Plasma Analyte Calibration Using Hematocrit Correction Factors
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Solution Overview
Problem
Existing analyzer units for measuring analytes in blood samples require complex and prone-to-overfitting multivariate polynomial calibration processes, necessitating time-consuming separation of whole-blood samples into plasma and red blood cells, and repeated calibration by operators.
Innovation Solution
A method involving curve fitting of a nonlinear functional relationship between hematocrit levels and analyte ratios in whole-blood samples to generate a hematocrit correction factor, allowing direct measurement of analyte amounts in plasma using a few calibration parameters, stored in analyzer units during design or manufacturing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If multivariate polynomial calibration is used to correct for hematocrit effects, then measurement accuracy is improved, but device complexity and calibration effort increase significantly
Solution Approach 1:
The patent extracts the essential calibration information into a single analyte-specific correction factor derived from bivariate polynomial calibration data. This correction factor captures the hematocrit effect for each analyte without requiring complex multivariate polynomial calculations during measurement, thus reducing device complexity while maintaining accuracy.
Solution Approach 2:
The patent transforms the calibration approach from using multiple polynomial coefficients to using a single corrected measurement parameter. By changing the parameter representation from multivariate polynomial coefficients to a single analyte-specific correction factor, the system maintains measurement accuracy while significantly reducing calibration complexity and overfitting risks.
2Measurement precision
If sample separation into plasma and red blood cells is performed, then measurement accuracy is improved, but time consumption increases
Solution Approach 1:
The patent introduces hematocrit as an intermediary parameter to account for the presence of red blood cells without requiring physical separation. By measuring hematocrit levels and applying analyte-specific correction factors, the system indirectly compensates for red blood cell interference, eliminating the need for time-consuming plasma separation while maintaining measurement accuracy.
3Measurement precision
If repeated calibration by operators is required, then measurement accuracy can be maintained, but operational complexity and down time increase
Solution Approach 1:
The patent performs calibration actions in advance during device manufacturing or design, determining analyte-specific correction factors before the device is deployed. This preliminary calibration eliminates the need for operators to perform repeated calibration procedures, significantly simplifying operation while maintaining measurement accuracy through pre-determined correction factors.
4Measurement precision
If complex multivariate polynomial calibration is used, then measurement accuracy is improved, but reliability decreases due to overfitting
Solution Approach 1:
The patent extracts the essential calibration information into a single analyte-specific correction factor, removing the complex multivariate polynomial components that cause overfitting. This extraction maintains the necessary measurement accuracy while eliminating the reliability issues associated with complex calibration models having too many parameters.
Solution Approach 2:
The patent applies a partial calibration approach by using bivariate polynomials with limited terms rather than full multivariate expansions. This partial action uses only the necessary calibration parameters to capture hematocrit effects for each analyte, avoiding excessive calibration complexity that would lead to overfitting and improve reliability.
Data Source
AI summary
Disclosed herein are embodiments of a method for calibrating a group of analyzer units, each analyzer unit of the group of analyzer units configured for determining an amount of an analyte in plasma of a whole-blood sample. The method comprises: providing a plurality of calibration whole-blood samples, the plurality of calibration whole-blood samples including calibration whole-blood samples having respective hematocrit levels, for each calibration whole-blood sample of the plurality of calibration whole-blood samples: measuring a hematocrit measurement value indicative of the hematocrit level of said calibration whole-blood sample, measuring a whole-blood measurement value indicative of an amount of the analyte in the calibration whole-blood sample using at least one calibration analyzer unit of said group of analyzer units, measuring a plasma measurement value indicative of an amount of the analyte in plasma of said calibration whole-blood sample, and computing a ratio between the whole-blood measurement value and the plasma measurement value; generating a nonlinear functional relationship between the computed ratios and the corresponding hematocrit measurement values by curve fitting of a nonlinear function parametrized by one or more calibration parameters, the curve fitting resulting in respective parameter values of the one or more calibration parameters; storing a representation of the fitted nonlinear function in each analyzer unit of the group of analyzer units to allow each analyzer unit of the group of analyzer units to compute a hematocrit correction factor.