Collision Cross Section Measurements Using Fourier Transform Ion Cyclotron Resonance Techniques

在化学系化学测量和成像项目的支持下，杨百翰大学的大卫·迪尔登和马修·阿斯普伦德教授和他们的学生正在设计一种新的方法来测量分子的形状，包括蛋白质等生物分子的折叠方式。虽然存在用于此类测量的高超技术，但这些技术需要专门的仪器。该团队正在开发新的技术，将这些功能扩展到现有仪器的另一类，只需最少的修改，使这些测量更广泛地可用。他们的方法还可能为某些应用程序提供增强的性能。这些测量很重要，因为就像畸形、错误折叠的降落伞可能无法正确展开一样，错误折叠的蛋白质分子(例如)不能正常工作，被认为是阿尔茨海默氏症？S或帕金森症？S等衰弱疾病的根本原因之一。对形状的灵敏检测对于了解分子是如何结合在一起和发挥作用以及在分子水平上可能出现什么问题至关重要。进行这项工作的学生将接受21世纪科学的基本技能培训，21世纪的科学是美国经济的基础。在这个项目中，研究生和本科生正在开发旨在测量气相离子碰撞截面的技术，而不需要专用的离子迁移率仪器。对这些测量采取了两种独立的方法。第一个研究是在傅里叶变换离子回旋共振质谱仪(FTICR/MS)中，当离子从相干轨道系综中散射出来时，信号的衰减。衰减率(以及相应的FTICR线宽)取决于碰撞横截面。第二种方法测量用来激发离子的射频电场和存在缓冲气体时的离子运动之间的相位滞后。这种方法克服了线宽方法固有的质量比和能量限制。通过研究超分子化学和结构生物化学中的问题，证明了这些技术的实用性。在这项工作的过程中，研究生接受高性能质谱学先进技术的培训，这些技术对生物技术行业和新兴的蛋白质组学领域至关重要。从事这项研究的许多有才华的本科生后来都攻读了研究生课程。这项研究中使用的仪器也可用于杨百翰大学的普通本科课程、分析化学和物理化学课程，该大学是美国研究生项目的化学和生物化学学士学生的重要提供者。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

With support from the Chemical Measurement and Imaging program in the Chemistry Division, Professors David Dearden and Matthew Asplund of Brigham Young University and their students are devising a new approach to measuring the shapes of molecules, including the way that biological molecules like proteins are folded. While superb techniques exist for such measurements, those techniques require specialized instrumentation. This team is developing new techniques to extend these capabilities to an additional class of existing instrumentation with only minimal modification, making these measurements more widely available. Their approach may also offer enhanced performance for some applications. These measurements are important because just as a misshapen, misfolded parachute may not unfurl correctly, misfolded protein molecules (for example) do not function properly and are believed to be among the root causes of debilitating conditions like Alzheimer?s or Parkinson?s diseases. Sensitive detection of the shape is essential to understanding how molecules fit together and function, and what can go wrong at the molecular level. Students carrying out this work are trained in skills essential to the 21st century science that is the foundation of the U.S. economy.In this project, graduate and undergraduate students are developing techniques designed to measure the collision cross sections of gas phase ions, without requiring a dedicated ion mobility instrument. Two independent approaches to these measurements are taken. The first examines signal decay as ions are scattered out of a coherently-orbiting ensemble in a Fourier transform ion cyclotron resonance mass spectrometer (FTICR/MS). The decay rate (and the corresponding FTICR linewidth) depends on the collision cross section. The second approach measures the phase lag between the radiofrequency electric field used to excite the ions and the ion motion in the presence of a damping buffer gas. This approach overcomes mass-to-charge and energy limits that are inherent in the linewidth method. The utility of these techniques is demonstrated by examining problems in supramolecular chemistry and structural biochemistry. In the course of this work, graduate students are trained in advanced techniques for high performance mass spectrometry that are vital for the biotechnology industry and the emerging field of proteomics. Many of the talented undergraduate students engaged in this research subsequently pursue graduate studies. The instrumentation used in this study is also made available for undergraduate courses in general, analytical and physical chemistry at BYU, which is a significant supplier of B.S. chemistry and biochemistry students to U.S. graduate programs.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.