Advanced ICP-MS techniques for overcoming interferences in LA-ICP-MS bioimaging

Importance of the Topic

Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has become a cornerstone technique in life sciences, particularly in metallomics, due to its ability to map trace elements with high sensitivity and spatial resolution. However, isobaric and polyatomic interferences frequently compromise elemental images, leading to false positives or loss of structural detail. Incorporating triple quadrupole ICP-MS (TQ-ICP-MS) alleviates these issues by selectively removing interfering species, thereby enhancing image contrast and analytical confidence.

Study Objectives and Overview

The main goal of this work was to demonstrate the advantages of triple quadrupole (TQ-O2) over single quadrupole (SQ-O2 and SQ-KED) modes for bioimaging by LA-ICP-MS. The study compares elemental distribution maps of phosphorous, sulfur, calcium, iron, selenium and sodium in plant and animal thin sections, highlighting improvements in interference removal and sensitivity.

Methodology and Instrumentation

The analytical platform consisted of a Teledyne CETAC LSX-213 G2+ laser ablation system coupled to a Thermo Scientific iCAP TQe ICP-MS. Instrument parameters were optimized via Qtegra ISDS autotune for efficient sample introduction and reaction cell performance.

• Measurement modes:
   • SQ-O2: single quadrupole with O2 reaction gas
   • SQ-KED: single quadrupole with He collision gas and kinetic energy discrimination
   • TQ-O2: triple quadrupole with O2 reaction gas, Q1 set to analyte mass and Q3 to product mass
  
• Laser settings:
   • Spot size: 25 µm, scan speed 75 µm/s, fluence 4.5 J/m2
   • Ablation cell: HelEx II, carrier He 0.8 L/min, makeup Ar 1 L/min
  
• Sample preparation:
   • Tobacco petioles: embedded in low-Ca hydroxyethyl cellulose, cryosectioned to 30 µm
   • Rat kidneys: fixed in Technovit®, sectioned to 5 µm
   • Rat livers: frozen, cryosectioned to 5 µm
  

Main Results and Discussion

• Tobacco petiole imaging:
 – Phosphorus and sulfur maps showed clear tissue structures in both SQ-O2 and TQ-O2 modes after mass-shift to MO+.
 – Calcium mapping suffered from residual Ar-based interferences in SQ-O2, yielding only hotspot signals. TQ-O2 mode entirely suppressed background, resolving fine trichome and idioblast distributions.

• Rat kidney imaging:
 – In SQ-O2 mode, Fe maps were dominated by 40Ar16O-derived background and Se signals at m/z 77 were too weak for visualization.
 – TQ-O2 enabled use of major isotopes (56Fe→56Fe16O, 80Se→80Se16O) by filtering Ar precursors in Q1, producing high-contrast images of tissue microstructures.

• Rat liver imaging:
 – Na distributions were robust in both SQ-KED and TQ-O2 modes, demonstrating minimal interference for this element.
 – Fe analysis in TQ-O2 on the major isotope achieved ten-fold higher count rates compared to SQ-KED on the minor isotope, illustrating the sensitivity advantage of TQ operation.

Benefits and Practical Applications

The incorporation of triple quadrupole technology into LA-ICP-MS workflows provides:

• Effective removal of isobaric and polyatomic interferences for critical elements (P, S, Ca, Se, Fe)
• Enhanced image contrast and structural detail in biological samples
• Ability to exploit major isotopes for improved sensitivity and quantitation
• Single-mode multi-element imaging without sacrificing spatial resolution

These improvements support applications in cancer research, plant nutrition studies, toxicology, pathology and agricultural analysis.

Future Trends and Opportunities

Emerging directions include:

• Integration of TQ-ICP-MS with complementary imaging modalities (e.g., optical, fluorescence)
• Automation and high-throughput bioimaging for single-cell and subcellular analysis
• Exploration of additional reaction gases to extend interference removal to a broader element range
• Advanced data processing and machine learning for quantitative elemental mapping

Conclusion

This study demonstrates that the Thermo Scientific iCAP TQe ICP-MS paired with LA sampling outperforms conventional single quadrupole approaches in bioimaging. Triple quadrupole operation achieves superior interference removal, higher sensitivity on major isotopes and more detailed elemental distributions, enabling reliable multi-element analysis in thin biological sections.