Automated high-throughput infusion ESI-MS with direct coupling to a microtiter plate

Area of Science:

• Analytical Chemistry
• Mass Spectrometry
• Instrumentation

Background:

• High-throughput analysis is crucial for drug discovery and chemical biology.
• Existing methods for automated sample introduction in ESI-MS can be complex and require separate fluid handling systems.

Purpose of the Study:

• To design and apply novel instrumentation for automated high-throughput infusion ESI-mass spectrometry.
• To enable direct sample introduction from microtiter plates without additional fluid delivery systems.

Main Methods:

• Development of a subatmospheric ESI interface for direct sample introduction from microtiter plates.
• Utilized a single fused-silica capillary as a combined sample delivery and spraying capillary.
• Implemented computer-controlled pneumatic valves for regulating sample aspiration and switching between sample and wash solutions.
• Integrated a flow-through wash device for efficient capillary rinsing between samples.

Main Results:

• Achieved sample analysis times of 10 seconds per sample.
• Demonstrated low sample consumption of 120 nL per analysis.
• Obtained a duty cycle of 40%, indicating efficient data acquisition.
• Successfully applied the system to analyze preparative HPLC fractions from small molecule combinatorial libraries.

Conclusions:

• The developed instrumentation offers an efficient and automated solution for high-throughput infusion ESI-MS.
• The subatmospheric ESI interface simplifies sample introduction from microtiter plates.
• This method is suitable for rapid analysis of diverse sample types, including combinatorial libraries.