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A Model of Electrokinetic Platform for Separation of Different Sizes of Biological Particles

  • Reda Abdelbaset
  • Yehya H. Ghallab
  • Hamdy Abdelhamid
  • Yehea Ismail
Conference paper
Part of the Advances in Intelligent Systems and Computing book series (AISC, volume 639)

Abstract

The dielectrophoresis (DEP) phenomena is a motion of uncharged polarizable particles in the direction of most field strength site within a non-uniform electric field. Unlike various techniques, the DEP is an effective technique for particles manipulation and separation of biological particles. The manipulation and separation of biological cells are necessary to various biomedical applications such as cell biology analysis, diagnostics, and therapeutics. The traveling-wave dielectrophoresis (twDEP) and levitation are major subcategories of electro-kinetic motions that are generated as a result of the interaction between a non-uniform electric field and polarizable particles. This article presents a model of an electrokinetic platform that has a working principle of dielectrophoresis phenomena and Printed Circuit Board (PCB) technology for separation of different sizes of biological particles such as microbeads (simulated biological cells) and the blood formed elements (platelets and red blood cells (RBCs)) using two configurations of microelectrodes (traveling and levitation).

Keywords

Dielectrophoresis Separation Traveling wave Levitation Platelets Red blood cells Microbeads COMSOL 

1 Introduction

The separation and manipulation of particles techniques gained the attention of scientists in all fields such as engineering, chemistry, physics and biology. The dielectrophoresis (DEP) is a competent technique for manipulation, identification, and sorting of biological cells by observing the response of non-polarized biological cells towards a non-uniform electric field which exists a force on the induced dipole of particles and then recognizing it [1, 2, 3, 4].

DEP is a preferable technique because of several advantages as follows: (1) it’s ability to manipulate and characterize the biological cells with high efficiency, whereas the dielectric properties (permittivity and conductivity) of biological cells over a specific range of frequencies of electric field able to identify cells. (2) cheaper because it does not need any expensive reagents like other techniques.

The direction and magnitude of DEP force that is generated by a specific design of microelectrodes depend on the properties of applied electrical potential such as (frequency, amplitude, and waveform), the size of the particle and the dielectric properties (permittivity and conductivity) of the cells compared to the surrounding medium [5, 6]. The implementation of electrokinetic platforms based on PCB technology is a challenge not intended by many scientists, therefore, this article earns the importance of proving that the PCB technology is capable and efficient to implement the electrokinetic platform.

The PCB technology is preferred due to several advantages as follows: low cost, widely available, re-workable and excellent shelf life [7]. The microbeads are fabricated plastic microspheres which are usually used to evaluate the performance of DEP electrokinetic platform.

The main concept of this paper is to prove the capability of the proposed electrokinetic platform based on PCB technology to identify the biological cells and separate between different sizes of biological cells. Identifications and sorting of biological cells play an important role in many biomedical applications such as laboratory devices. The rest of paper is categorized as follows: Sect. 2 illustrates the theory of dielectrophoresis phenomena. Section 3 shows the design of the proposed electrokinetic platform (twDEP microelectrodes array and levitation DEP microelectrodes). Section 4 presents a 2D model of the proposed electrokinetic platform and the tested particles (microbeads, platelets, and RBCs). The simulation results of the traveling wave DEP forces and levitation DEP forces which are existed on particles (microbeads 10 µm, 20 µm, platelets, and RBCs) are described in Sect. 5. Finally, Sect. 6 concludes this paper and summarizes the advantages of the presented model based on the simulation results.

2 Theory of Operation

The DEP phenomena depict the net force which is generated on polarizable particles because of a non-uniform electric field. The governing equation of the DEP force is: \( {\text{FDEP}} = (\rho \cdot \nabla ){\text{E}} \), where \( \rho \) is the effective polarization induced in the particle, \( {\nabla } \) is the gradient operator, and E is non-uniform electric field [9]. Close to the electrode surface, a particle may subject into a traveling force [10]:
$$ {\text{FDEP}} = 2\uppi\varepsilon_{o} \varepsilon_{m} {\text{R}}^{3} [{\text{Re}}\left( {\text{Ke}} \right){\nabla }{\text{E}}^{2} + 2{\text{Im}}\left( {\text{Ke}} \right){\nabla }\,{\text{x}}\,(E_{I} \,{\text{x}}E_{R} )] $$
(1)
$$ {\text{E}} = E_{R} + {\text{j}}\,E_{I} $$
(2)
Where \( \varepsilon_{o} \) is the permittivity of free space, \( \varepsilon_{m} \) is the relative permittivity of the surrounding medium, R is the radius of particle, \( E_{R} \) is the real part of electric field, \( E_{I} \) is the imaginary part of electric field, Im is the imaginary part, Re is the real part of CM and [Ke] is the Clausius-Mossotti factor (CM factor). The CM factor can be estimated as follows [10]:
$$ {\text{Ke}}(\varvec{\omega}) = \frac{{\varvec{\varepsilon}_{{\varvec{p} - }}^{ *}\varvec{\varepsilon}_{\varvec{m}}^{ *} }}{{\varvec{\varepsilon}_{{\varvec{p} + 2 }}^{ *}\varvec{\varepsilon}_{\varvec{m}}^{ *} }} $$
(3)
$$ {\varvec{\upvarepsilon}}_{{\mathbf{p}}}^{ *} = {\varvec{\upvarepsilon}}_{{\mathbf{p}}} - \frac{{{\mathbf{i}} {\varvec{\upsigma}}_{{\mathbf{p}}} }}{{\varvec{\upomega}}},{\varvec{\upvarepsilon}}_{{\mathbf{m}}}^{ *} = {\varvec{\upvarepsilon}}_{{\mathbf{m}}} - \frac{{{\mathbf{i}} {\varvec{\upsigma}}_{{\mathbf{m}}} }}{{\varvec{\upomega}}} $$
(4)
Where \( \varepsilon_{p} ,\varepsilon_{m} \) are the permittivity of particle and surrounding medium and \( \sigma_{p} \,and\,\sigma_{m} \) the conductivity of particle and surrounding medium, respectively, ω is the angular frequency of the electric field, the permittivity and conductivity of the surrounding medium and the particle, furthermore, the frequency of the applied electric field able to change the direction and the magnitude of DEP force by changing the sign and the magnitude of CM factor. The working principle of levitation is generating area at which the electric field being weaker than the electric field at surrounding areas, consequently, particles subjected to an induced force by the field [10]:
$$ {\text{FDEP}} = 2\uppi\varepsilon_{m} {\text{R}}^{3} \,{\text{Re}}\,\left[ {\text{Ke}} \right]\nabla {\text{E}}^{2} $$
(5)
The shell structure is added to DEP force in case of blood formed elements to apply double shell model of platelets and RBCs for more accuracy. However, the single shell model is preferred to microbeads. The complex permittivity \( {\varvec{\upvarepsilon}}_{{\mathbf{p}}}^{ *} \) is replaced by equivalent complex permittivity \( {\varvec{\upvarepsilon}}_{{{\mathbf{eq}}}}^{ *} \) of particles [11, 12, 13]:
$$ {\varvec{\upvarepsilon}}_{{{\mathbf{eq}}}}^{ *} =\upvarepsilon_{sh}^{*} \frac{{\left( {\frac{{\varvec{r}_{\varvec{o}} }}{{\varvec{r}_{\varvec{i}} }}} \right)^{3} + 2\left( {\frac{{\varepsilon_{p}^{*} -\upvarepsilon_{sh}^{*} }}{{\varepsilon_{p}^{*} + 2 \upvarepsilon_{sh}^{*} }}} \right)}}{{\left( {\frac{{\varvec{r}_{\varvec{o}} }}{{\varvec{r}_{\varvec{i}} }}} \right)^{3} - \left( {\frac{{\varepsilon_{p}^{*} -\upvarepsilon_{sh}^{*} }}{{\varepsilon_{p}^{*} + 2 \upvarepsilon_{sh}^{*} }}} \right)}} $$
(6)
where \( \varvec{r}_{\varvec{o}} \) and \( \varvec{r}_{\varvec{i}} \) are the outer and inner radius of the particle shell, respectively; \( \upvarepsilon_{sh}^{*} \) is the complex relative permittivity of the outer shell.

3 The Proposed Electro-Kinetic Platform

The microelectrodes array of twDEP configuration can be designed through numerous shapes such as (1) a concentric rings structure [14], (2) a planar linear interdigitated array [15]. The concentric rings micro-electrodes array is preferred because it leads to reduce the size of the electrokinetic platform. It increases the intensity of electric filed at the center line of electrodes due to its roundness of electrodes [16]. Furthermore, it is compatible with PCB technology as shown in Fig. 1.
Fig. 1.

The geometry and the applied electrical potential of (A) Traveling wave Configuration, and (B) Levitation Configuration.

The microelectrodes for DEP levitation configuration are categorized as three types: a cone plate levitation system, Ring dipole levitation system and a quadrupole levitation system [9]. The quadrupole microelectrodes design is preferred because of the difficulty of implementation of the first and second configuration using PCB technology as shown in Fig. 1.

4 2D Model of Microelectrodes Array

COMSOL Multiphysics 5.0 is preferred to simulate the proposed microelectrodes of the electrokinetic platform of traveling and levitation for manipulation and separation of (different sizes of microbeads, platelets and RBCs). The procedures of the model are subjected to two main stages as follows: a preprocessing stage including space dimension, applied physics and study, and a processing stage including the geometry, materials and applied physics conditions as shown in Fig. 2.
Fig. 2.

Flow chart of COMSOL model.

In processing stage, the geometry of the proposed electrokinetic platform is divided to two configurations as follows: (1) four concentric rings microelectrodes have a width of 150 µm, a space between each two successive electrodes of 450 µm, the radius of the first ring is 450 µm as shown in Fig. 1. (2) The system consists of four squares for levitation which are diverged at 100 µm, have 100 µm rib as shown in Fig. 1. The properties of materials of microelectrodes and platform substrate are defined using COMSOL material library. However, the properties of the tested particles and its’ mediums are defined as shown in Table 1. Furthermore, the applied electrical potential on both traveling and levitation configurations is described in Fig. 1. Firstly, for traveling configuration, 10 Vpp, 100 kHz Square wave in the sequence 0°–90°–180°–270° phase shift. Secondly, for levitation configuration, 10 Vpp, 100 kHz Square wave where 0° phase shift on two opposite squares and 180° phase shift on the other opposite squares. Normal physics controlled mesh option is preferred for the meshing of the proposed model which automatically creates meshes that are adapted to the physics in the model.
Table 1.

The properties of the tested particles and its’ mediums.

Particles type

Diameter

Permittivity

Conductivity

Microbeads

10 µm

20 µm

2.5 [18]

1E-12 S/m [18]

Platelets [12, 13, 14]

1.8 µm

50

0.25 S/m

RBCs [12, 13, 14]

5 µm

59

0.31 S/m

The properties of the shell of platelets and RBCs

The shell of

Thickness

Permittivity

Conductivity

Platelets [12, 13, 14]

8 nm

6

1 µS/m

RBCs [12, 13, 14]

9 nm

4.44

1 µS/m

The properties of Medium of particles

Medium

 

Permittivity

Conductivity

Deionized Water

 

78.5 [18]

5E-5 S/m [18]

Blood [12, 13, 14]

 

80

55 mS/m

5 Results and Discussion

In this part, the detailed results were presented to prove the ability of the proposed electrokinetic platform based on PCB technology in manipulating and separating different sizes of biological particles with high efficiency. All figures are produced by COMSOL unless otherwise stated. The motion of microbeads and blood formed elements under the effect of the DEP forces which is produced by both twDEP and levitation configurations is shown in Fig. 3.
Fig. 3.

The spread or particles above twDEP configuration, (A) the initial random spread, (B) the alignment of microbeads and (C) the alignment of blood formed elements. the spread or particles above levitation configuration, (D) the initial random spread, (E) the alignment of microbeads, and (F) the alignment of blood formed elements.

However, the separation of particles based on electrokinetic highly dependent on the different velocities of animated particles according to the particles kinetic energy under the effect of the proposed platform.

Figure 3(A) presents the initial random spread of particles (microbeads and blood formed elements) above the twDEP configuration before applying an electrical potential. Figure 3(B) presents the alignment of microbeads because of twDEP force. However, Fig. 3(C) presents the alignment of blood formed elements (platelets and RBCs) because of twDEP force. Figure 3(D) presents the initial random spread of particles (microbeads and blood formed elements) above the levitation configuration before applying an electrical potential. Figure 3(E) presents the alignment of microbeads because of levitation force. However, Fig. 3(F) presents the alignment of blood formed elements (platelets and RBCs) because of levitation force after applying an electrical potential.

A comparison between different sizes of microbeads (10 µm and 20 µm), in addition to blood formed elements (platelets and RBCs) as respect of dielectrophoretic force and particles kinetic energy is presented in Figs. 4, 5, 6 and 7 to show the ability of the proposed electrokinetic platform to separate between different sizes of biological particles by acquiring it different kinetic energies to move with different velocities as a result of Dep forces which are generated on particles by two configurations (twDEP and levitation). Figure 4(A) and (B) show the variation between the applied DEP forces under the effect of both twDEP and levitation configurations on microbeads. It is noticeable that there is a large difference between the applied DEP forces on both types of microbeads (10 µm and 20 µm), where, the applied DEP forces due to both configurations on 20 µm of microbeads are greater than the applied DEP forces on 10 µm of microbeads. Figure 5(A) and (B) show the variation between the gained kinetic energy under the effect of both twDEP and levitation configurations by microbeads. It is noticeable that there is a large difference between the gained kinetic energy by both types of microbeads (10 µm and 20 µm), where, the gained kinetic energy due to both configurations by 20 µm of microbeads is greater than the gained kinetic energy by 10 µm of microbeads. Figure 6(A) and (B) show the variation between the applied DEP forces under the effect of both twDEP and levitation configurations on blood formed elements (platelets and RBCs). It is noticeable that there is a large difference between the applied DEP forces on both types of blood formed elements (platelets and RBCs), where, the applied DEP forces due to both configurations on RBCs are greater than the applied DEP forces on platelets.
Fig. 4.

A comparison between two different sizes of microbeads 10 µm and 20 µm in DEP force (A) under the effect of the levitation configuration, and (B) under the effect of the twDEP configuration.

Fig. 5.

A comparison between two different sizes of microbeads 10 µm and 20 µm in particle kinetic energy: (A) under the effect of the levitation, and (B) under the effect of the twDEP.

Fig. 6.

A comparison between platelets and RBCs in DEP force (A) under the effect of levitation force, and (B) under the effect of the twDEP force.

Fig. 7.

A comparison between platelets and RBCs in Particle kinetic energy (A) under the effect of levitation force, and (B) under the effect of the twDEP force.

Figure 7(A) and (B) show the variation between the gained kinetic energy under the effect of both twDEP and levitation configurations by blood formed elements (platelets and RBCs). It is noticeable that there is a large difference between the gained kinetic energy by both types of blood formed elements (platelets and RBCs), where, the gained kinetic energy due to both configurations by RBCs is greater than the gained kinetic energy by platelets.

6 Conclusion

A 2D model of DEP electro-kinetic platform (twDEP and levitation configurations) based on PCB technology for separation of different sizes of biological particles such as microbeads and blood formed elements (platelets and RBCs) is described and explained. The simulation results show that there is a large difference in the applied DEP forces and particles kinetic energy (make particles move with different velocities) between different sizes of microbeads (10 µm and 20 µm) and different sizes of blood formed elements (platelets and RBCs), consequently, this confirm that the preferred electrokinetic platform able to separate between different sizes of biological particles such as (platelets and RBCs), where it is known that platelets are the smallest cells in blood, consequently, the proposed electrokinetic platform based on PCB technology is a good candidate to separate between the different biological particles.

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Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Reda Abdelbaset
    • 1
    • 2
  • Yehya H. Ghallab
    • 1
    • 2
  • Hamdy Abdelhamid
    • 2
  • Yehea Ismail
    • 2
  1. 1.Biomedical Engineering DepartmentHelwan UniversityHelwanEgypt
  2. 2.Center of Nano Electronics and Devices (CND) at Zewail City of Science and TechnologyThe American University in Cairo (AUC)CairoEgypt

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