SinS 2025: QTOF platforms see enhanced structural analysis through modulation-based 2D mass spectrometry 

Dr Steven Wright, principal scientist at Verdel Instruments, presented his technically ambitious approach to improve structural elucidation in complex chemical mixtures using quadrupole time-of-flight (QTOF) mass spectrometry. Speaking at the Solutions in Science 2025 conference in Brighton, UK, Dr Wright described how his team has retrofitted standard QTOF hardware with a modulation-based system adapted from Fourier transform ion cyclotron resonance (FTICR) techniques.

The aim of the development is to enable higher-confidence fragment–precursor matching without the need to rely on chromatographic separation. The team has introduced a form of ion modulation that encodes the mass-to-charge ratio (m/z) of ions as a modulation frequency, which is preserved through fragmentation. This approach allows fragments to be attributed to their precursors even in highly complex samples, addressing a longstanding challenge in mass spectrometry.

“The fragments of a modulated precursor ion inherit its modulation frequency.

“This gives us a way to extract frequency information from the fragment ions and trace them back to their parent molecules,” explained Wright.

The system records ion signals in the time domain as oscillations induced by radial excitation. These oscillations reflect the m/z of each ion, with lighter ions modulating faster than heavier ones. By applying a Fourier transform to these time-resolved signals, the system maps frequency components directly to ion mass. Fragmentation methods such as collision-induced dissociation and ultraviolet photodissociation (UVPD) have been synchronised with this modulation to preserve the frequency signature during ion breakdown.

In practice, the instrument produces a two-dimensional mass spectrum with conventional m/z on one axis and modulation frequency on the other. Each precursor ion and its fragments form a distinct line in this plot, improving the resolution and interpretability of data. Wright presented examples in which mixtures of peptides that produced congested spectra in one dimension became clearly resolved patterns when visualised as a two-dimensional map.

The team has applied the system to chemically characterise food matrices, including cocoa beans from different geographical regions. Using this method, they have successfully distinguished between shared and origin-specific compounds, demonstrating the technique’s potential for traceability and authenticity testing. In these experiments, modulation separated co-eluting species and allowed fingerprinting without chromatographic pre-treatment.

The approach also supports structural annotation with UVPD, in particular, enabling the identification of peptide fragment ions that are not typically accessible through CID. This includes low-mass fragments and ion types such as w- and a-ions, which has improved the team’s capacity to infer peptide sequence and molecular structure.

Dr Wright highlighted three broader implications of the technology:

It extends the capabilities of existing QTOF systems, allowing laboratories to achieve advanced structural analysis without investing in high-end platforms such as FTICR or Orbitrap.

It reduces the need for chromatographic separation, opening possibilities for high-throughput workflows, especially in applications such as forensic science, metabolomics and food quality control.

It facilitates more powerful data visualisation, with potential for future software tools to extract patterns and automate spectral interpretation.

By encoding structural information in the frequency domain and preserving it through ion fragmentation, Verdel Instruments has introduced a generalisable and retrofittable enhancement to routine mass spectrometry. The work presented suggests that modulation–fragmentation synchrony could become a foundational technique in the interpretation of complex mixtures, with broad applicability and minimal disruption to existing laboratory infrastructure.