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Synthesis & Heating Mechanisms of Magnetic Nanoparticles in Hyperthermia Treatment
1. Synthesis & Heating Mechanisms of Magnetic
Nanoparticles in Hyperthermia Treatment
Under the supervision of
Dr. R.K Kotnala
NPL
Submitted by:
Nikita Gupta
Mtech 2nd year
01140801014
2. INTRODUCTION
Magnetism and magnetic materials have been used for many decades in many modern medical
applications.
Physical properties which make magnetic materials attractive for biomedical applications are,
First, that they can be manipulated by an external magnetic field – this feature is useful for
separating, immunoassay and drug targeting, and
Second, hysteresis and other losses occur in alternating magnetic fields – this is useful in
hyperthermia applications.
The earliest known biomedical use of naturally occurring magnetic materials involves magnetite
(Fe3O4) or lodestone which was used by the Indian surgeon Sucruta around 2,600 years ago.
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4. Ferrites
Iron oxides such as hematite or magnetite (Fe3O4): first magnetic material, very stable and easy to synthesize.
Biocompatible, minimally toxic, used in many clinical studies
Reasonably large saturation magnetization (~90 emu/g). The most widely investigated types of magnetic nanoparticle
for biomedical applications.
Normally there are two types of structures in ferrites.
Regular spinel
Inverse spinel
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5. Types of ferrites
There are two types of ferrites:
Soft ferrites Low Coercivity means the material's magnetization can easily reverse direction without
dissipating much energy (hysteresis losses), while the material's high resistivity prevents eddy currents in the
core. Example-Mn, Ni, Fe, Mg
Hard ferrites High Coercivity means the materials are very resistant to becoming demagnetized, as in
Permanent Magnet. Due to high magnetic permeability. These are called Ceramic magnets . Example-Ba, Co
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6. Hyperthermia
Hyperthermia is an elevated body temperature due to failed thermoregulation.
Hyperthermia occurs when the body produces or absorbs more heat than it can
dissipate.
Hyperthermia can be created artificially by drugs or medical devices. Hyperthermia
therapy may be used to treat some kinds of cancer and other conditions, most
commonly in conjunction with radiotherapy. It is known that cancer cells show more
weakness to high temperatures compared with ordinary cells.
Hyperthermia system that is able to heat tumor cells above 43°C without damaging
normal tissues is required.
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7. Magnetic hyperthermia
Magnetic heat induction of magnetic nanoparticles provides various
advantages over conventional hyperthermia treatment
There are a number of therapeutic benefits of producing localized
heating, for example, have the sizes ranging from a few tens of
nanometers, and hence are easily absorbed by tumor cells, can
effectively cross the blood-brain-barrier, opening up a new modality of
treatment for brain tumors, can be easily manipulated in a colloidal
form with numerous drug delivery methods
8. Magnetic hyperthermia
The magnetic moments on nanoparticles will align with an external
magnetic field. As the external field changes direction, the magnetic
moment will also change direction. This produces dissipation leading to
heating. One of the major advantages of using magnetic fields to produce
heating is that they readily penetrate tissue.
However, heating the surrounding tissue can also produce unwelcome side-
effects so there are advantages strictly controlling the region under
treatment by using magnetic nanoparticles as the heating element.
Superparamagnetic nanoparticles absorb power from AC magnetic fields
and heat surrounding tissue via Neel or Brownian relaxation and Hysteresis
Loss 11/21/2015
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9. Relaxation in magnetic nanoparticles
Brownian Relaxation
With decreasing particle size the energy barrier for magnetization reversal
decrease too, and consequently thermal fluctuations lead to relaxation
phenomena.
The Brownian relaxation mechanism is characterized by the rotational Brownian
motion of nanoparticle itself. In this case, the energy barrier is determined by
the rotational friction within the medium.
In Brownian relaxation, entire particle rotates in a fluid.
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10. Neel Relaxation
Neel process is determined by the magnetic anisotropy energy of the
Superparamagnetic particles relative to the thermal energy.
It is relevant in fixed Superparamagnetic particles where no physical rotation of the
particle is possible.
Neel relaxation, direction of magnetization rotates in core
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12. Hysteresis losses
Ferromagnetic nanoparticles generate heat by hysteresis loss mechanism.
Hysteresis losses may be determined in a well known manner by integrating
the area of hysteresis loops, a measure of energy dissipated per cycle of
magnetization reversal.
Total heating is proportional to the frequency of the applied field and the
area of the magnetic hysteresis loop.
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13. 0 4 8 12 16
24
28
32
36
40
44
H2
O
-Fe2
O3
Fe3
O4
Temperature(
o
C)
Time (min)
Magnetic hyperthermia
The sample consisting
individual nanoparticles
(Fe3O4) heats 4-5 times faster
than the sample with clustered
nanoparticles (-Fe2O3).
This suggests that, at least for
these experimental conditions
(nanoparticle size, driving
frequency, sample viscosity,
etc.), Brownian relaxation is a
much more effective heating
mechanism than Neel
relaxation.
14. Experimental Method-Synthesis of magnesium ferrite by co-precipitation
method:Sample 1:
a) The desired metallic salts (Precursors,1:2) i.e. 0.01M of Mg(NO3)2.6H2O (i.e. 2.56gm in 10ml water) and
0.01M of Fe(NO3)3.9H2O (i.e. 8.08gm in 10ml water), are dissolved in de-ionized water and mix together in an
appropriate stoichiometric ratio in a beaker.
b) 0.2M Ammonium hydroxide solution is added for the precipitation at pH 9-10. The mixture is stirred for 3
hours with a slight warming followed by an overnight aging.
c) The collected precipitates comprising of the hydroxides of metal ions, ammonium nitrates and some water
contents, have been repeatedly washed with de-ionized water and ethanol in order to remove the excess
ammonia, any un-reacted species.
d) After that dried at 403 K in an oven to remove the water contents, followed by grinding the dry precipitate to
powder form, in order to break coarse particles uniformly.
e) The dried product obtained is calcinated at 350 °C for 2 hourss and then sintered at 750 °C for 4 hours in a
tube furnace
f) The grinding is done using an Agate mortar-pestle.
g) Then prepared 1M solution of magnesium ferrite in 1.5 ml of water (i.e. 0.299gms) for hyperthermia
application. 11/21/2015
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15. Sample 2: 4 times as compared to the sample 1
a) The desired metallic salts (Precursors,1:2) i.e. 0.01M of Mg(NO3)2.6H2O (i.e. 2.56*4=10.24gm in 40ml water)
and 0.01M of Fe(NO3)3.9H2O (i.e. 8.08*4=32.32gm in 40ml water), are dissolved in de-ionized water and mix
together in an appropriate stoichiometric ratio in a beaker.
b) 0.8M Ammonium hydroxide solution is added for the precipitation at pH 9-10. The mixture is stirred for 3
hours with a slight warming followed by an overnight aging.
c) The collected precipitates comprising of the hydroxides of metal ions, ammonium nitrates and some water
contents, have been repeatedly washed with de-ionized water and ethanol in order to remove the excess
ammonia, any un-reacted species.
d) After that dried at 403 K in an oven to remove the water contents, followed by grinding the dry precipitate to
powder form, in order to break coarse particles uniformly.
e) The dried product obtained was calcinated at 800 °C for 4 hours and then elevated the temperature up to
950 °C for 4 hours in a tube furnace
f) The grinding is done using an Agate mortar-pestle.
g) Then prepared 1M solution of magnesium ferrite in 3 ml of water (i.e. 0.599gms) for hyperthermia application.
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16. Characterization Techniques
The following characterizations have been potentially performed for the analysis of the synthesized samples.
1. Powder X-ray diffraction technique (XRD): Phase identification and Lattice parameters determination
The XRD pattern of the Magnesium Ferrite sample after being annealed at 950 degrees represents the typical Hexagonal Structure.
The increasing curve base of the MgF sample exhibits the Nano crystalline behavior of pure phase MgF.
According to Scherer Formula, crystallite size of MgF is 25 nm.
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17. 2. Vibrating sample magnetometer (VSM):
a) As prepared sample:
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21. Conclusion
In magnetic hyperthermia experiments, an alternating magnetic field is
applied to the nanoparticle sample and the variation of temperature is
measured with respect to time and graphs were plotted.
As the time increases, temperature was also increased linearly.
But at low frequencies, temperature increase was not enough for
hyperthermia treatment. We need the frequency above 500 KHz to
increase the temperature 2 degrees per minute.
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22. frequency 1KHZ 5KHz
Magnetic field
(Oe)
5 10 15 5 10 15
Time
(minutes)
15 15 15 15 15 15
Rise in
temperature of
sample 1 and
sample 2
(degrees)
0.5 0.5 1.5 1 0.2 1
0.6 0.4 0.5 0.2 0.5 0.3
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23. References
International Journal of Electronics and Communication Engineering & Technology (IJECET) Volume 2,
ELECTROMAGNETIC STUDIES ON NANO-SIZED MAGNESIUM FERRITE by A.M.BHAVIKATTI.
Heating of magnetic material by hysteresis effects-US 6599234 B1 by Bruce, Nathaniel Gray, Raffaele
Cammarano, Stephen Keith Jones.
Hyperthermia effect of magnetic nanoparticles under electromagnetic field by Giovanni Baldi, Giada Lorenzi,
Costanza Ravagli.
Ferrimagnetic MgFe2O4 nanoparticles for Intra-Arterial HYPERTHERMIA AGENT APPLICATIONS by
LEE SANGHOON.
Magnetic Nanomaterials for Hyperthermia based Therapy and Controlled Drug Delivery by Challa S. S. R.
Kumar and Faruq Mohammad.
Improved magnetic induction heating of nanoferrites for hyperthermia application. By V.M. Khot, A. B.
Salunkhe, J. M. Ruso, S. H. Pawar.
New magnetic implant material for interstitial hyperthermia Toshifumi Shimizu, Masaaki Matsui.
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