Voltammetric Biosensor Hematocrit Compensation

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Solution Overview

Problem

Conventional electrochemical methods for determining analyte concentrations in biological fluids, such as glucose in whole blood, face challenges including time-consuming processes, inaccuracy due to non-steady-state currents, and significant bias from hematocrit effects, which affect the accuracy of glucose measurements.

Innovation Solution

The use of voltammetric scanning techniques, including linear, cyclic, and acyclic scans, combined with semi-integral and semi-derivative data treatments, to measure currents and correct for hematocrit effects, providing a more accurate and faster method for determining analyte concentrations.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If coulometry is used to completely convert the entire volume of analyte, then accurate determination of analyte concentration is achieved, but the measurement process becomes time-consuming

Engineering Contradiction:
Improveanalyte concentration determination accuracyVSAvoidmeasurement time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent applies partial action by measuring current at a specific potential without requiring complete conversion of the entire analyte volume. Instead of waiting for the steady-state plateau region that coulometry requires, the method measures current during the rising phase of the voltammetric wave, achieving accurate concentration determination in a fraction of the time.

Inventive Principle:
Principle #16Partial or excessive action

Solution Approach 2:

The patent changes the measurement parameter from integrating total charge over time (coulometry) to measuring instantaneous current at a specific potential. This parameter change allows rapid determination of analyte concentration by capturing the current during the voltammetric scan without waiting for complete reaction completion.

Inventive Principle:
Principle #35Parameter changes

2Productivity

If amperometry is used to measure current at constant potential, then the measurement process is fast, but the current is non-steady-state leading to inaccuracy

Engineering Contradiction:
Improvemeasurement speedVSAvoidanalyte concentration determination accuracy
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent applies dynamics by using a scanning potential that changes with time rather than a constant potential. The linear or cyclic voltammetric scan dynamically adjusts the applied potential, allowing the system to capture both the rising and steady-state portions of the voltammetric wave, thereby achieving accurate measurements without requiring long waiting times.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The patent employs periodic action through cyclic voltammetry where the potential is scanned forward and backward in a repeating cycle. This periodic scanning allows multiple measurements to be taken during each cycle, providing both speed and accuracy by capturing current values during the steady-state regions of the cyclic wave.

Inventive Principle:
Principle #19Periodic action

3Adaptability or versatility

If conventional amperometry is used in whole blood samples, then glucose concentration can be measured, but significant bias occurs due to hematocrit effects

Engineering Contradiction:
Improveapplicability to whole blood samplesVSAvoidglucose measurement accuracy
Core Design Contradiction:
Adaptability or versatilityVSMeasurement precision

Solution Approach 1:

The patent uses an electrochemical mediator that shuttles electrons between the enzyme's redox center and the electrode. This intermediary approach allows the measurement to proceed through a multi-step electron transfer process that is less sensitive to hematocrit effects, as the mediator can diffuse through the blood sample matrix more effectively than direct electron transfer would allow.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the measurement parameters by using voltammetric scanning instead of constant potential amperometry. The scanning potential allows the system to identify and measure current at the specific potential where the mediator's redox reaction occurs, providing a measurement that is more selective and less affected by the complex matrix effects of whole blood including hematocrit variations.

Inventive Principle:
Principle #35Parameter changes

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 approach allows for rapid and accurate determination of analyte concentrations by isolating steady-state currents and reducing hematocrit-related biases, enhancing the precision of glucose measurements in whole blood samples.

Implementation Method 1

An electrochemical biosensor may use an analyte specific enzyme, such as glucose oxidase or glucose dehydrogenase, to catalyze the oxidation of glucose in a whole blood sample

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Implementation Method 2

to catalyze the oxidation of glucose in a whole blood sample

Methodology Applied
Scientific EffectOxidation: Oxidation

Implementation Method 3

The electrons acquired by the enzyme then may be moved to the electrode by a mediator, which is converted to a reduced form through oxidation of the enzyme

Methodology Applied
Scientific EffectRedox reaction: Redox Reactions

Implementation Method 4

The electrons acquired by the enzyme then may be moved to the electrode by a mediator

Methodology Applied
Scientific EffectElectron transfer:

Implementation Method 5

the reduced form of the mediator, such as the ferrocyanide species of the ferricyanide/ferrocyanide redox pair, is oxidized at the electrode to generate a measurable current

Methodology Applied
Scientific EffectElectrochemical oxidation: Oxidation

Data Source

PatentUS9784706B2Voltammetric systems for assaying biological analytes
Publication Date: 2017.10.10 ASCENSIA DIABETES CARE HLDG AG
  • US9784706B2 patent drawing
  • US9784706B2 patent drawing
  • US9784706B2 patent drawing

AI summary

The present invention relates to systems, methods, and devices for determining the concentration of an analyte in a sample. The use of linear, cyclic, or acyclic voltammetric scans and/or semi-integral, derivative, or semi-derivative data treatment may provide for increased accuracy when determining the concentration of an analyte in a sample. Hematocrit compensation in combination with the data treatments may reduce the hematocrit effect with regard to a glucose analysis in whole blood. In another aspect, fast scan rates may reduce the hematocrit effect.