Pulsed-Closure Assisted Continuous Atmospheric Pressure Interface for Miniature Ion Trap Mass Spectrometry with Enhanced Resolution and Sensitivity.

Resolution and sensitivity are critical performance metrics for miniature ion trap mass spectrometry, collectively determining their range of applications. This study presents a novel strategy for enhancing the resolution and sensitivity of continuous atmospheric pressure interfaced ion trap mass spectrometry operating under high pressure by developing a pulsed-closure assisted continuous atmospheric pressure interface (PCA-CAPI). Ion injection and trapping were achieved under relatively high pressures, while mass analysis was conducted at significantly reduced pressures by a deliberate pulsed closure of the normally open pinch valve after ion injection. The optimal closure time of the pinch valve was systematically determined, and performance improvements across various operating pressures were evaluated. After comprehensive optimization, the resolution and intensity were increased by 4.7-fold and 5.2-fold simultaneously. Additionally, excellent ion utilization efficiency and a limit of detection of 0.5 pg/μL were achieved. High stability was obtained with a relative standard deviation of 4.33%. The capability of the PCA-CAPI-ITMS to accurately resolve and detect adjacent ions, thereby preventing potential misidentification, was validated through the analysis of two drug mixtures. The successful implementation of PCA-CAPI-ITMS offers a promising pathway toward simplified vacuum systems and opens new possibilities for the development of higher-pressure ITMS, potentially enhancing the robustness and versatility of the technique.