生物单分子定量检测新方法及电化学发光共振能量转移
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摘要
本文分为生物单分子定量检测新方法及电化学发光共振能量转移两部分,其中第一章至第六章为第一部分,第七章至第九章为第二部分。
第一章主要对生物单分子激光诱导荧光检测涉及的各种检测方法及荧光探针进行了简要综述。在生物单分子激光诱导荧光检测中涉及的方法主要有共聚焦荧光显微术、全内反射荧光显微术、落射荧光显微术、双光子或多光子荧光显微术等。本章着重介绍了这些方法的原理及其在生物单分子定量研究中的应用,同时也对常用的荧光探针(包括有机荧光染料、纳米粒子、荧光蛋白及稀土离子等)的性质和应用做了简单介绍。
第二章中我们建立了一种电化学吸附富集结合全内反射荧光显微术超灵敏的单分子成像定量新方法。我们选择罗丹明6G、Alexa-488标记的羊抗鼠IgG、以及罗丹明6G标记的DNA作为研究对象,利用电化学富集将这些分子吸附到镀有铟锡氧化物的光透导电玻片上,然后利用高灵敏的电子增强型电感耦合器(EMCCD)对玻片上的荧光分子进行全内反射成像。通过一个三维移动控制器移动玻片实现对玻片的顺次成像,对每一个样品获取100帧图片,并对其上对应单分子的荧光点计数。电化学富集的方法提高了已报道的单分子检测方法的灵敏度,结果显示浓度范围在5×10-15到5×10-12 mol/L的罗丹明6G,3×10-15到2×10-12 mol/L的Alexa-488标记的羊抗鼠IgG和3×10-15到2×10-12 mol/L罗丹明6G标记的DNA荧光点数和物质的浓度都具有良好的线性关系。
第三章中我们建立了一种超灵敏的检测1.8 nL样品中蛋白质的单分子计数微阵列分析方法。有关微阵列芯片的单分子检测仅有少量文献报道,且这些工作都未能实现整个阵列点的成像。由于单分子检测是以检测到的单分子数作为定量基础,所以提高单分子计数微阵列分析法灵敏度的关键是将整个阵列点上的单分子完全成像。我们首先设计并研究出了微阵列单分子成像系统以实现整个阵列点的单分子成像,其次以量子点取代传统的有机荧光探针对生物分子进行标记,并针对量子点荧光闪烁问题提出了一种捕获微阵列上全部量子点图像的方法。再通过乙醇胺与牛血清白蛋白共同封闭基底降低背景使单分子计数微阵列分析法测定蛋白质的灵敏度比文献报道的方法提高100倍,达到1.8×10-21 mol(1080个分子)。该方法检测样品所需体积极小(1.8 nL),因此可以用来实现珍贵或者少量样品的多次取样测定。我们利用此方法测定了不同时间下人蜕膜基质细胞培养液中骨桥蛋白的含量,研究了活细胞中骨桥蛋白的表达动力学。
第四章中我们利用单分子计数微阵列分析法实现了单细胞内无PCR扩增的多种基因表达的定量测定。首先用将不同的DNA1 s点样至玻片上形成形成10个亚阵列,每个亚阵列包括9个点,每个阵列点的直径约为300μm。3μL由单细胞中的mRNA反转录的cDNAs溶液滴至玻片上的亚阵列,不同的cDNAs通过杂交反应结合至亚阵列的各个点上。然后,通过与QDs标记的检测DNA2(QDs-DNA2)杂交反应,cDNAs被QDs标记。最后,使用我们在第三章中应用的单分子阵列成像设备对微阵列成像,对应单个cDNA的亮点被计数定量。这一方法可以检测至3μL样品体积中2×10-16 mol/L的DNA(360个分子),利用微阵列,10个细胞中9种基因表达可以被平行定量。实验的结果依赖于亮点的个数而不是荧光强度,减少了测定误差,保证了结果的可靠性。此方法实现了无PCR扩增的单细胞中多个基因表达的同时定量测定。
第五章中我们利用亚微米粒径的磁珠作为标记物发展了一种新的简单易推广的可视单分子检测方法。以往单分子光学检测通常采用激光诱导荧光方法,常常需要高灵敏度的昂贵检测仪器,且荧光检测会受到荧光背景干扰和荧光标记物淬灭等影响。我们用粒径为300 nm的磁珠对DNA单分子标记,这些磁珠在普通光学显微镜下可以观察到。此可视单分子检测方法可以检测3μL样品中浓度低至4.0×10-16mol/L的DNA(720个分子),并实现了单细胞内多种基因的同时测定。这种直接可视的单分子检测方法有很多优点,首先普通光学显微镜即可对单分子信号成像,无需特殊的高灵敏仪器设备；其次由于单分子信号为磁珠的普通光学图像,背景不会干扰检测结果,且信号不会淬灭,因此保证了定量检测结果的可靠性。
第六章中我们利用链酶亲和素修饰的磁珠结合AMCA,FAM及Cy5三种荧光染料标记的DNA,制备各种颜色的编码微珠。单个微珠上可以结合上千个染料分子,根据结合三种染料的比例不同,可以实现多种颜色微珠的制备。我们利用制备的各种微珠实现不同生物分子的单分子编码检测。
第七章中我们对荧光共振能量转移(FRET)的原理及其在生物分析方面应用作了介绍。共振能量转移作为一种有力的生物分析工具在生物分子构型测定、免疫分析、核酸检测等方面广泛应用。半导体量子点(quantum dots, QD s)由于其优良的光学性能而被广泛应用于FRET体系中,将量子点作为能量供体或者受体引入生物发光共振能量转移(BRET)体系和化学发光共振能量转移(CRET)体系同样引起了人们的兴趣,本章也对QD在共振能量转移体系中的应用进行了综述。
第八章中我们建立了一种新的共振能量转移模式—电化学发光共振能量转移(ECRET).以往报道的共振能量转移根据供体激发方式的不同分为荧光共振能量转移、生物发光共振能量转移、化学发光共振能量转移。以电化学发光作为光源激发供体只有能量被受体淬灭的研究,而受体得到能量发射荧光的现象未见报道。我们以鲁米诺作为能量供体,量子点作为能量受体实现了ECRET。本章对基于该体系的ECRET进行了理论计算,而且将ECRET应用至测定蛋白质之间相互作用和蛋白质构型的变化。
第九章中我们研究了量子点作为能量供体,Cy5作为能量受体的电化学发光共振能量转移体系。对基于该体系的ECRET进行了理论计算,并将ECRET应用至测定蛋白质构型的变化。基于QDs-Cy5体系的ECRET不仅可以进行DNA的定性定量研究,也是蛋白质相互作用、蛋白质构型测定研究中一个有用的工具,它将为生命科学提供一种新的研究方法。
In chapter one, fluorescence methods in single-molecule detection (SMD) for biomolecules and fluorescent probes were reviewed briefly. The main fluorescence methods in SMD are confocal fluorescence microscopy (CFM), total internal reflection fluorescence microscopy (TIRFM), epi-fluorescence microscopy (EFM) and two-photon or multi-photon laser scanning fluorescence microscopy (TPFM, MPFM). The principles of these techniques and methods and their applications for quantification of biomolecules were reviewed. The fluorescent probes including organic dye, nanoparticles, fluorescent protein, rare-earth-metal ions were also described.
In chapter two, we developed an ultrasensitive quantitative single-molecule imaging method for fluorescent molecules using a combination of electrochemical adsorption accumulation and total internal reflection fluorescence microscopy (TIRFM). We chose rhodamine 6G (R6G, fluorescence dye) or goat anti rat IgG(H+L) (IgG(H+L)-488), a protein labeled by Alexa Fluor 488 or DNA labeled by 6-CR6G (DNA-R6G) as the model molecules. The fluorescent molecules were accumulated on a light transparent indium tin oxide (ITO) conductive microscope cover slip using electrochemical adsorption in a stirred solution. Then, images of the fluorescent molecules accumulated on the ITO coverslip sized 40×40μm were acquired using an objective-type TIRFM instrument coupled with a high-sensitivity electron multiplying charge coupled device. One hundred images of the fluorescent molecules accumulated on the cover slip were taken consecutively, one by one, by moving the cover slip with the aid of a three-dimensional positioner. Finally, we counted the number of fluorescent spots corresponding to single fluorescent molecules on the images. The linear relationships between the number of fluorescent molecules and the concentration were obtained in the range of 5×10-15 to 5×10-12 mol/L for R6G,3×10-15 to 2×10-12 mol/L for IgG(H+L)-488, and 3×10-15 to 2×10-12 mol/L for DNA-R6G.
In chapter three, a novel ultra-sensitive single-molecule-counting microarray assay (SMCMA) with a 1.8-nL sample volume for quantification of protein was developed using total internal reflection fluorescence microscopy coupled with fluorescent quantum dot (QD)-labeling. In life sciences, many protein microarray assays are required to detect proteins from small sample volumes and to describe low abundance levels in absolute terms (numbers or molar amounts). Therefore, in protein microarray assays, ultra-sensitive detection methods with ultra-small volumes have become increasingly important. SMD is rarely used in microarray assays, because the conventional scanners used in microarray assays cannot acquire images of single fluorescent molecules due to low sensitivity and resolution, and when SMD is used in microarray assays, the biggest difficulty is acquiring the whole microarray image. It is because the size of the images taken using SMD techniques is much less than that of a microspot on a microarray. In almost all reports concerning SMD-based microarray assays, only a part of each microspot was acquired. The readout system or method is crucial for the SMD-based microarray assays. In the SMCMA, a single-molecule microarray reader was used to acquire the whole images of microarrays at single-molecule level. Owing to the remarkably high photostability, QDs as labels are much better than fluorescent dyes and can withstand numerous illumination cycles without photoquenching during laser scanning the microarrays when acquiring single-molecule images. These perfect photochemical characteristics of QDs improved the signal and increased the sensitivity in the SMCMA. Using the present SMCMA, an amount as low as 1.8×10-21 mole (1080 molecules) for proteins in 1.8-nL samples could be detected. The SMCMA with 1.8-nL sample volume makes dynamic detection of protein expression for the same alive cells possible. Here, the SMCMA was applied to dynamically measure osteopontin (OPN) expression of decidual stromal cells (DSCs).
In chapter four, A novel ultra-sensitive and high-selective single-molecule-counting microarray assay (SMCMA) of DNA for single-cell multi-gene expression was developed using a single-molecule microarray reader coupled with fluorescent quantum dot (QD)-labeling. In the SMCMA, a microarray fabricated on a silanized glass coverslip consists of 10 subarrays with 9 spots for each subarray. Each spot with a diameter of-300μm is modified with different capture DNAs (DNA1). The cDNAs corresponding to mRNAs in a single cell are captured to the complementary capture DNAls at different spots of a subarray. After the cDNAs are labeled with QDs using QD-labeled detection DNAs, the image of the microassay is acquired using a single-molecule microarray reader. The amounts of the cDNAs are quantified by counting the bright dots corresponding to single cDNA molecules on the microassy. Using the SMCMA,2×10-16 mol/L DNA in 3 μL sample or as low as 360 molecules of mRNAs in a single cell can be detected. For a microarray, nine different genes in ten different cells can be quantified in parallel. Since quantification relies on the number of bright dots corresponding to single DNA molecules rather than their signal size, the reproducibility of the detected signal intensity becomes irrelevant, thus guaranteeing reliability of the results and reducing detection error. To our knowledge, this is the first report on PCR amplification-independent quantification of multi-gene expression profiling in single cells.
In chapter five, a novel visible SMD method for DNA analysis using conventional biological microscope was provided. In the method,300-nm-diameter magnet microbeads (MBs) as labels were bound to target DNA molecules immobilized on microarrays. Target DNA could be quantified based on counting the number of MBs corresponded to single target DNA molecules on the microarrays under a conventional microscope. Using the method, DNA as low as 1.2×10-21 mol (720 molecules) could be detected and multi-gene expression in single cell could be quantified. The method is simple without need of expensive instruments.
In chapter six, multicolor optical coding for DNA single-molecule-detection has been achieved by binding dye-DNAs to magnetic microbeads at different ratios. The AMCA, FAM and Cy5 as dyes were used. About one thousand of dyes could be binded to a bead. The use of different ratios of dyes could make multicolor besds. Using these encoded besds, single-molecule-detection for DNA was achieved. This coding technology is expected to open new opportunities in gene expression studies, highthroughput screening, and medical diagnostics
In chapter seven, the principal of fluorescence resonance energy transfer (FRET) and its biological application were reviewed briefly. The FRET as a powerful technique has been applied in measuring conformational change of biomolecules, immunnoassay and DNA analysis. Luminescent quantum dots (QDs) have been used in FRET, bioluminescence resonance energy transfer (BRET) and chemiluminescence resonance energy transfer (CRET) as acceptors or donors. The application of QDs in resonance energy transfer is also described.
In chapter eight, we developed a novel resonance energy transfer, electrochemiluminescence resonance energy transfer (ECRET). In the ECRET technique, the emitters of N-(4-aminobutyl)-N-ethylisoluminol/H2O2 system generated at an electrode through electrochemical reactions act as electrochemiluminescent donors to emit light with a maximum emission of 460 nm and the red fluorescent luminescent semiconductor nanocrystals (quantum dots, QDs), having a maximum emission at 655 nm, serve as acceptors. When a potential is applied to the electrode, the electrochemiluminescent donors transfer energy to the proximal ground-state QD acceptors, producing efficient ECRET. As a result, the QD acceptors emit a light with a longer wavelength of 655 nm than that of the electrochemiluminescent donors (460 nm). From the ECRET spectra consisting of ECL spectra of the electrochemiluminescent donors and emission spectra of the QD acceptors via ECRET, many biological events can be evaluated. We report the ECRET between the luminol molecules and the QDs in luminol-DNA-DNA-QD, luminol-protein-protein-QD and lumino-protein-QD conjugates immobilized on the Au electrode. The ECRET technique could be applied to the investigation of interactions between nucleic acids or proteins and conformational changes of DNA and protein.
In chapter nine, the ECRET between the QDs as donors and the Cy5 as acceptors was studied. The new ECRET system was applied to investigate the conformational changes of protein. The ECRET technique based on QDs-Cy5 system could provide a powerful tool to the study in chemistry and biology.
第一章主要对生物单分子激光诱导荧光检测涉及的各种检测方法及荧光探针进行了简要综述。在生物单分子激光诱导荧光检测中涉及的方法主要有共聚焦荧光显微术、全内反射荧光显微术、落射荧光显微术、双光子或多光子荧光显微术等。本章着重介绍了这些方法的原理及其在生物单分子定量研究中的应用,同时也对常用的荧光探针(包括有机荧光染料、纳米粒子、荧光蛋白及稀土离子等)的性质和应用做了简单介绍。
第二章中我们建立了一种电化学吸附富集结合全内反射荧光显微术超灵敏的单分子成像定量新方法。我们选择罗丹明6G、Alexa-488标记的羊抗鼠IgG、以及罗丹明6G标记的DNA作为研究对象,利用电化学富集将这些分子吸附到镀有铟锡氧化物的光透导电玻片上,然后利用高灵敏的电子增强型电感耦合器(EMCCD)对玻片上的荧光分子进行全内反射成像。通过一个三维移动控制器移动玻片实现对玻片的顺次成像,对每一个样品获取100帧图片,并对其上对应单分子的荧光点计数。电化学富集的方法提高了已报道的单分子检测方法的灵敏度,结果显示浓度范围在5×10-15到5×10-12 mol/L的罗丹明6G,3×10-15到2×10-12 mol/L的Alexa-488标记的羊抗鼠IgG和3×10-15到2×10-12 mol/L罗丹明6G标记的DNA荧光点数和物质的浓度都具有良好的线性关系。
第三章中我们建立了一种超灵敏的检测1.8 nL样品中蛋白质的单分子计数微阵列分析方法。有关微阵列芯片的单分子检测仅有少量文献报道,且这些工作都未能实现整个阵列点的成像。由于单分子检测是以检测到的单分子数作为定量基础,所以提高单分子计数微阵列分析法灵敏度的关键是将整个阵列点上的单分子完全成像。我们首先设计并研究出了微阵列单分子成像系统以实现整个阵列点的单分子成像,其次以量子点取代传统的有机荧光探针对生物分子进行标记,并针对量子点荧光闪烁问题提出了一种捕获微阵列上全部量子点图像的方法。再通过乙醇胺与牛血清白蛋白共同封闭基底降低背景使单分子计数微阵列分析法测定蛋白质的灵敏度比文献报道的方法提高100倍,达到1.8×10-21 mol(1080个分子)。该方法检测样品所需体积极小(1.8 nL),因此可以用来实现珍贵或者少量样品的多次取样测定。我们利用此方法测定了不同时间下人蜕膜基质细胞培养液中骨桥蛋白的含量,研究了活细胞中骨桥蛋白的表达动力学。
第四章中我们利用单分子计数微阵列分析法实现了单细胞内无PCR扩增的多种基因表达的定量测定。首先用将不同的DNA1 s点样至玻片上形成形成10个亚阵列,每个亚阵列包括9个点,每个阵列点的直径约为300μm。3μL由单细胞中的mRNA反转录的cDNAs溶液滴至玻片上的亚阵列,不同的cDNAs通过杂交反应结合至亚阵列的各个点上。然后,通过与QDs标记的检测DNA2(QDs-DNA2)杂交反应,cDNAs被QDs标记。最后,使用我们在第三章中应用的单分子阵列成像设备对微阵列成像,对应单个cDNA的亮点被计数定量。这一方法可以检测至3μL样品体积中2×10-16 mol/L的DNA(360个分子),利用微阵列,10个细胞中9种基因表达可以被平行定量。实验的结果依赖于亮点的个数而不是荧光强度,减少了测定误差,保证了结果的可靠性。此方法实现了无PCR扩增的单细胞中多个基因表达的同时定量测定。
第五章中我们利用亚微米粒径的磁珠作为标记物发展了一种新的简单易推广的可视单分子检测方法。以往单分子光学检测通常采用激光诱导荧光方法,常常需要高灵敏度的昂贵检测仪器,且荧光检测会受到荧光背景干扰和荧光标记物淬灭等影响。我们用粒径为300 nm的磁珠对DNA单分子标记,这些磁珠在普通光学显微镜下可以观察到。此可视单分子检测方法可以检测3μL样品中浓度低至4.0×10-16mol/L的DNA(720个分子),并实现了单细胞内多种基因的同时测定。这种直接可视的单分子检测方法有很多优点,首先普通光学显微镜即可对单分子信号成像,无需特殊的高灵敏仪器设备；其次由于单分子信号为磁珠的普通光学图像,背景不会干扰检测结果,且信号不会淬灭,因此保证了定量检测结果的可靠性。
第六章中我们利用链酶亲和素修饰的磁珠结合AMCA,FAM及Cy5三种荧光染料标记的DNA,制备各种颜色的编码微珠。单个微珠上可以结合上千个染料分子,根据结合三种染料的比例不同,可以实现多种颜色微珠的制备。我们利用制备的各种微珠实现不同生物分子的单分子编码检测。
第七章中我们对荧光共振能量转移(FRET)的原理及其在生物分析方面应用作了介绍。共振能量转移作为一种有力的生物分析工具在生物分子构型测定、免疫分析、核酸检测等方面广泛应用。半导体量子点(quantum dots, QD s)由于其优良的光学性能而被广泛应用于FRET体系中,将量子点作为能量供体或者受体引入生物发光共振能量转移(BRET)体系和化学发光共振能量转移(CRET)体系同样引起了人们的兴趣,本章也对QD在共振能量转移体系中的应用进行了综述。
第八章中我们建立了一种新的共振能量转移模式—电化学发光共振能量转移(ECRET).以往报道的共振能量转移根据供体激发方式的不同分为荧光共振能量转移、生物发光共振能量转移、化学发光共振能量转移。以电化学发光作为光源激发供体只有能量被受体淬灭的研究,而受体得到能量发射荧光的现象未见报道。我们以鲁米诺作为能量供体,量子点作为能量受体实现了ECRET。本章对基于该体系的ECRET进行了理论计算,而且将ECRET应用至测定蛋白质之间相互作用和蛋白质构型的变化。
第九章中我们研究了量子点作为能量供体,Cy5作为能量受体的电化学发光共振能量转移体系。对基于该体系的ECRET进行了理论计算,并将ECRET应用至测定蛋白质构型的变化。基于QDs-Cy5体系的ECRET不仅可以进行DNA的定性定量研究,也是蛋白质相互作用、蛋白质构型测定研究中一个有用的工具,它将为生命科学提供一种新的研究方法。
In chapter one, fluorescence methods in single-molecule detection (SMD) for biomolecules and fluorescent probes were reviewed briefly. The main fluorescence methods in SMD are confocal fluorescence microscopy (CFM), total internal reflection fluorescence microscopy (TIRFM), epi-fluorescence microscopy (EFM) and two-photon or multi-photon laser scanning fluorescence microscopy (TPFM, MPFM). The principles of these techniques and methods and their applications for quantification of biomolecules were reviewed. The fluorescent probes including organic dye, nanoparticles, fluorescent protein, rare-earth-metal ions were also described.
In chapter two, we developed an ultrasensitive quantitative single-molecule imaging method for fluorescent molecules using a combination of electrochemical adsorption accumulation and total internal reflection fluorescence microscopy (TIRFM). We chose rhodamine 6G (R6G, fluorescence dye) or goat anti rat IgG(H+L) (IgG(H+L)-488), a protein labeled by Alexa Fluor 488 or DNA labeled by 6-CR6G (DNA-R6G) as the model molecules. The fluorescent molecules were accumulated on a light transparent indium tin oxide (ITO) conductive microscope cover slip using electrochemical adsorption in a stirred solution. Then, images of the fluorescent molecules accumulated on the ITO coverslip sized 40×40μm were acquired using an objective-type TIRFM instrument coupled with a high-sensitivity electron multiplying charge coupled device. One hundred images of the fluorescent molecules accumulated on the cover slip were taken consecutively, one by one, by moving the cover slip with the aid of a three-dimensional positioner. Finally, we counted the number of fluorescent spots corresponding to single fluorescent molecules on the images. The linear relationships between the number of fluorescent molecules and the concentration were obtained in the range of 5×10-15 to 5×10-12 mol/L for R6G,3×10-15 to 2×10-12 mol/L for IgG(H+L)-488, and 3×10-15 to 2×10-12 mol/L for DNA-R6G.
In chapter three, a novel ultra-sensitive single-molecule-counting microarray assay (SMCMA) with a 1.8-nL sample volume for quantification of protein was developed using total internal reflection fluorescence microscopy coupled with fluorescent quantum dot (QD)-labeling. In life sciences, many protein microarray assays are required to detect proteins from small sample volumes and to describe low abundance levels in absolute terms (numbers or molar amounts). Therefore, in protein microarray assays, ultra-sensitive detection methods with ultra-small volumes have become increasingly important. SMD is rarely used in microarray assays, because the conventional scanners used in microarray assays cannot acquire images of single fluorescent molecules due to low sensitivity and resolution, and when SMD is used in microarray assays, the biggest difficulty is acquiring the whole microarray image. It is because the size of the images taken using SMD techniques is much less than that of a microspot on a microarray. In almost all reports concerning SMD-based microarray assays, only a part of each microspot was acquired. The readout system or method is crucial for the SMD-based microarray assays. In the SMCMA, a single-molecule microarray reader was used to acquire the whole images of microarrays at single-molecule level. Owing to the remarkably high photostability, QDs as labels are much better than fluorescent dyes and can withstand numerous illumination cycles without photoquenching during laser scanning the microarrays when acquiring single-molecule images. These perfect photochemical characteristics of QDs improved the signal and increased the sensitivity in the SMCMA. Using the present SMCMA, an amount as low as 1.8×10-21 mole (1080 molecules) for proteins in 1.8-nL samples could be detected. The SMCMA with 1.8-nL sample volume makes dynamic detection of protein expression for the same alive cells possible. Here, the SMCMA was applied to dynamically measure osteopontin (OPN) expression of decidual stromal cells (DSCs).
In chapter four, A novel ultra-sensitive and high-selective single-molecule-counting microarray assay (SMCMA) of DNA for single-cell multi-gene expression was developed using a single-molecule microarray reader coupled with fluorescent quantum dot (QD)-labeling. In the SMCMA, a microarray fabricated on a silanized glass coverslip consists of 10 subarrays with 9 spots for each subarray. Each spot with a diameter of-300μm is modified with different capture DNAs (DNA1). The cDNAs corresponding to mRNAs in a single cell are captured to the complementary capture DNAls at different spots of a subarray. After the cDNAs are labeled with QDs using QD-labeled detection DNAs, the image of the microassay is acquired using a single-molecule microarray reader. The amounts of the cDNAs are quantified by counting the bright dots corresponding to single cDNA molecules on the microassy. Using the SMCMA,2×10-16 mol/L DNA in 3 μL sample or as low as 360 molecules of mRNAs in a single cell can be detected. For a microarray, nine different genes in ten different cells can be quantified in parallel. Since quantification relies on the number of bright dots corresponding to single DNA molecules rather than their signal size, the reproducibility of the detected signal intensity becomes irrelevant, thus guaranteeing reliability of the results and reducing detection error. To our knowledge, this is the first report on PCR amplification-independent quantification of multi-gene expression profiling in single cells.
In chapter five, a novel visible SMD method for DNA analysis using conventional biological microscope was provided. In the method,300-nm-diameter magnet microbeads (MBs) as labels were bound to target DNA molecules immobilized on microarrays. Target DNA could be quantified based on counting the number of MBs corresponded to single target DNA molecules on the microarrays under a conventional microscope. Using the method, DNA as low as 1.2×10-21 mol (720 molecules) could be detected and multi-gene expression in single cell could be quantified. The method is simple without need of expensive instruments.
In chapter six, multicolor optical coding for DNA single-molecule-detection has been achieved by binding dye-DNAs to magnetic microbeads at different ratios. The AMCA, FAM and Cy5 as dyes were used. About one thousand of dyes could be binded to a bead. The use of different ratios of dyes could make multicolor besds. Using these encoded besds, single-molecule-detection for DNA was achieved. This coding technology is expected to open new opportunities in gene expression studies, highthroughput screening, and medical diagnostics
In chapter seven, the principal of fluorescence resonance energy transfer (FRET) and its biological application were reviewed briefly. The FRET as a powerful technique has been applied in measuring conformational change of biomolecules, immunnoassay and DNA analysis. Luminescent quantum dots (QDs) have been used in FRET, bioluminescence resonance energy transfer (BRET) and chemiluminescence resonance energy transfer (CRET) as acceptors or donors. The application of QDs in resonance energy transfer is also described.
In chapter eight, we developed a novel resonance energy transfer, electrochemiluminescence resonance energy transfer (ECRET). In the ECRET technique, the emitters of N-(4-aminobutyl)-N-ethylisoluminol/H2O2 system generated at an electrode through electrochemical reactions act as electrochemiluminescent donors to emit light with a maximum emission of 460 nm and the red fluorescent luminescent semiconductor nanocrystals (quantum dots, QDs), having a maximum emission at 655 nm, serve as acceptors. When a potential is applied to the electrode, the electrochemiluminescent donors transfer energy to the proximal ground-state QD acceptors, producing efficient ECRET. As a result, the QD acceptors emit a light with a longer wavelength of 655 nm than that of the electrochemiluminescent donors (460 nm). From the ECRET spectra consisting of ECL spectra of the electrochemiluminescent donors and emission spectra of the QD acceptors via ECRET, many biological events can be evaluated. We report the ECRET between the luminol molecules and the QDs in luminol-DNA-DNA-QD, luminol-protein-protein-QD and lumino-protein-QD conjugates immobilized on the Au electrode. The ECRET technique could be applied to the investigation of interactions between nucleic acids or proteins and conformational changes of DNA and protein.
In chapter nine, the ECRET between the QDs as donors and the Cy5 as acceptors was studied. The new ECRET system was applied to investigate the conformational changes of protein. The ECRET technique based on QDs-Cy5 system could provide a powerful tool to the study in chemistry and biology.
引文
1. Weiss, S., Fluorescence spectroscopy of single biomolecules [J]. Science 1999,283, (5408),1676-1683.
2. Schwille, P.; Kettling, U., Analyzing single protein molecules using optical methods [J]. Current Opinion in Biotechnology 2001,12, (4),382-386.
3. Zhang, X. L.; Li, L. L.; Li, L.; Chen, J.; Zou, G. Z.; Si, Z. K.; Jin, W. R., Ultrasensitive Electrochemical DNA Assay Based on Counting of Single Magnetic Nanobeads by a Combination of DNA Amplification and Enzyme Amplification [J]. Analytical Chemistry 2009,81, (5),1826-1832.
4. Tessler, L. A.; Reifenberger, J. G.; Mitra, R. D., Protein Quantification in Complex Mixtures by Solid Phase Single-Molecule Counting [J]. Analytical Chemistry 2009, 81,(17),7141-7148.
5. Moerner, W. E.; Orrit, M., Illuminating single molecules in condensed matter [J]. Science 1999,283, (5408),1670-1676.
6. Gai, H. W.; Wang, Q.; Ma, Y. F.; Lin, B. C., Correlations between molecular numbers and molecular masses in an evanescent field and their applications in probing molecular interactions [J]. Angewandte Chemie-International Edition 2005,44, (32), 5107-5110.
7. Rigler, R.; Mets, U.; Widengren, J.; Kask, P., Fluorescence correlation spectroscopy with high count rate and low background:analysis of translational diffusion [J]. European Biophysics Journal 1993,22, (3),169-175.
8. Craig, D. B.; Wong, J. C. Y.; Dovichi, N. J., Detection of Attomolar Concentrations of Alkaline Phosphatase by Capillary Electrophoresis Using Laser-Induced Fluorescence Detection [J]. Analytical Chemistry 1996,68,697-700.
9. Chen, D. Y.; Dovichi, N. J., Single-Molecule Detection in Capillary Electrophoresis: Molecular Shot Noise as a Fundamental Limit to Chemical Analysis [J]. Analytical Chemistry 1996,68,690-696.
10. Fister, J. C.; Jacobson, S. C.; Davis, L. M.; Ramsey, J. M., Counting single chromophore molecules for ultrasensitive analysis and separations on microchip devices [J]. Analytical Chemistry 1998,70, (3),431-437.
11. Loscher, F.; Bohme, S.; Martin, J.; Seeger, S., Counting of single protein molecules at interfaces and application of this technique in early-stage diagnosis [J]. Analytical Chemistry 1998,70, (15),3202-3205.
12. Chao, S. Y; Ho, Y. P.; Bailey, V. J.; Wang, T. H., Quantification of low concentrations of DNA using single molecule detection and velocity measurement in a microchannel [J]. Journal of Fluorescence 2007,17, (6),767-774.
13. Li, H. T.; Ying, L. M.; Green, J. J.; Balasubramanian, S.; Klenerman, D., Ultrasensitive coincidence fluorescence detection of single DNA molecules [J]. Analytical Chemistry 2003,75, (7),1664-1670.
14. Li, H. T.; Zhou, D. J.; Browne, H.; Balasubramanian, S.; Klenerman, D., Molecule by molecule direct and quantitative counting of antibody-protein complexes in solution [J]. Analytical Chemistry 2004,76, (15),4446-4451.
15. Agrawal, A.; Zhang, C. Y.; Byassee, T.; Tripp, R. A.; Nie, S. M., Counting single native biomolecules and intact viruses with color-coded nanoparticles [J]. Analytical Chemistry 2006,78, (4),1061-1070.
16. Dickson, R. M.; Norris, D. J.; Tzeng, Y L.; Moerner, W. E., Three-dimensional imaging of single molecules solvated in polys of poly(acrylamide)gels [J]. Science 1996,274,966-968.
17. Xu, X. H.; Yeung, E. S., Direct measurement of single-molecule diffusion and photodecomposition in free solution [J]. Science 1997,275, (5303),1106-1109.
18. Xu, X. H.; Yeung, E. S., Long-range electrostatic trapping of single-protein molecules at a liquid-solid interface [J]. Science 1998,281, (5383),1650-1653.
19. Ma, Y.; Shortreed, M. R.; Yeung, E. S., High-throughput single-molecule spectroscopy in free solution [J]. Analytical Chemistry 2000,72, (19),4640-4645.
20. Kang, S. H.; Yeung, E. S., Dynamics of single-protein molecules at a liquid/solid interface:implications in capillary electrophoresis and chromatography [J]. Analytical Chemistry 2002,74, (24),6334-6339.
21. Li, H. W.; Yeung, E. S., Direct observation of anomalous single-molecule enzyme kinetics [J]. Analytical Chemistry 2005,77, (14),4374-4377.
22. Singh-Zocchi, M.; Dixit, S.; Ivanov, V.; Zocchi, G., Single-molecule detection of DNA hybridization [J]. Proceeding of the National Academy of Sciences of the United States of America 2003,100, (13),7605-7610.
23. Kozuka, J.; Yokota, H.; Arai, Y.; Ishii, Y.; Yanagida, T., Dynamic polymorphism of single actin molecules in the actin filament [J]. Nature Chemical Biology 2006,2, (2),83-86.
24. Fang, X.; Tan, W., Imaging single fluorescent molecules at the interface of an optical fiber probe by evanescent wave excitation [J]. Analytical Chemistry 1999,71, 3101-3105.
25. Donner, S.; Li, H. W.; Yeung, E. S.; Porter, M. D., Fabrication of optically transparent carbon electrodes by the pyrolysis of photoresist films:approach to single-molecule spectroelectrochemistry [J]. Analytical Chemistry 2006,78, (8),2816-2822.
26. Lee, J. Y.; Li, J.; Yeung, E. S., Single-molecule detection of surface-hybridized human papilloma virus DNA for quantitative clinical screening [J]. Analytical Chemistry 2007,79, (21),8083-8089.
27. Wang, L.; Xu, G.; Shi, Z.; Jiang, W.; Jin, W., Quantification of protein based on single-molecule counting by total internal reflection fluorescence microscopy with adsorption equilibrium [J]. Analytica Chimica Acta 2007,590, (1),104-109.
28. Kang, S. H.; Kim, Y. J.; Yeung, E. S., Detection of single-molecule DNA hybridization by using dual-color total internal reflection fluorescence microscopy [J]. Analytical and Bioanalytical Chemistry 2007,387, (8),2663-2671.
29. Lee, S.; Lee, S.; Ko, Y H.; Jung, H.; Kim, J. D.; Song, J. M.; Choo, J.; Eo, S. K.; Kang, S. H., Quantitative analysis of human serum leptin using a nanoarray protein chip based on single-molecule sandwich immunoassay [J]. Talanta 2009,78, (2), 608-612.
30. Jiang, D.; Wang, L.; Jiang, W., Quantitative detection of antibody based on single-molecule counting by total internal reflection fluorescence microscopy with quantum dot labeling [J]. Analytica Chimica Acta 2009,634, (1),83-88.
31. Hanley, D. C.; Harris, J. M., Quantitative dosing of surfaces with fluorescent molecules:Characterization of fractional monolayer coverages by counting single molecules [J]. Analytical Chemistry 2001,73, (21),5030-5037.
32. Anazawa, T.; Matsunaga, H.; Yeung, E. S., Electrophoretic quantitation of nucleic acids without amplification by single-molecule imaging [J]. Analytical Chemistry 2002,74, (19),5033-5038.
33. Kerman, K.; Endo, T.; Tsukamoto, M.; Chikae, M.; Takamura, Y.; Tamiya, E., Quantum dot-based immunosensor for the detection of prostate-specific antigen using fluorescence microscopy [J]. Talanta 2007,71, (4),1494-1499.
34. Han, R.; Zhang, Y. W.; Dong, X. L.; Gai, H. W.; Yeung, E. S., Spectral imaging of single molecules by transmission grating-based epi-fluorescence microscopy [J]. Analytica Chimica Acta 2008,619, (2),209-214.
35. Jiang, D., Solid phase single-molecule counting of antibody binding to supported protein layers surface with low nonspecific adsorption [J]. Talanta 2010,82, 1003-1009.
36. Jiang, D. F.; Liu, C. X.; Wang, L.; Jiang, W., Fluorescence single-molecule counting assays for protein quantification using epi-fluorescence microscopy with quantum dots labeling [J]. Analytica Chimica Acta 2010,662, (2),170-176.
37. Chen, Y.; Muller, J. D.; Carlson, K. E.; Katzenellenbogen, J. A.; Gratton, E., Molecular aggregation and ligand-receptor interaction probed at the single molecule level using two-photon microscopy [J]. Biophysical Journal 1998,74, (2), A182-A182.
38. Farrer, R. A.; Previte, M. J. R.; Olson, C. E.; Peyser, L. A.; Fourkas, J. T.; So, P. T. C., Single-molecule detection with a two-photon fluorescence microscope with fast-scanning capabilities and polarization sensitivity [J]. Optics Letters 1999,24, (24),1832-1834.
39. Schuck, P. J.; Willets, K. A.; Fromm, D. P.; Twieg, R. J.; Moerner, W. E., Two-photon fluorescence microscopy of single-molecule emitters based on nonlinear optical chromophores [J]. Abstracts of Papers of the American Chemical Society 2004,228, U270-U271.
40. Wormald, S.; Zhang, J. G.; Krebes, D. L.; Mielke, L. A.; Silver, J.; Alexander, W. S.; Speed, T. P.; Nicola, N. A.; Hilton, D. J., The comparative roles of suppressor of cytokine signaling-1 and-3 in the inhibition and desensitization of cytokine signaling [J]. Journal of Biological Chemistry 2006,281, (16),11135-11143.
41. Musselmann, K.; Alexandrou, B.; Kane, B.; Hassell, J. R., Maintenance of the keratocyte phenotype during cell proliferation stimulated by insulin [J]. Journal of Biological Chemistry 2005,280, (38),32634-32639.
42. Tokunagaa, M.; Kitamurab, K.; Saitoa, K.; Iwaneb, A. H.; Yanagida, T., Single Molecule Imaging of Fluorophores and Enzymatic Reactions Achieved by Objective-Type Total Internal Reflection Fluorescence Microscopy [J]. Biochemical and Biophysical Research Communications 1997,235, (1),47-53.
43. Funatsu, T.; Harada, Y.; Tokunaga, M.; Saito, K.; Yanagida, T., Imaging of single fluorescent molecules and individual ATP turnovers by single myosin molecules in aqueous solution [J]. Nature 1995,374,555-559.
44. Li, J. W.; Lee, J. Y.; Yeung, E. S., Quantitative screening of single copies of human papilloma viral DNA without amplification [J]. Analytical Chemistry 2006,78, (18), 6490-6496.
45. Rosenthal, S. J., Bar-coding biomolecules with fluorescent nanocrystals [J]. Nature Biotechnology 2001,19, (7),621-622.
46. Gao, X. H.; Nie, S. M., Molecular profiling of single cells and tissue specimens with quantum dots [J]. Trends in Biotechnology 2003,21, (9),371-373.
47. Leatherdale, C. A.; Woo, W. K.; Mikulec, F. V.; Bawendi, M. G., On the absorption cross section of CdSe nanocrystal quantum dots [J]. Journal of Physical Chemistry B 2002,106, (31),7619-7622.
48. Dubertret, B.; Skourides, P.; Norris, D. J.; Noireaux, V.; Brivanlou, A. H.; Libchaber, A., In vivo imaging of quantum dots encapsulated in phospholipid micelles [J]. Science 2002,298, (5599),1759-1762.
49. Zhang, C. Y.; Johnson, L. W., Homogenous rapid detection of nucleic acids using two-color quantum dots [J]. Analyst 2006,131, (4),484-488.
50. Thurer, R.; Vigassy, T.; Hirayama, M.; Wang, J.; Bakker, E.; Pretsch, E., Potentiometric immunoassay with quantum dot labels [J]. Analytical Chemistry 2007,79, (13),5107-5110.
51. Gao, X. H.; Nie, S. M., Quantum dot-encoded mesoporous beads with high brightness and uniformity:Rapid readout using flow cytometry [J]. Analytical Chemistry 2004, 76, (8),2406-2410.
52. Sathe, T. R.; Agrawal, A.; Nie, S. M., Mesoporous silica beads embedded with semiconductor quantum dots and iron oxide nanocrystals:Dual-function microcarriers for optical encoding and magnetic separation [J]. Analytical Chemistry 2006,78, (16),5627-5632.
53. Ma, Q.; Wang, X. Y.; Li, Y. B.; Su, X. G.; Jin, Q. H., The use of COP quantum dot fluorescent microspheres in fluoro-immunoassays and a microfluidic chip system [J]. Luminescence 2007,22, (5),438-445.
54. Xie, C.; Xu, F. G.; Huang, X. Y.; Dong, C. Q.; Ren, J. C., Single Gold Nanoparticles Counter:An Ultrasensitive Detection Platform for One-Step Homogeneous Immunoassays and DNA Hybridization Assays [J]. Journal of the American Chemical Society 2009,131, (35),12763-12770.
55. Chen, J. J.; Wang, C. G.; Irudayaraj, J., Ultrasensitive protein detection in blood serum using gold nanoparticle probes by single molecule spectroscopy [J]. Journal of Biomedical Optics 2009,14, (4),040501-1-040501-3.
56. Zhao, X. J.; Bagwe, R. P.; Tan, W. H., Development of organic-dye-doped silica nanoparticles in a reverse microemulsion [J]. Advanced Materials 2004,16, (2), 173-176.
57. Wang, L.; Lofton, C.; Popp, M.; Tan, W. H., Using luminescent nanoparticles as staining probes for affymetrix GeneChips [J]. Bioconjugate Chemistry 2007,18, (3), 610-613.
58. Patterson, G. H.; Lippincott-Schwartz, J., A photoactivatable GFP for selective photolabeling of proteins and cells [J]. Science 2002,297, (5588),1873-1877.
59. Lippincott-Schwartz, J.; Patterson, G. H., Development and use of fluorescent protein markers in living cells [J]. Science 2003,300, (5616),87-91.
1. Zarrin, F.; Dovichi, N. J., Sub-picoliter detection with the sheath flow cuvette [J]. Analytical Chemistry 1985,57,2690-2692.
2. Nguyen, D. C.; Keller, R. A.; Jett, J. H.; Martin, J. C., Detection of single molecules of phycoerythrin in hydrodynamically focused flows by laser-induced fluorescence [J]. Analytical Chemistry 1987,59,2158-2161.
3. Peck, K.; Stryer, L.; Glazer, A. N.; Mathies, R. A., Single-molecule fluorescence detection:autocorrelation criterion and experimental realization with phycoerythrin [J]. Proceeding of the National Academy of Sciences of the United States of America 1989,86,4087-4091.
4. Shera, E. B.; Seitzinger, N. K.; Davis, L. M.; Keller, R. A.; Soper, S. A., Detection of single fluorescent molecules [J]. Chemical Physics. Letters 1990,174,553-557.
5. Soper, S. A.; Davis, L. M.; Shera, E. B., Detection and identification of single molecules in solution [J]. Journal of the Optical Society of America B 1992,9, 1761-1769.
6. Castro, A.; Fairfield, F. R.; Shera, E. B., Fluorescence detection and size measurement of single DNA molecules [J]. Analytical Chemistry 1993,65,849-852.
7. Goodwin, P. M.; Johnson, M. E.; Martin, J. C.; Ambrose, W. P.; Marrone, B. L.; Jett, J. H.; Keller, R. A., Rapid sizing of individual fluorescently stained DNA fragments by flow-cytometry [J]. Nucleic Acids Research 1993,21,803-806.
8. Soper, S. A.; Mattingly, Q. L.; Vegunta, P., Photon Burst Detection of Single near-Infrared Fluorescent Molecules [J]. Analytical Chemistry 1993,65,740-747.
9. Huang, Z.; Petty, J. T.; O'Quinn, B.; Longmire, J. L.; Brown, N. C.; Jett, J. H.; Keller, R. A., Large DNA fragment sizing by flow cytometry:application to the characterization of P1 artificial chromosome (PAC) clones [J]. Nucleic Acids Research 1996,24,4202-4209.
10. Rauer, B.; Neumann, E.; Widengren, J.; Rigler, R.;, Fluorescence correlation spectrometry of the interaction kinetics of tetramethylrhodamin alpha-bungarotoxin with torpedo californica acetylcholine receptor [J]. Biophysics. Chemistry.1996,58, 3-12.
11. Castro, A.; Williams, J. G, Single-molecule detection of specific nucleic acid sequences in unamplified genomic DNA [J]. Analytical Chemistry 1997,69, (19), 3915-20.
12. Sauer, M.; Zander, C.; Muller, R.; Ullrich, B.; Drenhage, K. H.; Kaul, S.; Wolfrum, J., Detection and identification of individual antigen molecules in human serum with pulsed semiconductor lasers [J]. Applied Physics B 1997,65,427-431.
13. Van Orden, A.; Machara, N. P.; Goodwin, P. M.; Keller, R. A., Single molecule identification in flowing sample streams by fluorescence burst size and intraburst fluorescence decay rate [J]. Analytical Chemistry 1998,70, (7),1444-1451.
14. Machara, N. P.; Goodwin, P. M.; Enderlein, J.; Semin, D. J.; Keller, R. A., Efficient detection of single molecules eluting off an optically trapped microsphere [J]. Bioimaging 1998,6, (1),33-42.
15. Castro, A.; Okinaka, R. T., Ultrasensitive, direct detection of a specific DNA sequence of Bacillus anthracis in solution [J]. Analyst 1999,125, (1),9-11.
16. Barnes, M. D.; Ng, K. C.; Whitten, W. B.; Ramsey, J. M., Detection of single rhodamine 6G molecules in levitated microdroplets [J]. Analytical Chemistry 1993, 65,2360-2365.
17. Lermer, N.; Barnes, M. D.; Kung, C.; Whitten, W. B.; Ramsey, J. M., High-efficiency molecular counting in solution:single-molecule detection in electrodynamically focused microdroplet streams [J]. Analytical Chemistry 1997,69,2115-2121.
18. Barnes, M. D.; Lermer, N.; Kung, C.; Whitten, W. B.; Ramsey, J. M.; Hill, S. C., Real-time observation of single-molecule fluorescence in microdroplet streams [J]. Optics Letters 1997,22,1265-1267.
19. Kung, C. Y.; Barnes, M. D.; Lermer, N.; Whitten, W. B.; Ramsey, J. M., Confinement and manipulation of individual molecules in attoliter volumes [J]. Analytical Chemistry 1998,70, (3),658-661.
20. Lee, Y. H.; Maus, R. G.; Smith, B. W.; Winefordner, J. D., Laser-Induced Fluorescence Detection of a Single Molecule in a Capillary [J]. Analytical Chemistry 1994,66,4142-4149.
21. Xue, Q.; Yeung, E. S., Differences in the chemical reactivity of individual molecules of an enzyme [J]. Nature 1995,373,681-683.
22. Castro, A.; Shera, E. B., Single-Molecule electrophoresis [J]. Analytical Chemistry 1995,67,3181-3186.
23. Craig, D. B.; Arriaga, E. A.; Wong, J. C. Y.; Lu, H.; Dovichi, N. J., Studies on Single Alkaline Phosphatase Molecules:Reaction Rate and Activation Energy of a Reaction Catalyzed by a Single Molecule and the Effect of Thermal Denaturation:The Death of an Enzyme [J]. Journal of the American Chemical Society 1996,118,5245-5253.
24. Chen, D. Y.; Dovichi, N. J., Single-Molecule Detection in Capillary Electrophoresis: Molecular Shot Noise as a Fundamental Limit to Chemical Analysis [J]. Analytical Chemistry 1996,68,690-696.
25. Guenard, R. D.; King, L. A.; Smith, B. W.; Winefordner, J. D., Two-Channel Sequential Single-Molecule Measurement [J]. Analytical Chemistry 1997,69, 2426-2433.
26. Chou, H. P.; Spence, C.; Scherer, A.; Quake, S., A microfabricated device for sizing and sorting DNA molecules. [J] Proceeding of the National Academy of Sciences of the United States of America 1999,96, (1),11-3.
27. Polakowski, R.; Craig, D. B.; Skelley, A.; Dovichi, N. J., Single molecules of highly purified bacterial alkaline phosphatase have identical activity [J]. Journal of the American Chemical Society 2000,122, (20),4853-4855.
28. Shortreed, M. R.; Li, H. L.; Huang, W. H.; Yeung, E. S., High throughput single-molecule DNA screening based be electrophoresis [J]. Analytical Chemistry 2000,72, (13),2879-2885.
29. Lagally, E. T.; Medintz, I.; Mathies, R. A., Single-molecule DNA amplification and analysis in an integrated microfluidic device [J]. Analytical Chemistry 2001,73, (3), 565-570.
30. Li, H. L.; Xue, G.; Yeung, E. S., Selective detection of individual DNA molecules by capillary polymerase chain reaction [J]. Analytical Chemistry 2001,73, (7), 1537-1543.
31. Ma, Y. F.; Shortreed, M. R.; Li, H. L.; Huang, W. H.; Yeung, E. S., Single-molecule immunoassay and DNA diagnosis [J]. Electrophoresis 2001,22, (3),421-426.
32. Zheng, J. J.; Yeung, E. S., Anomalous radial migration of single DNA molecules in capillary electrophoresis [J]. Analytical Chemistry 2002,74, (17),4536-4547.
33. Anazawa, T.; Matsunaga, H.; Yeung, E. S., Electrophoretic quantitation of nucleic acids without amplification by single-molecule imaging [J]. Analytical Chemistry 2002,74, (19),5033-5038.
34. Tan, W.; Yeung, E. S., Monitoring the Reactions of Single Enzyme Molecules and Single Metal Ions [J]. Analytical Chemistry 1997,69,4242-4248.
35. Nie, S.; Chiu, D. T.; Zare, R. N., Probing individual molecules with confocal fluorescence microscopy [J]. Science 1994,266,1018-1021.
36. Eigen, M.; Rigler, R., Sorting single molecules:application to diagnostics and evolutionary biotechnology [J]. Proceeding of the National Academy of Sciences of the United States of America 1994,91, (13),5740-7.
37. Nie, S. M.; Chiu, D. T.; Zare, R. N., Real-time detection of single molecules in solution by confocal fluorescence microscopy [J]. Analytical Chemistry 1995,67, 2849-2857.
38. Haab, B. B.; Mathies, R. A., Single Molecule Fluorescence Burst Detection of DNA Fragments Separated by Capillary Electrophoresis [J]. Analytical Chemistry 1995, 67,3253-3260.
39. Edman, L.; Mets, U.; Rigler, R., Conformational transitions monitored for single molecules in solution [J]. Proceeding of the National Academy of Sciences of the United States of America 1996,93, (13),6710-5.
40. Lyon, W. A.; Nie, S., Confinement and Detection of Single Molecules in Submicrometer Channels [J]. Analytical Chemistry 1997,69,3400-3405.
41. Loscher, F.; Bohme, S.; Martin, J.; Seeger, S., Counting of single protein molecules at interfaces and application of this technique in early-stage diagnosis [J]. Analytical Chemistry 1998,70, (15),3202-5.
42. Haab, B. B.; Mathies, R. A., Single-molecule detection of DNA separations in microfabricated capillary electrophoresis chips employing focused molecular streams [J]. Analytical Chemistry 1999,71, (22),5137-45.
43. Prummer, M.; Hubner, C. G.; Sick, B.; Hecht, B.; Renn, A.; Wild, U. P., Single-molecule identification by spectrally and time-resolved fluorescence detection [J]. Analytical Chemistry 2000,72, (3),443-7.
44. Knemeyer, J. P.; Marme, N.; Sauer, M., Probes for detection of specific DNA sequences at the single-molecule level [J]. Analytical Chemistry 2000,72, (16), 3717-24.
45. Byassee, T. A.; Chan, W. C.; Nie, S., Probing single molecules in single living cells [J]. Analytical Chemistry 2000,72, (22),5606-11.
46. Wabuyele, M. B.; Ford, S. M.; Stryjewski, W.; Barrow, J.; Soper, S. A., Single molecule detection of double-stranded DNA in poly(methylmethacrylate) and polycarbonate microfluidic devices [J]. Electrophoresis 2001,22, (18),3939-48.
47. Tadakuma, H.; Yamaguchi, J.; Ishihama, Y.; Funatsu, T., Imaging of single fluorescent molecules using video-rate confocal microscopy [J]. Biochemical and Biophysical Research Communications 2001,287, (2),323-7.
48. Dorre, K.; Stephan, J.; Lapczyna, M.; Stuke, M.; Dunkel, H.; Eigen, M., Highly efficient single molecule detection in microstructures [J]. Journal of Biotechnoogyl 2001,86, (3),225-36.
49. Dorre, K.; Stephan, J.; Eigen, M., Highly efficient single molecule detection in different micro-and submicrometer channels with cw exitation [J]. Single Molecules 2001,2,165-175.
50. Weston, K. D.; Dyck, M.; Tinnefeld, P.; Muller, C.; Herten, D. P.; Sauer, M., Measuring the number of independent emitters in single-molecule fluorescence images and trajectories using coincident photons [J]. Analytical Chemistry 2002,74, (20),5342-9.
51. Shelby, J. P.; Chiu, D. T., Mapping fast flows over micrometer-length scales using flow-tagging velocimetry and single-molecule detection [J]. Analytical Chemistry 2003,75, (6),1387-92.
52. Li, H.; Ying, L.; Green, J. J.; Balasubramanian, S.; Klenerman, D., Ultrasensitive coincidence fluorescence detection of single DNA molecules [J]. Analytical Chemistry 2003,75, (7),1664-70.
53. Prummer, M.; Sick, B.; Renn, A.; Wild, U. P., Multiparameter microscopy and spectroscopy for single-molecule analytics [J]. Analytical Chemistry 2004,76, (6), 1633-40.
54. Li, H.; Zhou, D.; Browne, H.; Balasubramanian, S.; Klenerman, D., Molecule by molecule direct and quantitative counting of antibody-protein complexes in solution [J]. Analytical Chemistry 2004,76, (15),4446-51.
55. Sun, B.; Chiu, D. T., Determination of the encapsulation efficiency of individual vesicles using single-vesicle photolysis and confocal single-molecule detection [J]. Analytical Chemistry 2005,77, (9),2770-6.
56. Fang, X.; Tan, W., Imaging single fluorescent molecules at the interface of an optical fiber probe by evanescent wave excitation [J]. Analytical Chemistry 1999,71, 3101-3105.
57. Ma, Y.; Shortreed, M. R.; Yeung, E. S., High-throughput single-molecule spectroscopy in free solution [J]. Analytical Chemistry 2000,72, (19),4640-5.
58. Kang, S. H.; Yeung, E. S., Dynamics of single-protein molecules at a liquid/solid interface:implications in capillary electrophoresis and chromatography [J]. Analytical Chemistry 2002,74, (24),6334-9.
59. Singh-Zocchi, M.; Dixit, S.; Ivanov, V.; Zocchi, G, Single-molecule detection of DNA hybridization [J]. Proceeding of the National Academy of Sciences of the United States of America 2003,100, (13),7605-10.
60. Li, H. W.; Yeung, E. S., Direct observation of anomalous single-molecule enzyme kinetics [J]. Analytical Chemistry 2005,77, (14),4374-7.
61. Hanley, D. C.; Harris, J. M., Quantitative dosing of surfaces with fluorescent molecules:characterization of fractional monolayer coverages by counting single molecules [J]. Analytical Chemistry 2001,73, (21),5030-7.
62. Agrawal, A.; Zhang, C.; Byassee, T.; Tripp, R. A.; Nie, S., Counting single native biomolecules and intact viruses with color-coded nanoparticles [J]. Analytical Chemistry 2006,78, (4),1061-70.
63. Donner, S.; Li, H. W.; Yeung, E. S.; Porter, M. D., Fabrication of optically transparent carbon electrodes by the pyrolysis of photoresist films:approach to single-molecule spectroelectrochemistry [J]. Analytical Chemistry 2006,78, (8),2816-22.
64. Wang, L.; Xu, G.; Shi, Z.; Jiang, W.; Jin, W., Quantification of protein based on single-molecule counting by total internal reflection fluorescence microscopy with adsorption equilibrium [J]. Analytica Chimica Acta 2007,590, (1),104-9.
65. Lee, J. Y.; Li, J.; Yeung, E. S., Single-molecule detection of surface-hybridized human papilloma virus DNA for quantitative clinical screening [J]. Analytical Chemistry 2007,79, (21),8083-9.
66. Yu, J. S.; Zhou, T. Y, The electrochemistry and thin-layer luminescence spectroelectrochemistry of rhodamine 6G at a 4,4'-bipyridine-modified gold electrode [J]. Journal of Electroanalytical Chemistry 2001,504, (1),89-95.
67. Moulton, S. E.; Barisci, J. N.; Bath, A.; Stella, R.; Wallace, G. G., Investigation of protein adsorption and electrochemical behavior at a gold electrode [J]. Journal of Colloid and Interface Science 2003,261, (2),312-9.
68. Ying, P.; Viana, A. S.; Abrantes, L. M.; Jin, G, Adsorption of human serum albumin onto gold:a combined electrochemical and ellipsometric study [J]. Journal of Colloid and Interface Science 2004,279, (1),95-9.
69. Moulton, S. E.; Barisci, J. N.; Bath, A.; Stella, R.; Wallace, G G, Investigation of Ig.G adsorption and the effect on electrochemical responses at titanium dioxide electrode [J]. Langmuir 2005,21, (1),316-22.
70. Hidalgo-Alvarez, R.; Galisteo-Gonzalez, F., The adsorption characteristics of immunoglobulins [J]. Heterogeneous Chemical. Review 1995,2,249-268.
71. Ganachaud, F.; ElaI''ssari, A.; Pichot, C.; Laayoun, A.; Cros, P., Adsorption of single-stranded DNA fragments onto cationic aminated latex particles [J]. Langmuir 1997,13,701-707.
1. Draghici, S.; Khatri, P.; Eklund, A. C.; Szallasi, Z., Reliability and reproducibility issues in DNA microarray measurements [J]. Trends in Genetics 2006,22, (2), 101-109.
2. Levicky, R.; Horgan, A., Physicochemical perspectives on DNA microarray and biosensor technologies [J]. Trends in Biotechnology 2005,23, (3),143-149.
3. Merkel, J. S.; Michaud, G. A.; Salcius, M.; Schweitzer, B.; Predki, P. F., Functional protein microarrays:just how functional are they [J]? Current Opinion in Biotechnology 2005,16, (4),447-452.
4. Predki, P. F., Functional protein microarrays:ripe for discovery [J]. Current Opinion in Chemical Biology 2004,8, (1),8-13.
5. Mir, K. U., Ultrasensitive RNA profiling:Counting single molecules on microarrays [J]. Genome Research 2006,16, (10),1195-1197.
6. Duggan, D. J.; Bittner, M.; Chen, Y. D.; Meltzer, P.; Trent, J. M., Expression profiling using cDNA microarrays [J]. Nature Genetics 1999,21,10-14.
7. Gerion, D.; Chen, F. Q.; Kannan, B.; Fu, A. H.; Parak, W. J.; Chen, D. J.; Majumdar, A.; Alivisatos, A. P., Room-temperature single-nucleotide polymorphism and multiallele DNA detection using fluorescent nanocrystals and microarrays [J]. Analytical Chemistry 2003,75, (18),4766-4772.
8. Zhou, X. C.; Zhou, J. Z., Improving the signal sensitivity and photo stability of DNA hybridizations on microarrays by using dye-doped core-shell silica nanoparticles [J]. Analytical Chemistry 2004,76, (18),5302-5312.
9. Schweitzer, B.; Wiltshire, S.; Lambert, J.; O'Malley, S.; Kukanskis, K.; Zhu, Z. R.; Kingsmore, S. F.; Lizardi, P. M.; Ward, D. C., Immunoassays with rolling circle DNA amplification:A versatile platform for ultrasensitive antigen detection [J]. Proceedings of the National Academy of Sciences of the United States of America 2000,97, (18),10113-10119.
10. Hesse, J.; Sonnleitner, M.; Sonnleitner, A.; Freudenthaler, G.; Jacak, J.; Hoglinger, O.; Schindler, H.; Schutz, G. J., Single-molecule reader for high-throughput bioanalysis [J]. Analytical Chemistry 2004,76, (19),5960-5964.
11. Hesse, J.; Jacak, J.; Kasper, M.; Regl, G.; Eichberger, T.; Winklmayr, M.; Aberger, F.; Sonnleitner, M.; Schlapak, R.; Howorka, S.; Muresan, L.; Frischauf, A. M.; Schutz, G. J., RNA expression profiling at the single molecule level [J]. Genome Research 2006,16, (8),1041-1045.
12. Li, L.; Tian, X. Z.; Zou, G. Z.; Shi, Z. K.; Zhang, X. L.; Jin, W. R., quantitative counting of single fluorescent molecules by combined electrochemical adsorption accumulation and total internal reflection fluorescence microscopy [J]. Analytical Chemistry 2008,80, (11),3999-4006.
13. Ballard, J. L.; Peeva, V. K.; deSilva, C. J. S.; Lynch, J. L.; Swanson, N. R., Comparison of Alexa Fluor (R) and CyDye (TM) for practical DNA microarray use [J]. Molecular Biotechnology 2007,36, (3),175-183.
14. Chan, W. C. W.; Nie, S. M., Quantum dot bioconjugates for ultrasensitive nonisotopic detection [J]. Science 1998,281, (5385),2016-2018.
15. Gerion, D.; Parak, W. J.; Williams, S. C.; Zanchet, D.; Micheel, C. M.; Alivisatos, A. P., Sorting fluorescent nanocrystals with DNA [J]. Journal of the American Chemical Society 2002,124, (24),7070-7074.
16. Maxwell, D. J.; Taylor, J. R.; Nie, S. M., Self-assembled nanoparticle probes for recognition and detection of biomolecules [J]. Journal of the American Chemical Society 2002,124, (32),9606-9612.
17. Murphy, C. J., Optical sensing with quantum dots [J]. Analytical Chemistry 2002,74, (19),520a-526a.
18. Rosenthal, S. J., Bar-coding biomolecules with fluorescent nanocrystals [J]. Nature Biotechnology 2001,19, (7),621-622.
19. Willner, I.; Patolsky, F.; Wasserman, J., Photoelectrochemistry with controlled DNA-cross-linked CdS nanoparticle arrays [J]. Angewandte Chemie-International Edition 2001,40, (10),1861-1864.
20. Ulstrup, J. C.; Skaug, K.; Figenschau, K. J.; Orstavik, I.; Bruun, J. N.; Petersen, G., Sensitivity of western blotting (compared with ELISA and immunofluorescence) during seroconversion after HTLV-Ⅲ infection [J]. Lancet 1986,1, (8490), 1151-1152.
21. Clark, D. A.; Blois, S.; Kandil, J.; Handjiski, B.; Manuel, J.; Arck, P. C., Reduced uterine indoleamine 2,3-dioxygenase versus increased Thl/Th2 cytokine ratios as a basis for occult and clinical pregnancy failure in mice and humans [J]. American Journal of Reproductive Immunology 2005,54, (4),203-216.
22. Chaouat, G.; Zourbas, S.; Ostojic, S.; Lappree-Delage, G.; Dubanchet, S.; Ledee, N.; Martal, J., A brief review of recent data on some cytokine expressions at the materno-foetal interface which might challenge the classical Thl/Th2 dichotomy [J]. Journal of Reproductive Immunology 2002,53, (1-2),241-256.
23. Renkl, A. C.; Wussler, J.; Ahrens, T.; Thoma, K.; Kon, S.; Uede, T.; Martin, S. F.; Simon, J. C.; Weiss, J. M., Osteopontin functionally activates dendritic cells and induces their differentiation toward a Thl-polarizing phenotype [J]. Blood 2005,106, (3),946-955.
24. Das, R.; Mahabeleshwar, G. H.; Kundu, G. C., Osteopontin induces AP-1-mediated secretion of urokinase-type plasminogen activator through c-Src-dependent epidermal growth factor receptor transactivation in breast cancer cells [J]. Journal of Biological Chemistry 2004,279, (12),11051-11064.
25. Wai, P. Y.; Kuo, P. C., Osteopontin:regulation in tumor metastasis [J]. Cancer and Metastasis Reviews 2008,27, (1),103-118.
1. Baro, D. J.; Levini, R. M.; Kim, M. T.; Willms, A. R.; Lanning, C. C.; Rodriguez, H. E.; Harris-Warrick, R. M., Quantitative single-cell-reverse transcription-PCR demonstrates that A-current magnitude varies as a linear function of shal gene expression in identified stomatogastric neurons [J]. The Journal of Neuroscience 1997,17, (17),6597-610.
2. Bengtsson, M.; Stahlberg, A.; Rorsman, P.; Kubista, M., Gene expression profiling in single cells from the pancreatic islets of Langerhans reveals lognormal distribution of mRNA levels [J]. Genome Research 2005,15, (10),1388-1392.
3. Chiang, M. K.; Melton, D. A., Single-cell transcript analysis of pancreas development [J]. Developmental Cell 2003,4, (3),383-393.
4. Collins, M. E.; Stevens, D. A.; Jenner, L. J.; Brownlie, J., A rapid method for mRNA detection in single-cell biopsies from preimplantation-stage bovine embryos [J]. Theriogenology 1995,43, (7),1227-38.
5. Danik, M.; Puma, C.; Quirion, R.; Williams, S., Widely expressed transcripts for chemokine receptor CXCR1 in identified glutamatergic, gamma-aminobutyric acidergic, and cholinergic neurons and astrocytes of the rat brain:A single-cell reverse transcription-multiplex polymerase chain reaction study [J]. Journal of Neuroscience Research 2003,74, (2),286-295.
6. Liss, B., Improved quantitative real-time RT-PCR for expression profiling of individual cells [J]. Nucleic Acids Research 2002,30, (17),-
7. Peixoto, A.; Monteiro, M.; Rocha, B.; Veiga-Fernandes, H., Quantification of multiple gene expression in individual cells [J]. Genome Research 2004,14, (10A), 1938-1947.
8. Tietjen, I.; Rihel, J. M.; Cao, Y. X.; Koentges, G.; Zakhary, L.; Dulac, C., Single-cell transcriptional analysis of neuronal progenitors [J]. Neuron 2003,38, (2),161-175.
9. Tkatch, T.; Baranauskas, G.; Surmeier, D. J., Kv4.2 mRNA abundance and A-type K+ current amplitude are linearly related in basal ganglia and basal forebrain neurons [J]. Journal of Neuroscience 2000,20, (2),579-588.
10. Tsuzuki, K.; Lambolez, B.; Rossier, J.; Ozawa, S., Absolute quantification of AMPA receptor subunit mRNAs in single hippocampal neurons [J]. Journal of Neurochemistry 2001,77, (6),1650-1659.
11. Bentwich, I.; Avniel, A.; Karov, Y.; Aharonov, R.; Gilad, S.; Barad, O.; Barzilai, A.; Einat, P.; Einav, U.; Meiri, E.; Sharon, E.; Spector, Y.; Bentwich, Z., Identification of hundreds of conserved and nonconserved human microRNAs [J]. Nature Genetics 2005,37, (7),766-770.
12. Hesse, J.; Jacak, J.; Kasper, M.; Regl, G.; Eichberger, T.; Winklmayr, M.; Aberger, F.; Sonnleitner, M.; Schlapak, R.; Howorka, S.; Muresan, L.; Frischauf, A. M.; Schutz, G. J., RNA expression profiling at the single molecule level [J]. Genome Research 2006,16, (8),1041-1045.
13. Mir, K. U., Ultrasensitive RNA profiling:Counting single molecules on microarrays [J]. Genome Research 2006,16, (10),1195-1197.
14. Duggan, D. J.; Bittner, M.; Chen, Y. D.; Meltzer, P.; Trent, J. M., Expression profiling using cDNA microarrays [J]. Nature Genetics 1999,21,10-14.
15. Gerion, D.; Chen, F. Q.; Kannan, B.; Fu, A. H.; Parak, W. J.; Chen, D. J.; Majumdar, A.; Alivisatos, A. P., Room-temperature single-nucleotide polymorphism and multiallele DNA detection using fluorescent nanocrystals and microarrays [J]. Analytical Chemistry 2003,75, (18),4766-4772.
16. Zhou, X. C.; Zhou, J. Z., Improving the signal sensitivity and photo stability of DNA hybridizations on microarrays by using dye-doped core-shell silica nanoparticles [J]. Analytical Chemistry 2004,76, (18),5302-5312.
1. Gross, P.; Farge, G.; Peterman, E. J.; Wuite, G. J., Combining optical tweezers, single-molecule fluorescence microscopy, and microfluidics for studies of DNA-protein interactions. Methods Enzymol 2010,475,427-453.
2. Gurunathan, K.; Levitus, M., Single-molecule fluorescence studies of nucleosome dynamics. Current Pharmaceutical Biotechnology 2009,10, (5),559-568.
3. Huang, Z.; Petty, J. T.; O'Quinn, B.; Longmire, J. L.; Brown, N. C.; Jett, J. H.; Keller, R. A., Large DNA fragment sizing by flow cytometry:application to the characterization of P1 artificial chromosome (PAC) clones. Nucleic Acids Research 1996,24,4202-4209.
4. Jiang, D.; Liu, C.; Wang, L.; Jiang, W., Fluorescence single-molecule counting assays for protein quantification using epi-fluorescence microscopy with quantum dots labeling [J]. Analytica Chimica Acta 2010,662, (2),170-176.
5. Jiang, D.; Wang, L.; Jiang, W., Quantitative detection of antibody based on single-molecule counting by total internal reflection fluorescence microscopy with quantum dot labeling [J]. Analytica Chimica Acta 2009,634, (1),83-88.
6. Kawashima, N.; Nakayama, K.; Itoh, K.; Itoh, T.; Ishikawa, M.; Biju, V., Reversible dimerization of EGFR revealed by single-molecule fluorescence imaging using quantum dots [J]. Chemistry 2010,16, (4),1186-1192.
7. Kumbhakar, M.; Kiel, A.; Pal, H.; Herten, D. P., Single-molecule fluorescence studies reveal long-range electron-transfer dynamics through double-stranded DNA [J]. Chemphyschem 2009,10, (4),629-633.
8. Lee, N. K.; Koh, H. R.; Han, K. Y.; Lee, J.; Kim, S. K., Single-molecule, real-time measurement of enzyme kinetics by alternating-laser excitation fluorescence resonance energy transfer [J]. Chemical Communications (Cambridge) 2010,46, (26),4683-4685.
9. Li, Q.; Liu, X.; He, Y., Single molecule fluorescence imaging of DNA at agarose surfaces by total internal reflection fluorescence microscopy [J]. Journal of Biomedical Nanotechnology 2009,5, (5),565-572.
10. Nienhaus, G. U., Single-molecule fluorescence studies of protein folding [J]. Methods Molecular Biology 2009,490,311-337.
11. Pugh, R. A.; Honda, M.; Spies, M., Ensemble and single-molecule fluorescence-based assays to monitor DNA binding, translocation, and unwinding by iron-sulfur cluster containing helicases [J]. Methoas 2010,51, (3),313-321.
12. Rauer, B.; Neumann, E.; Widengren, J.; Rigler, R.;, Fluorescence correlation spectrometry of the interaction kinetics of tetramethylrhodamin alpha-bungarotoxin with torpedo californica acetylcholine receptor [J]. Biophysical. Chemistry 1996,58, 3-12.
13. Ray, K.; Ma, J.; Oram, M.; Lakowicz, J. R.; Black, L. W., Single-molecule and FRET fluorescence correlation spectroscopy analyses of phage DNA packaging: colocalization of packaged phage T4 DNA ends within the capsid [J]. Journal of Molecular Biology 2010,395, (5),1102-1113.
14. Rigler, R., Fluorescence and single molecule analysis in cell biology [J]. Biochemical and Biophysical Research Communications 2010,396, (1),170-5.
15. Soper, S. A.; Mattingiy, Q. L.; Vegunta, P., Photon Burst Detection of Single near-Infrared Fluorescent Molecules [J]. Analytical Chemistry 1993,65,740-747.
16. Tanner, N. A.; Loparo, J. J.; van Oijen, A. M., Visualizing Single-molecule DNA Replication with Fluorescence Microscopy [J]. Journal of Visualized Experiments 2009,(32),1529.
17. van Mameren, J.; Gross, P.; Farge, G.; Hooijman, P.; Modesti, M.; Falkenberg, M.; Wuite, G. J.; Peterman, E. J., Unraveling the structure of DNA during overstretching by using multicolor, single-molecule fluorescence imaging [J]. Proceedings of the National Academy of Sciences of the United States of America 2009,106, (43), 18231-18236.
18. Yeung, K. M.; Lu, Z. J.; Cheung, N. H., Adsorption of bovine serum albumin on fused silica:Elucidation of protein-protein interactions by single-molecule fluorescence microscopy [J]. Colloids and Surfaces B:Biointerfaces 2009,69, (2),246-250.
19. Max, B.; Emil, W., Principles of Optics:Electromagnetic Theory of Propagation, Interference and Diffraction of Light, Seventh(expanded)Edition. Cambridge University Press 1999.孙葭荪译,北京：电子工业出版社,2009,10.
20. Festag, G.; Steinbruck, A.; Wolff, A.; Csaki, A.; Moller, R.; Fritzsche, W., Optimization of gold nanoparticle-based DNA detection for microarrays [J]. Journal of Fluorescence 2005,15, (2),161-170.
21. Gokarna, A.; Jin, L. H.; Hwang, J. S.; Cho, Y. H.; Lim, Y. T.; Chung, B. H.; Youn, S. H.; Choi, D. S.; Lim, J. H., Quantum dot-based protein micro-and nanoarrays for detection of prostate cancer biomarkers [J]. Proteomics 2008,8, (9),1809-1818.
22. Miao, W.; Bard, A. J., Electrogenerated chemiluminescence.72. Determination of immobilized DNA and C-reactive protein on Au(111) electrodes using tris(2,2'-bipyridyl)ruthenium(Ⅱ) labels [J]. Analytical Chemistry 2003,75, (21), 5825-5834.
23. Sapsford, K. E.; Medintz, I. L.; Golden, J. P.; Deschamps, J. R.; Uyeda, H. T. Mattoussi, H., Surface-immobilized self-assembled protein-based quantum dot nanoassemblies [J]. Langmuir 2004,20, (18),7720-7728.
24. Yeung, S. S.; Lee, T. M.; Hsing, I. M., Electrochemistry-based real-time PCR on a microchip [J]. Analytical Chemistry 2008,80, (2),363-368.
25. Lee, G. U.; Metzger, S.; Natesan, M.; Yanavich, C.; Dufrene, Y. F., Implementation of force differentiation in the immunoassay [J]. Analytical Biochemistry 2000,287, (2), 261-271.
26. Bustamante, C.; Smith, S. B.; Liphardt, J.; Smith, D., Single-molecule studies of DNA mechanics [J]. Current Opinion in Structural Biology 2000,10, (3),279-285.
27. van Oijen, A. M.; Blainey, P. C.; Crampton, D. J.; Richardson, C. C.; Ellenberger, T.; Xie, X. S., Single-molecule kinetics of lambda exonuclease reveal base dependence and dynamic disorder [J]. Science 2003,301, (5637),1235-1238.
28. Kim, S. J.; Blainey, P. C.; Schroeder, C. M.; Xie, X. S., Multiplexed single-molecule assay for enzymatic activity on flow-stretched DNA [J]. Nature Methods 2007,4, (5),397-399.
29. Lee, J. B.; Hite, R. K.; Hamdan, S. M.; Xie, X. S.; Richardson, C. C.; van Oijen, A. M., DNA primase acts as a molecular brake in DNA replication [J]. Nature 2006, 439, (7076),621-624.
30. Mulvaney, S. P.; Cole, C. L.; Kniller, M. D.; Malito, M.; Tamanaha, C. R.; Rife, J. C.; Stanton, M. W.; Whitman, L. J., Rapid, femtomolar bioassays in complex matrices combining microfluidics and magnetoelectronics [J]. Biosensors & Bioelectronics 2007,23,(2),191-200.
1. Fulton, R.J., McDade, R.L., Smith, P.L., Kienker, L.J., Kettman, J.R., Advanced multiplexed analysis with the FlowMetrix (TM) system [J]. Clinical Chemistry 1997, 43,1749-1756.
2. Steemers, F.J., Ferguson, J.A., Walt, D.R., Screening unlabeled DNA targets with randomly ordered fiber-optic gene arrays [J]. Nature Biotechnology 2000,18, 91-94.
3. Ferguson, J.A., Boles, T.C., Adams, C.P., Walt, D.R., A fiber-optic DNA biosensor microarray for the analysis of gene expression[J]. Nature Biotechnology 1996,14, 1681-1684.
4. Ferguson, J.A., Steemers, F.J., Walt, D.R., High-density fiber-optic DNA random microsphere arrays [J]. Analytical. Chemistry 2000,72,5618-5624.
5. Han, M.Y., Gao, X.H., Su, J.Z., Nie, S.M., Quantum-dot-tagged microbeads for multiplexed optical coding of biomolecules [J]. Nature Biotechnology 2001,19, 631-635.
1. Forster, T., Intramolecular energy migration and fluorescence [J]. Annals of Physics 1948, (2),55-75.
2. Stryer, L.; Haugland, R. P., Fluorescence Energy transfer:a spectroscopic ruler [J]. Proceeding of the National Academy of Sciences of the United States of America 1967,58, (2),719-726.
3. Palm, T.; Sale, K.; Brown, L.; Li, H. C.; Hambly, B.; Fajer, P. G., Intradomain distances in the regulatory domain of the myosin head in prepower and postpower stroke states:Fluorescence energy transfer [J]. Biochemistry 1999,38, (40),13026-13034.
4. Arimori, S.; Bell, M. L.; Oh, C. S.; Frimat, K. A.; James, T. D., Modular fluorescence sensors for saccharides [J]. Chemical Communications 2001, (18),1836-1837.
5. Jensen, K. K.; Martini, L.; Schwartz, T. W., Enhanced fluorescence resonance energy transfer between spectral variants of green fluorescent protein through zinc-site engineering [J]. Biochemistry 2001,40, (4),938-945.
6. von Bultzingslowen, C.; McEvoy, A. K.; McDonagh, C.; MacCraith, B. D., Lifetime-based optical sensor for high-level pCO(2) detection employing fluorescence resonance energy transfer [J]. Analytica Chimica Acta 2003,480, (2), 275-283.
7. Liu, S. X.; Fang, Y.; Hu, D. D.; Gao, G. L.; Ma, J. B., Complexation between poly(methacrylic acid) and poly(vinylpyrrolidone) [J]. Journal of Applied Polymer Science 2001,82, (3),620-627.
8. Elbanowski, M.; Mkowska, B., The lanthanides as luminescent probes in investigations of biochemical systems [J]. Journal of Photochemistry and Photobiology A: Chemistry 1996,99,85-92.
9. Bu, P. C.; Zhuang, J.; Feng, J.; Yang, D. L.; Shen, X.; Yan, X. Y, Visualization of CD 146 dimerization and its regulation in living cells [J]. Biochimica Et Biophysica Acta-Molecular Cell Research 2007,1773, (4),513-520.
10. Martin, S. F.; Hattersley, N.; Samuel, I. D. W.; Hay, R. T.; Tatham, M. H., A fluorescence-resonance-energy-transfer-based protease activity assay and its use to monitor paralog-specific small ubiquitin-like modifier processing [J]. Analytical Biochemistry 2007,363, (1),83-90.
11. Ganesan, S.; Ameer-beg, S. M.; Ng, T. T. C.; Vojnovic, B.; Wouters, F. S., A dark yellow fluorescent protein (YFP)-based Resonance Energy-Accepting Chromoprotein (REACh) for Forster resonance energy transfer with GFP [J]. Proceedings of the National Academy of Sciences of the United States of America 2006,103, (11),4089-4094.
12. Antia, M.; Islas, L. D.; Boness, D. A.; Baneyx, G.; Vogel, V., Single molecule fluorescence studies of surface-adsorbed fibronectin [J]. Biomaterials 2006,27, (5), 679-690.
13. Rega, M. F.; Reed, J. C.; Pellecchia, M., Robust lanthanide-based assays for the detection of anti-apoptotic Bcl-2-family protein antagonists [J]. Bioorganic Chemistry 2007,35, (2),113-120.
14. Wei, O. D.; Lee, M.; Yu, X.; Lee, E. K.; Seong, G. H.; Choo, J.; Cho, Y. W., Development of an open sandwich fluoroimmunoassay based on fluorescence resonance energy transfer [J]. Analytical Biochemistry 2006,358, (1),31-37.
15. Isaac, V. E.; Patel, L.; Curran, T.; Shen, C. A., Use of Fluorescence Resonance Energy Transfer To Estimate Intramolecular Distances in the Msx-1 Homeodomain [J]. Biochemistry 1995,34,15276-15281.
16. Clegg, R. M.; Urche, A. H.; Lilley, D. L., The solution structure of the four-way DNA junction at low-salt conditions:a fluorescence resonance energy transfer analysis [J]. Biophysical Journal 1994,66,99-109.
17. Miki, M.; Iio, T., Kinetics of Structural Changes of Reconstituted Skeletal Muscle Thin Filaments Observed by Fluorescence Resonance Energy Transfer [J]. The Journal of Biological Chemistry 1993,268,7101-7106.
18. Johnson, D. A.; Leathers, V. L.; Martinez, A. M.; Walsh, D. A.; Fletcher, W. H., Fluorescence Resonance Energy Transfer within a Heterochromatic cAMP-Dependent Protein Kinase Holoenzyme under Equilibrium Conditions:New Insights into the Conformational Changes That Result in cAMP-Dependent Activation [J]. Biochemistry 1993,32,6402-6410.
19. Graham, D. L.; Lowe, P. N.; Chalk, P. A., A method to measure the interaction of Rac/Cdc42 with their binding partners using fluorescence resonance energy transfer between mutants of green fluorescent protein [J]. Analytical Biochemistry 2001,296, (2),208-217.
20. Ghosh, S. S.; Eis, P. S.; Blumeyer, K.; Fearon, K.; Millar, D. P., Real time kinetics of restriction endonuclease cleavage monitored by fluorescence resonance energy transfer [J]. Nucleic Acids Research 1994,22,3155-3159.
21. Perkins, T. A.; Wolf, D. E.; Goodchild, J., Fluorescence Resonance Energy Transfer Analysis of Ribozyme Kinetics Reveals the Mode of Action of a Facilitator Oligonucleotide [J]. Biochemistry 1996,35,16370-16377.
22. Ueda, H.; Kubota, K.; Wang, Y.; Tsumoto, K.; Mahoney, W.; Kumagai, I.; Nagamune, T., Homogeneous noncompetitive immunoassay based on the energy transfer between fluorolabeled antibody variable domains (open sandwich fluoroimmunoassay) [J]. Biotechniques 1999,27, (4),738-742.
23. Sixou, S.; Szoka, F. C.; Green, G. A.; Giusti, B.; Zon, G.; Chin, D. J., Intracellular oligonucleotide hybridization detected by fluorescence resonance energy transfer (FRET) [J]. Nucleic Acids Research 1994,22,662-668
24. Morrison, L. E.; Halder, T. C.; Stols, L. M., Solution-phase detection of polynucleotides using interacting fluorescent labels and competitive hybridization [J]. Analytical Biochemistry 1989,183,231-244
25. Tyagi, S.; Kramer, F. R., Molecular beacons:probes that fluoresce upon hybridization [J]. Nature Biotechnology 1996,14,303-308.
26. Li, Y. S.; Zhou, X. Y.; Ye, D. Y, Molecular beacons:An optimal multifunctional biological probe [J]. Biochemical and Biophysical Research Communications 2008, 373, (4),457-461.
27. Palecek, E., Surface-attached molecular beacons light the way for DNA sequencing [J]. Trends in Biotechnology 2004,22, (2),55-58.
28. Tyagi, S.; Bratu, D. P.; Kramer, F. R., Multicolor molecular beacons for allele discrimination [J]. Nature Biotechnology 1998,16, (1),49-53.
29. Fang, X. H.; Li, J. W. J.; Perlette, J.; Tan, W. H.; Wang, K. M., Molecular beacons-Novel fluorescent probes [J]. Analytical Chemistry 2000,72, (23),747a-753a.
30. Williams, E. J.; Campbell, A. K., A homogeneous assay for biotin based on chemiluminescence energy transfer [J]. Anayticall. Biochemistry 1986 155, 249-255.
31. Huang, X. Y.; Li, L.; Qian, H. F.; Dong, C. Q.; Ren, J. C., A resonance energy transfer between chemiluminescent donors and luminescent quantum-dots as acceptors (CRET) [J]. Angewandte Chemie-International Edition 2006,45, (31),5140-5143.
32. Murphy, C. J., Optical sensing with quantum dots [J]. Analytical Chemistry 2002,74, (19),520a-526a.
33. Achermann, M.; Petruska, M. A.; Kos, S.; Smith, D. L.; Koleske, D. D.; Klimov, V. I., Energy-transfer pumping of semiconductor nanocrystals using an epitaxial quantum well [J]. Nature 2004,429, (6992),642-646.
34. Clapp, A. R.; Medintz, I. L.; Fisher, B. R.; Anderson, G. P.; Mattoussi, H., Can luminescent quantum dots be efficient energy acceptors with organic dye donors [J]? Journal of the American Chemical Society 2005,127, (4),1242-1250.
35.马慧莲；刘含智；王丽萍；徐淑坤；李惟,量子点的荧光共振能量转移在生物分析中的应用[J].分析化学评述与进展2005,33,1335-1338.
36.徐金钩；王尊本,荧光分析(第三版).科学出版社2006,66-273.
37. Hohng, S.; Ha, T., Single-molecule quantum-dot fluorescence resonance energy transfer [J]. Chemphyschem 2005,6, (5),956-960.
38. Clapp, A. R.; Medintz, I. L.; Mauro, J. M.; Fisher, B. R.; Bawendi, M. G.; Mattoussi, H., Fluorescence resonance energy transfer between quantum dot donors and dye-labeled protein acceptors [J]. Journal of the American Chemical Society 2004, 126,(1),301-310.
39. Medintz, I. L.; Clapp, A. R.; Mattoussi, H.; Goldman, E. R.; Fisher, B.; Mauro, J. M., Self-assembled nanoscale biosensors based on quantum dot FRET donors [J]. Nature Materials 2003,2, (9),630-638.
40. Wang, S. P.; Mamedova, N.; Kotov, N. A.; Chen, W.; Studer, J., Antigen/antibody immunocomplex from CdTe nanoparticle bioconjugates [J]. Nano Letters 2002,2, (8),817-822.
41. Wang, J. H.; Liu, T. C.; Cao, Y. C.; Hua, X. F.; Wang, H. Q.; Zhang, H. L.; Li, X. Q.; Zhao, Y. D., Fluorescence resonance energy transfer between FITC and water-soluble CdSe/ZnS quantum dots [J]. Colloids and Surfaces a-Physicochemical and Engineering Aspects 2007,302, (1-3),168-173.
42. Willard, D. M.; Carillo, L. L.; Jung, J.; Van Orden, A., CdSe-ZnS quantum dots as resonance energy transfer donors in a model protein-protein binding assay [J]. Nano Letters 2001,1,(9),469-474.
43. Algar, W. R.; Krull, U. J., Towards multi-colour strategies for the detection of oligonucleotide hybridization using quantum dots as energy donors in fluorescence resonance energy transfer (FRET) [J]. Analytica Chimica Acta 2007,581, (2), 193-201.
44. Nagasaki, Y.; Ishii, T.; Sunaga, Y.; Watanabe, Y.; Otsuka, H.; Kataoka, K., Novel molecular recognition via fluorescent resonance energy transfer using a biotin-PEG/polyamine stabilized CdS quantum dot [J]. Langmuir 2004,20, (15), 6396-6400.
45. Oh, E.; Hong, M. Y.; Lee, D.; Nam, S. H.; Yoon, H. C.; Kim, H. S., Inhibition assay of biomolecules based on fluorescence resonance energy transfer (FRET) between quantum dots and gold nanoparticles [J]. Journal of the American Chemical Society 2005,127, (10),3270-3271.
46. Medintz, I. L.; Trammell, S. A.; Mattoussi, H.; Mauro, J. M., Reversible modulation of quantum dot photoluminescence using a protein-bound photochromic fluorescence resonance energy transfer acceptor [J]. Journal of the American Chemical Society 2004,126, (1),30-31.
1. Jares-Erijman, E. A.; Jovin, T. M., FRET imaging [J]. Nature Biotechnology 2003,21, 1387-1395.
2. Miyawaki, A.; Sawano, A.; Kogure, T., Lighting up cells:labelling proteins with fluorophores [J]. Nature Cell Biology 2003, Suppl, S1-7.
3. Sapsford, K. E.; Berti, L.; Medintz, I. L., Materials for fluorescence resonance energy transfer analysis:Beyond traditional donor-acceptor combinations [J]. Angewandte Chemie-International Edition 2006,45, (28),4562-4588.
4. Roda, A.; Guardigli, M.; Michelini, E.; Mirasoli, M.; Pasini, P., Analytical bioluminescence and chemiluminescence [J]. Analytical Chemistry 2003,75, (.), 462A-470A.
5. Perroy, J.; Pontier, S.; Charest, P. G.; Aubry, M.; Bouvier, M., Real-time monitoring of ubiquitination in living cells by BRET [J]. Nature Methods 2004,1,203-208.
6. Pfleger, K. D. G.; Eidne, K. A., Illuminating insights into protein-protein interactions using bioluminescence resonance energy transfer (BRET) [J]. Nature. Methods 2006, 3,165.
7. So, M. K.; Xu, C. J.; Loening, A. M.; Gambhir, S. S.; Rao, J. H., Self-illuminating quantum dot conjugates for in vivo imaging [J]. Nature Biotechnology.2006,24, 339-343.
8. Williams, E. J.; Campbell, A. K., A Homogeneous Assay for Biotin Based on Chemiluminescence Energy-Transfer [J]. Analytical Biochemistry 1986,155, 249-255.
9. Grayeski, M. L.; Moritzen, P. A., Chemiluminescence energy transfer processes and micellar effects [J]. Langmuir 1997,13,2675-2680.
10. Huang, X. Y.; Li, L.; Qian, H. F.; Dong, C. Q.; Ren, J. C., A resonance energy transfer between chemiluminescent donors and luminescent quantum-dots as acceptors (CRET) [J]. Angewandte Chemie-International Edition 2006,45,5140-5143.
11. Liu, X.; Jiang, H.; Lei, J. P.; Ju, H. X., Anodic electrochemiluminescence of CdTe quantum dots and its energy transfer for detection of catechol derivatives [J]. Analytical Chemistry 2007,79,21,8055-8060.
12. Liu, X.; Ju, H. X., Coreactant enhanced anodic electrocherniluminescence of CdTe quantum dots at low potential for sensitive biosensing amplified by enzymatic cycle [J]. Analytical Chemistry 2008,80,14,5377-5382.
13. McCall, J.; Alexander, C.; Richter, M. M., Quenching of electrogenerated chemiluminescence by phenols, hydroquinones, catechols, and benzoquinones [J]. Analytical Chemistry 1999,71,13,2523-2527.
14. Shan, Y.; Xu, J. J.; Chen, H. Y, Distance-dependent quenching and enhancing of electrochemiluminescence from a CdS:Mn nanocrystal film by Au nanoparticles for highly sensitive detection of DNA [J]. Chemical Communications 2009,8,905-907.
15. Murphy, C. J., Optical sensing with quantum dots [J]. Analytical Chemistry 2002,74, 520A-526A.
16. Achermann, M.; Petruska, M. A.; Kos, S.; Smith, D. L.; Koleske, D. D.; Klimov, V. I., Energy-transfer pumping of semiconductor nanocrystals using an epitaxial quantum well [J]. Nature 2004,429,642-646.
17. Clapp, A. R.; Medintz, I. L.; Fisher, B. R.; Anderson, G. P.; Mattoussi, H., Can luminescent quantum dots be efficient energy acceptors with organic dye donors [J]? Journal of the American Chemical Society 2005,127,1242-1250.
18. Richter, M. M., Electrochemiluminescence (ECL) [J]. Chemical Review 2004,104, 3003-3036.
19. Tian, D.; Duan, C.; Wang, W.; Li, N.; Zhang, H.; Cui, H.; Lu, Y, Sandwich-type electrochemiluminescence immunosensor based on N-(aminobutyl)-N-ethylisoluminol labeling and gold nanoparticle amplification [J]. Talanta 2009,78, (2),399-404.
20. Medintz, I. L.; Clapp, A. R.; Mattoussi, H.; Goldman, E. R.; Mauro, J. M., Self-assembled nanoscale biosensors based on quantum dot FRET donors [J]. Nature Materials 2003,2,630-638.
21. Lakowicz, J. R., Principles of Fluorescence Spectroscopy,2nd ed. Kluwer Academic, New York; 1999.
22.李明月,基于磁球放大技术的电化学发光免疫分析方法及电化学发光共振能量转移。[M].山东大学硕士学位论文,2010,第二章。
23. Baugh, L.; Vogel, V., Structural changes of fibronectin adsorbed to model surfaces probed by fluorescence resonance energy transfer [J]. Journal of Biomedical Materials Research Part A 2004,69, (3),525-34.
24. Antia, M.; Islas, L. D.; Boness, D. A.; Baneyx, G.; Vogel, V., Single molecule fluorescence studies of surface-adsorbed fibronectin [J]. Biomaterials 2006,27, (5), 679-90.
25. Halter, M.; Antia, M.; Vogel, V., Fibronectin conformational changes induced by adsorption to liposomes [J]. Journal of Controlled Release 2005,101, (1-3),209-22.
26. Baneyx, G.; Baugh, L.; Vogel, V., Coexisting conformations of fibronectin in cell culture imaged using fluorescence resonance energy transfer [J]. Proceeding of the National Academy of Sciences of the United States of America 2001,98, 14464-14468.
1. Shan, Y.; Xu, J. J.; Chen, H. Y, Distance-dependent quenching and enhancing of electrochemiluminescence from a CdS:Mn nanocrystal film by Au nanoparticles for highly sensitive detection of DNA [J]. Chemical Communications 2009,8,905-907.
2. Myung, N.; Bae, Y.; Bard, A. J. Effect of Surface Passivation on the Electrogenerated Chemiluminescence of CdSe/ZnSe Nanocrystals [J]. Nano Letters 2003,3, 1053-1055.
3. Baneyx, G.; Baugh, L.; Vogel, V., Coexisting conformations of fibronectin in cell culture imaged using fluorescence resonance energy transfer [J]. Proceeding of the National Academy of Sciences of the United States of America 2001,98, 14464-14468.
4.胡晓飞,量子点电化学发光及量子点-Cy5体系电化学发光共振能量转移检测DNA[M]。山东大学硕士学位论文,2010,第二章。
5. Lakowicz, J. R. Principles of Fluorescence Spectroscopy,2nd ed. Kluwer Academic, New York,1999.
(1)Zarrin,F.；Dovichi,N.J.Anal.Chem.1985,57,2690-2692.
(2)Nguyen,D.C.；Keller,R.A.；Jett,J.H.；Martin,J.C.Anal.Chem.1987,59, 2158-2161.
(3)Peck,K.；Stryer,L.；Glazer,A.N.；Mathies,R.A.Proc.Natl.Acad Sci.U.S.A. 1989,86,4087-4091.
(4)Shera,E.B.；Seitzinger,N.K.；Davis,L.M.；Keller,R.A.；Soper,S.A.Chem. Phys.Lett.1990,,74,553-557.
(5)Soper,S.A.；Davis,L.M.；Shera,E.B.J.Opt.Soc.Am.B 1992,9,1761-1769.
(6)Castro,A.；Fairfield,F.R.；Shera,E.B.Anal.Chem.1993,65,849-852.
(7)Goodwin,P.M.；Johnson,M.E.；Martin,J.C.；Ambrose,W.P.；Marrone,B.L.； Jett,J.H.；Keller,R.A.Nucleic Acids Res.1993,21,803-806.
(8)Soper,S.A.；Mattingly,Q.L.；Vegunta,P.Anal.Chem.1993,65,740-747.
(9)Huang,Z.；Petty,J.T.；O'Quinil,B.；Longmire,J.L.；Brown,N.C.；Jett,J.H.； Keller,R.A.Nucleic Acids Res.1996,24,4202-4209.
(10)Rauer,B.；Neumann,E.；Widengren,J.；Rigler,R.Biophys.Chem.1996,58,3-12.
(11)Castro,A.；Williams,J.G.Anal.Chem.1997,69,3915-3920.
(12)Sauer,M.；Zander,C.；Muller,R.；Ullrich,B.；Drenhage,K.H.；Kaul,S.；Wolfrum, J.Appl.Phys.B 1997,65,427-431.
(13)Van Orden,A.；Machara,N.P.；Goodwin,P.M.；Keller,R.A.Anal.Chem.1998, 70,1444-1451.
(14)Machara,N.P.；Goodwin,P.M.；Enderlein,J.；Semin,D.J.；Keller,R.A. Bioimaging 1998,6,33-42.
(15)Castro,A.；Okinaka,R.T.Analyst 2000,125,9-11.
(16)Barnes,M.D.；Ng,K.C.；Whitten,W.B.；Ramsey,J.M.Anal.Chem.1993,65, 2360.2365.
(17)Lermer,N.；Barnes,M.D.；Kung,C.；Whitten,W.B.；Ramsey,J.M.Anal.Chem. 1997,69,2115-2121.
(18)Barnes,M.D.；Lermer,N.；Kung,C.；Whitten,W.B.；Ramsey,J.M.；Hill,S.C. Opt.Lett.1997,22,1265-1267.
(19)Kung,C.；Barnes,M.D.；Lermer,N.；Whitten,W.B.；Ramse y,J.M.Anal.Chem. 1998,70,658-661.
(20)Lee,Y H.；Maus,R.G；Smith,B.W.；Winefordner,J.D.Anal.Chem.1994,66, 4142.4149.
(21)Xue,Q.；Yeung,E.S.Nature 1995,373,681-683.
(22)Castro,A.；Shera,E.B.Anal.Chem.1995,67,3181.3186.
(23)Craig,D.B.；Arriaga,E.A.；Wong,J.C.Y；Lu,H.；Dovichi,N.J.Am.Chem. Soc.1996,118,5245-5253.
(24)Chen,D.Y.；Dovichi,N.J.Anal.Chem.1996,68,690.696.
(25)Guenard,R.D.；King,L.A.；Smith,B.W.；Winefordner,J.D.Anal.Chem.1997, 69,2426-2433.
(26)Fister,I.,J.C.；Jacobson,S.C.；Davis,L.M.；Ramsey,J.M.Anal.Chem.1998, 70,431-437.
(27)Chou,H.P.；Spence,C.；Scherer,A.；Quake,S.Proc.Natl.Acad.Sci.U.S.A.1999, 96.11-13.
(28)Polakowski,R.；Craig,D.B.；Skelley,A.；Dovichi,N.J.J.Am.Chem.Soc.2000, 122,4853-4855.
(29)Shortreed, M. R.; Li, H.; Huang, W. H.; Yeung, E. S. Anal. Chem.2000,72, 2879-2885.
(30)Lagally, E. T.; Medintz, I.; Mathies, R. A. Anal. Chem.2001,73,565-570.
(31)Li, H.; Xue, G.; Yeung, E. S. Anal. Chem.2001,73,1537-1543.
(32)Ma, Y.; Shortreed, M. R.; Li, H.; Huang, W.; Yeung, E. S. Electrophoresis 2001, 22,421-426.
(33)Zheng, J.; Yeung, E. S. Anal. Chem.2002,74,4536-4547.
(34)Anazawa, T.; Matsunaga, H.; Yeung, E. S. Anal. Chem.2002,74,5033-5038.
(35)Tan, W.; Yeung, E. S. Anal. Chem.1997,69,4242-4248.
(36)Nie, S.; Chiu, D. T.; Zare, R. N. Science 1994,266,1018-1021.
(37)Eigen, M.; Rigler, R. Proc. Natl. Acad. Sci. U.S.A.1994,91,5740-5747.
(38)Nie, S. M.; Chiu, D. T.; Zare, R. N. Anal. Chem.1995,67,2849-2857.
(39)Haab, B. B.; Mathies, R. A. Anal. Chem.1995,67,3253-3260.
(40)Edman, L.; Mets, U.; Rigler, R. Proc. Natl. Acad. Sci. U.S.A.1996,93, 6710-6715.
(41)Lyon, W. A.; Nie, S. Anal. Chem.1997,69,3400-3405,
(42)Loscher, F.; Bohme, S.; Martin, J.; Seeger, S. Anal. Chem.1998,70,3202-3205.
(43)Haab, B. B.; Mathies, R. A. Anal. Chem.1999,71,5137-5145.
(44)Prummer, M.; Hubner, C. G.; Sick, B.; Hecht, B.; Renn, A.; Wild, U. P. Anal. Chem.2000,72, 443-447.
(45)Knemeyer, J.; Marme, N.; Sauer, M. Anal. Chem.2000,72,3717-3724.
(46)Byassee, T. A.; Chan, W. C.; Nie, S. Anal. Chem.2000,72,5606-5611.
(47)Wabuyele, M. B.; Ford, S. M.; Stryjewski, W.; Barrow, J.; Soper, S. A. Electrophoresis 2001,22,3939-3948.
(48)Tadakuma, H.; Yamaguchi, J.; Ishihama, Y.; Funatsu, T. Biochem. Biophys. Res. Commun.2001,287,323-327.
(49)Dorre, K.; Stephan, J.; Lapczyna, M.; Stuke, M.; Dunkel, H.; Ei'gen, M. J. Biotechnol.2001,86,225-236.
(50)Dorre, K.; Stephan, J.; Eigen, M. Single Mol.2001,2,165-175.
(51)Weston, K. D.; Dyck, M.; Tinnefeld, P.; Miiller, C.; Herten, D. P.; Sauer, M. Anal. Chem.2002,74,5342-5349.
(52)Shelby, J. P.; Chiu, D. T. Anal. Chem.2003,75,1387-1392.
(53)Li, H.; Ying, L.; Green, J. J.; Balasubramanian, S.; Klenerman, D. Anal. Chem. 2003,75,1664-1670.
(54)Prummer, M.; Sick, B.; Renn, A.; Wild, U. P. Anal. Chem.2004,76,1633-1640.
(55)Li, H.; Zhou, D.; Browne, H.; Balasubramanian, S.; Klenerman, D. Anal. Chem. 2004,76,4446-4451.
(56)Sun, B.; Chiu, D. T. Anal. Chem.2005,77,2770-2776.
(57)Hirschfeid, T. Appl. Opt.1976,15,2965-2966.
(58)Dickson, R. M.; Norris, D. J.; Tzeng, Y. L.; Moerner, W. E. Science 1996,274, 966-969.
(59)Xu, X. H.; Yeung, E. S. Science 1997,275,1106-1109.
(60)Xu, X. H.; Yeung, E. S. Science 1998,281,1650-1653.
(61)Fang, X.; Tan, W. Anal. Chem.1999,71,3101-3105.
(62)Ma, Y.; Shortreed, M. R.; Yeung, E. S. Anal. Chem.2000,72,4640-4645.
(63)Kang, S. H.; Yeung, E. S. Anal. Chem.2002,74,6334-6339.
(64)Singh-Zocchi, M.; Dixit, S.; Ivanov, V.; Zocchi, G. Proc. Natl. Acad. Sci. U.S.A. 2003,100,7605-7610.
(65)Li, H. W.; Yeung, E. S. Anal. Chem.2005,77,4374-4377.
(66)Hanley, D. C.; Harris, J. M. Anal. Chem.2001,73,5030-5037.
(67)Agrawal, A.; Zhang, C.; Byassee, T.; Tripp, R. A.; Nie, S. Anal. Chem.2006,78, 1061-1071.
(68)Donner, S.; Li, H.; Yeung, E. S.; Porter, M. D. Anal. Chem.2006,78,2816-2822.
(69)Wang, L.; Xu, G.; Shi, Z.; Jiang, W.; Jin, W. Anal. Chim. Acta 2007,590,104-109.
(70)Lee, J.; Li, J.; Yeung, E. S. Anal. Chem.2007,79,8083-8089.
(71)Yu, J.; Zhou, T. J. Electroanal. Chem.2001,504,89-95.
(72)Bos, M. A.; Shervani, Z.; Anusiem, A. C. I.; Giesbers, M. N., W.; Kleijn, J. M. Colloids Surfaces B:Biointerfaces 1994,3,91-100.
(73)Moulton, S. E.; Barisci, J. N.; Bath, A. S., R.; Wallace, G. G. J. Colloid Interface Sci.2003,261,312-319.
(74)Ying, P.; Viana, A. S.; Abrantes, L. M.; Jin, G. J. Colloid Interface Sci.2004,279, 95-99.
(75)Moulton, S. E.; Barisci, J. N.; Bath, A.; Stella, R.; Wallace, G. G. J. Langmuir 2005,21,316-322.
(76)Hidalgo-Alvarez, R.; Galisteo-Gonzalez, F. Heterog. Chem. Rev.1995,2, 249-268.
(77)Ganachaud, F.; Elaissari, A.; Pichot, C.; Laayoun, A.; Cros, P. Langmuir 1997,13, 701-707.
(1)Predki,P.F.Current Curr.Opin.Chem.Biol.2004,8,8-13.
(2)Levicky,R.；Horgan,A.Trends Biotechnol.2005,23,143-149.
(3)Merkel,J.S.；Michaud,G.A.；Salcius,M.；Schweitzer,B.；Predki,P.F.Curr.Opin. Biotechnol.2005,16,447-452.
(4)Draghici,S.；Khatri,P.；Eklund,A.C.；Szallasi,Z.Trends Genet.2006,22,101-109.
(5)Templin,M.F.；Stoll,D.；Schrenk,M.；Traub,P.C.；Vohringer,C.F.；Joos,T.O.Drug Discov.Today 2002,7,815-822.
(6)Zhu,H.；Snyder,M.Curr Opin.Chem.Biol.2003,7,55-63.
(7)Templin,M.F.；Stoll,D.；Schwenk,J.M.；Potz,O.；Kramer,S.；Joos,T.O. Proteomics 2003,3,2155-2166.
(8)Koebel,M.；Zimmt,M.B.J.Phys.Chem.B 2005,109,16736-16743.
(9)Schweitzer,B.；Wiltshire,S.；Lambert,J.；O'Malley,S.；Kukanskis,K.；Zhu,Z.R.； Kingsmore,S.F.；Lizardi,P.M.；Ward,D.C.Proc.Natl.Acad.Sci.2000,97, 10113.10119.
(10)Hesse,J.；Sonnleitner,M.；Sonnleitner,A.；Freudenthaler,G.；Jacak,J.；Hoglinger,O.； Schindler,H.；Schutz,G.J.Anal.Chem.2004,76,5960-5964.
(11)Hesse,J.；Jacak,J.；Kasper,M.；Regl,G；Eichberger,T.；Winklmayr,M.；Aberger,F.； Sonnleitner,M.；Schlapak,R.；Howorka,S.；Muresan,L.；Frischauf,A.M.；Schutz, G.J.Genome Res.2006,16,1041-1045.
(12)Li,L.；Tian,X.；Zou,G.；Shi,Z.；Zhang,X.；Jin,W.Anal Chem 2008,80, 3999-4006.
(13)Singh,U.；Nicholson,G.；Urban,B.C.；Sargent,I.L.；Kishore,U.；Bernal,A.L. Reproductio,2005,129,631-637.
(14)Ballard,J.L.；Peeva,V.K.；deSilva,C.J.S.；Lynch,J.L.；Swanson,N.R.Mol. Biotechnol.2007,36,175-183.
(15)Murphy,C.J.Anal.Chem.2002,74,520a-526a.
(16)Rosenthal,S.J.Nat.Biotechnol.2001,19,621-622.
(17)Chan,W.C.W.；Nie,S.M.Science 1998,281,2016-2018.
(18)Willner,I.；Patolsky,F.；Wasserman,J.Angew Chem.Int.Edit.2001,40,1861-1864.
(19)Gerion,D.；Parak,W.J.；Williams,S.C.；Zanchet,D.；Micheel,C.M.；Alivisatos,A. P.J.Am.Chem.Soc.2002,124,7070-7074.
(20)Maxwell,D.J.；Taylor,J.R.；Nie,S.M.J.Am.Chem.Soc.2002,124,9606-9612.
(21)Ulstrup,J.C.；Skaug,K.；Figenschau,K.J.；Orstavik,I.；Bruun,J.N.；Petersen,G. Lancet 1986,1,1151-1152.
(22)Hernandez,F.H.；Escriche,J.M.Analyst 1984,109,1585-1588.
(23)Clark,D.A.；Blois,S.；Kandil,J.；Handjiski,B.；Manuel,J.；Arck,P.C.Am.J. Reprod.Immunol.2005,54,203-216.
(24)Chaouat,G；Zourbas,S.；Ostojic,S.；Lappree-Delage,G；Dubanchet,S.；Ledee,N.； Martal,J.,Reprod.Immunol.2002,53,241-256.
(25)Renkl,A.C.；Wussler,J.；Ahrens,T.；Thoma,K.；Kon,S.；Uede,T.；Martin,S.F.； Simon,J.C.；Weiss,J.M.Blood 2005,106,946-955.
(26)Das,R.；Mahabeleshwar,G H.；Kundu,G C.J.Biol.Chem.2004,279, 11051.11064.
(27)Wai,P.Y；Kuo,P.C.Cancer Metast.Rev.2008,27,103-118.
(1)Jares-Erijman, E. A.; Jovin, T. M. Nat. Biotech.2003,21,1387-1395.
(2)Miyawaki, A.; Sawano, A.; Kogure, T. Nat. Cell Biol.2003, Suppl, S1-S7.
(3)Sapsford, K. E.; Berti, L.; Medintz, I. L. Angew. Chem. Int. Edit.2006,45, 4562-4588.
(4)Roda, A.; Guardigli, M.; Michelini, E.; Mirasoli, M.; Pasini, P. Anal. Chem.2003,75, 462A-470A.
(5)Perroy, J.; Pontier, S.; Charest, P. G.; Aubry, M.; Bouvier, M. Nat. Methods 2004,1, 203-208.
(6)Pfleger, K. D. G.; Eidne, K. A. Nat. Methods 2006,3,165.
(7)So, M. K.; Xu, C. J.; Loening, A. M.; Gambhir, S. S.; Rao, J. H. Nat. Biotech.2006, 24,339-343.
(8)Williams, E. J.; Campbell, A. K. Anal. Biochem.1986,155,249-255.
(9)Grayeski, M. L.; Moritzen, P. A. Langmuir 1997,13,2675-2680.
(10)Huang, X. Y.; Li, L.; Qian, H. F.; Dong, C. Q.; Ren, J. C. Angew. Chem. Int. Edit. 2006,45,5140-5143.
(11)McCall, J.; C., A.; Richter, M. M.Anal. Chem.1999,71,2523-2527.
(12)Liu, X.; Jiang, H.; Lei, J.; Ju, H. Anal. Chem.2007,79,8055-8060.
(13)Liu, X.; Ju, H. Anal. Chem.2008,80,5377-5382.
(14)Shan, Y.; Xu, J. J.; Chen, H. Y. Chem. Commun.2009,905-907.
(15)Richter, M. M. Chem. Rev.2004,104,3003-3036.
(16)Lakowicz, J. R. Principles of Fluorescence Spectroscopy,2nd ed, Kluwer Academic, New York; 1999.
(17)Baneyx, G.; Baugh, L.; Vogel, V. Proc. Nat. Acad. Sci. USA 2001,98,14464-14468.
2. Schwille, P.; Kettling, U., Analyzing single protein molecules using optical methods [J]. Current Opinion in Biotechnology 2001,12, (4),382-386.
3. Zhang, X. L.; Li, L. L.; Li, L.; Chen, J.; Zou, G. Z.; Si, Z. K.; Jin, W. R., Ultrasensitive Electrochemical DNA Assay Based on Counting of Single Magnetic Nanobeads by a Combination of DNA Amplification and Enzyme Amplification [J]. Analytical Chemistry 2009,81, (5),1826-1832.
4. Tessler, L. A.; Reifenberger, J. G.; Mitra, R. D., Protein Quantification in Complex Mixtures by Solid Phase Single-Molecule Counting [J]. Analytical Chemistry 2009, 81,(17),7141-7148.
5. Moerner, W. E.; Orrit, M., Illuminating single molecules in condensed matter [J]. Science 1999,283, (5408),1670-1676.
6. Gai, H. W.; Wang, Q.; Ma, Y. F.; Lin, B. C., Correlations between molecular numbers and molecular masses in an evanescent field and their applications in probing molecular interactions [J]. Angewandte Chemie-International Edition 2005,44, (32), 5107-5110.
7. Rigler, R.; Mets, U.; Widengren, J.; Kask, P., Fluorescence correlation spectroscopy with high count rate and low background:analysis of translational diffusion [J]. European Biophysics Journal 1993,22, (3),169-175.
8. Craig, D. B.; Wong, J. C. Y.; Dovichi, N. J., Detection of Attomolar Concentrations of Alkaline Phosphatase by Capillary Electrophoresis Using Laser-Induced Fluorescence Detection [J]. Analytical Chemistry 1996,68,697-700.
9. Chen, D. Y.; Dovichi, N. J., Single-Molecule Detection in Capillary Electrophoresis: Molecular Shot Noise as a Fundamental Limit to Chemical Analysis [J]. Analytical Chemistry 1996,68,690-696.
10. Fister, J. C.; Jacobson, S. C.; Davis, L. M.; Ramsey, J. M., Counting single chromophore molecules for ultrasensitive analysis and separations on microchip devices [J]. Analytical Chemistry 1998,70, (3),431-437.
11. Loscher, F.; Bohme, S.; Martin, J.; Seeger, S., Counting of single protein molecules at interfaces and application of this technique in early-stage diagnosis [J]. Analytical Chemistry 1998,70, (15),3202-3205.
12. Chao, S. Y; Ho, Y. P.; Bailey, V. J.; Wang, T. H., Quantification of low concentrations of DNA using single molecule detection and velocity measurement in a microchannel [J]. Journal of Fluorescence 2007,17, (6),767-774.
13. Li, H. T.; Ying, L. M.; Green, J. J.; Balasubramanian, S.; Klenerman, D., Ultrasensitive coincidence fluorescence detection of single DNA molecules [J]. Analytical Chemistry 2003,75, (7),1664-1670.
14. Li, H. T.; Zhou, D. J.; Browne, H.; Balasubramanian, S.; Klenerman, D., Molecule by molecule direct and quantitative counting of antibody-protein complexes in solution [J]. Analytical Chemistry 2004,76, (15),4446-4451.
15. Agrawal, A.; Zhang, C. Y.; Byassee, T.; Tripp, R. A.; Nie, S. M., Counting single native biomolecules and intact viruses with color-coded nanoparticles [J]. Analytical Chemistry 2006,78, (4),1061-1070.
16. Dickson, R. M.; Norris, D. J.; Tzeng, Y L.; Moerner, W. E., Three-dimensional imaging of single molecules solvated in polys of poly(acrylamide)gels [J]. Science 1996,274,966-968.
17. Xu, X. H.; Yeung, E. S., Direct measurement of single-molecule diffusion and photodecomposition in free solution [J]. Science 1997,275, (5303),1106-1109.
18. Xu, X. H.; Yeung, E. S., Long-range electrostatic trapping of single-protein molecules at a liquid-solid interface [J]. Science 1998,281, (5383),1650-1653.
19. Ma, Y.; Shortreed, M. R.; Yeung, E. S., High-throughput single-molecule spectroscopy in free solution [J]. Analytical Chemistry 2000,72, (19),4640-4645.
20. Kang, S. H.; Yeung, E. S., Dynamics of single-protein molecules at a liquid/solid interface:implications in capillary electrophoresis and chromatography [J]. Analytical Chemistry 2002,74, (24),6334-6339.
21. Li, H. W.; Yeung, E. S., Direct observation of anomalous single-molecule enzyme kinetics [J]. Analytical Chemistry 2005,77, (14),4374-4377.
22. Singh-Zocchi, M.; Dixit, S.; Ivanov, V.; Zocchi, G., Single-molecule detection of DNA hybridization [J]. Proceeding of the National Academy of Sciences of the United States of America 2003,100, (13),7605-7610.
23. Kozuka, J.; Yokota, H.; Arai, Y.; Ishii, Y.; Yanagida, T., Dynamic polymorphism of single actin molecules in the actin filament [J]. Nature Chemical Biology 2006,2, (2),83-86.
24. Fang, X.; Tan, W., Imaging single fluorescent molecules at the interface of an optical fiber probe by evanescent wave excitation [J]. Analytical Chemistry 1999,71, 3101-3105.
25. Donner, S.; Li, H. W.; Yeung, E. S.; Porter, M. D., Fabrication of optically transparent carbon electrodes by the pyrolysis of photoresist films:approach to single-molecule spectroelectrochemistry [J]. Analytical Chemistry 2006,78, (8),2816-2822.
26. Lee, J. Y.; Li, J.; Yeung, E. S., Single-molecule detection of surface-hybridized human papilloma virus DNA for quantitative clinical screening [J]. Analytical Chemistry 2007,79, (21),8083-8089.
27. Wang, L.; Xu, G.; Shi, Z.; Jiang, W.; Jin, W., Quantification of protein based on single-molecule counting by total internal reflection fluorescence microscopy with adsorption equilibrium [J]. Analytica Chimica Acta 2007,590, (1),104-109.
28. Kang, S. H.; Kim, Y. J.; Yeung, E. S., Detection of single-molecule DNA hybridization by using dual-color total internal reflection fluorescence microscopy [J]. Analytical and Bioanalytical Chemistry 2007,387, (8),2663-2671.
29. Lee, S.; Lee, S.; Ko, Y H.; Jung, H.; Kim, J. D.; Song, J. M.; Choo, J.; Eo, S. K.; Kang, S. H., Quantitative analysis of human serum leptin using a nanoarray protein chip based on single-molecule sandwich immunoassay [J]. Talanta 2009,78, (2), 608-612.
30. Jiang, D.; Wang, L.; Jiang, W., Quantitative detection of antibody based on single-molecule counting by total internal reflection fluorescence microscopy with quantum dot labeling [J]. Analytica Chimica Acta 2009,634, (1),83-88.
31. Hanley, D. C.; Harris, J. M., Quantitative dosing of surfaces with fluorescent molecules:Characterization of fractional monolayer coverages by counting single molecules [J]. Analytical Chemistry 2001,73, (21),5030-5037.
32. Anazawa, T.; Matsunaga, H.; Yeung, E. S., Electrophoretic quantitation of nucleic acids without amplification by single-molecule imaging [J]. Analytical Chemistry 2002,74, (19),5033-5038.
33. Kerman, K.; Endo, T.; Tsukamoto, M.; Chikae, M.; Takamura, Y.; Tamiya, E., Quantum dot-based immunosensor for the detection of prostate-specific antigen using fluorescence microscopy [J]. Talanta 2007,71, (4),1494-1499.
34. Han, R.; Zhang, Y. W.; Dong, X. L.; Gai, H. W.; Yeung, E. S., Spectral imaging of single molecules by transmission grating-based epi-fluorescence microscopy [J]. Analytica Chimica Acta 2008,619, (2),209-214.
35. Jiang, D., Solid phase single-molecule counting of antibody binding to supported protein layers surface with low nonspecific adsorption [J]. Talanta 2010,82, 1003-1009.
36. Jiang, D. F.; Liu, C. X.; Wang, L.; Jiang, W., Fluorescence single-molecule counting assays for protein quantification using epi-fluorescence microscopy with quantum dots labeling [J]. Analytica Chimica Acta 2010,662, (2),170-176.
37. Chen, Y.; Muller, J. D.; Carlson, K. E.; Katzenellenbogen, J. A.; Gratton, E., Molecular aggregation and ligand-receptor interaction probed at the single molecule level using two-photon microscopy [J]. Biophysical Journal 1998,74, (2), A182-A182.
38. Farrer, R. A.; Previte, M. J. R.; Olson, C. E.; Peyser, L. A.; Fourkas, J. T.; So, P. T. C., Single-molecule detection with a two-photon fluorescence microscope with fast-scanning capabilities and polarization sensitivity [J]. Optics Letters 1999,24, (24),1832-1834.
39. Schuck, P. J.; Willets, K. A.; Fromm, D. P.; Twieg, R. J.; Moerner, W. E., Two-photon fluorescence microscopy of single-molecule emitters based on nonlinear optical chromophores [J]. Abstracts of Papers of the American Chemical Society 2004,228, U270-U271.
40. Wormald, S.; Zhang, J. G.; Krebes, D. L.; Mielke, L. A.; Silver, J.; Alexander, W. S.; Speed, T. P.; Nicola, N. A.; Hilton, D. J., The comparative roles of suppressor of cytokine signaling-1 and-3 in the inhibition and desensitization of cytokine signaling [J]. Journal of Biological Chemistry 2006,281, (16),11135-11143.
41. Musselmann, K.; Alexandrou, B.; Kane, B.; Hassell, J. R., Maintenance of the keratocyte phenotype during cell proliferation stimulated by insulin [J]. Journal of Biological Chemistry 2005,280, (38),32634-32639.
42. Tokunagaa, M.; Kitamurab, K.; Saitoa, K.; Iwaneb, A. H.; Yanagida, T., Single Molecule Imaging of Fluorophores and Enzymatic Reactions Achieved by Objective-Type Total Internal Reflection Fluorescence Microscopy [J]. Biochemical and Biophysical Research Communications 1997,235, (1),47-53.
43. Funatsu, T.; Harada, Y.; Tokunaga, M.; Saito, K.; Yanagida, T., Imaging of single fluorescent molecules and individual ATP turnovers by single myosin molecules in aqueous solution [J]. Nature 1995,374,555-559.
44. Li, J. W.; Lee, J. Y.; Yeung, E. S., Quantitative screening of single copies of human papilloma viral DNA without amplification [J]. Analytical Chemistry 2006,78, (18), 6490-6496.
45. Rosenthal, S. J., Bar-coding biomolecules with fluorescent nanocrystals [J]. Nature Biotechnology 2001,19, (7),621-622.
46. Gao, X. H.; Nie, S. M., Molecular profiling of single cells and tissue specimens with quantum dots [J]. Trends in Biotechnology 2003,21, (9),371-373.
47. Leatherdale, C. A.; Woo, W. K.; Mikulec, F. V.; Bawendi, M. G., On the absorption cross section of CdSe nanocrystal quantum dots [J]. Journal of Physical Chemistry B 2002,106, (31),7619-7622.
48. Dubertret, B.; Skourides, P.; Norris, D. J.; Noireaux, V.; Brivanlou, A. H.; Libchaber, A., In vivo imaging of quantum dots encapsulated in phospholipid micelles [J]. Science 2002,298, (5599),1759-1762.
49. Zhang, C. Y.; Johnson, L. W., Homogenous rapid detection of nucleic acids using two-color quantum dots [J]. Analyst 2006,131, (4),484-488.
50. Thurer, R.; Vigassy, T.; Hirayama, M.; Wang, J.; Bakker, E.; Pretsch, E., Potentiometric immunoassay with quantum dot labels [J]. Analytical Chemistry 2007,79, (13),5107-5110.
51. Gao, X. H.; Nie, S. M., Quantum dot-encoded mesoporous beads with high brightness and uniformity:Rapid readout using flow cytometry [J]. Analytical Chemistry 2004, 76, (8),2406-2410.
52. Sathe, T. R.; Agrawal, A.; Nie, S. M., Mesoporous silica beads embedded with semiconductor quantum dots and iron oxide nanocrystals:Dual-function microcarriers for optical encoding and magnetic separation [J]. Analytical Chemistry 2006,78, (16),5627-5632.
53. Ma, Q.; Wang, X. Y.; Li, Y. B.; Su, X. G.; Jin, Q. H., The use of COP quantum dot fluorescent microspheres in fluoro-immunoassays and a microfluidic chip system [J]. Luminescence 2007,22, (5),438-445.
54. Xie, C.; Xu, F. G.; Huang, X. Y.; Dong, C. Q.; Ren, J. C., Single Gold Nanoparticles Counter:An Ultrasensitive Detection Platform for One-Step Homogeneous Immunoassays and DNA Hybridization Assays [J]. Journal of the American Chemical Society 2009,131, (35),12763-12770.
55. Chen, J. J.; Wang, C. G.; Irudayaraj, J., Ultrasensitive protein detection in blood serum using gold nanoparticle probes by single molecule spectroscopy [J]. Journal of Biomedical Optics 2009,14, (4),040501-1-040501-3.
56. Zhao, X. J.; Bagwe, R. P.; Tan, W. H., Development of organic-dye-doped silica nanoparticles in a reverse microemulsion [J]. Advanced Materials 2004,16, (2), 173-176.
57. Wang, L.; Lofton, C.; Popp, M.; Tan, W. H., Using luminescent nanoparticles as staining probes for affymetrix GeneChips [J]. Bioconjugate Chemistry 2007,18, (3), 610-613.
58. Patterson, G. H.; Lippincott-Schwartz, J., A photoactivatable GFP for selective photolabeling of proteins and cells [J]. Science 2002,297, (5588),1873-1877.
59. Lippincott-Schwartz, J.; Patterson, G. H., Development and use of fluorescent protein markers in living cells [J]. Science 2003,300, (5616),87-91.
1. Zarrin, F.; Dovichi, N. J., Sub-picoliter detection with the sheath flow cuvette [J]. Analytical Chemistry 1985,57,2690-2692.
2. Nguyen, D. C.; Keller, R. A.; Jett, J. H.; Martin, J. C., Detection of single molecules of phycoerythrin in hydrodynamically focused flows by laser-induced fluorescence [J]. Analytical Chemistry 1987,59,2158-2161.
3. Peck, K.; Stryer, L.; Glazer, A. N.; Mathies, R. A., Single-molecule fluorescence detection:autocorrelation criterion and experimental realization with phycoerythrin [J]. Proceeding of the National Academy of Sciences of the United States of America 1989,86,4087-4091.
4. Shera, E. B.; Seitzinger, N. K.; Davis, L. M.; Keller, R. A.; Soper, S. A., Detection of single fluorescent molecules [J]. Chemical Physics. Letters 1990,174,553-557.
5. Soper, S. A.; Davis, L. M.; Shera, E. B., Detection and identification of single molecules in solution [J]. Journal of the Optical Society of America B 1992,9, 1761-1769.
6. Castro, A.; Fairfield, F. R.; Shera, E. B., Fluorescence detection and size measurement of single DNA molecules [J]. Analytical Chemistry 1993,65,849-852.
7. Goodwin, P. M.; Johnson, M. E.; Martin, J. C.; Ambrose, W. P.; Marrone, B. L.; Jett, J. H.; Keller, R. A., Rapid sizing of individual fluorescently stained DNA fragments by flow-cytometry [J]. Nucleic Acids Research 1993,21,803-806.
8. Soper, S. A.; Mattingly, Q. L.; Vegunta, P., Photon Burst Detection of Single near-Infrared Fluorescent Molecules [J]. Analytical Chemistry 1993,65,740-747.
9. Huang, Z.; Petty, J. T.; O'Quinn, B.; Longmire, J. L.; Brown, N. C.; Jett, J. H.; Keller, R. A., Large DNA fragment sizing by flow cytometry:application to the characterization of P1 artificial chromosome (PAC) clones [J]. Nucleic Acids Research 1996,24,4202-4209.
10. Rauer, B.; Neumann, E.; Widengren, J.; Rigler, R.;, Fluorescence correlation spectrometry of the interaction kinetics of tetramethylrhodamin alpha-bungarotoxin with torpedo californica acetylcholine receptor [J]. Biophysics. Chemistry.1996,58, 3-12.
11. Castro, A.; Williams, J. G, Single-molecule detection of specific nucleic acid sequences in unamplified genomic DNA [J]. Analytical Chemistry 1997,69, (19), 3915-20.
12. Sauer, M.; Zander, C.; Muller, R.; Ullrich, B.; Drenhage, K. H.; Kaul, S.; Wolfrum, J., Detection and identification of individual antigen molecules in human serum with pulsed semiconductor lasers [J]. Applied Physics B 1997,65,427-431.
13. Van Orden, A.; Machara, N. P.; Goodwin, P. M.; Keller, R. A., Single molecule identification in flowing sample streams by fluorescence burst size and intraburst fluorescence decay rate [J]. Analytical Chemistry 1998,70, (7),1444-1451.
14. Machara, N. P.; Goodwin, P. M.; Enderlein, J.; Semin, D. J.; Keller, R. A., Efficient detection of single molecules eluting off an optically trapped microsphere [J]. Bioimaging 1998,6, (1),33-42.
15. Castro, A.; Okinaka, R. T., Ultrasensitive, direct detection of a specific DNA sequence of Bacillus anthracis in solution [J]. Analyst 1999,125, (1),9-11.
16. Barnes, M. D.; Ng, K. C.; Whitten, W. B.; Ramsey, J. M., Detection of single rhodamine 6G molecules in levitated microdroplets [J]. Analytical Chemistry 1993, 65,2360-2365.
17. Lermer, N.; Barnes, M. D.; Kung, C.; Whitten, W. B.; Ramsey, J. M., High-efficiency molecular counting in solution:single-molecule detection in electrodynamically focused microdroplet streams [J]. Analytical Chemistry 1997,69,2115-2121.
18. Barnes, M. D.; Lermer, N.; Kung, C.; Whitten, W. B.; Ramsey, J. M.; Hill, S. C., Real-time observation of single-molecule fluorescence in microdroplet streams [J]. Optics Letters 1997,22,1265-1267.
19. Kung, C. Y.; Barnes, M. D.; Lermer, N.; Whitten, W. B.; Ramsey, J. M., Confinement and manipulation of individual molecules in attoliter volumes [J]. Analytical Chemistry 1998,70, (3),658-661.
20. Lee, Y. H.; Maus, R. G.; Smith, B. W.; Winefordner, J. D., Laser-Induced Fluorescence Detection of a Single Molecule in a Capillary [J]. Analytical Chemistry 1994,66,4142-4149.
21. Xue, Q.; Yeung, E. S., Differences in the chemical reactivity of individual molecules of an enzyme [J]. Nature 1995,373,681-683.
22. Castro, A.; Shera, E. B., Single-Molecule electrophoresis [J]. Analytical Chemistry 1995,67,3181-3186.
23. Craig, D. B.; Arriaga, E. A.; Wong, J. C. Y.; Lu, H.; Dovichi, N. J., Studies on Single Alkaline Phosphatase Molecules:Reaction Rate and Activation Energy of a Reaction Catalyzed by a Single Molecule and the Effect of Thermal Denaturation:The Death of an Enzyme [J]. Journal of the American Chemical Society 1996,118,5245-5253.
24. Chen, D. Y.; Dovichi, N. J., Single-Molecule Detection in Capillary Electrophoresis: Molecular Shot Noise as a Fundamental Limit to Chemical Analysis [J]. Analytical Chemistry 1996,68,690-696.
25. Guenard, R. D.; King, L. A.; Smith, B. W.; Winefordner, J. D., Two-Channel Sequential Single-Molecule Measurement [J]. Analytical Chemistry 1997,69, 2426-2433.
26. Chou, H. P.; Spence, C.; Scherer, A.; Quake, S., A microfabricated device for sizing and sorting DNA molecules. [J] Proceeding of the National Academy of Sciences of the United States of America 1999,96, (1),11-3.
27. Polakowski, R.; Craig, D. B.; Skelley, A.; Dovichi, N. J., Single molecules of highly purified bacterial alkaline phosphatase have identical activity [J]. Journal of the American Chemical Society 2000,122, (20),4853-4855.
28. Shortreed, M. R.; Li, H. L.; Huang, W. H.; Yeung, E. S., High throughput single-molecule DNA screening based be electrophoresis [J]. Analytical Chemistry 2000,72, (13),2879-2885.
29. Lagally, E. T.; Medintz, I.; Mathies, R. A., Single-molecule DNA amplification and analysis in an integrated microfluidic device [J]. Analytical Chemistry 2001,73, (3), 565-570.
30. Li, H. L.; Xue, G.; Yeung, E. S., Selective detection of individual DNA molecules by capillary polymerase chain reaction [J]. Analytical Chemistry 2001,73, (7), 1537-1543.
31. Ma, Y. F.; Shortreed, M. R.; Li, H. L.; Huang, W. H.; Yeung, E. S., Single-molecule immunoassay and DNA diagnosis [J]. Electrophoresis 2001,22, (3),421-426.
32. Zheng, J. J.; Yeung, E. S., Anomalous radial migration of single DNA molecules in capillary electrophoresis [J]. Analytical Chemistry 2002,74, (17),4536-4547.
33. Anazawa, T.; Matsunaga, H.; Yeung, E. S., Electrophoretic quantitation of nucleic acids without amplification by single-molecule imaging [J]. Analytical Chemistry 2002,74, (19),5033-5038.
34. Tan, W.; Yeung, E. S., Monitoring the Reactions of Single Enzyme Molecules and Single Metal Ions [J]. Analytical Chemistry 1997,69,4242-4248.
35. Nie, S.; Chiu, D. T.; Zare, R. N., Probing individual molecules with confocal fluorescence microscopy [J]. Science 1994,266,1018-1021.
36. Eigen, M.; Rigler, R., Sorting single molecules:application to diagnostics and evolutionary biotechnology [J]. Proceeding of the National Academy of Sciences of the United States of America 1994,91, (13),5740-7.
37. Nie, S. M.; Chiu, D. T.; Zare, R. N., Real-time detection of single molecules in solution by confocal fluorescence microscopy [J]. Analytical Chemistry 1995,67, 2849-2857.
38. Haab, B. B.; Mathies, R. A., Single Molecule Fluorescence Burst Detection of DNA Fragments Separated by Capillary Electrophoresis [J]. Analytical Chemistry 1995, 67,3253-3260.
39. Edman, L.; Mets, U.; Rigler, R., Conformational transitions monitored for single molecules in solution [J]. Proceeding of the National Academy of Sciences of the United States of America 1996,93, (13),6710-5.
40. Lyon, W. A.; Nie, S., Confinement and Detection of Single Molecules in Submicrometer Channels [J]. Analytical Chemistry 1997,69,3400-3405.
41. Loscher, F.; Bohme, S.; Martin, J.; Seeger, S., Counting of single protein molecules at interfaces and application of this technique in early-stage diagnosis [J]. Analytical Chemistry 1998,70, (15),3202-5.
42. Haab, B. B.; Mathies, R. A., Single-molecule detection of DNA separations in microfabricated capillary electrophoresis chips employing focused molecular streams [J]. Analytical Chemistry 1999,71, (22),5137-45.
43. Prummer, M.; Hubner, C. G.; Sick, B.; Hecht, B.; Renn, A.; Wild, U. P., Single-molecule identification by spectrally and time-resolved fluorescence detection [J]. Analytical Chemistry 2000,72, (3),443-7.
44. Knemeyer, J. P.; Marme, N.; Sauer, M., Probes for detection of specific DNA sequences at the single-molecule level [J]. Analytical Chemistry 2000,72, (16), 3717-24.
45. Byassee, T. A.; Chan, W. C.; Nie, S., Probing single molecules in single living cells [J]. Analytical Chemistry 2000,72, (22),5606-11.
46. Wabuyele, M. B.; Ford, S. M.; Stryjewski, W.; Barrow, J.; Soper, S. A., Single molecule detection of double-stranded DNA in poly(methylmethacrylate) and polycarbonate microfluidic devices [J]. Electrophoresis 2001,22, (18),3939-48.
47. Tadakuma, H.; Yamaguchi, J.; Ishihama, Y.; Funatsu, T., Imaging of single fluorescent molecules using video-rate confocal microscopy [J]. Biochemical and Biophysical Research Communications 2001,287, (2),323-7.
48. Dorre, K.; Stephan, J.; Lapczyna, M.; Stuke, M.; Dunkel, H.; Eigen, M., Highly efficient single molecule detection in microstructures [J]. Journal of Biotechnoogyl 2001,86, (3),225-36.
49. Dorre, K.; Stephan, J.; Eigen, M., Highly efficient single molecule detection in different micro-and submicrometer channels with cw exitation [J]. Single Molecules 2001,2,165-175.
50. Weston, K. D.; Dyck, M.; Tinnefeld, P.; Muller, C.; Herten, D. P.; Sauer, M., Measuring the number of independent emitters in single-molecule fluorescence images and trajectories using coincident photons [J]. Analytical Chemistry 2002,74, (20),5342-9.
51. Shelby, J. P.; Chiu, D. T., Mapping fast flows over micrometer-length scales using flow-tagging velocimetry and single-molecule detection [J]. Analytical Chemistry 2003,75, (6),1387-92.
52. Li, H.; Ying, L.; Green, J. J.; Balasubramanian, S.; Klenerman, D., Ultrasensitive coincidence fluorescence detection of single DNA molecules [J]. Analytical Chemistry 2003,75, (7),1664-70.
53. Prummer, M.; Sick, B.; Renn, A.; Wild, U. P., Multiparameter microscopy and spectroscopy for single-molecule analytics [J]. Analytical Chemistry 2004,76, (6), 1633-40.
54. Li, H.; Zhou, D.; Browne, H.; Balasubramanian, S.; Klenerman, D., Molecule by molecule direct and quantitative counting of antibody-protein complexes in solution [J]. Analytical Chemistry 2004,76, (15),4446-51.
55. Sun, B.; Chiu, D. T., Determination of the encapsulation efficiency of individual vesicles using single-vesicle photolysis and confocal single-molecule detection [J]. Analytical Chemistry 2005,77, (9),2770-6.
56. Fang, X.; Tan, W., Imaging single fluorescent molecules at the interface of an optical fiber probe by evanescent wave excitation [J]. Analytical Chemistry 1999,71, 3101-3105.
57. Ma, Y.; Shortreed, M. R.; Yeung, E. S., High-throughput single-molecule spectroscopy in free solution [J]. Analytical Chemistry 2000,72, (19),4640-5.
58. Kang, S. H.; Yeung, E. S., Dynamics of single-protein molecules at a liquid/solid interface:implications in capillary electrophoresis and chromatography [J]. Analytical Chemistry 2002,74, (24),6334-9.
59. Singh-Zocchi, M.; Dixit, S.; Ivanov, V.; Zocchi, G, Single-molecule detection of DNA hybridization [J]. Proceeding of the National Academy of Sciences of the United States of America 2003,100, (13),7605-10.
60. Li, H. W.; Yeung, E. S., Direct observation of anomalous single-molecule enzyme kinetics [J]. Analytical Chemistry 2005,77, (14),4374-7.
61. Hanley, D. C.; Harris, J. M., Quantitative dosing of surfaces with fluorescent molecules:characterization of fractional monolayer coverages by counting single molecules [J]. Analytical Chemistry 2001,73, (21),5030-7.
62. Agrawal, A.; Zhang, C.; Byassee, T.; Tripp, R. A.; Nie, S., Counting single native biomolecules and intact viruses with color-coded nanoparticles [J]. Analytical Chemistry 2006,78, (4),1061-70.
63. Donner, S.; Li, H. W.; Yeung, E. S.; Porter, M. D., Fabrication of optically transparent carbon electrodes by the pyrolysis of photoresist films:approach to single-molecule spectroelectrochemistry [J]. Analytical Chemistry 2006,78, (8),2816-22.
64. Wang, L.; Xu, G.; Shi, Z.; Jiang, W.; Jin, W., Quantification of protein based on single-molecule counting by total internal reflection fluorescence microscopy with adsorption equilibrium [J]. Analytica Chimica Acta 2007,590, (1),104-9.
65. Lee, J. Y.; Li, J.; Yeung, E. S., Single-molecule detection of surface-hybridized human papilloma virus DNA for quantitative clinical screening [J]. Analytical Chemistry 2007,79, (21),8083-9.
66. Yu, J. S.; Zhou, T. Y, The electrochemistry and thin-layer luminescence spectroelectrochemistry of rhodamine 6G at a 4,4'-bipyridine-modified gold electrode [J]. Journal of Electroanalytical Chemistry 2001,504, (1),89-95.
67. Moulton, S. E.; Barisci, J. N.; Bath, A.; Stella, R.; Wallace, G. G., Investigation of protein adsorption and electrochemical behavior at a gold electrode [J]. Journal of Colloid and Interface Science 2003,261, (2),312-9.
68. Ying, P.; Viana, A. S.; Abrantes, L. M.; Jin, G, Adsorption of human serum albumin onto gold:a combined electrochemical and ellipsometric study [J]. Journal of Colloid and Interface Science 2004,279, (1),95-9.
69. Moulton, S. E.; Barisci, J. N.; Bath, A.; Stella, R.; Wallace, G G, Investigation of Ig.G adsorption and the effect on electrochemical responses at titanium dioxide electrode [J]. Langmuir 2005,21, (1),316-22.
70. Hidalgo-Alvarez, R.; Galisteo-Gonzalez, F., The adsorption characteristics of immunoglobulins [J]. Heterogeneous Chemical. Review 1995,2,249-268.
71. Ganachaud, F.; ElaI''ssari, A.; Pichot, C.; Laayoun, A.; Cros, P., Adsorption of single-stranded DNA fragments onto cationic aminated latex particles [J]. Langmuir 1997,13,701-707.
1. Draghici, S.; Khatri, P.; Eklund, A. C.; Szallasi, Z., Reliability and reproducibility issues in DNA microarray measurements [J]. Trends in Genetics 2006,22, (2), 101-109.
2. Levicky, R.; Horgan, A., Physicochemical perspectives on DNA microarray and biosensor technologies [J]. Trends in Biotechnology 2005,23, (3),143-149.
3. Merkel, J. S.; Michaud, G. A.; Salcius, M.; Schweitzer, B.; Predki, P. F., Functional protein microarrays:just how functional are they [J]? Current Opinion in Biotechnology 2005,16, (4),447-452.
4. Predki, P. F., Functional protein microarrays:ripe for discovery [J]. Current Opinion in Chemical Biology 2004,8, (1),8-13.
5. Mir, K. U., Ultrasensitive RNA profiling:Counting single molecules on microarrays [J]. Genome Research 2006,16, (10),1195-1197.
6. Duggan, D. J.; Bittner, M.; Chen, Y. D.; Meltzer, P.; Trent, J. M., Expression profiling using cDNA microarrays [J]. Nature Genetics 1999,21,10-14.
7. Gerion, D.; Chen, F. Q.; Kannan, B.; Fu, A. H.; Parak, W. J.; Chen, D. J.; Majumdar, A.; Alivisatos, A. P., Room-temperature single-nucleotide polymorphism and multiallele DNA detection using fluorescent nanocrystals and microarrays [J]. Analytical Chemistry 2003,75, (18),4766-4772.
8. Zhou, X. C.; Zhou, J. Z., Improving the signal sensitivity and photo stability of DNA hybridizations on microarrays by using dye-doped core-shell silica nanoparticles [J]. Analytical Chemistry 2004,76, (18),5302-5312.
9. Schweitzer, B.; Wiltshire, S.; Lambert, J.; O'Malley, S.; Kukanskis, K.; Zhu, Z. R.; Kingsmore, S. F.; Lizardi, P. M.; Ward, D. C., Immunoassays with rolling circle DNA amplification:A versatile platform for ultrasensitive antigen detection [J]. Proceedings of the National Academy of Sciences of the United States of America 2000,97, (18),10113-10119.
10. Hesse, J.; Sonnleitner, M.; Sonnleitner, A.; Freudenthaler, G.; Jacak, J.; Hoglinger, O.; Schindler, H.; Schutz, G. J., Single-molecule reader for high-throughput bioanalysis [J]. Analytical Chemistry 2004,76, (19),5960-5964.
11. Hesse, J.; Jacak, J.; Kasper, M.; Regl, G.; Eichberger, T.; Winklmayr, M.; Aberger, F.; Sonnleitner, M.; Schlapak, R.; Howorka, S.; Muresan, L.; Frischauf, A. M.; Schutz, G. J., RNA expression profiling at the single molecule level [J]. Genome Research 2006,16, (8),1041-1045.
12. Li, L.; Tian, X. Z.; Zou, G. Z.; Shi, Z. K.; Zhang, X. L.; Jin, W. R., quantitative counting of single fluorescent molecules by combined electrochemical adsorption accumulation and total internal reflection fluorescence microscopy [J]. Analytical Chemistry 2008,80, (11),3999-4006.
13. Ballard, J. L.; Peeva, V. K.; deSilva, C. J. S.; Lynch, J. L.; Swanson, N. R., Comparison of Alexa Fluor (R) and CyDye (TM) for practical DNA microarray use [J]. Molecular Biotechnology 2007,36, (3),175-183.
14. Chan, W. C. W.; Nie, S. M., Quantum dot bioconjugates for ultrasensitive nonisotopic detection [J]. Science 1998,281, (5385),2016-2018.
15. Gerion, D.; Parak, W. J.; Williams, S. C.; Zanchet, D.; Micheel, C. M.; Alivisatos, A. P., Sorting fluorescent nanocrystals with DNA [J]. Journal of the American Chemical Society 2002,124, (24),7070-7074.
16. Maxwell, D. J.; Taylor, J. R.; Nie, S. M., Self-assembled nanoparticle probes for recognition and detection of biomolecules [J]. Journal of the American Chemical Society 2002,124, (32),9606-9612.
17. Murphy, C. J., Optical sensing with quantum dots [J]. Analytical Chemistry 2002,74, (19),520a-526a.
18. Rosenthal, S. J., Bar-coding biomolecules with fluorescent nanocrystals [J]. Nature Biotechnology 2001,19, (7),621-622.
19. Willner, I.; Patolsky, F.; Wasserman, J., Photoelectrochemistry with controlled DNA-cross-linked CdS nanoparticle arrays [J]. Angewandte Chemie-International Edition 2001,40, (10),1861-1864.
20. Ulstrup, J. C.; Skaug, K.; Figenschau, K. J.; Orstavik, I.; Bruun, J. N.; Petersen, G., Sensitivity of western blotting (compared with ELISA and immunofluorescence) during seroconversion after HTLV-Ⅲ infection [J]. Lancet 1986,1, (8490), 1151-1152.
21. Clark, D. A.; Blois, S.; Kandil, J.; Handjiski, B.; Manuel, J.; Arck, P. C., Reduced uterine indoleamine 2,3-dioxygenase versus increased Thl/Th2 cytokine ratios as a basis for occult and clinical pregnancy failure in mice and humans [J]. American Journal of Reproductive Immunology 2005,54, (4),203-216.
22. Chaouat, G.; Zourbas, S.; Ostojic, S.; Lappree-Delage, G.; Dubanchet, S.; Ledee, N.; Martal, J., A brief review of recent data on some cytokine expressions at the materno-foetal interface which might challenge the classical Thl/Th2 dichotomy [J]. Journal of Reproductive Immunology 2002,53, (1-2),241-256.
23. Renkl, A. C.; Wussler, J.; Ahrens, T.; Thoma, K.; Kon, S.; Uede, T.; Martin, S. F.; Simon, J. C.; Weiss, J. M., Osteopontin functionally activates dendritic cells and induces their differentiation toward a Thl-polarizing phenotype [J]. Blood 2005,106, (3),946-955.
24. Das, R.; Mahabeleshwar, G. H.; Kundu, G. C., Osteopontin induces AP-1-mediated secretion of urokinase-type plasminogen activator through c-Src-dependent epidermal growth factor receptor transactivation in breast cancer cells [J]. Journal of Biological Chemistry 2004,279, (12),11051-11064.
25. Wai, P. Y.; Kuo, P. C., Osteopontin:regulation in tumor metastasis [J]. Cancer and Metastasis Reviews 2008,27, (1),103-118.
1. Baro, D. J.; Levini, R. M.; Kim, M. T.; Willms, A. R.; Lanning, C. C.; Rodriguez, H. E.; Harris-Warrick, R. M., Quantitative single-cell-reverse transcription-PCR demonstrates that A-current magnitude varies as a linear function of shal gene expression in identified stomatogastric neurons [J]. The Journal of Neuroscience 1997,17, (17),6597-610.
2. Bengtsson, M.; Stahlberg, A.; Rorsman, P.; Kubista, M., Gene expression profiling in single cells from the pancreatic islets of Langerhans reveals lognormal distribution of mRNA levels [J]. Genome Research 2005,15, (10),1388-1392.
3. Chiang, M. K.; Melton, D. A., Single-cell transcript analysis of pancreas development [J]. Developmental Cell 2003,4, (3),383-393.
4. Collins, M. E.; Stevens, D. A.; Jenner, L. J.; Brownlie, J., A rapid method for mRNA detection in single-cell biopsies from preimplantation-stage bovine embryos [J]. Theriogenology 1995,43, (7),1227-38.
5. Danik, M.; Puma, C.; Quirion, R.; Williams, S., Widely expressed transcripts for chemokine receptor CXCR1 in identified glutamatergic, gamma-aminobutyric acidergic, and cholinergic neurons and astrocytes of the rat brain:A single-cell reverse transcription-multiplex polymerase chain reaction study [J]. Journal of Neuroscience Research 2003,74, (2),286-295.
6. Liss, B., Improved quantitative real-time RT-PCR for expression profiling of individual cells [J]. Nucleic Acids Research 2002,30, (17),-
7. Peixoto, A.; Monteiro, M.; Rocha, B.; Veiga-Fernandes, H., Quantification of multiple gene expression in individual cells [J]. Genome Research 2004,14, (10A), 1938-1947.
8. Tietjen, I.; Rihel, J. M.; Cao, Y. X.; Koentges, G.; Zakhary, L.; Dulac, C., Single-cell transcriptional analysis of neuronal progenitors [J]. Neuron 2003,38, (2),161-175.
9. Tkatch, T.; Baranauskas, G.; Surmeier, D. J., Kv4.2 mRNA abundance and A-type K+ current amplitude are linearly related in basal ganglia and basal forebrain neurons [J]. Journal of Neuroscience 2000,20, (2),579-588.
10. Tsuzuki, K.; Lambolez, B.; Rossier, J.; Ozawa, S., Absolute quantification of AMPA receptor subunit mRNAs in single hippocampal neurons [J]. Journal of Neurochemistry 2001,77, (6),1650-1659.
11. Bentwich, I.; Avniel, A.; Karov, Y.; Aharonov, R.; Gilad, S.; Barad, O.; Barzilai, A.; Einat, P.; Einav, U.; Meiri, E.; Sharon, E.; Spector, Y.; Bentwich, Z., Identification of hundreds of conserved and nonconserved human microRNAs [J]. Nature Genetics 2005,37, (7),766-770.
12. Hesse, J.; Jacak, J.; Kasper, M.; Regl, G.; Eichberger, T.; Winklmayr, M.; Aberger, F.; Sonnleitner, M.; Schlapak, R.; Howorka, S.; Muresan, L.; Frischauf, A. M.; Schutz, G. J., RNA expression profiling at the single molecule level [J]. Genome Research 2006,16, (8),1041-1045.
13. Mir, K. U., Ultrasensitive RNA profiling:Counting single molecules on microarrays [J]. Genome Research 2006,16, (10),1195-1197.
14. Duggan, D. J.; Bittner, M.; Chen, Y. D.; Meltzer, P.; Trent, J. M., Expression profiling using cDNA microarrays [J]. Nature Genetics 1999,21,10-14.
15. Gerion, D.; Chen, F. Q.; Kannan, B.; Fu, A. H.; Parak, W. J.; Chen, D. J.; Majumdar, A.; Alivisatos, A. P., Room-temperature single-nucleotide polymorphism and multiallele DNA detection using fluorescent nanocrystals and microarrays [J]. Analytical Chemistry 2003,75, (18),4766-4772.
16. Zhou, X. C.; Zhou, J. Z., Improving the signal sensitivity and photo stability of DNA hybridizations on microarrays by using dye-doped core-shell silica nanoparticles [J]. Analytical Chemistry 2004,76, (18),5302-5312.
1. Gross, P.; Farge, G.; Peterman, E. J.; Wuite, G. J., Combining optical tweezers, single-molecule fluorescence microscopy, and microfluidics for studies of DNA-protein interactions. Methods Enzymol 2010,475,427-453.
2. Gurunathan, K.; Levitus, M., Single-molecule fluorescence studies of nucleosome dynamics. Current Pharmaceutical Biotechnology 2009,10, (5),559-568.
3. Huang, Z.; Petty, J. T.; O'Quinn, B.; Longmire, J. L.; Brown, N. C.; Jett, J. H.; Keller, R. A., Large DNA fragment sizing by flow cytometry:application to the characterization of P1 artificial chromosome (PAC) clones. Nucleic Acids Research 1996,24,4202-4209.
4. Jiang, D.; Liu, C.; Wang, L.; Jiang, W., Fluorescence single-molecule counting assays for protein quantification using epi-fluorescence microscopy with quantum dots labeling [J]. Analytica Chimica Acta 2010,662, (2),170-176.
5. Jiang, D.; Wang, L.; Jiang, W., Quantitative detection of antibody based on single-molecule counting by total internal reflection fluorescence microscopy with quantum dot labeling [J]. Analytica Chimica Acta 2009,634, (1),83-88.
6. Kawashima, N.; Nakayama, K.; Itoh, K.; Itoh, T.; Ishikawa, M.; Biju, V., Reversible dimerization of EGFR revealed by single-molecule fluorescence imaging using quantum dots [J]. Chemistry 2010,16, (4),1186-1192.
7. Kumbhakar, M.; Kiel, A.; Pal, H.; Herten, D. P., Single-molecule fluorescence studies reveal long-range electron-transfer dynamics through double-stranded DNA [J]. Chemphyschem 2009,10, (4),629-633.
8. Lee, N. K.; Koh, H. R.; Han, K. Y.; Lee, J.; Kim, S. K., Single-molecule, real-time measurement of enzyme kinetics by alternating-laser excitation fluorescence resonance energy transfer [J]. Chemical Communications (Cambridge) 2010,46, (26),4683-4685.
9. Li, Q.; Liu, X.; He, Y., Single molecule fluorescence imaging of DNA at agarose surfaces by total internal reflection fluorescence microscopy [J]. Journal of Biomedical Nanotechnology 2009,5, (5),565-572.
10. Nienhaus, G. U., Single-molecule fluorescence studies of protein folding [J]. Methods Molecular Biology 2009,490,311-337.
11. Pugh, R. A.; Honda, M.; Spies, M., Ensemble and single-molecule fluorescence-based assays to monitor DNA binding, translocation, and unwinding by iron-sulfur cluster containing helicases [J]. Methoas 2010,51, (3),313-321.
12. Rauer, B.; Neumann, E.; Widengren, J.; Rigler, R.;, Fluorescence correlation spectrometry of the interaction kinetics of tetramethylrhodamin alpha-bungarotoxin with torpedo californica acetylcholine receptor [J]. Biophysical. Chemistry 1996,58, 3-12.
13. Ray, K.; Ma, J.; Oram, M.; Lakowicz, J. R.; Black, L. W., Single-molecule and FRET fluorescence correlation spectroscopy analyses of phage DNA packaging: colocalization of packaged phage T4 DNA ends within the capsid [J]. Journal of Molecular Biology 2010,395, (5),1102-1113.
14. Rigler, R., Fluorescence and single molecule analysis in cell biology [J]. Biochemical and Biophysical Research Communications 2010,396, (1),170-5.
15. Soper, S. A.; Mattingiy, Q. L.; Vegunta, P., Photon Burst Detection of Single near-Infrared Fluorescent Molecules [J]. Analytical Chemistry 1993,65,740-747.
16. Tanner, N. A.; Loparo, J. J.; van Oijen, A. M., Visualizing Single-molecule DNA Replication with Fluorescence Microscopy [J]. Journal of Visualized Experiments 2009,(32),1529.
17. van Mameren, J.; Gross, P.; Farge, G.; Hooijman, P.; Modesti, M.; Falkenberg, M.; Wuite, G. J.; Peterman, E. J., Unraveling the structure of DNA during overstretching by using multicolor, single-molecule fluorescence imaging [J]. Proceedings of the National Academy of Sciences of the United States of America 2009,106, (43), 18231-18236.
18. Yeung, K. M.; Lu, Z. J.; Cheung, N. H., Adsorption of bovine serum albumin on fused silica:Elucidation of protein-protein interactions by single-molecule fluorescence microscopy [J]. Colloids and Surfaces B:Biointerfaces 2009,69, (2),246-250.
19. Max, B.; Emil, W., Principles of Optics:Electromagnetic Theory of Propagation, Interference and Diffraction of Light, Seventh(expanded)Edition. Cambridge University Press 1999.孙葭荪译,北京：电子工业出版社,2009,10.
20. Festag, G.; Steinbruck, A.; Wolff, A.; Csaki, A.; Moller, R.; Fritzsche, W., Optimization of gold nanoparticle-based DNA detection for microarrays [J]. Journal of Fluorescence 2005,15, (2),161-170.
21. Gokarna, A.; Jin, L. H.; Hwang, J. S.; Cho, Y. H.; Lim, Y. T.; Chung, B. H.; Youn, S. H.; Choi, D. S.; Lim, J. H., Quantum dot-based protein micro-and nanoarrays for detection of prostate cancer biomarkers [J]. Proteomics 2008,8, (9),1809-1818.
22. Miao, W.; Bard, A. J., Electrogenerated chemiluminescence.72. Determination of immobilized DNA and C-reactive protein on Au(111) electrodes using tris(2,2'-bipyridyl)ruthenium(Ⅱ) labels [J]. Analytical Chemistry 2003,75, (21), 5825-5834.
23. Sapsford, K. E.; Medintz, I. L.; Golden, J. P.; Deschamps, J. R.; Uyeda, H. T. Mattoussi, H., Surface-immobilized self-assembled protein-based quantum dot nanoassemblies [J]. Langmuir 2004,20, (18),7720-7728.
24. Yeung, S. S.; Lee, T. M.; Hsing, I. M., Electrochemistry-based real-time PCR on a microchip [J]. Analytical Chemistry 2008,80, (2),363-368.
25. Lee, G. U.; Metzger, S.; Natesan, M.; Yanavich, C.; Dufrene, Y. F., Implementation of force differentiation in the immunoassay [J]. Analytical Biochemistry 2000,287, (2), 261-271.
26. Bustamante, C.; Smith, S. B.; Liphardt, J.; Smith, D., Single-molecule studies of DNA mechanics [J]. Current Opinion in Structural Biology 2000,10, (3),279-285.
27. van Oijen, A. M.; Blainey, P. C.; Crampton, D. J.; Richardson, C. C.; Ellenberger, T.; Xie, X. S., Single-molecule kinetics of lambda exonuclease reveal base dependence and dynamic disorder [J]. Science 2003,301, (5637),1235-1238.
28. Kim, S. J.; Blainey, P. C.; Schroeder, C. M.; Xie, X. S., Multiplexed single-molecule assay for enzymatic activity on flow-stretched DNA [J]. Nature Methods 2007,4, (5),397-399.
29. Lee, J. B.; Hite, R. K.; Hamdan, S. M.; Xie, X. S.; Richardson, C. C.; van Oijen, A. M., DNA primase acts as a molecular brake in DNA replication [J]. Nature 2006, 439, (7076),621-624.
30. Mulvaney, S. P.; Cole, C. L.; Kniller, M. D.; Malito, M.; Tamanaha, C. R.; Rife, J. C.; Stanton, M. W.; Whitman, L. J., Rapid, femtomolar bioassays in complex matrices combining microfluidics and magnetoelectronics [J]. Biosensors & Bioelectronics 2007,23,(2),191-200.
1. Fulton, R.J., McDade, R.L., Smith, P.L., Kienker, L.J., Kettman, J.R., Advanced multiplexed analysis with the FlowMetrix (TM) system [J]. Clinical Chemistry 1997, 43,1749-1756.
2. Steemers, F.J., Ferguson, J.A., Walt, D.R., Screening unlabeled DNA targets with randomly ordered fiber-optic gene arrays [J]. Nature Biotechnology 2000,18, 91-94.
3. Ferguson, J.A., Boles, T.C., Adams, C.P., Walt, D.R., A fiber-optic DNA biosensor microarray for the analysis of gene expression[J]. Nature Biotechnology 1996,14, 1681-1684.
4. Ferguson, J.A., Steemers, F.J., Walt, D.R., High-density fiber-optic DNA random microsphere arrays [J]. Analytical. Chemistry 2000,72,5618-5624.
5. Han, M.Y., Gao, X.H., Su, J.Z., Nie, S.M., Quantum-dot-tagged microbeads for multiplexed optical coding of biomolecules [J]. Nature Biotechnology 2001,19, 631-635.
1. Forster, T., Intramolecular energy migration and fluorescence [J]. Annals of Physics 1948, (2),55-75.
2. Stryer, L.; Haugland, R. P., Fluorescence Energy transfer:a spectroscopic ruler [J]. Proceeding of the National Academy of Sciences of the United States of America 1967,58, (2),719-726.
3. Palm, T.; Sale, K.; Brown, L.; Li, H. C.; Hambly, B.; Fajer, P. G., Intradomain distances in the regulatory domain of the myosin head in prepower and postpower stroke states:Fluorescence energy transfer [J]. Biochemistry 1999,38, (40),13026-13034.
4. Arimori, S.; Bell, M. L.; Oh, C. S.; Frimat, K. A.; James, T. D., Modular fluorescence sensors for saccharides [J]. Chemical Communications 2001, (18),1836-1837.
5. Jensen, K. K.; Martini, L.; Schwartz, T. W., Enhanced fluorescence resonance energy transfer between spectral variants of green fluorescent protein through zinc-site engineering [J]. Biochemistry 2001,40, (4),938-945.
6. von Bultzingslowen, C.; McEvoy, A. K.; McDonagh, C.; MacCraith, B. D., Lifetime-based optical sensor for high-level pCO(2) detection employing fluorescence resonance energy transfer [J]. Analytica Chimica Acta 2003,480, (2), 275-283.
7. Liu, S. X.; Fang, Y.; Hu, D. D.; Gao, G. L.; Ma, J. B., Complexation between poly(methacrylic acid) and poly(vinylpyrrolidone) [J]. Journal of Applied Polymer Science 2001,82, (3),620-627.
8. Elbanowski, M.; Mkowska, B., The lanthanides as luminescent probes in investigations of biochemical systems [J]. Journal of Photochemistry and Photobiology A: Chemistry 1996,99,85-92.
9. Bu, P. C.; Zhuang, J.; Feng, J.; Yang, D. L.; Shen, X.; Yan, X. Y, Visualization of CD 146 dimerization and its regulation in living cells [J]. Biochimica Et Biophysica Acta-Molecular Cell Research 2007,1773, (4),513-520.
10. Martin, S. F.; Hattersley, N.; Samuel, I. D. W.; Hay, R. T.; Tatham, M. H., A fluorescence-resonance-energy-transfer-based protease activity assay and its use to monitor paralog-specific small ubiquitin-like modifier processing [J]. Analytical Biochemistry 2007,363, (1),83-90.
11. Ganesan, S.; Ameer-beg, S. M.; Ng, T. T. C.; Vojnovic, B.; Wouters, F. S., A dark yellow fluorescent protein (YFP)-based Resonance Energy-Accepting Chromoprotein (REACh) for Forster resonance energy transfer with GFP [J]. Proceedings of the National Academy of Sciences of the United States of America 2006,103, (11),4089-4094.
12. Antia, M.; Islas, L. D.; Boness, D. A.; Baneyx, G.; Vogel, V., Single molecule fluorescence studies of surface-adsorbed fibronectin [J]. Biomaterials 2006,27, (5), 679-690.
13. Rega, M. F.; Reed, J. C.; Pellecchia, M., Robust lanthanide-based assays for the detection of anti-apoptotic Bcl-2-family protein antagonists [J]. Bioorganic Chemistry 2007,35, (2),113-120.
14. Wei, O. D.; Lee, M.; Yu, X.; Lee, E. K.; Seong, G. H.; Choo, J.; Cho, Y. W., Development of an open sandwich fluoroimmunoassay based on fluorescence resonance energy transfer [J]. Analytical Biochemistry 2006,358, (1),31-37.
15. Isaac, V. E.; Patel, L.; Curran, T.; Shen, C. A., Use of Fluorescence Resonance Energy Transfer To Estimate Intramolecular Distances in the Msx-1 Homeodomain [J]. Biochemistry 1995,34,15276-15281.
16. Clegg, R. M.; Urche, A. H.; Lilley, D. L., The solution structure of the four-way DNA junction at low-salt conditions:a fluorescence resonance energy transfer analysis [J]. Biophysical Journal 1994,66,99-109.
17. Miki, M.; Iio, T., Kinetics of Structural Changes of Reconstituted Skeletal Muscle Thin Filaments Observed by Fluorescence Resonance Energy Transfer [J]. The Journal of Biological Chemistry 1993,268,7101-7106.
18. Johnson, D. A.; Leathers, V. L.; Martinez, A. M.; Walsh, D. A.; Fletcher, W. H., Fluorescence Resonance Energy Transfer within a Heterochromatic cAMP-Dependent Protein Kinase Holoenzyme under Equilibrium Conditions:New Insights into the Conformational Changes That Result in cAMP-Dependent Activation [J]. Biochemistry 1993,32,6402-6410.
19. Graham, D. L.; Lowe, P. N.; Chalk, P. A., A method to measure the interaction of Rac/Cdc42 with their binding partners using fluorescence resonance energy transfer between mutants of green fluorescent protein [J]. Analytical Biochemistry 2001,296, (2),208-217.
20. Ghosh, S. S.; Eis, P. S.; Blumeyer, K.; Fearon, K.; Millar, D. P., Real time kinetics of restriction endonuclease cleavage monitored by fluorescence resonance energy transfer [J]. Nucleic Acids Research 1994,22,3155-3159.
21. Perkins, T. A.; Wolf, D. E.; Goodchild, J., Fluorescence Resonance Energy Transfer Analysis of Ribozyme Kinetics Reveals the Mode of Action of a Facilitator Oligonucleotide [J]. Biochemistry 1996,35,16370-16377.
22. Ueda, H.; Kubota, K.; Wang, Y.; Tsumoto, K.; Mahoney, W.; Kumagai, I.; Nagamune, T., Homogeneous noncompetitive immunoassay based on the energy transfer between fluorolabeled antibody variable domains (open sandwich fluoroimmunoassay) [J]. Biotechniques 1999,27, (4),738-742.
23. Sixou, S.; Szoka, F. C.; Green, G. A.; Giusti, B.; Zon, G.; Chin, D. J., Intracellular oligonucleotide hybridization detected by fluorescence resonance energy transfer (FRET) [J]. Nucleic Acids Research 1994,22,662-668
24. Morrison, L. E.; Halder, T. C.; Stols, L. M., Solution-phase detection of polynucleotides using interacting fluorescent labels and competitive hybridization [J]. Analytical Biochemistry 1989,183,231-244
25. Tyagi, S.; Kramer, F. R., Molecular beacons:probes that fluoresce upon hybridization [J]. Nature Biotechnology 1996,14,303-308.
26. Li, Y. S.; Zhou, X. Y.; Ye, D. Y, Molecular beacons:An optimal multifunctional biological probe [J]. Biochemical and Biophysical Research Communications 2008, 373, (4),457-461.
27. Palecek, E., Surface-attached molecular beacons light the way for DNA sequencing [J]. Trends in Biotechnology 2004,22, (2),55-58.
28. Tyagi, S.; Bratu, D. P.; Kramer, F. R., Multicolor molecular beacons for allele discrimination [J]. Nature Biotechnology 1998,16, (1),49-53.
29. Fang, X. H.; Li, J. W. J.; Perlette, J.; Tan, W. H.; Wang, K. M., Molecular beacons-Novel fluorescent probes [J]. Analytical Chemistry 2000,72, (23),747a-753a.
30. Williams, E. J.; Campbell, A. K., A homogeneous assay for biotin based on chemiluminescence energy transfer [J]. Anayticall. Biochemistry 1986 155, 249-255.
31. Huang, X. Y.; Li, L.; Qian, H. F.; Dong, C. Q.; Ren, J. C., A resonance energy transfer between chemiluminescent donors and luminescent quantum-dots as acceptors (CRET) [J]. Angewandte Chemie-International Edition 2006,45, (31),5140-5143.
32. Murphy, C. J., Optical sensing with quantum dots [J]. Analytical Chemistry 2002,74, (19),520a-526a.
33. Achermann, M.; Petruska, M. A.; Kos, S.; Smith, D. L.; Koleske, D. D.; Klimov, V. I., Energy-transfer pumping of semiconductor nanocrystals using an epitaxial quantum well [J]. Nature 2004,429, (6992),642-646.
34. Clapp, A. R.; Medintz, I. L.; Fisher, B. R.; Anderson, G. P.; Mattoussi, H., Can luminescent quantum dots be efficient energy acceptors with organic dye donors [J]? Journal of the American Chemical Society 2005,127, (4),1242-1250.
35.马慧莲；刘含智；王丽萍；徐淑坤；李惟,量子点的荧光共振能量转移在生物分析中的应用[J].分析化学评述与进展2005,33,1335-1338.
36.徐金钩；王尊本,荧光分析(第三版).科学出版社2006,66-273.
37. Hohng, S.; Ha, T., Single-molecule quantum-dot fluorescence resonance energy transfer [J]. Chemphyschem 2005,6, (5),956-960.
38. Clapp, A. R.; Medintz, I. L.; Mauro, J. M.; Fisher, B. R.; Bawendi, M. G.; Mattoussi, H., Fluorescence resonance energy transfer between quantum dot donors and dye-labeled protein acceptors [J]. Journal of the American Chemical Society 2004, 126,(1),301-310.
39. Medintz, I. L.; Clapp, A. R.; Mattoussi, H.; Goldman, E. R.; Fisher, B.; Mauro, J. M., Self-assembled nanoscale biosensors based on quantum dot FRET donors [J]. Nature Materials 2003,2, (9),630-638.
40. Wang, S. P.; Mamedova, N.; Kotov, N. A.; Chen, W.; Studer, J., Antigen/antibody immunocomplex from CdTe nanoparticle bioconjugates [J]. Nano Letters 2002,2, (8),817-822.
41. Wang, J. H.; Liu, T. C.; Cao, Y. C.; Hua, X. F.; Wang, H. Q.; Zhang, H. L.; Li, X. Q.; Zhao, Y. D., Fluorescence resonance energy transfer between FITC and water-soluble CdSe/ZnS quantum dots [J]. Colloids and Surfaces a-Physicochemical and Engineering Aspects 2007,302, (1-3),168-173.
42. Willard, D. M.; Carillo, L. L.; Jung, J.; Van Orden, A., CdSe-ZnS quantum dots as resonance energy transfer donors in a model protein-protein binding assay [J]. Nano Letters 2001,1,(9),469-474.
43. Algar, W. R.; Krull, U. J., Towards multi-colour strategies for the detection of oligonucleotide hybridization using quantum dots as energy donors in fluorescence resonance energy transfer (FRET) [J]. Analytica Chimica Acta 2007,581, (2), 193-201.
44. Nagasaki, Y.; Ishii, T.; Sunaga, Y.; Watanabe, Y.; Otsuka, H.; Kataoka, K., Novel molecular recognition via fluorescent resonance energy transfer using a biotin-PEG/polyamine stabilized CdS quantum dot [J]. Langmuir 2004,20, (15), 6396-6400.
45. Oh, E.; Hong, M. Y.; Lee, D.; Nam, S. H.; Yoon, H. C.; Kim, H. S., Inhibition assay of biomolecules based on fluorescence resonance energy transfer (FRET) between quantum dots and gold nanoparticles [J]. Journal of the American Chemical Society 2005,127, (10),3270-3271.
46. Medintz, I. L.; Trammell, S. A.; Mattoussi, H.; Mauro, J. M., Reversible modulation of quantum dot photoluminescence using a protein-bound photochromic fluorescence resonance energy transfer acceptor [J]. Journal of the American Chemical Society 2004,126, (1),30-31.
1. Jares-Erijman, E. A.; Jovin, T. M., FRET imaging [J]. Nature Biotechnology 2003,21, 1387-1395.
2. Miyawaki, A.; Sawano, A.; Kogure, T., Lighting up cells:labelling proteins with fluorophores [J]. Nature Cell Biology 2003, Suppl, S1-7.
3. Sapsford, K. E.; Berti, L.; Medintz, I. L., Materials for fluorescence resonance energy transfer analysis:Beyond traditional donor-acceptor combinations [J]. Angewandte Chemie-International Edition 2006,45, (28),4562-4588.
4. Roda, A.; Guardigli, M.; Michelini, E.; Mirasoli, M.; Pasini, P., Analytical bioluminescence and chemiluminescence [J]. Analytical Chemistry 2003,75, (.), 462A-470A.
5. Perroy, J.; Pontier, S.; Charest, P. G.; Aubry, M.; Bouvier, M., Real-time monitoring of ubiquitination in living cells by BRET [J]. Nature Methods 2004,1,203-208.
6. Pfleger, K. D. G.; Eidne, K. A., Illuminating insights into protein-protein interactions using bioluminescence resonance energy transfer (BRET) [J]. Nature. Methods 2006, 3,165.
7. So, M. K.; Xu, C. J.; Loening, A. M.; Gambhir, S. S.; Rao, J. H., Self-illuminating quantum dot conjugates for in vivo imaging [J]. Nature Biotechnology.2006,24, 339-343.
8. Williams, E. J.; Campbell, A. K., A Homogeneous Assay for Biotin Based on Chemiluminescence Energy-Transfer [J]. Analytical Biochemistry 1986,155, 249-255.
9. Grayeski, M. L.; Moritzen, P. A., Chemiluminescence energy transfer processes and micellar effects [J]. Langmuir 1997,13,2675-2680.
10. Huang, X. Y.; Li, L.; Qian, H. F.; Dong, C. Q.; Ren, J. C., A resonance energy transfer between chemiluminescent donors and luminescent quantum-dots as acceptors (CRET) [J]. Angewandte Chemie-International Edition 2006,45,5140-5143.
11. Liu, X.; Jiang, H.; Lei, J. P.; Ju, H. X., Anodic electrochemiluminescence of CdTe quantum dots and its energy transfer for detection of catechol derivatives [J]. Analytical Chemistry 2007,79,21,8055-8060.
12. Liu, X.; Ju, H. X., Coreactant enhanced anodic electrocherniluminescence of CdTe quantum dots at low potential for sensitive biosensing amplified by enzymatic cycle [J]. Analytical Chemistry 2008,80,14,5377-5382.
13. McCall, J.; Alexander, C.; Richter, M. M., Quenching of electrogenerated chemiluminescence by phenols, hydroquinones, catechols, and benzoquinones [J]. Analytical Chemistry 1999,71,13,2523-2527.
14. Shan, Y.; Xu, J. J.; Chen, H. Y, Distance-dependent quenching and enhancing of electrochemiluminescence from a CdS:Mn nanocrystal film by Au nanoparticles for highly sensitive detection of DNA [J]. Chemical Communications 2009,8,905-907.
15. Murphy, C. J., Optical sensing with quantum dots [J]. Analytical Chemistry 2002,74, 520A-526A.
16. Achermann, M.; Petruska, M. A.; Kos, S.; Smith, D. L.; Koleske, D. D.; Klimov, V. I., Energy-transfer pumping of semiconductor nanocrystals using an epitaxial quantum well [J]. Nature 2004,429,642-646.
17. Clapp, A. R.; Medintz, I. L.; Fisher, B. R.; Anderson, G. P.; Mattoussi, H., Can luminescent quantum dots be efficient energy acceptors with organic dye donors [J]? Journal of the American Chemical Society 2005,127,1242-1250.
18. Richter, M. M., Electrochemiluminescence (ECL) [J]. Chemical Review 2004,104, 3003-3036.
19. Tian, D.; Duan, C.; Wang, W.; Li, N.; Zhang, H.; Cui, H.; Lu, Y, Sandwich-type electrochemiluminescence immunosensor based on N-(aminobutyl)-N-ethylisoluminol labeling and gold nanoparticle amplification [J]. Talanta 2009,78, (2),399-404.
20. Medintz, I. L.; Clapp, A. R.; Mattoussi, H.; Goldman, E. R.; Mauro, J. M., Self-assembled nanoscale biosensors based on quantum dot FRET donors [J]. Nature Materials 2003,2,630-638.
21. Lakowicz, J. R., Principles of Fluorescence Spectroscopy,2nd ed. Kluwer Academic, New York; 1999.
22.李明月,基于磁球放大技术的电化学发光免疫分析方法及电化学发光共振能量转移。[M].山东大学硕士学位论文,2010,第二章。
23. Baugh, L.; Vogel, V., Structural changes of fibronectin adsorbed to model surfaces probed by fluorescence resonance energy transfer [J]. Journal of Biomedical Materials Research Part A 2004,69, (3),525-34.
24. Antia, M.; Islas, L. D.; Boness, D. A.; Baneyx, G.; Vogel, V., Single molecule fluorescence studies of surface-adsorbed fibronectin [J]. Biomaterials 2006,27, (5), 679-90.
25. Halter, M.; Antia, M.; Vogel, V., Fibronectin conformational changes induced by adsorption to liposomes [J]. Journal of Controlled Release 2005,101, (1-3),209-22.
26. Baneyx, G.; Baugh, L.; Vogel, V., Coexisting conformations of fibronectin in cell culture imaged using fluorescence resonance energy transfer [J]. Proceeding of the National Academy of Sciences of the United States of America 2001,98, 14464-14468.
1. Shan, Y.; Xu, J. J.; Chen, H. Y, Distance-dependent quenching and enhancing of electrochemiluminescence from a CdS:Mn nanocrystal film by Au nanoparticles for highly sensitive detection of DNA [J]. Chemical Communications 2009,8,905-907.
2. Myung, N.; Bae, Y.; Bard, A. J. Effect of Surface Passivation on the Electrogenerated Chemiluminescence of CdSe/ZnSe Nanocrystals [J]. Nano Letters 2003,3, 1053-1055.
3. Baneyx, G.; Baugh, L.; Vogel, V., Coexisting conformations of fibronectin in cell culture imaged using fluorescence resonance energy transfer [J]. Proceeding of the National Academy of Sciences of the United States of America 2001,98, 14464-14468.
4.胡晓飞,量子点电化学发光及量子点-Cy5体系电化学发光共振能量转移检测DNA[M]。山东大学硕士学位论文,2010,第二章。
5. Lakowicz, J. R. Principles of Fluorescence Spectroscopy,2nd ed. Kluwer Academic, New York,1999.
(1)Zarrin,F.；Dovichi,N.J.Anal.Chem.1985,57,2690-2692.
(2)Nguyen,D.C.；Keller,R.A.；Jett,J.H.；Martin,J.C.Anal.Chem.1987,59, 2158-2161.
(3)Peck,K.；Stryer,L.；Glazer,A.N.；Mathies,R.A.Proc.Natl.Acad Sci.U.S.A. 1989,86,4087-4091.
(4)Shera,E.B.；Seitzinger,N.K.；Davis,L.M.；Keller,R.A.；Soper,S.A.Chem. Phys.Lett.1990,,74,553-557.
(5)Soper,S.A.；Davis,L.M.；Shera,E.B.J.Opt.Soc.Am.B 1992,9,1761-1769.
(6)Castro,A.；Fairfield,F.R.；Shera,E.B.Anal.Chem.1993,65,849-852.
(7)Goodwin,P.M.；Johnson,M.E.；Martin,J.C.；Ambrose,W.P.；Marrone,B.L.； Jett,J.H.；Keller,R.A.Nucleic Acids Res.1993,21,803-806.
(8)Soper,S.A.；Mattingly,Q.L.；Vegunta,P.Anal.Chem.1993,65,740-747.
(9)Huang,Z.；Petty,J.T.；O'Quinil,B.；Longmire,J.L.；Brown,N.C.；Jett,J.H.； Keller,R.A.Nucleic Acids Res.1996,24,4202-4209.
(10)Rauer,B.；Neumann,E.；Widengren,J.；Rigler,R.Biophys.Chem.1996,58,3-12.
(11)Castro,A.；Williams,J.G.Anal.Chem.1997,69,3915-3920.
(12)Sauer,M.；Zander,C.；Muller,R.；Ullrich,B.；Drenhage,K.H.；Kaul,S.；Wolfrum, J.Appl.Phys.B 1997,65,427-431.
(13)Van Orden,A.；Machara,N.P.；Goodwin,P.M.；Keller,R.A.Anal.Chem.1998, 70,1444-1451.
(14)Machara,N.P.；Goodwin,P.M.；Enderlein,J.；Semin,D.J.；Keller,R.A. Bioimaging 1998,6,33-42.
(15)Castro,A.；Okinaka,R.T.Analyst 2000,125,9-11.
(16)Barnes,M.D.；Ng,K.C.；Whitten,W.B.；Ramsey,J.M.Anal.Chem.1993,65, 2360.2365.
(17)Lermer,N.；Barnes,M.D.；Kung,C.；Whitten,W.B.；Ramsey,J.M.Anal.Chem. 1997,69,2115-2121.
(18)Barnes,M.D.；Lermer,N.；Kung,C.；Whitten,W.B.；Ramsey,J.M.；Hill,S.C. Opt.Lett.1997,22,1265-1267.
(19)Kung,C.；Barnes,M.D.；Lermer,N.；Whitten,W.B.；Ramse y,J.M.Anal.Chem. 1998,70,658-661.
(20)Lee,Y H.；Maus,R.G；Smith,B.W.；Winefordner,J.D.Anal.Chem.1994,66, 4142.4149.
(21)Xue,Q.；Yeung,E.S.Nature 1995,373,681-683.
(22)Castro,A.；Shera,E.B.Anal.Chem.1995,67,3181.3186.
(23)Craig,D.B.；Arriaga,E.A.；Wong,J.C.Y；Lu,H.；Dovichi,N.J.Am.Chem. Soc.1996,118,5245-5253.
(24)Chen,D.Y.；Dovichi,N.J.Anal.Chem.1996,68,690.696.
(25)Guenard,R.D.；King,L.A.；Smith,B.W.；Winefordner,J.D.Anal.Chem.1997, 69,2426-2433.
(26)Fister,I.,J.C.；Jacobson,S.C.；Davis,L.M.；Ramsey,J.M.Anal.Chem.1998, 70,431-437.
(27)Chou,H.P.；Spence,C.；Scherer,A.；Quake,S.Proc.Natl.Acad.Sci.U.S.A.1999, 96.11-13.
(28)Polakowski,R.；Craig,D.B.；Skelley,A.；Dovichi,N.J.J.Am.Chem.Soc.2000, 122,4853-4855.
(29)Shortreed, M. R.; Li, H.; Huang, W. H.; Yeung, E. S. Anal. Chem.2000,72, 2879-2885.
(30)Lagally, E. T.; Medintz, I.; Mathies, R. A. Anal. Chem.2001,73,565-570.
(31)Li, H.; Xue, G.; Yeung, E. S. Anal. Chem.2001,73,1537-1543.
(32)Ma, Y.; Shortreed, M. R.; Li, H.; Huang, W.; Yeung, E. S. Electrophoresis 2001, 22,421-426.
(33)Zheng, J.; Yeung, E. S. Anal. Chem.2002,74,4536-4547.
(34)Anazawa, T.; Matsunaga, H.; Yeung, E. S. Anal. Chem.2002,74,5033-5038.
(35)Tan, W.; Yeung, E. S. Anal. Chem.1997,69,4242-4248.
(36)Nie, S.; Chiu, D. T.; Zare, R. N. Science 1994,266,1018-1021.
(37)Eigen, M.; Rigler, R. Proc. Natl. Acad. Sci. U.S.A.1994,91,5740-5747.
(38)Nie, S. M.; Chiu, D. T.; Zare, R. N. Anal. Chem.1995,67,2849-2857.
(39)Haab, B. B.; Mathies, R. A. Anal. Chem.1995,67,3253-3260.
(40)Edman, L.; Mets, U.; Rigler, R. Proc. Natl. Acad. Sci. U.S.A.1996,93, 6710-6715.
(41)Lyon, W. A.; Nie, S. Anal. Chem.1997,69,3400-3405,
(42)Loscher, F.; Bohme, S.; Martin, J.; Seeger, S. Anal. Chem.1998,70,3202-3205.
(43)Haab, B. B.; Mathies, R. A. Anal. Chem.1999,71,5137-5145.
(44)Prummer, M.; Hubner, C. G.; Sick, B.; Hecht, B.; Renn, A.; Wild, U. P. Anal. Chem.2000,72, 443-447.
(45)Knemeyer, J.; Marme, N.; Sauer, M. Anal. Chem.2000,72,3717-3724.
(46)Byassee, T. A.; Chan, W. C.; Nie, S. Anal. Chem.2000,72,5606-5611.
(47)Wabuyele, M. B.; Ford, S. M.; Stryjewski, W.; Barrow, J.; Soper, S. A. Electrophoresis 2001,22,3939-3948.
(48)Tadakuma, H.; Yamaguchi, J.; Ishihama, Y.; Funatsu, T. Biochem. Biophys. Res. Commun.2001,287,323-327.
(49)Dorre, K.; Stephan, J.; Lapczyna, M.; Stuke, M.; Dunkel, H.; Ei'gen, M. J. Biotechnol.2001,86,225-236.
(50)Dorre, K.; Stephan, J.; Eigen, M. Single Mol.2001,2,165-175.
(51)Weston, K. D.; Dyck, M.; Tinnefeld, P.; Miiller, C.; Herten, D. P.; Sauer, M. Anal. Chem.2002,74,5342-5349.
(52)Shelby, J. P.; Chiu, D. T. Anal. Chem.2003,75,1387-1392.
(53)Li, H.; Ying, L.; Green, J. J.; Balasubramanian, S.; Klenerman, D. Anal. Chem. 2003,75,1664-1670.
(54)Prummer, M.; Sick, B.; Renn, A.; Wild, U. P. Anal. Chem.2004,76,1633-1640.
(55)Li, H.; Zhou, D.; Browne, H.; Balasubramanian, S.; Klenerman, D. Anal. Chem. 2004,76,4446-4451.
(56)Sun, B.; Chiu, D. T. Anal. Chem.2005,77,2770-2776.
(57)Hirschfeid, T. Appl. Opt.1976,15,2965-2966.
(58)Dickson, R. M.; Norris, D. J.; Tzeng, Y. L.; Moerner, W. E. Science 1996,274, 966-969.
(59)Xu, X. H.; Yeung, E. S. Science 1997,275,1106-1109.
(60)Xu, X. H.; Yeung, E. S. Science 1998,281,1650-1653.
(61)Fang, X.; Tan, W. Anal. Chem.1999,71,3101-3105.
(62)Ma, Y.; Shortreed, M. R.; Yeung, E. S. Anal. Chem.2000,72,4640-4645.
(63)Kang, S. H.; Yeung, E. S. Anal. Chem.2002,74,6334-6339.
(64)Singh-Zocchi, M.; Dixit, S.; Ivanov, V.; Zocchi, G. Proc. Natl. Acad. Sci. U.S.A. 2003,100,7605-7610.
(65)Li, H. W.; Yeung, E. S. Anal. Chem.2005,77,4374-4377.
(66)Hanley, D. C.; Harris, J. M. Anal. Chem.2001,73,5030-5037.
(67)Agrawal, A.; Zhang, C.; Byassee, T.; Tripp, R. A.; Nie, S. Anal. Chem.2006,78, 1061-1071.
(68)Donner, S.; Li, H.; Yeung, E. S.; Porter, M. D. Anal. Chem.2006,78,2816-2822.
(69)Wang, L.; Xu, G.; Shi, Z.; Jiang, W.; Jin, W. Anal. Chim. Acta 2007,590,104-109.
(70)Lee, J.; Li, J.; Yeung, E. S. Anal. Chem.2007,79,8083-8089.
(71)Yu, J.; Zhou, T. J. Electroanal. Chem.2001,504,89-95.
(72)Bos, M. A.; Shervani, Z.; Anusiem, A. C. I.; Giesbers, M. N., W.; Kleijn, J. M. Colloids Surfaces B:Biointerfaces 1994,3,91-100.
(73)Moulton, S. E.; Barisci, J. N.; Bath, A. S., R.; Wallace, G. G. J. Colloid Interface Sci.2003,261,312-319.
(74)Ying, P.; Viana, A. S.; Abrantes, L. M.; Jin, G. J. Colloid Interface Sci.2004,279, 95-99.
(75)Moulton, S. E.; Barisci, J. N.; Bath, A.; Stella, R.; Wallace, G. G. J. Langmuir 2005,21,316-322.
(76)Hidalgo-Alvarez, R.; Galisteo-Gonzalez, F. Heterog. Chem. Rev.1995,2, 249-268.
(77)Ganachaud, F.; Elaissari, A.; Pichot, C.; Laayoun, A.; Cros, P. Langmuir 1997,13, 701-707.
(1)Predki,P.F.Current Curr.Opin.Chem.Biol.2004,8,8-13.
(2)Levicky,R.；Horgan,A.Trends Biotechnol.2005,23,143-149.
(3)Merkel,J.S.；Michaud,G.A.；Salcius,M.；Schweitzer,B.；Predki,P.F.Curr.Opin. Biotechnol.2005,16,447-452.
(4)Draghici,S.；Khatri,P.；Eklund,A.C.；Szallasi,Z.Trends Genet.2006,22,101-109.
(5)Templin,M.F.；Stoll,D.；Schrenk,M.；Traub,P.C.；Vohringer,C.F.；Joos,T.O.Drug Discov.Today 2002,7,815-822.
(6)Zhu,H.；Snyder,M.Curr Opin.Chem.Biol.2003,7,55-63.
(7)Templin,M.F.；Stoll,D.；Schwenk,J.M.；Potz,O.；Kramer,S.；Joos,T.O. Proteomics 2003,3,2155-2166.
(8)Koebel,M.；Zimmt,M.B.J.Phys.Chem.B 2005,109,16736-16743.
(9)Schweitzer,B.；Wiltshire,S.；Lambert,J.；O'Malley,S.；Kukanskis,K.；Zhu,Z.R.； Kingsmore,S.F.；Lizardi,P.M.；Ward,D.C.Proc.Natl.Acad.Sci.2000,97, 10113.10119.
(10)Hesse,J.；Sonnleitner,M.；Sonnleitner,A.；Freudenthaler,G.；Jacak,J.；Hoglinger,O.； Schindler,H.；Schutz,G.J.Anal.Chem.2004,76,5960-5964.
(11)Hesse,J.；Jacak,J.；Kasper,M.；Regl,G；Eichberger,T.；Winklmayr,M.；Aberger,F.； Sonnleitner,M.；Schlapak,R.；Howorka,S.；Muresan,L.；Frischauf,A.M.；Schutz, G.J.Genome Res.2006,16,1041-1045.
(12)Li,L.；Tian,X.；Zou,G.；Shi,Z.；Zhang,X.；Jin,W.Anal Chem 2008,80, 3999-4006.
(13)Singh,U.；Nicholson,G.；Urban,B.C.；Sargent,I.L.；Kishore,U.；Bernal,A.L. Reproductio,2005,129,631-637.
(14)Ballard,J.L.；Peeva,V.K.；deSilva,C.J.S.；Lynch,J.L.；Swanson,N.R.Mol. Biotechnol.2007,36,175-183.
(15)Murphy,C.J.Anal.Chem.2002,74,520a-526a.
(16)Rosenthal,S.J.Nat.Biotechnol.2001,19,621-622.
(17)Chan,W.C.W.；Nie,S.M.Science 1998,281,2016-2018.
(18)Willner,I.；Patolsky,F.；Wasserman,J.Angew Chem.Int.Edit.2001,40,1861-1864.
(19)Gerion,D.；Parak,W.J.；Williams,S.C.；Zanchet,D.；Micheel,C.M.；Alivisatos,A. P.J.Am.Chem.Soc.2002,124,7070-7074.
(20)Maxwell,D.J.；Taylor,J.R.；Nie,S.M.J.Am.Chem.Soc.2002,124,9606-9612.
(21)Ulstrup,J.C.；Skaug,K.；Figenschau,K.J.；Orstavik,I.；Bruun,J.N.；Petersen,G. Lancet 1986,1,1151-1152.
(22)Hernandez,F.H.；Escriche,J.M.Analyst 1984,109,1585-1588.
(23)Clark,D.A.；Blois,S.；Kandil,J.；Handjiski,B.；Manuel,J.；Arck,P.C.Am.J. Reprod.Immunol.2005,54,203-216.
(24)Chaouat,G；Zourbas,S.；Ostojic,S.；Lappree-Delage,G；Dubanchet,S.；Ledee,N.； Martal,J.,Reprod.Immunol.2002,53,241-256.
(25)Renkl,A.C.；Wussler,J.；Ahrens,T.；Thoma,K.；Kon,S.；Uede,T.；Martin,S.F.； Simon,J.C.；Weiss,J.M.Blood 2005,106,946-955.
(26)Das,R.；Mahabeleshwar,G H.；Kundu,G C.J.Biol.Chem.2004,279, 11051.11064.
(27)Wai,P.Y；Kuo,P.C.Cancer Metast.Rev.2008,27,103-118.
(1)Jares-Erijman, E. A.; Jovin, T. M. Nat. Biotech.2003,21,1387-1395.
(2)Miyawaki, A.; Sawano, A.; Kogure, T. Nat. Cell Biol.2003, Suppl, S1-S7.
(3)Sapsford, K. E.; Berti, L.; Medintz, I. L. Angew. Chem. Int. Edit.2006,45, 4562-4588.
(4)Roda, A.; Guardigli, M.; Michelini, E.; Mirasoli, M.; Pasini, P. Anal. Chem.2003,75, 462A-470A.
(5)Perroy, J.; Pontier, S.; Charest, P. G.; Aubry, M.; Bouvier, M. Nat. Methods 2004,1, 203-208.
(6)Pfleger, K. D. G.; Eidne, K. A. Nat. Methods 2006,3,165.
(7)So, M. K.; Xu, C. J.; Loening, A. M.; Gambhir, S. S.; Rao, J. H. Nat. Biotech.2006, 24,339-343.
(8)Williams, E. J.; Campbell, A. K. Anal. Biochem.1986,155,249-255.
(9)Grayeski, M. L.; Moritzen, P. A. Langmuir 1997,13,2675-2680.
(10)Huang, X. Y.; Li, L.; Qian, H. F.; Dong, C. Q.; Ren, J. C. Angew. Chem. Int. Edit. 2006,45,5140-5143.
(11)McCall, J.; C., A.; Richter, M. M.Anal. Chem.1999,71,2523-2527.
(12)Liu, X.; Jiang, H.; Lei, J.; Ju, H. Anal. Chem.2007,79,8055-8060.
(13)Liu, X.; Ju, H. Anal. Chem.2008,80,5377-5382.
(14)Shan, Y.; Xu, J. J.; Chen, H. Y. Chem. Commun.2009,905-907.
(15)Richter, M. M. Chem. Rev.2004,104,3003-3036.
(16)Lakowicz, J. R. Principles of Fluorescence Spectroscopy,2nd ed, Kluwer Academic, New York; 1999.
(17)Baneyx, G.; Baugh, L.; Vogel, V. Proc. Nat. Acad. Sci. USA 2001,98,14464-14468.