Fabrication and characterization of magnetic microrobots for three-dimensional cell culture and targeted transportation.
Fabrication and characterization of magnetic microrobots for three-dimensional cell culture and targeted transportation.
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DOI：
10.1002/adma.201301484
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发表时间：
2013-11-06
影响因子：
29.4
通讯作者：
Choi, Hongsoo
中科院分区：
文献类型：
--
作者：
Kim, Sangwon;Qiu, Famin;Kim, Samhwan;Ghanbari, Ali;Moon, Cheil;Zhang, Li;Nelson, Bradley J.;Choi, Hongsoo
医疗微型机器人正在被广泛研究的具体应用，如靶向药物输送，活检，热疗，放射性治疗，支架，体内消融，支架，传感和标记。[1]这些手术可以用微型机器人进行，这些机器人通过无线干预（如磁场）提供微创、精确靶向的局部治疗。[2-5]许多研究已经检查了磁致动的生物医学应用。磁管和转子已经被开发用于由磁致动驱动的敏感发动机和流体混合器。[6-9]在为医疗微型装置提出的各种应用中，靶向药物递送和微物体运输可以使用生物相容性和磁致动剂来实现。在先前的研究中，纳米颗粒、磁性颗粒和镍纳米线已被用作药物递送的平台。[10-13]螺旋和管状脂质微结构被开发作为药物递送平台，以克服诸如负载能力和推进效率差的问题。[14]对于螺旋微型机器人，[15-20]旋转运动引起平移速度，这是低雷诺数状态下最有效的推进方法之一。[21-24]为了使用磁致动螺旋泳动器运输细胞，配备有细胞夹持器的磁化聚合物螺旋由外部磁场控制。[20]这些螺旋微型机器人已被用于在三维空间中运输单个微球。微型机器人涂有薄钛（Ti）层，以获得更好的生物相容性和与细胞的亲和力;这通过在螺旋微型机器人上培养细胞得到证实。类似地，微球可以在微流体通道的流动流中传输，这使得微型机器人能够在微流体通道中的动态流中游泳。[25]本文报道了使用光固化聚合物的三维（3D）多孔微龛作为运输机的制造和表征。该结构涂有镍（Ni）用于磁致动，并涂有钛以确保可能的体内应用的生物相容性。制造的微型机器人无线旋转和使用磁性操纵器平移。实验测量了微机器人在垂直方向排列时，在水平方向上不同磁场梯度下的平移速度。复杂的操作也被证明是同步游泳和有针对性的跟踪。人胚肾（HEK）293细胞与微型机器人一起培养，以证明使用微型机器人作为多细胞转运体的可行性。与以前的微型机器人货物装置相比，使用定义明确的3D多孔结构在具有定制孔径的结构内培养多个细胞。微机器人内部含有细胞，可以在血液、尿液、脑脊液或玻璃体液等体液中通过磁力控制，将细胞运送到体内的目标位置。支架是一种多孔的3D结构，用于细胞粘附和组织器官再生的机械支持。[26-29] 3D细胞培养对于维持细胞的结构和功能复杂性非常重要，因为大多数体内环境都是3D的。具有可控孔隙率的多孔结构具有优于具有随机孔隙的支架的益处，因为它们表现出增强的特性，例如产生适当营养供应、均匀细胞分布和高细胞密度的能力。三维激光光刻提供了对样品的几何形状和孔隙率的出色控制，以及高分辨率。
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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影响因子：
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