Tissue Manipulation Using Nano-Particles Ferrofluids for Minimal Access Surgical Applications YU-SHENG LIN Submitted in accordance with the requirements for the degree of Doctor of Philosophy The University of Leeds School of Mechanical Engineering September, 2014 The candidate confirms that the work submitted is his own and that appropriate credit has been given where reference has been made to the work of others. This copy has been supplied on the understanding that it is copyright material and that no quotation from the thesis may be published without proper acknowledgement. - ii - Acknowledgements I would like to express my deepest gratitude to my Ph.D. supervisor, Professor Anne Neville for her constant support and guidance through my Ph.D. study. Her enthusiasm, the effort she put into the research and her patient all together make this thesis possible. I am grateful to thank two second supervisors, Dr Rupesh Roshan and Dr Tomasz Liskiewicz, who had supported me in daily research and discussions. I also would like to thank all who had helped this work develop well: the great clinical support from Professor David Jayne, Adrian Hood and Jenifer Barrie on the in-vivo study; the great technical support from Dr Peter Culmer and Dr Ali Alazmani in designing the ex-vivo experimental setup using LabVIEW; the technical support from Dr Nagitha Wijayathunga in characterising the particle migration using micro- CT scanner; the great support from Dr Yi-Fan Chou in processing images using Matlab. In addition, I would like to thank my two examiners, Professor Peter Brett and Dr Mark Wilson for the advices to make this thesis become better. I am indebted to the secretaries and technicians in the Mechanical Engineering Department in the University of Leeds for the assistant and helping the experimental work: Jacqueline Kidd, Fiona Slade, Ron Cellier, Ted Allwood, Graham Blyth, Graham Jakeman, Brian Leach, Mark Batchelor, Antony Wiese and Jane Tillotson. Besides, I want to thank the colleagues of the Surgical Technology (ST) group, the Institute of Functional Surfaces (iFS) and the former Institute of Engineering Thermofluids, Surfaces and Interfaces (iETSI), in particular, Abinesh Gnanavelu, Alfonso Lopez, Ashley Bell, Ashley Stratton-Powell, Hongyuan Zhao, James Chalder, Joe Lanigan, Karen Mitchell, Laura Sanders, Liuquan Yang, Louise Hunter, Michal Ciolkowski, Nicholas Raske, Wendy Cheong, William Mayfield, Yugal Rai, Yong Hua, Zahra Ehteshami . Yu-Sheng Lin 25.02.2015 - iii - 首先我要把完成這份論文的感動送給我的家人: 一直支持著和鼓勵我的父 母 妙美和瑛敏, 因為你們的栽培, 讓我能有勇氣和毅力完成這個研究. 另外在學 術和生活中不斷地引領著且啟發著我的姐姐 鈺維和哥哥 育宣, 已經在天國的 奶奶 林趙菊江, 還有陪伴著我唸書且照顧飲食和健康的女友 玉萍. 謝謝你們. 另外我要感謝一起在英國奮鬥過的朋友們, Tom, 鎮遠和 Iris 夫婦, 逸凡和 逸凡媽媽, 安頎 Angy, 大威 David, 國峰, 瓏文, Peppy, 任賢 Lucas, Michelle, 惠瑜 Elsa, 惠芳 Helen, Peter, 政閔和 Anna 夫婦, 庭緯, 懿恬, 逸帆, 淑薰, 啟瑞和毛寶 一家人, 敏禎, Vanessa, 芊霓, 肇君, Rachel, Evonne 以及許多來不及列在裡面的 朋友們, 謝謝你們. 還有要感謝的是遠在台灣持續給我鼓勵的朋友師長們, 謝謝你們. 林育昇 25.02.2015 - iv - Abstract Nano-scale Iron-Oxide ferrofluids exhibit a special property, ‘superparamagnetism’, that induces an attractive force toward an external magnetic field. The aim of this project is to investigate the use of ferrofluids for tissue retraction during Minimally Access Surgery (MAS). In the in-vivo porcine experiments, 0.3 ml of ferrofluid (200 mg/ml concentration) containing 10 nm particles is injected subserosally into the small bowel, respectively. A 0.6 T magnetic field is created using a combination of 10 mm and 20 mm diameter Neodymium Iron Boron magnets. The vertical retraction distance is measured up to 80 mm and video-recorded. The results demonstrate the capacity of ferrofluid to facilitate the tissue manipulation and analysis of the migration of the particles within the tissue using micro computed tomography (CT). A theoretical model developed to validate the experimental results is also beneficial for predicting retraction force. In conclusion, this feasibility study provides a protocol for systematically using small volumes of ferrofluid, without the need to mechanically grasp the tissue. - v - Contents Acknowledgements .................................................................................................... ii Abstract ..................................................................................................................... iv Contents ..................................................................................................................... v Nomenclature.......................................................................................................... viii Abbreviation .............................................................................................................. x Figures ...................................................................................................................... xii Tables ....................................................................................................................... xx Chapter 1 Introduction .................................................................................... 1 1.1 Background ............................................................................................... 1 1.2 Aims and Objectives ............................................................................... 12 1.3 Overview of the Thesis ........................................................................... 13 Chapter 2 Literature Review of Techniques Used for Tissue Manipulation .................................................................................................. 16 2.1 Conventional Graspers for Open Surgery and MAS .............................. 17 2.2 Alternative Methods for Tissue Manipulation in MAS .......................... 24 2.2.1 Vacuum Grasping........................................................................... 25 2.2.2 Magnetic Anchoring and Guidance System (MAGS) Grasping ......................................................................................... 27 2.2.3 Magnetic Fluid Grasping................................................................ 32 2.2.4 Specific Procedures for Tissue Manipulation ................................ 34 2.3 Conclusions ............................................................................................. 35 Chapter 3 Literature Review on Approaches for Adhesion Force Measurement .................................................................................................. 38 3.1 Adhesion Principle Involved in Tissue Manipulation ............................. 38 3.2 Adhesion Measurement from an Engineering Perspective ..................... 40 3.3 Review of Adhesion for Retraction ........................................................ 44 3.4 Magnetic Adhesion ................................................................................. 48 3.5 Conclusions ............................................................................................. 51 Chapter 4 Methodology for Tissue Manipulation Measurement .............. 53 4.1 Instrumental Adhesion Measurements – MUST TM Tester ...................... 53 4.1.1 A Sensoring System (Optical Fibre and Cantilever) ...................... 54 4.1.2 Motion Modules (Instrumental Module and Movable Module) .... 57 4.1.3 Configurations ................................................................................ 58 - vi - 4.2 Instrumental Adhesion Measurement – The MagRAT Tester ................ 59 4.2.1 Configurations ................................................................................ 59 4.2.2 A Force Sensor ............................................................................... 60 4.2.3 Motion Modules ............................................................................. 61 4.2.4 Magnetic Inducers .......................................................................... 63 4.2.5 HIRST Gaussmeter ........................................................................ 64 4.2.6 Instrumental an Injection Module .................................................. 64 4.2.7 Sensor of the Injection Module ...................................................... 66 4.2.8 Procedures of Adhesion Measurement........................................... 67 4.2.9 Procedures of Tissue Retraction Examination ............................... 71 4.3 Sample Specification ............................................................................... 72 4.4 Particle Sizing Measurement................................................................... 74 4.5 Particle Density Distributing Measurement ............................................ 75 4.6 Taguchi Method for Parametric Analysis ............................................... 77 4.7 In-vivo Experimental Arrangement ........................................................ 80 Chapter 5 Results from the Tissue Retraction Experiments ...................... 81 5.1 Ex-vivo Experiments ............................................................................... 81 5.1.1 Adhesion Force Profile .................................................................. 81 5.1.2 A Test of Plain Tissues .................................................................. 83 5.1.3 Tests of Various Ferrofluids and Magnetised Tissues ................... 84 5.1.4 Effect of Operation - Preload ......................................................... 89 5.1.5 Effect of Magnetic Field Strength .................................................. 90 5.1.6 Effect of Duration of Magnet Contact ........................................... 94 5.1.7 The Operation