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A New Era of High Resolution Accurate Mass Quantitation - The SCIEX ZenoTOF 7600 LC-MS/MS system

A New Era of High Resolution Accurate Mass Quantitation - The SCIEX ZenoTOF 7600 LC-MS/MS system
Credit: Sciex


Important considerations for quantitation

A consistent demand on the performance of all mass spectrometers is high sensitivity, and this is why the triple quadrupole (QQQ) is often favored for quantitative workflows. The fact that accurate mass instruments lose sensitivity because of their lower duty cycle is often overlooked. The ZenoTOF 7600 system provides a novel trapping/releasing technology which offers >90% duty cycle over the classical QTOF design shown to boost sensitivity by 4-20x. The high quality MS/MS spectra generated enables confident identification and quantitation of analytes. The wide intra- and inter- scan dynamic range allows low and high abundant analytes to be detected and quantified in the same run, ensuring accuracy and reproducibility of results. 


To provide good quantification, the instrument must scan fast enough so that each analyte is sampled sufficiently. As sample complexity increases, and/or chromatography runs shorten, the probability of co-elution becomes greater so speed is more important. Nominal mass instruments can monitor a great number of MRMs per cycle but not full scan MS/MS data. Some accurate mass instruments can operate at fast scan speeds, and many do by sacrificing MS/MS resolution and sensitivity. An advantage of SCIEX QTOF instruments is that mass resolution, mass accuracy and sensitivity are independent of scan speed.


Co-eluting isobaric analytes, contaminants and high background can also interfere with extraction of analytes when using nominal mass or intact precursor masses from high resolution full scan MS data, even at very high resolution. Using MS/MS level data for peak extraction and integration can greatly improve the quality of the quantification, as these interferences can be virtually eliminated. This enables lower detection and quantification limits and higher quantitative accuracy. 


Simultaneous quantitation and qualification workflows

The power of the Zeno trap can also be coupled with electron activated dissociation (EAD) fragmentation technology. The electron energies used in the novel tunable EAD device on the ZenoTOF 7600 system can be adjusted to suit the precursor of interest. Thus, both singly-charged precursors (such as lipids and metabolites) and multiply-charged precursors, (such as peptides) can be analysed. The ability to rapidly adjust the electron energy makes EAD compatible with fast UHPLC chromatography. 


Fragment-centric workflows are the design philosophy behind SCIEX QTOF instruments, with an aim to provide precise quantification of all molecule types without sacrificing the key fundamentals. Delivering fast scanning without sacrificing resolution or accuracy in either MS or MS/MS, enabling a wide intra- and inter-scan dynamic range (linear dynamic range, or LDR) and providing high sensitivity without compromising other performance specifications. With the introduction of the SCIEX ZenoTOF 7600 system, scientists can now achieve quantitative results at high speeds with high mass accuracy.  


Key features of the ZenoTOF 7600 system

• Overcome QTOF MS/MS duty cycle deficiencies with >90% ions injected into the TOF

• Sensitivity gains of up to 5-20x with Zeno trap pulsing   

• MS/MS scan rates of up to 133Hz   

• Improved high resolution MRM (MRMRHR) workflow

• Electron activated dissociation (EAD) with tunable fragmentation of all molecule types    


Product Specifications
Mass range TOF Mass range of up to 40 kDa. The precursor ion selection has a mass range (m/z) of 5–2,250 Da.
Scan speed TOF MS Maximum up to 25 Hz (25 spectra per second)
Scan speed TOF MS/MS Maximum up to 133 Hz (133 MS/MS spectra per second)
Mass resolution ≥42,000 (FWHM) measured on the (M+6H)6+ charge isotope cluster for bovine insulin at m/z 956
MS/MS duty cycle The instrument contains a Zeno trap that allows a ≥90% duty cycle for TOF MS/MS acquisition. The Zeno trap is available for full-scan MS/MS, MRMHR, Zeno SWATH DIA and IDA/DDA.
inear dynamic range (LDR) positive or negative ≥5 orders of magnitude from the limit of detection (LOD) without a signal reduction for both TOF MS and TOF MS/MS. The dynamic range is dependent on analyte and experimental conditions.
Intra-scan dynamic range Up to 4 orders of magnitude
Mass accuracy, external ≤2 ppm RMS over 12 hours of LC-MS acquisition time
Mass accuracy, internal ≤0.2 ppm absolute error as demonstrated on the m/z 813 fragment ion of Glu-Fibrinopeptide B. ≤0.5 ppm absolute error as demonstrated on the m/z 120 fragment ion of Glu-Fibrinopeptide B.
Mass accuracy, internal positive and negative mode <0.5 ppm RMS error of all peaks combined, when the spectrum has been internally calibrated over a mass range of m/z 100–2,000.
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