應用於基因傳遞之超音波導波管設計優化與評析

Optimization and Characterization of an UltrasonicWaveguide Probe Applied for Gene Delivery

許展榕(CHAN-JUNG HSU)

指導教授 ： 呂志誠

國立臺北科技大學/機電學院/機電整合研究所/碩士(2012年)

摘要

本研究目的在於優化超音波導波管輸出聲壓場。藉由Comsol Multiphysics多物理耦合軟體將壓電模組、聲學模組及固體力學模組予以耦合模擬出超音波聲場。於單一頻率下將圓柱型導波管施予不同倒圓角(fillet)及倒角(chamfer)尺寸，其量測結果顯示施予倒圓角22mm輸出聲場強度優於舊制超音波導波管聲壓強度22%。穴蝕效應(cavitation)分為穩態穴蝕效應(stable cavitation)與慣性穴蝕效應(inertial cavitation)，先前本研究團隊使用HAEC (human aortic endothelial cells, 人類主動脈內皮細胞)作為基因傳遞實驗的細胞。利用慣性穴蝕效應的特性，將基因送入HAEC內，慣性穴蝕效應亦指微氣泡會隨著時間反覆的收縮與膨脹最終破裂的現象，破裂所散發出來的能量能增強細胞膜的通透性以利於DNA送入細胞內，因此本文以微氣泡破裂的數目來判斷引發穴蝕效應的多寡。吾以倒圓角22mm超音波導波管與舊制超音波導波管分別施打超音波於兩種不同的商用微氣泡，並以顆粒計數器(Multisizer 3)觀察微氣泡殘留顆數，經由實驗結果顯示新制超音波導波管能使微氣泡能更有效的破裂，並且達成超音波導波管的優化。

關鍵字

多重物理耦合分析 ； 微氣泡 ； 穴蝕效應 ； 基因傳遞 ； 優化 ； 超音波

並列摘要

The study aimed to optimize the output sound pressure field of the ultrasonic waveguide tube. By using Comsol Multiphysics multi-physics coupling software to couple piezoelectric modules, acoustic modules, and solid mechanics module to simulate the ultrasonic sound field. Analyzing different fillet and chamfer sizes of the cylindrical waveguide tube under single frequency, And the result indicates that the output sound field of 22mm fillet is more intensive than the old sound pressure of ultrasonic waveguide tube by 22%. Cavitation is divided into stable cavitation and inertial cavitation, our research team used HAEC (human aortic of endothelial cells, human aortic endothelial cells) as an experimental gene transfer cells previously, and via the characteristic of inertial cavitation to deliver genes into HAEC; inertial avitation stands for the phenomenon of repeatedly contraction and expansion of micro-bubbles which eventually rupture, and the energy of rupture enhances the permeability of cell membrane that facilitate DNA transmitting into cells, hence determine the size of the cavitation by the number of rupture micro-bubbles. Apply ultrasound on two different commercial micro-bubbles by 22mm fillet ultrasonic waveguide tube and old ultrasonic waveguide tube, and observe the residual pieces of micro-bubbles by (Multisizer 3), and the experimental result indicates that the new ultrasonic waveguide tube enabled more efficient rupture of micro-bubbles and achieved the optimization of ultrasonic waveguide tube.

並列關鍵字

Comsol Multiphysics ； Microbubble ； Cavitation ； Gene delivery ； Optimization ； Ultrasonic

參考文獻

[25] 陳永裕，“超音波及靜磁場對基因傳遞效率影響之研究-體外細胞實驗”，碩士論文，國立台北科技大學機電整合所，台北，2007。

[40] 楊昇學,“單一穴蝕氣泡產生與破裂行為之試驗研究”,博士論文，國立交通大學土木研究所,2009

[47] 賴俊延，“超音波穴蝕效應於基因傳遞效率之研究”，碩士論文，國立台灣大學電機工程學研究所，台北，2005。

[51] 白啟宏，“靜磁場與超音波微氣泡轉染對於基因傳遞影響研究”，碩士論文，國立台北科技大學機電整合所，台北，2009。

[1] A. Halama, M. Kuliñski, T. Librowski, S. Lochyñski, “Polymer-based non-viral gene delivery as a concept for the treatment of cancer,” Pharmacol Reports, vol. 61, no. 6, 2009, pp. 993-999.