Magnetic and hydrogel composite materials for hyperthermia applications

Micron-sized magnetic particles (Fe3O4) were dispersed in a polyvinyl alcohol hydrogel to study their potential for hyperthermia applications. Heating characteristics of this ferrogel in an alternating magnetic field (375 kHz) were investigated. The results indicate that the amount of heat generated depends on the Fe3O4 content and magnetic field amplitude. A stable maximum temperature ranging from 43 to 47 degrees C was successfully achieved within 5-6 min. The maximum temperature was a function of Fe3O4 concentration. A specific absorption rate of up to 8.7 W/g Fe3O4 was achieved; this value was found to depend on the magnetic field strength. Hysteresis loss is the main contribution to the heating effect experienced by the sample.     

PNIPA/PEG多孔智能水凝胶的辐射合成与性能研究

采用辐射法合成了一系列具有合适相变温度和快速响应性能的PNIPA/PEG多孔智能水凝胶,用红外光谱分析了水凝胶的结构,并测定了水凝胶的溶胀动力学、平衡溶胀率和退溶胀动力学,研究了辐射剂量和成孔剂分子量对凝胶性能的影响.结果表明,PEG分子仅在聚合交联过程中充当成孔剂,不参与反应,反应后被除去;PNIPA/PEG水凝胶的平衡溶胀率(SR)随辐射剂量的升高而减小,其最低临界相转变温度(LCST)在37℃左右,且基本不受辐射剂量的影响;溶胀性能随着PEG分子量的增大而提高.     

A cylindrical-section ultrasound phased-array applicator for hyperthermia cancer therapy

A phased-array applicator geometry for deep localized hyperthermia is presented. The array consists of rectangular transducer elements forming a section of a cylinder that conforms to the body portals in the abdominal and pelvic regions. Focusing and scanning properties of the cylindrical-section array are investigated in homogeneous lossy media using appropriate computer simulations. The characteristic focus of this array is shown to be spatially limited in both transverse and longitudinal directions with intensity gain values suitable for deep hyperthermia applications. The ability of the cylindrical-section phased array to generate multiple foci using the field conjugation method is examined. The effect of the grating lobes on the power deposition pattern of the scanned field is shown to be minimal. Steady-state temperature distributions are simulated using a three-dimensional thermal model of the normal tissue layers surrounding a tumor of typical volume. The advantages and the limitations of this array configuration are discussed.     

Hyaluronic acid hydrogels for biomedical applications

Hyaluronic acid (HA), an immunoneutral polysaccharide that is ubiquitous in the human body, is crucial for many cellular and tissue functions and has been in clinical use for over thirty years. When chemically modified, HA can be transformed into many physical forms-viscoelastic solutions, soft or stiff hydrogels, electrospun fibers, non-woven meshes, macroporous and fibrillar sponges, flexible sheets, and nanoparticulate fluids-for use in a range of preclinical and clinical settings. Many of these forms are derived from the chemical crosslinking of pendant reactive groups by addition/condensation chemistry or by radical polymerization. Clinical products for cell therapy and regenerative medicine require crosslinking chemistry that is compatible with the encapsulation of cells and injection into tissues. Moreover, an injectable clinical biomaterial must meet marketing, regulatory, and financial constraints to provide affordable products that can be approved, deployed to the clinic, and used by physicians. Many HA-derived hydrogels meet these criteria, and can deliver cells and therapeutic agents for tissue repair and regeneration. This progress report covers both basic concepts and recent advances in the development of HA-based hydrogels for biomedical applications.     

Localised heating of tumours utilising injectable magnetic nanoparticles for hyperthermia cancer therapy

This study reports an investigation of hyperthermia cancer therapy utilising an alternating magnetic field to induce a localised temperature increase on tumours by using injectable magnetic nanoparticles. In-vitro and in-vivo experiments represent the feasibility of hyperthermia cancer therapy. A feedback temperature control system was first developed to keep the nanoparticles at a constant temperature to prevent overheating in the tumours such that a safer and more precise cancer therapy becomes feasible. By using the feedback temperature control system, magnetic nanoparticles can be heated up to the specific constant temperatures, 37, 40, 42, 45, 46 and 47degC, respectively, with a variation less than 0.2degC. With this approach, the in-vitro survival rate of tumour cells at different temperatures can be systematically explored. It was experimentally found that the survival rate of cancer cells can be greatly reduced while CT-26 cancer cells were heated above 45degC. Besides, localised temperatures increase as high as 59.5degC can be successfully generated in rat livers by using the proposed method. Finally, complete regression of tumour was achieved. The developed method used injectable magnetic nanoparticles and may provide a promising approach for hyperthermia cancer therapy.     

Polysaccharide-based magnetically responsive polyelectrolyte hydrogels for tissue engineering applications

Polysaccharide-based bionanocomposite hydrogels with functional nanomaterials were used in biomedical applications.Self-organization of xanthan gum and chitosan in the presence of iron oxide magnetic nanoparticles(Fe_3O_4MNPs)allowed us to form magnetically responsive polyelectrolyte complex hydrogels(MPECHs)via insitu ionic complexation using D-(+)-glucuronic acid?-lactone as a green acidifying agent.Characterization confirmed the successful formation of(and structural interactions within)the MPECH and good porous structure.The rheological behavior and compressive properties of the PECH and MPECH were measured.The results indicated that the incorporation of Fe_3O_4MNPs into the PECH greatly improved mechanical properties and storage modulus(G’).In vitro cell culture of NIH3T3 fibroblasts on MPECHs showed improvements in cell proliferation and adhesion in an external magnetic field relative to the pristine PECH.The results showed that the newly developed MPECH could potentially be used as a magnetically stimulated system in tissue engineering applications.     

Synthesis and characterizations of manganese ferrites for hyperthermia applications

In the last few years, magnetic nanoparticles have turned out to offer great potential in biomedical applications. This study was focused on Mn_xFe_1−xFe₂O₄ ferrite particles series with x ranging between 0 and 1. Manganese ferrites nanoparticles were prepared by co-precipitation method that allows a good control of their shape and size. The X-ray analysis indicated a crystallite size of the particles in the nanometers domain increasing with the Mn cation substitution level. Average grain size of the nanoparticles calculated from transmission electron microscopy images of the samples was ranging between 10.5 and 19.0 nm suggesting that the majority of the nanoparticles are monodomain. The hydrodynamic diameter of the water dispersed nanoparticles measured by dynamic light scattering was ranging between 60 and 105 nm proving the tendency of agglomeration. Vibrating sample magnetometer measurement confirmed the superparamagnetic behavior of the powders. The magnetic properties were analyzed considering the proposed cation distribution and Yafet–Kittel angles, while the specific absorption rate (SAR) measurement at 1.95 MHz frequency confirmed the influence of substitution level on magnetic properties and thermal transfer rate. From our results the highest value for specific absorption rate was 148.4 W g⁻¹ for Mn₂Fe₂O₄ at an AC field of 4500 A m⁻¹.     

Recent nanotheranostics applications for cancer therapy and diagnosis: A review

Nanotheranostics has attracted much attention due to its widespread application in molecular imaging and cancer therapy. Molecular imaging using nanoparticles has attracted special attention in the diagnosis of cancer at early stages. With the progress made in nanotheranostics, studying drug release, accumulation in the target tissue, biodistribution, and treatment effectiveness are other important factors. However, according to the studies conducted in this regard, each nanoparticle has some advantages and limitations that should be examined and then used in clinical applications. The main goal of this review is to explore the recent advancements in nanotheranostics for cancer therapy and diagnosis. Then, it is attempted to present recent studies on nanotheranostics used as a contrast agent in various imaging modalities and a platform for cancer therapy.     

Ultrasonic phased arrays with variable geometric focusing for hyperthermia applications

An ultrasonic applicator, which utilizes both electronic and variable geometric focusing, for deep-localized hyperthermia is investigated. The applicator is based around a linear phased array that furnishes its electronic focusing capability. The output of the array radiates through a spherical liquid-lens that provides the applicator a variable geometric focusing capability as well. A lens of this type adds dynamic focusing to the elevation dimension of the linear phased array. By controlling the volume of liquid in the lens (and thus the radius of curvature of its membrane), dynamic control of the geometrical focus can be achieved. Comparisons of computer simulations and experimental measurements of the field intensity distribution of a small-scale prototype applicator are presented. Important design parameters, such as the choice of the liquid for the lens and the size and number of array elements, are examined.     

Inverse problem in the hyperthermia therapy of cancer with laser heating and plasmonic nanoparticles

In this paper, laser-induced hyperthermia therapy of cancer is treated as a state estimation problem and solved with a particle filter method, namely the Auxiliary Sampling Importance Resampling algorithm. In state estimation problems, the available measured data are used together with prior knowledge about the physical phenomena, in order to sequentially produce estimates of the desired dynamic variables. Although the hyperthermia treatment of cancer has been addressed in the literature by different computational methods, these usually involved deterministic analyses. On the other hand, state space representation of the problem in a Bayesian framework allows for the analyses of uncertainties present in the mathematical formulation of the problem, as well as in the measured data of observable variables that might be eventually available. Two physical problems are considered in this paper, involving the irradiation with a laser in the near infrared range of a non-homogeneous cylindrical medium representing either a soft-tissue phantom or a skin model, both containing a tumour. The region representing the tumour is assumed to be loaded with nanoparticles in order to enhance the hyperthermia effects and to limit such effects to the tumour. The light propagation problem is coupled with the bioheat transfer equation in the present study. Simulated transient temperature measurements are used in the inverse analysis.     

Olive oil based novel thermo-reversible emulsion hydrogels for controlled delivery applications

Gels have been considered as a popular mode of delivering medicament for the treatment of sexually transmitted diseases (STDs) (e.g. human immunodeficiency virus, bacterial vaginosis, epididymitis, human papillomavirus infection and condylomata acuminata etc.). The present study discusses the development of novel olive oil based emulsion hydrogels (EHs) using sorbitan monopalmitate as the structuring agent. The developed EHs may be tried as drug delivery vehicle for the treatment of STDs. The formation of EHs was confirmed by fluorescence and confocal microscopy. FTIR studies suggested intermolecular hydrogen bonding amongst the components of the EHs. X-ray diffraction study suggested the amorphous nature of the EHs. The developed EHs have shown non-Newtonian flow behavior. The EHs were found to be biocompatible. The formulations were able to effectively deliver two model antimicrobial drugs (e.g. ciprofloxacin and metronidazole), commonly used in the treatment of the STDs.     

Energy absorption of gold nanoshells in hyperthermia therapy

The unique optical characteristics of a gold nanoshell motivate the application of nanoshell-based hyperthermia in drug delivery and cancer treatment. However, most of our understanding on energy absorption and heat transfer is still focused on individual particles, which may not be accurate for nanoshell aggregates in a real application due to the strong optical interaction of nanoshells. This paper investigates the relationship between the optical interaction and the interparticle distance in the visible and near-infrared regions by means of a finite-difference time-domain (FDTD) method. The objective is to explore the energy transportation mechanism, which is critical for hyperthermia therapy. From the numerical simulation results of different forms of nanoshell aggregates, including individual nanoshells, 1-D chains, 2-D arrays, and 3-D clusters, it was found that the interparticle distance plays a crucial role from the maximal absorption point of view. The interparticle distance affects both field enhancement and surface plasmon resonance position. The accurate prediction of energy absorption also helps the way nanoshells are populated in the tumor cell so as to prevent heat damage to healthy tissues in clinic applications. In the case of 3-D clusters, the laser energy decays exponentially along the wave propagation, and the penetration depth greatly depends on the interparticle distance. The closer the nanoshells are placed, the shorter the penetration depth is. The maximal total length for the laser penetration through the shell of gold nanoparticles is about a few hundred to several nanometers. The actual penetration depth primarily depends not only on the interparticle distance, but also on the size of the nanoshells as well as other factors. Since the absorption energy is concentrated on the surface clusters of nanoparticles, heat transfer mechanisms in metal-nanoparticles-based hyperthermia will differ from that in other hyperthermia. The information obtained from this paper will serve as a basis for further study of heat transfer in metal-nanoparticles-based hyperthermia.     

Magnetic nanoparticle-based solder composites for electronic packaging applications

Sn–Ag–Cu (SAC) alloys are regarded as the most promising alternative for traditional Pb–Sn solders used in electronic packaging applications. However, the higher reflow temperature requirement, possible intermetallic formation, and reliability issues of SAC alloys generate several key challenges for successful adoption of Pb-free solder for next generation electronic packaging needs. Localized heating in interconnects can alleviate thermal stresses by preventing subjection of entire package to the higher reflow temperatures associated with the SAC solders. It had been demonstrated that SAC solder–FeCo magnetic nanoparticles (MNPs) composite paste can be reflowed locally with AC magnetic fields, enabling interconnect formation in area array packages while minimizing eddy current heating in the printed circuit board.Solder/magnetic nanocomposite pastes with varying MNP concentration were reflowed using AC magnetic fields. Differential scanning calorimetry results show a reduced undercooling of the composite pastes with the addition of MNPs. TEM results show that the FeCo MNPs are distributed in Sn matrix of the reflowed solder composites. Optical and SEM micrographs show a decrease in Sn dendrite regions as well as smaller and more homogeneous dispersed Ag₃Sn with the addition of MNPs. The MNPs promote Sn solidification by providing more heterogeneous nucleation sites at relatively low undercoolings. The mechanical properties were measured by nanoindentation. The modulus, hardness, and creep resistance, increase with the MNP concentration. The enhanced mechanical properties are attributed to grain boundary and dispersion strengthening.The reflow of solder composites have been modeled based on eddy current power loss in the substrate and magnetic power losses in the solder bumps. Induction reflow of pure solder bumps (<300 μm) in an area array package using 500 Oe magnetic field at 300 kHz requires excessive eddy current power loss in the substrate, resulting in extreme temperatures that lead to blistering and delamination of the substrate. Solder–MNP composites with modest MNP loading showed temperature increases sufficient to achieve solder reflow when subjected to the same AC magnetic fields. Thermomechanical behavior of a solder joint was also modeled under cyclic temperature variations. The stress and strain are highly localized at the interface between solder and substrate. Plastic work accumulated per cycle can be used for lifetime prediction.In this article we review lead-containing and lead-free solder systems, and the electronic packaging technologies pertinent to soldering process. Recent research on the effects of MNPs on localized heating, microstructure evolution, mechanical properties, and thermomechanical reliability are summarized.     

Sol–gel synthesis, characterization, and in vitro compatibility of iron nanoparticle-encapsulating silica microspheres for hyperthermia in cancer therapy

We prepared iron nanoparticle-encapsulating silica (FeSi) microspheres and tested their suitability as thermal seeds for hyperthermia in cancer therapy. These microspheres were prepared by introducing a ferric ion (Fe³⁺) into microspheres of a SiO₂ gel matrix derived from the hydrolysis of tetramethoxysilane in a water-in-oil emulsion that was then heat-treated at 850?°C in an argon atmosphere. The particles obtained were 5–30?μm in size and had a saturation magnetization up to 21?emu?g^?1 and a coercive force of 86–133?Oe. Heat generation in an alternating current magnetic field of 300?Oe at 100?kHz was estimated to be 7.7–28.9?W?g^?1. The in vitro cell biocompatibility of the microspheres was assessed by culturing rat fibroblast Rat-1 cells in medium supplemented with microspheres containing 6.7?% of iron nanoparticles. At microsphere concentrations of <7.5?g?L^?1 proliferation of Rat-1 cells was not significantly inhibited.     

Poly(HEMA) hydrogels with controlled pore architecture for tissue regeneration applications

The technique for fabrication of soft porous hydrogels, in which both the size and the orientation of inner pores can be controlled, was developed. Three-dimensional hydrophilic gels based on poly[2-hydroxyethyl methacrylate] are designed as scaffolds for regeneration of soft tissues, e.g., nerve tissue. Anisotropic macropores of the size ranging from 10 to 50 μm were formed (1) by using a porogen-leaching method with a solid organic porogen, (2) by phase-separation during gelation in solvent-nonsolvent mixture, or (3) by combination of solid porogen elimination and phase-separation. As a porogen, poly(l-lactide) fibers were applied and consequently washed away under mild conditions to obtain desired spatial orientation of pores. Highly water-swollen polymer gels were characterized with high pressure (low vacuum) scanning electron microscopy (AquaSEM). The morphology of voids remaining after removing the solid PLLA porogen (the macropores) was clearly shown.     

Magnetic sensors and their applications

Magnetic sensors can be classified according to whether they measure the total magnetic field or the vector components of the magnetic field. The techniques used to produce both types of magnetic sensors encompass many aspects of physics and electronics. Here, we describe and compare most of the common technologies used for magnetic field sensing. These include search coil, fluxgate, optically pumped, nuclear precession, SQUID, Hall-effect, anisotropic magnetoresistance, giant magnetoresistance, magnetic tunnel junctions, giant magnetoimpedance, magnetostrictive/piezoelectric composites, magnetodiode, magnetotransistor, fiber optic, magnetooptic, and microelectromechanical systems-based magnetic sensors. The usage of these sensors in relation to working with or around Earth's magnetic field is also presented.     

Magnetic properties of cobalt-rare earth magnets for microwave applications

A family of sintered Co-rare earth alloys utilizing Sm, Pr, La, or Ce mischmetal has been developed. Each alloy is designed to optimize one of the following characteristics: 1) Magnets which exhibit magnetic energy products in excess of 20 MG . Oe; 2) Magnets which exhibit reversible demagnetization behavior in adverse fields up to 14 000 Oe; 3) Magnets using inexpensive rare earth metals to maximize the magnetic energy per unit cost. These alloys should extend the range of use of Co-rare earth magnets for microwave devices.