Electrochemical pH Modulation for High Vertical Resolution Biospecimen Imaging

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Solution Overview

Problem

Current imaging methods for biospecimens require expensive standalone systems or high-cost add-on equipment, limiting their accessibility and compatibility with existing microscopic instruments, especially for achieving high vertical resolution in biological applications.

Innovation Solution

The method involves labeling biospecimens with pH-sensitive labels and using electrochemical pH modulation by applying a potential or current to an electrode in a buffered solution containing a pH modulating agent, which causes a pH change adjacent to the electrode, triggering an optical signal for imaging, compatible with existing microscopic instruments.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If expensive standalone imaging systems or high-cost add-on equipment are used, then high vertical resolution imaging is achieved, but system cost and complexity increase

Engineering Contradiction:
Improvevertical resolutionVSAvoidsystem complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces complex optical/mechanical imaging systems with a simplified electrochemical system. Instead of using confocal microscopy with pinhole apertures or TIRF with specialized optical components, the invention uses an electrode with pH modulating agents that create localized pH changes to activate pH-sensitive fluorescent labels, achieving similar vertical resolution through electrochemical means rather than optical complexity

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent changes the parameter used for localized imaging from optical properties (in confocal/TIRF) to electrochemical pH parameters. By applying potential or current to the electrode, the pH modulating agents undergo redox reactions that locally change pH, which in turn activates or deactivates pH-sensitive fluorescent labels, enabling vertical resolution through pH parameter control rather than optical parameter control

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If specialized optical and physical components are used, then localized imaging with high vertical resolution is achieved, but equipment cost increases

Engineering Contradiction:
Improvevertical resolutionVSAvoidequipment cost
Core Design Contradiction:
Measurement precisionVSEase of manufacture

Solution Approach 1:

The patent employs inexpensive pH modulating agents (such as quinones, hydroquinones, or other redox-active compounds) that can be easily synthesized or obtained and are consumed in the electrochemical reactions. These cheap chemical agents replace expensive optical components, and their temporary consumption during imaging cycles mirrors the disposable nature principle, achieving cost-effective localized imaging

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The patent substitutes expensive specialized optical components (confocal pinholes, TIRF prisms, SPRF coupling structures) with a simple electrode and electrochemical pH modulating agents. The electrode is a basic electrochemical component, and the pH modulating agents are inexpensive chemicals, together replacing costly optical hardware while maintaining the ability to achieve localized high-vertical-resolution imaging

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

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 enables localized imaging with high vertical axial resolution, similar to confocal microscopy or TIRF microscopy, using electrochemical pH modulation to produce a pH modulation zone, allowing imaging of biospecimens with existing fluorescent microscopes at a lower cost and increased accessibility.

Implementation Method 1

applying a potential or a current to the electrode, whereupon the pH modulating agent causes a change in the pH value in a zone adjacent to the surface of the electrode

Methodology Applied
Scientific EffectElectrochemical reaction: Electrolysis

Implementation Method 2

causing the pH-sensitive label within the zone to produce an optical signal

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 3

the microstructures, when present, define a volume between the biospecimen and the surface, through which the pH modulating agent diffuses

Methodology Applied
Scientific EffectDiffusion: Diffusion

Data Source

PatentEP3906401B1Ph-modulated imaging of targets close to a solid surface
Publication Date: 2023.08.30 ROBERT BOSCH GMBH
  • EP3906401B1 patent drawingFigure 1A
  • EP3906401B1 patent drawingFigure 1B
  • EP3906401B1 patent drawingFigure 2

AI summary

Provided are methods for imaging a biospecimen, which involves the use of electrochemical pH modulation in combination with pH-sensitive labels to achieve localized imaging with a high vertical axial resolution.