Systems and methods for enzymatic A1C detection and quantification
Inventors
Hughes, Gary • Jesswein, Ryan • Werner, Brittney • Patwardhan, Aniruddha
Assignees
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Publication Number
US-11703513-B2
Publication Date
2023-07-18
Expiration Date
Abstract
A system for determining a concentration of hemoglobin A1C includes a first electrochemical test strip, the first electrochemical test strip providing for an HbA1C concentration; and a second electrochemical test strip, the second electrochemical test strip providing for the total amount of hemoglobin.
Core Innovation
The invention relates to a system for determining a percentage glycation of hemoglobin as HbA1C. The system uses an electrochemical analysis implemented with a first electrochemical test strip configured to provide an HbA1C concentration and a second electrochemical test strip configured to provide the total amount of hemoglobin.
The first electrochemical test strip uses fructosyl amino acid oxidase, a ruthenium hexamine trichloride mediator, Toyobo Neutral Proteinase (NEP-801) microbial metalloproteinase, and n-Tetradecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate as a surfactant. HbA1C is enzymatically addressed through an enzymatic processing scheme that releases fructosyl-amino-acid fragments such as fructosyl-valylhistidine (F-VH), and the electrochemical detection is driven by electron transfer associated with fructosyl amino acid oxidase.
The second electrochemical test strip includes a potassium ferricyanide solution with a lysing surfactant, identified as Polyethylene glycol tert-octylphenyl ether. Released hemoglobin reacts with the potassium ferricyanide solution to form methemoglobin, and the disclosed electrochemical scheme is described as suitable to avoid hemoglobin-variant (HbS/HbC) false-high results associated with immunochemical assays.
Claims Coverage
The relevant disclosure provides one independent claim defining the overall HbA1C percentage glycation system architecture and reagent components across two electrochemical strips, with additional dependent refinements. The inventive features include the two-strip architecture and five further claimed refinements.
Two electrochemical strips for HbA1C percentage glycation and total hemoglobin
A system comprising a first electrochemical test strip providing an HbA1C concentration using electrochemical analysis and a second electrochemical test strip providing the total amount of hemoglobin.
First electrochemical strip using fructosyl amino acid oxidase, ruthenium hexamine trichloride mediator, and NEP-801 with a specified surfactant
The first electrochemical test strip includes fructosyl amino acid oxidase, a ruthenium hexamine trichloride mediator, n-Tetradecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate as a surfactant, and Toyobo Neutral Proteinase (NEP-801) microbial metalloproteinase.
Second electrochemical strip using potassium ferricyanide with a lysing surfactant to form methemoglobin
The second electrochemical test strip includes a potassium ferricyanide solution with a lysing surfactant, where released hemoglobin reacts with the potassium ferricyanide solution to form methemoglobin, and the lysing surfactant is Polyethylene glycol tert-octylphenyl ether.
Direct electron transfer bypassing peroxide generation
Fructosyl amino acid oxidase directly transfers an electron to the ruthenium hexamine trichloride mediator and bypasses a peroxide generation step.
Interdigitated electrodes
The first and second electrodes are interdigitated.
Reagent applied by painting onto one electrode
A reagent is applied by painting onto one of the first and second electrodes.
Multi-strip holder architecture with additional analyte testing
The system includes a third test strip that tests for an additional analyte.
Non-redundant fourth analyte selection for a fourth strip
A fourth test strip tests for a fourth analyte selected from glucose, ketones, triglycerides, and lactate, where this analyte is non-redundant with the additional analyte.
Independent claim broadly covers a two-strip electrochemical system for HbA1C percentage glycation and total hemoglobin determination, with specified enzymatic and mediator components on the HbA1C strip and potassium-ferricyanide/methemoglobin chemistry on the total hemoglobin strip. The dependent refinements further specify the electrochemical pathway, electrode geometry, reagent application, and optional multi-analyte strip configurations.
Stated Advantages
Improved accuracy and NGSP certification.
Reduced hemoglobin-variant interference causing fewer false-high results associated with HbS/HbC.
Small sample volume.
Reduced user steps.
Electrochemical suitability for multi-analyte testing.
Documented Applications
Use as a point-of-care style electrochemical HbA1c determination system, including a multi-analyte panel format that can additionally test glucose, ketones, triglycerides, and lactate.
Total hemoglobin measurement on a separate electrochemical strip using methemoglobin formation from released hemoglobin reacted with potassium ferricyanide.
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