Particle Characterization in Solution Using DLS and Nano-DSF
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Solution Overview
Problem
Existing systems are unable to simultaneously measure protein aggregation and unfolding with high sensitivity, leading to incomplete understanding of denaturation mechanisms and inefficient formulation development for protein-based biopharmaceuticals.
Innovation Solution
A method combining dynamic light scattering (DLS) and nano-differential scanning fluorimetry (nano-DSF) is employed to analyze protein structure and aggregation in small sample volumes, allowing for rapid characterization of protein stability and folding within seconds.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional quality control methods are used to characterize particles in solution, then measurement accuracy is maintained, but measurement time is excessively long causing considerable delay
Solution Approach 1:
The patent combines dynamic light scattering (DLS) and differential scanning fluorimetry (DSF) measurements into a single integrated system, allowing simultaneous acquisition of particle size distribution and protein folding stability data. This merging of two separate measurement techniques into one system resolves the contradiction by providing comprehensive particle characterization with high accuracy while reducing total measurement time from minutes to seconds.
2Loss of information
If separate measurement systems are used for aggregation and folding analysis, then comprehensive characterization is achieved, but device complexity and measurement time increase
Solution Approach 1:
The patent creates a universal measurement platform that performs multiple functions: DLS for particle size and aggregation detection, and DSF for protein folding and stability analysis. This multi-functional system resolves the contradiction by providing comprehensive protein characterization (avoiding information loss) while using a single integrated device rather than multiple separate systems, thereby reducing device complexity.
3Productivity
If small sample volumes are used for rapid screening, then productivity is improved, but measurement sensitivity and accuracy deteriorate
Solution Approach 1:
The patent combines DLS and DSF measurements in a single system where both techniques contribute to characterizing the same small sample volume. The DSF component provides enhanced sensitivity for detecting protein folding changes in small volumes, while DLS simultaneously measures particle size. This combination resolves the contradiction by maintaining measurement precision and sensitivity even when using small sample volumes for high-throughput screening.
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 simultaneous measurement of protein denaturation and aggregation processes, providing real-time insights into protein stability and aggregation mechanisms, enhancing formulation development for biopharmaceuticals.
Implementation Method 1
determining characteristics of said particles in solution comprised in the sample based on a dynamic light scattering (DLS) measurement
Data Source
Figure 1A~1B
Figure 2~3
Figure 4A~4B
AI summary
The present invention relates to a method for measuring characteristics of particles in solution and to a device for performing the same, wherein said method comprises the steps of providing a vessel comprising a sample of said particles in solution, wherein the sample has preferably a volume between 0.1 µL and 15 µL, providing a monochromatic light source and a light detector, transmitting light from the monochromatic light source to the vessel comprising the sample, detecting light emitted from the vessel with the light detector, and determining characteristics of said particles in solution comprised in the sample based on a dynamic light scattering (DLS) measurement.