Topspec – Next generation precision antibody profiling – from science fiction to reality

Thermo Fisher Scientific (TF) (Bremen) GmbH/Germany is a world market leader in mass spectrometry. Product lines include high-resolution mass spectrometers (MS) for organic analysis, isotope ratio analysis, elemental analysis, and life science. Following development of breakthrough Hybrid Linear Trap- Orbitrap MS of LTQ Orbitrap family over the last decade, recent products of the company include an Orbitrap-only MS (Exactive Plus, Exactive EMR instruments), Hybrid Quadrupole-Orbitrap MS (Q Exactive family currently containing Q Exactive, Q Exactive Plus, Q Exactive HF, Q Exactive Focus instruments). The team in Bremen works together with a team at Thermo Fisher, San Jose, CA, one of the latest results being launch Tribrid Quadrupole-Linear Trap- Orbitrap instrument Orbitrap Fusion Lumos MS in 2015, Q Exactive HF-X in 2017 and Q Exactive UHMR in 2018. Both sites are also collaborating with the team at Thermo Fisher, Germering, Germany on development on nano- and micro-flow LC.

Key person within TopSpec:

Alexander A Makarov, PhD is Director of Global Research Life Science, Mass Spectrometry (Thermo Fisher Scientific (TFS), Germany, Bremen) and inventor of the Orbitrap mass analyzer. He is also professor of High Resolution Mass Spectrometry at Utrecht University (Netherlands). He has extensive expertise in instrument development and his invention of the Orbitrap mass analyzer in late 90s, changed the field of modern mass spectrometry.

He studied physics at Moscow Physics-Engineering Institute (MPEI) (Russia) where he obtained his pre-doctoral (Physics) and PhD (Physics and mathematics). After defending his PhD thesis in 1992 and joining the General Physics Institute of Russian Academy of Sciences, he became a post-doc in Warwick University where he got involved in tandem mass spectrometry. In 1996, Alexander joined a small high-tech company, HD Technologies, Manchester, UK where he started the concept of the Orbitrap mass analyzer. Proof-of-principle results were presented at the ASMS Conference and the term “Orbitrap analyzer” was used for the first time in 1999. Following the acquisition of HD Technologies by Thermo Corporation in 2000, Alexander concentrated his research on interfacing the analyzer to continuous rather than pulsed ion sources with the practical goal of incorporating an electrospray ion source. This resulted in the commercial release of a new LTQ Orbitrap tandem mass spectrometer in 2005 to the enthusiastic acceptance of the mass spectrometry community, especially by proteomics and metabolomics researchers. At TFS, he has continued to provide scientific guidance on the LTQ Orbitrap family of instruments (XL- 2007, ETD- 2008 Velos- 2009, Velos Pro and Elite -2011), Exactive family (Classic-2008, Plus- 2012, EMR- 2013), iCAP family (Q-2012, TQ- 2017), Q Exactive family (Classic- 2011, Plus- 2013, Focus and HF- 2014, HF-X- 2017, UHMR- 2018), Orbitrap Fusion family (2013, Lumos- 2015).

Pursuing the strategic goal of bringing Orbitrap technology into new analytical applications previously inaccessible to mass spectrometry, Dr. Makarov continues to drive improvements of the technology. This is illustrated by the introduction of a new generation of Orbitrap analyzers and enhanced Fourier transform algorithms.

Main Tasks in TopSpec:

Thermo Fisher Scientific will provide a modified Orbitrap mass spectrometer and will provide a State of the art Q Exactive instrument to the project which will be integrated with the Omni-trap. Thermo Fisher Scientific will also work on ion optics development, instrument control software and will provide expertise in analysis of intact proteins both under native and denaturing conditions.