Lipoprotein Purification via Gas-Phase Ion Mobility
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for measuring lipoprotein sizes in clinical settings are limited in accuracy and efficiency, particularly the Friedewald method, which is indirect and prone to errors, and other methods like ultracentrifugation and gel electrophoresis are time-consuming and prone to nonuniform chromogenicity issues.
Innovation Solution
A method involving differential charged-particle mobility analysis using a gas-phase electrophoretic-mobility molecular analyzer, which includes purifying lipoproteins by centrifugation with density-adjusted solutions and using polyanionic compounds and divalent cations to enhance recovery and analysis of lipoprotein subclasses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If the Friedewald method is used to measure LDL cholesterol, then the measurement process is simplified and can be performed with routine tests, but the accuracy is reduced due to indirect calculation and assumptions about VLDL concentration
Solution Approach 1:
The patent replaces indirect chemical calculation methods (Friedewald formula) with direct physical measurement using ion mobility analysis. The gas-phase ion mobility spectrometry directly measures lipoprotein particle size and concentration, eliminating the need for mathematical assumptions about VLDL:triglyceride ratios and providing accurate LDL cholesterol values through direct particle counting and sizing.
Solution Approach 2:
The patent changes the measurement parameter from indirect chemical concentration estimation to direct physical particle mobility measurement. By measuring the mobility of ions in a gas phase under controlled electric fields, the system directly determines lipoprotein particle characteristics (size, concentration, cholesterol content) without relying on biochemical assumptions or calculations.
2Measurement precision
If ultracentrifugation and gel electrophoresis are used to separate and analyze lipoprotein subclasses, then detailed subclass information can be obtained, but the analysis time is significantly increased and chromogenicity uniformity problems occur
Solution Approach 1:
The patent replaces time-consuming wet chemistry separation methods (ultracentrifugation taking hours, gel electrophoresis requiring incubation and staining) with rapid gas-phase ion mobility separation. The ion mobility analyzer separates lipoprotein subclasses in minutes based on their physical mobility characteristics, eliminating lengthy incubation, staining, and scanning steps while providing equivalent or superior subclass resolution.
Solution Approach 2:
The patent utilizes phase transition from liquid-phase biochemical separation to gas-phase physical separation. By volatilizing the sample and analyzing lipoproteins in the gas phase, the system achieves rapid separation based on ion mobility differences without the time-consuming liquid-phase processes of ultracentrifugation and gel electrophoresis, dramatically reducing analysis time while maintaining subclass discrimination capability.
3Measurement precision
If equilibrium density gradient ultracentrifugation is used to separate LDL subclasses, then accurate density-based classification can be achieved, but the procedure becomes expensive and time-consuming
Solution Approach 1:
The patent replaces expensive, low-throughput equilibrium density gradient ultracentrifugation with rapid, automated ion mobility analysis. The gas-phase system provides density-related separation based on particle mobility without requiring expensive ultracentrifuge equipment, specialized density gradient media, or manual fraction collection, thereby increasing throughput while maintaining accurate lipoprotein subclass classification.
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 provides enhanced recovery and analysis of lipoprotein subclasses, improving the accuracy and efficiency of lipoprotein size determination, reducing the time required for centrifugation and minimizing errors associated with other methods.
Implementation Method 1
differential charged-particle mobility analysis using a gas-phase electrophoretic-mobility molecular analyzer
Implementation Method 2
purifying lipoproteins by centrifugation with density-adjusted solutions
Data Source
Figure 1A~1D
Figure 2
Figure 3
AI summary
The invention provides apparatus and methods of preparation of lipoproteins from a biological sample, including HDL, LDL, Lp(a), IDL, and VLDL, for diagnostic purposes utilizing differential charged-particle mobility analysis methods. Further provided are methods for analyzing the size distribution of lipoproteins by differential charged-particle mobility, which lipoproteins are prepared by methods of the invention. Further provided are methods for assessing lipid-related health risk, cardiovascular condition, risk of cardiovascular disease, and responsiveness to a therapeutic intervention, which methods utilize lipoprotein size distributions determined by methods of the invention.