基于纳米金磁微粒的基因分型系统构筑及在氯吡格雷指导用药的应用研究
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摘要
研究背景：药物代谢的有效性和毒副作用影响着疾病的治疗效果及用药安全。遗传药理学及药物基因组学等相关研究表明,药物代谢酶的基因多态性是导致药物代谢个体差异的关键因素,因此从药物代谢酶基因多态性的检测出发,通过新的基因分型技术的应用而提供即时有效的个体差异信息,对于临床医生给处合理的治疗方案,在药物使用安全性、有效性及指导个体化用药方面具有重要意义。
即时检验或床旁检测(Point-of-Care Testing, POCT)是检验医学自动化和简单化发展的产物,其技术便捷、快速,不需要昂贵的仪器设备及专业的技术操作人员,随着高效快节奏社会运转模式的需要,POCT已经在医学健康领域,海关检疫、农牧业、林业、消防、环境和食品检测等多个领域得到了广泛应用。但目前多集中在基于免疫学范畴的快速层析检测,实现基因分型(即单核苷酸多态性检测)的产品还鲜有报道。
《中国心血管病报告2010》显示,我国每年300万人死于心血管疾病,居死因之首,其用药安全和有效性备受关注。氯吡格雷为抗血栓治疗临床一线用药,然而,约30%患者服用该药后疗效不佳,甚至产生严重不良反应。已有文献研究表明,氯吡格雷抵抗与细胞色素P450酶CYP2C19基因多态性相关,其中CYP2C19*2(c.681G>A)、 CYP2C19*3(c.636G>A)等位基因是增加心肌梗死、中风和支架内血栓再形成的主要影响因素。美国FDA发布氯吡格雷早期安全性信息公告,在说明书中添加黑框警告,警示语是基于对氯吡格雷抗血小板机理的认识,因为它主要依赖于细胞色素P450(CYP)体系对氯吡格雷的激活。CYP2C19功能减退的患者因为遗传多态性的缘故代谢氯吡格雷的能力差,急性冠脉综合征(ACS)和经皮冠状动脉介入后心血管不良事件的发病率高于CYP2C19功能正常的患者。因此,氯吡格雷具有潜在因减效而增加心血管事件风险,无法在弱代谢患者体内充分发挥作用,提示需开展CYP2C19功能遗传差异性的检验。
目的：本研究以纳米金磁微粒为载体,构建了适用于CYP2C19基因分型的POCT快速层析检测体系,围绕心血管相关疾病氯吡格雷个体化用药,以335例中国人心血管相关疾病的患者血液样本为研究对象,对氯吡格雷代谢相关联的P450酶CYP2C19*2(c.681G>A)、CYP2C19*3(c.636G>A)等位基因进行分型,并通过金标准的测序法对基于纳米金磁微粒的快速层析检测体系进行了评价。用统计学方法对基因型进行分析,揭示中国人心血管相关疾病的患者等位基因CYP2C19*2(c.681G>A)、 CYP2C19*3(c.636G>A)发生频率,进而对氯毗格雷药物代谢类型进行统计分析,为氯吡格雷个体化用药提供相应的理论及技术支持。
方法及主要研究结果：
1.利用水热合成法制备表面修饰有油酸分子、平均粒径为8nm、饱和磁化强度为55.1emu/g的单分散性的Fe304纳米粒子。采用氧化Fe304纳米粒子表面的油酸及表面活性剂协同作用使其转移至水相。以Fe3O4纳米粒子为种子,结合表面电荷作用利用原位自催化还原制备得到一种新型结构的Fe3O4/Au/Fe3O4花瓣状纳米金磁复合微粒。通过XRD、FT-IR、UV-Vis、VSM、EDS、ICP和HTEM等分析手段对产物进行了鉴定与表征。结果表明：其金磁复合微粒平均粒径为38nm,饱和磁化强度约为40.7emu/g,对抗地高辛单克隆抗体的固定化容量高达307gg/mg,光学特征吸收峰位于可见区的540nm左右,表面zeta-电位大于+30mV,是一种超顺磁性,胶态稳定性极好的纳米级金磁复合微粒。
2.通过对等位基因CYP2C19*(c.681G>A)、CYP2C19*3(c.636G>A)突变位点的引物设计及标记,利用AS-PCR扩增获得特定的扩增片段,标记有地高辛分子的PCR产物在与所构筑的基因分型检测体系中纳米金磁微粒表面抗地高辛单抗相互作用,通过侧向流层析技术便可实现CYP2C19的SNP (Single Nucleotide Polymorphisms,单核苷酸多态性)快速检测。以构建的质粒DNA为模版,选择AS-PCR方法,对快速层析检测系统进行条件的优化、性能评估,结果表明：lmg纳米金磁复合微粒标记地高辛单抗最佳用量为180μg,制备得到的SNP快速层析检测试纸条对突变位点检测的灵敏度可以达到0.1%。
3.以335例中国人心血管相关疾病的患者血样为研究对象,利用开发的基因分型快速层析检测方法结合测序对CYP2C19*2(c.681G>A)、CYP2C19*3(c.636G>A)的基因突变位点进行双盲检测,经过统计分析：两种方法对样本的检测结果均符合Hardy-Weinberg遗传平衡法则；以测序检测结果为标准,新开发的SNP快速层析检测方法准确率高于98%,两种检测方法的检出准确性不存在显著性差异；SNP快速层析检测方法检出率明显高于测序法,在检出率上存在极显著性差异,表明方法具有更高的灵敏度。对检测的中国人心血管相关患者血样的基因型进行统计分析,此类人群对药物氯吡格雷代谢类型分布为：快代谢：40.8%；中代谢：43.2%;慢代谢：16.0%。
以新型纳米金磁复合微粒为载体,建立的SNP快速层析检测方法,操作简单、便捷、快速且有着很高的特异性与灵敏度。该检测系统无需过高的技术操作壁垒,无需配置仪器设备,因此可普及于各级医疗机构、体检中心,只需具备规范的PCR实验室,即可将将个体化用药检测推向规范化和产业化进程,为疾病的临床药物开发研究及治疗研究奠定基础。
Background:The effectiveness of drug metabolism and its toxicity affects the disease's treatment effect and the drug's safety. Pharmacogenetics, pharmacogenomics and other related disciplines shows gene polymorphism of drug metabolizing enzymes are the reason for individual differences of drug metabolism. Therefore, a new detection technology that can ascertain the drug metabolism enzyme gene polymorphism and provided instant information on individual differences is of great significance to improve the efficacy and safety of drug and guide individual treatment.
Point-of-Care Testing (POCT), a technology developed from the medical laboratory automation and simplification, and owning to its convenience, rapidity, no need for expensive instruments and operations staff, is widely applied to medical health, customs and quarantine, farming and animal husbandry, forestry, environmental and food detection with the need of high-efficient and fast-paced society. However, the POCT are mostly used in rapid chromatographic detection based on the immunology and is seldom used for genotyping.
2010report on cardiovascular disease in China shows that3million people die of cardiovascular disease in every year and which is the top1leading causes of death for patients, therefore, much attention has been paid to its medication safety and effectiveness. Clopidogrel sulfate is a clinical first-line drug for antithrombotic therapy. However, about30%of patients after taking the drug have poor curative effect, even causing serious adverse reactions. Studies have shown that clopidogrel resistance is associated with the cytochrome P450enzyme CYP2C19gene polymorphisms, in which CYP2C19*2(c.681G>A) and CYP2C19*3(c.636G>A) is the main influence factors to increasing myocardial infarction, stroke, and stent thrombosis. FDA announced the clopidogrel early security public information which require to add black box warning in specification that the clopidogrel has a potential risk of increasing the cardiovascular events owing to being decreased drug efficacy. No functional CYP2C19*2(c.681G> A) and CYP2C19*3(c.636G> A) allele have the important effects on drug metabolism and the drug are unable to give full play to the role in the patients with weak metabolism.
Aim:To fabrication a gold magnetic composite nanoparticle (GoldMag NP) suitable for POCT system of CYP2C19genotyping for clopidogrel individual medication of cardiovascular and cerebrovascular disease. Furthermore, taken the335blood samples of cardiovascular patients as the research object, the CYP2C19*2and CYP2C19*3alleles of P450enzyme involved in the metabolism of clopidogrel were genotyped with the new POCT system and evaluated by gene sequencing technology which is an existing gold standard method. From the analysis of genotype by statistical method, the results revealed allele frequency of CYP2C19*2and CYP2C19*3. At last, the results of statistical correlation analysis between gene mutation and the type of clopidogrel metabolism provide a theoretical and technical support for clopidogrel individual medication.
Methods and Results:
1. The Fe3O4NPs were first prepared using the hydrothermal method, there are oleic molecules on the surface and the mean diameter of FeaO4NPs is8nm, with saturation magnetization55.1emu/g. To render the NPs water-soluble, we oxidized the oleic molecules on the surface of Fe3O4NPs and added CTAB surfactant to make the hydrophobic groups to hydrophilic groups on the surface of the nanoparticles. as-synthesized Fe3O4NPs as the core, prepared the new structure of Fe3O4/Au/Fe3O4petal shaped GoldMag NPs. As revealed by XRD、FT-IR、UV-Vis、VSM、EDS、ICP and HTEM, the mean diameter of the composite particles is38nm, characteristic absorption peak of the Fe3O4/Au composite nanoparticles is at540nm, with saturation magnetization40.7emu/g and coupling capacity of goat anti-mouse IgG307μg permilligram GoldMag NPs. TEM images illustrate GoldMag NPs were in30nm-sized sphere morphology, with large amount of8nm-sized Fe3O4nanoparticles dissolved. These as-synthesized nanoflowers dispersed in water possess good dispersion and stabilization and exhibit a zeta-potential above+30mV.
2. A SNP fast and sensitive chromatography strip for clopidogrel individual medication was designed and prepared. This novel fast chromatographic model was constructed through specific binding the gold magnetic composite nanoparticle marked digoxin monoclonal antibodies and the gene mutation primer of CYP2C19*2(681G>A) and CYP2C19*3(636G>A) alleles marked digoxin molecule. Condition optimization, performance evaluation and parameter confirmation were done through the constructed plasmid DNA and ultraviolet spectrophotometer. The results showed that this novel SNP fast chromatographic test strip has high specificity and the sensitivity can reach0.1%.
3. The335blood samples of cardiovascular and cerebrovascular patients in Shaanxi province were taken as the research object. The gene mutations of CYP2C19*2and CYP2C19*3allele of the samples were determined by the developed SNP fast chromatography technology and the sequencing method which is an existing gold standard method. The statistical results showed that the gene mutations frequency distributions of the two alleles are both comply with the laws of genetic equilibrium, and the accuracy of the novel technology are98%comparing the sequencing method and two methods do not exist significant differences in accuracy. However,the detectable rate of the novel method is much higher than the sequencing method and two methods exist significant differences. The statistical genotypes of these blood samples showed that the population percentage of clopidogrel metabolism type is40.8%for the fast metabolism,43.2%for the metabolism and16%for the slow metabolism, respectively.
Herein, simple, convenience and fast technology with high specificity and sensitivity genotyping method was developed based on the GoldMag NPs. This technology has no complex operation and doesn't need expensive instrument, so it can be easily popularized in all levels of medical institutions in a specifications PCR lab, and promote the individual medication detection to the standardization and industrialization, as well as lay a foundation for the research of clinical drug and disease treatment.
即时检验或床旁检测(Point-of-Care Testing, POCT)是检验医学自动化和简单化发展的产物,其技术便捷、快速,不需要昂贵的仪器设备及专业的技术操作人员,随着高效快节奏社会运转模式的需要,POCT已经在医学健康领域,海关检疫、农牧业、林业、消防、环境和食品检测等多个领域得到了广泛应用。但目前多集中在基于免疫学范畴的快速层析检测,实现基因分型(即单核苷酸多态性检测)的产品还鲜有报道。
《中国心血管病报告2010》显示,我国每年300万人死于心血管疾病,居死因之首,其用药安全和有效性备受关注。氯吡格雷为抗血栓治疗临床一线用药,然而,约30%患者服用该药后疗效不佳,甚至产生严重不良反应。已有文献研究表明,氯吡格雷抵抗与细胞色素P450酶CYP2C19基因多态性相关,其中CYP2C19*2(c.681G>A)、 CYP2C19*3(c.636G>A)等位基因是增加心肌梗死、中风和支架内血栓再形成的主要影响因素。美国FDA发布氯吡格雷早期安全性信息公告,在说明书中添加黑框警告,警示语是基于对氯吡格雷抗血小板机理的认识,因为它主要依赖于细胞色素P450(CYP)体系对氯吡格雷的激活。CYP2C19功能减退的患者因为遗传多态性的缘故代谢氯吡格雷的能力差,急性冠脉综合征(ACS)和经皮冠状动脉介入后心血管不良事件的发病率高于CYP2C19功能正常的患者。因此,氯吡格雷具有潜在因减效而增加心血管事件风险,无法在弱代谢患者体内充分发挥作用,提示需开展CYP2C19功能遗传差异性的检验。
目的：本研究以纳米金磁微粒为载体,构建了适用于CYP2C19基因分型的POCT快速层析检测体系,围绕心血管相关疾病氯吡格雷个体化用药,以335例中国人心血管相关疾病的患者血液样本为研究对象,对氯吡格雷代谢相关联的P450酶CYP2C19*2(c.681G>A)、CYP2C19*3(c.636G>A)等位基因进行分型,并通过金标准的测序法对基于纳米金磁微粒的快速层析检测体系进行了评价。用统计学方法对基因型进行分析,揭示中国人心血管相关疾病的患者等位基因CYP2C19*2(c.681G>A)、 CYP2C19*3(c.636G>A)发生频率,进而对氯毗格雷药物代谢类型进行统计分析,为氯吡格雷个体化用药提供相应的理论及技术支持。
方法及主要研究结果：
1.利用水热合成法制备表面修饰有油酸分子、平均粒径为8nm、饱和磁化强度为55.1emu/g的单分散性的Fe304纳米粒子。采用氧化Fe304纳米粒子表面的油酸及表面活性剂协同作用使其转移至水相。以Fe3O4纳米粒子为种子,结合表面电荷作用利用原位自催化还原制备得到一种新型结构的Fe3O4/Au/Fe3O4花瓣状纳米金磁复合微粒。通过XRD、FT-IR、UV-Vis、VSM、EDS、ICP和HTEM等分析手段对产物进行了鉴定与表征。结果表明：其金磁复合微粒平均粒径为38nm,饱和磁化强度约为40.7emu/g,对抗地高辛单克隆抗体的固定化容量高达307gg/mg,光学特征吸收峰位于可见区的540nm左右,表面zeta-电位大于+30mV,是一种超顺磁性,胶态稳定性极好的纳米级金磁复合微粒。
2.通过对等位基因CYP2C19*(c.681G>A)、CYP2C19*3(c.636G>A)突变位点的引物设计及标记,利用AS-PCR扩增获得特定的扩增片段,标记有地高辛分子的PCR产物在与所构筑的基因分型检测体系中纳米金磁微粒表面抗地高辛单抗相互作用,通过侧向流层析技术便可实现CYP2C19的SNP (Single Nucleotide Polymorphisms,单核苷酸多态性)快速检测。以构建的质粒DNA为模版,选择AS-PCR方法,对快速层析检测系统进行条件的优化、性能评估,结果表明：lmg纳米金磁复合微粒标记地高辛单抗最佳用量为180μg,制备得到的SNP快速层析检测试纸条对突变位点检测的灵敏度可以达到0.1%。
3.以335例中国人心血管相关疾病的患者血样为研究对象,利用开发的基因分型快速层析检测方法结合测序对CYP2C19*2(c.681G>A)、CYP2C19*3(c.636G>A)的基因突变位点进行双盲检测,经过统计分析：两种方法对样本的检测结果均符合Hardy-Weinberg遗传平衡法则；以测序检测结果为标准,新开发的SNP快速层析检测方法准确率高于98%,两种检测方法的检出准确性不存在显著性差异；SNP快速层析检测方法检出率明显高于测序法,在检出率上存在极显著性差异,表明方法具有更高的灵敏度。对检测的中国人心血管相关患者血样的基因型进行统计分析,此类人群对药物氯吡格雷代谢类型分布为：快代谢：40.8%；中代谢：43.2%;慢代谢：16.0%。
以新型纳米金磁复合微粒为载体,建立的SNP快速层析检测方法,操作简单、便捷、快速且有着很高的特异性与灵敏度。该检测系统无需过高的技术操作壁垒,无需配置仪器设备,因此可普及于各级医疗机构、体检中心,只需具备规范的PCR实验室,即可将将个体化用药检测推向规范化和产业化进程,为疾病的临床药物开发研究及治疗研究奠定基础。
Background:The effectiveness of drug metabolism and its toxicity affects the disease's treatment effect and the drug's safety. Pharmacogenetics, pharmacogenomics and other related disciplines shows gene polymorphism of drug metabolizing enzymes are the reason for individual differences of drug metabolism. Therefore, a new detection technology that can ascertain the drug metabolism enzyme gene polymorphism and provided instant information on individual differences is of great significance to improve the efficacy and safety of drug and guide individual treatment.
Point-of-Care Testing (POCT), a technology developed from the medical laboratory automation and simplification, and owning to its convenience, rapidity, no need for expensive instruments and operations staff, is widely applied to medical health, customs and quarantine, farming and animal husbandry, forestry, environmental and food detection with the need of high-efficient and fast-paced society. However, the POCT are mostly used in rapid chromatographic detection based on the immunology and is seldom used for genotyping.
2010report on cardiovascular disease in China shows that3million people die of cardiovascular disease in every year and which is the top1leading causes of death for patients, therefore, much attention has been paid to its medication safety and effectiveness. Clopidogrel sulfate is a clinical first-line drug for antithrombotic therapy. However, about30%of patients after taking the drug have poor curative effect, even causing serious adverse reactions. Studies have shown that clopidogrel resistance is associated with the cytochrome P450enzyme CYP2C19gene polymorphisms, in which CYP2C19*2(c.681G>A) and CYP2C19*3(c.636G>A) is the main influence factors to increasing myocardial infarction, stroke, and stent thrombosis. FDA announced the clopidogrel early security public information which require to add black box warning in specification that the clopidogrel has a potential risk of increasing the cardiovascular events owing to being decreased drug efficacy. No functional CYP2C19*2(c.681G> A) and CYP2C19*3(c.636G> A) allele have the important effects on drug metabolism and the drug are unable to give full play to the role in the patients with weak metabolism.
Aim:To fabrication a gold magnetic composite nanoparticle (GoldMag NP) suitable for POCT system of CYP2C19genotyping for clopidogrel individual medication of cardiovascular and cerebrovascular disease. Furthermore, taken the335blood samples of cardiovascular patients as the research object, the CYP2C19*2and CYP2C19*3alleles of P450enzyme involved in the metabolism of clopidogrel were genotyped with the new POCT system and evaluated by gene sequencing technology which is an existing gold standard method. From the analysis of genotype by statistical method, the results revealed allele frequency of CYP2C19*2and CYP2C19*3. At last, the results of statistical correlation analysis between gene mutation and the type of clopidogrel metabolism provide a theoretical and technical support for clopidogrel individual medication.
Methods and Results:
1. The Fe3O4NPs were first prepared using the hydrothermal method, there are oleic molecules on the surface and the mean diameter of FeaO4NPs is8nm, with saturation magnetization55.1emu/g. To render the NPs water-soluble, we oxidized the oleic molecules on the surface of Fe3O4NPs and added CTAB surfactant to make the hydrophobic groups to hydrophilic groups on the surface of the nanoparticles. as-synthesized Fe3O4NPs as the core, prepared the new structure of Fe3O4/Au/Fe3O4petal shaped GoldMag NPs. As revealed by XRD、FT-IR、UV-Vis、VSM、EDS、ICP and HTEM, the mean diameter of the composite particles is38nm, characteristic absorption peak of the Fe3O4/Au composite nanoparticles is at540nm, with saturation magnetization40.7emu/g and coupling capacity of goat anti-mouse IgG307μg permilligram GoldMag NPs. TEM images illustrate GoldMag NPs were in30nm-sized sphere morphology, with large amount of8nm-sized Fe3O4nanoparticles dissolved. These as-synthesized nanoflowers dispersed in water possess good dispersion and stabilization and exhibit a zeta-potential above+30mV.
2. A SNP fast and sensitive chromatography strip for clopidogrel individual medication was designed and prepared. This novel fast chromatographic model was constructed through specific binding the gold magnetic composite nanoparticle marked digoxin monoclonal antibodies and the gene mutation primer of CYP2C19*2(681G>A) and CYP2C19*3(636G>A) alleles marked digoxin molecule. Condition optimization, performance evaluation and parameter confirmation were done through the constructed plasmid DNA and ultraviolet spectrophotometer. The results showed that this novel SNP fast chromatographic test strip has high specificity and the sensitivity can reach0.1%.
3. The335blood samples of cardiovascular and cerebrovascular patients in Shaanxi province were taken as the research object. The gene mutations of CYP2C19*2and CYP2C19*3allele of the samples were determined by the developed SNP fast chromatography technology and the sequencing method which is an existing gold standard method. The statistical results showed that the gene mutations frequency distributions of the two alleles are both comply with the laws of genetic equilibrium, and the accuracy of the novel technology are98%comparing the sequencing method and two methods do not exist significant differences in accuracy. However,the detectable rate of the novel method is much higher than the sequencing method and two methods exist significant differences. The statistical genotypes of these blood samples showed that the population percentage of clopidogrel metabolism type is40.8%for the fast metabolism,43.2%for the metabolism and16%for the slow metabolism, respectively.
Herein, simple, convenience and fast technology with high specificity and sensitivity genotyping method was developed based on the GoldMag NPs. This technology has no complex operation and doesn't need expensive instrument, so it can be easily popularized in all levels of medical institutions in a specifications PCR lab, and promote the individual medication detection to the standardization and industrialization, as well as lay a foundation for the research of clinical drug and disease treatment.
引文
[1]Langreth R., Waldholz M. New era of personalized medicine:targeting drugs for each unique genetic profile [J]. Oncologist,1999,4(5):426-427.
[2]Allison M. Is personalized medicine finally arriving? [J]. Nat. Biotechnol.,2008,26(5): 509-517.
[3]Arnett, D.K, Claas, S.A., Lynch, A.I. Has pharmacogenetics brought us closer to personalized medicine for initial drug treatment of hypertension? [J]. Curr. Opin. Cardiol., 2009,24(4):333-339.
[4]Arteaga C. L., Baselga J. Impact of genomics on personalized cancer medicine [J]. Clin. Cancer Res.,2012,18(3):612-618.
[5]Auffray C, Charron D., Hood L. Predictive, preventive, personalized and participatory medicine:back to the future [J]. Genome Med.,2010,2(8):57-59.
[6]Weinshilboum R. Inheritance and drug response [J]. N. Engl. J. Med.,2003,348:538-549.
[7]Evans W.E., Relling M.V. Pharmacogenomics:translating functional genomics into rational therapeutics [J]. Science,1999,286:487-491.
[8]Ingelman-Sundberg M. Pharmacogenetics:all opportunity for a safer and more efficient pharmacotherapy [J]. J. Intern. Med.,2001,250(3):186-200.
[9]Nebert D.W., Vesell E.S. Advances in pharmacogenomics and individualized drug therapy: exciting challenges mat lie ahead [J]. Eta. J. Pharmacol.,2004,500(1-3):267-280
[10]Bepler G. Pharmacogenomics:a reality or still a promise [J]. Lung Cancer,2006,54 (2): 3-7.
[11]Abraham J., Earl H.M., Pharoah P.D., et al. Pharmacogenetics of cancer chemotherapy [J]. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer,2006,1766(2):168-183.
[12]Botstein D., Risch N. Discovering genotypes underlying human phenotypes:pase successes for mendelian disease, future approaches for complex disease [J]. Nature Genetics,2003,33(suppl):228-237.
[13]Reich D.E., Cargill M., Bolk S., et al. Linkage disequilibrium in the human genome [J]. Nature,2001,411(6834):199-204.
[14]Brown P.O., Hartwell L. Genomics and human disease variations on variation [J]. Nature Genetics,1998,18(1):91-93.
[15]Evans W.E., Reling M.V. Pharmacogenomics:translating functionalgenomics into rational therapeutics [J]. Science,1999,286(5439):487-491.
[16]Fujita K., Sasaki Y. Pharmacogenomics in drug-metabolizing enzymes catalyzing anticancer drugs for personalized cancer chemotherapy [J]. Curr. Drug Metab.,2007,8(6): 554-562.
[17]Licinio J., Wong M.L. Pharmacogenomics:the search for individualized therapies [M]. Weinheim:Wiley-VCH,2002:1-3.
[18]Wang L.W., Weinshilboum R.M. Phannacogenomics:candidate gene identification, functional validation and mechanisms [J]. Hum. Mol. GeneL,2008,17(R2):174-179.
[19]赵广荣,扬帆,元英进等。单核苷酸多态性检测方法的新进展[J]。遗传,2005,27(1)：123-129。
[20]汪维鹏,倪坤仪,周国华。单核苷酸多态性检测方法的研究进展[J]。遗传,2006,28(1)：117-126。
[21]高秀丽,景奉香,杨剑波等。单核苷酸多态性检测分析技术[J]。遗传,2006,27(1)：110-122。
[22]Sanger F., Nicklen S., Coulson A.R. DNA sequencing with chain-terminating inhibitors [J]. Proc. Natl. Acad. Sci. USA,1977,74:5463-7.
[23]Parkhurst K.M., Parkhurst L.J. Detection of point mutations in DNA by fluorescence energy transfer [J]. J. Biomed. Opt.,1996,1(4):435-441.
[24]Chen X.N., Levine L., Kwok P.Y. Fluorescence polarization in homogeneous nucleic acid analysis [J]. Genome Res.,1999,9(5):492-498.
[25]Ross P., Hall L., Smirnov I., et al. High level multiplex genotyping by MALDI-TOF mass spectrometry [J]. Nature Biotechnology,1998,16(13):1347-1351.
[26]Tang K., Fu D.J., Julien D., et al. Chip-based genotyping by mass spectrometry [J]. Proceedings of the National Academy of Sciences,1999,96(18):10016-10020.
[27]Ross P.L., Lee K., Belgrader P. Discrimination of single-nucleotide polymorphisms in human DNA using peptide nucleic acid probes detected by MALDI-TOF mass spectrometry [J]. Analytical Chemistry,1997,69(20):4197-4202.
[28]Adams M.D., Celniker S.E., Holt R.A., et al. The genome sequence of Drosophila melanogaster. Science [J].2000,287(5461):2185-2195.
[29]Ronaghi M., Karamohamed S., pettersson B., et al. Realtime DNA sequencing using detection of pyrophosphaterelease [J]. Anal. Biochem.,1996,242(1):84-89.
[30]Alderbom A., Kristofferson A., Hammerling U. Determination of single nucleotide polymorphisms by real-time pyrophosphate DNA sequencing [J]. Genome Research,2000, 10(8):1249-1258.
[31]Leuvering J.H., Thal P.J., Vander W.M., et al. Sol particle immunoassay (SPIA). J. Immunoassay [J],1980,1(1):77-91.
[32]Beggs M., Novotny M., Samp E., et al. A self performing chromatography immunoassay for the qualitative determination of HCG in urine and serum [J]. Clin. Chem.,1990, 36(6):104-108.
[33]Piepenburg O., Williams C.H., Stemple D.L. DNA Detection Using Recombination Proteins [J]. PLOS Biology,2006,4(7):1115-1121.
[34]Papanikos F., Iliadi A., Petropoulou M. Lateral flow dipstick test for genotyping of 15 beta-globin gene (HBB) mutations with naked-eye detection [J]. Analytica Chimica Acta, 2012,727(21):61-66.
[35]Chen Z.M., Jiang L.X., Chen Y.P., et al. Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction:randomised placebo-controlled trial [J]. Lancet, 2005,366(9497):1607-1621.
[36]Bhatt D.L., Bertrand M.E., Berger P.B., et al. Meta-analysis of randomized and registry comparisons of ticlopidine with clopidogrel after stenting [J]. J. Am. Coll. Cardiol.,2002, 39(1):9-14.
[37]Bhatt D.L. Overcoming 'resistance' to antiplatelet therapy:targeting the issue of nonadherence [J]. Nat. Rev. Cardiol.,2010,7(8):461-467.
[38]Paikin J.S., Eikelboom J.W., Cairns J.A., et al. New antithrombotic agents-insights from clinical trials [J]. Nat. Rev. Cardiol.,2010,7(9):498-509.
[39]Xie H.G., Zou J.J., Hu Z.Y., et al. Individual variability in the disposition of and response to clopidogrel:Pharmacogenomics and beyond [J]. Pharmacology & Therapeutics,2011,129(3):267-289.
[40]Gurbel P.A., Bliden K.P., Hiatt B.L., et al. Clopidogrel for coronary stenting:response variability, drug resistance, and the effect of pretreatment platelet reactivity [J]. Circulation,2003,107(23):2908-2913.
[41]Tate L.G. Characterization of phase I and phase II drug metabolism and the effect ofbeta-naphthoflavone in the liver and posterior kidlley of the channel catfish, Ictalurus punctatus [J]. Arch. Environ. Contam. Toxicol,1988,17(3):325-332.
[42]Josephy P.D., Guengerich E.P., Miners J.O. "Phase I and Phase II" drug metabolism: terminology that we should phase out? [J]. Drug Metab. Rev.,2005,37(4):575-580.
[43]Brandt J.T., Close S.L., Iturria S.J., et al. Common polymorphisms of CYP2C19 and CYP2C9 affect the pharmacokinetic and pharmacodynamic response to clopidogrel but not prasugrel [J]. Thromb Haemost,2007,5(12):2429-2436.
[44]Umemura K., Furuta T., Kondo K. The common gene variants of CYP2C19 affect pharmacokinetics and pharmcodynamics in an active metabolite of clopidogrel in healthy subjects [J]. Thromb Haemost,2008,6(8):1439-1441.
[45]Mega J.L., Close S.L., Wiviott S.D., et al. Cytochrome P450 polymorphisms and response to clopidogrel [J]. N. Engl. J. Med.,2009,360(4):354-362.
[46]Hulot J.S., Bura A., Villard E., et al. Cytochrome P450 2C19 loss-of-function polymorphism is a major determinant of clopidogrel responsiveness in healthy subjects [J]. Blood,2006,108(7):2244-2247.
[47]Fontana P., Hulot J.S., De Moerloose P., et al. Influence of CYP2C19 and CYP3A4 gene polymorphisms on clopidogrel responsiveness in healthy subjects [J]. Thromb Haemost, 2007,5(10):2153-2155.
[48]Giusti B., Gori A.M., Marcucci R., et al. Cytochrome P450 2C19 loss-of-function polymorphism, but not CYP3A4 IVS10+12G/A and P2Y12 T744C polymorphisms, is associated with response variability to dual antiplatelet treatment in high-risk vascular patients [J]. Pharmacogenet Genomics,2007,17(12):1057-1064.
[49]Kim K.A., Park P.W., Hong S.J., et al. The effect of CYP2C19 polymorphism on the pharmacokinetics and pharmacodynamics of clopidogrel:a possible mechanism for clopidogrel resistance [J]. Clin. Pharmacol. Ther.,2008,84(2):236-242.
[50]Bonello L., Camoin-Jau L. Adjusted clopidogrel loading doses according to vasodilator-stimulated phosphoprotein phosphorylation index decrease rate of major adverse cardiovascular events in patients with clopidogrel [J]. JACC,2008,51(14):1404-1411.
[51]Kim K.A., Park P.W., Hong S.J., et al. The effect of CYP2C19 polymorphism on the pharmacokinetics and pharmacodynamics of clopidogrel:a possible mechanism for clopidogrel resistance [J]. Clin. Pharmacol. Ther.,2008,84(2):236-42.
[52]张立德,纳米材料[M]。北京：化学工业出版社,2000。
[53]张志煜,崔作林。纳米技术与纳米材料[M]。北京：国防工业出版社,2000。
[54]李玲,向航,功能材料与纳米材料[M]。北京：化学工业出版社,2000。
[55]白春礼。纳米科学与技术[M]。昆明：云南科学技术出版社,1995。
[56]段波,肖建中。超微粉制备技术的现状与展望[J]。材料工程,1994,6：5-8。
[57]丁星兆,柳襄怀。纳米材料的结构性能及应用[J]。材料导报,1997,11(4)：1-5。
[58]Koch C.C. The synthesis and structure of nanocrystalline materials produced by mechanical attrition:a review [J]. Nanostructured Materials,1993,2(2):109-129.
[59]Zarur A.J., Ying J.Y. Reverse microemulsion synthesis of nanostructured complex oxides for catalytic combustion [J]. Nature,2000,403(6765):65-67.
[60]Marignier J.L., Belloni J., Delcourt M.O., et al. Microaggregates of non-noble metals and bimetallic alloys prepared by radiation-induced reduction [J]. Nature,1985, 317(6035):344-345.
[61]Sleytr, Uwe B., Mann, et al. Synthesis of cadmium sulfide superlattices using self-assembled bacterial s-layers [J]. Nature,1997,389(6651):585-587.
[62]Sun S.H., Murray C.B., Weller D. et al. Monodisperse FePt nanoparticles and ferromagnetic FePt nanocrystal superlattices [J]. Science,2000,287(5460):1989-1992.
[63]Wu H., Zhang R., Liu X.X., et al. Electrospinning of Fe, Co, and Ni nanofibers:synthesis, assembly, and magnetic properties [J]. Chem. Mater.,2007,19(14):3506-3511.
[64]Gesquiere A.J. Optical properties and spectroscopy of nanomaterials [J]. J. Am. Chem. Soc.,2010,132(10):3637-3638.
[65]Langhammer C., Larsson E.M., Kasemo B., et al. Indirect nanoplasmonic sensing: ultrasensitive experimental platform for nanomaterials science and optical nanocalorimetry [J]. Nano Lett.,2010,10(9):3529-3538.
[66]Kreibig U., Vollmer M. Optical properties of metal clusters [M]. Springer-Verlag, Berlin, Heidelberg,1995.
[67]Doerk G.S., Carraro C., Maboudian R. Single nanowire thermal conductivity measurements by raman thermography [J]. ACS Nano,2010,4(8):4908-4914.
[68]Goldsteina R.V., Morozov N.F. Mechanics of deformation and fracture of nanomaterials and nanotechnology [J]. Physical Mesomechanics,2007,10(5-6):235-246.
[69]Kim S.Y., Park H.S. Utilizing mechanical strain to mitigate the intrinsic loss mechanisms in oscillation metal nanowires [J]. Phys. Rev. Lett.,2008,101:215502(1-4).
[70]倪兴元,姚兰芳,沈军等。纳米材料的制备技术[M]。北京：化学工业出版社,2008：27-145。
[71]李群。纳米材料的制备与应用技术[M]。北京：化学工业出版社,2008：20-334。
[72]Park J., Joo J., Kwon S.G., et al. Synthesis of monodisperse spherical nanocrystals [J]. Angewandte Chemie, International Edition,2007,46(25):4630-4660.
[73]Tartaj P., Morales M.P., Verdaguer S.V., et al. The preparation of magnetic nanoparticles for applications in biomedicine[J]. Journal of Applied Physics D,2003,36(13):R182-R197.
[74]Lu A.H., Salabas E.L., Schiith F. Magnetic nanoparticles:synthesis, protection, functionalization, and application [J]. Angewandte Chemie, International Edition,2007, 46(8):1222-1244.
[75]吴伟,贺全国,陈洪。磁性纳米颗粒在生物传感器中的应用研究进展[J]。化学通报,2007,4：277-285。
[76]赵紫来,卞征云,陈朗星等。氧化铁磁性纳米颗粒的制备、表面修饰及在分离和分析中的应用[J]。化学进展,2006,18(10)：1288-1297。
[77]Morales M.P., Verdaguer S.V., Montero M.I., et al. Surface and internal spin canting in y-Fe2O3 nanoparticles [J]. Chemistry of Materials,1999,11(11):3058-3064
[78]Lu H.C., Yi G.S., Zhao S.Y., et al. Synthesis and characterization of multi-functional nanoparticles possessing magnetic, up-conversion fluorescence and bio-affinity properties [J]. Journal of Materials Chemistry,2004,14(8):1336-1341.
[79]Jeong J.R., Lee S.J., Kim J.D., et al. Magnetic properties of γ-Fe2O3 nanoparticles made by coprecipitation method [J]. Physica Status Solidi B:Basic Solid State Physics,2004, 241(7):1593-1596.
[80]陈亭汝,孙瑾。Fe304磁性纳米颗粒的共沉淀法制备研究[J]。应用化工,2009,38(2)：226-232。
[81]Neveu S., Bee A., Robineau M., et al. Size-selective chemical synthesis of tartrate stabilized cobalt ferrite ionic magnetic fluid [J]. Journal of Colloid and Interface Science, 2002,255(2):293-298.
[82]Burojeanu V.M., Fourne's L., Wattiaux A., et al. Cations distribution and magnetic properties of manganese ferrite powder prepared by coprecipitation from MnO2 and FeSO7·7H2O [J]. International Journal of Inorganic Materials,2001,3(6):525-529.
[83]Stober W., Fink A., Bohn E. Controlled growth of monodisperse silica spheres in the micron size range [J]. J. Colloid Interface Sci.,1968,26(1):62-69.
[84]Lu Z.Y., Dai J., Song X.N., et al. Facile synthesis of Fe3O4/SiO2 composite nanoparticles fromprimary silica particles [J]. Colloids and Surfaces A.,2008,317(1-3): 450-456.
[85]Frens G. Controlled nucleation for the regulation of the particle size in monodisperse gold suspensions [J]. Nature, Physical Science,1973,241(105):20-22.
[86]Claesson E.M., Philipse A.P. Monodisperse magnetizable composite silica spheres with tunable dipolar interactions [J]. Langmuir.,2005,21(21):9412-9419.
[87]Santra S., Tapec R., Theodoropoulou N., et al. Synthesis and characterization of silica-coated iron oxide nanoparticles in microemulsion:the effect of nonionic surfactants [J]. Langmuir,2001,17(10):2900-2906.
[88]Corr S.A., Gun'ko Y.K., Douvalis A.P., et al. Magnetite nanocrystals from a single source metallorganic precursor:metallorganic chemistry vs. biogeneric bacteria [J]. Journal of Materials Chemistry,2004,14(6):944-946.
[89]Perez L.J.A., Quintela L.M.A., Mira J., et al. Advances in the preparation of magnetic nanoparticles by the microemulsion method [J]. Journal of Physical Chemistry B,1997, 101(41):8045-8047.
[90]Meziani M.J., Liu P., Pathak P., et al. Stable suspension of crystalline Fe3O4 nanoparticles from in situ hot-fluid annealing [J]. Industrial & Engineering Chemistry Research,2006,45(4):1539-1541.
[91]Dresco P.A., Zaitsev V.S., Gambino R.J., et al. Preparation and properties of magnetite and polymer magnetite nanoparticles [J]. Langmuir,1999,15(6):1945-1951.
[92]Lee K.M., Sorensen C.M., Klabunde K.J., et al. Synthesis and characterization of stable colloidal Fe3O4 particles in water-in-oil microemulsions [J]. IEEE Transactions on Magnetics,1992,28(5):3180-3182.
[93]Si S.F., Li C.H., Wang X., et al. Magnetic monodisperse Fe3O4 nanoparticles [J]. Crystal Growth & Design,2005,5(2):391-393.
[94]Liang X., Wang X., Zhuang J., et al. synthesis of nearly monodisperse iron oxide and oxyhydroxide nanocrystals [J]. Advanced Functional Material,2006,16(14):1805-1813.
[95]Liu J., Sun Z.K., Deng Y.H., et al. Highly water-dispersible biocompatible magnetite particles with low cytotoxicity stabilized by citrate groups [J].Angewandte Chemie, International Edition,2009,48(32):5875-5879.
[96]耿明鑫,刘福田。水热法制备Fe304磁性纳米颗粒[J].济南大学学报,2009,23(2)：141-144。
[97]Deng H., Li X.L. Peng Q., et al. Monodisperse magnetic single-crystal ferrite microspheres [J]. Angewandte Chemie, International Edition,2005,44(18):2782-2785.
[98]Lu J., Jiao X.L., Chen D.R., et al. Solvothermal synthesis and characterization of Fe3O4 and γ-Fe2O3 nanoplates [J]. Journal of Physical Chemistry C,2009,113(10):4012-4017.
[99]Piticescu R.M., Piticescul R.R., Taloil D. et al. Hydrothermal synthesis of ceramic nanomaterials for functional applications [J]. Nanotechnology,2003,14(2):312-317.
[100]Kang S.J., Kocabas C., Ozel T., et al. High-performance electronics using dense, perfectly aligned arrays of single-walled carbon nanotubes [J]. Nature Nanotechnology 2007,2(4):230-236.
[101]Zhang C., Zhang Z.Y., Yu B.B. Application of the biological conjugate between antibody and colloid au nanoparticles as analyte to inductively coupled plasma mass spectrometry [J]. Anal. Chem.,2002,74(1):96-99.
[102]Jun Y.W., Huh Y.M., Choi J.S., et al. Nanoscale size effect of magnetic nanocrystals and their utilization for cancer diagnosis via magnetic resonance imaging [J]. Am. Chem. Soc.,2005,127(16):5732-5733.
[103]Lin J., Zhou W., Kumbhar A., et al. Gold-coated iron (Fe@Au) nanoparticles:synthesis, characterization, and magnetic field-induced self-assembly [J]. Solid State Chem.,2001, 159(1):26-31.
[104]Lyon J.L., Fleming D.A., Stone M.B., et al. Synthesis of Fe oxide core/Au shell nanoparticles by iterative hydroxylamine seeding [J]. Nano Lett.,2004,4(4):719-723.
[105]Cui Y.L., Hu D.D., Fang Y., et al. Preparation and mechanism of Fe3O4/Au core/shell super-paramagnetic microspheres [J]. Chnia Ser. B,2001,44(4):404-410.
[106]Bao J., Chen W., Liu T.T., et al. Bifunctional Au-Fe3O4 nanoparticles for protein separation [J]. ACS Nano.,2007,1(4):293-298.
[107]Zhang J., Post M., Veres T., et al. Laser-assisted synthesis of superparamagnetic Fe@Au core-shell nanoparticles [J]. Chem. B,2006,110(14):7122-7128.
[108]Wei Y.H., Klajn R., Pinchuk A. O., et al. Shape control and optical properties of Fe3O4-Au "nanoflowers" [J]. Small 2008,4(10):1635-1639.
[109]Wang L.Y., Luo J., Fan Q., et al. Monodispersed core-shell Fe3O4@Au nanoparticles [J]. Chem. B,2005,109(46):21593-21601.
[110]Wang L.Y., Park H.Y., Lim S., et al. Core@shell nanomaterials:gold-coated magnetic oxide nanoparticles [J]. Journal of Materials Chemistry,2008,18:2629-2635.
[111]Cho S. J., Idrobo J. C., Olamit J., et al. Growth mechanisms and oxidation-resistance of gold-coated iron nanoparticles [J]. Chem. Mater.,2005,17(12):3181-3186.
[112]Wang L.Y., Bai J.W., Li Y.J., et al. Multifunctional nanoparticles displaying magnetization and near-IR absorption [J]. Angew. Chem. Int. Ed.,2008,47(13):2439-2442.
[113]Cui Y. L., Hui W. L., Wang H. R., et al. Preparation and characterization of Fe3O4/Au composite particles [J]. Science in China (Series B).2004,47(7):152-158.
[114]Cui Y.L., Wang Y.N., Hui W.L., et al. The synthesis of goldmag nano-particles and their application for antibody immobilization [J]. Biomedical Microdevices,2005,7(2): 153-156.
[115]Giardiello M., McDonald T.O., Martin P., et al. Facile synthesis of complex multi-component organic and organic-magnetic inorganic nanocomposite particles [J]. J. Mater. Chem.,2012,22(47):24744-24752.
[116]Zhang H., Zhong X., Xu J.J., et al. Fe3O4/Polypyrrole/Au nanocomposites with core/shell/shell structure:synthesis, characterization, and their electrochemical properties [J]. Langmuir,2008,24(23):13748-13752.
[117]Qi D.W., Zhang H.Y., Tang J., et al. Facile synthesis of mercaptophenylboronic acid-functionalized core-shell structure Fe3O4@C@Au magnetic microspheres for selective enrichment of glycopeptides and glycoproteins [J]. J. Phys. Chem. C,2010,114(20): 9221-9226.
[118]Xu Z.C., Hou Y.L., Sun S.H. Magnetic core/shell Fe3O4/Au and Fe3O4/Au/Ag nanoparticles with tunable plasmonic properties [J]. J. Am. Chem. Soc,2007,129(28): 8698-8699.
[119]Peng S., Lei C, Ren Y., et al. Plasmonic-magnetic bifunctional nanoparticles [J]. Angew. Chem. Int. Ed.,2011,50(14); 3158-3163.
[120]Caruntu D., Cushing B.L., Carunt G., et al. Attachment of gold nanograins onto colloidal magnetite nanocrystals [J]. Chem. Mater.,2005,17(13):3398-3402.
[121]Yu H., Chen M., Rice P.M., et al. Dumbbell-like bifunctional Au-Fe3O4 nanoparticles [J]. Nano Lett.,2005,5(2):379-382.
[122]Wei Y. H., Klajn R., Anatoliy O, et al. Synthesis, shape control, and optical properties of hybrid Au/Fe3O4 "nanoflowers" [J]. Small,2008,4(10):1635-1639.
[123]Zhang H., Zhong X., Xu J. J., et al. Fe3O4/polypyrrole/Au nanocomposites with core/shell/shell structure:synthesis, characterization, and their electrochemical Properties [J]. Langmuir,2008,24(23):13748-13752.
[124]Gole A., Stone J. W., William R., et al. Murphy, iron oxide coated gold nanorods: synthesis, characterization, and magnetic manipulation [J]. Langmuir,2008,24 (12), 6232-6237.
[125]Park H.Y., Schadt M.J., Lim L., et al. Fabrication of magnetic Core@Shell Fe Oxide@Au nanoparticles for interfacial bioactivity and bio-separation [J]. Langmuir,2007,23 (17),9050-9056.
[126]Zhou X., Xu W. L., Wang Y., et al. Fabrication of Cluster/Shell Fe3O4/Au Nanoparticles and Application in Protein Detection via a SERS Method [J]. J. Phys. Chem. C,2010,114(46),19607-19613.
[127]Cho S. Jin., Jarrett B. R., Louie A. Y., et al. Gold-coated iron nanoparticles:a novel magnetic resonance agent for T1 and T2 weighted imaging [J]. Nanotechnology,2006, 17(3):640-645.
[128]Kim J. W., Kim Y. D., Antibiofouling colymer coated gold@iron oxide nanoparticle as a dual contrast agent for CT and MRI[J]. Bull. Korean Chem. Soc.,2009,30(8):185-190.
[129]Kang K. A., Jin H. Application of novel metal nanoparticles as optical/thermal agents in optical mammography and hyperthermic treatment for breast cancer [J]. Seamless Detection and Treatment,2010,10(1):123-125.
[130]Chao X., Zhang Z., li., Guo L., L., et al. A novel magnetic nanoparticle drug carrier for enhanced cancer chemotherapy [J]. P1OS ONE,2012,7(10):1-7.
[131]SHI F., Hui W., L., CUI Y., L. Surface modification and characterization of Fe3O4/Au composite nanoparticles [J]. NANO:Brief Reports and Reviews.2011,6,145-151.
[132]Chao X, Guo L., L., Zhao Y.,Yong., et al. PEG-modified GoldMag nanoparticles combined with the external magnetic fields for local drug delivery [J]. Journal of Drug Targeting,2011,19(3):161-167.
[133]Chao X, SHI F., Zhao Y.Y., et al. Cytotoxicity of Fe3O4/Au composite nanoparticles loaded with doxorubicin combined with magnetic field [J]. The journal Die Pharmazie, 2010,65:500-504.
[134]崔亚丽,杨璐,陈超等.磁酶免化学发光检测梅毒螺旋体抗体的方法[P].中国发明专利：200910219357.8。
[135]崔亚丽,邓晨,杨柳等.一种用磁性微粒从含微量核酸的样本中纯化DNA的方法[P].中国发明专利：201110314908.6。
[136]崔亚丽,石峰,惠文利。金磁微粒标记免疫层析快速检测方法[P].中国发明专利：201010222447.5。
[137]祖立闯,王金良,李娇等.胶体金免疫层析技术在动物疫病诊断上的应用[J].动物医学进展,2010,31(8)：101-105。
[138]严华,申厚凤。胶体金免疫层析技术的应用与展望[J].微生物学免疫学进展,2005,3：86-89。
[139]Zhuang J.Q., Guo M.J., Shen Z.Q. Application of Colloidal-gold Immuno-chromatography Assay(GICA) in Veterinary Clinical Diagnosis [J]. China Animal Health Inspection,2012,29(9)32-37
[140]Self C.H., Cook D. B., Advances in immunoassay technology [J]. Curr. Opin. Biotechnol.,1996,7(1):60-65.
[141]熊勇华,陈雪岚,陈媛。甲基苯丙胺的胶体金免疫层析检测卡的研制[J].卫生研究,2010,24(1)：120-122。
[142]孙秀兰,张银志,汤坚等.金标免疫层析试条检测样品中黄曲霉毒素B1的误差分析[J]。西北农林科技大学学报(自然科学版),2007,35(7)：188-192。
[143]林茹,李明珠,黄琦玲。半抗原免疫层析法在农药残留检测中的应用[J]。广东农业科学,2010,37(7)：230-233。
[144]万宇平,高东微,冯才伟等。检测三聚氰胺胶体金免疫层析试验的建立[J]。中国乳品工业,2010,38(10)：46-47。
[145]Matteucci E., Giampietro O. Point-of-care testing in diabetes care[J]. Mini Rev. Med. Chem.,2011,11(2):178-184.
[146]Lee-Lewandrowski E., Januzzi J. L., Grisson R., et al. Evaluation of first-draw whole blood, point-of-care cardiac markers in the context of the universal definition of myocardial infarction:a comparison of a multimarker panel to troponin alone and to testing in the central laboratory [J]. Arch Pathol Lab Med.,2011,135(4):459-463.
[147]Lee E.J., Shin S.D., Song K.J., et al. A point-of-care chemistry test for reduction of turnaround and clinical decision time [J]. Am. J. Emerg. Med.,2011,29(5):489-495.
[148]Jain A., Persaud J.W., Rao N., et al. Point of care testing is appropriate for national health service health check [J]. Ann. Clin. Biochem.,2011,48(2):159-165.
[149]Hjortshoj S., Venge P., Ravkilde J. Clinical performance of a new point-of-care cardiac troponin I assay compared to three laboratory troponin assays [J]. Clin. Chim. Acta,2011, 412(3-4):370-375.
[150]Cui Y. L., Hui W. L., Su J., et al. Fe3O4/Au composite nanoparticles and their optical properties [J]. Science in China (Series B).2005,48(4),273-278.
[151]SHI F., Hui W. L., Cui Y. L. Surface modification and characterization of composite nanoparticles. NANO:Brief Reports and Reviews [J].2011,6,145-151.
[152]Wang M., Peng M.L., Cheng W., et al., J. Nanosci. A novel approach for transferring oleic acid capped iron oxide nanoparticles to water phase [J]. Nanotechnol.,2011,11(4): 3688-3691.
[153]Goldstein J. A. Clinical relevance of genetic polymorphisms in the human CYP2C subfamily [J]. British journal of clinical pharmacology,2001,52(4):349-355.
[154]Di Y.M., Chow V.D., Yang L.P., et al. Structure, function, regulation and polymorphism of human cytochrome P450 2A6 [J]. Curr. Drug Metab.,2009,10(7):754-780.
[155]Xie H., Griskevicius L., Stahle L., et al. Pharmacogenetics of cyclophosphamide in patients with hematological malignancies [J]. Eur. J. Pharm. Sci.,2006,27(1):54-61.
[156]Hollopeter G, Jantzen H.M., Vincent D., et al. Identification of the platelet ADP receptor targeted by antithrombotic drugs [J]. Nature,2001,409(6817):202-207.
[157]Beitelshees A. L., McLeod H.L. Clopidogrel pharmacogenetics:promising steps towards patient care? [J]. Arterioscler Thromb. Vasc. Biol.2006,26(8):1681-1683.
[2]Allison M. Is personalized medicine finally arriving? [J]. Nat. Biotechnol.,2008,26(5): 509-517.
[3]Arnett, D.K, Claas, S.A., Lynch, A.I. Has pharmacogenetics brought us closer to personalized medicine for initial drug treatment of hypertension? [J]. Curr. Opin. Cardiol., 2009,24(4):333-339.
[4]Arteaga C. L., Baselga J. Impact of genomics on personalized cancer medicine [J]. Clin. Cancer Res.,2012,18(3):612-618.
[5]Auffray C, Charron D., Hood L. Predictive, preventive, personalized and participatory medicine:back to the future [J]. Genome Med.,2010,2(8):57-59.
[6]Weinshilboum R. Inheritance and drug response [J]. N. Engl. J. Med.,2003,348:538-549.
[7]Evans W.E., Relling M.V. Pharmacogenomics:translating functional genomics into rational therapeutics [J]. Science,1999,286:487-491.
[8]Ingelman-Sundberg M. Pharmacogenetics:all opportunity for a safer and more efficient pharmacotherapy [J]. J. Intern. Med.,2001,250(3):186-200.
[9]Nebert D.W., Vesell E.S. Advances in pharmacogenomics and individualized drug therapy: exciting challenges mat lie ahead [J]. Eta. J. Pharmacol.,2004,500(1-3):267-280
[10]Bepler G. Pharmacogenomics:a reality or still a promise [J]. Lung Cancer,2006,54 (2): 3-7.
[11]Abraham J., Earl H.M., Pharoah P.D., et al. Pharmacogenetics of cancer chemotherapy [J]. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer,2006,1766(2):168-183.
[12]Botstein D., Risch N. Discovering genotypes underlying human phenotypes:pase successes for mendelian disease, future approaches for complex disease [J]. Nature Genetics,2003,33(suppl):228-237.
[13]Reich D.E., Cargill M., Bolk S., et al. Linkage disequilibrium in the human genome [J]. Nature,2001,411(6834):199-204.
[14]Brown P.O., Hartwell L. Genomics and human disease variations on variation [J]. Nature Genetics,1998,18(1):91-93.
[15]Evans W.E., Reling M.V. Pharmacogenomics:translating functionalgenomics into rational therapeutics [J]. Science,1999,286(5439):487-491.
[16]Fujita K., Sasaki Y. Pharmacogenomics in drug-metabolizing enzymes catalyzing anticancer drugs for personalized cancer chemotherapy [J]. Curr. Drug Metab.,2007,8(6): 554-562.
[17]Licinio J., Wong M.L. Pharmacogenomics:the search for individualized therapies [M]. Weinheim:Wiley-VCH,2002:1-3.
[18]Wang L.W., Weinshilboum R.M. Phannacogenomics:candidate gene identification, functional validation and mechanisms [J]. Hum. Mol. GeneL,2008,17(R2):174-179.
[19]赵广荣,扬帆,元英进等。单核苷酸多态性检测方法的新进展[J]。遗传,2005,27(1)：123-129。
[20]汪维鹏,倪坤仪,周国华。单核苷酸多态性检测方法的研究进展[J]。遗传,2006,28(1)：117-126。
[21]高秀丽,景奉香,杨剑波等。单核苷酸多态性检测分析技术[J]。遗传,2006,27(1)：110-122。
[22]Sanger F., Nicklen S., Coulson A.R. DNA sequencing with chain-terminating inhibitors [J]. Proc. Natl. Acad. Sci. USA,1977,74:5463-7.
[23]Parkhurst K.M., Parkhurst L.J. Detection of point mutations in DNA by fluorescence energy transfer [J]. J. Biomed. Opt.,1996,1(4):435-441.
[24]Chen X.N., Levine L., Kwok P.Y. Fluorescence polarization in homogeneous nucleic acid analysis [J]. Genome Res.,1999,9(5):492-498.
[25]Ross P., Hall L., Smirnov I., et al. High level multiplex genotyping by MALDI-TOF mass spectrometry [J]. Nature Biotechnology,1998,16(13):1347-1351.
[26]Tang K., Fu D.J., Julien D., et al. Chip-based genotyping by mass spectrometry [J]. Proceedings of the National Academy of Sciences,1999,96(18):10016-10020.
[27]Ross P.L., Lee K., Belgrader P. Discrimination of single-nucleotide polymorphisms in human DNA using peptide nucleic acid probes detected by MALDI-TOF mass spectrometry [J]. Analytical Chemistry,1997,69(20):4197-4202.
[28]Adams M.D., Celniker S.E., Holt R.A., et al. The genome sequence of Drosophila melanogaster. Science [J].2000,287(5461):2185-2195.
[29]Ronaghi M., Karamohamed S., pettersson B., et al. Realtime DNA sequencing using detection of pyrophosphaterelease [J]. Anal. Biochem.,1996,242(1):84-89.
[30]Alderbom A., Kristofferson A., Hammerling U. Determination of single nucleotide polymorphisms by real-time pyrophosphate DNA sequencing [J]. Genome Research,2000, 10(8):1249-1258.
[31]Leuvering J.H., Thal P.J., Vander W.M., et al. Sol particle immunoassay (SPIA). J. Immunoassay [J],1980,1(1):77-91.
[32]Beggs M., Novotny M., Samp E., et al. A self performing chromatography immunoassay for the qualitative determination of HCG in urine and serum [J]. Clin. Chem.,1990, 36(6):104-108.
[33]Piepenburg O., Williams C.H., Stemple D.L. DNA Detection Using Recombination Proteins [J]. PLOS Biology,2006,4(7):1115-1121.
[34]Papanikos F., Iliadi A., Petropoulou M. Lateral flow dipstick test for genotyping of 15 beta-globin gene (HBB) mutations with naked-eye detection [J]. Analytica Chimica Acta, 2012,727(21):61-66.
[35]Chen Z.M., Jiang L.X., Chen Y.P., et al. Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction:randomised placebo-controlled trial [J]. Lancet, 2005,366(9497):1607-1621.
[36]Bhatt D.L., Bertrand M.E., Berger P.B., et al. Meta-analysis of randomized and registry comparisons of ticlopidine with clopidogrel after stenting [J]. J. Am. Coll. Cardiol.,2002, 39(1):9-14.
[37]Bhatt D.L. Overcoming 'resistance' to antiplatelet therapy:targeting the issue of nonadherence [J]. Nat. Rev. Cardiol.,2010,7(8):461-467.
[38]Paikin J.S., Eikelboom J.W., Cairns J.A., et al. New antithrombotic agents-insights from clinical trials [J]. Nat. Rev. Cardiol.,2010,7(9):498-509.
[39]Xie H.G., Zou J.J., Hu Z.Y., et al. Individual variability in the disposition of and response to clopidogrel:Pharmacogenomics and beyond [J]. Pharmacology & Therapeutics,2011,129(3):267-289.
[40]Gurbel P.A., Bliden K.P., Hiatt B.L., et al. Clopidogrel for coronary stenting:response variability, drug resistance, and the effect of pretreatment platelet reactivity [J]. Circulation,2003,107(23):2908-2913.
[41]Tate L.G. Characterization of phase I and phase II drug metabolism and the effect ofbeta-naphthoflavone in the liver and posterior kidlley of the channel catfish, Ictalurus punctatus [J]. Arch. Environ. Contam. Toxicol,1988,17(3):325-332.
[42]Josephy P.D., Guengerich E.P., Miners J.O. "Phase I and Phase II" drug metabolism: terminology that we should phase out? [J]. Drug Metab. Rev.,2005,37(4):575-580.
[43]Brandt J.T., Close S.L., Iturria S.J., et al. Common polymorphisms of CYP2C19 and CYP2C9 affect the pharmacokinetic and pharmacodynamic response to clopidogrel but not prasugrel [J]. Thromb Haemost,2007,5(12):2429-2436.
[44]Umemura K., Furuta T., Kondo K. The common gene variants of CYP2C19 affect pharmacokinetics and pharmcodynamics in an active metabolite of clopidogrel in healthy subjects [J]. Thromb Haemost,2008,6(8):1439-1441.
[45]Mega J.L., Close S.L., Wiviott S.D., et al. Cytochrome P450 polymorphisms and response to clopidogrel [J]. N. Engl. J. Med.,2009,360(4):354-362.
[46]Hulot J.S., Bura A., Villard E., et al. Cytochrome P450 2C19 loss-of-function polymorphism is a major determinant of clopidogrel responsiveness in healthy subjects [J]. Blood,2006,108(7):2244-2247.
[47]Fontana P., Hulot J.S., De Moerloose P., et al. Influence of CYP2C19 and CYP3A4 gene polymorphisms on clopidogrel responsiveness in healthy subjects [J]. Thromb Haemost, 2007,5(10):2153-2155.
[48]Giusti B., Gori A.M., Marcucci R., et al. Cytochrome P450 2C19 loss-of-function polymorphism, but not CYP3A4 IVS10+12G/A and P2Y12 T744C polymorphisms, is associated with response variability to dual antiplatelet treatment in high-risk vascular patients [J]. Pharmacogenet Genomics,2007,17(12):1057-1064.
[49]Kim K.A., Park P.W., Hong S.J., et al. The effect of CYP2C19 polymorphism on the pharmacokinetics and pharmacodynamics of clopidogrel:a possible mechanism for clopidogrel resistance [J]. Clin. Pharmacol. Ther.,2008,84(2):236-242.
[50]Bonello L., Camoin-Jau L. Adjusted clopidogrel loading doses according to vasodilator-stimulated phosphoprotein phosphorylation index decrease rate of major adverse cardiovascular events in patients with clopidogrel [J]. JACC,2008,51(14):1404-1411.
[51]Kim K.A., Park P.W., Hong S.J., et al. The effect of CYP2C19 polymorphism on the pharmacokinetics and pharmacodynamics of clopidogrel:a possible mechanism for clopidogrel resistance [J]. Clin. Pharmacol. Ther.,2008,84(2):236-42.
[52]张立德,纳米材料[M]。北京：化学工业出版社,2000。
[53]张志煜,崔作林。纳米技术与纳米材料[M]。北京：国防工业出版社,2000。
[54]李玲,向航,功能材料与纳米材料[M]。北京：化学工业出版社,2000。
[55]白春礼。纳米科学与技术[M]。昆明：云南科学技术出版社,1995。
[56]段波,肖建中。超微粉制备技术的现状与展望[J]。材料工程,1994,6：5-8。
[57]丁星兆,柳襄怀。纳米材料的结构性能及应用[J]。材料导报,1997,11(4)：1-5。
[58]Koch C.C. The synthesis and structure of nanocrystalline materials produced by mechanical attrition:a review [J]. Nanostructured Materials,1993,2(2):109-129.
[59]Zarur A.J., Ying J.Y. Reverse microemulsion synthesis of nanostructured complex oxides for catalytic combustion [J]. Nature,2000,403(6765):65-67.
[60]Marignier J.L., Belloni J., Delcourt M.O., et al. Microaggregates of non-noble metals and bimetallic alloys prepared by radiation-induced reduction [J]. Nature,1985, 317(6035):344-345.
[61]Sleytr, Uwe B., Mann, et al. Synthesis of cadmium sulfide superlattices using self-assembled bacterial s-layers [J]. Nature,1997,389(6651):585-587.
[62]Sun S.H., Murray C.B., Weller D. et al. Monodisperse FePt nanoparticles and ferromagnetic FePt nanocrystal superlattices [J]. Science,2000,287(5460):1989-1992.
[63]Wu H., Zhang R., Liu X.X., et al. Electrospinning of Fe, Co, and Ni nanofibers:synthesis, assembly, and magnetic properties [J]. Chem. Mater.,2007,19(14):3506-3511.
[64]Gesquiere A.J. Optical properties and spectroscopy of nanomaterials [J]. J. Am. Chem. Soc.,2010,132(10):3637-3638.
[65]Langhammer C., Larsson E.M., Kasemo B., et al. Indirect nanoplasmonic sensing: ultrasensitive experimental platform for nanomaterials science and optical nanocalorimetry [J]. Nano Lett.,2010,10(9):3529-3538.
[66]Kreibig U., Vollmer M. Optical properties of metal clusters [M]. Springer-Verlag, Berlin, Heidelberg,1995.
[67]Doerk G.S., Carraro C., Maboudian R. Single nanowire thermal conductivity measurements by raman thermography [J]. ACS Nano,2010,4(8):4908-4914.
[68]Goldsteina R.V., Morozov N.F. Mechanics of deformation and fracture of nanomaterials and nanotechnology [J]. Physical Mesomechanics,2007,10(5-6):235-246.
[69]Kim S.Y., Park H.S. Utilizing mechanical strain to mitigate the intrinsic loss mechanisms in oscillation metal nanowires [J]. Phys. Rev. Lett.,2008,101:215502(1-4).
[70]倪兴元,姚兰芳,沈军等。纳米材料的制备技术[M]。北京：化学工业出版社,2008：27-145。
[71]李群。纳米材料的制备与应用技术[M]。北京：化学工业出版社,2008：20-334。
[72]Park J., Joo J., Kwon S.G., et al. Synthesis of monodisperse spherical nanocrystals [J]. Angewandte Chemie, International Edition,2007,46(25):4630-4660.
[73]Tartaj P., Morales M.P., Verdaguer S.V., et al. The preparation of magnetic nanoparticles for applications in biomedicine[J]. Journal of Applied Physics D,2003,36(13):R182-R197.
[74]Lu A.H., Salabas E.L., Schiith F. Magnetic nanoparticles:synthesis, protection, functionalization, and application [J]. Angewandte Chemie, International Edition,2007, 46(8):1222-1244.
[75]吴伟,贺全国,陈洪。磁性纳米颗粒在生物传感器中的应用研究进展[J]。化学通报,2007,4：277-285。
[76]赵紫来,卞征云,陈朗星等。氧化铁磁性纳米颗粒的制备、表面修饰及在分离和分析中的应用[J]。化学进展,2006,18(10)：1288-1297。
[77]Morales M.P., Verdaguer S.V., Montero M.I., et al. Surface and internal spin canting in y-Fe2O3 nanoparticles [J]. Chemistry of Materials,1999,11(11):3058-3064
[78]Lu H.C., Yi G.S., Zhao S.Y., et al. Synthesis and characterization of multi-functional nanoparticles possessing magnetic, up-conversion fluorescence and bio-affinity properties [J]. Journal of Materials Chemistry,2004,14(8):1336-1341.
[79]Jeong J.R., Lee S.J., Kim J.D., et al. Magnetic properties of γ-Fe2O3 nanoparticles made by coprecipitation method [J]. Physica Status Solidi B:Basic Solid State Physics,2004, 241(7):1593-1596.
[80]陈亭汝,孙瑾。Fe304磁性纳米颗粒的共沉淀法制备研究[J]。应用化工,2009,38(2)：226-232。
[81]Neveu S., Bee A., Robineau M., et al. Size-selective chemical synthesis of tartrate stabilized cobalt ferrite ionic magnetic fluid [J]. Journal of Colloid and Interface Science, 2002,255(2):293-298.
[82]Burojeanu V.M., Fourne's L., Wattiaux A., et al. Cations distribution and magnetic properties of manganese ferrite powder prepared by coprecipitation from MnO2 and FeSO7·7H2O [J]. International Journal of Inorganic Materials,2001,3(6):525-529.
[83]Stober W., Fink A., Bohn E. Controlled growth of monodisperse silica spheres in the micron size range [J]. J. Colloid Interface Sci.,1968,26(1):62-69.
[84]Lu Z.Y., Dai J., Song X.N., et al. Facile synthesis of Fe3O4/SiO2 composite nanoparticles fromprimary silica particles [J]. Colloids and Surfaces A.,2008,317(1-3): 450-456.
[85]Frens G. Controlled nucleation for the regulation of the particle size in monodisperse gold suspensions [J]. Nature, Physical Science,1973,241(105):20-22.
[86]Claesson E.M., Philipse A.P. Monodisperse magnetizable composite silica spheres with tunable dipolar interactions [J]. Langmuir.,2005,21(21):9412-9419.
[87]Santra S., Tapec R., Theodoropoulou N., et al. Synthesis and characterization of silica-coated iron oxide nanoparticles in microemulsion:the effect of nonionic surfactants [J]. Langmuir,2001,17(10):2900-2906.
[88]Corr S.A., Gun'ko Y.K., Douvalis A.P., et al. Magnetite nanocrystals from a single source metallorganic precursor:metallorganic chemistry vs. biogeneric bacteria [J]. Journal of Materials Chemistry,2004,14(6):944-946.
[89]Perez L.J.A., Quintela L.M.A., Mira J., et al. Advances in the preparation of magnetic nanoparticles by the microemulsion method [J]. Journal of Physical Chemistry B,1997, 101(41):8045-8047.
[90]Meziani M.J., Liu P., Pathak P., et al. Stable suspension of crystalline Fe3O4 nanoparticles from in situ hot-fluid annealing [J]. Industrial & Engineering Chemistry Research,2006,45(4):1539-1541.
[91]Dresco P.A., Zaitsev V.S., Gambino R.J., et al. Preparation and properties of magnetite and polymer magnetite nanoparticles [J]. Langmuir,1999,15(6):1945-1951.
[92]Lee K.M., Sorensen C.M., Klabunde K.J., et al. Synthesis and characterization of stable colloidal Fe3O4 particles in water-in-oil microemulsions [J]. IEEE Transactions on Magnetics,1992,28(5):3180-3182.
[93]Si S.F., Li C.H., Wang X., et al. Magnetic monodisperse Fe3O4 nanoparticles [J]. Crystal Growth & Design,2005,5(2):391-393.
[94]Liang X., Wang X., Zhuang J., et al. synthesis of nearly monodisperse iron oxide and oxyhydroxide nanocrystals [J]. Advanced Functional Material,2006,16(14):1805-1813.
[95]Liu J., Sun Z.K., Deng Y.H., et al. Highly water-dispersible biocompatible magnetite particles with low cytotoxicity stabilized by citrate groups [J].Angewandte Chemie, International Edition,2009,48(32):5875-5879.
[96]耿明鑫,刘福田。水热法制备Fe304磁性纳米颗粒[J].济南大学学报,2009,23(2)：141-144。
[97]Deng H., Li X.L. Peng Q., et al. Monodisperse magnetic single-crystal ferrite microspheres [J]. Angewandte Chemie, International Edition,2005,44(18):2782-2785.
[98]Lu J., Jiao X.L., Chen D.R., et al. Solvothermal synthesis and characterization of Fe3O4 and γ-Fe2O3 nanoplates [J]. Journal of Physical Chemistry C,2009,113(10):4012-4017.
[99]Piticescu R.M., Piticescul R.R., Taloil D. et al. Hydrothermal synthesis of ceramic nanomaterials for functional applications [J]. Nanotechnology,2003,14(2):312-317.
[100]Kang S.J., Kocabas C., Ozel T., et al. High-performance electronics using dense, perfectly aligned arrays of single-walled carbon nanotubes [J]. Nature Nanotechnology 2007,2(4):230-236.
[101]Zhang C., Zhang Z.Y., Yu B.B. Application of the biological conjugate between antibody and colloid au nanoparticles as analyte to inductively coupled plasma mass spectrometry [J]. Anal. Chem.,2002,74(1):96-99.
[102]Jun Y.W., Huh Y.M., Choi J.S., et al. Nanoscale size effect of magnetic nanocrystals and their utilization for cancer diagnosis via magnetic resonance imaging [J]. Am. Chem. Soc.,2005,127(16):5732-5733.
[103]Lin J., Zhou W., Kumbhar A., et al. Gold-coated iron (Fe@Au) nanoparticles:synthesis, characterization, and magnetic field-induced self-assembly [J]. Solid State Chem.,2001, 159(1):26-31.
[104]Lyon J.L., Fleming D.A., Stone M.B., et al. Synthesis of Fe oxide core/Au shell nanoparticles by iterative hydroxylamine seeding [J]. Nano Lett.,2004,4(4):719-723.
[105]Cui Y.L., Hu D.D., Fang Y., et al. Preparation and mechanism of Fe3O4/Au core/shell super-paramagnetic microspheres [J]. Chnia Ser. B,2001,44(4):404-410.
[106]Bao J., Chen W., Liu T.T., et al. Bifunctional Au-Fe3O4 nanoparticles for protein separation [J]. ACS Nano.,2007,1(4):293-298.
[107]Zhang J., Post M., Veres T., et al. Laser-assisted synthesis of superparamagnetic Fe@Au core-shell nanoparticles [J]. Chem. B,2006,110(14):7122-7128.
[108]Wei Y.H., Klajn R., Pinchuk A. O., et al. Shape control and optical properties of Fe3O4-Au "nanoflowers" [J]. Small 2008,4(10):1635-1639.
[109]Wang L.Y., Luo J., Fan Q., et al. Monodispersed core-shell Fe3O4@Au nanoparticles [J]. Chem. B,2005,109(46):21593-21601.
[110]Wang L.Y., Park H.Y., Lim S., et al. Core@shell nanomaterials:gold-coated magnetic oxide nanoparticles [J]. Journal of Materials Chemistry,2008,18:2629-2635.
[111]Cho S. J., Idrobo J. C., Olamit J., et al. Growth mechanisms and oxidation-resistance of gold-coated iron nanoparticles [J]. Chem. Mater.,2005,17(12):3181-3186.
[112]Wang L.Y., Bai J.W., Li Y.J., et al. Multifunctional nanoparticles displaying magnetization and near-IR absorption [J]. Angew. Chem. Int. Ed.,2008,47(13):2439-2442.
[113]Cui Y. L., Hui W. L., Wang H. R., et al. Preparation and characterization of Fe3O4/Au composite particles [J]. Science in China (Series B).2004,47(7):152-158.
[114]Cui Y.L., Wang Y.N., Hui W.L., et al. The synthesis of goldmag nano-particles and their application for antibody immobilization [J]. Biomedical Microdevices,2005,7(2): 153-156.
[115]Giardiello M., McDonald T.O., Martin P., et al. Facile synthesis of complex multi-component organic and organic-magnetic inorganic nanocomposite particles [J]. J. Mater. Chem.,2012,22(47):24744-24752.
[116]Zhang H., Zhong X., Xu J.J., et al. Fe3O4/Polypyrrole/Au nanocomposites with core/shell/shell structure:synthesis, characterization, and their electrochemical properties [J]. Langmuir,2008,24(23):13748-13752.
[117]Qi D.W., Zhang H.Y., Tang J., et al. Facile synthesis of mercaptophenylboronic acid-functionalized core-shell structure Fe3O4@C@Au magnetic microspheres for selective enrichment of glycopeptides and glycoproteins [J]. J. Phys. Chem. C,2010,114(20): 9221-9226.
[118]Xu Z.C., Hou Y.L., Sun S.H. Magnetic core/shell Fe3O4/Au and Fe3O4/Au/Ag nanoparticles with tunable plasmonic properties [J]. J. Am. Chem. Soc,2007,129(28): 8698-8699.
[119]Peng S., Lei C, Ren Y., et al. Plasmonic-magnetic bifunctional nanoparticles [J]. Angew. Chem. Int. Ed.,2011,50(14); 3158-3163.
[120]Caruntu D., Cushing B.L., Carunt G., et al. Attachment of gold nanograins onto colloidal magnetite nanocrystals [J]. Chem. Mater.,2005,17(13):3398-3402.
[121]Yu H., Chen M., Rice P.M., et al. Dumbbell-like bifunctional Au-Fe3O4 nanoparticles [J]. Nano Lett.,2005,5(2):379-382.
[122]Wei Y. H., Klajn R., Anatoliy O, et al. Synthesis, shape control, and optical properties of hybrid Au/Fe3O4 "nanoflowers" [J]. Small,2008,4(10):1635-1639.
[123]Zhang H., Zhong X., Xu J. J., et al. Fe3O4/polypyrrole/Au nanocomposites with core/shell/shell structure:synthesis, characterization, and their electrochemical Properties [J]. Langmuir,2008,24(23):13748-13752.
[124]Gole A., Stone J. W., William R., et al. Murphy, iron oxide coated gold nanorods: synthesis, characterization, and magnetic manipulation [J]. Langmuir,2008,24 (12), 6232-6237.
[125]Park H.Y., Schadt M.J., Lim L., et al. Fabrication of magnetic Core@Shell Fe Oxide@Au nanoparticles for interfacial bioactivity and bio-separation [J]. Langmuir,2007,23 (17),9050-9056.
[126]Zhou X., Xu W. L., Wang Y., et al. Fabrication of Cluster/Shell Fe3O4/Au Nanoparticles and Application in Protein Detection via a SERS Method [J]. J. Phys. Chem. C,2010,114(46),19607-19613.
[127]Cho S. Jin., Jarrett B. R., Louie A. Y., et al. Gold-coated iron nanoparticles:a novel magnetic resonance agent for T1 and T2 weighted imaging [J]. Nanotechnology,2006, 17(3):640-645.
[128]Kim J. W., Kim Y. D., Antibiofouling colymer coated gold@iron oxide nanoparticle as a dual contrast agent for CT and MRI[J]. Bull. Korean Chem. Soc.,2009,30(8):185-190.
[129]Kang K. A., Jin H. Application of novel metal nanoparticles as optical/thermal agents in optical mammography and hyperthermic treatment for breast cancer [J]. Seamless Detection and Treatment,2010,10(1):123-125.
[130]Chao X., Zhang Z., li., Guo L., L., et al. A novel magnetic nanoparticle drug carrier for enhanced cancer chemotherapy [J]. P1OS ONE,2012,7(10):1-7.
[131]SHI F., Hui W., L., CUI Y., L. Surface modification and characterization of Fe3O4/Au composite nanoparticles [J]. NANO:Brief Reports and Reviews.2011,6,145-151.
[132]Chao X, Guo L., L., Zhao Y.,Yong., et al. PEG-modified GoldMag nanoparticles combined with the external magnetic fields for local drug delivery [J]. Journal of Drug Targeting,2011,19(3):161-167.
[133]Chao X, SHI F., Zhao Y.Y., et al. Cytotoxicity of Fe3O4/Au composite nanoparticles loaded with doxorubicin combined with magnetic field [J]. The journal Die Pharmazie, 2010,65:500-504.
[134]崔亚丽,杨璐,陈超等.磁酶免化学发光检测梅毒螺旋体抗体的方法[P].中国发明专利：200910219357.8。
[135]崔亚丽,邓晨,杨柳等.一种用磁性微粒从含微量核酸的样本中纯化DNA的方法[P].中国发明专利：201110314908.6。
[136]崔亚丽,石峰,惠文利。金磁微粒标记免疫层析快速检测方法[P].中国发明专利：201010222447.5。
[137]祖立闯,王金良,李娇等.胶体金免疫层析技术在动物疫病诊断上的应用[J].动物医学进展,2010,31(8)：101-105。
[138]严华,申厚凤。胶体金免疫层析技术的应用与展望[J].微生物学免疫学进展,2005,3：86-89。
[139]Zhuang J.Q., Guo M.J., Shen Z.Q. Application of Colloidal-gold Immuno-chromatography Assay(GICA) in Veterinary Clinical Diagnosis [J]. China Animal Health Inspection,2012,29(9)32-37
[140]Self C.H., Cook D. B., Advances in immunoassay technology [J]. Curr. Opin. Biotechnol.,1996,7(1):60-65.
[141]熊勇华,陈雪岚,陈媛。甲基苯丙胺的胶体金免疫层析检测卡的研制[J].卫生研究,2010,24(1)：120-122。
[142]孙秀兰,张银志,汤坚等.金标免疫层析试条检测样品中黄曲霉毒素B1的误差分析[J]。西北农林科技大学学报(自然科学版),2007,35(7)：188-192。
[143]林茹,李明珠,黄琦玲。半抗原免疫层析法在农药残留检测中的应用[J]。广东农业科学,2010,37(7)：230-233。
[144]万宇平,高东微,冯才伟等。检测三聚氰胺胶体金免疫层析试验的建立[J]。中国乳品工业,2010,38(10)：46-47。
[145]Matteucci E., Giampietro O. Point-of-care testing in diabetes care[J]. Mini Rev. Med. Chem.,2011,11(2):178-184.
[146]Lee-Lewandrowski E., Januzzi J. L., Grisson R., et al. Evaluation of first-draw whole blood, point-of-care cardiac markers in the context of the universal definition of myocardial infarction:a comparison of a multimarker panel to troponin alone and to testing in the central laboratory [J]. Arch Pathol Lab Med.,2011,135(4):459-463.
[147]Lee E.J., Shin S.D., Song K.J., et al. A point-of-care chemistry test for reduction of turnaround and clinical decision time [J]. Am. J. Emerg. Med.,2011,29(5):489-495.
[148]Jain A., Persaud J.W., Rao N., et al. Point of care testing is appropriate for national health service health check [J]. Ann. Clin. Biochem.,2011,48(2):159-165.
[149]Hjortshoj S., Venge P., Ravkilde J. Clinical performance of a new point-of-care cardiac troponin I assay compared to three laboratory troponin assays [J]. Clin. Chim. Acta,2011, 412(3-4):370-375.
[150]Cui Y. L., Hui W. L., Su J., et al. Fe3O4/Au composite nanoparticles and their optical properties [J]. Science in China (Series B).2005,48(4),273-278.
[151]SHI F., Hui W. L., Cui Y. L. Surface modification and characterization of composite nanoparticles. NANO:Brief Reports and Reviews [J].2011,6,145-151.
[152]Wang M., Peng M.L., Cheng W., et al., J. Nanosci. A novel approach for transferring oleic acid capped iron oxide nanoparticles to water phase [J]. Nanotechnol.,2011,11(4): 3688-3691.
[153]Goldstein J. A. Clinical relevance of genetic polymorphisms in the human CYP2C subfamily [J]. British journal of clinical pharmacology,2001,52(4):349-355.
[154]Di Y.M., Chow V.D., Yang L.P., et al. Structure, function, regulation and polymorphism of human cytochrome P450 2A6 [J]. Curr. Drug Metab.,2009,10(7):754-780.
[155]Xie H., Griskevicius L., Stahle L., et al. Pharmacogenetics of cyclophosphamide in patients with hematological malignancies [J]. Eur. J. Pharm. Sci.,2006,27(1):54-61.
[156]Hollopeter G, Jantzen H.M., Vincent D., et al. Identification of the platelet ADP receptor targeted by antithrombotic drugs [J]. Nature,2001,409(6817):202-207.
[157]Beitelshees A. L., McLeod H.L. Clopidogrel pharmacogenetics:promising steps towards patient care? [J]. Arterioscler Thromb. Vasc. Biol.2006,26(8):1681-1683.