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研究生: 劉佳峯
Liu, Chia-Feng
論文名稱: 基於微流體技術之微波髮夾型諧振器生物感測器於細胞檢測與分析
Microfluidics-Based Microwave Hairpin Resonator Biosensor for Biological Cell Detection and Analysis
指導教授: 張凌昇
Jang, Ling-Sheng
學位類別: 博士
Doctor
系所名稱: 電機資訊學院 - 電機工程學系
Department of Electrical Engineering
論文出版年: 2018
畢業學年度: 106
語文別: 英文
論文頁數: 55
中文關鍵詞: 髮夾型諧振器生物感測器微流體微機電系統SU-8生物細胞
外文關鍵詞: Hairpin resonator, Biosensor, Microfluidic, Micro-electro-mechanical-system (MEMS), SU-8, Biological cell
相關次數: 點閱:166下載:4
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  • 細胞阻抗分析已經是被深入研究的主題之一。藉由分析電阻抗,可觀察到細胞的生理狀態。然而,若是測量大量細胞再取其平均值,則數值會受各個細胞的變異所影響,而且也無法量化各個細胞的變異情形。因此,若要精確得知細胞參數,則必須在少量的細胞下操作。
    本論文以結合微流體技術的髮夾型微波諧振器做為生物感測器,用以感測生物細胞。以諧振器為基底的生物感測器,可將細胞捕捉結構規劃在兩諧振器相互耦合的區域。細胞的出現,直接改變了諧振器的耦合特性。藉由分析細胞和諧振器的干擾現象,來取得細胞的介電特性。再則,在微波的頻段,訊號可穿過細胞,不會有低頻時的電雙層效應,而可獲得更準確的細胞資訊。
    此生物感測器包含由聚二甲基矽氧烷(PDMS)和負光阻(SU-8)建構的微流道裝置和細胞捕捉結構。此微流道和細胞捕捉結構使用微機電系統(MEMS)技術來製作,用以協助測量液體介質中的生物細胞。此SU-8層僅需使用一道製程,即可同時扮演多重角色:建構細胞捕捉結構、定義銅電鍍之區域、與PDMS上板結合,形成封閉的微流道。此生物感測器之電極由高Q值諧振器組成,透過觀察2.17 GHz諧振頻率下的散射參數(S參數)來檢測生物細胞。藉由測量小鼠黑色素腫瘤細胞(B16F10)及其培養液(DMEM),觀察到細胞數量和S11響應的線性關係。接著使用諧振器之電容耦合等效電路模型來分析細胞及培養液,成功算出小鼠黑色素腫瘤細胞的介電常數為35.6。這些結果證明了髮夾型微波諧振器應用於分析生物細胞的潛力。

    Cell impedance analysis is one of theme and has been researched in depth. Impedance studies can indicate the pathological status of cells. However, parameters of cells based on average of large populations may be misleading by cellular heterogeneity. In order to get parameters of cells precisely, the technology of small amount of cells analysis was developed.
    In this work, a microwave hairpin resonator fabricated and integrated with microfluidics was used for the detection of biological cells. The resonant-based biosensors primarily determine the dielectric properties of cells based on the electromagnetic interaction between the resonator and the cells being tested. At microwave frequencies, the ability of the electromagnetic waves to penetrate into cells, contrary to low-frequency situations where the bi-lipidic membrane screens the fields, ensures access to rich information on cells.
    The biosensor was a microfluidic device constructed from polydimethylsiloxane (PDMS) and negative photoresist (SU-8) using micro-electro-mechanical-system (MEMS) technology to measure and characterize biological cells in a liquid medium. By using only one step of the SU-8 process, the SU-8 layer plays multiple roles: forming the cell trapping structures, defining the patterns for electroplating, and bonding with the PDMS cover plate. A biosensor with a high-Q dielectric resonator allowed the detection of biological cells by measuring the scattering parameter (S-parameter) responses at a resonant frequency of 2.17 GHz. Measurements and analyses of Dulbecco’s modified Eagle’s medium (DMEM) and B16F10 melanoma cells (mus musculus skin melanoma) were then performed to obtain the linear relationship between S11 responses and the number of cells. A model of coupled resonators in terms of capacitances was then used to analyze the effects of DMEM and the cells. Then, the relative dielectric constant of the B16F10 melanoma cell was found to be 35.6. The results demonstrate the potential of hairpin resonator sensors for the analysis of biological cells.

    中文摘要 ................................................I Abstract .............................................III ACKNOWLEDGEMENT ........................................V CONTENTS ............................................VIII LIST OF TABLES .........................................X LIST OF FIGURES .......................................XI CHAPTER 1 INTRODUCTION ................................1 1.1 Background and motivation ..........................1 1.2 Introduction to electrical biosensing methods ......2 1.3 Microwave biosensing ...............................3 1.4 Resonator-based biosensing .........................4 1.5 Microelectromechanical systems .....................5 1.6 Microwave hairpin filter for liquid detection ......6 1.7 Organization of the dissertation ..................11 CHAPTER 2 DESIGN AND METHOD ..........................12 2.1 Design basis ......................................12 2.1.1 Half-wavelength stepped impedance resonator (SIR)12 2.1.2 Hairpin resonators with internal coupled lines ..14 2.2 Simulation ........................................16 2.3 Modeling ..........................................19 CHAPTER 3 FABRICATION ................................21 3.1 Fabrication process ...............................21 3.2 Microchannel and cell trapping structures .........25 3.3 Electroforming ....................................26 CHAPTER 4 EXPERIMENTAL METHOD ........................31 4.1 Calibration .......................................31 4.2 Preparation of DMEM and B16F10 melanoma cells .....32 CHAPTER 5 RESULTS AND DISCUSSION .....................33 5.1 Analysis with S-parameters ........................33 5.2 Measurement results of B16F10 melanoma cells ......35 5.3 Characteristics of B16F10 melanoma cells ..........44 CHAPTER 6 CONCLUSIONS ................................46 REFERENCES ............................................48

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