Numerical investigation of ternary particle separation in a microchannel with a wall-mounted obstacle using dielectrophoresis

The ability to precisely manipulate target particles/cells from a complex mixture is essential in many applications of biology, medicine, engineering, and chemistry [1], [2], [3], [4], [5]. In recent decades, microfluidic technologies have become efficient tools for particle/cell manipulation due to their numerous advantages, such as using low sample and reagent volume consumption, low cost, high accuracy, short process time, high product purity, and high sensitivity and selectivity [6], [7]. Many particle separation techniques have been introduced in microfluidic platforms, generally categorized into passive and active methods [8], [9], [10]. Passive methods such as inertial, hydrodynamic filtration, and deterministic lateral displacement do not use external forces [11]. On the contrary, active methods such as flow cytometry, acoustophoresis, magnetophoresis, electrophoresis, dielectrophoresis (DEP), and optic use an external field to manipulate particles [12], [13]. Active methods deliver more accuracy, controllability, and separation efficiency than passive methods, hence widely investigated as potential alternatives [6], [9], [14]. Among all existing active methods, DEP has emerged as an effective and promising technique to manipulate particles and cells in microfluidic platforms [15], [16].

DEP occurs when a polarized particle interacts with a non-uniform electric field [16]. Depending on the polarization of the particle and medium, the particle can experience negative DEP (nDEP) or positive DEP (pDEP). If the polarization of the particle is higher than that of the medium, the particle will experience pDEP, and it will tend to move toward regions with higher electric field gradients. On the other hand, if the polarization of the medium is higher than the particle, the particle will experience nDEP, and it will deflect from the high-gradient regions. DEP-based methods for particle separation can be divided into continuous and batch methods [17]. In batch separation, one type of particles is trapped by the DEP force (nDEP or pDEP) while the other is suspended in the solution; the one that is suspended can be separated first. The early DEP microdevices have given insight into the method of batch particle separation [18], [19], [20], [21]. In recent years, the continuous separation approach has attracted more attention than the methods of batch separation due to its higher throughput and suitability for lab-on-a-chip (LOC) applications. As mentioned earlier, the presence of a non-uniform electric field is necessary to create DEP force. Various electrode structures have been proposed to create non-uniform electric field. Regarding the non-uniform electric field formation, DEP devices can generally be divided into insulator-based DEP (iDEP) and electrode-based DEP (eDEP). In iDEP devices, external electrodes and in-channel insulators are employed to create a non-uniform electric field [22], [23]. Insulators in the channel, such as posts, hurdles, or channel walls, squeeze the electric field to create local electric field gradients.

In eDEP devices, microelectrodes are placed inside the channel at a minimal distance from each other and create strong electric field gradients. Different electrode configurations such as interdigitated, castellated, oblique, curved, microwell, extruded, matrix and quadrupole are designed and used for continuous and batch separation in eDEP devices [24]. Among all electrode configurations, planar-angled electrode pairs are one of the most popular ones because of their simple manufacturing process and low cost, which have been repeatedly used for continuous separation. Alazzam et al. [25] presented a microfluidic device for continuously separating circulating tumour cells (CTC) from normal blood cells. The device consists of comb-liked planar electrode pairs, placed divergent and convergent to the flow for cell focusing and separation, respectively. Yunus et al. [26] examined the size-based separation of colloidal latex particles (1 μm particles from 0.5 μm ones and 2 μm particles from 1 μm ones) by utilizing planar-angled electrodes on the bottom and top of the channel. Azpiroz et al. [27] presented an innovative microelectrode structure for the size-based separation of microparticles. This device can precisely separate 5 μm particles from 10 μm ones. Dalili et al. [14] investigated the geometrical parameters of planar-angled electrodes to achieve higher throughput in the continuous manipulation of polystyrene (PS) particles.

Although many studies have been conducted on the continuous separation of particles using DEP, most of them cover the binary separation of particles. Of course, research for continuous separation of more than two types of particles have also been reported, but their number is limited. Kim et al. [28] presented a multitarget DEP-activated cell sorter chip (MT-DACS) containing two independent planar-angled electrode arrays for the ternary separation of particles/cells. They separated three types of PS particles, including 2, 5, and 10 μm particles. Using this device, they also successfully separated three distinct bacterial clones. Vahey and Voldman [29] introduced a microfluidic equilibrium separation method for the ternary separation of PS particles (1.6, 1.75, and 1.9 μm) in a medium with an electrical conductivity gradient. In this method, the separation of particles depends on equalizing their electrical conductivity with medium conductivity. When the particles arrive at a position where their conductivity is equal to the medium conductivity, they do not experience DEP force and only move along the flow direction towards the desired outlets. However, it should be noted that using a medium with an electrical conductivity gradient adds to the complexity of the device. Han et al. [30] presented a microdevice containing a planar interdigitated electrode array at an angle as a function of the particle size, enabling size-based separation of three types of PS particles (3, 5, and 10 μm). The microchannel is divided into three regions, each with an electrode array placed at a distinct angle concerning the flow direction. Recently, they introduced a microdevice containing a planar-angled electrode array for monitoring and quantifying the distribution of intracellular lipid levels of given microalgal cell populations [31]. Chuang et al. [32] performed a ternary separation of 1, 2.5, and 4.8 μm PS particles using a microdevice containing planar-angled electrode pairs. Hajari et al. [33] designed a microfluidic device containing two non-parallel planar-angled electrodes for separating different particles/cells according to their size. Dalili and Hoorfar [34] investigated the performance of sheath-assisted and sheathless microfluidic devices containing planar-angled electrode arrays for ternary separation of PS particles (5, 10, and 15 μm). The results showed that the sheathless design could achieve the highest throughput while the weak sheath-assisted design could achieve the highest yield and purity. They suggested combining the DEP focusing and weak sheath flows to reach the highest sample separation yield. Recently, we presented an advanced microfluidic device containing an innovative electrode structure named bi-gap electrode pair, capable of continuous separation of three different populations of particles, including 5, 10, and 20 μm PS particles using DEP [35]. This novel microdevice can process a maximum flow rate of 100 μLh−1 (25 μLh−1 for sample) with high purity using a 20 Vpp sinusoidal electric voltage. Table 1 presents the primary papers published in the last few years on the continuous separation of more than two types of particles/cells using DEP. Compared to the binary separation of particles, reported studies on separating more than two types of particles are relatively rare. Indeed, the continuous separation of more than two types of particles by DEP has always been challenging. In most of the research conducted in this field, complications such as using a complex electrode structure, using several independent electrode arrays, or applying special conditions in the medium, such as creating a gradient in its electrical conductivity, have been imposed on microfluidic systems. Ergo, several challenges such as the complexity of the manufacturing process, the reduction in purity and separation efficiency, the reduction in controllability and selectivity, and the increase of system sensitivity to disturbances such as the slight fluctuation of the syringe pump appear. These problems make it very difficult to achieve integrated, portable, and point-of-care microfluidic systems and limit the application of these systems to the research scale.

This paper presents the design of a 3D microchannel with a wall-mounted obstacle for the continuous separation of three different populations of particles (including 5, 10, and 20 μm PS particles) using DEP. The designed microchannel, which has one inlet and three outlets, consists of the focusing and separation zones. In the focusing zone, a planar-angled electrode pair at the bottom of the channel provides an appropriate DEP force to focus all the particles on one side of the channel. The separation zone consists of a planar-angled electrode pair at the bottom of the channel and a trapezoidal obstacle on the channel wall. Due to the presence of an obstacle in the microchannel and the resulting reduction in cross-section, the flow velocity increases locally. This local velocity gradient formed across the channel is the key factor in separating the three sizes of particles. To our knowledge, this is the first paper that employs a drag force gradient in a DEP separator design to separate three types of particles. Small particles pass over the electrode pair without significant deviation in the separation zone (due to the weak DEP force exerted on them) and go toward the first outlet. On the other hand, larger particles (10 and 20 μm) are deflected along the electrode pair due to experiencing a stronger DEP force. However, after reaching the high-velocity area, 10 μm particles pass over the electrode pair and go toward the second outlet. Due to the even stronger DEP force, the 20 μm particles are further deflected to the end of the electrode pair length in the lateral direction. An OpenFOAM code is developed to simulate and investigate the movement of particles in the microchannel. Further, the code is validated by comparing simulation results with performed experimental tests. After that, the effect of various operational and geometrical parameters such as obstacle height, applied voltage, electrode pairs angle, and flow rate on the separation of particles is investigated, and the results are analyzed in detail.

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