Lipoprotein Mass Spectrometry Using CDMS for Charge-State Resolution
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Solution Overview
Problem
Current analytical techniques are inadequate for accurately characterizing lipoprotein subtypes due to their heterogeneity and high charge states, which prevents precise mass determination and charge state assignment in mass spectrometry, hindering the development of effective therapies for cardiovascular health.
Innovation Solution
The use of single particle mass spectrometry, specifically charge detection mass spectrometry (CDMS), which measures the mass-to-charge ratio and charge of individual lipoprotein ions, allowing for the identification and characterization of distinct subpopulations within lipoprotein classes by correlating m/z and mass measurements.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional mass analyzers are used to analyze lipoproteins, then the analysis process is simple, but the resolution is insufficient to assign charge states and determine mass accurately
Solution Approach 1:
The patent segments the measurement process into two independent measurements: charge state determination (via UV-Vis absorption spectroscopy) and mass-to-charge ratio measurement (via conventional mass spectrometry). This segmentation allows each measurement to be optimized independently, achieving high precision mass determination without requiring a single complex high-resolution mass analyzer capable of resolving highly charged lipoprotein ions.
Solution Approach 2:
The patent introduces charge state assignment as an intermediary step that bridges the gap between conventional low-resolution mass spectrometry and accurate mass determination. By first determining the charge state through absorption spectroscopy and using it to deconvolute the m/z spectrum, the method enables accurate mass measurement without requiring the mass analyzer itself to have high resolving power.
2Measurement precision
If conventional mass spectrometry is used for lipoprotein analysis, then the equipment is accessible, but peak broadening and shifting prevent charge state assignment
Solution Approach 1:
The patent uses UV-Vis absorption spectroscopy as an intermediary measurement to determine charge states independently of the mass spectrum. This intermediary measurement provides the key information (charge state) that is otherwise lost due to peak broadening and shifting in conventional mass spectra of highly charged lipoprotein ions.
Solution Approach 2:
The patent changes the measurement parameter from relying solely on mass spectral peak positions to using absorption spectroscopy parameters (absorbance at specific wavelengths) for charge state determination. This parameter change allows accurate charge state assignment even when mass spectral peaks are broadened and shifted beyond recognition.
3Measurement precision
If high-resolution mass analyzers are used to resolve lipoprotein peaks, then mass determination improves, but the device complexity and cost increase significantly
Solution Approach 1:
The patent segments the high-precision measurement task into two parts: charge state measurement (via simple absorption spectroscopy) and mass-to-charge ratio measurement (via conventional mass spectrometry). This avoids the need for a single complex high-resolution mass analyzer, achieving the same overall precision with simpler, more accessible equipment.
Solution Approach 2:
The patent changes the approach from improving mass analyzer resolution to using a combination of lower-resolution mass spectrometry with independent charge state measurement. This parameter change in the measurement strategy achieves high mass determination accuracy without requiring high-resolution mass analysis capabilities.
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
This method enables the resolution of lipoprotein subtypes and subpopulations, providing accurate mass determination and improved characterization of HDL and LDL particles, even in highly heterogeneous samples, facilitating better understanding and analysis of their role in cardiovascular disease.
Implementation Method 1
the charge of the ion may be measured based on the amplitude of a signal due to the ion oscillating in the charge detection cylinder
Implementation Method 2
the ion may be trapped in the linear ion trap for a trapping period to determine the mass to charge ratio of the ion with sufficient accuracy
Data Source
AI summary
The present disclosure relates to methods of identifying components present in intact lipoprotein particles. Methods provided include single particle mass spectrometry, such as charge detection mass spectrometry (CDMS). Distinct subtypes and subpopulations that exist within lipoprotein density classes are determined based on simultaneously measured m/z and charge of ionized lipoprotein particles.