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Light Scattering Theory

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Dynamic light scattering is known as a fast and efficient screening method for aggregate / particle detection. It is widely used within biopharmaceutical development. DLS closes the gap between techniques like size exclusion chromatography (SEC), that measure small soluble aggregates and particle methods such as light obscuration (LO) or micro flow imaging (MFI). Due to a high sensitivity toward large species, even small impurities can be detected within the measurement range (0.5 nm – 1 µm). Please follow the link for more information.  

With the increasing interest in gene therapy products also the interested in AF4 is growing. However, AF4 methods are comparably complex to develop. While most people use AF4 only as separation technique. We are experts in AF4 theory and use the theory to get more information out of the technique (e.g. particle size distributions). If you want to get more information about AF4 theory please follow this link.

Sedimentation velocity analytical ultracentrifugation (SV-AUC) method is the established standard experiment when it comes to AUC. It is carried out at high rotational speed and the easiest way to obtain sample composition and species characteristics (e.g. molecular weight and frictional ratio). Follow this link to get more information about SV-AUC theory.

While sedimentation velocity is the standard AUC experiment, sedimentation equilibrium analytical ultracentrifugation (SE-AUC) nonetheless offers valuable information on an analyte.  SE-AUC is a first principle method for the determination of the molecular weight. Therefore, it is the method of choice to determine the molecular weight of your API in solution. Follow this link to get more information about SE-AUC theory.

ZentriForce Pharma’ strength is not restricted to expertise in analytical services. Our scientist are also actively involved in the further advances in the theory of hydrodynamic techniques. Please follow the link to a detailed description of the theory behind our analytical services, including some of our own research.  


General topics:

ZentriForce Pharma was founded as a service provider that specializes in hydrodynamic techniques for biopharmaceutical development. The focus lies on gene therapy products and biosimilarity studies. Follow the link to our company page for further information.

Please follow this link to our contact page

ZentriForce Pharma implemented a strict quality system to assure the highest tractability of results generated at our facility. We have a wide range of quality related standard operation procedures (SOPS) in place to assure the consistency and quality of our laboratory operations. Please follow the link to a description of our quality system. 

ZentriForce Pharma is your expert in analytical services, with focus on hydrodynamic techniques. Please follow the link to find out about our analytical services. 

ZentriForce Pharma offers a wide range of analytical techniques. Please follow the link to our analytical portfolio. 

ZentriForce Pharma is not merely an expert in analytical development. Our scientist are actively involved in further advances in the theory of hydrodynamic techniques. Follow the link to a detailed description of the theory behind our analytical services, including some of our own research

ZentriForce Pharma is always looking for motivated employees. Check out our career page for further information. 

Light Scattering Theory

Light scattering is a well-defined physical phenomenon that describes multiple physical processes in which light interacts with matter. In the field of particle analysis, the most interesting light scattering process is Rayleigh scattering, which describes the predominantly elastic scattering of light by solutes that are much smaller that the wavelength they scatter. The physical effect of Rayleigh scattering is used in two major applications. One is the detection of scattering intensity for static light scattering (SLS) applications. The other is the monitoring of fluctuations in scattering intensity for dynamic light scattering (DLS) measurement. For larger solutes (> 250 nm), additional light scattering effects, such as Mie scattering, are observable and must be considered in data evaluation.

Dynamic Light Scattering

Dynamic light scattering (DLS) is also known as photon correlation spectroscopy (PCS) and quasi-elastic light scattering (QELS). A steady laser beam is directed through a sample solution and scattered by the molecules within the volume that interacts with the beam. Due to constructive and destructive interference, the position of all molecules affects the intensity of the scattered light. Therefore, when the molecules change their positions in relation to each other, so does the intensity of the scattering signal. The time dependent change of the scattering signal is monitored, and an autocorrelation function is applied to the collected data. Depending on the size of the molecules the decay of the autocorrelation function is faster or slower. As the decay is mostly caused by the Brownian motion of the solutes, where smaller solutes cause a faster decay of the autocorrelation function. The decay provides information on parameters such as the hydrodynamic radius/diameter of the molecules. Due to the Z-based size distribution (signal intensity correlates with molecule radius to the power of six), larger species are weighted much more heavily than smaller species when the average size of a mixture of molecules is calculated. This effect allows the detection of even small numbers of large particles in presence of an excess of a smaller molecule. 

Static Light Scattering

While dynamic light scattering detects fluctuations in the light scattering intensity, static light scattering (SLS) usually measures the angle and concentration dependence of the light scattering intensity. While larger solutes show a larger signal at small compared to large angles, small solutes show a more homogeneous scattering signal.  From the angular distribution of the scattering signal the solute’s molecular weight and radius of gyration are obtained. In addition, the concentration dependence of the scattering signal may be collected, and from it the second osmotic virial coefficient is obtained. For more information about potential applications of interaction parameters in biopharmaceutical development, visit our interaction parameter page. In most cases, a multiangle light scattering (MALS) instrument is used for SLS measurements. The MALS instrument uses a flow cell with several fixed detectors. The advantage over traditional SLS instruments with a measurement chamber and a movable detector, which rotates around the sample, is the fast data acquisition. Online data collection from liquid chromatography separation of solutes is feasible (e.g. size exclusion chromatography and asymmetrical flow field-flow fractionation). 

ZentriForce Pharma was founded as a service provider specialized in hydrodynamic techniques used for biopharmaceutical development. The focus lies on gene therapy products and biosimilarity studies. For further information follow the link to our company page

Please follow this link to our contact page

ZentriForce Pharma implemented a strict quality system to assure the highest tractability of results generated at our facility. We have a wide range of quality related standard operation procedures (SOPS) in place to assure the consistency and quality of our laboratory operations. Please follow the link to a description of our quality system. 

ZentriForce Pharma is your expert in analytical services, with focus on hydrodynamic techniques. Please follow the link to find out about our analytical services. 

ZentriForce Pharma offers a wide range of analytical techniques. Please follow the link to our analytical portfolio. 

ZentriForce Pharma’ strength is not restricted to expertise in analytical services. Our scientist are also actively involved in the further advances in the theory of hydrodynamic techniques. Please follow the link to a detailed description of the theory behind our analytical services, including some of our own research.  

ZentriForce Pharma is always looking for motivated and dedicated employees. Check out our career page for further information. 

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ZentriForce Pharma has established a laboratory quality system that closely follows the extensive and detailed guidelines provided by the WHO and the principle of “writing what you do and doing what you write”. ZentriForce implements procedural, equipment and analytical SOPs. To date, close to 30 SOPs are in place.
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For gene therapy product development, traditional quality attributes as well as new quality attributes must be addressed. Our scientists have worked with a wide range of different gene therapy products, ranging from small DNA / RNA complexes over lyposome-based carrier systems and adeno-associated viruses (AAV) to viruses that are several hundred nanometers in size.
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Within biosimilarity studies attention is on the collection of evidence that proves that no differences (larger than method variability) in structure and purity exist between a proposed biosimilar and the reference product. Evidence is collected through extensive analytical testing.
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Despite being far less complex than full proteins, analytical handling of peptides is challenging. Species as small as peptide-based APIs require analytical instrumentation to be run at its physical limits. Expertise and extensive experience in working with such materials is imperative for successful method development. Our scientists have worked with a large number of peptide-based APIs, with sizes down to 1 kDa.
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ZentriForce Quality System
ZentriForce Pharma has established a laboratory quality system that closely follows the extensive and detailed guidelines provided by the WHO and the principle of “writing what you do and doing what you write”. ZentriForce implements procedural, equipment and analytical SOPs. To date, close to 30 SOPs are in place.
Click here for more information
Gene Therapy
For gene therapy product development, traditional quality attributes (e.g. purity) as well as new quality attributes (e.g. the ratio of particles that carry nucleic acids to empty particles) must be addressed. The diversity of approaches for gene therapy API analysis adds a further challenge to product characterization. Our scientists have worked with a wide range of different gene therapy products, ranging from small DNA / RNA complexes over lyposome-based carrier systems and adeno-associated viruses (AAV) to viruses that are several hundred nanometers in size.
Click here for more information
Biosimilarity
Within biosimilarity studies attention is on the collection of evidence that proves that no differences (larger than method variability) in structure and purity exist between a proposed biosimilar and the reference product. Evidence is collected through extensive analytical testing. The different focus between development and biosimilarity testing require an adjusted mindset and a customized study design for the respective task. ZentriForce Pharma can be a valuable partner on your way to release a biosimilar
Click here for more information
Peptides
Despite being far less complex than full proteins, analytical handling of peptides is challenging. Species as small as peptide-based APIs require analytical instrumentation to be run at its physical limits. Expertise and extensive experience in working with such materials is imperative for successful method development. Our scientists have worked with a large number of peptide-based APIs, with sizes down to 1 kDa. They will be valuable assets where expertise and consultation in analytical method development are concerned.
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