Instrument Development: A New Digitally Driven Triple Quadrupole Mass Spectrometer

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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.