Lipid Particle Abundance Analysis for Delivery Quality Control

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Solution Overview

Problem

Existing methods for evaluating the quality of lipid particles used for delivering substances to cells rely on fill ratios, which have a low correlation with delivery efficiency, leading to inconsistent and inaccurate quality control.

Innovation Solution

An analysis method that determines the abundance ratio of lipid particles containing an objective substance by measuring scattered light and fluorescence, providing a direct and accurate assessment of particle quality.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If fill ratio is used to evaluate lipid particle quality, then quality control can be performed, but the evaluation has low correlation with delivery efficiency leading to inaccurate quality control

Engineering Contradiction:
Improvequality evaluation accuracyVSAvoiddelivery efficiency correlation
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent uses fluorescence labeling to create optical signals that change based on the presence of objective substances. Fluorescently labeled antibodies or molecules bind to target antigens on lipid particles, producing detectable fluorescence signals that directly indicate the presence and quantity of encapsulated substances, providing accurate quality evaluation correlated with delivery efficiency.

Inventive Principle:
Principle #32Color changes

Solution Approach 2:

The patent replaces mechanical/chemical measurement methods (fill ratio calculation based on substance concentration) with optical detection methods (flow cytometry, fluorescence-activated cell sorting). This substitution enables direct visualization and quantification of individual lipid particles containing objective substances, significantly improving measurement precision and reliability of quality control.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Ease of manufacture

If fill ratio measurement is performed by measuring remaining objective substances in solution, then quality control is possible, but the method is indirect and inconsistent

Engineering Contradiction:
Improvequality control feasibilityVSAvoidfill ratio accuracy
Core Design Contradiction:
Ease of manufactureVSMeasurement precision

Solution Approach 1:

The patent introduces fluorescent labels as intermediary substances that bind to objective substances or target antigens on lipid particles. These fluorescent intermediaries serve as detectable proxies that directly indicate the presence of encapsulated substances, enabling precise and consistent measurement without relying on indirect calculations from remaining solution concentrations.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent employs fluorescence emission as an optical indicator to directly detect and quantify lipid particles containing objective substances. The fluorescence signal provides real-time, particle-by-particle information about encapsulation status, enabling accurate and consistent quality control measurements that correlate with actual delivery capability.

Inventive Principle:
Principle #32Color changes

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 abundance ratio method offers a more reliable index for evaluating lipid particle quality, ensuring consistent and stable delivery efficiency of substances to cells.

Implementation Method 1

a first substance which has lipid membrane permeability, binds to the objective substance

Methodology Applied
Scientific EffectLipid membrane permeability: Permeation

Implementation Method 2

includes a dye that generates fluorescence, irradiating step of irradiating mixture obtained from the mixing with light that excites to generate fluorescence

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 3

a first measuring step of the number of the plurality of lipid particles in the lipid particle group by detecting scattered light obtained from the mixture by the irradiating with the light

Methodology Applied
Scientific EffectScattered light: Scattering

Data Source

PatentEP4028754B1Analysis method, analysis substrate, analysis kit, and analysis apparatus
Publication Date: 2025.09.03 KK TOSHIBA
  • EP4028754B1 patent drawingFigure 1~2
  • EP4028754B1 patent drawingFigure 3
  • EP4028754B1 patent drawingFigure 4

AI summary

According to one embodiment, an analysis method is for determining an abundance ratio of first lipid particles containing an objective substance in a lipid particle group. The analysis method comprising irradiating a solution including the lipid particle group with light, measuring at least two of the total number of the plurality of lipid particles, the number of the first lipid particles, and the number of second lipid particles not containing the objective substance in the solution by detecting scattered light, and calculating an abundance ratio of the first lipid particles.