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IEEE TRANSACTIONS ON APPLIED SUPERCONDUCTIVITY, VOL. 26, NO.

4, JUNE 2016 4401305

Targeting Behavior of Magnetic Particles Under


Gradient Magnetic Fields Produced by
Two Types of Permanent Magnets
Quanliang Cao, Zhen Wang, Bo Zhang, Yang Feng, Shaozhe Zhang, Xiaotao Han, and Liang Li

Abstract—Fully understanding the dynamics of particles in- magnetophoresis where gradient magnetic forces arise due to
duced by magnetic fields with considering particle–particle inter- external inhomogeneous magnetic fields created by either elec-
action is an interesting and important issue for delivering magnetic tromagnets or permanent magnets [10], [11]. Nevertheless,
particles to a target site with a high efficiency. For this purpose,
permanent magnets with horizontal and vertical magnetization when magnetic particles are exposed to an externally applied
directions respectively have been taken for generating two types magnetic field, the magnetized particles will also interact with
of gradient magnetic fields, which are applied to produce similar each other leading to the formation of chain-like structures
gradient magnetic forces while with different magnetic interac- aligned with the field direction [12], [13]. This aggregation
tion forces between particles. On this basis, the distributions of behavior has recently been applied for manipulating magnetic
particles under the two gradient magnetic fields are investigated
and compared using Monte Carlo simulations. The results show particles with the aid of dynamic magnetic fields [14]–[16].
that the concentrated particles have chainlike structures and their However, it is also could exert some effects on the particle
distributions are configuration dependent with the magnetization distribution in the target region and will give rise to some
direction of permanent magnets: parallel and perpendicular to the problems in actual applications of magnetic targeting. Take the
bottom line for horizontal and vertical magnetization directions, magnetofection for example [17], although magnetic particles
respectively. Above all, a detailed microscopy study reveals that
the movement trajectories of magnetic particles are affected by can be moved from top to bottom under the action of gradient
both transport and aggregation behavior of particles and the magnetic forces generated by permanent magnets placed below
microscopic visualizations of particle distributions in the target the cell culture, these magnetic particles will also aggregate
region are in agreement with simulation predictions. into multi-particle clusters along the applied magnetic field.
Index Terms—Aggregation behavior, gradient magnetic field, And when the magnetic field direction is perpendicular to the
magnetic particles, magnetic targeting. container bottom, the aggregation behavior will result in a poor
efficiency of particle-cell contact. Such similar problems are
I. I NTRODUCTION often ignored in the previous studies or avoided in the studies
of magnetic separation by use of very low particle concentra-
M AGNETIC manipulation of micro- and nano-particles
under the action of gradient magnetic fields has drawn a
lot of attentions because of its potential biological and chemical
tions for minimizing the influence of the aggregation behavior
[18]. However, relatively high magnetic particle concentrations
should be used in many practical applications and thus more
applications such as drug targeting for medical treatment [1],
studies should be taken to understand the dynamic behavior of
[2], gene delivery [3], [4] and particle separation [5], [6]. And
magnetic particles with considering the particle-particle inter-
applications of the technology in microfluidics have also at-
action for optimizing magnetic field distribution and improving
tracted growing interest recently due to the multiple advan-
the system performance.
tages of the microscale effect, which have been reviewed in
This article aims to investigate the influence of particle-
several excellent papers [7]–[9]. Typically, the motion behav-
particle interactions on the targeting process through using
ior of magnetic particles is considered to be determined by
two types of gradient magnetic fields produced by permanent
magnets with horizontal and vertical magnetization directions.
Manuscript received October 20, 2015; accepted December 29, 2015. Date The magnetic force distributions which determine where the
of publication January 5, 2016; date of current version February 29, 2016.
This work was supported in part by the National Natural Science Foundation magnetic particles are more likely to be transported and ag-
of China under Grant 51407083 and Grant 51577083, and by the Program gregated are calculated and analyzed for predicting the motion
for New Century Excellent Talents in University under Grant NCET-13-0225. behavior of magnetic particles. Then these predictions were
(Corresponding author: Xiaotao Han.)
Q. Cao, Z. Wang, Y. Feng, S. Zhang, X. Han, and L. Li are with the qualitatively validated through Monte Carlo simulations and
Wuhan National High Magnetic Field Center and the State Key Laboratory of microscopic visualizations in the experiments.
Advanced Electromagnetic Engineering and Technology, Huazhong University
of Science and Technology, Wuhan 430074, China (e-mail: xthan@mail.hust.
edu.cn). II. T HEORETICAL A NALYSIS AND S IMULATION
B. Zhang is with the Key Laboratory of High Voltage Field Test Technique
of SGCC, Hubei Electric Power Research Institute, State Grid Hubei Electric As schematically illustrated in Fig. 1, magnetic particles are
Power Company, SGCC, Wuhan 430077, China. suspended in a water droplet subjected to external gradient
Color versions of one or more of the figures in this paper are available online
at http://ieeexplore.ieee.org. magnetic fields, which are produced by two types of permanent
Digital Object Identifier 10.1109/TASC.2016.2514716 magnets (40 mm high, 40 mm long and 40 mm thick) with
1051-8223 © 2016 IEEE. Personal use is permitted, but republication/redistribution requires IEEE permission.
See http://www.ieee.org/publications_standards/publications/rights/index.html for more information.
4401305 IEEE TRANSACTIONS ON APPLIED SUPERCONDUCTIVITY, VOL. 26, NO. 4, JUNE 2016

where − m→ is the magnetic moment of particle i, r is the


i ij


magnitude of vector − r→
ij from particles i to j, →

n i and t ij denote

− −→ −→ − →
the unit vectors given by ni = mi /mi and tij = rij /rij . Take a
−→
two-particle system in Fig. 2 for example, Fpp can be given by
 
−→ μ0 m 1 m 2 1 − 3 cos2 θ
Fpp = −∇(E12 ) = − ∇ . (3)
4π r12 3

Based on (3), the arrow plots of the two components of


interaction forces (x-component and y-component) induced by
horizontal and vertical magnetic fields in a 2-D model are
given in Fig. 2(b) and (c), respectively. Results indicate that
the magnetic interaction force is directly related to magnetic
Fig. 1. Schematic diagram of magnetic targeting systems with two types
of permanent magnets. (a) Permanent magnet with magnetization along the field distribution, in which particle P_2 always has a tendency
x-axis. (b) Permanent magnet with magnetization along the y-axis. to move towards particle P_1 under the action of this force and
become paired with each other along the direction of external
magnetic field, assuming the position of particle P_1 remains
magnetization along x-axis and y-axis, respectively. The dis-
fixed. Meanwhile, it can be seen that this type of magnetic
tance between the center region of water droplet and the magnet
force can be generated as long as particles are magnetized and
upper surface is set as 50 mm.
thus it can be induced in both uniform and gradient magnetic
The motion behavior of magnetic particles in solutions is
fields.
governed by several factors such as magnetic force, viscous drag
According to the above analysis, it can be concluded that the
force, gravity and inertia. Since magnetic force is the main power
transport and aggregation behavior of magnetic particles could
source for inducing subsequent motion of particles, the magnetic
both exist in gradient magnetic fields and they could be affected
force induced by the magnetic interactions between particles
by the parameters of gradient magnetic force and magnetic
and field will be analyzed to qualitatively predict the possible
field, respectively. For predicting the dynamic behavior of
distributional patterns of particles in the target region for the
magnetic particles in gradient magnetic fields generated by the
two configurations of magnet system. When magnetic particles
two types of magnet system in Fig. 1, the spatial distributions
are subjected to a magnetic field, there are mainly two types of
of the two parameters in a square region (2 × 2 mm2 ) where
magnetic forces acting on the magnetic particles. The one is
−−→ the magnetic particles are located are shown in Fig. 3. The
known as gradient magnetic force Fmp for transporting magnetic remanent magnetic flux density of permanent magnets is set
particles towards the target region which can be expressed as [19] as 1 T in the simulation. For the two cases, the directions of
−−→ −→ −→ −→ −→ gradient magnetic force are both along the negative y-axis and
Fmp = μ0 Vp (Mp · ∇)Ha = μ0 Vp f (Ha )(Ha · ∇)Ha
 thus magnetic particles will be attracted towards the surface of
−→ −→ permanent magnet in Fig. 1. Their difference lies in the mag-
μ0 Vp χm (Ha · ∇)Ha Ha < χm Msp , unsaturated
= −−→ −→ netic field distribution in which the magnetic field generated
μ0 Vp (Msp · ∇)Ha Ha ≥ χm Msp , saturated
by the permanent magnet in Fig. 1(a) is along negative x-axis,
(1) while the magnetic field in the other case is along y-axis. This
means that magnetic particles could aggregate to form chain-
where μ0 presents the permeability of free space, χm means
like clusters in x-direction and y-direction in the two cases, re-
measured magnetic susceptibility, Vp is the particle volume,
−→ spectively. Therefore, it can be supposed that magnetic particles
Ha is the applied magnetic field intensity at the particle center, will be transported in the same direction but with two types of
−→ −−→
Mp is the magnetization of the particle and Msp is saturation movement trajectories leading to different particle distributions
−→ in the target region. This point can been clearly seen in Fig. 4,
magnetization. Here, Mp is assumed to vary linearly with the
field intensity up to a saturation value of Msp . It can be seen that in which the final distributions of particles under the two types
this type of magnetic force is related to both the field strength of gradient magnetic fields in Fig. 3 are investigated by use of
and gradient of external magnetic field, which means that the cluster-moving Monte Carlo method. Initial 150 particles with
magnetic particles will experience no force under a uniform a radius of 3.5 μm are randomly generated in the upper part of
magnetic field. a square area (500 μm × 500 μm) in the center of the region
The other type of magnetic force is the magnetic interaction of interest in Fig. 3. It can be seen that these particles both
−→ move to the bottom with chain-like structures for obtaining
force Fpp between magnetized particles, which can be ex-
an equilibrium state in the two cases. However, the distribu-
pressed as the gradient of interaction energy between particles
tional patterns of particles are distinctly different in which
Eij based on a dipole-dipole interaction [20]:
  the generated under the gradient magnetic field in Fig. 3(a)
−→ μ0 mi mj −
→ −→ →
− −
→ − → →
− are distributed along the bottom line in Fig. 4(b), while multi-
Fpp = −∇(Eij) = −∇ ni ·nj −3( ni · tij )(nj · tij )
4πrij 3 particle clusters in the other case are distributed perpendicular
(2) to the bottom line in Fig. 4(c). The maximum displacement
CAO et al.: TARGETING BEHAVIOR OF MAGNETIC PARTICLES UNDER GRADIENT MAGNETIC FIELDS 4401305

Fig. 2. Magnetic interactions between particles in a dipole–dipole system. (a) Scheme of the system. (b) Arrow plot of interaction force under an external magnetic
field along the x-axis. (c) Arrow plot of interaction force under an external magnetic field along the y-axis. The black arrow inside of particles in (a) presents
magnetization direction, and the blue curved arrow shows the schematic illustration of particle motion path.

of particles in the aggregation process cannot be well reflected.


Several different approaches including numerical method based
on magnetic dipole-dipole model [23] and direct numerical
simulations based on a fluid-structure interaction model [24]
could be used to solve these problems, which are outside the
scope of this paper.

III. E XPERIMENTAL I NVESTIGATION


To qualitatively confirm the simulation predictions, micro-
scopic visualizations of magnetic particle distribution in the
targeting process were carried out. The used magnetic particles
are superparamagnetic microspheres produced by Spherotech.
The mean radius of these microspheres is approximately 3.5 μm
with a measured magnetic susceptibility of about 0.8 in the case
of low field. The motion of magnetic particles was recorded by a
Nikon SMZ-18 Stereo-Microscope with a built-in CCD-camera
producing up to 30 frames per second. The water droplet con-
taining magnetic particles with a volume fraction of 0.5% was
dripped on a toughened glass plate and was positioned 50 mm
away from the edge of permanent magnets. The centers of water
droplet and permanent magnets are kept in the same horizontal
plane in the experiments.
Fig. 5 presents the time evolution of particle distribution un-
der gradient magnetic field produced by the permanent magnet
with magnetization along x-axis. It can been seen that many
Fig. 3. Contour of magnetic flux density and arrow plots of magnetic field and
gradient magnetic force in a region of interest (2 × 2 mm2 ). (a) For permanent chain-like structures parallel to x-axis exist in Fig. 5(a) and this
magnet system in Fig. 1(a). (b) For permanent magnet system in Fig. 1(b). point is consistent with simulation results in Fig. 3(a) that the
direction of applied magnetic field in this case is along negative
x-axis. These chains move from top to bottom in the given
in one trial move and total steps in the simulations are set as photos under the action of gradient magnetic forces and the
1 μm and 90 000, respectively. The simulation data of applied lengths of these chains gradually become longer in the transport
magnetic fields for Fig. 4(b) and (c) are obtained by solving process since the neighboring small clusters have a tendency
the magnetostatic model in Fig. 1(a) and (b) via COMSOL to combine together, which can be clearly seen in the dotted
4.3b. Then these discrete data are transferred into MATLAB boxes in Fig. 5(a) and (b). Then after a while, magnetic particles
for interpolation and the following Monte Carlo simulations. are concentrated in the target region (the edge of water droplet)
The corresponding physical models and simulation procedure with an approximately linear structure along the horizontal axis
can be referred to existing Monte Carlo simulations [21], [22]. under combined action of transport and aggregation behavior,
Here, it should be noted that the presented simulations are shown in Fig. 5(c). This point is basically in accordance with
mainly used to predict the possible aggregate structures of nu- the simulated prediction relevant to aggregate structures of par-
merous magnetic particles under the action of magnetic fields, ticles in Fig. 4(b). For the sake of contrast, the magnetic particle
in which the hydrodynamic effect and detail dynamic behavior distribution under the gradient magnetic field produced by the
4401305 IEEE TRANSACTIONS ON APPLIED SUPERCONDUCTIVITY, VOL. 26, NO. 4, JUNE 2016

Fig. 4. Distribution of magnetic particles under gradient magnetic fields. (a) Initial distribution of particles in the absence of magnetic field. (b) Final distribution
of particles under magnetic field in Fig. 3(a). (c) Final distribution of particles under magnetic field in Fig. 3(b).

Fig. 5. Microscopy images of the distribution of magnetic particles under the action of a gradient magnetic field generated by the permanent magnet system in
Fig. 1(a) at different times. (a) t = 15 s. (b) t = 30 s. (c) t = 70 s.

Fig. 6. Microscopy images of the distribution of magnetic particles under the action of a gradient magnetic field generated by the permanent magnet system in
Fig. 1(b) at different times. (a) t = 30 s. (b) t = 45 s. (c) t = 75 s.

other permanent magnet system in Fig. 1(b) is given in Fig. 6. IV. C ONCLUSION
The similarities lie in that chain-like structures of particles Gradient magnetic fields have been used widely for deliv-
can be formed and transported towards the target region in ering magnetic particles towards a certain region, while only
the same directions, shown in Fig. 6(a) and (b). However, as transport behavior of particles induced by magnetic field gra-
predicted in Fig. 4(c), multi-particle clusters in this case are dient was considered in the most existing studies. According
mainly distributed along the vertical axis in Fig. 6(c). Compared to the theoretical analysis, two types of magnetic forces can
with the distribution of particles in Fig. 5(c), relatively less be induced by the interactions between particles and gradi-
magnetic particles are focused in the bottom of target region ent magnetic fields for dominating transport and aggregation
in Fig. 6(c) since many particles are piled on the particles behavior, respectively. To identify the effect of aggregation
in the substrate due to the aggregation phenomenon along behavior on the movement trajectory of magnetic particles, two
y-axis. Therefore, it can be supposed that the configuration types of gradient magnetic fields have been designed to produce
of magnetic targeting system in Fig. 1(b) should be more similar gradient magnetic forces acting on the particles while
efficient for medical applications such as magnetofection since with different directions of magnetic field. Experimental results
more magnetic particles carrying therapeutic gene could be show that neighboring magnetic particles are easy to form
concentrated for enhancing interactions between gene and cells. chain-like clusters and this phenomenon is accompanied by
It should be noted that relatively large particles are chosen the transport process leading to the distribution of concentrated
in the experiments for easy visualization and rapid analysis. magnetic particles in the target region varies with the magnetic
The obtained results have equal reference values for magnetic field direction. Future work will focus on investigating the
nanoparticles-based targeting systems since similar magnetic dynamic behavior of magnetic particles in detail in the targeting
aggregation phenomenon also widely exists in these systems process under the action of permanent magnets with arbitrary
[25], [26]. magnetization directions.
CAO et al.: TARGETING BEHAVIOR OF MAGNETIC PARTICLES UNDER GRADIENT MAGNETIC FIELDS 4401305

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