Direct Infusion Ion Mobility MS for Fast Multi-Omics Analysis
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Solution Overview
Problem
Conventional liquid chromatography-based methods for proteomics, lipidomics, and metabolomics are time-consuming and prone to issues, limiting throughput and analysis efficiency.
Innovation Solution
Direct infusion mass spectrometry with gas-phase separation using ion mobility techniques, such as drift-tube or trapped ion mobility spectrometry, to separate ions based on charge, shape, and collisional cross-section, eliminating the need for liquid chromatography and enabling faster analysis of complex mixtures.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If liquid chromatography is used for separation before mass spectrometry analysis, then the depth and breadth of proteome coverage is improved, but the analysis time increases significantly
Solution Approach 1:
The patent extracts and removes the liquid chromatography separation step from the traditional LC-MS workflow. By directly infusing the peptide mixture into the mass spectrometer without LC pre-separation, the method eliminates the time-consuming chromatographic process while maintaining comprehensive proteome coverage through data-independent acquisition and ion mobility separation.
Solution Approach 2:
The patent replaces the mechanical liquid-phase separation system (liquid chromatography) with a gas-phase separation approach using ion mobility spectrometry. This substitution eliminates the need for physical chromatographic columns and mobile phase flow, dramatically reducing analysis time while preserving separation capability through gas-phase ion sorting based on mobility differences.
2Measurement precision
If liquid chromatography is used for separation, then peptide identification accuracy is improved, but throughput is limited by column loading and re-equilibration time
Solution Approach 1:
The patent implements continuous direct infusion of the peptide mixture into the mass spectrometer without interruption for column re-equilibration. The ion mobility separator continuously sorts ions in the gas phase, enabling uninterrupted analysis and significantly increasing throughput compared to the cyclic nature of LC operations with repeated loading and re-equilibration steps.
Solution Approach 2:
The patent introduces ion mobility spectrometry as an intermediary separation mechanism between direct infusion and mass spectrometry detection. This intermediary gas-phase separation technique sorts ions based on mobility before they enter the mass analyzer, providing the necessary separation for accurate peptide identification without requiring liquid chromatography infrastructure.
3Loss of time
If direct infusion without liquid chromatography is used, then analysis time is reduced, but the complexity of peptide mixtures hinders detection
Solution Approach 1:
The patent adds a gas-phase separation dimension using ion mobility spectrometry to complement the direct infusion approach. By separating ions based on their mobility in the gas phase (a different dimension than liquid-phase chromatography), the method effectively reduces mixture complexity for detection while maintaining the speed advantage of direct infusion, enabling analysis of complex peptide mixtures without LC.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Enables high-throughput analysis of complex peptide mixtures, allowing for the identification and quantification of thousands of target species per hour without the need for liquid chromatography, enhancing the depth and breadth of proteome, lipidome, and metabolome coverage.
Implementation Method 1
Samples are directly infused and ionized by electrospray
Implementation Method 2
the resulting peptide cations are separated in the gas phase
Implementation Method 3
detection by data-independent acquisition mass spectrometry
Data Source
AI summary
The present invention provides methods and systems using gas-phase separation with mass spectrometry analysis instead of liquid chromatography, thereby enabling faster peptide, proteome, and multi-omic analysis. Also provided are improved methods and software for data independent acquisition. One embodiment referred to as Direct Infusion-Shotgun Proteome Analysis (DI-SPA) used with data-independent acquisition mass spectrometry (DIA-MS), resulted in targeted quantification of over 500 proteins within minutes of MS data collection (˜3.5 proteins/second). Enabling fast, unbiased protein and proteome quantification without liquid chromatography, DI-SPA offers a new approach to boosting throughput critical to drug and biomarker discovery studies that require analysis of thousands of proteomes. This invention is also able to perform complex multi-omic analysis of proteomes, lipidomes, and metabolomes on a single platform.