Lipoprotein Size Analysis via Dextran Sulfate Precipitation and Ion Mobility
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Solution Overview
Problem
Current methods for measuring lipoproteins, such as the Friedewald method and ultracentrifugation, are limited in accuracy and efficiency, particularly in determining the size distribution of lipoproteins, which is crucial for predicting cardiovascular disease risk, due to indirect calculations and time-consuming processes.
Innovation Solution
The use of differential charged-particle mobility analysis (DCPMA) involving polyanionic compounds like dextran sulfate and divalent cations for purifying lipoproteins, followed by analysis using a gas-phase electrophoretic-mobility molecular analyzer, allows for precise measurement of lipoprotein size distribution without the need for immunoaffinity reagents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If the Friedewald method is used to measure LDL cholesterol, then the measurement process is simplified and can be performed routinely, but the accuracy is limited due to indirect calculations and assumptions about VLDL concentration ratios
Solution Approach 1:
The patent replaces the chemical calculation-based Friedewald method with direct physical measurement using ion mobility analysis. This substitution eliminates the need for indirect calculations and assumptions about VLDL/LDL ratios, providing both routine throughput and accurate direct measurement of lipoprotein concentrations and sizes.
Solution Approach 2:
The invention changes the measurement parameter from indirect cholesterol concentration calculation to direct ion mobility-based particle size and concentration measurement. By measuring the physical properties of lipoproteins directly in the gas phase, the method achieves both speed and accuracy without relying on chemical assumptions.
2Manufacturing precision
If equilibrium density gradient ultracentrifugation is used to separate LDL subclasses, then the separation precision is high allowing identification of specific subclasses, but the process is time-consuming and expensive limiting its routine use
Solution Approach 1:
The patent replaces the lengthy ultracentrifugation process with rapid ion mobility analysis. The gas-phase electrophoretic mobility measurement separates and characterizes LDL subclasses in minutes rather than hours, achieving comparable or superior resolution without the time-consuming equilibrium centrifugation steps.
Solution Approach 2:
The invention uses periodic pulsed electric fields in the ion mobility analyzer to separate lipoprotein subclasses based on their drift velocities. This periodic action enables rapid separation and detection of different LDL subclasses without the prolonged continuous centrifugation required by traditional methods.
3Measurement precision
If vertical auto profile ultracentrifugation is used to measure lipoprotein sizes, then the size distribution can be determined, but the method requires complex ultracentrifugation equipment and procedures reducing ease of operation
Solution Approach 1:
The patent replaces complex ultracentrifugation-based size measurement with straightforward ion mobility analysis. The gas-phase electrophoretic mobility method requires minimal sample preparation and uses a compact analyzer that is easier to operate than ultracentrifuges, while providing accurate lipoprotein size distribution data.
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 accuracy and efficiency in determining lipoprotein size distribution, improving the assessment of cardiovascular disease risk and reducing the time required for analysis compared to traditional methods.
Implementation Method 1
The use of differential charged-particle mobility analysis (DCPMA) involving polyanionic compounds like dextran sulfate and divalent cations for purifying lipoproteins
Implementation Method 2
admixing a solution containing lipoproteins and non-lipoproteins with one or more polyanionic compounds and one or more cations; allowing a precipitate containing lipoproteins to form
Implementation Method 3
gas-phase electrophoretic-mobility molecular analyzer, allows for precise measurement of lipoprotein size distribution
Data Source
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.