Current Directions in Biomedical Engineering 2016; 2(1): 529–532
Open Access
Ankit Malhotra*, Felix Spieß, Corinna Stegelmeier, Christina Debbeler and
Kerstin Lüdtke-Buzug
Effect of key parameters on synthesis of
superparamagnetic nanoparticles (SPIONs)
DOI 10.1515/cdbme-2016-0117
Abstract: There are various methods to synthesize superparamagnetic nanoparticles (SPIONs) useful for MPI (magnetic particle imaging) and in therapy (Hypothermia) such
as co-precipitation, hydrothermal reactions etc. In this research, the focus is to analyse the effects of crucial parameters such as effect of molecular mass of dextran and temperature of the co-precipitation. These parameters play
a crucial role in the inherent magnetic properties of the
resulting SPIONs. The amplitude spectrum and hysteresis
curve of the SPIONs is analysed with MPS (magnetic particle spectrometer). PCCS (photon cross-correlation spectroscopy) measurements are done to analyse the size distribution of hydrodynamic diameter the resulting SPIONs.
Keywords: co-precipitation synthesis; MPI; photon
cross-correlation spectroscopy; SPIONs.
of the different parameters controlling the final output is
desired. In this study, the focus is on the classical synthesis
process called co-precipitation [3]. The co-precipitation
technique is one of the simplest and straight forward processes to obtain a large quantity of SPIONs. Through this
process iron oxides (Fe3 O4 ) could be easily prepared by
adding a mixture of ferric and ferrous salts in an aqueous
solution and precipitating with a base (ammonia, CH3 NH2 ,
or NaOH).
The co-precipitation process comprises of two stages:
a short burst of nucleation, once the concentration of the
species reaches critical supersaturation.
2Fe3+ + Fe2+ + 8OH−
Fe(OH)2 + 2Fe(OH)3
Followed by a slow growth of the nuclei through the
diffusion of the solutes to the surface of the nanoparticles.
Fe(OH)2 + 2Fe(OH)3
Fe3 O4 + 4H2 O
1 Introduction
In the past few years, there has been an immense
development in the field of SPIONs, which have shown
the capability for both, medical imaging and therapeutic
applications, for instance drug delivery and magnetic hyperthermia (MH). These particles are needed in the imaging fields like MRI (magnetic resonance imaging) as tracers
and particularly MPI [1, 2]. For MPI the SPIONs should
have high magnetization values, a hydrodynamic diameter
<150 nm and narrow particle size distribution.
To understand the behaviour of the SPIONs and to
tailor the particles for the specific modality, a careful study
*Corresponding author: Ankit Malhotra, Institute of Medical Engineering (IMT), University of Luebeck, Building 64, Ratzeburger Allee
160, 23562 Lübeck, Germany, E-mail: [email protected]
Felix Spieß, Corinna Stegelmeier, Christina Debbeler and
Kerstin Lüdtke-Buzug: Institute of Medical Engineering (IMT),
University of Luebeck, Building 64, Ratzeburger Allee 160,
23562 Lübeck, Germany, E-mail: [email protected]
(F. Spieß); [email protected] (C. Stegelmeier);
[email protected] (C. Debbeler); [email protected] (K. Lüdtke-Buzug)
2 Material and methods
As mentioned earlier, in this research the co-precipitation
technique is followed. The iron salts: iron(III) and iron(II)
in a ratio of 2:1, dextran and demineralized water are
placed in a three neck flask in an ice bath, followed
with addition of base at a constant rate under ultrasonic control [4]: Iron(III) (FeCl3 · 6H2 O ≥ 99% obtained,
from Carl Roth GmbH Karlsruhe, Germany) and Iron(II)
(FeCl2 · 4H2 O ≥ 99% obtained, from Merck kGaA, Darmstadt, Germany) is used. In two different synthesis series;
two kinds of dextran are used, T40 with molecular mass
of approx. 35,000–40,000 (Carl Roth GmbH Karlsruhe,
Germany) and T70 with molecular mass of approx. 70,000
(AppliChem GmbH, Darmstadt, Germany).
The flow rate of the base (here ammonia) is controlled with the help of an infusion pump (PERFUSOR
secura FT, B. Brown) which is 99 ml/h and the temperature of the reaction mixture is measured continuously
with a fibre optic thermometer (FOTEMP 4, OPTOCON AG).
This comprises of the nucleation phase followed by the
© 2016 Ankit Malhotra et al., licensee De Gruyter.
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 License.
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10–4
2
×10–6
T40 dextran
T70 dextran
10–6
1.5
T70 dextran
1
0.5
10–8
0
H
Spectral magnetic moment (Am 2/ Hz)
T40 dextran
10
–10
– 0.5
–1
10–12
10–14
– 1.5
–2
– 0.02 – 0.015 – 0.01 – 0.005
0
5
10
15
20
25
30
35
40
45
50
0
B
0.005
0.01
0.015
0.02
Harmonics
slow growth. In the growth phase the mixture is heated to
a definite temperature.
In this research, two sets of experiments are performed. In the first shown experiment, the effect of dextran on the synthesis process is evaluated by keeping all
the parameters constant except using different dextran of
different molecular weights (T40 and T70). In the second
experiment, the growth phase is analysed by taking out
samples at different temperatures to visualize the growth
of SPIONs with respect to final co-precipitation temperature. In these experiments dextran T70 is used. All the SPIONs are analysed with the MPS [5]. The size distribution
of the SPIONs is measured with NANOPHOX (Sympatec
GmbH).
Figure 2: Hysteresis curves of SPIONs with T70 and T40 dextran
coating.
0.25
T40 dextran
T70 dextran
0.2
0.15
l/ltot
Figure 1: Amplitude spectra of SPIONs with T70 and T40 dextran
coating.
0.1
0.05
0
0
3 Results
For characterization, the magnitude spectrum and the hysteresis curve are obtained by measuring MPS operating
at a frequency of approx. 25 kHz with a magnetic field
strength of 20 m/T.
3.1 Effect of dextran
As shown in Figure 1, the SPIONs with T70 dextran have
higher harmonics value as compared to T40 dextran.
Moreover, the area enclosed by the hysteresis curve generated with T70 dextran is bigger than T40 dextran as shown
in Figure 2.
This represents that the heating of the SPIONs with
T70 dextran in a field (or in the presence of a magnetic
field) will be higher, thus making these SPIONs.
More suitable for both hyperthermia and imaging. One
hypothesis could be that the SPIONs coated with T70 dextran have higher core diameter in comparison to T40 due to
50
100
150
200
250
300
350
400
450
500
r (mm)
Figure 3: PCCS measurement showing the particle size distribution
of the SPIONs prepared with T40 and T70 dextran.
difference of folding mechanisms of long chains of dextran
enabling more or less transport of iron precursors through
the dextran shell.
The hydrodynamic size distribution of the SPIONs
coated with T40 and T70 dextran is shown in Figure 3.
SPIONs coated with T70 dextran have smaller hydrodynamic diameter and give better amplitude and hysteresis
characteristics.
3.2 Effect of co-precipitation temperature on
synthesis
In this experiment, the SPIONs with T70 dextran are
prepared by following the same principle as stated in
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0.3
Initial temperature
20°C
20°C
10–6
50°C
50°C
60°C
60°C
0.2
70°C
70°C
10–8
80°C
80°C
0.15
0.1
10– 10
0.05
10– 12
0
200
10
– 14
0
5
10
15
20
25
30
35
40
45
50
Harmonics
4
Initial
20°C
30°C
2
50°C
60°C
1
400
500
600
700
800
r (nm)
show saturation making them suitable for imaging as well
as hyperthermia. The hydrodynamic size distributions of
the SPIONs at different co-precipitation temperatures are
shown in Figure 6. All the SPIONs have the same distribution of approx. 200 nm but different hydrodynamic
diameters except at 20°C the distribution is large as the
growth phase has just initialized and there are very large
particles present in the solution.
×10– 6
3
300
Figure 6: PCCS measurement showing the particle size distribution
of the SPIONs at different temperatures: from 20°C to 80°C.
Figure 4: Amplitude spectra of SPIONs obtained at different
temperatures from initial temperature to 80°C.
70°C
80°C
H
30°C
0.25
30°C
l/ltot
Spectral magnetic moment (Am 2/Hz)
10–4
0
–1
–2
4 Discussion and outlook
–3
–4
– 0.02
– 0.015
– 0.01
– 0.005
0
0.005
0.01
0.015
0.02
B
Figure 5: Hysteresis curve of SPIONs obtained at different
temperatures from initial temperature to 80°C.
materials and methods. In this study, the main focus is
on the growth phase of the synthesis. To get an insight
in the growth phase different samples are taken out at
temperature of 20°C, 30°C, 50°C, 60°C, 70°C and 80°C and
analysed by MPS. The amplitude spectra are shown in
Figure 4 and the hysteresis curves obtained are shown in
Figure 5.
Up to 30°C there is a weak or negligible signal from the
SPIONs, hence the nanoparticles are very small. Around
50°C to 80°C the SPIONs show an increased amplitude
signal, which makes them useful for imaging. The best
signal is obtained at a temperature of 50°C.
The same phenomena is observed in the hysteresis
curve. At initial temperatures up to 30°C the area within
the hysteresis loop is negligible. After 30°C there is a rise
in the area of hysteresis curves with 50°C showing the
best result. Moreover, at higher temperatures all the curves
In this study, the effect of dextran and temperature on
the co-precipitation process for synthesizing SPIONs for
MPI and hyperthermia is evaluated. It has been found
that the type of dextran or the molecular mass of the
dextran plays a significant role in the amplitude spectrum
as well as hysteresis which are the essential parameters for
quantifying the response of the SPIONs for imaging as well
as hyperthermia. With this study, it also has been found
that higher molecular mass dextran (T70) increases the
core diameter and hence better signal response from the
SPIONs. Temperature of the synthesis also plays a characteristic role in the final outcome of the SPIONs in terms of
amplitude response and hysteresis. It is established that in
co-precipitation method, high temperature leads to better
results but the effect is not so evident, after raising the
temperature to 50°C.
Author’s Statement
Research funding: We would like thank the German Federal Ministry of Education and Research (BMBF SAMBAPATI 13GW0069A) for supporting this project. Conflict of
interest: Authors state no conflict of interest. Material
and Methods: Informed consent: Informed consent is not
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applicable. Ethical approval: The conducted research is
not related to either human or animal use.
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