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Differential Scanning Calorimetry (DSC) Technology

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Differential scanning calorimetry (DSC), a powerful analytical tool for elucidating factors that affect the folding and stability of biomolecules, has been widely used to characterize the stability of proteins or other biomolecules in their native form. CD Formulation provides reliable analytical support for protein/peptide drug development and characterization with its advanced DSC technology.

What is Differential Scanning Calorimetry (DSC)?

DSC is a highly sensitive technique based on calorimetry. It does this by measuring the heat change associated with the thermal denaturation of a molecule when heated at a constant rate.

For protein samples, DSC curves provide information about thermal stability and, to a certain extent, are used to assess protein structural conformation. By measuring the heat flow associated with temperature-induced conformational changes in proteins, key thermodynamic parameters such as melting temperature (Tm), enthalpy change (ΔH), and heat capacity change (ΔCp) can be directly determined. These parameters provide key guidance for protein/peptide biopharmaceutical development, from protein engineering to formulation and process development to final product batch release testing, and as a key step in monitoring manufacturing.

Compared to other methods for assessing protein conformational thermal stability, DSC is cost-effective, requires minimal sample preparation steps, and provides a complete thermodynamic profile of the protein unfolding process.

Fig. 1 Dynamic light scatteringFig. 1 Schematic of a system for measurement and analysis of dynamic light scattering. (Minton AP, et al., 2016)

Our Services Related to Differential Scanning Calorimetry (DSC)

With decades of experience supporting protein/peptide biopharmaceutical development and manufacturing, our team of highly qualified experts can provide a range of DSC technology-related services to accelerate the implementation and success of your project.

DSC technology is considered the gold standard for biomolecule thermal stability analysis in protein engineering and biopharmaceutical formulation development.

Our DSC technology supports all stages of your protein/peptide drug development and manufacturing - from early research to late-release testing under GMP.

We provide the following DSC-related services, including but not limited to:

  • Characterization and screening of the most stable, potential protein/peptide or post-candidates.
  • Optimization of protein/peptide biopharmaceutical process and manufacturing conditions.
  • Screening of optimal conditions for protein/peptide liquid formulations.
  • Screening of protein/peptide therapeutics rapid stability indicator tests.
  • Protein-ligand interaction studies.

Procedure of Our Differential Scanning Calorimetry (DSC)

  • In our DSC experiment, a buffer is injected into the reference cell and the sample cell is injected with the sample solution, which is then heated at a constant scan rate.
  • The target protein/peptide is exposed to a temperature ramp, where the heat energy required for each temperature increase is recorded relative to a reference sample (e.g., formulation buffer), thereby obtaining the melting temperature (Tm) for each unfolding event of the protein.
  • The unfolding enthalpy (ΔH) of a protein or individual protein domain is calculated from the area under the melting curve. The enthalpy of protein unfolding is the area under the concentration-normalized DSC peak in units of calories (or joules) per mole.
  • Thermodynamic models are fitted to the data to obtain the Gibbs free energy (ΔG), calorimetric enthalpy (ΔH cal), Van’t Hoff enthalpy (ΔH vH), entropy (ΔS), and heat capacity change (ΔC p) associated with the transition.

Advantages of Our Differential Scanning Calorimetry (DSC) Technology

  • Short time consumption: This technology uses advanced experimental equipment and simple experimental methods to greatly shorten the time of protein stability analysis.
  • High sensitivity: The equipment used in the DSC service is highly sensitive, and high-quality data reports can be obtained with only a small amount of sample to be tested.
  • High quality: The service detects a variety of proteins and can test multiple samples at the same time.
  • High precision: The experimental equipment in the DSC technology is highly precise, and the fully automatic experimental operation method and data analysis program are used to greatly improve its accuracy.
  • Supports combined biophysical method and provides additional thermodynamic data and binding event parameters for verification and supplementation.
  • Our DSC platform is compatible with high-throughput screening and requires only a very small amount of protein, saving your resources and time.

Custom Differential Scanning Calorimetry (DSC) Services

Proteins & Peptides Stability and Thermal Denaturation Analysis

Thermal stability analysis can provide valuable information about the stability and structural integrity of proteins and peptides under different temperature conditions. Use our cutting-edge DSC technology to obtain information about protein/peptide secondary structure changes, such as protein unfolding and aggregation, to understand the thermal stability of your protein of interest and how different conditions affect its structure.

Higher-Order Structures (HOS) Proteins & Peptides Characterization

The ICH Q6B Guide for Biologics Test Procedures and Acceptance Criteria states that HOS characterization is a key component in defining the critical quality attributes (CQAs) of a protein or peptide. Using our cutting-edge DSC technology to obtain HOS data on proteins and peptides to guide your subsequent formulation development, process development, stability studies, etc.

Proteins & Peptides Comparability Studies

Comparability studies are key to ensuring that changes in manufacturing processes or formulation conditions don't adversely affect the quality, safety, and efficacy of protein/peptide therapeutic products. We use DSC technology to perform conformational comparability studies of protein/peptide therapeutic products according to the principles of the ICH Q5E guideline.

Why Choose Our Differential Scanning Calorimetry (DSC) Technology?

  • We have a team of experts with rich experience in performing DSC analytical method development and validation.
  • We have accumulated decades of expertise and successful project experience using DSC technology to support protein/peptide biopharmaceutical development.
  • Our laboratories are equipped with state-of-the-art equipment and technologies to support any type of protein characterization.
  • We provide flexible experimental design and customized solutions.
  • Fast turnaround time: detailed technical reports are provided within 5-7 days.

Publication

Published Data

Technology: DSC

Journal: J Vis Exp.

IF: 1.2

Published: 2017

Results:

The authors detail a DSC analytical procedure for evaluating protein thermal stability in an industrial setting. Different batches of two protein samples were selected for DSC analysis. The stability was investigated under different conditions, including formulation buffer and environmental factors (humidity and temperature). The results demonstrate that the procedure can be successfully used in a variety of characterization test packages for protein biologics, including stability and product comparability studies, and is a useful analytical tool for product formulation studies.

Fig. 2 The Effect of chemical detoxification on the protein structure.Fig. 2 The Effect of Chemical Detoxification on the Tertiary Structure of Protein 1. (Durowoju IB, et al., 2017)

CD formulation is designed to provide a powerful analytical tool for characterizing protein stability. Please feel free to contact us if you are interested in our services. Learn how our DSC technology can support the smooth implementation of your protein/peptide biopharmaceutical program.

References

  1. Gill P, Moghadam TT, Ranjbar B. Differential scanning calorimetry techniques: applications in biology and nanoscience. J Biomol Tech. 2010, 21(4):167-93
  2. Durowoju IB, Bhandal KS, Hu J, et al. Differential Scanning Calorimetry - A Method for Assessing the Thermal Stability and Conformation of Protein Antigen. J Vis Exp. 2017, (121):55262.
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