NMR Lipoprotein Analysis via Individual Lipid Component Fitting
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Solution Overview
Problem
Existing NMR spectrum analysis methods for lipoprotein-containing samples are inaccurate due to ill-conditioned spectral deconvolution and insufficient physical separation of lipoprotein fractions, leading to unreliable determination of lipoprotein concentrations.
Innovation Solution
A novel method that fits spectral functions representing individual lipid components over a broader spectral range, rather than specific lipoprotein classes or subclasses, to accurately determine lipoprotein concentrations by considering the behavior of lipid components within lipoprotein particles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If physical separation techniques are used to create reference lipoprotein classes, then reference values can be obtained, but inaccuracy is introduced due to inherent limitations of separation techniques
Solution Approach 1:
The patent extracts the lipid components from the complex lipoprotein structure and uses them as the basis for spectral functions. Instead of relying on physically separated lipoprotein classes, the method extracts individual lipid component spectra and combines them mathematically to represent lipoprotein subclasses, thereby avoiding the inaccuracy introduced by physical separation techniques.
2Device complexity
If only specific spectral regions (CH2 or CH3) are fitted to reduce complexity, then fitting operations become simpler, but comprehensive analysis of lipoprotein classes is compromised
Solution Approach 1:
The patent segments the lipoprotein analysis into individual lipid component contributions. Each lipid component (triglycerides, phospholipids, cholesterol, free fatty acids) is represented by its own spectral function covering the entire spectral range. This segmentation allows comprehensive analysis while maintaining manageable complexity through modular spectral functions.
Solution Approach 2:
The spectral functions are designed to be universal across different lipoprotein subclasses. Each lipid component's spectral function represents its contribution to all lipoprotein classes (VLDL, IDL, LDL, HDL), allowing the same set of spectral functions to analyze the entire lipoprotein profile without requiring subclass-specific functions.
3Ease of manufacture
If bell-shaped curves are used to simulate lipoprotein spectra based on ultracentrifugation fractions, then fitting can be performed, but the constant composition assumption limits accuracy
Solution Approach 1:
The patent changes the parameters used to represent lipoprotein spectra from fixed bell-shaped curves to variable combinations of individual lipid component spectral functions. Each lipid component's spectral function has parameters (amplitude, position, width) that can vary to reflect the actual composition of different lipoprotein subclasses, providing both ease of fitting and high accuracy.
Data Source
AI summary
Disclosed is a method for analyzing an NMR spectrum of a lipoprotein-containing sample. The method includes the following steps: a) defining a spectral range to be analyzed of at least 0.5 ppm of an NMR spectrum of a lipoprotein-containing sample; b) fitting a first spectral function of a first individual lipid component and at least one further spectral function of a further individual lipid component into the whole spectral range to be analyzed; and c) determining a concentration or an amount of the first individual lipid component and the further individual lipid component and therefrom a concentration or an amount of the first defined lipoprotein class or lipoprotein subclass in the lipoprotein-containing sample and optionally of each other defined lipoprotein class or lipoprotein subclass based on the fitting operations of step b).