超音波微氣泡之製備與生醫應用

Preparation and Biomedical Applications of Ultrasonic Microbubbles

鄭雅健(Ya-Jian Cheng)

指導教授 ： 李百祺

國立臺灣大學/電機資訊學院/電機工程學研究所/碩士(2007年)

https://doi.org/10.6342/NTU.2007.01307

摘要

超音波不僅被廣泛使用於醫學影像應用之中，亦能以熱效應及穴蝕效應搭配聚焦的特性，以非侵入的方式進行如以穴蝕效應引發的聲穿孔現象給藥、殺除、轉殖基因、清除血栓及打開血腦障壁等工作。搭配微氣泡，則可以降低引發穴蝕效應的閾值，在升溫小於1℃的情況下引發穴蝕，故，能在更安全的能量下操作生物材料或進行醫療。而取得自製的微氣泡能力是穴蝕效應生醫研究中關鍵的一環，自製適合的微氣泡能依實驗所需做修改，節省購買經費及應付進口醫療器材的麻煩，亦便利了未來修飾抗體、靶向性分子賦予微氣泡辨認特定細胞。本論文以定量化ICD測量為基準，成功自製一種高ICD、容易保存、使用前免活化之白蛋白全氟化丙烷微氣泡，並測試其於影像與生醫應用的可行性。為驗證穴蝕效應造成細胞死亡為立即性壞死或慢性細胞凋亡，亦進行實驗證明在千分之一的工作週率下，即使以1.21MPa引發微氣泡穴蝕效應，也無法顯著增加癌細胞的凋亡比。

關鍵字

超音波 ； 微氣泡 ； 自製超音波對比劑 ； 穴蝕效應 ； 細胞凋亡 ； 基因轉殖 ； 慣性穴蝕劑量

並列摘要

Application of ultrasound is not just limited to medical imaging, but also extends to non-invasive therapies such as drug-delivery, cancer cell annihilating, transfection, thrombolysis, and blood-brain barrier （abbreviated BBB） opening, etc. The operations can be accomplished utilizing thermal or cavitation effect and targeted by a focused transducer. With the aid of micro-bubbles, the cavitation threshold is lowered such that the temperature increment is smaller than 1℃, thereby a more secure dose for experiment and medical treatment could be conducted. However, restricted to medical regulations in Taiwan, commercial microbubbles are hard to be imported. Therefore self-made microbubbles become crucial in biomedical cavitation studies. Moreover, self-made micro-bubbles can be modified according to experimental need, and may attain target-identification by attaching antibodies or targeting-molecules. In this thesis, several kinds of self-made microbubbles were evaluated by means of ICD （Inertial Cavitation Dose） method. We have successfully develop a self-made albumin perfluorocarbon microbubble which has ideal properties of high ICD, stability, and it doesn’t need to be activated before use. Feasibility of self-made microbubbles as contrast agent was also investigated. In order to know whether apoptosis played a role in cavitation induced cell death, the Caspase-3 assay was conducted. According to the experiment result, no increment was observed in apoptosis rate even under the 1.21MPa and 0.1% duty cycle condition.

並列關鍵字

ultrasound ； microbubbles ； self-made ultrasound contrast agent ； cavitation ； apoptosis ； transfection ； inertial cavitation dose

參考文獻

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