Biosensor Electrode pH Gradient Control for Bubble Detection

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Solution Overview

Problem

Current biosensors face challenges in accurately and reliably detecting biomolecules due to limitations in sensitivity and cross-reactivity, particularly in aqueous solutions where pH modulation is complex, and the presence of bubbles can disrupt experiments, leading to false results.

Innovation Solution

A method and biosensor system utilizing a multisite array with pH-sensitive fluorescent proteins to detect bubbles and modulate pH independently at each test site, employing electrochemical agents and enzymes to control pH gradients, and a control unit to detect bubble presence and store location, enhancing sensitivity and specificity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If pH modulation is performed in aqueous solutions using conventional methods, then pH control is achieved, but the pH modulation becomes complex and less reliable

Engineering Contradiction:
ImprovepH control accuracyVSAvoidpH modulation complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The invention divides the pH control system into multiple independent working electrodes, each capable of independent pH modulation at its local test site. This segmentation allows each electrode to control pH independently without interfering with others, simplifying the overall control strategy while maintaining high precision at each site.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Each working electrode creates a localized pH gradient confined to its immediate vicinity through electrochemical reactions. The pH modulation is spatially differentiated, with each electrode affecting only its local test site rather than the entire solution, thereby achieving precise local control without global complexity.

Inventive Principle:
Principle #3Local quality

2Productivity

If bubbles are present in the aqueous solution, then the experiment can proceed, but false results occur due to bubble interference

Engineering Contradiction:
Improveexperiment throughputVSAvoiddetection accuracy
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The invention converts the harmful effect of bubbles into a useful detection signal. By measuring capacitance changes at each electrode, the system detects bubble presence and automatically identifies and excludes affected test sites from analysis. This transforms bubble interference from a source of false results into a quality control mechanism that improves overall reliability.

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

3Measurement precision

If multiple test sites are used in a biosensor array, then sensitivity and specificity can be improved, but cross-reactivity and background signals increase

Engineering Contradiction:
Improvedetection sensitivityVSAvoidcross-reactivity and background signals
Core Design Contradiction:
Measurement precisionVSObject-generated harmful factors

Solution Approach 1:

Each test site in the multi-site array has its own dedicated working electrode that independently modulates pH and detects bubbles. This local independence ensures that cross-reactivity or background signals at one site do not affect other sites, as each site operates with its own controlled pH environment and detection system.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The system uses real-time capacitance measurement feedback to detect bubbles at each test site. When a bubble is detected, the system automatically excludes that specific test site from final analysis, preventing bubble-induced false signals from compromising overall detection accuracy.

Inventive Principle:
Principle #23Feedback

4Adaptability or versatility

If pH is controlled at each test site independently, then binding efficiency can be optimized, but variations in pH modulation decrease accuracy

Engineering Contradiction:
Improvebinding efficiency optimizationVSAvoidpH modulation reproducibility
Core Design Contradiction:
Adaptability or versatilityVSMeasurement precision

Solution Approach 1:

The system employs pH-sensitive fluorescent proteins as real-time feedback sensors at each test site. These proteins report the actual pH conditions, allowing the system to monitor and verify pH modulation accuracy. This feedback mechanism identifies and excludes test sites with abnormal pH conditions, ensuring that only reliably modulated sites contribute to final results.

Inventive Principle:
Principle #23Feedback

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 system improves the accuracy and reliability of biomolecule detection by minimizing cross-reactivity and bubble interference, allowing for precise pH control and efficient bubble detection, thereby enhancing the fidelity of diagnostic tests.

Implementation Method 1

a pH sensitive probe which is a fluorescent protein or a green fluorescent protein

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 2

electrochemically reacting the electrochemical agent in the aqueous solution to generate H+

Methodology Applied
Scientific EffectElectrochemical reaction: Electrolysis

Data Source

PatentEP3320332B1Methods for generating ph/ionic concentration gradient near electrode surfaces for bubble detection using electrodes
Publication Date: 2021.03.03 ROBERT BOSCH GMBH
  • EP3320332B1 patent drawingFigure 1(a)~1(c)
  • EP3320332B1 patent drawingFigure 2~3
  • EP3320332B1 patent drawingFigure 4~5

AI summary

Device and methods for use in a biosensor comprising a multisite array of test sites, the device and methods being useful for modulating the binding interactions between a (biomolecular) probe or detection agent and an analyte of interest from a biological by modulating the pH or ionic gradient near the electrodes in such biosensor. An electrochemically active agent that is suitable for use in biological buffers for changing the pH of the biological buffers. Method for changing the pH of biological buffers using the electrochemically active agents. The methods of modulating the binding interactions provided in a biosensor, analytic methods for more accurately controlling and measuring the pH or ionic gradient near the electrodes in such biosensor, and analytic methods for more accurately measuring an analyte of interest in a biological sample.