Rhodamine Piperazine pH Sensor Agents for Cellular Monitoring

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current methods for measuring pH changes in biological and cellular environments are limited in sensitivity and specificity, particularly in detecting pH alterations across different cellular compartments.

Innovation Solution

Development of pH sensor agents with a rhodamine-class core structure and substituted piperazine groups that exhibit significant fluorescence changes in response to pH alterations, allowing for real-time detection and monitoring of pH shifts within cellular environments.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional pH measurement compounds are used, then pH changes can be measured, but sensitivity and specificity are limited

Engineering Contradiction:
ImprovepH detection sensitivityVSAvoiddetection specificity
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent modifies the molecular structure of rhodamine compounds by introducing substituted piperazine groups at specific positions (6 and 6′) to alter the pH sensitivity parameters. This structural parameter change enables the sensor to detect pH changes with enhanced sensitivity and specificity compared to conventional rhodamine compounds, directly resolving the technical contradiction between measurement precision and reliability.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention creates a composite molecular structure combining rhodamine core with substituted piperazine groups, forming a hybrid sensor agent that leverages the fluorescent properties of rhodamine and the pH-sensitive characteristics of piperazine. This composite structure achieves both high sensitivity and specificity for pH detection in biological environments.

Inventive Principle:
Principle #40Composite materials

2Productivity

If fluorescent sensor agents are used to detect pH changes, then real-time monitoring is enabled, but the complexity of the sensor structure increases

Engineering Contradiction:
Improvereal-time detection capabilityVSAvoidsensor molecular structure
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The sensor molecule is segmented into distinct functional domains: the rhodamine core provides fluorescent signal generation, while the substituted piperazine groups provide pH-sensitive switching capability. This segmentation allows each component to perform its specialized function efficiently, enabling real-time detection without requiring overly complex molecular architectures.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The rhodamine-piperazine composite structure serves multiple functions simultaneously: it acts as a fluorescent probe, a pH indicator, and a cell-permeable sensor agent. This multi-functionality enables real-time pH monitoring in living cells without requiring separate systems for each function, thereby reducing overall system complexity while maintaining high productivity.

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 pH sensor agents provide sensitive and specific detection of pH changes, enabling accurate monitoring of pH alterations across different cellular compartments, enhancing our understanding of biological processes and potential applications in cellular research and diagnostics.

Implementation Method 1

sensor agents are provided that exhibit a detectable change in fluorescence (e.g., fluorescence intensity) upon alteration of the pH of the surrounding environment

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentEP2823270B1pH SENSORS
Publication Date: 2022.05.04 PROMEGA CORP
  • EP2823270B1 patent drawingFigure 1A~1C
  • EP2823270B1 patent drawingFigure 1D~1E
  • EP2823270B1 patent drawingFigure 2A~2B

AI summary

Provided herein are fluorescent sensor agents, and methods of use and manufacture thereof. In particular, sensor agents are provided that exhibit a detectable change in fluorescence (e.g., fluorescence intensity) upon alteration of the pH of the surrounding environment (e.g., upon moving from one pH environment to another).