Next Generation IMS Instrumentation (pp 331-370)

我们建议更新对国家成像质谱学研究资源的资助 田纳西州纳什维尔范德比尔特大学医学院。上一个资金周期是 在推进IMS技术和将其应用于尖端生物项目方面都非常成功。在……里面 此次更新，我们寻求推动技术进步，以提供下一代功能，包括 亚微米空间分辨率、超高灵敏度和易用性工具，将提供给 非专家调查员。这项提议包含两个总体目标。首先，它提出要开创小说先锋 仪器技术、样品制备设备和方法以及数据分析/图像信息学 解决办法。后者是当前研究级IMS仪器的迫切需要，它将是 下一代仪器..其次，这项提议寻求简化整个成像过程，目前 需要专业知识和大量时间才能获得高质量、有意义的结果。实现这些全球目标 AIMS对于将这项技术引入生物和临床实验室具有重要意义。 建议的技术研究与开发(TRD)计划将提供 将满足用户社区当前许多需求的改进。TRD的具体进展 将专注于最大限度地提高仪器的灵敏度和空间分辨率。我们还将开发专业试剂 以及旨在提高敏感度、分子特异性和保存 样品制备和分析过程中的生物分子。我们建议开发下一代成像质量 常规使用的光谱仪，能够在高灵敏度下实现500 nm的空间分辨率。 此外，我们将开发能够共同注册和查看来自多个 例如通过图像融合过程的IMS和显微镜。最后，我们将开发新的 先进的生物计算算法来挖掘分子模式的成像数据并对图像进行归一化 从大型数据集中。这些正在开发的先进技术将集中在推动生物医学的重要领域 传染病、眼病、糖尿病和癌症项目(DBP)。 该资源的重要活动包括：与NIH的研究人员进行精选合作 受资助的研究项目将从发展中的IMS技术中受益匪浅。这包括 高空间分辨率成像、高质量分辨率仪器和先进的数据分析和 信息学能力。技术的培训和传播将继续通过以下方式完成 一年四天的现场培训课程，名为AIMS(高级成像质谱学)。此外, 培训和传播将通过接待个别访问调查人员、学生和研究员进行，以及 通过发表技术及其应用的研究成果，以及来自个人的 由该资源的教职员工举办的特邀研究讲座。

We propose to renew funding for the National Research Resource for Imaging Mass Spectrometry (IMS) at Vanderbilt University School of Medicine, Nashville TN. The previous funding cycle has been extremely successful in both advancing IMS technology and applying it to cutting edge biological projects. In this renewal, we seek to advance the technology to provide next generation capabilities that will encompass sub-micron spatial resolution, ultra-high sensitivity, and ease of use tools that will be made available to the non-expert investigator. This proposal contains two overarching aims. First, it proposes to pioneer novel instrument technologies, sample preparation devices and methods, and data analysis/image informatics solutions. The latter is a critical need for current research grade IMS instrumentation, and it will be essential for next-generation instruments.. Second, this proposal seeks to simplify the entire imaging process that currently requires expertise and significant time to get high quality, meaningful results. Achievement of these global aims is important to bring this technology into the biological and clinical laboratory. The proposed Technology Research & Development (TRD) program will provide performance improvements that will meet many of the current needs of the user community. Specific TRD advancements will focus on maximizing instrument sensitivity and spatial resolution. We will also develop specialty reagents and methodologies designed to enhance sensitivity, molecular specificity, and preserve the location of biomolecules during sample preparation and analysis. We propose to develop a next generation imaging mass spectrometer for routine use that is capable of achieving 500 nm spatial resolution at high sensitivity. Additionally, we will develop software capable of co-registering and viewing imaging data from multiple modalities such as IMS and microscopy through an image fusion process. Finally, we will develop new advanced bio-computational algorithms to mine imaging data for molecular patterns and to normalize images from large datasets. These developing advanced technologies will be focused on important driving biomedical projects (DBPs) in infectious disease, eye disease, diabetes, and cancer. Important activities of the Resource include: selected collaborations with investigators who have NIH sponsored research projects that would significantly benefit from the developing IMS technology. This includes high spatial resolution imaging, high mass resolving power instrumentation and advanced data analysis and informatics capabilities. Training and dissemination of the technology will continue to be accomplished through a yearly on-site four day training course termed AIMS (Advanced Imaging Mass Spectrometry). In addition, training and dissemination will occur through hosting individual visiting investigators, students, and fellows, and through publication of the research outcomes for both the technology and its applications, and from individual invited research lectures presented by the faculty of the Resource.