Periodic Reporting for period 2 - PAT4Nano (Process Analytical Technology Tools for Real-Time Physical and Chemical Characterization of Nanosuspensions)
Berichtszeitraum: 2021-11-01 bis 2023-10-31
PAT4Nano has developed different, complementary particle size measurement technologies for in- and online real-time monitoring of concentrated industrial nanosuspensions. Concentrated nanosuspensions are found throughout modern industrial manufacturing, e.g. Active Pharmaceutical Ingredients (APIs), paints and inks, and materials used in green energy processes. Nanosuspensions have unique physical and chemical properties which determine the end material or product performance. Accurate measurement of nanoparticle size and distribution during manufacturing or processing is therefore critical. Continuous, rapid, and reliable real-time data from PAT4Nano tools will provide more comprehensive process information than current offline measurements, enabling users to obtain insights into the fundamental dynamics of nanoparticle-based processes. This data enables real-time process control and feed-forward loops to correct for process variances, leading to better end product consistency and higher process efficiencies. To achieve this, PAT4Nano used an integrated, end user-driven, approach where end user partners, Agfa-Gevaert, Janssen Pharmaceutica, and Johnson Matthey, helped defining operational needs and thus technology requirements, which leads to better instrument design. PAT4Nano focussed on applications in pharmaceuticals, inks/pigments, and materials for catalysis, batteries, and glass manufacture supplied by these end users.
The overall project objectives comprise 6 elements:
1. Develop a suite of nanosuspension particle size measurement tools, using different measurement principles and modes of operation to accommodate the wide variety of industrial nanosuspension types which need to be monitored. These include: online laser diffraction (on-LD), Raman spectroscopy (Raman), ultrasound nano-particle sizer (UNPS), online spatially resolved dynamic light scattering (on-SR-DLS), and a DLS probe (in-DLS).
2. Harvest relevant information about particles, samples, industrial processes, and engineering parameters to ensure that the measurements can be implemented effectively in an industrial context.
3. Validate technique performance (or combination of methods) using both standards and end-user provided samples to ensure that the measurement results are consistent, real, and comparable.
4. Demonstrate the efficacy of each method on multiple industrial sample types and manufacturing processes.
5. Use multi-PAT approaches where necessary to characterisation of both chemical and physical parameters from industrial processes that require more comprehensive monitoring methods.
6. Commercialize the developed solutions by a series of actions including but not limited to: targeted digital marketing, conference and workshop attendance and end-user introductions.
The overall project objectives comprise 6 elements:
1. Develop a suite of nanosuspension particle size measurement tools, using different measurement principles and modes of operation to accommodate the wide variety of industrial nanosuspension types which need to be monitored. These include: online laser diffraction (on-LD), Raman spectroscopy (Raman), ultrasound nano-particle sizer (UNPS), online spatially resolved dynamic light scattering (on-SR-DLS), and a DLS probe (in-DLS).
2. Harvest relevant information about particles, samples, industrial processes, and engineering parameters to ensure that the measurements can be implemented effectively in an industrial context.
3. Validate technique performance (or combination of methods) using both standards and end-user provided samples to ensure that the measurement results are consistent, real, and comparable.
4. Demonstrate the efficacy of each method on multiple industrial sample types and manufacturing processes.
5. Use multi-PAT approaches where necessary to characterisation of both chemical and physical parameters from industrial processes that require more comprehensive monitoring methods.
6. Commercialize the developed solutions by a series of actions including but not limited to: targeted digital marketing, conference and workshop attendance and end-user introductions.
Online measurement of concentrated nanosuspensions is complicated. To facilitate efficient development of measurement technologies, an extensive information gathering was undertaken in the first phase of the project. Information about relevant chemical and physical characteristics for different nanosuspensions supplied by industrial end-users, changes in sample properties during processing relevant to PAT measurements, and optimal sampling and measurement configurations for each PAT solution was collected and reported. This information is critical for development of individual measurement technologies, implementation of multi-PAT methods (combinations of different measurement technologies), and robust validation of techniques, and their eventual deployment by end users. Specified data handling and processing procedures were developed and agreed for each measurement methodology and included in Characterization Data forms (CHADAs). Data was collected from silica and polystyrene Certified Reference Materials (CRM’s) using all PAT4Nano technologies. This unique data is used to determine the efficacy of each measurement method and forms the basis of the validation methodology for future industrial use. Individual PS measurement methods have been (cross-) validated from lab to process scale at various partner sites using different sample types (certified reference samples (CRMs), secondary standards (Sec.Stds) industrial process model samples (IPMs) and end user tests samples (EUTS)). The dataset for the CRM samples has been published on Zenodo (DOI 10.5281/zenodo.7701665). All measurement technologies made significant advances during the project, with the development of prototypes and capability demonstrations. A prototype sampling loop and coupling was designed, assembled and validated for processing equipment using representative sample types. MultiPAT approaches and concepts for nanosuspension analysis have been developed and validated. Relevant end user materials and processes have been selected. Materials have been supplied for validation purposes to all instrument manufacturers, PAT tool integration and validation from pilot to commercial scale manufacturing equipment has been performed for selected end user processes.
Progress beyond the state of the art: The key advancement delivered is real-time monitoring of particle size and distribution for industrial nanosuspension manufacturing. This has been done by developing a suite of individual and multi-PAT analytical technologies to replace current offline analysis tools. This will help to address current unmet needs for better process understanding and control in nanosuspension processing. New advances have been made, including:
• An online microdilution device coupled to SR-DLS, an online sampling loop coupled to a laser diffraction instrument,
• An online DLS probe capable of measuring particle size characteristics on-line during processing,
• A SR-LPD (Large Particle Detection) device for detection of oversizers.
• A Raman based measurement methodology for nano- and micron-sized particle measurements proven for multiple industrial nanosuspensions.
• An Ultrasound spectroscopy-based particle size measurement approach, proven for multiple industrial nanosuspensions.
Results obtained: A series of technologies, capable of measuring (concentrated) nanosuspensions online, has been successfully developed. The ability to measure online, will reduce analysis time from multiple hours (for current offline methods) to minutes. By application of the PAT4Nano technologies (either individually or as multi-PAT combinations), nanosuspensions with concentrations >30% w/w, sizes of 10 nm to 10 µm, and varying chemical compositions are now measurable online. Potential impacts: PAT4Nano outputs and technologies will facilitate more optimal nanomaterial production by providing more efficient process monitoring and control leading to better material and process understanding. This facilitates increased nanomaterial use in different sectors like speciality materials & chemicals, pharmaceutical products, consumer products, and manufacturing raw materials. Potential industrial impacts of PAT4Nano include reduction of the time and resources required for nanomaterial development and upscaling. The real-time PAT4Nano characterisation tools will support process development and understanding at all scales, by more effectively linking process performance with product attributes yielding better control of nanosuspension product quality and reliability, improved product lifetimes, and associated environmental benefits.
• An online microdilution device coupled to SR-DLS, an online sampling loop coupled to a laser diffraction instrument,
• An online DLS probe capable of measuring particle size characteristics on-line during processing,
• A SR-LPD (Large Particle Detection) device for detection of oversizers.
• A Raman based measurement methodology for nano- and micron-sized particle measurements proven for multiple industrial nanosuspensions.
• An Ultrasound spectroscopy-based particle size measurement approach, proven for multiple industrial nanosuspensions.
Results obtained: A series of technologies, capable of measuring (concentrated) nanosuspensions online, has been successfully developed. The ability to measure online, will reduce analysis time from multiple hours (for current offline methods) to minutes. By application of the PAT4Nano technologies (either individually or as multi-PAT combinations), nanosuspensions with concentrations >30% w/w, sizes of 10 nm to 10 µm, and varying chemical compositions are now measurable online. Potential impacts: PAT4Nano outputs and technologies will facilitate more optimal nanomaterial production by providing more efficient process monitoring and control leading to better material and process understanding. This facilitates increased nanomaterial use in different sectors like speciality materials & chemicals, pharmaceutical products, consumer products, and manufacturing raw materials. Potential industrial impacts of PAT4Nano include reduction of the time and resources required for nanomaterial development and upscaling. The real-time PAT4Nano characterisation tools will support process development and understanding at all scales, by more effectively linking process performance with product attributes yielding better control of nanosuspension product quality and reliability, improved product lifetimes, and associated environmental benefits.