Fabrication and characterization of magnetic microrobots for three‐dimensional cell culture and targeted transportation

S Kim, F Qiu, S Kim, A Ghanbari, C Moon… - Advanced …, 2013 - Wiley Online Library
Advanced Materials, 2013Wiley Online Library
Medical microrobots are being widely studied for specific applications, such as targeted drug
delivery, biopsy, hyperthermia, radioactive therapy, scaffolding, in-vivo ablation, stenting,
sensing, and marking.[1] These operations can be carried out with microrobots that offer a
minimally invasive, accurately targeted, localized therapy via wireless intervention, such as
magnetic fields.[2–5] Numerous studies have examined the biomedical applications of
magnetic actuation. Magnetic tubes and rotors have been developed for sensitive engines …
Medical microrobots are being widely studied for specific applications, such as targeted drug delivery, biopsy, hyperthermia, radioactive therapy, scaffolding, in-vivo ablation, stenting, sensing, and marking.[1] These operations can be carried out with microrobots that offer a minimally invasive, accurately targeted, localized therapy via wireless intervention, such as magnetic fields.[2–5] Numerous studies have examined the biomedical applications of magnetic actuation. Magnetic tubes and rotors have been developed for sensitive engines and fluid mixers driven by magnetic actuation.[6–9] Among the various applications proposed for medical micro-devices, targeted drug delivery and micro-object transportation can be implemented using biocompatible and magnetically actuated agents. In previous studies, nanoparticles, magnetic particles, and nickel nanowires have been used as platforms for drug delivery.[10–13] Helical and tubular lipid microstructures were developed as drug delivery platforms to overcome problems such as the poor loading capacity and propulsion efficiency.[14] For helical microrobots,[15–20] rotational motion induces translational velocity, which is one of the most effective propulsion methods in the low Reynolds number regime.[21–24] To transport cells using magnetically actuated helical swimmers, a magnetized polymer helix, equipped with a cell gripper, is controlled by external magnetic fields.[20] These helical microrobots have been used to transport a single microsphere in three dimensions. The microrobots were coated with a thin titanium (Ti) layer for better biocompatibility and affinity with the cells; this was confirmed by culturing cells on the helical microrobots. Similarly, microspheres can be transported in the flowing streams of microfluidic channels, which enable the microrobots to swim in the dynamic flow in the microfluidic channel.[25] This paper reports the fabrication and characterization of three-dimensional (3D) porous micro-niches as a transporter using a photocurable polymer. The structures were coated with nickel (Ni) for magnetic actuation, and with Ti to ensure biocompatibility for possible in-vivo applications. The fabricated microrobots were rotated wirelessly and translated using a magnetic manipulator. Translational velocities were measured experimentally for different magnetic field gradients in the horizontal direction when the microrobots were aligned in vertical direction. Complex manipulations were also demonstrated by synchronized swimming and targeted tracking. Human embryonic kidney (HEK) 293 cells were cultured with the microrobot to demonstrate the feasibility of using microrobots as multicell transporters. Compared with previous microrobotic cargo devices, a well-defined 3D porous structure was used to culture multiple cells inside a structure with a customized pore size. A microrobot containing cells inside can be controlled magnetically in body fluids such as blood, urine, cerebrospinal fluid, or vitreous humor, to transport the cells to a target position in the body.
A scaffold is a porous 3D structure that is used for cell adhesion and mechanical support for tissue and organ regeneration.[26–29] A 3D cell culture is important for sustaining the structural and functional complexities of the cells, because most in-vivo environments are 3D. Porous structures with controllable porosity have benefits over scaffolds with random pores, because they exhibit enhanced characteristics, such as the ability to produce the proper nutrient supply, uniform cell distribution, and high cell density. Three-dimensional laser lithography offers excellent control over the geometry and porosity of the sample, as well as high …
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