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Controlled linear movement of nanoparticles in suspension by homogeneous magnetic field gradients 13 12 1 Carlos David Amaya Jaramillo , José Javier Serrano Olmedo , Milagros Ramos Gómez , Francisco 1 del Pozo Guerrero 1. Center for Biomedical Technology (CTB), Campus Montegancedo28223 Pozuelo de Alarcón, Madrid, Spain 2. Center for Biomedical Research Network -Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Av. Monforte de Lemos, 3-5. Pabellón 11. Planta 0, Madrid, Spain 3. Secretary of Higher Education, Science, Technology and Innovation (SENESCYT),Alpallana E7-123 Pasaje Martín Carrión Edificio "Caminosdel Parque" LOCAL No. 3, Quito, Ecuador [email protected] Abstract The product of alternating gradient force and constant filed magnet is the main phenomenon to attract objects but, if the constant magnetic field and gradient magnetic are large enough it is possible to move magnetic nanoparticles and guide them in one directionand crash the MNP (magnetic nano-particle) against cells and produce cell death, this is possible due to the shape of Helmholtz coils and produce a gradient magnetic and control it by circulating current in the coils. The distance traveled by magnetic nanoparticles depends on: current and amount of nanoparticles clustered. We have designed and build an experimental set-up from a combination of a constant magnetic field and a time varying, homogeneous gradient magnetic field (Fig. 1). The higher the particle mass is the higher the linear momentum it acquires so that the mechanical interaction with cell (soft material) is more destructive. However, too large particles, for instance, equal or higher than the typical cell size, probably would cause only displacements of the cells, if they are free, since very large speeds are not easy to achieve inside a viscous fluid like water. On the opposite side, small particles could be too small if they simply punch the external cell membrane, or other inner cell membranes, causing the aperture of a hole, so small that the cell restores itself before any further damage is caused by, for instance, excessive interchange of fluids or ions through it. Then, our particles must be of size about or slightly higher than 1um that is the upper limit of nanoparticles used in Biolistic[1]. A large particle size is better because the magnetization is larger for the same magnetizing external field. Therefore, we suggest that particles from300 nm to 2µm. High magnetization can lead to the creation of clusters, filaments in shape, of mechanical characteristics depending on several conditions like the particle concentration, the viscosity of the media, the presence of other material in suspension and the strength of the magnetic field. In case of low concentration, the filaments are made of a few particles[2]. To control movement of MNP, we use a square current of 7A frequency 1 and 50 [Hz]in the coils (Fig. 2), and produce a magnetic field (Fig. 3) to move MNP in a concentration of 50 [µg/ml] from 30 to 60 [min]. This instrument could be useful to: cause cell death due to, damage caused by the movement of the MNPs interacting with cells; or treatment for thrombosis produced by the movement of the MNP to weaken the material that obstructs the blood flow. 132 1N1 cells were preincubated with different types of MNPs and introduced in the instrument described above to test the efficiency ofhomogeneous magnetic field gradient to promote cell death. Cell viability was assessed using the calcein and propidium iodide assay. (Fig. 4) Figure 4 and figure 5 show the resultsobtained by homogeneous magnetic field gradient application after treating 1321N1 and MC3T3-E1 cells with MNPs. The highest cell death rates were obtained preincubating cells with2m MNPs. References [1] B. R. Frame, H. Zhang, S. M. Cocciolone, L. V. Sidorenko, C. R. Dietrich, S. E. Pegg, S. Zhen, P. S. Schnable, and K. Wang,Vitr. Cell. Dev. Biol. - Plant, vol. 36, no. 1, “Production of transgenic maize from bombarded type II callus: Effect of gold particle size and callus morphology on transformation efficiency”, (2000), pages. 21–29. [2] E. Zhang, M. F. Kircher, M. Koch, L. Eliasson, S. N. Goldberg, and E. Renström, ACS Nano, vol. 8, no. 4,“Dynamic Magnetic Fields Remote-Control Apoptosis via Nanoparticle Rotation”, Apr. (2014), pages. 3192–3201. Figures Front view Top View Figure 1: Helmholtz coil inside permanent magnetic field Figure 3: Magnetic field produced by coils Figure 2: Gradient magnetic field produced by coils Control 1Hz 50Hz Figure 4: Cell viability after magnetic field treatments. 132 1N1 cells were stained with propidium iodide to visualize dead cells (red) at different irradiation frequency. Scale bar 500m. A B Figure 5:A. Viability of 1321N1 cells exposed to magnetic field treatments controlled by a current square of 7A frequency from 1 to 50 [Hz] for 60 min. B. Cell viability in MC3T3-E1 cell line after 30 and 60 min of exposure to 50Hz magnetic fields, as evaluated by calcein /propidium iodide assay