Sample-Specific MS/MS Methods in High-Throughput Mass Spectrometry.

Area of Science:

• Analytical Chemistry
• Mass Spectrometry
• Drug Discovery

Background:

• High-throughput mass spectrometry (HT-MS) is crucial for accelerating drug discovery by enabling rapid analysis of large sample sets.
• Current HT-MS platforms face challenges in applying specific data acquisition methods to individual samples within a continuous data stream.
• Chromatographic-free HT-MS technologies offer increased sample readout speed but require advanced data handling strategies.

Purpose of the Study:

• To develop a novel approach for real-time activation of sample-specific MS/MS data acquisition methods on HT-MS platforms.
• To address the challenges of method setting in continuous data acquisition for high-throughput analyses.
• To enhance the usability and robustness of HT-MS for drug discovery and other high-throughput applications.

Main Methods:

• Integration of real-time sample loading status detection.
• Development of an automated system to trigger sample-specific MS/MS data acquisition methods.
• Implementation on a high-throughput acoustic ejection mass spectrometry platform.
• Validation across multiple reaction monitoring (MRM), high-resolution MRM (MRM ^HR ), and information-dependent acquisition modes.

Main Results:

• Demonstrated effective method switching based on real-time sample status.
• Achieved high signal reproducibility across various data acquisition window durations.
• Validated the approach across different MS/MS acquisition modes (MRM, MRM ^HR , IDA).
• Confirmed the user-friendly and robust nature of the developed solution.

Conclusions:

• The novel approach successfully integrates real-time sample status to enable dynamic method switching in HT-MS.
• This advancement simplifies method setting for HT-MS, improving efficiency and reproducibility.
• The solution expands the applicability of HT-MS platforms in drug discovery and other high-throughput analytical fields.