Meso Scale Discovery SECTOR Imager 6000

描述（由申请人提供）：本提案的目标是购买最先进的多功能检测系统，用于检测可溶性分子（细胞因子，生长因子，代谢标志物，激素，炎症介质，其他临床标志物），以支持，增强和满足美国国立卫生研究院资助的德克萨斯大学西南分校的一组多个研究人员的专业技术需求。主要用户群体在免疫学、激素产生、细胞信号传导和分化研究以及可溶性因子产生等各个领域进行研究。所有研究人员都需要拟议的仪器，以加强对正在进行的项目中正在解决的问题的科学见解。随着我们对各种疾病的免疫学基础的了解不断加深，越来越清楚的是，免疫细胞群不是同质的，它们以一系列复杂的组合产生细胞因子。这些细胞因子需要以越来越多和深入的方式进行研究，以了解它们在细胞间功能调节以及治疗环境中的确切作用。在生长因子和激素受体的研究中，最近的一些报道表明，这些受体作为传感器可以协调调节控制其配体细胞内水平的基因表达并诱导细胞分化。与细胞因子一样，单个样品（体液、细胞培养上清、细胞裂解液）中存在的分子阵列可能非常复杂。虽然这些分子可以通过传统的酶联免疫吸附试验（ELISA）方法检测，最近也可以通过细胞头阵列系统检测，但在单个样品中同时检测多个分子是不可能的，特别是在少量可用于评估的情况下，如在临床/转化研究中经常出现的情况。在这个新系统中，独特的电化学发光检测方法的可用性将允许这种多路分析，并大大增加我们对各种细胞类型和可溶性分子及其受体之间相互作用的理解。此外，生物信息学还可以对多参数数据进行强大的利用和分析。我们在这里提出了我们提案的理由和基本原理，引用了各种具体的例子，说明该工具将如何为正在进行的美国国立卫生研究院资助的研究提供更深入的见解，并概述了将使NCRR SIG计划顺利实施的强有力的机构承诺。

DESCRIPTION (provided by applicant): The objectives of this proposal are to purchase a state-of-the-art multiplex assay system for the detection of soluble molecules (cytokines, growth factors, metabolic markers, hormones, mediators of inflammation, other clinical markers) in order to support, enhance and fulfill the specialized technologic needs of a group of multiple NIH-funded researchers at UT Southwestern. The major user group conducts research in varied areas of immunology, hormone production, studies of cell signaling and differentiation, and soluble factor production. All investigators require the proposed instrument in order to enhance scientific insight into the questions being addressed in ongoing projects. As our understanding of the immunologic basis of various disease situations grows, it is becoming increasingly clear that populations of immune cells are not homogeneous and produce cytokines in a complex array of combinations. These cytokines need to be studied in an increasingly multiplexed and in depth fashion in order to understand their precise role in intercellular modulation of function as well as in therapeutic settings. In the study of growth factor and hormone receptors, several recent reports indicate that these receptors serve as sensors that can coordinately regulate the expression of genes controlling the intracellular levels of their ligands and induce cell differentiation. As with cytokines, the array of molecules present in a single sample (body fluid, cell culture supernatant, cell lysate) can be extraordinarily complex. While these molecules can be detected by conventional ELISA methods and, more recently, by cytometric bead array systems, robust simultaneous detection of multiple molecules in a single sample has not been possible, especially where small quantities may be available for evaluation, as is often the case in clinical/translational research. Availability of the unique electrochemiluminescence detection methodology in this novel system will allow such multiplexed analyses and add substantially to our understanding of the interplay between various cell types and a host of soluble molecules and their receptors. In addition, powerful utilization and analysis of multi-parametric data can be attained through bioinformatics. We present here the justification and rationale for our proposal, cite various specific examples of how the instrument would provide greater insight into ongoing NIH-funded research and outline the strong institutional commitment that will enable the smooth implementation of the NCRR SIG program. PROJECT NARRATIVE: Analysis of soluble molecules is a critical component of contemporary basic, translational, and clinical research. However, the ability to dissect complex biological fluids is hampered by inadequate methods. We propose to purchase the Meso Scale Discovery SECTOR(r)Imager 6000 reader. The instrument has multiplexing, wide dynamic range, sensitivity, and high throughput capabilities that are not present on currently available instrumentation at UT Southwestern or on other instruments in the market. The instrument is unique in its ability to simultaneously analyze multiple soluble molecules present in a wide variety of samples