Controlling action potentials with magnetoelectric nanoparticles.

Non-invasive or minutely invasive and wireless brain stimulation that can target any region of the brain is an open problem in engineering and neuroscience with serious implications for the treatment of numerous neurological diseases. Despite significant recent progress in advancing new methods of neuromodulation, none has successfully replicated the efficacy of traditional wired stimulation and improved on its downsides without introducing new complications. Due to the capability to convert magnetic fields into local electric fields, MagnetoElectric NanoParticle (MENP) neuromodulation is a recently proposed framework based on new materials that can locally sensitize neurons to specific, low-strength alternating current (AC) magnetic fields (50Hz 1.7 kOe field). However, the current research into this neuromodulation concept is at a very early stage, and the theoretically feasible game-changing advantages remain to be proven experimentally. To break this stalemate phase, this study leveraged understanding of the non-linear properties of MENPs and the nanoparticles' field interaction with the cellular microenvironment. Particularly, the applied magnetic field's strength and frequency were tailored to the M - H hysteresis loop of the nanoparticles. Furthermore, rectangular prisms instead of the more traditional "spherical" nanoparticle shapes were used to: (i) maximize the magnetoelectric effect and (ii) improve the nanoparticle-cell-membrane surface interface. Neuromodulation performance was evaluated in a series of exploratory in vitro experiments on 2446 rat hippocampus neurons. Linear mixed effect models were used to ensure the independence of samples by accounting for fixed adjacency effects in synchronized firing. Neural activity was measured over repeated 4-min segments, containing 90 s of baseline measurements, 90 s of stimulation measurements, and 60 s of post stimulation measurements. 87.5 % of stimulation attempts produced statistically significant (P < 0.05) changes in neural activity, with 58.3 % producing large changes (P < 0.01). In negative controls using either zero or 1.7 kOe-strength field without nanoparticles, no experiments produced significant changes in neural activity (P > 0.05 and P > 0.15 respectively). Furthermore, an exploratory analysis of a direct current (DC) magnetic field indicated that the DC field could be used with MENPs to inhibit neuron activity (P < 0.01). These experiments demonstrated the potential for magnetoelectric neuromodulation to offer a near one-to-one functionality match with conventional electrode stimulation without requiring surgical intervention or genetic modification to achieve success, instead relying on physical properties of these nanoparticles as "On/Off" control mechanisms. ONE-SENTENCE SUMMARY: This in vitro neural cell culture study explores how to exploit the non-linear and anisotropic properties of magnetoelectric nanoparticles for wireless neuromodulation, the importance of magnetic field strength and frequency matching for optimization, and demonstrates, for the first time, that magnetoelectric neuromodulation can inhibit neural responses.

Nanomedicine and nanobiotechnology applications of magnetoelectric nanoparticles.

Unlike any other nanoparticles known to date, magnetoelectric nanoparticles (MENPs) can generate relatively strong electric fields locally via the application of magnetic fields and, vice versa, have their magnetization change in response to an electric field from the microenvironment. Hence, MENPs can serve as a wireless two-way interface between man-made devices and physiological systems at the molecular level. With the recent development of room-temperature biocompatible MENPs, a number of novel potential medical applications have emerged. These applications include wireless brain stimulation and mapping/recording of neural activity in real-time, targeted delivery across the blood-brain barrier (BBB), tissue regeneration, high-specificity cancer cures, molecular-level rapid diagnostics, and others. Several independent in vivo studies, using mice and nonhuman primates models, demonstrated the capability to deliver MENPs in the brain across the BBB via intravenous injection or, alternatively, bypassing the BBB via intranasal inhalation of the nanoparticles. Wireless deep brain stimulation with MENPs was demonstrated both in vitro and in vivo in different rodents models by several independent groups. High-specificity cancer treatment methods as well as tissue regeneration approaches with MENPs were proposed and demonstrated in in vitro models. A number of in vitro and in vivo studies were dedicated to understand the underlying mechanisms of MENPs-based high-specificity targeted drug delivery via application of d.c. and a.c. magnetic fields. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Size-dependent intranasal administration of magnetoelectric nanoparticles for targeted brain localization.

The brain is a massive network of neurons which are interconnected through chemical and electrical field oscillations. It is hard to overestimate the significance of the ability to control chemical and physical properties of the network at both the collective and single-cell levels. Most psychiatric and neurodegenerative diseases are typically characterized by certain aberrations of these oscillations. Recently, magnetoelectric nanoparticles (MENs) have been introduced to achieve the desired control. MENs effectively enable wirelessly controlled nanoelectrodes deep in the brain. Although MENs have been shown to cross the blood-brain barrier via intravenous (IV) administration, achieving adequate efficacy of the delivery remains an open question. Herein, through in vivo studies on a mouse model, we demonstrate at least a 4-fold improved efficacy of the targeted delivery of MENs across BBB via intranasal administration compared to an equivalent IV administration.

Colossal Magnetoelectric Effect in Core-Shell Magnetoelectric Nanoparticles.

Magnetoelectric coefficient values of above 5 and 2 V cm-1 Oe-1 in 20 nm CoFe2O4-BaTiO3 and NiFe2O4-BaTiO3 core-shell magnetoelectric nanoparticles were demonstrated. These colossal values, compared to 0.1 V cm-1 Oe-1 commonly reported for the 0-3 system, are attributed to (i) the heterostructural lattice-matched interface between the magnetostrictive core and the piezoelectric shell, confirmed through transmission electron microscopy, and (ii) in situ scanning tunneling microscopy nanoprobe-based ME characterization. The nanoprobe technique allows measurements of the ME effect at a single-nanoparticle level which avoids the charge leakage problem of traditional powder form measurements. The difference in the frequency dependence of the ME value between the two material systems is owed to the Ni-ferrite cores becoming superparamagnetic in the near-dc frequency range. The availability of novel nanostructures with colossal ME values promises to unlock many new applications ranging from energy-efficient information processing to nanomedicine and brain-machine interfaces.

Dielectric Elastomer Artificial Muscle: Materials Innovations and Device Explorations.

Creating an artificial muscle has been one of the grand challenges of science and engineering. The invention of such a flexible, versatile, and power efficient actuator opens the gate for a new generation of lightweight, highly efficient, and multifunctional robotics. Many current artificial muscle technologies enable low-power mobile actuators, robots that mimic efficient and natural forms of motion, autonomous robots and sensors, and lightweight wearable technologies. They also have serious applications in biomedical devices, where biocompatibility, from a chemical, flexibility, and force perspective, is crucial. It remains unknown which material will ultimately form the ideal artificial muscle. Anything from shape memory alloys (SMAs) to pneumatics to electroactive polymers (EAPs) realize core aspects of the artificial muscle goal. Among them, EAPs most resemble their biological counterparts, and they encompass both ion-infusion and electric field based actuation mechanisms. Some of the most investigated EAPs are dielectric elastomers (DEs), whose large strains, fracture toughness, and power-to-weight ratios compare favorably with natural muscle. Although dielectric elastomer actuators (DEAs) only entered the artificial muscle conversation in the last 20 years, significant technological progress has reflected their high potential. Research has focused on solving the core issues surrounding DEAs, which includes improving their operational ranges with regard to temperature and voltage, adding new functionality to the materials, and improving the reliability of the components on which they depend. Mechanisms designed to utilize their large-strain actuation and low stiffness has also attracted attention. This Account covers important research by our group and others in various avenues such as decreasing viscoelastic losses in typical DE materials, increasing their dielectric constant, and countering electromechanical instability. We also discuss variable stiffness polymers, specifically bistable electroactive polymers, which, notably, open DEAs to structural applications typically unattainable for soft-actuator technologies. Furthermore, we explore advancements related to highly compliant and transparent electrodes, a crucial component of DEAs capable of achieving high actuation strain. We then cover noteworthy applications, including several novel devices for soft robotics and microfluidics, and how those applications fit within other major developments in the field. Finally, we conclude with a discussion of the remaining challenges facing current DEA technology and speculate on research directions that may further advance DE-based artificial muscles as a whole. This Account serves as a stepping stone into the field of EAPs, which, through the work of researchers worldwide, are positioned as a potential challenger to conventional actuator technologies.