燒結成塊微孔隙過濾元件與真空模組之整合與封裝及其應用於全血血漿分離

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研究生：	王政麟 Wang, Zheng-Lin
論文名稱：	燒結成塊微孔隙過濾元件與真空模組之整合與封裝及其應用於全血血漿分離 Compact and Efficient Sintered Porous Filters Driven with Vacuum Modules for Plasma Separation from Whole Blood
指導教授：	洪健中 Hong, Chien-Chong 劉通敏 Liou, Tong-Miin
口試委員:	張晃猷 Chand, Hwan-You 劉承賢 Liu, Cheng-Hsien
學位類別：	碩士 Master
系所名稱：	工學院 - 動力機械工程學系 Department of Power Mechanical Engineering
論文出版年：	2017
畢業學年度：	105
語文別：	英文
論文頁數：	99
中文關鍵詞：	燒結成塊微孔隙過濾元件、真空模組、形狀記憶高分子、血漿過濾、定點照護
外文關鍵詞：	sintered porous filters, vacuum module, shape memory polymer, plasma separation, point-of-care testing
相關次數：	點閱：2 下載：0
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在醫院進行血液檢測通常需要很長的處理時間、複雜的程序並且須要專業的技術人員，因此無法達成即時且有效的醫療照護。為了避免在生物標記物的檢測過中紅血球的干擾，特別是在光學感測當中，紅血球會從血液中被分離出來以作為血液的分析與診斷。目前大部分的被動式血球微過濾器僅能分離出少量的血漿且須要一定的分離時間，然而對於可整合式的晶片上血球微過濾器仍需要搭配真空吸力來源才能達到定點照護與現場分析之目標。本研究論文提出並製作燒結成塊微孔隙過濾元件以及整合形狀記憶高分子真空模組之生醫晶片，就目前文獻回故而言本研究所提出之長度575 μm燒結成塊微孔隙過濾元件是最短的血球微過濾器結構，其長度僅有目前研究文獻的三分之ㄧ。對於人血全血血漿分離，本研究所提出之晶片設計在人血樣本HCT為33 %的條件下，可達到47.76 %之血漿抽取百分比，此外其晶片設計可在5分鐘內分離出2.81 µL之高純度血漿。本研究開發的晶片設計具有無須外接導管、微量樣本需求、易於使用、易於整合、成本效益高、自動控制以及片上廢品樣品儲存和處置等優點。此研究論文所提出之燒結成塊微孔隙過濾元件與真空模組整合之生醫晶片與傳統檢測儀器相比，具有易於使用、易於整合、成本效益高、高分離效率、高血漿分離量、分離時間快速等優點，未來將可與生醫感測器整合於同一微流道晶片，達到定點照護之目標。

Blood tests taken in hospitals typically need long processing time, complicated procedures, and professional technicians, which cannot provide immediate and effective medical care. To avoid red blood cells (RBCs) interference during biomarkers detection, especially in optical sensing, RBCs are separated from the plasma for blood analysis and diagnosis. Most available on-chip passive plasma separators or filters only output low plasma volume with long separation time. On-chip plasma filters remain to be improved by adding a vacuum source for realizing lab-on-a-chip devices in point-of-care testing or on-site analysis. For this study, we designed, fabricated, and characterized on-chip sintered porous filters with a shape-memory-polymer vacuum module for blood/plasma separation. To author’s knowledge, the proposed 575 μm-length filters are the shortest, about one third of those reported in literatures. For human whole-blood separation, extraction efficiency of 47.76 % was achieved with a hematocrit (HCT) of 33 %. Moreover, the separated plasma volume reached up to 2.81 μL within 5 mins. Compared with the traditional detection instrument, the proposed on-chip sintered porous filters integrated with vacuum modules have the advantages of ease of use, ease of integration, cost effectiveness, high efficiency and large volume of plasma separation, on-chip waste sample storage and disposal, and fast driving time.

Chapter 1 Introduction    1
1    Point-of-care Testing (POCT)    1
2    Blood Analysis for Clinical Diagnostics    5
3    Plasma Separation    5
3.1    Traditional Plasma Separation Methods    7
3.2    Off-Chip Plasma Separators    7
3.3    On-Chip Plasma Separator    12
3.3.1    Passive Plasma Separators    13
3.3.2    Vacuum-Powered Plasma Separators    18
4    Porous Microstructures    25
5    Research Motivation    26
6    Research Objective    26
7    Thesis Outlines    27
Chapter 2 Design and Materials    29
1    Lab-on-a-Chip Design    29
1.1    On-Chip Sintered Porous Filters for Plasma Separation    32
1.1.1    Material Selection    32
1.1.2    Material Characterization    33
1.1.3    Mold Design for Precise Assembly of Beads    34
1.2    Shape-Memory-Polymer Vacuum Modules    34
2    Analytical Model for Plasma Separation    36
3    Summary    41
Chapter 3 Fabrication and Integration    42
1    Lab-on-a-Chip Fabrication Process    42
1.1    On-Chip Sintered Porous Filters    42
1.1.1    Evaporative Assembly of Beads    45
1.1.2    Analysis of Pore Size between Beads    47
1.1.3    Variation Analysis    48
1.2    Shape-Memory-Polymer Vacuum Modules    49
2    Integration of Sintered-Polymer Filters with Vacuum Modules on a chip    56
3    Summary    58
Chapter 4 Experimental Results    59
1.    Experimental Setup    59
2.    Experimental Plans for Clinical Trials    60
3.    Plasma Separation from whole blood samples    61
3.1    Commercial Plasma Separators    61
3.2    Passive Plasma Separators    63
3.3    Isolated-Beads Plasma Separators with Vacuum Modules    64
3.4    Isolated-Beads Reinforced by Multiple Branch Microstructures    65
3.5    Plasma Separation Using the Developed Vacuum-Powered Sintered Porous Filters    69
4.    Comparisons    75
5.    Discussion    75
6.    Summary    77
Chapter 5 Conclusions    78
1    Main Results    78
2    Research Contributions    80
3    Suggestions for Future Work    84
Appendix    …………………………………………………………………………..86
Reference    …………………………………………………………………………..92
Profile of the Author    98

                                

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