阻抗及壓電感測技術於生物醫學上之應用發展

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陳靖容(Ching-Jung Chen) 查詢紙本館藏

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論文名稱

阻抗及壓電感測技術於生物醫學上之應用發展
(Development of impedimetric and piezoelectric sensing technology for biomedical applications)

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摘要(中)

由於老齡化社會趨勢的增加，於自我照護的階段需要有一個工具，可以快速、方便、準確地檢測出疾病的症狀。而生物傳感器即可做為低成本、高效率的檢測裝置應用在我們的日常生活中。本研究將進一步的利用材料科學，化學科學和電子科學，對於阻抗式及壓電式感測技術進行研究及討論。論文中針對不同換能器的研究，以辨識層，換能器和感測電路三個部分來共同建構生物感測系統。其中根據不同的檢測標的，利用一般表面化學處理程序，將專一性的辨識層有效建構在感測器表面。並因為感測器與辨識層的結合，已成功得到阻抗式感測器對於去氧核糖核酸，蛋白質和動物細胞進行感測及應用。其各感測標的物是透過辨識層的專一性捕捉，及換能器的電子信號轉換而完成特定的感測分析。而另一個部分是利用鋯鈦酸鉛壓電元件，做為新型微重量感測器的研究，主要藉由共振頻率的變化來對於生物分子的重量、大小進行感測。這兩種(阻抗式和壓電式)傳感器的研究在本論文中，皆展現出以微製程技術製備感測晶片，以及訊號讀取電路的系統整合。隨後，本論文也對於感測器實際應用上的考量要素，以不同實驗案例，對於阻抗式及壓電式生物感測器在生物醫學及商品化進行評估及討論。

摘要(英)

As the potential threat of an aging society increases, there is great need for a tool that can quickly, conveniently, and accurately detect the symptom of any disease at the self-care stage. Biosensors can essentially serve as a low-cost and highly efficient device for this purpose in addition to other day-to-day applications. This study discusses advances in impedimetric and piezoelectric sensor technology, which draw on the disciplines of materials, chemistry, and electronics. This study shows that a biosensor with a difference transducer consists of three components, a reorganization layer, a transducer, and an output circuit system. According to different detection targets, the reorganization layer of this study follows common immobilization procedures for efficacious attachment on the transducer surface. Based on different immobilization procedures, this study successfully uses the impedance sensor applied in DNA, protein, and animal cells. Then, a “specific reorganization layer” recognizes a specific analyte to show that the electrical signal utilizes a converted impedance sensor. The other part of the study develops a lead zironate titanate (PZT) chip as a novel sensitive gravimetric biosensor by reducing size and using the resonance feature in biomolecule detection. Two types of transducers in this article, impedimetric and piezoelectric, provide the microfabrication technique of sensing chip and readout circuit formation. Subsequently this article discusses a few practical factors in several experiments as different case studies affecting biomedical application and commercialization of impedimetric and piezoelectric biosensors.

關鍵字(中)

★ 細胞
★ 蛋白質
★ 去氧核糖核酸
★ 生物感測器
★ 阻抗
★ 壓電

關鍵字(英)

★ protein
★ DNA
★ biosensors
★ impedimetric
★ cells
★ piezoelectric

論文目次

Content
中文摘要………………………………………………………………II
Abstract………………………………………………………………III
Content ………………………………………………………………Ⅴ
List of Tables……………………………………………………VIII
List of Figures………………………………………………………IX
Chapter 1 Overview of Biosensor…………………………………1
1.1 Introduction………………………………………………1
1.2 The performance factors of biosensor………………6
1.3 The consideration of biosensor development………7
1.4 Current status of biosensor…………………………9
1.5 Summary……………………………………………………12
Chapter 2
A new PZT piezoelectric sensor for gravimetric applications using the resonance-frequency detection……………………………………………………………14
2.1 Abstract……………………………………………………14
2.2 Introduction………………………………………………15
2.3 Research Methodology………………………………………18
2.3.1 Preparation of Piezoelectric Chip…………………18
2.3.2 Characterization of Piezoelectric Layers…………20
2.3.3 Detection System Fabrication…………………………21
2.4 Results and discussion…………………………………22
2.4.1 Properties of PZT Thin Film …………………………22
2.4.2 Leakage Current Analysis………………………………25
2.4.3 Ferroelectric Hysteresis Properties………………25
2.4.4 Detection System Characterization…………………26
2.5 Summary……………………………………………………31
Chapter 3
Development of a capacitance measurement system for human serum albumin detection……………………………………………33
3.1 Abstract……………………………………………………33
3.2 Introduction………………………………………………34
3.3 The capacitance measurement system fabrication ……………………………………………………35
3.3.1 Micro fabrication of interdigitated chip…………35
3.3.2 SAMs formation and chip preparation………………36
3.3.3 Impedance measurements and Capacitive HSA detection system measurements……………………………………37
3.4 Results and discussion…………………………………38
3.5 Summary……………………………………………………44
Chapter 4
Impedance-based analysis of mouse L929 cells growth was using a novel portable detection system………………………46
4.1 Abstract……………………………………………………46
4.2 Introduction………………………………………………47
4.3 Research Methodology……………………………………49
4.3.1 Chemicals and Materials………………………………49
4.3.2 Cell culture………………………………………………50
4.3.3 Interdigitating microelectrodes fabrication……50
4.3.4 Cells impedace measurement……………………………51
4.3.5 Protable impedance measurement system……………52
4.4 Results and discussion…………………………………53
4.4.1 Physical properties of the biosensor………………53
4.4.2 Equivalent circuit analysis…………………………55
4.4.3 Impedance measurement…………………………………59
4.5 Summary……………………………………………………63
Chapter 5
A capacitance sensor system for oligonucleotide hybridization detection……………………………………………64
5.1 Abstract……………………………………………………64
5.2 Introduction………………………………………………65
5.3 Research Methodology……………………………………67
5.3.1 Preparation of interdigitated chip…………………67
5.3.2 Surface modification……………………………………68
5.3.3 Detection system fabrication…………………………70
5.4 Results and Discussion…………………………………71
5.4.1 Physical properties of the chip……………………71
5.4.2 Surface modification for oligonucleotide detecting ………………………………………………………………72
5.4.3 Automatic capacitance detection system……………75
5.5 Summary……………………………………………………78
Chapter 6 Conclusion and future work…………………………79
6.1 Conclusio…………………………………………………………79
6.2 Future work………………………………………………………82
Reference 84
List of Tables
Table.1-1 Possible bioreceptor molecules and their requirements for structural integrity and signals generated.………………………………………………………………3
Table.2-1 Comparison of sensitivity characteristics of gravimetric sensors…………………………………………………32
Table.3-1 Comparison of detection characteristics of different assay method……………………………………………45
Table.4-1 Result of fitting parameter values in the equivalent circuit for different culture times with an initial cell density of 5 × 104 cells/ml (N≧3)……………57
List of Figures
Fig.1- 1 Biosensor configuration………………………………1
Fig.1- 2 Various biosensor configurations.…………………8
Fig.2- 1 The structure of the PZT piezoelectric sensor (a) the top view of the PZT resonator (b) the cross section of the metal/ferroelectric/metal (MFM) arrangement ………………………………………………………………20
Fig.2- 2 The detection system of experimentation…………22
Fig.2- 3 SEM images of (a) grainy morphology (b) the cross-section of the PZT layer…………………………………24
Fig.2- 4 XRD pattern of PZT (52/48) films are shown……24
Fig.2- 5 Polarization electric (P-E) field hysteresis loop of the PZT chip.………………………………………………26
Fig.2- 6 The PZT resonator frequency characteristic.……29
Fig.2- 7 Schematic diagram of the resonance-frequency detection circuit.…………………………………………………29
Fig.2- 8 Characteristic of the resonance frequency variation from the detection system (a) the hardware of the measurement system (b) the signal was connected to the monitor.………………………………………………………………30
Fig.2- 9 Frequency shift versus of BSA load for piezoelectric sensor…………………………………………………………………31
Fig.3- 1 Schematic procedure of the SAMs for HSA immobilization.………………………………………………………36
Fig.3- 2 A block diagram of the capacitance detection system.…………………………………………………………………38
Fig.3- 3 The Bode plot before and after HSA immobilization.………………………………………………………41
Fig.3- 4 Equivalent circuit model for HSA detection on the chip surface.……………………………………………………41
Fig.3- 5 The capacitance detection system and hardware. ………………………………………………………………42
Fig.3- 6 Impedance changes in HSA detection for different concentrations and times.…………………………………………42
Fig.3- 7 The linear correlation between impedance changes and HSA detection at 5 min with the capacitance detection system.…………………………………………………………………43
Fig.4- 1 Fabrication process of the interdigitating microelectrodes………………………………………………………51
Fig.4- 2 Block diagram of impedance detection system……53
Fig.4- 3 Analysis of the physical properties of the interdigitating electrodes (a) Optical microscopy image of interdigitating chip surface. (b) Capacitance of interdigitating electrodes in air at 500 Hz to 1 MHz.……55
Fig.4- 4 Equivalent circuit model for cell adhesion on the electrode surface.……………………………………………56
Fig.4- 5 Optical microscopy graph of L929 cell growth on the electrode surface at different culture times (initial density: 5 × 104 cells/ml).………………………………………59
Fig.4- 6 Impedance measurement by the detection system (a) The hardware of the measurement system and (b) impedance signal displayed on the monitor.………………60
Fig.4- 7 Change in impedance recorded by the different devices at different cell culture times up to 48 h.………62
Fig.5- 1 A cross- sectional diagram of the interdigitated sensing chip.…………………………………………………………68
Fig.5- 2 Bomolecular structure of hybridized DNA on the silicon chip…………………………………………………………70
Fig.5- 3 A block diagram of the capacitance detection system.…………………………………………………………………71
Fig.5- 4 An interdigitated sensing unit of the array chip. The inset is a sensor array bonded on a PCB board. ………………………………………………………………72
Fig.5- 5 AFM images of the interelectrode area. (a) is the hybridization surface, and (b) is the nonhybridization surface.…………………………………………74
Fig.5- 6 Capacitance measurement using the detection system: (a) hardware of the measurement system, and (b) capacitance signal displayed on the monitor.………………76
Fig.5- 7 Measured capacitances of the interdigitated electrode array for DNA (a) hybridization and (b) nonhybridization monitoring.……………………………………77

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指導教授

辛裕明、蔡章仁(Jang-Zern Tsai)

審核日期

2010-8-19

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