Computers and Chemical Engineering 126 (2019) 204–217

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Computers and Chemical Engineering

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

Surrogate modeling of phase equilibrium calculations using adaptive

sampling
Corina Nentwich∗, Sebastian Engell
Department of Biochemical and Chemical Engineering, TU Dortmund University, Emil-Figge-Str. 70, Dortmund 44221, Germany

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

Article history: Equation of state models as the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) model are
Received 1 December 2018 accurate and reliable prediction models for phase equilibria. But due to their iterative nature, they are
Revised 4 April 2019
difficult to apply in chemical process optimization, because of long computation times. To overcome this
Accepted 8 April 2019
issue, surrogate modeling – replacing a complex model by a black-box model – can be used. A novel sur-
Available online 11 April 2019
rogate modeling strategy for phase equilibria is presented, combining the training of a classifier model
Keywords: with regression models for the phase composition using a mixed adaptive sampling method. We discuss
Surrogate models the selection of the parameters of the sampling algorithm and a suitable stop criterion for the exam-
Adaptive sampling ple ternary liquid-liquid equilibrium system of n-decane, dimethylformamide and 1-dodecene in detail.
Phase equilibria The sequential mixed adaptive sampling method is compared to the one-shot Latin hypercube sampling
PC-SAFT design.
© 2019 Elsevier Ltd. All rights reserved.

1. Introduction
In computer-based process optimization, the reliability of the
optimization result depends on the quality of the process model. In
order to obtain an accurate representation of the process, models
based on first principles are usually preferred.
In the modeling of chemical processes, phase equilibria play an
important role. For example, the solubility of a feed material in
the reaction solution significantly influences the speed of reaction,
and the accurate computation of the composition of the vapor and
liquid phases in equilibrium is fundamental to the modeling of dis-
tillation columns.
For phase equilibrium calculations, activity coefficient models
or equations of state models can be employed. Activity coefficient
models require less computational effort, but are not applicable at
elevated pressures, close to critical temperatures, and for multi-
component systems. For such systems, equations of state models
should be preferred (Merchan and Wozny, 2016; Schäfer et al.,
2014). For complex phase systems, advanced equations of state
models as the PC-SAFT model are suitable for accurate predictions
over a broad range of operating conditions. The PC-SAFT model
has been applied to a wide range of different systems (Kleiner
et al., 2009; Kontogeorgis and Folas, 2010; Tumakaka et al., 2005).
However, in order to solve phase equilibria using equation of state
∗
Corresponding author.
E-mail address: corina.nentwich@tu-dortmund.de (C. Nentwich).
models, the density root problem as well as the phase equilib-
rium conditions must be fulfilled, which requires the use of em-
bedded calculations that lead to a significant computational effort.
This makes these advanced thermodynamic models difficult to use
for process optimization.
In order to overcome this issue, the surrogate modeling
methodology can be applied. Surrogate modeling is understood
here as replacing a complex model by a simpler black-box model.
One can distinguish between two different classes of surrogate
modeling problems: classification problems with two or more dis-
crete outputs and regression problems with one or more continu-
ous outputs that are approximated.
As the quality of the surrogate model is dependent on the
choice of the training points, sampling is an important aspect of
the surrogate modeling process. Since sampling involves computa-
tionally intense evaluations of the original function, the sampling
objective is to sample as few points as possible with a maximum
gain of information on the modeled phenomenon.
There are mainly two approaches for sampling: sampling once
(one-shot) or adaptive sampling. In many applications, one-shot
space-filling designs, such as the Latin hypercube sampling (LHS),
Monte-Carlo or Halton sequences are used to fit surrogate mod-
els. However, in many applications, the modeled quantities exhibit
complex responses as discontinuities or a strong curvature in spe-
cific regions of the input space. In space-filling designs, such com-
plex structures are often not approximated well. For these cases,
adaptive or sequential sampling designs can be used. In this con-
text, the terms of exploration – sampling in a space-filling man-

https://doi.org/10.1016/j.compchemeng.2019.04.006
0098-1354/© 2019 Elsevier Ltd. All rights reserved.
 C. Nentwich and S. Engell / Computers and Chemical Engineering 126 (2019) 204–217 205

ner – and exploitation – more dense sampling in regions with j

where xi is the molar fraction of component i = 1, . . . , NC in phase
complex behavior of the original function – are used. The trade- j (feed, phase A or phase B),  is the phase fraction of phase A.
off between exploration and exploitation is a recent field of re- On the other hand, the thermodynamic equilibrium conditions
search. Cozad et al. (2014) and Kleijnen and Van Beers (2004) fo- (Eq. (3)–(5)) have to hold.
cus on exploitation. The mixed adaptive sampling approach pro-
posed in Eason and Cremaschi (2014), which was further improved TA = TB (3)
by Jin et al. (2016), uses two equally weighted sampling objectives,
while the recent work of Garud et al. (2017) proposes an approach pA = pB (4)
of adaptive weighting of the two sampling objectives.
Prior to sampling, the input and output variables of the sur- μAi = μBi , (5)
rogate modeling problem have to be defined. For a chemical sys-
where Tj ,andpj μij
are the temperature, pressure and chemical
tem, the composition, temperature and pressure define the num-
potential of component i in phase j. Inserting the definition of the
ber of phases and the composition of these. Modeling the phase
chemical potential μi as given in Eq. (6), Eq. (5) leads to the isofu-
j
composition of a mixture in the range where the transition be-
gacity criterion in Eq. (7):
tween a one-phase and a two-phase mixture occurs with a regres-
 
sion model leads to a discontinuity in the output space. In general, f ij
discontinuities in the output space are hard to approximate with μ = μ (T , p ) + RT · ln
i
j id
i
re f
(6)
pre f
surrogate models in an accurate fashion. Restricting the valid input
range to a region which is biphasic in any case as in other work fiA = fiB , (7)
(Nentwich and Engell, 2016) avoids discontinuities in the output where μid
i
is the ideal chemical potential at temperature T and ref-
space, but overconstrains the operating range which is not desir- erence pressure pref , R is the universal gas constant and fi is the
j
able in process optimization. fugacity of component i in phase j.
To cope with this problem, a novel surrogate modeling strategy In order to solve the isofugacity criterion (Eq. (7)), the fugacity
for phase equilibria is investigated in this contribution. A classifier for each component i has to be expressed for each phase. Since
is trained on the obtained data in order to identify the biphasic this is specific for the chosen thermodynamic model, it is shown
region. In a second step, regression models are used to model the in more detail for equation of state models in the next subsection.
compositions of the two phases if the point is classified as being
biphasic. This approach makes the use of equation of state mod- 2.2. Application of equation of state models
els possible within chemical process simulation and optimization,
since the computationally expensive frequent solution of the phase j
The fugacity fi of a component i in phase j can be expressed in
equilibrium is avoided. To obtain accurate classifier and regression
terms of its fugacity coefficient ϕi as shown in Eq. (8).
j
models without calling the original thermodynamic model exten-
sively for sampling, a mixed adaptive sampling scheme is applied. fij = xij ϕij p j . (8)
As a case study, the process of the hydroformylation of 1-
dodecene performed in a thermomorphic solvent system is exam- Since the following equations in this section are all phase-specific,
ined. The proposed surrogate modeling strategy is demonstrated the index for the phase j is not shown for convenience.
for the modeling of the liquid-liquid equilibrium of the ternary sys- The thermodynamic behavior of a system can be described by
tem n-decane, dimethylformamide and 1-dodecene, which is cal- modeling the Helmholtz energy. The fugacity coefficient ϕ i can also
culated using the PC-SAFT equation of state model. For the consid- be formulated in terms of the residual Helmholtz energy ares as
ered case study, the mean computation times were 5.1 seconds per shown in Eq. (9).
phase equilibrium calculation using PC-SAFT which could be re-     
∂ ares 
NC
∂ ares
duced to 0.003 seconds by applying the developed surrogate mod- ln ϕi = ares + − xj + Z − 1 − ln Z, (9)
els on a standard computer (Windows 7, 3.6 GHz dual core In- ∂ xi j=1
∂xj
tel(R) i7, 18 GB RAM).
where xi is the molar fraction of component i in the phase and Z
is the compressibility factor of the phase.
2. First principles modeling of phase equilibria The compressibility factor Z can be calculated by solving the
density root problem:
In this section, the phase equilibrium problem is defined and  
the solution procedure when applying equation of state models, ∂ ares
Z =1+ρ (10)
e. g. PC-SAFT, is described. The results of this iterative procedure ∂ρ
are used to provide data to train a surrogate model which com-
p = Zkb T ρ , (11)
putes the equilibrium by a simple function call.
where ρ is the molar density number, kb is the Boltzmann con-
stant, p is the pressure and T is the temperature.
2.1. The phase equilibrium conditions
Depending on the chemical system considered, a thermody-
namic model for the Helmholtz energy ares must be chosen.
The simplest approach to describe a phase equilibrium is a
Here we use the PC-SAFT equation of state model, since the
standard two-phase flash model in which the phase equilibrium
model is capable of not only modeling temperature-dependent LLE,
problem can be divided into two sub problems. On the one hand,
but also the solubility of supercritical components such as the syn-
the component and mass balance conditions (Eq. (1)–(2)) have to
thesis gas in the reaction mixture of the considered process de-
be fulfilled.
scribed in Section 5.
i = xi + (1 − )xi
xin A B
(1)
2.2.1. PC-SAFT
NC 
  The Perturbed-Chain Statistical Associating Fluid Theory
0= xAi − xi ,
B
(2) (PC-SAFT) equation of state model is one of the most detailed
i=1 predictive models for phase equilibrium calculations. The model
206 C. Nentwich and S. Engell / Computers and Chemical Engineering 126 (2019) 204–217
Fig. 1. Scheme of the solution procedure when applying a flash model based on an equation of state model.
was developed by Gross and Sadowski (2001). In this approach,
a molecule is modeled as a chain which is formed by spherical
segments. The interaction of different chains is described by
the repulsive behavior of a hard-chain reference system in the
perturbation theory of Barker and Henderson (1967). Besides
this repulsive hard-chain interaction (hc), the attractive inter-
action term of the dispersion (disp) is considered and a series
of additional attractive interactions can be accounted for, e. g.
association (assoc) and polar interactions (dipole).
The residual Helmholtz energy (ares ) is described as the sum of
the different interactive effects, as shown in Eq. (12):
ares = ahc + adisp + aassoc + adipole .
2.2.2. The solution procedure using PC-SAFT
The solution of the phase equilibrium is done by an external
model call of a standard two-phase pT-flash model implementation
of Merchan and Wozny (2016), using the MATLAB toolbox AdiMat
(Bischof et al., 2002) for the partial derivatives of ares in Eqs. (9)–
(10).
The equation system given by Eqs. (1), (2) and (7) can be re-
duced by introducing equilibrium factors κ ,
ϕiA xAi
κi = = .
ϕiB xBi
The resulting equation system is called the Rachford-Rice equation
(Eq. (14)) which has to be solved for the phase fraction of phase A
 (see also Eq. (2)),

NC
xin κ − 1)
i ( i
= 0.
1 −  + κi
i=1
The iterative calculations that are necessary to simulate a process
model using a flash model call to solve the phase equilibrium are
summarized in Fig. 1.
In order to solve the overall balance equations, the process
solver chooses values for all process variables in the 1st itera-
tion. Given the process conditions, the thermodynamic model is
called.
First, the density root problem (Eqs. (10)–(11)) is solved to ob-
tain values for the compressibility factor Z and the density number
ρ of each phase. Then it is possible to calculate the fugacity coeffi-
cients ϕi for each component i in phase j with the given composi-
j
tion xi , the compressibility factor Zj and density number ρ j at the
j
conditions T and p (see Eq. (9)). The equilibrium factors κ i are cal-
culated (Eq. (13)) and the Rachford-Rice equation (14) is solved for
the phase fraction . This value is used to update the composition
j
xi by using Eqs. (1) and (13). For this new composition, the den-
sity root problem is again solved. This is repeated until the values
j
xi do not change significantly anymore.
j
The new values for xi are taken as new values for solving the
overall balance equations in the next iteration of the process solver,
which will have an effect on the values of all process variables in
this iteration. If they change, the thermodynamic model is called
again. The overall process model is solved as soon as the chosen
j
values for xi at the chosen process conditions are equal to the so-
lution of the flash model call at these conditions. As this takes sev-
eral iterations of the process solver and thus several calls of the
(12) thermodynamic model, this procedure is time-consuming for pro-
cess models using few phase equilibria calculated with an equa-
tion of state and prohibitively slow in the optimization of complex
process models with many phase equilibria. Therefore it is advan-
tageous to replace this implicit phase equilibrium calculation by an
explicit surrogate model.
2.3. The local model methodology
There are different possibilities of introducing explicit approx-
imation models in order to reduce the computational effort that
is needed to solve the phase equilibrium problem. The local
(13) model methodology was originally introduced to provide an ap-
proximation of κ i (Eq. (13)). The first approaches used simplified
concentration-independent expressions for κ i (Boston and Britt,
1978; Leesley and Heyen, 1977). Since these models have been
shown to be not very accurate, they were extended by e.g. modify-
ing the Margules model to introduce concentration-dependencies
(Chimowitz et al., 1983; 1984). Since these models are in general
(14)
very limited with respect to their range of validity, e.g. because
of being related to a reference state, the model parameters have
to be updated as soon as the solution procedure has moved away
from the current range of validity. In later work, the expression lo-
cal model is also used as a term for linearized transformations or
simplified partial derivatives of thermodynamic properties in gen-
eral. Several works estimate the optimal update method and fre-
quency, e.g. (Macchietto et al., 1986; Støren and Hertzberg, 1994).
For dynamic simluation and control studies, the application of such
simple models is advantageous, since the states do not change
very fast during the solution procedure. For process design and
optimization, this is not feasible due to the fast change of states
(Perregaard et al., 1992).
Using approximations which are valid in a broader range to
avoid parameter update makes it necessary to employ more com-
plex model structures. Also, the phase equilibrium still has to be
solved during the solution of the balance equations of the process.
 C. Nentwich and S. Engell / Computers and Chemical Engineering 126 (2019) 204–217
Our surrogate modeling approach is a promising alternative and is
discussed in detail in the next section.
2.4. The surrogate modeling problem
First a decision on the inputs and outputs of the surrogate
model has to be made. The most intuitive method for representing
phase equilibrium calculations is the approximation of the misci-
bility gap. Analogous to the last section, the number of outputs
can be reduced by introducing the distribution coefficient of each
component Ki (Eq. (15)) as the output instead of the molar fraction
xj,i of the component i in each phase j:
n˙ i,A xi,A · n˙ A xi,A xi,B − xi,in
Ki = = = · ,
n˙ i,in xi,in · n˙ in xi,in xi,B − xi,A
where n˙ i,A and n˙ i,in are the molar flows of component i in phase
A and in the feed of a continuous separation process. n˙ A and n˙ in
denote the total molar flows of phase A and of the feed.
The distribution coefficient is only defined within the miscibil-
ity gap, which is changing its shape for different temperatures. In
order to model the shift of the biphasic region, a classifier is intro-
duced. The distribution coefficient can then be approximated by a
continuous regression model and the regression model is used only
if the classifier assigns the point to the biphasic region, otherwise
the concentrations remain unchanged.
Prior to the training of the models, sample points have to be
selected and the original thermodynamic model must be evaluated
for these points which is time-consuming. Approaches to the selec-
tion of sample points are discussed in the next section.
3. Sampling
Especially for the case of expensive model evaluations, the goal
of devising a sampling procedure is to sample as few points as
possible but nonetheless get a model of good accuracy over the
full range of inputs of interest. As the training locations have a
strong effect on the accuracy of the surrogate model, finding the
best sampling locations is an important aspect. A common ap-
proach is to equidistantly cover the complete input-space which
is referred to as space-filling or exploratory sampling design. This
approach has the advantage that the original model can be eval-
uated in a one-shot manner, since no previous knowledge of the
original function is needed. A brief overview of one-shot space-
filling sampling designs is given in Section 3.1. The drawback of
this sampling method is that the behavior of the original func-
tion is not taken into account in the selection. The consequence
is that regions of complex structures as discontinuities or a strong
curvature are often not covered by enough samples to capture the
true behavior with the surrogate model. An illustrative example is
shown in Fig. 2.
In this example, the 1-dimensional input x is mapped to an 1-
dimensional output y. While for smaller values of x the chosen
Fig. 2. Illustrative example of a space-filling sampling design (cross: sample loca-
tion).
207
sampling frequency might be sufficient, the behavior of the orig-
inal function at larger values of x is not captured by the few sam-
ples in this region, the local minima and the local maximum are
missed. The sampling objective to cover such regions with a more
dense sampling design is referred to as exploitative sampling de-
sign. Since knowledge about the behavior of the original function
in different regions of the input space is needed, these designs can-
not be executed in a one-shot manner. They are implemented in
sequential sampling approaches which are reviewed in Section 3.2.
Since both exploratory and exploitative sampling objectives are im-
portant to achieve a good performance of the surrogate model with
few sampling points, they are combined in this work. Our algo-
rithm is based on the approach of Eason and Cremaschi (2014),
which is explained in more detail in Section 3.3.1. Modifications of
(15)
the algorithm are explained in Section 3.3.2 and the stop criterion
is discussed in Section 3.3.3.
3.1. One-shot designs
Since agglomerations of samples can occur in random sampling
designs as Monte Carlo methods, most one-shot sampling designs
uniformly cover the input space. They are based on geometric pat-
terns as dividing the inputs space into grids or on the use of math-
ematical characteristics of sampling functions.
The latter is applied in quasi-random sampling methods which
share the characteristic of a low discrepancy. The discrepancy of a
sequence is connected to the uniform distribution of the sample
locations, as it tends to zero when the number of samples tends to
infinity in a fixed interval (Niederreiter, 1992).
One example is the Halton sequence sampling method
(Halton, 1960) which is commonly applied in surrogate modeling
problems. The Halton sequence sampling is choosing the ith sam-
ple location in the input space, xi , based on the Halton sequence
 
xi =  p1 (i ),  p2 (i ), . . . ,  pd (i ) , (16)
where pj is the jth radical inverse function (see Eq. (17)) with
pj as base, being the jth prime number and d is the input space
dimension.

inf
 p j (i ) = ak (i ) p−k
j
−1
, (17)
k=0
where ak (i) are the digit expansion coefficients of the integer i in
base pj ,

inf
i= ak (i ) pkj . (18)
k=0
This sampling design is deterministic and the number of samples
can be chosen freely.
Full-factorial or partial-factorial sampling designs address the
space-filling objective by dividing the input space into discrete lev-
els and locate samples at combinations of these different levels.
This provides a good space coverage, but at the cost of having a
huge sample set size, being the number of levels to the power of
the number of input features in the case of a full factorial design.
In Latin hypercube sampling (LHS), the input space is also di-
vided into discrete levels. However, in contrast to classical factorial
designs, the LHS design does not use all combinations of these lev-
els. Instead, the intervals for each factor in the input space are de-
fined as layers. In each layer only one sample is placed randomly.
Fig. 3 shows two examples of LHS designs for a 2-dimensional in-
put space.
As a design as shown in Fig. 3b should be preferred over a de-
sign as shown in Fig. 3a, an optimization is performed, maximizing
208 C. Nentwich and S. Engell / Computers and Chemical Engineering 126 (2019) 204–217

3.3. Mixed adaptive sequential design

The applied mixed adaptive sequential sampling approach is

based on an algorithm (Eason and Cremaschi, 2014) which com-
bines the space-filling objective with an estimation of the model
prediction variance for choosing new points.

Fig. 3. LHS design examples for a 2-dimensional input space.
the minimum distance between sample points. Thus, the space-
filling objective is reached and the number of samples can be cho-
sen freely. A review of one-shot sampling designs can be found in
Simpson et al. (1997). To combine the exploratory sampling objec-
tive with an exploitative sampling objective, the sampling proce-
dure has to be done in a sequential manner. Sequential sampling
designs are discussed in the next section.
3.3.1. Principle
In each iteration, c new candidates are proposed without eval-
uating the original function. For each candidate j, j = 1, . . . , c, the
minimum distance dj to the n = 1, . . . , N points that are already
present in the current design and the jackknife variance s2j of the
model predictions for each candidate are determined. The ith sub-
set model, i = 1, . . . , NSS, is trained on NSS − 1 subsets, analogous
to cross validation methods, e. g. subset model 1 is trained on sub-
sets 2 to NSS, leaving out the samples in subset 1 for training.
Candidates with the largest value of ηj (see Eq. (20)) are selected,
the corresponding outputs are calculated and the procedure is re-
peated until a stopping criterion is met.
dj s2j
ηj = + , (20)
max j d j max j s2j

3.2. Sequential designs where dj is the minimum Euclidean distance (Eq. (21)) between
the candidate and the current design point and s2j is the jackknife
There are applications in which it is reasonable to use purely variance (Eq. (22)) calculated by the weighted average (Eq. (23))
space-filling sequential sampling designs (see Crombecq et al., of the jackknife pseudo values y˜ ji of each candidate j predicted by
2011), but generally they are addressing the trade-off between ex- subset model i (Eq. (24)).
ploration and exploitation. Starting from a small initial sampling
design, new sample points are chosen from a set of candidates for dj = min x j − xn 2 (21)
n∈{1,...,N}
which the true function evaluation has not yet been performed.
NSS 
 2
Since the behavior of the original function is unknown prior to 1
s2j = · y˜ ji − y˜¯ j (22)
the function evaluations and the initial sampling design consists NSS(NSS − 1 )
i=1
only of few points, complex regions have to be identified by an
1 
NSS
exploratory part of the sampling objective before they can be ex-
y˜¯ j = · y˜ ji (23)
ploited by an exploitative part of the sampling objective. NSS
i=1
The nature of the sampling objective is in many works de-
termined based upon characteristics of the chosen surrogate y˜ ji = NSS · yˆ(0) − (NSS − 1 ) · yˆ(−i ) , (24)
model. where yˆ(0 ) is the prediction for candidate j of the overall model,
For example, the expected improvement function (Eq. (19)) that trained on all i = 1, . . . , NSS subsets and yˆ(−i ) is the prediction for
was introduced as a sampling objective by Jones et al. (1998) uses candidate j of subset model i.
the ability of Kriging surrogates (see Section 4) to give an estimate The candidates with the highest value of ηj are selected and
on the standard deviation of the predicted value. added to the sampling design. For these selected sampling loca-
    tions the original function is evaluated and the sampling design is
  ymin − yˆ ymin − yˆ
EI (x ) = ymin − yˆ(x ) ·  + s(x ) , (19) updated. The number of added points is determined by the selec-
s (x ) s tion factor SF (Eq. (25)).

where ymin is the current minimum value in the original function cadd = SF · N, (25)
evaluations, yˆ(x ) is the surrogate model prediction at sampling lo-
where cadd is the number of selected points and N is the number of
cation x and s(x) is the standard error predicted by the Kriging sur-
candidates. So the number of additional samples increases in each
rogate model at x.
round.
There are also methods which are in principle applicable
Modifications of this sampling method are explained in the next
for different surrogate models. Crombecq et al. (2009) use a
section.
Voronoi-mosaic for the input space in order to explore regions
with few points and connect this with local linear models at
each candidate point in order to meet the exploitative objective. 3.3.2. Extension of the algorithm
Cozad et al. (2014) apply the approach of maximizing the error In the application at hand, the classifier is trained on all sam-
between surrogate model predictions and the true function value, ples in the current design, while the regression models are trained
which is resulting in a high number of original function evalua- only on the samples in the biphasic region to avoid discontinuities
tions. in the output space. In consequence, the subsets are not of equal
In contrast, the mixed adaptive sequential sampling design that size. In order to consider this for the jackknife variance calcula-
is further developed in this work avoids this by using a predic- tion, Eqs. (22)–(24) are changed to the modified jackknife variance
tion variance estimator for the exploitative part of the sampling calculation:
objective. In the following sections, the algorithm from Eason and 
NSS
1  2
Cremaschi (2014) and the modifications proposed in this work are s2j = · y˜ ji − y˜¯ j (26)
N (N − Ni )
discussed. i=1
 C. Nentwich and S. Engell / Computers and Chemical Engineering 126 (2019) 204–217 209


NSS a Kriging-based approach for the deterministic global optimization
N − Ni
y˜¯ j = NSS · y˜ ji (27) of processes including a distillation column. Cozad et al. (2014) use
i=1 I=1 N − NI the model building tool ALAMO and combine different basis func-
y˜ ji = N · y ˆ (0 ) − (N − Ni ) · yˆ(−i ) , (28) tions to model a solid sorbent adsorber in the optimization of
a carbon capture process. Beykal et al. (2018) use the optimiza-
where N is the total number of samples in the current design and
tion framework ARGONAUT (AlgoRithms for Global Optimization
Ni is the number of samples in subset i. Thus the subset model
ofcoNstrAined grey-box compUTational problems) to apply differ-
predictions of subset models that are based on more samples are
ent types of surrogate models as grey-box constraints for compu-
accounted with a higher weight for the modified jackknife variance
tationally demanding derivative-free global optimization problems.
calculation.
Olofsson et al. (2018) use Gaussian processes in the Bayesian multi-
Since both the classifier and the regression models should be
objective optimization of a biological tissue engineering applica-
considered in the exploitative criterion, the variance term for the
tion. Recent reviews of surrogate modeling applications in model-
decision criterion ηj in Eq. (20) is chosen according to Eqs. (29)–
ing, feasibility analysis and optimization are given in Bhosekar and
(30):
Ierapetritou (2018) and McBride and Sundmacher (2019).
s2j 1 s2class, j 1 s2appr, j In this work, Support Vector Machine (SVM) models are cho-
= + (29) sen for the classification problem and ordinary Kriging models are
max j s2j 2 max j s2class, j 2 max j s2appr, j
chosen for the regression problem. The choice of the models and
their structure has been taken in a pre-study which showed that
s2appr, j 1  s2appr,i, j
NC
models of this structure are suitable model approaches for the case
= , (30)
max j s2appr, j NC
i=1
max j s2appr,i, j study. Generally, the applied sampling method does not exploit any
surrogate-dependent characteristic and can thus be applied for any
where s2class, j is the modified jackknife variance of the classifier other type of surrogate model.
predictions of candidate j and s2appr,i, j is the modified jackknife
variance of the regression model predictions of candidate j for 4.1. Classification using SVM
component i = 1, . . . , NC.
The basic idea of Support Vector Machines (SVM) is to design
3.3.3. Stop criterion a hyperplane function y(x) as given in Eq. (34) that separates the
In any sequential sampling approach a criterion is training data into two groups.
needed to terminate the sampling procedure. Eason and Cre-
maschi (2014) propose the slope ratio α as: 
S
  y (x ) = ai yt,i k(x, si ) + b, (34)
 Error slope from iteration i − 1 to i 
α =  . (31) i
max(Error slope in iterations ≤ i ) 
where ai are model parameters, k(x, si ) is the kernel function
As the number of iterations increases, the slope ratio is declining. value at input x with respect to the support vector input si with
A lower threshold value ε for α is set to terminate the algorithm. i = 1, . . . , S being the index of the S support vectors and yt,i being
Since two different types of models are involved in this work, a the corresponding output to the support vector input si and b is a
classifier and regression models, the total slope ratio α tot is defined constant model parameter. The kernel function can be chosen ar-
analogous to Eq. (29)–(30) as a weighted sum of the slope ratios of bitrarily. In this work, a polynomial of 3rd order has been selected
the different models (see Eqs. (32)–(33). in the prestudy (see Eq. (35)).
1 αclass 1 αappr  3
αtot = + (32) k(x, si ) = 1 + xT si (35)
2 max(αclass ) 2 max(αappr )
The distance between the hyperplane and the nearest training data
points (margin) is maximized by choosing the support vectors and
αappr 1  αappr,i
NC
= (33) estimating the model parameters ai and b by solving a reformula-
max(αappr ) NC max(αappr,i )
i=1 tion of the optimization problem in Eq. (36) (Bishop, 2006)
The considered error metrics that are applied to α class and α appr,i 1
 
are discussed in Section 4.3. max min yn wT
(sn ) + b , (36)
w,b ||w|| n
During the course of the mixed adaptive sampling method, the
classification and regression models are trained several times. A where w is a function of ai given in Eq. (37) and
is the kernel
brief introduction into the surrogate models that are used in this function dependent decomposition function, see Eq. (38)
work is given in the next section.

S
w= ai yt,i
(si ) (37)
4. Surrogate models
i

Classifiers and regression models are commonly used to solve k(x, x ) =

(x )T
(x ). (38)
different problems in the field of chemical engineering. Examples
By the optimization, the maximum margin when applying a cer-
of classification problems in this field are e. g. fault detection and
tain number of support vectors is achieved. For estimating the
diagnosis (Chiang et al., 2004; Onel et al., 2018) and drug de-
model parameters, the MATLAB Statistics and Machine Learning
sign (Byvatov et al., 2003). The application of surrogate models
toolbox is used (MATLAB, 2017).
for regression problems to reduce the computational effort is gain-
ing increasing popularity (see Cremaschi, 2015). Henao and Mar-
avelias (2011) use neural networks to represent process units in a 4.2. Regression using Kriging models
superstructure optimization, Caballero and Grossmann (2008) use
Kriging models to model the relationship of different variables in Kriging is an interpolation approach that originates from the
a distillation column simulation and Keßler et al. (2019) propose field of geostatistics and was introducted by Krige (1951) and
210 C. Nentwich and S. Engell / Computers and Chemical Engineering 126 (2019) 204–217
Matheron (1963). The predictor function y(x) consists of a regres-
sion and a correlation term, as shown in Eq. (39):
y ( x ) = f ( x )T β + r ( x )T γ ,
where f(x) is the vector of regression basis function and r(x) is the
correlation function vector of input x, β and γ are model parame-
ters. The correlation function vector is defined as in Eq. (40):
r ( x ) = [R ( θ , s 1 , x ) , . . . , R ( θ , s m , x ) ] ,
T
where R is the correlation function which is chosen to be Gaussian
in this work (see Eq. (41)), θ ∈ Rn is a parameter vector and si are
the m input locations used for the design of the model.
n
R(θ , a, b) = exp(−θk (|a − b| )2 )
k=1
The model parameter β in Eq. (39) is the generalized least squares
solution regarding the training set (see Eq. (42)), γ is defined as in
Eq. (43).
 −1
β = FtT Rt−1 Ft FtT Rt−1 yt
γ= Rt−1 (yt − Ft β ),
where Ft is the basis function vector, Rt the correlation function
vector and yt is the output value. The index t indicates that these
functions are evaluated at the i = 1, . . . , m training input loca-
tions si and are thus constant parameters in the prediction func-
tion.
There are different variants of the Kriging approach, depending
on the form of the regression term. In simple Kriging, the regres-
sion term is a known constant β ( f (x ) = 1), whereas in ordinary
Kriging, the regression term is a constant parameter β ( f (x ) = 1)
estimated by generalized least squares. In universal Kriging, inde-
pendent basis functions f(x) are used.
For estimating the model parameters, the MATLAB toolbox
DACE is used (Lophaven et al., 2002).
Kriging models provide a direct estimation of the prediction
variance. As the jackknife variance has shown to be a superior
method in comparison (Kleijnen and Van Beers, 2004) and to
ensure that the proposed method is applicable to any surrogate
model type, the Kriging prediction variance is not applied in this
work.
In order to have an indication of the quality of the surrogate
models, suitable validation measures have to be applied. The ap-
plied methods are explained in the following.
4.3. Surrogate model validation
To compare the quality of different models, performance criteria
are evaluated for a test set. As a quality criterion for the classifica-
tion models, the percentage of misclassified samples of the test set
Misc, as defined in Eq. (44), is used.
100% 
Ntest
Misc = |yˆclass (x j ) − yclass (x j )|,
2Ntest
j=1
where Ntest is the test set size, yˆclass (x j ) is the classifier model pre-
diction for test sample input xj and yclass (xj ) is the actual class of
test sample xj from the original model calculation.
For the regression models, the Mean Absolute Error MAE (as de-
fined in Eq. (45)) with respect to the predictions of the test set is
used as the error criterion.
1 
Ntest
MAEi = |yˆi,appr (x j ) − yi,appr (x j )|,
Ntest
j=1
where yˆi,appr (x j ) is the surrogate model prediction for test sample
input xj and yi,appr (xj ) is the actual output value for component i
from the original model. Using these error metrics for testing the
(39)
model prediction quality for a large test set of 50 0 0 original func-
tion evaluations, the model quality can be evaluated in this work.
For calculating the stop criterion, a measure of the model qual-
ity has to be defined. For the calculation of the modified jack-
knife variance (Eq. (28)), subset models yˆ(−k ) are trained on all
(40) subset samples except for subset k. The predictions of each sub-
set model yˆ(−k ) for the subset k can then be used for calculating a
cross-validation error. In this case, the percentage of misclassified
samples CVE(MisC) and the mean absolute cross-validation error of
component i CVE(MAE)i are applied:
(41) 100% 
Ntrain
 
CV E (MisC ) = CV E (MisC ) x(jk ) , (46)
2Ntrain
j=1
   (−k)  (k)   
CV E (MisC ) x(jk ) = yˆclass x j − yclass x(jk )  (47)
(42)
1 
Ntrain
 
CV E (MAE )i = CV E (MAE )i x(jk ) , (48)
Ntrain
(43) j=1
      
CV E (MAE )i x(jk ) = yˆi,appr x(jk ) − yi,appr x(jk ) ,
(−k )
(49)
(−k ) (k ) (−k )
where yˆclass (x j ) and yˆi,appr (x(jk) ) are the predictions of the sub-
set models trained on all subsets but subset k for sample in-
put xj belonging to subset k and for component i. yclass (x(jk ) ) and
yi,appr (x(jk ) ) are the actual output values from the original model
for input xj belonging to subset k and for component i.
In the following, the case study to which the mixed adaptive
sampling method is applied for training the SVM classifier and
Kriging models is described.
5. Case study
As a case study, the process of the hydroformylation of 1-
dodecene to the main product n-tridecanal has been chosen
(Kiedorf et al., 2014). This process has been developed up to the
technical realization in two miniplants in the collaborative research
center/transregio 63 “Integrated chemical processes in liquid multi-
phase systems” InPROMPT. Two different strategies of tunable sol-
vent systems have been pursued. The reaction has been performed
in a microemulsion process by employing surfactants in the mini-
plant at TU Berlin (Illner et al., 2018; Müller et al., 2017). The
process considered here is performed in a ThermoMorphic solvent
System (TMS). The process has been modeled in detail (Hentschel
et al., 2014; Kaiser et al., 2016; Kiedorf et al., 2014; McBride et al.,
2016; McBride and Sundmacher, 2015) and was realized and it-
eratively optimized online in a miniplant (Dreimann et al., 2017;
Hernández and Engell, 2016; Zagajewski et al., 2016). It also was
investigated in several optimization studies, see e. g. (Hentschel
(44) et al., 2015; 2014; Keßler et al., 2017; Steimel and Engell,
2016).
A TMS is composed of a polar (P in Fig. 4) and a non-polar sol-
vent (N in Fig. 4), in this case DMF and n-decane. This leads to a
temperature-dependent miscibility gap with a middle-polar com-
ponent (M in Fig. 4), in this case 1-dodecene and tridecanal.
The reaction is performed at an elevated temperature, so
that the reaction mixture forms one homogeneous liquid reac-
tion phase, as shown in Fig. 4a. After leaving the reactor, the
mixture is cooled down. Due to the temperature-dependent mis-
(45) cibility gap, the mixture decomposes into two liquid phases,
as shown in Fig. 4b. The catalyst system for this process
 C. Nentwich and S. Engell / Computers and Chemical Engineering 126 (2019) 204–217 211

Table 2
Considered ranges for sampling of the surrogate model input variables
temperature T, feed fractions of n-decane xn−decane,in , DMF xDMF,in and 1-
dodecene x1−dodecene,in for the LLE calculations at 1 bar.

Input variable range

T [K] 298.15 − 343.15

xn−decane,in 0−1
xDMF,in 0−1
x1−dodecene,in 0−1

Fig. 4. TMS process scheme (Brunsch, 2013).

plication of the mixed adaptive sampling method for this task are
discussed in the next sections.

6. Results

In this section, the mixed adaptive sampling algorithm is ap-

Fig. 5. TMS process flow sheet (Nentwich and Engell, 2016).
(Rh(acac)(CO)2 /Biphephos) is polar, therefore the polar phase is
recycled to the reactor, while the non-polar phase, which is rich
in product, is further purified in the downstream process.
The translation of this process into a process flow sheet is de-
picted in Fig. 5.
In the considered process, the reactor can be operated at tem-
peratures between 358 K and 378 K and pressures between 10 bar
and 30 bar (Hernandez et al., 2018), while the heat exchanger and
decanter are operated at a pressure of 1 bar and temperatures be-
tween 298.15 K and 343.15 K. The accurate description of the sol-
ubility of the supercritical reactants hydrogen and carbon monox-
ide in the reaction mixture as well as the temperature-dependent
LLE are crucial for predicting the performance of the process. Dur-
ing the investigation of this process, thermodynamic models accu-
rately describing the behavior of all phase equilibria have been de-
veloped using PC-SAFT (Schäfer et al., 2012; 2014; Vogelpohl et al.,
2013; 2014). The goal of our work is to perform process optimiza-
tion based upon these models. In this paper we only discuss the
replacement of the PC-SAFT LLE model of the decanter by surro-
gate models.
The ternary LLE of the solvents n-decane and DMF with the
feed n-dodecene is considered here. The pure component PC-SAFT
parameters are shown in Table 1.
The binary interaction of the components is described by the
binary interaction parameters:
plied to the case study of the ternary LLE of 1-dodecene, n-decane
and DMF. The choice of the sampling parameters which are the
number of subsets NSS (Section 6.1.1) and the selection factor SF
(Section 6.1.2) is discussed first. The obtained models are compared
with models that are based on a conventional LHS design of the
same size in Section 6.2 to see the benefits of the sequential sam-
pling approach. In order to analyze the performance of the models
and to be able to compare different models, one large test set with
50 0 0 sample points that have been evaluated by PC-SAFT serves
as reference for the error measures MisC, the fraction of misclas-
sified samples (see Eq. (44)), and MAEi , the mean absolute error
(see Eq. (45)). In Sections 6.1 and 6.2, the results are discussed for
the mixed adaptive sampling runs that are evaluated up to a high
number of iterations. The choice of the stop-criterion is discussed
in Section 6.3.
6.1. Decision on sampling parameters
In order to decide on a suitable parametrization of the algo-
rithm, several mixed adaptive sampling runs were performed. The
runs for each combination of algorithm parameters SF and NSS
were performed each 5 times. First, the impact of the number of
subsets NSS on the model performance is analyzed.
6.1.1. Number of subsets
The number of subsets NSS is connected to the exploitative ob-
jective of the mixed adaptive sampling algorithm. To find a crite-
rion that reflects the impact of NSS on the selection of candidates,
the part of the variance criterion of the total criterion value η (see
Eq. (20)) for the selected new samples cadd in each iteration pRCV
is analyzed:

ki j = −0.0 0 0315 T /K + 0.1159 (50) s2j

pRCV = , (52)
for DMF/n-decane,
η j · max j s2j

ki j = −0.0 0 0311 T /K + 0.1128
for DMF/1-dodecene and ki j = 0 for n-decane/1-dodecene, taken
from Schäfer et al. (2012).
The considered ranges for sampling of the input variables for
surrogate modeling are shown in Table 2. The results of the ap-
(51) where the index j in this case refers only to selected candidates
cadd in each iteration of the algorithm. Plotting this measure in a
box plot over the number of iterations for a low number of subsets
(in this case NSS = 2) in Fig. 6 reveals that the influence of the
variance criterion on the decision is changing over the course of
the algorithm.

Table 1
Pure component PC-SAFT parameters of the considered components.

Component reference M (g/mol) m (−) σ (Å) ε /k (K) μ (D) T range (K)

n-decane Gross and Sadowski (2002) 142.285 4.6627 3.8384 243.87 243–617
DMF Schäfer et al. (2012) 73.095 2.3660 3.6359 312.99 4.12 300–630
1-dodecene Schäfer et al. (2012) 168.320 5.0091 3.9413 254.86 1.70 310–630
212 C. Nentwich and S. Engell / Computers and Chemical Engineering 126 (2019) 204–217
Fig. 6. Boxplot of pRCV over the iterations of the sampling algorithm for NSS = 2
and SF = 0.4 with 25%- and 75%-percentiles (box), median (line in box), minimum
and maximum (bars) and outliers (markers), based on all selected points in 5 runs.
Fig. 7. Boxplot of pRCV over the iterations of the sampling algorithm for NSS = 18
and SF = 0.4 with 25%- and 75%-percentiles (box), median (line in box), minimum
and maximum (bars) and outliers (markers), based on all selected points in 5 runs.
The median is at 45 − 64% in the first 4 iterations and decreases
to 0.1% in the following iterations. While for a low number of iter-
ations, the 25%- and 75%-percentiles have a broad spread of about
40%, they narrow to a range of  pRCV = 3% in the last iteration.
There are several outliers indicated, 6 out of the 380 selected sam-
ples in the 7th iteration, 20 out of the 530 selected samples in the
8th iteration and 423 out of the 2040 selected samples in the last
iteration. A similar behavior can be observed for a large number of
subsets (in this case NSS = 18) as shown in Fig. 7.
The decrease of the median pRCV over the course of the itera-
tions is faster initially in this case than for NSS = 2. After the 4th
iteration, the median is already at 23% and decreases to 0.1% in the
last iteration. Also, a narrowing of the 25%- and 75%-percentiles
can be seen. In the last iterations there are outliers indicated in
the box plot, 154 out of the 2040 selected samples in the last iter-
ation.
This trend of a decreasing pRCV over the course of the algo-
rithm shows that the impact of the exploitative sampling objective
on the selection of points is stronger in the first iterations of the
mixed adaptive sampling algorithm, while in later iterations only
the space-filling objective is pursued by adding new sample points
to the sample set. Choosing a higher NSS strengthens this effect.
The impact of NSS on the performance of the surrogate models
Fig. 8. MisC over the iterations of the sampling algorithm for SF = 0.4 and NSS = 2
and NSS = 18 showing the mean(markers), minimum and maximum(bars) of each
5 runs.
Fig. 9. MAEi for component i over the iterations of the sampling algorithm for
SF = 0.4 and NSS = 2 and NSS = 18 showing the mean(markers), minimum and
maximum(bars) of each 5 runs.
is discussed in the following. For analyzing the influence of the
number of subsets NSS on the surrogate model performance, we
distinguish between the classifier model performance and the per-
formance of the Kriging models. In Fig. 8, the MisC with respect to
the test set is shown for NSS = 2 and NSS = 18.
Differences in the performance for the runs with NSS = 2 and
NSS = 18 can be seen in the first 5 iterations. In the following iter-
ations, the difference is minor. Regarding the spread of the perfor-
mance over the each 5 runs, the spread is broader for the runs
with the NSS = 2 configuration. At a high number of iterations,
this difference decreases. For the same runs of the sampling algo-
rithm, the results of the MAEi for the three different components
are shown in Fig. 9.
Considering the mean of the results of all 5 runs, the differ-
ence between the NSS = 2 and NSS = 18 runs can mainly be seen
in the component DMF. In iterations 2 to 4 of the mixed adaptive
sampling algorithm, the performance for the predictions of KDMF is
superior for NSS of 18. At a higher number of iterations, the dif-
ferences are minor. Similar as for the MisC, the spread of the MAEi
results in each iteration is broader for the runs with NSS = 2.
As we want to design a reliable method with as small variance
in the performance as possible, the value of NSS = 18 is chosen for
further analysis. The number of subsets NSS is equal to the number
of models that have to be trained for each subset (see Eq. (24)), so
 C. Nentwich and S. Engell / Computers and Chemical Engineering 126 (2019) 204–217 213

Fig. 10. MisC over the classifier sample size of the sampling algorithm for NSS = Fig. 11. MAEi for each component i over the Kriging sample size of the sampling al-
18 and SF = 0.2 and SF = 0.6 showing the mean(markers), minimum and maxi- gorithm for NSS = 18 and SF = 0.2 and SF = 0.6 showing the mean(markers), mini-
mum(bars) of each 5 runs. mum and maximum(bars) of each 5 runs.

the computational effort of the method will increase significantly

if a surrogate model is applied which needs a computationally ex-
pensive training method which is not the case for the models used
here. In these cases, a lower value could be preferred.
In the next section, the choice of the selection factor SF is dis-
cussed.

6.1.2. Selection factor

In this section, the number of subsets is kept constant at NSS =
18 and different selection factors SF are considered. Again, the per-
formance of the classifier model and of the Kriging models are
discussed separately. Fig. 10 shows the MisC-value of the classifier
models for the mixed adaptive sampling with NSS = 18 and 5 runs
each with SF = 0.2 and SF = 0.6 respectively.
The error decreases with the sample size for both cases, but the
performance is different. The MisC value is lower for runs with a
lower selection factor of SF = 0.2 compared to the case of SF = 0.6.
The mean MisC at a sample size of 266 is at 2.3% for SF = 0.2,
while being 3.4% for a sample size of 261 for SF = 0.6. In the last
iterations, the MisC-difference between the two cases is minor, the
mixed adaptive approach obtains a classifier model with a mean
test set error of MisC = 1.04% at 1648 sample points with SF = 0.2
and for SF = 0.6 MisC = 1.02% at 1712 sample points. Thus can be
concluded that a lower selection factor leads to better performing
classifier models at low sample sizes.
The behavior of the Kriging models with respect to the selec-
tion factor is different. Fig. 11 shows the mean MAE-values of the
Kriging models for the mixed adaptive sampling with NSS = 18 and
5 runs with SF = 0.2 and SF = 0.6.
In contrast to the classifier model, the Kriging models generated
at lower sample sizes are generally performing better in the case
of a higher selection factor. At a lower sample size of 104 sample
points, the MAEi for component DMF is 0.012 for the SF = 0.2 runs,
while being at a lower value of 0.007 at a similar training sample
size of 103 sample points for the SF = 0.6 case. At higher sample
sizes of more than about 240 sample points, the difference is mi-
nor.
The results are based on the same mixed adaptive sampling
runs as those shown in Fig. 10, but the training data sample size
is reduced since only the biphasic samples are used to train the
Kriging models.
The results show that a compromise between classifier and
Kriging model performance has to be found. As a compromise,
the medium selection factor SF = 0.4 is considered in the fur-
ther investigation. The performance of this parametrization of the
Fig. 12. MisC over the classifier sample size of the sampling algorithm for
NSS = 18 and SF = 0.4 and same-sized LHS design-based models, showing the
mean(markers), minimum and maximum(bars) of each 5 runs.
mixed adaptive sampling algorithm at a chosen number of subsets
NSS = 18 and SF = 0.4 is compared with the conventional one-shot
space-filling design LHS, which is discussed in the next section.
6.2. Comparision with LHS design-based models
To compare the results of the mixed adaptive sampling algo-
rithm with LHS, for the sample size in each iteration of the sequen-
tial sampling algorithm, 5 LHS designs of the same size were set
up. The performance plots discussed are based on classifier mod-
els and Kriging models which were trained on these LHS designs
and on the models trained by 5 runs of the mixed adaptive sam-
pling algorithm with SF = 0.4 and NSS = 18. First considering the
mean classifier model performance, the models trained with the
mixed adaptive sampling algorithm at any sample size outperform
the LHS design-based models as can be seen in Fig. 12.
Especially at medium sample sizes, e. g. 521 sample points, the
difference in the mean performance is significant with MisC =
1.1% more misclassified samples for the LHS design-based classi-
fiers compared to the models trained by the sequential approach.
At high sample sizes, the difference is smaller. For training the
classifier models, the mixed adaptive approach leads to a superior
performance than using the purely space-filling design.
214 C. Nentwich and S. Engell / Computers and Chemical Engineering 126 (2019) 204–217

Fig. 13. MAEi for the Ki of the three components over the Kriging sample size of the sequential sampling algorithm for NSS = 18 and SF = 0.4 showing the mean(markers),
minimum and maximum(bars) of each 5 runs of the models trained in the mixed adaptive sampling algorithm and the models based on LHS designs.

Fig. 14. MAEi of xi of the three components in the non-polar and polar phase over the Kriging sample size of the sequential sampling algorithm for NSS = 18 and SF = 0.4
showing the mean(markers), minimum and maximum(bars) of each 5 runs of the models trained in the mixed adaptive sampling algorithm and the models based on LHS
designs.

For the Kriging models, the performance difference is not as
pronounced. The comparison is shown in separate diagrams for
each component of the mixture in Fig. 13.
It can be seen that, also for the Kriging models, the perfor-
mance using adaptive sampling is better in the medium sam-
ple size range around 500 samples. While in general the perfor-
mance differences for Ki -predictions are small for the components
n-decane and 1-dodecene, the difference in the component DMF is
larger. The fraction of biphasic samples is lower in the sampling
designs generated by the mixed adaptive sampling compared to
the same-sized LHS designs. Although the training sample size in
the last iteration is lower, the performance of the Kriging mod-
els trained within the mixed adaptive sampling design is similar
to the LHS design-based models. This shows that by combining
the exploratory and the exploitative sampling objective, the perfor-
mance of the Kriging models is superior to LHS design-based mod-
els at a same number of biphasic samples, e. g. the MAEn−decane is
at 0.0011 for a sample size of 519 in the sequential approach, while
being at 0.0020 at a similar sample size of 490 in the LHS design.
At the same sample sizes, the MAEi for DMF is 0.0017 in the se-
quential and 0.0041 in the LHS design-based approach, while for
1-dodecene it is 0.0010 and 0.0019. The errors with respect to the
corresponding molar fractions xi of each component i in each non-
polar and polar phase are shown in Fig. 14.
In general, the results for the composition of the polar phase
are similar for models based on both sampling approaches. For
predicting the non-polar phase composition, the models obtained
from the sequential approach are superior for all three compo-
nents. In the last iteration of the mixed adaptive sampling al-
gorithm, the MAEi of xn−decane in the non-polar phase is 0.0010,
0.0015 for xDMF and 0.0006 for x1−dodecene . For the LHS design-
based models, the MAEi are 0.0013 for xn−decane , 0.0019 for xDMF
and 0.0 0 06 for x1−dodecene , although the models are based on a big-
ger sample size of 974 in contrast to 724 in the last iteration of the
mixed adaptive sampling algorithm.
As the composition of the non-polar phase is determining the
design of the process design for further purification (see Fig. 5),
a reliable surrogate model has to be obtained. But as the quality
of the surrogate model is not known prior to training, the num-
ber of samples required to obtain surrogate models with a suffi-
cient performance is not known when using a one-shot design. A
comparison of the computation time of the mixed adaptive sam-
pling algorithm with a LHS design of the same size is shown in
Table 3.

Table 3
Mean computation time and standard deviation of the each 5 runs when applying the mixed adaptive sampling algorithm and LHS
design for a given total sample size, performed on a standard computer (Windows 7, 3.6 GHz dual core Intel(R) i7, 18 GB RAM).

Sample size 35 49 69 97 136 190 266 372 521 729 1021 1429

Mean adaptive [min] 3.83 5.22 7.32 9.91 14.27 19.98 29.25 40.20 56.25 79.10 111.45 156.68
Mean LHS [min] 3.47 4.76 6.97 11.14 15.24 20.74 29.05 39.22 56.44 81.69 107.37 148.79
Std adaptive [min] 0.54 0.52 0.65 1.01 0.93 1.21 1.12 1.87 0.53 2.44 4.74 5.50
Std LHS [min] 0.75 0.59 1.34 1.10 1.94 1.82 2.29 3.28 2.06 14.67 8.70 5.53
 C. Nentwich and S. Engell / Computers and Chemical Engineering 126 (2019) 204–217 215

Overall, the differences are not significant. As an advantage of

applying the sequential approach, the information on the current
samples in each iteration can be exploited to define a suitable stop
criterion of the algorithm. This is discussed in the next section.

6.3. Stop criterion

In the previous sections, the error measures of MisC and

MAEi were calculated regarding a large test set to ensure com-
parability of the model performance. For the practical use of
the sequential sampling method, an error estimate based on the
available sample points at the current iteration of the sequential
sampling approach should be applied. As discussed in Section 4.3,
the modified jackknife variance calculation requires the genera-
tion of NSS subset models which are each trained on NSS − 1 sub-
sets (see Section 3.3.2) and can thus be used for NSS-fold cross- Fig. 16. CVE(MAE)i (left axis) and CVE(MisC) (right axis) of the xi of the three com-
validation to calculate CVE(MAE)i and CVE(MisC) (see Eqs. (46)– ponents in the non-polar and polar phase over the iterations of run 1, the blue line
indicates a threshold value of ε = 0.01. (For interpretation of the references to color
(49)). As Eason and Cremaschi (2014) apply the slope ratio crite- in this figure legend, the reader is referred to the web version of this article.)
rion of α tot ≤ ε (see sec. 3.3.3), where ε is a lower threshold, this
stop criterion is discussed first. Since the value of ε has to be pre-
defined, a suitable value has to be found. For their case studies,
Eason and Cremaschi (2014) propose ε to be equal to 0.03, but
it has to be noted that in their work another error measure, the
summed squared error SSE, was used. To find an adequate value
for the given case, α tot is at first calculated based on the test set
error measures MAEi and MisC according to Eq. (32). The resulting
α tot for the 5 runs with the configuration SF = 0.4 and NSS = 18 is
given in Fig. 15.
The red line indicates a threshold of ε = 0.03. It can be seen
that the threshold value of 0.03 is not applicable in this case, al-
though the MAEi and MisC are not changing significantly anymore
(see also Figs. 12 and 13). Only run 2 and 3 would have stopped
at iteration 8 and 11 respectively. Running the sequential sampling
algorithm longer until this value of ε is achieved can be unpro-
ductive. The resulting surrogate model may be more accurate, but
the errors in the last iteration are in the order of magnitude of
MAEi ≈ 0.001 or lower (see Fig. 14). Measuring a liquid composi-
tion with such an accuracy is hardly possible. As a consequence, Fig. 17. LLE phase diagram of the PC-SAFT predictions (lines) and surrogate model
one could choose a higher value for ε to stop at an earlier itera- predictions (markers) at 300 K (blue) and 340 K (red). (For interpretation of the
references to color in this figure legend, the reader is referred to the web version
tion, but the user has no indication of the quality of the resulting
of this article.)
models when choosing this value and as can be seen in Fig. 15, this
leads to the different mixed adaptive sampling runs being stopped
at different iterations of the algorithm.
A more practical solution to this problem is to define an abso-
lute value for the accuracy that should be achieved. As an example,
CVE(MAE)i and CVE(MisC) for the sample set at the different itera-
tions of run 1 are shown in Fig. 16.
Defining the required accuracy to be CV E (MAE )i = 0.01 as in-
dicated by the blue line, the algorithm would be stopped in
this case at iteration 11 with CV E (MAE )n−decane = 0.005 in the
non-polar phase and 0.003 in the polar phase, CV E (MAE )DMF =
0.009 in the non-polar phase and 0.005 in the polar phase,
CV E (MAE )1−dodecene = 0.004 in the non-polar phase and 0.002 in
the polar phase and CV E (MisC ) = 0.018. By this, an estimate of the
model accuracy is available and can be used to adapt the proposed
method to case study dependent requirements.
Predictions of the phase diagram that were calculated using the
resulting surrogate models are compared to the original PC-SAFT
model predictions in Fig. 17.
The Kriging models show a good prediction accuracy for the
phase diagram at both temperatures. The classifier classified all
samples correctly in this test case.
The applied surrogate modeling strategy has shown to be suit-
Fig. 15. α tot based on the test set error measures MAEi and MisC over the iterations
of 5 runs, the red line indicates a threshold value of ε =0.03. (For interpretation able to replace expensive thermodynamic model calls. The ap-
of the references to color in this figure legend, the reader is referred to the web plication of the mixed adaptive sampling scheme leads to better
version of this article.) performing surrogate models compared to a conventional purely
216 C. Nentwich and S. Engell / Computers and Chemical Engineering 126 (2019) 204–217
space-filling design. The sequential nature of the algorithm gives
the user more flexibility in the construction of surrogate models of
a predefined accuracy.
7. Conclusions
As equation of state models as PC-SAFT often are not directly
applicable in process optimization due to the computational ex-
pense of the iterative computations, this work aims at replacing
the expensive thermodynamic model calls by explicit computations
of surrogate models. In order to combine explorative and exploita-
tive samling objectives to find the best sample locations, the mixed
adaptive sampling approach by Eason and Cremaschi (2014) has
been extended to a novel surrogate modeling strategy for phase
equilibrium calculations which is in particular suitable for LLE
models.
Modeling the composition of the different phases of the system
leads to discontinuities in the output space as the mixture disinte-
grates at certain operating conditions. To obtain models which are
valid in the full operating range of interest, the change in the num-
ber of phases also has to be modeled. This is done by the applica-
tion of a classifier model. For the prediction of the composition of
the different phases, suitable regression models are then applied.
The goal of our work is to train surrogate models that provide a
very high prediction accuracy over the full operating range of rel-
evant process conditions so that the models can be used in pro-
cess optimization without retraining which is why nonlinear clas-
sification and regression models are used. This is in contrast to us-
ing local approximations that possibly have to be retrained during
the course of the optimization. Of course, monitoring of the range
of the variables is still necessary in the optimization so that the
surrogate models are not employed beyond their domain of valid-
ity, where the models would have to be retrained. In this work,
this approach has been applied to the operating range of interest
for the ternary liquid-liquid equilibrium of n-decane, dimethylfor-
mamide and 1-dodecene, applying a SVM classifier and ordinary
Kriging models as the regression method, as part of the goal to
make an efficient process optimization applying a complex ther-
modynamic model as PC-SAFT for all phase equilibria in the pro-
cess of hydroformylation of 1-dodecene possible.
The choice of the parameters of the mixed adaptive sampling
algorithm was discussed in detail. A large number of subsets NSS
improves the quality of the surrogate models that are trained with
the adaptive sampling approach. For the selection factor SF a com-
promise between classifier and regression model performance had
to be made. The classifier model performance is best when the SF
is small and for the regression models the opposite is true.
The models that were trained using the mixed adaptive sam-
pling algorithm with the configuration NSS = 18 and SF = 0.4 were
compared to models based on conventional one-shot Latin hyper-
cube designs, revealing that the mixed adaptive approach obtains
better performing classification and regression models at a similar
computational expense.
The algorithm should be stopped at an accuracy that is satis-
factory for the purpose, e. g. considering the accuracy of the mea-
surements. As a stop criterion, the slope ratio turned out to be
not useful in this case. The definition of threshold values for cross-
validation errors should be preferred.
Further improvements to the algorithm could be achieved by
adjusting the weighting of the exploratory objective, the classifier
and the regression models in the overall sampling objective (see
Eq. (20) and Eqs. (29)–(30)).
The next step will be the use of the surrogate models in pro-
cess optimization. The classifier model can be implemented as a
constraint that defines the valid operating range within the bipha-
sic region of the separator (see Fig. 5), while the regression models
predict the phase composition.
Acknowledgment
This work is part of the Collaborative Research Center/
Transregio 63 “Integrated Chemical Processes in Liquid Multi-
phase Systems” (subproject D1). Financial support by the Deutsche
Forschungsgemeinschaft (DFG, German Research Foundation) is
gratefully acknowledged (TRR 63).
The authors also thank Roderich Wallrath, Clemens Lindscheid,
Maximilian Cegla, Radoslav Paulen, Marina Rantanen Modéer, Si-
mon Wenzel, Shreya Bhatia and Anoj-Winston Gladius for their
support.
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