Controlled In Vivo Swimming of a Swarm of Bacteria-Like Microrobotic Flagella
Controlled In Vivo Swimming of a Swarm of Bacteria-Like Microrobotic Flagella
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DOI：
10.1002/adma.201404444
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发表时间：
2015-05-20
影响因子：
29.4
通讯作者：
Nelson, Bradley J.
中科院分区：
文献类型：
--
作者：
Servant, Ania;Qiu, Famin;Nelson, Bradley J.
DOI：10.1002/adma. 201404444微型机器人的游泳，如螺旋推进[9，10]行波推进[11]或用磁场梯度拉动。[12]如果微米颗粒和纳米颗粒表现出手性几何形状，例如螺旋形状而不是对称形状，则可以产生非往复运动。这个概念已被用于螺旋推进式游泳。几个研究小组使用不同的技术报道了这种螺旋微结构的制造，例如掠射角沉积[13]和自滚动技术。[14-16]在以前的研究中，我们设计了一种手性微结构，使用双光子聚合[17]和光敏聚合物直接激光写入（DLW）显示细菌鞭毛的螺旋几何形状。[18通过用磁性材料涂覆这种聚合物螺旋，产生了稳定的磁性结构，其表现出与细菌鞭毛相似的尺寸和几何形状，并且能够通过磁致动控制“游泳”。在这些微结构上施加适当频率的时间恒定和旋转的磁场，确实允许沿着螺旋的纵轴沿着产生稳定的动态运动，并发生推进。[18]这些磁性螺旋结构被称为人工细菌鞭毛（ABFs），可以通过弱强度旋转磁场（< 10 mT）精确控制，这在生物医学应用中具有巨大的潜力，例如靶向药物递送。[6，7，20]在我们以前的工作中，用含有荧光团和药物模型的脂质体实现了ABF的功能化，并且可以在体外将货物递送到细胞[21，22]，以证明使用ABF作为活性药物递送装置的可能性。在这项工作中，我们用近红外探针（NIR-797）描述了ABFs的表面功能化，通过设计具有细菌鞭毛的螺旋几何形状结合3D-荧光成像的微结构来优化ABF的产生。DLW与双光子聚合[17]和光敏聚合物。[18]通过用磁性材料涂覆这种聚合物螺旋，成功地制备了表现出与细菌鞭毛相似的尺寸和几何形状的稳定的磁性结构。在适当频率下的时间恒定磁场的旋转允许沿着螺旋的纵轴沿着产生稳定的动态运动，从而允许发生推进。图1A示出了所制造的ABF。可以获得不同尺寸的ABF的螺旋体，例如长度为8 μm（图1A（a））和16 μm（图1A（B））。在DLW之后，聚合物主体涂覆有50 nm厚的Ni层和5 nm的Ti层。磁性材料如Ni使我们能够无线控制ABF，Ti用于改善ABF的生物相容性。
DOI: 10.1002/adma. 201404444 swimming of microrobots such as helical propulsion,[9, 10] traveling wave propulsion [11] or pulling with magnetic field gradients.[12] If a micro-and nanoparticle exhibits a chiral geometry such as a helical shape rather than a symmetrical shape, then a non-reciprocal motion can be generated. This concept has been used for helical propulsion-based swimming. The fabrication of such helical microstructures was reported by several research groups using different techniques, such as glancingangle deposition [13] and self-rolling technology.[14–16] In previous studies, we designed a chiral microstructure displaying the helical geometry of bacterial flagella using direct laser writing (DLW) with two-photon polymerization [17] and photosensitive polymers.[18, 19] By coating this polymeric helix with magnetic materials, a stable magnetic structure that exhibited a similar size and geometry to bacterial flagella and capable of controlled “swimming” by magnetic actuation was generated. The application of a temporally constant and rotating magnetic field at appropriate frequencies on these microstructures allowed indeed stable dynamic motion to be produced along the longitudinal axis of the helix and propulsion occurred.[18] These magnetic helical structures, called artificial bacterial flagella (ABFs), could be precisely controlled by weak-strength rotating magnetic fields (< 10 mT), that has great potential for biomedical applications, such as targeted drug delivery.[6, 7, 20] In our previous work, the functionalization of ABFs with liposomes containing fluorophores and drug models was achieved and a cargo could be delivered in vitro to cells [21, 22] to demonstrate the possibility of using ABFs as active drug delivery devices. In this work, we describe the surface functionalization of ABFs with near-infrared probes (NIR-797) that allowed whole-body optical (fluorescence) imaging to track for the first time in vivo the magnetically controlled navigation of a swarm of functionalized ABFs (f-ABFs) in the peritoneal cavity of a mouse.The production of ABFs was optimized by designing a microstructure with the helical geometry of bacterial flagella combining 3D-DLW with two-photon polymerization [17] and photosensitive polymers.[18] By coating this polymeric helix with magnetic materials, stable magnetic structures that exhibit a similar size and geometry to bacterial flagella were successfully prepared. The rotation of temporally constant magnetic field at appropriate frequencies allowed the generation of stable dynamic motion along the longitudinal axis of the helix and consequently allowed propulsion to occur. Figure 1A shows the fabricated ABFs. The helical bodies of ABFs could be obtained in different sizes, such as 8 µm (Figure 1 A (a)) and 16 µm (Figure 1 A (b)) in length. Following DLW, the polymeric bodies were coated with 50 nm-thick layer of Ni and 5 nm layer of Ti. Magnetic material such as Ni enabled us to wirelessly control ABFs, and Ti was used to improve the biocompatibility of the