Labs on Chip : Principles, Design and Technology book cover
1st Edition

Labs on Chip
Principles, Design and Technology

ISBN 9781138076280
Published January 8, 2019 by CRC Press
1178 Pages 837 B/W Illustrations

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Book Description

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.

Table of Contents





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


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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