Integrating Electrostatic Adsorption-Laser Desorption/Ionization-MS with a Derivative Full-Spectrum Internal Standard...

Area of Science:

• Analytical Chemistry
• Biomarker Discovery
• Mass Spectrometry

Background:

• Acylcarnitines (ACs) are key biomarkers for metabolic diseases, but current detection methods face limitations.
• Conventional techniques like LC-MS and FI-MS suffer from complex sample prep, low throughput, and interferences.
• MALDI-MS methods struggle with background noise and reproducibility issues.

Purpose of the Study:

• To develop an innovative mass spectrometry platform for improved acylcarnitine profiling.
• To overcome the limitations of existing methods for enhanced sensitivity and throughput.
• To provide a robust solution for clinical diagnostics and newborn screening.

Main Methods:

• Developed a dual-innovation platform combining sulfonic acid-gold nanoparticle-decorated silicon nanowires (Sulfo-Au-SiNWs) for electrostatic adsorption-laser desorption/ionization (EALDI).
• Implemented a full-spectrum internal standard (FS IS) strategy using d6-ethanol derivatization for simultaneous quantification.
• Validated the platform using urine and dried blood spot samples against FI-ESI-MS/MS.

Main Results:

• The Sulfo-Au-SiNWs substrate increased AC signal intensity by ~300%, enabling detection of previously undetectable ACs.
• Achieved detection limits below 0.01 μmol/L with high spike recovery rates (96-112%) and rapid sample processing (seconds per sample).
• Demonstrated excellent agreement (ρ > 0.95) with traditional methods and successfully identified IEM patient profiles.

Conclusions:

• The EALDI-MS/FS IS platform offers a high-throughput, high-coverage, and quantitatively robust solution for acylcarnitine analysis.
• This workflow significantly improves upon existing mass spectrometry techniques for clinical acylcarnitine profiling.
• The platform is well-suited for routine clinical diagnostics and newborn screening applications.