Periodic Reporting for period 1 - LIBRA (LIGHT BASED MULTISENSING DEVICE FOR SCREENING OF PATHOGENS AND NUTRIENTS IN BIOREACTORS)
Période du rapport: 2023-01-01 au 2024-06-30
LIBRA introduces a benchtop smart multi-sensing system for the automatable screening of cultivation processes in bioreactors.
The project pursues the following objectives:
Obj 1: Develop miniaturized PICs as Raman spectroscopy and Refractive index sensing modules
Obj 2: Develop a disposable microfluidics and pre-treatment module
Obj 3: Design and develop advanced data analysis, management and presentation
Obj 4: Provide efficient and reliable AI techniques for contamination prediction
Obj 5: Integrate the individual modules into LIBRA advanced multi-sensing system
Obj 6: Demonstrate and validate the system for the detection of pathogens and nutrients in bioreactors.
Obj 7: Evaluate the increased yield and reduced waste throughout the value chain for end-products and achieve at least 50% reduced energy consumption throughout the whole bioreactor production process.
The project pursues the following objectives:
Obj 1: Develop miniaturized PICs as Raman spectroscopy and Refractive index sensing modules
Obj 2: Develop a disposable microfluidics and pre-treatment module
Obj 3: Design and develop advanced data analysis, management and presentation
Obj 4: Provide efficient and reliable AI techniques for contamination prediction
Obj 5: Integrate the individual modules into LIBRA advanced multi-sensing system
Obj 6: Demonstrate and validate the system for the detection of pathogens and nutrients in bioreactors.
Obj 7: Evaluate the increased yield and reduced waste throughout the value chain for end-products and achieve at least 50% reduced energy consumption throughout the whole bioreactor production process.
In the first 18 months, significant advancements were made in respect to the LIBRA objectives:
- Objective 1: The objective of developing miniaturized Photonic Integrated Circuits (PICs) on the TriPleX platform for Raman spectroscopy sensing and refractive index sensing has progressed significantly by M18. The work is focused on developing both active and passive PICs, each serving distinct roles within the LIBRA system. By considering the progress on tasks related to LioniX International and completion of them is considered that the progress of the project is in line with the given deadlines.
-Objective 2: In the LIBRA project, dummy Photonic Integrated Circuits (PICs) were placed in microfluidic modules optimized for development, allowing microscope access to the PIC surface. When permanent magnets were activated, pathogens bound to magnetic beads were successfully concentrated on the PIC surface. A preconcentration unit, developed with DEMCON, was designed to be reusable, separating it from the disposable aMZI microfluidic module to reduce plastic waste. Although tested only with magnetic beads (not pathogens), the unit achieved a preconcentration factor of 2.3x. Notably, LIBRA's unique "FcMBL beads" can capture any bacterial species, surpassing commercial options.
-Objective 3: The LIBRA project advanced data analysis by organizing Raman data into time-series datasets and conducting extensive Exploratory Data Analysis (EDA) to clean and optimize the data. Key features were identified, dimensionality reduction techniques were applied, and feature engineering was used to enrich the dataset, resulting in a well-prepared dataset for machine learning model training.
- Objective 4: The LIBRA project developed AI models for contamination prediction by integrating sensory data from multiple sources and using Neuroevolution techniques for rapid and efficient model creation. The models were designed for accuracy, adaptability, and included Explainable AI features for transparency and user trust.
-Objective 5: Deliverable D2.4 of the project presented a concept design for the LIBRA system, based on user interviews and risk assessments. It included details on cartridge designs and sub-systems. Currently, technical partners are finalizing the detailed design, and DEMCON has developed a plan for integrating LIBRA prototypes for system verification and validation, outlined in deliverable D2.5.
-Objective 6: By month 18, a lab system for real-time measurements on passive aMZI and Raman chips was developed with Optagon, Lionix, and NTUA. The first batch of aMZI chips and the alignment and microfluidic systems were tested successfully, and the system is now prepared for testing biofunctionalized aMZI chips with specific bioanalytes.
- Objective 7: ECOVAMED assessed the carbon footprint of various monoclonal antibodies (mAbs) from a pharmaceutical company, calculating new emission factors for high-impact single-use consumables like bags, filters, and tubing. They also estimated global savings in time, energy, waste, and raw materials for these products, and studied key aspects of photosynthetic experiments based on CNR's experiences.
- Objective 1: The objective of developing miniaturized Photonic Integrated Circuits (PICs) on the TriPleX platform for Raman spectroscopy sensing and refractive index sensing has progressed significantly by M18. The work is focused on developing both active and passive PICs, each serving distinct roles within the LIBRA system. By considering the progress on tasks related to LioniX International and completion of them is considered that the progress of the project is in line with the given deadlines.
-Objective 2: In the LIBRA project, dummy Photonic Integrated Circuits (PICs) were placed in microfluidic modules optimized for development, allowing microscope access to the PIC surface. When permanent magnets were activated, pathogens bound to magnetic beads were successfully concentrated on the PIC surface. A preconcentration unit, developed with DEMCON, was designed to be reusable, separating it from the disposable aMZI microfluidic module to reduce plastic waste. Although tested only with magnetic beads (not pathogens), the unit achieved a preconcentration factor of 2.3x. Notably, LIBRA's unique "FcMBL beads" can capture any bacterial species, surpassing commercial options.
-Objective 3: The LIBRA project advanced data analysis by organizing Raman data into time-series datasets and conducting extensive Exploratory Data Analysis (EDA) to clean and optimize the data. Key features were identified, dimensionality reduction techniques were applied, and feature engineering was used to enrich the dataset, resulting in a well-prepared dataset for machine learning model training.
- Objective 4: The LIBRA project developed AI models for contamination prediction by integrating sensory data from multiple sources and using Neuroevolution techniques for rapid and efficient model creation. The models were designed for accuracy, adaptability, and included Explainable AI features for transparency and user trust.
-Objective 5: Deliverable D2.4 of the project presented a concept design for the LIBRA system, based on user interviews and risk assessments. It included details on cartridge designs and sub-systems. Currently, technical partners are finalizing the detailed design, and DEMCON has developed a plan for integrating LIBRA prototypes for system verification and validation, outlined in deliverable D2.5.
-Objective 6: By month 18, a lab system for real-time measurements on passive aMZI and Raman chips was developed with Optagon, Lionix, and NTUA. The first batch of aMZI chips and the alignment and microfluidic systems were tested successfully, and the system is now prepared for testing biofunctionalized aMZI chips with specific bioanalytes.
- Objective 7: ECOVAMED assessed the carbon footprint of various monoclonal antibodies (mAbs) from a pharmaceutical company, calculating new emission factors for high-impact single-use consumables like bags, filters, and tubing. They also estimated global savings in time, energy, waste, and raw materials for these products, and studied key aspects of photosynthetic experiments based on CNR's experiences.
WP2
The concept design for the LIBRA system, based on user interviews and risk assessments, detailing cartridge designs for various modules and sub-systems.
WP3
The design phase for the active and passive photonic integrated circuits (PICs), including components like the External Cavity Laser (ECL), asymmetric Mach-Zehnder interferometers (aMZIs), and spectrometers, has been completed with extensive performance simulations. The first generation of active PICs has been successfully fabricated and is undergoing initial functional testing, showing promising results. Fabrication of the passive PICs is expected to finish by early September, after which they will be integrated with the active PICs for further testing and validation.
Potential impact of WP3: Impact in photonic integration technology for a more competitive European photonic industry and impact in multi-sensing based on photonics.
WP4
- Dummy PICs enclosed in microfluidic modules that were optimised for development
- Pathogens bound to magnetic beads were observed to concentrate on the PIC surface when permanent magnets were engaged.
- A preconcentration unit was developed in collaboration with DEMCON.
- The preconcentration unit has been tested with magnetic beads but without pathogens. The beads were successfully preconcentrated using permanent magnets, leading to a preconcentration factor of 2.3x in our preliminary design.
- Unique in LIBRA is that our “FcMBL beads” can capture any bacterial species, unlike commercially available beads.
Potential impact of WP4: Supporting a European open strategic autonomy in key integration and packaging technologies and related manufacturing value chains, Reinforcing European industrial leadership in high performance multi-sensing systems and components for sectors such as healthcare and well-being, environmental monitoring and protection, transport and automated driving, manufacturing, aerospace and security.
WP5
The detailed design is currently ongoing while DEMCON has developed a plan for integrating and validating the LIBRA prototypes. For the Proof-of-principle tests a setup is build for active alignment test, Initial testing have been performed of syringe pumps driving and Simulation studies are ongoing for the optical performance (MNPs on aMZI) of the photonic sensor for bacteria detection.
Potential impact of WP5: Supporting a European open strategic autonomy in key integration and packaging technologies and related manufacturing value chains
WP6
This WP is related to the validation of the photonic module and the overall system. Up to date, T6.1 has been finalized, real samples have been characterized by gold standard techniques while also a Raman library of nutrients used in bioreactors has been developed. T6.2 is active and is related to the testing of the photonic chips. Up to date the passive aMZI chips have been tested for bulk measurements and the system is ready for testing with targeted analytes.
The concept design for the LIBRA system, based on user interviews and risk assessments, detailing cartridge designs for various modules and sub-systems.
WP3
The design phase for the active and passive photonic integrated circuits (PICs), including components like the External Cavity Laser (ECL), asymmetric Mach-Zehnder interferometers (aMZIs), and spectrometers, has been completed with extensive performance simulations. The first generation of active PICs has been successfully fabricated and is undergoing initial functional testing, showing promising results. Fabrication of the passive PICs is expected to finish by early September, after which they will be integrated with the active PICs for further testing and validation.
Potential impact of WP3: Impact in photonic integration technology for a more competitive European photonic industry and impact in multi-sensing based on photonics.
WP4
- Dummy PICs enclosed in microfluidic modules that were optimised for development
- Pathogens bound to magnetic beads were observed to concentrate on the PIC surface when permanent magnets were engaged.
- A preconcentration unit was developed in collaboration with DEMCON.
- The preconcentration unit has been tested with magnetic beads but without pathogens. The beads were successfully preconcentrated using permanent magnets, leading to a preconcentration factor of 2.3x in our preliminary design.
- Unique in LIBRA is that our “FcMBL beads” can capture any bacterial species, unlike commercially available beads.
Potential impact of WP4: Supporting a European open strategic autonomy in key integration and packaging technologies and related manufacturing value chains, Reinforcing European industrial leadership in high performance multi-sensing systems and components for sectors such as healthcare and well-being, environmental monitoring and protection, transport and automated driving, manufacturing, aerospace and security.
WP5
The detailed design is currently ongoing while DEMCON has developed a plan for integrating and validating the LIBRA prototypes. For the Proof-of-principle tests a setup is build for active alignment test, Initial testing have been performed of syringe pumps driving and Simulation studies are ongoing for the optical performance (MNPs on aMZI) of the photonic sensor for bacteria detection.
Potential impact of WP5: Supporting a European open strategic autonomy in key integration and packaging technologies and related manufacturing value chains
WP6
This WP is related to the validation of the photonic module and the overall system. Up to date, T6.1 has been finalized, real samples have been characterized by gold standard techniques while also a Raman library of nutrients used in bioreactors has been developed. T6.2 is active and is related to the testing of the photonic chips. Up to date the passive aMZI chips have been tested for bulk measurements and the system is ready for testing with targeted analytes.