Direct Copper Measurement via Immuno-Capture and Chelation
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Solution Overview
Problem
Current methods for measuring free copper concentrations in biological samples, particularly for conditions like Wilson disease, are inaccurate due to the estimation of non-ceruloplasmin-bound copper (NCC) based on incorrect assumptions, leading to physiologically impossible negative results.
Innovation Solution
Direct measurement of labile-bound copper in biological samples by removing ceruloplasmin using an immuno-capture reagent and then contacting the sample with a chelator to isolate and quantify labile-bound copper, providing an accurate assessment of copper concentrations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If NCC is estimated using the formula based on total copper and ceruloplasmin levels, then the measurement process is simple, but the measurement precision deteriorates leading to physiologically impossible negative results
Solution Approach 1:
The patent extracts and directly measures free copper (NCC and LBC) from the total copper pool by removing ceruloplasmin-bound copper through immuno-capture. This separates the measurement of free copper from total copper, eliminating the need for estimation formulas that lead to negative values while providing direct accurate measurement of the clinically relevant parameter.
2Ease of manufacture
If the copper/CP ratio is assumed to be six copper atoms per CP molecule, then the calculation is straightforward, but the measurement precision deteriorates because the actual ratio varies with disease state
Solution Approach 1:
The patent changes the fundamental parameter from assuming a fixed copper/CP ratio to directly measuring free copper concentrations using immuno-capture and chelation. This eliminates the need to account for variable copper/CP ratios in different disease states, as the measurement directly quantifies free copper without relying on ratio assumptions.
3Reliability
If total blood copper and CP levels are measured directly, then the measurement method is established and reliable, but the measurement precision of free copper deteriorates due to indirect estimation
Solution Approach 1:
The patent segments total copper into two distinct measurable components: ceruloplasmin-bound copper (measured via immuno-capture) and free copper (NCC and LBC, measured in the supernatant). This segmentation allows direct measurement of free copper using established techniques applied to separated fractions, resolving the contradiction between reliability of established methods and precision of free copper measurement.
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 eliminates the issue of negative results and provides a reliable, direct measurement of free copper levels, improving diagnostic accuracy for copper metabolism-associated disorders.
Implementation Method 1
removing ceruloplasmin from a biological sample to obtain a non-ceruloplasmin sample
Implementation Method 2
contacting the non-ceruloplasmin sample with a chelator which binds to labile-bound copper
Data Source
AI summary
This disclosure relates to methods of measuring copper concentrations in biological samples. More particularly, this disclosure relates to methods of measuring non-ceruloplasmin-bound copper concentrations and/or labile-bound copper concentrations in biological samples. Such methods are particularly useful in management and treatment of metabolism-associated diseases or disorders.