臺灣博碩士論文加值系統

本實驗中，我們成功開發金奈米比色法探針檢測人類血清白蛋白。我們添加氫氧化鈉於色胺酸與四氯金酸混合溶液中合成色胺酸金奈米粒子。藉由人類血清白蛋白與色胺酸之間的配位結合，人類血清白蛋白會因為與金奈米粒子表面的色胺酸作用，保護金奈米粒子以避免在5×磷酸鹽緩衝溶液中發生鹽類誘導聚集的現象，溶液仍呈紅色。但沒有人類血清白蛋白保護的金奈米粒子，色胺酸金奈米粒子在5×磷酸鹽緩衝溶液中會發生鹽類誘導聚集，使溶液呈藍紫色。為了確認人類血清白蛋白與色胺酸的配位結合，我們添加界面活性劑將蛋白質變性或添加競爭配位結合的藥物與人類血清白蛋白作用。實驗結果說明這些都會影響人類血清白蛋白與金奈米粒子表面色胺酸的配位結合，使得色胺酸金奈米粒子於高鹽環境下發生鹽類誘導聚集。此外，相較於其他蛋白質，只有血清白蛋白在最佳化5×磷酸鹽緩衝溶液(pH 7.4)的條件下能保護金奈米粒子。隨著不同濃度的人類血清白蛋白，用肉眼便能觀測到100 nM人類血清白蛋白能造成的色胺酸金奈米粒子顏色變化。藉由紫外/可見光分光光譜儀，可以檢測人類血清白蛋白的最低可偵測濃度約為60 nM。在尿液樣品應用方面，其最低可偵測濃度為120 nM。因此色胺酸金奈米粒子可以做為高選擇性與高靈敏度的比色探針檢測人類血清白蛋白。

A gold nanoparticle-based colorimetric probe for the detection of human serum albumin (HSA) was developed in this study. We synthesized the tryptophan-stabilized gold nanoparticles (Trp-AuNPs) by mixing tryptophan with tetrachloroauric acid at the alkaline solution. Due to the ligand binding between HSA and tryptophan, HSA would interact with the tryptophan on gold nanoparticles surface and prevent the Trp-AuNPs from the salt-induced aggregation. The Trp-AuNPs were red in color and exhibited absorption at 530 nm. Without HSA, the salt-induced aggregation of Trp-AuNPs would occur in 5× phosphate buffer saline (PBS) and result in the appearance of a new absorption at 700 nm. To confirm the ligand binding between HSA and tryptophan, we used the surfactants to denature HSA or added a competitive ligand binding drug to interact with HSA. The results showed that both of them would influence the interaction between HSA and tryptophan and cause the Trp-AuNPs to aggregate. Compared with several proteins, only the serum albumin could prevent the Trp-AuNPs from salt-induced aggregation under the optimized condition (5× PBS, pH 7.4). The concentration of HSA can be visualized about 100 nM by the naked eyes through the color change of Trp-AuNPs and determined by UV-vis spectroscopy with the lowest detectable concentration of 60 nM. Therefore, Trp-AuNPs can be employed for highly selective and sensitive colorimetric detection of HSA.

摘 要 i
Abstract iii
目錄 vi
圖目錄 ix
表目錄 xi
一、金奈米粒子比色法 1
1.1 簡介 1
1.2 金奈米粒子的形成 2
1.3 金奈米粒子的穩定劑種類 4
1.4 局部表面電漿共振 5
1.5 交聯式聚集 10
1.6 非交聯式聚集 12
1.7 總結 16
二、人類血清白蛋白 17
2.1 簡介 17
2.2 微量白蛋白尿 19
2.3 尿液中白蛋白的檢驗方法 22
三、應用色胺酸合成金奈米粒子於比色法檢測血清白蛋白 24
3.1 簡介 24
3.2 儀器裝置 26
3.3 試藥 27
3.4 實驗方法 28
3.4.1 合成色胺酸修飾的金奈米粒子 28
3.4.1.1 改變色胺酸和四氯金酸的濃度比例 28
3.4.1.2 改變氫氧化鈉的濃度 29
3.4.1.3 改變氫氧化鈉添加的順序 30
3.4.1.4 傅立葉轉換紅外光譜鑑定 30
3.4.2 人類血清白蛋白樣品之配製 32
3.4.3 色胺酸金奈米比色法檢測人類血清白蛋白之實驗方法 33
3.4.3.1 檢測人類血清白蛋白 33
3.4.3.2 穿透式電子顯微鏡觀測 35
3.4.3.3 則塔電位測量 36
3.4.3.4 酸鹼值最佳化 37
3.4.3.5 磷酸鹽緩衝溶液濃度最佳化 38
3.4.3.6 檢測變性後的人類血清白蛋白 38
3.4.3.7 檢測與地西泮混合後的人類血清白蛋白 40
3.4.3.8 蛋白質選擇性測試 40
3.4.3.9 不同表面修飾的金奈米粒子 41
3.4.3.10 檢測不同濃度的人類血清白蛋白 42
3.5 實驗結果與討論 43
3.5.1 合成色胺酸金奈米粒子 43
3.5.1.1 改變色胺酸和四氯金酸的濃度比例之結果 43
3.5.1.2 改變氫氧化鈉的濃度之結果 47
3.5.1.3 改變添加氫氧化鈉的順序之結果 50
3.5.1.4 傅立葉轉換紅外光譜鑑定與文獻比較 52
3.5.2色胺酸金奈米比色法檢測人類血清白蛋白 54
3.5.2.1 檢測人類血清白蛋白定性 54
3.5.2.2 穿透式電子顯微鏡觀測結果 57
3.5.2.3 則塔電位測量結果 59
3.5.2.4 酸鹼值最佳化結果 60
3.5.2.5 磷酸鹽緩衝溶液濃度測試結果 62
3.5.2.6 檢測變性後的人類血清白蛋白結果 64
3.5.2.7 檢測與地西泮混合後的人類血清白蛋白結果 69
3.5.2.8 蛋白質選擇性測試結果 70
3.5.2.9 不同表面修飾的金奈米粒子結果 73
3.5.2.10 檢測不同濃度的人類血清白蛋白結果 76
四、結論 82
五、參考文獻 84

[1] D. Vilela; M. C. Gonzalez; A. Escarpa, "Sensing colorimetric approaches based on gold and silver nanoparticles aggregation: Chemical creativity behind the assay. A review". Anal. Chim. Acta 2012, 751, 24-43.
[2] T. N. Dung; D. J. Kim; K. S. Kim, "Controlled synthesis and biomolecular probe application of gold nanoparticles". Micron 2011, 42, 207-227.
[3] G. Frens, "Controlled nucleation for the regulation of the particle size in monodisperse gold suspensions". Nat. Phys. Sci. 1973, 241, 20-22.
[4] W. Zhao; M. A. Brook; Y. F. Li, "Design of gold nanoparticle-based colorimetric biosensing assays". ChemBioChem 2008, 9, 2363-2371.
[5] K. A. Willets; R. P. Van Duyne, "Localized surface plasmon resonance spectroscopy and sensing". Annu. Rev. Phys. Chem. 2007, 58, 267-297.
[6] P. K. Jain; M. A. El-Sayed, "Noble metal nanoparticle pairs: effect of medium for enhanced nanosensing". Nano Lett. 2008, 8, 4347-4352.
[7] P. N. Njoki; I. I. S. Lim; D. Mott; H. Y. Park; B. Khan; S. Mishra; R. Sujakumar; J. Luo; C. J. Zhong, "Size correlation of optical and spectroscopic properties for gold nanoparticles". J. Phys. Chem. C 2007, 111, 14664-14669.
[8] H. Jans; Q. Huo, "Gold nanoparticle-enabled biological and chemical detection and analysis". Chem. Soc. Rev. 2012, 41, 2849-2866.
[9] X. O. Liu; M. Atwater; J. H. Wang; Q. Huo, "Extinction coefficient of gold nanoparticles with different sizes and different capping ligands". Colloids Surf., B 2007, 58, 3-7.
[10] S. K. Ghosh; T. Pal, "Interparticle coupling effect on the surface plasmon resonance of gold nanoparticles: From theory to applications". Chem. Rev. 2007, 107, 4797-4862.
[11] Z. Y. Zhong; S. Patskovskyy; P. Bouvrette; J. H. T. Luong; A. Gedanken, "The surface chemistry of Au colloids and their interactions with functional amino acids". J. Phys. Chem. B 2004, 108, 4046-4052.
[12] R. Elghanian; J. J. Storhoff; R. C. Mucic; R. L. Letsinger; C. A. Mirkin, "Selective colorimetric detection of polynucleotides based on the distance-dependent optical properties of gold nanoparticles". Science 1997, 277, 1078-1081.
[13] W. Xu; X. J. Xue; T. H. Li; H. Q. Zeng; X. G. Liu, "Ultrasensitive and Selective Colorimetric DNA Detection by Nicking Endonuclease Assisted Nanoparticle Amplification". Angew. Chem.-Int. Edit. 2009, 48, 6849-6852.
[14] X. J. Xue; F. Wang; X. G. Liu, "One-step, room temperature, colorimetric detection of mercury (Hg2+) using DNA/nanoparticle conjugates". J. Am. Chem. Soc. 2008, 130, 3244-3245.
[15] K. L. Ai; Y. L. Liu; L. H. Lu, "Hydrogen-bonding recognition-induced color change of gold nanoparticles for visual detection of melamine in raw milk and infant formula". J. Am. Chem. Soc. 2009, 131, 9496-9497.
[16] R. K. Bera; A. Anoop; C. R. Raj, "Enzyme-free colorimetric assay of serum uric acid". Chem. Commun. 2011, 47, 11498-11500.
[17] Q. Qian; J. J. Deng; D. L. Wang; L. F. Yang; P. Yu; L. Q. Mao, "Aspartic acid-promoted highly selective and sensitive colorimetric sensing of cysteine in rat brain". Anal. Chem. 2012, 84, 9579-9584.
[18] J. J. Deng; P. Yu; L. F. Yang; L. Q. Mao, "Competitive coordination of Cu2+ between cysteine and pyrophosphate Ion: toward sensitive and selective sensing of pyrophosphate Ion in synovial fluid of arthritis patients". Anal. Chem. 2013, 85, 2516-2522.
[19] S. Kim; M. S. Eom; S. K. Kim; S. H. Seo; M. S. Han, "A highly sensitive gold nanoparticle-based colorimetric probe for pyrophosphate using a competition assay approach". Chem. Commun. 2013, 49, 152-154.
[20] Y. R. Kim; R. K. Mahajan; J. S. Kim; H. Kim, "Highly sensitive gold nanoparticle-based colorimetric sensing of mercury(II) through simple ligand exchange reaction in aqueous media". ACS Appl. Mater. Interfaces 2010, 2, 292-295.
[21] Y. Zhou; S. X. Wang; K. Zhang; X. Y. Jiang, "Visual detection of copper(II) by azide- and alkyne-functionalized gold nanoparticles using click chemistry". Angew. Chem.-Int. Edit. 2008, 47, 7454-7456.
[22] W. X. Xue; G. X. Zhang; D. Q. Zhang, "A sensitive colorimetric label-free assay for trypsin and inhibitor screening with gold nanoparticles". Analyst 2011, 136, 3136-3141.
[23] S. Mandal; A. Gole; N. Lala; R. Gonnade; V. Ganvir; M. Sastry, "Studies on the reversible aggregation of cysteine-capped colloidal silver particles interconnected via hydrogen bonds". Langmuir 2001, 17, 6262-6268.
[24] H. X. Li; L. Rothberg, "Colorimetric detection of DNA sequences based on electrostatic interactions with unmodified gold nanoparticles". Proc. Natl. Acad. Sci. U. S. A. 2004, 101, 14036-14039.
[25] H. X. Li; L. J. Rothberg, "Label-free colorimetric detection of specific sequences in genomic DNA amplified by the polymerase chain reaction". J. Am. Chem. Soc. 2004, 126, 10958-10961.
[26] C. W. Liu; Y. T. Hsieh; C. C. Huang; Z. H. Lin; H. T. Chang, "Detection of mercury(II) based on Hg(2+)-DNA complexes inducing the aggregation of gold nanoparticles". Chem. Commun. 2008, 2242-2244.
[27] Y. Jiang; H. Zhao; Y. Q. Lin; N. N. Zhu; Y. R. Ma; L. Q. Mao, "Colorimetric detection of glucose in rat brain using gold nanoparticles". Angew. Chem.-Int. Edit. 2010, 49, 4800-4804.
[28] Z. D. Wang; J. H. Lee; Y. Lu, "Label-free colorimetric detection of lead ions with a nanomolar detection limit and tunable dynamic range by using gold nanoparticles and DNAzyme". Adv. Mater. 2008, 20, 3263-3267.
[29] J. Oishi; Y. Asami; T. Mori; J.-H. Kang; T. Niidome; Y. Katayama, "Colorimetric enzymatic activity assay based on noncrosslinking aggregation of gold nanoparticles induced by adsorption of substrate peptides". Biomacromolecules 2008, 9, 2301-2308.
[30] Y. M. Chen; C. J. Yu; T. L. Cheng; W. L. Tseng, "Colorimetric detection of lysozyme based on electrostatic interaction with human serum albumin-modified gold nanoparticles". Langmuir 2008, 24, 3654-3660.
[31] Y. Y. Xu; L. Deng; H. Wang; X. Y. Ouyang; J. Zheng; J. S. Li; R. H. Yang, "Metal-induced aggregation of mononucleotides-stabilized gold nanoparticles: an efficient approach for simple and rapid colorimetric detection of Hg(II)". Chem. Commun. 2011, 47, 6039-6041.
[32] Q. P. Shen; W. H. Li; S. Y. Tang; Y. F. Hu; Z. Nie; Y. Huang; S. Z. Yao, "A simple "clickable" biosensor for colorimetric detection of copper(II) ions based on unmodified gold nanoparticles". Biosens. Bioelectron. 2013, 41, 663-668.
[33] J. H. Kim; B. H. Chung, "Naked eye detection of mutagenic DNA photodimers using gold nanoparticles". Biosens. Bioelectron. 2011, 26, 2805-2809.
[34] X. M. He; D. C. Carter, "Atomic-stucture and chemistry of human serum albumin". Nature 1992, 358, 209-215.
[35] T. Bo; J. Pawliszyn, "Characterization of bovine serum albumin-tryptophan interaction by capillary isoelectric focusing with whole column imaging detection". J. Chromatogr. A 2006, 1105, 25-32.
[36] H. Hodl; J. Koidl; M. G. Schmid; G. Gubitz, "Chiral resolution of tryptophan derivatives by CE using canine serum albumin and bovine serum albumin as chiral selectors". Electrophoresis 2006, 27, 4755-4762.
[37] J. Yang; D. S. Hage, "Role of binding capacity versus binding strength in the separation of chiral compounds on protein-based high-performance liquid chromatography columns - Interactions of D- and L-tryptophan with human serum albumin". J. Chromatogr. A 1996, 725, 273-285.
[38] U. Kragh-Hansen; V. T. G. Chuang; M. Otagiri, "Practical aspects of the ligand-binding and enzymatic properties of human serum albumin". Biol. Pharmacol. Bull. 2002, 25, 695-704.
[39] J. Ghuman; P. A. Zunszain; I. Petitpas; A. A. Bhattacharya; M. Otagiri; S. Curry, "Structural basis of the drug-binding specificity of human serum albumin". J. Mol. Biol. 2005, 353, 38-52.
[40] J. Arthur J. Patek, Harold Mankin, Henry Colcher, Alice Lowell and David P. Earle, Jr., "The effects of intravenous injection of concentrated human serum albumin upon blood plasma, ascites and renal functions in three patients with cirrhosis of the liver". J. Clin. Invest. 1947, 27 135-144.
[41] A. I. Ivanov; E. A. Korolenko; E. V. Korolik; S. P. Firsov; R. G. Zhbankov; M. K. Marchewka; H. Ratajczak, "Chronic liver and renal diseases differently affect structure of human serum albumin". Arch. Biochem. Biophys. 2002, 408, 69-77.
[42] R. D. E. William W. Faloon, T. Lynch Murphy, Arnold M. Cooper, and Charles S. Davidson, "An evaluation of human serum albumin in the treatment of cirrhosis of the liver". J. Clin. Invest. 1949, 28, 583-594.
[43] G. D'Amico; C. Bazzi, "Pathophysiology of proteinuria". Kidney Int. 2003, 63, 809-825.
[44] M. A. Kessler; A. Meinitzer; W. Petek; O. S. Wolfbeis, "Microalbuminuria and borderline-increase albumin excretion determined with a centrifugal analyzer and the Albumin Blue 580 fluorescence assay". Clin. Chem. 1997, 43, 996-1002.
[45] C. Khawali; A. Andriolo; S. R. G. Ferreira, "Comparison of methods for urinary albumin determination in patients with type 1 diabetes". Brazilian J. Med. Biol. Res. 2002, 35, 337-343.
[46] A. S. Levey; K. U. Eckardt; Y. Tsukamoto; A. Levin; J. Coresh; J. Rossert; D. de Zeeuw; T. H. Hostetter; N. Lameire; G. Eknoyan, "Definition and classification of chronic kidney disease: A position statement from Kidney Disease: Improving Global Outcomes (KDIGO)". Kidney Int. 2005, 67, 2089-2100.
[47] J. Karalliedde; G. Viberti, "Microalbuminuria and cardiovascular risk". Am. J. Hypertens. 2004, 17, 986-993.
[48] S. C. Satchell; J. E. Tooke, "What is the mechanism of microalbuminuria in diabetes: a role for the glomerular endothelium?". Diabetologia 2008, 51, 714-725.
[49] 陳建銘, 糖尿病腎病變. 腎臟與透析 民國94年, pp 117-122.
[50] 黃清意、賴世偉、林正介, 蛋白尿與微量白蛋白尿. 基層醫學 民國95年, pp 163-167.
[51] D. Sviridov; B. Meilinger; S. K. Drake; G. T. Hoehn; G. L. Hortin, "Coelution of other proteins with albumin during size-exclusion HPLC: Implications for analysis of urinary albumin". Clin. Chem. 2006, 52, 389-397.
[52] Y. W. Wu; J. F. Liu; T. X. Xiao; D. Y. Han; H. L. Zhang; J. C. Pan, "Field-amplified sample injection for the determination of albumin and transferrin in human urines by MEKC". Electrophoresis 2009, 30, 668-673.
[53] E. A. Bessonova; L. A. Kartsova; A. U. Shmukov, "Electrophoretic determination of albumin in urine using on-line concentration techniques". J. Chromatogr. A 2007, 1150, 332-338.
[54] S. Choi; E. Y. Choi; H. S. Kim; S. W. Oh, "On-site quantification of human urinary albumin by a fluorescence immunoassay". Clin. Chem. 2004, 50, 1052-1055.
[55] Y. N. Hong; C. Feng; Y. Yu; J. Z. Liu; J. W. Y. Lam; K. Q. Luo; B. Z. Tang, "Quantitation, Visualization, and Monitoring of Conformational Transitions of Human Serum Albumin by a Tetraphenylethene Derivative with Aggregation-Induced Emission Characteristics". Anal. Chem. 2010, 82, 7035-7043.
[56] J. Tursen; A. M. Wang; W. D. Qin, "Electrophoretic separation of acidic and basic proteins in the presence of micromolar concentrations of an ionic liquid". Microchim. Acta 2011, 174, 63-71.
[57] Y. H. Ding; Y. Shu; L. L. Ge; R. Guo, "The effect of sodium dodecyl sulfate on the conformation of bovine serum albumin". Colloid Surf. A-Physicochem. Eng. Asp. 2007, 298, 163-169.
[58] N. Gull; S. Chodankar; V. K. Aswal; P. Sen; R. H. Khan; D. Kabir ud, "Spectroscopic studies on the interaction of cationic surfactants with bovine serum albumin". Colloid Surf. B-Biointerfaces 2009, 69, 122-128.
[59] N. P. a. H. G. Brittain, Analytical applications of circular dichroism. 1994.
[60] Y. F. Wang; J. Y. Gao; P. L. Dubin, "Protein separation via polyelectrolyte coacervation: Selectivity and efficiency". Biotechnol. Prog. 1996, 12, 356-362.
[61] C. Z. Wang; C. A. Lucy, "Oligomerized phospholipid bilayers as semipermanent coatings in capillary electrophoresis". Anal. Chem. 2005, 77, 2015-2021.
[62] O. Kokpinar; D. Harkensee; C. Kasper; T. Scheper; R. Zeidler; O. W. Reif; R. Ulber, "Innovative modular membrane adsorber system for high-throughput downstream screening for protein purification". Biotechnol. Prog. 2006, 22, 1215-1219.
[63] Y. Lu; C. L. Yan; S. Y. Gao, "Preparation and recognition of surface molecularly imprinted core-shell microbeads for protein in aqueous solutions". Appl. Surf. Sci. 2009, 255, 6061-6066.
[64] C. W. Chang; S. P. Chu; W. L. Tseng, "Selective extraction of melamine using 11-mercaptoundecanoic acid-capped gold nanoparticles followed by capillary electrophoresis". J. Chromatogr. A 2010, 1217, 7800-7806.
[65] Y. Jv; B. X. Li; R. Cao, "Positively-charged gold nanoparticles as peroxidiase mimic and their application in hydrogen peroxide and glucose detection". Chem. Commun. 2010, 46, 8017-8019.
[66] P. Selvakannan; S. Mandal; S. Phadtare; A. Gole; R. Pasricha; S. D. Adyanthaya; M. Sastry, "Water-dispersible tryptophan-protected gold nanoparticles prepared by the spontaneous reduction of aqueous chloroaurate ions by the amino acid". J. Colloid Interface Sci. 2004, 269, 97-102.
[67] C. C. W. a. E. J. Baran, "Spectroscopic and Magnetic Behaviour of the Copper (II) Complex of L-Tryptophan". Acta Farm. Bonaerense 2004, 23, 339-342.
[68] M. Iosin; P. Baldeck; S. Astilean, "Study of tryptophan assisted synthesis of gold nanoparticles by combining UV-Vis, fluorescence, and SERS spectroscopy". J. Nanopart. Res. 2010, 12, 2843-2849.
[69] B. Aswathy; S. Suji; G. S. Avadhani; R. Aswathy; S. Suganthi; G. Sony, "Microwave assisted one pot synthesis of biocompatible gold nanoparticles in Triton X-100 aqueous micellar medium using tryptophan as reducing agent". J. Mol. Liq. 2011, 162, 155-158.
[70] W. H. Gao; J. Xi; Y. S. Chen; S. Xiao; X. Q. Wang; J. Li; J. C. Xiao; Y. W. Chen, "Hydrogen-Bonding Recognition-Induced Colorimetric Determination of Hydrazine Based on the Tryptophan Capped Gold Nanoparticles". J. Spectrosc. 2013.
[71] J. F. Liu; Y. W. Wu; Y. H. Cheng; X. W. Zhou; H. L. Zhang; D. Y. Han, "Micellar electrokinetic chromatography assay for the simultaneous quantification of urinary transferrin and albumin". Microchim. Acta 2009, 165, 285-290.
[72] C. Y. Lin; W. L. Tseng, "Selective enrichment of albumin in biological samples by CE using segmental filling with sodium octyl sulfate in the background electrolyte". Electrophoresis 2009, 30, 532-539.
[73] C. J. Huang; C. C. Lu; T. Y. Lin; T. C. Chou; G. B. Lee, "An electrochemical albumin-sensing system utilizing microfluidic technology". J. Micromech. Microeng. 2007, 17, 835-842.
[74] K. Omidfar; A. Dehdast; H. Zarei; B. K. Sourkohi; B. Larijani, "Development of urinary albumin immunosensor based on colloidal AuNP and PVA". Biosensors &; Bioelectronics 2011, 26, 4177-4183.
[75] L. X. Zhao; J. M. Lin; Z. J. Li, "Comparison and development of two different solid phase chemiluminescence ELISA for the determination of albumin in urine". Anal. Chim. Acta 2005, 541, 199-207.
[76] W. Laiwattanapaisal; P. Saythanu; P. Nubtueboon; T. Tencomnao; R. Santiyanont, "A High-throughput Nonimmunological Method for Determination of Microalbuminuria Based on Utilization of Albumin Blue 580". Labmedicine 2008, 39, 727-729.
[77] W. E. Owen; W. L. Roberts, "Performance characteristics of an HPLC assay for urinary albumin". Am. J. Clin. Pathol. 2005, 124, 219-225.
[78] L. Marko; G. A. Molnar; Z. Wagner; K. Boddi; T. Koszegi; Z. Szabo; Z. Matus; I. Szijarto; A. Merei; G. Nagy; I. Wittmann, "Measurement of the modification and interference rate of urinary albumin detected by size-exclusion HPLC". Physiol. Meas. 2009, 30, 1137-1150.
[79] J. Shiea; Y. T. Cho; Y. H. Lin; C. W. Chang; L. H. Lo; Y. C. Lee; H. L. Ke; W. J. Wu; D. C. Wu, "Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to rapidly screen for albuminuria". Rapid Commun. Mass Spectrom. 2008, 22, 3754-3760.
[80] Y. T. Cho; Y. S. Chen; J. L. Hu; J. Shiea; S. M. Yeh; H. C. Chen; Y. C. Lee; D. C. Wu, "The study of interferences for diagnosing albuminuria by matrix-assisted laser desorption ionization/time-of-flight mass spectrometry". Clin. Chim. Acta 2012, 413, 875-882.