Biosensor pH Control via Segmented Electrodes

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Solution Overview

Problem

Current biosensors face challenges in accurately and reliably controlling pH levels in biological solutions, particularly in multiplexed measurement platforms, due to complex systems with buffer components, co-solvents, and interfering electrochemically active components, which affects the sensitivity and specificity of biomolecular analyte detection.

Innovation Solution

A method and device for modulating pH or ionic concentration near electrode surfaces in biosensors using electrochemically active agents, enzymes, and buffer inhibitors to produce H+ or OH- ions, allowing for precise control of local pH gradients at multiple test sites, integrated with CMOS or TFT technology.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional pH control methods are used in biosensors, then pH modulation can be achieved, but reliability and reproducibility deteriorate due to complex buffer systems and interfering electrochemically active components

Engineering Contradiction:
ImprovepH control reliabilityVSAvoidsystem complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent divides the pH control function into separate working electrodes, each independently controlling pH at specific test sites. This segmentation allows reliable pH control at each site without interference from other sites, addressing the reliability issue while managing system complexity through modular electrode design.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent implements local pH control at each test site using individual working electrodes, creating different pH conditions at different locations. This local quality approach enables reliable and reproducible pH modulation specific to each detection site, overcoming the limitations of global pH control in complex buffer systems.

Inventive Principle:
Principle #3Local quality

2Adaptability or versatility

If multiple test sites are used in a biosensor array, then multiplexed detection capability is improved, but pH control accuracy deteriorates due to variations in local pH modulation

Engineering Contradiction:
Improvemultiplexed detection capabilityVSAvoidpH control accuracy
Core Design Contradiction:
Adaptability or versatilityVSMeasurement precision

Solution Approach 1:

The patent assigns individual working electrodes to control pH at each test site in the multiplexed array. This segmentation ensures that each test site receives precise pH control independent of other sites, maintaining measurement accuracy while enabling multiplexed detection across multiple sites.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent employs feedback control where the potential applied to each working electrode is adjusted based on measured parameters to maintain target pH conditions. This feedback mechanism ensures accurate and reproducible pH control across multiple test sites, addressing the precision issue while preserving multiplexed capability.

Inventive Principle:
Principle #23Feedback

3Manufacturing precision

If electrochemically active agents are used to modulate pH, then binding efficiency can be optimized, but cross-reactivity increases due to interfering electrochemically active components in biological samples

Engineering Contradiction:
Improvebinding efficiencyVSAvoidcross-reactivity
Core Design Contradiction:
Manufacturing precisionVSObject-affected harmful factors

Solution Approach 1:

The patent creates localized pH environments at each test site that optimize binding efficiency for specific analyte-probe interactions. By controlling pH locally rather than globally, the system can optimize binding conditions without the electrochemically active interference affecting the entire system, thus reducing cross-reactivity while maintaining binding efficiency.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent uses pH as an intermediary parameter to control binding interactions. By modulating pH through electrochemical control of working electrodes, the system optimizes binding efficiency indirectly through pH adjustment rather than direct chemical interaction, reducing cross-reactivity with electrochemically active components in the sample.

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

Enables accurate, reliable, and reproducible detection of biomolecular analytes by optimizing binding efficiencies and reducing cross-reactivity, thereby improving the sensitivity and specificity of diagnostic tests in multiplexed assays.

Implementation Method 1

oxidizing or reducing the electrochemically active agent

Methodology Applied
Scientific EffectOxidation: Oxidation

Implementation Method 2

oxidizing or reducing the electrochemically active agent

Methodology Applied
Scientific EffectReduction: Reduction

Implementation Method 3

reacting the electrochemically active agent, the enzyme, the enzyme substrate, or a combination thereof in the aqueous solution to produce H+

Methodology Applied
Scientific EffectElectrochemical reaction: Redox Reactions

Implementation Method 4

enzymatically oxidizing or reducing the enzyme substrate

Methodology Applied
Scientific EffectEnzymatic oxidation: Oxidation

Implementation Method 5

enzymatically oxidizing or reducing the enzyme substrate

Methodology Applied
Scientific EffectEnzymatic reduction: Reduction

Implementation Method 6

adding one or more enzymes immobilized onto magnetic micro- or nano-particles to the aqueous solution; adding an enzyme substrate to the aqueous solution; and enzymatically oxidizing or reducing the enzyme substrate

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Implementation Method 7

adding one or more enzymes immobilized onto magnetic micro- or nano-particles to the aqueous solution

Methodology Applied
Scientific EffectMagnetic particle transport: Magnetism

Implementation Method 8

adding a buffer inhibitor to the aqueous solution; inhibiting the diffusion of H+

Methodology Applied
Scientific EffectDiffusion inhibition: Diffusion Barrier

Data Source

PatentEP3708673B1Method and device for electronically controlling the ph of a solution
Publication Date: 2025.03.26 ROBERT BOSCH GMBH
  • EP3708673B1 patent drawingFigure 1(a)~1(c)
  • EP3708673B1 patent drawingFigure 2~3
  • EP3708673B1 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 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.