Dynamic light scattering (DLS) or photon correlation spectroscopy is one of the most popular light scattering techniques that measuring the particle size distribution. This popular technique allows particle sizing down to 1 nm in diameter. Creative Biolabs provides automated DLS technology to aid your drug discovery process.
DLS is a physical technique, which is capable of determining the particle size of very small particles and polymers in solution, even at low sample concentrations. The sample is illuminated by a laser beam and the temporal fluctuations are analyzed at a known scattering angle θ by means of the intensity or photon autocorrelation function. Elaborated multi-angle instruments can determine the full particle size distribution. In addition to measuring small molecules, DLS can also be used to probe the behavior of complex fluids, such as concentrated polymer solutions.
Creative Biolabs has a world-class DLS system for measuring the effective size of molecules. Our novel DLS plate reader has incomparable advantages which require as little as 50 microliter sample volumes, utilizing disposable microplates (up to 1536 samples), and detecting chemical aggregates at compound concentrations in the range of 3 to 10°M. This non-invasive technique yields valuable information of drug leads. Our platform facilitates formerly laborious and time-consuming measurements, such as aggregates screening or optimal crystallization conditions determination. We can measure amounts of large particles (aggregates) not detected by other means.
DLS has several applications to support drug discovery process:
Leads and Targets Size Characterization
DLS can be used to characterize the size of various particles including proteins and small compounds. Particle concentration, type of ions in the medium can also be detected.
Detection of Aggregate Formation
High throughput combinatorial techniques are often used for new drugs discovery. However, a high throughput of automation does not guarantee a more fruitful drug discovery and development process due to false-positives encountered during the screening of compound libraries. One false-positives mechanism refers to aggregate-based inhibitors. This aggregation happens under suitable bioassay buffer conditions, and then non-specifically inhibits receptors and enzymes, producing a false-positive result. Discovery of aggregate-based inhibitors represents a new tool for drug discovery.
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Figure 1. Protein measurement using the Plate Reader: Comparison of sources A and B in pH 5 buffer. Note the perfect well-to-well reproducibility of the measurements. (Jocks and Roessner 2009/2010)
DLS is extremely sensitive to the presence of aggregates as the molecular weight dependence of the particle scattering intensity. As such, DLS is an ideal tool for identifying promiscuous inhibitors. DLS measures the compounds aggregate by detecting whether the hydrodynamic radius of the particle increases. If compounds aggregate, a larger population of particles with larger radius will appear. Temperature can be added as a variable to analyze temperature-depended molecular stability.
Biodistribution and Pharmacokinetics Determination by Combining Nanosized Colloidal Gold
Nanosized colloidal gold is well-suited for therapeutic and biotechnology applications. It has no toxicity in vivo, while its fine size allows it to cross a cell membrane with no harmful to a cell. Furthermore, gold nanoparticles suspended within aqueous media have a strong affinity for biological macromolecules, which form biological ligands around the ion. Colloidal gold enables researchers to develop drug-nanoparticle conjugates to determine a drug's biodistribution and pharmacokinetics.
The pharmacokinetic properties of colloidal gold conjugates are strongly influenced by particle size. As such, controlling the particle size of colloidal gold is therefore of great importance. DLS provides a solution to the need for quick and reliable quality control by offering aggregation studies of nanoparticles with high sensitivity and accuracy.
For more detailed information, please feel free to contact us or directly sent us an inquiry.
Reference
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