Newsletter No. 427

4 No. 427, 19.11.2013 I n the famous speech ‘There’s Plenty of Room at the Bottom’ delivered in 1959, Richard Feynman, renowned American physicist and Nobel laureate in physics, foretold that a small machine would be invented that could travel to the heart of the body through a blood vessel and examine the organ. He described this as ‘swallowing the surgeon’. The stirring speech inspired the development of a brand new research area—nano technology. Feynman’s wild idea has materialized, to a certain extent, after four decades of research. Applying a similar concept, a capsule-like endoscope came into being around 2000 to capture images inside the small intestine. The pill-sized video capsule is advanced through the digestive tract by the peristalsis of the intestine while the technology of controlling the device’s track is still unfledged. Prof. Zhang Li ( photo ) of the Department of Mechanical and Automation Engineering, in collaboration with researchers from the Daegu Gyeongbuk Institute of Science and Technology (DGIST), Korea; and ETH Zurich, Switzerland, has innovated a new magnetically manipulated microrobot capable of transporting an appropriate volume of cells and therapeutic drugs to specific areas of the human body—a great leap forward in the development of wirelessly-controlled medical microrobots. The research results have been featured as the cover story in Advanced Materials released on 6 November. The development of microrobot requires interdisciplinary knowledge including mechatronics, materials science, biology, control and automation, etc. The device—with 100 microns in length and 40 in width—is as tiny as the radius of the cross-section of a strand of hair. It is almost impossible to install mechatronic components such as a motor. Researchers found that utilizing magnetic fields to actuate the robot, which is coated with nickel for magnetic actuation, and with titanium to ensure biocompatibility for possible in vivo applications in blood vessels or bodily fluids is a promising method. However, how should the microrobot move in bodily fluid? Professor Zhang made reference to the movement of microorganisms and took into account certain variables including the viscosity and velocity of the liquid, the shape and magnitude of the device, as well as the limitations of applying magnetic field as field strength decays rapidly with increase in distance from source. With a series of careful experiments and complex calculations, he found that rotating helical propellers is likely one of the best choices for in vivo applications. The shape of the device has been improved upon continuously. Most of the early microrobots were spiral-shaped with a small body to carry drugs. In his recent research, Professor Zhang and his collaborators constructed photocurable polymer three-dimensional scaffolds with controllable porosity for different treatment purposes. He said the new design made a breakthrough 微型機械—穿梭體內的外科醫生 Microrobot—The Surgeon inside the Body 美 國著名物理學家、諾貝爾物理學獎得獎人理查 德  • 費曼（Richard Feynman）在1959年的著名演 講「底下還有廣大空間」中，預言將來會發展出微型機械， 沿人體血管游走到心臟檢查，並形容這猶如「將外科醫生 吞下去」，這篇前瞻性的演說，可謂開拓了納米技術這個新 的研究領域。 天馬行空的意念，經過近四十年的研究和試驗，竟逐步實 現。應用類似概念的膠囊式內視鏡約於2000年面世，主要 用作拍攝小腸內壁情況，但它要靠小腸蠕動來推進，而控 制膠囊移動途徑的技術仍未發展成熟。 機械與自動化工程學系 張立 教授（ 圖 ）與韓國大邱慶北科 學技術院及瑞士蘇黎世聯邦理工學院的研究人員合作， 最近成功研發一款以磁力操控的微型機械裝置，可穿梭 於人體內，預計將來可精準傳送幹細胞及藥物至人體的特 定部位作靶向治療，以及協助細胞組織再生，使無線操控 微型醫療機械的發展邁進了重要的一步。研究結果刊登 於國際知名學術期刊《先進材料》11月6日號的封面。 微型機械的發展涉及機械電子學、材料科學、生物科學、 控制及自動化等多種前沿學科的知識。由於裝置體積太 小，長度只有一百微米左右，厚約四十微米，即約一條髮 絲的半徑，要在其上裝設馬達等機電零件，驅動它在人體 血管或液體中前行，近乎不可能。研究人員發現以磁場控 制這種無線驅動模式是可行方法，所以在設置塗上鎳。而 為了確保體內應用的生物穩定相容性，塗層也加進了鈦。 然而，可以如何在體液中前進，張教授參考了微生物的移 動方式和各種可變因數，包括流體的黏性和速度、機械的 形狀和體積，再考慮磁場強度會隨着與機械距離漸遠而 急速減弱這限制，經過多方實驗及複雜運算，得出以螺旋 式的模式前進，是機械在活體內最佳的推進方式之一。 機械裝置的形狀設計亦經過不斷改良，過往此類微型機 械多是螺旋型，盛藥量有限，在最新發表的研究中，張教 授與合作者建構了一個三維的光聚合高分子多孔微型支 架，孔隙大小形狀可因應不同的醫療目的所需的藥量而控 制。他說新設計突破了原有微型機械載藥量不足的限制， 他形容：「我希望可設計一輛貨車，而非只是私家車。」此 外，三維結構相較平面的二維結構，更接近活體環境，在 微型支架上培殖細胞，可保存所培殖細胞結構和功能上 的複雜性。 新的微型機械在微創醫療方面有極大的應用潛力，有望應 用於治療癌症、腦梗中風和視網膜退化。張教授表示，如 開腦手術或眼部手術，病人要面對開刀風險，使用微型機 械便可直接治療或修復壞死細胞，減少入侵性醫療方式所 引發的副作用。 張教授坦言，現時研究只屬起步階段，還要在動物及人體 測驗其功效，預計至少要十年始能應用。張教授一直專注 研究微納米機械的運動方式及動力學特性，現時與中大的 研究團隊致力從微型機械的結構設計及材料特性，改善其 智能及性能。他的研究結果曾多次登於著名期刊，如《晶 片實驗室》、《先進材料》和《今日材料》。 in the quantity of drug delivered. ‘I want to design a truck, not a car.’ Moreover, having a three-dimensional structure for cell culture, compared to two-dimensional in which the cell is cultured on a flat surface, is important for sustaining the structural and functional complexities of the cells because it is much closer to the in vivo environment. The new technology has the potential to revolutionize minimally invasive medical treatment and can lead to targeted treatment of various diseases such as cancer, cerebral infarction and retinal degeneration. Professor Zhang said traditional treatment involves surgery which poses risks to patients. The new method allows accurate cell and drug delivery to the needed part directly for tissue regeneration and targeted therapy which can prevent side-effects triggered by invasive methods. However, the technology is still in its infancy and the next step is to test the microrobot on animals and later on humans. Professor Zhang estimated that it will take at least a decade to put it into trial run. Professor Zhang has devoted himself to the development of magnetic micro- and nanorobots. He is currently leading the CUHK research team to improve the performance, intelligence and design of these micro-devices by paying close attention to their locomotion and dynamic properties in fluid. His research results have been highlighted in a number of renowned journals, such as Lab on a Chip , Advanced Materials , and Materials Today . Sangwon Kim, Famin Qiu, Samhwan Kim, Ali Ghanbari, Cheil Moon, Li Zhang, Bradley J. Nelson, Hongsoo Choi: Magnetic Microrobots: Fabrication and Characterization of Magnetic Microrobots for Three-Dimensional Cell Culture and Targeted Transportation. Advanced Materials 2013, 41, page 5829. Copyright Wiley-VCH Verlag GmbH & Co. KGaA. Reproduced with permission