Ketone Sensor Background Subtraction for Low-Concentration Detection

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Solution Overview

Problem

Existing biosensors face challenges in accurately measuring low ketone concentrations due to significant background interference from compounds like ascorbate and uric acid, leading to reduced sensitivity and accuracy in continuous ketone monitoring, particularly for diabetes patients at risk of diabetic ketoacidosis.

Innovation Solution

A method involving a ketone sensing electrode with a ketone-responsive enzyme and redox mediator, and a background sensing electrode with only a redox mediator, applying a potential less than +40 mV, followed by alternating disconnection and reconnection to measure ketone signals by subtracting background interference.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If a standard biosensor is used to measure ketone concentrations, then the ketone signal can be detected, but background interference from compounds like ascorbate and uric acid reduces measurement accuracy, especially at low ketone concentrations below 1 mM

Engineering Contradiction:
Improveketone measurement accuracyVSAvoidbackground interference signal
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The measurement process is segmented into distinct phases: a background measurement phase where the background sensing electrode measures interference from ascorbate and uric acid, and a ketone measurement phase where the ketone sensing electrode measures total signal. This segmentation allows separate quantification and subtraction of background interference from ketone signal, improving accuracy at low concentrations

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

A redox mediator is introduced as an intermediary substance that facilitates electron transfer between the enzyme-catalyzed ketone oxidation reaction and the electrode. The mediator (such as osmium complex or ferricyanide) enables sensitive detection of ketone oxidation products while allowing selective measurement at controlled potentials, improving signal detection capability

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If the sensing electrode is continuously connected to the circuit, then continuous monitoring is achieved, but charge accumulation is limited and sensitivity is reduced

Engineering Contradiction:
Improvecontinuous monitoring capabilityVSAvoidsensing sensitivity
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

The electrode is periodically disconnected from the circuit to allow charge accumulation during idle periods, then reconnected for measurement. This periodic disconnection-connection cycle enables both continuous monitoring capability and enhanced sensitivity through charge buildup, resolving the contradiction between continuous operation and sensitivity

Inventive Principle:
Principle #19Periodic action

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

Enhances ketone sensitivity and accuracy by reducing background interference, enabling reliable continuous ketone monitoring even at low concentrations, thereby preventing complications like diabetic ketoacidosis.

Implementation Method 1

a ketone sensing electrode comprising a ketone-responsive enzyme and a redox mediator

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Implementation Method 2

a ketone sensing electrode comprising a ketone-responsive enzyme and a redox mediator

Methodology Applied
Scientific EffectRedox reaction: Redox Reactions

Implementation Method 3

a ketone sensing electrode comprising a ketone-responsive enzyme and a redox mediator

Methodology Applied
Scientific EffectElectron transfer: Redox Reactions

Implementation Method 4

applying a potential less than +40 mV to provide a steady state

Methodology Applied
Scientific EffectElectrochemical potential control: Electric Field

Implementation Method 5

The ketone sensing electrode and background sensing electrode can be simultaneously or sequentially disconnected from the circuit to allow a charge to accumulate for a set period of time

Methodology Applied
Scientific EffectCharge accumulation: Capacitance

Implementation Method 6

The ketone signal can be measured by subtracting a signal obtained from the background sensing electrode from a signal obtained from the ketone sensing electrode

Methodology Applied
Scientific EffectDifferential measurement:

Data Source

PatentUS20250213152A1Background interference mitigation for high sensitivity ketone sensing
Publication Date: 2025.07.03 ABBOTT DIABETES CARE INC
  • US20250213152A1 patent drawing
  • US20250213152A1 patent drawing
  • US20250213152A1 patent drawing

AI summary

The present disclosure relates to a method of improving the sensitivity of sensing ketones that includes providing i) a ketone sensing electrode comprising a ketone-responsive enzyme and a redox mediator; and ii) a background sensing electrode comprising a redox mediator and no ketone-responsive enzyme and applying a potential less than +40 mV to provide a steady state. The ketone sensing electrode and background sensing electrode can be simultaneously or sequentially disconnected from the circuit to allow the charge to accumulate for a set period of time. After sufficient charge has been built up, both electrodes can be reconnected to the circuit. The ketone signal can be measured by subtracting a signal obtained from the background sensing electrode from a signal obtained from the ketone sensing electrode. The present disclosure further relates to a ketone sensor comprising a first sensing electrode that senses ketone and a second sensing electrode that senses the background.