Cocktail Effect in High-Entropy Oxide (FeCoNiCuZn)_xO_y Enables Universal Metabolite Detection for LDI-MS Bioanalysis

Area of Science:

• Analytical Chemistry
• Materials Science
• Biotechnology

Background:

• Surface-Assisted Laser Desorption/Ionization Mass Spectrometry (SALDI-MS) offers advantages like low noise and salt tolerance.
• Developing universal, sensitive, and reproducible matrices for SALDI-MS remains a challenge.

Purpose of the Study:

• To synthesize and evaluate high-entropy oxide nanoparticles (HEO NPs) as a novel nanomatrix for LDI-MS.
• To investigate the mechanism behind HEO NPs' performance in LDI-MS.
• To demonstrate the clinical utility of HEO NPs for cancer diagnostics.

Main Methods:

• Synthesis of high-entropy oxide nanoparticles (HEO NPs).
• Application of HEO NPs as a nanomatrix in LDI-MS for metabolite detection.
• Mechanistic studies on photothermal conversion and carrier dynamics.
• Validation using AI for cancer discrimination in clinical samples.

Main Results:

• HEO NPs demonstrated minimal background, excellent reproducibility, and broad metabolite coverage (amino acids, organic acids, nucleotides).
• HEO NPs outperformed conventional organic matrices and single-metal oxides in LDI-MS.
• Mechanistic studies revealed a "cocktail effect" optimizing electronic and surface properties for enhanced analyte ionization.
• The HEO-based LDI-MS platform achieved accurate discrimination of kidney, bladder, and prostate cancers (AUC > 0.97) when coupled with an AI model.

Conclusions:

• HEO NPs represent a high-performance nanomatrix for LDI-MS, overcoming limitations of existing matrices.
• The synergistic multielement effect in HEO NPs enhances LDI-MS efficiency.
• The developed platform shows significant potential for noninvasive metabolic diagnostics and clinical translation in urological cancer detection.