Multi-dimensional TOF-SIMS analysis for effective profiling of disease-related ions from the tissue surface

Area of Science:

• Biomolecular analysis
• Mass spectrometry
• Medical diagnostics

Background:

• Time-of-flight secondary ion mass spectrometry (TOF-SIMS) is vital for identifying disease-indicative molecules on tissue surfaces.
• Enhanced ionization is crucial for TOF-SIMS to detect more ions, but systematic exploration of enhancement methods is lacking.

Purpose of the Study:

• To introduce and evaluate a multi-dimensional SIMS (MD-SIMS) approach.
• To assess the combined utility of TOF-SIMS and metal-assisted SIMS (MetA-SIMS) for enhanced disease biomarker detection.

Main Methods:

• Developed and applied MD-SIMS, integrating conventional TOF-SIMS with MetA-SIMS.
• Analyzed paired cancer and adjacent normal tissue samples using both TOF-SIMS and MetA-SIMS sequentially.

Main Results:

• MetA-SIMS detected more unique ions (533) compared to TOF-SIMS (206).
• Of commonly detected ions, 250 showed increased intensity with MetA-SIMS, aiding cancer vs. normal tissue discrimination.
• MD-SIMS analysis yielded a greater number of discriminatory ions, improving tissue separation.

Conclusions:

• MD-SIMS offers a comprehensive strategy for identifying disease-specific ions.
• This integrated approach enhances the sensitivity and specificity of TOF-SIMS for biomarker discovery in patient tissues.