LUMINESCENT QUANTUM DOTS AS BIOLOGICAL LABELS

新探针、均质分析和小型化设备的发展，使得化合物或特定结合事件的方向检测在基础研究、临床诊断和药物开发方面产生了影响。新颖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。这些进步正被应用于基因序列、蛋白质、感染性生物和各种其他靶标的检测、定位。本提案的主要目标是通过将生物分子偶联到半导体量子点（纳米晶体）来开发一类新的生物检测标签。量子点是通过它们强烈的光致发光来检测的，附着的生物分子可以识别特定的分析物，如蛋白质、DNA或病毒。我们小组最近的研究开发了一种简单的程序，可以将高度发光的量子点（ZnS-capped CdSe）溶解在水中；水溶性量子点具有生物相容性，可以与大分子共价连接（SCIENCE, 281, 2106-2018, 1998）。与有机染料相比，这种新型luminesc3nt标签具有明显的优势，如发射波长大小可调，光谱形状对称，以及在单一波长下同时激发。本提案的主要目标是通过将生物分子偶联到半导体量子点（纳米晶体）来开发一类新的生物检测。量子点是通过它们强烈的光致发光来检测的，附着的生物分子可以识别特定的分析物，如蛋白质、DNA或病毒。我们小组最近的研究开发了一种简单的程序，可以将高度发光的量子点（ZnS-capped CdSe）溶解在水中；水溶性量子点具有生物相容性，可以与大分子共价连接（SCIENCE, 281, 2106-2018, 1998）。与有机染料相比，这种新型发光标签具有明显的优势，如发射波长大小可调，光谱形状对称，以及在单一波长下同时激发。提出的研究将系统地检查各种量子点生物偶联物的生物学和生物医学应用。基本材料将包括II-VI族（cd和CdSe）和III-V族（InP和InAs）半导体，其发射波长从蓝色到近红外可调。无机封盖层将用于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结合——蛋白质和核酸。研究人员还将开发一些策略来控制量子点的光学特性，例如用有机发色团来猝灭量子点的发光。量子点生物偶联物有望以大量和冻干形式提供，广泛分布到科学界。

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.