Time-of-Flight MS
Time-of-flight mass spectrometers (TOF MS) are widely used analytical instruments in life science research. As the name suggests, they determine an ion’s mass-to-charge ratio (m/z) by measuring the time it takes to travel through the instrument’s flight tube and reach the detector. TOF MS can operate in different configurations, including single-stage instruments, multi-stage TOF/TOF systems, and hybrid quadrupole-TOF (Q-TOF) instruments. In a TOF analyzer, ions are accelerated under defined kinetic energy toward a detector, either in a straight beam or via reflection. The flight time, over a fixed distance, is directly related to the ion’s m/z, generating a spectrum that allows compound identification. Modern TOF instruments are often coupled with gas chromatography (GC-TOF), matrix-assisted laser desorption ionization (MALDI-TOF), or other analyzers such as quadrupoles.read more
Key Features
- TOF mass spectrometers are equipped with two detectors: a linear detector positioned at the end of the flight tube and a reflector detector that collects ions redirected by a reflectron. The reflectron functions both to correct variations in the initial kinetic energy of ions with the same mass, preventing shifts in their apparent m/z, and to extend the ion flight path, thereby enhancing resolution.
- TOF can be equipped with MALDI-2 technology, a post-ionization technique that significantly boosts ion yields while reducing ion suppression effects, delivering signal intensities up to 1–3 orders of magnitude higher than conventional MALDI experiments.
- At the heart of specific TOF systems lies the innovative N-optic TOF design, engineered to deliver superior mass accuracy and resolution. By minimizing measurement variability and ensuring consistent ion transmission, the N-optic design provides researchers with confidence in both routine analyses and advanced workflows, even when working with highly heterogeneous biologics.
- A novel ion path and detector design delivers femtogram-level sensitivity within a compact footprint, while maintaining long-term robustness and reliability through advanced ion source technology, wide dynamic range, and extended detector protection.
- An integrated ambient ionization source enables direct analysis of samples in their native state with little or no preparation, providing clean, high-resolution, and reproducible mass spectra.
- Ultrahigh resolving power of over 75,000 across a wide mass range, combined with sub-ppm mass accuracy, ensures precise precursor selection and reliable fragmentation without artifacts.
Applications
- Structural characterization of biologics: TOF MS is widely applied in the biopharmaceutical field, including top-down sequencing of biotherapeutics and biosimilars, glycan structure analysis and confirmation, and the determination and localization of disulfide, scrambled, or trisulfide bonds. Optimized for intact mass analysis, subunit analysis, and high-quality peptide mapping, this system enables detailed structural assessment of biotherapeutics to support development, quality control, and regulatory compliance.
- Spatially resolved multi-omics analysis: The TOF MS enables comprehensive molecular profiling across multiple omics workflows by combining high-speed, high-sensitivity electrospray ionization (ESI) with high-resolution MALDI imaging. This dual capability supports applications such as spatially resolved molecular distribution studies, biomarker discovery, tissue-based metabolomics, and integrated proteomics, lipidomics, and glycomics analyses, providing both structural and spatial insights into complex biological samples.
- Intact mass analysis for biotherapeutic characterization: One of the most impactful applications of the TOF system is in intact mass analysis. This workflow allows scientists to rapidly assess the complete molecular weight of biotherapeutics without the need for extensive sample preparation or digestion. By delivering high-resolution spectra, the system enables detection of subtle mass shifts that may result from glycosylation, oxidation, or other post-translational modifications. Such insights are critical for confirming molecular integrity, evaluating product consistency across manufacturing lots, and ensuring regulatory compliance. The ability to perform intact mass analysis on a compact benchtop system not only simplifies laboratory workflows but also accelerates decision-making in biopharmaceutical development.
- Overcoming duty cycle limitations for enhanced sensitivity: The integration of pulsed ion injection enables more than 90% of ions to be injected into the analyzer, delivering up to 5–20× sensitivity gains. This breakthrough overcomes traditional MS/MS duty cycle limitations, allowing confident identification and quantification of low-abundance species across diverse molecular classes.
- High-sensitivity detection for complex sample analysis: Ideal for non-targeted analysis of complex matrices, TOF MS allows researchers in fields such as environmental monitoring, food safety, and pharmaceuticals to uncover low-abundance compounds with high confidence and rich spectral detail.
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