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  • 學位論文

一種微流體粒子分析元件的阻抗頻譜發展與應用

The development of a microfluidic particle-analyzing device by impedance spectroscopy

指導教授 : 林致廷

摘要


流式細胞技術於分子生物學、生理學、檢驗技術上皆扮演著舉足輕重的腳色。而其中雷射光學方式利用分析細胞通過反射或折射的螢光,常用來作為精準的單一細胞分析。但此種方式常受限於龐大的儀器體積、專業人才使用等高成本,常僅在醫療或研究機構做準確細胞篩選檢測。因此電阻抗式流式細胞技術因而被提出,用來作為體積小、操作簡易、成本低的可攜式裝置。本研究即延續已初步設計的搭載新型平面式電極的電阻抗式流式細胞技術,加以討論在交流電訊號下不同頻率對其分析不同粒子特性的影響,找出適當的使用頻寬。並且利用一系列實驗來佐證不同頻率下分析的能力。找出頻寬後,透過基板材質與不同電極設計來拓寬此使用頻寬來達到更佳的儀器使用效果。最後使用新型電極設計來進行一系列的實驗,來驗證本研究的元件,具有在高操作頻率下判斷直徑6和10微米的聚苯乙烯粒子、具-COOH基的該粒子、二氧化矽、三聚氰胺、鐵磁粒子、人急性單核性白血病细胞(THP1)等種類的能力。本研究所改良基板與電極的元件,可同時偵測粒子和細胞大小、位置、種類的資訊,來對初步疾病篩檢目的有重要的參考意義。

並列摘要


Flow cytometry takes up an important role in molecular and cellular biology, physiology and diagnosis techniques. One of flow cytometry method, the laser light system, utilizes analysis on reflection and refraction of fluorescent light from a passing cell. It is always implemented as a precise single cell analysis. But this method is always constrained to high cost such as a huge equipment size and professional use. It could be only practiced in medical or research institution for accurate cell sorting and detection. Therefore, impedance flow cytometry is then proposed to be a small, easy and low-cost portable device. This research then follows the preliminarily designed impedance flow cytometry with new coplanar electrode design. It discusses the influence of device impedance spectroscopy on analyzing different particle properties by finding out an adequate operational frequency range. By experiments, its ability will be demonstrated to analyze under multi-frequencies. When finding out the frequency bandwidth, a better sensing performance of the device will be achieved by considering substrate materials and new electrode spatial designs. At last, the new device with a specific electrode design will be verified by a set of experiments. It demonstrates the ability of differentiating 6μm and 10μm plain polystyrene, carboxylated polystyrene, silica, melamine, magnetic beads and THP1 Cell. The proposed device with modified substrate and electrode design could classify bead and cell’s size, position and type, which has imperative meaning for initial disease diagnosis purpose.

參考文獻


Chia-Hong Gao and Chih-Ting Lin, “A microfluidic particle-analyzing device with novel coplanar electrode design based on impedance sensing,” Master Thesis, Graduate Institute of Electronics Engineering, July, 2016.
P. Estrela, S. D. Keighley, P. Li and P. Migliorato, “Application of Thin Film Transistors to Label-Free Electrical Biosensors,” IEEE International Symposium on Industrial Electronics, July, 2008.
T. Rim et al, “Electrical Characteristics of Doped Silicon Nanowire Channel Field-Effect Transistor Biosensors,” IEEE SENSORS JOURNAL, Vol. 17, No. 3, 2017.
R. Adzhri et al, “FET-Based Biosensors with Back-Gate Coupling Towards the Electrical Pre-amplification of Cardiac Troponin I Detection,” IEEE-ICSE 2016, Kuala Lumpur, Malaysia, 2016.
Pei-Wen Yen et al, “LuEmerging Electrical Biosensors for Detecting Pathogens and Antimicrobial Susceptibility Tests,” Current organic chemistry, Vol. 18, p. 165-172, 2014.

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