Periodic Reporting for period 1 - GALILEO (The first wide range flow sensor to unlock microfluidic cell analyses for preclinical studies)
Reporting period: 2023-05-01 to 2024-04-30
The average cost of developing a new drug is a staggering 1 billion €. All new drug candidates in the development pipeline must undergo a thorough preclinical screening for safety and efficacy before being trialed in humans. Today this requires the use of models that include a combination of cell culture in dishes and animal tests. The major problem with existing models is that they do not predict the results of human clinical outcomes very well. Animals fail to replicate human responses 90% of the time due to species differences, and cell models in dishes still largely lack basic physical stimuli such as flow to mimic blood vessels.
Recent legislation has recognized this critical need for improved models to accelerate drug development, in particular, the need for alternatives to animal models that better mimic human outcomes. Indeed, nearly 200 million animals are used in biomedical research worldwide, a number that could be reduced substantially by alternative technologies that support the “Three Rs principle” (replacement, reduction and refinement) of animals in testing.
One highly promising strategy is a technology called microfluidics. This technology enables the fine control of fluid flow over cells in culture, a hallmark of the native cell environment. Flow enables real-time control of nutrient and gas exchange, drug dosing and residence time, molecular gradients and shear stress. In addition, microfluidics enables the isolation and manipulation of single cells for analysis of cellular diversity and heterogeneity, diagnostics and drug screening at resolution unattainable on a population level.
Innovative dynamic microfluidic cell cultures, particularly organ-on-chip and 3D cell culture platforms, aim at improving drug candidate selection and facilitating trials, and clearly appear to be the next great step for the future of drug research and development. Their use could increase the success of clinical drug trials and decrease R&D costs by 10-26%, as they are more physiologically relevant than static culture flasks widely used today.
However, existing microfluidic sensors for accurately monitoring flow over a relevant
range are the main limiting factor in the use of microfluidics for cell culture, analysis and screening. To solve this important problem and address the main needs expressed by the market and end users, we are developing GALILEO, the first wide-range flow sensor to surpass the state of the art.
Recent legislation has recognized this critical need for improved models to accelerate drug development, in particular, the need for alternatives to animal models that better mimic human outcomes. Indeed, nearly 200 million animals are used in biomedical research worldwide, a number that could be reduced substantially by alternative technologies that support the “Three Rs principle” (replacement, reduction and refinement) of animals in testing.
One highly promising strategy is a technology called microfluidics. This technology enables the fine control of fluid flow over cells in culture, a hallmark of the native cell environment. Flow enables real-time control of nutrient and gas exchange, drug dosing and residence time, molecular gradients and shear stress. In addition, microfluidics enables the isolation and manipulation of single cells for analysis of cellular diversity and heterogeneity, diagnostics and drug screening at resolution unattainable on a population level.
Innovative dynamic microfluidic cell cultures, particularly organ-on-chip and 3D cell culture platforms, aim at improving drug candidate selection and facilitating trials, and clearly appear to be the next great step for the future of drug research and development. Their use could increase the success of clinical drug trials and decrease R&D costs by 10-26%, as they are more physiologically relevant than static culture flasks widely used today.
However, existing microfluidic sensors for accurately monitoring flow over a relevant
range are the main limiting factor in the use of microfluidics for cell culture, analysis and screening. To solve this important problem and address the main needs expressed by the market and end users, we are developing GALILEO, the first wide-range flow sensor to surpass the state of the art.
In project GALILEO we are developing a new flow sensor that pushes beyond the current state of the art for biological model applications. Perfusion cell cultures and assays provide specific challenges that include circulating cells, sticky nutrients, cell secretions and high sensitivity to shear stress and small liquid volumes. We are guided by ongoing close contact with end users of this technology (pioneers, major stakeholders, key opinion leaders, and frontline bench researchers). Armed with detailed knowledge of the main challenges today with existing flow control for cell assays, our team of engineers is developing the GALILEO flow sensor to cover a wider range of flow rates than currently available in a single microfluidic flow sensor. GALILEO will also be the first flow sensor able to detect a build up of biological material inside the sensor (fouling) that is a common cause of drift in measurement accuracy and to alert the user.
The development of the GALILEO sensor is being done with iterative prototyping and internal benchmark testing in order to characterize the performance of the sensor and approach our target competitive advantages. Currently external “beta” testing of the sensor prototype is underway. This phase involves 6 external beta testers across a variety of application areas, both in academia and industry, and will provide vital feedback on the functionality, performance and ease of use of the GALILEO flow sensor, as well as help us evaluate its technology fit for real-world applications for subsequent optimization and adjustment of the technology during the second year of the project.
The development of the GALILEO sensor is being done with iterative prototyping and internal benchmark testing in order to characterize the performance of the sensor and approach our target competitive advantages. Currently external “beta” testing of the sensor prototype is underway. This phase involves 6 external beta testers across a variety of application areas, both in academia and industry, and will provide vital feedback on the functionality, performance and ease of use of the GALILEO flow sensor, as well as help us evaluate its technology fit for real-world applications for subsequent optimization and adjustment of the technology during the second year of the project.
Through testing and end user feedback, project GALILEO will result in a new flow sensor innovation (technology output) to unlock challenges and bottlenecks in the field of microfluidics for cell biology, analysis, cell handling and other multi-modal technologies. Benchmarking to date of the GALILEO beta prototype has shown promising results all within 1% absolute accuracy, with an innovative base + cartridge format, enabling a fully replaceable flow path and with interchangeable cartridges, each defining a piece of the entire possible range with the GALILEO flow sensing technology.
Our patented technology will contribute to EU competitiveness and innovation, strengthening the European economy and local technology supply chain. Our active participation in standards working groups and networks will translate to the implementation of standards in microfluidic instrumentation and protocols, towards interoperability, reproducibility, technology adoption and open science in the field.
Knowledge-based outputs will include demonstrations of state of the art applications enabled by GALILEO for perfusion cell culture. We will also provide education material towards technology adoption, ease of use, and validation.
Our patented technology will contribute to EU competitiveness and innovation, strengthening the European economy and local technology supply chain. Our active participation in standards working groups and networks will translate to the implementation of standards in microfluidic instrumentation and protocols, towards interoperability, reproducibility, technology adoption and open science in the field.
Knowledge-based outputs will include demonstrations of state of the art applications enabled by GALILEO for perfusion cell culture. We will also provide education material towards technology adoption, ease of use, and validation.