Highly Fluorescent Magnetic Nanoclusters for Effective and Multiplexed Separation

描述（由申请人提供）：有效分离稀有细胞和鉴定细胞特征子集的能力可以提供从癌症诊断到干细胞治疗的重要预后和治疗意义。这些细胞的稀有性质对分离和分析方法的功能性和稳健性提出了特别的挑战。纳米技术可以提供新的和实际的解决方案，以迎接这一挑战。该提案的广泛目标是开发上级纳米颗粒试剂与独特的分离方案的组合，该分离方案可应用于稀有细胞的高效和多重分离。这些纳米颗粒剂将基于具有上级荧光性质和精确可调磁矩的高荧光磁性纳米团簇（HFMN）。HFMN将提供一个优秀的平台技术，不仅允许优化的磁性控制，以有效分离稀有细胞，而且还有助于使用专门设计的外部磁场梯度控制多路复用细胞分离。 此外，HFMN的上级荧光信号将允许同时跟踪和原位生物医学分析，用于细胞类型鉴定和诊断或治疗评价。的 具体目标是：1）合成具有最佳荧光亮度和可调磁性的HFMN。2)HFMN用于全血样本中稀有细胞的高效分离和鉴定。3)展示HFMN与专门设计的外部磁场梯度控制相结合的先进能力，用于全血样本中稀有细胞的多重分离和鉴定。这种高质量的多功能纳米颗粒和独特的磁性分离方案在商业上可用时，可以显着推进稀有细胞分离和分析的现有技术，并最终有助于改善许多患者的细胞诊断和治疗。 公共卫生相关性：本研究的目标是开发新型纳米颗粒试剂，高荧光磁性纳米团簇，以及专门设计的磁性分离方案，用于高效和多重分离和鉴定稀有细胞。 成功实现这一目标可以显着推进稀有细胞分离和分析的现有技术，包括循环肿瘤细胞和治疗细胞，如T细胞和干细胞，并最终有助于改善许多患者的细胞诊断和治疗。

DESCRIPTION (provided by applicant): The ability to effectively isolate rare cells and identify subset of cell characteristics could provide significant prognostic and therapeutic implications ranging from cancer diagnostics to stem cell therapies. The rare nature of these cells imposes particular challenge on the functionality and robustness of the separation and analysis methodology. Nanotechnology could provide novel and practical solutions to meet such challenge. The broad objective of this proposal is to develop superior nanoparticle reagents in combination with a unique separation scheme that could be applied for highly effective and multiplexed separation of rare cells. These nanoparticle agents will be based on the highly fluorescent magnetic nanoclusters (HFMN) with superior fluorescent properties and precisely tunable magnetic moments. HFMN will provide an excellent platform technology that not only allows optimized magnetic control for effective separation of rare cells, but also facilitates multiplexed cell separation using a specifically designed external magnetic field gradient control. In addition, the superior fluorescent signal of HFMN will allow simultaneous tracking and in situ biomedical analysis for cell type identification and for diagnostic or therapeutic evaluations. The specific aims are: 1) Synthesize HFMN with optimal fluorescent brightness and tunable magnetic properties. 2) Apply HFMN for efficient rare cell separation and identification in whole blood samples. 3) Demonstrate the advanced capability of HFMN in combination with a specifically designed external magnetic field gradient control for multiplexed separation and identification of rare cells in whole blood samples. Such high quality multifunctional nanoparticles and the unique magnetic separation scheme when made commercially available, could significantly advance the current technology in rare cell separation and analysis, and ultimately contribute to improved cellular diagnosis and therapy for many patients. PUBLIC HEALTH RELEVANCE: The goal of this research is to develop novel nanoparticle reagents, the highly fluorescent magnetic nanoclusters, and a specifically designed magnetic separation scheme for highly effective and multiplexed separation and identification of rare cells. Success in achieving this goal could significantly advance the current technology in rare cell separation and analysis including circulating tumor cells and therapeutic cells such as T-cells and stem cells, and ultimately contribute to improved cellular diagnosis and therapy for many patients.