External Radiofrequency Magnetic Field Research Articles

Antibiotic depot system with radiofrequency controlled drug release

Drug depot systems have traditionally relied on the spontaneous dissolution and diffusion of drugs or prodrugs from a reservoir with constant exposure to the surrounding physiological fluids. While this is appropriate for clinical scenarios that require constant plasma concentration of the drug over time, there are also situations where multiple bursts of the drug at well-defined time intervals are preferred. This work presents a drug depot system that enables repeated on-demand release of antibiotics in precise doses, controlled by an external radiofrequency magnetic field. The remotely controlled depot system consists of composite microcapsules with a core-shell structure. The core contains micronized drug particles embedded in a low-melting hydrophobic matrix. The shell is formed by a hydrogel with immobilised magnetic nanoparticles that facilitate local heat dissipation after exposure to a radiofrequency magnetic field. When the melting point of the core material is locally exceeded, the embedded drug particles are mobilised and their surface is exposed to the external aqueous phase. It is shown that drug release can be controlled in an on/off manner by a chosen sequence and duration of radiofrequency pulses. The capacity of the depot system is shown to be significantly higher than that of purely diffusion-controlled systems containing a pre-dissolved drug. The functionality of the depot system is demonstrated in vitro for the specific case of norfloxacin acting on E. coli.

Enhancing silica surface deprotonation by using magnetic nanoparticles as heating agents

In this work, we investigate the possibility of using magnetic nanoparticles embedded into the silica to locally heat up the silica-water interface where the increase in temperature of nanoparticles is induced by an external radio-frequency magnetic field. Through the use of the theoretical model, it is shown that such the process leads to an increase in the total negative charge of the silica surface due to the deprotonation of silanol groups. It is also shown that the efficiency of such an electric charging process depends on the size of nanoparticles. Moreover, the optimal size of nanoparticles allowing for a maximum charging efficiency is determined. This observation may prove to be very important from the point of view of potential applications as it may allow to fine-tune chemical reactions on the silica surface. Some aspects of this work related to the magnetically heated nanoparticles were verified by the experiment.

Nanomagnetite-embedded PLGA Spheres for Multipurpose Medical Applications.

We report on the synthesis and evaluation of biopolymeric spheres of poly(lactide-co-glycolide) containing different amounts of magnetite nanoparticles and Ibuprofen (PLGA-Fe3O4-IBUP), but also chitosan (PLGA-CS-Fe3O4-IBUP), to be considered as drug delivery systems. Besides morphological, structural, and compositional characterizations, the PLGA-Fe3O4-IBUP composite microspheres were subjected to drug release studies, performed both under biomimetically-simulated dynamic conditions and under external radiofrequency magnetic fields. The experimental data resulted by performing the drug release studies evidenced that PLGA-Fe3O4-IBUP microspheres with the lowest contents of Fe3O4 nanoparticles are optimal candidates for triggered drug release under external stimulation related to hyperthermia effect. The as-selected microspheres and their chitosan-containing counterparts were biologically assessed on macrophage cultures, being evaluated as biocompatible and bioactive materials that are able to promote cellular adhesion and proliferation. The composite biopolymeric spheres resulted in inhibited microbial growth and biofilm formation, as assessed against Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans microbial strains. Significantly improved antimicrobial effects were reported in the case of chitosan-containing biomaterials, regardless of the microorganisms’ type. The nanostructured composite biopolymeric spheres evidenced proper characteristics as prolonged and controlled drug release platforms for multipurpose biomedical applications.

Frequency-Controlled Wireless Passive Thermopneumatic Micromixer

This paper reports a novel wireless control of a thermopneumatic zigzag micromixer achieved by selectively activating two passive wireless heaters enabled by an external radiofrequency magnetic field. The two heaters, which are designed to have different resonant frequency (f r ) values of 100 and 130 MHz, are selectively activated by modulating the field frequency to their corresponding f r values. Each heater is responsible for heating an air-heating chamber that is connected to a loading reservoir through a microdiffuser element, while the solutions pumped from each reservoir are mixed in a zigzag micromixing element that ends with an outlet hole. Mixing is achieved in a relatively short mixing length of a 2 mm, and was investigated over a low range of Reynold's number (Re) ≤ 10 that is suitable various biomedical applications. The numerically simulated and measured results of the proposed micromixer have shown mixing efficiencies values higher than 82% for the whole range of Re. The optimal activation switching time of the heaters is 10 s, at which the micromixer achieves a steady value of the maximum mixing efficiency after ~65 s. The micromixer provides mixing-ratio controllability with a maximum flow rate and pressure drop of ~3.4 μL/min and ~385.22 Pa, respectively.

Frequency-controlled wireless shape memory polymer microactuator for drug delivery application.

This paper reports the wireless Shape-Memory-Polymer actuator operated by external radio frequency magnetic fields and its application in a drug delivery device. The actuator is driven by a frequency-sensitive wireless resonant heater which is bonded directly to the Shape-Memory-Polymer and is activated only when the field frequency is tuned to the resonant frequency of heater. The heater is fabricated using a double-sided Cu-clad Polyimide with much simpler fabrication steps compared to previously reported methods. The actuation range of 140μm as the tip opening distance is achieved at device temperature 44°C in 30s using 0.05W RF power. A repeatability test shows that the actuator's average maximum displacement is 110μm and standard deviation of 12μm. An experiment is conducted to demonstrate drug release with 5 μL of an acidic solution loaded in the reservoir and the device is immersed in DI water. The actuator is successfully operated in water through wireless activation. The acidic solution is released and diffused in water with an average release rate of 0.172μL/min.

Remotely Triggered Activation of TGF- With Magnetic Nanoparticles

Growth factors or cytokines have demonstrated the potential to alter and manipulate the biological activity of cells via binding and activation of cell surface receptors. Changes induced by cytokines can range from simple changes in the cellular motility and proliferation to more complex biological actions, such as stem-cell differentiation. Transforming growth factor beta (TGF-β) exhibits the typical functionality of a growth factor, as it is pleiotropic and causes myriad responses in a number of cell types. This multifunctional nature gives the TGF-β a great potential for therapeutic applicationsparticularly in regenerative medicine. However, this multifunctionality till now has limited its usage in vivo, since upon injection, the cytokine may activate nefarious signaling pathways, such as those associated with tumor formation. In addition to this problem, the short half-lives of cytokines also places constraints on their delivery, as the majority of the injected biomolecule will not have a sufficient biological lifetime to reach the desired target location. Therefore, the methods of targeting the growth factors to specific sites in the body will prove crucial to their successful clinical implementation. Here, we describe a novel growth-factor targeting and activation strategy based on the delivery of energy from external alternating magnetic fields to magnetic nanoparticles to which a latent TGF-β has been conjugated. We demonstrate the successful conjugation of a latent TGF-β to the surface of poly(ethylene glycol)-coated iron oxide nanoparticles, and subsequent triggered release of an active TGF-β from its latent complex on the application of an external radio frequency magnetic field. This preliminary study highlights the potential of magnetic activation to remotely control the TGF-β activity in vivo, reducing the dangerous off-target side effects and offering a path to clinical implementation of this growth factor for regenerative medicine applications.

Wireless Displacement Sensing of Micromachined Spiral-Coil Actuator Using Resonant Frequency Tracking

This paper reports a method that enables real-time displacement monitoring and control of micromachined resonant-type actuators using wireless radiofrequency (RF). The method is applied to an out-of-plane, spiral-coil microactuator based on shape-memory-alloy (SMA). The SMA spiral coil forms an inductor-capacitor resonant circuit that is excited using external RF magnetic fields to thermally actuate the coil. The actuation causes a shift in the circuit's resonance as the coil is displaced vertically, which is wirelessly monitored through an external antenna to track the displacements. Controlled actuation and displacement monitoring using the developed method is demonstrated with the microfabricated device. The device exhibits a frequency sensitivity to displacement of 10 kHz/μm or more for a full out-of-plane travel range of 466 μm and an average actuation velocity of up to 155 μm/s. The method described permits the actuator to have a self-sensing function that is passively operated, thereby eliminating the need for separate sensors and batteries on the device, thus realizing precise control while attaining a high level of miniaturization in the device.

Analysis of micropatterned wireless resonant heaters for wireless-control of MEMS thermal actuators

This paper reports a study on wireless radiofrequency (RF) power transfer to and heat generation in micropatterned coils for wireless control of thermally-driven microdevices. Inductor-capacitor circuits with the planar spiral coils act as RF receivers as well as frequency-sensitive wireless heaters that selectively produce heat when resonated with external RF magnetic fields. Electrical and thermal characterizations are performed using two sets of microfabricated circuits with varying numbers of turns and fill ratios defined in the spiral coils. The measurements in electrical parameters of the circuits, coupling coefficient, power transfer efficiency, and heat generation have been evaluated and parameters show good consistency between them. These tests reveal maximum power transfer efficiency and steady-state temperature of ~35 and 99 °C, respectively, for the coil with a fill ratio of 0.55. The reported results will serve as a basis for the design of the wireless heater, which provide a promising path to radio-control of thermoresponsive actuators such as shape-memory alloys and hydrogels.

Wireless microfluidic control with integrated shape-memory-alloy actuators operated by field frequency modulation

This paper reports wireless microfluidic control enabled by the selective operation of multiple bulk-micromachined shape-memory-alloy actuators using external radiofrequency magnetic fields. Each shape-memory-alloy actuator is driven by a wireless resonant heater which generates heat only when the field frequency is tuned to the resonant frequency of the heater. Multiple actuators coupled with the heater circuits that are designed to have different resonant frequencies in the range of 135–295 MHz are selectively and simultaneously controlled by modulating the field frequency to the resonant frequencies of the corresponding heaters. A wireless microsyringe device that has three actuator–heater components and a flexible parylene reservoir is developed. The 5 µl reservoir is squeezed by the 5 mm long cantilever-type actuators to eject controlled amount of liquid from the reservoir. Using the device with an acidic solution loaded in the reservoir, sequential modifications of the pH level in the liquid are experimentally demonstrated through the selective control of the three actuators. The thermal characterization of the actuator using infrared imaging shows a temperature increase of 50 °C in 4 s and the full activation of the actuator in 8 s with 300 mW field output power.

Frequency-controlled wireless shape-memory-alloy microactuators integrated using an electroplating bonding process

This paper reports the wireless control of bulk-micromachined shape-memory-alloy actuators using external radiofrequency magnetic fields and its application to microgrippers. The frequency-sensitive wireless resonant heater to which the gripper actuator is bonded is activated only when the field frequency is tuned to the resonant frequency of the heater. A batch-compatible bonding technique based on photo-defined copper electroplating is developed to mechanically and thermally couple the gripper with the planar heater circuit fabricated using copper-clad polyimide film. The actuation range of 600 μm as the tip opening distance is obtained with normally closed 5-mm long grippers at a device temperature of 92 °C. The field frequency range to which the devices with 140-MHz resonant frequency respond is measured to be ∼13 MHz about the resonant frequency. The manipulation of vertically aligned carbon-nanotube forests is experimentally demonstrated. Mechanical stress tests for the bond formed by the developed electroplating bonding method show a shear strength greater than 40 MPa.

Control of Enzymatic Activities by Magnetite Nanoparticles

ABSTRACTEnzymes are proteins that catalyze chemical reactions, participating in almost all processes in the cell to achieve significant reaction rates and serving a wide variety of functions inside living organisms. Here, we intended to control enzymatic activities by applying external radio frequency magnetic field (RFMF) through nanosized antenna. Ribonuclease A (RNase A), which is a relative small protein that cleave single-stranded RNA, was conjugated to magnetite nanoparticles (NP) by non-covalent interaction. The diameters of Fe3O4 nanoparticles are less than 10nm. External RFMF was applied, and the enzymatic activities of RNase A were tuned at different levels by varying the frequencies and incubation times. Comparison results by using water bath were also presented.

M�ssbauer Spectra of Vibrating Soft Ferromagnets in Reversing Magnetic Field

The Mossbauer absorption by a soft ferromagnetic film is analyzed when it vibrates as a whole and its magnetization periodically reverses under the influence of an external radiofrequency magnetic field. The instantaneous and averaged over time absorption cross-sections are shown to depend strongly on the relative phase of the coherent vibrations and reversing magnetic field at the nucleus.

Effect of magnetic field reversals on the shape of Mössbauer spectra

AbstractThe Mössbauer effect in soft magnetic materials subject to an external radiofrequency magnetic field is analyzed. Assuming the magnetic field at the nucleus to have only one component which periodically alternates general formulas for the emission spectrum as well as for absorption and scattering cross‐sections are obtained. They are applied to the step‐like and harmonic field models. Besides, the expressions are derived for the instantaneous cross‐sections being periodical functions of time. Transient effects are regarded, which arise when a constant magnetic field changes its direction to the opposite one.