Wearable Cortisol Sensor Using Redox-Mediated Aptamer Detection

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Solution Overview

Problem

Current on-body biofluid sensing technologies are limited to detecting high-concentration analytes due to sensitivity constraints and lack of suitable in-situ labeling strategies, making it difficult to access low-abundant analytes like cortisol in sweat, which are valuable for health monitoring.

Innovation Solution

A wearable device and methodology using label-free electrochemical impedance spectroscopy with cortisol-recognizing DNA aptamers covalently immobilized on a gold electrode, combined with a protective layer containing a redox couple to enhance sensitivity and stability, allowing for the detection of low cortisol concentrations in biofluids.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional sensing interfaces are used for on-body analyte sensing, then high-concentration analytes (mM to μM level) can be detected, but low-abundant analytes (nM to pM level) such as hormones cannot be detected due to sensitivity constraints

Engineering Contradiction:
Improvedetection sensitivityVSAvoidanalyte concentration
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The patent introduces an intermediary signaling system using redox-active species (such as ferricyanide/ferrocyanide couple) that mediates between the target analyte binding event and the electrochemical detection. This intermediary amplifies the signal by generating measurable current changes through redox reactions, enabling detection of low-concentration analytes that would otherwise be below the detection limit of conventional interfaces

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the detection parameter from direct measurement of analyte concentration to measurement of electrochemical signal intensity (current, potential, or impedance) generated by redox reactions. This parameter transformation enables highly sensitive detection by converting subtle binding events into amplified electrochemical signals that can be precisely measured

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If a redox couple is used to enhance detection sensitivity, then low-concentration analytes can be detected, but the sensing interface becomes unstable over time due to etching of the gold electrode surface by cyanide ions

Engineering Contradiction:
Improvedetection sensitivityVSAvoidlong-term stability
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent extracts or removes the harmful cyanide ions from the sensing interface by using alternative redox couples that do not contain cyanide, or by physically separating the redox couple from direct contact with the gold electrode surface. This eliminates the etching mechanism while preserving the beneficial signal amplification effect of the redox reactions

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent converts the potentially harmful interaction between cyanide ions and gold electrode into a beneficial situation by either replacing the cyanide-containing redox couple with a benign alternative (such as ferricyanide/ferrocyanide that does not etch gold), or by using the redox couple in a configuration where the harmful effect is prevented while the signaling function is maintained

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

3Adaptability or versatility

If DNA aptamers are immobilized on the electrode surface for specific analyte recognition, then selectivity is improved, but the sensing surface is gradually removed by etching from CN− released by the redox couple

Engineering Contradiction:
Improveanalyte recognition specificityVSAvoidreceptor layer stability
Core Design Contradiction:
Adaptability or versatilityVSStability of the object's composition

Solution Approach 1:

The patent removes the source of cyanide ions from the system by selecting redox couples that do not release CN−, or by physically isolating the redox couple from the electrode surface where the DNA aptamers are immobilized. This prevents the etching mechanism that would otherwise degrade the receptor layer and maintain long-term stability

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent introduces a protective intermediary layer or uses an intermediary redox couple that mediates between the detection function and the DNA aptamer layer, preventing direct contact between harmful cyanide ions and the receptor layer while maintaining the signaling function

Inventive Principle:
Principle #24Intermediary (Mediator)

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 approach enables highly sensitive detection of cortisol at nanomolar levels, maintaining stability over time and minimizing interference from non-target analytes, with demonstrated accuracy comparable to gold standard techniques like HPLC, and can be applied to various biofluids for health monitoring.

Implementation Method 1

The detection principle is based on changes of an interfacial resistance of the electrode, which can be measured in the presence of a reversible redox couple or probe [Fe(CN)6]3−/[Fe(CN)6]4− using electrochemical impedance measurements

Methodology Applied
Scientific EffectRedox reactions: Redox Reactions

Implementation Method 2

cortisol-recognizing DNA aptamers as capture probes or receptors, which are covalently immobilized on a surface of a gold electrode by way of thiol-gold chemical bonding

Methodology Applied
Scientific EffectChemical bonding: Chemical Bonding

Implementation Method 3

the surface of the electrode is partially blocked because of the formation of aptamer-cortisol complexes, resulting in the detection of an increase of the interfacial electron-transfer resistance

Methodology Applied
Scientific EffectAdsorption: Adsorption

Data Source

PatentUS20210153783A1Wearable device for in-situ analysis of hormones
Publication Date: 2021.05.27 RGT UNIV OF CALIFORNIA
  • US20210153783A1 patent drawing
  • US20210153783A1 patent drawing
  • US20210153783A1 patent drawing

AI summary

A wearable device for biofluid analysis includes a set of sensing electrodes, and the set of sensing electrodes includes a working electrode which includes: (1) abase electrode including a sensing surface; (2) capture probes immobilized on the sensing surface; and (3) a protective layer e disposed on the sensing surface and including a redox couple within the protective layer.