LUMINESCENT QUANTUM DOTS AS BIOLOGICAL LABELS

新的探针，均相测定和微型化设备，允许化合物或特异性结合事件的方向检测的发展正在基础研究，临床诊断和药物开发的影响。新型荧光和发光技术对于实现更高的速度和自动化尤为重要。这些进展正在应用于基因序列、蛋白质、感染性生物体和各种其他靶标的检测和定位。该提案的主要目标是通过将生物分子缀合到半导体量子点（纳米晶体）来开发一类新的生物检测标记。量子点通过其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。我们小组最近的研究已经开发出一种简单的方法，其允许高度发光的量子点（ZnS-封端的CdSe）溶解在水中;水溶性量子点是生物相容的，并且可以共价连接到大的生物分子（SCIENCE 281，2106-2018，1998）。与有机染料相比，这类新的发光标记物具有显著的优势，如尺寸可调的发射波长，对称的光谱形状，以及在单一波长下的同时激发。这个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）结合来开发一类新的生物检测。量子点通过其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。我们小组最近的研究已经开发了一种简单的程序，其允许高度发光的量子点（ZnS-封端的CdSe）溶解在水中;水溶性量子点是生物相容的，并且可以共价连接到大的生物分子（SCIENCE 281，2106-2018，1998）。与有机染料相比，这类新的发光标记物提供了显著的优点，例如尺寸可调的发射波长、对称的光谱形状以及在单个波长处的同时激发。拟议的研究将系统地研究各种量子点生物共轭物的生物和生物医学应用。基本材料将包括II-VI族（CdS和CdSe）和III-V族（InP和InAs）半导体，发射波长可从蓝色到近红外调谐。无机覆盖层将用于提高光稳定性和发光量子产率。这些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，例如用有机发色团猝灭量子点发光。预计量子点生物缀合物将以冻干形式大量提供，以广泛分发给科学界。

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.