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研究生: 邱俊賢
Chiu, Chun-Hsien
論文名稱: 無針式微型噴注之注射特性及其在內視鏡治療術之應用
Characterization of Needle-Free Micro-Injection and Its Applications in Endoscopic Therapeutics
指導教授: 王覺寬
Wang, Muh-Rong
學位類別: 博士
Doctor
系所名稱: 工學院 - 航空太空工程學系
Department of Aeronautics & Astronautics
論文出版年: 2010
畢業學年度: 98
語文別: 英文
論文頁數: 187
中文關鍵詞: 微噴注無針式注射穿透明膠豬結腸
外文關鍵詞: Micro injection, Needle-free injection, Penetration, Gelatin gel, Porcine colon
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  • 本文發展一無針微噴注注射系統,探討微噴注之噴注特性及穿透軟性固體材料之穿透特性,並將此無針微噴注注射系統應用於內視鏡治療術上。其中微噴嘴孔的直徑為250 μm和300 μm,所使用的工作流體為水,工作壓力為15 bar ~125 bar,所使用的軟性固體材料有30%明膠與豬結腸。微噴注之流體動態特性實驗結果顯示微噴流之質量流率隨工作壓力增加而增加及以隨噴口大小變大而增加;而微噴流的噴流出口速度只隨噴注壓力的增加而增加,不隨噴嘴孔徑的大小及噴注時間變化,噴注壓力從15 bar增加至125 bar,其噴流出口速度由40 m/s增加至110 m/s,其注射功率為1.7 W~46.7 W。由實驗的結果所得到的微噴注器噴流係數,CD,當雷諾數介於15,000~40,000時,CD約為0.7,當雷諾數為10,000到15,000時,CD趨近於0.75。本研究第二部分以壓縮試驗與深壓穿透試驗等方法探討明膠及豬結腸等軟性固體材料之機械特性;壓縮實驗結果顯示,30%明膠與豬結腸之楊氏模數分別為0.037±0.013 MPa與0.0089±0.0036 MPa;深壓穿透實驗結果顯示,30%明膠與豬結腸之破裂應力分別為0.694±0.043 MPa與1.077±0.333 MPa。第三部分之微噴注穿透明膠的實驗結果顯示脈衝式微噴流對軟性固體材質之穿透深度可以藉由注射壓力、噴嘴直徑和注射時間來控制,其貫穿深度隨著注射壓力、注射功率與注射能量的增加而增加。微噴注穿透明膠的過程可分為四個階段: 彈性變形階段、穿透階段、彈性回復階段及穩定階段,當直徑為250μm與300μm的微噴嘴衝擊30%明膠時,得到最終穿透深度分別可達11.4mm和12.5mm。噴注穿透率隨噴注功率增加而遞增,但隨噴注時間增加而遞減,由增加噴注功率所造成的效應為穿透率較大的噴注穿透,由噴注時間造成的效應為噴注穿透率較小的噴注穿透。本文亦提出無針微噴注穿透30%明膠的穿透性能工作地圖,可提供給研究者及設備操作者參考之用。於脈衝式微噴注穿透豬結腸實驗顯示,噴注功率高於16 W的微噴注注射會穿透整個豬結腸腸壁組織,所以應用於豬結腸之注射實驗必須低於16 W的噴注功率。再應用此自製之無針式注射系統於內視鏡治療術,並進一步進行內視鏡用微噴注性能測試與體外豬結腸之組織抬升實驗。內視鏡用無針注射乃採用兩段式噴注方式,第一階段為高壓穿透噴注過程,此階段為噴注穿透豬結腸組織黏膜層;第二階段為組織抬升噴注過程,此階段將抬升液體注入豬結腸組織之次黏膜層以產生組織抬升之效果,由於抬升液體會逐漸往鄰近組織滲透消散,所以抬升後之組織會逐漸回復,此抬升消散過程由高速攝影機記錄再進一步分析。組織穿透實驗的結果顯示當第一階段噴注功率在0.5 W以上均可穿透豬結腸之黏膜層,第二階段組織抬升過程,當噴注功率達0.1 W以上時,均可成功地將抬升液體注入組織之次黏膜層。使用5 cP之褐藻膠溶液之抬升消散半衰期都比甘油溶液(5~30 cP)之抬升消散半衰期長。而使用5~30 cP之褐藻膠溶液之抬升消散半衰期都超過60分鐘。而且使用的抬升液體為褐藻膠溶液及甘油溶液進行組織抬升之抬升高度消散半衰期分別為60分鐘,30分鐘均能符合臨床上手術所需之組織抬升維持時間。本研究成功地將本文所發展之內視鏡無針噴注注射系統應用於體外組織黏膜抬升。待此治療技術發展完成,將可應用於管道腫瘤之治療,如消化道、膽道、尿道等,提供方便,經濟且提升治療之效果。

    This dissertation investigates the mechanisms and performance of micro-jets and the penetration of micro-jets into soft solid materials using a homemade needle-free micro-jet injection system. The application of endoscopic tissue elevation using the needle-free micro-jet injection system also describes in this paper. The first part of this research is to study the characterization of the micro-jet. The experiments were performed using micro-jet with orifice 250 μm and 300 μm. The test results show that the micro-jet velocity increases from 40 m/s to 114 m/s as the injection pressure increased from 15 bar to 125 bar and result in the jet power from 1.7 W to 46.7 W. The injection force with the standoff distance of 2 mm increases from 10.3 to 96.4 g. The discharge coefficient, CD of both injectors is about 0.7 over the range of Reynolds numbers from 15,000 to 40,000. At lower values of Reynolds numbers (10,000 to 15,000), CD approaches 0.75. The second part describes the measurement of the mechanical properties using compression test and deep penetration test. Experimental results show that the Young’s modulus of 30% gelatin gel and porcine colon measured by compression test are 0.037±0.013 MPa and 0.0089±0.0036 MPa, respectively. The failure stress of 30% gelatin gel and porcine colon measured by deep penetration test are 0.694±0.043 MPa and 1.077±0.333 MPa, respectively. The performance of the pulsed micro-jet and its penetration on the solid soft material is described in the third part of this dissertation. According to the test results, it is concluded that the penetration of the micro-jets into solid soft materials is essentially controlled by the injection pressure and the orifice diameter. It is observed that the compression followed penetrated inside the gel after the micro-jet impingement. The micro-jet compression and penetration is increased along both the axial and transverse directions in the gel. As the pulsed micro-jet is stopped to supply water, the penetration reduces in both the axial and transverse directions. The penetration process can be divided into 4 phases, the elastic deformation phase, the penetrating phase, the elastic recovering phase and the stable phase. In the test case, the final penetration depth reaches 11.4 mm and 12.5 mm by using the orifice of 250 μm and 300 μm, respectively. The fourth part in this research applies the needle-free micro-injection system to endoscopic therapeutics. The performance of the endoscopic needle-free injection system on the tissue elevation of the porcine colon is investigated. The working fluids include normal saline, glycerin and alginate solutions. The tissue is first penetrated into the mucosal layer and lifted up due to the second-step injection of the working fluids into the tissue. It is then recovered due to the diffusion of the working medium to the neighboring tissue. The processes are recorded by the high speed camera for further analysis. Results show that the alginate solution with higher rheologic property has the advantage to supply higher flow rate under the same operational condition. Moreover, with the viscosity of 5 cp, the half-life time of the alginate solution is longer than that of the glycerin solution. Tests over the viscosity ranging from 5 cp to 30 cp with alginate solution indicate that the half-life time increases with viscosity and the half-life time is more than 60 min, which is long enough for the snare resection of the tumor through the endoscope.
    We successfully applied this endoscopic needle-free micro-jet injection system in tissue elevation. After completion of this treatment technology, it will be applied to tumor treatment, such as the gastrointestinal tract, biliary tract, urinary tract, etc., to provide a convenient, economical and effective operation of endoscopic therapeutics.

    摘要 I 誌謝 III 第一章 緒論 V 第二章 實驗儀器與設備 VII 第三章 微噴注之動態特性研究 VIII 第四章 軟性固體材料之機械特性量測及分析 IX 第五章 無針噴注注射穿透軟性固體材料之性能及特性 X 第六章 無針噴注注射系統於內視鏡治療術之應用 XI 第七章 結論 XII 第八章 未來工作之建議 XIV ABSTRACT XVII CONTENTS XIX LIST OF TABLES XIV LIST OF FIGURES XXV NOMENCLATURE XXXIV CHAPTER Ⅰ INTRODUCTION 1 1.1 Historical Background 2 1.2 Current Clinical Applications 6 1.3 Related Research on Needle-free Jet Injection 9 1.3.1 Dependence of Jet Penetration into Soft Solid Materials on Jet Characteristics 9 1.3.2 Mechanisms of Penetration 12 1.3.3 Driving Schemes of Needle-free Jet Injection 16 1.4 Fluid Dynamics of Liquid Jet 20 1.5 Solid Soft Materials 29 1.5.1 Gelatin 29 1.5.2 Large Intestine 30 1.5.3 Mechanical Properties of Solid Soft Materials and Measuring Methods 33 1.6 Endoscopy 42 1.6.1 Introduction to Endoscopy 42 1.6.2 Endoscopic Tissue Elevation 44 1.7 Motivation and objectives 45 1.8 Dissertation Outline 46 CHAPTER Ⅱ EXPERIMENTAL FACILITY AND INSTRUMENTATION 48 2.1 Micro-injectors 48 2.2 Needle-Free Jet Injection System 49 2.3 Experimental Facility and Methods for Jet Characterization 53 2.3.1 Jet Flow Visualization 54 2.3.2 Liquid Mass flow Rate and Jet Velocity 55 2.3.3 Injection Power of Micro-Jets 56 2.3.4 Discharge coefficient, CD of a Jet 57 2.3.5 Data Acquisition 57 2.3.6 Injection Pressure and Injection Force 57 2.4 Manufacture Process and Preparation of Soft Solid Materials 62 2.4.1 Manufacture Process and Preparation of Gelatin Gel Samples 62 2.4.2 Preparation of Porcine Colons 63 2.5 Mechanical Properties of Soft Solid Materials 64 2.5.1 Young’s Modulus and Critical Stress of Failure (Failure Stress) of Materials 64 2.5.2 Uniaxial Compression Test 66 2.5.3 Deep Penetration Test 67 2.6 Jet Penetration into Soft Solid Materials 71 2.6.1 Visualization and Penetration Process Analysis 73 2.6.2 Penetration Depth and volume of infection of Micro-jets Penetration into Gelatin Gels 74 2.6.3 Penetration rate of Micro-jets Penetration into Gelatin Gels 75 2.6.4 Penetration of Porcine Colons by Micro-jets 75 CHAPTER III DYNAMIC PROCESSES OF MICRO-INJECTIONS 76 3.1 Characteristics of Micro-jets 76 3.1.1 Liquid Mass Flow Rate of Continuous-Pulse Micro-jets 78 3.1.2 Delivery Volume of Single-Pulse Micro-jets 79 3.1.3 Jet Velocities of Micro-jets 81 3.1.4 Injection Force and Jet Velocity 82 3.1.5 Discharge Coefficients of Micro-jets 85 3.1.6 Jet Powers of Micro-jets 87 3.2 Flow Visualization of Micro-jets 88 3.2.1 Flow Visualization of Transient Process of Micro-jets 89 3.2.2 Flow Visualization of Steady State Micro-jets 93 3.3 Summary 94 CHAPTER IV MEASUREMENT OF MECHANICAL PROPERTIES OF SOFT SOLID MATERIALS 96 4.1 Uniaxial Compression Test 96 4.2 Deep Penetration Test 97 4.2.1 Strain-Stress Curve of Deep Penetration Test 97 4.2.2 Influence of the Penetration Locations on Failure Stress of Porcine Colons 98 4.2.3 Influence of the Strain Rate on Failure Stress of Porcine Colons and gelatin gels 100 4.3 Summary 101 CHAPTER V PENETRATION OF SOFT SOLID MATERIALS BY NEEDLE-FREE MICRO-INJECTIONS 103 5.1 Penetration of Gelatin Gels by Single-Pulse Micro-jets 103 5.1.1 Evolution of Micro-jets Penetration into Gelatin Gels 103 5.1.2 Evolution of Penetration Process of Gelatin Gel 110 5.1.3 Dependence of Penetration Depth on Jet Power of Micro-jet Injections 114 5.1.4 Dependence of Penetration Depth on Total Injection Energy of Micro-injections 116 5.1.5 Dependence of Lc and Lm on Jet Power of Micro-jet Injections 118 5.1.6 Penetration Rate of Micro-jet Injections Penetration into Gelatin Gel 121 5.1.7 Working Region for Needle-free Micro-injection penetrations into Gelatin Gels 123 5.2 Penetration of Porcine Colons 125 5.3 Summary 128 CHAPTER VI THERAPEUTIC ENDOSCOPY APPLICATION OF NEEDLE-FREE JET INJECTION 131 6.1 Endoscopic Needle-free Jet Injection System 133 6.2 Characterization of the Endoscopic Needle-free Micro-jets 134 6.2.1 Dependence of Liquid Mass Flow Rate on Injection Pressure 136 6.2.2 Dependence of Injection Power on Injection Pressure 142 6.2.3 Discharge Coefficient (CD) of Endoscopic Needle-free Injection 143 6.3 In Vitro Test without Endoscope 145 6.3.1 Effect of Injection Properties on Penetrating the Mucosal Layer of Porcine Colon 148 6.3.2 Effect of Elevation Fluids on Tissue Elevation 149 6.3.3 Evolution of Tissue Elevation 151 6.3.4 Effect of Working Fluids Property on Half Life Time of Tissue Elevation 153 6.4 Endoscopic Treatment of Experimental Conditions with Cryotherapy 155 6.5 In Vitro Test with Endoscope 159 6.6 Summary 163 CHAPTER VII CONCLUSIONS 166 CHAPTER VIII SUGGESTIONS FOR FUTURE RESEARCH 169 REFERENCES 172 APPENDIX A CALCULATION OF DEEP PENERATION STRAIN 183 PUBLICATION LIST 185 VITA 187

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