Temperature-responsive fluorescent particles for detection of biomolecules

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Existing methods for detecting biomolecules, such as ELISA, digital ELISA, SMC Immunoassay Technology, and immunochromatography, are either too complex, time-consuming, or lack sensitivity for early detection of diseases and infections, particularly at low concentrations.

Innovation Solution

Development of temperature-responsive fluorescent particles and probes that utilize squaric acid derivatives in lipid vesicles, which switch between fluorescence emission and quenching based on phase transitions, allowing for simple and rapid detection and quantification of biomolecules by measuring fluorescence changes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If ELISA method is used for detecting biomolecules, then high specificity can be obtained, but operations such as reagent washing and enzymatic reaction are complicated and time-consuming

Engineering Contradiction:
ImprovespecificityVSAvoidoperation complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent utilizes the gel-liquid crystal phase transition of lipid vesicles at specific temperatures. The fluorescent molecule is incorporated into the lipid vesicle membrane, and its fluorescence emission is controlled by the phase state of the membrane. At gel phase (lower temperature), fluorescence is quenched; at liquid crystal phase (higher temperature), fluorescence is emitted. This phase transition mechanism replaces complex enzymatic reactions and washing steps with a simple temperature-controlled optical signal change, achieving high specificity without operational complexity

Inventive Principle:
Principle #36Phase transitions

Solution Approach 2:

The patent changes the temperature parameter to control the phase transition of lipid vesicles and thereby control fluorescence emission. By adjusting temperature, the system transitions between signal-off (gel phase) and signal-on (liquid crystal phase) states. This parameter change approach simplifies the detection process from multiple complex steps to a single temperature-controlled measurement, maintaining high specificity while eliminating operational complexity

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If digital ELISA method is used for detecting biomolecules, then high sensitivity can be realized, but operations are more complicated and more time-consuming than conventional ELISA method

Engineering Contradiction:
Improvedetection sensitivityVSAvoidmeasurement time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent employs phase transition of lipid vesicles to generate detectable fluorescence signals directly, eliminating the need for enzymatic amplification steps required in digital ELISA. The phase transition provides a direct optical readout that is both sensitive and rapid, achieving high detection sensitivity without the time-consuming microdroplet manipulation and enzymatic reaction steps of digital ELISA

Inventive Principle:
Principle #36Phase transitions

Solution Approach 2:

The patent extracts and utilizes only the essential detection function from complex ELISA methods by using temperature-controlled phase transition of fluorescent lipid vesicles. This extraction approach removes unnecessary operational steps (washing, enzymatic reactions, microdroplet handling) while retaining the core capability of sensitive biomolecule detection, thereby reducing measurement time while maintaining sensitivity

Inventive Principle:
Principle #2Taking out (Extraction)

3Ease of operation

If immunochromatography method is used for detecting biomolecules, then simple operation can be achieved, but sensitivity is low and false negative rate is high

Engineering Contradiction:
Improveoperation simplicityVSAvoiddetection sensitivity
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent introduces temperature as a controllable parameter to enhance the sensitivity of simple detection. By changing temperature to trigger phase transition, the system achieves signal amplification and improved detection sensitivity while maintaining operational simplicity. The temperature-controlled fluorescence emission provides a clear optical signal that overcomes the visual judgment limitations of immunochromatography

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses phase transition of lipid vesicles to create a highly sensitive detection system that remains operationally simple. The phase transition provides a binary signal (fluorescence on/off) that is easily detectable and eliminates visual judgment variability, achieving both simplicity and high sensitivity simultaneously by leveraging the intrinsic optical properties of phase-transiting fluorescent vesicles

Inventive Principle:
Principle #36Phase transitions

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 rapid and sensitive detection of low-concentration biomolecules with high specificity and simplicity, adaptable to various detection devices and conditions, overcoming limitations of existing methods.

Implementation Method 1

when this compound is incorporated into a lipid vesicle exhibiting a gel-liquid crystal phase transition, the fluorescence emission is not observed at a temperature at which the lipid vesicle is in the gel phase, but a strong fluorescence emission appears by heating a dispersion of the lipid vesicle to convert its phase into a liquid crystal phase

Methodology Applied
Scientific EffectGel-liquid crystal phase transition: Phase Change

Implementation Method 2

the fluorescent molecule is quenched by aggregation when in the gel phase and it emits fluorescence by disaggregation when in the liquid crystal phase

Methodology Applied
Scientific EffectAggregation-induced quenching:

Data Source

PatentUS12480943B2Temperature-responsive fluorescent particles for detection of biomolecules
Publication Date: 2025.11.25 NANOTHETA CO LTD
  • US12480943B2 patent drawing
  • US12480943B2 patent drawing
  • US12480943B2 patent drawing

AI summary

Provided is a temperature-responsive fluorescent particle comprising at least one type of fluorescent molecule in a molecular assembly comprising and constituted by at least one type of amphiphilic molecule, wherein the fluorescent molecule emits fluorescence when the molecular assembly is in the liquid phase and it is quenched when the molecular assembly is in the solid phase, due to a temperature-responsive solid-liquid phase transition, so that fluorescence emission and quenching of the fluorescent molecule are reversibly switched in a temperature responsive manner. Also provided is a temperature-responsive fluorescent probe comprising the temperature-responsive fluorescent particle the surface of which is modified with a biomolecule recognition element, and methods for detecting and quantitatively determining a biomolecule with the temperature-responsive fluorescent probe.