Analytica Chimica Acta 1158 (2021) 338414

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Analytica Chimica Acta

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

A computational simulation of electromembrane extraction based on

Poisson - Nernst - Planck equations
Roshanak Dolatabadi a, Ali Mohammadi a, **, Mostafa Baghani b, *
a
Department of Drug and Food Control, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
b
School of Mechanical Engineering, College of Engineering, University of Tehran, P.O. Box 11155-4563, Tehran, Iran

h i g h l i g h t s g r a p h i c a l a b s t r a c t

Developing a 2D numerical model for

electromembrane extraction.

Modeling the electro-driven extrac-
tion process through PoissoneNernst
ePlanck equations.

The finite-element approach is
employed to solve the governing
equations.

The model is successful in prediction
of main features observed in experi-
ments for basic drugs.

Analyte diffusivity, distribution co-
efficients and level of protonation are
major effective variables.

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

Article history: Electromembrane extraction (EME) has attracted a great deal of interest in researchers because of its
Received 26 December 2020 advantages. For analysis, design and optimization purposes, understanding the ion transport mecha-
Received in revised form nisms in the organic supported liquid membrane (SLM) is of prominent importance, where the interplay
3 March 2021
between the passive diffusion and electric-driven mass transport across SLM affects the mass transfer. In
Accepted 12 March 2021
Available online 16 March 2021
present work, a 2D numerical simulation is developed to examine the mass transfer behavior and the
analyte recovery in EME devices. The presented model is capable of describing the effect of different
parameters on the recovery of the EME setup. Initial analyte concentration in the sample solution, SLM
Keywords:
Electromembrane extraction
thickness, applied potential, permittivity, diffusion coefficient, and the reservoir pH within both the
Drug concentration sample and acceptor, can be considered as process variables. Predicted results revealed that the most
Computational model important factors playing key role in EME, are the analyte diffusivity, distribution coefficient of the
Nernst-Planck-Poisson equations analyte as well as the level of protonation in both the donor and acceptor solutions. The proposed model
Finite element method is helpful in predicting the mass transfer behavior of the EME process in practical applications.
© 2021 Elsevier B.V. All rights reserved.

1. Introduction

Scaling down the analytical instruments, such as those used in

sample preparation, has been continuously developing in the last
* Corresponding author.
decades [1,2]. Sample treatment should be simple, automated,
** Corresponding author.
E-mail addresses: alimohammadi@tums.ac.ir (A. Mohammadi), baghani@ut.ac.ir miniaturized, fast, inexpensive, and safe [3]. Solid phase [4e7],
(M. Baghani). single drop [8], and hollow fiber liquid phase microextraction [9,10]

https://doi.org/10.1016/j.aca.2021.338414
0003-2670/© 2021 Elsevier B.V. All rights reserved.
R. Dolatabadi, A. Mohammadi and M. Baghani
have been introduced to address the issues that where unreachable
with traditional methods. Regardless of their great characteristics,
some downsides were observed during their application. For
instance, microfibers in solid phase microextraction are expensive,
organic drop may get unstable in single drop microextraction, and
in hollow fiber liquid phase microextraction the extraction is time-
consuming. Therefore, new techniques have been developed to
resolve these problems [11,12].
Electromembrane extraction (EME) is a microextraction tech-
nique introduced for the first time in 2006 [13]. The dominating
principle for EME is depicted in Fig. 1. Target analytes are being
extracted from a sample solution, via a thin supported liquid
membrane (SLM) to an acceptor solution, where the SLM contains
an organic solvent (such as NOPE or 1-octanol) immobilized in a
porous hollow fiber. The driving force for EME is an electric field
applied over the SLM, generated by a power supply [13e16].
Numerical simulations are helpful for understanding the SLM
mass transport. Mass transport models discussing SLM processes
are categorized into two main approaches. As the first approach,
some studies characterized the mass transfer across the SLM based
on mass transfer resistances in donor, SLM and acceptor phases,
where the mass transfer resistances are described by mass transfer
parameters for each phase such as the analyte diffusivity, pH, and
partitioning coefficients. This approach is simple, but it involves
calibrating all mass transfer parameters against experimental tests
[17e21]. To find the concentration distribution at different phases,
the second approach requires solving a series of partial differential
equations [22,23]. However, both these approaches are appropriate
for just one-dimensional description of the phenomena and do not
provide predictions where 2D or 3D distributions are desirable.
Experimental observations reveal that the applied electric po-
tential as well as the organic solvent composition are key param-
eters in EME [24]. To appropriately analyze, design, and optimize
the mass transport in EME, we need an accurate model to simulate
the whole process. In an early work to model EME, the analyte flux
across the SLM was formulated by Gjelstad et al. [24]. This relation
was based on a simple reduced form of Nernst-Planck equation
borrowed from the literature, which was useful to understand
some phenomena occurring in SLM. However, it did not determine
how the applied electric potential on SLM should be computed.
Besides, it did not provide any prediction for extraction times or
recoveries, since the time-dependent effects have not been dealt
with in this model. In 2020, Hansen et al. [25] modified this model
to consider the effect of ion-balance introduced as the ratio
Fig. 1. Schematic of the equipment for EME.
2
Analytica Chimica Acta 1158 (2021) 338414
between the total amount of ions in the donor and acceptor, while
the major assumptions of the model remain the same. In other
attempts to model the EME, Gjelstad et al. [26] and Seip et al. [27]
proposed a time-dependent model to describe the governing
phenomena during EME. To account for the time-dependent dis-
tribution of analytes, a simplified kinetic model was proposed,
where the main assumptions were: (a) considering a lag time for
the residence of the ions in the SLM, (b) the rate determining stage
of the process is the transport within the SLM, (c) the convection is
large enough so that mass transport in sample or acceptor solutions
do not limit the rate, and ultimately (d) the transport in the SLM is
one-dimensional, and after a long time the entire analytes are
accumulated in the acceptor. Compared to the work of Gjelstad
et al. [24], this model presents more details about the process, but
still does not specify how the electric potential distribution should
be evaluated or how the analytes are distributed along the SLM
thickness or the acceptor solution. To consider the effect of applied
electric potential, they have assumed that the distribution co-
efficients are voltage-dependent. Whereas a voltage distribution is
being developed is the system, it should be pointed out that, which
voltages should be selected to show the dependence of the po-
tential to the distribution coefficients. In another work, Restan et al.
[28] in 2020, introduced a simple theoretical model to discuss the
effect of pH for EME of hydrophobic basic analytes (logP > 2) under
their acidebase equilibria together with partitioning of species to
the SLM. In 2020, Drobnjak et al. [29] made use of a numerical
model to find electric potential distribution for EME with vials
made of conducting polymer. However, they did not solve the
diffusion problem and only reported the electric voltage across the
SLM.
These works provide good insight to the phenomena and are
helpful, but they are zero-dimensional in space and cannot give
practical quantitative predictions [24,26,27,30]. Different parame-
ters such as electrodes distance and shape, setup geometry, applied
voltage distribution and pH of the solutions can affect the EME
recovery and should be taken into account in any attempt to model
EME [16,24]. Although the available studies on EME experiments
are numerous, mathematical models are still scarce, despite being
are of high importance for the design and active control for the
optimum use of these devices.
In this paper, it is aimed to develop a numerical model to study
the effects of different parameters, i.e., applied potential, pH of
donor and acceptor phases, and distance of electrodes on EME. The
analyte’s concentration distribution in the donor, SLM and acceptor
phases over time are examined in detail. As discussed earlier, there
are few mathematical models available in literature, where none of
them considered the analytes distribution in the sample, SLM and
acceptor phases. More importantly, the Poisson Nernst Planck
equations as the main governing equations have not been solved
simultaneously in previous works. Solving these equations enables
us to better understand the diffusion patterns in different parts of
the EME system.
2. Governing equations
In this paper, the electric potential, is denoted by f. To find the
electric field, one may write [31,32]:
E ¼  Vf (1)
where E stands for the electric field intensity vector and V denotes
the gradient operator. Besides, the constitutive equation to intro-
duce the dielectric model can be given as [31,32]:
R. Dolatabadi, A. Mohammadi and M. Baghani Analytica Chimica Acta 1158 (2021) 338414

D ¼ ε0 εr E
in which ε0 ¼ 8:854  1012 F=m and εr are the permittivity of
vacuum and relative permittivity of the medium, respectively; and
D expresses the electric displacement or electric flux density vector.
The Poisson equation is used to model the distribution of the
electric flux density vector, as [31,32]:
V:D ¼ rv
P
where rv ¼ F N i¼1 ci zi . Besides, ci and zi are the i’th species con-
centration and charge, respectively. (V: denotes the divergence
operator.) Since the dimensions in this modeling are in the order of
microns and higher (much larger than the Debye length which is
below 50 nm), the electro-neutrality condition can be applied,
P
which gives N i¼1 ci zi x0.
The well-known Nernst-Planck equation is used to predict the
electro-diffusion of ion species in terms of ion concentration. In
addition to mass transfer due to the passive diffusion, the ionic
species transfer by migration under an electric field should also be
considered. Therefore, the mass balance becomes [31]:
vci
þ V:Ji þ u:Vci ¼ Ri
vt
Ji ¼  Di Vci  zi um;i Fci Vf
in which the flux vector of the ith ionic species is shown by Jj; ci
represents the concentration of species i, Di is its diffusion coeffi-
cient, zi denotes its ionic charge, and um,i is its ionic mobility and F
refers to Faraday’s constant (96,485 [C/mol]). It is noted that u and
Ri are used to consider the fluid velocity, and generation and
destruction of species i, respectively, which in this work have been
neglected. Moreover, for the sake of simplicity, the deformations of
the SLM are ignored.
The Nernst-Einstein equation in many cases is applied to asso-
ciate the species mobility to its diffusivity Di by Ref. [31]:
Di
um;i ¼
RT
II The top and bottom walls of the setup ðU3 Þ are rigid, ion-
(2) impervious, and uncharged. The electric potential is contin-
uous at the SLM-electrolyte interfaces ðU4 Þ and ðU5 Þ.
III No external pressure gradient is applied along the setup
IV The ions partitioning occurs at the SLM-electrolyte in-
terfaces. It could happen due to changes in the electrostatic
and/or van der Waals interaction forces of the ions. One
important phenomenon, for instance, is variation in the
electrostatic self-energies of ions arising from the permit-
(3) tivity difference, called the Born energy. The distribution
coefficient, Pi , specifies the ratio of the interfacial ionic con-
centrations inside and outside the SLM, where applying the
Boltzmann distribution, is given as [33]:
ci;M Dwi
Pi ¼ ¼ expð Þ (7)
ci kB T
where kB denote the Boltzmann constant and Dwi stand for the
energy difference of the ith ionic species. ci;M denotes the analyte
concentration inside the membrane at its interfaces. This param-
eter determines that how hydrophobic or hydrophilic the analyte is.
It should be highlighted that since the donor and acceptor solutions
may have different pH’s and the partition coefficient is highly
dependent to the pH, different partition coefficients for the left and
(4)
right walls of the SLM should be assumed in the modeling. Thus, we
have [34]:
(5) 
Pi;s ¼ ci;M ci;s (8)
where Pi;s denotes the partition coefficient at the interface of the
sample and SLM, and ci;s shows the analyte concentration in the
sample. At the sample/SLM interface, the flux continuity should
also be satisfied in the form of [34]:
Di;s Vci;s þ zi;s um;i;s Fci;s Vfs ¼ Di;M Vci;M þ zi;M um;i;M Fci;M VfM
(9)
Similar conditions are required for the SLM and acceptor solu-
tion interface as:

(6)
Pi;a ¼ ci;M ci;a (10)

where T is the absolute temperature. The boundary conditions

associated with Eqs. (1)e(6) are tabulated in Table 1 based on the
nomenclature given in Fig. 2. To determine the boundary condi-
tions, the following assumptions are made:
I The left wall of the donor reservoir (sample), ðU1 Þ is exposed
to an electric potential of Vapp , while the right wall of the
acceptor reservoir ðU2 Þ is grounded.
Di;M Vci;M þ zi;M um;i;M Fci;M VfM ¼ Di;a Vci;a þ zi;a um;i;a Fci;a Vfa
(11)
in which Pi;a stands for the partition coefficient at the interface of
the SLM and acceptor, and ci;s is the analyte concentration in the
acceptor solution.
Recovery for each analyte is computed according to:

Table 1
The boundary conditions associated with the computational domain in Fig. 2b. The parameter n is the outward normal vector.

Surface Electric potential Ionic conservation

U1 constant voltage bias ion-impenetrable

4 ¼ Vapp n,Nj ¼ 0
U2 Grounded ion-impenetrable
4 ¼0 n,Nj ¼ 0
U3 Uncharged ion-impenetrable
n,V4 ¼ 0 n,Nj ¼ 0
U4 Pi;s ¼ ci;M =ci;s
Di;s Vci;s þ zi;s um;i;s Fci;s Vfs ¼ Di;M Vci;M þ zi;M um;i;M Fci;M VfM
U5 Pi;a ¼ ci;M =ci;a
Di;M Vci;M þ zi;M um;i;M Fci;M VfM ¼ Di;a Vci;a þ zi;a um;i;a Fci;a Vfa

3
R. Dolatabadi, A. Mohammadi and M. Baghani Analytica Chimica Acta 1158 (2021) 338414

Fig. 2. Electromembrane extraction; (a) schematic of the equivalent setup of the system under consideration; (b) boundary conditions used in the system. The setup has the length
LN , the sample width wd , the SLM width ws , and the acceptor width wa and connects two identical large reservoirs filled with aqueous HCl solutions.

function for u. This relation allows us to properly address the

H
ca;final dV
na;final V practical problems. However, in this work, it is assumed that the
R¼  100 ¼ H a  100
ns;initial cs;initial dV
Vs
where ns;initial and na;final stand for the number of analyte moles
initially available in the sample phase and finally in the acceptor
phase, respectively. Va is the volume of acceptor phase, Vs the
sample volume, ca;final the final concentration of analyte in the
acceptor solution and cd;initial is the initial analyte concentration in
the donor solution.
The effective diffusion coefficient of the SLM is found through
the following relation in terms of its porosity ~ε and tortuosity t
[35e37]:
Dm;i ¼ Di u ¼ Di~ε=t
As this ratio decreases, the diffusivity in SLM and therefore its
transport capability decreases; i.e., a lower extraction efficiency.
It is worth noting that increasing the analyte ion concentration
lowers the diffusion coefficients in the SLM. In other words, the
efficiency of the membrane decreases, as the process goes on. To
consider this effect on the diffusion coefficients of the ions across
the membrane, one may assume a monotonically-decreasing
nonlinear diffusion phenomenon occurring across the SLM in
(12)
capability of the SLM remains the same along the extraction pro-
cess. It is also noted that the pH in both the donor and acceptor
phases may change during the extraction. However, in most cases
this pH change is not that significant and buffers are used to avoid
this effect. Thus, it is assumed that pH remains almost fixed during
the process.
3. Solution procedure
Equations (1)e(6) are a set of coupled nonlinear partial differ-
ential equations to which no analytical solution can be found for
different geometries and boundary conditions. In this work, the
(13) governing equations are numerically solved subject to the associ-
ated boundary conditions in COMSOL Multiphysics 5.6, a software
working based on finite element method. The coupled Nernst-
Planck-Poisson (PNP) equations were employed to compute the
ionic concentration, as well as the electric potential distributions. A
total number of ~32,000 type free triangular mesh elements was
found to be adequate to arrive at mesh-independent outcomes.
Extremely fine meshes were used near the SLM walls to arrive at
the correct solution. The mesh network used in all simulations

Fig. 3. The mesh network used in all simulations.

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R. Dolatabadi, A. Mohammadi and M. Baghani Analytica Chimica Acta 1158 (2021) 338414

Table 2 presenting different numerical simulations. The sample analyte

Geometric values of the EME setup. concentration, the SLM thickness, the applied voltage, the permit-
Parameter Description Value tivity, as well as the diffusion coefficient, the reservoir pH in both
the sample and acceptor phases can be considered for parametric
CD Drug concentration in donor phase  2:6  103 mM
LN Length of setup 31 mm study. It is attempted to simulate a real EME setup; for this purpose,
wa Acceptor thickness 600mm geometrical parameters are assumed as listed in Table 2, while the
wd Donor thickness 4:5 mm material model parameters used in the numerical simulations are
ws SLM thickness 200mm shown in Table 3. In this paper, basic drugs are considered, implying
that the EME setup is cation-selective. It is worthwhile to mention
that in EME experiments, a stirrer mixed agitates the whole setup
Table 3
to accelerate the extraction process and ensure efficient convection
Parameters required for simulation of EME.
in the donor solution. This means the ion transport in the sample is
Parameter Description Value much faster than without stirring, and the time-consuming part of
DD Diffusivity of drug ions 1:0  1011 m2 =s the process is the ion transport across the organic SLM, acceptor
u Porosity to tortuosity ratio of the SLM x0:1 solution and only its neighboring media in the sample solution.
R Universal gas constant 8:3145 J=ðmol:KÞ This issue has been implemented in the modeling by applying a
F Faraday constant 96500 C=mol
larger diffusion coefficient for the analyte in the donor phase,
KB Boltzmann constant 1:381  1023 J=K
which makes the sample have a monotonous ions concentration
T Absolute temperature 298:15 K
ε=ε0 Relative permittivity of solutions 80 distribution all over the donor solution.
εm =ε0 Relative permittivity of SLM 10 [38] In the following since we are interested in real-world drugs,
Dropridol as a basic drug is used in the donor solution. In Fig. 4,
different pairs of pH, (pHs, pHa), for the sample and acceptor are
which led to convergent results is illustrated in Fig. 3. The direct examined. Fig. 4a illustrates the effect of acceptor pH and applied
MUMPS solver with a maximum relative tolerance of 108 was voltage on the EME recovery, while pHs ¼ 2. As expected, higher
applied. electric potentials give higher recoveries. For this drug, at pH ¼ 2,
logD ¼ 0.46 and z ¼ 1; at pH ¼ 5, logD ¼ 1.26 and z ¼ 0.98; at
4. Results and discussions pH ¼ 7, logD ¼ 2.82 and z ¼ 0.36 [39]. Considering these distri-
bution coefficients, one may realize that the drug is hydrophilic at
In this section, the proposed model results are reported by pH ¼ 2. At pH ¼ 5, it is hydrophobic to some extent, while, at

Fig. 4. Predicted recoveries at different voltages and different acceptor pH’s for a) pHs ¼ 2, b) pHs ¼ 5, c) pHs ¼ 7. d) Predicted recovery in sample, SLM and acceptor (solid lines
stand for the case with pHs ¼ pHa ¼ 2, V ¼ 50v, while dash-dot lines denote the case with pHs ¼ 5, pHa ¼ 2, V ¼ 20v).

5
R. Dolatabadi, A. Mohammadi and M. Baghani Analytica Chimica Acta 1158 (2021) 338414

50
Sample SLM Acceptor
40
Drug concentration [ ppm ]

SLM pHs=5, pHa=2, V=50v

30 t = 30 s
t = 3 min
t = 6 min
20 t = 8 min

10

0
4 4.2 4.4 4.6 4.8 5 5.2
x-position [ mm ]
Fig. 5. The drug concentration distribution at different times across donor, SLM and
acceptor. It should be noted that only a portion of the donor phase which has a
gradient in distribution has been shown. Fig. 7. Effect of smaller diffusion coefficient at different sample and acceptor pH’s
where D0 ¼ 1011 m2/s.

pH ¼ 7, its hydrophobicity gets very high. Thus, apparently it seems

acting as a better solution compared to (2, 5). Since at pHa ¼ 5 the
that the best candidate for the sample and acceptor pH’s are (7, 2).
ion charge is almost the same, a smaller distribution coefficient at
However, the analyte ion charge dependence to pH, which is
pHa ¼ 2 allows us to reach a higher recovery. Fig. 4b examines the
playing a key role in reaching to high recoveries in EME, necessarily
impact of the same parameters at pHa ¼ 5. The pH pair of (5, 2)
does not follow the same trend as distribution coefficient. It should
makes the extraction faster than (2, 2). This is stemming from the
be noted that there are two competing phenomena that are of high
fact that pHs ¼ 5 corresponds to a higher distribution coefficient,
importance in selection of the best donor and acceptor solutions.
which means the analyte is more likely to migrate to SLM. At pH
Now, looking at Fig. 4a, it is revealed that the pH pair of (2, 2) is
condition of (5, 2), we also have the best pHa because a low logD
leads to a fast ion migration from the SLM to the acceptor phase,
while its ion charge has been preserved. In all cases, where pHa ¼ 7,
the drug is so hydrophobic that it would not simply leave the SLM.
On the other hand, its ionic charge diminishes to 0.35. Hence, the
recovery drops to smallest values.
For pHs ¼ 7, in spite of its great distribution coefficient, the drug
loses a large part of its charge which makes the EME more slowly.
Possessing a higher charge along with a large logD can potentially
be a good donor. This means, although at pHs ¼ 7 we have a high
distribution coefficient, due to its small charge, it fails to be the
most desirable pH for the sample. Arranging the recoveries based
on the sample and acceptor solutions pH, one may find the
following order:

Fig. 6. The drug concentration contours (pHs ¼ 2, pHa ¼ 2, and V ¼ 50v) it is note-
worthy that only a portion of the donor phase which has a meaningful gradient in
distribution has been shown. Fig. 8. Electric potential distribution across the donor, SLM and acceptor.

6
R. Dolatabadi, A. Mohammadi and M. Baghani Analytica Chimica Acta 1158 (2021) 338414

Fig. 9. Variation of Ionic charge and logD of some different drugs versus pH. Data are taken from Ref. [39].

observed in the donor during extraction, with a steady rise in the

amount accumulated in the acceptor phase. Despite the lower
ð5; 2Þ > ð2; 2Þ > ð5; 5Þ > ð2; 5Þ > ð7; 2Þ > ð7; 5Þ > ð5; 7Þ > ð2; 7Þ > ð7; 7Þ applied voltage, because of a larger logD for pHs ¼ 5, the depletion
(14) rate is higher. For the case of (5, 2) under 20 v, a large portion of the
ions are accumulated in the SLM, while the remaining ions go into
This type of trend which implies a best pair of pH exists for each
the acceptor solution. This behavior acts similar to a capacitance
analyte, is in agreement with experimental observations reported
that releases the drug ions in a decaying exponential format. This
in literature [40]. It should be noted that this order is not solely
type of behavior has been experimentally observed and reported
based on the distribution coefficient difference at SLM interfaces, or
for different drugs by Seip et al. [27]. On the other hand, this
just the ionic charge. A combination of these parameters along with
capacitance-like response is faster for the case of (2, 2) under 50 v. A
the SLM properties and applied potential affect the pH selection
higher applied electric potential together with small values of
procedure and therefore EME recovery.
logD’s at both interfaces of the SLM make the SLM release faster the
To arrive at a better understanding of the ions’ migration, the
accumulated ions.
relevant recoveries in the sample, SLM and acceptor are depicted
The analyte concentration distribution along the ion migration
for the pH pair of (5, 2) under applied voltage of 20 v, and pH pair of
direction across the donor, SLM and acceptor solution at different
(2, 2) under 50 v in Fig. 4d. The analyte ions are depleted from the
times is shown in Fig. 5. As an example, the case with pHs ¼ 5,
sample in a short time. Gjelstad et al. [26] and Seip et al. [27] in
pHa ¼ 2, and V ¼ 50v has been reported in this Fig, where it can
their experiments also mentioned that a rapid depletion was
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R. Dolatabadi, A. Mohammadi and M. Baghani Analytica Chimica Acta 1158 (2021) 338414

Fig. 10. Recovery of the EME system at extraction time of 15 min and voltage of 20 V for a) Ciprofloxacin, logP ¼ 0.81, (basic), (1,5); b) Ciprofloxacin, logP ¼ 0.81, (acidic), (11,11);
c) Topiramate, logP ¼ 0.13, (acidic), (12,12); d) Amisulpride, logP ¼ 0.25, (basic), (7,7); e) Sitagliptin, logP ¼ 1.26, (basic), (8,6); f) Buspirone, logP ¼ 1.78, (basic), (7,5); g) Warfarin,

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R. Dolatabadi, A. Mohammadi and M. Baghani Analytica Chimica Acta 1158 (2021) 338414

provide us useful information about the kinetics of the entire

process. It should be pointed out that only a portion of the donor
phase which has a gradient in ions distribution has been plotted in
Fig. 5. At the early stages of the EME, e.g., 30 s, due to the high value
of logD ¼ 1.26, at the donor/SLM interface, the analyte is more
willing to exit the donor and reside in SLM. After 6 min, this time at
the SLM/acceptor interface the small logD ¼ 0.46 acts as a positive
driver to expedite the extraction. At this time, a significant fraction
of the analyte ions moves more toward the other side of the SLM
which is in contact with the acceptor. In the meantime, some ions
pass the SLM, while the others gain more energy to overcome the
energy level required to get out of the SLM. Now, if we give enough
time to the process to keep on, one may observe that at 6 min,
almost all the analyte ions have migrated to the acceptor, where
most of them have resided next to the grounded electrode. To give a
more graphical insight to the mass transfer process, the analyte
concentration contours for the case with pHs ¼ 2, pHa ¼ 2, and
V ¼ 50v are plotted in Fig. 6. Fig. 11. Average recovery of the EME system for simultaneous extraction of Topiramate
Fig. 7 is devoted to examining the effect of the analyte diffusion and Warfarin.
coefficient on the predicted EME recovery. It is revealed that this
parameter is of high importance in the modeling. Smaller diffusion
containing for example acidic drugs of Topiramate and Warfarin,
coefficient significantly reduces the recovery in all cases. Since this
where their best pair of (pHs, pHa) was (12,12) and (7,9), respec-
parameter is active in both the non-electric and electric driven
tively (see Fig. 10). However, the average system recovery meets its
terms in Nernst-Planck equation, its amplification or decrease
maximum at (pHs, pHa) ¼ (13,13). The applied conditions are the
highly affects the entire extraction operation.
same as those reported for Fig. 10.
The distribution of electric potential across the sample solution,
The following items can be included in the model to more
organic SLM and acceptor solution is depicted in Fig. 8. Whereas the
realistically simulate this electro-driven diffusion process.
electro-neutrality condition stands accurate in all cases in this pa-
per, electric potential does not vary much during the simulation.
i. The real 3D setup should be simulated to arrive at a more
Thus, only one distribution has been given for each applied voltage.
reliable model. In this paper, only the space between the
The organic SLM has a much larger electric resistance and much
electrodes has been considered in a 2D model.
smaller permittivity compared to the donor and acceptor phases;
ii. The effect of fluid velocity can be added to the model through
hence, its voltage drop is more abrupt.
simultaneously solving the Navier-Stokes equations to ac-
To show the capability of the presented model for different basic
count for the convective term present in Nernst-Planck
and acidic drugs with various logP’s, the system recovery is opti-
diffusion equation.
mized for different pHs and pHa. The distribution of the ionic charge
iii. The analyte may deprotonate partly during passing through
as well as the logD of the drugs are illustrated in Fig. 9. It is inter-
the organic SLM. This can be due to the material and
esting that for Ciprofloxacin, depending on the pH, it can play role
geometrical properties of the SLM. The level of this depro-
as both acidic and basic analytes. However, due to its low
tonation as well as possible ion pairing can be applied to the
logP ¼ 0.81, as shown in Fig. 10a and 10b, the system recovery is
model. However, it involves specific experiments to have
very small. One may observe from Fig. 10 that generally by
necessary evidences.
increasing the logP of the drug, its recovery increases. However, this
iv. The analyte molecules could be trapped in the SLM pores and
rise depends on the ionic charge of the drug at both phases and its
reduce the efficiency of the SLM by lowering the analyte
relevant logD’s. It should be noted that for acidic drugs, in the
diffusion coefficient over time. This issue has not been
simulations the locations of electrodes have been switched. The
considered in present work.
best pair of pH of the system for each drug is shown on the caption
v. It is assumed that no electrolysis occurs around the
of Fig. 10.
electrodes.
In this paper, it was attempted to present a mathematical
vi. High voltages could lead to electrochemical degradation
modeling of the electromembrane extraction. Employing the
which has not been included in this model. This effect could
coupled Nernst-Planck-Poisson equations subjected to necessary
explain the smaller recoveries in experiments.
boundary conditions associated with the problem, the ionic con-
vii. The effect of double layers on the analyte recovery over the
centrations of the species, and the electric potential distributions
extraction can be considered in the modeling especially for
were computed in a 2D field consisting of the donor solution,
thin SLMs.
organic SLM and acceptor solution. The proposed model was suc-
viii. The possible effect of salts in the sample solution on the
cessful in qualitatively reproduction of the experimental observa-
analyte recovery should also be accounted for.
tions available in literature.
ix. It is assumed that the permittivity and electric resistance of
It is noted that employing this model, one can study the
the SLM remain the same during the extraction, while in
simultaneous extraction of different analytes and optimize the
practice it may lose a part of its resistance which leads to a
conditions for the best recovery of all analytes at the same time,
smaller electric potential drop across the SLM and conse-
which is obviously different from the optimized conditions for only
quently lowers the total recovery of the whole system.
each analyte. Fig. 11 depicts the average recovery for a solution

logP ¼ 2.74, (acidic), (7,9); h) Hydroxy chloroquine, logP ¼ 2.89, (basic), (8,6); i) Mycophenolic acid, logP ¼ 3.53, (acidic), (10,12); j) Haloperidol, logP ¼ 3.66, (basic), (7,4). The best
pair of pH of the system (pHs, pHa) for each drug is shown in parentheses.

9
R. Dolatabadi, A. Mohammadi and M. Baghani
It should be noted even though these modifications can improve
the validity of the proposed model; however, most of them involve
detailed experiments to appropriately calibrate the proposed
model.
5. Conclusion
In this paper, it was attempted to present a mathematical
modeling of the electromembrane extraction. Employing the
coupled Nernst-Planck-Poisson equations subjected to necessary
boundary conditions associated with the problem, the ionic con-
centrations of the species, and the electric potential distributions
were computed in a 2D field consisting of the donor solution,
organic SLM and acceptor solution. The proposed model was suc-
cessful in qualitatively reproduction of the experimental observa-
tions available in literature.
In this paper for the first time, numerical methods (finite
element method) were used to solve the coupled governing equa-
tions (Nernst Planck and Poisson equations) in two dimensions,
while in previous studies on modeling of EME only one-
dimensional qualitative results were discussed. Moreover, this
model enables us to optimize different effective parameters of EME.
For example, in Fig. 10, such optimization was carried out to find the
best pHs and pHa in order to maximize the system recovery. Such
approach can be used for finding other parameters, for example one
may change the electrode locations, shapes and distances and
examine their effect on the system recovery. To the best knowledge
of the authors, there is no other works available in literature with
such features. Besides, with the aid of this model, one can inves-
tigate the simultaneous extraction of different analytes and find the
conditions for the highest recovery of all analytes at the same time,
which may differ from those of each analyte. The presented model
is a useful tool can be applied in analysis and design of different
analytes in EME. It also can help the researchers to arrive at a better
understanding of the phenomena occurring in EME. However,
some aspects should be added to this model to give more reliable
predictions especially under conditions that have not been
assumed in this modeling.
CRediT authorship contribution statement
Roshanak Dolatabadi: Methodology, Software, Validation,
Writing e original draft. Ali Mohammadi: Conceptualization,
Methodology, Writing e review & editing, Supervision. Mostafa
Baghani: Methodology, Software, Writing e review & editing,
Supervision.
Declaration of competing interest
The authors declare that they have no known competing
financial interests or personal relationships that could have
appeared to influence the work reported in this paper.
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