Quantitative laser diffraction (qLD)
Quantitative laser diffraction (qLD) is an effective technique for simultaneously quantifying nanometer- and submicron-sized aggregates.
qLD records the angle-dependent scattering intensity of laser light passing through a liquid sample containing dispersed particles. Using the Mie scattering theory, the technique can be used to calculate particle size as an equivalent spherical diameter (ESD). With known optical properties of the particle under investigation, quantitative data can be obtained. In case of protein particles in liquid formulations, a size-range from about 150 nm to 20 μm can be covered in one measurement.
A clear benefit of qLD is its enormous size range.
Compared to the orthogonal technique dynamic light scattering [DLS], qLD is less influenced by intense light scattering of larger particles, as it analyzes light scattering patterns rather than intensity. qLD can cover higher particle concentrations than resonant mass measurement [RMM], but is surpassed by flow imaging microscopy [FIM] in its ability to analyze low particle concentrations.
The relatively large sample volume and extensive sample cell cleaning procedures have prevented qLD to become a widely used technique. However, qLD is employed as a research tool to validate results of orthogonal techniques.
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S. Zölls, R. Tantipolphan, M. Wiggenhorn, G. Winter, W. Jiskoot, W. Friess, A. Hawe, Particles in therapeutic protein formulations, Part 1: overview of analytical methods., J. Pharm. Sci. 101  914–35. doi:10.1002/jps.23001.