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1 s2.0 S0304885322009787 Main
1 s2.0 S0304885322009787 Main
A R T I C L E I N F O A B S T R A C T
Keywords: We describe a setup able to generate a rotating or alternating low-frequency (up to 10 Hz) magnetic field (up to
Setup 120 mT) for biological applications inside a 6 cm in diameter and 5 cm in height cylindrical space. It is suitable to
Cell death insert several Petri dishes for cell death experiments and mice for in vivo ones. Since a particular attention was
Rotating magnetic field
given to the field homogeneity, it is based on a six-pole electromagnet. The characteristics of the field are
Stator
Electromagnet
changed by varying the phase, amplitude or frequency of the electrical currents going through the coils, using a
micro-controller-based human–machine interface and a RL chopper, which is described. The results of the
magnetic simulations run to optimize the global design are provided. The cooling of the electromagnet is done
using a chiller, and the sample temperature regulation using an air blower. All details on the mechanical,
electrical and electronic elements, on the mounting, and on the programing are provided, so the setup can be
reproduced. Suggestions for a further improvement of the electrical efficiency are given. This setup has already
been used to demonstrate the possibility to kill cells using targeted magnetic nanoparticles and low-frequency
magnetic fields.
1. Introduction Recently, our group also published results confirming the efficiency
of low-frequency magnetic fields and magnetic nanoparticles to kill cells
In 2010, Dong-Hyun et al. [1] described a new anti-tumoral treat [17]. For this study, the amplitude and frequency values were screened
ment based on the injection of ferromagnetic microdiscs inside a me to determine the values maximizing cell death. Two oscillating modes of
dium containing tumoral cells. Thanks to the functionalization of the the magnetic field were also compared: rotating and alternating. We
microdisc surfaces, cell tumor membranes were targeted by these could demonstrate that the rotating one was more efficient, as expected
microdiscs. After the application of a low-frequency alternating mag theoretically [18]. There was also an optimal frequency, although its
netic field (up to 60 Hz and 13 mT), the mechanical oscillation of exact origin is still unclear. To explore the influence of these various
microdiscs induced cell death and cellular membrane degradations. parameters, a dedicated magnetic field generator was used.
Similar results were obtained by Leulmi et al. [2] in 2016. Since then, Generators for the treatment of tumors with low-frequency fields are
several research teams have published interesting results involving tu most of the time electromagnets producing alternating magnetic fields
moral cell death induced by low-frequency magnetic fields and different [3,4,6–14]. Rotating magnetic fields are less represented and are
micro- or nano- objects: nickel nanowires [3,4], nanocubes [5] or generally produced by moving magnets [5,15,16,19]. To our knowl
nanospheres [6–16]. Different strategies of treatment were also studied: edge, the only article presenting a magnetic field generator able to
with [3,5,7,9,10,14] or without specific targeting produce low-frequency rotating and alternating magnetic field is based
[4,6,8,11,12,13,15,16]. on moving magnets [16]. In this setup, the oscillation mode switches
* Corresponding author at: Université de Toulouse, INSA, UPS, LPCNO (Laboratoire de Physique et Chimie des Nano-Objets), 135 Avenue de Rangueil, F-31077
Toulouse, France.
E-mail address: jcarrey@insa-toulouse.fr (J. Carrey).
https://doi.org/10.1016/j.jmmm.2022.170093
Received 4 March 2022; Received in revised form 5 September 2022; Accepted 19 October 2022
Available online 25 October 2022
0304-8853/© 2022 Elsevier B.V. All rights reserved.
N. Hallali et al. Journal of Magnetism and Magnetic Materials 564 (2022) 170093
from alternating (up to 100 mT and 8 Hz) to rotating (up to 200 mT at 2 3. Influence of electromagnet geometry on field amplitude and
Hz) by changing the sample localization inside the setup which causes homogeneity
problems of field homogeneity. Moreover, tuning the amplitude is only
possible by changing the magnets, which is not convenient and limits the 3.1. Number of poles
range of accessible values. In the present article, an electromagnet
permitting to change the amplitude, frequency and oscillation mode of The magnetic field homogeneity must be quantified to select the best
the field by controlling the current going through the coils is presented. configuration. In this way two studies are presented below: (i) the in
More specifically, it is able to generate rotating or alternating magnetic fluence of the magnetic pole number on the magnetic field homogeneity
fields with an amplitude ranging from 0 to 120 mT with frequencies at mid-height of the electromagnet and (ii) magnetic field uniformity
from 0 to 10 Hz. according to the electromagnet’s height. All these observations were
During the conception of our setup, attention was paid to create a achieved thanks to COMSOL simulations and were used to choose the
homogeneous magnetic field. Indeed, in addition to the torque-induced final dimensions of our electromagnet. In COMSOL, the magnetic
cell death, several groups have used strong magnetic field gradients to module was used with standard hypotheses and models. The materials
induce biological responses [20]. Sometimes, it can be difficult to data (conductivity, permittivity) were the ones provided by the
discriminate if biological response is due to the presence of the field or to software.
the field gradient. The gradient in our setup was thus kept to a minimum, The magnetic field uniformity, for electromagnets with a different
in order to discard any effect other than the torque in our experiments. number of magnetic poles, was quantified by calculating the magnetic
Its conception and technical characteristics are detailed below, as field variance inside a slice of gap at mid-height of the electromagnet
well as possible improvements. (where the magnetic field amplitude is maximal). For each simulated
electromagnet, the gap had the same diameter, equal to 5 cm. This value
2. Generalities on electromagnets. will be justified below. The magnetic field variance (ΔB2) was calculated
from the magnetic field map, which consists in a triangular mesh, with a
An alternating magnetic field can be generated by a single pair of magnetic field value associated to each node, and reads:
electromagnets, as shown in Fig. 1(a). The magnetic field amplitude and ∑n
frequency are controlled by those of the electrical current. To create a (Bc − Bi)2 2
ΔB2 = i=0 [T ]
rotating magnetic field, it is necessary to have several electromagnets, n
the resulting magnetic field being the sum of the one generated by each with Bc the magnetic field value at the center, Bi the magnetic field
electromagnet. Each of them is named magnetic pole and the space value of one node inside the gap, and n the number of nodes inside the
between them is named gap. Electromagnets have to be arranged in gap.
space (i.e. space shift) so that, with an adequate value of phase shift According to Fig. 3, by comparing the results for 3 coils and 3 pairs of
between the current circulating inside the coils, the resulting magnetic coils it is possible to note that paired coils produce a more uniform
field rotates. Fig. 1(b) represents two pairs of coils angle shifted in space magnetic field than unpaired ones. Moreover, the figure evidences that
and traversed by two alternating electrical currents with the same increasing the number of magnetic poles increases the field uniformity.
amplitude and the same frequency but phase shifted in time. The phase Aiming at simplifying the realization of the electrical generator, we
shifts depend on the number of coil pairs: for instance, with two, three or selected the configuration with 3 pairs of coils since the variance of the
four pairs of coils, shift value equals π/2, 2π/3 or π/4, respectively. field was in accordance with our needs and three-phase generators are
In the remaining of this part, we will consider electromagnets dis more documented than fourth or fifth ones. From now, only this
playing a geometry similar to a stator core (see Fig. 2). This geometry configuration will be considered. In this case, to generate a rotating or
minimizes the leaks of magnetic field, focusing the latter at the center of alternating magnetic field, the phase current associated with each pair of
the stator core, creating a rather strong field in the gap. The free space coils must be equal to the values shown in Table 1:
between each tip (usually named stator teeth) is a notch and is generally
filled with coil wires.
Fig. 1. Illustration of magnetic field generators, the + symbol permits to identify the rotational direction of the coil winding. Coils with the same color have the same
winding rotational direction. (a) Two identical coils facing each other to generate an alternating magnetic field (AMF). (b) Two pairs of coils angle shifted in space to
produce a uniform rotating magnetic field (RMF).
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N. Hallali et al. Journal of Magnetism and Magnetic Materials 564 (2022) 170093
Fig. 2. Illustration of several magnetic cores (with 2, 3 or 4 magnetic poles) and the corresponding coil arrangement.
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N. Hallali et al. Journal of Magnetism and Magnetic Materials 564 (2022) 170093
Fig. 4. Illustration of the electromagnet magnetic core in its final geometry. (a) 3D view. (b) top view with the six notches (in blue) and the gap (in green).
Fig. 5. Magnetic field parameters as a function of electromagnet height G extracted from COMSOL simulations. (a) Magnetic field at the gap center as a function of
the position for different G values. (b) and (c) are extracted from (a) and show the (b) maximum magnetic field value and (c) thickness of homogeneity (h) at the gap
center. In (c), the equation is the linear fit of the data, shown as a plain line.
electromagnet height of 7 cm is enough to get an homogeneity thickness currents generated inside the material are limited. We simulated using
of 5 cm, the field inside this zone being at least equal to 133 mT (92% of COMSOL the influence on the electromagnet properties of three types of
142 mT). Thus we choose to limit the electromagnet height to 7 cm materials: Fe-Si, Fe-Co and soft iron (see supplementary material). The
because the magnetic field characteristics were adequate for our pur choice of material does not have an influence on the maximum magnetic
pose; this also permits to limit the electromagnet weight and cost. field into the gap. We thus chose to work with silicon steel because of its
good corrosion resistance (better than soft iron) which is an important
3.3. Influence of core material point for our setup since the electromagnet is then immerged inside an
aqueous cooling liquid. Moreover, its electrical resistance is larger than
The influence of the magnetic core material on the magnetic field the one of soft iron, and it is possible to use assemblies of silicon iron
amplitude generated inside the gap was then investigated. For this kind sheet, which both prevent the generation of eddy current inside the core.
of application, the perfect material has a low coercive magnetic field HC
(soft magnetic material), a high saturation magnetization, and eddy
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N. Hallali et al. Journal of Magnetism and Magnetic Materials 564 (2022) 170093
4. Electromagnet manufacturing latter further, blue Stycast epoxy resin (2850 FT) and catalyst 24LV (7 %
m) were spread on each layer of the coil before winding the next one.
This part is focused on setup production, which can be split in 4 The electrical characteristics of each pair of coils are detailed in
steps: (i) electromagnet core manufacturing, (ii) electromagnet core Table 2, and are close to the one obtained from COMSOL simulations:
winding, (iii) power generation, (iv) cooling system.
Fig. 6. Photography of electromagnet core and coils. (a) Electromagnet core. (b) First method of assembling (see text). The yellow box shows the separated coils and
the red one the 3D-printed coil supports. The right image shows the assembled coils. (c) Second method of assembling (see text). Picture of the coils winded on the
individual teeth. (d) CAD picture of the home-made object used to assemble individual teeth.
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N. Hallali et al. Journal of Magnetism and Magnetic Materials 564 (2022) 170093
Fig. 7. Electrical system designed to generate variable magnetic fields. (a) Schematic representation of the electric system. L1, L2 and L3 represent each pairs of coils.
(b) and (c) Pictures of the system.
PWMs are transmitted to power inverters to control MOS transistors, electrical current goes through L3 according to its winding rotational
which act as fast switches for the DC electrical current provided by an direction [illustrated by the + symbol in Fig. 7(a)]. In this configuration
external DC power source (EA-PS-3080-20C, Elektro-automatik). The with three pairs of coils, if B0 is the magnetic field amplitude generated
chopped electrical currents (output A, output B and output C) passing by L3, the resulting alternating magnetic field amplitude Btot = 1.5B0 .
through the transistor outputs are then connected to the coil pairs (L) According to Table 2 and to the specificity of the delta configuration
such as: L1 is between outputs B and C, L2 is between outputs A and B, L3 described above, it is possible to deduce that a current amplitude I0 of 10
is between outputs A and C. In this configuration and with a large A is able to generate a magnetic field B0 around 80 mT so that Btot equals
enough PWM frequency (at least 100 higher than the required alter 120 mT.
nating electrical current frequency) it is possible to generate a sinusoidal Finally, note that each pair of coils reacts like a RL electrical circuit
signal: this is the principle of the RL chopper. (or low pass filter), so the electrical power required to drive the coils is
Because the phase signal voltage varies from 0 V to the one provided frequency dependent. Table 2 allows to deduce the cut-off frequency of
by the external DC power source (in our case: 80 V), the electrical cur the circuit: fc = 2π(L−R M) ≈ 6.7 Hz. At this frequency, for the same elec
rent out of the power inverter is an alternating signal with a positive trical tension powered by the DC source, the electrical current is
mean value (the same for each phase). In this case, the magnetic field √̅̅̅
attenuated by a factor 2 compared to its value at lower frequency.
generated by each pair of coils is an alternating magnetic field with a
Above this frequency, the electrical current still decreases following Ix =
positive mean value, not suitable if one wants to generate a pure alter
nating or rotating magnetic field inside the gap. To avoid this problem,
I0
√̅̅̅̅̅̅̅̅
x2 +1
with = ffc . To compensate this phenomenon we used a slightly
the pairs of coils are linked together in a delta configuration, as shown in oversized DC source able to provide electrical current up to 10 A for
Fig. 7(a). In this configuration, the electrical current going through each frequencies larger than 6.7 Hz. However, above 10 Hz the decrease of
pair of coils becomes an alternating signal with a null mean value. It is electrical current becomes too important, which explains why this setup
important to note that, in this delta configuration, generating a rotating is limited to 10 Hz. Fig. 7(c) shows the home-made power controller and
magnetic field requires the three outputs (A, B and C) to be phase shifted power inverter; all PCB card circuits are detailed in SI-Fig. 2, permitting
as described in Table 1. In this case, the resulting magnetic field an easy reproduction of this setup.
amplitude Btot = 1.5B0 , with B0 the magnetic field amplitude of one pair
of coils. 4.3. Cooling
To generate an alternating magnetic field, in order to obtain the
phase shifts displayed in Table 1, output B has to be turned off. For an With an alternating current of 10 A, the dissipated power equals 375
alternating magnetic field, L1 and L2 are connected in series and in W, whatever the frequency (and 750 W with a DC signal of 10A on each
parallel of L3. Thus, the electrical current going through L3 is twice output). Thus, to avoid damaging the electromagnet by its own heating,
higher than the one of L2 and L1. Moreover, the current in L3 is naturally a cooling system was designed to absorb the heated generated when the
in phase opposition with respect to the one in L2 or L1 since when the magnetic field is on.
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N. Hallali et al. Journal of Magnetism and Magnetic Materials 564 (2022) 170093
To achieve this cooling system, an airtight box was designed (ERM, 5.2. Windings
France) in PMMA and stainless steel [see Fig. 8(a)]. It allows a pres
surized circulation (3 bar maximum) of cooling liquid (glycol water) and Our numerical simulations suggest another way to wind the coil
permits to rotate the electromagnet by 90◦ to achieve experiments on allowing an increase of the magnetic field generated inside the gap for
Cellview dishes (vertical position) or small animals (horizontal posi an identical electrical power. This winding − named “stator winding” −
tion). The dimensions of the box are available in SI-Fig. 3. Glycol water consists in winding a coil between two diametrically opposed notches as
is cooled by a chiller (TAEevo Tech Mini 05, MTA, France) with a shown in Fig. 9(a). The stator winding generates a magnetic field 50%
cooling power of 2.15 kW, which is large enough to absorb the dissi higher than the standard winding [see Fig. 9(b)] at an equivalent elec
pated power. Fig. 8(b) illustrates the complete setup with its different trical power, associated with a similar increase of the coil inductance.
parts: electromagnet, electronics and cooling system. However, the major inconvenient of the stator configuration is the
Finally, to maintain the gap at 37 ◦ C during experiment on cells, a hot winding itself. Indeed, as shown in SI-Fig. 6, the classical method using a
air blower was developed (see SI-Fig. 4 and the associated text). For single wire to make one coil takes too much space above and below the
experiments on mice, it is preconized to use thermo-regulated mouse electromagnet and prevents winding of the two other coils. We did not
bead. find a way to solve this problem but let it open to potential ingenious
An alternative and cheaper version of the box is also possible, but it readers which might succeed in finding a way to solve it, which could
limits experiments to Cellview dishes since only the vertical position is permit to take advantage of the gain in energy.
available. In this case, the box is not an airtight one but is a simple
plastic container with a hole on the top permitting to insert the samples
inside a plastic tube leading to the electromagnet’s gap (see SI-Fig. 5). A 5.3. Frequency limitation
table comparing the cost of these two versions is available in SI-Tab.1.
This second version is the one which was used in Ref.[17]: it could As mentioned in part IV.2, magnetic field generation is frequency
allow our group to demonstrate the efficiency of magneto-mechanical limited by the intrinsic electrical properties of coils (see R and L values
treatments on tumoral cells, especially when the magnetic field rotates. in Table 2). For this reason, the maximal frequency usable is 10 Hz. To
push this limit to a higher value we proposed three different solutions:
5. Optimizations (i) Use of powerful generator. Our setup was able to reach 10 Hz
because we use an oversized power generator: the power required to run
The setup presented in the previous part could be optimized in order a 1 (10) Hz current was around 375 (3 8 5) W, respectively. With the
to obtain a higher energy efficiency. The following parts concerns three same setup, reaching 100 Hz with a current of 10 A would require a
optimization ways that we suggest, but have not been implemented on 1000 W power generator. In this case, it is also necessary to check if the
our setup. The first one concerns the thermal regulation of the setup and electrical components connected to the power DC source are able to
the last two should permit to generate a larger magnetic field or fre support higher voltages. It is important to note that even if the DC power
quency with the same electric power, or the same magnetic field with a source is increased, the maximal dissipated thermal power would stay
lower electrical power. constant since it only depends on the electrical current amplitude and
electrical resistance (R).
(ii) Wind smaller coils. In this case, coils inductance would decrease
5.1. Thermal regulation
and the cut-off frequency would be higher. However, this means the use
of smaller electromagnet, and thus a smaller homogeneity height [see
Another version of the cooling system, certainly more expensive,
Fig. 5(a)].
consists on the use of a thermo-regulated circulating bath allowing
(iii) Use of electrical resonance. By placing a capacitor in series with
heating or cooling the glycol–water to maintain the gap at a certain
each coil it is possible to compensate the attenuation caused by RL cir
temperature (37 ◦ C for example). In this way, in function of the magnetic
cuit for a specific frequency, the resonant frequency (fR ) such as fR =
field amplitude and thus in function of the electrical power used, totally 1
√̅̅̅̅̅̅̅̅̅̅̅̅, with C the capacitance value of the capacitor. Then, with a
or a part of the thermal energy produced by Joule effect by the elec 2π (L− M)C
tromagnet would be used to heat the gap. capacitor box connected to each coil it becomes possible to select
Fig. 8. Setup pictures. (a) Airtight box containing the stainless steel tube permitting the insertion of Cellview dishes or mice into the gap. (b) Complete setup.
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N. Hallali et al. Journal of Magnetism and Magnetic Materials 564 (2022) 170093
Fig. 9. Presentation of the “stator winding”. (a) Illustrations from COMSOL simulations of the standard and stator windings for a similar electromagnet core; only one
phase has been winded, for clarity. (b) Comparison of the magnetic field amplitude inside the gap for the two types of winding. The electrical density equals 294 kA/
cm2 (corresponding to 10 A and 400 coils turns with a 1.7 × 0.8 mm2 copper wire). The magnetic field values are normalized by the one obtained with the
standard winding.
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N. Hallali et al. Journal of Magnetism and Magnetic Materials 564 (2022) 170093
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