植入式生物傳感器(包括人工耳蝸、心臟起搏器…等等)對生物本體來說屬於外來物質，而植入過程與植入後無法避免一些併發症的產生(例如腫瘤形成、感染等等病症)以及植入式材料與宿主間相互作用(蛋白質的貼附、急性/慢性炎症反應、異物反應與纖維化組織包覆)，進而影響了植入物元件的功用及效能。本實驗以超奈米鑽石薄膜(UNCD)作為植入式微晶片的披覆層以改善/降低植入式材料與宿主間相互作用。我們以Si晶元模擬微晶片基板，經5 % HF前處理以及利用超聲波振盪方式在Si微晶片表面製造刮痕以利鑽石晶種的孕核，利用微波電漿增強化學氣相沉積法 ( Micro Plasma Enhanced Chemical Vapor Deposition ( MPECVD ) ) 方式在( 1 % H2 ) : Ar/CH4環境下成長UNCD薄膜，在電化學表現方面以循環伏安法( CV )給予低電壓( -1至0.5 V )與高電壓( -5至5 V)檢測披覆UNCD薄膜的Si微晶片的漏電流，可得到低的漏電流值1.56x10-6 A/cm2及5.27x10-5 A/cm2並針對不同厚度的UNCD鑽石薄膜與漏電流值的關係,發現隨著UNCD薄膜厚度從0.317 μm增加至1.53 μm ，其漏電流值會遞減，分別從1.56x10-6 A/cm2降至8.07x10-7 A/cm2 及5.27x10-5降至2.31x10-5 A/cm2，此外還探討材料的特性影響了炎症反應或纖維化組織厚度的影響，因此我們以不同材料(Ti、Si、H/O-UNCD、H/O-Graphite及臨床使用的Ti-6Al-4V)植入在5-7周大BALB/cByJNarl小白鼠皮下植入1、3、6個月，觀察植入所引發的纖維化組織厚度，並比較了碳材料表面形貌、親/疏水性對纖維蛋白原( Fibrinogen )的吸附、單核細胞趨化蛋白( Monocyte Chemoattractant Protein-1 ( MCP-1) ) 、腫瘤壞死因子-α ( Tumor necrosis factor - alpha ( TNF-α ) )、免疫淋巴細胞分泌的 ( Interleukin – 4 ( IL-4) 與引發的纖維化組織厚度，統計結果得知材料表面越平坦，表面積越小，材料表面水的吸附能越低，Fibrinogen吸附的量越少，同時也能抑制急性炎症反應中MPC-1與TNF-α，因此在短期( 1 M )與長期( 3 M )免疫反應會形成較薄的纖維化組織厚度，而對於MCP-1越少而言，能抑制TNF-α的量，進而在長期免疫反應中會形成較厚的纖維化組織厚度。

Implantable biosensors (including cochlear implants, pacemakers ... etc.) are belongs to foreign substances to human bodies, so it cannot avoid some of the complications with the implant during or after implantation process (such as a tumor, infection, etc. illness). The immune reactions beween inter-implantable materials and host (protein attachment, acute/chronic inflammatory reaction, foreign body reaction and fibrosis coated), always affects the function of the implant components and performance. In this study, using ultra-nanocrystalline diamond thin film (UNCD) as implantable microchip encasulation layer to improve / reduce the interactions betwwen inter-implanted material and host tissue. Using microwave plasma enhanced chemical vapor deposition (MPECVD) under Ar-rich (99%)/CH4 (1%) plasma to grow double-sdied coated UNCD film on 5% HF pretreated Si microchips. The electrochemical performance with cyclic voltammetry (CV) by applying low-voltage (-1 to 0.5 V) and high voltage (-5 to 5 V) to detecte leakage current density of Si microchips coated with UNCD films. With the increasing of UNCD film thickness increases from 0.317 μm to 1.53 μm, which the leakage current value is decremented, that reduced from 1.56x10-6 A / cm2 to 8.07x10-7 A / cm2 at -1V and 5.27x10-5 to 2.31x10-5 A / cm2 at 5V. Then, we also investigate the influence of the inflammatory response or fibrotic tissue thickness with the properties of material, so we use different materials (Ti, Si, H / O-UNCD, H / O-Graphite and clinical use of Ti-6Al-4V) to implant subcutaneously into the 5-7-week-old BALB/cByJNarl mice for 1,3 and 6 months to observe thickness of fibrotic tissue formation. In comaprision with surface morphology and wettability of materials, absorbed proteins observed on materials, and monocyte chemoattractant protein (Monocyte Chemoattractant Protein-1 (MCP-1)), tumor necrosis factor -α (Tumor necrosis factor - alpha (TNF-α)) and Interleukin-4 (IL-4) secreted by immune cells, and fibrotic tissue thickness induced by different materails, statistical results show that the smmother surface, the smaller surface area. Less water wettability results less absorbed fibrinogen adsorption, which further not only decreased the acute inflammatory response in MCP-1 and TNF-α, but also caused thinner fibrous tissue.

摘要 1
ABSTRATE 3
表目錄 9
第一章、緒論 10
1-1 植入式傳感器 10
1-1-1 植入式傳感器的應用 10
1-2 異物反應 (Foreign body response) 15
1-2-1傷口-植入物表面相互作用 16
1-2-2急性炎症反應(Acute inflammation) 19
1-2-3 慢性炎症( Chronic inflammation ) 20
1-2-4巨噬細胞/異物巨細胞 ( Macrophage/FBGC) 22
1-2-5纖維化/纖維包覆 (Fibrosis/Fibrous Encapsulation) 23
1-3克服目前植入式瓶頸 25
1-4鑽石薄膜特性&應用 29
第二章、材料與實驗方法 32
2-1實驗目的與設計 32
2-2 Si微晶片前處理 34
2-3鑽石薄膜成核成長 35
2-4 材料特性鑑定 36
材料生物相容性探討 39
第三章、結果與討論 41
披覆UNCD的Si微晶片包覆性、穩定性及生物相容性的探討 41
3-1 Si微晶片前處理對披覆UNCD的Si微晶片漏電流的影響 41
3-2披覆不同UNCD薄膜厚度的Si微晶片對漏電流與纖維化組織厚度的影響 42
3-3 UNCD薄膜厚度對纖維化組織的影響與植入後薄膜穩定性的探討 45
3-4 碳材料表面親/疏水性與表面形貌對炎症反應及纖維化組織的影響 49
3-5 材料特性、炎症反應、纖維化組織厚度相互關係 57
第4章、討論 60
4-1 Si 微晶片表面前處理對披覆UNCD的Si微晶片漏電流的影響 60
4-2披覆不同厚度UNCD薄膜對纖維化組織與植入穩定性的探討 60
4-3 碳材料表面親/疏水性與表面形貌對炎症反應及纖維化組織厚度的影響 61
第五章 結論 63
補充 64

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