Instrument Development: A New Digitally Driven Triple Quadrupole Mass Spectrometer

在化学系化学测量和成像项目的支持下，华盛顿州立大学的Peter Reilly教授和他的团队正在设计和改进生物和化学分析方法，将一种重要的分析方法“质谱法”从模拟操作转换为数字操作。其目的是扩大适用性和提高结果的质量，与将电话从模拟转换为数字所带来的改进相媲美。该项目的重点是一种被称为三重四极质谱仪的仪器，这种仪器在医院和医学实验室中经常用于进行诊断测试。数字转换旨在通过提高仪器的速度、分辨率、质量范围和灵敏度来扩大可执行的测试的数量和类型。除了这项提议的重要科学目标之外，培养高技能的仪器科学家是一个新兴的国家需求，将通过这项努力和由此产生的合作来解决。Reilly小组发明了一种新的数字波形生成方法，他们最近用于开发数字质量滤波器。与传统的模拟分析仪（即正弦）相比，数字滤波器可以在更高的稳定区域工作，而不会损失质量范围，与商用同类产品相比，提供更好的灵敏度，分辨率和分析速度。他们现在正在使用数字波形技术创建一个数字三重四极质谱仪（DQ3MS），通过提高m/z（质量：电荷比）3000 （Q3MS可访问）的性能和扩展可访问的m/z范围，两者都优于商用仪器（Q3MS）。这将大大扩大串联质谱（MS/MS）可以分析的生物分子的范围和类型。需要开发具有更大质量范围的仪器来直接和快速地测量和量化表达蛋白的分布，分析复合物及其相互作用。数字驱动质谱仪有望提高以生物为基础的科学的发现速度。这项工作的预期效益包括：1)培训和教育分析化学和生物质谱领域的未来科学家，2)改变用质谱分析生物分子和粒子的范式，3)通过快速定量生物分子及其相互作用和过程建立分析生物学领域。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值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 Division of Chemistry, Professor Peter Reilly and his group at Washington State University are devising and enhancing methods of biological and chemical analysis by converting an important method of analysis called “mass spectrometry” from analog to digital operation. The aim is to expand applicability and to enhance the quality of results, comparable to the improvements derived from the conversion of telephones from analog to digital. The project focuses on a type of instrument called a triple quadrupole mass spectrometer that is routinely used in hospitals and medical laboratories to perform diagnostic tests. The digital conversion seeks to expand the number and types of tests that can be performed by enhancing the instrument’s speed, resolution, mass range, and sensitivity. Beyond the important scientific goals of this proposal, the training of highly skilled instrumentation scientists is an emerging national need that will be addressed by this effort and the collaborations that will result. The Reilly group has invented a new digital waveform generation method that they recently used to develop a digital mass filter. Relative to a conventional analog analyzer (i.e., sine), the digital filter can operate in higher stability zones without loss of mass range, providing significantly better sensitivity, resolution, and speed of analysis compared to commercial counterparts. They are now using the digital waveform technology to create a digital triple quadrupole mass spectrometer (DQ3MS) both to outperform commercial instruments (Q3MS) both by improving performance at m/z (mass:charge ratio) 3000 (accessible by Q3MS) and extending the accessible m/z range. This should substantially expand the range and types of biological molecules that can be analyzed by tandem mass spectrometry (MS/MS). The development of instrumentation with increased mass range is needed to directly and rapidly measure and quantify the distribution of expressed proteins, analyze complexes and their interactions. Digitally driven mass spectrometers are expected to increase the rate of discovery in the biology-based sciences. The anticipated benefits arising from the proposed work include: 1) training and education of future scientists in the area of analytical chemistry and biological mass spectrometry, 2) changing the paradigm for analyzing biological molecules and particles by mass spectrometry, and 3) establishing the area of analytical biology by rapidly quantifying biomolecules, their interactions and processes.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.