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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 王安邦(An-Bang Wang) | |
dc.contributor.author | Po-Hsuan Fang | en |
dc.contributor.author | 方柏璇 | zh_TW |
dc.date.accessioned | 2021-06-15T06:08:25Z | - |
dc.date.available | 2016-08-26 | |
dc.date.copyright | 2011-08-26 | |
dc.date.issued | 2011 | |
dc.date.submitted | 2011-08-18 | |
dc.identifier.citation | [1] 台灣腎臟醫學會, 2010, 慢性腎臟病防治手冊, 行政院衛生署國民健康局.
[2] http://en.wikipedia.org [3] http://www.creatinemonohydrate.net/, http://www.creatinemonohydrate.net/. [4] Pugia, M. J., Lott, J. A., Wallace, J. F., Cast, T. K., and Bierbaum, L. D., 2000, 'Assay of creatinine using the peroxidase activity of copper-creatinine complexes,' Clin Biochem, 33(1), pp. 63-70. [5] Zuo, Y. G., Wang, C. J., Zhou, J. P., Sachdeva, A., and Ruelos, V. C., 2008, 'Simultaneous Determination of Creatinine and Uric Acid in Human Urine by High-Performance Liquid Chromatography,' Anal Sci, 24(12), pp. 1589-1592. [6] Carling, R. S., Hogg, S. L., Wood, T. C., and Calvin, J., 2008, 'Simultaneous determination of guanidinoacetate, creatine and creatinine in urine and plasma by un-derivatized liquid chromatography-tandem mass spectrometry,' Ann Clin Biochem, 45, pp. 575-584. [7] Rodriguez, J., Berzas, J. J., Castaneda, G., Mora, N., and Rodriguez, M. J., 2004, 'Very fast and direct capillary zone electrophoresis method for the determination of creatinine and creatine in human urine,' Anal Chim Acta, 521(1), pp. 53-59. [8] Fung, K. K., Chan, C. P. Y., and Renneberg, R., 2009, 'Development of a creatinine enzyme-based bar-code-style lateral-flow assay,' Anal Bioanal Chem, 393(4), pp. 1281-1287. [9] Kroll, M. H., Roach, N. A., Poe, B., and Elin, R. J., 1987, 'Mechanism of Interference with the Jaffe Reaction for Creatinine,' Clin Chem, 33(7), pp. 1129-1132. [10] Schulte, T. H., Bardell, R. L., and Weigl, B. H., 2002, 'Microfluidic technologies in clinical diagnostics,' Clin Chim Acta, 321(1-2), pp. 1-10. [11] Ko, S., Kim, B., Jo, S. S., Oh, S. Y., and Park, J. K., 2007, 'Electrochemical detection of cardiac troponin I using a microchip with the surface-functionalized poly(dimethylsiloxane) channel,' Biosens Bioelectron, 23(1), pp. 51-59. [12] Du, Z., Colls, N., Cheng, K. H., Vaughn, M. W., and Gollahon, L., 2006, 'Microfluidic-based diagnostics for cervical cancer cells,' Biosens Bioelectron, 21(10), pp. 1991-1995. [13] Kwon, K. W., Choi, S. S., Lee, S. H., Kim, B., Lee, S. N., Park, M. C., Kim, P., Hwang, S. Y., and Suh, K. Y., 2007, 'Label-free, microfluidic separation and enrichment of human breast cancer cells by adhesion difference{,' Lab Chip, 7(11), pp. 1461-1468. [14] Grabowska, I., Chudy, M., Dybko, A., and Brzozka, Z., 2005, 'Determination of creatinine in clinical samples based on flow-through microsystem,' Anal Chim Acta, 540(1), pp. 181-185. [15] Laiwattanapaisal, W., Songjaroen, T., Maturos, T., Sappat, A., and Tuantranont, A., 2009, 'Portable microfluidic system for determination of urinary creatinine,' Anal Chim Acta, 647(1), pp. 78-83. [16] Songjaroen, T., Maturos, T., Sappat, A., Tuantranont, A., and Laiwattanapaisal, W., 2009, 'Portable microfluidic system for determination of urinary creatinine,' Anal Chim Acta, 647(1), pp. 78-83. [17] Do, J., Lee, S., Han, J. Y., Kai, J. H., Hong, C. C., Gao, C. A., Nevin, J. H., Beaucage, G., and Ahn, C. H., 2008, 'Development of functional lab-on-a-chip on polymer for point-of-care testing of metabolic parameters,' Lab Chip, 8(12), pp. 2113-2120. [18] Singh, A. K., Hatch, A. V., Herr, A. E., Throckmorton, D. J., and Brennan, J. S., 2006, 'Integrated preconcentration SDS-PAGE of proteins in microchips using photopatterned cross-linked polyacrylamide gels,' Anal Chem, 78(14), pp. 4976-4984. [19] Singh, A. K., Meagher, R. J., Hatch, A. V., and Renzi, R. F., 2008, 'An integrated microfluidic platform for sensitive and rapid detection of biological toxins,' Lab Chip, 8(12), pp. 2046-2053. [20] McDevitt, J. T., Christodoulides, N., Tran, M., Floriano, P. N., Rodriguez, M., Goodey, A., Ali, M., and Neikirk, D., 2002, 'A microchip-based multianalyte assay system for the assessment of cardiac risk,' Anal Chem, 74(13), pp. 3030-3036. [21] Sohn, Y. S., Goodey, A., Anslyn, E. V., McDevitt, J. T., Shear, J. B., and Neikirk, D. P., 2005, 'A microbead array chemical sensor using capillary-based sample introduction: toward the development of an 'electronic tongue',' Biosens Bioelectron, 21(2), pp. 303-312. [22] McDevitt, J. T., Christodoulides, N., Floriano, P. N., Miller, C. S., Ebersole, J. L., Mohanty, S., Dharshan, P., Griffin, M., Lennart, A., Ballard, K. L. M., King, C. P., Langub, M. C., Kryscio, R. J., and Thomas, M. V., 2007, 'Lab-on-a-chip methods for point-of-care measurements of salivary biomarkers of periodontitis,' Oral-Based Diagnostics, 1098, pp. 411-428. [23] Pamula, V., Sista, R., Hua, Z. S., Thwar, P., Sudarsan, A., Srinivasan, V., Eckhardt, A., and Pollack, M., 2008, 'Development of a digital microfluidic platform for point of care testing,' Lab Chip, 8(12), pp. 2091-2104. [24] Srinivasan, V., Pamula, V. K., and Fair, R. B., 2004, 'An integrated digital microfluidic lab-on-a-chip for clinical diagnostics on human physiological fluids,' Lab Chip, 4(4), pp. 310-315. [25] http://www.micronics.net/products/research-and-development/access-cards. [26] Stevens, D. Y., Petri, C. R., Osborn, J. L., Spicar-Mihalic, P., McKenzie, K. G., and Yager, P., 2008, 'Enabling a microfluidic immunoassay for the developing world by integration of on-card dry reagent storage,' Lab Chip, 8(12), pp. 2038-2045. [27] Whitesides, G. M., Martinez, A. W., Phillips, S. T., Carrilho, E., Thomas, S. W., and Sindi, H., 2008, 'Simple telemedicine for developing regions: Camera phones and paper-based microfluidic devices for real-time, off-site diagnosis,' Anal Chem, 80(10), pp. 3699-3707. [28] Whitesides, G. M., Martinez, A. W., and Phillips, S. T., 2008, 'Three-dimensional microfluidic devices fabricated in layered paper and tape,' P Natl Acad Sci USA, 105(50), pp. 19606-19611. [29] Cho, Y. K., Lee, B. S., Lee, Y. U., Kim, H. S., Kim, T. H., Park, J., Lee, J. G., Kim, J., Kim, H., and Lee, W. G., 2011, 'Fully integrated lab-on-a-disc for simultaneous analysis of biochemistry and immunoassay from whole blood,' Lab Chip, 11(1), pp. 70-78. [30] Oh, K. W., and Ahn, C. H., 2006, 'A review of microvalves,' J Micromech Microeng, 16(5), pp. R13-R39. [31] Terry, S. C., Jerman, J. H., and Angell, J. B., 1979, 'Gas-Chromatographic Air Analyzer Fabricated on a Silicon-Wafer,' Ieee T Electron Dev, 26(12), pp. 1880-1886. [32] Yobas, L., Durand, D. M., Skebe, G. G., Lisy, F. J., and Huff, M. A., 2003, 'A novel integrable microvalve for refreshable Braille display system,' J Microelectromech S, 12(3), pp. 252-263. [33] Li, H. Q., Roberts, D. C., Steyn, J. L., Turner, K. T., Yaglioglu, O., Hagood, N. W., Spearing, S. M., and Schmidt, M. A., 2004, 'Fabrication of a high frequency piezoelectric microvalve,' Sensor Actuat a-Phys, 111(1), pp. 51-56. [34] Rich, C. A., and Wise, K. D., 2003, 'A high-flow thermopneumatic microvalve with improved efficiency and integrated state sensing,' J Microelectromech S, 12(2), pp. 201-208. [35] Liu, R. H., Bonanno, J., Yang, J. N., Lenigk, R., and Grodzinski, P., 2004, 'Single-use, thermally actuated paraffin valves for microfluidic applications,' Sensor Actuat B-Chem, 98(2-3), pp. 328-336. [36] Hartshorne, H., Backhouse, C. J., and Lee, W. E., 2004, 'Ferrofluid-based microchip pump and valve,' Sensor Actuat B-Chem, 99(2-3), pp. 592-600. [37] Lagally, E. T., Simpson, P. C., and Mathies, R. A., 2000, 'Monolithic integrated microfluidic DNA amplification and capillary electrophoresis analysis system,' Sensor Actuat B-Chem, 63(3), pp. 138-146. [38] Quake, S. R., Unger, M. A., Chou H. P., Thorsen T, and A, S., 2000, ' Monolithic microfabricated valves and pumps by multilayer soft lithography,' Science, 288(133), p. 6. [39] Song, W. H., Kwan, J., Kaigala, G. V., Hoang, V. N., and Backhouse, C. J., 2008, 'Readily integrated, electrically controlled microvalves,' J Micromech Microeng, 18(4), pp. -. [40] Madou, M., Zoval, J., Jia, G. Y., Kido, H., Kim, J., and Kim, N., 2006, 'Lab on a CD,' Annu Rev Biomed Eng, 8, pp. 601-628. [41] Duffy, D. C., Gillis, H. L., Lin, J., Sheppard, N. F., and Kellogg, G. J., 1999, 'Microfabricated centrifugal microfluidic systems: Characterization and multiple enzymatic assays,' Anal Chem, 71(20), pp. 4669-4678. [42] Gliere, A., and Delattre, C., 2006, 'Modeling and fabrication of capillary stop valves for planar microfluidic systems,' Sensor Actuat a-Phys, 130, pp. 601-608. [43] Cho, H., Kim, H. Y., Kang, J. Y., and Kim, T. S., 2007, 'How the capillary burst microvalve works,' J Colloid Interf Sci, 306(2), pp. 379-385. [44] Chen, J. M., Huang, P. C., and Lin, M. G., 2008, 'Analysis and experiment of capillary valves for microfluidics on a rotating disk,' Microfluid Nanofluid, 4(5), pp. 427-437. [45] Gorkin, R., Park, J., Siegrist, J., Amasia, M., Lee, B. S., Park, J. M., Kim, J., Kim, H., Madou, M., and Cho, Y. K., 2010, 'Centrifugal microfluidics for biomedical applications,' Lab Chip, 10(14), pp. 1758-1773. [46] Luong, T. D., Phan, V. N., and Nguyen, N. T., 2011, 'High-throughput micromixers based on acoustic streaming induced by surface acoustic wave,' Microfluid Nanofluid, 10(3), pp. 619-625. [47] Bousse, L., Cohen, C., Nikiforov, T., Chow, A., Kopf-Sill, A. R., Dubrow, R., and Parce, J. W., 2000, 'Electrokinetically controlled microfluidic analysis systems,' Annu Rev Bioph Biom, 29, pp. 155-181. [48] Hoffman, R. L., 1975, 'Study of Advancing Interface .1. Interface Shape in Liquid-Gas Systems,' J Colloid Interf Sci, 50(2), pp. 228-241. [49] Dussan, E. B., 1979, 'Spreading of Liquids on Solid-Surfaces - Static and Dynamic Contact Lines,' Annu Rev Fluid Mech, 11, pp. 371-400. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/47608 | - |
dc.description.abstract | 慢性腎臟病(chronic kidney disease)在台灣的盛行率位居全世界第二,主要是由於國人對此疾病的自知率相當低,因此發展一個居家照護的腎功能檢測裝置有其必要性。肌酸酐(creatinine)為人體定量產生之物質,其在血液及尿液中的濃度可做為判斷腎功能正常與否的標準。但抽血在居家照護之執行上有所不易,故本研究利用實驗式晶片(lab-on-a-chip)的概念,將醫院的生化分析步驟整合至可拋棄式晶片上,以定量分析尿液中的肌酸酐。又由於尿液的濃度變異度大,須加上測量其他物質誠如白蛋白(albumin)來推斷腎功能。
目前對肌酸酐之檢測,依試劑之種類有免疫型與化學型兩種。許多研究團隊使用免疫型的試劑來增加檢測之專一性,然而其試劑昂貴、保存較為困難;因此本論文採用成本較低的化學型試劑,但後者在定量與程序上需做精密控制,以提高其精確度,為達此目標,市面上有離心式的微流系統(centrifugal microfluidics),此系統藉由晶片旋轉的離心力克服液體於微流道之毛細力,達到一系列的晶片功能。本研究則在文獻上首次利用重力平衡毛細力的方式製作毛細-重力閥門,進而控制流體的移動。此簡單之方法同時具省能源與在無電力源下亦可操作之優點。 此外,本研究使用壓克力做為晶片,無動件的設計可減少製作成本,並可做為可拋棄式之基材。理論分析影響毛細-重力閥門的參數後,可改變流道的幾何結構,並旋轉晶片至特定的角度,以進行一系列的檢測步驟,誠如定量3.6μL的尿液、分別添加A、B兩種試劑產生催化及呈色反應、混合反應物等功能。再者,肌酸酐濃度是藉由測量混合物於510nm下之光學密度(optical density)變化而得。 本裝置依目前醫檢標準作業之規範,可在二十分鐘完成肌酸酐之檢測步驟,而測試肌酸酐濃度之光學系統也具穩定性,由實際測量不同人體尿液樣本得知,此新方法所測出之結果與醫院量測具有一致性。在未來,此多功能之晶片可再配合尿液白蛋白(albumin)的檢測,以得出白蛋白對肌酸酐的比值(albumin to creatinine ratio),如此即可做為實際居家照護腎功能檢測之用。 | zh_TW |
dc.description.abstract | The prevalence of chronic kidney disease (CKD) has become an important issue in Taiwan. This is mainly due to the lack of prevention awareness, which may lead to critical delays in treatment. Point-of-care testing (POCT) allows for diagnostic testing near the site of the patients, and may avoid the need for hemodialysis. Therefore, it is necessary to develop a POCT device to evaluate the renal function.
Creatinine is a chemical found in steady levels in humans, so the concentration in blood and urine is a standard to evaluate the renal function. Since blood is not easily obtained in point-of-care testing, we aim to quantitatively measure the concentration of urinary creatinine. This can be done by integrating the process of biochemical analysis in the hospital onto a small device based on the concept of “lab-on-a chip”. Though the concentration of creatinine fluctuates with the volume of urine, other analyses such as albumin assay can be measured as well to determine the renal function. There has been much research using expensive immunoassay to enhance the specificity of the biochemical analysis. To lower the cost of the analysis, chemical reagents were used instead. Since we aim to quantitatively measure urinary creatinine, metering and sequential steps on chip are required to increase the precision of the chemical assay. Centrifugal microfluidics is considered one of the most commonly used platform for lab-on-a-chip. It allows a serial process to perform on a plastic substrate without complex fabrication. In this research, we applied a novel and simple approach to control the liquid on the microfluidic chip. Gravitational force, instead of centrifugal force, is used to overcome the capillary force generated at the capillary valve. This valve is called the “capillary-gravitational valve”. There has been, however, no research focusing on integrating the serial process of detecting urinary creatinine onto a microfluidic system by such an approach. And this simple method is power-saving, and can be operated without electricity. Furthermore, PMMA was used as the substrate to reach disposability. No external components were mounted onto the chip, reducing the time and the cost of fabrication. By analyzing the parameters of the capillary-gravitational valve and altering the geometry of the microchannels, metering, adding catalytic and colorimetric reagents sequentially, and mixing could be done by simply rotating the chip to certain angles. The concentration of creatinine was determined by measuring the change of optical density at 510 nm. The optical system was calibrated by first measuring the optical density corresponding to different concentrations of the red dye. The calibration curve shows good linearity. The on-chip creatinine assay was also compared with the creatinine assay processed by the standard in-lab method. Good consistency of the two results indicates the feasibility of the approach we proposed. The serial functions were demonstrated by this device and the process was performed within 20 minutes according to the standard process performed in the hospital. Real urine samples from different people were measured and compared with clinical methods, showing high consistency. This novel approach can be further incorporated with the detection of albumin to derive the urine albumin to creatinine ratio (ACr). In this case, the device can be used to the real time determination of renal function for point-of-care use in practice. | en |
dc.description.provenance | Made available in DSpace on 2021-06-15T06:08:25Z (GMT). No. of bitstreams: 1 ntu-100-R98543025-1.pdf: 3509610 bytes, checksum: cc9a0b4819e34039226fd7355e1021db (MD5) Previous issue date: 2011 | en |
dc.description.tableofcontents | 口試委員會審定書 i
誌謝 ii 中文摘要 iv ABSTRACT vi CONTENT viii LIST OF FIGURES xi LIST OF TABLES xviii NOMENCLATURE xix Chapter 1 Introduction 1 1.1 Research Background 1 1.1.1 Chronic Kidney Disease (CKD) 1 1.1.2 Determination of Urinary Creatinine 2 1.1.3 Urinary Creatinine Assay in Clinical Laboratories 4 1.1.4 Lab-on-a-Chip 7 1.2 Literature Review 8 1.2.1 Integration of Multiple Functions on Chip 8 1.2.2 Microvalves 19 1.2.3 Comparison of Pumping Techniques 27 1.3 Motivation 31 1.4 Objective 33 Chapter 2 Theory 34 2.1 Capillary Pressure in a Circular Tube (∆Pcircular) 34 2.2 Capillary Pressure in a Square Tube (∆Psquare) 35 2.3 Burst Pressure (∆Pb) in a Capillary Valve 35 2.4 Capillary-Gravitational Valve 37 2.5 Capillary-Gravitational Valve in a Slug Flow 38 2.6 Capillary-Gravitational Valve with a Loading Hole 40 Chapter 3 Experimental 42 3.1 Setup of the Rotational Platform 42 3.2 Measurement of Contact Angle and Surface Tension 43 3.3 Fabrication of Microfluidic Chip 44 3.4 Design of the Microfluidic Chip 45 3.5 Serial Process 46 3.5.1 Preloading of Reagent A and Reagent B 47 3.5.2 Loading for Users 48 3.5.3 Serial Functions of the Urine Chip 49 3.6 Optical System 49 3.6.1 Fabrication of the Detection Chamber 49 3.6.2 Calibration of the Optical System 51 3.6.3 Mixing Performance 51 3.7 Creatinine Assay 52 3.8 Real Sample Test 53 Chapter 4 Results and Discussions 54 4.1 Metering 54 4.1.1 Equilibrium Contact Angle (θc), Advancing Contact Angle (θa) and Receding Contact Angle (θr) 54 4.1.2 The Wedge Angle (α) 59 4.1.3 Process of Metering 62 4.1.4 Precision of Metering 65 4.1.5 Lchamber /Wchamber vs. ΔPb, max 67 4.2 Adding Reagents 69 4.2.1 Width of the Channel (wchannel) 69 4.3 Liquid Guiding 73 4.3.1 Remained Liquid in the Channel 73 4.3.2 Holes in the Microchannel 76 4.3.3 Remained Liquid above the Detection Chamber 77 4.4 Mixing and Detection 78 4.4.1 Calibration of the Optical System 78 4.4.2 Mixing in the Channel 81 4.5 Serial Function of the Urine Chip 83 4.6 Creatinine Assay 85 4.7 Real Sample Test 92 4.8 Miniature of the Device 94 Chapter 5 Conclusions 96 Chapter 6 Future Work 98 6.1 Enhancement of Mixing Performance 98 6.2 Albumin/Creatinine Ration (ACr) 98 6.3 Simplifying the Optical System 98 REFERENCE 99 | |
dc.language.iso | en | |
dc.title | 毛細-重力閥門及其在整合式尿液肌酸酐檢測晶片
之研究與應用 | zh_TW |
dc.title | Design and Investigation of Capillary-Gravitational Valve in an Integrated Urine-Chip for Creatinine Detection | en |
dc.type | Thesis | |
dc.date.schoolyear | 99-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 林啟萬,許金川,李雨,陳林祈 | |
dc.subject.keyword | 慢性腎臟病,尿液肌酸酐,定量檢測,時序控制,實驗式晶片,光學密度, | zh_TW |
dc.subject.keyword | Chronic Kidney Disease,Urinary Creatinine,Quantitative Analysis,Serial Process,Lab-on-a-Chip,Optical Density, | en |
dc.relation.page | 104 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2011-08-19 | |
dc.contributor.author-college | 工學院 | zh_TW |
dc.contributor.author-dept | 應用力學研究所 | zh_TW |
顯示於系所單位: | 應用力學研究所 |
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