Development and characterization of optical imaging probes

光学成像探头的开发和表征

• 批准号: 10699713
• 负责人: Keir Neuman
• 金额: $ 17.42万
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10699713
• 关键词: Address; Antibodies; Binding; Blinking; Bromides; Carbon nanoparticle; Carboxylic Acids; Cesium; Characteristics; Chemical Structure; Chemistry; Detection; Development; Diamond; Drug Delivery Systems; Dyes; Fingerprint; Fluorescence; Fluorescent Probes; Goals; In Vitro; Individual; Label; Lead; Magnetism; Measurement; Measures; Methods; Microscope; Multimodal Imaging; Nitrogen; Noise; Nucleosome Core Particle; Optics; Penetration; Property; Protocols documentation; Publishing; Scheme; Side; Signal Transduction; South Korea; Surface; Surface Properties; Techniques; Testing; Tissues; United States National Institutes of Health; Universities; Woman; Work; biomaterial compatibility; density; fluorescence imaging; fluorophore; functional group; imaging approach; imaging probe; imaging study; improved; in vivo; in vivo evaluation; in vivo imaging; individual response; interest; molecular imaging; multimodality; nano; nanocrystal; nanodiamond; nanoparticle; nanoparticle delivery; novel; novel strategies; optical imaging; particle; perovskite; single molecule

Currently, there is one overarching project focused on functionalizing and characterizing fluorescent nanodiamonds: We are working on functionalizing and characterizing nitrogen vacancy center fluorescent nanodiamonds (FNDs) for use as multi-modal imaging probes. These are attractive fluorescence particles for in vivo and in vitro tracking and imaging studies as they are bright, non-blinking fluorophores that are excited in the green (560 nm) and emit in the far red spectrum (680-800 nm), which has superior tissue penetration and signal-to-noise characteristics compared with shorter wavelengths. Moreover, diamond is inert and the fluorescence arises from the nitrogen vacancy so the core particle contains no organic dyes or other potentially toxic material that would be problematic for in vivo applications. Remarkably, the FNDs can be as small as 10 nm, which is also advantageous for biocompatibility and clearing. We have established protocols to functionalize FNDs for biomedical applications. We recently published work describing methods to enhance the density of carboxylic acid groups on the surface of FNDs, and demonstrated that this approach enables the robust functionalization of FNDS with more than 10 different biologically important functional groups. This work provides a means of overcoming the inherent variability and inhomogeneity in the surface properties of FNDs and other carbon nanoparticles. Following up on our work developing FNDs as biocompatible multimodal probes for the development and detection of latent fingerprints, we worked with our collaborator, Junsang Cho, in the Department of Chemistry, Duksung Women's University, South Korea, to develop highly stanble cesium lead bromide perovskite nanocrystals as fluorescent probes for the detection of latent fingerprints. Work is continuing to expand the functionalization of the FNDs to produce multi-modal particles that can serves as both targeted fluorescent nanoparticles and drug delivery agents employing a novel mesoporous polydopamine encapsulation approach. Using a recently developed micro-mirror TIRF microscope combined with a magnetic tweezers, we developed a method to simultaneously determine the size and brightness of individual FNDs in a massively parallel measurement. This is an important measurement for the characterization of FNDs that has previously been exceedingly low throughput. This new approach allow affords us the opportunity to simultaneously measure the magnetic response of individual FNDs as a function of their size and brightness.

目前，有一个主要项目专注于功能化和表征荧光纳米金刚石： 我们正致力于功能化和表征氮空位中心荧光纳米金刚石（FND）用作多模态成像探针。这些是用于体内和体外跟踪和成像研究的有吸引力的荧光颗粒，因为它们是明亮的、不闪烁的荧光团，其在绿色（560 nm）中激发并在远红光谱（680-800 nm）中发射，与较短波长相比，其具有上级组织穿透和信噪比特性。此外，金刚石是惰性的，并且荧光由氮空位产生，因此核颗粒不含有机染料或其他可能有毒的材料，这些材料对于体内应用是有问题的。值得注意的是，FND可以小至10 nm，这对于生物相容性和清除也是有利的。我们已经建立了用于生物医学应用的功能化FND的方案。 我们最近发表的工作描述了提高FND表面上羧酸基团密度的方法，并证明了这种方法能够使FNDS具有超过10种不同的生物学重要官能团的强大功能化。 这项工作提供了一种克服FND和其他碳纳米颗粒表面性质固有的可变性和不均匀性的方法。 在我们开发FND作为生物相容性多模态探针用于开发和检测潜在指纹的工作之后，我们与我们的合作者Junsang Cho在韩国Duksung Women's University化学系合作，开发高度稳定的铯铅溴化钙钛矿纳米晶体作为荧光探针用于检测潜在指纹。 工作正在继续扩大FND的功能化，以产生多模态颗粒，其可以用作靶向荧光纳米颗粒和药物递送剂，采用新型介孔聚多巴胺封装方法。 使用最近开发的微镜TIRF显微镜结合磁镊子，我们开发了一种方法，同时确定在大规模并行测量中的单个FND的大小和亮度。 这是一个重要的测量表征FND，以前已经非常低的吞吐量。 这种新方法使我们有机会同时测量单个FND的磁响应，作为其大小和亮度的函数。