1st Edition

Labs on Chip Principles, Design and Technology

By Eugenio Iannone Copyright 2015
    1178 Pages 837 B/W Illustrations
    by CRC Press

    1178 Pages 837 B/W Illustrations
    by CRC Press

    Labs on Chip: Principles, Design and Technology provides a complete reference for the complex field of labs on chip in biotechnology. Merging three main areas— fluid dynamics, monolithic micro- and nanotechnology, and out-of-equilibrium biochemistry—this text integrates coverage of technology issues with strong theoretical explanations of design techniques. Analyzing each subject from basic principles to relevant applications, this book:

    • Describes the biochemical elements required to work on labs on chip
    • Discusses fabrication, microfluidic, and electronic and optical detection techniques
    • Addresses planar technologies, polymer microfabrication, and process scalability to huge volumes
    • Presents a global view of current lab-on-chip research and development
    • Devotes an entire chapter to labs on chip for genetics

    Summarizing in one source the different technical competencies required, Labs on Chip: Principles, Design and Technology offers valuable guidance for the lab-on-chip design decision-making process, while exploring essential elements of labs on chip useful both to the professional who wants to approach a new field and to the specialist who wants to gain a broader perspective.





    Section I: Biological Chemistry

    Elements of Organic Chemistry


    Thermodynamic and Chemical Properties of Solutions

    Thermodynamic State Functions

    Chemical Properties of Solutions

    Chemical Equilibrium in Reactions among Solutes

    Reaction Kinetics


    Solvability in a Polar Solvent

    Organic Chemistry Building Blocks

    Hydrocarbons: Types and Structure

    Functional Groups


    Polymerization and Polymer Types

    Polymeric Materials Structure

    Polymers for Microfabrication Main Properties

    Microscopic Models of Macromolecule Solutions

    Implicit Solvent Models for Solution in Equilibrium

    Chemical Reactions between Macromolecules: The Perfect Gas of Macromolecules

    Collisions and Reaction Kinetics


    Elements of Biochemistry


    Structural Organization of Biochemical Macromolecules

    General Properties of Macromolecules

    Organization and Structure of the Cell


    Classes of Biological Macromolecules

    Protein Structure and Chemistry

    Protein Chemical Structure

    Protein Stereography: Secondary Structure

    Protein Stereography: Tertiary Structure

    Role of Proteins in Biochemistry


    Immunoglobulin G Structure

    Classification of Human Immunoglobulin

    Enzymatic Catalysis

    The Basic Principle of Enzymes Working

    Kinetics of Enzyme-Catalyzed Reactions

    Dependency of Enzyme Kinetics on Enzyme Type and Environment

    Enzyme Inhibition

    Enzymatic Catalysis Thermodynamics

    Nucleic Acids

    Deoxyribonucleic Acid

    Ribonucleic Acid Structure

    RNA Types and Roles


    Free Fatty Acids


    Membrane Lipids







    Biochemical Assays and Sequencing Techniques


    Assay Procedure and Preparation

    Cells Lysis Techniques

    Nucleic Acid Extraction from Cell Lysates

    Protein Extraction from Cell Lysates

    Protein Hydrolysis

    DNA Amplification by Polymerase Chain Reaction

    PCR Efficiency

    PCR Alternative Procedures

    Enzymatic Assays

    Detection Methods in Enzymatic Assays


    Liquid Column Chromatography

    High-Performance Liquid Chromatography

    Alternatives to Adsorption Liquid-Phase Chromatography


    Electrophoresis Gel Types

    Protein Electrophoresis

    Nucleic Acid Electrophoresis


    Structure and Thermodynamic of Antigen–Antibody Neutralization

    Kinetic of Antigen–Antibody Neutralization

    Immunoassay Processes

    Western Blot or Immunoelectrophoresis

    Enzyme-Linked Immunosorbent Assay

    Flow Cytometry Assay

    Nucleic Acid Sequencing

    First-Generation Fragment Sequencing

    Second-Generation Fragment Sequencing

    Third-Generation Fragment Sequencing

    Fragmenting and Assembly Methods

    Protein Sequencing and Structural Assessment

    Protein Sequencing

    Protein Structure Assessment


    Section II: Lab-on-Chip Technology

    Planar Technology


    Planar Process Flow of a Lab on Chip

    Front-End Process Flow

    Back-End Process Flow

    Production Testing Techniques

    In-Field Testing

    Micro- and Nano-Fabrication Fabs

    Clean Rooms

    Fabrication Materials: Silicon, Silica on Silicon and Pure Silica Wafers

    Planar Technology Cost Model

    Industrial Cost Models

    Industrial Cost Estimation for Microfluidic-Based Labs on Chip


    Wafer Cleaning

    Photoresist Deposition

    Mask Alignment

    Photoresist Exposure

    Post-Exposure Processes

    Photolithography Definition

    Electron Beam Lithography


    Wet Etching Techniques

    Plasma Characteristics and Plasma Generation for Planar

    Plasma Characteristics and Plasma Generation for Planar Processes

    Dry Etching Techniques


    Chemical Vapor Deposition

    Physical Vapor Deposition

    Other Physical Deposition Techniques

    Wafer Bonding


    Adhesive Wafer Bonding

    Direct Wafer Bonding

    Wafer Alignment


    Polymer Technology


    Soft Lithography

    Micro-Contact Printing

    Micro-Transfer Molding

    Micro-Molding in Capillaries and Micro-Replica Molding

    Deposition Techniques

    Polymer Film Deposition through Spray Coating

    Polymer Knife Coating

    Plasma-Enhanced Polymerization

    Langmuir–Blodgett Deposition

    Patterning Techniques

    Inkjet printing



    Thin Wall Injection Molding

    Hot Embossing

    Lithographie, Galvanik und Abformung

    Deep X-Ray Lithography for LIGA

    X-Ray Lithography


    Laser Ablation

    Laser Ablation Basics and Mechanism

    Parameters of Laser Ablation

    Laser Ablation Alternative Processes


    Back-End Technologies


    Back-End Requirements and Process Flow

    Hybrid Integration

    Chip-on-Chip Integration

    Multi-Chip Packaging

    Bonding Techniques in Micro-Fabrication


    Laser Welding


    Eutectic Bonding

    Back-End Processes

    Wafer Dicing and Die Attach

    Electronic Interface Fabrication

    Microfluidic Interface Fabrication

    Optical Interface Fabrication

    Temperature Control

    Heaters and Thermistors

    Temperature Stabilization by Peltier Elements

    Heating Micro-Systems


    Section III: Lab-on-Chip Design

    Fluid Dynamics in Microfluidic Circuits


    Kinematic of Fluid Motion

    The Continuous Fluid Model

    Fluid Motion Description

    Continuity Equation

    Fluid Dynamics

    The Momentum Evolution Equation

    The Energy Evolution Equation

    Newtonian Liquids Flow in Lab-on-Chip Ducts: Simplified Model

    The Liquid Flow in a Microfluidic Duct: Poiseuille Flow

    Interfaces Phenomena and Droplets

    Non-Newtonian Fluids

    Solutions Dynamics: Diffusion

    Diffusion Models

    The Diffusion Coefficient

    Diffusion Equation Basic Solutions: Free Diffusion

    Diffusion Equation Basic Solutions: Diffusion in Limited Volumes

    The Chemical–Diffusion Model: Examples

    Diffusion–Convection Model: Examples


    Ions Electrophoresis

    Stern and Debye Layers

    Protein and Nucleic Acids Electrophoresis


    Electrophoresis of Neutral Particles (Dielectrophoresis)



    Magnetostatic Basics


    Bead Concentration Evolution


    Microfluidic Building Blocks


    Fluid Flow Control: Microvalves

    Control Microvalves

    Active Microvalves

    Microvalve Design Considerations

    Microvalve Performance Comparison

    Fluid Flow Generation: Micropumps

    Mechanical Micropumps

    Capillary Micropumps

    Electromagnetic Micropumps

    Comparison among Different Micropump Architectures

    Sample Preparation: Micromixers

    Lamination Mixers

    Chaotic Advection Micromixers

    Active Micromixers

    Comparison among Different Micromixer Architectures

    Sample Purification: Filters

    Hydrodynamic Filters

    Electrophoresis Filters

    Membrane Filters

    Microdroplets in Microfluidic Circuits

    Droplet Stability and Breaking Down

    Microdroplet Break

    Droplet Generation

    T Junction Droplet Generator

    Stream Focus Droplet Generator

    Micropumps for Droplet Flow

    Thermocapillary Micropumps

    Electrowetting Micropumps


    Surface Functionalization


    Surface Activation for Labs on Chip

    Noncovalent Chemical Surface Activation

    Covalent Chemical Surface Activation

    Activation of Different Substrates

    Glass Surface Activation

    Polymer Surface Activation

    Metal Layer Activation

    Nanoparticle Activation and Functionalization

    Surface Activation Using Carbon Nanotubes

    Carbon Nanotube Nature and Growth

    Carbon Nanotube Functionalization

    Antibody and Aptamer Surface Functionalization

    Antibody Monolayers on Activated Surfaces

    Aptamer Monolayers on Functionalized Surfaces

    Stability of Functionalized Surfaces for Labs on Chip

    On-Chip Cells Immobilization

    Immobilization through Adhesion Molecules

    Immobilization in Gel

    Immobilization in Artificial Structures


    Electronic Detection


    Detection System Parameters

    Impedance Detection

    Non-Faradaic Impedance Detection

    Faradaic Impedance Detection

    Impedance-Based Cell Detection and Cell Activity Analysis

    Impedance Measurement Techniques

    Voltammetry Detection

    Step Voltammetry or Chronoamperometry

    Variable Potential Voltammetry

    Electrodes for Voltammetry Detection

    Amperometry Detection

    Amperometry Enzymatic Detection

    Amperometry Detection with Integrated Capillary Electrophoresis

    Alternate On-Chip Amperometry Methods

    Mechanical Detection Based on Microcantilevers

    Static Cantilever-Based Detection

    Dynamic Cantilever-Based Detection

    Piezo-Resistive Cantilever Displacement Measure

    Calorimetric Detection

    Enzymatic Dynamic Calorimeter Detection

    On-Chip Calorimeters


    Optical Detection


    Elements of Optics

    Light Description by Waves and Photons

    Classical Description of Interaction of Light with Matter

    Quantum Description of Interaction of Light with Matter

    Light Detection

    Integrated Optical Circuits

    Lab-on-Chip Spectroscopy

    Absorption Spectroscopy

    Fluorescence Spectroscopy

    Surface Plasmon Resonance

    Plasmons: Definition and Properties

    Surface Plasmon Immunoassay Detection

    Localized Plasmon Resonance Detection

    Lab-on-Chip Interferometry


    Building Blocks for Genetics


    On-Chip DNA Purification

    Cell Lysis

    Nucleic Acid Extraction

    On-Chip PCR Amplification

    Stationary PCR Amplification

    Continuous-Flow and Droplet-Based PCR Amplification

    On-Chip Nucleic Acid Assays

    Complete Sequencing Integration

    Lab-on-Chip Integrating Sequencing Subsystems


    Appendix 1: Convention for Organic Formulas and Molecules Stereographic Representation

    Appendix 2: Building Blocks of Proteins

    Appendix 3: Conventions for Mathematical Notations

    Appendix 4: Time-Scale Separation Method

    Appendix 5: Elements of Bio-Electrochemistry

    Appendix 6: Detection Requirements of Selected Clinical Blood Tests



    Eugenio Iannone is CEO and founder of Dianax S.R.L., a start-up company operating in the lab-on-chip field. He is an IEEE Engineering in Medicine and Biology Society and American Chemical Society member, as well as an author of three books and over 100 peer-reviewed journal papers. After receiving the Italian Laurea degree in engineering (classical version) from Sapienza – Università di Roma, he served as a researcher at Fondazione Ugo Bordoni, joined Pirelli s.p.a., and subsequently worked at Cisco. Since 2009, his research has focused on labs on chip. In 2011, he founded the Dianax Study Group, dedicated to lab-on-chip research.

    "... a bright example of a truly interdisciplinary text. I was much impressed by its completeness. ... useful for a broad class of readers."
    —Fabrizio Frezza, Sapienza – Università di Roma, Italy