pH-Sensitive Quencher Amplifies Fluorescence Intensity

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Solution Overview

Problem

Current sensors face challenges in detecting analyte concentrations over narrow ranges with high sensitivity, as existing technologies do not effectively utilize pH-sensitive fluorophores and quenchers to enhance fluorescence intensity changes in response to pH variations relevant to analyte concentrations.

Innovation Solution

The development of an analyte-sensitive substance comprising a pH-sensitive fluorophore, a pH-sensitive quencher, and an ionophore, which together provide a local pH related to analyte concentrations, with the quencher-modified intensity function exhibiting a greater rate of change than the intrinsic intensity function, enhancing sensitivity through fluorescence quenching mechanisms.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If a fluorophore is configured to selectively bind to an analyte such that binding quenches the fluorescence, then the fluorescence intensity can be used to determine analyte concentration, but the sensor cannot effectively detect analyte concentrations over narrow ranges with high sensitivity

Engineering Contradiction:
Improveanalyte concentration detection precisionVSAvoiddetection range adaptability
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent applies parameter changes by introducing a pH-sensitive quencher that modifies the fluorescence intensity function's parameters. The quencher's pH-dependent quenching behavior transforms the intrinsic intensity function into a quencher-modified intensity function with enhanced sensitivity (greater rate of change) over a specific pH range, enabling precise detection within narrow analyte concentration ranges while maintaining adaptability through pH control

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs composite materials by combining multiple functional components: a fluorophore, a pH-sensitive quencher, and an ionophore. This composite analyte-sensitive substance integrates the binding capability of the ionophore with the fluorescence properties of the fluorophore and the quenching mechanism of the pH-sensitive quencher, creating a system that achieves both high sensitivity and appropriate detection range adaptability

Inventive Principle:
Principle #40Composite materials

2Measurement precision

If the intrinsic intensity function of a pH-sensitive fluorophore is used directly, then the fluorescence intensity changes with pH, but the rate of change is insufficient for high-sensitivity detection

Engineering Contradiction:
Improvefluorescence intensity measurement precisionVSAvoidsensor composition complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent introduces a pH-sensitive quencher as an intermediary component that mediates between the fluorophore and the pH environment. This quencher amplifies the pH response by providing an additional quenching mechanism that increases the rate of change of fluorescence intensity with pH, thereby enhancing measurement precision without requiring fundamental changes to the fluorophore itself

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent creates a composite analyte-sensitive substance combining the fluorophore, pH-sensitive quencher, and ionophore. This composite structure achieves enhanced sensitivity through the synergistic interaction of components while maintaining a relatively simple overall sensor design, as the complexity is confined to the molecular composition rather than the sensor architecture

Inventive Principle:
Principle #40Composite materials

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 configuration allows for increased sensitivity in detecting analyte concentrations by amplifying fluorescence intensity changes, enabling precise measurement of analyte concentrations across specified ranges, thereby improving the accuracy of analyte detection in various environments.

Implementation Method 1

an ionophore that is configured to provide a local pH within the analyte-sensitive substance related to a concentration of an analyte proximate the analyte-sensitive substance

Methodology Applied
Scientific EffectIonophore-mediated pH transduction:

Implementation Method 2

a pH-sensitive fluorophore that is configured to fluoresce with a fluorescence intensity that increases or decreases as a function of the local pH over a range of pH values according to an intrinsic intensity function

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 3

a pH-sensitive quencher that is configured to quench the pH-sensitive fluorophore to an extent that increases or decreases as a function of the local pH within the range of pH values

Methodology Applied
Scientific EffectFluorescence quenching:

Data Source

PatentUS11635378B1Method for increasing sensor resolution by spectrally stacking responsive dyes
Publication Date: 2023.04.25 VERILY LIFE SCIENCES LLC
  • US11635378B1 patent drawing
  • US11635378B1 patent drawing
  • US11635378B1 patent drawing

AI summary

An analyte-sensitive substance is provided that has an optical property related to the concentration of an analyte. The analyte-sensitive substance includes an ionophore or other substance configured to provide a local pH, within the analyte-sensitive substance, that is related to the concentration of the analyte proximate the analyte-sensitive substance. The analyte-sensitive substance further includes a pH-sensitive fluorophore that increases or decreases its intrinsic fluorescence intensity with the local pH across a specified range of pH values. The analyte-sensitive substance further includes a pH-sensitive quencher configured to increase the slope of the change of fluorescence intensity of the pH-sensitive fluorophore across the specified range of pH values. The analyte-sensitive substance may further include an ionic additive configured to adjust the local pH such that the specified range of pH values corresponds to a range of analyte concentration values of interest.