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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/86741完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 王兆麟(Jaw-Lin Wang) | |
| dc.contributor.author | Chien-Ying Ho | en |
| dc.contributor.author | 何建穎 | zh_TW |
| dc.date.accessioned | 2023-03-20T00:14:43Z | - |
| dc.date.copyright | 2022-08-03 | |
| dc.date.issued | 2022 | |
| dc.date.submitted | 2022-07-28 | |
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Chu, Y.-C., et al., Elevation of intra-cellular calcium in nucleus pulposus cells with micro-pipette-guided Ultrasound. Ultrasound in Medicine & Biology, 2021. 47(7): p. 1775-1784. 31. 超音波原理與硬體介紹. Available from: https://www.itriwater.org.tw/technology/More?id=125. 32. Snehota, M., et al., Therapeutic ultrasound experiments in vitro: Review of factors influencing outcomes and reproducibility. Ultrasonics, 2020. 107. 33. Nelson, T.R., et al., Ultrasound biosafety considerations for the practicing sonographer and sonologist. 2009. 34. engineering solutions. Available from: https://en.engineering-solutions.ru/ultrasound/theory/#2. 35. Azhari, H., Ultrasound: medical imaging and beyond (an invited review). Current pharmaceutical biotechnology, 2012. 13(11): p. 2104-2116. 36. Sezer, N. and M. Koç, A comprehensive review on the state-of-the-art of piezoelectric energy harvesting. Nano Energy, 2021. 80: p. 105567. 37. Guo, Y.J., et al., ERK/MAPK signalling pathway and tumorigenesis. 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Qiu, Z., et al., The Mechanosensitive Ion Channel Piezo1 Significantly Mediates Ultrasonic Stimulation of Neurons. Available at SSRN 3397112, 2019. 45. Shi, M., et al., Glial cell-expressed mechanosensitive channel TRPV4 mediates infrasound-induced neuronal impairment. Acta neuropathologica, 2013. 126(5): p. 725-739. 46. Chu, Y.-C., et al., Piezoelectric stimulation by ultrasound facilitates chondrogenesis of mesenchymal stem cells. The Journal of the Acoustical Society of America, 2020. 148(1): p. EL58-EL64. 47. 劉禹呈, 超音波與壓電刺激對人體間質幹細胞遷移與軟骨細胞聚合、重排的影響. 2022, 國立台灣大學碩士論文. 48. Carter, B.J., Adeno-associated virus and the development of adeno-associated virus vectors: a historical perspective. Molecular therapy, 2004. 10(6): p. 981-989. 49. Kong, T., et al., Role of the extracellular signal-regulated kinase 1/2 signaling pathway in ischemia-reperfusion injury. Frontiers in physiology, 2019: p. 1038. 50. Aoki, K., et al., Processive phosphorylation of ERK MAP kinase in mammalian cells. Proceedings of the National Academy of Sciences, 2011. 108(31): p. 12675-12680. 51. Maik-Rachline, G., A. Hacohen-Lev-Ran, and R. Seger, Nuclear ERK: mechanism of translocation, substrates, and role in cancer. International journal of molecular sciences, 2019. 20(5): p. 1194. 52. 吳振吉. 遺傳性聽損. 2015; Available from: https://www.ntuh.gov.tw/gene-lab-mollab/Fpage.action?muid=4050&fid=3868. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/86741 | - |
| dc.description.abstract | 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。 | zh_TW |
| dc.description.abstract | 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. | en |
| dc.description.provenance | Made available in DSpace on 2023-03-20T00:14:43Z (GMT). No. of bitstreams: 1 U0001-1007202217314700.pdf: 8932111 bytes, checksum: c8e4d649d3426de729954a375ee1fbea (MD5) Previous issue date: 2022 | en |
| dc.description.tableofcontents | 審定書 ....... I 致謝 II 摘要 IV Abstract V 發表著作 VI 目錄 VII 圖目錄 XIV 表目錄 XVIII 第一章緒論 1 1.1研究背景 1 1.2超音波於動物實驗中的問題 2 1.2.1超音波用於動物實驗研究文獻探討 2 1.2.2動物實驗與體外實驗差異性 2 1.3聚焦超音波探頭開發 5 1.3.1聚焦超音波 5 1.3.2為動物實驗所設計之聚焦超音波探頭及組件 5 1.4更多不同的刺激模式 6 1.5小鼠膝關節傷害裝置設計 8 第二章 材料與方法 9 2.1力學波 9 2.1.1聲波 9 2.1.2超音波 9 2.1.2.1聲輻射力(Acoustic Radiation Force) 9 2.1.2.2聲流(Acoustic Streaming) 10 2.1.2.3空蝕(Cavitation) 10 2.1.2.4聲強度(acoustic intensity) 11 2.1.2.5佔空比(Duty Factor, DF)、脈衝重現週期(Pulse Repetition Period) 12 2.1.2.6聲阻抗(acoustic impedance) 12 2.2波動力學 13 2.2.1波傳模式 13 2.2.2波的折射(refraction)、反射(reflection) 14 2.3影像用超音波 16 2.3.1 A mode 16 2.3.2 B mode 16 2.3.3 M mode 17 2.3.4 Doppler mode 17 2.4設備介紹、校正 18 2.4.1超音波探頭 18 2.4.1.1壓電效應(Piezoelectric) 19 2.4.2水聽器(hydrophone) 20 2.4.3波形產生器(function generator) 20 2.4.4功率放大器(power amplifier) 21 2.4.5示波器(oscilloscope) 21 2.4.6脈衝產生接收器(pulser ＆ receiver ) 22 2.4.7 Cellex超音波訊號輸出器 22 2.4.8溫度量測(thermocouple) 23 2.4.9波速量測(鋁合金、水) 24 2.4.9.1水波速量測 24 2.4.9.2鋁合金波速量測(AL6061T6) 24 2.4.10螢光珠(fluospheres) 25 2.5生物實驗的驗證方法與介紹 26 2.5.1髓核細胞(Nucleus Pulposus Cells, NP) 26 2.5.2細胞繼代 27 2.5.3西方墨點法(Western Blot) 27 2.5.4 ERK1/2 (Extracellular Regulated Protein Kinases) 28 2.5.5 TR-Cisplatin (Texas Red-Cisplatin) 28 2.5.6 MIA (mono-iodoacetate) 29 2.5.7 Weight-bearing 29 2.5.8 Mankin grading system 29 第三章 聚焦超音波探頭設計與驗證 30 3.1設計目的 30 3.2設計原理 30 3.2.1數值逼近法 31 3.2.1.1討論 32 3.2.1.2模擬驗證 33 3.2.2公式法 33 3.2.2.1討論 35 3.2.2.2模擬驗證 36 3.2.2.3公式法的簡化 36 3.2.3綜合比較(由臺大醫工所林宇宣提供[40]) 37 3.2.3.1聚焦深度 38 3.2.3.2折射率 38 3.2.3.3聚焦點特性 40 3.3聚焦超音波探頭設計 41 3.3.1聚焦探頭設計 41 3.3.2套筒設計 42 3.4量測驗證 45 3.4.1聲場量測 45 3.4.1.1量測及實驗用容器 45 3.4.1.2聲場分佈 46 3.4.2其他特性 49 3.4.2.1不同頻率的超音波壓電片對輸出之影響 49 3.4.2.2溫度量測 50 3.5生物實驗驗證 52 3.5.1組織實驗(耳蝸組織) 52 3.5.1.1實驗架設(聚焦超音波探頭) 52 3.5.1.2微能量超音波增強體外培養之耳蝸毛細胞對於化療藥物的吸收率(由臺大醫院耳鼻喉科吳振吉醫師團隊提供) 53 3.5.1.3討論 56 3.5.2大鼠實驗(膝關節炎模型) 57 3.5.2.1實驗架設(聚焦超音波探頭、套筒) 57 3.5.2.2超音波誘導的壓電刺激促進退化性關節炎大鼠的恢復 58 3.5.2.3實驗結果(由台大醫院復健科吳爵宏醫師團隊提供) 60 3.5.2.4討論 62 3.5.3崽鼠實驗 62 3.5.3.1實驗架設 62 3.5.3.2 超音波增加腺相關病毒進入內耳細胞的感染率(由吳振吉醫師團隊提供) 63 第四章 可產生剪力之聚焦超音波探頭設計與驗證 66 4.1設計目的 66 4.2設計原理 67 4.3產生剪力之聚焦超音波探頭設計 68 4.3.1探頭設計 68 4.3.2套筒及其他配合件設計 69 4.3.2.1套筒 69 4.3.2.2固定板材質選用與手持握把設計 70 4.4量測驗證 71 4.4.1聲場量測 71 4.4.1.1聲場分佈 71 4.4.1.2流場速度分析(螢光珠實驗) 73 4.5生物實驗驗證 77 4.5.1細胞實驗(髓核細胞) 77 4.5.1.1實驗架設 77 4.5.1.2剪力加超音波刺激有效調控髓核細胞內ERK1/2的磷酸化 78 4.5.2組織實驗(耳蝸組織) 81 4.5.2.1實驗架設(超音波加剪力探頭) 81 4.5.2.2超音波加剪力刺激增強體外培養之耳蝸毛細胞對於化療藥物的吸收(由臺大醫院耳鼻喉科吳振吉醫師團隊提供) 81 4.5.3大鼠實驗(膝關節炎模型) 84 4.5.3.1實驗架設(超音波加剪力探頭、套筒) 84 4.5.3.2超音波誘導的壓電刺激促進退化性關節炎大鼠的恢復 85 4.5.3.3實驗結果(由台大醫院復健科吳爵宏醫師團隊提供) 85 第五章 小鼠膝關節傷害裝置設計開發及其他實驗 89 5.1設計目的 89 5.2設計原理 90 5.2.1小鼠膝關節傷害裝置 90 5.2.2小鼠膝關節之超音波刺激與治療 92 5.2.3小鼠膝關節傷害及超音波刺激治療實驗 94 5.3探討細胞上之間隙連接(Gap junction)受超音波刺激後之影響 95 5.3.1背景與動機 95 5.3.2實驗架設 96 5.3.3實驗結果 96 第六章 結論與未來展望 101 6.1結論 101 6.1.1聚焦超音波探頭設計開發 101 6.1.2不同層級的生物實驗驗證 101 6.1.3超音波加剪力刺激 101 6.1.4小鼠膝關節傷害裝置 102 6.2未來展望 102 參考文獻 104 | |
| dc.language.iso | zh-TW | |
| dc.subject | 微能量超音波 | zh_TW |
| dc.subject | 膝關節傷害模型 | zh_TW |
| dc.subject | 超音波及剪力 | zh_TW |
| dc.subject | 壓電效應 | zh_TW |
| dc.subject | 聚焦超音波裝置開發 | zh_TW |
| dc.subject | 微能量超音波 | zh_TW |
| dc.subject | 膝關節傷害模型 | zh_TW |
| dc.subject | 超音波及剪力 | zh_TW |
| dc.subject | 壓電效應 | zh_TW |
| dc.subject | 聚焦超音波裝置開發 | zh_TW |
| dc.subject | Very-low-intensity ultrasound | en |
| dc.subject | Focus ultrasound device design | en |
| dc.subject | piezoelectric effect | en |
| dc.subject | Ultrasound and shear force | en |
| dc.subject | Knee injury model | en |
| dc.subject | Very-low-intensity ultrasound | en |
| dc.subject | Focus ultrasound device design | en |
| dc.subject | piezoelectric effect | en |
| dc.subject | Ultrasound and shear force | en |
| dc.subject | Knee injury model | en |
| dc.title | 適用於動物及細胞實驗之超音波探頭設計 | zh_TW |
| dc.title | The design of ultrasound probes for animal and cell experiments | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 110-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 吳振吉(Chen-Chi Wu),李百祺(Pai-Chi Li) | |
| dc.subject.keyword | 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, | zh_TW |
| dc.subject.keyword | Very-low-intensity ultrasound,Focus ultrasound device design,piezoelectric effect,Ultrasound and shear force,Knee injury model, | en |
| dc.relation.page | 107 | |
| dc.identifier.doi | 10.6342/NTU202201378 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2022-07-28 | |
| dc.contributor.author-college | 工學院 | zh_TW |
| dc.contributor.author-dept | 醫學工程學研究所 | zh_TW |
| dc.date.embargo-lift | 2022-08-03 | - |
| 顯示於系所單位： | 醫學工程學研究所 | |
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