A New Mass Spectrometry Method for Analyzing Complex Samples

Jul 15, 2014
By Spectroscopy Editors

 width=This interview with Steven J. Ray, an Associate Scientist in the Department of Chemistry at Indiana University in Bloomington, Indiana, discusses his work with a new form of mass spectrometry (MS) for analyzing complex samples. Ray's research focuses on time- and polarization-dependent fluorescence spectroscopy, novel sources for atomic emission and atomic and ambient mass spectrometry, various sample introduction systems, and most recently, time-of-flight mass spectrometers for plasma-source and biomolecular MS. He has been selected to receive the 2014 Lester W. Strock Award, which is being given in recognition of a seminal paper published in 2011 (1) that reduced to practice the technique of distance-of-flight (DOF) MS. The award is sponsored by the New England Regional Section of the Society for Applied Spectroscopy and will be formally presented at the SAS National Meeting on September 30, 2014, at the SciX 2014 Conference in Reno, Nevada.

Your 2011 paper on the instrumental implementation of distance-of-flight MS described a new MS method for separating and quantifying components of complex samples (1). How is the DOF approach different from time-of-flight (TOF) mass spectrometry?

Time-of-flight MS accelerates ions to the same energy and then uses the time required for the ions to traverse a field-free region to calculate the mass-to-charge ratio (m/z). In contrast, distance-of-flight MS accelerates all ions to an m/z-dependent velocity and allows them to separate in a field-free region over a fixed time period. Over that period, lighter ions (that is, lower m/z ions) will travel a longer distance than ions of larger m/z. As the name implies, DOF-MS uses the distance an ion travels to measure the ion’s m/z.

What are the advantages of the DOF technique compared with TOF-MS?

The two approaches are really complementary. Like TOF-MS, the DOF-MS approach has a very rapid spectral generation rate, an unrestricted upper mass limit, and a high transmission efficiency; it also permits simultaneous observation of the mass spectrum. However, DOF-MS is capable of physically separating ions of different m/z in space. This means that DOF-MS does require a position-sensitive ion detector, but if that detector is an array, each array element can be tailored to the ion flux of the particular m/z striking it. Further, since DOF-MS measures m/z based on distance, the detector elements need not have a particularly rapid response. Thus, for applications such as isotope-ratio measurement, there is a distinct advantage in the multichannel detector scheme.

What technological advances enabled the construction of the detection system for the DOF-MS approach?

Luckily, DOF-MS has a very simple structure and shares many components with TOF-MS instruments, so we were able to adapt many extant technologies. Perhaps the greatest technological opportunity is in the position-sensitive ion detector. Our group has been working with others at the University of Arizona and Pacific Northwest National Laboratory to develop new detectors for mass spectrometry for some time — the latest is known as the focal plane camera (FPC). The system is a monolithic semiconductor chip possessing an array of ion collection electrodes, each of which is connected to dedicated high-gain current-integration circuit. The development of the focal plane camera with the DOF-MS technique provides a lot of synergy.

Has the DOF-MS system been improved since the publication of the original paper in 2011?

Greatly.  We have begun to understand how to adapt the ion-focusing optics to the requirements of DOF-MS. Continual, stepwise refinement also always helps, and we currently can achieve signal-to-noise ratio (S/N) performance on par with our plasma-source TOF-MS systems.

What impact has the introduction of the DOF technique had in the MS community?

The DOF-MS technique is still in its infancy, so it is difficult to say. Interestingly, and as often happens, the development of DOF-MS has spawned a number of associated projects. For example, our work in DOF-MS led directly to new focusing strategy for TOF-MS that we have termed “Zoom-TOF.” The concept there is to provide enhanced mass resolution over a small window of the overall mass range in TOF-MS by exploiting some of the focusing techniques developed for DOF-MS. Interestingly, by limiting the mass range of interest, Zoom-TOF is able to increase the S/N of the measurement while also improving mass resolving power.

What is the focus of your current research with mass spectrometry, and what are the next steps in your research?

We continue to develop DOF-MS. Most recently, and in collaboration with Professor Chris Enke, originator of the DOF-MS concept, we have adapted the method for use with matrix-assisted laser desorption–ionization (MALDI) for the detection and collection of ions of ultrahigh mass. There are a lot of advantages to the application. Like TOF-MS, DOF-MS has no intrinsic upper mass limit. Just as importantly, the position-sensitive ion detectors we use detect ion charge, and thus have no mass bias associated with them. Finally, the ability to physically separate ions of different m/z means that DOF-MS is well suited to “soft-landing” mass spectrometry. In the soft-landing MS strategy, ions are mass-separated and then collected on a secondary surface for further study by other chemical analysis approaches. Taken together, these factors are quite advantageous for detection, separation, and collection of ions of ultrahigh m/z. We believe the approach holds a great deal of promise.


(1) A.W. Graham, S.J. Ray, C.G. Enke, C.J. Barinaga, D.W. Koppenaal, and G.M. Hieftje, J. Am. Soc. Mass Spectrom. 22(1), 110–117 (2011). Doi: 10.1007/s13361-010-00