Dual-Reporter Electrochemical Sensor Drift Correction

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Solution Overview

Problem

Electrochemical aptamer-based sensors face accuracy issues due to baseline signal drift in complex samples like whole blood, and manufacturing variability leads to inconsistencies in sensor performance.

Innovation Solution

Dual-reporter electrochemical sensors with a sensing redox reporter that responds to target binding and a reference redox reporter insensitive to target binding, used in a differential fashion to correct for signal drift and variability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If E-AB sensors are operated in complex samples like whole blood, then real-time monitoring capability is achieved, but baseline signal drift occurs reducing measurement accuracy

Engineering Contradiction:
Improvereal-time monitoring capabilityVSAvoidmeasurement accuracy
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

A reference redox reporter is introduced as an intermediary element that does not interact with the target analyte but experiences the same environmental drift effects. This reference reporter serves as a mediator to quantify and correct the baseline drift, allowing accurate measurement of target binding signals even in complex samples like whole blood.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The system continuously monitors the reference redox reporter signal and uses this feedback to dynamically correct the sensing reporter signal. By comparing the reference signal against a baseline, the system calculates drift correction factors that are applied in real-time to maintain measurement accuracy throughout continuous monitoring operations.

Inventive Principle:
Principle #23Feedback

2Ease of manufacture

If manufacturing processes are simplified, then ease of manufacture is improved, but sensor-to-sensor variability increases

Engineering Contradiction:
Improvefabrication simplicityVSAvoidsensor-to-sensor consistency
Core Design Contradiction:
Ease of manufactureVSManufacturing precision

Solution Approach 1:

Each sensor is equipped with a reference redox reporter that provides real-time feedback on the actual number of reporters present and their functional state. This feedback mechanism allows the system to normalize and correct for manufacturing variations, making the sensor output independent of fabrication inconsistencies.

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The sensor performs self-correction by using its own reference reporter to detect and compensate for manufacturing variability. The ratiometric comparison between sensing and reference reporters enables each sensor to self-normalize its output, eliminating the need for complex external calibration procedures.

Inventive Principle:
Principle #25Self-service

3Device complexity

If a single redox reporter is used, then device complexity is reduced, but the ability to correct for signal drift is lost

Engineering Contradiction:
Improvesensor structure simplicityVSAvoidsignal drift correction capability
Core Design Contradiction:
Device complexityVSMeasurement precision

Solution Approach 1:

The sensing function is segmented into two independent reporter elements: a sensing redox reporter that interacts with the target analyte and a reference redox reporter that monitors environmental drift. This segmentation allows the system to separately measure target binding and drift effects, then mathematically combine the signals to extract accurate target concentration information.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The reference redox reporter performs multiple functions: it monitors baseline drift, normalizes sensor-to-sensor variability, and provides a reference signal for ratiometric calculation. This multi-functionality is achieved through a simple additional reporter element that experiences the same environmental conditions without interacting with the target.

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 dual-reporter approach significantly reduces signal drift in complex samples, enhancing measurement accuracy and stability, allowing for reliable deployment in point-of-care and in vivo applications.

Implementation Method 1

an electrode-bound, redox reporter-modified aptamer that undergoes a conformational change upon target binding. This conformational change alters the accessibility of the reporter relative to the electrode, producing a target-induced change in current between the redox reporter and the electrode.

Methodology Applied
Scientific EffectRedox reactions: Redox Reactions

Data Source

PatentEP3515303B1Drift correction method for dual-reporter electrochemical sensors
Publication Date: 2023.03.08 RGT UNIV OF CALIFORNIA
  • EP3515303B1 patent drawingFigure 1A~1B
  • EP3515303B1 patent drawingFigure 2A
  • EP3515303B1 patent drawingFigure 2B

AI summary

The invention encompasses novel methods of operating electrochemical sensors such as aptamer-based sensors to analyze complex samples, such as flowing whole blood both in vitro or in vivo. In such environments, electrochemical sensors are often subject to drift, which complicates the interpretation of sensor output in terms of target concentration. The method of the invention utilizes a dual-reporter recognition element that generates a first, sensing current that is responsive to target binding and to environmental factors and a second, reference current that is only affected by environmental factors. The reference current provides information about environmentally-induced drift, which allows the drift effect to be subtracted out. By removing drift artifacts, electrochemical sensors may be deployed to analyze complex samples, such as whole blood, in vivo.