Periodic Reporting for period 1 - TOMAC (TOMAC: Bioinspired Flow Generation in Tubeless Organ-on-a-chip using Magnetic Artificial Cilia)
Période du rapport: 2024-04-01 au 2025-09-30
TOMAC addresses a pressing challenge in drug development: the high failure rate of drug candidates in clinical trials (over 90%) despite promising preclinical results. A key reason is the limited predictive capacity of animal models, still widely used but poorly reflecting human physiology. This results not only in financial losses, but also in delayed patient access to effective therapies.
To improve preclinical predictability and reduce animal use, Organ-on-a-Chip (OoC) technology has emerged as a game changer. OoCs are microfluidic devices that simulate human organ functions by culturing human cells in controlled, dynamic environments. While evidence increasingly supports their superior relevance over animal models, e.g. liver-chips identifying toxicity in drugs missed by traditional methods, their industry uptake is still limited. A major barrier is the lack of compatibility with standard operating procedures (SOPs) in pharmaceutical R&D, particularly in terms of automation, scalability, and ease of use.
One of the critical challenges is the generation of physiological flow, which is essential to mimic in vivo organ function (e.g. blood flow in vessels, shear stress in the gut). Existing solutions typically use bulky, external pump systems with tubing, which prevent automation and introduce variability. Thus, users face a trade-off between physiological relevance and compatibility with industry workflows.
TOMAC overcomes this barrier by introducing the Magnetic Artificial Cilia (MAC) pump: a compact, tubeless, modular flow generation system inspired by biological cilia. The MAC pump consists of a disposable chip with micro-actuated magnetic cilia and an external actuation system that operates without physical connection. This allows full automation and plug-and-play integration with existing OoC platforms, in a format compatible with standard well-plate-based workflows used in pharmaceutical labs.
The objectives of TOMAC are:
1. To develop and miniaturize the MAC pump for compatibility with industrial OoC setups;
2. To demonstrate physiological flow generation in commercial organ-chips (e.g. ibidi endothelium-on-chip);
3. To validate the system's performance against pharmaceutical SOPs;
4. To initiate commercialization via a TU/e spin-off.
The expected impact is multifold. Technologically, TOMAC makes it feasible to integrate true physiological flow into automated, high-throughput OoC systems. Commercially, it enables organ-chip providers to meet pharma requirements, thus accelerating industry adoption. Societally, it contributes to the reduction of animal testing and facilitates more predictive drug screening. Economically, the MAC pump has the potential to lower R&D costs by 10–26% per developed drug, translating to an estimated €100–700 million per compound, by reducing attrition in clinical phases.
To improve preclinical predictability and reduce animal use, Organ-on-a-Chip (OoC) technology has emerged as a game changer. OoCs are microfluidic devices that simulate human organ functions by culturing human cells in controlled, dynamic environments. While evidence increasingly supports their superior relevance over animal models, e.g. liver-chips identifying toxicity in drugs missed by traditional methods, their industry uptake is still limited. A major barrier is the lack of compatibility with standard operating procedures (SOPs) in pharmaceutical R&D, particularly in terms of automation, scalability, and ease of use.
One of the critical challenges is the generation of physiological flow, which is essential to mimic in vivo organ function (e.g. blood flow in vessels, shear stress in the gut). Existing solutions typically use bulky, external pump systems with tubing, which prevent automation and introduce variability. Thus, users face a trade-off between physiological relevance and compatibility with industry workflows.
TOMAC overcomes this barrier by introducing the Magnetic Artificial Cilia (MAC) pump: a compact, tubeless, modular flow generation system inspired by biological cilia. The MAC pump consists of a disposable chip with micro-actuated magnetic cilia and an external actuation system that operates without physical connection. This allows full automation and plug-and-play integration with existing OoC platforms, in a format compatible with standard well-plate-based workflows used in pharmaceutical labs.
The objectives of TOMAC are:
1. To develop and miniaturize the MAC pump for compatibility with industrial OoC setups;
2. To demonstrate physiological flow generation in commercial organ-chips (e.g. ibidi endothelium-on-chip);
3. To validate the system's performance against pharmaceutical SOPs;
4. To initiate commercialization via a TU/e spin-off.
The expected impact is multifold. Technologically, TOMAC makes it feasible to integrate true physiological flow into automated, high-throughput OoC systems. Commercially, it enables organ-chip providers to meet pharma requirements, thus accelerating industry adoption. Societally, it contributes to the reduction of animal testing and facilitates more predictive drug screening. Economically, the MAC pump has the potential to lower R&D costs by 10–26% per developed drug, translating to an estimated €100–700 million per compound, by reducing attrition in clinical phases.
The activities performed and results achieved are presented below in relation to the technical and scientific objectives defined in the TOMAC project:
1. Development of a miniaturized magnetic actuation system suitable for Organ-on-a-Chip applications
We explored multiple concepts for realizing a compact magnetic actuation setup capable of driving the MAC pump while meeting the functional and dimensional constraints of OoC systems.
- For the disposable MAC-chip, this effort led to the design of a microfluidic plate featuring integrated wells and microchannels. The configuration allows commercial organ-chips to be connected from below via a click-in mechanism, enabling modular use in a multi-unit format.
- For the actuation system, we determined that the existing permanent magnet system—based on conical tilting motion—did not provide the desired range of physiological flow rates. Drawing from earlier work in the ERC AdG “BioPlan”, we identified a moving magnet belt system as a promising alternative. A miniaturized, non-bulky version of this system was developed successfully, achieving significantly higher flow rates up to 150 microliters per minute.
2. Pilot test with commercial organ-chip provider (ibidi GmbH) & 3. Validation of the OoC system against standard operating procedures
To demonstrate and validate physiological flow generation in a commercial organ-chip, we conducted a pilot study at ibidi GmbH using their organ-on-chip. While the pilot confirmed the system’s ability to produce physiological flow, it also revealed challenges. Specifically, we directly observed that the usability of the system was lower than anticipated, particularly with respect to ease of setup and integration. Concurrently, our in-house R&D revealed significant complexity in fabricating the disposable MAC-chip at scale.
These findings, combined with commercial and fundraising considerations, led us to broaden our application scope beyond Organ-on-a-Chip. We shifted focus toward the wider 3D cell culture market, aiming to create a dynamic and scalable cell culture platform compatible with standard well-plate formats. This platform retains the same magnetic actuation system but replaces the original MAC-chip with a redesigned disposable called MACplate.
The MACplate is substantially easier to fabricate and has demonstrated much better usability in internal experiments. First results with iPSC-derived kidney organoids, in collaboration with Erasmus MC, have shown promising indications of improved cell viability and differentiation. This innovation was protected through a US provisional patent filed in June 2025.
1. Development of a miniaturized magnetic actuation system suitable for Organ-on-a-Chip applications
We explored multiple concepts for realizing a compact magnetic actuation setup capable of driving the MAC pump while meeting the functional and dimensional constraints of OoC systems.
- For the disposable MAC-chip, this effort led to the design of a microfluidic plate featuring integrated wells and microchannels. The configuration allows commercial organ-chips to be connected from below via a click-in mechanism, enabling modular use in a multi-unit format.
- For the actuation system, we determined that the existing permanent magnet system—based on conical tilting motion—did not provide the desired range of physiological flow rates. Drawing from earlier work in the ERC AdG “BioPlan”, we identified a moving magnet belt system as a promising alternative. A miniaturized, non-bulky version of this system was developed successfully, achieving significantly higher flow rates up to 150 microliters per minute.
2. Pilot test with commercial organ-chip provider (ibidi GmbH) & 3. Validation of the OoC system against standard operating procedures
To demonstrate and validate physiological flow generation in a commercial organ-chip, we conducted a pilot study at ibidi GmbH using their organ-on-chip. While the pilot confirmed the system’s ability to produce physiological flow, it also revealed challenges. Specifically, we directly observed that the usability of the system was lower than anticipated, particularly with respect to ease of setup and integration. Concurrently, our in-house R&D revealed significant complexity in fabricating the disposable MAC-chip at scale.
These findings, combined with commercial and fundraising considerations, led us to broaden our application scope beyond Organ-on-a-Chip. We shifted focus toward the wider 3D cell culture market, aiming to create a dynamic and scalable cell culture platform compatible with standard well-plate formats. This platform retains the same magnetic actuation system but replaces the original MAC-chip with a redesigned disposable called MACplate.
The MACplate is substantially easier to fabricate and has demonstrated much better usability in internal experiments. First results with iPSC-derived kidney organoids, in collaboration with Erasmus MC, have shown promising indications of improved cell viability and differentiation. This innovation was protected through a US provisional patent filed in June 2025.
1. The miniaturised actuation system goes beyond the state-of-the art, which includes either bulky setups not suitable for Organ-on-Chip applications, or electromagnets which require substantial cooling for their operation, making then unsuitable for Organ-on-Chip applications as well. In contrast, our system is compact, incubator-compatible, and based on permanent magnets, enabling metachronal actuation of magnetic artificial cilia (MAC) to generate physiological flow.
The MACplate represents a novel concept that extends the functionality of standard well plate formats by integrating embedded microchannels and magnetic cilia arrays, thereby transforming static culture wells into dynamic 3D cell culture environments. The MACplate maintains full compatibility with automated liquid handling systems and pharmaceutical workflows.
2,3.: The immediate focus is to validate the full MAC system— (MACnet) and actuation unit—in the initial beachhead market: Transwell-based barrier models. Validation will be conducted through paid pilot collaborations with potential customers, with the dual goal to:
a) Functionally validate the platform and generate biological performance data;
b) Assess commercial viability, specifically customer willingness to pay and the added value in terms of experimental quality, scalability, and automation.
4: The project has resulted in the successful establishment of a spin-off company, ARTIC Technologies, under an exclusive licensing agreement with Eindhoven University of Technology (TU/e). The agreement covers the original WO patent for the magnetic actuation system as well as related know-how from the Microsystems group in the field of microscale fluid manipulation using magnetic artificial cilia.
ARTIC Technologies has raised €630,000 in initial funding and is led by two Managing Directors, Dr. Hossein Amirabadi and Ms. Laure van der Sanden. The team currently includes two full-time R&D engineers.
The MACplate represents a novel concept that extends the functionality of standard well plate formats by integrating embedded microchannels and magnetic cilia arrays, thereby transforming static culture wells into dynamic 3D cell culture environments. The MACplate maintains full compatibility with automated liquid handling systems and pharmaceutical workflows.
2,3.: The immediate focus is to validate the full MAC system— (MACnet) and actuation unit—in the initial beachhead market: Transwell-based barrier models. Validation will be conducted through paid pilot collaborations with potential customers, with the dual goal to:
a) Functionally validate the platform and generate biological performance data;
b) Assess commercial viability, specifically customer willingness to pay and the added value in terms of experimental quality, scalability, and automation.
4: The project has resulted in the successful establishment of a spin-off company, ARTIC Technologies, under an exclusive licensing agreement with Eindhoven University of Technology (TU/e). The agreement covers the original WO patent for the magnetic actuation system as well as related know-how from the Microsystems group in the field of microscale fluid manipulation using magnetic artificial cilia.
ARTIC Technologies has raised €630,000 in initial funding and is led by two Managing Directors, Dr. Hossein Amirabadi and Ms. Laure van der Sanden. The team currently includes two full-time R&D engineers.