A novel non-invasive intervention for removing occlusions from shunts using an abrading magnetic microswarm.

Objective: Shunts are often employed as internal medical devices for draining aberrant fluids from organs. However, depositions of calcification in the shunt walls lead to its failure, requiring frequent replacements. The current surgical procedures for implanting shunts are invasive. Methods: This paper introduces a novel, non-invasive approach for eliminating shunt deposits. In this non-invasive intervention, a swarm of magnetic nanoparticles (MNPs) guided by an external magnetic field removes the shunt deposition. A prototype device was fabricated to provide a proof of concept. MNPs were steered within the shunt channel containing calcification layers and successfully abraded the deposition layer. The proof-of-concept experiments used a moving magnetic field ranging from 0.1 to 0.3 T and a velocity between 1 to 12 cm/s. The average nanoparticles size was 45nm. Five diverse contact theories predicted the amount of wear and indentation depth created by the abrading microswarm. Results: Experimental results confirm that MNPs under a moving magnetic field can abrade shunt deposits. Also, there is a direct relation between the intensity of the magnetic field, the speed of magnet movement, and the rate of abrading the calcification deposits. The simulation results showed that the Hoeprich model deviated 12.1% from the experimental results and was the most suitable model. Conclusion & significance: This research has introduced a novel minimally invasive approach to remove shunt depositions that can reduce the number of revision surgeries and prevent surgical complications

Studies of Different Swarm Modes for the MNPs Under the Rotating Magnetic Field

The principal constraint in the application of the microrobots in drug delivery is swarm control. The rotating magnetic field has shown the potential of capturing and controlling the swarm of magnetic nanoparticle-based microrobots. Despite various experimental studies to capture the swarm of the magnetic nanoparticle-based microrobot in a rotating magnetic field, a simulation platform for the swarm of aggregated magnetic nanoparticles (MNPs) has not been introduced. This study proposes a simulation platform to study the swarm of aggregated magnetic nanoparticles in a rotating field. An experimental setup was developed to investigate the different swarm modes in a rotating magnetic field, and the results show an agreement between the experimental and simulation results for the micro- and nanoparticles. The effects of the environmental parameters (initial dispersion of nanoparticles), process parameters (magnetic field intensity, frequency, actuation time), and geometrical parameters (particle diameter) were studied to describe the swarm behavior in a rotating magnetic field. These studies revealed the role of each parameter in creating the swarm and showed how the size of aggregates can be controlled. The presented approach can be used to design the magnetic nanoparticle-based microrobots effectively

A Soft Magnetic Core can Enhance Navigation Performance of Magnetic Nanoparticles in Targeted Drug Delivery

Magnetic nanoparticles (MNPs) are a promising candidate for use as carriers in drug delivery systems. A navigation system with real-time actuation and monitoring of MNPs is inevitably required for more precise targeting and diagnosis. In this paper, we propose a novel electromagnetic navigation system with a coil combined with a soft magnetic core. This system can be used for magnetic particle imaging (MPI) and electromagnetic actuator functions with a higher steering force and enhanced monitoring resolution. A soft magnetic core with coils can increase the magnetic gradient field. However, this also generates harmonic noise, which makes it difficult to acquire MNP monitoring signals with MPI. Therefore, the use of amplitude modulation magnetic particle imaging (AM MPI) is suggested. AM MPI uses a low-amplitude excitation field combined with a low-frequency drive field. Using this system, the measured signal becomes less sensitive to the soft magnetic core. Based on the new MPI scheme and the combination of the coil with the magnetic cores, the proposed navigation system can implement one-dimensional (1-D) MNP navigation and 2-D MPI. The proposed navigation system can shorten the 1-D guidance time by about 25% for MNPs in the size range of 45-60 nm and give an improved 2-D imaging resolution of 43%, compared with an air-coil structure

A Novel Magnetic Actuation Scheme to Disaggregate Nanoparticles and Enhance Passage across the Blood–Brain Barrier

The blood–brain barrier (BBB) hinders drug delivery to the brain. Despite various efforts to develop preprogramed actuation schemes for magnetic drug delivery, the unmodeled aggregation phenomenon limits drug delivery performance. This paper proposes a novel scheme with an aggregation model for a feed-forward magnetic actuation design. A simulation platform for aggregated particle delivery is developed and an actuation scheme is proposed to deliver aggregated magnetic nanoparticles (MNPs) using a discontinuous asymmetrical magnetic actuation. The experimental results with a Y-shaped channel indicated the success of the proposed scheme in steering and disaggregation. The delivery performance of the developed scheme was examined using a realistic, three-dimensional (3D) vessel simulation. Furthermore, the proposed scheme enhanced the transport and uptake of MNPs across the BBB in mice. The scheme presented here facilitates the passage of particles across the BBB to the brain using an electromagnetic actuation scheme

A Learnt Approach for the Design of Magnetically Actuated Shape Forming Soft Tentacle Robots

Soft continuum robots have the potential to revolutionize minimally invasive surgery. The challenges for such robots are ubiquitous; functioning within sensitive, unstructured and convoluted environments which are inconsistent between patients. As such, there exists an open design problem for robots of this genre. Research currently exists relating to the design considerations of on-board actuated soft robots such as fluid and tendon driven manipulators. Magnetically reactive robots, however, exhibit off-board actuation and consequently demonstrate far greater potential for miniaturization and dexterity. In this letter we present a soft, magnetically actuated, slender, shape forming ‘tentacle-like’ robot. To overcome the associated design challenges we also propose a novel design methodology based on a Neural Network trained using Finite Element Simulations. We demonstrate how our design approach generates static, two-dimensional tentacle profiles under homogeneous actuation based on predefined, desired deformations. To demonstrate our learnt approach, we fabricate and actuate candidate tentacles of 2 mm diameter and 42 mm length producing shape profiles within 8% mean absolute percentage error of desired shapes. With this proof of concept, we make the first step towards showing how tentacles with bespoke magnetic profiles may be designed and manufactured to suit specific anatomical constraints

Magnetic microrobot control using an adaptive fuzzy sliding-mode method

The magnetic medical microrobots are influenced by diverse factors such as the medium, the geometry of the microrobot, and the imaging procedure. It is worth noting that the size limitations make it difficult or even impossible to obtain reliable physical properties of the system. In this research, to achieve a precise microrobot control using minimum knowledge about the system, an Adaptive Fuzzy Sliding-Mode Control (AFSMC) scheme is designed for the motion control problem of the magnetically actuated microrobots in presence of input saturation constraint. The AFSMC input consists of a fuzzy system designed to approximate an unknown nonlinear dynamical system and a robust term considered for mismatch compensation. According to the designed adaptation laws, the asymptotic stability is proved based on the Lyapunov theorem and Barbalat's lemma. In order to evaluate the effectiveness of the proposed method, a comparative simulation study is conducted

Steering Algorithm for a Flexible Microrobot to Enhance Guidewire Control in a Coronary Angioplasty Application

Magnetically driven microrobots have been widely studied for various biomedical applications in the past decade. An important application of these biomedical microrobots is heart disease treatment. In intravascular treatments, a particular challenge is the submillimeter-sized guidewire steering; this requires a new microrobotic approach. In this study, a flexible microrobot was fabricated by the replica molding method, which consists of three parts: (1) a flexible polydimethylsiloxane (PDMS) body, (2) two permanent magnets, and (3) a micro-spring connector. A mathematical model was developed to describe the relationship between the magnetic field and the deformation. A system identification approach and an algorithm were proposed for steering. The microrobot was fabricated, and the models for steering were experimentally validated under a magnetic field intensity of 15 mT. Limitations to control were identified, and the microrobot was steered in an arbitrary path using the proposed model. Furthermore, the flexible microrobot was steered using the guidewire within a three-dimensional (3D) transparent phantom of the right coronary artery filled with water, to show the potential application in a realistic environment. The flexible microrobot presented here showed promising results for enhancing guidewire steering in percutaneous coronary intervention (PCI)

Studies on Aggregated Nanoparticles Steering during Deep Brain Membrane Crossing

Many central nervous system (CNS) diseases, such as Alzheimer’s disease (AD), affect the deep brain region, which hinders their effective treatment. The hippocampus, a deep brain area critical for learning and memory, is especially vulnerable to damage during early stages of AD. Magnetic drug targeting has shown high potential in delivering drugs to a targeted disease site effectively by applying a strong electromagnetic force. This study illustrates a nanotechnology-based scheme for delivering magnetic nanoparticles (MNP) to the deep brain region. First, we developed a mathematical model and a molecular dynamic simulation to analyze membrane crossing, and to study the effects of particle size, aggregation, and crossing velocities. Then, using in vitro experiments, we studied effective parameters in aggregation. We have also studied the process and environmental parameters. We have demonstrated that aggregation size can be controlled when particles are subjected to external electromagnetic fields. Our simulations and experimental studies can be used for capturing MNPs in brain, the transport of particles across the intact BBB and deep region targeting. These results are in line with previous in vivo studies and establish an effective strategy for deep brain region targeting with drug loaded MNPs through the application of an external electromagnetic field

A Needle-Type Microrobot for Targeted Drug Delivery by Affixing to a Microtissue.

A needle-type microrobot (MR) for targeted drug delivery is developed to stably deliver drugs to a target microtissue (MT) for a given period time without the need for an external force after affixing. The MRs are fabricatedby 3D laser lithography and nickel (Ni)/titanium oxide (TiO2 ) layers are coated by physical vapor deposition. The translational velocity of the MR is 714 µm s-1 at 20 mT and affixed to the target MT under the control of a rotating magnetic field. The manipulability of the MR is shown by using both manual and automatic controls. Finally, drug release from the paclitaxel-loaded MR is characterized to determine the efficiency of targeted drug delivery. This study demonstrates the utility of the proposed needle-type MR for targeted drug delivery to MT with various flow rates in vitro physiological fluidic environments

Studies of aggregated nanoparticles steering during magnetic-guided drug delivery in the blood vessels

Magnetic-guided targeted drug delivery (TDD) systems can enhance the treatment of diverse diseases. Despite the potential and promising results of nanoparticles, aggregation prevents precise particle guidance in the vasculature. In this study, we developed a simulation platform to investigate aggregation during steering of nanoparticles using a magnetic field function. The magnetic field function (MFF) comprises a positive and negative pulsed magnetic field generated by electromagnetic coils, which prevents adherence of particles to the vessel wall during magnetic guidance. A commonly used Y-shaped vessel was simulated and the performance of the MFF analyzed; the experimental data were in agreement with the simulation results. Moreover, the effects of various parameters on magnetic guidance were evaluated and the most influential identified. The simulation results presented herein will facilitate more precise guidance of nanoparticles in vivo