SYNTHESIS OF LANTHANIDE ENCODED MICROSPHERES

镧系元素编码微球的合成

• 批准号: 7598420
• 负责人: Gabriel P. Lopez
• 金额: $ 4.19万
• 依托单位: LOS ALAMOS NAT SECTY-LOS ALAMOS NAT LAB
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7598420
• 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; Numbers; One-Step dentin bonding system; Population; Predisposition; Preparation; Production; Range; Reaction; Reagent; Research; Research Personnel; Resources; Silanes; Silicon Dioxide; Source; Surface; Terbium; United States National Institutes of Health; Universities; base; butyl methacrylate; cost; desire; functional group; luminescence; monomer; particle; polymerization; silane; size; 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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 新墨西哥州大学正在开发一些基于乳液聚合和气溶胶合成的微球生产方法。这些方法将适用于形成均匀的微珠群体，所述微珠群体在直径上是单分散的并且掺入已知浓度的发光镧系元素，例如铽和铕络合物。 由于许多镧系元素络合物的相对高的成本，单分散微粒的直接合成（与多分散颗粒的尺寸分级相反）将是非常有利的，并且将为流式细胞术试剂的生产提供足够的通量。 由于镧系元素的敏感性降低的发光产率的水合作用，我们将开发一种方法，其封装在极性无机和非极性有机微球主机如下所述。 在大多数情况下，包封与共轭分子络合的镧系元素离子可能是有利的。 天线 以增加光致发光截面[54]。 许多铽和铕络合物是市售的（Aldrich，斯特雷姆），镧系元素标记物也是市售的。（英杰公司），其具有一系列激发特性。 镧系元素在无机盐中的包覆。 我们的第一个目标将是开发用于以明确定义的浓度封装发光镧系离子的单分散二氧化硅颗粒的简便且可再现的生产方法。 UNM的洛佩斯等人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（参见图14）。[55个] 在这种方法中，已被证明是有益的无机和有机主体在颗粒中的结合，均匀的气溶胶液滴与所需的前体产生使用振动孔气溶胶发生器。 使用这种方法，我们将介绍已知浓度的光致发光铽和铕配合物。我们将优化分子水平的分散和总颗粒发光，使直接检测镧系元素的光致发光使用新的声聚焦流式细胞仪开发的NFCR。 这些基于二氧化硅的珠粒将易于通过已建立的基于硅烷的偶联化学进行表面生物功能化[56]。 稀土元素在有机聚合物微球中的包覆。 由于上述与水合镧系元素的潜在低发光相关的问题，我们的第二个目标将是开发基于有机单体的乳液聚合的方法，用于容易地制备掺入镧系元素离子的单分散颗粒。 基于乳液的聚合是众所周知的，但是本体乳液方法通常产生具有多分散尺寸（通常在对数正态尺寸分布中）的颗粒[57]。 对于流式细胞术应用，非常希望使用均匀尺寸的颗粒群，因此，我们将开发用于直接形成包封镧系元素的单分散聚合物颗粒的方法。 为此，我们将使用哈佛大学开发的用于形成稳定的单分散乳液液滴的微流体注射方法[58]。通过NSF资助的合作，形成这种单分散液滴的方法最近被转移到UNM。 图14所示的液滴在UNM制造和使用的微流体装置中产生。 我们将开发这样的乳液液滴的稳定化方法，将它们与有机单体如苯乙烯、甲基丙烯酸甲酯和甲基丙烯酸正丁酯以及发光镧系元素络合物一起装载，并引发聚合反应以形成均匀的微球。 用于形成微球的这种乳液聚合方法是特别强大的，因为能够在一个步骤中形成核-壳结构，其中表面涂覆有生物分子反应性官能团。