MagHelix™ Dynamic Light Scattering (DLS)

Assessing the developability of drug candidates in the early stage of drug development is important to reduce the risk of costly downstream failure. Dynamic light scattering (DLS), also known as photon correlation spectroscopy, has become one of the main techniques for evaluating the aggregation, stability, and viscosity of therapeutic proteins, monoclonal antibodies, peptide drugs, and other biopharmaceuticals due to its ability to measure the size distribution of macromolecules and nanoparticles. Moreover, this technique can also be utilized to identify promiscuous inhibitors from hit compounds screened from small molecule compound libraries.

Creative Biostructure has advanced DLS equipment that can provide fully automated DLS services to complete some high-throughput screening programs. In the fully automated, microplate reader format, DLS constitutes a high-throughput biophysical screening approach for early assessment of the developability and formulation conditions of candidates. Compared with the traditional cuvette-based DLS, high-throughput (HT)-DLS performed on microplates can usually provide 10-100 times measurements.

Brief Introduction to Dynamic Light Scattering (DLS)

DLS measures the translational diffusion coefficients (D_t) of colloids and nanoparticles in solution by quantifying the dynamic fluctuations in scattered light. The particle size and size distributions are calculated from the diffusion coefficients according to the hydrodynamic radius (R_h) or the hydrodynamic diameter (d_h). This non-invasive, non-perturbative technology can measure the size of very small particles (from less than 1 nanometer to several micrometers) at low sample concentrations. Due to the molecular weight dependence of particle scattering intensity, this technique is sensitive to the presence of aggregates, which makes DLS a particularly effective approach for assessing stability and aggregation. Furthermore, viscosity can be quantified with DLS using probe particles.

Figure 1. The schematic of DLS technology.

Capabilities and Advantages of our MagHelix™ Dynamic Light Scattering (DLS) services:

• We support high-throughput DLS based on microplates (96-, 384- or 1536-well microplates), which can quickly and accurately perform an early evaluation of the developability and optimal formulation conditions of candidate molecules.
• We have many years of experience in using DLS to evaluate the size and size distribution of aggregates, including small molecules, proteins, liposomes, virus-like particles, nanoparticles, etc.
• The aggregation and stability of therapeutic proteins, therapeutic antibodies, nanosized colloidal gold, and other biological agents can be detected with a very small amount of samples.
• We can utilize DLS to identify promiscuous inhibitors from potential lead candidates. These promiscuous inhibitors have concentration-dependent inhibitory properties while exhibiting non-drug-like characteristics.
• The protein-protein, protein-nucleic acid, and protein-small molecule interactions can also be investigated by DLS.
• As experts in X-ray crystallography, we use DLS to analyze the homogeneity of sample solutions before obtaining high-resolution crystal structures.

Creative Biostructure has mastered a variety of popular biophysical approaches and techniques to provide a wealth of information for the screening, validation, characterization, and optimization of potential candidates in drug discovery programs. If you would like to know more, please feel free to contact us and our drug discovery specialist can provide professional consultation for you.

References

1. Stetefeld J.; et al. Dynamic light scattering: a practical guide and applications in biomedical sciences. Biophysical Reviews. 2016, 8(4): 409-427.
2. Carvalho P M.; et al. Application of light scattering techniques to nanoparticle characterization and development. Frontiers in Chemistry. 2018, 6: 237.