This paper presents an optimal design strategy for therapeutic magnetic micro carriers (TMMC) guided in real time by a magnetic resonance imaging (MRI) system. As aggregates of TMMCs must be formed to carry the most amount of drug and magnetic actuation capability, different clustering agglomerations could be arranged. Nevertheless, its difficult to predict the hydrodynamic behavior of any arbitrary-shaped object due to the nonlinear hydrodynamic effects. Indeed, the drag effect is related not only to the properties of the bolus but also to its interaction with the fluid viscosity, the freestream velocity and the container geometry. In this work, we propose a mathematical framework to optimize the TMMC aggregates to improve the steering efficiency in experimental endovascular conditions. The proposed analysis is carried out on various sizes and geometries of microcarrier: spherical, ellipsoid-like and chain-like of microsphere structures. We analyze the magnetophoretic behavior of such designs to exhibit the optimal configuration. Based on the optimal design of the boluses, experimental investigations were carried out in mm-sized fluidic artery phantoms to demonstrate the steerability of the magnetic bolus using a proof-of-concept setup. The experiments demonstrate the steerability of the magnetic bolus under different velocity, shear-stress and trajectory constraints with a laminar viscous fluidic environment. Preliminary experiments with a MRI system confirms the feasibility of the steering of these TMMCs in hepatic artery microchannel phantom.

To enhance locoregional therapies for liver cancer treatment, we propose in this study a mathematical model to optimize the transcatheter arterial delivery of therapeutical agents. To maximize the effect of the treatment and minimize adverse effects on the patient, different mathematical models of the tumor growth are considered in this study to find the optimal number of the therapeutic drug-loaded magnetic nanoparticles to be administered. Three types of therapy models are considered, e.g., angiogenesis inhibition therapy, chemotherapy and radiotherapy. We use state-dependent Riccati equations (SDRE) as an optimal control methodology framework to the Hahnfeldt's tumor growth formulation. Based on this, design optimal rules are derived for each therapy to reduce the growth of a tumor through the administration of appropriate dose of antiangiogenic, radio- and chemo-therapeutic agents. Simulation results demonstrate the validity of the proposed optimal delivery approach, leading to reduced intervention time, low drug administration rates and optimal targeted delivery.

Abstract-This paper presents an optimal control strategy for navigation of multiple magnetic microbeads for future drug targeting applications. To transport the drugs, we use therapeutic magnetic microbeads as navigable agents controlled by magnetic gradients. The main difficulty is to control independently each therapeutic agent along a trajectory with the same magnetic gradient fields. This study proposes an optimal control methodology to control a group of different therapeutic agents at desired states. Based on a dynamic model of group of magnetic microbeads, controllability and observability conditions are formulated and simulated. Based on the proposed theoretical analysis a linear quadratic with integral action control (LQI) has been chosen to be applied to the microbeads system. Finally, an experimental investigation is carried out in millimeter-sized fluidic artery vessels to demonstrate the controllability and stability of two magnetic microbeads under different velocity and trajectory constraints with a laminar viscous fluidic environment.

This paper presents an optimal design strategy for magnetic targeting of therapeutic drugs. In this study, to maximize the effect of the treatment and minimize adverse effects on the patient, a mathematical model have been developed to find the number and the size of the boluses with respect to the growth of a tumor. Using these models, control strategies are developed to establish a schedule that allows the physician to administer the medication while respecting borne by the patient doses. To transport the drugs, we use therapeutic magnetic boluses composed of magnetic particles aggregates as navigable agents controlled by magnetic gradients. Based on the optimal design of the bolus, an experimental investigation is carried out in millimeter-sized fluidic artery vessels to demonstrate the steerability of the magnetic bolus under different velocity, shearstress and trajectory constraints with a laminar viscous fluidic environment.

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This paper analyses the interaction forces between two magnetic boluses for future drug targeting applications. To transport the drugs, it is necessary to convey several therapeutic magnetic boluses using magnetic gradients. The main difficulty is to control a group of different therapeutic boluses at desired states, despite the presence of interaction forces between boluses. To overcome this issue and designing robust control strategies, it is important to fully understand these interactions forces. Based on a dipole-dipole interaction model and dynamic modeling of two magnetic boluses, the magnetic and non magnetic forces are expressed. Finally, an experimental investigation is carried out in a tank under the presence of the magnetic field in order to to assess the prevalence between the magnetic and the non-magnetic interaction forces.

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International audienceThis paper analyses the motion control of two magnetic microrobots in the microfluidic channel for future drug targeting applications. To transport the drugs, it is necessary to inject and control the motion of multiple therapeutic magnetic microrobots using magnetic gradients. The main difficulty is to control a group of different therapeutic microrobots at desired states, despite the presence of interaction forces between microrobots. To overcome this issue, the solution is to consider two rather spaced microrobots which are controlled along the x-axis using magnetic gradients and an oscillatory magnetic field. This magnetic interaction force is expressed based on a dipoledipole interaction model and dynamic modeling of two magnetic microrobots. The oscillatory magnetic field is used to overcome the surface forces between microrobots and microfluidic walls. Finally, an experimental investigation is carried out in a simple channel under the presence of the magnetic field and magnetic gradient forces in order to analyze the motion control of two magnetic microrobots using the combination of magnetic gradient and oscillatory magnetic fields. Also, we will assess the prevalence of the magnetic interaction forces between two microrobots. © 2017 IEEE