簡易檢索 / 詳目顯示

研究生: 杜孟哲
Tu, Meng-Che
論文名稱: 一種可偵測人類血清白蛋白之光學式生物感測器
An Optical Biosensor for Human Serum Albumin Detection
指導教授: 游萃蓉
Yew, Tri-Rung
口試委員: 張晃猷
Chang, Hwan-You
彭慧玲
Peng, Hwei-Ling
學位類別: 碩士
Master
系所名稱: 工學院 - 材料科學工程學系
Materials Science and Engineering
論文出版年: 2011
畢業學年度: 99
語文別: 中文
論文頁數: 78
中文關鍵詞: 人類血清白蛋白生物感測器光二極體量子點
外文關鍵詞: Human serum albumin, Biosensor, Photodiode, Quantum dot
相關次數: 點閱:2下載:0
分享至:
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報
  • 本論文主要研究利用簡單且體積小的光學裝置,並以光學機制作為量測人類血清白蛋白(human serum albumin, HSA)之生物感測器。
    在本研究中之生物感測器製備方式,是將玻璃洗淨後,經 3-aminopropyltriethoxysilane (APTES) 或1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC)/N-Hydroxysuccinimide (NHS)改質玻璃表面,使玻璃表面具有生物相容性後,而後依序接合上人類血清白蛋白抗體 (anti-HSA, AHSA)、小牛血清蛋白阻斷(bovine serum albumin, BSA),及不同濃度之HSA,最後修飾上具 655 nm發光波長的硒化鎘(CdSe) / 硫化鋅(ZnS)量子點(QD),吹乾後,再以405 nm雷射激發量子點,使之發出655 nm螢光並以感光二極體(photodiode)量取接收光量後產生之電流,藉此作為人HSA濃度之定量檢測。
    在以感光二極體擷取 QDs 所發出螢光,進行HSA生物感測器定量分析上,乃利用半導體參數分析儀(semiconductor parameter analyzer),在直流電下測量由不同濃度之HSA與其接合之QDs所貢獻之電流變化量,來定量分析HSA之濃度。結果顯示當HSA的濃度越高,所產生的光電流也就越大,並且在2x10-4 mg/ml到2x10-1 mg/ml之間呈線性關係,其HSA偵測極限為3.2x10-5 mg/ml。
    本研究利用光學機制,藉由量測接合HSA及QDs後所發出之螢光強度的改變,定量HSA濃度,並成功驗證此機制之可行性,跟傳統螢光式的光學生物感測器相比,本研究獨特之處在於此感測器的光源為二極體雷射,而光偵測器為感光二極體,兩者皆為體積小、低成本的電子元件,並可搭配透鏡與濾鏡,組成簡單且攜帶方便的光學系統,此簡易的光學系統具有易整合於生物晶片、分析結果可即時輸出、低成本等優點,對蛋白質檢測上有極大應用潛力。


    In this study, an optical biosensor for human serum albumin (HSA) detection was demonstrated utilizing a simple and small volume optical system.
    For the fabrication process of the optical biosensor, the glass sensing surface was modified by 3-aminopropyltriethoxysilane (APTES) or 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) / N-Hydroxysuccinimide (NHS) to improve the biocompatibility. Following that, the sensing surface was modified with anti-human serum albumin (AHSA), blocked by bovine serum albumin (BSA), conjugated with targeted HSA, and finally bonded with AHSA-modified quantum dots (emission wavelength : 655 nm) for HSA detection after N2 drying.
    The photocurrent contributed by various concentrations of HSA was measured and quantified by semiconductor parameter analyzer under DC condition in this work. Results showed that the photocurrent increased linearly as the HSA conjugation increased from 2x10-4 mg/ml to 2x10-1 mg/ml, with a detection limit of 3.2□10-5 mg/ml.
    In summary, this study has successfully demonstrated the feasibility of utilizing optical mechanism (by measuring the photocurrent change of photodetector induced by fluorescence intensity change before and after HSA, and QDs conjugating) to quantify human serum albumin (HSA) concentration. Compared to the traditional fluorescence biosensors, both diode laser light source and photodetector were low-cost and small-volume electronics in this work. This portable, simple optical system consisted of lens, filter, diode laser, and photodetector, exhibiting advantages of ease to be integrated with biochips, timely output, and low cost, that can be used for future protein detection.

    摘要 I Abstract III 誌謝 V 目錄 VIII 圖目錄 XI 表目錄 XVII 蛋白質中英對照表 XVIII 第一章 緒論 1 第二章 文獻回顧 3 2.1 電化學生物感測器簡介 4 2.1.1 電流式生物感測器 4 2.1.2 電位式生物感測器 5 2.1.3 阻抗式生物感測器 5 2.2 光學生物感測器簡介 7 2.2.1 化學發光法 7 2.2.2 表面電漿共振光學式生物感測器 9 2.2.3 螢光光學式生物感測器 10 2.3 人類血清白蛋白檢測 12 第三章 實驗流程與方法 16 3.1 量子點/人類血清白蛋白抗體混合溶液的製備 18 3.2 玻璃表面改質 20 3.2.1 3-氨基丙基三甲氧基甲矽烷(APTES)表面改質 20 3.2.2 EDC/NHS表面改質 22 3.3 人類血清白蛋白抗體與小牛血清蛋白的接合與確認流程 24 3.3.1 人類血清白蛋白抗體與小牛血清蛋白接合流程 24 3.3.2 人類血清白蛋白抗體與小牛血清蛋白確認流程 27 3.4 人類血清白蛋白和螢光劑接合與確認流程 29 3.5 電性量測原理介紹 31 3.5.1 光學系統介紹 31 3.5.2 感光二極體基本工作原裡 34 3.6 儀器簡介 35 3.6.1 原子力電子顯微鏡(Atomic Force Microscopy) 35 3.6.2 螢光顯微鏡(Fluorescence Microscopy) 37 3.6.3 電性量測儀器 39 第四章 實驗結果與討論 40 4.1 感光二極體特性 40 4.2 利用螢光抗體確認生物感測器表面改質 42 4.2.1 人類血清白蛋白抗體和小牛血清蛋白接合之確認 42 4.2.2 人類血清白蛋白接合之確認 47 4.2.3 不同濃度人類血清白蛋白接合之確認 50 4.3 利用原子力顯微鏡觀察生物感測器改質表面形貌 52 4.4 感光二極體電流量測 54 4.4.1 電壓量測範圍分析 56 4.4.2 量子點溶液之光電流量測 58 4.4.3 人類血清白蛋白之定量機制 60 4.4.4 定量人類血清白蛋白之理論計算 64 第五章 結論 69 第六章 未來展望 71 第七章 參考文獻 72 本研究產出之論文發表 78   圖目錄 圖2.1 阻抗式生物感測器示意圖 [25]。 6 圖2.2 光敏靈(luminol)的放光機制[29-30]。 8 圖2.3表面電漿震盪(surface plasmon resonance, SPR)感測裝置示意圖[30]。 9 圖2.4三明治結構(sandwich structure)螢光生物感測器示意圖。11 圖3.1本研究之實驗流程圖。 17 圖3.2人類血清白蛋白抗體(AHSA)與量子點(QD)接合而形成(AHSA-QD)複合體示意圖。 19 圖3.3 APTES之結構式。 21 圖3.4 APTES分子間先脫去二乙醇基團,接著在SiO2表面脫水形成生物親和性薄膜。 21 圖3.5 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)的結構示意圖。 22 圖3.6 N-Hydroxysuccinimide (NHS)的結構示意圖。 23 圖3.7 (a)酸洗後,玻璃基板產生氫氧基,(b) EDC活化氫氧基形成O-acylisourea group,(c) NHS取代EDC 形成NHS-activated carboxylic acid group,及(d)抗體取代NHS使生物感測性具有專一性。 23 圖3.8 室溫環境中利用水平震盪器,在90 rpm轉速下、於PBS溶液中搖晃1小時以固定AHSA和BSA。 25 圖3.9 (a)以APTES or EDC/NHS 改質後生物感測器之玻璃表面,(b)鍵結上AHSA後,以及完成(c)利用BSA阻斷未經抗體接合之區域。 26 圖3.10 (a)未經抗體修飾的玻璃,直接修飾上BSA,再浸入anti-IgG- FITC,於室溫下,以水平震盪器在90 rpm轉速下水平搖晃1小時之玻璃基座。(b)先經過AHSA以及BSA修飾的生物感測器,浸入anti-IgG-FITC中,於室溫下以水平震盪器在90 rpm轉速下水平搖晃1小時後之玻璃基座。而後利用螢光顯微鏡來驗證BSA的效應,以及AHSA鍵結的情形。 28 圖3.11 (a)接合HSA,(b)接合AHSA-QD,以及(c)接合AHSA-FITC之玻璃基座。 30 圖3.12光學系統以及光路的示意圖,二極體雷射(diode laser)發出405 nm 的紫光,紫光激發了生物感測器(biosensor)表面的螢光劑,放出長波長的螢光( AHSA-QD: 655 nm;AHSA-FITC: 528 nm),螢光經過透鏡(lens)被聚焦後,再通過濾鏡(long pass filter)到達感光二極體(photodiode)表面,輸出光電流訊號。而405 nm紫光雷射通過玻璃表面的穿透光(transparent beam)以及反射光(reflection beam)皆被光束截止器吸收,如此可避免因為散射,而使感光二極體輸出的訊號雜訊增加。 32 圖3.13光學系統及各零件放大圖,此系統包含了二極體雷射光源 (diode laser)、聚焦透鏡 (lens)、長波長通過濾鏡 (long pass filter)、光二極體(photodiode)以及光束截止器(beam dump) 。 33 圖3.14 (a)長波長通過濾鏡(long pass filter),(b)感光二極體(photodiode, Hamamatsu, S1133-01)規格表。 33 圖3.15 本研究使用之原子力顯微鏡(AFM, DI 3100),位於清華大學材料系R124。 36 圖3.16國立清華大學分子醫學所張晃猷教授實驗室提供之螢光光學顯微鏡,型號為OLYMPUS BX51。 38 圖3.17本研究使用之電性量測儀(semiconductor parameter analyzer,Agilent/HP 4155),位於清華大學材料系物性實驗室。39 圖4.1 雷射光輸出功率與光二極體電流關係圖,紅色空心方塊表示655 nm光源沒有通過濾鏡,直接進入光二極體的輸出電流強度;紅色實心方塊表示655 nm光源通過濾鏡,進入光二極體後的輸出電流強度;紫色空心三角形表示405 nm光源沒有通過濾鏡,直接進入光二極體的輸出電流強度;紫色實心三角形表示405 nm光源通過濾鏡,進入光二極體後的輸出電流強度。 41 圖4.2 玻璃基底(左側)分別經(a) APTES改質後,(b) EDC/NHS改質後先以BSA修飾,再修飾anti-IgG-FITC後之螢光顯微鏡觀察結果,(c) APTES改質後,(d) EDC/NHS改質後,修飾anti-IgG-FITC後之螢光顯微鏡觀察結果。四張圖比對後顯示BSA成功地阻斷非專一性的位置,即無AHSA的區域。 43 圖4.3 玻璃基底(左側)分別經(a) APTES改質,及(b) EDC/NHS改質後,依照順序修飾人類血清白蛋白抗體AHSA、BSA後在螢光顯微鏡下觀測之結果;(c) APTES改質,(d) EDC/NHS改質後依照順序修飾AHSA、BSA以及anti-IgG-FITC後在螢光顯微鏡下觀測之結果,結果顯示AHSA成功地接合在經過修飾的玻璃表面。 46 圖4.4 玻璃基底(左側)分別經(a) APTES,(b) EDC/NHS改質後,接合上AHSA、BSA及HSA的所得之螢光顯微鏡圖。玻璃基底(左側)分別經(c) APTES,(d) EDC/NHS改質後,接上AHSA、BSA及HSA後,緊接著接上AHSA-FITC所得之螢光顯微鏡圖。玻璃基底(左側)分別經(e) APTES,(f) EDC/NHS改質後,接合上AHSA、BSA及HSA後,緊接著接合上AHSA-QD所得之螢光顯微鏡圖。 49 圖4.5 玻璃基座(右側)經過AHSA、BSA修飾過後,接著經(a) 2x10-5 mg/ml,(b) 2x10-3 mg/ml,以及(c) 2x10-1 mg/ml的HSA接合後,緊接著接合過量的AHSA-QD複合溶液,在螢光顯微鏡下所得圖片,由圖可以看出量子點接合的HSA濃度越高,螢光強度越強。 51 圖4.6 玻璃表面依序經(a) APTES表面改質後,(b)接合AHSA以後,(c)接合BSA之後,(d)接合HSA之後,以及(e)接合AHSA-QD複合體後之玻璃表面原子力顯微鏡 (AFM) 圖及表面粗糙度值。 53 圖4.7 (a)接合HSA的試片,以及被405 nm雷射激發後所量測到被激發的655 nm螢光之光電流(IHSA),(b)接合量子點後的試片,被405 nm雷射激發後所量測被激發出的655 nm螢光之光電(IQD),兩試片的電流差ΔI1 = IQD - IHSA。 55 圖4. 8標準二極體曲線I-V d的形狀,紅色圓圈處為過電壓零時(Vd=0)的電流值,也就是所取的光電流 –I ph 的負值。 57 圖4.9 不同量子點溶液濃度與光電流變化(ΔI2=IQD-IPBS)的關係曲線。 59 圖4.10 一系列不同濃度人類血清蛋白(HSA)在濃度(a)0.2 mg/ml, (b) 2x10-2 mg/ml,(c) 2□10-3 mg/ml,(d) 2□10-4 mg/ml,(e) 2 □10-5 mg/ml,及(f) 2 □10-6 mg/ml下量測所得之光電流值(IHSA),以及再接合完量子點之光電流值(IQD)。(n=3)。 62 圖4.11光電流與HSA濃度之關係圖,其中 為量自已接合量子點之不同濃度之HSA, 為未接合量子點之的螢光電流對於不同濃度之HSA。 63 圖4.12光電流變化(ΔI1 = IQD-IHSA)與接合有量子點之人類血清白蛋白(HSA)濃度關係圖。(n=3) 63 圖4.13最密排列一層AHSA於玻璃上。 64 圖4. 14雷射光僅激發溶液中1/10的量子點示意圖。 66 表目錄 表2.1國際期刊已報導關於HSA感測器可測靈敏度與範圍之整理[38-44]。 15  

    [1] L. C. Clark, Jr., and C. Lyons, "Electrode Systems for Continuous Monitoring in Cardiovascular Surgery.", Ann. NY. Acad. Sci., 1965, 102(1), 29-45
    [2] J. H. T. Luong, K. B. Male, and J. D. Glennon, "Biosensor Technology: Technology Push versus Market Pull", Biotechnol. Adv., 2008, 26, 492-500
    [3] S. R. Khetani, and S. N. Bhatia, "Microscale Culture of Human Liver Cells for Drug Development", Nat. Biotechnol., 2008, 26(1), 120-126
    [4] D. C. Rockeyl, and D. M. Bissell, "Noninvasive Measures of Liver Fibrosis", Hepatology, 2006, 43(2), S113-S120
    [5] I. Moser, G. Jobst, P. Svasek, M. Varahram, and G. Urban, "Rapid Liver Enzyme Assay with Miniaturized Liquid Handling System Comprising Thin Film Biosensor Array", Sensor Actuat. B, 1997, 44, 377-380
    [6] S. Babu, S. M., L. Zubkov, S. Murthy, and E. Papazoglou, "A PMMA microcapillary quantum dot linked immunosorbent assay (QLISA)." Biosens. Bioelectron., 2009, 24, 3467-3474

    [7] J. Li, C. Xu, Z. Zhang, Y. Wang, H. Peng, Z. Lu, and M. Chan. "A DNA-detection platform with integrated photodiodes on a silicon chip.", Sensor Actuators B, 2009, 106(1): 378-382

    [8] Y. C. Lu, Y. S. C., Y. Y. Chen, A. C. Shu, H. Y. Hsu, H. Y. Chang, and T. R. Yew, "Bacteria detection utilizing electrical conductivity.", Biosens. Bioelectron., 2008, 23, 1856-1861

    [9] M. Vidal, M. P., S. Santos, T. Tavares, J. Hossfeld, C. Preininger, and A. Oliva, "Fluorescence IgG immunosensor based on a micro flow cell containing controlled pore glass as immobilisation support.", Analyst, 2000, 125: 1387-1391

    [10] C. H. Yeh, W. T. C., H. P. Lin, T. C. Chang, and Y. C. Lin, "A newly developed immunoassay method based on optical measurement for Protein A detection", Talanta, 2010, 83, 55-60

    [11] C. Siegmann-Thoss, R. Renneberg, J. F. C. Glatz, and F. Spener, " Surface functionalization of poly(epsilon-caprolactone) improves its biocompatibility as scaffold material for bioartificial vessel prostheses ", Journal of Biomedical Materials Research Part B-Applied Biomaterials, 2011, 98B(1), 89-100

    [12] M.L. Mena, P. Yáñez-Sedeño and J.M. Pingarrón, "A comparison of different strategies for the construction of amperometric enzyme biosensors using gold nanoparticle-modified electrodes.", Anal. Biochem., 2005, 336(1), 20-27

    [13] T. M. O’Regan, M. Pravda, C. K. O’Sullivan, and G. G. Guilbault, "Development of a disposable immunosensor for the detection of human heart fatty-acid binding protein in human whole blood using screen-printed carbon electrodes. ", Talanta, 2002, 57, 501–510

    [14] T. M. O’Regan, L. J. O’Riordan, M. Pravda, C. K. O’Sullivan, and G. G. Guilbault, "Direct detection of myoglobin in whole blood using a disposable amperometric immunosensor. ", Anal. Chim. Acta, 2002, 460, 141–150

    [15] D. R. Th_evenot, K. Toth, R. A. Durst, and G. S. Wilson, "Electrochemical Biosensors: Recommended Definitions and Classification. ",Pure Appl. Chem., 1999, 71(12), 2333–2348

    [16] C. Ercole, M. D. Gallo, M. Pantalone, S. Santucci, L. Mosiello, C. Laconi, and A. Lepidi, "A biosensor for Escherichia coli based on a potentiometric alternating biosensing (PAB) transducer. ", Sens. Actuators, B, 2002, 83, 48–52

    [17] G. A. J. Besselink, R. B. M. Schasfort, and P. Bergveld, "Modification of ISFETs with a monolayer of latex beads for specific detection of proteins. ", Biosens. Bioelectron., 2003, 18, 1109–1114

    [18] M. Kamahori, Y. Ishige, and M. Shimoda, "A novel enzyme immunoassay based on potentiometric measurement of molecular adsorption events by an extended-gate field-effect transistor sensor.", Biosens. Bioelectron., 2007, 22, 3080–3085

    [19] A. G. Gehring, D. L. Patterson, and S. I. Tu, "Use of a light-addressable potentiometric sensor for the detection of Escherichia coli O157:H7. ", Anal. Biochem., 1998, 258, 293–298

    [20] M. Billah, H. C. W. Hays, and P. A. Millner, "Development of a myoglobin impedimetric immunosensor based on mixed self-assembled monolayer onto gold.", Microchim. Acta, 2008, 160, 447–454

    [21] X. Chen, Y. Wang, J. Zhou, W. Yan, X. Li and J. J. Zhu, "Electrochemical DNA Biosensor Based on Nanoporous Gold Electrode and Multifunctional Encoded DNA−Au Bio Bar Codes. ", Anal. Chem., 2008, 80, 2133–2140

    [22] S. Viswanathan, H. Radecka and J. Radecki, "Electrochemical biosensors for food analysis. ", Monatsh. Chem., 2009, 140, 891–899

    [23] A. L. Newman, K. W. Hunter, W. D. Stanbro, "The capacitive affinity sensor: a new biosensor, in: Proceedings of the Second International Meeting on Chemical Sensors.", Bordeaux 1986,
    7–10, 596–598

    [24] A. Guiseppi-Eliea, L. Kocha, S. H. Finley, and G. E. Wnek, "The effect of temperature on the impedimetric response of bioreceptor hosting hydrogels. ", Biosens. Bioelectron., 2011, 26, 2275-2280

    [25] A. G. E. Saum, R. H. Cumming, and F. J. Rowell, "Detection of protease activity in the wetted surface of gelatin-coated electrodes in air by AC impedance spectroscopy.", Biosens. Bioelectron., 2000, 15, 305-313

    [26] F. Darain, P. Yager, K. L. Gan and S. C. Tjin, "On-chip detection of myoglobin based on fluorescence.", Biosens. Bioelectron., 2009, 24, 1744–1750

    [27] M. Yang, Y. Kostov, H. A. Bruck and A. Rasooly, "Gold nanoparticle-based enhanced chemiluminescence immunosensor for detection of Staphylococcal Enterotoxin B (SEB) in food. ", Anal. Chem., 2008, 80, 8532–8537

    [28] H. Huang, X. L. Zheng, J. S. Zheng, J. Pan and Y. P. Pu, "Rapid analysis of alpha-fetoprotein by chemiluminescence microfluidic immunoassay system based on super-paramagnetic microbeads.", Biomed. Microdevices, 2009, 11, 213–216

    [29] J. Lind, G. Merenyi, T. E. Eriksen, "Chemiluminescence mechanism of cyclic hydrazides such as luminol in aqueous solutions. ", J. Am. Chem. Soc., 1983, 105, 7655-7661

    [30] G. Merenyi, J. Lind, T. E. Eriksen,. " Luminol chemiluminescence: chemistry, excitation, emitter. ", J. Biolumin. Chemilumin. 1990, 5, 53-56

    [31] T. M. Chinowsky, J. G. Quinn, D. U. Bartholomew, R. Kaiser and J. L. Elkind, "Performance of the Spreeta 2000 integrated surface plasmon resonance affinity sensor. ", Sens. Actuators, B, 2003, 91, 266–274

    [32] B. N. Feltis, B. A. Sexton, F. L. Glenn, M. J. Best, M. Wilkins and T. J. Davis, "A hand-held surface plasmon resonance biosensor for the detection of ricin and other biological agents. ", Biosens. Bioelectron., 2008, 23, 1131–1136

    [33] J. Ziegler, M. Zimmermann, P. Hunziker and E. Delamarche, "High-Performance Immunoassays Based on Through-Stencil Patterned Antibodies and Capillary Systems. ", Anal. Chem., 2008, 80, 1763–1769.

    [34] W. J. Parak, T. Pellegrino and C. Plank, " Labelling of cells with quantum dots. ", Nanotechnology 2005, 16, R9-R25.

    [35] A. Morarka, S. Agrawal, S. Kale, A. Kale, S. Ogale, K. Paknikar, and D. Bodas, "Quantum dot based immunosensor using 3D circular microchannels fabricated in PDMS. ", Biosens. Bioelectron., .2011, 26, 3050-3053

    [36] K. Kerman, T. Endo, M. Tsukamoto, M. Chikae, Y. Takamura, and E. Tamiya, "Quantum dot-based immunosensor for the detection of prostate-specific antigen using fluorescence microscopy.", Talanta, 2007, 71, 1494–1499

    [37] J. -F. Magnaval, R. Fabre, P. Maurières, J. -P. Charlet and B. Larrard. “Application of the Western blotting procedure for the immunodiagnosis of human toxocariasis”, Biomedical and Life Sciences, 1991, 77, 697-702

    [38] K. Y. Park, Y. S. Sohn, C. K. Kim, H. S. Kim, Y. S. Bae, and S.Y. Choi, “Development of FET-Type Albumin Sensor for Diagnosing Nephritis”, Biosens. Bioelectron., 2008, 23, 1904-1907

    [39] C. J. Huang, C. C. Lu, T. Y. Lin, T. C. Chou, and G. B. Lee, “An Electrochemical Albumin-Sensing System Utilizing Microfluidic Technology”, J. Micromech. Microeng., 2007, 17, 835–842

    [40] M. C. Chuang, C. C. Liu, and M. C. Yang, “An Electrochemical Tyrosinase-Immobilized Biosensor for Albumin—Toward a Potential Total Protein Measurement.”, Sensor Actuat. B, 2006, 114, 357–363
    [41] S. B. Tolani, M. Craig, R. K. DeLong, K. Ghosh, and A. K. Wanekaya, “Towards Biosensors Based on Conducting Polymer Nanowires”, Anal. Bioanal. Chem., 2009, 393, 1225–1231

    [42] B. Wongkittisuksa, C. Limsakula, P. Kanatharana, W. Limbut, P. Asawatreratanakul, S. Dawan, S. Loyprasert, and P. Thavarungkul, " Development and application of a real-time capacitive sensor. ", Biosens. Bioelectron., .2011, 26, 2466-2472

    [43] Y. H. Ahn, J. S. Lee, and Y. T. Chang, “Selective Human Serum Albumin Sensor from the Screening of a Fluorescent Rosamine Library.”, J. Comb. Chem., 2008, 10, 376-380

    [44] M. De, S. Rana, H. Akpinar, O. R. Miranda, R. R. Arvizo, U. H. F. Bunz, and V. M. Rotello, “Sensing of Proteins in Human Serum Using Conjugates of Nanoparticles and Green Fluorescent Protein”, Nat. Chem., 2009, 1, 461-465

    [45] B.V.Chikkaveeraiah, V. Mani, V. Patel, S. Gutkind, J.F.Rusling, “Microfluidic electrochemical immunoarray for ultrasensitive detection of two cancer biomarker proteins in serum” Biosens. Bioelectron., 2011, 26, 4477-4483


    無法下載圖示 全文公開日期 本全文未授權公開 (校內網路)
    全文公開日期 本全文未授權公開 (校外網路)

    QR CODE