Ion Sensor Copolymer Reversible Calcium Detection

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Solution Overview

Problem

Current calcium ion sensors, such as Fura-2, have limitations in detecting extracellular calcium concentrations due to high association constants and irreversible sensing capabilities, making them unsuitable for in vivo applications and integration into devices.

Innovation Solution

A copolymer with carboxyl groups and an aggregation-induced emission compound is developed, allowing reversible fluorescence detection of polyvalent metal ions like calcium, which can be immobilized on a solid base for device integration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If a sensor with high association constant pKa (such as Fura-2) is used, then the sensor can detect intracellular calcium ion concentration (nM order), but it cannot detect extracellular calcium ion concentration (mM order)

Engineering Contradiction:
Improvecalcium ion concentration detection rangeVSAvoidapplicability to different calcium concentration environments
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent changes the association constant parameter by using a polymer with multiple carboxyl groups instead of a small molecule sensor. The polymer's multiple carboxyl groups work cooperatively to bind calcium ions, effectively lowering the association constant from pKa 6-10 to pKa 2-4, which enables detection of extracellular calcium concentrations in the mM range while maintaining detection capability across different concentration environments

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs a composite structure where a polymer backbone with multiple carboxyl groups is combined with an aggregation-induced emission (AIE) compound. This composite material achieves both the desired low association constant for extracellular detection and reversible fluorescence response, resolving the contradiction between detection range and adaptability

Inventive Principle:
Principle #40Composite materials

2Reliability

If a sensor with high association constant is used, then the sensor achieves irreversible sensing capability, but it becomes difficult to integrate with devices

Engineering Contradiction:
Improvesensing capabilityVSAvoidintegration difficulty
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent introduces dynamic reversibility to the sensing mechanism. The polymer sensor with low association constant (pKa 2-4) enables reversible binding of calcium ions, allowing the sensor to respond dynamically to changing calcium concentrations. This reversibility facilitates device integration by enabling continuous monitoring and resetting capabilities, eliminating the irreversibility problem of traditional sensors

Inventive Principle:
Principle #15Dynamics

3Device complexity

If a small molecule sensor is used, then the sensor structure is simple, but the sensor cannot be immobilized on solid base material for device integration

Engineering Contradiction:
Improvesensor structureVSAvoidimmobilization capability
Core Design Contradiction:
Device complexityVSEase of manufacture

Solution Approach 1:

The patent transitions from a small molecule sensor to a polymer sensor with repeating units containing carboxyl groups. This segmented polymeric structure provides multiple binding sites along the polymer chain, enabling effective immobilization on solid base materials through multiple attachment points. The polymer nature maintains relatively simple structure while dramatically improving manufacturability and device integration capability

Inventive Principle:
Principle #1Segmentation

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 copolymer enables sensitive and reversible detection of calcium ions, suitable for both intracellular and extracellular applications, and can be integrated into devices for real-time measurement of calcium concentrations.

Implementation Method 1

the copolymer binds to polyvalent metal ions such as calcium ions to thereby generate fluorescence by the aggregation-induced emission compound

Methodology Applied
Scientific EffectAggregation-induced emission: Fluorescence

Data Source

PatentUS10444249B2Ion sensor
Publication Date: 2019.10.15 THE JAPAN SCI & TECH AGENCY
  • US10444249B2 patent drawing
  • US10444249B2 patent drawing
  • US10444249B2 patent drawing

AI summary

Provided is a compound including a repeating unit (A) having a carboxyl group on a side chain thereof and a repeating unit (B) having a carboxylate group having an ester residue exhibiting an aggregation-induced emission capability on a side chain thereof and the compound is useful as a polyvalent metal ion sensor such as calcium ions that is capable of reversible sensing and of being integrated into a device.