Periodic Reporting for period 1 - PAT4Nano (Process Analytical Technology Tools for Real-Time Physical and Chemical Characterization of Nanosuspensions)
Okres sprawozdawczy: 2020-05-01 do 2021-10-31
PAT4Nano is developing and will deploy different, yet 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 one 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 uses an integrated, end user-driven, approach where end user partners, Agfa-Gevaert, Janssen Pharmaceutica, and Johnson Matthey, help define operational needs and thus technology requirements, which leads to better instrument design. PAT4Nano is initially focus 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. These include: online laser diffraction (on-LD), Raman spectroscopy (Raman), ultrasound nano-particle sizer (UNPS), spatially resolved diffusive wave spectroscopy (SR-DWS), spatially resolved dynamic light scattering (SR-DLS), and 2D-cross-correlation DLS (CC-DLS). This is being done to accommodate the wide variety of industrial nanosuspension types which need to be monitored.
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. Commercialise the developed solutions by a series of actions including but not limited to: targeted digital marketing, end-user introductions, conference and workshop attendance, development of strategic partnerships.
Continuous, rapid, and reliable real-time data from PAT4Nano tools will provide more comprehensive process information than current offline measurements enabling one 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 uses an integrated, end user-driven, approach where end user partners, Agfa-Gevaert, Janssen Pharmaceutica, and Johnson Matthey, help define operational needs and thus technology requirements, which leads to better instrument design. PAT4Nano is initially focus 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. These include: online laser diffraction (on-LD), Raman spectroscopy (Raman), ultrasound nano-particle sizer (UNPS), spatially resolved diffusive wave spectroscopy (SR-DWS), spatially resolved dynamic light scattering (SR-DLS), and 2D-cross-correlation DLS (CC-DLS). This is being done to accommodate the wide variety of industrial nanosuspension types which need to be monitored.
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. Commercialise the developed solutions by a series of actions including but not limited to: targeted digital marketing, end-user introductions, conference and workshop attendance, development of strategic partnerships.
In 18 months much has been achieved despite COVID19. Briefly:
• Project Management: An extensive Microsoft Teams site was developed and implemented for efficient online project management. The site securely holds >75 GB of data and facilitates the easy transfer of information between all nine partners and 70+ personnel involved in the project. This has also involved ~100 online meetings to date. For a complex project like PAT4Nano with multiple technologies being developed simultaneously the fast, efficient exchange of information was critical.
• Dissemination: A website was designed, content developed, and implemented (www.pat4nano.com). Various members of the consortium have presented about PAT4Nano at several online conferences and PAT4Nano has held several online webinars.
• Information Generation: Online measurement of concentrated nanosuspensions is difficult, and to facilitate efficient development of measurement technologies an extensive series of online meetings and information gathering was undertaken. This data which included 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 configuration for each PAT solution. 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.
• Certified Reference Material (CRM) data: Data was collected from silica and polystyrene CRM’s using all PAT4Nano technologies and data /results reported internally. This unique data is used to determine the efficacy of each measurement method and forms the basis of a validation methodology for their future industrial use.
• End-user Test Sample (EUTS) analysis: Industrial end-users provided sample materials to all technology developers and extensive data was collected on the EUTS and was presented at various meetings online.
• Technology Development (WP2): All measurement technologies made significant advances during the first 18-months, with the development of prototypes and capability demonstrations.
• Project Management: An extensive Microsoft Teams site was developed and implemented for efficient online project management. The site securely holds >75 GB of data and facilitates the easy transfer of information between all nine partners and 70+ personnel involved in the project. This has also involved ~100 online meetings to date. For a complex project like PAT4Nano with multiple technologies being developed simultaneously the fast, efficient exchange of information was critical.
• Dissemination: A website was designed, content developed, and implemented (www.pat4nano.com). Various members of the consortium have presented about PAT4Nano at several online conferences and PAT4Nano has held several online webinars.
• Information Generation: Online measurement of concentrated nanosuspensions is difficult, and to facilitate efficient development of measurement technologies an extensive series of online meetings and information gathering was undertaken. This data which included 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 configuration for each PAT solution. 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.
• Certified Reference Material (CRM) data: Data was collected from silica and polystyrene CRM’s using all PAT4Nano technologies and data /results reported internally. This unique data is used to determine the efficacy of each measurement method and forms the basis of a validation methodology for their future industrial use.
• End-user Test Sample (EUTS) analysis: Industrial end-users provided sample materials to all technology developers and extensive data was collected on the EUTS and was presented at various meetings online.
• Technology Development (WP2): All measurement technologies made significant advances during the first 18-months, with the development of prototypes and capability demonstrations.
Progress beyond the state of the art:
The key advance to be delivered is real-time monitoring of particle size and distribution for industrial nanosuspension manufacturing. This will be done by developing a suite of individual and multi-PAT analytical technologies to replace current slow, offline analysis tools. This will help to address current unmet needs for better process understanding and control in nanosuspension processing. New advances have already been made, including:
• IP-LSP, working on SR-DWS discovered a new microfluidic based solution for measuring particle size characteristics in extremely highly concentrated suspensions.
• The Raman spectroscopy-based particle size measurement approach being developed by NUIG has been proven for multiple industrial nanosuspensions.
Expected results:
All technologies being developed will be capable of measuring concentrated nanosuspensions online, and this ability to measure online, will reduce analysis time from multiple hours (for current offline methods) to minutes. It is expected that between all the PAT4Nao technologies (either individually or as multi-PAT combinations), nanosuspensions with concentrations >50% w/w, sizes of 10 nm to 10 µm, and varying chemical compositions will be measurable online.
Potential impacts
PAT4Nano outputs and commercialised 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:
• Reducing 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.
• Better control of nanosuspension product quality and reliability, improved product lifetimes, and associated environmental benefits.
The key advance to be delivered is real-time monitoring of particle size and distribution for industrial nanosuspension manufacturing. This will be done by developing a suite of individual and multi-PAT analytical technologies to replace current slow, offline analysis tools. This will help to address current unmet needs for better process understanding and control in nanosuspension processing. New advances have already been made, including:
• IP-LSP, working on SR-DWS discovered a new microfluidic based solution for measuring particle size characteristics in extremely highly concentrated suspensions.
• The Raman spectroscopy-based particle size measurement approach being developed by NUIG has been proven for multiple industrial nanosuspensions.
Expected results:
All technologies being developed will be capable of measuring concentrated nanosuspensions online, and this ability to measure online, will reduce analysis time from multiple hours (for current offline methods) to minutes. It is expected that between all the PAT4Nao technologies (either individually or as multi-PAT combinations), nanosuspensions with concentrations >50% w/w, sizes of 10 nm to 10 µm, and varying chemical compositions will be measurable online.
Potential impacts
PAT4Nano outputs and commercialised 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:
• Reducing 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.
• Better control of nanosuspension product quality and reliability, improved product lifetimes, and associated environmental benefits.