Non-Resonant Second Harmonic Detection for Solute Aggregation Analysis

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Solution Overview

Problem

Existing methods for determining the aggregation state of a solute in a solvent are limited by high detection limits, unspecificity, and the need for resource-intensive separation processes, making it difficult to reliably detect and measure solubility limits, especially for poorly soluble compounds.

Innovation Solution

A method utilizing pulsed laser illumination and detection of non-resonant second harmonic photons to determine the aggregation state of a solute in a solvent, allowing for ultra-sensitive and resource-efficient observation of solute aggregation without the need for separation processes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If linear light scattering methods (nephelometry) are used to detect aggregates, then the method is fast and versatile, but the detection limit is high (at least 20 μM) and the method is unspecific

Engineering Contradiction:
Improvedetection limitVSAvoidmeasurement speed
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent changes the detection parameter from linear light scattering intensity to second harmonic generation signal intensity. This parameter change enables detection at much lower concentrations (below 20 μM) while maintaining measurement speed, as the SHG signal provides enhanced sensitivity to aggregate formation without requiring the high concentrations needed for linear scattering methods.

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If separation methods (filtration, centrifugation, HPLC) are used to measure dissolved compounds, then the solubility can be determined, but the process is resource-intensive and generates waste

Engineering Contradiction:
Improvesolubility measurement accuracyVSAvoidconsumables and waste
Core Design Contradiction:
Measurement precisionVSLoss of substance

Solution Approach 1:

The patent extracts the aggregation information directly from the solution using second harmonic generation detection, eliminating the need for physical separation processes. By detecting the SHG signal from aggregates in the liquid phase, the method obtains solubility data without requiring filtration, centrifugation, or chromatography, thus avoiding consumable waste and resource consumption.

Inventive Principle:
Principle #2Taking out (Extraction)

3Measurement precision

If second harmonic generation is used to detect aggregates, then structural sensitivity and selectivity are improved, but the signal is weak and requires careful optimization

Engineering Contradiction:
Improvestructural sensitivityVSAvoidsignal strength
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent uses the solvent as an intermediary to enhance the detection signal. By measuring the second harmonic generation signal from the solvent molecules surrounding the aggregates, the method amplifies the structural information about solute aggregates. The solvent acts as a mediator that converts the structural arrangement of aggregates into an enhanced optical signal, improving detectability without requiring direct detection of the solute aggregates themselves.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 method enables reproducible and sensitive measurements of solute aggregation, distinguishing between monomers and aggregates with high precision, and determining solubility limits with improved accuracy and reduced waste compared to traditional methods.

Implementation Method 1

Second harmonic scattering (SHS) is a second-order nonlinear optical method where two incoming photons interacting with a material or substance combine into a second harmonic (SH) photon that is the sum of the frequencies of the incoming photons

Methodology Applied
Scientific EffectSecond harmonic scattering: Second Harmonic Generation

Implementation Method 2

Light scattering is known for observing the aggregation of substances. Light scattering occurs when light encounters non-uniformities and deviates from its otherwise straight trajectory

Methodology Applied
Scientific EffectLight scattering: Scattering

Data Source

PatentEP4542204A1Method, computer readable medium and apparatus for determining an aggregation state of a solute in a solvent
Publication Date: 2025.04.23 ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE (EPFL)
  • EP4542204A1 patent drawingFigure 1
  • EP4542204A1 patent drawingFigure 2
  • EP4542204A1 patent drawingFigure 3~4

AI summary

Method for determining an aggregation state of a solute in a solvent, comprising: illuminating (702), with a laser source, at least one mixture comprising the solute and the solvent with a pulsed laser beam, detecting (704), with a detector, a portion of the pulsed laser beam, wherein the portion of the pulsed laser beam has interacted with the at least one mixture, characterized in that detecting (704) a portion of the pulsed laser beam comprises: detecting non-resonant second harmonic photons, wherein the non-resonant second harmonic photons issue from an interaction of the pulsed laser beam with the solvent of the at least one mixture, and determining (706) at least one value indicative of the non-resonant second harmonic photons detected for the at least one mixture, and in that the method further comprises: determining (708) at least one characteristic for an aggregation behavior of the solute in the solvent on the basis of the at least one value indicative of the detected non-resonant second harmonic photons determined for the at least one mixture. A computer readable medium and an apparatus (300, 400, 500, 600) are described.