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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 李百祺 | zh_TW |
| dc.contributor.advisor | Pai-Chi Li | en |
| dc.contributor.author | 古哲瑋 | zh_TW |
| dc.contributor.author | Zhe-Wei Gu | en |
| dc.date.accessioned | 2026-02-26T16:35:57Z | - |
| dc.date.available | 2026-02-27 | - |
| dc.date.copyright | 2026-02-26 | - |
| dc.date.issued | 2026 | - |
| dc.date.submitted | 2026-02-05 | - |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/101673 | - |
| dc.description.abstract | 本研究開發一款可整合於臨床 25-gauge 微針管腔內之微型化光纖式光聲雙模態裝置，旨在建立可於微創介入條件下進行局部能量導引之技術平台。本研究以眼科脈絡膜上腔(suprachoroidal space, SCS)注射作為主要驗證情境，因其雖具靠近後極部之優勢，但藥物仍受外層血–視網膜屏障(outer blood–retinal barrier, oBRB)限制而難以有效滲透；此外，傳統外部激發方式亦常受限於系統體積、對位困難與能量在組織中的衰減，使其在眼內等狹小解剖空間中難以提供穩定且可控的能量作用。基於此，本研究採用光纖作為能量導引介面以縮小系統尺寸並降低對位需求，除可用於眼內治療外，亦具延伸至其他微創介入場景之應用潛力。本研究以 200 μm 光纖端面為基礎，製備具半穿透特性之光聲薄膜，使單一 808 nm 奈秒脈衝雷射激發時可同軸同步產生穿透光與光聲超音波負壓，分別用於光致液滴氣化(optical droplet vaporization, ODV)與聲致液滴氣化(acoustic droplet vaporization, ADV)，以降低傳統雙源系統在空間對位與時序同步上的實作負擔；此外，針對微型化後可能導致之聲壓輸出不足，本研究進一步透過材料工程提升光聲轉換效率，包含調整 PDMS 交聯度至高交聯比例(3:1)並加入 Super P 導電碳黑作為吸光填料，藉由優化薄膜之吸收與透光配置以兼顧光學穿透與聲學輸出，使裝置在 60% 激發條件下可達 2914 mJ/cm² 光通量與 −752 kPa 峰值負壓，且於較低能量條件下仍可穩定觸發奈米液滴氣化。實驗結果顯示，奈米液滴氣化所誘發之瞬態機械效應，能顯著提升高阻力仿體中之藥物傳輸表現，且該增益效果可隨激發參數(如作用時間)進行調控。螢光定量分析進一步指出，藥物釋放量隨激發時間累積而增加，惟擴散增益與介質阻力呈現負相關趨勢。而能量對照組(相同激發條件下但不含奈米液滴、不發生氣化)未能產生相同程度之增益，支持主要效果來自氣化事件所伴隨之機械擾動。此外，活體前導試驗亦初步界定可行之安全操作參數範圍，整體顯示本系統具提升局部遞送效率並支持後續轉譯醫學評估之應用潛力。 | zh_TW |
| dc.description.abstract | This study develops a miniaturized fiber-based photoacoustic dual-mode device that can be integrated within the lumen of a clinical 25-gauge microneedle, aiming to establish a technical platform for localized energy guidance during minimally invasive interventions. The ophthalmic suprachoroidal space (SCS) injection was selected as the primary validation scenario. Although the SCS offers the advantage of proximity to the posterior pole, drug delivery is typically hindered by the outer blood-retinal barrier (oBRB), resulting in limited effective permeability. Furthermore, traditional external excitation methods are often constrained by bulky system dimensions, alignment difficulties, and energy attenuation in tissues, limiting their ability to deliver stable, controllable energy effects in confined anatomical spaces, such as the intraocular environment. To address these challenges, this study employs an optical fiber as an energy guidance interface to minimize system size and reduce alignment requirements. Beyond intraocular therapy, this design has the potential to be extended to other minimally invasive intervention scenarios. Using a 200 μm fiber tip, a semi-transparent photoacoustic film was fabricated, allowing a single 808 nm nanosecond-pulsed laser to coaxially and synchronously generate transmitted light for optical droplet vaporization (ODV) and photoacoustic ultrasonic negative pressure for acoustic droplet vaporization (ADV). This approach significantly reduces the implementation burden regarding spatial alignment and temporal synchronization associated with traditional dual-source systems. To address potential insufficient acoustic pressure output following miniaturization, photoacoustic conversion efficiency was enhanced through materials engineering. By adjusting the polydimethylsiloxane (PDMS) cross-linking ratio to a high proportion (3:1) and incorporating Super P conductive carbon black as a light-absorbing filler, the film's absorption and transmission configuration were optimized to balance optical penetration and acoustic output. Consequently, the device achieved a light fluence of 2914 mJ/cm2 and a peak negative pressure of −752 kPa under 60% excitation conditions, enabling stable triggering of nanodroplet vaporization even at lower energy levels. Experimental results indicated that transient mechanical effects induced by nanodroplet vaporization significantly enhanced drug delivery performance in high-resistance phantoms, with the gain effect being tunable via excitation parameters (e.g., duration). Quantitative fluorescence analysis further revealed that cumulative drug release increased with excitation time; however, the diffusion gain showed a negative correlation with medium resistance. The energy control group (under identical excitation conditions but without nanodroplets/vaporization) failed to achieve a comparable degree of gain, supporting the conclusion that the primary enhancement arises from mechanical perturbations associated with vaporization events. Furthermore, in vivo pilot trials preliminarily defined a feasible range of safe operating parameters. Overall, these results demonstrate the system's potential for enhancing local delivery efficiency and supporting subsequent translational medical evaluations. | en |
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| dc.description.provenance | Made available in DSpace on 2026-02-26T16:35:57Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 目次
致謝 i 中文摘要 ii Abstract iii 目次 v 圖次 ix 表次 xiii 第一章 緒論 1 1.1 視網膜疾病治療與臨床挑戰 . . . . . . . . . . . . . . . . . . . . . . 1 1.2 眼內藥物遞送的挑戰與外部能量輔助策略 . . . . . . . . . . . . . . 2 1.3 研究動機 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 1.4 研究目標與貢獻 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 第二章 光纖式光聲裝置與奈米液滴汽化之原理 6 2.1 眼內藥物傳遞之生理屏障 . . . . . . . . . . . . . . . . . . . . . . . . 6 2.1.1 眼前節與玻璃體動態屏障 . . . . . . . . . . . . . . . . . . . . . . 6 2.1.2 血–視網膜屏障 (BRB) 之結構與功能 . . . . . . . . . . . . . . . . 7 2.2 超音波與奈米液滴汽化之物理機制 . . . . . . . . . . . . . . . . . . 8 2.2.1 奈米液滴結構與相變理論 . . . . . . . . . . . . . . . . . . . . . . 8 2.2.2 液滴汽化之物理觸發與瞬態機械效應 . . . . . . . . . . . . . . . 8 2.2.3 液滴汽化引發之聲穿孔作用機制 . . . . . . . . . . . . . . . . . . 10 2.3 光纖式光聲雙模態整合裝置原理 . . . . . . . . . . . . . . . . . . . . 11 2.3.1 光聲效應與薄膜材料特性 . . . . . . . . . . . . . . . . . . . . . . 11 2.3.2 雙模態整合原理與現況瓶頸 . . . . . . . . . . . . . . . . . . . . 12 2.3.3 光聲協同激發之微觀時序動力學 . . . . . . . . . . . . . . . . . . 14 2.4 光纖式光聲裝置於眼內藥物遞送之應用潛力 . . . . . . . . . . . . . 16 2.4.1 脈絡膜上腔注射 (SCS) 與眼內遞藥挑戰 . . . . . . . . . . . . . . 16 2.4.2 光纖式光聲裝置於 SCS 之整合應用概念 . . . . . . . . . . . . . 17 2.4.3 小結 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 第三章 研究方法與系統設計 19 3.1 光纖式光聲裝置之製備 . . . . . . . . . . . . . . . . . . . . . . . . . 19 3.2 金奈米液滴製備 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 3.2.1 製備流程 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 3.2.2 金奈米液滴的螢光標記與純化 . . . . . . . . . . . . . . . . . . . 22 3.2.3 液滴粒徑量測 . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 3.3 光纖光聲雙模態系統與量測方法 . . . . . . . . . . . . . . . . . . . . 23 3.3.1 能量來源與光路耦合 . . . . . . . . . . . . . . . . . . . . . . . . 23 3.3.2 光纖式光聲雙模態實驗系統配置 . . . . . . . . . . . . . . . . . . 24 3.3.3 雙模態能量量測 . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 3.4 螢光藥物釋放與離心定量 . . . . . . . . . . . . . . . . . . . . . . . . 27 3.4.1 實驗設置 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 3.4.2 激發與離心定量流程 . . . . . . . . . . . . . . . . . . . . . . . . 28 3.4.3 資料分析 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 3.5 仿體模型與螢光模型藥物通透實驗 . . . . . . . . . . . . . . . . . . 29 3.5.1 仿體製備 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 3.5.2 螢光藥物通透實驗設置與激發分組 . . . . . . . . . . . . . . . . 29 3.5.3 螢光擴散觀測與定量 . . . . . . . . . . . . . . . . . . . . . . . . 30 3.6 活體動物模型與眼部組織安全性評估 . . . . . . . . . . . . . . . . . 31 3.6.1 動物倫理與準備 . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 3.6.2 活體光聲能量激發與參數篩選 . . . . . . . . . . . . . . . . . . . 31 3.6.3 組織收集與病理切片分析 . . . . . . . . . . . . . . . . . . . . . . 32 第四章 實驗結果與討論 33 4.1 光纖式光聲裝置之特性分析 . . . . . . . . . . . . . . . . . . . . . . 33 4.1.1 未塗佈光纖之光耦合效率 . . . . . . . . . . . . . . . . . . . . . . 33 4.1.2 光纖核心直徑對雙模態輸出之影響 . . . . . . . . . . . . . . . . 34 4.1.3 PDMS 交聯度對光聲轉換效率與光學特性之影響 . . . . . . . . . 37 4.1.4 碳材種類與混摻比例對雙模態輸出之影響 . . . . . . . . . . . . 38 4.1.5 最佳化微型光聲裝置之雙模態輸出特性 . . . . . . . . . . . . . . 40 4.2 雙模態激發下之液滴汽化行為 . . . . . . . . . . . . . . . . . . . . . 42 4.2.1 光纖尺寸對汽化穩定性之影響 . . . . . . . . . . . . . . . . . . . 42 4.2.2 材料優化對微型裝置汽化效能之提升 . . . . . . . . . . . . . . . 44 4.3 藥物釋放效率定量 . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 4.3.1 雷射能量強度對螢光釋放之影響 . . . . . . . . . . . . . . . . . . 46 4.3.2 作用時間對藥物釋放之累積效應 . . . . . . . . . . . . . . . . . . 47 4.4 仿體模型藥物通透性驗證 . . . . . . . . . . . . . . . . . . . . . . . . 48 4.4.1 擴散影像之定性觀察 . . . . . . . . . . . . . . . . . . . . . . . . 49 4.4.2 激發能量對擴散面積的增益效果 . . . . . . . . . . . . . . . . . . 50 4.5 活體動物模型與眼部組織安全性評估 . . . . . . . . . . . . . . . . . 52 4.5.1 組織病理學型態觀察 . . . . . . . . . . . . . . . . . . . . . . . . 52 4.5.2 視網膜厚度之描述性量測分析 . . . . . . . . . . . . . . . . . . . 54 第五章 討論 55 5.1 光聲複合薄膜之材料改質與輸出最佳化討論 . . . . . . . . . . . . . 55 5.1.1 奈米碳材微觀結構與光聲轉換效能 . . . . . . . . . . . . . . . . 55 5.1.2 PDMS 配方與幾何結構對光聲性能之影響 . . . . . . . . . . . . . 56 5.2 微型化雙模態裝置之臨床轉化優勢與遞送效能 . . . . . . . . . . . . 58 5.2.1 微創整合與同軸激發之雙重優勢 . . . . . . . . . . . . . . . . . . 58 5.2.2 主動式藥物釋放調控與組織通透增益 . . . . . . . . . . . . . . . 59 5.3 本研究之實驗限制 . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61 5.3.1 活體樣本數與統計推論之侷限 . . . . . . . . . . . . . . . . . . . 61 5.3.2 仿體模型缺乏生理動態機制 . . . . . . . . . . . . . . . . . . . . 61 第六章 結論與未來展望 63 6.1 結論 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 6.2 未來工作與展望 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64 6.2.1 動物實驗與組織安全性之系統性驗證 . . . . . . . . . . . . . . . 64 6.2.2 oBRB 體外細胞模型與離體組織 . . . . . . . . . . . . . . . . . . 64 6.2.3 藥物–液滴結合與水膠緩釋平台之整合開發 . . . . . . . . . . . . 65 參考文獻 67 | - |
| dc.language.iso | zh_TW | - |
| dc.subject | 光聲效應 | - |
| dc.subject | 眼內藥物遞送 | - |
| dc.subject | 金奈米液滴 | - |
| dc.subject | 脈絡膜上腔注射 | - |
| dc.subject | 聲學激發相變液滴汽化 | - |
| dc.subject | 光學激發相變液滴汽化 | - |
| dc.subject | 外層血-視網膜屏障 | - |
| dc.subject | photoacoustic effect | - |
| dc.subject | Intraocular Drug Delivery | - |
| dc.subject | gold nanodroplets | - |
| dc.subject | Suprachoroidal Injection | - |
| dc.subject | Acoustic Droplet Vaporization | - |
| dc.subject | Optical Droplet Vaporization | - |
| dc.subject | Outer Blood-Retinal Barrier | - |
| dc.title | 微型化光纖結合光聲薄膜與奈米液滴汽化應用於眼部藥物遞送之可行性研究 | zh_TW |
| dc.title | Feasibility Study of Ocular Drug Delivery Using Miniaturized Photoacoustic-film-coated Optical Fibers and Nanodroplet Vaporization | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 114-1 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 謝寶育;鄭耿璽;沈哲州 | zh_TW |
| dc.contributor.oralexamcommittee | Bao-Yu Hsieh;Geng-Shi Jeng;Che-Chou Shen | en |
| dc.subject.keyword | 光聲效應,眼內藥物遞送金奈米液滴脈絡膜上腔注射聲學激發相變液滴汽化光學激發相變液滴汽化外層血-視網膜屏障 | zh_TW |
| dc.subject.keyword | photoacoustic effect,Intraocular Drug Deliverygold nanodropletsSuprachoroidal InjectionAcoustic Droplet VaporizationOptical Droplet VaporizationOuter Blood-Retinal Barrier | en |
| dc.relation.page | 77 | - |
| dc.identifier.doi | 10.6342/NTU202600651 | - |
| dc.rights.note | 同意授權(限校園內公開) | - |
| dc.date.accepted | 2026-02-08 | - |
| dc.contributor.author-college | 電機資訊學院 | - |
| dc.contributor.author-dept | 生醫電子與資訊學研究所 | - |
| dc.date.embargo-lift | 2031-02-03 | - |
| 顯示於系所單位： | 生醫電子與資訊學研究所 | |
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| ntu-114-1.pdf 未授權公開取用 | 35.1 MB | Adobe PDF | 檢視/開啟 |
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