MSACL 2016 EU Plenary Abstract

Frontiers of Orbitrap Mass Spectrometry

Alexander Makarov
Thermo Fisher Scientific

Bio: Alexander Makarov was born in a Siberian town of Irkutsk in 1966 and went to study to Moscow Engineering Physics institute where he also obtained his PhD. After 2 post-doc years in Warwick Univ., he joined a small high-tech company HD Technologies in Manchester (UK). There he has started his work on the Orbitrap mass analyzer. Following the acquisition of the firm by Thermo Electron Corp. in 2000, Alexander has provided scientific leadership of the Orbitrap R&D which led to the commercial launch of LTQ Orbitrap mass spectrometer in 2005 and subsequent numerous extensions of this technology. He has received Award for Distinguished Contribution in Mass Spectrometry of ASMS, Science and Technology Award of HUPO, Thomson medal of IMSF and others. His hobbies include traveling, mountain skiing, roller-blading. He holds position of Director of Research, Life Science Mass Spectrometry in Bremen

Authorship: Alexander Makarov
Thermo Fisher Scientific (Bremen) GmbH, Bremen, Germany

Short Abstract

The talk provides an overview of a short but eventful history of Orbitrap mass spectrometry, from laying down the first principles of the technology to its current status in mainstream mass spectrometry as the leading technique for high-resolution, high mass accuracy quantitative analysis. While describing new possibilities arising from the recent extensions of two latest families of instruments, Fusion and (Q) Exactive, a special emphasis is placed on technical solutions that enhance quantitative analysis in these instruments. Future trends and perspectives of Orbitrap mass spectrometry are discussed, particularly in relation to high-throughput clinical analysis.

Long Abstract

The widespread adoption and use of Orbitrap mass spectrometry has been driven by its characteristic ability to acquire high-resolution, high mass accuracy data for qualitative and quantitative analysis. Increasing speed of chromatographic separations imposes ever increasing requirements on throughput of mass spectrometric analysis and demand higher spectral acquisition rates, improved spectral quality and better control of different ion optical devices within mass spectrometers.

The Orbitrap mass analyzer is the first high-performance mass analyzer which employs trapping of ions in electrostatic fields. Originating from an ideal (and therefore never realized) Kingdon trap, this analyzer can provide high performance analytical characteristics only when it is highly integrated with the ion injection process. The advent of pulsed injection from an external ion storage device allowed the Orbitrap analyzer to enter mainstream mass spectrometry, initially as a part of a hybrid instrument. Since its introduction the utility of the Orbitrap has been extended by coupling with additional capabilities such as higher-energy dissociation (HCD), ETD, FAIMS, UVPD, ion mobility and different ionization techniques such as MALDI, in-vacuum EI/CI, APPI, etc.

Recent improvements in these directions are exemplified for Q Exactive and Orbitrap Fusion families of instruments, with numerous new modes of operation enabled by parallelization of detection and ion processing and concerted operation of different ion-optical devices. A special emphasis is made on technical solutions that allow quantitative analysis in these instruments, despite Orbitrap analyzer being of an ion trapping type. New modes of data-independent, targeted and top-down acquisition are overviewed.

It is shown that quantitative analysis in Orbitrap mass spectrometry is now highly feasible due to a unique combination of high space charge capacity of the C-trap, improved control over the number of stored ions, intelligent filling and high sensitivity with built-in high mass accuracy, resolving power and dynamic range of analyzer.

The performance of new Orbitrap-based instruments is described in comparison to their predecessors as well as to time-of-flight and high-field FT-ICR instruments. Examples of instrument application to real-world clinical samples are presented.

In conclusion, future trends and perspectives of Orbitrap mass spectrometry are discussed, including its inroads into emerging areas of mass spectrometric analysis. It is shown that Orbitrap-based mass spectrometers possess compelling potential as an (ultra-) high resolution platform not only for high-end proteomic applications but also for screening, trace and targeted analysis and (in particular) clinical analysis by LC/ and GC/MS.

Financial Disclosure

GrantsyesEU Horizons 2020
SalaryyesThermo Fisher Scientific
Board MemberyesEditorial boards of MCP and other journals
Stockyes Thermo Fisher Scientific
ExpensesyesThermo Fisher Scientific

IP Royalty: yes

IP Desc:from patents at Thermo Fisher Scientific

Planning to mention or discuss specific products or technology of the company(ies) listed above: