Toward Single-Molecule Nanomechanical Mass Spectrometry

迈向单分子纳米机械质谱

• 批准号: 6861426
• 负责人: MICHAEL L ROUKES
• 金额: $ 18.27万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6861426
• 关键词: bioengineering /biomedical engineering; biotechnology; electrospray ionization mass spectrometry; mass spectrometry; microfluidics; nanotechnology; proteomics; technology /technique development

DESCRIPTION (provided by applicant): Mass spectrometry (MS) is emerging as one of the most important tools for proteomics. Modern MS protocols, recently developed for identification of low concentration analytes in the presence of very large backgrounds, have been central to many important advances in systems biology. However, these protocols are accompanied with important limitations, especially in terms of their sensitivity and ease of methodology. Advances emerging from nanoscience may offer new approaches to MS. Recently, using nanoelectromechanical systems (NEMS) in vacuo, the proposers have demonstrated mass sensing at the 7 zeptogram level -- the mass of an individual 4 kilodalton molecule. This represents a million-fold improvement over the most recent state-of-the-art laboratory demonstrations using microscale devices, and a billion-fold improvement over commercial devices. Yet the work is still in its infancy; significant further improvements with NEMS are imminent. In this initial (R21) effort, the proposers will make the crucial initial steps to transform this advance in nanoscience into a real technology that is directly applicable to biological mass spectrometry. A significant amount of research will now be required to transform this unprecedented mass sensitivity into a usable and efficient new form of MS. Realizing this transformation is the principal focus and intent of the proposed work. NEMS-MS offers the promise of sensitivity down to the single-molecule level. A new single-molecule, NEMS-based mass spectrometry (NEMS-MS) would enable powerful new assays utilizing extremely minute amounts of precious/rare analyte. In contrast to genomics research -- where gene amplification can produce large amounts of identical analytes enabling more "conventional" MS protocols -- extreme sensitivity is crucial for proteomics. If successful, this exploratory program will provide benchmark demonstrations of single-molecule mass sensing, chart a methodical course toward the realization of single-molecule mass spectrometry for proteomics, and assemble a next-phase effort (R01) for the full realization of this vision. The collaborative team includes some of the forefront practitioners of proteomic-based mass spectrometry, of nanodevice physics and microfluidics, and of novel surface chemistry approaches to MS.

描述（由申请人提供）：质谱（MS）正在成为蛋白质组学最重要的工具之一。现代MS协议，最近开发的低浓度的分析物的存在下，非常大的背景识别，已在系统生物学的许多重要进展的核心。然而，这些协议都伴随着重要的限制，特别是在其灵敏度和方法的易用性。纳米科学的进步可能会为MS提供新的方法。最近，在真空中使用纳米机电系统（NEMS），提案者已经证明了在7 zeptogram水平上的质量传感-单个4千道尔顿分子的质量。这代表了使用微型设备的最新最先进的实验室演示的百万倍改进，以及商业设备的十亿倍改进。然而，这项工作仍处于起步阶段; NEMS的重大进一步改进迫在眉睫。 在这个最初的（R21）努力中，提议者将采取关键的最初步骤，将纳米科学的这一进步转化为直接适用于生物质谱的真实的技术。现在需要大量的研究将这种前所未有的质量敏感性转化为一种可用的和有效的新形式的MS。实现这种转变是拟议工作的主要重点和意图。 NEMS-MS提供了低至单分子水平的灵敏度的承诺。一种新的单分子、基于NEMS的质谱法（NEMS-MS）将能够利用极微量的珍贵/稀有分析物进行强大的新分析。与基因组学研究相反，基因扩增可以产生大量相同的分析物，从而实现更“传统”的MS方案，极端的灵敏度对蛋白质组学至关重要。如果成功的话，这个探索性的计划将提供单分子质量传感的基准演示，绘制实现蛋白质组学单分子质谱的有条不紊的过程，并为全面实现这一愿景组装下一阶段的努力（R 01）。该合作团队包括一些基于蛋白质组学的质谱法，纳米器件物理学和微流体学以及MS的新型表面化学方法的前沿实践者。