Differential Scanning Calorimetry Using Immiscible Separation Fluids
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Solution Overview
Problem
Conventional differential scanning calorimetry (DSC) systems face difficulties in analyzing high concentration protein solutions due to gel formation, which blocks the sample cell and is hard to clean, limiting measurements to dilute protein concentrations, whereas therapeutic protein solutions require higher concentration analysis.
Innovation Solution
The method involves injecting a sample plug surrounded by immiscible separation fluids to maintain concentration and prevent gel formation, along with a pressure subsystem to rapidly depressurize and repressurize the sample cell, facilitating gel breakdown and cleaning.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If high concentration protein samples are analyzed using conventional DSC systems, then the thermal properties of therapeutic protein solutions can be measured, but gel formation blocks the sample cell and makes cleaning difficult
Solution Approach 1:
The sample is segmented into a small concentrated plug surrounded by separation fluids, preventing gel from blocking the entire cell. The gel forms only in the small sample volume rather than throughout the whole cell, making removal much easier.
Solution Approach 2:
Separation fluids act as intermediaries between the sample plug and the cell walls, preventing direct contact between the high concentration protein and the cell surface. This intermediary layer prevents gel adhesion to the cell walls.
2Ease of operation
If manual cleaning with fuming nitric acid is used to remove gel, then gel can be disintegrated, but the process is time-consuming and hazardous to operators
Solution Approach 1:
The patent converts the harmful gel formation into a beneficial feature by using the gel's own properties against it. The gel forms in the small sample plug but can be easily disrupted by simple pressure cycling or flushing, transforming the problematic gel into a manageable byproduct that actually helps identify the sample position.
Solution Approach 2:
The sample plug is designed as a disposable, small-volume element that contains the problematic high concentration protein. After analysis, only this small plug needs to be removed rather than cleaning the entire cell, making the cleaning process trivial and eliminating the need for hazardous chemicals.
3Quantity of substance
If small volume of highly concentrated sample is used, then DSC measurements can be performed on cleanable volumes, but hydrodynamic dispersion dilutes the sample concentration
Solution Approach 1:
Separation fluids with matched viscosity and density act as intermediaries that suppress hydrodynamic dispersion. These fluids create a stable environment around the sample plug, preventing diffusion and maintaining concentration gradients during the measurement process.
Solution Approach 2:
The patent changes the physical parameters of the surrounding fluids (viscosity, density, flow rate) to optimize the stability of the sample plug. By carefully selecting separation fluids with appropriate properties, the system maintains sample concentration while allowing small volume injection.
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 allows for reliable DSC measurements on high concentration protein solutions, enabling the analysis of samples with concentrations up to 100 mg/ml and beyond, while ensuring efficient cleaning of the sample cell without the need for hazardous chemicals.
Implementation Method 1
The first and second separation fluid on either side of the sample plug may counteract hydrodynamic dispersion of the sample, maintaining the concentration of the sample in the sample plug
Implementation Method 2
the first separation fluid and the second separation fluid may be immiscible with water. For example, a fluid immiscible with water may be one which maintains an interface between the fluid and water without forming a solution at the interface
Implementation Method 3
along with a pressure subsystem to rapidly depressurize and repressurize the sample cell, facilitating gel breakdown and cleaning
Implementation Method 4
heating the sample cell and reference cell; and determining thermal properties of the sample using DSC analysis
Data Source
AI summary
A method of determining thermal properties of a sample using differential scanning calorimetry (DSC), the method comprises injecting a first separation fluid, a sample plug, and a second separation fluid into a sample cell. The first separation fluid and the sample plug have a first separation interface, and the sample plug and the second fluid have a second separation interface. The method further comprises injecting a reference fluid into a reference cell, heating the sample cell and reference cell, and determining thermal properties of the sample using DSC analysis.