Chemical Product Formulation Design and Optimization Methods Techniques and Case Studies Ali Elkamel Full Chapter PDF

Chemical Product Formulation Design
and Optimization: Methods,

Techniques, and Case Studies Ali
Elkamel
Visit to download the full and correct content document:
https://ebookmass.com/product/chemical-product-formulation-design-and-optimizatio
n-methods-techniques-and-case-studies-ali-elkamel/
More products digital (pdf, epub, mobi) instant
download maybe you interests ...
Hydrogen Sulfide: Chemical Biology Basics, Detection

Methods, Therapeutic Applications, and Case Studies
Michael D Pluth
https://ebookmass.com/product/hydrogen-sulfide-chemical-biology-
basics-detection-methods-therapeutic-applications-and-case-
studies-michael-d-pluth/
Program Evaluation: Methods and Case Studies 9th

Edition, (Ebook PDF)
https://ebookmass.com/product/program-evaluation-methods-and-
case-studies-9th-edition-ebook-pdf/
Psychoanalytic Case Formulation 1st Edition, (Ebook

PDF)
https://ebookmass.com/product/psychoanalytic-case-
formulation-1st-edition-ebook-pdf/
Towards Sustainable Chemical Processes: Applications of

Sustainability Assessment and Analysis, Design and
Optimization, and Hybridization and Modularization 1st
Edition Jingzheng Ren
https://ebookmass.com/product/towards-sustainable-chemical-
processes-applications-of-sustainability-assessment-and-analysis-
design-and-optimization-and-hybridization-and-modularization-1st-
Tools For Chemical Product Design From Consumer
Products to Biomedicine 1st Edition Mariano Martín
https://ebookmass.com/product/tools-for-chemical-product-design-
from-consumer-products-to-biomedicine-1st-edition-mariano-martin/
Stochastic Global Optimization Methods and Applications

to Chemical, Biochemical, Pharmaceutical and
Environmental Processes 1st Edition Ch. Venkateswarlu
Satya Eswari Jujjavarapu
https://ebookmass.com/product/stochastic-global-optimization-
methods-and-applications-to-chemical-biochemical-pharmaceutical-
and-environmental-processes-1st-edition-ch-venkateswarlu-satya-
eswari-jujjavarapu/
Chipless RFID Authentication: Design, Realization and

Characterization Zeshan Ali
https://ebookmass.com/product/chipless-rfid-authentication-
design-realization-and-characterization-zeshan-ali/
Tidal Energy Systems: Design, Optimization and Control

1st Edition
https://ebookmass.com/product/tidal-energy-systems-design-
optimization-and-control-1st-edition/
Numerical Methods and Optimization in Finance [2nd ed.]

Manfred Gilli
https://ebookmass.com/product/numerical-methods-and-optimization-
in-finance-2nd-ed-manfred-gilli/
Downloaded from https://onlinelibrary.wiley.com/doi/ by ibrahim ragab - Cochrane Germany , Wiley Online Library on [14/01/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Chemical Product Formulation Design and Optimization
Chemical Product Formulation Design and
Methods, Techniques, and Case Studies
Navid Omidbakhsh
Hesham Alhumade
Optimization
Keyvan Nowruzi
Thomas Duever
Ali Elkamel
Authors All books published by WILEY-VCH are carefully
produced. Nevertheless, authors, editors, and
Prof. Ali Elkamel publisher do not warrant the information
University of Waterloo contained in these books, including this book,
Department of Chemical Engineering to be free of errors. Readers are advised to keep
200 University Avenue West in mind that statements, data, illustrations,
N2L 3G1 NK procedural details or other items may
Canada inadvertently be inaccurate.
Prof. Hesham Alhumade

King Abdulaziz University Library of Congress Card No.: applied for
Chemical and Materials Engineering
21589 Jeddah British Library Cataloguing-in-Publication Data
Saudi Arabia A catalogue record for this book is available
from the British Library.
Dr. Navid Omidbakhsh
Johnson & Johnson Company Bibliographic information published by the
R&D Advanced Sterilization Products Deutsche Nationalbibliothek
33 Technology Drive The Deutsche Nationalbibliothek lists this
CA publication in the Deutsche
United States Nationalbibliografie; detailed bibliographic
data are available on the Internet at
Dr. Keyvan Nowruzi <http://dnb.d-nb.de>.
Johnson & Johnson Company
Associate Research Fellow © 2023 WILEY-VCH GmbH, Boschstr. 12,
33 Technology Drive 69469 Weinheim, Germany
CA
United States All rights reserved (including those of
translation into other languages). No part of
Prof. Thomas Duever this book may be reproduced in any form – by
Professor of Chemical Engineering and photoprinting, microfilm, or any other
Dean of Engineering means – nor transmitted or translated into a
Toronto Metropolitan University machine language without written permission
350 Victoria Street from the publishers. Registered names,
Toronto, ON trademarks, etc. used in this book, even when
M5B 2K3, Canada not specifically marked as such, are not to be
considered unprotected by law.
Cover Image: Shutterstock
Print ISBN: 978-3-527-33264-9
ePDF ISBN: 978-3-527-68963-7
ePub ISBN: 978-3-527-68964-4
oBook ISBN: 978-3-527-68962-0
Cover Design ADAM DESIGN, Weinheim,

Germany
Typesetting Straive, Chennai, India
v
Contents
Preface ix
About the Authors xi
1 Introduction 1
1.1 Chemical Product Engineering 1
1.2 Chemical Product Design 2
1.3 Product Design and Computer-Aided Product Design 4
References 6
2 Some Typical Applications of Chemical Product Design and

Intellectual Property 7
2.1 Natural Fiber Plastic Composites 7
2.2 Wheat Straw Polypropylene Composites 10
2.3 Modeling Natural Fiber Polymer Composites 12
2.4 Graphene Composites 14
2.5 Corrosion Protection Using Polymer Composites 15
2.6 Intellectual Property 17
References 19
3 Mathematical Principles for Chemical Product Design 23

3.1 Factorial and Fractional Factorial Design 23
3.2 Response Surface Methods and Designs 25
3.3 D-Optimal Designs 26
3.4 Bayesian Design of Fractional Factorial Experiments 27
3.5 Regression Analysis 27
3.6 Artificial Neural Networks 28
3.7 Mixture Design of Experiments 31
3.8 Multiway Principal Component Analysis 35
3.8.1 Model-based Principal Component Analysis (MB-PCA) 37
3.8.2 MPLS Analysis Using NIPALS 38
References 39
4 Disinfectant Formulation Design 41

4.1 Introduction 41
4.2 Disinfectants Characteristics 42
vi Contents
4.2.1 Antimicrobial Tests 42

4.2.2 Stability Tests 43
4.2.3 Corrosion Tests 43
4.3 Toxicity of Disinfectants 44
4.3.1 Harmful (Xn) 45
4.3.2 Severe Eye Damage, Xi (R41) 45
4.3.3 Eye Irritant, Xi (R36) 46
4.3.4 Skin Irritant, Xi (R38) 46
4.3.5 Respiratory Irritant, Xi (R37) 47
4.4 Experimental Design for Antimicrobial Activity 47
4.4.1 Prior Knowledge 48
4.4.2 Historical Data Augmentation 49
4.4.3 Linear Least Squares Regression Analysis 49
4.4.4 Artificial Neural Networks 51
4.5 Experimental Design for Stability of Hydrogen Peroxide 54
4.5.1 Historical Data Analysis 54
4.5.2 Historical Data Augmentation Using Bayesian D-optimality
Approach 55
4.6 Experimental Design for Corrosion 61
4.6.1 Preliminary Experimental Design 62
4.6.2 Response Surface Methodology 63
4.6.3 Artificial Neural Networks 64
4.7 Final Formulation Optimization 66
4.7.1 Optimization 67
4.7.2 Optimized Formulation Verification 69
4.7.3 Comparing the Optimized Formulations to an Available Product 70
4.8 Conclusion 70
References 71
5 Streptomyces Lividans 66 for developing a Minimal Defined

Medium for Recombinant Human Interleukin-3 73
5.1 Introduction 73
5.2 Materials and Methods 74
5.2.1 Microorganism and Medium 74
5.2.2 Analytical Methods 74
5.2.3 Experimental Design and Data Analysis 76
5.3 Results and Discussion 78
5.3.1 Starvation Trails 78
5.3.2 Screening Mixture Experiments 80
5.3.3 Defined Medium Optimization by Mixture Design Method 82
5.4 Conclusion 87
References 87
6 Multivariate Modeling of a Chemical Toner Manufacturing

Process 91
6.1 Introduction 91
6.1.1 Process and Data Description 92
6.1.2 Model Cross-Validation 93
Contents vii

6.3 Conclusion 101
References 102
7 Wheat Straw Fiber Size Effects on the Mechanical Properties

of Polypropylene Composites 105
7.1 Introduction 105
7.2 Materials and Methods 108
7.2.1 Materials 108
7.2.2 Fiber Preparation and Size Measurement 108
7.2.3 Fiber Thermal and Chemical Analysis 109
7.2.4 Composite Sample Preparation and Properties Measurement 109
7.3 Results and Discussions 110
7.3.1 Fiber Fractionation and Size Measurement 110
7.3.2 Fiber Thermal and Chemical Analysis 113
7.3.3 Fiber Size Reduction During Compounding Process 114
7.3.4 Composite Flexural Properties 117
7.3.5 Composite Impact Properties 118
7.3.6 Composite-Specific Properties 120
7.4 Conclusion 122
References 122
8 Framework for Product Design of Wheat Straw Polypropylene

Composite 125
8.2 Product Design Framework for WS-PP Composite 128
8.3 Response Surface Models 130
8.3.1 The Design of Mixture Experiment 131
8.3.2 Materials and Methods 133
8.3.3 Results and Discussion 134
8.3.3.1 Flexural Modulus 134
8.3.3.2 Izod Impact Strength 136
8.3.3.3 Other Properties 137
8.4 Case Study 138
8.5 Conclusion 144
References 145
9 Product Design for Gasoline Blends to Control Environmental

Impact Using Novel Sustainability Indices: A Case Study 147
9.2 Methodology 148
9.2.1 The Impacts of Gasoline Blends on Octane Number (ON) 148
9.2.2 The Impacts of Blending Ethanol and Gasoline on Mileage 149
9.2.3 The Effects of Ethanol, Methanol, and Isooctane on the Octane Number
of Gasoline Blends 150
9.2.4 The Impacts of E5, M5, and I5 on Heat Value, Mileage,
and Price 150
viii Contents
9.2.5 Impacts of E5, M5, and I5 on Environment in Potential Environmental

Impacts (PEIs) 152
9.2.6 The Impacts of E5, M5, and I5 on Safety Risk 154
9.2.7 Selecting the Best Blend Through the Analytic Hierarchy
Process (AHP) 155
9.3 Results 158
9.4 Conclusion 160
References 161
10 Corrosion Protection of Copper Using

Polyetherimide/Graphene Composite Coatings 163
10.2 Experimental 164
10.2.1 Material 164
10.2.2 Composite Preparation, Coating, and Curing 165
10.2.3 Morphology Characterization 165
10.2.4 Adhesion 165
10.2.5 Electrochemical Measurement 166
10.3.1 Morphology 167
10.3.2 Adhesion 170
10.3.3 Potentiodynamic Measurements 170
10.3.4 Impedance 174
10.4 Conclusion 177
References 177
11 Optimization of Mechanical Properties of Polypropylene

Montmorillonite Nanocomposites 181
11.2 Methodology 183
11.3 Mathematical Models 183
11.4 Optimization Mechanism 183
11.5.1 Minimizing the Cost of PP-OMMT 185
11.5.2 Minimizing the Variance Between Desired Properties 187
11.6 Conclusion 192
References 193
12 Product Selection and Business Portfolio for Long-Range

Financial Stability: Case Study from the Petrochemical
Industry 195
12.2 Manufacturing Strategy and Product Selection Tools 196
12.3 Model Development 199
12.4 Illustrative Case Study 201
12.5 Conclusion 205
References 205
Index 207
ix
Preface
Chemical product design is a very important topic in the chemical industry. While
commodity chemicals have been the main area for chemical engineering focus in the
past several decades, specialty chemicals have been gaining more and more attention
in recent years. Therefore, accelerating the development process and optimizing the
formulation of chemical products would be of great benefit. With this change already
happening in the industry, chemical engineering education and training have not
changed enough to train engineers to fill positions in the product design field.
This book aims at providing the reader with a detailed understanding of the
product design, related statistical techniques, and optimization, and gives real-life
case studies for disinfectant formulations, optimization of defined medium, the
formulation of biocomposites, etc. This book can be used as a supplemental text-
book for chemical engineering students in a chemical product design course or to
R&D product formulation engineers so that they become familiar with the efficient
techniques used in developing new formulations. The book contains 11 chapters as
follows:
● Chapters 1 and 2: Introduction to the current product design process
● Chapter 3: Background to the related mathematical and statistical techniques
● Chapters 4–12: Cases studies
Chapters 1 and 2 introduce the reader to the current methodologies used for
designing new products in chemical industries and outlines the disadvantages of
the current processes and the need for improvement.
Chapter 3 gives a background about the theories of the methodologies used
to accelerate new product development. These methodologies include factorial
designs, mixture designs, optimal designs, linear and nonlinear regression analysis,
machine learning techniques (i.e. artificial neural networks), and multi-way
principal component analysis.
Chapters 4–11 present seven case studies to illustrate the process of product
design and its practical implications. The first case study covers optimization of
a disinfectant formulation, the second one presents optimization of a defined
medium, the third case deals with product improvement in a chemical toner
manufacturing process using multivariate modeling, the fourth case presents over
two chapters the design of wheat straw polypropylene composites, the fifth case
x Preface
employs simulation to formulate gasoline blends, the sixth case presents the design
of a corrosion protection coating using polyetherimide/graphene composites,
and finally the seventh case study deals with the optimization of the mechanical
properties of polypropylene-organically modified montmorillonite (PP-OMMT)
nanocomposites. The book ends with Chapter 12 that illustrates how to proceed in
selecting products to invest for business sustainability.
All chapters are equipped with clear illustrations, figures, and tables to help the
reader understand the included topics.
Many people contributed directly or indirectly to this book. We wish to pay our
gratitude and our respects to the late Professor Park Reily with whom we have
collaborated on research articles related to the topics in this book and have learned
a great deal from him. Also, this book would not have been possible without the
interactions we had with past graduate students. Although we give credit and refer-
ences in the appropriate chapters, we would like to vouch our words of appreciation
to Rois Fatoni, Hossein Ordouei, Youssef Al Herz, and Hassan Khorami. Special
thanks go also to the Wiley publishing team (Elke Maase, Katherine Wong, and
Lesley Jebaraj) for their professional work and for being patient with us. Last but
not least, we extend great appreciation to our friends and families.
xi
About the Authors
Ali Elkamel is Professor of Chemical Engineering at the University of Waterloo.

He is also cross-appointed in Systems Design Engineering. Prof. Elkamel holds a
BSc in Chemical Engineering and a BSc in Mathematics from Colorado School of
Mines, MSc in Chemical Engineering from the University of Colorado-Boulder, and
PhD in Chemical Engineering from Purdue University – West Lafayette, Indiana.
His specific research interests are in computer-aided modelling, optimization, and
simulation with applications to energy production planning, carbon management,
sustainable operations, and product design. Prof. Elkamel supervised over 90
graduate students (of which 35 are PhDs) and more than 30 post-doctoral fel-
lows/research associates, and his trainees all obtain good jobs in the chemical
process industry and in academia. He has been funded for several research projects
from government and industry. Among his accomplishments are the Research
Excellence Award, the Excellence in Graduate Supervision Award, the Outstanding
Faculty Award, the Best Teacher Award, and the Industrial engineering and
Operations Management (IEOM) Outstanding Service and Distinguished Educator
Award. He has written more than 370 journal articles, 145 proceedings, and 45
book chapters and has been an invited speaker on numerous occasions at academic
institutions throughout the world and at national and international conferences.
He is also a co-author of five books; two recent books were published by Wiley and
entitled Planning of Refinery and Petrochemical Operations and Environmentally
Conscious Fossil Energy Production.
Hesham Alhumade is a skilled engineer with experience in chemical industry
and enthusiastic assistant professor of chemical and material engineering with
extensive research, teaching, supervision, and administration experience. He is
meticulous and methodical in approach to all tasks, guaranteeing high-quality
results in line with learning specifications. Dr. Alhumade was recently appointed as
the president of the chemical engineering chapter of the Saudi Council of Engineers.
His research interests include polymer nanocomposites, renewable energy, catalyst,
solar systems, and fuel cell. He is currently working on developing pyrolysis
techniques for biomass conversion to biofuel to meet the growing global demand for
alternative and green sources of energy in addition to the current industrial demand
for adequate waste management process. In oil and gas industry, he has conducted
promising research in the field of synthesis and functionalization of catalyst for
xii About the Authors
hydrocarbon conversion and oil upgrading purposes. His research interests include
modeling and simulation of fluid dynamics in porous media and synthesis of
nanocomposites materials for various electrochemical applications including fuel
cells, supercapacitors, batteries, and corrosion mitigation. Dr. Alhumade received
the SABIC Distinguished Award in 2006.
Navid Omidbakhsh is Director of Early R&D and Advanced Research for
Advanced Sterilization Products (ASP), where he leads the innovation and techni-
cal feasibility of new concepts for future products. Prior to joining ASP, Navid was
Vice President of Open Innovation and Intellectual Property for Virox Technologies
and held a key role in the development of Virox’s globally registered products
and company’s exponential growth. Before Virox, Navid was an R&D engineer
for Henkel in surface technology field. Navid has earned his PhD in chemical
engineering from the University of Waterloo, Waterloo, Ontario, Canada, where his
main research area was on the development of a systematic method to optimize
chemical products/formulations. Navid holds several patents and peer-reviewed
publications in the area of product design, disinfectants, and sterilization formu-
lations and systems. Navid is also an alumnus of Harvard Business School, where
he completed programs on business, management, and innovation. He is also a
licensed professional engineer of Ontario, Canada.
Keyvan Nowruzi is a principal scientist at ASP. He has a BS in chemical engi-
neering from Sahand University of Technology, Tabriz, Iran; an MSc in chemical
engineering from Tehran Polytechnic University; and a PhD in biochemical engi-
neering from the University of Waterloo, Canada. Prior to joining ASP, he has served
as a post-doctoral fellow at the University of Guelph, Canada for four years and a
staff scientist for Akkim Kimya San. Ve Tic. A. Ş. for one year. He has been with ASP
for six years. Dr. Nowruzi has contributed in few inventions patented worldwide and
has several publications in peer-reviewed journals and international conferences.
Thomas Duever is Dean of the Faculty of Engineering and Architectural
Science and a professor of chemical engineering at Toronto Metropolitan University
(TMU). Prior to his role at TMU, Dr. Duever served as chair in the Department
of Chemical Engineering at the University of Waterloo for nine years, navigating
the department toward unprecedented growth. He has also taught industrial short
course in experimental design and polymer reaction engineering.
Dr. Duever is an accomplished researcher with interests including applied statis-
tics, experimental design, polymer reaction engineering, and product development.
He has written more than 100 articles in journals and conference proceedings to his
credit and has supervised the research projects of over 35 graduate students.
Dr. Duever is a registered professional engineer in the Province of Ontario, a
fellow of the Chemical Institute of Canada, and a fellow of the Canadian Academy of
Engineering. He holds PhD, masters, and bachelor degrees in chemical engineering
from the University of Waterloo.
1
Introduction
1.1 Chemical Product Engineering

Current globalization trends have resulted in a fierce competition between
multinational companies for gaining more market share. Startup companies, on the
other hand, also try to play in this game by offering differentiated or disruptive prod-
ucts that would potentially change the game and dynamics in each market segment.
The main tool for technological companies to compete, however, remains their
product offerings, and how they can serve the customers and address their needs.
Any profitable market invites new entrants which creates competition. Companies
try to accelerate their product development processes to launch more differentiated
products to stay ahead of the game, while even reducing their costs. This is of
course not a trivial task for scientists and engineers to take on. Furthermore,
customers nowadays have been poised to see newer products and can quickly
switch to other companies with better product offerings if the “newer” products are
not commercialized quick enough, as the life cycle of the current products keeps
becoming shorter. Brand loyalty does not exist as it used to be a few decades ago,
and customers can quickly switch if they find a product with better features. An
obvious example is the smartphone market, and that companies fiercely compete
to introduce new products every year. Imagine one of the incumbents misses one
product launch by a few months, and how catastrophic financial outcome they can
encounter. In many cases, these new products are only simple modifications to
existing technologies, but even these “small modifications” should carry enough
value proposition to convince buyers among all choices they have. This competition
is of course not limited to electronics market and is widespread in all industries,
from cosmetics to pharmaceuticals and consumer to agriculture. In all these market
segments, research and development teams work closely with their marketing
counterparts to identify market needs and trends to stay ahead of the curve. There
is no exaggeration to say that in the current market, innovation is like oxygen for
the business, and without that any business will soon become irrelevant. Naturally,
innovation can only be monetized if it is translated into a new product and capture
revenue. This is why freshness index, i.e. the ratio of new products contributing
to the revenue of the company over total revenue, is considered as a key success
metric for most companies. A faster commercialization cannot be achieved without
Chemical Product Formulation Design and Optimization: Methods, Techniques, and Case Studies,
First Edition. Ali Elkamel, Hesham Alhumade, Navid Omidbakhsh, Keyvan Nowruzi, and Thomas Duever.
© 2023 WILEY-VCH GmbH. Published 2023 by WILEY-VCH GmbH.
2 1 Introduction
a lean and agile product development process, and therefore it is very important
that companies spend their R&D dollars very wisely and try to avoid less efficient
development methodologies.
Product design can have various interpretations, among them is the definition
as the entire procedures required to deliver a product with defined properties that
serve a specific need in society or industry based on inputs from various segments.
For instance, inputs from the industry of how the product may serve and what spec-
ifications should be considered during the manufacturing process. Items that can be
considered include environmental and regional regulations. An example of environ-
mentally friendly product design is the manufacturing of a greenhouse ventilation
system, where the house is designed to attenuate energy consumption and maintain
required rate of fresh air exchange. In such a process of product design of a household
air exchanger, various elements need to be considered including heat and humidity.
In addition, material selection is a significant factor in the manufacturing of such a
device to take into consideration environmental impacts such as energy conserva-
tion, corrosion, and exhaust gases, if any. The topic of product design has become
even more important with the growing changes in industry and regulation to pro-
tect the environment. For example, the manufacturing process of synthetic textile
fiber has been continuously developing since 1950. Starting wth a global produc-
tion of less than 10 million mt in the 1950 and undergoing a 10-fold increase by
2017, the effective utilization of fibers in various applications was achieved through
product design studies that were caried out on the development of various proto-
types utilizing statistical software packages. In general, the process of product design
encompasses the following steps: market needs, ideas, material selection, and finally
manufacturing and process control and optimization.
Many of the products we touch and feel today have come out of a chemical plant
one way or another. These products cannot be missed even in any quick visit to a
grocery store. Consumer products (e.g. detergents), cosmetics, health care products
(e.g. disinfectants, sanitizers), adhesives, pharmaceuticals, etc., are all examples of
chemical products. Therefore, chemical product design (CPD) is a very important
market segment and deserves enough attention in improving product development
methodologies. Chemical product engineering is the science and art of creating
chemical products, a much larger concept encompassing CPD. In other words,
chemical product engineering can be seen as the general background of knowledge
and practice supporting the concrete task of designing chemical products and their
manufacturing processes.
1.2 Chemical Product Design

One of the crucial challenges facing modern corporations and industry is the
growing competitive and dynamics market. A successful business requires con-
tinuous monitoring of consumers’ needs and delivering valuable products at
competitive prices and high quality, while addressing environmental regulations.
Therefore, researchers from various fields of industry including but not limited
1.2 Chemical Product Design 3
to management, marketing, and engineering design always devote attention to

development of new products and issues associated with the fabrication of the
products such as environmental concerns. When designing a new product, different
factors are usually combined such as strategic and technical effort. Here, strategic
planning is required to deliver a successful launch of the product, while technical
effort focuses on design, manufacturing, control, and process optimization aspects.
Therefore, a growing number of researchers from different fields of engineering
including chemical engineering have devoted attention to the area of efficient
design of new products.
Specialty chemical products include petrochemicals, pharmaceuticals, green
chemicals, food products, household care consumables, and cosmetics. In differ-
ent sectors, chemical products are undergoing continuous changes to meet the
expectations of the consumers in addition to continuously stricter environmental
requirements. The fabrication of a chemical product is a multistage process starting
from synthesis, design, optimization, operation, and control. The successful execu-
tion of the previous steps would transform raw materials into valuable products.
Furthermore, the design of a chemical product requires deep understanding of
the properties of the materials and usage functions. Chemical products can be
classified into six categories as follows: specialty chemicals, bioproducts, formulated
products, devices, technology-based products, and virtual chemicals, where each
category has a special identity. For example, specialty chemicals can be defined
as pure compounds that are delivered in small quantities and may serve specific
functions. Formulated products such as cosmetics and food represent a large
market and can be defined as combined systems where various raw materials are
blended together to deliver a multifunctional product with specific appearance and
properties. Continued development in health care applications triggers the need
to develop bioproducts that include biomaterials, tissue, and metabolic elements.
Most of pharmaceutical drugs are now derived from biological sources rather than
traditional synthetic chemicals. Moreover, products that cannot be classified as pure
compounds, mixture, or fabricated biomaterials may include devices that carry out
a physical or chemical transformation.
There have been major changes in the chemical industry during the last two
decades. The dominance of commodity chemicals has been eroded by a newer
emphasis on products such as specialty chemicals [1]. These chemicals include but
are not limited to detergents, cosmetics, pharmaceutical drugs, fertilizers, adhe-
sives, and many more. Today, there are many companies and industries that have
focused on developing such products and are in fierce competition with each other
for market share. Chemical process industries have always launched successful new
products. However, the dynamic and demanding markets require companies to
adopt a more systematic approach to bring the new product to the market faster and
cheaper to guarantee competitiveness. Chemical Product Design and Engineering
is becoming more important as a consequence of this change. While customer
needs and product differentiation for competition purposes are significant drivers
to faster develop products, global warming and climate change require newer
products to have less environmental impact. Increased awareness by both people
4 1 Introduction
and governments, and media’s increased attention to this important topic, has led
governments to impose more stringent environmental regulations which puts even
more pressure on companies to try to reduce waste and carbon footprint. It would
be obvious for companies to try to optimize processes and product formulations to
deliver the same performance using “less” chemicals in a faster time and using less
resources. The million-dollar question to ask is how to achieve this, or simply how
to do more with less? In this book, we are trying to answer this question partially
and our focus will be on chemical and biological product mixtures.
In summary, the dynamic nature of the chemical and biochemical industries,
intense competition for market share, and emergence of more strict environmental
regulations require deployment of innovative product development methods to
address increasing demands for faster, leaner, and optimized products.
1.3 Product Design and Computer-Aided Product Design

CPD can be defined as a systematic procedure or framework of methodologies
and tools whose aim is to provide a more efficient and faster design of chemical
products able to meet market demands. From the practical standpoint, Cussler and
Moggridge [2] simply defined product design as a procedure consisting of four steps:
(i) defining the needs, (ii) generating ideas to meet the needs, (iii) selecting the best
ideas, and (iv) manufacturing the product. Generating ideas and selecting the best
ideas are the most time-consuming steps. These two steps traditionally involved
an exhaustive search by trial-and-error methods which often ended up with no
significant results. One way to overcome this problem is by using computer-aided
techniques to identify very quickly a set of promising candidates and select a subset
of likely final products, from which the desired properties can be identified through
experiments (Figure 1.1).
The first step in Figure 1.1 is the predesign, or problem formulation step. Steps 2
and 3 represent, respectively, two types of product design problems: molecular
design and mixture/blend design. In the molecular design, the objective is to find a
chemical product that exhibits certain functional properties. The invention of new
fuel additives and solvents in organic synthesis are examples of this type of design.
In the mixture/blend design, the objective is to find a recipe of chemical ingredients
which give desirable final product properties. Examples of this type of design are
the design of fuel blends and polymer blends, including polymer composites and
additives. The associated computer-aided designs for the two CPDs are called
computer-aided molecular design (CAMD) and computer-aided mixture/blend
design (CAMb D).
Chemical products are judged by consumers not from their technical specifica-
tions but rather by the functional and performance attributes which are usually
described by a set of performance indices. These indices are determined by three fac-
tors: (i) the composition and physicochemical properties of materials that constitute
the product; (ii) product structure, which is dependent on the manufacturing
process; and (iii) product usage conditions. The relationship between performance
1.3 Product Design and Computer-Aided Product Design 5
Product design Process-product design
CAMD
Generate alternatives
Predesign
Process design
Needs and goals
Product manufacturing and testing
CAMbD
Generate alternatives
Figure 1.1 The design process for product design.
Property prediction:
Given: Obtain:
Information on compound
Properties of the compound
structure
CAMD & CAMbD
Given: Obtain:
Information on desired Compound structures having
properties and type of the desired properties and
compound their “recipe”
Figure 1.2 Chemical product design (CAMD, CAMb D) are “reverse” of property prediction
problems.
indices and product composition, product ingredients’ properties, and product

structure has been mathematically systematized through the concept of property
function. In generic terms, the CPD can be defined as: given a set of desired
(target) needs, determine a chemical product (molecule or mixture) that satisfies
these needs. Based on this definition and the concept of property function, the
CPD problem can be described as a “reverse property prediction,” as illustrated in
Figure 1.2, where the needs are defined through product properties [3].
A simple framework for CPD is illustrated in Figure 1.3. Different aspects of CPD
are represented by methods for CAMD, CAMb D, analysis, and model validation,
while different calculation options are represented by tools of process simulation,
pure component property estimation, mixture property estimation, and search
engines for data retrieval from databases. Although the two-directional arrows in
Figure 1.3 show the connection between two adjacent methods or tools, they are
meant to indicate that all the tools and methods are connected to each other.
In any CPD problem, property functions and property models play important
roles. While the framework is flexible enough to handle a large range of CPD
6 1 Introduction
Figure 1.3 A simplified

Process simulation CAMD
framework for computer-aided
chemical product design.
Pure component
CAMbD
properties
Mixture properties Analysis
Database Model validation
problems, the currently available methods and tools can only solve a relatively
small percentage of these problems. This is because the property models that are
currently available are unable to predict the needed properties within an acceptable
limit of uncertainty.
The framework, however, can give a great contribution to creating property mod-
els and database development in a systematic way. This will reduce time and effort
in the early stages of the product design process and subsequently bring the product
to the market cheaper and faster.
The remainder of this book is organized as follows: Chapter 2 surveys a variety
of applications associated with CPD, while Chapter 3 covers tools commonly used
to accelerate product development. Chapters 4–12 provide illustrative case studies
related to CPD and formulation.
References
1 Lee, N.-J. and Jang, J. (1997). Performance optimisation of glass fibre mat
reinforced polypropylene composites using statistical experimental design. Polym.
Test. 16: 497–506.
2 Cussler, E.L. and Moggridge, G.D. (2011). Chemical Product Design. Cambridge
University Press. ISBN: 9781139035132.
3 Halvarsson, S., Edlund, H., and Norgren, M. (2008). Properties of medium-density
fibreboard (MDF) based on wheat straw and melamine modified urea
formaldehyde (UMF) resin. Ind. Crops Prod. 28: 37–46.
7
Some Typical Applications of Chemical Product Design and

Intellectual Property
2.1 Natural Fiber Plastic Composites

The use of natural fibers as reinforcement in composite materials dates back to
3000 years ago when ancient Egyptians used clay reinforced with wheat straw as
materials to build walls of their houses. In the automotive industry, Henry Ford
developed the first prototype composite car made from hemp fibers in 1942. Due to
economic constraints at that time, however, the car was not commercially produced.
Since then, numerous attempts have been made to incorporate natural fibers into
automotive components. The pressure to produce fuel-efficient, low-polluting
vehicles has become the major driving force for the increasing use of natural fibers
in automotive parts. The inclusion of natural fibers will make it possible to reduce
the utilization of petroleum-based polymeric materials. It will also increase the fuel
efficiency due to car’s lighter weight and will result in an easier product end-of-life,
i.e. waste management. Today, several car manufacturers are using natural fiber
composites in their products. Some examples of the applications are presented in
Table 2.1.
Both thermoplastic and thermoset resins were being used in automotive
industries. However, since thermoplastic resins are easily recyclable, they exhibit
less environmental impact than the thermoset resins. Therefore, industries such as
automotive industry is using more thermoplastics than thermosets. For automotive
industry, the key advantage of thermoplastics is that they can be reprocessed or
recycled, thus reducing the amount of scrap material during manufacturing and
allowing easy recovery and recycling of materials at the end-of-life cycle. Due to the
lower thermal stability of natural fibers, the number of thermoplastics which can be
used to make composite materials is limited to those thermoplastics with processing
temperatures that do not exceed the temperature for degradation or burning the
plant fibers (typically below 210 ∘ C). Polypropylene (PP) and polyethylene are
the most commonly used thermoplastic polymer matrices with plant natural
fibers.
There are various natural fibers with broad ranges of sizes and properties
available to be used as fibers in composites, such as cotton, jute, flax, hemp, sisal,
coir, bamboo, wood, pineapple, ramie, coconut leaves, and so on. The choice of
fibers mainly depends on the final composite product specifications and their
8 2 Some Typical Applications of Chemical Product Design and Intellectual Property
Table 2.1 Automotive manufacturers, model, and components using natural fibers [1].
Manufacturer Model and application
Audi A2, A3, A4, A4Avant, A6, A8, Roadstar, Coupe: Seat back, side and
back door panel, boot lining, hat rack, spare tire lining
BMW 3, 5, and 7 series and others: Door panels, headliner panel, boot
lining, seat back
Daimler-Chrysler A, C, E, S class: Door panels, windshield/dashboard, business table,
piller cover panel;
A class, Travego bus: exterior under body protection trim; M class:
Instrumental panel
(Now in S class: 27 parts manufactured from biofibers, weight 43 kg)
Fiat Punto, Brava, Marea, Alfa Romeo 146, 156
Ford Mondeo CD 162, Focus: Door panels, B-piller, boot liner
Opel Astra, Vectra, Zafira: Headliner panel, door panels, pillar cover
panel, instrumental panel
Peugeot New model 406
Renault Clio
Rover Rover 2000 and others: Insulation, rear storage shelf/panel
Saab Door panels
SEAT Door panels, seat back
Volkswagen Golf A4, Passat Variant, Bora: Door panel, seat back, boot lid finish
panel, boot liner
Volvo C70, V70
Mitsubishi Space star: Door panels; Colt: Instrumental panels
application. However, flax, hemp, and kenaf fibers are favored, because they have
excellent combinations of economic and functional properties [1].
The basic rule of reinforcement is that stresses to the material must be transmit-
ted from the polymer matrix to the fiber. To get the optimum reinforcement to the
polymer matrix, a fiber must have certain attributes. The length of the fibers and
the aspect ratio (length/diameter) of the fibers should be controlled to each specific
type of resin and application. Much of the research in the area of fiber-reinforced
plastics has been done using glass fibers. Glass fibers have uniform diameter and
can be made to any required length. Therefore, the length and aspect ratio are easily
controlled in the case of glass fibers. The fiber alignment is also a significant factor
for composite strength. Fibers randomly oriented will lose their reinforcement effect
by up to 80%. In cases where usage of continuous fibers is prohibited due to process
constraints, discontinuous fibers are used. In this case, stress cannot be transmitted
from the matrix polymer to the fibers across the fiber ends. Fibers with the size longer
than a critical minimum length lc are required for these discontinuous fibers [2].
Since stresses must be transmitted across the boundaries between polymer matrix
and the fiber, the properties of fiber–polymer composites are influenced by the
2.1 Natural Fiber Plastic Composites 9
strength of the bond between the phases (interface). Providing strong interfacial
bonds can be very challenging because it is not easy to wet hydrophilic natural fiber
surfaces with generally hydrophobic viscous (molten) polymers. Coupling agents
play an important role to bind the matrix and the fibers together at the interface.
Coupling agents for more inert polymers like polyolefins are often acid-modified
versions of the matrix polymer, with maleic anhydride-grafted polypropylene
(MA-g-PP) as a prime example. MA-g-PP is widely used as a coupling agent in
composites reinforced with cellulose fibers. The treatment of cellulose fiber with
hot MA-g-PP copolymers provides the covalent bonds across the interface.
The mechanism of the reactions, which is basically divided into two steps: acti-
vation of the copolymer by heating and esterification of cellulose, is illustrated in
Figure 2.1. After this treatment, the surface energy of the fibers almost reaches the
surface energy of the matrix. Thus, a better wettability and a higher interfacial adhe-
sion are obtained. The PP chain permits segmental crystallization and cohesive cou-
pling between the modified fiber and the PP matrix.
Some recent research publications show that one of the focuses of the ongoing
research activities is to understand the effect of coupling agents on polymer blends
and composites. With the aid of scanning electron microscopy (SEM), the coupling
or dispersion mechanism and the fracture behavior can be evaluated by observing
O O
PP chain
PP chain
HO C CH2 C CH2
O
+ H2O
HO C CH C C CH C
O O
(a)
O
Cellulous fiber
O C CH2
O
O C CH C
C CH2
OH
Cellulous fiber
O
+ O
OH O
C CH C
Cellulous fiber
O C CH2
O
O O C CH C
H H
O
(b)
Figure 2.1 Illustration of coupling mechanism of cellulose fiber and maleic acid-grafted
polypropylene: (a) copolymer activation and (b) cellulose esterification.
the morphology of the fractured surface of the composite. Differential scanning

calorimetry (DSC) is usually applied to examine the crystallization behavior.
However, to the best of our knowledge, no literature exists discussing the opti-
mum proportion of such coupling agents in systems containing PP and wheat straw
to provide maximum benefits of composite mechanical properties. The precise infor-
mation related to the optimum proportion is absolutely needed when we want to
commercially produce the natural fiber plastic composite.
Another important issue that needs to be addressed is the fiber quality. Compared
to mineral and synthetic fibers, natural fibers have a broader range of fiber size and
mechanical properties. That is because of the differences in variety and maturity
of the plants, handling the straw before processing the fiber (bales and storage),
and the method for manufacturing the straw fiber by grinding and sieving. There
is a real need for a quality assurance protocol for natural fibers to be established,
especially when fibers are to be used in technical applications like the automotive
parts.
2.2 Wheat Straw Polypropylene Composites

The use of wheat straw as a filler in plastic composites has received considerable
attention in recent years. Many factors have caused this interest, such as the limited
supply of wood fibers, environmental impacts, and government policies. However,
the main attractiveness of using wheat straw in plastic composites comes from its
potential to become a serious competitor to the other natural fibers: its lower price
and feedstock stability. The estimated worldwide production of wheat straw was
approximately 540 million tons in 2007. The price of wheat straw in 2008, in Ontario,
based on the annual average was around US$ 0.20–0.30/kg. In August 2010, the price
of raw jute in India was about US$ 0.65–0.80/kg.
Currently, the major application of wheat straw in Ontario is for horse bedding
or mushroom composting. Wheat straw fiber is also used to make panel and other
building system components such as walls and roofs. Extensive efforts are still in
progress to discover new applications of wheat straw in sectors which need highly
engineered, structured materials such as the automotive industry.
Many researchers from different disciplines have studied wheat straw polypropy-
lene composites (WSPPCs). Despite the different objectives, focus, and scales of
observations, all the studies followed typical approaches in composite science.
In general, the study of composite materials involves three aspects: composition
selection, manufacturing process, and property investigation. A summary of the
studies of WSPPC system is presented in Table 2.2.
Various mechanical [3], chemical [4], thermomechanical [5], chemo-mechanical
[3], and biological [6] techniques have been used to pretreat wheat straw fiber before
they are compounded with PP matrices from different types and grades.
In general, there are three types of PP: PP homopolymer, PP random copolymer,
and PP impact copolymer. The choice of PP types depends on many factors such as
the process to be used, the esthetic and mechanical function of the final product, and
Table 2.2 Examples of variables in the formulation and manufacturing of wheat straw polypropylene composites.
Composition selection
Manufacturing Property
Matrix system Filler system Additives process investigations
Polypropylene (properties) Wheat straw (properties) Product structure purpose: Processing techniques Mechanical
● Various grades (melt flow ● Coupling agent: ● Extrusion ● Tensile strength
Chemical
index, MFI) ● Injection molding ● Flexural strength
properties – composition: Product manufacturing
● Blends (mixtures of grades) ● Compression molding ● Flexural modulus
● Cellulose purpose:
● Combined with recycled PP ● Antioxidant ● Thermoforming ● Impact strength
● Hemicelluloses
● Lignin ● Lubricant Fiber architecture Thermal

● Waxes Product usage purpose: ● Fiber orientation ● Deflection temp.
Physical properties: ● UV stabilizer ● Web/woven fiber ● Crystallization temp.
● Fiber length ● Colorant ● Melting temp.
● Aspect ratio ● Heat stabilizer ● Degree of crystallization
Fiber pretreatment: Other

● Mechanical: ground fiber, ● Rheological
long fiber ● Water absorption
● Chemical: acid ● Dimensional stability
hydrolysis, chemical ● Acoustical
pulping
● Thermomechanical:
steam explosion
● Chemo-mechanical
● Biological: fungi,
enzymes
Components’ proportion: volume percentage, weight percentage Processing variables Various methods and
standards
special additive requirements. Homopolypropylene suitable for injection molding

was the most frequently used type of PP reported in literatures, with melt flow index
ranges from 3 to 30.
PP matrix was also combined with other polymer matrices for a specific purpose,
such as recycled PP for environmental purposes and polyethylene terephthalate
(PET) for technical purposes. Extrusion and injection molding are the most fre-
quently used methods for making the composites, while compression molding has
also been reported. Most studies used fibers with length of 0.5–5 mm, while the use
of flour wheat straw with particle size <0.5 mm or mechanically split wheat straw
fiber resulting in up to 10-cm-long fiber has also been reported [7].
Many kinds of additives have been added to maintain or to improve composite
structural, processing, and usage properties. The type of additives primarily depends
on the requirement of final applications. For example, applications exposed to sun-
light require UV stabilizer and applications exposed to high temperatures require
heat stabilizers.
Despite the extensive studies resulting in better understanding of WSPPC system
and its potential application in sectors which need highly engineered materials, only
a few successful applications have been reported. This is probably due to the lack
of systematic database and reliable property models needed in manufacturing pro-
cesses. Product design approach and computer-aided product design methods are
probably one of the best solutions to overcome this problem.
2.3 Modeling Natural Fiber Polymer Composites
Traditionally, modeling a composite system is carried out by dividing the system into
three main parts: composite composition selection, processing condition, and final
composite properties. Following this framework, three different kinds of modeling
strategies were conducted as illustrated in Figure 2.2.
First, the final composite properties are modeled as a function of composition
selection. These obtained models are commonly called structural property models.
Second, the final composite properties are modeled as a function of the processing
conditions. These models are called processing property models. Finally, based on
(2) Processing optimization
Composition Manufacturing Property

selection process investigation
Engineering
application
(1) Composites design (3) Property

relationships
Figure 2.2 Schematic presentation of composite system and composite modeling strategy.
2.3 Modeling Natural Fiber Polymer Composites 13
Table 2.3 Discrepancies between theory and experimental work in natural fiber
composite [9].
Issue Theory Experimental
Fiber shape and size – Uniform shape – Non-uniform shape

– Constant dimensions – Distributions of length and
thickness
Fiber orientation – Unidirectional, or – Some degree of
– Isotropy (random misalignment, or
orientation) – Not completely isotropic
Fiber interface – The fiber and matrix are well – Imperfect bonding between
bonded the fiber and matrix
– Introduction of coupling
agent is difficult to be
mechanically modeled
Fiber modulus – Assume fiber modulus is the – Fiber or filler is anisotropic
same in all directions
Matrix considerations – Assume matrix is isotropic – Polymer chain orientation
– Presence of polymer
crystallites
Fiber concentration – Ignores particle–particle – Particle–particle interactions
effects interactions and agglomerations
– Ignores change in viscosity – Changes in viscosity can alter
– Ignores agglomerations morphology during injection
molding
– Changes in crystalline
morphology
the level of correlation between properties such as the trade-off relationship between
strength and toughness of composites, the final composite properties are investigated
to develop models that address such correlations between properties. Once the var-
ious models were constructed, they can be manipulated and then be combined to
simulate the composite system [8].
Despite the well-established mechanistic modeling in composite science,
researchers seem to face many difficulties in using the mechanistic approach
to model natural fiber polymer composites. There are several issues where the
composite theories are difficult to be applied in natural fiber plastic composite, as
summarized in Table 2.3.
A few modifications of available composite models have been proposed to
overcome these problems. Shibata and coworkers proposed a method to calculate
the fiber orientation coefficient in modeling flexural properties of PP with kenaf and
bagasse fiber. The Kelly–Tyson Modified Rule of Mixture and the Bowyer–Bader
model were used to introduce a model that can take into consideration the supercrit-
ical and subcritical length distributions of fibers in a hemp fiber PP composite [10].
A geometrical approach of cuboidal shape has been used to model the epidermal
surface and parenchyma surface of wheat straw compounded in a PP matrix. Those
modifications, however, only covered the individual issue of the complex natural
fiber plastic composite system.
Alternatively, some researchers used experimental design methods to develop

statistical models of natural fiber plastic composites. Adapting previous work of
statistical experimental design of glass fiber mat PP composite, Costa and coworkers
used a 22 ⋅31 factorial design to develop statistical models of flexural properties as
functions of the amount of coupling agent, the type of PP matrix, and the compo-
nents’ proportion of PP –wood fiber composites. The use of semiempirical models
and artificial neural network (ANN) has also been reported. ANNs were considered
by many as a powerful tool in composite property prediction and composite design.
Neural network-based analysis was applied to fiber-length’s probability density
estimations. The estimates were combined with Griffith theory (the effectiveness
of natural fibers) and Halpin–Tsai model to predict the flexural properties of PP
natural fiber composites [11].
There were only few reports on statistical modeling of natural fiber plastic
composite, and none of those covered the combination of PP and wheat straw.
2.4 Graphene Composites

A growing number of studies focuses on developing chemical products with
advanced properties with minimum impacts on the environment. Examples of
these studies are the development of polymer composites for wide field of appli-
cation including corrosion protection. The development of the incorporation and
dispersion of graphene particles in a polymer matrix has recently initiated studies
in various fields of science and engineering. This is attributed to the considerable
improvement in properties that cannot usually be achieved using composites with
other nanofillers or virgin polymers. However, the extent of the enhancement in
various properties can be directly related to the degree of dispersion of the graphene
particles in the polymer matrix. Furthermore, it is interesting to observe that such
an enhancement in the properties of a polymer matrix can be achieved at a very low
loading of the fillers [12–15]. These improvements in the properties, for example,
but not limited to tensile strength, storage modulus, and electrical conductivity
have been observed on various polymer resin such as epoxy, polyethylene, PP,
polystyrene, and polyimide. The degree of dispersion of graphene in a polymer
matrix plays an important role in the degree of the improvement of the various prop-
erties. Therefore, various preparation methods have been established to maximize
dispersion of graphene for the purpose of achieving the optimum performances
with minimum loadings of fillers.
There are three main approaches for incorporation of graphene in a polymer
matrix. First is the in situ polymerization method, where graphene is first swollen
within the liquid monomer. Then based on the hosting polymer, a suitable initiator
is introduced to the filler solution, and polymerization is initiated usually by
thermal energy or radiation. The second method is known as the solution method,
where a solvent is used in which the polymer or prepolymer is solubilized, and
graphene is allowed to swell. The advantage of this approach is that graphene can
be easily dispersed in various solvents such as water, acetone, and toluene which
2.5 Corrosion Protection Using Polymer Composites 15
are attributed to the weak forces that stack the layers of graphene together. Here,
the polymer adsorbs onto the delaminated graphene thin sheets, and once the
solvent is evaporated, the sheets reassemble in a form of sandwiching the resin
to form the composites. Another advantage of this method is the possibility of
synthesis of intercalated composites using polymers with low or even no polarity.
However, a considerable amount of solvent might be required to achieve an
optimum dispersion of the fillers, and this is considered a disadvantage of the
approach since solvent removal can be a critical issue. Finally, graphene composites
can also be synthesized using the melt intercalation method without the need to
a solvent as the main advantage. In this technique, graphene is mixed with the
hosting polymer matrix in molten state. Typically, a thermoplastic polymer is mixed
mechanically with graphene at certain temperatures using conventional methods,
such as extrusion and injection molding, and as a result graphene composites
are formed.
2.5 Corrosion Protection Using Polymer Composites

The implementation of graphene and glass flake composites have been widely
reported in various fields and applications [16]. However, only studies that have
focused on using graphene and glass flake composites for corrosion protection
purposes are reported here.
There are different approaches for the implementation of graphene and graphene
composites as protective coatings on metals substrates. However, the majority of the
previous studies have used the expensive chemical vapor deposition (CVD) approach
for deposition of graphene on various metals substrate. Another coating approach is
electrophoretic deposition (EPD), which is a colloidal forming process. In EPD, elec-
trostatically charged colloidal particles in a stable suspension are deposited onto an
oppositely charged metal substrate by introducing a DC electric field to the system.
Furthermore, a post EPD treatment, normally a heat treatment is usually required in
order to eliminate the coatings’ porosity [17]. In comparison to CVD, this approach
is very versatile, fast, and cost-effective in producing a coating with well-controlled
microstructure on a wide range of metals substrates. This is attributed to easiness
in this method in controlling various variables such as dimensions, stoichiometry,
deposition time and rate, thickness in addition to uniformity. Therefore, this method
can be considered a substitute to other techniques such as slurry dipping, thermal
spraying, sputtering, and CVD [18]. Despite the remarkable advantages of EPD, it
has an intrinsic disadvantage compared to other colloidal approaches such as dip
and slurry coating, where EPD cannot be used in applications or fields where the
liquid medium is water. This is due to the fact that application of a voltage to water
will initiate the evolution of hydrogen and oxygen at the metal substrate and con-
sequently attenuate the quality of the deposits. Moreover, it should be noted that
the quality of coatings prepared by EPD will also depend on the electrical nature
of the electrodes, where metal substrates with low conductivity are usually more
difficult to coat.
In addition to graphene-based coating prepared using CVD and EPD, promising

observations have been reported using graphene-based adhesive composites such as
epoxy and polyimide graphene composites. The possibility of using adhesive com-
posites in various environments in addition to the low maintenance cost, simple
preparation steps, and the possibility of applying these coatings on various metal
substrates explains why these coatings are usually more preferable than coatings
prepared using CVD or EPD. In addition to these remarkable properties, these resins
combine other outstanding properties such as high thermal and chemical stabil-
ity, temperature durability, low dielectric constant, and thermal expansion coeffi-
cient [19–21]. A number of studies have focused on the probability of enhancing
various valuable properties of polymer including corrosion protection by the incor-
poration of pristine graphene [13]. For example, polyimide/graphene composites
coatings have been recently prepared by thermal imidization, and the incorpora-
tion of graphene resulted in remarkable enhancement in the corrosion inhibition
property of the coating [13]. In parallel, an environmental-friendly anticorrosion
epoxy/graphene composite coating on cold rolled steel has been prepared and cured
at room temperature without using any type of solvent [12]. Similar to the previous
study, the corrosion protection property of the coating has been examined using Tafel
polarization and electrochemical impedance spectroscopy (EIS), where both tests
revealed an enhancement in both corrosion protection and gas barrier properties as
a result of incorporating graphene in the epoxy resin. In addition, the hydrophobic
property of this coating has been enhanced by modifying the surface of the coat-
ing using a cast. As a result of this surface modification, attenuation on the water
and corrosive media adsorption has been reported on the epoxy/graphene coating
surface.
In addition to the simple incorporation of pristine graphene in polymer com-
posites or CVD coating with graphene, many researchers have focused on the
functionalization of graphene and the influences of such functionalization on
various properties including corrosion resistance. For instance, a recent study
revealed that the corrosion protection of epoxy and graphene oxide (GO) compos-
ites coatings can be enhanced by attaching titanium dioxide on the GO surface using
3-aminopropyltriethoxysilane as coupling agents [22]. Another study investigated
the incorporation of fluorographene particles into polyvinyl butyral composite coat-
ings for corrosion protection purposes. The study revealed that shielding property
could remarkably enhance the corrosion resistance of the coating by blocking the
diffusion paths of corrosive elements and moisture [23]. Recently, the influences
of the incorporation of functionalized GO in epoxy composites, through the wet
transfer of amino-functionalized GO, on the corrosion resistance property of epoxy
coating were investigated. The study demonstrated that significant enhancement in
the corrosion mitigation property of epoxy can be achieved by improving both ionic
resistance and barrier properties.
A growing number of studies have focused on the utilization of glass flake as filler
in polymer composites. This incorporation has delivered enhancement in various
properties such as thermal and viscoelastic properties [24] in addition to corrosion
mitigation. For example, the long-term performance of epoxy/glass composites as
2.6 Intellectual Property 17
corrosion protection coatings on cold rolled steel was investigated in chloride-rich

environment which illustrated that the incorporation of glass flake in the epoxy
resin may extend the life span of the coated metal substrates. Furthermore, the
study revealed that glass flake may deliver further corrosion protection compared to
other fillers such as clay [25]. In addition to epoxy, the incorporation of glass flake
in various polymer composites was assessed and encouraging corrosion resistance
properties were observed on different metal substrates [26–28]. Here, reported
illustrative case studies will demonstrate the possibility of developing graphene
composites with advanced corrosion-resistant properties with minimum impact of
the environment.
2.6 Intellectual Property

A patent is a contract between the inventor and the government, in that the inventor
discloses his or her invention to the public, for the benefit of sharing the knowledge
about details of a new invention with the public, in return for a time-limited exclu-
sivity. Patent is only enforceable in the countries that it has been granted. Patents
play a very significant role in the success of companies. Imagine that, if an idea is
not patent-protected, once found to be commercially successful can be very soon
copied by competitors. This can be really brutal for many companies, especially for
start-ups or smaller size companies, who do not have the luxury of market reach
of larger and established competitors. In fact, these larger companies can not only
copy these products, but also they could improve product features since they have
much larger research and development (R&D) capabilities, and having access to a
much broader market, they will crush the smaller company who originally came
up with the product concept. In fact, one of the main strategies of start-ups is to
patent (or at least file for a patent) their novel concept, and once they have prelimi-
nary technical feasibility and promising data for the true value proposition of their
product, they can negotiate with larger companies for either licensing or acquisi-
tion. It can also happen that these companies will attract funds usually from cap-
ital ventures all the way from concept development to commercialization of their
products.
For the case of larger and dominant companies, patents are also extremely
important, as they help them to keep competitors away from launching me-too
products, and therefore their profit margins will remain very healthy. An obvious
example is the case of pharmaceutical companies, and until a product is still
patent-protected, the drug price will be significantly high, but as soon as the patent
expires, the “generic” products (you can read it “me-too” products) drive the price
significantly down, as a result of a price war. Arguably, without patent protection,
it may not even make a financial case in the first place to develop pharmaceutical
products, since most of the costs are associated with the R&D of these products.
That said, while hundreds of millions of dollars are spent on developing a new
pharmaceutical drug, the actual cost of scale-up and manufacturing are very
minimal relatively speaking, and the price markup is mainly to cover for the earlier
investment made in developing the product, and therefore it is an imperative for the
company to count on this significant price margin to finally have a positive return
on investment, which usually takes a few years to happen. If competitors could
copy them on day 1, the return on investment for most of these products would be
negative and no for-profit company would be encouraged to develop products such
as pharmaceuticals. In this case, the only source for new pharmaceutical drugs
would be limited to government-sponsored labs and universities. Although capable,
they are not nearly as equipped, efficient, and agile as pharmaceutical companies
to have such a robust cadence of new products in their pipeline on a consistent
manner.
Companies may decide to only protect the inventions used for to protect their
products, to avoid competitors from copying them. This is the main objective of
attempting to patent an invention and is defined as defensive strategy. Besides this,
some companies may try to protect inventive subject matter in adjacent fields to try to
hinder their competitors’ product development activities in those fields by creating
these “land mines” in the relevant patent landscape. Although effective in slowing
down competitors in these adjacent fields, this strategy does not generate tangible
return on investment, and therefore this approach is usually avoided in difficult
financial circumstances. Once patents are granted, it is the patent owner company’s
responsibility that their patents will not be infringed, by constantly monitoring the
market for any products that may fall under claims of the patents.
Although patent filing and prosecution process creates more work for their
inventors, and that they may not be directly compensated for their value added by
their inventions, they provide recognition for the inventors by their peers. Patents
are typically considered as one of the main matrices in assessing a scientist or
engineer’s creativity. The more patents a scientist or engineer has, the better their
resume will look like, and the prouder they will be in front of their peers. Some
companies also try to further encourage their prolific inventors by monetary awards
such as paying when their patent application is submitted and when they are
granted.
Before any new product development, it is wise to perform a landscape search to
understand the patent field, and the technologies and product features and meth-
ods that have already been patent protected. This activity can be extremely useful
since it avoids wasting millions of dollars on new product development only to then
realize that the developed technology is already patent-protected. It is advisable that
the landscape search be updated in regular intervals during product development to
avoid any missing relevant prior art and also to identify new publications that may
become relevant. Once the product is fully developed, a freedom-to-operate (FTO)
search is also performed to ensure that the product does not infringe any patents.
Companies often also watch their field on a regular basis for the emerging technolo-
gies and the new published patents, and therefore their subject matter experts are
usually up to date with work related to their expertise. It is also possible to gues-
timate where companies are spending their R&D dollars by reviewing their patent
portfolio, with an 18-month lag of course since patent applications are published
18 months after they are filed. This provides valuable insight for companies when
they try to monitor their competitors activities and can somewhat forecast what their
next products will be.
References 19
Similar to scientific literatures that can help scientists and engineers with
their research, patents can also be useful to learn about the prior art; however,
patents should be considered with grain of salt, since these documents are not
peer-reviewed and more subject to error. Regardless, they provide an invaluable
source to learn from what has been done in the past in any given field. Fortunately,
patents are publicly available (except for the patent applications that have not been
published yet as well as those designated under national security programs) and
can be freely accessed. Among the most popular patent databases are the United
States Patent Office [29], the European Patent Office [30], and Google Patents [31].
These databases can be used to search by different subjects, such as keywords about
the subject of interest using Boolean expressions, assignee, inventor, title, etc. There
are also subscription-based patent databases which provide more user-friendly
access for a fee. Some of these services include Derwent Innovation, LexisNexis
TotalPatent One, and PatBase.
Many patents in the chemical, biological, and pharmaceutical fields involve a
mixture of chemicals rather than a unique new molecule. Given that each chemical
in a formulation possesses a specific function, it is often obvious to use a mixture
of chemicals to deliver a final product characteristic. For example, imagine a disin-
fectant formulation, which contains more than one antimicrobial active ingredient,
and that the inventor files a patent application for their disinfectant formulation.
Since it is generally obvious that the addition of two different antimicrobial agents
will increase the disinfection capability of the solution, the inventor has to prove
that there is an “unexpected” synergy by mixing the two chemicals. Synergy means
that the combined effect of these two chemicals is more than the mere additional
effect of one to another, and this synergy is hard to quantify and measure using
conventional one-factor-at-a-time methodology. However, using designed experi-
ments taught in this book, one can easily identify “interactions,” i.e. synergy (if the
interaction is positive). Therefore, providing such synergy proofs based on statistical
analysis provide an objective determination of synergistic activities between the two
antimicrobial active ingredients here and can easily rebut an obviousness rejection
by the examiner. Otherwise, trying to argue synergy would be very subjective and
does not provide a strong rationale. From another perspective, using these designed
experiments help identify these synergies/interactions, which otherwise can be
missed, and therefore equips inventors with reliable tools to capture and quantify
any “unexpected” results in any mixture, if exist.
References
1 Anderson, M.J. and Whitcomb, P.J. (1998). Find the most favorable formulations.
Chem. Eng. Prog. 94: 63–67.
2 Araujo, J.R., Waldman, W.R., and De Paoli, M.A. (2008). Thermal properties of
high density polyethylene composites with natural fibres: coupling agent effect.
Polym. Degrad. Stab. 93: 1770–1775.
3 Le Digabel, F., Boquillon, N., Dole, P. et al. (2004). Properties of thermoplastic
composites based on wheat-straw lignocellulosic fillers. J. Appl. Polym. Sci. 93:
428–436.
4 Edwards, M.F. (2006). Product engineering: some challenges for chemical

engineers. Chem. Eng. Res. Des. 84: 255–260.
5 Esfandiari, A. (2008). The statistical investigation of mechanical properties of
PP/natural fibers composites. Fibers Polym. 9: 48–54.
6 Fornes, T.D. and Paul, D.R. (2003). Modeling properties of nylon 6/clay
nanocomposites using composite theories. Polymer (Guildf). 44: 4993–5013.
7 Gani, R. (2004). Computer-aided methods and tools for chemical product design.
Chem. Eng. Res. Des. 82: 1494–1504.
8 Lee, N.-J. and Jang, J. (1997). Performance optimisation of glass fibre mat
reinforced polypropylene composites using statistical experimental design. Polym.
Test. 16: 497–506.
9 Sain, M., Suhara, P., Law, S., and Bouilloux, A. (2005). Interface modification
and mechanical properties of natural fiber-polyolefin composite products.
J. Reinf. Plast. Compos. 24: 121–130.
10 Mittal, V. (2008). Modeling the behavior of polymer-layered silicate
nanocomposites using factorial and mixture designs. J. Thermoplast. Compos.
Mater. 21: 9–26.
11 Panthapulakkal, S., Zereshkian, A., and Sain, M. (2006). Preparation and
characterization of wheat straw fibers for reinforcing application in injection
molded thermoplastic composites. Bioresour. Technol. 97: 265–272.
12 Chang, K.-C., Hsu, M.-H., Lu, H.-I. et al. (2014). Room-temperature cured
hydrophobic epoxy/graphene composites as corrosion inhibitor for cold-rolled
steel. Carbon N. Y. 66: 144–153.
13 Alhumade, H., Abdala, A., Yu, A. et al. (2016). Corrosion inhibition of copper
in sodium chloride solution using polyetherimide/graphene composites. Can. J.
Chem. Eng. https://doi.org/10.1002/cjce.22439.
14 Singh, B.P., Jena, B.K., Bhattacharjee, S., and Besra, L. (2013). Development
of oxidation and corrosion resistance hydrophobic graphene oxide-polymer
composite coating on copper. Surf. Coatings Technol. 232: 475–481. https://doi
.org/10.1016/j.surfcoat.2013.06.004.
15 Alhumade, H., Yu, A., Elkamel, A. et al. (2016). Enhanced protective properties
and UV stability of epoxy/graphene nanocomposite coating on stainless steel.
Express Polym. Lett. 10: https://doi.org/10.3144/expresspolymlett.2016.96.
16 Kuilla, T., Bhadra, S., Yao, D. et al. (2010). Recent advances in graphene based
polymer composites. Prog. Polym. Sci. 35: 1350–1375. https://doi.org/10.1016/j
.progpolymsci.2010.07.005.
17 Boccaccini, A.R., Roether, J.A., Thomas, B.J.C. et al. (2006). The electrophoretic
deposition of inorganic nanoscaled materials a review. J. Ceram. Soc. Jpn. 114:
1–14.
18 der Biest, O.O. and Vandeperre, L.J. (1999). Electrophoretic deposition of
materials. Annu. Rev. Mater. Sci. 29: 327–352.
19 Hourston, D.J. and Lane, J.M. (1992). The toughening of epoxy resins with
thermoplastics: 1. Trifunctional epoxy resin-polyetherimide blends. Polymer
(Guildf). 33: 1379–1383.
References 21
20 Crosby, A.J. and Lee, J.-Y. (2007). Polymer nanocomposites: the “nano” effect on
mechanical properties. Polym. Rev. 47: 217–229.
21 Noor, A.K. and Venneri, S.L. (1994). Flight-Vehicle Materials, Structures, and
Dynamics: Advanced Metallics, Metal-Matrix and Polymer-Matrix Composites.
American Society of Mechanical Engineers.
22 Yu, Z., Di, H., Ma, Y. et al. (2015). Preparation of graphene oxide modified by
titanium dioxide to enhance the anti-corrosion performance of epoxy coatings.
Surf. Coat. Technol. 276: 471–478.
23 Yang, Z., Sun, W., Wang, L. et al. (2016). Liquid-phase exfoliated fluorographene
as a two dimensional coating filler for enhanced corrosion protection
performance. Corros. Sci. 103: 312–318.
24 Ehsani, M., Khonakdar, H.A., and Ghadami, A. (2013). Progress in Organic
Coatings Assessment of morphological, thermal, and viscoelastic properties of
epoxy vinyl ester coating composites: role of glass flake and mixing method.
Prog. Org. Coatings. 76: 238–243. https://doi.org/10.1016/j.porgcoat.2012.09.010.
25 Nematollahi, M., Heidarian, M., Peikari, M. et al. (2010). Comparison between
the effect of nanoglass flake and montmorillonite organoclay on corrosion
performance of epoxy coating. Corros. Sci. 52: 1809–1817. https://doi.org/10
.1016/j.corsci.2010.01.024.
26 Sathiyanarayanan, S., Azim, S.S., and Venkatachari, G. (2008). Corrosion
protection coating containing polyaniline glass flake composite for steel.
Electrochim. Acta 53: 2087–2094. https://doi.org/10.1016/j.electacta.2007.09.015.
27 Wang, G. and Yang, J. (2011). Progress in Organic Coatings Influences of glass
flakes on fire protection and water resistance of waterborne intumescent fire
resistive coating for steel structure. Prog. Org. Coatings. 70: 150–156. https://doi
.org/10.1016/j.porgcoat.2010.10.007.
28 Santana, J.J., González, S., and Souto, R.M. (2010). Resistance of metallic
substrates protected by an organic coating containing glass flakes. Prog. Org.
Coat. 68: 240–243. https://doi.org/10.1016/j.porgcoat.2010.01.005.
29 United States Patent and Trademark Office. www.uspto.gov.
30 European Patent Office. https://worldwide.espacenet.com/.
31 Google Patents. https://patents.google.com/.
23
Mathematical Principles for Chemical Product Design
3.1 Factorial and Fractional Factorial Design
We start here by providing a tutorial on factorial and fractional factorial design.

The description is concise, and the interested reader should refer to various text-
books on these topics including [1–4]. Many experiments involve the study of the
effects of two or more factors. Usually, a factorial experimental design is the most
efficient statistical tool for this purpose. In a factorial design, all possible combi-
nations of the factors’ levels are investigated. For example, if there are “a” levels
of factor “A” and “b” levels of factors “B,” the full experiment contains all “a × b”
treatment combinations.
The effect of a factor in a factorial design is defined as the amount of change in
response when the factor is changed. Since this reflects the change in the primary
factors of interest in the experiment; it is called a “main effect.” In some experiments,
the response is not simply a linear combination of the changes in the factors. When
this occurs, there are said to be interactions [5].
One approach to product optimization is to use the traditional “one-factor-at-
a-time” approach. This involves varying one factor while keeping the others at
constant levels. Although simple, this often requires a considerable amount of
experimental work and may be costly. The major benefit of applying a factorial
design is the reduced number of experiments that need to be carried out using a
choice of the best experimental points to get maximum information. This results in
more efficient experimental design. Furthermore, to avoid misleading conclusions,
a factorial design is often necessary when interactions may be present. Finally,
the factorial design allows the effect of a given factor to be determined at several
levels of the other factors, so, the conclusions are valid over a range of experimental
conditions [1].
Factorial designs are widely used in experiments involving several factors where it
is necessary to study the joint effect of the factors of a response. The most widely used
design is the 2k factorial, which studies k factors, each at only two levels. These levels
maybe quantitative, such as two values of temperature, pressure, or time; or they
may be qualitative, such as two machines, two operators, or perhaps the presence
and absence of a factor.
24 3 Mathematical Principles for Chemical Product Design
Since each factor is considered at high (+) and low (−) levels, a complete repli-
cate of such a design requires 2k observations and is called a 2k factorial design.
This design enables an experimenter to investigate “k” factors with a relatively small
number of runs. Consequently, it is particularly useful in the early stages of an exper-
imental investigation when there are usually many factors to be studied.
To design the experiments, the factor levels need to be established, and the
sequence of experimental trials should be randomized [1].
Since there are only two levels for each factor, the response is assumed linear over
the range of the chosen factor levels. This is often adequate, particularly in the early
stages of a study.
As the number of factors in a 2k factorial design increases, the number of runs
required for a complete replicate of the design rapidly outgrows the resources of
most experiments. The full factorial experiment provides an experimenter with
enough information to evaluate the whole set of main effects as well as all inter-
action effects. The main effects and lower order interactions are usually the most
significant terms [6]. In fact, one is usually capable of determining the main effects
and the lower order interactions by performing a fraction of the complete factorial
design with little loss of information. Such a design is called a “fractional factorial”
design (FFD). A 2k−p fractional factorial design containing 2k–p runs is called a 21p
fraction of the 2k complete design, or more simply a 2k−p fractional factorial design.
A potential concern regarding the fractional or full factorial design is the assump-
tion of linearity in the factor effects. When it is clear that the relationship is not
necessarily perfectly linear, some amount of nonlinearity can be accommodated by
adding interaction terms to a main effect or first-order model, resulting in:
∑
k
∑
k
∑
y = 𝛽0 + 𝛽j xj + 𝛽ij xi xj + 𝜀 (3.1)
j=1 i<j
where 𝜀 denotes the noise or error observed in the response y and xj is a coded vari-
able. The relationship between the coded variable xj and its natural variable X j is
defined by the following equation:
Xj − (Xj,high + XJ,low )∕2
xj = (3.2)
(Xj,high − XJ,low )∕2
The model is now capable of handling some curvature in the response function. This
curvature, of course, results from the twisting of the plane induced by the interaction
terms 𝛽 ij xi xj .
In some situations, the curvature in the response function cannot be adequately
modeled by Eq. (3.1). In such cases, a logical model to consider is
∑
k
∑∑ ∑
k
y = 𝛽0 + 𝛽j xj + 𝛽ij xi xj + 𝛽jj xj2 + 𝜀 (3.3)
j=1 i<j j=1
where the 𝛽 jj denote pure second order or quadratic effects. Two-level fractional
or full factorials do not provide sufficient data to estimate models given by 3.3.
However, adding center points to the 2k design will allow for a test to determine if
second-order effects are required. Also, they allow an independent estimate of the
3.2 Response Surface Methods and Designs 25
experimental error to be obtained. These center points consist of nc replicate runs at

the points xj = o (j = 1, 2, …, k). One important reason for adding the replicate runs
at the design center is that center points do not affect the usual effect estimates in a
2k design.
3.2 Response Surface Methods and Designs
Often, there is some curvature in the relationship between a response and the inde-
pendent variables that fractional factorial design cannot handle. In such cases, a
method needs to be applied to detect and estimate the curvature. The 3k design is
a possible choice by an experimenter who is concerned about the curvature in the
response function [1].
However, it should be noted that this design is not necessarily the most efficient
one, and the number of experiments increases exponentially as the number of inde-
pendent factors increases. One excellent way of addressing this issue is to augment
the already performed 2k or 2k−p design with axial runs and extra center points. Such
a design is called a central composite design or CCD. A CCD can be built up sequen-
tially. Often, when we are at a point on the response surface that is remote from the
optimum, there is little curvature in the system, and the first-order model will be
appropriate. The objective here is to lead the experimenter rapidly and efficiently
along a path of improvement toward the general vicinity of the optimum. Once the
region of the optimum has been found, the linear 2k or 2k−p design can be augmented
to form a CCD and a more elaborate model, such as the second-order model, may be
employed.
This sequential strategy of experimentation is usually far more efficient than run-
ning a 3k factorial design.
85 Contours of
90 85 constant
80 response
Region of the Region of
optimum operability for
75 the process
Path of
improvement 70
65
Current
operating
conditions 60
Figure 3.1 The sequential nature of CCD.

Figure 3.2 Face-centered composite design.
0
1
0
−1 −1
−1 0 1
Usually, the initial estimate of the operating conditions or product formulation

will be far from the actual optimum. In such cases, the experimenter wants to move
rapidly toward the vicinity of the optimum. The method of steepest ascent is a pro-
cedure for moving sequentially in the direction of the maximum increase in the
response. When the experimenter reaches the vicinity of the optimum response, a
second-order model must be employed to estimate the curvature.
It is important for the second-order model to provide good predictions throughout
the region of interest [1]. In other words, the model should have a reasonably consis-
tent and stable variance of the predicted response at points of interest. It is suggested
that the design should be rotatable since the variance of the predicted response will
be the same for all points with the same distance from the center. In such a design,
the value of 𝛼 is determined by:
1
𝛼CCD = (nf ) 4 (3.4)
However, in some cases, the region of interest is cubical rather than spherical.
An example would be a product formulation for which the lowest range cannot be
less than 0%. In these situations, a useful variation of the CCD is the face-centered
composite design or the face-centered cube, in which 𝛼 = 1 as depicted in Figure 3.2.
3.3 D-Optimal Designs

Many classical symmetrical designs have desirable characteristics, one of which is
called D-optimality. The D-optimality concept can also be applied to select a design
when the classical symmetrical designs cannot be used, such as when the experi-
ments chosen by a classical design are too large or when one wants to apply models
that deviate from the usual first or second order ones [7].
D-optimality states that among all matrices that can be chosen from the matrix
of candidate points 𝜉 N , the one that leads to a model matrix X that minimizes the
determinant of the so-called dispersion matrix (X′ X)−1 is optimal.
′
Max𝜉n ≡n {Det(X ∗′ X ∗ )} = Min𝜉n ≡n {Det(X ∗ X ∗ )−1 } (3.5)
where 𝜉 n ≡n represents the group of all matrices 𝜉 n , 𝜉 n chosen from 𝜉 N .
Minimizing the determinant of the dispersion matrix in the above equation is
equivalent to maximizing the determinant of the information matrix (X ′ X).
3.5 Regression Analysis 27
3.4 Bayesian Design of Fractional Factorial Experiments
In many practical cases, for example, in our case study of disinfection formulation
optimization in Chapter 4, some prior data are available. If conventional fractional
factorial designs or D-optimal techniques are applied, one might not take advan-
tage of the information hidden in the prior data to “optimally” design further tests.
To address this issue, a Bayesian design can be contemplated, which can fully take
advantage of the prior knowledge and lead to the optimal design.
It is shown [8] that the design matrix, M, can be calculated as
{ }
1
M = Det I + 2 XUX′ (3.6)
𝜎
Defining G = M × Det{U −1 } leads to the following more practical equation:
{ }
1
G = Det U −1 + 2 X ′ X (3.7)
𝜎
where U is the p × p prior information covariance matrix, p is the number of param-
eters in the model used in D-optimality design, 𝜎 2 is the error variance, X is a n × p
matrix of n optimal experiments, and I is the n × n identity matrix.
3.5 Regression Analysis
Regression analysis is a statistical technique for investigating and modeling the rela-
tionship between variables. A regression model that involves more than one regres-
sor variable is called a multiple regression model.
Suppose that the antimicrobial activity of a disinfectant (in log reduction) depends
on raw material concentrations in the formulation. A multiple linear regression
model that might describe the relationship is
y = 𝛽0 + 𝛽1 x1 + 𝛽2 x2 + … + 𝛽k xk + 𝜀 (3.8)
where y denotes the response and x1 to xk are the predictor variables.

The term linear is used because Eq. (3.8) is a linear function of the unknown
parameters (𝛽 0 , 𝛽 1 , …, 𝛽 k ).
Multiple linear regression models are often used as empirical models or approx-
imating functions. That is, the true functional relationship between y and x1 to xk
is unknown, but over certain ranges of the regressor variables, the linear regression
model is an adequate approximation to the true unknown functions.
Models that are more complex in structure than Eq. (3.8) might also be analyzed
by multiple linear regression techniques. For example, a model might have terms
√
such as xj2 , xj3 , xj , xi xj , x1 , etc.
j
The method of least squares can be used to estimate the regression coefficients
in the Eq. (3.8). Suppose that n > k observations are available, yi denotes the ith
observed response and xi, j represents the ith observation or level of regressor xj . It is
also assumed that the error term 𝜀 in the model has E(𝜀) = 0, Var(𝜀) = 𝜎 2 , and the
errors are not correlated. It can be shown that the least-squares estimator of 𝛽 is
𝛽̂ = (X ′ X)−1 X ′ y (3.9)
where
⎡1 x11 x12 x1k ⎤
⎢ ··· ⎥
1 x x x2k ⎥
x = ⎢ 21 22
⎢ ⋮ ⋱ ⋮ ⎥
⎢1 x x · · · xnk ⎥⎦
⎣ n1 n2
⎡y1 ⎤ ⎡𝛽̂0 ⎤ ⎡ 𝜀1 ⎤
⎢ ⎥ ⎢̂ ⎥ ⎢ ⎥
y 𝛽 𝜀
y = ⎢ 2 ⎥ , 𝛽̂ = ⎢ 1 ⎥ , and 𝜀 = ⎢ 2 ⎥
⎢⋮⎥ ⎢⋮⎥ ⎢⋮⎥
⎢y ⎥ ⎢̂ ⎥ ⎢𝜀 ⎥
⎣ n⎦ ⎣ 𝛽n ⎦ ⎣ n⎦
′
provided that the inverse of (X X) exists. This matrix will always exist if the
regressors are linearly independent, that is, if no column of the X matrix is a linear
combination of the other columns.
Since 𝛽̂ is an estimator of 𝛽, therefore, the estimate of the vector of y can be
calculated as
y = X 𝛽̂
̂ (3.10)
where
⎡̂
y1 ⎤ ⎡𝜀̂1 ⎤
⎢̂ ⎥ ⎢ ⎥
y 𝜀̂
y = ⎢ 2 ⎥ 𝜀̂ = ⎢ 2 ⎥
̂
⎢⋮⎥ ⎢⋮⎥
⎢̂ ⎥ ⎢ 𝜀̂ ⎥
⎣ yn ⎦ ⎣ n⎦
3.6 Artificial Neural Networks

Machine learning models (e.g., artificial neural networks) are nonlinear modeling
approaches and an alternative to multiple linear regression modeling. These
techniques will be useful especially if there is a nonlinear relationship between
input and output factors, and consequently linear regression models cannot model
the situation accurately. An artificial neural network (ANN) for example is an
information-processing paradigm that is inspired by the way biological nervous
systems, such as the brain, process information. The key element of this paradigm
is the novel structure of the information processing system. It is composed of a
large number of highly interconnected processing elements (neurons) working
in unison to solve specific problems. ANNs, like people, learn by example. An
ANN is configured for a specific application, such as pattern recognition or data
classification, through a learning process. Learning in biological systems involves
adjustments to the synaptic connections that exist between the neurons. This is true
of ANNs as well.
Neural networks, with their remarkable ability to derive meaning from compli-
cated or imprecise data, can be used to extract patterns and detect trends that are too
complex to be noticed by either humans or other computer techniques. A trained
neural network can be thought of as an “expert” in the category of information it
3.6 Artificial Neural Networks 29
has been given to analyze. This expert can then be used to provide projections given
new situations of interest and answer “what if” questions.
In ANN, neurons are arranged in parallel layers, with each neuron forming
weighted connections to all layers. In between lies at least one layer, termed the
hidden layer. Hidden layers act as feature detectors, and according to universal
approximation theory, a network with a single hidden layer with a sufficiently large
number of neurons can map any input to any output, with an arbitrary degree of
accuracy. In addition, there is a “bias” neuron that is connected to all neurons in the
hidden layer and the output layer. The bias neuron accepts no inputs and supplies
an invariant output. Bias neurons are added to the hidden and output layers to
preserve the universal approximation of the network. Figure 3.3 shows a typical
three-layered ANN with “I” input neurons, “H” hidden neurons, and “O” output
neurons.
The number of input and output neurons is determined by the nature of the prob-
lem under study. The number of neurons in the hidden layer is often determined by
the required degree of accuracy and is therefore a parameter in formulating an ANN
model. The input neurons transmit their inputs to the neurons in the hidden layer,
thus acting as distribution channels. The neurons in the hidden and output layers
calculate their inputs by performing a weighted summation of all the outputs they
receive from the preceding layer. Their outputs, on the other hand, are calculated by
transforming their inputs using a nonlinear transfer function. The most widely used
transfer function is the “S”-shaped logistic sigmoid transfer function. This transfer
1 2
2 3 1
k m n
xˆ k yˆ on
Input layer Hidden layer Output layer
Figure 3.3 Architecture of a hidden layer feed-forward neural network.

function is continuously differentiable, monotonic, symmetric, bounded between 0

and 1, and its derivative can be expressed in terms of the function itself. The function
and its derivative are
1
f (x) = (3.11)
1 + e−x
df (x)
= f (x)(1 − f (x)) (3.12)
dx
This necessitates the normalization of input/output data so that they are in the
same range of the transfer function used. The normalization of inputs also avoids
overflows due to very large or very small weights. Data can be normalized using:
z − zmin
̂z = (3.13)
zmax − zmin
where z is the normalized value; and zmin and zmax are the minimum and maxi-
mum values of z, respectively, which may be an input or an output variable. Table 3.1
shows the inputs and outputs of neurons in different layers in the ANN. In this table,
xk is the normalized network input to input neuron k, ̂y0n is the network output neu-
xy
ron n, and the general form Wab is the weight emanating from neuron a in layer x
and terminating at neuron b in the subsequent layer y.
ANN training is an optimization process, in which an error function is minimized
by adjusting the weights. When an input training pattern is introduced to the ANN,
it calculates an output. This network output is compared with the actual output pro-
vided by the user. The difference is used by the optimization technique to train the
network. The error function to be minimized is the individual sum-squared-error Ej ,
which is given by
0 ( )
∑
Ej = ̂ynj − y0nj (3.14)
j=1
where ̂ ynj and y0nj are the jth measured and the predicted network outputs that cor-
respond to the jth input, respectively. Therefore, the training process requires a for-
ward pass to calculate an output and a backward pass to update the weights. Min-
imizing Ej implies that for each forward pass made, a backward pass should be
carried out.
The development of an artificial neural network model usually consists of two
steps. The first step is a training stage, where the network is subjected to a training set
Table 3.1 Input and output neurons for a network architecture containing
input, output, and one hidden layer.
Layer Neuron Input to the neuron Output from the neuron
Input k ̂
xk yon = ̂
̂ xk
∑I
1
Hidden m h
xm = yik wih
km
+ bm yhm = ( h)
k=0 1 + exp −xm
∑H
Output n xno = yhm who
mn + bn yon = xno
m=0
of input/output patterns. The second step is a testing stage, where the performance
of the network is tested on patterns that have not been “seen” by the network during
the training stage.
3.7 Mixture Design of Experiments

Mixture design of experiments, or experimental design of mixtures, is a subclass of
response surface methodology (RSM). RSM is used to study relationships between
measured dependent variables (responses) and independent/explanatory variables
(factors). The main idea of RSM is to use a sequence of designed experiments to
obtain optimal response(s). The optimum desired response(s) can be found by a
regression analysis of data collected from designed experiments called response sur-
face designs. Factorial design, fractional factorial design, and composite design are
examples of response surface designs.
In mixture design, the measured response is assumed to depend only on the
proportions of ingredients in the mixtures, not on the amounts of the mixture.
The Experiment of Lemonade is a famous example to show how the conventional
response surface design does not apply well to experiments with mixtures [9].
In this kind of experiment, the objective is to find the composition of water and
lemonade that give the optimum taste. A 22 factorial design of experiment was
carried out as presented in Table 3.2. It can be seen that run #4 is a replication of run
#1. Both actually have the same proportion of water and lemonade. In addition, the
design only covered approximately one-third of the design space. In other words,
factorial design requires more experiments for less information when it was applied
to experiments with mixtures.
The unique feature of mixture experiments is that the sum of all of q components
proportion must equal to 1, meaning that all independent variables xi correlate to
each other, i.e.
∑
q
xi = x1 + x2 + … + xq = 1.0 (3.15)
i=1
xi ≥ 0, i = 1,2, … , q (3.16)
The experimental region for a mixture experiment with q components is called
simplex, which is regularly a sided figure with q vertices in q − 1 dimensions.
Table 3.2 A 22 (two factors – two levels) factorial design

of the lemonade experiment.
Run # Lemons level Water level Taste
1 Low (−) Low (−) Good

2 High (+) Low (−) Sour
3 Low (–) High (+) Weak
4 High (+) High (+) Good
X1 Figure 3.4 Simplex

coordinate system for a
three-component mixture.
0.8
0.6
2
0.4
0.
0.
2
0.
4
0.
4
6
0.
0.
6
8
0.
0.
8
X2 X3
The coordinate system for mixture proportions is a simplex coordinate system.

The simplex coordinate system for a three-component mixture is presented by
Figure 3.4.
To accommodate a polynomial equation to represent response surface over the
entire simplex region, an arrangement consisting of evenly distributed points called
lattice has to be constructed. A [q,m] simplex lattice design, therefore, is a design of
points for a q components mixture to accommodate an mth degree polynomial of a
response surface. Examples of simplex lattice designs are shown in Figure 3.5.
x1 = 1 x1 = 1
x1 = 2
3
, x3 = 1
3
, x2 = 0
x 1 = x3 = 1
2
, x2 = 0 x1 = x3 = 1
2
, x2 = 0
x1 = 1 x1 = 1
x2 = 1 A (3, 2) Lattice x3 = 1 x2 = 1 A (3, 3) Lattice x3 = 1
x4 = 1 x4 = 1
x2 = 1 x2 = 1
x3 = 1 x3 = 1
A (4, 2) Lattice A (4, 3) Lattice
Figure 3.5 Examples of a [q,m] simplex lattice design.

Because the independent variables x are not unique, the standard polynomial
model has been modified to become a canonical mixture polynomial model. In
general, the canonical or Scheffe forms of the mixture models are as follows:
∑
q
Linear∶ E(y) = 𝛽i xi (3.17)
i=1
∑
q
∑∑
q
Quadratic∶ E(y) = 𝛽i xi + 𝛽ij xi xj (3.18)
i=1 i < j=2
∑
q
∑∑
q
∑∑
q
Full cubic∶ E(y) = 𝛽i xi + 𝛽ij xi xj + 𝛿ij xi xj (xi − xj )
i=1 i < j=2 i < j=2
∑∑∑ q
+ 𝛽ijk 𝛽i 𝛽j 𝛽k (3.19)
i < j < k=3
∑
q
∑∑
q
∑∑
q
Special cubic∶ E(y) = 𝛽i xi + 𝛽ij xi xj + 𝛿ij xi xj
i=1 i < j =2 i < j =2
∑∑∑ q
+ 𝛽ijk 𝛽i 𝛽j 𝛽k (3.20)
i < j< k=3
The models can be used to construct a response surface and a contour plot as illus-
trated in Figure 3.6.
The response surface of a linear polynomial model is a planar surface over the sim-
plex region. The quadratic polynomial model consists of linear blending terms and
quadratic blending terms. Therefore, the response surface of a quadratic polynomial
model is a curved surface, which consists of a planar surface plus a curvature sur-
face representing the quadratic term. The response surfaces of linear and quadratic
Figure 3.6 Response surface

and contour plot of a
response over a
three-component simplex
region.
Thickness response
x3 (1.00)
x1 (0.00)
x2 (0.00)
x2 (1.00)
x3 (0.00)
x1 (1.00)
canonical polynomial model of a three component mixture were depicted in a pre-

vious study [10].
There are many variations of mixture design problems. One of the variations is the
addition of upper and lower bounds on some of the component proportions. Con-
strained mixture design and pseudo-simplex design are examples of design strategies
for such problems. Various types of mixture designs for various mixture design prob-
lems, as well as data analysis and model building techniques are discussed earlier.
In some cases, nonmixture variables are involved in the problem and affect the
responses. These variables are called as process variables z. One possible strategy to
tackle this case is through the use of Process-Mixture Design. This design combines
the standard mixture design with factorial or fractional factorial design for process
variables as illustrated in Figure 3.7.
The standard canonical polynomial model is combined with the process model
to constitute a response surface model. For instance, the overall response model of
problem with a three-component mixture and three process variables may follow
this equation:
[ 3 ]
∑3
∑ ∑ 3
∑
3
∑ ∑ ∑3
E(y) = 𝛾i xi +
0
𝛾ij xi xj +
0
𝛾i xi +
l
𝛾ij xi xj z1
l
i=1 i<j l=1 i=1 i<j

[ 3 ]
∑∑
3
∑ ∑ ∑
3
+ 𝛾ilm xi + 𝛾ijlm xi xj z1 zm
l<m i=1 i<j
[ 3 ]
∑ ∑ ∑
3
+ 𝛾i xi +
123
𝛾ij xi xj z1 z2 z3 + 𝜖
123
(3.21)
i=1 i<j
A common application of mixture design of experiment is product formula-

tion, where a product is formed by mixing several components together. Successful
2 x Plasticizer x1 Plasticizer
1.00 1 z2 1.00
2
(−, +) 5
(+, +)
2 2 2 2
14 12 0.00 0.00
0.00 13 0.00
6
11 10
8 7
2 2 9 6 2 2 2 2
7
1.00 1.00 1.00 1.00
0.00 x2 Plasticizer 0.00 x3 Plasticizer
x2 Plasticizer x3 Plasticizer Thickness
Thickness
z1
1.00 x1 Plasticizer 1.00 x1 Plasticizer
2 2
(−, −) (+, −)
2 8 9 2 2 14 12 2
0.00 0.00 0.00 13 0.00
11
7
6 10
5 9 2
2 2 2 2 2
8
1.00 1.00 1.00 1.00
x2 Plasticizer 0.00 x2 Plasticizer 0.00 x3 Plasticizer
Thickness Thickness
Figure 3.7 A process-mixture designs with a Three-component mixture design and a 22

factorial design of process variables z1 and z2.
Another random document with
no related content on Scribd:
through the mask they wear. And if a man has the face of a man but
the heart of a fox then certainly while such a man beholds his own
face, you shall see the other creature in him.”
Hearing that, the youth Huathia was much amazed at the magic
of the thing and, holding it so that the face of his herder friend was
shown in the mirror, saw, not the rough bearded face of the man
alone, all knotted like a tree-trunk, but a face that was full of
kindness and gentleness, at which he was glad.
So he placed the wonderful mirror in his bag and carried it about
with him. The next day, while he was leaning against the trunk of a
tree and playing on his flute, he seemed to hear a whispering, and
putting his reed away he listened intently. Still and small, still and
small were the voices that he heard, as tree-head bent to tree-head
and leaf murmured to leaf, but soon he caught the rumour that ran,
and learned the tale that in the country of the rich man there was a
creature timorous and frail, whose gentle heart was heavy with
sorrow, and that an unknown evil brooded dark.
No time lost he then, seeing that there was something of worth
that he could possibly do, but gave the care of the goats and llamas
to his friend, took his arrows and bow, his bag with a little food and
the wonderful mirror, and after bidding his friend good-bye set off for
the land of the rich man. What was strange was that while all had
been silent in the soft green woods that morning, except for the
sound of his flute, no sooner had he started on his way than a gay
chorus came from the bright birds and the world was full of mirth. So,
well content, he went on his way, a ragged herdsman, but light of
heart and strong of limb and brave.
Into the land of the rich man he went and came in time to a place
where sat the maiden under a tree, doves at her feet and glittering
humming-birds about her head. When Suso saw the youth her heart
leaped for joy, for she knew him for a kind lad, though never before
had she set eyes on him.
“Are you a beggar and poor?” she asked. “For here there is
plenty for all.”
“I am no beggar,” he answered, “and for myself I am well content
with what I have. But it has been whispered about the world and I
have heard the tale, that there is a great sorrow upon you, and that
some unknown evil is destroying the beauty and the bliss of this
place, so I have come to do what is to be done.”
At that Suso said no more but rose up and took Huathia by the
hand and led him to her father. It was a day on which the good man
was very weak, but seeing that his daughter was pleased with her
new companion he ordered his servants to spread a table under the
trees, and the three of them had a feast of goat’s milk and fruit, and
cassava bread, though the father could eat but little. Then Huathia
took his flute and played sweet music until the world seemed full of
peace, and gripping grief had vanished. Suso, too, sang sweetly, so
that for a moment the father thought that the shadow that was upon
him was but a dream and might pass.
They talked long and long, the three of them, and Huathia
learned much about the rich man’s failing strength, whereupon it
came to him somehow, that by means of his wonderful mirror he
might perchance discover what evil thing was about that place. To
him the rich man said:
“If with this mirror you can find the hidden evil thing and can
restore my strength again, then there is nothing too great that I own
which may not be yours for the asking.”
“There is but one thing I want,” said Huathia. “For I love Suso the
gentle and would marry her.”
The rich man thought long after this speech, stroking the hair of
Suso who sat at his knee, for it had not entered into his mind that his
daughter might be the gift which the youth demanded as his price.
But looking at the maiden he saw that her eyes were cast down,
though for a moment they had looked up swiftly as Huathia spoke.
Then, too, it was certain that since the youth had been there, the
song of the birds was louder in the thicket and the green of the trees
brighter.
So the father said thoughtfully: “If you find the cause of the
trouble that is upon me and relieve it so that I am healed again, then
you may have my daughter for your wife, though you must promise
me that you will stay in this place.”
That, Huathia promised readily enough, and stooped to Suso and
kissed her, and having done so, went away to the dark pool in the
woods to sleep, at the very moment the stepmother came out of the
house to join her husband and his daughter.
III
As it happened that night, there was a thin new moon, and the
youth slept but little because of the croaking noise made by the
frogs. Presently, full awake, he sat up, and it seemed to him that the
air was full of noise, not only of frogs but of the hooting of owls and
the whirring of bats, and looking he saw the strange sight of a great
white toad with two heads, and presently about that fearful thing
other things gathered. From rock and hole came unclean creatures,
abominable serpents and centipedes and great gray spiders, and all
these gathered in a circle, the two-headed toad in the centre. With
wide-open eyes Huathia watched, although the sight of so much that
was noisome came near to benumbing and stupefying him, and
incomplete shapes seemed to be looking at him with evil eyes from
the black depth of the forest.
Soon the owl began to mourn and the song fell into words and
the youth heard this:
“Who knows where hides our queen? Hoo! Hoo!”
And first one creature and then another answered:
“The toad, our queen, lies hid unsought

Beneath the stone that men have wrought.”
And so it went on, a mad and horrible concert, with bat and owl
and great ghost-moth whirling about on silent wings, until sickened of
it all Huathia rose up and clapping his hands to his ears fled from the
place. And when he had gained a quiet and lonely spot he sat down,
but in his ears rang what he had heard:

So he wondered and wondered where could be the stone that
men had wrought, and the story that men had told of a great temple
on the mountains came to him. But that place seemed too far away.
When it was full day the youth went to the house, and in time the
rich man came forth and greeted him. Then came the stepmother,
who fixed her large dark eyes on Huathia, not looking at him straight,
but sideways. Suso came shortly afterward and the youth could not
take his eyes from her. It seemed to him that she was the most
beautiful of living things as she sat on her stool by the side of her
father, her hair touched by the golden light so that it seemed to be as
full of ripples as a sun-kissed brook. So there was pleasant talk while
they ate, and, after, a drinking-in of soft music as Huathia played on
his flute. Suso sang when Huathia had finished, and though her song
had a touch of sadness in it, it seemed to her pleased father that all
on earth that was soft and shapely and fair was gathered there in
that garden, until catching the eye of his wife he was reminded that
his life was flowing away, and the old grief came upon him.
Somehow talk fell upon Huathia and his mirror and the strange
way in which he had found it, and he took it from his bag. As he
looked in it, Suso came and stood behind him, so that he saw the
reflection of her face and the true picture of herself, and there was a
gentleness there, the gentleness of the dove and the purity of the
flower. The rich man came, too, looking over Huathia’s shoulder and
saw his own reflection. But what the youth saw was a face that
denoted great bravery and kindness. Seeing all this the stepmother
stretched her hand across the table and took the mirror, gazing at
the picture of her own dark beauty. Then Huathia stepped to her side
and looked into the disc. He saw, not the dark eyes and night-black
hair that she saw, not the face of a proud woman, but the face of a
toad, and when she held the polished silver further off, the better to
see, the toad-face changed, so that he saw a double-headed toad.
But of that she knew nothing and did not even guess that he knew
her for a vile witch and no true woman. And as she continued to
gaze and her thoughts wandered, so did new things come into the
picture that Huathia saw, and he beheld about her neck two writhing
white snakes, a sight so horrible that he could scarcely hold his
countenance or prevent himself from calling out. Having seen to her
content, the woman rose from her stool and left the room.
The rich man, already tired, for his night’s sleep did not revive
him, stood up and beckoned to the youth to give him an arm. Suso
supported him on the other side and so they walked slowly to a seat
beneath a great flowering bush near the house. Having found his
seat and being wrapped in his feather mantle by Suso, he asked the
youth to play the flute again. Huathia was ready and willing, but
somehow the memory of the two-headed toad and the two white
snakes made him nervous, and when he put his flute to his lips no
sweet sounds came, but instead rude noises like the hissing of
snakes and the croaking of frogs and the screeching of parrots. Even
Suso stopped her ears and her father bade the youth cease his
noise.
“Are you of those who make my last days the wearier with your
noises?” he asked sorrowfully. Then he added: “For many nights I
have dreamed of toads with two heads and of snakes that hung over
me, and now you come with your flute and the noises that such evil
things make. I had expected better of you, Huathia, seeing that I
have treated you as a son.”
Huathia earnestly assured him that he had no wish to do other
than to make music, and he ended by saying: “There is, I am sure,
some enchantment in this place, for though the sun is warm I feel a
chill, as if some clammy thing enfolded me.”
He shivered as he spoke, though he was a lad whose blood ran
warm; not afraid, not given to idle fancies. Of a sudden his eyes fell
upon a large grindstone that lay near by. It was a stone so great that
two men could hardly make shift to raise it, and so it had been left
there for years and grasses had grown about it. But when Huathia
saw it, there leaped into his mind the song that he had heard:

It had meant little in the night, but in a flash he saw that the
grindstone was a stone wrought by men. So fitting an arrow to his
bow he handed the weapon to Suso, telling her to shoot whatever
evil thing was discovered when he lifted the stone. With a great effort
he raised the stone suddenly, heavy though it was, lifting it high
above his head, and there, in a hollow place where the stone had
been, sat a large, white, double-headed toad.
“Shoot, Suso, shoot!” commanded the father. “Let not that evil
thing escape. It is the creature that torments me at night.”
Swift flew the arrow and it pierced the body of the toad. At the
same moment there fell from the roof of the house two monstrous
white serpents where they had lain hidden. Like lightning Huathia,
having seized the bow, sent two arrows flying, and each serpent was
cut into halves. In less than three moments three evil things died,
and it was like the sun coming from a cloud-veil, the way in which joy
came to that place. The weakness of the father fell from him like a
cloak. The bodies of the toad and the snakes withered and
shrivelled, and as a light breeze sprang up, what was left of them
was blown away as dust. There were soft stirrings in the thicket and
the whole world burst into song. So both father and daughter knew
then that the witcheries were gone and the evil creatures vanished
for ever, and that all the trouble that had been upon that place came
from the wicked stepmother.
So youth and maiden were married, and the father soon regained
his health and strength, and in all the world there were no happier
people than they.
THE TALE OF THE LAZY PEOPLE
N Colombia, it seems, there were always monkeys, or if not

always, at least as far as the memory of man goes. An old historian
named Oviedo noted that and wrote: “When the Christians make an
expedition to the interior and have to pass by woods, they ought to
cover themselves well with their bucklers . . . for the monkeys throw
down nuts and branches at them. . . . I knew one, a servant. This
man threw a stone at a monkey, who caught it and returned it with
such force that it knocked out four or five of Francisco’s teeth, and I
know this to be true for I often saw the said Francisco, always
without his teeth.”
Now one day a man told me the tale of the monkeys, and he
talked and talked as he smoked, until the stars came out and shone
clear and steady and the air was heavy with perfume, and owls and
bats floated strangely, as they will do, and when he had finished he
still talked, taking up forgotten ends of his tale and winding in and
about, making a long affair of a short matter. But then he had nothing
else to do but to talk and was mighty pleased, it seemed, to have
someone to listen to him. Then, when we should have been
sleeping, he went on talking, picking out a piece of the tale here and
another piece there, and explaining until I was well nigh like to get
the story tangled myself. But here is the meat of it:
Long, long ago there were no monkeys, and the trees were so full
of fruit, and the vines of grapes, that the people became lazy, and at
last did little but eat and sleep, being too idle to carry away the rinds
and skins of the fruit that they lived on, and certainly too lazy to clean
their thatched houses.
It was very pleasant at first, but soon not so pleasant, for winged
things that bit and stung came in thousands to feed on the things
thrown aside, and they, too, grew lazy, finding so much to eat ready
at hand, and when people tried to brush them away there was a loud
and angry buzz and much irritated stinging, so that soon every one
was wonder-struck, not knowing exactly what to do. For a time it
seemed easier to move the little village to a new spot and to build
new houses, for the dwellings were light affairs and in a day or less a
good house could be built. But then they lived by a lake from which
the water for drinking was taken, and as it was but a little body of
water, it was not long before the people had built right round the still
pool and so were back again at the starting place. As for the stinging
flies, they were soon worse than the mosquitoes, while a great wasp
with pink head and legs and bands of black and gold on its body,
though very pretty to see, was worst of all. So it was no easy matter
to know what to do, and there was much talk and much argument,
and all that the people agreed on was that something had to be
done, and that, very soon.
One day there came to the village a queer and rather faded kind
of man, ragged and tattered and torn as though he had scrambled
for miles through the thorn-bush forest. He had rough yellow hair,
and queer wrinkles at the corners of his eyes which made him look
as if he were smiling. It was late in the afternoon when he came and
the people were taking their rest after the noon meal, so no one took
much notice of him although he went here and there, looking at
things, and so walked round the lake. But the curiosity of everyone
was excited when he was seen to make a basket, which he did
quickly, and then commence to gather up the fruit skins and rinds in
one place. Now and then some one or other raised himself in his
hammock, with a mind to talk to him, but it seemed almost too much
trouble, and when some great blue-winged butterfly fluttered past or
some golden-throated humming-bird flashed in the sunlight, their
eyes wandered away from the old man and they forgot him again. So
the sunlight died and the forest was a velvet blackness and everyone
slept, though the old man still worked on, and the next morning when
the people awoke he was still working diligently, though he had but a
small place cleared after all.
The very thought that any one would work all night made the
head man shiver with a kind of excitement, yet he was very curious
to know why the stranger went to so much trouble, seeing that he
neither lived there nor was of the lake men. At the same time it made
his spirit droop to think that if the place was to be cleared up, he and
everyone else had a mountain of work in sight. So Tera, the head
man, called to Cuco, who was his servant, telling him to bring the
stranger to him, and Cuco, who was very respectful, said that he
would attend to it. Then Cuco did his part by calling Yana and
delivering the message to him. And Yana in turn told his servant,
Mata, who told his servant, Pera, who told his servant, Racas, who
told a boy, so that at last the message reached the old man. Then
back went the old man, handed by the boy to Racas, by Racas to
Pera, by Pera to Mata, by Mata to Yana, and by Yana to Cuco, so
that at last he stood before Tera, the head man, and the others,
being curious to know what was afoot, gathered about.
“What is your name, from where do you come, and what do you
want?” asked Tera, putting his three questions at once, to save
trouble. Then the head man looked at those about him with a little
frown, as much as to say, “Note how wisely I act,” and each man
who had heard, seeing that the head man looked his way, nodded at
his neighbour, as though calling attention to the wisdom of the head
man, so all went very well. But the little old man stood there very
simply, making no fuss at all and quite unimpressed with the
greatness of the great man.
“I want to work,” he answered. “I want to be told what you want
done and to see that it is done.”
To be sure, the language that he spoke was one new to those
who listened, but somehow they seemed to understand. But the
thing that he said they found truly astonishing and could hardly
believe their ears. But the head man, though as astonished as any
one there, quickly regained his composure and asked this question:
“What is your trade?”
“I have no trade,” said the old man. “But I get things done.”
“What kind of things?”
“All kinds of things.”
“Do you mean big things, like house-building and all that?” asked
the head man.
“Yes. And little things too, which are really big things when you
come to consider,” said the old man, but that seemed an odd if not a
silly thing to say, the head man thought.
“Little things left undone soon become big things,” explained the
old man, and waved his hand in the direction of a heap of fruit skins
and husks near by.
“Yes. Yes. But you must not preach to us, you know,” said Tera a
little testily. “Tell me the names of the trades you have.”
So the little old man began to tell, naming big things and very
little things, things important and things not important at all, and
having finished, asked very politely whether any one there had
anything to be done. As for pay he said that he wanted none at all
and would take none, and he said that because some of those
gathered about him began offering him things.
For instance, Pera said: “If you work for me, I will let you have
one fish out of every ten that you catch, for I am a fisherman.” And
Racas pushed him aside, saying: “But I will do better, for I am
supposed to be fruit gatherer and will give you two things for every
ten you gather.” And so it went, each bidding higher than his
neighbour, until it came to the turn of the man whose duty it was to
gather the rinds and fruit skins. He said, “I will let you have, not one
out of ten, nor two out of ten, nor five out of ten that you gather, but
ten out of ten, if you will work for me.” At that the old man said quite
positively that he would take no pay at all.
No more was said then and the little old man turned away without
as much as bowing to the head man, seeing which the head man
waved his hand and said: “You may go, and so that you will lose no
time, you need not bow to me.” And all the rest gathered there said
very hastily: “Nor need you bow to me, either.”
The old man took small notice of any one, but went away singing,
for he had a gay, light-hearted disposition, and having reached the
place he had cleared, he took flat pieces of wood and began cutting
out figures like little men, and each figure had a kind of handle that
looked like a long tail. Nor did he cease whittling until he had made
at least twenty wooden figures for each man in the village. Being
finished he stood up to stretch his legs and straighten his back, and
when the people asked him what the little figures were for, he
shrugged his shoulders but spoke never a word. Then he lifted the
figures that he had made, one by one, and set them upright in the
sand until there was a long row of them, and took his place in front of
them, like a general before his army. It was beautiful to look at, for
one figure was as like another as one pin is like another, and for a
moment even the old man stood admiring the line. After a moment
he waved his hand in a peculiar way, spoke some magic word, and
waved his hand again, at which each of the figures came to life and
nodded its head, seeing which all the people laughed and clapped
their hands. The ragged man bade them make no noise, but watch.
“Since you do not like to work,” he said, “I have made twenty
figures for each of you, and they will work for you without pay, doing
what you require them to do; only observe this, you must not give
any figure more than one particular job. And now let each man or
woman clap his hands three times, then call out the name of the
thing to be done.”
When he had said this, the figures started running, twenty
gathering in a circle about each man there, bowing from the hips and
straightening themselves again, so that their tails of wood went up
and down like pump-handles.
“Now see,” said the ragged man, “you have things to work for
you, and as I call out, the figures will stand forth, each ready to do
his task.” And he began calling, thus:
“Armadillo hunters, stand forth!” and a hundred and more active
figures ran together like soldiers.
So he named others in order as:
Bread makers.
Cassava gatherers.
Despolvadores, who would gather up dust.
Esquiladors, who would shear the goats.
Farsante men, whose work was to amuse tired men.
Guardas, to keep order about the place.
Horneros, or bakers.
Industriosos, who were to do odd jobs everywhere.
Jumentos, whose work it was to carry burdens.
Labradores, to do heavy work and clear away garbage.
Moledores, to grind the corn.
Narradores, who told stories, related gossip and so on.
Olleros, or pot makers.
Pocilga figures, to attend to the pigs.
Queseros, to make cheese from goat’s milk.
Rumbosos, or proud-looking things to walk in parades.
Servidores, or food carriers.
Trotadores, to run errands.
Vaqueros, to attend to the cows.
So everyone was well pleased and each one had his twenty
figures to do all that needed to be done, and all that day there was a
great scraping and cleaning and carrying and currying and hurrying
and scurrying. Silently the little figures worked, never stopping, never
tiring, never getting in one another’s way, and all that the living
people had to do was to rest and watch the men of wood, and keep
their brains free for higher things. For it must be remembered that
before the old man came there with his wonderful gift, the people
had complained that there was so much to be done that they had no
time to write poems or to make songs or to create music, and that
with the daily tasks abolished their brains would be more active.
Not two days had passed before the children of the place
complained that they did not have a chance and that they had so
much to do, what with hunting for things lost, looking after their small
brothers and sisters, keeping things in order, trying to remember
things they were told, cleaning things, and a dozen other tasks, that
they really had no time to play, much less to study. So they went in a
body to the old man and asked him to give each child twenty figures
to do odd things. There was a great deal of fire and expression in his
eyes when he made answer that if the children really needed help he
would lose no time in providing it. But the young people were quite
positive that they were overworked, and the long and short of it was
that the old man whittled out many, many more figures, and in
another twenty-four hours each and every boy and girl had his own:
Abaniquero, or fan maker, so that none had to pluck a palm leaf.
Baliquero figure, to carry letters and messages.
Cabrero, to look after the goats.
Desalumbrado, to hunt for things in the dark.
Enseñador, or private teacher, who was never to scold.
Florista, to save them the trouble of gathering flowers.
Guasón figure, to amuse them.
Hojaldarista, whose work it was to make cakes.
Juego figure, to arrange games.
Keeper of things.
Lector, to read and tell stories.
Mimo, to act as clown.
Niñera, to look after younger children.
Obediencia figure, to make others obey.
Postor, to buy things for them.
Quitar figures, to take things away when children tired.
Recordación figures, or rememberers.
Solfeadors, to sing to them.
Tortada men, to make pies.
Volantes, as servants.
So things seemed to be going very well, and before a month had
passed in all that place there was not a thing out of order, soiled,
broken, bent, lost, misplaced, undone, unclean, or disorderly. Neither
man nor woman nor child had to worry; dinners were always
prepared, fruits gathered, beds made, houses in perfect order, and
all was spick and span. All that the grown-up people had to do was
to look on, and no one was proud of the order in his house because
every other house in the place was as orderly. As for the children,
they had nothing at all to do but to eat, drink, rest, and sleep. Then,
presently, more figures were called for as this one or that wanted a
larger house, a finer garden, or grander clothes.
But as the wooden figures became more numerous and as no
figure could do more than one task, the ragged man had to make
figures for the figures and servants for the servants, for as things
went on, there had to be more fruit gatherers, more water carriers,
more scavengers, more cooks, because the figures had to eat and
drink. Thus it came to pass that before long, instead of their being
twenty figures for each man, there were sixty or seventy, with new
ones coming from the old man’s knife every day. Soon the lively
manikins were everywhere, inside houses as well as outside, thick
as flies in summer and certainly a great deal more persistent, for
there could be no closing of doors against the manikins. Indeed, had
anything like that been attempted there would have been a great cry
for special door-openers. So, many houses were quite cluttered with
wooden men, those who were on duty rushing about until it made the
head swim to look at them, and those who were resting or sleeping,
for soon they learned to rest and to sleep, lying about the floors,
piled up in corners, or hanging to rafters by their tails. All that
increase in help had made for the production of a thousand or more
guardas, whose task it was to keep order, and they were
everywhere, alert and watchful and officious, and the real people had
to step about very gingerly sometimes, to avoid treading on them
and annoying them.
At last there came a day when the people began to grow a little
tired of doing nothing, and they told one another that a little help was
a very good thing, but help in excess, too much of a good thing
altogether. So there was a meeting and much talk and the manikin
narradors, whose duty it was to carry gossip and the news, were
very busy, rushing from here to there with their scraps of information.
“It is very clear that something must be done,” said Tera, the
head man.
“But everything is being done,” answered the little old man. “If
everything is done, something must be done.”
“I did not mean that,” said Tera, who seemed a little testy. “I
meant to say that these wooden men must be kept in their places.”
“But they are in their places,” replied the old man. “Their place is
everywhere because they do everything, so they are in their places.”
“You see, the days are so very long, so very dull,” said the man
who wished to have time that he might become a poet. “At the shut
of day we are not weary.”
“We do not want to be petted,” said another.
“The trouble is,” sighed a fat man, “you can’t be happy when
everything is done for you.”
“And we don’t want to be nobodies,” shouted another.
Another said very mournfully: “It seems to me that when these
wooden things do things with our things, then the things that they do
and make and care for are not our things.”
“Too many ‘things’ in that speech,” said the fat man.
“Well, there are too many things,” answered the other. “Look at
me. I used to be gardener and now I’m nothing. When my garden is
dug and planted and tended and watered and the very flowers
plucked by these wooden things, and when other wooden things pick
up the leaves and pull the weeds and do everything, then my garden
does not seem to be mine.” He added after awhile: “I hope you know
what I mean, because it is not very clear to me, yet it is so. I
remember——”
At that the little old man put up his hand and said: “But that is
against the contract. You must not try to remember, really you must
not, because there are manikins to do all the remembering, if you
please.”
“Well, but I think——” began the man, when he was again
interrupted.
“Please do not think,” said the little old man. “We have things to
do the thinking, if you please.” He thought for a moment, his bent
forefinger on his lips, then he said: “I’ll see what can be done. It is
clear that you are not satisfied, although you have everything that
you asked for and certainly all the time that you want.”
“Let us do something,” murmured Tera.
“I’m afraid there is nothing that you can do,” said the little old
man, “because, as you see, everything is done, and when everything
is done it is quite clear that something cannot be left to be done. The
only thing that is clear is that there is nothing to be done.”
At that the meeting broke up and each went to his own hammock
to think things over, and soon the general cry was: “We must have
elbow room.” And hearing that, the little old man went to work and
whittled more figures of wood, a whole army of them, ten for each
living man, woman, and child, and in voices that creaked like
wooden machinery they marched hither and thither, crying: “Elbow
room. Elbow room!”
Soon there was confusion. It was manikin against manikin for a
time, the Elbow-room-ers thrusting and pushing the other working
manikins, some going about their work with frantic haste, others
interfering with them, clutching at them and at the things they
carried, a tangled knot of them sometimes staggering, to go down
with a crash. Soon in every house was a jangling tumult, manikins
and men running about in houses and dashing out into the open
spaces outside; the noise of slamming doors and breaking pots; the
clamour of animals. Above all could be heard everywhere cries of
“We want elbow room! We want elbow room!” Soon men were
running away from the houses with those strange swift manikins
hanging to them sometimes beating them, while other manikins
threw things out of the doors and through windows, food and
household things. And excited children fled too, while their manikins
ran at their sides, some chattering, some acting the clown as was
their duty, some telling stories as they ran, while other strange little
figures of wood ran bearing heavy burdens. It was all a dreadful mix-
up with no one knowing what to do, no one knowing where to go,
and everywhere the manikins who were guardas, or order keepers,
ran about, tripping people and manikins alike in the effort to stop the
rush. But when the day was near its end there were no people in the
houses and the hammocks swung idly, for all the men and women
and children, even the white-haired grandfathers and grandmothers,
had fled to the further side of the lake, where they could have elbow
room, leaving the houses and all that was in them to the manikins.
The next day, the people plucked their fruit for themselves and it
seemed as though fruit was never sweeter. The water that they
carried from the lake tasted better and cooler than water had for
many a long day, and when night came they were happily tired and
slept well, without any manikin to swing their hammocks and sing to
them. And in the morning they woke early to discover the pink and
gold of the sunrise most wonderful to see, and there was music in
the sound of the wind among the grasses. So as the day passed
they were both amazed and astonished at the wonderful and
beautiful things that they had almost forgotten, the sight of butterflies
fluttering from flower to flower, the shadows chasing across the hills,
the richness of the green earth and the blueness of the sky, the gold
of sunlight on the leaves, the rippling water and the bending trees;
indeed the memory of the manikin days was like a fearful nightmare.
Very light-hearted then they grew and the world was full of the music
of their laughter and song, and briskly they worked, enjoying it all,
building new houses and making things to put in them.
Meanwhile in the village things had gone queerly. For one thing
the Elbow-room-ers kept up their crowding and pushing, so that the
manikins trying to work at their old tasks (and there were many who
went on just as before) were sadly hindered. There were other
figures of wood with nothing to do, since the people they served
were gone, and these fell to quarrelling among themselves and grew
mischievous. For instance, the pot makers and the pot cleaners fell
out, and the pot cleaners started to break the pots so that the pot
makers would have more work to do. That meant that the clay
gatherers and the clay diggers had to work harder, then because
they worked harder, though to be sure all their work meant nothing
and was little more than idle bustle, they grew hungrier and wanted
more to eat. Because of all that the fruit gatherers had more to do
and the water carriers had to work harder and the cassava bread
makers had to bake as they had never baked before. That brought
the fire builders into it, and of course the wood gatherers also, for
they too had to work harder and to eat more, so still more work came
on the food bringers. And all the time the Elbow-room-ers rushed
about, always in groups of ten, driving and commanding, rushing on
workers and sweeping them aside. So everywhere were little figures
hurrying one after the other, going to and fro, busy about nothing,
quarrelling about nothing, fighting about nothing.
The trouble came when the Elbow-room-ers interfered with the
dogs and the cats, the goats and the hens, pushing and hustling
them. For the animals, disliking all the disorder and clatter, fell upon
the manikins, workers and idlers alike. Seeing that, the household
utensils took a hand and the very pots and kettles ran or rolled or
fell, spilling hot water over the wooden things with pump-handle tails.
The very embers from the fires leaped into the fray. All the while from
the metates in which the corn had been ground came a low growling,
and the growling formed itself into words:
Day by day you tortured us—
Grind, grind, grind.
Holi! Holi!
Huqui! Huqui!
Bring to us the torturers—

Let them feel our power now—

Grind. Grind. G R I N D !
So the metates turned and turned, going round and round without
hands, and presently an Elbow-room-er that was struggling with a
corn-grinder stumbled, and both fell between the grinding stones and
in a moment were crushed to powder. In a flash house utensils and
animals learned the new trick, and in every house manikins were
pushed into the grinding stones. Then sparks began to fly and roofs
to catch on fire and manikins bolted here and there in confusion,
sometimes jamming in doorways, there were so many and all in such
disorder. Then came dazzling, flickering lightning and a great rain, so
that for very safety the manikins fled to the forest and climbed the
trees. And there they have lived ever since, for they grew hair and
became monkeys. But the remembrance of all that passed stayed
with them, and in their hearts to this very day is no love for man, and
for that very reason when a Christian passes through a forest he
must look well to himself, lest the manikins in revenge try to hurt him
by casting nuts and branches at his head.

Chemical Product Formulation Design and Optimization Methods Techniques and Case Studies Ali Elkamel Full Chapter PDF

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Chemical Product Formulation Design and Optimization Methods Techniques and Case Studies Ali Elkamel Full Chapter PDF

Uploaded by

Copyright:

Available Formats

Chemical Product Formulation Design

and Optimization: Methods,

Hydrogen Sulfide: Chemical Biology Basics, Detection

Program Evaluation: Methods and Case Studies 9th

Psychoanalytic Case Formulation 1st Edition, (Ebook

Towards Sustainable Chemical Processes: Applications of

Stochastic Global Optimization Methods and Applications

Chipless RFID Authentication: Design, Realization and

Tidal Energy Systems: Design, Optimization and Control

Numerical Methods and Optimization in Finance [2nd ed.]

Methods, Techniques, and Case Studies

Prof. Hesham Alhumade

Cover Design ADAM DESIGN, Weinheim,

2 Some Typical Applications of Chemical Product Design and

3 Mathematical Principles for Chemical Product Design 23

4 Disinfectant Formulation Design 41

4.2.1 Antimicrobial Tests 42

5 Streptomyces Lividans 66 for developing a Minimal Deﬁned

6 Multivariate Modeling of a Chemical Toner Manufacturing

6.2 Results and Discussion 97

7 Wheat Straw Fiber Size Effects on the Mechanical Properties

8 Framework for Product Design of Wheat Straw Polypropylene

9 Product Design for Gasoline Blends to Control Environmental

9.2.5 Impacts of E5, M5, and I5 on Environment in Potential Environmental

10 Corrosion Protection of Copper Using

11 Optimization of Mechanical Properties of Polypropylene

12 Product Selection and Business Portfolio for Long-Range

About the Authors

Ali Elkamel is Professor of Chemical Engineering at the University of Waterloo.

1.1 Chemical Product Engineering

1.2 Chemical Product Design

to management, marketing, and engineering design always devote attention to

1.3 Product Design and Computer-Aided Product Design

Product design Process-product design

Figure 1.1 The design process for product design.

CAMD & CAMbD

indices and product composition, product ingredients’ properties, and product

Figure 1.3 A simpliﬁed

Mixture properties Analysis

Database Model validation

Some Typical Applications of Chemical Product Design and

2.1 Natural Fiber Plastic Composites

Manufacturer Model and application

the morphology of the fractured surface of the composite. Differential scanning

2.2 Wheat Straw Polypropylene Composites

● Lignin ● Lubricant Fiber architecture Thermal

● Fiber length ● Colorant ● Melting temp.

● Aspect ratio ● Heat stabilizer ● Degree of crystallization

Fiber pretreatment: Other

hydrolysis, chemical ● Acoustical

special additive requirements. Homopolypropylene suitable for injection molding

2.3 Modeling Natural Fiber Polymer Composites

(2) Processing optimization

Composition Manufacturing Property

(1) Composites design (3) Property

Issue Theory Experimental

Fiber shape and size – Uniform shape – Non-uniform shape

Alternatively, some researchers used experimental design methods to develop

2.4 Graphene Composites

2.5 Corrosion Protection Using Polymer Composites

In addition to graphene-based coating prepared using CVD and EPD, promising

corrosion protection coatings on cold rolled steel was investigated in chloride-rich

2.6 Intellectual Property