ultraDAWN
Product Overview
Product Description
Real-Time Operation
Process Analytical Technology
Applications
Software
Specifications
Other MALS Instruments
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A breakthrough in process analytical technology for production of nanoparticles, biopharmaceuticals and polymers.
Real-Time Multi-Angle Light Scattering
ultraDAWN™ measures multi-angle light scattering and reports the results – molecular weight, size and particle concentration – in real time. With RT-MALS, critical quality attributes (CQAs) can be monitored directly, for rapid feedback on product and process quality.
Benefits of RT-MALS
- Accelerate process development and scale-up
- Increase yield, reduce overall time until lot release
- Maintain product quality with confidence
Where MALS and PAT meet
The ultraDAWN is a unique member of the DAWN® family of MALS instruments. Instead of residing in the analytical lab like Wyatt’s other MALS instruments, it is adapted to pilot plants and production environments. OBSERVER™ software is used to calculate and report molar mass and size, 30 times per minute, as opposed to ASTRA’s post-separation, detailed off-line analysis and reporting.
PAT instrumentation is well-known and typically monitors process parameters such as pH, temperature, pressure and feedstock, which are tied indirectly to product properties and quality. UltraDAWN revolutionizes process development with its continuous, direct measurements of actual product properties.
Built in the NEON platform, ultraDAWN provides an intelligent user interface indicating real-time and time sequences of molar mass, size and/or particle concentration as well as system health diagnostics and event history. With photodetectors at eighteen scattering angles plus one more to measure light transmitted through the flow cell, the ultraDAWN provides a solution for:
- Macromolecules: Mw from 103 to 109 g/mol and Rg 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
Process integration options
Process integration options
- 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
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.
RT-MALS for PAT
A PAT strategy that incorporates ultraDAWN for RT-MALS sees reduced development time and fewer samples sent to off-line analytical labs. With real-time CQA analysis, process margins can be optimized and attribute drifts detected immediately, reducing discarded product and increasing yield.
RT-MALS in Lab R&D
RT-MALS can be implemented early in process development – at pilot plant scales and even smaller, such as regular production of small batches of material for R&D use. Experience with lab-scale RT-MALS paves the way for effective implementation on the production floor.
RT-MALS in Scale-up from Lab to Manufacturing
Scaling up often means re-developing the process, requiring off-line analysis of numerous samples collected from intermediate and final steps. RT-MALS greatly accelerates scale-up: it provides real-time feedback, indicating the effect of method tweaks on CQAs, while simultaneously reducing effort and the number of samples analyzed off-line.
Unlike complex at-line PAT devices, ultraDAWN can simply be left in the process flow upon completion of scale up, for continuous or periodic monitoring of the final process.
RT-MALS on the Manufacturing Floor
ultraDAWN and OBSERVER software are simple, robust technologies that may be employed in different ways during serial production. During initial stages, technicians can visually monitor molar mass and size, intervening in the process as needed. With increasing confidence in the capabilities and reliability of RT-MALS, engineers may implement fully-automated process control using OBSERVER’s configurable triggers. In both cases, all data can be reviewed post-production to determine if any deviations were encountered.
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.
OBSERVER RT-MALS software acquires real-time multi-angle light scattering data from ultraDAWN, then calculates and reports molar mass, radius, and/or particle concentration, thirty times each minute. When the RT-MALS results deviate from specifications or reach the process endpoint, OBSERVER can send a trigger to control the process, via analog voltage or digitally via OPC.
GMP requirements are fulfilled by operating OBSERVER as an OPC server for SIPAT or DeltaV.
| Measurements | |
| Molar Mass Range | 1 kDa to 1 GDa1 |
| Molecular Size Range (Rg) | 10 to 250 nm1 |
| Data Acquisition Range | 30 measurements/min |
| Accuracy | 5%2 |
| Repeatability | 2% |
| Fluidics | |
| Solvent Compatibility | All-solvent compatible (aqueous and organic). Wetted materials are 316 stainless steel, fused silica and Kalrez. |
| Maximum Flow Rate | 5 mL/min @ 1 cP3 |
| Maximum Viscosity | 30 cP |
| Optics | |
| MALS Detectors | High-gain, high dynamic range photodiodes at 18 detection angles. |
| Electronics | |
| Analog Inputs | 4 differential analog inputs with 24 bit resolution. Input range -10 V to +10 V |
| Analog Outputs | 2 analog outputs from user selectable measurements channels -10 V to +10 V |
| Other Inputs/Outputs | Alarm in, Alarm out/retransmit |
| Computer Interface | Ethernet |
| Front Panel Display | 257 mm, 24-bit color, high-resolution touch screen for instrument control, signals and diagnostics. May be used with gloves. |
| Dimensions | 58 cm (L) x 36 cm (W) x 26 cm (H) |
1Depending on dn/dc, the sample concentration and process conditions, this is typical.
2Assuming sample and ambient temperature are at calibration temperature, typically 21 °C. Accuracy margin increases to 6% when ambient temperature deviates by 5 °C from calibration temperature, and to 7.5% when sample temperature deviates by -5/+7 °C from calibration temperature.
3Maximum flow rate decreases with viscosity.
Host PC requirements may be found in Computer Requirements.
Specifications subject to change without notice.
Other MALS Instruments
DAWN® - The most sensitive MALS detector available, anywhere. Incorporates detectors at 18 angles to determine molar masses from 200 Da to 1 GDa and radii from 10 – 500 nm.
- Standard option: ambient temperature
- Heated/cooled option: -15 °C to +150 °C
- High-temperature option: ambient to +210 °C
The DAWN offers special options to handle fluorescent samples: fluorescence-blocking filters and an infrared, 785 nm laser.
miniDAWN® - Second only to the DAWN in sensitivity. Incorporates detectors at 3 angles to determine molar masses from 200 Da to 10 MDa and radii from 10 – 50 nm. Ambient only.
microDAWN® - The first MALS detector for UHPLC, with interdetector dispersion as low as 1.5 µL. Incorporates detectors at 3 angles to determine molar masses from 200 Da to 20 MDa and radii from 10 – 50 nm. Ambient only.