Periodic Reporting for period 1 - Dypha (Dypha: adding the dimension of time to cell culture)
Reporting period: 2024-04-01 to 2025-03-31
The international δypha Consortium has received a European Innovation Council Transition grant for bringing Sync Biosystems’ technology from pilot to product. Industrial and research leaders, integral members of the consortium, participate as end users: Charles River Laboratories, Princess Máxima Center for Pediatric Oncology and Bambino Gesù Children’s Hospital. With dedicated showcases, they will demonstrate how the technology impacts their drug development assays and their search for better therapies for patients. To translate the results from the in vitro technology to patient-relevant levels, consortium partner ESQlabs will develop specific physiologically-based computational models. The goal of δypha is to improve cell culture and drug testing with automated and continuous fluidic control in standard cell culture plates.
The preclinical drug development pipeline presents opportunities to improve efficiency, with over 90% of drugs failing in clinical trials. To accomplish this, the predictivity of currently used cell culture models needs to be further increased. One of the aspects missing in current cell culture systems is the right time scale of changes in the cell culture medium. Many processes in the human body have time scales in the order of seconds, minutes or hours. In standard cell culture used for drug testing, however, this kinetic component is not incorporated. Being able to apply dynamic alterations in the cellular environment is crucial for advancing our understanding of cellular behavior. Similarly, researchers could use such alterations for simulating fluctuating drug concentrations as seen in patients, enabling a more accurate exploration of the complex relationships between drug exposure and its therapeutic or adverse effects. However, because user-friendly technology to dynamically control cell culture conditions is lacking, scientists currently rely heavily on animal models to study drug kinetics. Potential limits in translatability of results obtained in animals to the human situation, coupled with the goal of reducing or even replacing animal models (3Rs Principle), underscores the need for developing alternatives in biomedical research.
Sync Biosystems solves this problem by connecting cell culture devices to their fluidic control system. The technology is based on a specifically designed adapter, connecting standard cell culture devices to the automated fluidic control system, thereby allowing the supply of user-defined drug concentrations at any given point in time. This gives cell culture biologists the ability to control how the medium or drug concentrations change over time, without changing their regular workflow. Based on clinical data we know that the order and timing of supplying different drug combinations can have a huge effect on the ability to kill tumor cells. With the δypha technology we can now test different drug combinations in an informed and automated manner. One of the reasons why control is difficult is because the cell culture should not experience any shear stress or turbulence, making it challenging to change the environment of the cells. Traditional (automatic) pipettes cause such effects while Sync Biosystems’ solution has been proven to be more gentle than a pipette – even allowing cells in suspension to be automatically refreshed while keeping cell loss at the very minimum. The key to this lies in the design of the plug-and-play adaptor.
The preclinical drug development pipeline presents opportunities to improve efficiency, with over 90% of drugs failing in clinical trials. To accomplish this, the predictivity of currently used cell culture models needs to be further increased. One of the aspects missing in current cell culture systems is the right time scale of changes in the cell culture medium. Many processes in the human body have time scales in the order of seconds, minutes or hours. In standard cell culture used for drug testing, however, this kinetic component is not incorporated. Being able to apply dynamic alterations in the cellular environment is crucial for advancing our understanding of cellular behavior. Similarly, researchers could use such alterations for simulating fluctuating drug concentrations as seen in patients, enabling a more accurate exploration of the complex relationships between drug exposure and its therapeutic or adverse effects. However, because user-friendly technology to dynamically control cell culture conditions is lacking, scientists currently rely heavily on animal models to study drug kinetics. Potential limits in translatability of results obtained in animals to the human situation, coupled with the goal of reducing or even replacing animal models (3Rs Principle), underscores the need for developing alternatives in biomedical research.
Sync Biosystems solves this problem by connecting cell culture devices to their fluidic control system. The technology is based on a specifically designed adapter, connecting standard cell culture devices to the automated fluidic control system, thereby allowing the supply of user-defined drug concentrations at any given point in time. This gives cell culture biologists the ability to control how the medium or drug concentrations change over time, without changing their regular workflow. Based on clinical data we know that the order and timing of supplying different drug combinations can have a huge effect on the ability to kill tumor cells. With the δypha technology we can now test different drug combinations in an informed and automated manner. One of the reasons why control is difficult is because the cell culture should not experience any shear stress or turbulence, making it challenging to change the environment of the cells. Traditional (automatic) pipettes cause such effects while Sync Biosystems’ solution has been proven to be more gentle than a pipette – even allowing cells in suspension to be automatically refreshed while keeping cell loss at the very minimum. The key to this lies in the design of the plug-and-play adaptor.
Within this project, we have made significant progress to bring the δypha technology to the market. The main achievements that have been reached include the definition of the δypha beta system. The team successfully conceptualized a beta system that interfaces with an upscaled µFluidic Adaptor, despite initial challenges with sealing issues. Together with end users, the system was designed to fit the current end user workflow. In addition, the project secured their first customer interactions. These paid pilot projects ahead of schedule, demonstrating the practical application and market potential of the technology.
The δypha project has made significant progress in developing a user-friendly δypha Beta System and upscaling the µFluidic Adaptor (µFA). Despite initial challenges with sealing issues, the team successfully created an improved version, the µFA v2.0 which is smaller, more efficient, and capable of de- and recoupling. This new design has been validated through simulations and experiments, showing low shear stress on cells and efficient medium replacement. The project also demonstrated the relevance of δypha technology through experiments with human intestinal organoids, where preliminary data showed improved consistency and uniformity compared to manual methods. Additionally, the project has made strides in validating the market potential, generating revenue from pilot projects, and refining the product-market fit through customer interactions.