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The work presents the fabrication and characterisation of a new liquid metal filled magnetorheological elastomer (LMMRE) comprising liquid metal microdroplets and metallic magnetic microparticles&lt;sup&gt;1&lt;/sup&gt;. The conductive network formed by liquid metal droplets and solid metal microparticles in the matrix imparts conductivity to LMMRE (Fig. 1). Both isotropic and anisotropic LMMREs were fabricated either without or with an external magnetic field.&lt;br/&gt;&lt;br/&gt;For the case of isotropic LMMRE, compared to conventional composites, this LMMRE uniquely reaches a maximum resistance in the relaxed state and can drop sharply under any mechanical deformation, including compression, stretching, bending, and twisting. This indicates that the LMMRE can exhibit an unconventional negative piezoresistive effec. The mechanical and thermal properties of LMMRE were further studied. Several proof-of-concept applications based on LMMRE such as wearable joint sensors and intelligent heating devices were also demonstrated. For example, the LMMRE can be used to detect the movement of human joints. A LMMRE strip was attached to the index finger, then the finger bent repeatedly with the maximum bending angles of 45° and 90°, respectively. The resistance change-time curve reflects the accurate response of the LMMRE sensor to different angles and its stability under cyclic loading (Fig. 2). Therefore, this LMMRE has the potential to be applied for developing highly sensitive flexible sensors for wearable devices.&lt;br/&gt;&lt;br/&gt;After that, we created and studied an anisotropic LMMRE using the magnetic field alignment method. We show that magnetically aligning the particles prior to curing the LMMRE produces different results. Namely, the conductivity of the anisotropic LMMRE—in the absence of deformation—improves significantly by several orders of magnitude in all directions compared to the isotropic LMMRE with the same composition. In addition, the resistivity changes of the anisotropic LMMRE under mechanical deformation and its anisotropic piezoresistive properties are also significantly different from isotropic LMMRE. Along the particle alignment direction, the resistivity of anisotropic LMMRE increases sharply with strain. In contrast, in the direction perpendicular to the particle chains, its resistivity decreases monotonically with strain. Besides, the anisotropic LMMRE is also more sensitive to mechanical deformation along the particle alignment direction. Furthermore, we discovered that the mechanical, magnetic and thermal properties of the anisotropic LMMRE also exhibit significant anisotropy. Harnessing these unique properties, we demonstrated several applications based on anisotropic LMMRE such as soft tactile logic devices and an improved intelligent heating device.

**References:**

1. G. Yun, S.Y. Tang, S. Sun, D. Yuan, Q. Zhao, L. Deng, S. Yan, H. Du, M.D. Dickey and W. Li, Nature Communications, Vol. 10, p.1300 (2019)

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 Study of Liquid Metal Filled Magnetorheological Elastomers

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The work presents the fabrication and characterisation of a new liquid metal filled magnetorheological elastomer (LMMRE) comprising liquid metal microdroplets and metallic magnetic microparticles1. The conductive network formed by liquid metal droplets and solid metal microparticles in the matrix imparts conductivity to LMMRE (Fig. 1). Both isotropic and anisotropic LMMREs were fabricated either without or with an external magnetic field. For the case of isotropic LMMRE, compared to conventional composites, this LMMRE uniquely reaches a maximum resistance in the relaxed state and can drop sharply under any mechanical deformation, including compression, stretching, bending, and twisting. This indicates that the LMMRE can exhibit an unconventional negative piezoresistive effec. The mechanical and thermal properties of LMMRE were further studied. Several proof-of-concept applications based on LMMRE such as wearable joint sensors and intelligent heating devices were also demonstrated. For example, the LMMRE can be used to detect the movement of human joints. A LMMRE strip was attached to the index finger, then the finger bent repeatedly with the maximum bending angles of 45° and 90°, respectively. The resistance change-time curve reflects the accurate response of the LMMRE sensor to different angles and its stability under cyclic loading (Fig. 2). Therefore, this LMMRE has the potential to be applied for developing highly sensitive flexible sensors for wearable devices. After that, we created and studied an anisotropic LMMRE using the magnetic field alignment method. We show that magnetically aligning the particles prior to curing the LMMRE produces different results. Namely, the conductivity of the anisotropic LMMRE—in the absence of deformation—improves significantly by several orders of magnitude in all directions compared to the isotropic LMMRE with the same composition. In addition, the resistivity changes of the anisotropic LMMRE under mechanical deformation and its anisotropic piezoresistive properties are also significantly different from isotropic LMMRE. Along the particle alignment direction, the resistivity of anisotropic LMMRE increases sharply with strain. In contrast, in the direction perpendicular to the particle chains, its resistivity decreases monotonically with strain. Besides, the anisotropic LMMRE is also more sensitive to mechanical deformation along the particle alignment direction. Furthermore, we discovered that the mechanical, magnetic and thermal properties of the anisotropic LMMRE also exhibit significant anisotropy. Harnessing these unique properties, we demonstrated several applications based on anisotropic LMMRE such as soft tactile logic devices and an improved intelligent heating device.

**References:**

1. G. Yun, S.Y. Tang, S. Sun, D. Yuan, Q. Zhao, L. Deng, S. Yan, H. Du, M.D. Dickey and W. Li, Nature Communications, Vol. 10, p.1300 (2019)

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Magnetism plays an instrumental role in biomedical applications and healthcare, both from the perspectives of devices and techniques. In particular, Magnetic Resonance Imaging (MRI, [1]) addresses the magnetization induced on the patients’ constituent matter when subject to a magnetic field, and exploits the time-varying signal resulting from the contribution of the ubiquitous hydrogen nuclei spins for high quality spatial reconstructions. At present, MRI is the only available medical imaging technique known to deliver high resolution images of deep biological tissues in vivo and without harmful ionizing radiation. However, MRI does not come without its own limitations. In particular, it is much more efficient at detecting soft tissues and fluids than hard, solid samples. This is due to the weak, short-lived signals emitted by the latter, by cause of dipolar magnetic interactions between neighboring spins in the sample, which constitute a noisy environment that decoheres the quantum nature of the MR signal. The environment’s contribution averages out for soft tissues, but not so for solids, where nuclei are approximately fixed with respect to each other in the laboratory reference frame. This explains the scarcity of useful (with diagnostic value) MR images of dental tissues [2-4], the hardest in the human body. Furthermore, the MRI scanners employed so far use static magnetic field strengths ranging from 4 to 12 T, which makes them large and expensive. At around 1 M$ per Tesla [5], this precludes their penetration in dental clinics. In this symposium, devoted to evaluating the transition of biomagnetic research from laboratory to clinical environments, we present a new, inexpensive approach to MRI of combined hard and soft biological tissues, with a view on dental applications [6]. We will show 3D reconstructions of human teeth (Figures 1 and 2), as well as a rabbit head and a cow femur, all obtained at a field strength of only 260 mT. These images are, to the best of our knowledge, the first featuring soft and hard tissues simultaneously at sub-Tesla fields, and have been acquired in a home-made special-purpose MRI scanner designed with the goal of demonstrating dental imaging at low field settings. We also present two recently patented sequences for efficient encoding of spatial information and image reconstruction: VIEWS (Volumetric Image Encoding Without k-Space) and MASSIF (Magic Angle Spinning of Spatially Inhomogeneous Fields). These are key players in the roadmap we envision to shorten scan times from several hours, as in our first prototype, to a few minutes, as desired for clinical applications.

**References:**

[1] Haacke, E. Mark, et al. Magnetic resonance imaging: physical principles and sequence design. Vol. 82. New York:: Wiley-Liss, 1999. [2] Weiger, Markus, et al. "High-resolution ZTE imaging of human teeth." NMR in Biomedicine 25.10 (2012): 1144-1151. [3] Idiyatullin, Djaudat, et al. "Dental magnetic resonance imaging: making the invisible visible." Journal of endodontics 37.6 (2011): 745-752. [4] Mastrogiacomo, Simone, et al. "Magnetic Resonance Imaging of Hard Tissues and Hard Tissue Engineered Bio-substitutes." Molecular Imaging and Biology (2019): 1-17. [5] Sarracanie, Mathieu, et al. "Low-cost high-performance MRI." Scientific Reports 5 (2015): 15177. [6] Algarín, José Miguel, et al. "Simultaneous imaging of hard and soft biological tissues in a low-field dental MRI scanner." Scientific Reports 10 (2020): 21470.

**Images:**

![](https://assets.underline.io/uploads/markdown_image/1/image/6feb2d6202cc6897130f3a2a8eb5112c.jpg)
(a) Picture of the scanned rabbit head. (b) Picture of a rabbit skull. (c) Top: Single slices for 90 us dead time with PETRA; middle: the same slices for 1 ms dead time; bottom: difference between the above images.

![](https://assets.underline.io/uploads/markdown_image/1/image/1e40f4cf67c994af04ff3b7c6402f824.jpg)
(a) 2 dimensional slices of four human teeth embedded in a piece of pork ham (PETRA). (b) Photograph of the sample.

 Hard Tissue Magnetic Resonance Imaging with Fast Control of Intense Magnetic Fields

The median survival of glioblastoma, the main primitive brain tumor, 15 months. The progress of imaging, surgery, robotic, chemoradiotherapy, as well as last generation molecular biology and targeted therapy did not provide any curative strategies. Innovative therapies are warranted to increase our therapeutical efficacy. Magnetic nano and micro particles are widely studied for biomedical applications such as contrast agents for MRI, regenerative medicine, cell sorting, tissue engineering, protein purification, hyperthermia or magnetofection. For cancer therapy, Magnetic Particles (MP) offer new perspectives for untreated diseases such as glioblastoma. Indeed, new pharmacotherapies struggle to prove their efficacy while therapies based on physical effect, such as Tumor Treating Fields demonstrate promising results. An approach based on mechanical destruction of cancerous cells by low-frequency vibration of magnetic particles, that we call Treatment by Magneto-Mechanical Effect of Particles (TMMEP) has been studied for several years. Kim et al. first showed that they were able to reduce glioma cancer cells viability from 90% by applying a 20 Hz alternating field on cells incubated with permalloy microdisks. Master et al. put superparamagnetic iron oxide nanoparticles (SPIONs) on breast cancer cells and applied a 100 kA/m alternating magnetic field at 50 Hz for a total of 30 min, with 10 min on / 5 min off patterns. They demonstrated a reduction in cell viability up to 75%. Interestingly, they showed that healthy cells were less affected by the treatment because of different cell mechanical properties. A comparative study of cylindrical particles with different length and diameter was conducted by Wong et al. They showed that MP with smaller diameter have a better efficacy with about 75% of cell viability after application of a biaxial pulsed magnetic field thanks to 4 coils. In vivo study on an orthotopic model of glioblastoma was conducted by Cheng et al. In a preliminary approach, they injected cancerous cells mixed with disks microparticles in brain mice and showed a better survival of mice submitted to a daily exposition of a 1 T rotating magnetic field at 20 Hz for 1 h. In this work, we used permalloy microdisks submitted to a Rotating Magnetic Field (RMF) and optimized in in vitro assay the particle concentration, magnetic field amplitude, and duration of exposure. We demonstrate here a strong lethal effect of TMMEP in vitro. We conducted in vivo assay on an orthotopic model of glioblastoma on mice but could not demonstrate efficacy of the treatment. We explain this failure by a strong difference in cell mechanical properties between in vitro and in vivo assay. To face this difficulty, we propose an in vitro 3D model by the use of spheroids put in a gel which can then be treated as a tumor and enable to mimic particle injection and RMF exposure. We also developed a 3D gel model mimicking peri-tumoral invasion of glioblastoma cells. Similarly, to the spheroid model, no effect was observed on the tumor proliferating cell in the core of the tumor. Moreover, migrating cells outside the core were strongly altered in their migration by the mechanical stimulation. Indeed, the data in the literature that supported our approach to TMMEP are essentially in vitro experimental results and no evaluation of TMMEP had yet been performed on an in vitro 3D model. Only a few articles showed in vivo efficacy, but the only survival benefit has been obtained with particles injected at the same time as the cells. The use of spheroids and organoids for the study of cancer and its treatments is now booming. Taking into account the importance of mechanical properties in tumor development, this model, placed in between 2D cell culture and animal experiments, mimics the architecture and heterogeneity of the tumor microenvironment. Closer to the in vivo tumor environment, this technique enables to better optimize and test in vitro treatments before moving to the preclinical phase, thus reducing the number of animals used in medical research. Preclinical models have been also extensively questioned, poorly mimicking the human disease. We demonstrated that results obtained in 2D culture are not relevant for the in vivo situation. Similarly, classical animal models are also poorly relevant, harboring a few invasive cells in the peritumoral area that is the main driver for tumor relapse. The model developed in this study will be crucial to modelize potential effect of magnetic vibration. The anti-invasive properties of magnetic vibration discovered using this innovative model could be explained by the specificity of the cell cytoskeleton in the migrating machinery, potentially highly sensitive to mechanical impact. A new preclinical strategy is emerging using new models to detect potential therapeutical effect of nano-magnetic vibrations. Similarly, a new design of the clinical trials should be implemented using highly cognitive trials, multimodal imaging including mechanical imaging and in situ molecular and cellular analysis of the tumor after local delivery of magnetic particles and mechanical actuation. These new translational paradigms also warrant a rigorous ethical analysis.

**References:**

Cécile Naud, François Berger, Hélène Joisten et al. Cancer treatment by magneto-mechanical effect of particles, a review. Nanoscale Adv., 2020, 2, 3632. Jain KK. A Critical Overview of Targeted Therapies for Glioblastoma. Front Oncol. 2018;8(October):1–19. Kim D-H, Rozhkova EA, Ulasov I V, Bader SD, Rajh T, Lesniak MS, et al. Biofunctionalized magnetic-vortex microdiscs for targeted cancer-cell destruction. Nat Mater. 2010;9(2):165–71. Master AM, Williams PN, Pothayee N, Zhang R, Vishwasrao HM, Golovin YI, et al. Remote Actuation of Magnetic Nanoparticles for Cancer Cell Selective Treatment Through Cytoskeletal Disruption. Sci Rep. 2015;1(919):1–13. Zhang E, Kircher MF, Koch XM, Eliasson L, Goldberg SN, Renstrom E. Dynamic Magnetic Fields Remote-Control Apoptosis via Nanoparticle Rotation. ACS Nano. 2014;8(4):3192–201. Leulmi S, Chauchet X, Morcrette M, Ortiz G, Joisten H, Sabon P, et al. Triggering the apoptosis of targeted human renal cancer cells by the vibration of anisotropic magnetic particles attached to the cell membrane. Nanoscale. 2015;7(38):15904–14. Wong DW, Gan WL, Liu N, Lew WS. Magneto-Actuated cell apoptosis by biaxial pulsed magnetic field. Sci Rep . 2017;7(1):1–8. Cheng Y, Muroski ME, Petit DCMC, Mansell R, Vemulkar T, Morshed RA, et al. Rotating magnetic field induced oscillation of magnetic particles for in vivo mechanical destruction of malignant glioma. J Control Release. 2015 Feb;223:75–84. Mansell R, Vemulkar T, Petit DCMC, Cheng Y, Murphy J, Lesniak MS, et al. Magnetic particles with perpendicular anisotropy for mechanical cancer cell destruction. Sci Rep. 2017;7(1):1–7. Fong ELS, Harrington DA, Farach-Carson MC, Yu H. Heralding a New Paradigm in 3D Tumor Modeling. Biomaterials. 2016;108:197–213.

**Images:**

![](https://assets.underline.io/uploads/markdown_image/1/image/ba8b6c4eeab8d4b2dfb813ca3884c747.jpg)
Figure 1: Spheroid model for preclinical mechanical stimulation testing. 1) mechanical stimulation using Halbach cylinder 2) in situ local delivery of magnetic nanoparticles.

![](https://assets.underline.io/uploads/markdown_image/1/image/d0c76220555207e62848ace21d7b64c5.jpg)
Figure 2

 Nanoviber: magnetic nanovibrations for brain tumor therapy: the translational road also needs innovation

Transition metal elements play many essential roles in the normal functioning of the human brain. These elements are transported, stored, and used by a vast range of proteins and enzymes. In most examples they are bound as individual metal ions (such as cobalt in vitamin B12), but some mineralized forms (such as the iron oxide core in ferritin) are also present. Neurodegenerative disorders (an umbrella term encompassing many forms of dementia and movement disorders), exhibit complex pathological changes within the central nervous system and beyond. Among these changes, altered patterns of transition metal element storage and utilization are generally observed in neurodegenerative disorders, as reviewed by others (e.g. Mezzaroba 2019). Magnetism plays key roles both in distinguishing the post-mortem materials properties of transition metals in biology, and in the clinical detection of transition metals in brain tissues (Collingwood & Telling, 2016). To advance the field, it is necessary to be able to image and quantify these transition metal elements in the human brain with sensitivity and specificity. From an analytical perspective, these brain compartments are effectively dilute systems, and the abundance, distribution, and material properties of the respective metal elements in their local environments vary greatly between cell types, tissues, and brain regions, and this in turn has implications for detection. The earliest histochemistry studies of post-mortem tissue revealled the heterogeneity of elements throughout the brain architecture, for example with Perls staining for iron. The ways in which these metals are bound affects staining efficacy, and efforts have been made to quantify metal ion concentrations in brain tissue as a function of brain region and ageing (e.g. Hallgren & Sourander 1958). Imaging transition metals within the living human brain with sensitivity and specificity presents many challenges. Transcranial sonography has shown sensitivity to tissue iron concentration, and scope to apply Dual-Energy Computed Tomography to image the most abundant elements is being explored. The most widely recognised opportunity came with the advent of Magnetic Resonance Imaging (MRI), which created the opportunity for sensitive, if not specific, clinical imaging of iron in the human brain (Drayer 1986). Subsequent efforts to improve specificity have included i) Bartzokis’ approach with sequential MRI scans using two distinct (B0) magnetic fields, which enable measurement of the field-dependent transverse relaxation increase associated with ferritin-encapsulated iron oxide nanoparticles (e.g. Bartzokis 2000), and ii) Quantitative Susceptibility Mapping, a method utilizing phase images to determine magnetic susceptibility distributions within tissues to thereby infer chemical composition (e.g. Haacke 2015). Post-mortem analysis continues to play an important role in testing the relationships between the properties of transition metals in brain tissue, and the signals detected with clinically-applicable methods. Magnetometry methods enable the proportion of iron present as iron oxide to be distinguished and characterized, although historically this has been applied to bulk samples, so spatial distribution information has not been preserved. Opportunities for magnetic imaging continue to evolve, and recently we demonstrated the application of synchrotron X-ray Magnetic Circular Dichroism to image the magnetic properties of post-mortem tissue from Alzheimer’s disease patients at sub-micron spatial resolution (Everett 2018). Meanwhile, the relative distribution of transition metals can be measured with outstanding sensitivity and specificity using focused beam synchrotron X-ray fluorescence imaging, creating the opportunity to correlate these distributions with high resolution quantitative MRI (Finnegan 2019). These findings can in turn inform interpretation of clinical MRI data. In conclusion, current developments in both post-mortem and clinical imaging are supporting efforts to determine whether altered patterns of transition metals can be used as biomarkers, and to investigate the extent to which disease-associated changes in the regulation of transition metals may provide insight into the pathogenesis of neurodegenerative disorders.

**References:**

G. Bartzokis and T. Tishler, Cell Mol. Biol., Vol. 46, p.821 (2000) J. Collingwood and N. Telling, Iron Oxides: from Nature to Applications, Chap. 7, p143 (2016) B. Drayer, P. Burger, R. Darwin et. al., AJR Am. J. Roentgenol. Vol. 147, p.103 (1986) J. Everett, J. Collingwood, V. Tjendana-Tjhin et. al., Nanoscale, Vol. 10, p.11782 (2018) M. Finnegan, N. Visanji, I. Romero-Canelon et. al., J. Neurosci. Methods, Vol. 319, p.28 (2019) E. Haacke, S. Liu, S. Buch et. al., Magnetic Resonance Imaging, Vol. 33, p.1 (2015) B. Hallgren and P. Sourander, J. Neurochem. Vol. 3, p.41 (1958) L. Mezzaroba, D. Alfieri, A. Simão, and E. Reiche, Neurotoxicology, Vol. 74, p.230 (2019)

**Images:**

 Imaging and Quantifying Transition Metal Ion Distribution in the Human Brain for Early Detection and Diagnosis of Neurodegenerative Disorders

The power released by magnetic nanoparticles (MNPs) submitted to an alternating driving field in the typical frequency range used in therapeutic treatments based on magnetic hyperthermia is studied using a rate-equation approach in which MNPs are modelled as double-well systems with randomly distributed easy axes. Taking into account the temperature dependency of MNP magnetization and anisotropy, a detailed picture of their hysteretic properties and of the resulting heating efficiency. The temperature variation in a host medium is then studied by solving a simple, radial Fourier equation with two typical boundary conditions. The time evolution of the temperature increment of the medium turns out to be strongly affected by the non-monotonic temperature dependence of the power released by NPs (see Figure 1a); the direct consequences on the heating efficiency make the determination of the specific loss power (SLP) and the resulting maximum temperature from the initial slope of the heating curve misleading. An alternative, sounder method to measure the average power released by magnetic nanoparticles and the SLP is proposed [1]. Another way of optimizing the performance of MNPs as heat generators consists in applying non-harmonic driving-field waveforms, with notable advantages with respect to the effects of harmonic magnetizing fields of same frequency and amplitude [2]. This improvement is related to the presence of fast, quasi-adiabatic transformations where the occupancy numbers in the two potential wells are virtually frozen, resulting in largely off-equilibrium magnetization states and in hysteresis loops with a greater area. In particular, changes of the inclination of the trapezoidal waveform’s lateral sides are also shown to induce controlled changes in the specific loss power generated by the activated nanoparticles (Figure 1b). Specific issues typical of the therapeutic practice of hyperthermia, such as the need for fine tuning of the optimal treatment temperature in real time, the possibility of combining sequential treatments at different temperatures, the ability to substantially reduce the heating transient in a hyperthermia treatment are properly addressed and overcome by making use of versatile non-harmonic driving fields of trapezoidal shape [3]. In the light of our results, features, methods, advantages and dangers of MNP-assisted precision nanomedicine are assessed in a more accurate way, and the efficiency of magnetic hyperthermia treatments is improved.

**References:**

[1] G. Barrera, P. Allia, P. Tiberto, Nanoscale, 2020,12, 6360. [2] P. Allia, G. Barrera, P. Tiberto, Phys. Rev. Applied, 2019, 12, 034041. [3] G. Barrera, P. Allia, P. Tiberto, Nanoscale Advances, 2020, 2, 4652.

**Images:**

![](https://assets.underline.io/uploads/markdown_image/1/image/aceca2e127ef31688d27f6c19470c419.jpg)
(a) Left: Time evolution of the temperature increment. Right: released power by NPs as a fuction of temperature. (b) Temperature increment as a function of time for selected inclination of the trapezoidal waveform lateral sides.

 Heating efficiency of magnetic nanoparticles for magnetic hyperthermia: effects of temperature and driving-field waveform

In the last months, due to the COVID-19 pandemic, we have become familiar with the expression “rapid tests” referred to fast and easy-to-use bioanalytical devices to detect viral proteins or antibodies generated by the patient’s immune system in response to the infection. The same type of rapid tests is extremely interesting to detect cancer biomarkers for disease screening and early diagnosis. Besides the fast response, the optimal technology should be low-cost, easy to use, and portable. The rapid tests rely on the lateral flow immunoassay (LFIA) technique [1]. The LFIA substrate is a strip of nitrocellulose membrane along which the liquid sample containing the molecule of interest can flow by capillary action. Before this flow, the analyte is specifically tagged with fluorescent enzymes or particles to make it visible. Two lines of recognition molecules are immobilized across the strip: (i) the test line, formed by a molecule that captures the tagged molecule of interest, and (ii) the control line, at which the unbound tags are trapped. The LFIA technique is used for point-of-care detection of various biomarkers; the best known is the pregnancy hormone in the popular home pregnancy tests that we can buy in the pharmacy and use ourselves with no prescription. There are some limitations for LFIA expansion, mainly their sensitivity and limit of quantification, which are not sufficient for some biomedical applications. Despite their limitations, WHO highly encourages the research into their performance and utility for disease surveillance [2]. There are two crucial ways in which magnetism can contribute effectively to improve the performance of rapid diagnostic tests: magnetic nanotags and magnetic sensing. The use of magnetic particles to tag the biomolecule of interest can have several advantages compared to non-magnetic tags (used for optical detection): magnetic immuno-concentration, magnetic detection, and long-lasting signal. Once the biomolecule is tagged by magnetic particles, the magnetic pre-concentration or isolation of the target biomolecule can be achieved by a magnetic gradient that attracts them and allow their separation from the original medium. This is enormously advantageous to increase the sensitivity of any technique that is applied after it. We can then detect the particles through a magnetic sensor without interferences from the paper strip or the biological fluid. Finally, the magnetic signal coming from the particles in the test line perdures in time and is insensitive to the paper strip aging or staining [3]. We recently developed a bio-detection method based on LFIA using superparamagnetic labels combined with an inductive sensor for reading out their signal. We proved the viability of the technique for quantifying prostatic cancer biomarkers [3] and toxic biogenic amines [4] in the range of interest. In this work, we have developed a lateral flow immunoassay (LFIA) system to detect plasma-derived extracellular vesicles (EV). These small (micro- or nano-sized) membrane structures are released by cells to mediate intercellular communication. Given that they carry proteins and micro-RNA specific to their cell of origin, they are nowadays thoroughly studied as disease biomarkers. We used superparamagnetic iron oxide nanoparticles coated with a double layer of oleic acid [5] as reporter labels. They were conjugated to antibodies against proteins expressed in the EVs surface, specifically CD-63 and CD-147. The latter is in higher concentrations in patients with colorectal cancer [6]. We used different concentrations of EVs purified from human plasma to perform LFIA tests to calibrate the system. Fig. 1 shows some of the LFIA strips obtained for such calibration. Subsequently, the strips were analyzed by a commercial reflectance sensor and our magnetic inductive sensor. The results for the assays with CD63 are shown in Fig. 2. We can appreciate that the linear range extends to all the concentration range understudy for the magnetic sensor. The tendency to saturation that we observe with the optical reader is typical of the immunoassays and is caused by the available antibodies' occupation. Given that the reflectance signal comes only from the particles at the surface of the membrane, the saturation is achieved at lower concentrations than in the magnetic one, which comes from the whole volume. Besides this obvious advantage, the magnetic sensor provides better linearity (even taking a reduced linear range of concentration for the optical signal) and a lower limit of detection (three times smaller for CD63 and two times smaller for CD147). We must emphasize that the analyte has not been magnetically pre-concentrated for these measurements. Such a technique will be studied in an ongoing investigation to increase further the sensitivity of the magnetic LFIA aiming at a rapid, portable technology for liquid biopsy applied to colorectal cancer screening. Acknowledgements This work was supported by the Spanish Ministry of Economy and Competitiveness (grant MAT2017-84959-C2-1-R), the Principality of Asturias (IDI/2018/000185) and the Council of Gijón/IUTA (SV-20-GIJON-1-22).

**References:**

[1] C. Parolo, A. Sena-Torralba, J.F. Bergua, et al., Nat Protoc., Vol. 15(12), p.3788 (2020) [2] https://www.who.int/news-room/commentaries/detail/advice-on-the-use-of-point-of-care-immunodiagnostic-tests-for-covid-19 [3] D. Lago-Cachón, M. Oliveira-Rodríguez, M. Rivas, et al., IEEE Magn. Lett., Vol. 8, p. 1 (2017) [4] A. Moyano, M. Salvador, J. C. Martínez-García, et al., Anal. Bioanal. Chem, Vol. 411, p. 6615 (2019) [5] D. Bica, L. Vékás, M.V. Avdeev, et al., J. Magn. Magn. Vol. 311, p. 17 (2007). [6] Y. Yoshioka, N. Kosaka, Y. Konishi, et al., Nat. Commun. Vol. 5, p. 1 (2014)

**Images:**

![](https://assets.underline.io/uploads/markdown_image/1/image/f92db3f9ddab9742d7c6522ff6432089.jpg)
LFIA strips performed to test the concentration of human-plasma circulating EVs expressing CD63.

![](https://assets.underline.io/uploads/markdown_image/1/image/0b555f1683f3ae239395a4ececf06bc3.jpg)
Calibration of CD63 LFIAs using the magnetic (black) and optical (orange) readers.

 Magnetic Bio-Sensing of Plasma-Derived Extracellular Vesicles for Cancer Screening

Transcranial magnetic stimulation (TMS)1,2 is a widely available technology employing strong ( up to 4 T) pulsed (up to 300 Hz) magnetic fields for diagnostics of brain functions and treatment of various brain disorders. It is currently approved for clinical application in patients with drug-resistant depression2,3, while a spectrum of new indications is emerging5-10. The current paradigm of TMS biological effects implies magnetic induction of Eddy currents in the brain cortical neurons as the leading action mechanism. However, the effects of the TMS-like magnetic fields on non-neuronal cells and some artificial systems is almost unknown. Based on literature analysis4,11-24 and our pilot experimental data, we hypothesize, that the transcranial and extracranial repetitive magnetic stimulation employing pulsed magnetic fields (MFs) generated by TMS devices can have immunomodulatory effects, affect the growth of brain and extracranial malignant tumours and applied in drug delivery control to the cells. This motivated us to explore the effects of designed 18 regimes of patterned repetitive magnetic stimulation (PRMS) on tumor cells of brain (glioblastoma multiforme, GBM) and pancreatic (pancreatic ductal adenocarcinoma) cancers and on microglia (immune cells of the brain). We also tested the effect of PRMS on a drug release from polymer nanoparticles in aqueous environment. A standard TMS device “Magstim Rapid2” with Double 70mm Air Film Coil was applied to the cell cultures spatially configured to correspond to a peak MF of 0.6 T, 0.25-50 Hz frequency, with sessions of 300 or 600 pulses. PRMS selectively modulated the viability and functional polarisation of immune-stimulated microglia in a frequency/intensity-dependent manner (Figure 1) and affected the proliferation/viability of GBM astrocytes and pancreatic cancer cells (frequency- and pulse number-dependent up- and downregulation) (Figure 2). Finally, we show the triggering of the efficient drug release from biocompatible polymer nanoparticles by the 50 Hz/2 min PRMS mode. Our pioneering findings demonstrate the potential of PRMS performed with using of re-purposed TMS equipment for immunomodulation, cancer treatment, brain repair and regeneration. We thank Sydney Vital Translational Cancer Centre (for seed grant) and Medilink Australia (for providing the “Magstim”).

**References:**

1. Barker AT, et al.: Neurosurgery 1987, 20:100-9. 2. Rossini PM, et al. U: Clinical neurophysiology 2015, 126:1071-107. 3. Post A, Keck ME: Journal of Psychiatric Research 2001, 35:193-215. 4. Funk RH, et al.: Prog Histochem Cytochem 2009, 43:177-264. 5. Nardone R, et al.: Brain research bulletin 2020, 159:44-52. 6. Gao F, et al.: J Neurosurg Sci 2017, 61:514-22. 7. Rose DK, et al.: Stroke Res Treat 2014, 2014:305236. 8. Jin Y, et al.: Pain Physician 2015, 18:E1029-46. 9. Pérocheau D, et al.: Joint, bone, spine : revue du rhumatisme 2014, 81:22-6. 10. Peng L, et al.: Medicine 2019, 98:e15572. 11. Vazana U, et al.: J Neurosci 2016, 36:7727-39. 12. Antov Y, et al.: Biophysical journal 2005, 88:2206-23. 13. Shankayi Z, et al.: Electromagn Biol Med 2014, 33:154-8. 14. Towhidi L, et al.: Radiol Oncol 2012, 46:119-25. 15. Adey WR, Sheppard AR: in Mechanistic Approaches to Interactions of Electric and Electromagnetic Fields with Living Systems: Springer, 1987. pp. 365-87. 16. Cullen CL, Young KM: Front Neural Circuits 2016, 10:26. 17. Yamaguchi S, et al.: Bioelectromagnetics 2006, 27:64-72. 18. Golovin YI, et al.: Journal of controlled release 2015, 219:43-60. 19. Kim DH, et al.: Nat Mater 2010, 9:165-71. 20. Master AM, et al.: Scientific reports 2016, 6:33560. 21. Wong W, et al.: Scientific reports 2017, 7:10919. 22. Maniotis N, et al.: Journal of Magnetism and Magnetic Materials 2019, 470:6-11. 23. Pickard M, Chari D.: Nanomedicine 2010, 5:217-32. 24. Pickard MR, Chari DM: Int J Mol Sci 2010, 11:967-81.

**Images:**

![](https://assets.underline.io/uploads/markdown_image/1/image/675949e68680cf21b88464bc22e3c533.jpg)
Figure 1. Effect of PRMS generated by a TMS device on viability of murine microglial BV-2 cells cultured in vitro. The cells’ viability was evaluated by MTT assay in 24 h after performing magnetic treatment. Mean absorbance is directly proportional to the number of viable cells. The left bar represents absorbance in control (untreated group), and the next bars to the right represent the measurements in the cells’ cultures treated with different regimes of PRMS.

![](https://assets.underline.io/uploads/markdown_image/1/image/88bd8af725285a4c5a0ad3eb1f3c5956.jpg)
Figure 2. Effect of PRMS generated by a TMS device on viability of human pancreatic cancer cells (PANC-1) cultured in vitro. The cells’ viability was evaluated by MTT assay in 24 h after performing magnetic treatment. Mean absorbance is directly proportional to the number of viable cells. The left bar represents absorbance in control (untreated group), and the next bars to the right represent the measurements in the cells cultures treated with different regimes of PRMS. Green dashed lines indicate the borders of CI95% for mean absorbance in control (untreated group; the left bar).

 Potential effects of TMS magnetic fields beyond the conventional neurostimulation



Conventional magnetorheological (MR) fluids are colloidal suspensions prepared by dispersion of magnetisable particles in non-magnetic liquid carriers. Interestingly, they exhibit a remarkable rheological change (so-called MR effect) upon the application of a magnetic field. The reason for this is the magnetic field-guided colloidal assembly of the dispersed magnetisable particles. The self-assembly can be controlled through the field configuration (DC, AC or combinations) and most of the investigations reported in the literature focus on DC fields. In this communication we show that the use of AC fields alone or in combination of DC fields are capable to generate exotic structures with enhanced MR effect (i.e. larger viscoelastic moduli and yield stresses).

**References:**



**Images:**





 Magnetorheology in Unsteady Triaxial Fields

As the fight against Covid-19 pandemic continues, we have learned that the blood clotting caused by Covid-19 is the main issue making this disease much more server than any flu or pneumonia. Doctors are seeing an alarming number of COVID-19 patients with blood clots — gel-like clumps in the blood that cause serious problems: internal bleeding, heart attack and stroke [1]. Autopsies have also found blood clots not only in the lungs of these victims, but throughout their bloodstream [2]. The microscopic image in Fig.1 illustrates that as the red blood cells stack together to form clots, their surfaces are blocked, compromising their oxygen function. When the blood clots get bigger, they can block blood circulation and trigger heart attack or stroke. Dr. Kanthi et.al recently claim that sever Covid-19, same as AP Syndrome, induces antibody to attack the phospholipid in red cell membrane, triggering blood clotting [3]. These blood clots take most platelets, creating high risk for internal bleeding. Currently blood thinners are the only medicine used to reduce the blood clot formation in server Covid-19 patients. Unfortunately, blood thinner medicines do not disassemble the blood clots. Moreover, they increase the risk of bleeding, serious, or even life threatening. In fact, many patients were not saved by these medicines. Therefore, a new, safe and reliable approach to disassemble blood clots for Covid-19 patients is urgently needed. Here I am presenting our magnetorheology (MR) technology [4] to treat Covid-19 patients with thrombosis: applying a strong magnetic field along the patients’ arm. When the blood clots come to the magnetic field with blood circulation, they will be disassembled. Red cells will be freed, the blood oxygenation function will be recovered, internal bleeding can be avoided, the blood viscosity along the flow direction will be reduced, turbulence will be suppressed, and cardiovascular accident can be prevented. Blood is a liquid suspension consisting mainly of red cells in plasma. The volume fraction of red cells is 40-50%. The amount of white blood cells and platelets in the blood is very small. Therefore, blood clots are actually aggerates of red cells (Fig.1). A typical human red cell is a biconcave disk (Fig.2a), with its diameter about 7.7 μm and the thickness decreasing from 2.5 µm at its edge to 0.8–1 µm at its center. The cytoplasm of the red cell contains hemoglobin, a metalloprotein containing heme groups that temporarily bind oxygen molecules taken up from the lungs and release them throughout the body. To allow efficient diffusion of oxygen, the full surface area of the red cells need to be available. When the blood form clots such as in Fig.1, surfaces of red cells are blocked and oxygen uptake and delivery is impeded. As the hemoglobin in red cells is an iron containing protein, deoxygenated red cells are paramagnetic. We are utilizing this property to disassemble blood clots (Fig.2). Red cells are polarized in a magnetic field. Because red cell is a disk, the strongest polarization is along the diameter direction. In a strong magnetic field, red cells will tilt to make their disk surface parallel to the field. Each red cell obtains an induced magnetic dipole moment. As shown in Fig.2b, when the red blood cells stack each other as in the clots, the interaction between neighboring red cells is strongly repulsive. This force is proportional to the square of magnetic field. If the applied magnetic field stronger than one Tesla, this repulsive force is strong enough to break the toughest blood clots, rouleaux [4,5]. As blood clots are mainly aggregates of red cells, once red cells are disassembled, platelets and other components are also released; internal bleeding risk is reduced. The magnetic field will further align the released red cells to form short chains along the diameter direction (Fig.2c). In such chains, the surface of red cells is fully exposed, excellent for their normal oxygen functions. Fig.2d shows a microscopic image of such short chain. Also shown in Fig.2d, we apply the magnetic field along the blood flow direction. The short chains is parallel to the blood flow. As the chains are streamlined in the flow direction, the blood viscosity along the flow direction is considerably reduced. Meanwhile, the short chains resist any motion in the directions perpendicular to the flow. The treated blood thus suppresses turbulence or disturbed motion as any disturbed flow cannot survive without motions in the directions perpendicular to the flow [4,6]. The blood circulation and red cell function will thus be greatly improved and cardiovascular accident can be prevented. Of course, after the magnetic field is turned off, these short chains will be eventually broken and the red cells will become wholly independent, flowing inside the plasma (Fig.2e). Our lab tests [4] have confirmed that this MR technology can effectively disassemble rouleaux [6]. As the newly formed blood clots in Covid19 patients should be weaker than rouleaux, we expect that this technology can safely and effectively disassemble them and help the patients to recover.

**References:**

1. Z. Varga, et al , www.thelancet.com Vol 395, pp 1417-1418, May 2, 2020. 2. https://www.webmd.com/lung/news/20200424/blood-clots-are-another-dangerous-covid-19-mystery 3. Y. Zuo et al, Science Translational Medicine, 12. eabd3876 (2020) 4, R. Tao, et al., Systems and method for reducing the viscosity of blood, suppressing turbulence n blood circulation, and curing rouleaux. PCT/US2017/059446 (https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2018085330) 5. N. Abramson, BLOOD, V107, I 11, 4205-4205 (2006) 6. R. Tao, K. Huang, Physical Review E 84, 011905 (2011).

**Images:**

![](https://assets.underline.io/uploads/markdown_image/1/image/6b64306da497c2fe6f2556b8eeaa213b.jpg)
Fig.1 Blood clots found in coronavirus patients’ blood.

![](https://assets.underline.io/uploads/markdown_image/1/image/ac8be56cb6be363d3ac421eb3b6622ed.jpg)
Fig.2 (a) Red blood cell. (b) The strong magnetic field breaks the blood clot. (c) The released red cells form short chains along the diameter-magnetic field direction. (d) The microscopic image of a short red-cell chain. The magnetic field improves blood circulation. (e) After the magnetic field is off, the red cells will eventually become wholly independent within the plasma.

 Disassembling Blood Clots and Improving Blood Oxygenation With Magnetorheology For Covid-19 Patients

Smart materials can change key physical properties in response to external stimuli. To achieve adaptive design performance regardless of environmental changes, demand for smart materials technology has greatly increased. Magnetorheological (MR) composites are a class of smart materials that can rapidly and reversibly control adjust their damping and stiffness properties in response to external magnetic field. MR composites consist of micron-size soft magnetic particles in a non-magnetic carrier matrix. MR composites can be divided into three major classes based on matrix materials: MR fluids (MRFs), MR foams, and MR elastomers (MREs). The rheological properties of MRFs, which use liquid as the carrier matrix, can be controlled in response to an external magnetic field. MRFs have been widely applied to a variety of hydraulic actuators to produce a controllable damper force or torque. MR foams are composed of either non-magnetic porous metal foam filled with MRF or have particles embedded in a porous elastomeric foam. Because of their light weight and high compliance, MR foams exhibit large changes in baseline stiffness and are candidate smart materials for space applications, as well as vibration and acoustic absorption applications. MREs, which use a non-porous solid elastomer as the carrier matrix, have controllable viscoelastic properties. MREs can used to retrofit passive rubber isolators and mounts in vibration and shock mitigation systems to provide improved and adaptive performance. MRFs typically exhibit sedimentation because of the large density difference between carbonyl Fe particles (density of 7.9 g/ml) and the non-magnetic carrier fluid (e.g., silicone oil has a density of 0.97 g/ml). Unlike MRFs, the Fe particles in MR foams and MREs are permanently dispersed. Because particles are embedded in the carrier matrix, MR foams and MREs show less MR effect than MRFs where particles can migrate and agglomerate. To increase MR effects in MREs, research [1-4] to encapsulate MRFs in MREs has been reported. It should be noted that MR foams have porous carrier matrix and may be not possible to encapsulate MRF into MR foam. In this study, MRF encapsulated elastomers (MREEs) are fabricated and their controllable stress behaviors are experimentally evaluated. Two design configurations are studied for MREEs: the first is MRF and permanent magnet (PM) embedded inside MREEs, and the second is MRF only embedded in MREEs. MREEs with PM can be passively and actively activated, but MREEs without PM can be only activated by external magnetic field produced by an electromagnet. A sample MREE (Figure 1) encapsulates an MRF composed of 35 vol% carbonyl Fe dispersed in a 1,000 cSt silicone oil. The silicone rubber was as soft as 00-20. The diameter and height of this sample was nominally 2.6” and 0.37”, respectively. The compressive stress-strain curve of the MREEs both without and with applied magnetic field were measured by a MTS machine. Figure 2 presents the measured field-dependent compressive stress curves of the MREE. As seen in this figure, the compressive stress curves of the MREE can be continuously adjusted in response to current input. Also, the hysteresis loop also increased as the applied current inputs. This physically implies that the dissipated energy increased. In the full paper, the effect of two different magnetic flux directions (i.e., positive and negative coil currents) will be presented. The compressive stress curve of the MREEs can also be affected by the strain rate, as in impact events. To illustrate such strain rate effects, the compressive stress curves over a range of strain rates will be also presented. From the measured hysteresis loop, the dissipated energy can also determined. In addition, the MREEs can be stacked for accommodating larger compressive displacement. In this study, the effect of two different stackable situations (one is attractive PMs configuration and the other is repulsive PMs configuration) on the compressive stress curve will be evaluated. From the results presented in this study, the controllable stress capability of the MREEs will be presented for a range of operating conditions.

**References:**

[1] D. York, X. Wang, and F. Gordaninejad, “A new MR fluid-elastomer vibration isolator,” J. Intel. Mater. Syst. and Struct, 18: 1221-1225 (2007). [2] D. York, X. Wang, F. Gordnaniejad, “A new magnetorheological mount for vibration control,” J. Vibr Acoust., 133: 031003 (2011). [3] A. K. Bastola, L. Li and M. Paudel, |A hybrid magnetorheological elastomer developed by encapsulation of magnetorheological fluid,” Journal of Materials Science, Vol. 53, pp. 7004-7016 (2018). [4] A. K. Bastola, E. Ang, M. Paudel, L. Li, “Soft hybrid magnetorheological elastomer: gap bridging between MR fluid and MR elastomer,” Colloids and Surfaces A, Vol. 583, 123975 (2019).

**Images:**

![](https://assets.underline.io/uploads/markdown_image/1/image/c7b4531d44116ed3566e15610b99a51e.jpg)
Figure 1. MRF encapsulated elastomers (MREEs).

![](https://assets.underline.io/uploads/markdown_image/1/image/84dd4f6d08b64d7a6a8dcdde1ea3c75f.jpg)
Figure 2. Field-dependent compressive stress curves of the MREE.

 Controllable Stress of Magnetorheological Fluid Encapsulated Elastomers

Magnetorheological (MR) elastomers as composite materials of magnetizable particles in an elastomer matrix are the soft solid relatives of the better known MR fluids [1]. They preferably consist of silicone elastomer filled with dispersed iron particles [2]. MR elastomers exhibit interesting viscoelastic properties, which strongly depend on the elastomer stiffness and the particle concentration and are controllable by a magnetic field. With rising iron particle concentration, the basic stiffness in terms of the elastic storage modulus increases, as expected. In a strong magnetic field, the storage modulus can be enhanced by a factor of about 10 (see Figure 1). A corresponding increase is observed also for the viscous loss modulus (see Figure 1). These effects are particularly pronounced for MR elastomers with soft silicone matrices, which exhibit low molecular crosslinking densities. In common MR elastomers, the iron particles are randomly distributed in the surrounding matrix material due to the mixing of the particles with the liquid silicone precursors in the preparation process. However, it is also possible to prepare MR elastomers with anisotropic particle distribution [3]. In order to achieve this modification, a magnetic field is applied already in the preparation procedure before and during the chemical crosslinking of the silicone elastomer in a thermal process, where the particles are arranged to chains along the magnetic field, in analogy to MR fluids. The magneto-mechanical properties of anisotropic MR are significantly different from those of their isotropic counterparts. A strong increase of the storage modulus of the anisotropic composites is observed already with lower iron particles concentrations. In other investigations, the magnetic properties of MR elastomer cubes with isotropic and anisotropic particle arrangements were studied and compared. Similar to MR fluids, even with high concentrations of iron particles, the magnetic susceptibility of MR elastomers is extremely low in comparison with pure solid iron, which is due to the dispersed distribution of the iron particles in the composite. The measured susceptibility of the anisotropic MR elastomer with a magnetic field perpendicular to the iron particle chains is comparable to the corresponding values of the isotropic samples. However, it could be shown that the susceptibility parallel to the particle chains in the anisotropic MR elastomer is significantly higher due to the particle contacts in this direction. Numerous interesting applications become possible with MR elastomers. Generally known are applications in vibration reduction. Here, the focus is on tunable vibration absorbers due to the dominant elastic behavior of elastomers [4] in contrast to the more viscous characteristics of MR fluids. However, promising exploitation potential of MR elastomers arises also for actuation devices, where an MR elastomer body deforms in a magnetic field. A speciality of these MR elastomer-based actuators is the possibility to realize different types of actuation depending on the orientation of the magnetic field. A basic type of actuation is caused by the linear deformation of an MR elastomer body in a corresponding magnetic field. Due to magnetic attraction forces on the soft-magnetic iron particles by a specially shaped yoke part in the magnetic circuit, the MR elastomer body such as a disk is deformed into a preferred direction. This type of actuator can be used for human-machine interfaces, where haptic feedback is required, when the user touches the interface. Another interesting application of linear MR elastomer actuators are pumping units. In these units, the periodic linear deformation of the actuator sucks the medium to be transported through a non-return valve into a chamber and pushes it out through another non-return valve. Moreover, with MR elastomers also another type of actuators with radial motion may be realized. In a magnetic field with radial orientation between an inner yoke and an annular outer yoke, a ring-shaped body of MR elastomer between the two yokes leaving an annular gap to the inner yoke can expand radially and close the gap (see Figure 2). This unusual kind of radial actuation offers a high potential for various applications. Especially interesting are valves with a ring-shaped opening, where the degree of closing is controlled by the magnetic field strength, i.e. the current in the coil of the electromagnet, and the corresponding radial deformation of the MR elastomer ring. With this mechanism, proportional valves can be realized. Another possible application of radial MR elastomer actuators are locking devices. Here, MR elastomer rings bridge the annular gaps between an inner rotatable shaft and an outer housing, Thereby blocking the rotation, when the magnetic field is activated. It could be demonstrated that locking torques of about 5 Nm can be achieved in a device with two MR elastomer rings. The locking effect is stronger than with an MR fluid in a device with a corresponding geometrical configuration. In this symposium contribution, material properties of MR elastomers and various actuator designs for different applications are discussed.

**References:**

[1] J. D. Carlson and M. R. Jolly, MR fluid, foam and elastomer devices. Mechatronics 10, 555-569 (2000) [2] W. H. Li and M. Nakano, Fabrication and characterization of PDMS based magnetorheological elastomers, Smart Materials and Structures 22, 055035 (2013) [3] H. Böse and R. Röder, Magnetorheological Elastomers with high variability of their mechanical properties, J. Phys.: Conf. Ser. 149, 012090 (2009) [4] X. Z. Zhang and W. H. Li, Adaptive Tuned Dynamic Vibration Absorbers Working with MR Elastomers, Smart Structures & Systems 5, 517-529 (2009)

**Images:**

![](https://assets.underline.io/uploads/markdown_image/1/image/6744c1ad7d09ab43fe3a6705230d8b92.jpg)
Figure 1: Dependence of the storage modulus (left) and the loss modulus (right) of MRE composites with different carbonyl iron particle (CIP) concentrations on the magnetic flux density

![](https://assets.underline.io/uploads/markdown_image/1/image/9279471e448a328b9b3c131a71d3e93a.jpg)
Figure 2: MRE actuator with radial expansion for proportional valve applications in the inactivated state (annular gap open, left) and activated state (annular gap closed, right)

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