Whereas MALS is traditionally used in the analytical laboratory, it can also be utilized to develop, monitor and control production processes for nanoparticles, biopharmaceuticals and polymers. RT-MALS, which determines molar mass (Mw), radius (R or Rg) and particle concentration in real time, is used in PAT environments to indicate a process endpoint, collect the appropriate fraction or flag deviations from acceptable product attribute values. This technique is implemented with an ultraDAWN™ MALS instrument and OBSERVER™ software.Benefits of RT-MALS:
In-line - For continuous processes that take place at flows below 5 mL/min, such as microfluidic drug encapsulation or chromatographic purification steps, in-line RT-MALS provides the shortest feedback loop while the ultraDAWN samples the entire process stream.
On-line - When processing takes place within a fixed volume such as a homogenizer, or when the process flow is greater than 5 mL/min, a bypass stream is diverted from the manufacturing process to the ultraDAWN. RT-MALS data are produced in near-real-time.
The ultraDAWN™ RT-MALS instrument is part of the DAWN family of multi-angle light scattering instruments, incorporating detectors at 18 scattering angles plus one for light transmitted through the flow cell. Unlike the DAWN, miniDAWN and microDAWN instruments which are optimized for use with analytical HPLC and UHPLC, ultraDAWN is appropriate for process environments. It is the only MALS instrument that integrates with OBSERVER™ software, providing solutions for:
RT-MALS monitors particle radius and triggers when within the specified range, to differentiate from smaller proteins or DNA and larger cell fragments and collect virus-enriched fractions.
RT-MALS monitors particle concentration in the course of tangential flow filtration. and triggers when above the specified end point, to terminate the process step.
RT-MALS monitors molecular weight and triggers when below the specified end point, to terminate the homogenization process. See AN8005: RT-MALS end-point determination of a polysaccharide depolymerization process.
RT-MALS monitors radius and triggers if outside the specified range, to divert out-of-spec product from contaminating the collection vessel. See AN8006: In-line monitoring of liposome size by RT-MALS.