pH-Sensitive Aptamer Sensors for Regeneratable Biomarker Monitoring
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Solution Overview
Problem
Existing biosensors fail to address the challenges of continuous monitoring of biomarker concentrations in home, community, and workplace settings due to the reusability of the immobilized bio-recognition elements.
Innovation Solution
Electrochemical sensors for the detection and quantification of analytes are provided. The sensors can be used to accurately and rapidly detect and/or quantify analytes of interest. The sensors described herein employ aptamers (e.g., pH-sensitive aptamer switches) that exhibit a high binding affinity towards an analyte of interest. The aptamers can thus serve as the sensing interface of the electrochemical sensors. When pH-sensitive aptamer switches are employed, the sensor can possess an allosteric nucleic acid-functionalized surface that exhibits pH-tunable performance via a potentiometric sensing strategy. For example, the sensor can comprise a FET-based potentiometric sensor that includes an allosteric nucleic acid-functionalized surface that exhibits pH-tunable performance. Following analyte binding, sensing capability can be restored by altering the pH of the medium in contact with the sensor (first decreasing binding affinity for the analyte of interest, the sensor can comprise a FET-based potentiometric sensor that includes an allosteric nucleic acid-functionalized surface that exhibits pH-tunable performance. For example, the sensor can comprise a FET-based potentiometric sensor that includes an allosteric nucleic acid-functionalized surface that exhibits pH-tunable performance. Following analyte binding, sensing capability can be restored by altering the pH of the medium in contact with the sensor (first decreasing binding affinity for the analyte of interest, causing it to be released, followed by restoring pH to increase affinity, thereby restoring affinity for the analyte of interest). pH can be controlled using an electrode (e.g., a Pd electrode) positioned in proximity to the nucleic acid-functionalized surface. This electrode can be used to reversibly and focally control the pH of the microenvironment in contact with the nucleic acid-functionalized surface, allowing for sensor regeneration to be performed with minimal perturbation of the surrounding medium.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional biosensing techniques (ELISA, CE, GC, HPLC) are used for biomarker detection, then measurement precision is improved, but device complexity and ease of operation worsen due to requiring centralized equipment and trained personnel
Solution Approach 1:
The patent extracts the core biosensing function from complex centralized equipment and implements it in a simplified portable device. The biosensor chip contains immobilized bio-recognition elements that perform detection locally, eliminating the need for large-scale equipment like HPLC or GC systems while maintaining detection capability for biomarkers in complex environments
Solution Approach 2:
The biosensor is designed for autonomous operation without requiring trained personnel. The device integrates sample processing, detection, and analysis functions that automatically execute, enabling users with minimal training to perform biomarker monitoring in home, community, or workplace settings
2Productivity
If biosensor chips are used for continuous monitoring, then productivity is improved, but reliability worsens due to limited reusability of immobilized bio-recognition elements
Solution Approach 1:
The patent employs pH-sensitive aptamer switches that change their binding parameters in response to pH variations. By adjusting pH conditions, the aptamers can be switched between high-affinity binding states for analyte capture and low-affinity states for analyte release, enabling regeneration of the sensing surface and repeated use of the biosensor chip
Solution Approach 2:
The biosensor incorporates dynamically controllable aptamer switches rather than static recognition elements. The aptamers can transition between bound and unbound states through pH modulation, allowing the sensor to be regenerated and reused multiple times for continuous monitoring applications
3Loss of substance
If extreme conditions (heating, UV exposure, concentrated chemicals) are used to dissociate targets from aptamers, then loss of substance is reduced by enabling regeneration, but object-generated harmful factors increase due to damage to surrounding medium
Solution Approach 1:
The patent uses mild pH changes instead of extreme conditions to control aptamer-target binding. By adjusting pH to physiological ranges, the aptamers release bound analytes and regenerate without requiring heating, UV exposure, or concentrated chemicals that would damage the surrounding medium or biological samples
Solution Approach 2:
The patent introduces pH as an intermediary parameter to control the binding affinity of aptamers. This intermediary mechanism allows indirect control of analyte release through pH-sensitive conformational changes in the aptamers, avoiding direct application of harsh dissociation conditions that would harm the surrounding environment
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
These sensors are flexible, biocompatible, and implantable, enabling continuous monitoring of biomarkers in various applications, including regeneratable wearable electronics and bioimplants, with rapid and accurate detection of small molecules like cocaine and dopamine.
Implementation Method 1
their noncovalent interactions with the corresponding targets (e.g., hydrogen bonds, electrostatic bonds, Van der Waals forces) are reversible in nature
Implementation Method 2
their noncovalent interactions with the corresponding targets (e.g., hydrogen bonds, electrostatic bonds, Van der Waals forces) are reversible in nature
Implementation Method 3
their noncovalent interactions with the corresponding targets (e.g., hydrogen bonds, electrostatic bonds, Van der Waals forces) are reversible in nature
Implementation Method 4
pH can be controlled using an electrode (e.g., a Pd electrode) positioned in proximity to the nucleic acid-functionalized surface. This electrode can be used to reversibly and focally control the pH of the microenvironment
Data Source
AI summary
Described herein are sensors for detecting an analyte of interest in a sample. These sensors can comprise a potentiometric sensor comprising a surface functionalized with a pH-sensitive aptamer switch that specifically binds the analyte of interest, wherein the pH-sensitive aptamer switch is operatively coupled to the potentiometric sensor such that binding of the analyte of interest by the pH-sensitive aptamer switch induces a measurable change in the potentiometric sensor; and an auxiliary electrode in proximity to the surface, wherein the electrode is configured to alter a pH of a microenvironment in contact with the surface, thereby reversibly shuttling the pH-sensitive aptamer switch between a first state wherein it specifically binds the analyte of interest and a second state wherein it does not specifically bind the analyte of interest.