SBIR Phase I: Radial-position Controlled Lanthanide Doped Nanocrystals as Time-resolved Fluorescence Imaging Agents

这个小型企业创新研究(SBIR)第一阶段项目将开发高亮度和稳定的稀土掺杂半导体纳米晶作为时间分辨荧光(TRF)成像剂。稀土络合物具有非常长的荧光寿命，因此在时间分辨荧光成像中被用作荧光探针，以最大限度地减少通常以短荧光寿命为特征的自发荧光。然而，镧系元素探针长期存在的困难--例如与生物分子的不稳定性和较差的兼容性--限制了它们的应用。本项目拟开发的稀土掺杂半导体纳米晶具有亮度高、稳定性好、表面修饰容易与蛋白质、DNA等生物分子兼容等优点，可广泛应用于TRF成像。生物成像在生命和生物医学科学中应用的扩大为显像剂创造了新的市场机遇；其中，市场是巨大的，到2009年将从目前的40亿美元增长到50亿美元以上。新型稀土TRF显像剂的商业化将在很大程度上取决于产品发光效率和稳定性的提高。该项目的技术将产生更广泛的影响，使时间分辨荧光成像在生命和生物医学科学中得到更广泛的使用。

This Small Business Innovation Research (SBIR) Phase I project will develop highly bright and stable lanthanide doped semiconductor nanocrystals as Time-Resolved Fluorescence (TRF) imaging agents. Lanthanide chelates have exceptionally long fluorescence lifetimes, and thus are used as fluorescent probe in the time-resolved fluorescent imaging to minimize the autofluorescence which is typically characterized by a short fluorescence lifetime. However long-standing difficulties with lanthanide probes - e.g. the instability and poor compatibility with biomolecule, have limited their applications. The lanthanide doped semiconductor nanocrystals to be developed in this program would have the advantageous features of high brightness, high stability, easily surface modification to be compatible with biomolecules such as protein and DNA; and thus can be widely used in TRF imaging. The expansion of applications of bioimaging in the life and biomedical sciences is creating new market opportunity for imaging agents; of which, the market is huge and will grow from current $4.0 billion to above $5.0 billion before 2009. The commercialization of new type of lanthanide based TRF imaging agents will largely depend on the improvements in the luminescent efficiency and stability of the products. The broader impact of the technology from this project will be to enable more extensive use of time-resolved fluorescence imaging in the life and biomedical sciences.