Computers and Chemical Engineering 147 (2021) 107252

Contents lists available at ScienceDirect

Computers and Chemical Engineering

journal homepage: www.elsevier.com/locate/compchemeng

Review

Process systems engineering – The generation next?

E N Pistikopoulos a,∗, Ana Barbosa-Povoa b, Jay H Lee c, Ruth Misener d, Alexander Mitsos e,
G V Reklaitis f, V Venkatasubramanian g, Fengqi You h, Rafiqul Gani c,i,∗
a
Texas A&M Energy Institute & Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX 77843-3251, USA
b
Center for Management Studies, Engineering and Management Department, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001
Lisboa, Portugal
c
Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, South Korea
d
Department of Computing, Imperial College London, SW7 2AZ, UK
e
Process Systems Engineering (AVT.SVT), RWTH Aachen University, Forckenbeckstraße 51, Room A.211 52074, Aachen, Germany
f
School of Chemical Engineering, Purdue University, 480 Stadium Mall Drive, West Lafayette, IN 47907-2100, USA
g
Department of Chemical Engineering. Columbia University, New York, NY 10027, USA
h
Robert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY 14853, USA
i
PSE for SPEED Company, Skyttemosen 6, DK-3450 Allerod, Denmark

a r t i c l e i n f o a b s t r a c t

Article history: Process Systems Engineering (PSE) is the scientific discipline of integrating scales and components de-
Received 19 November 2020 scribing the behavior of a physicochemical system, via mathematical modelling, data analytics, design,
Revised 24 January 2021
optimization and control. PSE provides the ‘glue’ within scientific chemical engineering, and offers a sci-
Accepted 25 January 2021
entific basis and computational tools towards addressing contemporary and future challenges such as in
Available online 2 February 2021
energy, environment, the ‘industry of tomorrow’ and sustainability. This perspective article offers a guide
Keywords: towards the next generation of PSE developments by looking at its history, core competencies, current
Process systems engineering status and ongoing trends.
Synthesis-design
Optimization
© 2021 Elsevier Ltd. All rights reserved.
Control
Modelling
Supply chain

1. Introduction “Process systems engineering is all about the development of sys-

The term Process Systems Engineering (PSE) was proposed at
the 1st Process Systems Engineering conference in Kyoto in 1982,
although some of the core topics of PSE have been part of the en-
gineering disciplines for a long time. According to Sargent (1983),
Abbreviations: 3D, 3-dimensional; AE, Algebraic equation; AI, Artificial intelli-
gence; AR, Augmented reality; C&B, Chemical & biochemical; C&BE, Chemical &
biochemical engineering; CACE, Computers and Chemical Engineering; CAMD, Com-
puter aided molecular design; CAPI, Computer aided process intensification; COVID-
19, Name of the disease caused by the novel coronavirus; DAC, Direct air capture;
DAE, Differential and algebraic equation; IoT, Intenet of things; LCA, Life cycle as-
sessment; LP, Linear programming; MILP, Mixed integer linear programming; MINLP,
Mixed integer nonlinear programming; ML, Machine learning; MPC, Model predic-
tive control; MR, Mixed reality; NLP, Nonlinear programming; PCA, Principal com-
ponent analysis; PDAE, Partial differential algebraic equation; PI, Process intensifi-
cation; PID, Proportional, integral and derivative (controller); PSE, Process systems
engineering; QC, Quantum computing; RL, Reinforcement learning; RTO, Real-time
optimization; VR, Virtual reality.
∗
Corresponding authors.
E-mail addresses: stratos@tamu.edu (E.N. Pistikopoulos), rgani2018@gmail.com
(R. Gani).
tematic techniques for process modelling, design and control”. He
further explains, “Some formulate their synthesis, design and/or
control problem, or some useful simplification of it, in precise
mathematical terms, and then seek to exploit the mathematical
structure to obtain an effective algorithm, while others seek in-
sight on the problem structure from physical intuition”. To solve
these process engineering problems from different domains, a set
of PSE methods and software tools (to be called PSE techniques)
are needed.
From a technical point of view, chemical and biochemical
(C&B) engineers, for example, work with unit operations (be it at
industrial-scale, pilot-scale, micro-scale or nano-scale) for the pur-
poses of chemical and/or biochemical synthesis followed by down-
stream separations, which are all based on phenomena such as
thermodynamics, reactions (chemical, biochemical, or thermal con-
versions), and transport (mass, heat and momentum). In this way,
C&B engineers solve problems with the help of PSE techniques re-
lated to process synthesis and design (Westerberg, 2004), process
analysis (Venkatasubramanian et al., 2003a,b), process operation
(Wan et al, 2005), process control (Morari and Lee, 1999), pro-

https://doi.org/10.1016/j.compchemeng.2021.107252
0098-1354/© 2021 Elsevier Ltd. All rights reserved.
E.N. Pistikopoulos, A. Barbosa-Povoa, J.H. Lee et al.
cess optimization (Biegler and Grossmann, 2004), etc., of chemi-
cal and biochemical processes needed to manufacture the prod-
ucts required by society. This implies that the scope and signifi-
cance of chemical and biochemical engineering (C&BE), and there-
fore PSE, are potentially quite broad. Note, however, processes and
products from closely related application areas, such as the phar-
maceutical, agrochemical and food sectors, also need to be de-
signed, operated and/or optimized. Therefore, the scope of PSE
techniques is wider than any single domain where it is applied,
as evidenced by the increasing role and significance of PSE tech-
niques within Chemical, Biochemical, Food, Pharmaceutical and re-
lated domains of engineering. The reader is also directed to the
following review articles on PSE: Sargent (2004) gives a brief
overview of the progress of PSE since its beginning around 1980;
Grossmann (2004) discusses the expanded role of process sys-
tems engineering from product discovery to enterprise wide op-
timization; Klatt and Marquardt (2009) highlight academic and
industrial perspectives on the research and applications of PSE;
Stephanopoulos and Reklaitis (2011) review a history of develop-
ment of PSE from Solvay to modern bio- and nano-technology;
Grossmann and Harjunkoski (2019) highlight academic and indus-
trial perspectives on the research and applications of PSE together
with a brief introduction on the history of PSE and a discussion on
the major research accomplishments in the areas of process sim-
ulation, conceptual design and synthesis, process control, process
operations and optimization.
Over the past decades, as the demand for better and more ver-
satile products and their corresponding flexible and smart manu-
facturing processes has increased (Grossmann, 2004), so has the
need for increased knowledge on related topics and the demands
on PSE techniques, such as, advances in modelling (Bhosekar and
Ierapetritou 2018); data analytics (Ning and You, 2017); enterprise-
wide optimization (Laínez et al., 2012); computer-aided chemi-
cal product design (Austin et al., 2016); integration of product-
process design, including techno-economic and sustainability anal-
ysis (Zhang et al., 2016); liver function as an engineering function
(Ashworth et al., 2016) and machine learning (Lee et al., 2018).
Moreover, society currently faces grand challenges like climate
change, growing global population and resource limitations, which
require innovative solutions regarding the way products and ser-
vices are provided and the need for global action through an opti-
mized cooperative approach towards effective climate change mit-
igation (Galán-Martín et al., 2018) and sustainable resource man-
agement (Guillén-Gosálbez et al., 2019). In this way, PSE tools and
applications are evolving with the needs of society.
The objective of this paper is to present a multi-layered view
of PSE, through which its scope, significance and future role, as
well as the associated needs and/or contributions, can be better
understood. This view highlights the important outcomes of PSE
within the associated engineering discipline and profession. Here,
the multi-layered view of Gani et al., (2020) is adopted to high-
light various aspects of PSE with respect to C&BE as the main engi-
neering discipline. In this multi-layered view, the inner core funda-
mental layer involves process-product related activities where ap-
plication of the fundamental concepts of PSE help to design, build
and operate manufacturing processes that convert specific raw ma-
terials to desired products. The middle interface, i.e., the expand-
ing layer involves resources-efficiency related activities where im-
proved understanding of the concepts and combination of science
and engineering lead to the development of new technologies that
when applied, lead to more sustainable engineering solutions. The
outer unifying layer involves activities that impact societal chal-
lenges where industrial development helps to address challenges
that when resolved would lead to a more sustainable society. Here,
integration of knowledge, such as ideas, disciplines, methodologies,
etc., plays a major role. The current status and the future trends
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Computers and Chemical Engineering 147 (2021) 107252
of PSE are discussed next with respect to education, research and
practice. The perspectives of PSE in terms of the challenges that
need to be tackled and the opportunities that are available to ex-
ploit are highlighted in the next section. The paper ends with some
concluding remarks.
2. Multi-layered view of PSE
To understand the multi-layered view of PSE, it is necessary to
understand first the role of PSE techniques in problem solution,
their scope and significance with respect to future extensions, and
additions to these techniques with respect to expanded application
horizon over time. Two solution options to synthesis-design of a
product and its associated manufacturing process are highlighted
in Fig. 1, for purposes of illustration of the concept in a simplified
form. Option 1 (reality) highlights the common experiment-based
solution approach, while option 2 (virtual reality) highlights a typ-
ical computer-aided systems solution approach, which includes: a)
data and models to represent the system under investigation by a
set of mathematical equations; b) numerical solvers for simulation
and/or optimization; c) work-flow, that is, the sequence of calcu-
lation steps (method or algorithm) needed to solve the problem.
These constitute the three main items needed for problem solu-
tion (Sargent, 1983). While modelling, data analysis and numeri-
cal solvers are the means (tools) to solve the problem, the work-
flow (method or algorithm) is needed to guide the user through
the different solution steps together with their own corresponding
tools. For example, a numerical solver needs an algorithm to solve
the equations, while a modelling tool needs a procedure to create
a model object. Similarly, process-product synthesis and/or design
need a collection of methods, tools and associated data within a
PSE technique.
Fig. 1 also suggests the need for an integrated approach, where
data obtained from reality is used to generate the model for vir-
tual reality, based on which solution alternatives are quickly de-
termined. Such alternatives can be further analyzed and verified
through experiments (reality). By expanding the search space, and
thereby the model application range, additional data can be col-
lected based on planned design of experiments. Furthermore, al-
ternative models can be constructed and additional objectives may
be considered, for example related to environmental, operability
or other drivers. Note also, that other PSE activities (not shown in
Fig. 1), such as control, planning and scheduling of operations, etc,
can also be considered in a similar fashion.
The multi-layered view adopted for PSE is shown in Fig. 2,
where three inter-connected layers are highlighted. The concept
(Gani et al., 2020) can be understood through the following logic;
Horizontal - left: input of resources to the system, right: outcome
in terms of conversion to products; Vertical - bottom: (intellec-
tual) input from PSE, top: impact on the system (society) due to
increased knowledge and available products. Layers – inner-most:
core topics defining the discipline, outer-most: topics that define
the contributions of PSE to society.
In Fig. 2, moving from left to right, material, economic, envi-
ronmental and societal aspects are systematically considered and
analyzed. That is, from resources (raw materials, utilities such as
energy and water, etc), higher valued products are obtained in the
inner-layer by applying PSE techniques; considering demand and
availability of such resources, the products are further improved
and the processes become more efficient in the middle-layer
through advanced PSE-techniques; by adding considerations, such
as resource location, type, recovery, etc., the optimal products
with minimum wastes and desired environmental impacts, etc.,
can be obtained at various scales (plant, industrial parks, country,
region, etc.) in the outer-layer through an integrated PSE work-
flow. Fig. 2 also highlights that in order to obtain (incremental)
E.N. Pistikopoulos, A. Barbosa-Povoa, J.H. Lee et al. Computers and Chemical Engineering 147 (2021) 107252

Fig. 1. Example of problem solution with PSE techniques.

Fig. 2. The multi-layered view of process systems engineering. Note: increasing details of the same resources (such as raw materials) and utilities (such as energy and water)
are considered at each layer. (AI: Artificial Intelligence; ML: Machine Learning; MPC: Model Predictive Control; PI: Process Intensification).

improvements at different layers, a better understanding of the
concepts that lead to new technologies is needed. Moving from
bottom to top in Fig. 2, input of knowledge gradually leads to
wider problem definitions and solutions. The incorporation of such
fundamental domain knowledge helps develop and extend core
PSE products, for example, (i) toward the design and operation
of a manufacturing process (inner-layer), (ii) toward the devel-
opment of sustainable technologies (middle-layer), (iii) toward
wider societal considerations in circular economy and sustainable
development of society (outer-layer).
2.1. Core (fundamental) layer
At the core/fundamental level (for example, with respect to
a domain like C&BE), the conversion of specific raw materials to
desired chemicals-based products takes place through appropriate
processing routes, while also utilizing resources such as energy,
water, materials, man-power, etc. to achieve the desired objectives.
The role of PSE topics (and techniques) is to provide the means to
obtain the desired solution, as well as to understand and operate
the manufacturing process. The list of core PSE topics, adopted
from Grossmann and Harjunkoski (2019), is given in Table 1, where
their corresponding role is highlighted, together with their under-
lying methods, tools and typical outcomes of their application.
The objective of product synthesis and/or design could be to
identify the molecular structure (for example, for single species
products) of a chemical with desired values for a set of target
properties; the objective of process synthesis, design, control is
to help manufacture the designed product; the objective of prod-
uct application is to verify that the manufactured product actually
does satisfy the intended need of society. For example, consider
the use of a solvent (a single species product) in a solvent-based
separation (application process for product) as well as conversion
of raw material to an identified solvent (manufacturing process for
product). Topics such as process monitoring and control, produc-
tion planning and supply chain optimization, and safe and reliable
operation, may also play an important role. Finally, to perform the
above roles, models based on first-principles or system identifica-

3
E.N. Pistikopoulos, A. Barbosa-Povoa, J.H. Lee et al.
Table 1
Relations between core PSE methods and tools, their role and their expected results for core (fundamental) layer topics.
Role of topics∗ Methods and/or tools
Numerical analysis, statistical Simulators, data analytics
analysis & computer science
Synthesis Product-process synthesis methods
Design Product-process design procedures
Optimization Mathematical programming
techniques
Systems, control theory Process control strategies and
algorithms
∗
Note: Models and modelling methods play important role in all the topics
tion and model-based PSE techniques (such as process simulators
and numerical solvers for optimization) are needed.
In the era of data analytics, statistical analysis tools, includ-
ing design of experiments, nonlinear regression/state estimation
methods, multivariate statistical methods (such as various forms
of PCA, Bayesian inference, etc.) and modeling of uncertainty for
robustness and reliability quantification also constitute core topics
(Ning and You, 2018; Rossi et al., 2019).
2.2. Middle (extending) layer
In the core layer, it is normally assumed that the selected raw
materials and resources are available in the amounts needed. These
assumptions, however, may not be valid if resources availability,
their demands and their relations to prices are also considered,
thereby, changing the techno-economic results from the core layer.
That is, to launch a successful product-process, use of resources,
such as energy and water, need to be optimized together with
efficient management of raw material supply-demand, economics,
products distribution and environmental impacts. Also, safety is-
sues, both related to risk avoidance for plant operators as well as
for the community, are important concerns. Management of these
risks via quantitative risk assessment at the systems level is an
essential element in any technical project. PSE again provides the
means to achieve these objectives.
This increased scope and significance of the problem solution
require extensions of the core topics-based PSE techniques, as ad-
ditional features are added increasing the scope, size and complex-
ity. Thereby, models representing the wider system may become
larger, multi-scale and nonlinear. Optimization with such mod-
els will then require robust solution strategies and efficient uti-
lization of computation resources (hardware as well as software)
for problems of different types (rigorous simulation, large discrete
and/or nonlinear optimization problems, AI techniques, discrete
and/or dynamic operations, etc.). Larger data-sets with the under-
lying uncertainties and statistical models capturing the probabil-
ity density functions of these uncertainties will need to be de-
veloped and employed in sustainability and life cycle studies as
well as in consideration of robustness/reliability and safety aspects
of these systems. The application of such model-based and/or big
data analytics-based PSE techniques will then result in the devel-
opment of sustainable, efficient and reliable process technologies.
Table 2 provides an indicative list of advances required and the
means to achieve them.
2.3. Outer (unifying) layer
As highlighted in Fig. 2, different resources are needed to
obtain the products needed by society. Their availability could
be location dependent and their utilization could be technology
dependent, which may result in harmful environmental impacts.
4
Computers and Chemical Engineering 147 (2021) 107252
Outcome
Understand behavior, understand
effect of uncertainty, intelligent
systems
Synthesis of molecules, materials,
process flowsheets
Define the optimized product-process
allocations
Optimized (problem) solutions
Process and plant-wide control
structures, controller designs
For example, non-renewable energy sources are available in finite
quantities only at certain locations on earth. While the technology
for their use is well developed, their utilization causes greenhouse
gas emissions. Renewable energy sources on the other hand may
be available in greater quantity at wider locations and times;
their use may be limited by available technologies but may cause
less environmental impacts. Water resources may also not be
uniformly available on earth and recycle of treated wastewater
becomes necessary. Similarly, available land for food production is
limited. Given that the global population may surpass 10 billion
by 2050 (Vooradi et al., 2018) and the current COVID-19 and
future pandemics, society is facing a grand challenge, known as
the water-energy-food-health nexus (WEFRAH, Mohtar, 2019).
Through the unification of ideas, knowledge, disciplines, etc.,
the PSE techniques from the core and middle layers can be
further extended, for example toward sustainable development
(Bakshi, 2019) and circular economy (Avraamidou et al., 2020). The
focus here is to improve the structure of the manufacturing value
and supply chain network (distributed versus decentralized manu-
facturing options, modular designs, etc), as well as the quality of
manufactured products (or related services). The premise is that
such a circular economy systems engineering approach will drive
down the need for resources (materials, energy, capital, etc) use,
while also ensuring that society (the consumer) is able to at least
maintain the current quality of life and comfort. To achieve this
objective, societal needs and drivers with respect to limited avail-
ability of resources ought to be implemented. From a PSE perspec-
tive, this requires unification of different domain knowledge to-
gether with other disciplines (e.g., ecology, sociology, ethics, po-
litical sciences, economics), involving stakeholders, decision and
policy makers, and others. The outcome is a set of optimal prod-
ucts, designs and supply chains generating minimum net wastes
and consuming less resources (raw material, energy, water, etc.).
As the scope of inquiry is expanded to the outer layer, uncertain-
ties have an increasingly larger impact. Consequently, part of the
outcome of any sustainability study must be quantified estimates
of risks to product quality, resource consumption and waste gener-
ation (Ning and You, 2018).
2.4. Link amongst layers
The three layers are strongly linked, that is, demands from the
outer layers require increased know-how from the inner layers to
meet them. For example, as the need for reliable finished prod-
ucts produced at lower costs and environmental footprints grows,
the need for better integration of the numerous operational steps
involved in the processing of these products also increases, pre-
senting opportunities and challenges to find better, more reliable
and innovative process alternatives (Tula et al., 2020a), simulta-
neous materials and product design (Stankiewicz and Yan, 2019)
and tools applied to sustainability thinking (Guillén-Gosálbez et al.,
E.N. Pistikopoulos, A. Barbosa-Povoa, J.H. Lee et al. Computers and Chemical Engineering 147 (2021) 107252

Table 2
Relations between advanced PSE methods and tools, their role and their expected results for the middle layer.

Core PSE topic New topic Increased scope

Modelling1 Multiscale; data analytics Wider range of systems covered

Product synthesis-design Machine learning; hybrid methods Innovative products through a combination of
theory and AI
Process synthesis-design Process intensification; environmental impact; Smart manufacturing leading towards circular
sustainability economy
Control Integration of design, optimization, control, Inherently safer and economically improved
and safety process operation respecting posed
constraints; consistent product quality
Numerical2 Multi-criteria optimization; discrete-dynamic Ability to solve a wider range of mathematical
simulation problems (simulation and optimization)
Planning, scheduling, and supply chain Reactive or proactive scheduling; integrated Optimal operations of a wider scope and
planning and scheduling; supply chain range of products and processes across scales
optimization
Note: 1: Modelling includes all aspects of model generation and system representation by a set of mathematical equations, model parameter iden-
tification and use of advanced statistical methods;
2: Numerical includes numerical methods (solvers) to solve mathematically formulated problems – note that there may be overlap between mod-
elling and numerical methods such as model parameter identification though optimization.

Fig. 3. Link between layers: a) multiscale modelling links the core PSE topics to solve problems in different engineering domains; b) systems engineering links the core
and/or middle layer PSE topics to provide solutions to society.

2019). As one moves from the inner layers to the outer, the scope
and significance of the problems tackled, the solutions found and
the knowledge required broaden. Consider for example, a mul-
tiscale approach to product development in the area of micro-
structured products where the key to success is to first identify
the desired end-use properties of a micro-structured product at the
small-scale, and subsequently to control product quality and pro-
duction efficiency by manipulating the microstructure formation at
the process scale leading to a novel product with less waste and
energy consumption (Charpentier, 2009). Hence, the three layers
together require appropriate interdisciplinary/multidisciplinary ap-
proaches.
Fig. 3 illustrates different relations between the layers, scope
of problems solved and the significance of the discipline. Fig. 3a
highlights the use of a middle-layer topic (multi-scale modelling)
embedded with core PSE techniques (synthesis, design, simula-
tion, optimization, data analytics and control) to solve problems
in different engineering domains. Fig. 3b illustrates the outer layer
(unified systems engineering) together with embedded core and/or
middle layer PSE techniques provide solutions needed by society.
Note that in these figures only a selection of topics is highlighted.
3. Current status & future trends of PSE
This section highlights the current status and future trends of
PSE in research, in education and in practice.
3.1. PSE research
It is beyond the scope of this paper to cover all the
topics of PSE. Therefore, a selection of topics from the
core, middle and outer layers are highlighted here. A his-
torical overview of PSE can be found in a virtual is-
sue of CACE journal (https://www.journals.elsevier.com/
computers- and- chemical- engineering/article- selections/
a- historical- perspective- of- process- systems- engineering) con-
taining a collection of 25 papers covering a wide range of
topics published during the period 1977-2012. Another good
source for papers on PSE research is the CACE journal thematic
and conference special issues (https://www.journals.elsevier.
com/computers- and- chemical- engineering/special- issues). See
Section 3.4 for an overview on the current status of PSE tools,
which are results of PSE research.

5
E.N. Pistikopoulos, A. Barbosa-Povoa, J.H. Lee et al.
3.1.1. Synthesis & design
In the multi-layered view of C&BE and PSE, in the inner (core)
layer, PSE techniques involve the synthesis and/or design of the
process or product; in the middle (extending) layer, PSE techniques
involve integration of aspects of product-process synthesis and/or
design; in the outer (unifying) layer PSE techniques involve the
development of product and/or process with a view to address-
ing the grand challenges. Traditionally, PSE techniques in process
synthesis and/or design employed heuristics or knowledge-based
approaches (Siirola et al. 1971; Douglas, 1985). With the avail-
ability of process models and numerical solver algorithms, math-
ematical programming-based synthesis and/or design approaches
started to be developed (Papoulias and Grossmann 1983; El-
Halwagi and Manousiouthakis 1989). Currently, with advances in
modelling, computer science and numerical and computational al-
gorithms, hybrid solution approaches (Tula et al., 2017) that com-
bine characteristics from both of the aforementioned approaches,
are finding increasing interest and application. Recent reviews
highlight the current status and future trends on process synthesis
(Cremaschi, 2015), on product-process synthesis-design is given by
(Martin and Adams, 2017), and current trend on the use of math-
ematical programming techniques in process synthesis (Chen and
Grossmann, 2017). A selection of topics of current and future re-
search interest are highlighted below (not ordered in any priority
– two examples are given on each highlighted topic):
• Process synthesis and design: The trend is to develop tech-
niques for energy efficient solutions, such as, mathemati-
cal programming-based computationally efficient optimization
models for preliminary distillation column design and separa-
tion energy targeting (Ryu and Maravelias, 2020); hybrid sepa-
ration schemes (Skiborowski et al., 2014).
• Product synthesis and design: Selection and design of solvents
continue to attract much attention, for example, solvents for
chemical reactions (Zhou et al., 2015). Design of therapeutic
proteins (Papathanasiou, Kontoravdi, 2020) is a promising new
trend.
• Model-based integrated approaches for product and process syn-
thesis and design: Schilling et al. (2017) report the inte-
grated design of Organic Rankine Cycle and working fluid;
Gopinath et al (2016) report the simultaneous optimization of
molecular design and separation process design; and, Badr and
Sugiyama (2020) highlight PSE issues related to process, cell
and product for the production of monoclono antibodies.
• Process intensification: Intensified distillation operations incor-
porating systematic enumeration at successive levels of intensi-
fication, including thermal coupling, multi-effect configuration,
heat and mass integration, and dividing wall columns that can
lead to globally optimal designs has been recently proposed
by (Jiang and Agrawal, 2019), while superstructure-based pro-
cess intensification has been proposed by Demirel et al. (2017).
Tian et al., (2018) provide a thorough review on process inten-
sification.
3.1.2. Numerical & computational aspects: solver algorithms
PSE has a long history of working with and developing new
cutting-edge numerical methods. The two key tasks that PSE has
focused on are: i) optimization methods, comprising a variety
of formulations, most notably mixed-integer linear and nonlin-
ear programs, dynamic optimization and hierarchical optimiza-
tion (semi-infinite, bilevel, trilevel), and ii) simulation/optimization
of dynamic systems with hybrid discrete-continuous (or in some
case equivalently non-smooth) nature. PSE researchers use exist-
ing solver software, but also develop new solvers. This solver soft-
ware may rely on packages for linear algebra and linear optimiza-
tion, so the solver software itself is multi-layered. The numerical
6
Computers and Chemical Engineering 147 (2021) 107252
approaches developed by PSE researchers are used in a variety of
computational tools, both open-source and commercial. Henao and
Maravelias (2011) propose a framework for surrogate-based su-
perstructure optimization and recently, Mencarelli et al., 2020 has
given a review of superstructure-based optimization approaches in
PSE. A selection of topics of current and future research interest is
ishighlighted below (not ordered in any priority – two examples
are given on each highlighted topic):
• Nonlinear equations systems: PSE researchers later developed
more general-purpose methods for solving nonlinear systems
of equations (Tolsma and Barton, 20 0 0) and local nonlinear
optimization (Biegler and Zavala, 2009). Global dynamic opti-
mization remains a challenge despite very strong contributions
from the PSE community (Scott and Barton, 2013). In particu-
lar global optimal control is extremely challenging (Houska and
Chachuat, 2014). See also Table 5 for a list of available optimiza-
tion solver tools.
• Mixed integer nonlinear optimization: MINLP is now actively in-
vestigated in many fields, e.g. operations research (Belotti et al.,
2013). The wide range of difficult MINLP arising in PSE appli-
cations has spurred developing numerical methods, especially
with respect to the special mathematical structure existing in
PSE use cases (Boukouvala et al., 2016). See also Table 5 for a
list of available optimization solver-tools.
• Model uncertainty quantification: The growing interest in ro-
bust design and operation as well as risk quantification cou-
pled with the increasing availability of data are raising the
opportunity and need for effective methods for model uncer-
tainty quantification (Rossi et al., 2019). Also, problem solution
under uncertainty has attracted much attention, for example,
Kasivisvanathan et al. (2014) in process synthesis and design;
Cardoso et al. (2015) in supply chain optimization; and Dias and
Ierapetritou (2016) in integrated scheduling and control.
• Large-scale PSE problems: Exploiting the special mathematical
structure inherent in large-scale PSE problems is key towards
being able to solve industrially-relevant problem instances.
Over the years, the PSE community had the advantage of know-
ing the problems and as such developing the solvers so that
they can utilize the structure, either automatically or manually.
For example, PSE researchers have developed specialized MINLP
methods for generalized pooling problems (Baltean-Lugojan and
Misener, 2018). Many problems have integer variables which
can be dealt with by a number of ways (Kilinc and Sahini-
dis, 2018).
3.1.3. Process control
Process control has been an integral aspect of PSE from the
beginning. Traditionally, the scope of process control was limited
to the regulation of key process variables (around some predeter-
mined operating condition or trajectories) in the presence of dis-
turbances and design errors so that products of required specifica-
tion could be produced safely and consistently. With the develop-
ment of optimal control theories and later computational methods
enabling large-size practical applications, its scope has widened to
address economics like the minimization of energy consumption,
or maximization of the productivity. The simultaneous treatment
of regulation and economic optimization is important as economic
optimization tends to push the process operation towards an in-
tersection of constraints where precise control (e.g. constraint han-
dling) becomes critical to success.
The future holds more exciting challenges for process control
research as new developments in machine learning and data sci-
ence offer opportunities for advances. This, in combination of the
society’s drive towards better product quality and cleaner pro-
cesses, will serve to fuel future control research.
E.N. Pistikopoulos, A. Barbosa-Povoa, J.H. Lee et al.
• Regulation of key process variables: Traditionally, the scope of
process control has been limited to the regulation of key pro-
cess variables (around some predetermined operating condition
or trajectories) in the presence of disturbances and design er-
rors so that products of required specification could be pro-
duced safely and consistently.
• Model-based optimal control: A model-based optimal control
technique called model predictive control (MPC), which solves
a dynamic optimization problem at each sample time on-line,
has become the workhorse of oil refineries and petrochemical
plants (Morari and Lee, 1999). An interesting trend is to apply
advanced modelling techniques in this method and reinforce-
ment learning (RL), a machine learning technique which can
learn optimal decision policies from data received while inter-
acting with the environment, may hold significant potential for
process optimization and control as the data-based learning al-
lows for a more natural handling of the current obstacles to
more widespread use of MPC such as its computational com-
plexity and ability to account for model error (Bhosekar and
Ierapetritou, 2018; Shin et al., 2019).
• Model-based real-time optimization (RTO): The trend is to ex-
tend control applications to multiple units and even an entire
plant. Typically, some internal decompositions are used to de-
sign MPC controllers of reasonable sizes which connect to the
plantwide RTO. The RTO can then connect with market infor-
mation and other operational layers (e.g., scheduling) to com-
plete the hierarchy of enterprise-wide optimization. Tighter in-
tegration between the layers is becoming increasingly impor-
tant given the volatile market condition and diversified product
portfolio (Daoutidis et al., 2018).
• Control and sustainability: Two interesting trends are observed.
First, as the demand for cleaner production with less energy
use and waste generation increases, the processes become more
intensified and tightly integrated, which in turn leads to more
challenging control problems (Nikačević et al., 2012). Second is
to view control as a general dynamic decision-making in an un-
certain environment, which renders the control thinking and
methods highly useful in other applications like energy grid op-
eration and planning/scheduling (Shin et al., 2017).
3.1.4. Planning & scheduling, supply chain
Planning and scheduling activities involve the management of
plant resources in order to guarantee the transformation of raw
materials into final products so as to satisfy customer require-
ments. Minimizing costs, reduce utilities consumption and opti-
mizing stock levels are some of the goals pursued. To achieve
these goals, PSE techniques play a key role, especially when deal-
ing with batch processes where the presence of multipurpose re-
sources calls for their optimized usage while exploring operations
flexibility to deal with the production of several competing product
recipes.
Additionally, process supply chain are complex systems incor-
porating a set of interrelated entities responsible for the sourcing,
production and distribution of a large set of chemical-based and/or
bio-based products (Papageorgiou, 2009; Garcia and You, 2015).
The diversity of materials and information flows, entities character-
istics, and often-present conflicting objectives within an inherent
uncertainty context renders the management of these systems a
challenge. The PSE community has been addressing some of these
challenges, as reviewed in Barbosa-Póvoa (2014).
• Operations scheduling, including uncertainty: Scheduling aims to
optimally allocate limited resources to processing tasks over
time in an industrial process, where each task requires cer-
tain amounts of specified resources (from materials and equip-
ment units to utilities and manpower) for a specific time inter-
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Computers and Chemical Engineering 147 (2021) 107252
val called the processing time. Efficient time solutions and the
capacity to deal with unexpected deviations ( uncertainty indi-
cate two important trends (Li and Ierapetritou, 2008). Tight for-
mulations have been derived (Maravelias and Sung, 2009) and
robust optimization has been explored (Ning and You, 2017).
• Planning and supply chain optimization: Systems-wide opti-
mization of operations across the entirety of a supply chain
is more crucial now than ever to a company’s competitive-
ness. Globalization and modern communications technologies
have provided a myriad of opportunities for improving supply
chain performance (Garcia and You, 2015). The PSE commu-
nity has long been a pioneer in developing answers and solu-
tions to satisfy this great research and industrial need (Barbosa-
Póvoa and Pinto, 2020). Due to its strong industrial relevance,
supply chain optimization not only provides various academic
research opportunities through industrial needs, but also fos-
ters and strengthens many industry-academia collaborations
(Stephanopoulos and Reklaitis, 2011)
• Multi-scale modelling and integration: Multi-scale modelling is
necessary for accurately integrating materials and informa-
tion flows across multiple spatial and temporal scales of sup-
ply chains (Varma et al., 2007). Integrated design, planning,
scheduling and supply chain may lead to large-scale, simultane-
ous optimization across spatial and over temporal scales. Solv-
ing such large-scale, complex, multi-scale planning, scheduling
and supply chain problems poses a technical challenge that
further emphasizes the need of PSE methods and tools that
can bridge the spatial and temporal scales of the supply chain
(Yue et al., 2014).
• Incorporating sustainability concerns into supply chain: While
the field of supply chain optimization has traditionally fo-
cused on economic objectives, the advent of sustainability con-
cerns have added new dimensions that are increasingly cru-
cial in supply chain design (Barbosa-Póvoa et al., 2018). Sus-
tainable supply chain problems are typically addressed through
the life cycle optimization approach, which integrates life cycle
analysis (LCA) with multi-objective supply chain optimization
(You et al., 2012). A key research challenge in this area is to de-
velop quantitative measures and models for the various crite-
ria of interest, especially those without clear physical definition
such as social sustainability (Guillén-Gosálbez et al., 2019).
3.1.5. Intelligent systems, AI, machine learning and data analytics
The long-anticipated promise of artificial intelligence (AI) in
chemical engineering, after 35+ years of valiant attempts, seminal
innovations, and dashed hopes, seems to be here, finally (Lee et al.,
2018; Venkatasubramanian, 2019). The surprising advances in AI
during the last decade, machine learning (ML) in particular, result
in AlphaGo, autonomous cars, Alexa, Watson, and other such sys-
tems, suggesting that AI’s time has arrived to address large-scale
practical problems. But, as with earlier AI breakthroughs, such as
expert systems in the 1980s and neural networks in the 1990s,
there is also a tendency to overestimate the promise of these ad-
vances, following the Gartner hype-cycle. Nevertheless, the impact
of AI in PSE this time around is going to be quite significant. AI
will impact all three layers – core fundamental, middle expanding,
and unifying. In this section, only topics related to the middle ex-
panding layer are highlighted. Note that process-product synthesis-
design; solver algorithms and associated software tools; process
control; planning, scheduling and supply chain; and, unification,
integration and networks are employing more and more aspects
of AI, ML and data analytics.
• Data-driven methods for CAMD – Use of hybrid methods: Some
recent examples include simultaneous fault detection and di-
agnosis using nonlinear support vector machine-based fea-
E.N. Pistikopoulos, A. Barbosa-Povoa, J.H. Lee et al.
ture selection (Onel et al. 2018), machine learning for smart
process manufacturing (Shang and You, 2019) and condition-
based monitoring and maintenance of manufacturing assets
(Ganesh et al 2020). Alshehri et al. (2020) review recently the
state of the art on the use of deep learning and knowledge-
based methods for computer-aided molecular design (CAMD).
• Data-driven methods for CAMD – Use of ML for catalyst design
and discovery: The objective is to make substantial progress
through systematic storage and access of catalytic reaction data
in a curated form for common use. Recent open-source ef-
forts such as the Stanford Catalysis-Hub Database [https://www.
catalysis-hub.org/.] and the Atomistic Machine Learning Pack-
age (Khorshidi and Peterson, 2016) are commendable steps in
this direction.
• Domain specific representations: In this context, the recent con-
tributions on automatic reaction network generation and reac-
tion synthesis planning (Coley et al., 2018) are important devel-
opments. The automation of higher-levels of decision-making
highlights the need to model symbolic relationships (in addi-
tion to numeric ones) between concepts or entities, i.e., an on-
tology. While there has been some work recently on ontologies
in process engineering (Remolona et al., 2017), much more re-
mains to be done, particularly for materials design.
• AI-based optimization: Another area ripe for AI-based ap-
proaches is optimization, which has many applications in PSE
(Ning and You, 2019). For example, Schweidtmann and Mit-
sos (2019) demonstrate embedded artificial neural networks
in a McCormick relaxations framework with favorable results.
Ning and You (2018) discuss data-driven stochastic robust opti-
mization under uncertainty.
3.1.6. Unification, integration & networks
As pointed out in Fig. 2, PSE techniques at the outer (unifying)
layer consider multiple disciplines, networks, data sources, con-
cepts, domain systems, etc., to solve problems leading to overall
societal benefits. In principle, the PSE techniques from the core
(fundamental) and middle (expanding) layers are integrated and
adopted in the outer unifying layer to tackle the challenges facing
the PSE community and beyond. Four recent trends are highlighted
as examples in this section.
• Circular economy systems engineering: Circular econ-
omy has been proposed as a new sustainability paradigm
(Geissdoerfer et al., 2017). The unification of the concepts of
circular economy, sustainability, resources recovery, etc., with
product development, process design and retrofit activities has
been highlighted by Avraamidou et al., (2020).
• Integration: Integration of multiple methods and tools from dif-
ferent domains and disciplines is attracting increasing atten-
tion, for example, a computational framework for integrating
campaign scheduling, dynamic optimization and optimal con-
trol in multi-unit batch processes (Rossi et al., 2017) and a
grand unification of process design, control, and scheduling as
Utopia or reality (Burnak et al., 2019).
• Energy systems: The sources of energy and their converted
forms are different at different locations on earth and so is their
application in different forms. As pointed out by Edgar and
Pistikopoulos (2018), smart manufacturing and energy systems
are inter-related, which needs to be considered for sustainable
development. Challenges in water management within energy
systems (Guerra and Reklaitis, 2018) and opportunities for en-
ergy systems engineering (Demirhan et al., 2019) are worth in-
vestigating.
• Health-care: PSE techniques are finding increasingly impor-
tant roles in the health-care sector, spanning a wide range of
applications from therapeutic product and associated process
8
Computers and Chemical Engineering 147 (2021) 107252
design (Manca, 2018), real time management of manufactur-
ing operations for these therapies (Su et al., 2019), modelling
of the action of the therapy within the body and personal-
ized strategies for the administration of the therapies (Fuentes-
Gari et al. 2015). The use of PSE tools in the development and
process design for chemically or biologically synthesized thera-
peutic products has accelerated substantially as a result of the
trend of replacing traditional batch with continuous processing
(Ierapetritou et al., 2016).
3.2. PSE education
Problem solving, which is also a central feature of PSE, is a
field of education that has received much attention from the aca-
demic community, not just in engineering but almost everywhere
(Perkins, 2002). The objective in this case is to enhance the ca-
pabilities of graduates to meet the future challenges they will be
facing. The important issue is what approaches to employ for de-
velopment of problem-solving skills at different levels. Here, as a
systems approach provides significant aids to the integration of
learning in the basic and engineering sciences across the whole
curriculum, it can be employed in curriculum design and imple-
mentation such that the C&BE graduates benefit to the maximum
extent from their learning. Varma and Grossmann (2014) examined
the evolution of chemical engineering education and identified the
trends that have been impacted by shifts in academic research
and industry needs. Cameron and Lewin (2009) have pointed out
teaching approaches and content at unit learning level and at the
curriculum level. Like the domain engineering discipline, the dif-
ferent layers of PSE topics are closely related to three level edu-
cation systems. That is, the core PSE topics and their associated
techniques are taught mainly at the undergraduate (BSc) level. The
augmented PSE techniques from the middle layer and the unifica-
tion options from the outer layer are mainly covered at the grad-
uate (MSc and/or PhD) level. Note that topics covered at the grad-
uate level are more related to research, while the topics covered
at the undergraduate level make the engineer ready for practice in
industry.
In the early 1980s when PSE was introduced as a discipline, the
three core PSE topics found in the curriculum at the undergrad-
uate level were, process control, process design and process syn-
thesis, all promoting the use of a systems approach. According to
Cameron et al. (2019), the core elements of PSE education changed
and now include system modelling and simulation; optimization;
dynamics and control; process and plant design. At the graduate
level, the trend in PSE education is mainly dependent on whether
or not faculty members in the PSE area are present. If there are
none, it is likely that no graduate PSE courses would be offered.
Otherwise, graduate courses and/or topics covered would depend
on the expertise of the faculty members involved. Also at the un-
dergraduate level, many PSE topics are not at all considered unless
there is a history of strong PSE faculty at the department. Top-
ics such as advanced modelling (multiscale, machine learning, data
analytics), mathematical programming (optimization), process dy-
namics and advanced control, sustainable process synthesis-design,
planning and scheduling, supply chain management optimization,
and more recently chemical product synthesis, smart manufac-
turing and data analytics, are examples of graduate level courses
based on the outer-layer topics. Thesis projects at undergraduate
and graduate levels also give the opportunity to educate C&B engi-
neers with the middle and outer layer topics related to PSE.
The way PSE education is practiced in different countries and
universities is not the same. Even though there is no agreed stan-
dard defining the core body of knowledge and practice, there are
currently a small set of textbooks on process design, process con-
trol and optimization, as well as process simulators (Aspen Plus,
E.N. Pistikopoulos, A. Barbosa-Povoa, J.H. Lee et al.
Table 3
Institutions versus PSE skills for associated business activities.
Company type Users of PSE techniques
Manufacturing Operators: use core skills to operate manufacturing
processes; R&D: use core skills plus a combination of
skills from the outer layers; Decision-makers: need good
overall skills from all layers
Engineering (& consulting) Problem solvers: use core plus different combinations of
skills from different layers depending on the problem
being solved
Software vendor Software developers: use core plus different
combinations of skills from different layers depending on
the specific software product being developed
Research institution Developers of methods and technologies: use and
advance through research the topic from any layer that is
under investigation
gPROMS, Pro/II, etc.) and other software tools (see Table 5) that
are being widely used. That is, whatever the C&B engineer learns
at the undergraduate level, the opportunity is there to augment
their skills for tackling complex engineering problems using the
systems approach together with PSE techniques. The current trend
(Cameron et al. 2019) is to provide opportunities to enhance PSE
components in the core curriculum and to use such components
to aid curriculum integration.
The progress of science and technology is faster than ever and
there is a continuous pressure to integrate new approaches, meth-
ods, tools, and technologies into C&BE in general and PSE educa-
tion in particular. A challenge for those involved in PSE education
is to find ways to incorporate the outer layer topics as part of the
undergraduate curriculum as well as to consider:
• Topics that are well established, but are updated to include new
development, e.g., data analysis and machine learning, model
predictive control
• Topics that are attracting increasing interest (ethics; resources
recovery; circular economy; large and complex systems; new
technologies such as process intensification; techniques for data
processing in addition to filtering and state estimation, e.g.,
black-box modelling, machine learning, etc.)
• New technology for education (how, when and where can vir-
tual reality (VR), augmented reality (AR) and/or mixed reality
(MR) technologies be integrated into PSE educational activities
to derive significant benefit in learning about complex phenom-
ena and system behaviors).
• Online teaching options (how PSE is supposed to handle vir-
tual teaching / remote learning in the pandemic and the soci-
etal changes that will come about from it, for example, how to
run an undergrad controls lab when the students are not al-
lowed to go in it?)
An important characteristic for C&B graduates with specializa-
tion in PSE principles should be the ability to engage with gradu-
ates from other disciplines, highlighting their training to efficiently
combine data, topics, solutions, etc., from diverse disciplines into
an integrated complete solution. That is, promote the systems ap-
proach to tackling real problems while serving their future employ-
ers and society.
3.3. PSE practice
In this section, the current status and future trends of PSE prac-
tice are highlighted in terms of the types of companies that em-
ploy personnel with PSE techniques-based skills (to be called PSE
skills), the types of skills that are needed and the corresponding
human resources who provide them. Table 3 gives a classification
of institutions (company types), the PSE skills that they use, for
their associated business activities. As the data in Table 3 indicates,
9
Computers and Chemical Engineering 147 (2021) 107252
Business activity
Selling of manufactured products (commodity, specialized
chemicals, blends-formulations, devices, etc.)
Sell design of processes; evaluate process and/or product
performance
Develop and sell software tools needed by industry,
research institutions and academia
Develop and disseminate new and improved theory,
models, model-based methods and technologies
human resources with PSE skills are needed for the daily opera-
tion of processes mainly for the manufacturing companies. To keep
the manufacturing processes running as specified, companies em-
ploy engineers with mainly core PSE skills. However, to improve
the process operations, or to evaluate the environmental impact of
process operations, or to monitor resources-products supply chain
issues, etc., additional skills based on engineering-science topics
from the middle layer are needed. At a higher level the decision-
makers within the companies need to have an overview of the
challenges and contributions needed for sustainable development
of society together with the skills from the lower levels. Engineer-
ing companies including consulting companies are also end-users
of PSE techniques, but they employ the skills to develop the de-
signs based on which manufacturing processes are built and op-
erated. As in the manufacturing companies, human resources with
different sets of skills from different layers are needed. Note that
there are companies who are not end-users of PSE techniques but
developers of PSE tools based on PSE methods developed by them-
selves, or, usually in academic institutions. The skills needed for
these companies (software vendors) depend on their specific prod-
uct (software tools) and a combination of skills from mainly the
core and middle layers. The final class of companies are research
institutions that are not connected to universities. The research
area depends on the objectives of the institution and may involve
topics from one or more layers. They could be considered as tech-
nology developers.
A brief overview is now given in terms of a selection of PSE
techniques that are commonly used, the PSE methods as well as
tools that are also developed as products, and the future trends in
terms scope and significance of PSE techniques.
• Applications of process control: Most industrial applications of
process control have been based on linear models identified
through plant tests but applications based on detailed first
principles models have also begun to appear for applications
like polymerization (Qin and Badgwell, 2003). MPC has also
spawned a number of successful startups (e.g. DMC Corp., Profi-
matic, Adersa) offering controller design software packages and
consulting services and these small startups later got merged to
bigger companies like Honeywell, AspenTech, ABB, and Schnei-
der Electric.
• PSE methods that are being developed: The PSE techniques that
are widely used in process synthesis and design are in the ar-
eas of heat exchanger networks and separation process syn-
thesis and/or design (mainly distillation column). Recent trend
has been to extend to integrated heat-mass exchange sys-
tems and process intensification. In the area of product de-
sign, the main applications have been in solvent selection and
its integration with separation process design. Chen and Gross-
E.N. Pistikopoulos, A. Barbosa-Povoa, J.H. Lee et al.
mann (2017) give an overview on the PSE techniques in this
area.
• PSE solvers that are being developed: As pointed out in
Section 3.1.2, the PSE community routinely contributes in the
area of numerical methods and computation techniques in the
form of solver algorithms and software tools. Many of the soft-
ware tools, such as model equation solvers (i.e., solution of
AEs, DAEs, PDAEs) and optimization methods (i.e., LP, NLP, MILP,
MINLP) are also finding increased use and interest. Many of
these solver algorithms are being employed by software vendor
companies in their tools that are made available to end-user
companies. Table 5 lists some of the most widely used solvers.
• PSE tools that are being developed: The biggest users of PSE-
based software tools, such as process simulators, are end-user
manufacturing companies, consulting and engineering compa-
nies as well as research institutions. Other specialized software
tools are used mainly by special groups within the institutions,
depending on the problems they are solving or their current re-
search needs. Table 5 lists some of the tools that have recently
been developed.
Some additional issues:
• Industry 4.0: The fourth industrial revolution will continue from
the third with the adoption of computers and automation and
enhance it with smart and autonomous systems fueled by data
and artificial intelligence (Shang and You, 2019). PSE methods
and tools are uniquely positioned to support the transition of
industry and will facilitate the “digitalization” of process man-
ufacturing systems to better leverage and integrate with model-
based systems engineering, AI, industrial IoT, communication
technologies and ML, among others.
• Dissemination of developments from academia to industry: An ef-
ficient dissemination of PSE techniques from academia (who
are the developers) to industry (who are the users) is neces-
sary to continuously update and improve the production chal-
lenges (Barbosa-Póvoa and Pinto, 2020). The current channel of
dissemination via the software vendor companies needs to be
revisited in light of the time needed for their transfer, if ever.
• Academia-industry collaboration: An efficient collaboration be-
tween industry and academia may contribute to resolve the
problems of dissemination between industry and academia. For
example, industry needs PSE techniques to reliably and effi-
ciently solve their problems, while academia needs details of
industrial problems so that their PSE techniques can be tested
and verified before releasing them for industrial use. That is,
a two-way exchange is necessary. Development of benchmarks
such as those proposed recently can contribute positively in
this aspect (Sass et al., 2020).
Other issues such as how a process will be controlled and op-
erated in the future, the software and hardware implications, cy-
ber security, sustainable of existing processes and many more have
been addressed by Harjunkoski et al., (2014) and Grossmann and
Harjunkoski (2019).
3.4. Status of PSE-tools
Among the major products of PSE that have made significant
impacts in education, research and practice are software tools, and
among them, the process simulator (see Section 3.1.2) that has
made the greatest impact. Some kind of process simulator is used
routinely in teaching of process design, in research on process de-
sign related problems as well as in daily practice of process en-
gineering in industry. Indeed, the impact of PSE can be appreci-
ated by the fact that currently, at any given time on earth, there
is somebody who is using a product of PSE, most commonly a
10
Computers and Chemical Engineering 147 (2021) 107252
process simulator, in education, research or practice. This is par-
ticularly relevant today in the context of ‘digital-twin’ model de-
velopment, as part of Smart Manufacturing and model-based au-
tomation. Table 4 lists the usage of a selected set of PSE tools in
education, research and practice. [Note: The contents of this table
are based on the authors’ knowledge of education at institutions with
strong PSE focus. It is possible that at some institution product de-
sign, health/safety and sustainability/LCA would be "++++" in Edu-
cation, while Optimization and pplanning/scheduling would probably
be “+” or zero in education. Table 4 therefore should be considered
as a starting point for discussions on what should be used in edu-
cation, research and practice according to the needs, availability and
expertise. The number of “+” is therefore subjective and could vary
by institutions/users]. Table 5 lists a selection of the software tools
with the provider, reference and other details. From Table 4, it can
be noted that use of a process simulator performing steady state
simulations is currently a routine option in education, research and
in practice. A process simulator performs mass and energy balance
calculations for a given process flowsheet together with design de-
tails of the associated unit operations. However, use of a dynamic
process simulator is not so common, neither is a discrete event
operation-process simulator. Note that a simulator needs models to
represent the system being studied and solvers to solve the model
equations. Other tools listed in Table 4 may also need models and
solvers, but in addition, they need specific algorithms (sequence of
calculation steps) to solve specific problems. The current status of
the development and use of PSE techniques and the future trends
are discussed in the sections below. Note that many of the tools
listed in Table 5 are developed within the PSE community.
4. Generation next? Towards circular economy systems
engineering
In Section 3, the current status and future trends were high-
lighted in terms of PSE education, PSE research and PSE practice.
In this section, through Fig. 4 a view of the “generation next” is
presented together with specific challenges that should be tackled
by taking advantage of opportunities that are available.
As shown in Fig. 4, the goal of PSE is to contribute to the
sustainable development of society through circular economy sys-
tems engineering, measured in terms of resources (materials that
are converted to needed products; utilities in terms of energy and
water that are needed to operate the plants; human resources in
terms of doing the needed work), services (contributes to the func-
tions of society, for example, mobility or transport services; health-
care services; education services and many more) and products
(needed to sustain society at some standards). Circular economy
systems engineering can provide a platform of growth for “The
Generation Next?” direction of PSE - as it contains almost all the
ingredients of core competencies, mobilizes all the “domain sys-
tems engineering” capabilities and offers a distinct direction to-
wards addressing the ultimate societal challenge. However, consid-
ering the laws of thermodynamics, as it is not possible to achieve
perfect reversibility, the objective (“how” in Fig. 4) is to increase
the time horizon of use of a resource to as long as possible. Al-
ternatively, before a specific service or product becomes infeasible,
replacing it with another one that performs better in a sustain-
able form, can also contribute to sustainable society. The “means”
to achieve these objectives is through the PSE techniques from all
levels. To tackle the challenges, PSE skills from all three layers need
to be further developed so that novel and innovative solutions that
are more efficient in terms of resources utilization, multiple func-
tions and less impact on the environment, for example, can be
found. To meet the challenges facing us, innovative and more sus-
tainable solutions are needed. Under “research”, a selection of re-
search topics that maybe of interest are listed. The perspectives are
E.N. Pistikopoulos, A. Barbosa-Povoa, J.H. Lee et al. Computers and Chemical Engineering 147 (2021) 107252

Table 4
Selected list of software tools and their usage (5+: wide usage; 4+: routine usage; 3+: used
when needed; 2+: used in special cases; 1+: very limited usage; blank – data not available).

Software tools Type Usage

Education Research Practice

Modelling Model generator + +++ +

Equation solver +++ ++++ ++
Data analysis + +++ ++
Process simulator Steady state +++++ +++++ +++++
Dynamic ++ +++ ++
Discrete ++ ++++
Solver algorithms Optimization +++ ++++
Process synthesis Heat exchanger ++++ ++++ ++++
Separation network ++ ++++
Flowsheet + ++ +
Process design Sizing, costing +++++ +++++ +++++
Product design Single molecules + ++
Process control Design, verification ++ ++ ++++
Numerical solvers Optimization +++ +++++ +++
Equation solver ++++ +++++ +++
Process analysis Sustainability + +++ +++
LCA + +++ +++
Environmental impact + +++ +++
Analysis Hazards & risk ++ +++ +++
Safety ++ ++++ ++++
Planning & scheduling Deterministic ++++ +++++ ++
Stochastic + +++

Fig. 4. View of “generation next”; note – the research topics are only a selection, not ordered in terms of any priority

highlighted in terms of: a) Development based on current needs,
and b) Needed development based on future needs.
4.1. Development based on current needs
This section covers areas of PSE (includes methods, tools, mod-
els, etc., that could be regarded as products of PSE) that need to
be further developed so current problems can be solved to obtain
improved solutions (for example, more reliable PI solutions, better
operation of processes, novel products, etc.). Selected topics where
application of PSE techniques may directly or indirectly contribute
towards achieving the goals of circular economy are highlighted
below:
• Synthesis-design of sustainable processes: Sustainable process de-
signs require optimal integration networks that supply utilities
such as energy and water with networks that use these utilities
in the conversion of selected raw materials to desired products.
Wastes, not only generated by manufacturing systems but also
from product use such as medicine, food, and construction, that
cause problems of resource availability as well as pollution are
also topics of interest.
• Adaptive MPC for process control: Topics such as incorporating
model uncertainty information in the design and adaptive MPC,
which can change its parameters according to the sensed sys-
tem dynamics, could be worth investigating.
• Multiscale modelling: PSE techniques need to applicable to prob-
lems across multiple scales, ranging from molecular and mate-
rials design, to device development and optimization, to unit
operations, to process design, operations and control, and to
supply chain, infrastructure and ecosystems levels. The tempo-
ral scales of these decisions could span from seconds in dynam-
ics and control problems, to years in design and strategic plan-
ning problems. There is a growing research and practical need
of developing multiscale modelling techniques that could effec-
tively contribute to intelligent decision-making across two or
more levels.
• Integrated problem solution: Integration of methods to solve a
wider set of problems such as integration of synthesis-design

11
E.N. Pistikopoulos, A. Barbosa-Povoa, J.H. Lee et al. Computers and Chemical Engineering 147 (2021) 107252

Table 5
List of a selection of software tools used by the PSE community.

Tool Purpose Brief description Tool name Reference

Process simulator
Integrated systems
Equation solving
Optimization solvers
Modelling
Steady state simulation, dynamic simulation, Aspen (Plus, Dynamics, HYSYS) (https://www.aspentech.com/en/products)
optimization
Steady state simulation, optimization CHEMCAD Che Che (https://www.chemstations.com)
Steady state-dynamic simulation, optimization gPROMS https://www.psenterprise.com/products/
gproms
Steady state simulation, optimization PRO/II (https:
//sw.aveva.com/engineer-procure-construct/
process- engineering- and- simulation/
pro- ii- process- engineering)
Steady state simulation-modelling ProMax https://www.bre.com/ProMax-Main.aspx
Steady state -dynamic simulation, UNISIM (https:// www.honeywellprocess.com/en-US/
optimization explore/products/advanced-applications/
unisim/Pages/default.aspx)
Modeling, simulation, optimization IDAES Miller et al. 2018
Superstructure-based optimization Super-O Bertran et al. 2017
Integrated tool for process control ProCACD Tula et al., 2020b
Process synthesis, design, intensification ProCAFD Tula et al. 2017
Product synthesis-design OptCAMD (ProCAPD) Liu et al. 2019
Process synthesis PyoSIN Chen and Grossmann, 2017
Product synthesis-design ProCAPD Liu et al. 2019
Model-based process control & optimization PAROC Pistikopoulos et al. 2015
Model-based risk analysis TECSMART Venkatasubramanian and Zhang 2016
DAE solver ACADO Houska et al. 2011
CasADi Andersson et al. 2019
DAEPACK Tolsma & Barton, 2000
Dyos Caspari et al. 2019
PyoMO-dae Nicholson et al. 2018
Auxiliary variable ANTIGONE Misener and Floudas, 2014
BARON Tawarmalani and Sahinidis, 2005
GloMIQO Misener and Floudas, 2013
SCIP Vigerske and Gleixner, 2018
Convex MINLP DICOPT Duran and Grossmann, 1986
SHOT Lundell et al., 2018
α ECP Westerlund and Pörn, 2002
Factorable programming EAGO Wilhelm and Stuber, 2020
MAiNGO Bongartz et al., 2018
NLP iPOPT Wächter and Biegler, 2006
Parametric optimization toolbox POP Oberdieck et al. 2017
α BB OCTERACT https://octeract.com
α BB Adjiman et al., 1998
Modelling, equation-solver, optimization ALAMO Wilson and Sahinidis, 2017
ARGONAUT Boukouvala and Floudas, 2017
Aspen Custom Modeller (https://www.aspentech.com/en/products)
GAMS Brooke et al. 1988
gPROMS https://www.psenterprise.com/products/
gproms
JuMP Dunning et al., 2017
Matlab https:
//se.mathworks.com/products/matlab.html
MoT Fedorova et al. 2015
Simulink https:
//se.mathworks.com/products/simulink.html
Pyomo Miller et al. 2018
3D modelling software ANSYS-Fluent ANSYS Inc.
COMSOL COMSOL Inc.

of a chemical product and its sustainable manufacturing pro-
cess together with operability issues such as control and safety,
or, integration of methods to achieve sustainable process design
through process intensification. Methods for simultaneous ma-
terial and process design are needed, for example, in develop-
ment of DAC (direct air capture of CO2 from air) technologies,
membrane-based reaction-separation intensified operations.
• ML and big data-based hybrid methods: While classic PSE models
are mostly based on mechanistic modelling, ML and big-data
based methods offer exciting opportunities to complement with
the mechanistic modelling approach. Initial work in the PSE
community identifies the resulting hybrid mechanistic/data-
driven models as a key path towards extending classical pro-
cess systems engineering approaches with new capabilities to
address challenging problems, such as optimization problems
with black-box constraints and/or constraints of known func-
tional form, as well as simulation models incorporating compo-
nents both learned from data and derived from known physical
properties.
• Supply chain domains: Extension of the process supply chains
to encompass a larger set of sectors, for example, chemicals, oil
and shale gas; pharmaceutical; agri-food; and biomass, involv-
ing scientific and technological breakthroughs related to devel-
opment of new materials and process that are designed, oper-
ated and efficiently and sustainably integrated into global sup-
ply chain systems.

12
E.N. Pistikopoulos, A. Barbosa-Povoa, J.H. Lee et al.
Fig. 5. Computer-aided framework for smart manufacturing (Edgar and Pistikopoulos, 2018).
• Intelligent systems: Pharma and health-care are areas where PSE
techniques have already started to contribute and can be ex-
tended to develop systems supporting personalized health care,
intelligent systems for drug delivery, pharmaco-kinetics, image
processing in diagnostic systems.
• Unification of methods and software tools: Multiscale and mul-
tidisciplinary nature of problems will demand software tools
with new modelling tools capable of representing systems in
different scales, solvers capable of solving larger and more
complex equation systems, algorithms providing work-flow and
data-flow for a wide range of problems, and computer-aided
systems that incorporate different tools for specific applications,
such as sustainable process design and smart manufacturing. A
framework for a smart manufacturing tool is shown in Fig. 5.
4.2. Development based on future needs
This section covers the areas of PSE that need to be developed
so that it would be possible to tackle problems of the future. The
objective of PSE techniques should be to make a big impact in the
quest for significantly better and more sustainable alternatives to
those that are currently available. This will enable the practitioners
to inform and/or explain decision makers on how to manage the
complexity that leads to sustainable decisions and achievement of
engineering circular economy. Note that only a selection of topics
is highlighted and they are not listed in any specific priority:
• PSE techniques ready to tackle the needs for a future pandemic:
The COVID-19 pandemic has highlighted the need for a number
of PSE techniques that can contribute to better planning, im-
proved data-driven forecasting of events, better management of
13
Computers and Chemical Engineering 147 (2021) 107252
resources, faster manufacturing and delivery of drugs, more ef-
fective design and management of clinical trials and associated
supply chains and many more.
• Resilience of integrated networks and supply chains: Increased
flexibility within supply chains to tackle the challenges of glob-
alization, unforeseen disturbance, sustainability, etc., will pro-
vide challenges as well opportunities to the PSE community.
• Materials and process design: The role of (advanced) materials in
process intensification and illustrated with numerous examples
of various types of materials that are able to intensify chemi-
cal and catalytic reactions, mass transfer, heat transfer, and mo-
mentum transfer processes, respectively.
• Extension of PSE to other domains: Incorporating aspects of
smart manufacturing, reaction engineering, energy systems
engineering, the water-energy-food-environment-health nexus
point to the increasing potential, scope and significance of PSE.
• Hybrid systems: An important goal for the PSE community
should be to aid in the design of novel chemicals and chemi-
cal based products, which may require aspects of deep learning
and model data-based hybrid systems. Although data science
can provide practical guidance, a more robust understanding of
the involved systems and processes are needed, in addition to
first principles-based understanding and insight of the underly-
ing phenomena.
• Model uncertainty: Quantification of model uncertainty, through
hierarchical Bayesian frameworks, which offer a promising ap-
proach for extracting relationships from data and thus leading
to possible interpretations of such relationships and also to rec-
oncile disparate data sets as well as identifying outliers in such
data sets.
E.N. Pistikopoulos, A. Barbosa-Povoa, J.H. Lee et al.
• Quantum computing (QC): QC has the potential to disrupt exist-
ing beliefs on Moore’s law on computing and will most likely
set a paradigm of new beliefs for the digital world. Due to its
unique capabilities that are quite different from that of clas-
sical computers in terms of speed and methods of operations,
QC can provide opportunities to the PSE community in prob-
lems related to process optimization and process data analytics
to consider more complex and previously intractable problems
of fundamental importance and industrial needs. Also, continu-
ously adapting PSE methods and algorithms to parallel comput-
ing and other advances in computing need to be considered.
• Benchmarks: collection of benchmarks in optimization, process
synthesis, computer-aided molecular design could contribute
greatly to the development and testing of new PSE techniques.
5. Conclusions
In this perspective article, it has been discussed how the scien-
tific evolution and ongoing growth of Process Systems Engineering
has been building on its historical core competencies in theoretical
developments and computational tools for analysis, modelling, op-
timization, design and control of integrated systems. At the same
time, it was argued that the versatility and effective penetration
of the PSE methods and computational tools offer a systematic
platform to impact on current and future societal, industrial and
scientific challenges that require a holistic, systems approach for
analysis, synthesis and design. Moving towards Circular Economy
Systems Engineering may provide the next generation of the PSE’s
thinking and practice in the next twenty years.
Declaration of Competing Interest
The authors are current and previous editors of the journal.
References
Adjiman, C S, Androulakis, I P, Floudas, C A, 1998. A global optimization method,
α BB, for general twice differentiable NLPs-II. Implementation and computa-
tional results. Comput. Chem. Eng. 22, 1159–1179.
Alshehri, A S, Gani, R, You, F, 2020. Deep learning and knowledge-based
methods for computer-aided molecular design—toward a unified approach:
state-of-the-art and future directions. Comput. Chem. Eng. 141, 107005.
Andersson, J A, Gillis, J, Horn, G, Rawlings, J B, Diehl, M, 2019. CasADi: a software
framework for nonlinear optimization and optimal control. Math. Programm.
Comput. 11 (1), 1–36.
Ashworth, W, Rerez-Galvan, C, Davies, N, Lockhart Bogle, I D, 2016. Liver function
as an engineering system. AIChE J. 62, 3285–3297.
Austin, N D, Sahinidis, N V, Trahan, D W, 2016. Computer-aided molecular de-
sign: an introduction and review of tools, applications, and solution techniques.
Chem. Eng. Res. Des. 116, 2–26.
Avraamidou, S S, Baratsas, G, Tian, Y, Pistikopoulos, E N, 2020. Circular economy - a
challenge and an opportunity for process systems engineering. Comput. Chem.
Eng. 133, 106629. doi:10.1016/j.compchemeng.2019.106629.
Badr, S, Sugiyama, H, 2020. A PSE perspective for the efficient production of mono-
clonal anti-bodies: integration of process, cell and product design aspects. Curr.
Opin. Chem. Eng. 27, 121–128.
Bakshi, B R, 2019. Toward sustainable chemical engineering: the role of process sys-
tems engineering. Ann. Rev. Chem. Biomol. Eng. 10, 265–288.
Baltean-Lugojan, R, Misener, R, 2018. Piecewise parametric structure in the pooling
problem: from sparse strongly-polynomial solutions to NP-hardness. J. Global
Optim. 71, 655–690.
Barbosa-Póvoa, 2014. Process supply chains management - where are we? Where
to go next? Front. Energy Res.-Process Energy Syst. Eng. doi:10.3389/fenrg.2014.
0 0 023.
Barbosa-Póvoa, A, Pinto, J, 2020. Process supply chains: perspectives from academia
and industry. Comput. Chem. Eng. 132, 106606.
Barbosa-Póvoa, A P, da Silva, C, Carvalho, A, 2018. Opportunities and challenges in
sustainable supply chain: an operations research perspective. Eur. J. Oper. Res.
268 (2), 399–431.
Belotti, P, Kirches, C, Leyffer, S, Linderoth, J, Luedtke, J, Mahajan, A, 2013. Mixed-in-
teger nonlinear optimization. Acta Numer. 22, 1–131.
Bertran, M-O, Frauzem, R, Sanchez-Arcilla, A S, Zhang, L, Woodley, J M, Gani, R, 2017.
A generic methodology for processing route synthesis and design based on su-
perstructure optimization. Comput. Chem. Eng. 106, 892–910.
Bhosekar, A, Ierapetritou, M, 2018. Advances in surrogate based modeling, feasibility
analysis, and optimization: a review. Comput. Chem. Eng. 108, 250–267.
14
Computers and Chemical Engineering 147 (2021) 107252
Biegler, LT, Grossmann, I E, 2004. Retrospective on optimization. Comput. Chem.
Eng. 28 (8), 1169–1192.
Biegler, LT, Zavala, V M, 2009. Large-scale nonlinear programming using IPOPT:
an integrating framework for enterprise-wide dynamic optimization. Comput.
Chem. Eng. 33 (3), 575–582.
Bongartz, D, Najman, J, Scholl, S, Mitsos, A, 2018, MAiNGO: McCormick Based Al-
gorithm for Mixed Integer Nonlinear Global Optimization, Technical Report,
RWTH-Aachen. (https://git.rwth-aachen.de/avt.svt/public/maingo).
Boukouvala, F, Misener, R, Floudas, C A, 2016. Global optimization advances in
mixed-integer nonlinear programming, MINLP, and constrained derivative-free
optimization, CDFO. Eur. J. Oper. Res. 252 (3), 701–727.
Boukouvala, F, Floudas, C A, 2017. ARGOUNAUT: algorithms for global optimiza-
tion of constrained grey-box computational problems. CDFO. Optim. Lett. 11 (5),
895–913.
Brooke, A, Kendrick, D, Meeraus, A, Raman, R, 1988. GAMS: a User’s Guide. The Sci-
entific Press, Redwood City, California.
Burnak, B, Diangelakis, N A, Pistikopoulos, E N, 2019. Towards the grand unification
of process design, control, and scheduling - utopia or reality? Processes 7 (7),
461.
Cameron, I T, Lewin, D R, 2009. Curricular and pedagogical challenges for enhanced
graduate attributes in CAPE. Comput. Chem. Eng. 33 (10), 1781–1792.
Cameron, I T, Engell, S, Georgakis, C, et al., 2019. Education in process systems engi-
neering: why it matters more than ever and how it can be structured. Comput.
Chem. Eng. 126, 102–112.
Caspari, A, Bremen, A M, Faust, J M M, Jung, F, Kappatou, C D, Sass, S, Vaupel, Y,
Hannemann-Tamás, R, Mhamdi, A, Mitsos, A, 2019. Dyos-a framework for opti-
mization of large-scale differential algebraic equation systems. Comput. Aided
Chem. Eng. 46, 619–624.
Cardoso, S, Barbosa-Povoa, A P, Relvas, S, 2015. Resilience metrics in the assessment
of complex supply-chains performance under demand uncertainty. OMEGA - Int.
J. Manage. Sci. 56, 53–73.
Charpentier, J C, 2009. Perspective on multiscale methodology for product design
and engineering. Comput. Chem. Eng. 33 (5), 936–946.
Chen, Q, Grossmann, I E, 2017. Recent developments and challenges in optimiza-
tion-based process synthesis. Ann. Rev. Chem. Biomol. Eng. 8, 249–283.
Coley, C W, Green, W H, Jensen, K F, 2018. Machine learning in computer-aided
synthesis planning. Acc. Chem. Res. 51, 1281–1289.
Cremaschi, S, 2015. A perspective on process synthesis: challenges and prospects.
Comput. Chem. Eng. 81 (2), 130–137.
Daoutidis, P, Lee, J H, Harjunkoski, I, Skogestad, S, Baldea, M, Georgakis, C, 2018. In-
tegrating operations and control: a perspective and roadmap for future research.
Comput. Chem. Eng. 115, 179–184.
Demirhan, C D, Tso, W W, Ogumerem, G S, Pistikopoulos, E N, 2019. Energy systems
engineering - a guided tour. BMC Chem. Eng. 1, 11.
Demirel, S E, Li, J, Hasan, M M F, 2017. Systematic process intensification using
building blocks. Comput. Chem. Eng. 105 (2).
Dias, L S, Ierapetritou, M G, 2016. Integration of scheduling and control under un-
certainties: review and challenges. Chem. Eng. Res. Des. 116, 98–113.
Douglas, J, 1985. A hierarchical decision procedure for process synthesis. AIChE J. 31
(30), 353–362.
Dunning, I, Huchette, J, Lubin, M, 2017. JuMP: a modeling language for mathematical
optimization. SIAM Rev. 59 (2), 295–320.
Duran, M A, Grossmann, I E, 1986. An outer-approximation algorithm for a class of
mixed-integer nonlinear programs. Math. Program. 36, 307–339.
Edgar, T F, Pistikopoulos, E N, 2018. Smart manufacturing and energy systems. Com-
put. Chem. Eng. 114, 130–144.
El-Halwagi, M, Manousiouthakis, V, 1989. Synthesis of mass exchange networks.
AIChE J. 35 (8), 1233–1244.
Fedorova, M, Sin, G, Gani, R, 2015. Computer-aided modelling template: concept and
application. Comput. Chem. Eng. 83, 232–247.
Fuentes-Garí, M, Velliou, E, Misener, R, Pefani, E, Rende, M, Panoskaltsis, N, 2015.
A systematic framework for the design, simulation and optimization of per-
sonalized healthcare: making and healing blood. Comput. Chem. Eng. 81,
80–93.
Galán-Martín, A, Pozo, C, Azapagic, A, Grossmann, I E, Mac Dowell, N, 2018. Time
for global action: an optimised cooperative approach towards effective climate
change mitigation. Energy Environ. Sci. 11 (3), 572–581.
Gani, R, Bałdyga, J, Biscans, B, Brunazzi, E, Charpentier, J C, Drioli, E, et al., 2020.
A multi-layered view of chemical and biochemical engineering. Chem. Eng. Res.
Des. 155, 133–145.
Ganesh, S, Su, Q, Vo, D L B, Pepka, N, Rentz, B, Vann, L, Yazdanpanah, O’Connor, T,
Nagy, Z, Reklaitis, GV, 2020. Design of condition-based maintenance framework
for process operations management in pharmaceutical continuous manufactur-
ing. Intl. J. Pharmaceut. 587, 119621.
Garcia, D J, You, F, 2015. Supply chain design and optimization: challenges and op-
portunities. Comput. Chem. Eng. 81, 153–170.
Geissdoerfer, M, Savaget, P, Bocken, N M P, Hultink, E J, 2017. The circular economy
– a new sustainability paradigm? J. Cleaner Prod. 143, 757–768.
Gopinath, S, Jackson, G, Galindo, A, Adjiman, C S, 2016. Outer approximation algo-
rithm with physical domain reduction for computer-aided molecular and sepa-
ration process design. AIChE J. 62, 3484–3504.
Grossmann, I E, 2004. Challenges in the new millennium: product discovery and
design, enterprise and supply chain optimization, global life cycle assessment.
Comput. Chem. Eng. 29 (1), 29–39.
Grossmann, I E, Harjunkoski, I, 2019. Process systems engineering: academic and
industrial perspectives. Comput. Chem. Eng. 126, 474–484.
E.N. Pistikopoulos, A. Barbosa-Povoa, J.H. Lee et al.
Guerra, O J, Reklaitis, G V, 2018. Advances and challenges in water management
within energy systems. Renewable Sustainable Energy Rev. 82 (3), 4009–4019.
Guillén-Gosálbez, G, You, F, Galán-Martín, Á, Pozo, C, Grossmann, I E, 2019. Process
systems engineering thinking and tools applied to sustainability problems: cur-
rent landscape and future opportunities. Curr. Opin. Chem. Eng. 26, 170–179.
Harjunkoski, I, Maravelias, C T, Bongers, P, Castro, P M, Engell, S, Grossmann, I E,
Hooker, J, Méndez, C, Sand, G, Wassick, J, 2014. Scope for industrial applications
of production scheduling models and solution methods. Comput. Chem. Eng. 62,
161–193.
Henao, C A, Maravelias, C T, 2011. Surrogate-based superstructure optimization
framework. AIChE J. 57 (5), 1216–1232.
Houska, B, Chachuat, B, 2014. Branch-and-lift algorithm for deterministic global op-
timization in nonlinear optimal control. J. Optim. Theory Appl. 162 (1), 208–248.
Houska, B, Ferreau, H J, Diehl, M, 2011. ACADO toolkit—an open-source framework
for automatic control and dynamic optimization. Optimal Control Appl. Methods
32 (3), 298–312.
Ierapetritou, M, Muzzio, F, Reklaitis, G V, 2016. Perspectives on the continuous man-
ufacturing of powder-based pharmaceutical processes. AIChE J. 62 (6). doi:10.
1002/aic.15210.
Jiang, Z, Agrawal, R, 2019. Process intensification in multicomponent distillation: a
review of recent advancements. Chem. Eng. Res. Des. 147, 122–145.
Kasivisvanathan, H, Ubando, A T, Ng, D K, Tan, R R, 2014. Robust optimization for
process synthesis and design of multifunctional energy systems with uncertain-
ties. Ind. Eng. Chem. Res. 53 (8), 3196–3209.
Khorshidi, A, Peterson, A A, 2016. Amp : a modular approach to machine learning
in atomistic simulations. Comput. Phys. Commun. 207, 310–324.
Kilinc, M, Sahinidis, N V, 2018. Exploiting integrality in the global optimization of
mixed-integer nonlinear programming problems with BARON. Optim. Methods
Softw. 33 (3), 540–562.
Klatt, K U, Marquardt, W, 2009. Perspectives for process systems engineering—per-
sonal views from academia and industry. Comput. Chem. Eng. 33 (3), 536–550.
Laínez, J M, Schaefer, E, Reklaitis, G V, 2012. Challenges and opportunities in en-
terprise-wide optimization in the pharmaceutical industry. Comput. Chem. Eng.
47, 19–28.
Lee, J H, Shin, J, Realff, M J, 2018. Machine learning: overview of the recent pro-
gresses and implications for the process systems engineering field. Comput.
Chem. Eng. 114, 111–121.
Li, Z., Ierapetritou, M., 2008. Process scheduling under uncertainty: review and chal-
lenges. Comput. Chem. Eng. 32 (4–5), 715–727.
Liu, Q, Zhang, L, Liu, L, Du, J, Tula, A K, Eden, M, Gani, R, 2019. OptCAMD: an opti-
mization- based framework and tool for molecular and mixture product design.
Comput. Chem. Eng. 124, 285–301.
Lundell, A, Kronqvist, J, Westerlund, T, 2018, The supporting hyperplane op-
timization toolkit: a polyhedral outer approximation based convex MINLP
solver utilizing a single branching tree approach. (https://www.researchgate.net/
publication/327746282_The_Supporting_Hyperplane_Optimization_Toolkit)
Quantitative systems pharmacology, 2018. In: Manca, D. (Ed.), Computer Aided
Chemical Engineering, 42. Elsevier, Amsterdam.
Maravelias, C T, Sung, C, 2009. Integration of production planning and scheduling:
overview, challenges and opportunities. Comput. Chem. Eng. 33, 1919–1930.
Martín, M, Adams, T A, 2017. Future directions in process and product synthesis and
design. Comput. Chem. Eng. 128, 421–436.
Mencarelli, L, Chen, Q, Pagot, A, Grossmann, I E, 2020. A review on superstructure
optimization approaches in process system engineering. Comput. Chem. Eng.
136, 106808.
Miller, D C, Siirola, J D, Agarwal, D, Burgard, A P, Lee, A, Eslick, J C, Sahinidis, N
V, 2018. Next generation multi-scale process systems engineering framework.
Comput. Aided Chem. Eng. 44, 2209–2214.
Misener, R, Floudas, C A, 2013. GloMIQO: global mixed-integer quadratic optimizer.
J. Global Optim. 57 (1), 3–50.
Misener, R, Floudas, C A, 2014. ANTIGONE: algorithms for continuous/integer global
optimization of nonlinear equations. J. Global Optim. 59 (2–3), 503–526.
Mohtar, R, 2019. WEFRAH: Water-Energy-Food-Health Nexus Renewable Resources
Initiative. https://www.aub.edu.lb/fafs/WEFRAH/Pages/default.aspx.
Morari, M, Lee, J H, 1999. Model predictive control: past, present and future. Com-
put. Chem. Eng. 23 (4–5), 667–682.
Nicholson, B, Siirola, J D, Watson, J P, Zavala, V M, Biegler, L T, 2018. pyomo. dae: a
modeling and automatic discretization framework for optimization with differ-
ential and algebraic equations. Math. Programm. Comput. 10 (2), 187–223.
Nikačević, N M, Adrie Huesman, E M, Van den Hof, P M J, Stankiewicz, A I, 2012.
Chemical engineering and processing. Process Intensification 52, 1–15.
Ning, C, You, F, 2017. A data-driven multistage adaptive robust optimization
framework for planning and scheduling under uncertainty. AIChE J. 63 (10),
4343–4369.
Ning, C, You, F, 2018. Data-driven stochastic robust optimization: general computa-
tional framework and algorithm leveraging machine learning for optimization
under uncertainty in the big data era. Comput. Chem. Eng. 111, 115–133.
Ning, C, You, F, 2019. Optimization under uncertainty in the era of big data and
deep learning: when machine learning meets mathematical programming. Com-
put. Chem. Eng. 125, 434–448.
Oberdieck, R, Diangelakis, N A, Pistikopoulos, E N, 2017. Explicit model predictive
control: a connected graph approach. Automatica 76, 103–112.
Onel, M, Kieslich, C A, Guzman, Y A, Floudas, C A, Pistikopoulos, E N, 2018. Big data
approach to batch process monitoring: simultaneous fault detection and diag-
nosis using nonlinear support vector machine-based feature selection. Comput.
Chem. Eng. 115, 46–63.
15
Computers and Chemical Engineering 147 (2021) 107252
Papageorgiou, L G, 2009. Supply chain optimisation for the process industries: ad-
vances and opportunities. Comput. Chem. Eng. 33 (12), 1931–1938.
Papoulias, S A, Grossmann, I E, 1983. A structural optimization approach in pro-
cess synthesis—II: heat recovery networks. Comput. Chem. Eng. 7 (6), 707–
721.
Papathanasiou, M M, Kontoravdi, C, 2020. Engineering challenges in therapeutic
protein product and process design. Curr. Opin. Chem. Eng. 27, 81–88.
Perkins, J, 2002. Education in process systems engineering: past, present and future.
Comput. Chem. Eng. 26, 283–293.
Pistikopoulos, E N, Diangelakis, N A, Oberdieck, R, Papathanasiou, M M, 2015.
PAROC—an integrated framework and software platform for the optimisation
and advanced model-based control of process systems. Chem. Eng. Sci. 136,
115–138.
Qin, S J, Badgwell, T A, 2003. A survey of industrial model predictive control tech-
nology. Control Eng. Pract. 11, 733–764.
Remolona, M F M, Conway, Balasubramanian, M F, Fan, S, Feng, L, Gu, Z, 2017. Hy-
brid ontology-learning materials engineering system for pharmaceutical prod-
ucts: Multi-label entity recognition and concept detection. Comput. Chem. Eng.
107, 49–60.
Rossi, F, Casas-Orozco, D, Reklaitis, G V, Manenti, F, 2017. A computational frame-
work for integrating campaign scheduling, dynamic optimization and opti-
mal control in multi-unit batch processes. Comput. Chem. Eng. 107, 184–
220.
Rossi, F, Mockus, L, Manenti, F, Reklaitis, G V, 2019. Present and future of model
uncertainty quantification in process systems engineering. Chem. Eng. Tran. 74,
625–630.
Ryu, J, Maravelias, C T, 2020. Computationally efficient optimization models for pre-
liminary distillation column design and separation energy targeting. Comput.
Chem. Eng., 107072.
Sargent, R W H, 1983. Advances in modelling and analysis of chemical process sys-
tems. Comput. Chem. Eng. 7, 219–237.
Sargent, R W H, 2004. 25 years of progress in process systems engineering. Comput.
Chem. Eng. 28, 437–439.
Sass, S, Faulwasser, T, Hollermann, D E, Kappatou, C D, Sauer, D, Schütz, T, Shu, D
Y, Bardow, A, Gröll, L, Hagenmeyer, V, Müller, D, Mitsos, A, 2020. Model com-
pendium, data, and optimization benchmarks for sector-coupled energy sys-
tems. Comput. Chem. Eng. 135, 106760.
Schilling, J, Tillmanns, D, Lampe, M, Hopp, M, Gross, J, Bardow, A, 2017. From
molecules to dollars: integrating molecular design into thermo-economic pro-
cess design using consistent thermodynamic modeling. Mol. Syst. Des. Eng. 2
(3), 301–320.
Schweidtmann, A M, Mitsos, A, 2019. Deterministic global optimization with artifi-
cial neural networks embedded. J. Optim. Theory Appl. 180 (3), 925–948.
Scott, J K, Barton, P I, 2013. Improved relaxations for the parametric solutions of
ODEs using differential inequalities. J. Global Optim. 57 (1), 143–176.
Shang, C, You, F, 2019. Data analytics and machine learning for smart process man-
ufacturing: recent advances and perspectives in the big data era. Engineering 5
(6), 1010–1016.
Shin, J H, Badgwell, T A, Liu, K-H, Lee, J H, 2019. Reinforcement learning – overview
of recent progress and implications for process control. Comput. Chem. Eng. 127,
282–294.
Shin, J H, Lee, J H, Realff, M, 2017. Operational planning and optimal sizing of mi-
crogrid considering multi-scale wind uncertainty. Appl. Energy 195, 616–633.
Siirola, J J, Powers, G J, Rudd, D F, 1971. Synthesis of system designs: III. Toward a
process concept generator. AIChE J. 17 (3), 677–682.
Skiborowski, M, Harwardt, A, Marquardt, W, 2014. Conceptual design of distilla-
tion-based hybrid separation processes. Ann. Rev. Chem. Biomol. Eng. 4 (1), 45.
Stankiewicz, A I, Yan, P, 2019. The missing link unearthed: materials and process
intensification. Ind. Eng. Chem. Res. 2019. doi:10.1021/acs.iecr.9b01479.
Stephanopoulos, G, Reklaitis, G V, 2011. Process systems engineering: from Solvay
to modern bio- and nanotechnology. A history of development, successes and
prospects for the future. Chem. Eng. Sci. 66, 4272–4306.
Su, Q, Ganesh, S, Moreno, M, Bommireddy, Y, Gonzalez, M, Reklaitis, G V, Nagy, Z K,
2019. A perspective on Quality-by-Control (QbC) in pharmaceutical continuous
manufacturing. Comput. Chem. Eng. 125, 216–231.
Tawarmalani, M, Sahinidis, N V, 2005. A polyhedral branch-and-cut approach to
global optimization. Math. Program. 103 (2), 225–249.
Tian, Y, Demirel, S.E., Hasan, M F, Pistikopoulos, E N, 2018. An overview of pro-
cess systems engineering approaches for process intensification: state of the art.
Chem. Eng. Process. 133, 160–210.
Tolsma, J, Barton, P I, 20 0 0. DAEPACK: an open modeling environment for legacy
models. Ind. Eng. Chem. Res. 39 (6), 1826–1839.
Tula, A K, Babi, D K, Bottlaender, J, Eden, M R, Gani, R, 2017. A computer-aided
software-tool for sustainable process synthesis-intensification. Comput. Chem.
Eng. 105, 74–95.
Tula, A K, Eden, M R, Gani, R, 2020. Computer-aided process intensification: chal-
lenges, trends and opportunities. AIChE J. 66, e16819.
Tula, A K, Wang, J, Chen, X, Mansouri, S S, Gani, R, 2020. ProCACD: a computer-aided
versatile tool for process control. Comput. Chem. Eng. 136, 106771.
Varma, V A, Reklaitis, G V, Blau, G E, Pekny, J F, 2007. Enterprise-wide modeling &
optimization—an overview of emerging research challenges and opportunities.
Comput. Chem. Eng. 31 (5–6), 692–711.
Varma, A, Grossmann, I E, 2014. Evolving trends in chemical engineering education.
AIChE J. 60 (11), 3692–3700.
Venkatasubramanian, V, 2019. The promise of artificial intelligence in chemical en-
gineering: is it here, finally? AIChE J. 65 (2), 466–478.
E.N. Pistikopoulos, A. Barbosa-Povoa, J.H. Lee et al.
Venkatasubramanian, V, Zhang, Z, 2016. TeCSMART: a hierarchical framework for
modeling and analyzing systemic risk in sociotechnical systems. AIChE J. 62 (9),
3065–3084.
Venkatasubramanianm, V, Rengaswamy, R, Yin, K, Kavuri, S N, 2003a. A review of
process fault detection and diagnosis: Part I: quantitative model-based methods.
Comput. Chem. Eng. 27, 293–311.
Venkatasubramanianm, V, Rengaswamy, R, Kavuri, S N, 2003b. A review of process
fault detection and diagnosis: Part II: qualitative models and search strategies.
Comput. Chem. Eng. 27, 313–326.
Vigerske, S, Gleixner, A, 2018. SCIP: global optimization of mixed-integer nonlin-
ear programs in a branch-and-cut framework. Optim. Methods Softw. 33 (3),
563–593.
Vooradi, R, Bertran, M-O, Frauzem, R, Anne, S B, Gani, R, 2018. Sustainable chemical
processing and energy-carbon dioxide management: review of challenges and
opportunities. Chem. Eng. Res. Des. 131, 440–464.
Wächter, A, Biegler, L T, 2006. On the implementation of an interior-point filter
line-search algorithm for large-scale nonlinear programming. Math. Program.
106 (1), 25–57.
Wan, X, Pekny, J F, Reklaitis, G V, 2005. Simulation-based optimization with surro-
gate models—application to supply chain management. Comput. Chem. Eng. 29,
1317–1328.
16
Computers and Chemical Engineering 147 (2021) 107252
Westerberg, A, 2004. A retrospective on design and process synthesis. Comput.
Chem. Eng. 28 (4), 447–458.
Westerlund, T, Pörn, R, 2002. Solving pseudo-convex mixed integer optimization
problems by cutting plane techniques. Optim. Eng. 3 (3), 253–280.
Wilhelm, M, Stuber, M D, 2020. EAGO: easy advanced global optimization in Julia.
Optim. Methods Softw. 1–26. doi:10.1080/10556788.2020.1786566.
Wilson, Z T, Sahinidis, N V, 2017. The ALAMO approach to machine learning. Com-
put. Chem. Eng. 106, 785–795.
You, F., Tao, L., Graziano, D.J., Snyder, S.W., 2012. Optimal design of sustainable cellu-
losic biofuel supply chains: multiobjective optimization coupled with life cycle
assessment and input–output analysis. AIChE J. 58 (4), 1157–1180.
Yue, D., You, F., Snyder, S.W., 2014. Biomass-to-bioenergy and biofuel supply chain
optimization: overview, key issues and challenges. Comput. Chem. Eng. 66,
36–56.
Zhang, L, Babi, D K, Gani, R, 2016. New vistas in chemical product and process de-
sign. Ann. Rev. Chem. Biomol. Eng. 7, 557–582.
Zhou, T, Lyu, Z, Qi, Z, Sundmacher, K, 2015. Robust design of optimal solvents
for chemical reactions – a combined experimental and computational strategy.
Chem. Eng. Sci. 137, 613–625.