The Orbitrap mass analyser is rightfully considered to be one of the newest analysers in mass spectrometry (MS). Its roots, however, can be traced back to 1923 when Kingdon proposed the principle of orbital trapping. Experiments over the decades did show that charged particles could be trapped in electrostatic fields, but from the point of mass separation, all set-ups offered no more than a very basic, low-performance result. This served to limit the application of orbital trapping to spectroscopy, and no attempts of mass analysis were reported in literature.
As Dr. Alexander A. Makarov joined a small high-tech start-up company called HD Technologies (Manchester, UK) in the mid-1990s, the creative “can-do” atmosphere of a young and ambitious team led to the deviation from the beaten path of time-of-flight (TOF) MS. Alexander’s efforts moved towards discovering new ways of reaching high resolution and mass accuracy in MS. Ultimately, this led to the synthesis of the orbital trapping principle with image current detection from Fourier-transform ion cyclotron resonance (FT ICR) MS and injection methods from TOF MS, which later culminated in the first Orbitrap mass analyzer.
With a shortage of funding, winning a small SMART award from the UK government allowed the team to purchase parts for an experimental set-up. This set-up with a laser source was built mostly by Alexander himself with the help of his colleagues including Robert Lawther in engineering, Andy Hoffmann in electronics, and Dr. Steve Davis in science.
1999After the first spectra was obtained in October 1998, this set-up showed increasingly high resolving power with 150,000 reached by the middle of 1999. These results were first reported in 1999 at the annual conference of American Society for Mass Spectrometry in Dallas, TX. However, this trap was only a minor factor in the decision by Thermo Corporation to acquire HD Technologies, a key event in January 2000.
Consequently, Alexander concentrated his efforts on interfacing the Orbitrap mass spectrometer to continuous rather than pulsed ion sources. Work on the Orbitrap was expanded and Mark Hardman was hired to work on the project full-time. A year later, the first data was generated using an external RF-only storage for accumulating large numbers of ions and their rapid injection into the Orbitrap mass analyzer. Further expansion of the research group added such crucial people as Alexander Kholomeev (electronic engineer) and Dr. Eduard Denisov (scientist). Then the team began to concentrate on the ion-optical, mechanical and physical design of the Orbitrap technology platform.
The team faced tough technical challenges with the vacuum, power supplies, detection system, and more. But work continued on the goal of developing a powerful machine that would be useful for practical applications. The team was energized by Thermo’s decision in July of 2002 to close the factory in Manchester and transfer the Orbitrap research and the project team to Bremen, Germany. The efforts of the Masslab group culminated in a working instrument that was moved in January 2003 to the laboratory of Prof. Graham Cooks in Indiana’s Purdue University where the system continues to perform today.
Meanwhile, the team and the Orbitrap project found a good home at Thermo’s Bremen factory. Limitations of axial storage, production challenges, shortcomings of electronics and vacuum technology more than once threatened to limit performance, nevertheless each time the Thermo team invented novel solutions to solve these problems. As the project gained momentum, more indispensable talent joined the group including Dr. Stevan Horning (project manager), Wilko Balschun (mechanical engineer), Oliver Lange (instrument software), Frank Czemper and Oliver Hengelbrock (electronic engineers), Dr. Gerhard Jung and Dr. Kerstin Strupat (scientists), Wilfried Huels (testfield) and others.
Together, the team met the major milestone of the commercial release of a new LTQ Orbitrap tandem mass spectrometer at the June 2005 ASMS Conference in San Antonio, Texas. Thus, the Orbitrap became the first fundamentally new mass analyzer introduced to researchers for more than 20 years. The Orbitrap became an instant success and thousands of these instruments are already being adopted by leading laboratories worldwide.
2007Further extensions of LTQ Orbitrap instrument include options for higher-energy collision dissociation (HCD) in 2007, electron-transfer dissociation (ETD) in 2008/2009, and matrix-assisted laser desorption/ionization (MALDI) in 2008.
Another addition to the family of Orbitrap instruments included a single-stage mass spectrometer, Exactive, launched in 2008.
2011The 2011 introduction of the tandem mass spectrometer, Q Exactive, expanded the reach of Orbitrap-based MS to the benchtop for routine analysis in proteomics along with metabolism, metabolomics, environmental, food and safety analysis. Several hundreds of these instruments are already being used in these fields.
Also introduced in 2011, the next generation Orbitrap Elite and enhanced Fourier transform algorithms allow for increased speed, higher resolving power and improved analysis quality to keep pace with the demands of ultra-high pressure chromatography. In addition, enhancements to the Q Exactive, such as parallel filling and detection along with superimposing several ion species in a single FTMS spectrum, open a new chapter in the development of techniques and entire Fourier transform MS.
Over the coming years, the talented team at the Masslab in Germany will continue to collaborate on advancements to the Orbitrap portfolio so Thermo’s customers have the best tools available for both large and small molecule mass spectrometry applications.