Next-Generation Clinical Mass Spectrometry Platform

描述(申请人提供)：质谱学现已成为生物研究实验室的基本工具，被广泛用于鉴定具有临床意义的多肽和蛋白质。然而，在基质辅助激光解吸/电离(MALDI)和电喷雾电离(MALDI)等使能方法问世20多年后，质谱学在蛋白质临床常规检测中的应用只取得了微弱的成功。这在很大程度上可能归因于这样一个事实，即目前没有协调一致的企业系统地定制和生产专门的分析平台和匹配的标准化分析，以满足临床从业者的规格和需求。在这个项目中，我们通过汇集MALDI设计、生产和应用MALDI的先驱-飞行时间质谱学和质谱学免疫分析-这两项技术将结合在一起，形成下一代临床质谱学平台来应对这一问题。这些团队成员还有临床内分泌学和人口蛋白质组学领域的专家，他们的指导对于确定常规临床应用的平台规格和主导分析以及产生数据以支持对蛋白质多样性在人类人口中的重要性的理解至关重要。在这个项目中，一个跨学科的工业和学术团队将设计和建造一个新的、专用的高性能质谱学平台，以满足临床规范，并将其和伴随的标准化分析转化为可在临床研究中使用的工具。这个团队的小企业成员拥有独特的专业知识、知识产权和设施，不仅可以开发新的质谱学平台和分析方法，还可以调集必要的资源，使该项目的结果在第三阶段投入商业使用。该计划的完成将影响(人类人口中蛋白质微异质性)科学知识鸿沟，与基础和临床研究的众多当前和未来的重大研究机会保持一致。此外，还将创建一个可扩展的翻译机制，通过增加对已知临床重要蛋白质以及其他新的候选生物标记物的更多分析，将其扩展到本计划的初始范围之外，并更深入到长期临床市场。因此，我们预计我们的下一代临床质谱学平台将在临床场景中得到更多的使用，其中标准化技术通常应用于已知标记物，以帮助定义病理生物学的潜在疾病、疾病患者的临床状态，并作为目前在全球范围内进行的大量基于蛋白质的发现工作所产生的新型生物标记物先进工作流程的一部分。 与公共健康相关：该计划通过制作一种新的、高信息含量的工具来解决在多肽和蛋白质的基础生物医学研究和临床监测(微观异质性)中经常遇到的重大科学知识差距，从而与公共健康相关。因此，我们预计我们的下一代临床质谱学平台将在当前和未来的临床场景中增加使用，在这些场景中，标准化技术通常应用于标志物，以监测个人的健康状况，帮助了解病理生物学的潜在疾病，并作为目前在全球范围内进行的大量基于蛋白质的发现工作所产生的新生物标志物的工作流程的一部分

DESCRIPTION (provided by applicant): Mass spectrometry is now established as an essential tool in the biological research laboratory and is widely used for characterizing clinicaly significant peptides and proteins. However, more than twenty years after the advent of the enabling approaches of matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization, there has been only marginal success in the implementation of mass spectrometry in routine clinical determination of proteins. In large part, this may be attributed to the fact that t present there is no concerted enterprise that systematically tailors and produces devoted analytical platforms and matched standardized assays to meet the specifications and needs of clinical practitioners. In this project we respond to this problem by assembling pioneers in the design, production and application of MALDI-time-of-flight mass spectrometry and mass spectrometric immunoassay: two technologies that will be combined to form a Next- Generation Clinical Mass Spectrometry Platform. These team members are joined by experts in the fields of Clinical Endocrinology and Population Proteomics, whose guidance is essential in defining platform specifications and lead assays for routine clinical application, as well as for producing the data that underpin an understanding of the importance of protein diversity in the human population. In this project a cross-disciplinary Industrial and Academic team will design and build a new, dedicated high-performance mass spectrometry platform to clinical specifications, and translate it and accompanying standardized assays into tools that can be exploited in clinical research. The small business members of this team possess unique expertise, intellectual property, and facilities not only to develop the new mass spectrometry platform and assays but also to marshall the resources needed to make the results of the project commercially available in phase III. Completion of this Program will impact a Scientific Knowledge Gap (of protein microheterogeneity in human populations) aligned with numerous current and future Significant Research Opportunities in Basic and Clinical Research. Also a scalable Translational Mechanism will be created that expands beyond the initial scope of this Program and deeper into long-term clinical markets by adding more assays towards known clinically significant proteins, as well as other new candidate biomarkers. Consequently, we anticipate the increased use of our Next-Generation Clinical Mass Spectrometry Platform in clinical scenarios where standardized technologies are routinely applied toward known markers to help define pathobiology's underlying disease, the clinical status of individuals with disease, and as part of advanced workflows toward novel biomarkers stemming from numerous protein-based discovery efforts currently ongoing worldwide. PUBLIC HEALTH RELEVANCE: The Program relates to public health by producing a new, high information content tool that addresses a significant scientific knowledge gap commonly encountered in the Basic Biomedical Research and Clinical Monitoring of peptides and proteins (micro heterogeneity). Consequently, we anticipate the increased use of our Next-Generation Clinical Mass Spectrometry Platform in immediate and future clinical scenarios where standardized technologies are routinely applied toward markers to monitor the health status of individuals, to help understand pathobiology's underlying disease, and as part of workflows toward new biomarkers stemming from numerous protein-based discovery efforts currently ongoing worldwide