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研究生:陳燦議
研究生(外文):Tsan-I Chen
論文名稱:多頻率結構輔助式介電泳細胞分離裝置
論文名稱(外文):A Dielectrophoresis Cell Separation Device Using Multiple Frequencies and Micro-structures
指導教授:劉承賢劉承賢引用關係
指導教授(外文):Cheng-Hesien Liu
學位類別:碩士
校院名稱:國立清華大學
系所名稱:動力機械工程學系
學門:工程學門
學類:機械工程學類
論文種類:學術論文
論文出版年:2004
畢業學年度:92
語文別:英文
論文頁數:57
中文關鍵詞:細胞分離細胞分類介電泳微機電系統
外文關鍵詞:cell separationcell sortingdielectrophoresisMEMS
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微機電系統(MEMS)發展至今已逾二十餘年,近年來由於生物科技發展迅速,微機電於生醫領域亦有廣大的應用面。目前發展的生醫微晶片包括細胞分離晶片(Cell Sorting\Separation Chip)、細胞裂解晶片(Cell Lysis Chip)、聚合脢鏈鎖反應晶片(PCR Chip)、去氧核醣核酸檢測晶片(DNA Detection Chip)等。此類晶片可經由製程整合後成一實驗室晶片(Lab-On-a-Chip)以作為全功能的疾病檢測分析晶片。本研究主要針對細胞分離部分設計一新型晶片以取代傳統分離方式。過去已有不少利用微機電技術分離細胞的文獻發表,包括微過濾器(Micro Filter)、微水力開關(Hydraulic Switch)、介電泳等。其中微過濾器有細胞阻塞的顧慮,而微水力開關則需要外加即時偵測裝置,而以介電泳方式來分離對細胞的選擇性為最佳,然而受限於單一頻率的訊號供給,以致於無法同時分離多種細胞。本文首先提出多頻率介電泳的概念,配合結構的設計,同時施加多種頻率的訊號於晶片上,期望能分離多種細胞。
本論文從細胞分離晶片的文獻回顧談起,經過設計理論分析來評估構想的可行性並訂定設計規範,佐以數值模擬軟體驗證後,將整體概念以微機電製程實現,另外,設計電路作為晶片的驅動訊號控制器並完成測試。最後利用聚苯乙烯(Polystyrene)與玻璃微粒子模擬細胞完成初步的實驗結果。
MEMS (Micro Electro Mechanical Systems) have been developed over twenty years. Because of the rapid development of biological technology, there are a lot of applications for MEMS in bio-medical field. The bio-chips developed nowadays include cell sorting\separation chip, cell lysis chip, PCR (Polymer Chain Reaction) chip, DNA detection chip etc. These chips could be integrated into a Lab-On-a-Chip system for full functional disease detection and analysis. This thesis focuses on cell sorting\separation and the design of a new chip in substitution for traditional cell separation process. There are a few MEMS cell separation measurements have been presented, including micro filter, micro hydraulic switch and dielectrophoresis. Therefore, the micro filter has stuffing problem while the hydraulic switch requires extra external real-time detection. Dielectrophoresis has been known as a powerful tool for cell separation because of its good cell selectivity. Presently, the published dielectrophoretic cell sorting methods are limited to separate no more than three cell types due to the single frequency signal. We firstly proposed the concept of multi-frequency dielectrophoresis. With special structure design, we can separate multiple cell types by applying multiple frequencies simultaneously.
The thesis starts with the survey of literatures, via theoretical analysis to evaluate the feasibility of design concept and to define the design regulations. Through numerical analysis, the design concepts are verified and realized by MEMS fabrication process. Furthermore, a driving signal generator is also designed and tested. Finally, we use polystyrene beads and glass beads to simulate cells to complete the preliminary experimental results.
1. Introduction-----1
1.1 Background and Motivation
1.2 Survey of Literature
1.2.1 Structural Filtration
1.2.2 Hydraulic Separation
1.2.3 Gravity-Driven Separation
1.2.4 Dielectrophoretic Separation
2. Theoretical Analysis and Design Concept-----10
2.1 Domain Knowledge - Dielectrophoresis
2.2 Design Concept
3. Simulation and Analysis-----18
3.1 Simulation with ANSYS
3.1.1 Derivations from ANSYS
3.2 CFDRC Simulation
4. Fabrication-----33
4.1 Fabrication Process
4.2 Microfabrication Results
5. Driving Circuit Design-----41
5.1 Circuit Layout
5.2 Waveform Testing
6. Experimental Results-----46
6.1 Experimental Setup
6.2 Preliminary Testing
6.3 Device Testing
7. Conclusion-----56
7.1 Summary
7.2 Future Work
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