HbA1C Lateral Flow Assay Correcting Hemoglobin Variant Interference
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Solution Overview
Problem
Current Point-of-Care devices for measuring HbA1C, such as the A1CNow®, produce false high results in patients with hemoglobin variants HbS and HbC, leading to significant bias and reducing the accuracy of blood glucose monitoring, especially in populations with high frequencies of these variants.
Innovation Solution
The development of a system using a first lateral flow test strip with an antibody-microparticle stripe and a strongly denaturing sample treatment buffer, which includes sodium perchlorate or other oxidizing agents, to improve the specificity and reduce bias by enhancing the binding between antibodies and microparticles, thereby correcting for interference from HbS and HbC variants.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If a standard immunochemistry-based system is used to measure HbA1C, then the measurement process is simple and quick, but the results are inaccurate in patients with hemoglobin variants HbS and HbC due to false high readings
Solution Approach 1:
The patent applies preliminary action by treating the blood sample with a denaturing buffer before the immunochemistry assay. This pre-treatment step modifies the hemoglobin variants (HbS and HbC) to prevent them from interfering with the antibody binding, thereby eliminating the source of measurement error before the actual HbA1C detection occurs. The denaturing buffer causes conformational changes in the variant hemoglobins that prevent their abnormal binding behavior.
Solution Approach 2:
The patent changes the chemical parameters of the sample environment by introducing a denaturing buffer with specific pH and chemical composition. This parameter change affects the structural properties of hemoglobin variants, causing them to unfold or change conformation in a way that eliminates their interfering effects. The buffer modifies the physical-chemical state of the sample to achieve selective correction of variant interference while preserving HbA1C integrity.
2Adaptability or versatility
If hemoglobin variants HbS and HbC are present in the sample, then the population coverage is improved, but the measurement results show significant bias with false high readings up to 30%
Solution Approach 1:
The patent converts the harmful effect of hemoglobin variants into a beneficial outcome by using a denaturing buffer that specifically targets and modifies the variant structures. The same structural features that cause interference (the variant amino acid sequences) are exploited by the denaturing buffer to induce conformational changes that eliminate the interference. This transforms the previously harmful variant presence into a condition that can be selectively corrected, allowing accurate measurement even in populations with high frequencies of HbS and HbC.
3Measurement precision
If antibodies are used to detect HbA1C, then the specificity for glycated hemoglobin is improved, but hemoglobin variants cause false binding and elevated results
Solution Approach 1:
The patent introduces a denaturing buffer as an intermediary substance between the sample and the antibody detection system. This intermediary modifies the hemoglobin variants in a controlled manner, creating a transformed state that no longer binds aberrantly to antibodies. The buffer acts as a mediator that selectively affects variant hemoglobins while leaving HbA1C intact, thereby protecting the antibody-HbA1C interaction from interference without requiring changes to the antibody itself or the detection methodology.
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
The system significantly reduces bias caused by Hb variants, achieving accurate HbA1C measurements by improving the binding between antibodies and microparticles, thereby enhancing the reliability of blood glucose monitoring.
Implementation Method 1
a strongly denaturing sample treatment buffer, which includes sodium perchlorate or other oxidizing agents
Data Source
AI summary
A system for determining a concentration of hemoglobin A1C includes a first lateral flow test strip, the first lateral flow test strip providing for a percent of HbA1C concentration; a second lateral flow test strip, the second lateral flow test strip providing for the total amount of hemoglobin; an antibody-microparticle stripe on each of the first and second lateral flow test strips; a conjugate stripe on each of the first and second lateral flow test strips; and a sample treatment buffer. The sample treatment buffer is strongly denaturing, and antibodies in the antibody-microparticle strip are covalently bound to microparticles.