High-fidelity genotyping and therapeutic oligonucleotides analysis by liquid-phase ion trap coupled with mass
Xinyan Fu1, Jie Hong2, Song Lu3
1School of Medical Technology, Beijing Institute of Technology, Beijing 100081, China.
Abstract:
Rapid and accurate nucleic acid analysis is essential for disease diagnostics and drug development, yet persistent metal cation interference severely limits mass spectrometry's effectiveness. We developed a liquid-phase ion trap (LPIT) system that utilizes strong electric fields to simultaneously dissociate metal contaminants and enrich purified nucleic acid ions directly in solution. This dual-action mechanism simplifies complex mass spectra, achieving up to a 48-fold improvement in mass accuracy and a 100-fold enhancement in signal intensity for intact DNA molecules. The platform's versatility was demonstrated through high-resolution genetic variation analysis, rapid influenza virus subtyping from raw PCR products, and precise impurity detection in therapeutic drugs. By eliminating laborious pretreatment, the LPIT-ESI-MS system establishes a robust platform for high-fidelity genotyping and the rigorous analysis of therapeutic oligonucleotides, accelerating both clinical diagnostics and biopharmaceutical quality control.
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