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，方法是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，提高结果质量，与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称为三重四极质谱仪的仪器，该仪器通常用于医院和医学实验室进行诊断测试。 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展可以执行的测试的数量和类型。 除了这项提案的重要科学目标之外，培训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，他们最近使用该方法开发了数字质量滤波器。 相对于传统的模拟分析器（即，正弦），数字滤波器可以在更高的稳定性区工作，而不会损失质量范围，与商业同行相比，提供了更好的灵敏度，分辨率和分析速度。 他们现在正在使用数字波形技术来创建数字三重四极杆质谱仪（DQ 3 MS），通过提高m/z（质荷比）3000（可通过Q3 MS访问）的性能和扩展可访问的m/z范围来超越商业仪器（Q3 MS）。 这将大大扩展可以通过串联质谱法（MS/MS）分析的生物分子的范围和类型。需要开发具有增加的质量范围的仪器，以直接和快速地测量和定量表达的蛋白质的分布，分析复合物及其相互作用。数字驱动的质谱仪有望提高基于生物学的科学的发现率。拟议工作的预期效益包括：1）在分析化学和生物质谱领域对未来科学家的培训和教育，2）改变通过质谱分析生物分子和颗粒的范例，以及3）通过快速定量生物分子建立分析生物学领域，该奖项反映了NSF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.