Salvador Pané

An Integrated Microrobotic Platform for On‐Demand, Targeted Therapeutic Interventions

The presented microrobotic platform combines together the advantages of self-folding NIR light sensitive polymer bilayers, magnetic alginate microbeads, and a 3D manipulation system, to propose a solution for targeted, on-demand drug and cell delivery. First feasibility studies are presented together with the potential of the full design.

Soft micromachines with programmable motility and morphology

Nature provides a wide range of inspiration for building mobile micromachines that can navigate through confined heterogenous environments and perform minimally invasive environmental and biomedical operations. For example, microstructures fabricated in the form of bacterial or eukaryotic flagella can act as artificial microswimmers. Due to limitations in their design and material properties, these simple micromachines lack multifunctionality, effective addressability and manoeuvrability in complex environments. Here we develop an origami-inspired rapid prototyping process for building self-folding, magnetically powered micromachines with complex body plans, reconfigurable shape and controllable motility. Selective reprogramming of the mechanical design and magnetic anisotropy of body parts dynamically modulates the swimming characteristics of the micromachines. We find that tail and body morphologies together determine swimming efficiency and, unlike for rigid swimmers, the choice of magnetic field can subtly change the motility of soft microswimmers.

Mobility experiments with microrobots for minimally invasive intraocular surgery.

PURPOSE To investigate microrobots as an assistive tool for minimally invasive intraocular surgery and to demonstrate mobility and controllability inside the living rabbit eye. METHODS A system for wireless magnetic control of untethered microrobots was developed. Mobility and controllability of a microrobot are examined in different media, specifically vitreous, balanced salt solution (BSS), and silicone oil. This is demonstrated through ex vivo and in vivo animal experiments. RESULTS The developed electromagnetic system enables precise control of magnetic microrobots over a workspace that covers the posterior eye segment. The system allows for rotation and translation of the microrobot in different media (vitreous, BSS, silicone oil) inside the eye. CONCLUSIONS Intravitreal introduction of untethered mobile microrobots can enable sutureless and precise ophthalmic procedures. Ex vivo and in vivo experiments demonstrate that microrobots can be manipulated inside the eye. Potential applications are targeted drug delivery for maculopathies such as AMD, intravenous deployment of anticoagulation agents for retinal vein occlusion (RVO), and mechanical applications, such as manipulation of epiretinal membrane peeling (ERM). The technology has the potential to reduce the invasiveness of ophthalmic surgery and assist in the treatment of a variety of ophthalmic diseases.

Chitosan Electrodeposition for Microrobotic Drug Delivery

A method to functionalize steerable magnetic microdevices through the co-electrodeposition of drug loaded chitosan hydrogels is presented. The characteristics of the polymer matrix have been investigated in terms of fabrication, morphology, drug release and response to different environmental conditions. Modifications of the matrix behavior could be achieved by simple chemical post processing. The system is able to load and deliver 40-80 μg cm(-2) of a model drug (Brilliant Green) in a sustained manner with different profiles. Chitosan allows a pH responsive behavior with faster and more efficient release under slightly acidic conditions as can be present in tumor or inflamed tissue. A prototype of a microrobot functionalized with the hydrogel is presented and proposed for the treatment of posterior eye diseases.

Undulatory Locomotion of Magnetic Multilink Nanoswimmers

Micro- and nanorobots operating in low Reynolds number fluid environments require specialized swimming strategies for efficient locomotion. Prior research has focused on designs mimicking the rotary corkscrew motion of bacterial flagella or the planar beating motion of eukaryotic flagella. These biologically inspired designs are typically of uniform construction along their flagellar axis. This work demonstrates for the first time planar undulations of composite multilink nanowire-based chains (diameter 200 nm) induced by a planar-oscillating magnetic field. Those chains comprise an elastic eukaryote-like polypyrrole tail and rigid magnetic nickel links connected by flexible polymer bilayer hinges. The multilink design exhibits a high swimming efficiency. Furthermore, the manufacturing process enables tuning the geometrical and material properties to specific applications.

Degradable Magnetic Composites for Minimally Invasive Interventions: Device Fabrication, Targeted Drug Delivery, and Cytotoxicity Tests

Superparamagnetic nanoparticles and a functional, degradable polymer matrix based on poly(ethylene glycol) are combined to enable fully degradable magnetic microdevices for minimally invasive biomedical applications. A bioinspired helical microrobot platform mimicking Escherichia coli bacteria is fabricated and actuated using weak rotating magnetic fields. Locomotion based on corkscrew propulsion, targeted drug delivery, and low-degradation-product cytotoxicity are demonstrated.

Hybrid Helical Magnetic Microrobots Obtained by 3D Template‐Assisted Electrodeposition

Hybrid helical magnetic microrobots are achieved by sequential electrodeposition of a CoNi alloy and PPy inside a photoresist template patterned by 3D laser lithography. A controlled actuation of the microrobots by a rotating magnetic field is demonstrated in a fluidic environment.

Grain Boundary Segregation and Interdiffusion Effects in Nickel–Copper Alloys: An Effective Means to Improve the Thermal Stability of Nanocrystalline Nickel

Nanocrystalline (nc) Ni films show pronounced grain growth and suffer from concomitant deterioration of their mechanical and magnetic properties after annealing at relatively low temperatures (T(ANN) ≥ 475 K). This constitutes a drawback for their applicability as coatings or in components of miniaturized devices. This work reveals that the thermal stability of nc Ni is significantly improved by controllably alloying Ni with Cu, by means of electrodeposition, to form a Ni(1-x)Cu(x) solid solution. To tune the composition of such nc alloys, Ni(1-x)Cu(x) films are deposited galvanostatically using an electrolytic bath containing Ni and Cu sulfate salts as electroactive species, saccharine as grain-refining agent, and applying current densities ranging from -10 to -40 mA cm(-2). The enhanced thermal stability is ascribed to segregation of a Cu-rich phase at the Ni(1-x)Cu(x) grain boundaries, which acts as a shielding layer against grain growth. As a result, high values of hardness (in excess of 6 GPa) remain in nc Ni(1-x)Cu(x) for x ≥ 0.3, even after annealing at T(ANN) ≥ 575 K. From a magnetic point of view, Ni(1-x)Cu(x) films possess lower coercivity values than pure nc Ni films, both in the as-prepared and annealed states, thus offering potential advantages for certain soft magnetic applications.

Toward targeted retinal drug delivery with wireless magnetic microrobots

Retinal vein occlusion is an obstruction of blood flow due to clot formation in the retinal vasculature, and is among the most common causes of vision loss. Currently, the most promising therapy involves injection of t-PA directly into small and delicate retinal vessels. This procedure requires surgical skills at the limits of human performance. In this paper, targeted retinal drug delivery with wireless magnetic microrobots is proposed. We focus on four fundamental issues involved in the development of such a system: biocompatible coating of magnetic microrobots, diffusion-based drug delivery, characterization of forces needed to puncture retinal veins, and wireless magnetic force generation. We conclude that targeted drug delivery with magnetic microrobots is feasible from an engineering perspective, and the idea should now be explored for clinical efficacy.

Artificial Swimmers Propelled by Acoustically Activated Flagella

Recent studies have garnered considerable interest in the field of propulsion to maneuver micro- and nanosized objects. Acoustics provide an alternate and attractive method to generate propulsion. To date, most acoustic-based swimmers do not use structural resonances, and their motion is determined by a combination of bulk acoustic streaming and a standing-wave field. The resultant field is intrinsically dependent on the boundaries of their resonating chambers. Though acoustic based propulsion is appealing in biological contexts, existing swimmers are less efficient, especially when operating in vivo, since no predictable standing-wave can be established in a human body. Here we describe a new class of nanoswimmer propelled by the small-amplitude oscillation of a flagellum-like flexible tail in standing and, more importantly, in traveling acoustic waves. The artificial nanoswimmer, fabricated by multistep electrodeposition techniques, compromises a rigid bimetallic head and a flexible tail. During acoustic excitation of the nanoswimmer the tail structure oscillates, which leads to a large amplitude propulsion in traveling waves. FEM simulation results show that the structural resonances lead to high propulsive forces.