E-DNA Sensor Electron Transfer Kinetics Drift Correction

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Solution Overview

Problem

Receptor-based electrochemical sensors face challenges with drift correction and calibration in complex samples like whole blood, particularly for frequency-insensitive recognition elements and aptamers, where standard methods like kinetic differential measurement (KDM) are not applicable, and calibration processes are cumbersome and impractical for in vivo applications.

Innovation Solution

Incorporating a secondary charge transfer-modulating moiety co-deposited with the recognition element, which does not respond to the target but modulates electron transfer kinetics, enhancing gain and frequency dependence, enabling drift correction and calibration-free operation by providing a reference signal that drifts in parallel with the measurement signal.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If kinetic differential measurement (KDM) is used for drift correction, then signal drift is corrected and signal-to-noise ratio is enhanced, but this approach is not applicable to frequency-insensitive recognition elements and aptamers

Engineering Contradiction:
Improvedrift correctionVSAvoidapplicability to frequency-insensitive recognition elements
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

A secondary charge transfer-modulating moiety is introduced as an intermediary component co-deposited with the recognition element. This moiety does not respond to the target analyte but modulates electron transfer kinetics to create frequency-dependent signal behavior, enabling KDM drift correction in frequency-insensitive sensors.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If calibration processes are used to account for sensor-to-sensor variation, then measurement accuracy is improved, but calibration is cumbersome and impractical for in vivo applications

Engineering Contradiction:
Improvemeasurement accuracyVSAvoidcalibration practicality
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The sensor system performs self-calibration through the co-deposited secondary moiety that provides a reference signal. This reference signal drifts in parallel with the measurement signal, automatically compensating for sensor-to-sensor variation and eliminating the need for external calibration procedures in in vivo settings.

Inventive Principle:
Principle #25Self-service

3Power

If a secondary charge transfer-modulating moiety is co-deposited with the recognition element, then gain is enhanced and frequency dependence is improved, but device complexity increases

Engineering Contradiction:
Improvesensor gainVSAvoidsensor structure
Core Design Contradiction:
PowerVSDevice complexity

Solution Approach 1:

The secondary charge transfer-modulating moiety is merged with the recognition element through co-deposition on the electrode surface. This combining of two functional components (target-responsive recognition element and frequency-modulating moiety) achieves enhanced gain and frequency dependence while maintaining a unified sensor structure.

Inventive Principle:
Principle #5Merging (Combining)

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 accurate, calibration-free measurement of target concentrations in complex samples, including whole blood, with improved signal-to-noise ratio and extended operational use in vivo, overcoming the limitations of sensor-to-sensor variation and drift.

Implementation Method 1

sensing is enabled where such binding induces a change in the kinetics of electron transfer between the recognition element and other elements of the sensor

Methodology Applied
Scientific EffectElectron transfer: Redox Reactions

Implementation Method 2

The redox reporter-functionalized recognition element is bound to or otherwise associated with an electrode. When energized by application of a voltage and/or current pulse, the redox reporter exchanges electrons with the electrode, generating a measurable signal.

Methodology Applied
Scientific EffectElectrochemical reaction: Redox Reactions

Data Source

PatentUS20220225910A1Modulating Electron Transfer Kinetics in E-DNA-type Sensors
Publication Date: 2022.07.21 RGT UNIV OF CALIFORNIA
  • US20220225910A1 patent drawing
  • US20220225910A1 patent drawing
  • US20220225910A1 patent drawing

AI summary

Improved electrochemical sensors wherein the recognition element is co-deposited with a secondary, charge transfer modulating moiety, for example an oligonucleotide. The secondary moiety modulates electron transfer kinetics to enhance the frequency dependence of sensor gain, enabling the use of kinetic differential drift correction techniques and like measurements that require a target insensitive signal drifts in parallel with target-dependent output. The secondary moiety also increases the gain and signal to noise of the sensor and can be used to enable calibration-free measurement. Accurate drift-corrected in vivo sensor use with multiple measurements of analyte concentration per minute in flowing blood is demonstrated.