Particle Size Distribution Analysis via SEC
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Solution Overview
Problem
Current methods for analyzing particle characteristics, such as size exclusion chromatography (SEC), often fail to represent the true sample composition due to larger particles being prevented from passing through the column, necessitating expensive and time-consuming validation techniques like analytical ultracentrifugation (AUC). Additionally, previous workflows require multiple instruments and manual data processing, reducing throughput and consistency.
Innovation Solution
A method involving a first measurement using a particle characterization technique, followed by sample flow to a particle separating device for separation, and a second measurement to determine if all particles have passed through, potentially using the same or alternative techniques, allowing for the identification of lost particles and reducing the need for costly validation methods.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If size exclusion chromatography is used to separate particles, then particle separation is achieved, but larger particles are prevented from passing through the column resulting in loss of sample representation
Solution Approach 1:
The patent performs a first measurement of the entire sample before SEC separation to establish the true particle size distribution. This preliminary measurement captures all particles including large aggregates that would be excluded by the SEC column, allowing subsequent correction of the separation data to represent the complete sample composition.
Solution Approach 2:
The patent compares the first measurement (pre-separation) with the second measurement (post-separation) to identify and quantify particles that were lost during SEC separation. This feedback loop enables correction of the separation data by adding back the missing particle populations, particularly large aggregates, to achieve accurate representation of the original sample.
2Measurement precision
If analytical ultracentrifugation is used to validate SEC measurements, then accurate particle characterization is achieved, but the process becomes expensive and time consuming
Solution Approach 1:
The patent uses a simplified measurement approach that copies the essential function of AUC validation. By performing measurements before and after SEC separation and comparing the results, the method replicates the validation capability of AUC using more accessible and faster techniques, eliminating the need for expensive and time-consuming ultracentrifugation while maintaining accuracy.
Solution Approach 2:
The patent makes a single particle characterization instrument perform multiple functions: it measures the entire sample before separation, measures the separated fractions after SEC, and provides validation by comparing both datasets. This multi-functional approach replaces the need for separate specialized instruments like AUC, reducing both cost and time while maintaining comprehensive particle characterization capability.
3Adaptability or versatility
If multiple instruments with different measurement modalities are used to cover large particle size range, then comprehensive particle analysis is achieved, but the process becomes complex and reduces throughput
Solution Approach 1:
The patent enables a single particle characterization instrument to perform multiple measurement functions by configuring it to measure samples in different states (before and after SEC separation). This universal approach allows one instrument to cover the full particle size range that would otherwise require multiple specialized instruments, simplifying the system while maintaining comprehensive analysis capability across monomers, oligomers, and large aggregates.
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 approach provides a true representation of the sample composition post-separation, potentially eliminating the need for expensive validation techniques like AUC, improving throughput by using a single platform for multiple measurements and enhancing consistency by comparing pre- and post-separation data.
Implementation Method 1
Size exclusion chromatography (SEC) is often used to separate a sample based on particle size or mass
Data Source
AI summary
A method and an apparatus for characterising a sample comprising particles is disclosed. The method comprises performing a first measurement on the sample using a first particle characterisation technique; flowing the sample from the first particle characterisation technique to a particle separating device; separating the sample with the particle separating device; and performing a second measurement on the separated sample. The apparatus is configured to perform the method, and comprises a measurement system for performing measurements according to a first particle characterisation technique and a particle separating device for separating samples comprising particles.