A NEW METHOD FOR THE ANALYSIS OF VITAMIN D

维生素 D 分析的新方法

• 批准号: 8934122
• 负责人: Fred E Regnier
• 金额: $ 48.04万
• 依托单位: NOVILYTIC, LLC
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8934122
• 关键词: Adsorption; Aliquot; Alkylation; Americas; Antibodies; Biological Assay; Biological Products; Blood; Blood Cells; Blood Tests; Blood capillaries; Blood specimen; Caliber; Carrier Proteins; Cell membrane; Cells; Charge; Clinical; Collection; Data; Development; Digestion; Dimensions; Drops; Drug Formulations; Energy-Generating Resources; Filtration; Fingers; Foundations; Health; Healthcare; Heart; Human; Immune; Individual; Intervention; Laboratories; Marketing; Mass Spectrum Analysis; Membrane; Methods; Microfluidics; Monitor; Monoclonal Antibodies; Peptides; Pharmaceutical Preparations; Phase; Physicians; Plasma; Preparation; Process; Process Assessment; Production; Proteins; Proteomics; Reagent; Sales; Sampling; Serum; Shipping; Ships; Site; Spectrometry, Mass, Electrospray Ionization; Speed; Stream; Structure; System; Technology; Temperature; Testing; Text; Therapeutic Agents; Time; Trypsin; Validation; Venipunctures; Vitamin D; Vitamin D Analog; Work; Writing; base; blood fractionation; capillary; cost; ionization; new technology; operation; point of care; quality assurance; research clinical testing; therapeutic protein

DESCRIPTION (provided by applicant): Most clinical assays begin with blood collection in a laboratory setting. The Gates foundation and many others have recognized and attempted to deal with the fact that in much of the world clinical testing is done in a primitive setting. The luxury of having a phlebotomist to draw blood with a laboratory to prepare serum or plasma for analysis is not universal at many points-of-care, even in America. The most significant component of this proposal is that the world will obtain a plasma extraction technology that produces a small, reproducible aliquot of plasma without an energy source or human intervention. Moreover, 2.5 or 6 �L plasma samples collected in this manner can be transported dry on a collection disc to a central laboratory by courier or mail. The technology proposed to accomplish this is based on blood fractionation by frontal loading of a miniature assemblage of membranes where plasma is transported through multiple membrane layers by capillary action. Blood cells are removed via a combination of adsorption and filtration as plasma migrates to a 6.4 mm diameter collection disc at the bottom of the membrane stack during roughly three min. Stripping (delaminating) the upper, cell bearing membrane layers from the system exposes the plasma loaded collection disc which dries in roughly 10 min. These dried samples can be transported from almost anywhere in to world to a laboratory for analysis within 24 hr. This plasma extraction technology is being developed and validated as component of a mass spectrometry (MS) analysis of vitamin D analogues. As part of the vitamin D test proposed and developed in Phase I, a reagent was developed (SecoSET) that derivatizes vitamin D species with high selectivity. The function of SecoSET is to impart a permanent positive charge to vitamin D species that increases their ionization efficiency in electrospray ionization MS and concomitantly reduces their LOQ.

描述(申请人提供)：大多数临床化验都是从实验室采血开始的。盖茨基金会和许多其他基金会已经认识到并试图解决这样一个事实，即在世界上的大部分地区，临床测试都是在原始的环境中进行的。在许多医疗机构，甚至在美国，让抽血师在实验室采集血液以准备血清或血浆进行分析的奢侈做法并不普遍。这一提议最重要的组成部分是，世界将获得一种血浆提取技术，这种技术可以在没有能源或人工干预的情况下产生小的、可重复的等量血浆。此外，通过这种方式采集的2.5%或6�L血浆样本可以通过快递或邮件的方式在采集盘上干燥地运送到中心实验室。提出的实现这一目标的技术是基于血液分离，通过正面加载微型膜组件，其中血浆通过毛细管作用通过多个膜层传输。在大约三分钟内，随着血浆迁移到位于膜堆底部的直径6.4 mm的收集盘上，血细胞通过吸附和过滤的组合被去除。从系统中剥离(分层)上层细胞承载的膜层使等离子体加载的收集盘暴露，该收集盘在大约10分钟内干燥。这些干燥的样品可以在24小时内从世界上几乎任何地方运送到实验室进行分析。这种血浆提取技术正在开发中，并作为维生素D类似物的质谱仪(MS)分析的组成部分得到验证。作为第一阶段提出和开发的维生素D测试的一部分，开发了一种试剂(SecoSET)，它可以高选择性地衍生维生素D物种。SecoSET的作用是给维生素D物种一个永久的正电荷，从而提高它们在电喷雾电离MS中的电离效率，同时降低它们的LOQ。