An actuator system for actuating magnetic artificial cilia

Abstract

An actuator system for actuating a plurality of magnetic artificial cilia (MAC). The actuator system includes: a clamping system with an aligning feature such as a recess for accommodating a MAC chip that includes the MAC; a motor with a rotatable shaft; and a rotatable assembly that is rotatable by the shaft. The rotatable assembly includes a magnet wheel with a first cavity accommodating a permanent magnet. The first cavity is located in the magnet wheel and is configured such that the magnet is off-centered from an axis of rotation defined by the shaft.

Description

[0001] An actuator system for actuating magnetic artificial cilia

[0002] Technical field

[0003] The present disclosure relates to actuator systems for actuating magnetic artificial cilia (MAC). Furthermore, the present disclosure relates to an organ-on-a- chip (OoC) platform including such actuator systems.

[0004] Background

[0005] Artificial cilia are hair-like structures that can be engineered to mimic motion and function of biological cilia found in various organisms. They have the potential to revolutionize microfluidics, where they can be used as micropumps, microsensors, microrobots, and self-cleaning and antifouling surfaces, making them highly versatile tools for a range of applications in (bio)engineering. For example, artificial cilia have been used to create fluid flow in microfluidic chip-based models of human tissues, enabling the study of biological processes in a controlled environment. As research in this field continues to progress, it is expected that the use of artificial cilia will become increasingly prevalent in a range of fields, leading to new discoveries and applications that have the potential to improve human health and advance scientific understanding.

[0006] Magnetic actuation is a method used for actuating MAC, which involves the use of external magnetic fields. The MAC often are fabricated from elastomeric materials containing magnetic nano- or microparticles. This approach offers several advantages over other actuation methods (e.g., electrical), including the flexibility of not requiring a mechanical connection between the MAC and the external source, which decreases dead volume and the risk of contamination, and which enhances ease-of-use.

[0007] Two main technologies used to generate external magnetic fields are electromagnets and permanent magnets. The choice is a trade-off between versatility in cilia motion, accessible space, and magnetic field strength.

[0008] Electromagnets offer the most versatile control over the direction and strength of the field, but they produce relatively small field strengths, unless the electromagnets are large, and a single electromagnet generates fixed field lines so that the magnetic field can only be varied in strength, not in spatial distribution or direction. In order to achieve the desired field which allows for time-dependency of the spatial field distribution, multiple electromagnets must be arranged in a specific configuration and individually driven, which can obstruct optical visibility or accessibility of the samples. The use of a rotating (or otherwise moving) permanent magnet provides an affordable and accessible external actuation method. However, the current setups are often bulky and involve a "design for purpose" approach, where the end application must have a clear and mostly fixed requirement for both the cilia motion and the corresponding magnetic field.

[0009] A known system 100 based on a rotating magnetic plate 102 is shown in Fig. 1. The known system 100 includes a manual linear XYZ translational stage 104 at the bottom, a motor 106, a magnet 108 with an offset r, d with respect to its rotation axis 110. A supporting transparent glass plate 112 and a thin layer (e.g., 100 pm) of PDMS 114 is used to fixate a chip 116 including MAC 118. The setup may be mounted on a stereo microscope. While this solution provides a means for MAC actuation, it is hindered by its large size, lack of user-friendliness, and incompatibility with life science and drug development workflows. Additionally, it lacks scalability and cannot accommodate the required scale-up or integration into multi-well plate formats.

[0010] Summary

[0011] A summary of aspects of certain examples disclosed herein is set forth below. It should be understood that these aspects are presented merely to provide the reader with a brief summary of these certain embodiments and that these aspects are not intended to limit the scope of this disclosure. Indeed, this disclosure may encompass a variety of aspects and / or a combination of aspects that may not be set forth.

[0012] The present disclosure aims to overcome the drawbacks identified in the background section. In particular, the present disclosure aims miniaturization and modularity of an actuation setup, and an optimal range of magnetic field strength between the cilia and the actuation setup. This is achieved by the actuator system of the present disclosure.

[0013] According to an aspect of the present disclosure, an actuator system is presented for actuating a plurality of MAC. The actuator system may include a clamping system including an aligning feature such as a recess for accommodating a MAC chip, wherein the plurality of MAC are located. The actuator system may further include a motor including a shaft that is rotatable by the motor. The actuator system may further include a rotatable assembly that is rotatable by the shaft from a first side of the rotatable assembly and positionable with respect to the plurality of MAC using the clamping system from a second side of the rotatable assembly opposite of the first side. The rotatable assembly may include a magnet wheel including a first cavity for accommodating a permanent magnet. The rotatable assembly may further include the permanent magnet positioned in the first cavity. The first cavity may be located on the second side of the magnet wheel and it may be configured such that the magnet is off- centered from an axis of rotation defined by the shaft.

[0014] In an embodiment, the MAC chip may be or may include a MAC micropumping module.

[0015] In an embodiment, the magnet wheel may include a counterweight to the magnet to balance the magnet wheel along the axis of rotation.

[0016] In an embodiment, the magnet wheel may include a second cavity located on the first side of the magnet wheel and centered along the axis of rotation. The rotatable assembly may further include a shaft holder arranged to attach the shaft to the magnet wheel within the second cavity.

[0017] In an embodiment, the magnet wheel may include one or more through holes from a third side of the magnetic wheel to the second cavity, the third side being substantially perpendicular to the first and second sides. Each through hole may be arranged to accommodate a grub screw to secure the magnetic wheel to the motor shaft through the shaft holder. The shaft holder may be deformable by the grub screw to clamp the shaft holder to the shaft.

[0018] In an embodiment, the shaft holder may be cylindrically shaped. The shaft holder may include a slanted indentation arranged to receive the grub screw. The shaft holder may be semi-slit for slit clamping the shaft by the grub screw.

[0019] In an embodiment, the shaft holder may be made of a non-magnetic material, such as a non-magnetic stainless steel.

[0020] In an embodiment, the magnet wheel may be made of a non-magnetic material, such as a non-magnetic stainless steel.

[0021] In an embodiment, the magnet may have one of the following shapes: a rectangular shape; a cube shape, a cuboid shape; a cylinder shape. In an embodiment, the actuator system may further include a casing. The casing may be arranged between the clamping system and the motor. The casing may accommodate the rotatable assembly.

[0022] In an embodiment, the casing may be made of a nonmagnetic material, such as aluminum.

[0023] In an embodiment, the actuator system may further include a cover that covers the motor and the rotatable assembly. The cover may be attachable to the clamping system.

[0024] In an embodiment, the magnet may be repositionable within the magnet wheel.

[0025] In an embodiment, the first cavity may be arranged to accommodate the magnet in one of two or more positions.

[0026] In an embodiment, the actuator system may further include a second magnet. The second magnet may be disposed on a second side of the MAC chip, the magnet being located on a first side of the MAC chip.

[0027] In an embodiment, the second magnet may be off-centered from the axis of rotation defined by the shaft.

[0028] In an embodiment, the relative positions of the magnet and the second magnet may be adjustable in all three planes.

[0029] In an embodiment, the first cavity may be located on the second side of the magnet wheel and off-centered from the axis of rotation defined by the shaft.

[0030] In an embodiment the magnet in the first cavity may cross or touch the axis of rotation.

[0031] In an embodiment, the magnet may be positioned at a distance from the axis of rotation allowing a visualization of the MAC chip in a reflection mode.

[0032] In an embodiment, the magnet and the second magnet may each be positioned at a distance from the axis of rotation allowing visualization of the MAC chip in a transmission mode.

[0033] In an embodiment, the actuator system may be attachable to an OoC platform via the clamping system.

[0034] In an embodiment, the MAC chip may be fluidically connectable to an OoC module through the OoC platform. The magnet may be arranged to actuate the plurality of MAC to create a fluid flow to the OoC module. According to an aspect of the present disclosure, an OoC platform is proposed. The OoC platform may include an actuator system having one or more of the abovedescribed features. The OoC platform may be arranged to accommodate an OoC module that is connectable to the actuator system. The actuator system may be arranged to accommodate a plurality of MAC that are located in a MAC chip. The OoC module and the MAC chip may be fluidically connectable through the OoC platform.

[0035] In an embodiment, the OoC platform may include a microfluidic channel network for fluidically connecting the OoC module to the MAC chip.

[0036] In an embodiment, multiple OoC modules may be fluidically connectable to the MAC chip, e.g., through the microfluidic channel network in the OoC platform.

[0037] In an embodiment, the OoC platform may further include a medium reservoir. The medium reservoir may be fluidically connected to an inflow of the MAC chip.

[0038] In an embodiment, the OoC platform may further include a medium reservoir. The medium reservoir may be fluidically connected to an inflow and an outflow of the MAC chip to form a recirculating system.

[0039] In an embodiment, the OoC platform may further include a waste reservoir. The waste reservoir may be fluidically connected to an outflow of the MAC chip.

[0040] In an embodiment, the OoC platform may include a plurality of actuator systems. Each actuator system may be connectable to a separate OoC module. Alternatively, each actuator system may be connectable to a plurality of OoC modules.

[0041] In an embodiment, the OoC platform may further include one or more sensor modules for sensing a flow rate or properties of the content of the OoC platform (e.g., related to fluids or cells).

[0042] Brief description of the Drawings

[0043] Embodiments of the present disclosure will now be described, by way of example only, with reference to the accompanying schematic drawings in which corresponding reference symbol indicate corresponding parts, in which:

[0044] Fig. 1 shows a known magnetic actuation system based on a rotating magnetic plate;

[0045] Figs. 2-4 show example embodiments of actuator systems; Fig. 5 shows a schematic overview of an example two-magnet system of an actuator system;

[0046] Fig. 6 shows an example embodiment of an OoC platform including a plurality of actuator systems;

[0047] Fig. 7 shows an example of a magnet wheel part of an actuator system;

[0048] Fig. 8 shows an example of a shaft holder part of an actuator system;

[0049] Fig. 9 shows an example of a motor part of an actuator system;

[0050] Fig. 10 shows an example casing part of an actuator system;

[0051] Fig. 11 shows an example clamping system part of an actuator system; and

[0052] Fig. 12 shows an example cover part of an actuator system.

[0053] The figures are intended for illustrative purposes only, and do not serve as restriction of the scope of the protection as laid down by the claims.

[0054] Detailed description

[0055] It will be readily understood that the components of the embodiments as generally described herein and illustrated in the appended figures could be arranged and designed in a wide variety of different configurations. Thus, the following more detailed description of various embodiments, as represented in the figures, is not intended to limit the scope of the present disclosure but is merely representative of various embodiments. While the various aspects of the embodiments are presented in drawings, the drawings are not necessarily drawn to scale unless specifically indicated.

[0056] The described embodiments are to be considered in all respects only as illustrative and not restrictive. The scope of the present disclosure is, therefore, indicated by the appended claims rather than by this detailed description. All changes which come within the meaning and range of equivalency of the claims are to be embraced within their scope.

[0057] Reference throughout this specification to features, advantages, or similar language does not imply that all of the features and advantages that may be realized with the present disclosure should be or are in any single example of the present disclosure. Rather, language referring to the features and advantages is understood to mean that a specific feature, advantage, or characteristic described in connection with an embodiment is included in at least one embodiment of the present disclosure. Thus, discussions of the features and advantages, and similar language, throughout this specification may, but do not necessarily, refer to the same example.

[0058] Furthermore, the described features, advantages, and characteristics of the present disclosure may be combined in any suitable manner in one or more embodiments. One skilled in the relevant art will recognize, in light of the description herein, that the present disclosure may be practiced without one or more of the specific features or advantages of a particular embodiment. In other instances, additional features and advantages may be recognized in certain embodiments that may not be present in all embodiments of the present disclosure. Reference throughout this specification to "one embodiment," "an embodiment," or similar language means that a particular feature, structure, or characteristic described in connection with the indicated embodiment is included in at least one embodiment of the present disclosure. Thus, the phrases "in one embodiment," "in an embodiment," and similar language throughout this specification may, but do not necessarily, all refer to the same embodiment.

[0059] The absence of a representative human test model in preclinical drug development, coupled with the limitations of animal models and two-dimensional (2D) in vitro models, presents challenges such as poor predictability, ethical concerns, high costs, low throughput, and inadequate physiological relevance. The emergence of advanced in vitro models, such as organoids, bio-printed tissues, and OoC systems, has aimed to improve predictability and throughput while reducing costs. The integration of advanced three-dimensional (3D) cell cultures within a physiologically relevant dynamic micro-environment, enabled by OoC technology, offers promising solutions for researchers. However, challenges related to complexity, robustness, and the need for novel ideas to enhance technology adoption still persist.

[0060] The present disclosure provides innovative technology including an enhanced actuator system that aims to enhance the usability and robustness of OoC systems. This technology uses bio-inspired MAC, for example as micropumps, which are controlled by a magnetic field to induce fluid flow.

[0061] A first example embodiment of an enhanced actuator system 200 is shown in Fig. 2, which shows a cross-sectional diagram representing the integration of a miniaturized magnetic artificial cilia system onto an OoC platform 218, positioned in an "upside-down" orientation. The actuator system 200 is a modular and miniaturized artificial cilia actuation setup tailored for use in an OoC platform 218, preferably following the requirements of the ISO 22916:2022(E) regulation for microfluidic devices. The requirements of this ISO regulation include suitability for the incubator, modularity, fabrication with standard machining techniques, optical accessibility, and magnetic flux density at the middle of the cilia. In an example embodiment, the magnetic flux density at the middle of the cilia may be >80 mT.

[0062] Manipulation of cilia enables the exploration of various techniques, including micropumping and microsensors. In the present disclosure, the focus is on micropumping. By actuating the cilia in a tilted conical motion, a cell-friendly fluid flow may be created within the chip, eliminating the need for external tubing.

[0063] As shown in Fig. 2, the actuator system 200 forms a miniaturized actuation setup and may include a magnet wheel 202, a clamping system 204 (implemented via any suitable mechanical, magnetic or other means, e.g., for removably attaching a MAC chip to the actuator system), a casing 206, a shaft holder 208, a cover 210, and a motor 212, e.g., a Maxon EC 20™ flat motor with integrated electronics. A magnet 214 may be positioned within the magnet wheel 202 to actuate a plurality of MAC in a cilia chip 216 when the cilia chip is mounted to the actuator system 200. The cilia chip 216 is an example of a MAC chip or a MAC micropumping module. The cilia chip 216 may include a MAC patch wherein MACs are disposed on a carrier and / or a micropumping module. Typically, actuator system 200 with cilia chip 216 will be mounted on an OoC platform 218.

[0064] In order to actuate the MAC, a permanent magnet 214 may be used. This magnet possesses a strong magnetic field, allowing for more space and facilitating easier access to the microfluidic device.

[0065] The magnet 214 may be positioned in a cavity of the magnetic wheel. This cavity is located on the side of the magnet wheel facing the cilia chip 216. Furthermore, the first cavity may be off-centered from the axis of rotation defined by the shaft of the motor such that the magnet 214 in the first cavity crosses or touches the axis of rotation.

[0066] In an example embodiment, the magnet 214 may be a 7 mm by 7 mm permanent magnet cube. The magnetic flux density fields may be >80 mT. In this example, an optimal available space between the cilia patch in the cilia chip 216 and the permanent magnet 214, allows for a rotating range of 0.88 to 1.12 mm from the edge of the 7 mm by 7 mm magnet cube. In this example, a cilia patch with a width of 2 mm may be used.

[0067] A second example embodiment of an enhanced actuator system 300 is shown in Fig. 3, which shows a cross-sectional diagram representing the integration of a miniaturized magnetic artificial cilia system onto an OoC platform 318, positioned in an "upside-down" orientation. Similar to the actuator system 200, the actuator system 300 is a modular and miniaturized artificial cilia actuation setup for use in an OoC platform 318, preferably following the requirements of the ISO 22916:2022(E) regulation for microfluidic devices.

[0068] As shown in Fig. 3, the actuator system 300 forms a miniaturized actuation setup and may include a magnet wheel 302, a repositionable magnet 314 / 315, a clamping system 304 (implemented via any suitable mechanical, magnetic or other means), a casing 306, a shaft holder 308, a cover 310, and motor 312, e.g., a Maxon EC 20™ flat motor with integrated electronics. Typically, actuator system 300 with cilia chip 316 will be mounted on an OoC platform 318.

[0069] The magnet 314 / 315 may be positioned within the magnet wheel 302 to actuate a plurality of MAC in a cilia chip 316 when the cilia chip is mounted to the actuator system 300. The actuator system 300 is similar to the actuator system 200 of Fig. 2, with the addition that the magnet 314 / 315 may be repositionable, e.g., at a first position as depicted in Fig. 3 as the magnet 314 or at a second position as depicted in Fig. 3 as the magnet 315. A cavity in the magnet wheel 302 may accommodate the magnet 314 / 315 in the different positions.

[0070] A third example embodiment of an enhanced actuator system 400 is shown in Fig. 4, which shows a cross-sectional diagram representing the integration of a miniaturized magnetic artificial cilia system onto an OoC platform 418, positioned in an "upside-down" orientation, wherein the setup includes a two-magnet system. Similar to the actuator system 300, the actuator system 400 is a modular and miniaturized artificial cilia actuation setup for use in an OoC platform 418, preferably following the requirements of the ISO 22916:2022(E) regulation for microfluidic devices.

[0071] As shown in Fig. 4, the actuator system 400 forms a miniaturized actuation setup and may include a magnet wheel 402, a two-magnet system 414 / 415, 420, a clamping system 404 (implemented via any suitable mechanical, magnetic or other means), a casing 406, a shaft holder 408, a cover 410, and motor 412, e.g., a Maxon EC 20™ flat motor with integrated electronics. Typically, actuator system 400 with cilia chip 416 will be mounted on an OoC platform 418.

[0072] The first magnet 414 / 415 may be repositionable, similar to the magnet 314 / 315 of Fig. 3. Alternatively, the first magnet 414 / 415 may be accommodated within a cavity at a fixed position, similar to the magnet 214 of Fig. 3.

[0073] In a two-magnet system such as shown in Fig. 4, the first magnet 414 / 415 may be positioned within the magnet wheel 402 to, together with a second magnet 420, actuate a plurality of MAC in the cilia chip 416 when the cilia chip is mounted to the actuator system 400. The second magnet 420 may be positioned in or on the OoC platform 418, such that the first magnet 414 / 415 and the second magnet 420 are positioned on opposite sides of the cilia chip 416, such as shown in Fig. 4.

[0074] With the two-magnet system, such as shown in Fig. 4, cilia actuation may be achieved at larger distances from the rotating magnet 414 / 415 compared to a one- magnet system such as shown in Figs. 2 and 3, while keeping the second magnet 420 at a fixed position. The two-magnet system enables an eccentric placement of the rotating magnet 414 / 415 with respect to the rotating motor axis, and therefore allowing uninterrupted cilia visualization under reflected as well as transmission microscopy modes.

[0075] In a two-magnet system, control over the magnetic field and its direction may be achieved by adjusting the relative position of the two magnets 414 / 415, 420 in all the three x, y and z planes. In principle, different cilia actuation profiles over different areas are achievable with the two-magnet system by employing magnets of different sizes or adopting various relative motions between the first magnet 414 / 415 and the second magnet 420 or selecting different locations in space around the two magnets 414 / 415, 420.

[0076] In an example embodiment of a two-magnet system, a cilia patch may be positioned at a distance of 1.5 mm from the inner upper edge of the second magnet 420 in the vertical direction and 1.5 mm in the horizontal direction (relative to the positioning of the actuator system 400 as shown in Fig. 4). The magnetic field direction near the cilia chip may change from vertical to near horizontal direction with a half cycle rotation relative to the second magnet 420, i.e., by an angle of 180°. The total distance between the first magnet 414 / 415 and the second magnet 420 may be set at 6 mm, implying cilia actuation at 4.5 mm from the bottom face of the rotating first magnet 414 / 415.

[0077] Compared to a one-magnet system, a two-magnet system enables to further miniaturize the actuator system, because the first magnet 414 / 415 may be reduced in size without affecting the field intensity; this enables to use a smaller motor 412 as well. Thus, the two-magnet system enables to realize more versatile magnetic fields.

[0078] Fig. 5 shows a schematic overview of an example two-magnet system 500, wherein a permanent first magnet 514 and a second magnet 520 determine the instantaneous cilia orientation along the magnetic field direction. Magnetic field lines 530 are illustrated in Fig. 5 and in the zoomed box 522 as dashed and solid lines. Two distinct scenarios are illustrated: cilia 524 exhibiting maximum curvature under the solid field lines, and cilia 526 in an upright and straight configuration under the dashed field lines. In this example, maximum curvature (524) may be achieved by the magnetic flux density and the field direction existing between the first magnet 514 and the second magnet 520 when the first magnet 514 is at the left extreme position in Fig. 5. In this example, the upright and straight configuration (526) may be achieved by the magnetic flux density and the field direction existing between the first magnet 514 and the second magnet 520 when the first magnet 514 has rotated by 180° to the right extreme position in Fig. 5. The central axis 528 represents the motor shaft rotational axis.

[0079] The actuator system of the present disclosure, such as actuator system 200, 300, 400 or 500, may be used in an OoC platform 650, an example of which is shown in Fig. 6. One or more actuator systems may be used in an OoC platform. In the example of Fig. 6, six actuator systems 600 are used in the OoC platform 650. For each actuator system 600, the OoC platform 650 may include a MAC chip 616, such as cilia chip 216, 316, 416, that may be interconnected with one or more OoC modules 652, a medium reservoir 654, a waste reservoir 656, and / or one or more sensor modules, through fluidic connections and / or microchannels.

[0080] In an example embodiment, the OoC platform 650 may include a microfluidic channel network for fluidically connecting the OoC module 652 to the MAC chip 616. In an example embodiment, multiple OoC modules 652 may be fluidically connectable to one MAC chip 616, e.g., through the microfluidic channel network in the OoC platform.

[0081] In an example embodiment, the OoC platform 650 may further include one or more sensor modules for sensing a flow rate or properties of the content of the OoC platform (e.g., related to fluids or cells). An output of the flow rate sensing may advantageously be used to control the actuating system for regulating the generated fluid flow.

[0082] In the example of Fig. 6, the OoC module 652 is positioned on top of the MAC chip 616, on the other side of a platform body 618 relative to the actuator system 600. The body 618 of the OoC platform may be referred to as “docking plate” and may include an internal microfluidic channel network to which the various modules may be connected. Other configurations are possible, e.g., where the OoC module 652 is located at a different location, but still connected to the MAC chip and / or a MAC micropumping module through the microfluidic channel network in the OoC platform.

[0083] In the example of Fig. 6, the MAC chip 616 and the OoC modules 652 are located on different sides of the platform body 618. Other configurations are possible, e.g., where the MAC chip 616 and one or more of the OoC modules 652 are located on the same side of the platform body 618. In the latter example, the actuator system 600 and one or more of the OoC modules 652 may be located on the same side of the platform body 618.

[0084] Figs. 7A-7C show an example of a magnetic wheel 700, such as magnetic wheel 202, 302 or 402. Fig. 7A shows a 3D representation of the magnet wheel 700, including the cavity 702 for accommodating a magnet, such as magnet 214, 314 / 315 or 414 / 415. Also shown is a counterweight 704. An exemplary counterweight may be or include a protruding part of the magnet wheel that is sized and dimensioned to counterbalance a rotating magnet that typically has a different density than the material of the magnet wheel. Fig. 7B shows a 3D schematic overview of the magnetic wheel 700 from the side opposite of Fig. 7A. Fig. 7C shows a bottom surface (relative to the actuator system as shown in the examples of Figs. 2, 3 and 4) of the magnetic wheel 700, showing the counterweight 704 and the cavity 702 for the magnet. In an exemplary embodiment, a counterweight may be an element separate from the magnet wheel. In such embodiments, the magnet and the counterweight may be placed in the same cavity or different cavities created for that purpose. For a two-magnet system such as shown in Fig. 4, the cavity 702 to hold the magnet may be created at an eccentric location different from a cavity in a one-magnet system such as shown in Figs. 2 and 3.

[0085] The cavity 702 may be created such that the magnet that is provided in the cavity 702 rotates along a specific axis, i.e., the cavity 702 is located off-centered from the axis of rotation defined by the shaft of the motor through the center 706 of the magnetic wheel 700. The cavity 702 may further be located such that the magnet in the cavity crosses or touches the axis of rotation. The cavity 702 may securely house the magnet. In some embodiments, the cavity 702 may be extended to the opposite side of the axis of rotation to also house the counterweight. The magnet (and counterweight, where applicable) may be retained in the cavity by means of friction or any other suitable mechanism.

[0086] To achieve wheel balance, the counterweight 704 may be used, taking into account the magnet's dimensions and axial position.

[0087] To accommodate a shaft holder, an example of which is shown in Figs. 8A-8B, a blind hole may be present at the center 706 of the magnetic wheel 700. In an example embodiment, this blind hole may have a diameter of 6 mm and a depth of 4.9 mm. Two through holes, e.g., of 2.45 mm in diameter, may be positioned on opposite side of the side of the magnetic wheel 700 to secure the shaft holder using, e.g., grub screws.

[0088] In an example embodiment, the magnet wheel 700 may be made from nonmagnetic stainless steel.

[0089] Figs. 8A-8B show an example of a shaft holder 800. Fig. 8A shows a 3D schematic overview of a shaft holder 800. Fig. 8B shows a 2D schematic overview of a bottom surface (relative to the actuator system as shown in the examples of Figs. 2, 3 and 4) of the shaft holder 800. Figs. 8A and 8B show a semi-slit 802 and a cavity through hole 804 for accommodating the motor shaft.

[0090] In an example embodiment, the shaft holder 800 may be made from nonmagnetic stainless steel.

[0091] In order to enable the rotation of the magnet wheel 700, the shaft holder 800 may be securely attached to the motor shaft. The connection between the motor shaft and the shaft holder may be based on a slit clamp technique, which offers several advantages. These advantages include a high torque capacity, ability to handle high axial loads, provision for axial location, ease of hub replacement, fatigue resistance, simple position adjustment, and cost-effectiveness. The shaft holder 800 is an example of a semi-slit shaft holder, utilizing the semi-slit 802, which is particularly advantageous in an axial assembly, such as the actuator system 200, 300 or 400. The shaft holder 800 ensures a secure clamping without causing any damage. The clamping process may involve screwing a grub screw into the slanted indentation 806 located around the shaft holder 800. The slanted indentation directs the force from the grub screws on the shaft holder towards the magnetic wheel, thereby resisting slipping out of the shaft holder and ensuring a firm attachment of the magnetic wheel with the shaft holder.

[0092] Fig. 9 shows a 3D schematic overview of an example motor 900, such as motor 212, 312 or 412. The shaft 902 of the motor 900 is arranged to rotate the magnetic wheel 700. Preferably, the shaft 902 is connected to the magnetic wheel 700 via a shaft holder 800, but other means may be used for attaching the shaft 902 to the magnetic wheel 700.

[0093] Fig. 10 shows a 3D schematic overview of an example casing 1000, such as casing 206, 306 or 406. Inside the casing 1000, the magnetic wheel 700 may be accommodated. The motor 900 may be attached on top (relative to the casing 1000 as shown in Fig. 10) of the casing 1000, allowing the shaft 902 of the motor 900 to go through center hole 1002 of the casing 1000 and attach to the magnetic wheel 700, e.g., via a shaft holder 800.

[0094] In an example embodiment, the motor 900 may be fastened to the casing 1000, e.g., using one or more screws such as M2 screws. Hereto, screw holes 1004, in this example three screw holes 1004, may be created in the casing 1000.

[0095] The casing 1000 holding the magnetic wheel 700 may be attached to the actuator system via a clamping system, such as shown in Fig. 11 , e.g., using one or more screws such as M2 screws. Hereto, further screw holes 1006 may be created in the casing 1000.

[0096] A through hole 1008 may be created in the casing 1000, which aligns with the slanted indentation 806 and allows for a grub screw to be screwed into the slanted indentation 806.

[0097] Fig. 11 shows a 3D schematic overview of an example clamping system 1100, such as clamping system 204, 304 or 404. The clamping system 1100 may be used to attach the casing 1000, e.g., via screw holes 1102 of the clamping system 1100 and the further screw holes 1006 of the casing 1000.

[0098] The clamping system 1100 may further be used to attach a cover, such as shown in Fig. 1200, e.g., via screw holes 1104. In this example, four screw holes 1104 may be used for attaching the cover. The same screw holes 1104 may be used for attaching the actuator system to an OoC platform, such as actuator system 200, 300, 400 or 600 to OoC platform 218, 318, 418 or 618, respectively.

[0099] The clamping system 1100 may include a recess 1106 for accommodating a cilia chip, such as cilia chip 216, 316, 416 or 616, or one or more other types of aligning features for accommodating the cilia chip in a predetermined position with respect to the actuator system.

[0100] Fig. 12 shows a 3D schematic overview of an example cover 1200, such as cover 210, 310 or 410. The cover 1200 may be attached to the clamping system 1100, e.g., via screw holes 1202 of the cover 1200 and screw holes 1104 of the clamping system 1100. The same screws may be used for attaching the cover 1200 to the clamping system 1100 and to an OoC platform. The cover may protect the internals of the actuator system, e.g., from humidity or dust. This allows the actuator system to be used, e.g., in a humid incubator environment.

[0101] An actuator system, such as actuator system 200, 300, 400 or 600, may thus be modularly formed by a cover 1200, a clamping system 1100, a casing 1000, a magnet wheel 700, a motor 900, and optionally a shaft holder 800. The actuator system may accommodate a cilia chip to be actuated by the actuator system and may be used with an OoC platform such as OoC platform 218, 318, 418 or 650.

[0102] Instead of using screws to interconnect the various parts of the actuator system, other attachment means may be used or a mixture of attachment means may be used. For example, one or more parts may be interconnected using magnets or a modular, e.g., universal, building block system including matching protrusions and / or depressions and / or self-locating structures.

[0103] In the above examples, the magnet 214, 314 / 315, 414 / 415, 514, and the second magnet 420, 520 are shown as having a cube or cuboid shape. It will be understood that these magnets may have any other form factor, such as a cylinder shape or any other shape. In a two-magnet system the magnet may be similarly shaped or differently shaped. The cavity for holding the magnet in the magnetic wheel, such as cavity 702, may be shaped accordingly.

Claims

CLAIMS1. An actuator system (200, 300, 400, 600) for actuating a plurality of magnetic artificial cilia, MAC, the actuator system comprising: a clamping system (204, 304, 404, 1100) comprising an aligning feature such as a recess (1106) for accommodating a MAC chip (216, 316, 416, 616) comprising the plurality of MAC; a motor (212, 312, 412, 900) comprising a shaft (902) rotatable by the motor; and a rotatable assembly that is rotatable by the shaft from a first side of the rotatable assembly and positionable with respect to the plurality of MAC using the clamping system from a second side of the rotatable assembly opposite of the first side, the rotatable assembly comprising: a magnet wheel (202, 302, 402, 700) comprising a first cavity (702) for accommodating a permanent magnet (214, 314 / 315, 414 / 415, 514), and the permanent magnet positioned in the first cavity, wherein the first cavity is located on the second side of the magnet wheel and configured such that the magnet is off-centered from an axis of rotation (528) defined by the shaft.

2. The actuator system according to claim 1 , wherein the first cavity is off-centered from the axis of rotation (528) defined by the shaft.

3. The actuator system according to any one of the preceding claims, wherein the magnet wheel comprises a counterweight (704) to the magnet to balance the magnet wheel along the axis or rotation.

4. The actuator system according to any one of the preceding claims, wherein the magnet wheel comprises a second cavity (706) located on the first side of the magnet wheel and centered along the axis of rotation, and wherein the rotatable assembly further comprises a shaft holder (208, 308, 408, 800) arranged to attach the shaft to the magnet wheel within the second cavity.

5. The actuator system according to claim 4, wherein the magnet wheel comprises one or more through holes (708) from a third side of the magnetic wheel to the second cavity, the third side being substantially perpendicular to the first and second sides, wherein each through hole is arranged to accommodate a grub screw to secure the magnetic wheel to the shaft through the shaft holder, and wherein the shaft holder is deformable by the grub screw to clamp the shaft holder to the shaft.

6. The actuator system according to claim 5, wherein the shaft holder is cylindrically shaped and comprises a slanted indentation (806) arranged to receive the grub screw, and wherein the shaft holder is semi-slit for slit clamping the shaft by the grub screw.

7. The actuator system according to any one of the claims 4-6, wherein the shaft holder is made of a non-magnetic material, such as a non-magnetic stainless steel.

8. The actuator system according to any one of the preceding claims, wherein the magnet wheel is made of a non-magnetic material, such as a non-magnetic stainless steel.

9. The actuator system according to any one of the preceding claims, wherein the magnet has one of: a cube shape; a cuboid shape; a cylinder shape.

10. The actuator system according to any one of the preceding claims, further comprising a casing (206, 306, 406, 1000), wherein the casing is arranged between the clamping system and the motor, and wherein the casing accommodates the rotatable assembly.

11. The actuator system according to claim 10, wherein the casing is made of a nonmagnetic material, such as aluminum.

12. The actuator system according to any one of the preceding claims, further comprising a cover (210, 310, 410, 1200) that covers the motor and the rotatable assembly, wherein the cover is attachable to the clamping system.

13. The actuator system (300, 400) according to any one of the preceding claims, wherein the magnet (314 / 315, 414 / 415) is repositionable within the magnet wheel.

14. The actuator system according to claim 13, wherein the first cavity is arranged to accommodate the magnet in one of a plurality of positions.

15. The actuator system according to any one of the preceding claims, further comprising a second magnet (420, 520), wherein the second magnet is disposed on a second side of the MAC chip, the magnet being located on a first side of the MAC chip.

16. The actuator system according to claim 15, wherein the second magnet is off- centered from the axis of rotation defined by the shaft.

17. The actuator system according to claim 15 or claim 16, wherein the relative positions of the magnet and the second magnet are adjustable in all three planes.

18. The actuator system according to any one of the claims 1-17, wherein the first cavity is located on the second side of the magnet wheel and off-centered from the axis of rotation (528) defined by the shaft.

19. The actuator system according to claim 18, wherein the magnet in the first cavity crosses or touches the axis of rotation.

20. The actuator system according to any one of the claims 1-17, wherein the magnet is positioned at a distance from the axis of rotation allowing a visualization of the MAC chip in a reflection mode.

21. The actuator system according to any one of the claims 1-17, wherein the magnet and the second magnet are each positioned at a distance from the axis of rotation allowing visualization of the MAC chip in a transmission mode.

22. The actuator system according to any one of the preceding claims, wherein the actuator system is attachable to an organ-on-a-chip, OoC, platform (218, 318, 418, 518) via the clamping system.

23. The actuator system according to claim 22, wherein the MAC chip is fluidically connectable to an OoC module (652) through the OoC platform, and wherein the magnet is arranged to actuate the plurality of MAC to create a fluid flow to the OoC module.

24. The actuator system according to any one of the claims 1-23, wherein the MAC chip comprises a MAC micropumping module.

25. The actuator system according to any one of the claims 1-23, wherein the recess is arranged for accommodating a MAC micropumping module.

26. An organ-on-a-chip, OoC, platform (650) comprising an actuator system (200, 300, 400, 600) according to any one of the claims 1-25, wherein the OoC platform is arranged to accommodate one or more OoC modules (652) that is connectable to the actuator system, wherein the actuator system is arranged to accommodate a plurality of magnetic artificial cilia, MAC, comprised in a MAC chip (216, 316, 416, 616), and wherein the OoC module and the MAC chip are fluidically connectable through the OoC platform.

27. The OcC platform according to claim 26, further comprising a microfluidic channel network arranged to fluidically connect the OoC module to the MAC chip.

28. The OcC platform according to claim 26 or claim 27, wherein multiple OoC modules are fluidically connectable to one MAC chip.

29. The OoC platform according to any one of the claims 26-28, further comprising a medium reservoir (654), wherein the medium reservoir is fluidically connected to an inflow of the MAC chip.

30. The OoC platform according to any one of the claims 26-28, further comprising a medium reservoir (654), wherein the medium reservoir is fluidically connected to an inflow and an outflow of the MAC chip to form a recirculating system.

31. The OoC platform according to any one of the claims 26-30, further comprising a waste reservoir (656), wherein the waste reservoir is fluidically connected to an outflow of the MAC chip.

32. The OoC platform according to any one of the claims 26-31 , comprising a plurality of actuator systems (600), wherein each actuator system is connectable to a separate OoC module.

33. The OoC platform according to any one of the claims 26-31 , comprising a plurality of actuator systems (600), wherein each actuator system is connectable to a plurality of OoC modules.

34. The OoC platform according to any one of the claims 26-33, further comprising one or more sensor modules for sensing one or more of: a flow rate; properties of a content of the OoC platform.

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