SYNTHESIS OF LANTHANIDE ENCODED MICROSPHERES

镧系元素编码微球的合成

• 批准号: 8169399
• 负责人: Gabriel P. Lopez
• 金额: $ 3.34万
• 依托单位: LOS ALAMOS NAT SECTY-LOS ALAMOS NAT LAB
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8169399
• 关键词: Aerosols; Architecture; Caliber; Characteristics; Chemistry; Collaborations; Complex; Computer Retrieval of Information on Scientific Projects Database; Coupling; Detection; Emulsions; Encapsulated; Europium; Figs - dietary; Flow Cytometry; Fractionation; Funding; Gel; Grant; Hydration status; Injection of therapeutic agent; Institution; Ions; Label; Lanthanoid Series Elements; Methacrylates; Methods; Microfluidic Microchips; Microfluidics; Microspheres; Molecular; New Mexico; One-Step dentin bonding system; Population; Predisposition; Preparation; Production; Reaction; Reagent; Research; Research Personnel; Resources; Silanes; Silicon Dioxide; Source; Surface; Terbium; United States National Institutes of Health; Universities; base; butyl methacrylate; cost; functional group; luminescence; monomer; particle; polymerization; silane; surface coating

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A number of methods for the production of microspheres based on emulsion polymerization and aerosol synthesis are being developed at the University of New Mexico. These methods will be adapted for the formation of uniform populations of microbeads that are monodisperse in diameter and that incorporate known concentrations of luminescent lanthanides, such as terbium and europium complexes. Direct synthesis of mondisperse microparticles (as opposed to size fractionation of polydisperse particles) will be highly advantageous because of the relatively high cost of many lanthanide complexes and will provide sufficient throughput for the production of flow cytometry reagents. Because of the susceptibility of lanthanides reduction in luminescence yield by hydration, we will develop a method for their encapsulation in both polar inorganic and apolar organic microspherical hosts as described below. In most cases it may be advantageous to encapsulate lanthanide ions that are complexed to conjugated molecular "antennae" to increase photoluminescence cross-section [54]. A number of terbium and europium complexes are commercially available (Aldrich, Strem) as are lanthanide labels. (Invitrogen) that have a range of excitation characteristics. Encapsulation of Lanthanides in Inorganic Hosts. Our first aim will be to develop methods for the facile and reproducible production of monodisperse silica particles that encapsulate luminescent lanthanide ions in well-defined concentrations. Lopez, et al. at UNM have recently developed sol-gel methods for production of monodisperse silica microparticles from aerosol droplets (see Fig. 14). [55] In this method, which has been shown to be conducive to the incorporation of inorganic and organic hosts in the particles, uniform aerosol droplets with the desired precursors are generated using a vibrating orifice aerosol generator. Using this method we will introduce known concentrations of photoluminescent terbium and europium complexes. We will optimize the molecular level dispersal and total particle lumimescence to enable direct detection of lanthanide photoluminescence using new acoustically focused flow cytometers developed by the NFCR. These silica-based beads will be readily amenable to surface biofunctionalization by established silane based coupling chemistry [56]. Encapsulation of Lanthanides in Organic Polymeric Microbeads. Because of the issue identified above related to the potential low luminescence of hydrated lanthanides, our second aim will be to develop methods based on emulsion polymerization of organic monomers for the facile preparation of monodisperse particles that incorporate lanthanide ions. Emulsion based polymerizations are well known, but bulk emulsion methods generally result in particles with polydisperse sizes (generally in a log-normal size distribution) [57]. For flow cytometry applications it is highly desirable to use particle populations of uniform size, and thus, we will develop methods for direct formation of monodispersed polymeric particles encapsulating lanthanides. To do so we will use microfluidic injection methods for forming stable monodisperse emulsion droplets developed at Harvard University [58]. Through an NSF funded collaboration, the methods for forming such monodisperse droplets have recently been transferred to UNM. The droplets shown in Fig. 14 were generated in microfluidic devices fabricated and utilized at UNM. We will develop methods of stabilization of such emulsion droplets, of loading them with organic monomers such as styrene, methyl methacrylate and n-butyl methacrylate, together with luminescent lanthanide complexes, and initiating polymerization reactions to form uniform microspheres. Such emulsion polymerization methods for forming microspheres are especially powerful because of the ability to form core-shell architectures in which are surface coated with biomolecule-reactive functional groups in one step.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 新墨西哥大学正在开发许多基于乳液聚合和气溶胶合成的微球生产的方法。这些方法将适用于直径单分散的微粒均匀种群的形成，并结合了已知浓度的发光灯笼，例如Terbium和Europium Complexs。 直接合成Mondisperse微粒（与多分散颗粒的尺寸分馏相对）将是有利的，因为许多兰烷化复合物的成本相对较高，并且将为流式细胞测量试剂的产生提供足够的吞吐量。 由于水合通过水合降低发光产量的敏感性，我们将开发一种方法，用于在极性无机和极性有机微磷宿主中封装，如下所述。 在大多数情况下，封装与共轭分子“触角”相吻合以增加光致发光横截面[54]可能是有利的。 许多Terbium和Europium Complexs都可以商购（Aldrich，Strem），以及灯笼标签。具有一系列激发特征的（Invitrogen）。 无机宿主中灯笼的封装。 我们的第一个目的是开发用于单分散二氧化硅颗粒的可容纳和可再现产生的方法，该二氧化硅颗粒以明确的浓度封装了发光的灯笼离子。 洛佩兹等。在UNM上，最近开发了用于从气溶胶液滴生产单分散二氧化硅微粒的溶胶 - 凝胶方法（见图14）。 [55]在这种方法中，已证明有利于将无机和有机宿主掺入颗粒中，使用振动孔口气溶胶发生器产生具有所需前体的均匀气溶胶液滴。 使用这种方法，我们将引入已知的光致发光terbium和Europium复合物。我们将使用NFCR开发的新的声学浓缩流式细胞仪来优化分子水平的分散和总颗粒发光，以直接检测兰烷化光致发光。 这些基于二氧化硅的珠将很容易通过建立的基于硅烷的耦合化学来应对表面生物功能化[56]。 有机聚合微粒中灯笼的封装。 由于上述问题与水合灯笼的潜在低发光有关，因此我们的第二个目标是基于有机单体的乳液聚合来开发方法，以使单分散粒子的易于制备，以融合灯笼离子。 基于乳液的聚合是众所周知的，但是散装乳液方法通常会导致具有多分散大小的颗粒（通常在对数正态分布中）[57]。 对于流式细胞仪应用，非常需要使用均匀尺寸的粒子群，因此，我们将开发直接形成单分散的聚合物聚合物颗粒封装灯笼的方法。 为此，我们将使用微流体注入方法来形成哈佛大学开发的稳定的单分散乳液液滴[58]。通过NSF资助的合作，形成此类单分散液滴的方法最近已转移到UNM。 图14中所示的液滴是在制造并在UNM上使用的微流体设备中生成的。 我们将开发这种乳液液滴的稳定方法，以将它们加载到苯乙烯，甲基丙烯酸甲酯和N-丁基甲基丙烯酸甲酯以及发光的灯笼型灯笼复合物以及启动聚合反应以形成均匀的微壳的情况下。 这种用于形成微球的乳液聚合方法特别有力，因为能够在一个步骤中形成核心壳体系结构，在其中表面涂有生物分子反应性官能团。