Particle Characterization Using DLS and Nano-DSF in Small Samples
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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 protein stability and potential immune reactions, and require lengthy analysis times for characterizing particles in solution.
Innovation Solution
A method combining dynamic light scattering (DLS) and nano-differential scanning fluorimetry (nano-DSF) is used to analyze protein structure and aggregation in small sample volumes, allowing for rapid, simultaneous measurement of intra- and inter-particle processes, including denaturation and aggregation, within a single device.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional separate measurement systems are used for protein aggregation and unfolding analysis, then measurement completeness is improved, but analysis time increases significantly
Solution Approach 1:
The patent combines two separate measurement systems (DLS for aggregation and DSF for unfolding) into a single integrated device that can perform both measurements simultaneously on the same sample, thereby reducing analysis time while maintaining measurement completeness
Solution Approach 2:
The integrated device is designed with multi-functional capability to perform both dynamic light scattering measurements for aggregation detection and differential scanning fluorimetry measurements for unfolding detection within a single system, eliminating the need for separate measurements
2Quantity of substance
If small sample volumes are used for protein characterization, then sample consumption is reduced, but measurement sensitivity decreases
Solution Approach 1:
By combining DLS and DSF measurements in a single integrated device, the system achieves sufficient measurement sensitivity with small sample volumes (as low as 10-20 µL) because both measurement modalities contribute complementary information about protein aggregation and unfolding simultaneously
3Loss of information
If comprehensive protein stability analysis is performed, then understanding of protein behavior is improved, but measurement complexity increases
Solution Approach 1:
The integrated device combines DLS and DSF measurement capabilities into a single system with unified sample handling, allowing comprehensive protein stability analysis (both aggregation and unfolding) to be performed without requiring multiple separate instruments and complex sample transfer procedures
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 fast and accurate characterization of protein stability and aggregation in real-time, reducing analysis time from minutes to seconds, and providing insights into protein behavior under varying conditions for improved formulation development.
Implementation Method 1
characterize particles in a solution on the basis of dynamic light scattering
Implementation Method 2
in combination with differential scanning fluorimetry (DSF)
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.