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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 簡俊超 | zh_TW |
| dc.contributor.advisor | Jun-Chau Chien | en |
| dc.contributor.author | 葉修誠 | zh_TW |
| dc.contributor.author | Hsiu-Cheng Yeh | en |
| dc.date.accessioned | 2024-04-09T16:13:22Z | - |
| dc.date.available | 2024-04-10 | - |
| dc.date.copyright | 2024-04-09 | - |
| dc.date.issued | 2024 | - |
| dc.date.submitted | 2024-03-25 | - |
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Dagenais, "Electroless remetallization of aluminum bond pads on CMOS driver chip for flip-chip attachment to vertical cavity surface emitting lasers (VCSEL''s)," in IEEE Transactions on Components and Packaging Technologies, vol. 22, no. 2, pp. 299-306, June 1999. [15] H. M. Jafari, K. Abdelhalim, L. Soleymani, E. H. Sargent, S. O. Kelley and R. Genov, "Nanostructured CMOS Wireless Ultra-Wideband Label-Free PCR-Free DNA Analysis SoC," in IEEE Journal of Solid-State Circuits, vol. 49, no. 5, pp. 1223-1241, May 2014. [16] S. Hwang, C. N. LaFratta, V. Agarwal, X. Yu, D. R. Walt and S. Sonkusale, "CMOS Microelectrode Array for Electrochemical Lab-on-a-Chip Applications," in IEEE Sensors Journal, vol. 9, no. 6, pp. 609-615, June 2009. [17] A. Manickam, C. A. Johnson, S. Kavusi, and A. Hassibi, "Interface design for CMOS-integrated Electrochemical Impedance Spectroscopy (EIS) biosensors," Sensors, vol. 12, no. 11, pp. 14467-14488, Oct. 2012. [18] M. M. M. Arshad, I. Ahmad, A. Jalar and G. Omar, "The effects of zincation process on aluminum bond pad surfaces for electroless nickel immersion gold (ENIG) deposition," 2004 IEEE International Conference on Semiconductor Electronics, Kuala Lumpur, Malaysia, 2004, pp. 7 pp.-. [19] M. Schienle et al., "A fully electronic DNA sensor with 128 positions and in-pixel A/D conversion," in IEEE Journal of Solid-State Circuits, vol. 39, no. 12, pp. 2438-2445, Dec. 2004. [20] L. Li, X. Liu and A. J. Mason, "Die-level photolithography and etchless parylene packaging processes for on-CMOS electrochemical biosensors," 2012 IEEE International Symposium on Circuits and Systems (ISCAS), Seoul, Korea (South), 2012, pp. 2401-2404. [21] 光輝陳, 小兵李, 海祥賴, 小芳黎, "Study on the step plating of electroless nickel plating on PCB," Printed Circuit Information, no. 28, pp. 30-37, Mar. 2020. [22] J.-C. Chien, A. Ameri, E.-C. Yeh, A. N. Killilea, M. Anwar, and A. M. Niknejad, "A high-throughput flow cytometry-on-a-CMOS platform for single-cell dielectric spectroscopy at microwave frequencies," Lab on a Chip, vol. 18, no. 14, pp. 2065-2076, 2018. [23] C. F. Woolley, M. A. Hayes, P. Mahanti, S. D. Gilman, and T. Taylor, "Theoretical Limitations of Quantification for Noncompetitive Sandwich Immunoassays," Anal. Bioanal. Chem., vol. 407, no. 28, pp. 8605-8615, Nov. 2015. [24] G. Acciaroli, M. Vettoretti, A. Facchinetti, and G. Sparacino, “Calibration of minimally invasive continuous glucose monitoring sensors: State-of-the-art and current perspectives,” MDPI Biosensors, vol. 8, no. 24, pp. 1–17, Mar. 2018. [25] C. F. Woolley, M. A. Hayes, P. Mahanti, S. D. Gilman, and T. Taylor, “Theoretical limitations of quantification for noncompetitive sandwich immunoassays,” Anal. Bioanal. Chem., vol. 407, no. 28, pp. 8605–8615, Sep. 2015. [26] D. A. Armbruster and T. Pry, “Limit of blank, limit of detection and limit of quantitation,” Clin. Biochem. Rev., vol. 29, pp. S49–S52, Aug. 2008. [27] L. R. Schoukroun-Barnes, F. C. Macazo, B. Gutierrez, J. Lottermoser, J. Liu, and R. J. White, “Reagentless, structure-switching, electrochemical aptamer-based sensors,” Annu. Rev. Anal. Chem., vol. 9, no. 1, pp. 163–181, Jun. 2016. [28] F. Ricci et al., “Surface chemistry effects on the performance of an electrochemical DNA sensor,” Bioelectrochemistry, vol. 76, nos. 1–2, pp. 208–213, Mar. 2009. [29] M. Augustyniak et al., “A 24×16 CMOS-based chronocoulometric DNA microarray,” in IEEE Int. Solid-State Circuits Conf. (ISSCC) Dig. Tech. Papers, Feb. 2006, pp. 59–68. [30] A. Agarwal et al., “A 4 μW, ADPLL-based implantable amperometric biosensor in 65 nm CMOS,” in IEEE Symp. VLSI Circuits, Dig. Tech. Paper, Jun. 2017, pp. C108–C109. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/92545 | - |
| dc.description.abstract | 核酸電化學生物感測器利用合成核酸適體檢測目標分子是否存在與其濃度，提供即時檢測，無須額外試劑。本篇論文旨在發展微電極晶片生物感測器，將此核酸電化學反應的優勢進一步擴大，以做到隨身且即時的藥物濃度檢測。論文中提出一種嶄新的方法，使用計時安培法搭配取樣電路在兩個電壓間循環跳動，可以將每次量測所需的時間減少10倍以上，進一步大量減少功耗。除此之外，基於FET電壓緩衝訊號讀出電路的架構，更是可以將輸入參考電流噪聲降低千倍，來應對在晶片微電極上所需要之極大的動態範圍。
本篇論文花費了大量時間使用卡那黴素與氨芐西林適體測試晶片上微電極的抗壓性，使用了電子束蒸鍍金鹽與無電鍍鎳浸金來製造微電極，針對電極的抗腐蝕、導電性、與適體的黏著力還有持久力，做了許多測試，望能找出一個最佳的後製程方法來製造晶片。結果顯示在底材為鋁的電極上進行電化學反應將會遇到極大的困難，難以克服良率與持久性的問題。 在電路上則成功驗證了FET做為電壓緩衝的可行性，在使用三種濃度(0.1 毫莫耳, 1 毫莫耳, 10毫莫耳)的亞甲藍液的測試下，成功觀察到氧化還原反應造成電子動力學的改變，對於下一版本是勢在必行。 | zh_TW |
| dc.description.abstract | The nucleic acid electrochemical biosensor utilizes synthetic nucleic acid aptamers to detect the presence and concentration of target molecules, providing real-time detection without the need for additional reagents. This thesis aims to develop a small on-chip electrode biosensor to further expand the advantages of this nucleic acid electrochemical reaction, achieving portable and real-time drug concentration detection. A novel approach is proposed in this thesis, using chronoamperometry combined with sample and hold circuit to cyclically jump between two voltages, reducing the time required for each measurement by more than tenfold and significantly reducing power consumption. Furthermore, based on the structure of the FET voltage-buffered signal readout circuit, input refer current noise can be reduced by a factor of a thousand to address the substantial dynamic range required for on-chip microelectrodes.
Considerable effort has been devoted to testing the resistance of on-chip electrodes to kanamycin and ampicillin aptamers, using e-beam evaporated gold and electroless nickel immersion gold plating to manufacture the microelectrodes. Various tests have been conducted to assess the electrode''s resistance to corrosion, conductivity, aptamer adhesion, and durability, aiming to identify the optimal post-processing method for chip fabrication. The results indicate significant challenges in conducting electrochemical reactions on electrodes with aluminum substrates, making it difficult to overcome issues related to yield and durability. On the circuit side, the feasibility of using FET as a voltage buffer has been successfully validated. Testing with three concentrations (0.1 mM, 1 mM, 10 mM) of methylene blue solution has successfully observed changes in electron kinetics caused by oxidation-reduction reactions, making it imperative for the next version. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2024-04-09T16:13:22Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2024-04-09T16:13:22Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 口試委員會審定書 i
誌謝 ii 中文摘要 iii ABSTRACT iv CONTENTS v LIST OF FIGURES vii LIST OF TABLES x Chapter 1 Introduction 1 1.1 Aptamer-Based Electrochemical Biosensor 1 1.2 Electroanalytical Chemistry Techniques 2 1.2.1 Cyclic Voltammetry (CV) 2 1.2.2 Square Wave Voltammetry (SWV) 3 1.2.3 Chronoamperometry (CA) 4 1.3 Three-Electrode System vs Two-Electrode System 5 1.4 Sensor Readout Circuit 6 Chapter 2 Electrode preparation 10 2.1 Design of Microelectrode Array 10 2.2 Post-Processing for Improved Electrochemical Sensing & Chip Biocompatibility 11 2.3 Au Deposition By E-beam 13 2.3.1 Electrodes Pre-treatment 15 2.3.2 Spin coater and photoresistor 15 2.3.3 Exposure and Development 20 2.3.4 E-beam Au deposition and Lift-off 21 2.4 ENIG 25 2.5 Preparation Procedures for Chip Measurement 26 Chapter 3 Sensing Mechanism 30 3.1 Fundamentals of Design Approach 30 3.1.1 Measurement Uncertainty 30 3.1.2 Limit of Detection 31 3.1.3 Dissociation Constant (KD) 31 3.2 Signal Analysis and Design Specification 33 3.2.1 Mathematical Simulation of Noise Impact on CA mode 33 3.2.2 Electrode Surface Interactions 34 3.3 Electrochemical-Sensing Interface Circuits 36 3.3.1 Traditional Readout Circuit Analysis 36 3.3.2 Proposed Ultra-Low-Noise FET-Buffered 39 3.3.3 Sample-and-Hold Sensor Architecture 40 3.3.4 Circuit Implementation 42 Chapter 4 Experimental Results and Conclusion 46 4.1.1 Fabrication Challenges and Electrochemical Performance of On-Chip Electrodes 47 4.1.2 Assessing ET Kinetics with Varied Methylene Blue Concentrations by Readout Circuit 52 Chapter 5 Future Works 57 REFERENCE 58 | - |
| dc.language.iso | en | - |
| dc.title | 微電極核酸電晶片生物感測器 | zh_TW |
| dc.title | On-chip Small Electrodes Aptamer-based Biosensor | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 112-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 李尉彰;廖育德 | zh_TW |
| dc.contributor.oralexamcommittee | Wei-Chang Li;Yu-Te Liao | en |
| dc.subject.keyword | 生物感測器,核酸,小電極, | zh_TW |
| dc.subject.keyword | On-chip electrode,Aptamer,Biosensor, | en |
| dc.relation.page | 61 | - |
| dc.identifier.doi | 10.6342/NTU202400806 | - |
| dc.rights.note | 同意授權(限校園內公開) | - |
| dc.date.accepted | 2024-03-26 | - |
| dc.contributor.author-college | 電機資訊學院 | - |
| dc.contributor.author-dept | 電子工程學研究所 | - |
| 顯示於系所單位： | 電子工程學研究所 | |
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