摘要
真菌毒素在全球范围内威胁农作物和农产品的安全,造成的直接或间接经济损失严重,同时经由污染的农产品和食品可对人体健康产生严重危害甚至死亡,其中尤以黄曲霉毒素和赭曲霉毒素毒性最大、污染最为严重。传统检测方法如薄层色谱、高效液相色谱以及酶联免疫吸附在检测时间、设备成本或操作等方面存在局限。基于金属纳米粒子的光学生物传感方法具有快速、简单的优势,是一种潜在的解决手段。其中金纳米棒这种各向异性的一维纳米材料,因独特的光学特性,在近年来备受关注。
本课题以花生、谷物等农产品中常见的真菌毒素黄曲霉毒素B1(aflatoxin B1,AFB1)和赭曲霉毒素A (ochratoxin A, OTA)为检测对象,以特异性单克隆抗体和适配体(aptamer)为生物识别元件,分别建立了基于金纳米棒局域等离子体共振(localized surface plasmon resonance, LSPR)吸收光谱和动态光散射(dynamic light scattering, DLS)的生物传感方法和定量检测模型。首次探索了基于金纳米棒的多种生物传感方式对小分子真菌毒素的简单、快速检测,为农产品中真菌毒素的现场测定提供了一种新思路。
本文的主要内容和研究结果如下：
(1)分析和研究了贯穿整个课题的纳米材料-金纳米棒的物理和化学特性。基于透射电子显微镜、紫外-可见-近红外吸收光谱和拉曼光谱、动态光散射、电感耦合等离子体质谱等手段对实验室制备的金纳米棒的尺寸、水合粒径、浓度和光谱特性等进行了表征。稳定性研究结果显示：金纳米棒在不同pH(2-13范围内)的CTAB溶液中均表现出较高的稳定性；在高浓度CTAB体系中,金纳米棒抗离子强度的稳定性较强；金纳米棒与浓度在0-10mM或大于100mM的磷酸盐缓冲液混合后比较稳定。金纳米棒特性分析是本课题研究的基础,也是金纳米棒分析和应用的理论依据。
(2)以甲胎蛋白(a-fetoprotein, AFP)为模型,尝试和比较了基于末端和全表面抗体修饰的金纳米棒的不同免疫传感应用。1)建立了基于末端修饰的金纳米棒的直接免疫传感方法：通过直观的金纳米棒LSPR波长的偏移来识别金纳米棒端面AFP结合后周围环境折射率的变化,此方法线性检测范围相对较窄,对设备要求较高；通过吸收强度变化来识别金纳米棒末端修饰的AFP分子,可建立定量模型,但检测性能不理想。2)建立了基于全表面抗体修饰的金纳米棒直接聚集的免疫传感方法：金纳米棒纵向LSPR偏移与AFP标准溶液(0.25-4.0nM)线性定量模型的检测限和定量限分别为0.18和0.60nM；金纳米棒LSPR吸收强度与在PBS缓冲液中AFP标准溶液(0.25-4.0nM)定量模型的检测限和定量限分别为0.04和0.14nM,选择性试验中干扰蛋白所引起的吸收强度信号与单纯AFP的信号相比变化小于5.3%。结果表明,金纳米棒直接聚集导致的等离子体共振耦合信号增强为小分子真菌毒素的定量检测提供了可行性。
(3)建立了一种基于金纳米棒竞争分散方式的免标记、简单一步快速检测的免疫传感方法,并将其用于农产品中黄曲霉毒素B1的测定。功能化的GNR-AFB1-BSA偶联物与AFB1特异性单克隆抗体混合后发生不可逆的聚集,导致金纳米棒吸收强度的下降以及水合粒径的显著增大；当样本中游离AFB1分子存在时,可与GNR-AFB1-BSA偶联物竞争结合到特异性抗体上,使得金纳米棒在溶液中呈分散的状态。所建立传感方法可有效避免复杂环境应用时因非特异性聚集而产生的假信号。金纳米棒的吸收强度被用作传感信号,同时液体样本中金纳米棒平均水合粒径的测量也被用作传感的方法。研究了不同抗体浓度对金纳米棒聚集程度和AFB1定量检测结果的影响：当抗体浓度为15μg/mL时,所建立吸收强度与AFB1浓度的线性定量模型的检测限为0.035ng/mL,但检测范围较窄(0.1-1.0ng/mL);当抗体浓度为25μg/mL时,线性定量模型的检测限为0.16ng/mL,线性检测范围为0.5-20ng/mL,满足欧盟标准的测定需求。利用其他三种黄曲霉毒素和四种农产品中常见真菌毒素对所建立的免疫传感器的选择性进行评估。并将建立的传感方法应用于真实花生样本的分析,经计算加标回收率在94.2%-117.3%范围内。结果表明,基于金纳米棒竞争分散方式的免疫传感方法可快速、简单定量检测AFB1,同时对真实样本的测定具有良好的准确度和可信度。
(4)探索了基于金纳米棒肩并肩与头碰头组装结构的适配体传感器(aptasensor)用于赭曲霉毒素A的快速、灵敏检测。修饰在金纳米棒全表面和两个端面的适配体与互补脱氧核糖核苷酸(deoxyribonucleic acid,DNA),在一定条件下可发生核酸杂交(hybridization),诱导金纳米棒发生肩并肩或头碰头的组装,形成链状结构；当溶液中存在目标配体OTA小分子时,适配体构象发生变化,形成G-四聚体结构将OTA埋在其中,此时适配体无法与互补DNA杂交,金纳米棒组装结构减少,可实现真菌毒素OTA的检测。本文构建并表征了金纳米棒肩并肩和头碰头两种组装结构,其中肩并肩组装的金纳米棒的等离子体耦合更为显著,可进一步用于OTA的测定。将两种全表面修饰的金纳米棒探针与不同浓度的OTA标准溶液(0-100ng/mL)混合,结果显示：随着OTA浓度增大,金纳米棒纵向LSPR吸收强度逐渐增大。由此根据706nm波长处吸收强度可以建立OTA定量检测的方法。同时利用农产品中其他五种常见的真菌毒素评估基于金纳米棒肩并肩组装结构的适配体传感器的特异性。结果表明,基于金纳米棒肩并肩组装结构的光学适配体传感方法具有高灵敏、高特异性定量测定农产品中OTA的潜力。
(5)搭建了真菌毒素检测用便携式快速检测平台,并将其应用于花生样本中AFB1含量的测定。基于该平台,应用金纳米棒竞争分散的传感方法建立AFB1标准溶液浓度与吸收强度之间的关系。在0-5.0ng/mL浓度范围时,金纳米棒吸收强度(709nm)与AFB1浓度呈线性关系,检测限为0.066ng/mL,线性检测范围为0.22-5.0ng/mL。利用该平台可测定当地农贸市场购买的新鲜花生和实验室保存8个月的花生样本中的AFB1含量,加标回收率理想分别为97.6%和95.7%,检测结果与高效液相色谱标准方法的测定结果基本一致。结果表明,基于此平台的真菌毒素检测用新型光学纳米生物传感器具有测量结果准确可信、分析成本低、快速、体积小便于携带等特点,适用于真菌毒素的现场检测。
The damage of crops and agro-products caused by mycotoxins induces serious economic losses directly and indirectly on a global scale. Many mycotoxins can cause serious harm to human health and even death in people through mycotoxin-contaminated food, especially aflatoxins and ochratoxins which are most toxic and polluted. Traditional detection methods such as thin layer chromatography (TLC), high performance liquid chromatography (HPLC) and enzyme-linked immuno sorbent assay (ELISA) are sensitive; however, more rapid, simple, and cost-effective approaches are still requested by the food industry. More recently optical biosensors coupled with metal nanoparticles provides a promising potential approach for the purpose, which is perhaps one of the most powerful and simple nanosensing methods available. Wherein gold nanorods (GNRs) as one kind of anisotropy one-dimensional materials, have received much attention in the past decade due to their unique optical properties.
In this study, aflatoxin B1(AFB1) and ochratoxin A (OTA) in common agro-products like peanuts and grain were selected as detection target of interest. Biosensing methods and quantitative detection models based on localized surface plasmon resonance (LSPR) absorption spectra and dynamic light scattering (DLS) of GNRs have been established, with biological recognition elements of specific monoclonal antibody and aptamer. It is the first time to explore the available biosensing approaches based on GNRs for rapid and simple discrimination of mycotoxins, providing a new platform for on-site testing of mycotoxin contamination in common agro-products.
The main contents and results are summarized as follows:
(1) The physical and chemical properties of GNRs were studied initially. Various techniques including transmission electron microscopy (TEM), UV-vis-NIR absorption spectra, dynamic light scattering and inductively coupled plasma mass spectrometry (ICP-MS) were used for size, hydrodynamic diameter, concentration and optical property characterization of GNRs. The results of stability study showed that:GNRs could keep stable in CTAB solution of different pH environment (pH value from2to13); higher stability of GNRs could been observed under strong ionic strength conditions at a higher CTAB concentration, and GNRs got irreversible aggregation while mixing with NaCl solution concentration greater than160mM; GNRs could keep stable in biological analyzing buffer of phosphate buffered saline (PBS) with concentration in the range of0-10mM or greater than100mM. It provided theoretical basis for analysis and application based on GNRs.
(2) Different biosensing method based on end and satellite antibody modified GNRs were established and compared, using alpha-fetoprotein (AFP) as a model analyte which is one of the major markers for hepatocellular tumors. Direct immune sensing method with end modified GNRs was investigated. Change in refractive index of surrounding environment after AFP binding was recognized according to shift of longitudinal LSPR wavelength, however the linear detection range of this method was narrow (0.25-1.0nM) with high requirement of equipment in resolution and signal to noise ratio. Absorption intensity of normalized spectra could also been used for AFP sensing (0.25-14.3nM), however the detection performance was not ideal. For immune sensing approach with satellite modified GNRs, dramatic aggregation of GNRs was induced by the interaction between target proteins and capture antibodies. Associated wavelength red-shifts and intensity decreases in the absorption peak of GNRs were observed with increasing concentrations of target AFP. It was illustrated that this method can be used reliably to detect AFP protein in PBS solution at concentrations of picomolar level with a wide quantification range from0.25to4.0nM. The limit of detection and quantification based on wavelength shift was0.18and0.60nM, and based on absorption intensity was0.04and0.14nM, respectively. The complication of interfering proteins in the sample showed negligible effects on the detection results. It is expected that plamon coupling based signal enhancement caused by GNR aggregation would be applicable for discrimination of mycotoxins in agro-products at low concentrations.
(3) A promising one-step and label-free optical biosensor was illustrated for determination of AFB1that is most commonly found in foods and highly dangerous even at very low concentrations. In this research, GNRs were employed as a sensing platform, which showed high stability under high ionic strength conditions without addition of any stabilizing agent. GNR-AFB1-BSA (bovine serum albumin) conjugates aggregated after mixing with free antibodies, resulting in significant changes in absorption intensity. At the same time the existence of AFB1molecules in samples caused dispersion of nanorods, as a result of competitive immune-reaction with antibodies. By taking advantages of the competitive dispersion of GNRs, the developed method could effectively reduce false results caused by undesirable aggregation, which is a big problem for spherical gold nanoparticles. Absorption intensity of UV-vis spectra served as the sensing indicator, with dynamic light scattering measurement as another sensing tool. While the concentration of AFB1antibody was15μg/mL, the biosensing system could detect AFB1standard PBS solution linearly from0.1to1.0ng/mL, with a low limit of detection (LOD) of0.035ng/mL. While the concentration of AFB1antibody was25μg/mL, the designed biosensing system could detect AFB1in a linear range from0.5to20ng/mL, with a good correlation coefficient of0.99. And the limit of detection was0.16ng/mL, indicating an excellent sensitivity with absorbance result. The recoveries of the spiked AFB1in real peanut samples ranged from94.2%to117.3%. Therefore the proposed nano-biosensor was demonstrated to be sensitive, selective, and simple, providing a viable alternative for rapid screening of toxins in agriculture products and foods.
(4) Rapid and sensitive aptasensors based on GNR side-by-side and end-to-end assemblies were explored for OTA screening. Aptamer and complementary DNA (cDNA) modified on satellite and end faces of GNRs hybridized under certain conditions, resulting in chain-like structure induced by side-by-side and end-to-end assembly of GNRs. The conformation of aptamer changed in the presence of free OTA molecule in solution, forming a G-quartet of OTA aptamer. As a result, the GNR assemblies reduced with the increasing of OTA concentration, which could been used for OTA detection. GNR side-by-side and end-to-end sassemblies were characterized and optimized. Plasmon coupling of side-by-side GNR assembly was observed stronger than that of end-to-end assembly, which was potential for OTA detecton. Thus, satellite-modified GNR-aptamer and GNR-cDNA probes mixed well and reacted with different concentration of OTA standard solution (0-100ng/mL), and the absorption intensity of GNRs at706nm could be employed as signal indicator for quantification of OTA. Other five mycotoxins common in agro-products were detected for evaluation the selectivity of the proposed aptasensor. It was indicated that the optical aptasensor based on GNR side-by-side assemblies could been potential for OTA discrimination with high sensitivity and specificity.
(5) A portable and rapid detecting platform for mycotoxin was constructed, and applied for determination of AFB1content in peanut samples. The relationship between AFB1concentration and absorption intensity of UV-vis spectra at709nm was set up using the platform based on competitive dispersion of GNRs. AFB1in standard PBS solution could be detected linearly from0.22to5.0ng/mL, with a low limit of detection of0.066ng/mL. AFBl in fresh and stored peanut samples purchased from local agricultural market were detected, resulting in ideal spiked recoveries of97.6%and95.7%, respectively. Additionally, the measurement results kept consistent with standard method of HPLC results. Therefore it was indicated that the novel optical nano biosensor based on the portable platform was promising for on-site detection of mycotoxins, with advantages of accurate, reliable and fast measurements, cost-effective, small-size and easy to carry.
引文
1.计成.霉菌毒素与饲料食品安全.北京：化学工业出版社.2007.
2. Forgacs, J. Mycotoxicoses-the neglected diseases. Feedstuffs.1962,34:124-134.
3. Bennett, J. W., Klich, M. Mycotoxins. Clinical Microbiology Reviews.2003,16(3):497-516.
4. Wogan, G. N. Chemical nature and biological effects of the aflatoxins. Bacteriological Reviews.1966,30(2): 460-470.
5. Mishra, H. N., Das, C. A review on biological control and metabolism of aflatoxin. Critical Reviews in Food Science and Nutrition.2003,43(3):245-264.
6. Wild, C. P., Turner, P. C. The toxicology of aflatoxins as a basis for public health decisions. Mutagenesis.2002, 17(6):471-481.
7.张艺兵,鲍蕾,褚庆华.农产品中真菌毒素的检测分析.北京：化学工业出版社.2006.
8. Aflatoxin Contamination of Maize in Africa.accessed [2010-6-18]. http://www.fas.org/blog/nutshell/2010/06/aflatoxin-contamination-of-maize-in-africa/.
9. A ProMED-mail post.accessed [2011-12-31]. http://www.promedmail.org/direct.php?id=20111231.3719.
10. Duarte, S. C, Lino, C. M., Pena, A. Mycotoxin food and feed regulation and the specific case of ochratoxin A:a review of the worldwide status. Food Additives and Contaminants:Part A.2010,27(10):1440-1450.
11. Pohland, A. E., Nesheim, S., Friedman, L. Ochratoxin A-a review-(Technical report). Pure and Applied Chemistry. 1992,64(7):1029-1046.
12. Universidad de Cordoba:Aspergillus Mich.ex Fr. accessed http://www.uco.es/aerobiologia/hongos/aspergil.htm.
13. Mycotoxins. Food and Agriculture Organization of United Nations.accessed http://www.coffee-ota.org/mycotoxins_what.asp.
14. CAST. Mycotoxins:Economic and Health Risks. Council for Agricultural Science and Technology.1989.
15. Magan, N., Olsen, M. Mycotoxins in food:detection and control. Cambridge:Woodhead Publishing.2004.
16.王世平.食品安全检测技术.北京：中国农业大学出版社,2009.
17. EU. (2010) European Union. Commission Regulation (EU) No105/2010.
18. EU. (2010) European Union. Commission Regulation (EU) No106/2010.
19.王君,刘秀梅.部分市售食品中总黄曲霉毒素污染的监测结果.中华预防医学杂志,2006,40(1)：33-37.
20.马皎洁,邵兵,林肖惠,于红霞,李凤琴.我国部分地区2010年产谷物及其制品中多组分真菌毒素污染状况研 究.中国食品卫生杂志.2011,23(6)：481-488.
21.杨家玲.我国主要食品中赭曲霉毒素A调查与风险评估[硕士论文].咸阳：西北农林科技大学.2008.
22.中华人民共和国卫生部.(2011)GB 2761-2011食品安全国家标准—食品中真菌毒素限量.
23.中华人民共和国国家质量监督检验检疫总局.(2004)GB/T 19539-2004饲料中赭曲霉毒素A的测定.
24.中华人民共和国卫生部.(2006)GB/T5009.23-2006食品中黄曲霉毒素B1、B2、G1、G2的测定.
25. Lin, L., Zhang, J., Wang, P., Wang, Y., Chen, J. Thin-layer chromatography of mycotoxins and comparison with other chromatographic methods. Journal of Chromatography A.1998,815(1):3-20.
26. Turner, N. W., Subrahmanyam, S., Piletsky, S. A. Analytical methods for determination of mycotoxins:A review. Analytica Chimica Acta.2009,632(2):168-180.
27.孙秀兰.食品中黄曲霉毒素B1金标免疫层析检测方法研究[博士论文].无锡：江南大学.2005.
28. Reinhard, H., Zimmerli, B. Reversed-phase liquid chromatographic behavior of the mycotoxins citrinin and ochratoxin A. Journal of Chromatography A.1999,862(2):147-159.
29. Valenta, H. Chromatographic methods for the determination of ochratoxin A in animal and human tissues and fluids. Journal of Chromatography A.1998,815(1):75-92.
30. Hernandez, M. J., Garcia-Moreno, M. V., Duran, E., Guillen, D., Barroso, C. G. Validation of two analytical methods for the determination of ochratoxin A by reversed-phased high-performance liquid chromatography coupled to fluorescence detection in musts and sweet wines from Andalusia. Analytica Chimica Acta.2006,566(1):117-121.
31. Calleri, E., Marrubini, G., Brusotti, G., Massolini, G., Caccialanza, G. Development and integration of an immunoaffinity monolithic disk for the on-line solid-phase extraction and HPLC determination with fluorescence detection of aflatoxin B1 in aqueous solutions. Journal of Pharmaceutical and Biomedical Analysis.2007,44(2): 396-403.
32.李冬阳.用于毒素检测的酶联免疫吸附测定(ELISA)研究[博士论文].杭州：浙江大学.2012.
33.杨利国,胡绍旭,魏平华.酶免疫测定技术.南京：南京大学出版社.1998.
34.黄飚.赭曲霉毒素A和黄曲霉毒素B1的超微量免疫分析[博士论文].无锡：江南大学.2006.
35. Pei, S. C., Li, Y. H., Zhang, Y. Y., Cai, L., Lee, W. J. Detection of aflatoxin B, in corn, rice, and barley by ELISA, using a heavy-chain IgG(2b) Isotype monoclonal antibody. Journal of the American Society of Brewing Chemists. 2010,68(1):10-14.
36. Alcaide, F. J. E., Aguilar, S. A. Validation study of immunochemical ELISA assay for ochratoxin a quantification in dessert wines from sun-dried grapes. Ciencia E Tecnica Vitivinicola.2008,23(1):53-60.
37. Goryacheva, I. Y., Saeger, S. D., Eremin, S. A., Peteghem, C. V. Immunochemical methods for rapid mycotoxin detection:Evolution from single to multiple analyte screening:A review. Food Additives and Contaminants.2007, 24(10):1169-1183.
38. Zheng, M., Richard, J., Binder, J. A review of rapid methods for the analysis of mycotoxins. Mycopathologia.2006, 161(5):261-273.
39.蒋雪松.用于有机磷农药残留检测的免疫生物传感器的研究[博士论文].杭州：浙江大学.2008.
40. Updike, S. J., Hicks, G. P. The enzyme electrode. Nature.1967,214:986-989.
41. Bellan, L. M., Wu, D., Langer, R. S. Current trends in nanobiosensor technology. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology.2011,3(3):229-246.
42. Valiev, R. Materials science:nanomaterial advantage. Nature.2002,419(6910):887-889.
43. Wang, J. Nanomaterial-based amplified transduction of biomolecular Interactions. Small.2005,1(11):1036-1043.
44. Mulvaney, P. Surface plasmon spectroscopy of nanosized metal particles. Langmuir.1996,12(3):788-800.
45. Shipway, A. N., Katz, E., Willner, I. Nanoparticle arrays on surfaces for electronic, optical, and sensor applications. ChemPhysChem.2000,1(1):18-52.
46.鞠烷光,张学记,约瑟夫.王.纳米生物传感：原理、发展与应用.北京：科学出版社.2012.
47. Jokerst, J. V., Raamanathan, A., Christodoulides, N., Floriano, P. N., Pollard, A. A., Simmons, G. W., Wong, J., Gage, C., Furmaga, W. B., Redding, S. W., McDevitt, J. T. Nano-bio-chips for high performance multiplexed protein detection:Determinations of cancer biomarkers in serum and saliva using quantum dot bioconjugate labels. Biosensors and Bioelectronics.2009,24(12):3622-3629.
48. Wang, L., Chen, W., Ma, W., Liu, L., Ma, W., Zhao, Y., Zhu, Y., Xu, L., Kuang, H., Xu, C. Fluorescent strip sensor for rapid determination of toxins. Chemical Communications.2011,47(5):1574-1576.
49. Luo, X., Morrin, A., Killard, A. J., Smyth, M. R. Application of nanoparticles in electrochemical sensors and biosensors. Electroanalysis.2006,18(4):319-326.
50. Ambrosi, A., Airo, F., Merkoci, A. Enhanced gold nanoparticle based ELISA for a breast cancer biomarker. Analytical Chemistry.2009,82(3):1151-1156.
51. Liu, M., Jia, C., Huang, Y., Lou, X., Yao, S., Jin, Q., Zhao, J., Xiang, J. Highly sensitive protein detection using enzyme-labeled gold nanoparticle probes. Analyst.2010,135(2):327-331.
52. Wang, Y., Liu, B. Conjugated polymer as a signal amplifier for novel silica nanoparticle-based fluoroimmunoassay. Biosensors and Bioelectronics.2009,24(11):3293-3298.
53. Boisselier, E., Astruc, D. Gold nanoparticles in nanomedicine:preparations, imaging, diagnostics, therapies and toxicity. Chemical Society Reviews.2009,38(6):1759-1782.
54. Thakor, A., Jokerst, J., Zavaleta, C., Massoud, T., Gambhir, S. Gold nanoparticles:a revival in precious metal administration to patients. Nano Letters.2011,11(10):4029-4036.
55. Jain, P., Huang, X., El-Sayed, I., El-Sayed, M. Review of some Interesting surface plasmon resonance-enhanced properties of noble metal nanoparticles and their applications to biosystems. Plasmonics.2007,2(3):107-118.
56. de Heer, W. A. The physics of simple metal clusters:experimental aspects and simple models. Reviews of Modern Physics.1993,65(3):611-676.
57. Tokonami, S., Yamamoto, Y., Shiigi, H., Nagaoka, T. Synthesis and bioanalytical applications of specific-shaped metallic nanostructures:A review. Analytica Chimica Acta.2012,716(0):76-91.
58. Stewart, M. E., Anderton, C. R., Thompson, L. B., Maria, J., Gray, S. K., Rogers, J. A., Nuzzo, R. G. Nanostructured plasmonic sensors. Chemical Reviews.2008,108(2):494-521.
59. Kreibig, U., Vollmer, M. Optical properties of metal clusters. Berlin:Springer.1995.
60. Link, S., El-Sayed, M. A. Spectral properties and relaxation dynamics of surface plasmon electronic oscillations in gold and silver nanodots and nanorods. The Journal of Physical Chemistry B.1999,103(40):8410-8426.
61.李心.纳米金颗粒在生物光学传感及成像中的一些应用研究[博士论文].杭州：浙江大学.2010.
62. Anker, J. N., Hall, W. P., Lyandres, O., Shah, N. C., Zhao, J., Van Duyne, R. P. Biosensing with plasmonic nanosensors. Nature Materials.2008,7(6):442-453.
63.吴同.特定形态贵金属纳米粒子的制备及其在生物小分子与环境无机高子分析中的应用研究[博士论文].重庆：西南大学.2009.
64. Lal, S., Link, S., Halas, N. J. Nano-optics from sensing to waveguiding. Nature Photonics.2007,1(11):641-648.
65. Link, S., El-Sayed, M. A. Size and temperature dependence of the plasmon absorption of colloidal gold nanoparticles. The Journal of Physical Chemistry B.1999,103(21):4212-4217.
66.凌剑.银纳米粒子的局域表面等离子体共振散射在生化药物分析中的应用研究[博士论文].重庆：西南大学.2009.
67. Haiss, W., Thanh, N. T. K., Aveyar, J., Fernig, D. G. Determination of size and concentration of gold nanoparticles from UV-vis spectra. Analytical Chemistry.2007,79(11):4215-4221.
68. Haes, A. J. Localized surface plasmon resonance spectroscopy for fundamental studies of nanoparticle optics and applications to biosensors[Doctoral Dissertation]. Evanston, Illinois:Northwestern University.2004.
69. Willets, K. A., Van Duyne, R. P. Localized surface plasmon resonance spectroscopy and sensing. Annual Review of Physical Chemistry.2007,58:267-297.
70.毕宁.金纳米粒子的合成及其在局域表面等离子体共振传感器中的应用[博士论文].长春：吉林大学.2012.
71. Nath, N., Chilkoti, A. A colorimetric gold nanoparticle sensor to interrogate biomolecular interactions in real time on a surface. Analytical Chemistry.2002,74(3):504-509.
72. Nath, N., Chilkoti, A. Label-free biosensing by surface plasmon resonance of nanoparticles on glass:optimization of nanoparticle size. Analytical Chemistry.2004,76(18):5370-5378.
73. Frederix, F., Friedt, J.-M., Choi, K.-H., Laureyn, W., Campitelli, A., Mondelaers, D., Maes, G., Borghs, G. Biosensing based on light absorption of nanoscaled gold and silver particles. Analytical Chemistry.2003,75(24): 6894-6900.
74. Elghanian, R., Storhoff, J. J., Mucic, R. C., Letsinger, R. L., Mirkin, C. A. Selective colorimetric detection of polynucleotides based on the distance-dependent optical properties of gold nanoparticles. Science.1997,277(5329): 1078-1081.
75. Cao, Y. C., Jin, R., Mirkin, C. A. Nanoparticles with Raman spectroscopic fingerprints for DNA and RNA detection. Science.2002,297(5586):1536-1540.
76. Rosi, N. L., Giljohann, D. A., Thaxton, C. S., Lytton-Jean, A. K. R., Han, M. S., Mirkin, C. A. Oligonucleotide-modified gold nanoparticles for intracellular gene regulation. Science.2006,312(5776):1027-1030.
77. Sonnichsen, C., Reinhard, B. M., Liphardt, J., Alivisatos, A. P. A molecular ruler based on plasmon coupling of single gold and silver nanoparticles. Nature Biotechnology.2005,23(6):741-745.
78. Zhao, W., Brook, M. A., Li, Y. Design of gold nanoparticle-based colorimetric biosensing assays. ChemBioChem. 2008,9(15):2363-2371.
79. Yguerabide, J., Yguerabide, E. E. Light-scattering submicroscopic particles as highly fluorescent analogs and their sse as tracer labels in clinical and biological applications:I. theory. Analytical Biochemistry.1998,262(2):137-156.
80. Storhoff, J. J., Lucas, A. D., Garimella, V., Bao, Y. P., Muller, U. R. Homogeneous detection of unamplified genomic DNA sequences based on colorimetric scatter of gold nanoparticle probes. Nature Biotechnology.2004, 22(7):883-887.
81. Dykman, L., Khlebtsov, N. Gold nanoparticles in biomedical applications:recent advances and perspectives. Chemical Society Reviews.2012,41(6):2256-2282.
82. Sepulveda, B., Angelome, P. C., Lechuga, L. M., Liz-Marzan, L. M. LSPR-based nanobiosensors. Nano Today.2009, 4(3):244-251.
83. Talley, C. E., Jackson, J. B., Oubre, C., Grady, N. K., Hollars, C. W., Lane, S. M., Huser, T. R., Nordlander, P., Halas, N. J. Surface-enhanced raman scattering from individual Au nanoparticles and nanoparticle dimer substrates. Nano Letters.2005,5(8):1569-1574.
84. Hinterwirth, H., Kappel, S., Waitz, T., Prohaska, T., Lindner, W., Lammerhofer, M. Quantifying thiol ligand density of self-assembled monolayers on gold nanoparticles by iductively coupled plasma-mass spectrometry. ACS Nano. 2013,7(2):1129-1136.
85. Tang, H.-W., Lu, W., Che, C.-M., Ng, K.-M. Gold nanoparticles and imaging mass spectrometry:double imaging of latent fingerprints. Analytical Chemistry.2010,82(5):1589-1593.
86. Huang, X. H., Neretina, S., El-Sayed, M. A. Gold nanorods:from synthesis and properties to biological and biomedical applications. Advanced Materials.2009,21(48):4880-4910.
87. Huang, X., E1-Sayed, M. A. Gold nanoparticles:optical properties and implementations in cancer diagnosis and photothermal therapy. Journal of Advanced Research.2010,1(1):13-28.
88. Gans, R. The form of ultramicroscopic gold particles. Annals of Physics.1912,37(5):881-900.
89.王春刚.金纳米棒的表面修饰及其生物识别的研究[博士论文].长春：东北师范大学.2007.
90. Link, S., Mohamed, M. B., El-Sayed, M. A. Simulation of the optical absorption spectra of gold nanorods as a function of their aspect ratio and the effect of the medium dielectric constant. The Journal of Physical Chemistry B. 1999,103(16):3073-3077.
91.王健.基于金纳米棒的生物传感与癌症的光热治疗研究[博士论文].重庆：西南大学.2012.
92. Chen, H., Shao, L., Li, Q., Wang, J. Gold nanorods and their plasmonic properties. Chemical Society Reviews.2013.
93. Xu, L., Kuang, H., Wang, L., Xu, C. Gold nanorod ensembles as artificial molecules for applications in sensors. Journal of Materials Chemistry.2011,21(42):16759-16782.
94. Mitamura, K., Imae, T. Functionalization of gold nanorods toward their applications. Plasmonics.2009,4(1):23-30.
95. Murphy, C. J., Thompson, L. B., Alkilany, A. M., Sisco, P. N., Boulos, S. P., Sivapalan, S. T., Yang, J. A., Chernak, D. J., Huang, J. The many faces of gold nanorods. The Journal of Physical Chemistry Letters.2010,1(19): 2867-2875.
96. Vigderman, L., Khanal, B. P., Zubarev, E. R. Functional gold nanorods:synthesis, self-assembly, and sensing applications. Advanced Materials.2012,24(36):4811-4841.
97. Huang, H., Chen, S., Liu, F., Zhao, Q., Liao, B., Yi, S., Zeng, Y. Multiplex plasmonic sensor for detection of different metal ions based on a single type of gold nanorod. Analytical Chemistry.2013,85(4):2312-2319.
98. He, W., Huang, C. Z., Li, Y. F., Xie, J. P., Yang, R. G., Zhou, P. F., Wang, J. One-step label-free optical genosensing system for sequence-specific DNA related to the human immunodeficiency virus based on the measurements of light scattering signals of gold nanorods. Analytical Chemistry.2008,80(22):8424-8430.
99. Wang, X., Li, Y., Wang, H., Fu, Q., Peng, J., Wang, Y., Du, J., Zhou, Y., Zhan, L. Gold nanorod-based localized surface plasmon resonance biosensor for sensitive detection of hepatitis B virus in buffer, blood serum and plasma. Biosensors and Bioelectronics.2010,26(2):404-410.
100. Zhen, S. J., Huang, C. Z., Wang, J., Li, Y. F. End-to-end assembly of gold nanorods on the basis of aptamer protein recognition. The Journal of Physical Chemistry C.2009,113(52):21543-21547.
101. Kitazaki, H., Mori, T., Kang, J.-H., Niidome, T., Murata, M., Hashizume, M., Katayama, Y. A colorimetric assay of protein kinase activity based on peptide-induced coagulation of gold nanorods. Colloids and Surfaces B: Biointerfaces.2012,99(0):7-11.
102. Liu, X., Dai, Q., Austin, L., Coutts, J., Knowles, G., Zou, J., Chen, H., Huo, Q. A one-step homogeneous immunoassay for cancer biomarker detection using gold nanoparticle probes coupled with dynamic light scattering. Journal of the American Chemical Society.2008,130(9):2780-2782.
103. Huang, Y.-F., Chang, H.-T., Tan, W. Cancer cell targeting using multiple aptamers conjugated on nanorods. Analytical Chemistry.2008,80(3):567-572.
104. Wang, J., Zhang, P., Li, J. Y., Chen, L. Q., Huang, C. Z., Li, Y. F. Adenosine-aptamer recognition-induced assembly of gold nanorods and a highly sensitive plasmon resonance coupling assay of adenosine in the brain of model SD rat. Analyst.2010,135(11):2826-2831.
105. Parab, H. J., Jung, C., Lee, J.-H., Park, H. G. A gold nanorod-based optical DNA biosensor for the diagnosis of pathogens. Biosensors and Bioelectronics.2010,26(2):667-673.
106. Yasun, E., Gulbakan, B., Ocsoy, I., Yuan, Q., Shukoor, M. I., Li, C., Tan, W. Enrichment and detection of rare proteins with aptamer-conjugated gold nanorods. Analytical Chemistry.2012,84(14):6008-6015.
107. Huang, X., El-Sayed, I. H., Qian, W., El-Sayed, M. A. Cancer cell imaging and photothetmal therapy in the near-infrared region by using gold nanorods. Journal of the American Chemical Society.2006,128(6):2115-2120.
108. Wang, L., Zhu, Y., Xu, L., Chen, W., Kuang, H., Liu, L., Agarwal, A., Xu, C., Kotov, N. A. Side-by-side and end-to-end gold nanorod assemblies for environmental toxin sensing. Angewandte Chemie International Edition. 2010,49(32):5472-5475.
109. Zhu, Y., Kuang, H., Xu, L., Ma, W., Peng, C., Hua, Y., Wang, L., Xu, C. Gold nanorod assembly based approach to toxin detection by SERS. Journal of Materials Chemistry.2012,22(6):2387-2391.
110. Zhu, Y., Xu, L., Ma, W., Xu, Z., Kuang, H., Wang, L., Xu, C. A one-step homogeneous plasmonic circular dichroism detection of aqueous mercury ions using nucleic acid functionalized gold nanorods. Chemical Communications.2012,48(97):11889-11891.
111. Li, X., Qian, J., Jiang, L., He, S. L. Fluorescence quenching of quantum dots by gold nanorods and its application to DNA detection. Applied Physics Letters.2009,94(6).
112. Chen, G., Jin, Y., Wang, L., Deng, J., Zhang, C. Gold nanorods-based FRET assay for ultrasensitive detection of Hg2+. Chemical Communications.2011,47(46):12500-12502.
113. Wang, Y., Li, Y. F., Wang, J., Sang, Y., Huang, C. Z. End-to-end assembly of gold nanorods by means of oligonucleotide-mercury(ii) molecular recognition. Chemical Communications.2010,46(8):1332-1334.
114. Zhu, Y., Qu, C., Kuang, H., Xu, L., Liu, L., Hua, Y., Wang, L., Xu, C. Simple, rapid and sensitive detection of antibiotics based on the side-by-side assembly of gold nanorod probes. Biosensors and Bioelectronics.2011,26(11): 4387-4392.
115. Singh, A. K., Senapati, D., Wang, S., Griffin, J., Neely, A., Candice, P., Naylor, K. M., Varisli, B., Kalluri, J. R., Ray, P. C. Gold nanorod based selective identification of Escherichia coli bacteria using two-photon Rayleigh scattering spectroscopy. ACS Nano.2009,3(7):1906-1912.
116. Wang, C., Irudayaraj, J. Gold nanorod probes for the detection of multiple pathogens. Small.2008,4(12): 2204-2208.
117. Norman, R. S., Stone, J. W., Gole, A., Murphy, C. J., Sabo-Attwood, T. L. Targeted photothermal lysis of the pathogenic bacteria, Pseudomonas aeruginosa, with gold nanorods. Nano Letters.2007,8(1):302-306.
118. Wang, L., Jin, Y., Deng, J., Chen, G. Gold nanorods-based FRET assay for sensitive detection of Pb2+ using 8-17DNAzyme. Analyst.2011,136(24):5169-5174.
119. Yu, C. X., Irudayaraj, J. Multiplex biosensor using gold nanorods. Analytical Chemistry.2007,79(2):572-579.
120. Wang, C., Irudayaraj, J. Multifunctional magnetic-optical nanoparticle probes for simultaneous detection, separation, and thermal ablation of multiple pathogens. Small.2010,6(2):283-289.
121. Perez-Juste, J., Pastoriza-Santos, I., Liz-Marzan, L. M., Mulvaney, P. Gold nanorods:synthesis, characterization and applications. Coordination Chemistry Reviews.2005,249(17-18):1870-1901.
122. Murphy, C. J., Sau, T. K., Gole, A. M., Orendorff, C. J., Gao, J., Gou, L., Hunyadi, S. E., Li, T. Anisotropic metal nanoparticles:synthesis, assembly, and optical applications. The Journal of Physical Chemistry B.2005,109(29): 13857-13870.
123. Jana, N. R., Gearheart, L., Murphy, C. J. Wet chemical synthesis of high aspect ratio cylindrical gold nanorods. Journal of Physical Chemistry B.2001,105(19):4065-4067.
124. Nikoobakht, B., El-Sayed, M. A. Preparation and growth mechanism of gold nanorods (NRs) using seed-mediated growth method. Chemistry of Materials.2003,15(10):1957-1962.
125. Liu, M. Z., Guyot-Sionnest, P. Mechanism of silver(I)-assisted growth of gold nanorods and bipyramids. Journal of Physical Chemistry B.2005,109(47):22192-22200.
126. Smith, D. K., Korgel, B. A. The importance of the CTAB surfactant on the colloidal seed-mediated synthesis of gold nanorods. Langmuir.2008,24(3):644-649.
127. Becker, J., Trugler, A., Jakab, A., Hohenester, U., Sonnichsen, C. The optimal aspect ratio of gold nanorods for plasmonic bio-sensing. Plasmonics.2010,5(2):161-167.
128. Murdock, R. C., Braydich-Stolle, L., Schrand, A. M., Schlager, J. J., Hussain, S. M. Characterization of nanomaterial dispersion in solution prior to in vitro exposure using dynamic light scattering technique. Toxicological Sciences. 2008,101(2):239-253.
129. Goldburg, W. Dynamic light scattering. American Journal of Physics.1999,67(12):1152-1160.
130. Hunter, R. J. Zeta potential in colloid science:principles and applications. London:Academic Press.1981.
131. Xu, R. Progress in nanoparticles characterization:sizing and zeta potential measurement. Particuology.2008,6(2): 112-115.
132. Link, S., El-Sayed, M. A. Spectroscopic determination of the melting energy of a gold nanorod. The Journal of Chemical Physics.2001,114(5):2362-2368.
133. Gole, A., Murphy, C. J. Azide-derivatized gold nanorods:functional materials for "click" chemistry. Langmuir.2007, 24(1):266-272.
134.陈贝贝.基于ICP-MS的联用技术及其在生命体系中元素与形态分析的应用[博士论文].武汉：武汉大学.2010.
135. Kneipp, K., Kneipp, H., Itzkan, I., Dasari, R. R., Feld, M. S. Ultrasensitive chemical analysis by Raman spectroscopy. Chemical Reviews.1999,99:2957-2976.
136. Sau, T. K.., Murphy, C. J. Room temperature, high-yield synthesis of multiple shapes of gold nanoparticles in aqueous solution. Journal of the American Chemical Society.2004,126(28):8648-8649.
137. Orendorff, C. J., Murphy, C. J. Quantitation of metal content in the silver-assisted growth of gold nanorods. Journal of Physical Chemistry B.2006,110(9):3990-3994.
138. Ha, T. H., Koo, H.-J., Chung, B. H. Shape-controlled syntheses of gold nanoprisms and nanorods influenced by specific adsorption of halide ions. The Journal of Physical Chemistry C.2006,111(3):1123-1130.
139. Gou, L. F., Murphy, C. J. Fine-tuning the shape of gold nanorods. Chemistry of Materials.2005,17(14):3668-3672.
140. Johnson, C. J., Dujardin, E., Davis, S. A., Murphy, C. J., Mann, S. Growth and form of gold nanorods prepared by seed-mediated, surfactant-directed synthesis. Journal of Materials Chemistry.2002,12(6):1765-1770.
141. Jain, P. K., Lee, K. S., El-Sayed,1. H., El-Sayed, M. A. Calculated absorption and scattering properties of gold nanoparticles of different size, shape, and composition:applications in biological imaging and biomedicine. The Journal of Physical Chemistry B.2006,110(14):7238-7248.
142. Liao, H., Hafner, J. H. Gold nanorod bioconjugates. Chemistry of Materials.2005,17(18):4636-4641.
143. Chen, H. J., Kou, X. S., Yang, Z., Ni, W. H., Wang, J. F. Shape-and size-dependent refractive index sensitivity of gold nanoparticles. Langmuir.2008,24(10):5233-5237.
144. Ferhan, A. R., Guo, L., Kim, D.-H. Influence of ionic strength and surfactant concentration on electrostatic surfacial assembly of cetyltrimethylammonium bromide-capped gold nanorods on fully immersed glass. Langmuir.2010, 26(14):12433-12442.
145. Sethi, M., Joung, G., Knecht, M. R. Stability and electrostatic assembly of Au nanorods for use in biological assays. Langmuir.2009,25(1):317-325.
146. Gao, J., Bender, C. M., Murphy, C. J. Dependence of the gold nanorod aspect ratio on the nature of the directing surfactant in aqueous solution. Langmuir.2003,19(21):9065-9070.
147. Yang, D., Cui, D. Advances and prospects of gold nanorods. Chemistry-An Asian Journal.2008,3(12):2010-2022.
148. Thierry, B., Ng, J., Krieg, T., Griesser, H. J. A robust procedure for the functionalization of gold nanorods and noble metal nanoparticles. Chemical Communications.2009,0(13):1724-1726.
149. Kopwitthaya, A., Yong, K.-T., Hu, R., Roy, I., Ding, H., Vathy, L. A., Bergey, E. J., Prasad, P. N. Biocompatible PEGylated gold nanorods as colored contrast agents for targeted in vivo cancer applications. Nanotechnology.2010, 21(31):315101.
150. Hwang, S.-Y., Tao, A. R. Biofunctionalization of gold nanorods. Pure and Applied Chemistry.2011,83(1):233-241.
151. Yu, C., Varghese, L., Irudayaraj, J. Surface modification of cetyltrimethylammonium bromide-capped gold nanorods to make molecular probes. Langmuir.2007,23(17):9114-9119.
152. Caswell, K. K., Wilson, J. N., Bunz, U. H. F., Murphy, C. J. Preferential end-to-end assembly of gold nanorods by biotin-streptavidin connectors. Journal of the American Chemical Society.2003,125(46):13914-13915.
153. Chang, J.-Y., Wu, H., Chen, H., Ling, Y.-C., Tan, W. Oriented assembly of Au nanorods using biorecognition system. Chemical Communications.2005,0(8):1092-1094.
154. Chen, C.-D., Cheng, S.-F., Chau, L.-K.., Wang, C. R. C. Sensing capability of the localized surface plasmon resonance of gold nanorods. Biosensors and Bioelectronics.2007,22(6):926-932.
155. Teramura, Y., Iwata, H. Label-free immunosensing for alpha-fetoprotein in human plasma using surface plasmon resonance. Analytical Biochemistry.2007,365(2):201-207.
156. Qiang, Z., Yuan, R., Chai, Y., Wang, N., Zhuo, Y., Zhang. Y., Li, X. A new potentiometric immunosensor for determination of alpha-fetoprotein based on improved gelatin-silver complex film. Electrochimica Acta.2006, 51(18):3763-3768.
157. Liu, X., Wu, H., Zheng, Y., Wu, Z., Jiang, J., Shen, G., Yu, R. A sensitive electrochemical immunosensor for a-fetoprotein detection with colloidal gold-based dentritical enzyme complex amplification. Electroanalysis.2010, 22(2):244-250.
158. Chang, Y.-F., Chen, R.-C., Lee, Y.-J., Chao, S.-C., Su, L.-C., Li, Y.-C., Chou, C. Localized surface plasmon coupled fluorescence fiber-optic biosensor for alpha-fetoprotein detection in human serum. Biosensors and Bioelectronics. 2009,24(6):1610-1614.
159. Yu, C., Irudayaraj, J. Quantitative evaluation of sensitivity and selectivity of multiplex nanoSPR biosensor assays. Biophysical Journal.2007,93:3684-3692.
160. Nikoobakht, B., Wang, J., El-Sayed, M. A. Surface-enhanced Raman scattering of molecules adsorbed on gold nanorods:off-surface plasmon resonance condition. Chemical Physics Letters.2002,366(1-2):17-23.
161. Foucault, R., Birke, R. L., Lombardi, J. R. SERS of surfactants in monolayer and multibilayer forms on an electrified Ag surface. Langmuir.2003,19(21):8818-8827.
162. Bensebaa, F., Zhou, Y., Brolo, A., Irish, D., Deslandes, Y., Kruus, E., Ellis, T. Raman characterization of metal-alkanethiolates. Spectrochimica Acta Part A:Molecular and Biomolecular Spectroscopy.1999,55(6): 1229-1236.
163. Piermarini, S., Micheli, L., Ammida, N. H. S., Palleschi, G., Moscone, D. Electrochemical immunosensor array using a 96-well screen-printed microplate for aflatoxin B, detection. Biosensors and Bioelectronics.2007,22(7): 1434-1440.
164. Ammida, N. H. S., Micheli, L., Palleschi, G. Electrochemical immunosensor for determination of aflatoxin B| in barley. Analytica Chimica Acta.2004,520(1):159-164.
165. Tan, Y., Chu, X., Shen, G.-L., Yu, R.-Q. A signal-amplified electrochemical immunosensor for aflatoxin B1 determination in rice. Analytical Biochemistry.2009,387(1):82-86.
166. Li, Y., Liu, X., Lin, Z. Recent developments and applications of surface plasmon resonance biosensors for the detection of mycotoxins in foodstuffs. Food Chemistry.2012,132(3):1549-1554.
167. Wu, S., Duan, N., Zhu, C., Ma, X., Wang, M., Wang, Z. Magnetic nanobead-based immunoassay for the simultaneous detection of aflatoxin B1 and ochratoxin A using upconversion nanoparticles as multicolor labels. Biosensors and Bioelectronics.2011,30(1):35-42.
168. Jin, X., Jin, X., Chen, L., Jiang, J., Shen, G., Yu, R. Piezoelectric immunosensor with gold nanoparticles enhanced competitive immunoreaction technique for quantification of aflatoxin B1. Biosensors and Bioelectronics.2009,24(8): 2580-2585.
169. Liu, B.-H., Hsu, Y.-T., Lu, C.-J., Yu, F.-Y. Detecting aflatoxin B1 in foods and feeds by using sensitive rapid enzyme-linked immunosorbent assay and gold nanoparticle immunochromatographic strip. Food Control.2012.
170. Abhijith, K. S., Thakur, M. S. Application of green synthesis of gold nanoparticles for sensitive detection of aflatoxin B1 based on metal enhanced fluorescence. Analytical Methods.2012,4(12):4250-4256.
171. Zhang, M., Qing, G., Xiong, C., Cui, R., Pang, D.-W., Sun, T. Dual-responsive gold nanoparticles for colorimetric recognition and testing of carbohydrates with a dispersion-dominated chromogenic process. Advanced Materials. 2012,25(5):749-754.
172. Pinto, M. R., Schanze, K. S. Amplified fluorescence sensing of protease activity with conjugated polyelectrolytes. Proceedings of the National Academy of Sciences of the United States of America.2004,101(20):7505-7510.
173. Yin, S., Leen, V., Van Snick, S., Boens, N., Dehaen, W. A highly sensitive, selective, colorimetric and near-infrared fluorescent turn-on chemosensor for Cu2+ based on BODIPY. Chemical Communications.2010,46(34):6329-6331.
174. Rurack, K., Kollmannsberger, M., Resch-Genger, U., Daub, J. A selective and sensitive fluoroionophore for HgIl, AgI, and CuIl with virtually decoupled fluorophore and receptor units. Journal of the American Chemical Society. 2000,122(5):968-969.
175. McQuade, D. T., Hegedus, A. H., Swager, T. M. Signal amplification of a "turn-on" sensor:harvesting the light captured by a conjugated polymer. Journal of the American Chemical Society.2000,122(49):12389-12390.
176.朱颖越.基于金纳米材料的藻毒素检测新方法的建立[博士论文].无锡：江南大学.2012.
177. Zhang, D., Li, P., Zhang, Q., Zhang, W. Ultrasensitive nanogold probe-based immunochromatographic assay for simultaneous detection of total aflatoxins in peanuts. Biosensors and Bioelectronics.2011,26(6):2877-2882.
178. Reiter, E. V., Cichna-Markl, M., Chung, D.-H., Zentek, J., Razzazi-Fazeli, E. Immuno-ultrafiltration as a new strategy in sample clean-up of aflatoxins. The Journal of Separation Science.2009,32(10):1729-1739.
179. Jans, H., Liu, X., Austin, L., Maes, G., Huo, Q. Dynamic light scattering as a powerful tool for gold nanoparticle bioconjugation and biomolecular binding studies. Analytical Chemistry.2009,81(22):9425-9432.
180. Cervino, C., Weber, E., Knopp, D., Niessner, R. Comparison of hybridoma screening methods for the efficient detection of high-affinity hapten-specific monoclonal antibodies. Journal of immunological methods.2008,329(1): 184-193.
181. Zhang, D., Li, P., Yang, Y., Zhang, Q., Zhang, W., Xiao, Z., Ding, X. A high selective immunochromatographic assay for rapid detection of aflatoxin B1. Talanta.2011,85(1):736-742.
182. Li, P., Zhang, Q., Zhang, W. Immunoassays for aflatoxins. TrAC-Trend in Analytical Chemistry.2009,28(9): 1115-1126.
183. Maragos, C. M. Recent advances in the development of novel materials for mycotoxin analysis. Analytical and Bioanalytical Chemistry.2009,395(5):1205-1213.
184.杨锡辉,孔维军,杨美华,赵明,欧阳臻.适配子识别技术在真菌毒素快速分析中的应用.分析化学.2013,41(2)：297-306.
185. Prieto-Simon, B., Noguer, T., Campas, M. Emerging biotools for assessment of mycotoxins in the past decade. TrAC Trends in Analytical Chemistry.2007,26(7):689-702.
186. Zhou, S. N., Lai, E. P., Miller, J. D. Analysis of wheat extracts for ochratoxin A by molecularly imprinted solid-phase extraction and pulsed elution. Analytical and Bioanalytical Chemistry.2004,378(8):1903-1906.
187. Van Houwelingen, A., De Saeger, S., Rusanova, T., Waalwijk, C., Beekwilder, J. Generation of recombinant alpaca VHH antibody fragments for the detection of the mycotoxin ochratoxin A. World Mycotoxin Journal.2008,1(4): 407-417.
188.严喜鸾.基于核酸适配体化学发光检侧新技术的研究[博士论文].上海：复旦大学.2009.
189. Wu, S., Yang, Z., Zhang, L. Selection and application of aptamer for aflatoxin B,. CN102517289A.2012.
190. Le, L. C., Cruz-Aguado, J. A., Penner, G. A. Aptamer ligands for aflatoxins and zearalenone and their use in agricultural and food analysis. WO2011020198A1.2011.
191. Yang, C., Lates, V., Prieto-Simon, B., Marty, J.-L., Yang, X. Aptamer-DNAzyme hairpins for biosensing of Ochratoxin A. Biosensors and Bioelectronics.2012,32(1):208-212.
192. McKeague, M., Bradley, C. R., Girolamo, A. D., Visconti, A., Miller, J. D., DeRosa, M. C. Screening and initial binding assessment of fumonisin B1 aptamers. International journal of molecular sciences.2010,11(12):4864-4881.
193. Cruz-Aguado, J. A., Penner, G. Determination of ochratoxin A with a DNA aptamer. Journal of Agricultural and Food Chemistry.2008,56(22):10456-10461.
194. Cruz-Aguado, J. A., Penner, G. Fluorescence polarization based displacement assay for the determination of small molecules with aptamers. Analytical Chemistry.2008,80(22):8853-8855.
195. 何婧琳.基于构象转换和聚合酶反应的核酸适配体传感分析方法及应用研究[博士论文].长沙：湖南大学.2010.
196. Song, S., Wang, L., Li, J., Fan, C., Zhao, J. Aptamer-based biosensors. TrAC Trends in Analytical Chemistry.2008, 27(2):108-117.
197. Van Dorst, B., Mehta, J., Bekaert, K., Rouah-Martin, E., De Coen, W., Dubruel, P., Blust, R., Robbens, J. Recent advances in recognition elements of food and environmental biosensors:A review. Biosensors and Bioelectronics. 2010,26(4):1178-1194.
198. Barthelmebs, L., Hayat, A., Limiadi, A. W., Marty, J.-L., Noguer, T. Electrochemical DNA aptamer-based biosensor for OTA detection, using superparamagnetic nanoparticles. Sensors and Actuators B:Chemical.2011,156(2): 932-937.
199. Bonel, L., Vidal, J. C., Duato, P., Castillo, J. R. An electrochemical competitive biosensor for ochratoxin A based on a DNA biotinylated aptamer. Biosensors and Bioelectronics.2011,26(7):3254-3259.
200. Wu, J., Chu, H., Mei, Z., Deng, Y., Xue, F., Zheng, L., Chen, W. Ultrasensitive one-step rapid detection of ochratoxin A by the folding-based electrochemical aptasensor. Analytica Chimica Acta.2012.
201. Wang, J., Munir, A., Zhou, H. S. Au NPs-aptamer conjugates as a powerful competitive reagent for ultrasensitive detection of small molecules by surface plasmon resonance spectroscopy. Talanta.2009,79(1):72-76.
202. Wang, J., Zhou, H. S. Aptamer-based Au nanoparticles-enhanced surface plasmon resonance detection of small molecules. Analytical Chemistry.2008,80(18):7174-7178.
203. Chen, J., Fang, Z., Liu, J., Zeng, L. A simple and rapid biosensor for ochratoxin A based on a structure-switching signaling aptamer. Food Control.2012,25(2):555-560.
204. De Girolamo, A., Le, L., Penner, G., Schena, R., Visconti, A. Analytical performances of a DNA-ligand system using time-resolved fluorescence for the determination of ochratoxin A in wheat. Analytical and Bioanalytical Chemistry.2012,403(9):2627-2634.
205. Hianik, T. Biosensors for detection of ochratoxin A. Netherlands:Springer.2012.
206. Wang, G., Wang, Y., Chen, L., Choo, J. Nanomaterial-assisted aptamers for optical sensing. Biosensors and Bioelectronics.2010,25(8):1859-1868.
207. Liu, J., Lu, Y. Preparation of aptamer-linked gold nanoparticle purple aggregates for colorimetric sensing of analytes. Nature Protocols.2006,1(1):246-252.
208. Liu, J., Lu, Y. Fast colorimetric sensing of adenosine and cocaine based on a general sensor design involving aptamers and nanoparticles. Angewandte Chemie.2006,118(1):96-100.
209. Lu, Y., Liu, J. Functional DNA nanotechnology:emerging applications of DNAzymes and aptamers. Current opinion in Biotechnology.2006,17(6):580-588.
210. Yang, C., Wang, Y., Marty, J.-L., Yang, X. Aptamer-based colorimetric biosensing of ochratoxin A using unmodified gold nanoparticles indicator. Biosensors and Bioelectronics.2011,26(5):2724-2727.
211. Wei, W., Li, S., Qin, L., Xue, C., Millstone, J. E., Xu, X., Schatz, G. C., Mirkin, C. A. Surface plasmon-mediated energy transfer in heterogap Au-Ag nanowires. Nano Letters.2008,8(10):3446-3449.
212. Mannelli,I., Marco, M. P. Recent advances in analytical and bioanalysis applications of noble metal nanorods. Analytical and Bioanalytical Chemistry.2010,398(6):2451-2469.
213. Hu, X., Gao, X. Multilayer coating of gold nanorods for combined stability and biocompatibility. Physical Chemistry Chemical Physics.2011,13(21):10028-10035.
214. Wang, J., Zhu, G., You, M., Song, E., Shukoor, M.1., Zhang, K., Altman, M. B., Chen, Y., Zhu, Z., Huang, C. Z., Tan, W. Assembly of aptamer switch probes and photosensitizer on gold nanorods for targeted photothermal and photodynamic cancer therapy. ACS Nano.2012,6(6):5070-5077.
215. Xu, L., Kuang, H., Xu, C., Ma, W., Wang, L., Kotov, N. A. Regiospecific plasmonic assemblies for in situ Raman spectroscopy in live cells. Journal of the American Chemical Society.2012,134(3):1699-1709.
216. Boland, T., Ratner, B. Direct measurement of hydrogen bonding in DNA nucleotide bases by atomic force microscopy. Proceedings of the National Academy of Sciences.1995,92(12):5297-5301.
217.杨淑华.金纳米棒-适配子偶联物的研制及其在体内外肿瘤热疗中的应用研究[博士论文].北京：中国人民解放军军事医学科学院.2010.
218. Hu, X., Cheng, W., Wang, T., Wang, E., Dong, S. Well-ordered end-to-end linkage of gold nanorods. Nanotechnology.2005,16(10):2164.
219. Jain, T., Roodbeen, R., Reeler, N. E., Vosch, T., Jensen, K. J., Bjornholm, T., Norgaard, K. End-to-end assembly of gold nanorods via oligopeptide linking and surfactant control. Journal of colloid and interface science.2012,376(1): 83-90.
220. Funston, A. M., Novo, C., Davis, T. J., Mulvaney, P. Plasmon coupling of gold nanorods at short distances and in different geometries. Nano Letters.2009,9(4):1651-1658.
221. Jain, P. K., Eustis, S., El-Sayed, M. A. Plasmon coupling in nanorod assemblies:optical absorption, discrete dipole approximation simulation, and exciton-coupling model. The Journal of Physical Chemistry B.2006,110(37): 18243-18253.
222.杨海.环境与食品安全快速检测技术研究[博士论文].武汉：华中科技大学.2006.
223.中华人民共和国农业部.(2007)NY/T 1286-2007花生黄曲霉毒素B1的测定高效液相色谱法.