SYNTHESIS OF LANTHANIDE ENCODED MICROSPHERES

镧系元素编码微球的合成

• 批准号: 7956781
• 负责人: Gabriel P. Lopez
• 金额: $ 3.22万
• 依托单位: LOS ALAMOS NAT SECTY-LOS ALAMOS NAT LAB
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7956781
• 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; Sorting - Cell Movement; 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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 新墨西哥大学正在开发多种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，这些微珠的直径是单分散的，并且包含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成本相对较高，单分散微粒的直接合成（与多分散粒子的尺寸分级相反）将非常有利，并且将为流式细胞术试剂的生产提供足够的通量。 由于镧系元素容易因水合而降低发光产量，我们将开发一种将其封装在极性无机和非极性有机微球主体中的方法，如下所述。 在大多数情况下，封装与共轭分子“天线”复合的镧系离子可能是有利的，以增加光致发光横截面[54]。 许多铽和铕络合物以及镧系元素标记都可以在市场上买到（Aldrich、Strem）。 （Invitrogen）具有一系列激发特性。 无机主体中镧系元素的封装。 我们的首要目标是开发一种简单且可重复生产单分散二氧化硅颗粒的方法，该颗粒以明确的浓度封装发光稀土离子。 洛佩兹等人。新墨西哥大学最近开发了溶胶-凝胶方法，用于从气溶胶液滴中生产单分散二氧化硅微粒（见图 14）。 [55]该方法已被证明有利于将无机和有机主体掺入颗粒中，使用振动孔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，我们将引入已知浓度的光致发光铽和铕络合物。我们将优化分子水平的分散和总颗粒发光，以便使用 NFCR 开发的新型声聚焦流式细胞仪直接检测镧系元素光致发光。 这些基于二氧化硅的珠子很容易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]。 将镧系元素封装在有机聚合物微珠中。 由于上述问题与水合镧系元素的潜在低发光有关，我们的第二个目标是开发基于有机单体乳液聚合的方法，以轻松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，但本体乳液方法通常会产生具有多分散尺寸的颗粒（通常呈对数正态尺寸分布）[57]。 对于流式细胞术应用，非常需要使用尺寸均匀的颗粒群，因此，我们将开发直接形成封装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微流体注射方法来形成稳定的单分散乳液液滴[58]。通过 NSF 资助的合作，形成这种单分散液滴的方法最近已转移到新墨西哥大学。 图 14 所示的液滴是在新墨西哥大学制造和使用的微流体装置中产生的。 我们将开发稳定此类乳液液滴的方法，将苯乙烯、甲基丙烯酸甲酯和甲基丙烯酸正丁酯等有机单体与发光的稀土配合物一起负载到乳液液滴中，并引发聚合反应以形成均匀的微球。 这种用于形成微球的乳液聚合方法特别有效，因为它能够一步形成表面涂覆有生物分子反应性官能团的核-壳结构。