Single-Molecule Mass Spectrometry Enabled by Nanomechanical Systems (NEMS-MS)

描述（由申请人提供）：质谱法是蛋白质组学最重要的工具之一。特别重要的是，最近实施了新的方案，用于在非常大的背景下鉴定低浓度分析物。基于nems的质谱分析（NEMS-MS）可以为极稀有或稀释的分析物提供补充和强大的新分析方法。如果成功，该计划将与世界蛋白质组质谱领域的杰出领导者密切合作，最终实现生物质谱新方法的原型演示，提供前所未有的分辨率。下面的应用程序显示了实现单分子NEMS-MS的系统过程。我们已经从理论上证明了基于纳米机电系统（NEMS）的质量探测器的固有分辨率远低于1da。这对生物质谱（MS）领域的影响是深远的。继我们成功的r21资助的试点项目之后，我们已经实现了单分子NEMS实时质量检测的首次演示，我们提出了一个为期5年的研究和开发项目（R01），以开发紧凑型，下一代高通量单分子分辨率质谱仪。这些将基于微流体接口NEMS的大规模集成。

DESCRIPTION (provided by applicant): Mass spectrometry is one of the most important tools for proteomics. Especially important are new protocols recently implemented for the identification of low- concentration analytes in the presence of very large backgrounds. NEMS-based mass spectrometry (NEMS-MS) can provide complementary and powerful new assays for extremely rare or dilute analytes. If successful, the proposed program will culminate in prototype demonstrations of new methods for biological mass spectrometry providing unprecedented resolution - carried out in close collaboration with the world's preeminent leaders in the field of proteomic mass spectrometry. The application below charts a methodical course toward the realization of single-molecule NEMS-MS. We have shown theoretically that the intrinsic resolution of nanoelectromechanical systems (NEMS) -based mass detectors is well below 1 Da. For the field of biological mass spectrometry (MS) the implications of this are profound. To follow-on from our successful R21-funded pilot program - in which we have achieved the first demonstration of single-molecule NEMS mass detection in real time - we propose a 5- year research and development program (R01) to develop compact, next-generation, high-throughput mass spectrometers with single-molecule resolution. These will be based on the large-scale integration of microfluidic-interfaced NEMS. PUBLIC HEALTH RELEVANCE: Proteomics is the study of the biological machinery that underlies all life processes - and it is key to biomedical and pharmaceutical research. The paramount tool for protein identification is mass spectrometry (MS), but existing tools typically work only if hundreds of millions of identical molecules can be extracted from cell cultures for analysis. This project proposes to develop a new technique from nanoscience, already validated in prototype form, allowing MS studies at the single-molecule level that will unambiguously elucidate the details of biochemical networks that give cells their function.