LUMINESCENT QUANTUM DOTS AS BIOLOGICAL LABELS

允许直接检测化合物或特定结合事件的新探针、均质分析和微型设备的发展正在对基础研究、临床诊断和药物开发产生影响。新的荧光和发光技术对于实现更高的速度和自动化尤为重要。这些进展正被应用于基因序列、蛋白质、感染性生物和各种其他目标的检测和定位。这一提议的主要目标是通过将生物分子连接到半导体量子点(纳米晶体)来开发一类新的生物检测标记。量子点通过它们强烈的光致发光被检测到，附着的生物分子识别特定的分析物，如蛋白质、DNA或病毒。我们团队最近的研究开发了一种简单的方法，允许高发光量子点(带帽的硫化锌)在水中增溶；可溶于水的量子点具有生物相容性，并且可以共价连接到大的生物分子上(Science 281,2106-2018,1998)。与有机染料相比，这种新型发光3NT标签具有发射波长大小可调、光谱形状对称以及在单一波长下同时激发等显著优势。这一提议的主要目标是通过将生物分子与半导体量子点(纳米晶体)结合来开发一种新的生物检测方法。量子点通过它们强烈的光致发光被检测到，附着的生物分子识别特定的分析物，如蛋白质、DNA或病毒。我们团队最近的研究开发了一种简单的方法，允许高发光量子点(带帽的硫化锌)在水中增溶；可溶于水的量子点具有生物相容性，并且可以共价连接到大的生物分子上(Science 281,2106-2018,1998)。与有机染料相比，这种新型发光标记具有发射波长大小可调、光谱形状对称以及在单一波长下同时激发等显著优点。这项拟议的研究将系统地检查各种用于生物和生物医学应用的量子点生物偶联物。基本材料将包括II-VI族(Cd和CdSe)和III-V族(InP和InAs)半导体，发射波长从蓝色到近红外可调。将使用无机封顶层来提高光稳定性和发光量子产率。被封顶的量子点将与两大类生物分子-蛋白质和核酸-结合。还将开发策略来操纵量子点的光学性质，例如用有机生色团猝灭量子点的发光。预计量子点生物偶联物将大量以亲脂形式提供，以便广泛分发给科学界。

The development of new probes, homogeneous assays, and miniaturized devices that allow for the direction detection of compounds or specific binding events is having an impact in basic research, clinical diagnostics, and drug development. Novel fluorescent and luminescent technologies are especially important for the implementation of greater speed and automation. These advances are being applied to the detection, localization of gene sequences, proteins, infectious organisms, and a variety of other targets. The primary goal of this proposal is to develop a new class of biological detection labels by conjugating biological molecules to semiconductor quantum dots (nanocrystals). The quantum dots are detected by their intense photoluminescence, and the attached biomolecules recognize specific analytes such as proteins, DNA, or viruses. Recent research in our group has developed a simple procedure that allows highly luminescent quantum dots (ZnS-capped CdSe) to be solubilized in water; the water-soluble quantum dots are biocompatible and can bo covalently linked to large biomolecules (SCIENCE 281, 2106-2018, 1998). In comparison with organic dyes, this new class of luminesc3nt labels offers significant advantages such as size-tunable emission wavelength, symmetric spectral shapes, and simultaneous excitation at a single wavelength. The primary goal os this proposal is to develop a new class of biological detection by conjugating biological molecules to semiconductor quantum dots (nanocrystals). The quantum dots are detected by their intense photoluminescence, and the attached biomolecules recognize specific analytes such as proteins, DNA, or viruses. Recent research in our group has developed a simple procedure that allows highly luminescent quantum dots (ZnS-capped CdSe) to be solubilized in water; the water- soluble quantum dots are biocompatible and can be covalently linked to large biomolecules (SCIENCE 281, 2106-2018, 1998). In comparison with organic dyes, this new class of luminescent labels offers significant advantages such as size-tunable emission wavelength,, symmetric spectral shapes, and simultaneous excitation at a single wavelength. The proposed research will systematically examine a variety of quantum dot bioconjugates for biological and biomedical applications. The basic materials will include group II-VI (Cds and CdSe) and group III-V (InP and InAs) semiconductors, with emission wavelengths tunable from the blue to the near infrared. An inorganic capping layer will be used to improve the photostability and luminescence quantum yields. The capped quantum dots will be conjugated to two broad categories of biological molecules-proteins and nucleic acids. Strategies will also be developed to manipulate the quantum dot optical properties, such as the quenching of quantum dot luminescence with organic chromophores. Quantum dot bioconjugates are expected to be available in large quantities and in lyphophilized forms, for broad distribution to the scientific community.