Full utilization of a mass spectrometer using on-demand sharing with multiple LC units

Area of Science:

• Analytical Chemistry
• Biochemistry
• Mass Spectrometry

Background:

• Liquid chromatography-mass spectrometry (LC/MS) throughput is often limited.
• Existing systems sharing a mass spectrometer (MS) do not fully utilize the MS duty cycle for maximum throughput.

Purpose of the Study:

• To develop and demonstrate an LC/MS system capable of flexibly recruiting a variable number of LC units to fully utilize the MS duty cycle.
• To enable high-throughput analysis for applications like large-volume biochemical assays and drug discovery.

Main Methods:

• Construction of a modular MS system designed to recruit any number of LC units based on application demands.
• Development of a method to port existing LC/MS methods to the new system for optimized MS utilization.
• Demonstration using a prototypical system with eight LC units and 1-minute chromatographic separations.

Main Results:

• A prototypical eight-unit LC/MS system was constructed and validated.
• Achieved an average LC/MS analysis time of 10.5 seconds per sample for 384-well plate format with 1-minute separations.
• Successfully applied the system to large-volume biochemical assays and analysis of diverse molecular entities in drug discovery.

Conclusions:

• The developed flexible LC/MS system significantly enhances throughput by optimizing MS duty cycle utilization.
• This plug-and-play system allows for application-specific recruitment of LC units, offering a scalable solution for high-throughput analysis.
• The system demonstrates potential for accelerating drug discovery efforts through efficient large-scale biochemical assay analysis.