Next-Generation Clinical Mass Spectrometry Platform

描述（由申请人提供）：质谱法现已被确立为生物研究实验室中的重要工具，并广泛用于表征临床重要的肽和蛋白质。然而，在基质辅助激光解吸/电离（MALDI）和电喷雾电离等使能方法出现二十多年后，在常规临床蛋白质测定中实施质谱法仅取得了微薄的成功。在很大程度上，这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用的分析平台和匹配的标准化测定，以满足临床从业人员的规格和需求。在这个项目中，我们通过组装MALDI-飞行时间质谱和质谱免疫分析的设计，生产和应用的先驱来应对这个问题：这两种技术将结合起来形成下一代临床质谱平台。这些团队成员由临床内分泌学和群体蛋白质组学领域的专家加入，他们的指导对于定义常规临床应用的平台规范和铅测定以及产生支持理解人类蛋白质多样性重要性的数据至关重要。 在这个项目中，一个跨学科的工业和学术团队将设计和建立一个新的，专用的高性能质谱平台，以临床规范，并将其和配套的标准化分析转化为可以在临床研究中利用的工具。该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平台和分析，还可以马歇尔所需的资源，使项目的结果在第三阶段商业化。该计划的完成将影响科学知识差距（人群中蛋白质微异质性），与基础和临床研究中的许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，通过增加更多针对已知临床重要蛋白质以及其他新的候选生物标志物的检测，扩展到该计划的初始范围之外，并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平台在临床场景中的使用会增加，其中标准化技术通常应用于已知标记物，以帮助确定病理生物学的基础疾病，疾病个体的临床状态，并作为先进工作流程的一部分，从目前全球正在进行的众多基于蛋白质的发现工作中获得新的生物标志物。 公共卫生相关性：该计划涉及公共卫生，通过生产一种新的，高信息含量的工具，解决了在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。因此，我们预计在当前和未来的临床场景中，我们的下一代临床质谱平台的使用将增加，其中标准化技术将常规应用于标记物，以监测个体的健康状况，帮助了解病理生物学的潜在疾病，并作为目前全球正在进行的众多基于蛋白质的发现工作中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