Micro-magnetofluidics in microfluidic systems: A review

Sensors and Actuators B 224 (2016) 1–15

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Sensors and Actuators B: Chemical journal homepage: www.elsevier.com/locate/snb

Review

Micro-magnetofluidics in microfluidic systems: A review Ruey-Jen Yang a , Hui-Hsiung Hou a , Yao-Nan Wang b , Lung-Ming Fu c,d,∗ a

Department of Engineering Science, National Cheng Kung University, Tainan 701, Taiwan Department of Vehicle Engineering, National Pingtung University of Science and Technology, Pingtung 912, Taiwan c Graduate Institute of Materials Engineering, National Pingtung University of Science and Technology, Pingtung 912, Taiwan d Department of Biomechatronics Engineering, National Pingtung University of Science and Technology, Pingtung 912, Taiwan b

a r t i c l e

i n f o

Article history: Received 22 July 2015 Received in revised form 14 October 2015 Accepted 16 October 2015 Available online 19 October 2015 Keywords: Micro-magnetofluidics Ferrofluid Magnetic nanoparticles Magnetic field Microfluidics

a b s t r a c t Ferrofluids have many traditional applications in the electrical, mechanical and optical fields, including transformers, dampers, imaging systems, and so on. However, in more recent years, the potential provided by ferrofluids to manipulate tiny quantities of liquid by means of external magnetic fields has attracted great interest in the microfluidics domain; resulting in the emergence of a new branch of scientific known as micro-magnetofluidics. This study reviews recent applications of micro-magnetofluidics techniques to six common microfluidic functions, namely micromixing, pumping, focusing, sorting, droplet formation and transfer phenomena. For each function, the fundamental interaction mechanisms between the ferrofluid and the magnetic field are described and the main experimental and numerical results are discussed. Crown Copyright © 2015 Published by Elsevier B.V. All rights reserved.

Contents 1. 2.

3.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Ferrofluidic applications in microfluidic systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 2.1. Mixing [7–36] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 2.2. Pumping and valve [37–60] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 2.3. Focusing [61–78] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 2.4. Sorting [79–95] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 2.5. Droplet formation [96–119] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 2.6. Transfer phenomena [120–140] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 Acknowledgement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 Appendix A. Supplementary data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 Biography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

1. Introduction Microfluidic systems have many advantages over their traditional macroscale counterparts, including a large surface-tovolume ratio, a fast reaction time, a low cost and a minimal sample/reagent consumption. Consequently, as micro-electromechanical systems (MEMS) techniques have matured, a wide

∗ Corresponding author at: Department of Biomechatronics Engineering, National Pingtung University of Science and Technology, Pingtung 912, Taiwan. E-mail address: [email protected] (L.-M. Fu). http://dx.doi.org/10.1016/j.snb.2015.10.053 0925-4005/Crown Copyright © 2015 Published by Elsevier B.V. All rights reserved.

variety of microfluidic devices for use in the industrial, chemical, biological and medical fields have been proposed [1]. In traditional microfluidic devices, the fluid flow is manipulated by external pressure driving forces or electrical fields. However, while such methods enable the precise control of extremely small quantities of sample and/or reagent, they have several disadvantages, including larger Joule heating effects, vary sensitive to contamination, and at least in its major applications in analysis. Thus, the potential for manipulating the fluid flow in microfluidic channels via magnetic forces has attracted growing interest in recent years. To achieve this goal requires the use of so-called ferrofluids, namely colloidal suspensions of single domain magnetic

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Fig. 1. Schematic illustration of ferrofluid-driven micromixer for on-chip titration of bilirubin and HSA. Reprinted from Ref. [8] with permission of John Wiley and Sons.

particles in a carrier liquid [2]. The particles typically have a diameter of around 5–20 nm, and are composed of a magnetic material such as maghemite, magnetite or cobalt ferrite. In operation, the nanoparticles are kept suspended in the carrier fluid by either an electrical double layer (EDL) or a surfactant/polymer coating, and undergo both translational and rotational Brownian motion under the effects of a magnetic field. The magnetic fields become increasingly controlled by the flexible arrangement of external or internal magnets in a microfluidic environment, and thus, they can effectively enhance the capability of manipulating magnetic particles. Many studies have demonstrated the feasibility of achieving a precise control over the response and properties of ferrofluids through an appropriate manipulation of the external magnetic force [2]. Accordingly, the integration of magnetic manipulation technology with microfluidics has advanced rapidly in the biological and chemical fields, and has given rise to a new scientific field known as micro-magnetofluidics [3,4]. The literature contains several excellent studies on the design of magnetic systems [5] and the interactions between magnetism and microfluidics [6]. The present paper provides a comprehensive review of recent studies on the application of micro-magnetofluidics to six common microfluidic operations, namely mixing, pumping, particle focusing, cell sorting, droplet formation and transfer phenomena. For each application, the main principles of the proposed approach are introduced and discussed and the corresponding experimental and numerical results described. In general, the review provides a useful insight into the latest developments in the micro-magnetofluidics field and will hopefully serve to inspire further work in the field in the future.

Cao et al. [10] proposed a simple active microfluidic mixing device in which fluid mixing was achieved under the effects of periodic magnetic body forces induced by a hybrid magnetic field consisting of a static gradient magnetic field and an external AC uniform magnetic field. The performance of the proposed device was evaluated by means of two-dimensional COMSOL Multiphysics simulations. It was shown that the mixing system achieved a mixing efficiency of around 97–99% within 8 s at a distance of 600 ␮m from the mixing channel inlet. Hajiani and Larachi [11] performed Taylor dispersion tests in a capillary tube in which suspended magnetic nanoparticles (MNPs) were subjected to a low Reynolds number shear flow field and three different types of magnetic field, namely a uniform transverse rotating magnetic field (TRMF), a uniform transverse oscillating magnetic field (TOMF), and a uniform axial static magnetic field (ASMF) (Fig. 2). The results showed that the TRMF mode increased the degree of lateral mixing. However, no significant change in the lateral mixing efficiency was observed

2. Ferrofluidic applications in microfluidic systems 2.1. Mixing [7–36] Oh et al. [7] developed a T-shaped micromixer in which chaotic advection mixing was achieved within the main channel via the magnetically-induced oscillation of two ferrofluidic slugs in parallel intersecting sub-channels. The mixing performance was investigated for various perturbation frequencies and flow rates. It was shown that the mixing rate and optimal mixing state were achieved as the Strouhal number increased from 0.2 to 0.4. Sun et al. [8] presented a PMMA microfluidic chip-CE device with a multi-segment circular-ferrofluid-driven micromixing injector (Fig. 1). In the proposed device, bilirubin, HSA and buffer solution were introduced into the circular mixing channel by means of a high-voltage microfluidic power supply. The bilirubin-HSA solution was then mixed by rotating a ferrofluidic plug around the circular channel under the effects of a translating magnet. The experimental results showed that the titration process between HSA and bilirubin could be successfully completed within three mixing cycles.

Fig. 2. (a) Schematic drawing depicts dispersion of a tracer blob in Poiseuille flow with parabolic laminar velocity profile. (b) Schematic of the experimental setup including two-pole three phase magnet and glass-made capillary tube at the center. (c) Upfront view of magnet with a capillary set vertically and coaxially with magnet bore, a uniform horizontal magnetic field imposed across capillary tube hosting a flow of MNP-laden suspension. Reprinted from Ref. [11] with permission of Elsevier.

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Fig. 3. Flow pattern with d = 250 ␮m and M = 80000 A/m. The velocity vectors are indicated by arrows, and the magnetic field contours are indicated by solid lines. The right figure shows the solute concentration distribution, where the arrows indicate the contact line between two fluids with different solute concentrations. Reprinted from Ref. [12] with permission of Elsevier.

in the TOMF mode. Finally, in the ASMF mode, the lateral mixing effect was suppressed by static field locks. Wei and Lee [12] proposed a high-performance magnetic fluid micromixer based on two offset tapered permanent magnets. Fig. 3 shows the magnetic field, flow pattern and species concentration distribution for the case of an inter-magnet offset distance of d = 250 ␮m and a saturation magnetization of M = 80000 A/m. It is seen that four vortex structures are formed in the central channel. These structures increase the interfacial contact area between the two species, and therefore improve the mixing performance between them. The authors in [16–19] proposed a magnetic microfluidic mixer in which an electromagnet driven by an AC power source was used to induce transient interactive flows between a ferrofluid and de-ionized (DI) water (Fig. 4). The external magnetic field caused the ferrofluid to expand significantly and uniformly toward the miscible water; resulting in the formation of an extremely large number of fine finger-like structures at the fluid interface in both the upstream and the downstream regions of the microchannel. The numerical and experimental results showed that a high mixing efficiency (>95.0%) was achieved within 2.0 s at a distance 0.3 mm downstream of the mixing channel inlet (Fig. 5, for color bar 1 ferrofluid, 0 DI water). Kitenbergs et al. [25] examined the feasibility of magnetic micro-convection as a mixing tool for microfluidics systems using an experimental setup consisting of a current-carrying

Fig. 4. Photograph of microfluidic mixer chip with AC-driven electromagnet. Reprinted from Ref. [16] with permission of John Wiley and Sons.

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coil and a Hele-Shaw cell. The evolution of the mixing performance over time was evaluated for various values of the magnetic field in the range of 0–13.3 mT (Fig. 6). The experimental results showed that a relative mixing efficiency of around ∼45% could be achieved over a large 0.5 mm distance in 0.4 s given the application of a magnetic field of less than 15 mT. Munir et al. [26] presented a magnetic micromixer comprising a mixing channel and two time-dependent current-carrying conductors. The effects of the magnetic particle size, inlet velocity of the fluid entering the system, and switching frequency of the magnetic field on the mixing performance within the channel were evaluated by means of two-dimensional COMSOL Multiphysics simulations. Concentration profiles were obtained both with and without magnetic actuation, respectively, and with and without mixing barriers at the top and bottom of the channel to create turbulent flow. Overall, the results showed that magnetically actuated mixing is more efficient than passive mixing strategies. Rida and Gijs [31] proposed a method for microfluidic mixing and assaying using self-assembled porous structures of magnetic microbeads referred to as magnetorheological structures (MRS). It was shown that the application of a local time-dependent magnetic field prompted a rotational motion of the MRSs, which led to an enhanced fluid mixing effect though the formation of rotating vortex flow structures (Fig. 7). The experimental results showed that a mixing efficiency of 95% could be achieved within a mixing distance of as little as 400 ␮m given a flow rate of 0.5 cm/s. Zhu and Nguyen [35] performed a numerical and experimental investigation into the mixing effect induced by the susceptibility gradient between a diamagnetic fluid and a ferrofluid. Notably, the mixing effect was achieved using a uniform magnetic field with an intensity of less than 10 mT. Fig. 8 shows the simulated velocity and concentration fields within the mixing chamber with and without a magnetic field, respectively. In the absence of a magnetic field, the pressure-driven flow follows stable paths from the inlet to the exit of the chamber, and mixing occurs primarily as a result of molecular diffusion. By contrast, when a magnetic field is applied, chaotic secondary flow structures are formed as a result of magnetic susceptibility mismatches, and hence the mixing performance is improved. The maximum mixing efficiency was shown to be around 90%. Table 1 shows the brief comparison for magnetic micromixer of other listed references. 2.2. Pumping and valve [37–60] Hatch et al. [37] presented a prototype microfluidic micropump, in which magnetically-actuated plugs of ferrofluid were used to achieve both pumping and valving functions. The proposed device consisted of a circular microchannel containing one stationary plug between the inlet and outlet of the channel and one movable plug, serving as a piston, which rotated around the channel under the effects of a translating magnetic field. The experimental results showed that the pump was capable of achieving a pumping rate of up to 8 ␮l/min with minimal backpressure given a stepping motor velocity of 8 rpm. Fu et al. [39,40] proposed a circular ferrofluidic micropump consisting of two ferrofluidic plugs contained within a PMMA microchannel and driven by a rotating stepping motor (Fig. 9). The proposed device was shown to achieve a maximum flow rate of 128 ␮l/min with zero pressure head given a channel width of 1000 ␮m and a stepping motor velocity of 10 rpm. Lok et al. [44] proposed a closed-loop polymerase chain reaction (PCR) system, in which a ferrofluidic plug was used to reduce the evaporation of the PCR sample in the thermal lysis step by blocking the opening of the circular PCR chamber. Sun et al. [45] presented a miniaturized PCR device in the form of a circular closed-loop ferrofluid-driven microchip (Fig. 10). In the proposed device, a small ferrofluidic plug was driven by an external magnet around the circular microchannel, thereby propelling the PCR

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Fig. 5. Comparison of simulated and experimental concentration distributions in the same upstream region of the mixing channel at t: (a) 0 s, (b) 0.5 s, and (c) 2.0 s. Reprinted from Ref. [18] with permission of John Wiley and Sons.

Fig. 6. (a) Snapshots of magnetic micro-convection development over time for various magnetic field strengths. (Note that field of view is 0.5 mm × 0.5 mm). (b) Spatiallyaveraged concentration time dependence given the magnetic fields shown in (a). Reprinted from Ref. [25] with permission of Elsevier.

Fig. 7. (a) Schematic diagram of the microfluidic structure and the iron parts. The photographs (b–e) are taken at different locations and represent the fluorescent intensity over the channel, (d) 20 Hz, and (e) 5 Hz. Reprinted from Ref. [31] with permission of American Chemical Society.

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Table 1 Microfluidic magnetic mixer. Ref.

First author

Year

Type

Channel width and height (␮m)

Mixing index

Kind of magnetic force

Material

[13] [14] [15] [20] [21] [22] [23] [24] [27] [28] [29] [30] [32] [33] [34] [36]

Lien Qian Ryu Mao Tsai Lee Affanni Roy Lin Lund-Olesen Holzinger Derks Zhou Vergauwe Wittbracht Ergin

2007 2005 2004 2007 2009 2009 2010 2009 2013 2008 2012 2011 2015 2014 2012 2015

Rotary micromixer MHD stirrers mixer Stir-bar mixer Active mixer Semi-active mixer Active mixer MHD stirrers mixer Microsphere-based mixer Active mixer Active mixer Active mixer Near-surface mixer Active mixer Digital microfluidics Active mixer Magnetic mixer

1000, 100 4000, 2000 400, 25 300, 103 300, 200 100, 10 1000, 500 n/r 40 mm × 40 mm (chip) 200, 200 n/r 100, 100 200, 60 1.4 mm × 1.4 mm (chip) 77, 14 n/r

93% 98% 98.55% 78% 95% 96% 90% 99% 95% 90% n/r n/r 99.64% n/r 90% n/r

Magnetic bead, 2.8 ␮m, DC MHD stirrer, DC Stir-bar, 16 ␮m thick, AC Magnetic nanoparticle, 10 nm, AC Fe3 O4 particle, 9 nm, Magnet Magnetic particle, 4 ␮m, AC MHD stirrer, AC Magnetic particle, 2.65 ␮m, DC Magnetic bead, 2.8 ␮m, DC Magnetic bead, 3 ␮m, AC Magnetic bead, 2 ␮m, EB-system Magnetic bead, 20 ␮m, gravitation Fe3 O4 nanoparticle, 20 nm, DC Ferromagnetic particle, 3 ␮m, DC Magnetic bead, 1.05 ␮m, DC Magnetic particle, 10 nm, DC

PDMS PDMS – glass PDMS PDMS PDMS – glass PDMS PCB – glass n/r PDMS Wafer Silicon n/r PDMS Glass wafer PDMS n/r

n/r: not report.

Fig. 9. Schematic illustration of circular ferrofluidic micropump [39].

Fig. 8. Simulated velocity and concentration fields in mixing chamber: (a) no magnetic field; and (b) with magnetic field. Reprinted from Ref. [35] with permission of Royal Society of Chemistry.

mixture sequentially through three different temperature zones. The results showed that the PCR amplification of a 500 bp lambda DNA fragment could be completed within 4 min. Chang et al. [48] developed a magnetically-actuated immunoassay chip

incorporating a circular microchannel, in which an analytical reagent was immobilized at four different reaction zones and the sample was rotated through each reaction zone in turn by means of a ferrofluidic plug actuated by a permanent magnet attached to the rotor of a stepper motor. Ashouri et al. [50] presented a PMMA micropump containing two ferrofluidic plugs, namely one plug to serve as an inlet/outlet valve and a second plug to serve as a piston in driving the working fluid. The performance of the proposed device was investigated using water as the working fluid. The experimental results showed that a flow rate of 135 ␮l/min and a backpressure of up to 255 Pa could be achieved given a pumping frequency of 1 Hz. Pal et al. [51]

Fig. 10. Ferrofluid-driven chip in which reaction mixture is driven sequentially through three different temperature zones by means of ferrofluidic plug in order to perform PCR. Reprinted from Ref. [45] with permission of Royal Society of Chemistry.

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Fig. 11. (a) Schematic of the thermomagnetic pump unit. (b) Close up of the heater. Reprinted from Ref. [51] with permission of Elsevier.

developed a miniature thermomagnetic pump, in which ferrofluid was driven through a glass capillary tube by means of suitably imposed temperature and magnetic field gradients (Fig. 11). It was shown that the pump was capable of producing a pressure head of approximately 345 Pa in the zero discharge condition and a maximum discharge rate of up to 1200 ml/min. Ando et al. [53] presented a ferrofluidic pump based on three ferrofluidic masses serving as a plunger and two valves, respectively. The performance of the pump was evaluated experimentally in terms of the valve drop pressure, the valve efficiency in the OPEN state, and the liquid volume handled per pumping cycle. The maximum flow rate was shown to be of the order of 0.9 ± 0.1 ml/min. Ozbey et al. [55] performed COMSOL Multiphysics simulations to investigate the ferrofluid pumping effect generated by the dynamic magnetic field produced by two rotating permanent magnets (Fig. 12). The simulation results showed that a maximum flow rate of 100 ␮l/s was achieved given a rotation angle of 30◦ . Mohammadzadeh et al. [57] performed unsteady threedimensional numerical simulations to compare the flow-head performance of nozzle-diffuser and Tesla valveless ferrofluidic micropumps (Fig. 13), respectively, at low working frequencies. The results showed that for all values of the working frequency,

Fig. 12. Magnetic field produced around mini-tube by two facing magnets. Reprinted from Ref. [55] with permission of Springer.

the nozzle-diffuser micropump achieved a greater flow rate than the Tesla type pump. However, for higher working frequencies, the Tesla micropump created a greater pressure head. Yamahata et al. [59] presented a plastic micropump consisting of two check valves designed to convert the periodic motion of a ferrofluidic plug into quasi-continuous flow. Using water as the working fluid, the pump achieved a flow rate of up to 30 ␮l/min and a backpressure of up to 25 mbar. Table 2 shows the brief comparison for magnetic micro-pump and -valve of other listed references. 2.3. Focusing [61–78] Focusing particles into a tight stream is an essential step in many applications, such as microfluidic cell cytometry and particle sorting. Liang et al. [61,62] proposed a method for focusing nonmagnetic particles carried by a ferrofluid flow through a T-shaped microchannel using a single permanent magnet (Fig. 14). In the proposed method, the particles were injected through one of the inlets of the T-shaped microchannel and were deflected away from the magnet as a result of a negative magnetophoresis effect. The particles were subsequently confined to the center plane of the channel by means of a water flow injected through the opposite side of the T-shaped channel. Wilibanks et al. [64] and Zeng et al. [65,66] presented methods for concentrating diamagnetic particles in ferrofluid flows by means of two repulsive or attractive magnets positioned symmetrically or asymmetrically on either side of a particle-flowing channel (Fig. 15). In general, the results showed that for a symmetric placement of the magnets, a pair of symmetric counter-rotation circulations of concentrated particles was formed in the microchannel, which increased in size and progressed in the

Fig. 13. Ferrofluidic micropumps with no-moving-part valves: (a) nozzle-diffuser, and (b) Tesla. Reprinted from Ref. [57] with permission of Springer.

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Table 2 Microfluidic magnetic pump and valve. Ref.

First author

Year

Type

Chamber or channel size

Flow rate

Kind of magnetic force

Material

[41] [42] [43] [46] [47] [49] [52] [54] [56] [58] [60]

Chiu Hartshorne Yamahata Haeberle Patel Kavˇciˇc Kang Shen Das Cai van den Beld

2012 2004 2005 2007 2007 2009 2011 2011 2013 2015 2015

Valveless pump Pump and valve Valve micropump Micropump MHD micropump Microscale pump MHD micropump Active-valve micropump MHD micropump Actuated valve Micropump

150 ␮m × 100 ␮m 50 ␮m × 40 ␮m Ø 0.7 mm Ø 5 mm 800 ␮m × 350 ␮m 12 ␮m × 6 ␮m 2 mm × 0.5 mm Ø 3 mm 0.5 mm × 0.5 mm 100 ␮m × 200 ␮m 100 ␮m × 23 ␮m

0.52 nL/min n/r 5 ml/min 0.9 ml/min 12.25 ␮l/min Pumping velocity 5 ␮m/s 2.83 ␮l/min 2.4 ml/min 24 ␮l/min n/r 0.3 nL/min

Micro-coil, DC Ferrofluid particle, magnet Eletromagnet, AC Stationary magnet, DC AC Silica bead, 2.6 ␮m, AC DC MHD Arc-shaped magnets, DC DC MHD Magnets AC

PDMS – glass Glass PDMS – glass PDMS n/r PDMS PDMS PDMS Polymeric PMMA – PDMS PDMS

n/r: not report.

Fig. 14. Diamagnetic particle focusing mechanism in T-shaped microchannel with single permanent magnet. Reprinted from Ref. [61] with permission of Springer.

downstream direction over time. By contrast, for an asymmetric placement of the magnets, a single asymmetric circulation of particles was formed in the channel, which remained approximately unchanged in both size and position as time elapsed. In addition, the results showed that the focusing effect improved with a reducing flow rate or an increasing magnetic particle size. Lee et al. [69] performed computational fluid dynamics (CFD) simulations to investigate the magnetic focusing of nanoparticles suspended in a ferrofluid flow through a T-shaped microchannel.

The results confirmed the experimentally-observed focusing effect reported in [62]. In addition, it was shown that the particle focusing effectiveness improved as the flow rate of the ferrofluid and water reduced. Cao et al. [71] performed COMSOL Multiphysics simulations to investigate the magnetic nanoparticle (MNP) concentration in a ferrofluid flow between two symmetrically positioned permanent magnets as a function of the inlet velocity, magnetic field strength, magnet geometry and remanent flux density orientation. The simulation results revealed that the MNP concentration

Fig. 15. Microfluidic chip for diamagnetic particle concentration: (a) magnet configuration utilized to embed the two attracting permanent magnets. (b) Photo of the microchip. (c) Ferrofluid micro-flow between two permanent magnets. Reprinted from Ref. [64] with permission of AIP Publishing LLC.

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Fig. 16. Liquid–liquid plug flow in cylindrical microchannel, and experimental setup. Reprinted from Ref. [73] with permission of AIP Publishing LLC.

reduced for higher values of the flow velocity and lower values of the magnetic field strength. By contrast, the MNP concentration increased with an increasing magnet height. Finally, it was found that when the remanent flux densities of the two magnets were orientated perpendicular to one other, the MNPs were repelled from both the center of the magnet system and the corner. Kurup and Basu [73] presented a passive technique for particle concentration in water-in-oil plugs based on the interaction between particle sedimentation and the recirculating vortices formed in plug flow in a cylindrical microfluidic channel (Fig. 16). The results showed that the concentration effect could be controlled by changing the flow velocity and enabled a particle collection efficiency of almost 100% to be obtained. Afshar et al. [75] presented a magneto-microfluidic technique for the threedimensional focusing of magnetic microparticles into a single streamline with longitudinal inter-particle spacing. It was shown that the proposed technique enabled the particles to be focused in the center of the channel with a one-by-one alignment using only a single sheath flow (and hence, a single external pump). Table 3 shows the brief comparison for microfluidic magnetic focusing of other listed references.

uniform particle mixture entering into the main-branch of the T-microchannel can be automatically divided into two distinct streams after passing through the magnet region. The sorted magnetic and diamagnetic particles will then each flow through one side-branch of the T-microchannel due to the even split of the ferrofluid flow at the T-junction, followed by a continuous collection at the corresponding outlet reservoir. Zeng et al. [85] proposed a method for separating cells of particles in a microchannel by means of two offset magnets. In the proposed approach, the first magnet focused the particle mixture to a single stream, while the second magnet displaced the aligned particles to different flow paths based on their size; enabling their continuous collection in the downstream region (Fig. 18). The feasibility of the proposed approach was demonstrated by separating polystyrene beads with diameters of 3 ␮m and 10 ␮m in 0.05 EMG 408 ferrofluid with an average flow rate of 0.6 mm/s. Song et al. [87] presented a fully-integrated electromagnetic cell sorting system capable of separating magnetic beads while maintaining a biocompatible temperature of 37 ◦ C by means of Joule heating in the electromagnet (Fig. 19). The experimental results

2.4. Sorting [79–95] Separating target particles [79] from a heterogeneous mixture is an important step in many chemical, biomedical and labeledcell applications [80,81]. Liang et al. [83] showed that replacing the diamagnetic aqueous medium in a T-shaped microchannel with a ferrofluid significantly improved the separation of magnetic and diamagnetic particles as a result of the opposite magnetophoresis effects exerted on the two types of particle (Fig. 17). The

Fig. 17. Separation mechanisms of magnetic and diamagnetic particles suspended in (a) 0.1 × EMG 408 ferrofluid, and (b) DI water.

Fig. 18. (a) Photo of microfluidics chip. (b) Separation mechanisms of diamagnetic particles and cells in ferrofluid flow through a straight microchannel using two offset magnets.

Reprinted from Ref. [83] with permission of AIP Publishing LLC.

Reprinted from Ref. [85] with permission of Elsevier.

R.-J. Yang et al. / Sensors and Actuators B 224 (2016) 1–15

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Table 3 Microfluidic magnetic focusing. Ref.

First author

Year

Type

Channel size

Kind of magnetic force

Material

[63] [67] [68]

Zabow Moser Liu

2002 2009 2009

Capillary focusing Magnet actuation Cell manipulation

300 ␮m × 50 ␮m 100 ␮m × 100 ␮m n/r

Magnet bead, 2.8 ␮m, DC Supermagnetic bead, 1.0 ␮m, magnet, AC Eletromagnet, magnetic bead, AC, DC

[70]

Karimi

2013

Focusing and sorting cells

n/r

Magnetic bead, DC, AC

[72] [76] [77] [78]

Ali-Cherif Kumar Munir Giudice

2012 2014 2014 2015

Magnetic tweezers Digital microfluidic Magnetic tagged Separation of magnetic particle

Ø 600 ␮m 160 ␮m × 160 ␮m 10 ␮m × 5 ␮m 200 ␮m × 50 ␮m

Magnetic particle, 80 nm, AC Dynabeads, 2.8 ␮m, AC Magnetic beads, 50–150 nm, AC Dynabeads, 10 ␮m, AC

PDMS PDMS PDMS glass PMMA PDMS glass PMMA n/r Glass wafer Numerical PDMS – glass

n/r: not report.

Fig. 19. Schematic illustrations of on-chip microelectromagnet/microfluidic system. (a) On-chip microelectromaget. (b) Microfluidic system. Reprinted from Ref. [87] with permission of Elsevier.

showed that the proposed device achieved separation efficiencies of 87.2%, 91.8% and 92.4% given applied currents of 0.5 A, 1.0 A and 1.5 A, respectively. Nawarathna et al. [89] presented a plastic microfluidic device with integrated nanoscale magnetic traps (NSMTs) for separating magnetic and non-magnetic beads in such applications as cell sorting and immunomagnetic cell separation. It was shown that the device achieved a high separation efficiency at flow rates in the range of 25–250 ␮l/min and provided a robust, rapid and simple solution for target species sorting in various pointof-care applications. Tasi et al. [92] presented a microfluidic system in which a magnetic field was used to sort paramagnetic beads by deflecting them in a direction normal to the microflow (Fig. 20). The numerical and experimental results showed that the distribution of the deflected beads at the channel exit depended on the bead size, the intensity of the magnetic field, the fluid velocity, the fluid viscosity, and the geometry of the channel. Table 4 shows the brief comparison for mcirofluidic magnetic sorting of other listed references.

current direction. It was shown both theoretically and experimentally that the peak velocity of the droplets increased with a higher magnetic field, a lower oil viscosity and a larger droplet size. The generation and manipulation of ferrofluidic droplets can be achieved either passively or actively. In passive methods, the droplets are formed and controlled using specific channel geometries such as L-junction or T-junction channels (Fig. 22) [105,106] and some form of flow-focusing technique [108–110]. However, such methods only allow the manipulation of droplets by hydrodynamic means. Consequently, Tan et al. [106] reported an active method for the formation and manipulation of ferrofluid droplets

2.5. Droplet formation [96–119] The formation of microdroplets in microchannels has been extensively studied and applied. However, there are very few studies on ferrofluid droplet generation in microchannels. The actuation concept described can be used for transport and sorting applications in droplet-based microfluidics. Nguyen et al. [96–98] investigated the kinematics and deformation of ferrofluid droplets driven by a pair of planar coils fabricated on either side of a double-sided printed circuit board (PCB) (Fig. 21). In performing the experiments, the ferrofluid droplets were polarized by a uniform magnetic field produced by a pair of permanent magnets and trapped in a virtual channel (potential well) formed by the two planar coils with the same current direction. Finally, the droplets were driven through the channel by the two coils with an opposite

Fig. 20. (a) Schematic illustration of microfluidic multi-target sorter. Note that inlets 1 and 2 are flow-focusing fluid inlets and inlet 3 is bead suspension inlet channel. (b) Flow of beads through separation channel adjacent to permanent magnet(s). Reprinted from Ref. [92] with permission of Royal Society of Chemistry.

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Table 4 Microfluidic magnetic sorting. Ref.

First author

Year

Type

Channel or chip size

Kind of cell

Kind of magnetic force

Material

[82]

Mirowski

2005

5 mm × 10 mm, chip

Magnetic particle

Wu

2010

60 mm × 32 mm, chip

Hematopoietic stem cell

[86]

Plouffe

2011

[88] [91]

Liang Kogot

2012 2014

Magnet bead, 1 ␮m, magnet Supermagnetic bead, 4.5 ␮m, AC Magnetic bead, 0.525 ␮m, magnet Particles, 5, 15 ␮m, magnet n/r

Silicon

[84]

Manipulation and sorting Counting and sorting

[93]

Pivetal

[94]

Hyun

2000 ␮m × 500 ␮m

MCF-7 cell

200 ␮m × 40 ␮m n/r

Polystyrene Escherichia coli (E. coli)

2014

Magnetic particle tagged cell Particles separation Microfluidic magnetic sorting Cell fishing

250 ␮m × 50 ␮m

E. coli, Acinetobacter

2015

Cell sorting

2000 ␮m × 400 ␮m

Circulating tumor cell (CTC)

Supermagnetic bead, 50 nm, magnet array Magnetic bead, 15 ␮m, magnet array

PDMS PDMS – glass PDMS n/r Silicon wafer – PDMS PDMS

n/r: not report.

simulations to investigate the formation process of ferrofluid droplets in a microfluidic flow-focusing configuration under a uniform magnetic field. The simulations focused specifically on the effects of the magnetic Bond number and susceptibility on the droplet size. The results showed that the volume of the droplet increased with an increasing Bond number and susceptibility. Wu et al. [110] investigated the formation and breakup dynamics of ferrofluid droplets in a microfluidic flow-focusing device given various flow rates and three different magnetic field conditions, namely no magnetic field (NM), radial magnetic field (RM) and axial magnetic field (AM) (Fig. 23). The experimental results showed that while the presence of a magnetic field increased the size of the droplets, the relative effect of the magnetic field reduced as the flow rate increased. Table 5 shows the brief comparison for microfluidic magnetic droplet of other listed references. 2.6. Transfer phenomena [120–140] Fig. 21. Manipulation of microferrofluid droplets using planar coils. Reprinted from Ref. [96] with permission of AIP Publishing LLC.

at a microfluidic T-junction using the magnetic field produced by a small permanent magnet with a diameter of 3 mm. It was shown that the presence of the magnet caused the single domain magnetite particles within the nanofluid to become aligned along the direction of the magnetic field and to form droplets as a result of the attraction force between them. In the absence of a magnetic field, the droplet size reduced with an increasing flow rate. However, given the presence of a magnetic field, the droplet diameter depended on a complex interaction between the magnetic field gradient, the magnetization of the ferrofluid, and the relative position of the magnet. Sheu et al. [108] investigated the two-phase flow focusing formation of water-based Fe3 O4 ferrofluid (dispersed phase) in a silicon oil (continuous phase) flow in a microfluidic flow-focusing microchannel for various values of the Capillary number (Ca) and flow rate ratio (Qr). Liu et al. [109] performed finite volume

Fig. 22. Formation of ferrofluid droplets at microfluidic T-junction. Reprinted from Ref. [105] with permission of AIP Publishing LLC.

Xuan et al. [120] used the Lattice-Boltzmann method to examine the flow and heat transfer properties of ferrofluids at the mesoscopic level. It was found that the flow and thermal processes were both sensitive to the direction and magnitude of the external magnetic field. For example, the heat transfer performance was enhanced when the magnetic field gradient was parallel to the direction of flow. Jafari et al. [122] conducted CFD simulations to investigate the heat transfer performance of a kerosene-based ferrofluid [123] in cylindrical geometries. The results revealed that an aggregation of the magnetic particles in the ferrofluid caused a reduction in the heat transfer performance. However, the heat

Fig. 23. Schematic diagram of the microfluidic device, and formation sequence of ferrofluid droplets in the dripping regime. Reprinted from Ref. [110] with permission of Royal Society of Chemistry.

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Table 5 Microfluidic magnetic droplet. Ref.

First author

Year

Type of droplet

Channel size

Droplet size

Kind of magnetic force

Material

[99]

Lehmann

2006

Static magnetic field

2 cm × 3 cm, chip

10 ␮l

PCB

[100]

Sin

2011

Magnetic and hydrodynamic driven

n/r

0.5–1 nl

[101]

Shibata

2011

Ø 200 ␮m

n/r

[104]

Poesio

2014

Lee

2014

Pillar arrays, Ø = 2 ␮m, h = 8 ␮m 200 ␮m × 50 ␮m

1–10 ␮l

[107]

Magnetic field, bidrop interface Ferrofluid droplets, DC and AC driven Magnet, DC driven

[112]

Nurumbetov

2012

Ø 1.62 mm

D 282–418 ␮m

[113]

Yoon

2013

Double-emulsion droplet, hydrodynamic driven Magnet driven

Magnet bead, 250 nm–6 ␮m Supermagnetic bead, 8.8, 2.8 ␮m, AC Ferrofluid, electromagnet Ferrofluid particle, 30 nm Magnet bead, 2.8 ␮m Fe3 O4 particle, 20 nm

400 ␮m × 50 ␮m

D 170–190 ␮m

[114]

Li

2014

W 100 ␮m

D 55–85 ␮m

[115]

Kim

2014

Khalil

2014

400 ␮m × 97 ␮m capillary Ø 179 ␮m n/r

D 63–102 ␮m

[116]

n/r

[117]

Moon

2014

500 ␮m × 55 ␮m

n/r

[118]

Brouzes

2015

50 ␮m × 25 ␮m

0.2 nl

[119]

Mats

2015

Janus droplet, DC electric field Magnetic and hydrodynamic driven Permanent magnet driven Microfluidic conformal coating, magnet driven Magnetic and hydrodynamic forces Magnetic and hydrodynamic driven

n/r

20 ␮l

11 nl

Fe3 O4 particle, 50 nm BiFeO3 , Fe3 O4 nanoparticles Fe3 O4 particle, 6.5 nm Magnet nanoparticles Non-spherical magnetic particles – 35 ␮m × 20 ␮m Magnetic particles Supermagnetic particle, 1 ␮m

Glass wafer

Glass PCB PDMS Glass capillary

PDMS PDMS PDMS, glass capillary Glass PDMS

PDMS Glass

n/r: not report.

transfer performance improved when the magnetic field was oriented perpendicular to the temperature gradient. Goharkhah and Ashjaee [128] and Ghasemian et al. [129] conducted a numerical investigation into the convective heat transfer performance of water-based Fe3 O4 ferrofluid in the presence of an alternating non-uniform magnetic field produced by eight line source dipoles imposed on several parts of the channel (Fig. 24). It was shown that

for each value of the alternating magnetic field frequency, the optimal value of the heat transfer was independent of the magnetic field intensity, but increased with an increasing Reynolds number. Lajvardi et al. [136] investigated the convective heat transfer behavior of Fe3 O4 water-based ferrofluid flowing through a heated copper tube under laminar conditions in the presence of a magnetic field. The heat transfer performance was found to improve as

Fig. 24. Variation over time of flow streamlines and temperature distribution around two adjacent magnetic dipoles (t1 = 12 s, t2 = 12.25 s and t3 = 12.5 s). Reprinted from Ref. [128] with permission of Elsevier.

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R.-J. Yang et al. / Sensors and Actuators B 224 (2016) 1–15

Table 6 Microfluidic magnetic transport. Ref.

First author

Year

Type

Channel size

Kind of transport

Kind of magnetic force

Material

[124]

Bau

2003

MHD controlled fluidic

n/r

Control fluidic

n/r

[125]

Lehmann

2008

Magnetic actuation

200 ␮m × 50 ␮m

Particle transport

[126]

Song

2009

Cell labeling

150 ␮m × 25 ␮m

Jurkat cell transport

[127]

Su

2015

Fish pathogen

7.4 cm × 5.9 cm, chip

NNV RNA 2 transport

[130]

García-Arribas

2011

GMI detection

Chamber, 10 ␮l

Particle transport

[131]

Afshar

2011

Particle size separation

200 ␮m × 100 ␮m

Particle transport

[132] [133]

Weng Hale

2013 2014

Magnetogas-dynamic flow DNA separation

n/r 75 mm × 25 mm, chip

Heat transfer DNA isolation

[134]

Chatterjee

2011

Microfluidic sensor

Particle transport

[137]

Fulcrand

2011

Magnetic actuator

100 ␮m × 100 ␮m, sensor width 78 ␮m 500 ␮m × 100 ␮m, micro-coil, 5 ␮m × 5 ␮m

Alumina particle, 10 ␮m, MHD Magnetic particles, 1–30 ␮m, AC Dynabead, 4.5 ␮m, magnet Magnetic bead, 4.5 ␮m, DC Silica particle, 2 ␮m, AC Dynabeads, 1.05 and 2.83 ␮m, magnet Electromagnet Dynabeads, 2.8 ␮m, magnet Magnetic bead, 1 ␮m, DC, AC Magnetic bead, 2.8 ␮m, DC, AC

Particle transport

Glass PDMS PMMA – glass COC PDMS Numerical Glass PDMS PDMS

n/r: not report.

the magnetic field intensity and ferrofluid concentration increased. Lai et al. [138] investigated the dynamic bioprocessing and microfluidic transport control of magnetic nanoparticles (MNPs) in laminar-flow devices (Fig. 25). A novel strategy was presented for exploiting the sharply reversible change in size and magnetophoretic mobility of the MNPs to perform bioseparation and target isolation under continuous flow processing conditions. The feasibility of the proposed strategy was demonstrated using a simple H-filter microfluidic system with fluorescently-labeled streptavidin complexed to biotinylated pH-responsive MNPs. The experimental results showed that around 80% of the target streptavidin was successfully captured by the H-filter given the application of a suitable magnetic field. Yassine et al. [140] presented a microfluidic chip for trapping and isolating cells tagged with superparamagnetic beads for selective treatment and analysis. In the proposed device, the tagged cells were first trapped in the main channel by soft ferromagnetic discs and then transported into side chambers for isolation by means of tapered gold conductive paths. The performance of the proposed device was evaluated experimentally using E. coli (K12 strand) tagged with 2.8 lm SPBs. The results confirmed that the E-coli cells were successfully trapped and isolated in the side chambers and were unharmed by the

magnetic transport processes. Table 6 shows the brief comparison for mcirofluidic magnetic transport of other listed references. 3. Conclusions This study has provided a comprehensive review of the main developments in the micro-magnetofluidics field in recent years. The review has focused specifically on the application of micro-magnetofluidics techniques to six common microfluidic applications, namely micromixing, pumping, focusing, sorting, droplet formation and transfer phenomena. For each of the considered applications, it has been shown that given the use of a ferrofluid with an appropriate concentration and a magnetic field with a suitable magnitude and orientation, a significant improvement in the device performance can be achieved relative to that obtained in the absence of a magnetic field. Overall, this review has confirmed the exciting potential of magnetic actuation as a means of manipulating tiny fluid flows within microfluidic architectures. Compared to traditional electrical- and pressure-based techniques, magnetic actuation schemes have several important advantages, including a simpler operation, a greater reliability, and the ability to control both the flow and the transfer properties of the manipulated fluid. The discussions within this review are necessarily somewhat brief. However, it is hoped that they will nonetheless provide a useful source of reference for those already working within the field, and will serve as an inspiration for those just entering the field or contemplating doing so. Acknowledgement The authors would like to thank the financial support provided by the Ministry of Science and Technology of Taiwan under grant no. MOST 103-2320-B-020-001-MY3, MOST 103-2221-E-020-025MY3, and MOST 103-2622-B-020-007-CC2. Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.snb.2015.10.053. References

Fig. 25. Schematic illustration of target analyte separation in microfluidic channel facilitated by pH-responsive magnetic nanoparticles under isothermal conditions. Reprinted from Ref. [138] with permission of Royal Society of Chemistry.

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Biographies Ruey-Jen Yang received the Ph.D. degree from the University of California at Berkeley in 1982. From 1982 to 1993, he was a Research Scientist and Engineer at Scientific Research Associates and Rockwell International. He moved back to Taiwan in 1993 and now he is a Professor of Engineering Science Department at National Cheng Kung University, Tainan, Taiwan, R.O.C. His research interests are microflow physics, computational fluid dynamics, vortex dynamics, and bifurcation theory. Hui-Hsiung Hou received the Ph.D. degrees in engineering science from National Cheng Kung University (NCKU), Tainan, Taiwan, R.O.C., in 2013. He is currently postdoc training with the Department of Engineering Science at NCKU. His graduate and postdoc work was focused on analysis and application of microfluid systems. Yao-Nan Wang received M.S. and Ph.D. degrees from the Department of Mechanical Engineering from National Cheng Kung University (NCKU), Taiwan, in 2003 and 2008, respectively. He is currently an Associate Professor in the Department of Vehicle Engineering at National Pingtung University of Science and Technology. His current research involves thermo-fluid engineering and integration of microdevices. Lung-Ming Fu received M.S. and Ph.D. degrees in Engineering Science from National Cheng Kung University (NCKU), Taiwan, in 1997 and 2001. He had his postdoc training in Department of Engineering Science at NCKU during 2002–2003. He is currently a professor in the Graduate Institute of Materials Engineering at National Pingtung University of Science and Technology. His research interests are in Microfluidic systems, MEMS fabrication technologies, Micro-sensor and Computational fluid dynamics.