Letter Cite This: ACS Appl. Nano Mater. XXXX, XXX, XXX−XXX
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Anisotropic Magnetic Supraparticles with a Magnetic Particle Spectroscopy Fingerprint as Indicators for Cold-Chain Breach Stephan Müssig,† Tim Granath,† Tim Schembri,† Florian Fidler,‡ Daniel Haddad,‡ Karl-Heinz Hiller,‡ Susanne Wintzheimer,† and Karl Mandel*,†,§ †
Chemical Technology of Materials Synthesis, University of Wuerzburg, Roentgenring 11, 97070 Würzburg, Germany Magnetic Resonance and X-ray Imaging Department, Development Center X-ray Technology EZRT, Fraunhofer Institute for Integrated Circuits IIS, Am Hubland, 97074 Würzburg, Germany § Fraunhofer Institute for Silicate Research ISC, Neunerplatz 2, 97082 Würzburg, Germany Downloaded via 185.46.84.235 on July 24, 2019 at 00:26:16 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.
‡
S Supporting Information *
ABSTRACT: Magnetic particle spectroscopy (MPS) is used in this work to obtain a magnetic fingerprint signal from anisotropic supraparticles, i.e., microrods assembled from superparamagnetic iron oxide nanoparticles. Exceeding its intended purpose of nanoparticle characterization for biomedical magnetic particle imaging, it is shown that MPS is capable of resolving structural differences between the anisotropic alignment of individual nanoparticles and its isotropic counterpart. Additionally, orientation-dependent MPS signal variations of anisotropic supraparticles are identifiable. This finding enables the detection of cold-chain breaches (for instance, during delivery of a product that needs to be cooled all of the time) by recording the initial and final MPS signals of microrod samples integrated into the container of a frozen product. KEYWORDS: magnetic particles, supraparticles, detectors, magnetic particle spectroscopy, magnetic sensor, cold-chain breach
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assembled from individual nanoparticles.14 It was found that the structure of the magnetic nanoparticles in the supraparticles has a fingerprint nature, resulting in a distinct MPS signal; thus, such supraparticles can be used as objects carrying a unique code.14 In this work, supraparticles of anisotropic nature were studied, namely, micron-sized rod supraparticles, assembled from superparamagnetic iron oxide nanoparticles.15 MPS reveals that the anisotropic assembly of iron oxide nanoparticles strongly enhances the relative amplitude signal intensity of their higher harmonics. Furthermore, alignment of the microrods in the external field yields orientationdependent signal variations, as will be shown in the following. This ultimately enables applications such as using these microrods as indicators to prove that a cold-chain is secured, as demonstrated in this work. The employed superparamagnetic iron oxide nanoparticles with a diameter of ∼10 nm (depicted in Figure S2a) exhibit a certain curve progression of the amplitude intensity as a function of higher harmonics when measured in MPS as a dispersion (ferrofluid; Figure 1a). These nanoparticles could
agnetic particle spectroscopy (MPS) is a means to measure the magnetization behavior of powder or liquid samples by applying a sinusoidal magnetic field.1,2 Because of its fast measurement speed, sensitive signal acquisition, and easy setup, MPS provides a feasible alternative to conventional magnetization measurement devices, such as vibrating-sample magnetometers. If magnetic particles exhibit nonlinear magnetization curves, the frequency spectrum of the magnetization response consists of higher harmonics, which is typically analyzed.2 A more detailed description of this principle can be found in the Supporting Information. So far, MPS mainly acts as an easy-touse device to quickly characterize magnetic nanoparticles regarding their applicability in biomedical magnetic particle imaging (MPI).3,4 To study how the MPS or MPI signals of magnetic particles are altered depending on their properties, various parameters, including their size,5 shape,6 relaxation effects,7 and matrix interactions,8 have been investigated. A better understanding thereof would enable tailoring of nanoparticles for different fields ranging from biomaterials,9 bioassays10 and biomedicine11 to materials science12 and physics.13 Recently, it was demonstrated by us that MPS is also suitable to characterize and distinguish different isotropic superstructures, so-called supraparticles, i.e., microparticles © XXXX American Chemical Society
Received: May 24, 2019 Accepted: July 17, 2019 Published: July 17, 2019 A
DOI: 10.1021/acsanm.9b00977 ACS Appl. Nano Mater. XXXX, XXX, XXX−XXX
Letter
ACS Applied Nano Materials
Figure 1. Amplitude intensity normalized to the corresponding fundamental intensity as a function of the higher harmonics of the employed iron oxide nanoparticles (black solid line) assembled into isotropic (red dotted line) and anisotropic (microrod; blue dashed line) supraparticles measured via MPS with a frequency of 20.1 kHz (a). TEM images exhibit the anisotropic (b and c) and isotropic (d and e) nanostructured supraparticle morphologies.
between individual iron oxide nanoparticles within the assembly, as was described for nanoparticle dispersions16 and supraparticles,14 or by its anisotropic structural arrangement. In order to synthesize supraparticles from the iron oxide nanoparticles, which are not anisotropic but rather spherical in nature, precipitation of silica onto the nanoparticles was performed once more but this time without the presence of a magnetic field. Indeed, in contrast to the formation of anisotropic rods in the presence of a magnetic field (Figure 1b,c), the absence of a magnetic field during synthesis yields almost isotropic assemblies (Figure 1d,e; more TEM micrographs are shown in Figure S2e−g). The isotropic supraparticles exhibit diameters ranging from approximately 150 nm to 8 μm. These structural differences are observable in MPS measurements: The signals obtained for the isotropic supraparticles deviate only slightly from those of the pure (individual) iron oxide nanoparticles and do not show any significant signal enhancement, as is the case for the anisotropic structures. (It should be noted that the standard deviation is only identifiable for the isotropic supraparticles due to their lower absolute signal intensities compared to the other samples. Typically the standard deviation is below 1%.) Furthermore, when supraparticles with smaller aspect ratios, i.e., degrees of anisotropy, are analyzed as described in a recent work,15 the measured MPS signal is lowered for slightly anisotropically shaped supraparticles (as depicted in Figure S3). This finding indicates that it is indeed the anisotropic shape that is responsible for the signal intensification in MPS, and it is apparently not just an altered (isotropic) interparticle interaction. To further confirm this, the samples were cooled to 60 K at zero magnetic field (zero-field-cooled, ZFC) and subsequently heated to 300 K at a small external magnetic field. During heatup, a maximum in the magnetization of the sample is observed at the blocking temperature TB, above which the sample behaves superparamagnetically. The sample is then cooled to 60 K again while the small magnetic field is
be turned into supraparticles by the precipitation of traces of silica onto them (Scheme 1).15 Scheme 1. Microrods Formed from Superparamagnetic Iron Oxide Nanoparticles by the Addition of a Silica Source and an Antisolvent to the Particle Suspension with Application of a Magnetic Fielda
a
Adapted with permission from ref 15. Copyright 2017 American Chemical Society.
When this supraparticle formation is conducted in the presence of a magnetic field, anisotropic rodlike structures can be obtained [Figure 1b,c, transmission electron microscopy (TEM) micrographs; more micrographs are depicted in Figure S2b−d].15 These structures exhibit diameters ranging from 30 to 300 nm and lengths between 100 nm and 10 μm. Notably, the amplitude intensity measured with MPS for these anisotropic supraparticles increases more than 14-fold at the 15th harmonic, compared to the iron oxide nanoparticles in the nonassembled state (Figure 1a). As the deposited silica is diamagnetic, the MPS signal of the microrods still originates exclusively from the iron oxide nanoparticles. Thus, the signal intensification is not related to intrinsic nanoparticle properties but must be related to the formation of the superstructures, i.e., the supraparticles. However, it needs to be determined whether the signal change is caused by modified interactions B
DOI: 10.1021/acsanm.9b00977 ACS Appl. Nano Mater. XXXX, XXX, XXX−XXX
Letter
ACS Applied Nano Materials
When microrods are immobilized in the matrix with statistical orientation (Figure 2d), their signal curves decay faster. From these findings, two conclusions can be drawn: Evidently, the signal of the microrods is dependent on their relative orientation toward the external (applied) magnetic field direction in MPS. When the microrods are oriented in parallel to the external field, their signals intensify compared to those of the statistical orientation. Consequently, as the oriented microrods in a fixed matrix exhibit signal curves identical with those of dispersed microrods in water, a second conclusion is adduced: When these supraparticles are dispersed and can freely rotate (Figure 2c), a macroscopic alignment of the microrods parallel to the external magnetic field occurs during the MPS measurements. Interestingly, the signal does not depend on whether the microrods are mobile in the different media but rather depends solely on their orientation toward the magnetic field. This may be explained by increased interactions between the individual nanoparticles when the external field is applied along the long axis of the microrods compared to weaker interactions for deviating fields.20 When isotropic supraparticles (Figure 1d,e) are used for the same experiment, no signal variations between the aligned and statistically oriented supraparticles are observable, confirming their negligible anisotropy, as depicted in Figure S5. For a more detailed analysis of the direction dependence, the anisotropic microrod supraparticles were oriented in other spatial directions relative to the external magnetic field direction in MPS measurements. Their diverging orientation was confirmed by analyzing acrylate with incorporated microrods via laser scanning microscopy (LSM), as depicted in Figure S6. The samples where the microrod supraparticles are oriented in parallel (Figure 3b) and perpendicular (Figure 3e) with respect to an external magnetic field exhibit signal curves with the highest and lowest intensities (Figure 3a), respectively. The samples where the microrod supraparticles
still present (field-cooled, FC). The results of these ZFC/FC measurements (depicted in Figure S4) for both samples are very much alike. This indicates that there is no significant difference in the nanoparticle interaction in either of the structures; i.e., the interparticle interaction among the nanoparticle building blocks is the same for the isotropic and anisotropic cases. Because anisotropic structures are defined by their direction-dependent properties, the question arose whether the orientation of the microrod assemblies in a composite influences their MPS signal as well. For this purpose, microrods were added to an acrylate solution. By application of a magnetic field, the microrods align their long axes along the field gradient. While the microrods were oriented as desired, the monomer solution was polymerized via UV light, thus immobilizing the microrods in the polymer matrix (more detailed information is given in the experimental section in the Supporting Information). It was shown that changing the particle surroundings leads to a decreased MPS amplitude intensity for particles with magnetic cores larger than a critical value, which is typically in the range of 20 nm particle diameter. This critical value is dependent on many factors including the hydrodynamic size, temperature, magnetic core size, applied external magnetic field strength, and anisotropy constant. Recent studies suggested that for these cores the magnetic moment relaxation is usually dominated by Brownian relaxation. However, when the surroundings are changed by binding of proteins or immobilization of the particles, relaxation is retarded because of delayed or completely disabled Brownian relaxation, leading to an amplitude decrease.10,17−19 In our case, when the excitation field Hext in MPS is applied parallel to the long axis of the microrods (Figure 2b), the signal
Figure 2. Amplitude intensity normalized to the corresponding fundamental intensity as a function of the higher harmonics of microrod supraparticles mobile in a dispersion (blue dotted line) and immobilized in parallel (red dashed line) and statistical (black solid line) orientations toward an external magnetic field Hext measured via MPS with a frequency of 20.1 kHz (a). The schematically depicted parallel-immobilized (b) and mobile (c) samples exhibit different signals compared to the statistically immobilized microrods (d).
Figure 3. Amplitude intensity normalized to the corresponding fundamental intensity as a function of the higher harmonics of differently oriented and immobilized microrod supraparticles toward an external magnetic field Hext measured via MPS with a frequency of 20.1 kHz (a). Parallelly (b) and perpendicularly (e) oriented samples exhibit signal curves with the highest and lowest intensities, respectively. Samples where the microrod supraparticles are oriented in a 45° angle (c) and statistically (d) exhibit signals with intensities that are between those of the “parallel” and “perpendicular” samples representing their intermediate structural alignment compared to the aforementioned samples.
(Figure 2a) is identical compared to microrods in dispersion (Figure 2c). As the microrods consist of sufficiently small (
