適用於動物及細胞實驗之超音波探頭設計

The design of ultrasound probes for animal and cell experiments

何建穎(Chien-Ying Ho)

指導教授 ： 王兆麟

國立臺灣大學/工學院/醫學工程學研究所/碩士(2022年)

https://doi.org/10.6342/NTU202201378

摘要

超音波因為指向性良好、空間解析度高的特點在工程及醫學領域上被廣泛的運用，在現今已是一項發展純熟的技術，其中用於臨床方面有超音波影像、熱消融、熱治療、骨癒合等用途，甚至在治療某些疾病上已獲得美國食品藥品監督管理局(FDA)的認可，因此在近年來也有許多超音波相關的研究探討某些疾病藉由超音波治療的可行性或是從超音波引發的生物機制著手，舉凡基因治療、藥物遞送、神經調節、細胞再生等都可有機會透過超音波的治療來達成，然而在目前的研究中還有許多的生物機制尚未明朗。
在超音波刺激體外實驗中所取得的研究成果可能面臨與動物實驗的結果有所差異，可能因為細胞、組織在長久的體外培養下已失去原有的性質，抑或是使用不同的刺激裝置造成實驗誤差，基於動物實驗的重要性，本研究以動物實驗的超音波刺激設備為出發點設計一個適應性良好的聚焦超音波探頭及組件，能夠在不同實驗對象例如細胞、組織、動物的超音波刺激實驗中使用，並以一系列的生物實驗驗證探頭的有效性，除此之外，在生物實驗驗證過程中也發現超音波在各個實驗中所扮演的角色，例如活化訊號傳遞機制、增加細胞對藥物吸收情形或是由超音波介導的壓電效應等；然而，許多研究也指出細胞膜上有許多對於機械力敏感的受器感受到機械力刺激模式不同可能活化更多的反應機制。
本研究中針對動物實驗的超音波刺激裝置設計開發，希望提供實驗人員一個適應性良好的刺激裝置，有助於探討動物對於超音波刺激產生的效應，更在未來能以此設計概念做為基礎，設計適合不同刺激對象的超音波裝置，最後也可以用於人體實驗並且導入治療計畫中。

關鍵字

微能量超音波 ； 聚焦超音波裝置開發 ； 壓電效應 ； 超音波及剪力 ； 膝關節傷害模型

並列摘要

Ultrasound has been widely used in engineering and medical applications due to its directivity, spatial resolution and maturity in technology development. Among the medical applications, ultrasound imaging, thermal ablation, thermal therapy and fracture healing are applications already approved by the FDA. Recently, there has been increasing attention to the application of ultrasound for therapeutic treatments from either clinical feasibility or basic cellular mechanism perspectives. Noticeable ultrasound facilitated applications include gene therapy, drug delivery, neuromodulation, and cell therapy. However, how exactly some of these applications work remains unclear at the moment.
Results obtained from in vitro experiments might not be reproducible in vivo as cells behave differently in a culture environment. The translation is certainly more challenging for ultrasound stimulation as not only the cells/tissues are in a different environment, the intensity required could also be different. This study aims at designing ultrasound probes suitable for animal studies while can also be used for in vitro investigation. This can facilitate the dosage translation between in vitro and in vivo studies. We also explore designs that can deliver unique loading to cellular receptors for maximal efficacy.
We hope the probes developed in this study can provide a flexible tool for both in vitro and in vivo studies, enabling more animal studies for proof of concept validation. These probes can also serve as the basis for upscaling to clinical trials with real patients.

並列關鍵字

Very-low-intensity ultrasound ； Focus ultrasound device design ； piezoelectric effect ； Ultrasound and shear force ； Knee injury model

參考文獻

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