Milliplex FlexMAP 3D

描述(由申请人提供)：生物标记物的发现和验证是改进疾病诊断和管理的关键组成部分。在传染病领域，生物标记物对改善医疗保健的巨大影响可以通过艾滋病毒RNA分析来说明。这些检测能够识别处于感染早期阶段的个人，那些有可能更快发展为艾滋病和死亡的人，以及那些抗逆转录病毒治疗(ART)失败的人。在许多其他领域，生物标记物验证的状态还没有接近这样的成功水平。例如，最近的数据已经确定，大约一半的艾滋病毒携带者(PLWH)患有艾滋病毒相关的神经认知障碍(HAND)，尽管检测不到艾滋病毒RNA水平，这清楚地表明需要新的生物标志物来提高对发病机制和临床管理的理解。UCSD HIV神经行为研究中心(HNRC)二十多年来一直是神经艾滋病领域的领先者，并发表了重要的生物标记物发现，包括将生物标记物与手和ART的变化联系起来的数据。HNRC拥有大量的数据和标本，这些数据和标本来自长期的重点工作，这将作为正在进行的生物标记工作的基础，包括现有的NIH资助的项目。该奖项的主要目标将是使用现代测量方法来识别生物标记物，这些生物标记物将有利于疾病的诊断和管理，特别是艾滋病毒的神经并发症。这项共享仪器赠款的主要科学目标将是识别和验证生物标记物，这些生物标记物将为手部和重要的神经毒性并存疾病的发病机制和临床管理提供信息，如合并感染和药物使用。主要的服务目标将是支持加州大学圣地亚哥分校的其他项目，不仅通过与其他研究人员共享仪器，而且通过提供分析性能、标本管理和数据分析方面的专业知识。所选择的购买仪器是米利波尔FlexMAP 3D分析系统。该系统包括一个多路悬浮阵列读取器，一个自动洗板机，以及专门的软件来校准仪器和读取结果。与较旧的悬浮阵列系统相比，FlexMAP 3D每孔能够测量更多的分析物，具有更高的精确度、显著扩展的动态范围和更高的吞吐量。总而言之，这些属性将提高我们分析的准确性，同时更好地保存我们宝贵的标本资源，并实现更有效的时间管理。如果成功，这一奖项将导致更好地了解疾病如何损害大脑，将识别预测手部风险的生物标记物，并改善对这种疾病和其他疾病的管理。

DESCRIPTION (provided by applicant): Biomarker discovery and validation is a critical component for improving diagnosis and management of diseases. In the field of Infectious Diseases, the dramatic impact that biomarkers can have on improving medical care can be illustrated by HIV RNA assays. These assays have enabled identification of individuals at very early stages of infection, those at risk for more rapid progression to AIDS and death, and those who fail antiretroviral therapy (ART). The state of biomarker validation in many other areas has not approached this level of success. For example, recent data have identified that approximately half of people living with HIV (PLWH) have HIV-associated neurocognitive disorders (HAND) despite undetectable HIV RNA levels, clearly indicating the need for new biomarkers to improve understanding of pathogenesis and clinical management. The UCSD HIV Neurobehavioral Research Center (HNRC) has been a leader in NeuroAIDS for more than two decades and has published important biomarker findings, including data linking biomarkers to HAND and changes with ART. The HNRC has a large repository of data and specimens from this long period of focused work and this will serve as the basis for ongoing biomarker work, including existing, NIH-funded projects. The overarching aim of this award will be to use modern measurement methods to identify biomarkers that will favorably impact diagnosis and management of diseases, particularly neurologic complications of HIV. The primary scientific objective of this Shared Instrumentation Grant will be to identify and validate biomarkers that will inform pathogenesis and clinical management of HAND and important neurotoxic comorbid conditions, such as co-infections and substance use. The primary service objective will be to support other projects at UCSD, not only by sharing the instrument with other investigators but by providing expertise in assay performance, specimen management, and data analysis. The selected instrument for purchase is the Millipore FlexMAP 3D assay system. The system includes a multiplex suspension array reader, an automated plate washer, and specialized software to calibrate the instrument and read results. Compared with older suspension array systems, the FlexMAP 3D is capable of measuring substantially more analytes per well, has much improved accuracy, substantially expanded dynamic range, and higher throughput. Together, these attributes will improve the accuracy of our analyses while better conserving our precious specimen resource and enabling more efficient time management. If successful, this award will lead to better understanding of how diseases injure the brain, will identify biomarkers that predict risk for HAND, and improve the management of this condition and others.