
“CONFEDERATE” MILITARY LEGISLATION.
February 28, 1861, (four days before the inauguration of Mr.

Lincoln)—The “Confederate” Congress passed a bill providing—
1st. To enable the Government of the Confederate States to
maintain its jurisdiction over all questions of peace and war, and to
provide for the public defence, the President be, and he is hereby
authorized and directed to assume control of all military operations
in every State, having reference to a connection with questions
between the said States, or any of them, and Powers foreign to
themselves.
2d. The President was authorized to receive from the several States
the arms and munitions of war which have been acquired from the
United States.
3d. He was authorized to receive into Government service such
forces in the service of the States, as may be tendered, in such
number as he may require, for any time not less than twelve months,
unless sooner discharged.
March 6, 1861—The President was authorized to employ the
militia, military and naval forces of the Confederate States to repel
invasion, maintain rightful possession of the territory, and secure
public tranquillity and independence against threatened assault, to
the extent of 100,000 men, to serve for twelve months.
May 4, 1861—One regiment of Zouaves authorized.
May 6, 1861—Letters of marque and reprisal authorized.
1861, August 8—The Congress authorized the President to accept
the services of 400,000 volunteers, to serve for not less than twelve
months nor more than three years after they shall be mustered into
service, unless sooner discharged.
The Richmond Enquirer of that date announced that it was
ascertained from official data, before the passage of the bill, that
there were not less than 210,000 men then in the field.
August 21—Volunteers authorized for local defence and special
service.
1862, January—Publishers of newspapers, or other printed matter
are prohibited from giving the number, disposition, movement, or
destination of the land or naval forces, or description of vessel, or
battery, fortification, engine of war, or signal, unless first authorized
by the President or Congress, or the Secretary of War or Navy, or
commanding officer of post, district, or expedition. The penalty is a
fine of $1,000 and imprisonment not over twelve months.
1862, February—The Committee on Naval Affairs were instructed
to inquire into the expediency of placing at the disposal of the
President five millions of dollars to build gunboats.
1862—Bill passed to “regulate the destruction of property under
military necessity,” referring particularly to cotton and tobacco. The
authorities are authorized to destroy it to keep it from the enemy;
and owners, destroying it for the same purpose, are to be
indemnified upon proof of the value and the circumstances of the
destruction.
1862, April 16—The first “conscription” bill became a law.
1864, February. The second conscription bill became a law.
The Richmond Sentinel of February 17, 1864, contains a synopsis
of what is called the military bill, heretofore forbidden to be printed:
The first section provides that all white men residents of the
Confederate States, between the ages of seventeen and fifty, shall be
in the military service for the war.
The second section provides that all between eighteen and forty-
five, now in service, shall be continued during the war in the same
regiments, battalions, and companies to which they belong at the
passage of this act, with the organization, officers, &c., provided that
companies from one State organized against their consent, expressed
at the time, with regrets, &c., from another State, shall have the
privilege of being transferred to the same arm in a regiment from
their own State, and men can be transferred to a company from their
own State.
Section three gives a bounty eight months hence of $100 in rebel
bonds.
Section four provides that no person shall be relieved from the
operations of this act heretofore discharged for disability, nor shall
those who furnished substitutes be exempted, where no disability
now exists; but exempts religious persons who have paid an
exemption tax. * * *
The tenth section provides that no person shall be exempt except
the following: ministers, superintendents of deaf, dumb, and blind,
or insane asylums; one editor to each newspaper, and such
employees as he may swear to be indispensable; the Confederate and
State public printers, and the journeymen printers necessary to
perform the public printing; one apothecary to each drug store, who
was and has been continuously doing business as such since October
10, 1862; physicians over 30 years of age of seven years’ practice, not
including dentists; presidents and teachers of colleges, academies
and schools, who have not less than thirty pupils; superintendents of
public hospitals established by law, and such physicians and nurses
as may be indispensable for their efficient management.
One agriculturist on such farm where there is no white male adult
not liable to duty employing fifteen able-bodied slaves, between
sixteen and fifty years of age, upon the following conditions:
The party exempted shall give bonds to deliver to the Government
in the next twelve months, 100 pounds of bacon, or its equivalent in
salt pork, at Government selection, and 100 pounds of beef for each
such able-bodied slave employed on said farm at commissioner’s
rates.
In certain cases this may be commuted in grain or other
provisions.
The person shall further bind himself to sell all surplus provisions
now on hand, or which he may raise, to the Government, or the
families of soldiers, at commissioner’s rates, the person to be allowed
a credit of 25 per cent. on any amount he may deliver in three
months from the passage of this act; Provided that no enrollment
since Feb. 1, 1864, shall deprive the person enrolled from the benefit
of this exemption.
In addition to the above, the Secretary of War is authorized to
make such details as the public security requires.
The vote in the House of Representatives was—yeas, 41; nays, 31.
GUERRILLAS.
1862, April 21—The President was authorized to commission such

officers as he may deem proper, with authority to form bands of
partisan rangers, in companies, battalions or regiments, either as
infantry or cavalry, to receive the same pay, rations, and quarters,
and be subject to the same regulations as other soldiers. For any
arms and munitions of war captured from the enemy by any body of
partisan rangers, and delivered to any quartermaster at designated
place, the rangers shall pay their full value.[18]
The following resolution, in relation to partisan service, was
adopted by the Virginia Legislature, May 17, 1862:
Whereas, this General Assembly places a high estimate upon the
value of the ranger or partisan service in prosecuting the present war
to a successful issue, and regards it as perfectly legitimate; and it
being understood that a Federal commander on the northern border
of Virginia has intimated his purpose, if such service is not
discontinued, to lay waste by fire the portion of our territory at
present under his power.
Resolved by the General Assembly, That in its opinion, the policy
of employing such rangers and partisans ought to be carried out
energetically, both by the authorities of this State and of the
Confederate States, without the slightest regard to such threats.
By another act, the President was authorized, in addition to the
volunteer force authorized under existing laws, to accept the services
of volunteers who may offer them, without regard to the place of
enlistment, to serve for and during the existing war.
1862, May 27—Major General John B. Floyd was authorized by the
Legislature of Virginia, to raise ten thousand men, not now in service
or liable to draft, for twelve months.
1862, September 27—The President was authorized to call out and
place in the military service for three years, all white men who are
residents, between the ages of thirty-five and forty-five, at the time
the call may be made, not legally exempt. And such authority shall
exist in the President, during the present war, as to all persons who
now are, or hereafter may become eighteen years of age, and all
persons between eighteen and forty-five, once enrolled, shall serve
their full time.
THE TWENTY-NEGRO EXEMPTION LAW.
1862, October 11—Exempted certain classes, described in the

repealing law of the next session, as follows:
The dissatisfaction of the people with an act passed by the
Confederate Congress, at its last session, by which persons owning a
certain number of slaves were exempted from the operation of the
conscription law, has led the members at the present session to
reconsider their work, and already one branch has passed a bill for
the repeal of the obnoxious law. This bill provides as follows:
“The Congress of the Confederate States do enact, That so much of
the act approved October 11, 1862, as exempts from military service
‘one person, either as agent, owner, or overseer, on each plantation
on which one white person is required to be kept by the laws or
ordinances of any State, and on which there is no white male adult
not liable to military service, and in States having no such law, one
person, as agent, owner, or overseer on such plantation of twenty
negroes, and on which there is no white male adult not liable to
military service;’ and also the following clause in said act, to wit: ‘and
furthermore, for additional police of every twenty negroes, on two or
more plantations, within five miles of each other, and each having
less than twenty negroes, and on which there is no white male adult
not liable to military duty, one person, being the oldest of the owners
or overseers on such plantations,’ be and the same are hereby
repealed; and the persons so hitherto exempted by said clauses of
said act are hereby made subject to military duty in the same manner
that they would be had said clauses never been embraced in said
act.”
THE POSITION OF DOUGLAS.
After the President had issued his first call, Douglas saw the
danger to which the Capitol was exposed, and he promptly called
upon Lincoln to express his full approval of the call. Knowing his
political value and that of his following Lincoln asked him to dictate
a despatch to the Associated Press, which he did in these words, the
original being left in the possession of Hon. George Ashmun of
Massachusetts:
“April 18, 1861, Senator Douglas, called on the President, and had
an interesting conversation, on the present condition of the country.
The substance of it was, on the part of Mr. Douglas, that while he was
unalterably opposed to the administration in all its political issues,
he was prepared to fully sustain the President, in the exercise of all
his Constitutional functions, to preserve the Union, maintain the
Government, and defend the Federal Capitol. A firm policy and
prompt action was necessary. The Capitol was in danger, and must
be defended at all hazards, and at any expense of men and money.
He spoke of the present and future, without any reference to the
past.”
Douglas followed this with a great speech at Chicago, in which he
uttered a sentence that was soon quoted on nearly every Northern
tongue. It was simply this, “that there now could be but two parties,
patriots and traitors.” It needed nothing more to rally the Douglas
Democrats by the side of the Administration, and in the general
feeling of patriotism awakened not only this class of Democrats, but
many Northern supporters of Breckinridge also enlisted in the Union
armies. The leaders who stood aloof and gave their sympathies to the
South, were stigmatized as “Copperheads,” and these where they
were so impudent as to give expression to their hostility, were as
odious to the mass of Northerners as the Unionists of Tennessee and
North Carolina were to the Secessionists—with this difference—that
the latter were compelled to seek refuge in their mountains, while the
Northern leader who sought to give “aid and comfort to the enemy”
was either placed under arrest by the government or proscribed
politically by his neighbors. Civil war is ever thus. Let us now pass to
THE POLITICAL LEGISLATION INCIDENT TO THE WAR.
The first session of the 37th Congress began July 4, 1861, and
closed Aug. 6. The second began December 2, 1861, and closed July
17, 1862. The third began December 1, 1862 and closed March 4,
1863.
All of these sessions of Congress were really embarrassed by the
number of volunteers offering from the North, and sufficiently rapid
provision could not be made for them. And as illustrative of how
political lines had been broken, it need only be remarked that
Benjamin F. Butler, the leader of the Northern wing of Breckinridge’s
supporters, was commissioned as the first commander of the forces
which Massachusetts sent to the field. New York, Pennsylvania, Ohio
—the great West—all the States, more than met all early
requirements. So rapid were enlistments that no song was as popular
as that beginning with the lines:
“We are coming, Father Abraham,
Six hundred thousand strong.”
The first session of the 37th Congress was a special one, called by
the President. McPherson, in his classification of the membership,
shows the changes in a body made historic, if such a thing can be, not
only by its membership present, but that which had gone or made
itself subject to expulsion by siding with the Confederacy. We quote
the list so concisely and correctly presented:
MEMBERS OF THE 37TH CONGRESS.
March 4, 1861, to March 4, 1863.

Hannibal Hamlin, of Maine, President of the Senate.
SENATORS.
Maine—Lot M. Morrill, Wm. Pitt Fessenden.

New Hampshire—John P. Hale, Daniel Clark.
Vermont—Solomon Foot, Jacob Collamer.
Massachusetts—Charles Sumner, Henry Wilson.
Rhode Island—James F. Simmons,[19] Henry B. Anthony.
Connecticut—James Dixon, Lafayette S. Foster.
New York—Preston King, Ira Harris.
New Jersey—John B. Thomson,[19] John C. Ten Eyck.
Pennsylvania—David Wilmot, Edgar Cowan.
Delaware—James A. Bayard, Willard Saulsbury.
Maryland—Anthony Kennedy, James A. Pearce.[19]
Virginia.[19]
Ohio—Benjamin F. Wade, John Sherman.
Kentucky—Lazarus W. Powell, John C. Breckinridge.[19]
Tennessee—Andrew Johnson.
Indiana—Jesse D. Bright,[19] Henry S. Lane.
Illinois—O. H. Browning,[19] Lyman Trumbull.
Missouri—Trusten Polk,[19] Waldo P. Johnson.[19]
Michigan—Z. Chandler, K. S. Bingham.[19]
Iowa—James W. Grimes, James Harlan.
Wisconsin—James R. Doolittle, Timothy O. Howe.
California—Milton S. Latham, James A. McDougall.
Minnesota—Henry M. Rice, Morton S. Wilkinson.
Oregon—Edward D. Baker,[19] James W. Nesmith.
Kansas—James H. Lane, S. C. Pomeroy.
REPRESENTATIVES.
Galusha A. Grow, of Pennsylvania, Speaker of the House.

Maine—John N. Goodwin, Charles W. Walton,[19] Samuel C.
Fessenden, Anson P. Morrill, John H. Rice, Frederick A. Pike.
New Hampshire—Gilman Marston, Edward H. Rollins, Thomas
M. Edwards.
Vermont—E. P. Walton, Jr., Justin S. Morrill, Portus Baxter.
Massachusetts—Thomas D. Eliot, James Buffinton, Benjamin F.
Thomas, Alexander H. Rice, William Appleton,[19] John B. Alley,
Daniel W. Gooch, Charles R. Train, Goldsmith F. Bailey,[19] Charles
Delano, Henry L. Dawes.
Rhode Island—William P. Sheffield, George H. Browne.
Connecticut—Dwight Loomis, James E. English, Alfred A.
Burnham,[19] George C. Woodruff.
New York—Edward H. Smith, Moses F. Odell, Benjamin Wood,
James E. Kerrigan, William Wall, Frederick A. Conkling, Elijah
Ward, Isaac C. Delaplaine, Edward Haight, Charles H. Van Wyck,
John B. Steele, Stephen Baker, Abraham B. Olin, Erastus Corning,
James B. McKean, William A. Wheeler, Socrates N. Sherman,
Chauncey Vibbard, Richard Franchot, Roscoe Conkling, R. Holland
Duell, William E. Lansing, Ambrose W. Clark, Charles B. Sedgwick,
Theodore M. Pomeroy, Jacob P. Chamberlain, Alexander S. Diven,
Robert B. Van Valkenburgh, Alfred Ely, Augustus Frank, Burt Van
Horn, Elbridge G. Spalding, Reuben E. Fenton.
New Jersey—John T. Nixon, John L. N. Stratton, William G.
Steele, George T. Cobb, Nehemiah Perry.
Pennsylvania—William E. Lehman, Charles J. Biddle,[19] John P.
Verree, William D. Kelley, William Morris Davis, John Hickman,
Thomas B. Cooper,[19] Sydenham E. Ancona, Thaddeus Stevens, John
W. Killinger, James H. Campbell, Hendrick B. Wright, Philip
Johnson, Galusha A. Grow, James T. Hale, Joseph Baily, Edward
McPherson, Samuel S. Blair, John Covode, Jesse Lazear, James K.
Moorhead, Robert McKnight, John W. Wallace, John Patton, Elijah
Babbitt.
Delaware—George P. Fisher.
Maryland—John W. Crisfield, Edwin H. Webster, Cornelius L. L.
Leary, Henry May, Francis Thomas, Charles B. Calvert.
Virginia—Charles H. Upton,[19] William G. Brown, John S. Carlile,
[19]
Kellian V. Whaley.
Ohio—George H. Pendleton, John A. Gurley, Clement L.
Vallandigham, William Allen, James M. Ashley, Chilton A. White,
Richard A. Harrison, Samuel Shellabarger, Warren P. Noble, Carey
A. Trimble, Valentine B. Horton, Samuel S. Cox, Samuel T.
Worcester, Harrison G. Blake, Robert H. Nugen, William P. Cutler,
James R. Morris, Sidney Edgerton, Albert G. Riddle, John Hutchins,
John A. Bingham.
Kentucky—Henry C. Burnett,[19] James S. Jackson,[19] Henry
Grider, Aaron Harding, Charles A. Wickliffe, George W. Dunlap,
Robert Mallory, John J. Crittenden, William H. Wadsworth, John W.
Menzies.
Tennessee—Horace Maynard,[19] Andrew J. Clements,[19] George
W. Bridges.[19]
Indiana—John Law, James A. Cravens, W. McKee Dunn, William
S. Holman, George W. Julian, Albert G. Porter, Daniel W. Voorhees,
Albert S. White, Schuyler Colfax, William Mitchell, John P. C.
Shanks.
Illinois—Elihu B. Washburne, Isaac N. Arnold, Owen Lovejoy,
William Kellogg, William A. Richardson,[19] John A. McClernand,[19]
James C. Robinson, Philip B. Fouke, John A. Logan.[19]
Missouri—Francis P. Blair, Jr., James S. Rollins, John B. Clark,[19]
Elijah H. Norton, John W. Reid,[19] John S. Phelps,[19] John W. Noell.
Michigan—Bradley F. Granger, Fernando C. Beaman, Francis W.
Kellogg, Rowland E. Trowbridge.
Iowa—Samuel R. Curtis,[19] William Vandever.
Wisconsin—John F. Potter, Luther Hanchett,[19] A. Scott Sloan.
Minnesota—Cyrus Aldrich, William Windom.
Oregon—Andrew J. Thayer.[19]
Kansas—Martin F. Conway.
MEMORANDUM OF CHANGES.
The following changes took place during the Congress:
IN SENATE.
Rhode Island—1862, Dec. 1, Samuel G. Arnold succeeded James F.

Simmons, resigned.
New Jersey—1862, Dec. 1, Richard S. Field succeeded, by
appointment, John R. Thompson, deceased Sept. 12, 1862. 1863,
Jan. 21, James, W. Wall, succeeded, by election, Richard S. Field.
Maryland—1863, Jan. 14, Thomas H. Hicks, first by appointment
and then by election succeeded James A. Pearce, deceased Dec. 20,
1862.
Virginia—1861, July 13, John S. Carlile and Waitman T. Willey,
sworn in place of Robert M. T. Hunter and James M. Mason,
withdrawn and abdicated.
Kentucky—1861, Dec. 23, Garrett Davis succeeded John C.
Breckinridge, expelled December 4.
Indiana—1862, March 3, Joseph A. Wright succeeded Jesse D.
Bright, expelled Feb. 5, 1863, Jan. 22, David Turpie, superseded, by
election, Joseph A. Wright.
Illinois—1863, Jan. 30, William A. Richardson superseded, by
election, O. H. Browning.
Missouri—1861, Jan. 24, R. Wilson succeeded Waldo P. Johnson,
expelled Jan. 10. 1862, Jan. 29, John B. Henderson succeeded
Trusten Polk, expelled Jan. 10.
Michigan—1862, Jan. 17, Jacob M. Howard succeeded K. S.
Bingham, deceased October 5, 1861.
Oregon—1862, Dec. 1, Benjamin F. Harding succeeded Edward D.
Baker, deceased Oct. 21, 1862.
IN HOUSE OF REPRESENTATIVES
Maine—1862, December 1, Thomas A. D. Fessenden succeeded

Charles W. Walton, resigned May 26, 1862.
Massachusetts—1861, December 1, Amasa Walker succeeded
Goldsmith F. Bailey, deceased May 8, 1862; 1861, December 2,
Samuel Hooper succeeded William Appleton, resigned.
Connecticut—1861, December 2, Alfred A. Burnham qualified.
Pennsylvania—1861, December 2, Charles J. Biddle qualified;
1862, June 3, John D. Stiles succeeded Thomas B. Cooper, deceased
April 4, 1862.
Virginia—1861, July 13, John S. Carlile resigned to take a seat in
the Senate; 1861, December 2, Jacob B. Blair, succeeded John S.
Carlile, resigned; 1862, February 28, Charles H. Upton unseated by a
vote of the House; 1862, May 6, Joseph Segar qualified.
Kentucky—1862, December, 1, George H. Yeaman succeeded
James S. Jackson, deceased; 1862, March 10, Samuel L. Casey
succeeded Henry C. Burnett, expelled December 3, 1861.
Tennessee—1861, December 2, Horace Maynard qualified; 1862,
January 13, Andrew J. Clements qualified; 1863, February 25,
George W. Bridges qualified.
Illinois—1861, December 12, A. L. Knapp qualified, in place of J. A.
McClernand, resigned; 1862, June 2, William J. Allen qualified, in
place of John A. Logan, resigned; 1863, January 30, William A.
Richardson withdrew to take a seat in the Senate.
Missouri—1862, January 21, Thomas L. Price succeeded John W.
Reid, expelled December 2, 1861; 1862, January 20, William A. Hall
succeeded John B. Clark, expelled July 13, 1861; 1862, May 9, John
S. Phelps qualified.
Iowa—1861, December 2, James F. Wilson succeeded Samuel R.
Curtis, resigned August 4, 1861.
Wisconsin—1863, January 26, Walter D. McIndoe succeeded
Luther Hanchett, deceased November 24, 1862.
Oregon—1861, July 30, George K. Shiel succeeded Andrew J.
Thayer, unseated.
Louisiana—1863, February 17, Michael Hahn qualified; 1863,
February 23, Benjamin F. Flanders qualified.
Lincoln, in his message, recited the events which had transpired

since his inauguration, and asked Congress to confer upon him the
power to make the conflict short and decisive. He wanted 400,000
men, and four hundred millions of money, remarking that “the
people will save their government if the government itself will do its
part only indifferently well.” Congress responded by adding an
hundred thousand to each request.
There were exciting debates and scenes during this session, for
many of the Southern leaders remained, either through hesitancy or
with a view to check legislation and aid their section by adverse
criticism on the measures proposed. Most prominent in the latter list
was John C. Breckinridge, late Vice-President and now Senator from
Kentucky. With singular boldness and eloquence he opposed every
war measure, and spoke with the undisguised purpose of aiding the
South. He continued this course until the close of the extra session,
when he accepted a General’s commission in the Confederate army.
But before its close, Senator Baker of Oregon, angered at his general
course, said in reply to one of Breckinridge’s speeches, Aug. 1st:
“What would the Senator from Kentucky, have? These speeches of
his, sown broadcast over the land, what clear distinct meaning have
they? Are they not intended for disorganization in our very midst?
Are they not intended to destroy our zeal? Are they not intended to
animate our enemies? Sir, are they not words of brilliant polished
TREASON, even in the very Capitol of the Republic?” [Here there were
such manifestations of applause in the galleries, as were with
difficulty suppressed.]
Mr. Baker resumed, and turning directly to Mr. Breckinridge,
inquired:
“What would have been thought, if, in another Capitol, in another
republic, in a yet more martial age, a Senator as grave, not more
eloquent, or dignified than the Senator from Kentucky, yet with the
Roman purple flowing over his shoulders, had risen in his place,
surrounded by all the illustrations of Roman glory, and declared that
the cause of the advancing Hannibal was just, and that Carthage
ought to be dealt with in terms of peace? What would have been
thought if, after the battle of Cannæ, a Senator there had risen in his
place, and denounced every levy of the Roman people, every
expenditure of its treasure, and every appeal to the old recollections
and the old glories?”
There was a silence so profound throughout the Senate and
galleries, that a pinfall could have been heard, while every eye was
fixed upon Breckinridge. Fessenden exclaimed in deep low tones, “he
would have been hurled from the Tarpeian Rock!”
Baker resumed:
“Sir, a Senator himself learned far more than myself, in such lore,
(Mr. Fessenden) tells me, in a low voice, he would have been hurled
from the Tarpeian Rock.” It is a grand commentary upon the
American Constitution, that we permit these words of the Senator
from Kentucky, to be uttered. I ask the Senator to recollect, to what,
save to send aid and comfort to the enemy, do these predictions
amount to? Every word thus uttered, falls as a note of inspiration
upon every Confederate ear. Every sound thus uttered, is a word,
(and falling from his lips, a mighty word) of kindling and triumph to
the foe that determines to advance.
The Republicans of the North were the distinctive “war party,” i. e.,
they gave unqualified support to every demand made by the Lincoln
administration. Most of the Democrats, acting as citizens, did
likewise, but many of those in official position, assuming the
prerogative of a minority, took the liberty in Congress and State
Legislature to criticise the more important war measures, and the
extremists went so far, in many instances, as to organize opposition,
and to encourage it among their constituents. Thus in the States
bordering the Ohio and Mississippi rivers, organized and individual
efforts were made to encourage desertions, and the “Knights of the
Golden Circle,” and the “Sons of Liberty,” secret societies composed
of Northern sympathizers with the South, formed many troublesome
conspiracies. Through their action troops were even enlisted in
Southern Indiana, Illinois and Missouri for the Confederate armies,
while the border States in the Union sent whole regiments to battle
for the South. The “Knights of the Golden Circle” conspired to release
Confederate prisoners of war, and invited Morgan to raid their
States. One of the worst forms of opposition took shape in a
conspiracy to resist the draft in New York city. The fury of the mob
was several days beyond control, and troops had to be recalled from
the front to suppress it. The riot was really political, the prejudices of
the mob under cover of resistance to the draft, being vented on the
negroes, many of whom were killed before adequate numbers could
be sent to their succor. The civil authorities of the city were charged
with winking at the occurrence, and it was afterwards ascertained
that Confederate agents really organized the riot as a movement to
“take the enemy in the rear.”
The Republican was as distinctively the war party during the Great
Rebellion, as the Whigs were during the Revolution, the Democratic-
Republicans during the War of 1812, and the Democrats during the
War with Mexico, and, as in all of these war decades, kept the
majority sentiment of the country with them. This is such a plain
statement of facts that it is neither partisan to assert, nor a mark of
party-fealty to deny. The history is indelibly written. It is stamped
upon nearly every war measure, and certainly upon every political
measure incident to growing out of the rebellion.
These were exciting and memorable scenes in the several sessions
of the 37th Congress. During the first many Southern Senators and
Representatives withdrew after angry statements of their reasons,
generally in obedience to calls from their States or immediate homes.
In this way the majority was changed. Others remained until the
close of the first session, and then more quietly entered the rebellion.
We have shown that of this class was Breckinridge, who thought he
could do more good for his cause in the Federal Congress than
elsewhere, and it is well for the Union that most of his colleagues
disagreed with him as to the propriety and wisdom of his policy. If all
had followed his lead or imitated his example, the war would in all
probability have closed in another compromise, or possibly in the
accomplishment of southern separations. These men could have so
obstructed legislation as to make all its early periods far more
discouraging than they were. As it was the Confederates had all the
advantages of a free and fair start, and the effect was traceable in all

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Labs on Chip: Principles, Design and

Technology Eugenio Iannone

Advanced Multicore Systems On Chip Architecture On Chip

Biota Grow 2C gather 2C cook Loucas

System on Chip Interfaces for Low Power Design 1st

Network on Chip Security and Privacy Prabhat Mishra

Calm Technology Principles and Patterns for Non

Sustainable Wireless Network-On-chip Architectures 1st

High-Density Integrated Electrocortical Neural

© 2015 by Taylor & Francis Group, LLC

© 2015 by Taylor & Francis Group, LLC

© 2015 by Taylor & Francis Group, LLC

© 2015 by Taylor & Francis Group, LLC

Laser-Based Optical Detection of Explosives

© 2015 by Taylor & Francis Group, LLC

Boca Raton London New York

CRC Press is an imprint of the

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No claim to original U.S. Government works

International Standard Book Number-13: 978-1-4665-6073-4 (eBook - PDF)

© 2015 by Taylor & Francis Group, LLC

Section I Biological Chemistry

Chapter 1 Elements of Organic Chemistry....................................................................................3

© 2015 by Taylor & Francis Group, LLC

1.3.2.6 Ketone Functional Group.................................................... 48

Chapter 2 Elements of Biochemistry........................................................................................... 95

© 2015 by Taylor & Francis Group, LLC

2.4.2 Classification of Human Immunoglobulin........................................ 135

Chapter 3 Biochemical Assays and Sequencing Techniques..................................................... 183

© 2015 by Taylor & Francis Group, LLC

3.2.2.2 Spin Column-Based Nucleic Acid Extraction................... 189

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3.8 Nucleic Acid Sequencing................................................................................ 249

Section II Lab on Chip Technology

Chapter 4 Planar Technology..................................................................................................... 279

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4.4.2 Industrial Cost Estimation for Microfluidic-Based Labs

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4.9.2.2 Bond Quality of Adhesive Wafer Bonding........................ 382

Chapter 5 Polymer Technology.................................................................................................. 401

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5.7.2.1 Substrate Absorption and Reflection of the Laser

Chapter 6 Back-End Technologies............................................................................................. 457

Section III Lab on Chip Design

Chapter 7 Fluid Dynamics in Microfluidic Circuits.................................................................. 521

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7.3 Fluid Dynamics.............................................................................................. 530

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Chapter 8 Microfluidic Building Blocks.................................................................................... 637

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8.5.3.1 Size-Exclusion Membrane Filters...................................... 741

Chapter 9 Surface Functionalization......................................................................................... 785

Chapter 10 Electronic Detection.................................................................................................. 825

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10.3 Impedance Detection...................................................................................... 828

Chapter 11 Optical Detection...................................................................................................... 917

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11.2.4 Light Detection..................................................................................940

Chapter 12 Building Blocks for Genetics.................................................................................. 1021

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12.3.1.2 Bubble Formation and Evaporation Prevention............... 1037

Appendix 1: Convention for Organic Formulas and Molecules Stereographic

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