George Stafford and 25 years of Ion Trap Innovation

Innovation has always been the driver of new technology development at Thermo Fisher Scientific. Valuable contributions from several University collaborators helped George Safford convert this core value into significant contributions to the field of ion trap mass spectrometry over the past 25 years.

Dr. Stafford has relied on two ways to discover or invent new technology: first, pursuing an insightful observation leading to the understanding of an inherent principle and this in turn leading to product development; second, manipulating an existing technology or process in different and completely opposite ways and observing its behavior in an altered state leading to the discovery or invention of a totally new technology. Stafford believes that both of these methods have been instrumental in the development of highly sensitive ion trap mass spectrometers over the last 25 years.

During the late seventies Stafford was working on gas chromatography (GC) chemical ionization (CI) mass spectrometry (MS) at Finnigan Corporation (now part of Thermo Scientific). Professor Donald Hunt at the University of Virginia who served as a consultant to the company had previously proposed to him that using negative CI for molecules such as pesticides may help improving detection limits using a mass spectrometer. While working with negative and positive ions, Stafford stumbled upon a key observation. He observed that the electron multiplier detector was able to identify a negative ion generated by the source, even when the detector was actually set to detect positive ions. This occurred to him when the mass spectra suggested to him that it was indeed that of negative ions albeit with a significantly lower intensity. This led to the insight that after the negative ions passed through and were analyzed by the mass filter; a very small fraction of negative ions would be converted into positive ions because of the RF fringe voltages and thus would be detected by the electron multiplier operating in the positive ion mode. By incorporating a dynode operated at a high DC voltage, Stafford observed that the ions could be intentionally accelerated to hit the surface of the dynode at the exit of the mass filter. He further observed that the efficiency of the positive to negative ion conversion improved by at least a thousand fold. This was an instance where keen observation led to new technology development.

Inspired by Ray March’s talk during the 1979 American Society of Mass Spectrometry (ASMS) conference (Seattle, Washington ) and John Todd’s pioneering work in ion traps, Stafford started working on developing ion trap mass spectrometers. Typically a mass spectrometer detected ions that were transmitted or remained stable through the analyzer. During the summer of 1979, Stafford decided to build and test a conventional quadrupole ion trap, but instead tried to operate it in a different or opposite scan method. Rather than detect stably trapped ions in the quadrupole ion trap, he decided to try the opposite and detect ions that became unstable and were ejected from the ion trap. Stafford figured that by trapping all the ions of interest at once and then scanning the device to cause ions to become sequentially unstable in m/z, he would be able to detect all ions with a much higher sensitivity. This was a completely new paradigm at that time and this innovative approach led to the development of the first commercial ion trap mass spectrometer.

The significance of such technologies pertaining to the development of quadrupole ion traps and electron multiplier ion detectors cannot be less emphasized. Fields of study such as Proteomics have been significantly benefited by the development of ion trap technology that lets researchers detect attomol levels of sample.

Stafford ’s research and development group at Thermo is involved in several collaborations with external scientists to further develop mass spectrometry and associated applications. For instance, many developments have been pioneered by Professors Donald Hunt and Graham Cooks (Purdue University) in the areas of tandem mass spectrometry analysis, mass range, mass resolution and proteomics. Professor Cooks has previously worked and continues to work on developing tandem mass analysis on quadrupole ion trap instruments and devising methods to identify and characterize small molecules and proteins. Professor Cooks is also working on atmospheric pressure ionization techniques for improving protein coverage. Other collaborative projects with Professor Cooks include miniaturization of ion trap mass spectrometers and soft landing of ions on surface in order to help characterization of protein substances. Professor Hunt on the other hand is actively working on improving coverage and lowering detection limits on the Thermo Scientific LTQ™. Professor Hunt is also working on Electron Transfer Dissociation (ETD), a new technique which promises to produce more efficient and more complete product ion spectra. ETD in combination with ion traps has the potential to accelerate the use of Top-Down Proteomics.

These last 25 years have been exciting for Life Science research and much is due to tremendous advances in mass spectrometry technology and in specific ion trap technology. Stafford played a key role in this progression from detecting an unstable ion 25 years ago to the development of the modern day ultra sensitive LTQ linear ion trap. It is only mind-boggling what we can expect to see 25 years from now.