Fast and ultra-sensitive screening of PFAS in surface waters using a novel TIMS-QTOF MS and large volume injection

Significance of the topic

Per- and polyfluoroalkyl substances (PFAS) are persistent, bioaccumulative environmental contaminants of high concern for human health and ecosystems. Sensitive and comprehensive screening methods are essential for monitoring low-concentration PFAS in surface waters, supporting regulatory compliance, source tracking, and identification of emerging PFAS and degradation products that are not covered by targeted lists. Combining high sensitivity with non-targeted capabilities improves detection breadth and informs remediation and policy decisions.

Study objectives and overview

This study evaluated a new small-molecule trapped ion mobility spectrometry quadrupole time-of-flight platform (timsMetabo, Bruker) and an associated non-targeted workflow for fast, ultra-sensitive screening of PFAS in surface water. The aims were to (1) assess sensitivity (LOD/LOQ) for regulated PFAS using large-volume injection without time-consuming solid-phase extraction (SPE), (2) evaluate novel instrument modes and acquisition strategies to expand mass/mobility coverage and spectral richness, and (3) demonstrate application to real-world surface water samples from an 18-site survey, including detection of precursors and degradation products beyond routine targeted lists.

Methods and workflow

Samples and standards:

• A 40-compound regulated PFAS mix (Wellington EPA-1633STK) was spiked into surface water and pure water in a dilution series (0.1–100 ng/L) to determine LODs and LOQs.
• Surface water samples from 18 sites (recent Dutch study) were analyzed for real-world evaluation and non-target screening.

Chromatography and injection:

• Bruker Elute+ SL UHPLC system with large-volume injection (100 µL) and a rapid 9.6-minute gradient.
• Analytical column: Phenomenex Gemini C18, 3 µm, 50 × 2.0 mm; Restek delay column used to minimize background contamination.
• Mobile phases: 2 mM ammonium acetate in water (A) and 2 mM ammonium acetate in methanol (B); column oven at 40 °C.

Mass spectrometry and acquisition strategies:

• Instrument: Bruker timsMetabo (small-molecule TIMS-QTOF), evaluated alongside timsTOF Pro 2 in related work.
• Ion source: VIP-HESI, operated in negative mode for PFAS analysis.
• Scan modes: TIMS-bbCID and PASEF/TIMS-DDA-MoRE (Mobility Range Enhancement), scan range m/z 30–1,000.
• Collision energy (CE) sweeping approach (continuous sweep from 10 to 70 eV and narrower 10–30 eV ranges) was applied to generate richer MS/MS spectra compared with conventional stepped CE.
• Data processing: MetaboScape for non-target workflows; Bruker TASQ used for targeted calibration/quantitation.

Non-target workflow:

• Data acquisition used TIMS-DDA-MoRE or PASEF for data-dependent MS/MS collection across mobility space.
• Athena Ion Processor (AIP) and MetaboScape facilitated feature extraction, library matching (regulated PFAS), suspect screening, and de novo annotation of unknown features.

Instrumentation used

• Bruker timsMetabo (TIMS-QTOF small-molecule platform) and timsTOF Pro 2 (comparison study).
• Bruker Elute+ SL UHPLC with large-volume injection capability.
• Phenomenex Gemini C18 column (3 µm, 50 × 2.0 mm) and Restek delay column (5 µm, 50 × 2.1 mm).
• VIP-HESI ion source (negative ion mode).
• Acquisition modes: TIMS-bbCID, PASEF/TIMS-DDA-MoRE, and Mobility Range Enhancement (MoRE).
• Software and processing: MetaboScape, Athena Ion Processor (AIP), TASQ for calibration/quantitation.

Main results and discussion

Analytical performance:

• Limits of detection (LODs) reached as low as 0.1 ng/L (ppt) for 23 PFAS, including PFNA; 33 compounds had LODs ≤0.3 ng/L; 37 compounds ≤1 ng/L. LOQs were determined alongside LODs in blank surface water or pure water where matrix contamination prevented determination in surface water.
• CE sweeping (10–70 eV) produced substantially richer and more informative MS/MS spectra than conventional CE stepping, improving confidence in structural annotation across PFAS with diverse fragmentation behavior.

Non-targeted findings in environmental samples:

• A total of 137 features in the surface water samples were annotated as PFAS-related, with site-to-site variability across 18 sampling locations reflecting local sources, use patterns, and infrastructure.
• Higher PFAS molecular diversity was observed at sites 1, 13, and 17; lower diversity at sites 4 and 15.
• Non-target workflows identified multiple PFAS precursors and degradation products not present on current regulatory screening lists—species likely to be missed by targeted LC-TQ methods.

Workflow advantages and limitations:

• Large-volume injection (100 µL) without SPE enabled rapid sample throughput (9.6-minute gradient) while achieving sub-ng/L sensitivity for many regulated PFAS in relatively clean matrices (surface/drinking water).
• Integration of TIMS (ion mobility) with DDA strategies and CE sweeping improved spectral coverage and annotation confidence, aiding de novo identification and library matching.
• Limitations include potential matrix interferences in more complex samples (e.g., wastewater, biosolids) where SPE or cleanup may still be required, and the dependence on spectral libraries and suspect lists for high-confidence identification.

Benefits and practical applications

• Rapid, ultra-sensitive screening of PFAS in surface and drinking water monitoring without routine SPE for simple matrices, enabling higher sample throughput.
• Complementary role to LC-triple quadrupole targeted assays: timsMetabo non-target workflows detect regulated PFAS while also revealing unexpected precursors and degradation products for more complete contamination profiling.
• Enhanced spectral richness from CE sweeping and ion mobility separation increases annotation confidence for regulatory reporting, source identification, and research into PFAS transformation pathways.

Future trends and potential applications

• Broader adoption of ion mobility–enabled high-resolution platforms combined with advanced acquisition strategies (e.g., CE sweeping, MoRE) will improve detection of low-abundance and isomeric PFAS species.
• Machine learning and automated spectral annotation tools integrated with large, curated PFAS libraries will accelerate non-target identification and reduce manual validation effort.
• Standardization of non-target workflows and inter-laboratory studies will be necessary for regulatory acceptance and routine monitoring implementation.
• For complex matrices, hybrid approaches that combine high-sensitivity direct injection for simple matrices and selective SPE/enrichment for challenging samples will be optimized.
• Expansion of suspect/list databases to include newly discovered precursors and degradants identified by non-target studies will inform monitoring and risk assessment.

Conclusions

The timsMetabo TIMS-QTOF platform with Mobility Range Enhancement, Athena Ion Processor, and collision energy sweeping enables fast, ultra-sensitive PFAS screening in surface waters. Large-volume injection coupled with a short UHPLC gradient provided sub-ng/L LODs for many regulated PFAS while non-target workflows annotated numerous additional PFAS-related features, including precursors and degradation products not covered by routine targeted lists. The approach offers a powerful complement to targeted LC-TQ analyses for environmental monitoring and research, with continued need for matrix-specific validation and library development.

References

1. Liwara et al., Comprehensive PFAS screening of Dutch surface waters using timsTOF Pro 2 and PASEF, Environmental Pollution, 2026, DOI: 10.1016/j.envpol.2026.127846.
2. Wellington Laboratories, EPA-1633 Standard (EPA-1633STK) PFAS standard mix (used for LOD/LOQ determination).