Real-Time MALS


Real-time multi-angle light scattering - RT-MALS for PAT

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:
  • Accelerate process development and scale-up
  • Increase yield, reduce overall time until lot release
  • Maintain product quality with confidence
Benefits

Real-Time Operation

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.

Inline

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.

Online

ultraDAWN™

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:

  • Macromolecules: Mw (weight-average molar mass) from 103 to 109 g/mol and Rg (rms radius) from 10 to 250 nm
  • Nanoparticles: Z-average radius from 10 to 250 nm and corresponding particle concentration (concentration range depends on particle size)
UltraDAWN offers versatile options for PAT, including:
  • In-line or on-line configuration
  • Process or slipstream flow rates from 0.1 mL/min to 5 mL/min
  • Integration with production control software via OPC

Real-Time MALS Applications
Virus purification

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.

TFF concentration

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.

Polysaccharide depolymerization

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.

Liposome homogenization

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.