Modular system and underwater 3D bioprinter including the modular system

Abstract

The modular system (1) insertable into a closed environment (20), such as a tank containing a fluid, comprises a base (2) with a working surface (3) movable along a plane of motion, an upright structure (9) restrained on one side of the base (2) and extending from said side, and a support head (10) for supporting a tool or accessory. The upright structure (9) further comprises guide means (11) for guiding the support head (10) along a direction (Z) intersecting the plane of motion, sliding means (14) for sliding the support head (10) along the guide means (11), at least one motor (M) for the sliding means (14), and a box-like container (15) with a sealing gasket for housing the motor (M). The modular system (1) further comprises at least one tubular body (21) for the electric wires of the motor (M).

Description

[Technical Field]

[0001] The present invention relates to a modular system and an underwater 3D bioprinter comprising the modular system. [Background technology]

[0002] The present invention is applicable to operations and processes in the fields of biology and biotechnology, in particular to the manufacture of medical devices (Class III implantable devices) by 3D printing.

[0003] The category of underwater 3D printers is known and is described, for example, in document WO 2020 / 252624.

[0004] Other 3D bioprinters are known that use additive manufacturing processes to create structures that can replicate the properties and interactions of natural tissues using synthetic or naturally occurring materials, living cells, and active biomolecules. Currently, 3D bioprinters are certified, but ensuring the certification process for printed products is complicated. This is due to the fact that 3D bioprinters cannot be sterilized, only disinfected—that is, they cannot be placed in an autoclave (as required by FDA standards for biological sterility)—and that there is always at least one moving axis above the printing bed. Friction in the mechanism can introduce particles into the printed product, potentially contaminating it. Disclosure of the Invention In this situation, the technical problem underlying the present invention is to propose a modular system and an underwater 3D bioprinter equipped with the modular system that overcomes the above-mentioned drawbacks of the prior art.

[0005] In particular, one object of the present invention is to propose a modular system and an underwater 3D bioprinter equipped with said modular system that can be sterilized and immersed in a fluid that can prevent the intrusion of external agents during the production process.

[0006] Another object of the present invention is to provide a versatile modular system.

[0007] Another object of the present invention is to propose an underwater 3D bioprinter equipped with such a modular system capable of printing implantable medical devices (class III).

[0008] The stated technical problem and the stated objectives are satisfactorily achieved by a modular system that can be inserted into a closed environment, such as a tank containing a fluid. a base portion having an operating surface movable along an operating plane defined by a first direction and a second direction inclined relative to each other; an upright structure constrained to and extending from one side of the base; a support head for the tool or accessory; Furthermore, the upright structure a guide means for guiding the support head along a third direction intersecting the plane of motion; a sliding means for sliding the support head along the guide means; at least one motor operatively acting on the sliding means; a box-shaped housing portion for housing the motor, the box-shaped housing portion having a sealing gasket; The modular system further comprises at least one tubular body forming a tubular cavity for electrical wires connected to the motor.

[0009] In one embodiment, the guide means and sliding means are constructed from PTFE or nylon or EPDM or stainless steel or medical grade inert material.

[0010] In one embodiment, the guide means comprises two posts spaced apart from one another and a support on which the head is mounted, the support being arranged between the posts and constrained to be slidable along the posts, and the sliding means comprising a nut connected to a corresponding threaded portion of the support.

[0011] In one embodiment, the upright structure is rotatably mounted relative to the base and is capable of closing the top of the base.

[0012] In one embodiment, the base portion comprises: A plate portion, a first guide means for guiding the plate portion along a first direction; and second guide means for guiding the plate portion along a second direction, and the operating surface is the surface of the plate portion.

[0013] In one embodiment, the plate is attached to the first guide means, and the first guide means is attached to the second guide means.

[0014] In one embodiment, the base and upstanding structures are provided with a coating having a roughness of less than 0.5 μm.

[0015] The stated technical problem and stated objectives are The described modular system and an extrusion printing means mounted on a support head of the modular system; a printing table attached to the working surface; This is fully achieved by an underwater 3D bioprinter comprising a control unit for extrusion printing means.

[0016] In one embodiment, the printing bed can be flat, formed as a hemisphere, or connected to a rotation system.

[0017] In one embodiment, the printing bed is of the refrigerated type and is configured to reach temperatures as low as -34°C in 20 seconds.

[0018] In one embodiment, the underwater 3D bioprinter comprises a culture medium and a system for stimulating the culture medium, wherein the extrusion printing means comprises one or more extruders configured to remove / introduce a medium from / to the culture medium.

[0019] In one embodiment, the underwater 3D bioprinter comprises a rotatable tubular biochemical reactor, the biochemical reactor containing a culture medium.

[0020] In one embodiment, the printing bed contains one or more materials for creating the printed product, and the printing bed further comprises members or tools for moving or adapting the one or more materials.

[0021] The stated technical problem and stated objectives are The described modular system and at least a first gripper mounted on a support head of the modular system; a detection system mounted on the working surface of the modular system; and at least a second gripper attached to the detection system.

[0022] The stated technical problem and stated objectives are The described modular system and a detection system mounted on the working surface of the modular system; a plate portion disposed above the detection system; This is satisfactorily achieved by a weighing machine fitted to the support head of the modular system and provided with a cover that protects it from interaction with the laminar flow. [Brief explanation of the drawings]

[0023] Further features and advantages of the present invention will become more apparent from the following schematic and therefore non-limiting description of preferred but non-exclusive embodiments of a modular system and an underwater 3D bioprinter comprising said modular system, as shown in the accompanying drawings. [Figure 1-2] 1 shows a perspective view of a modular system according to the present invention in two adjacent configurations, one with a coating and one without a coating. [Figure 3] FIG. 2 is a schematic front view of one of the modular systems of FIG. 1. [Figure 4] FIG. 2 is a schematic side view of one of the modular systems of FIG. 1. [Figure 5] 1 is a schematic side view of an underwater 3D bioprinter according to the present invention. FIG. [Figure 6] FIG. 6 is a schematic diagram of a (frozen) embodiment of the print bed of the underwater 3D bioprinter of FIG. [Figures 7a-7e] 6A-6C are schematic diagrams of different embodiments of the printing platform of the underwater 3D bioprinter of FIG. [Figure 8] FIG. 6 is a schematic diagram of an embodiment of the printing bed (with microscope) of the underwater 3D bioprinter of FIG. [Figure 9a-9b] 6A and 6B are schematic side and top views, respectively, of the underwater 3D bioprinter embodiment (medium exchange) of FIG. 5. [Figure 10a-10b] 6A and 6B are schematic side and detailed views, respectively, of an embodiment (rotation system) of the underwater 3D bioprinter of FIG. 5. [Figure 11] 1 is a schematic side view of a dynamometer according to the present invention; [Figure 12] 1 is a schematic side view of a weighing device according to the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0024] Referring to the figures, reference number 1 denotes a modular system. As will become clear from the following description, the system is a single-axis modular system that can be assembled to form a final multi-axis device equipped with accessories such as a 3D printer, a scale or dynamometer, a system for exchanging cell media, a microscope with LEDs, and / or a mixer.

[0025] The modular system 1 further comprises a base unit 2 with an operating surface 3. The operating surface 3 is movable along a working plane defined by a first direction X and a second direction Y which are inclined relative to one another. The first direction X and the second direction Y are preferably perpendicular to one another. In terms of a Cartesian coordinate system, the first direction is the x-axis and the second direction is the y-axis, or vice versa. The plane in question is therefore the xy-plane.

[0026] Preferably, the modular system 1 comprises first guiding means 4 for guiding the working surface 3 along a first direction X and second guiding means 5 for guiding the working surface 3 along a second direction Y.

[0027] Preferably, the base portion 2 includes a plate portion 6. The working surface 3 is a surface of the moving block 6, particularly the upper surface.

[0028] Preferably, the plate 6 is a solid body, for example a parallelepiped. Preferably, the plate 6 is made of PEEK or steel (for example AISI 316L) or medical grade aluminium.

[0029] In the embodiment described and shown here, the plate 6 is mounted to the first guide means 4 which in turn is mounted to the second guide means 5 .

[0030] In particular, the first guide means 4 comprises a first guide to which the plate 6 is slidably mounted. In particular, the first guide means 4 comprises a sliding block 7 to which the plate 6 is mounted. The sliding block 7 is slidably mounted on the first guide 4. The sliding block 7 and the first guide 4 together form a linear reciprocating ball guide.

[0031] The second guide means 5 comprises a slide 8 which is slidable in a groove.

[0032] In another embodiment not shown, the first guide of the first guiding means 4 is two parallel cylindrical rods.

[0033] The second guides of the second guiding means 5 are two cylindrical rods parallel to each other and arranged below the cylindrical rods of the first guiding means 4. In particular, the second cylindrical rods are arranged below opposite ends of the first cylindrical rod.

[0034] The modular system 1 comprises a support member on which the first guide 4 is arranged and a moving block that supports the working surface 3. The support member also serves as a support for the moving block.

[0035] The support member is slidably mounted in the second guide, and in particular, two opposite ends of the support member are mounted in the second guide.

[0036] The working surface 3 can therefore be moved forward or backward, to the right or left, relative to a point in the plane of action.

[0037] The modular system 1 comprises an upright structure 9 fixed to one side of the base part 2. The upright structure 9 extends away from the base part 2.

[0038] The modular system 1 comprises a support head 10 for a tool or accessory. Depending on the tool or accessory attached to the head 10, the modular system 1 can perform any of the functions listed above. The head 10 thus serves as a universal connection system that can be used for a variety of different functional purposes.

[0039] The head 10 is mounted on an upright structure 9 .

[0040] The upright structure 9 comprises guiding means 11 for guiding the head 10 along a third direction intersecting the plane of motion. Preferably, the third direction is orthogonal to the plane of motion and therefore also orthogonal to the first and second directions. In particular, again referring to a Cartesian coordinate system, the third direction can be identified as the z-axis.

[0041] The guide means 11 preferably comprises two posts spaced apart from one another. The upright structure 9 comprises a support 12 to which the head 10 is mounted and constrained to slide along the two posts 11. The support 12 preferably comprises two sleeves 13 at two opposite ends, each sleeve 13 being constrained to slide along a respective post 11.

[0042] The upright structure 9 comprises sliding means 14 for sliding the support head 10 along the guide means 11 .

[0043] Preferably, the sliding means 14 is of the screw-nut type.

[0044] Alternatively, the sliding means 14 can be of the belt rack type or of the electromagnetic linear actuator type.

[0045] The upright structure 9 comprises at least one motor M for the sliding means 14 and a box-like housing 15 provided with a sealing gasket that houses the motor M. This allows the modular system 1 to be used reliably underwater.

[0046] The modular system 1 can be inserted into a closed environment 20. The base 2 and the upright structure 9 together with their components are housed within the environment 20.

[0047] The modular system 1 comprises at least one tubular body 21 extending partly inside and partly outside the environment 20. The tubular body 21 forms a tubular cavity suitable for routing the electrical wires (cables) of the motor M.

[0048] This allows all components, such as control units, that are not strictly essential for the mechanical operation of the final device obtained by incorporating one or more tools or accessories into the modular system 1 to be located outside the environment 20.

[0049] For example, the closed environment 20 is a tank filled with at least one fluid. The fluid can be a liquid or a gas. Preferably, the fluid is a gas. For example, the liquid is VHP or H2O2. If the modular system 1 is used for the manufacture of electronic components, in particular for the manufacture of microprocessors with subsequently doped biological materials, the fluid can be ammonia-based.

[0050] The final device is submersible, so it can remain in the production environment during typical high-pressure, high-temperature cleaning cycles that use aggressive chemicals, or it can be closed and transported like a briefcase and disinfected at the destination before use.

[0051] For example, if the modular system 1 is immersed in a liquid fluid, contaminant particles will be stopped at the surface of the liquid, if it is placed in an ammonia environment, it will prevent the product, for example the sensor, from being oxidized by the air or, more precisely, by the oxygen contained in the air, or if it is placed in a vapor that reacts with the production materials, it will be able to interact directly with the production process.

[0052] Alternatively, the modular system 1 can be inserted into an isolation device 22 suitable for delimiting the contamination controlled environment 20. For example, the isolation device 22 can be an isolator or a laminar flow hood.

[0053] For use in this type of closed environment 20, it is preferable to use a coating of the modular system 1 with a roughness of less than 0.5 μm and a sloped surface (>1%). In this way, the modular system 1 is not only sterilizable but can also be easily disinfected in all applications that do not require sterilization.

[0054] More preferably, the roughness is less than 0.1 μm.

[0055] Preferably, the guide means 11 and sliding means 14 are made of PTFE or nylon or EPDM or stainless steel or medical grade inert material, in other words the material must be self-lubricating and sterilizable, i.e. suitable for autoclaving.

[0056] For sterilization purposes, the guide means 11 and the sliding means 14 are provided with bearings provided with sealing gaskets, i.e. bearings suitable for sterilization, or alternatively without bearings.

[0057] As mentioned above, the sliding means 14 is preferably of the screw-nut type.

[0058] In the embodiment described and illustrated here, the sliding means 14 comprises a nut connected to a corresponding threaded portion of the support 12 .

[0059] The nut 14 is preferably disposed between the two posts 11 .

[0060] In the preferred embodiment shown in the figures, the upright structure 9 comprises two frame parts 16, each of which houses one of the two support columns 11. The support head 10 is located between the two frame parts 16.

[0061] Preferably, the upright structure 9 is a frame having an angular "U" shape when viewed from the front, such that the box-like housing portion 15 forms the base of the "U" and the two frame portions 16 form the parallel arms of the "U".

[0062] The nut 14 is preferably in the center of the "U" shaped frame.

[0063] The upright structure 9 is preferably rotatably mounted to the base part 2 so that it can be closed like a briefcase onto the base part 2. In other words, the upright structure 9 is attached to the base part 2 by a hinge.

[0064] The modular system 1 preferably comprises an interconnection 17 between the base 2 and the upright structure 9. The upright structure 9 is hinged to the interconnection 17. For example, the interconnection 17 is a flange.

[0065] As mentioned, the system 1 is modular. In this respect, Figure 1 shows two adjacent modular systems 1. The two modular systems share an operating surface 3. To achieve this, they must share a first guide means 4. In this case, the first guide 4 moves over the entire length (x-axis) of both base parts 2. The operating surface 3 can be rotated on the x-axis or any combination useful for modularity can be realized.

[0066] The underwater 3D biochemical printer (bioprinter) that is the subject of the present invention is designated by the reference numeral 100 and is described below.

[0067] The underwater 3D bioprinter 100 comprises a modular system 1 and an extrusion printing means 110 mounted on the modular system 1. In this way, the extrusion printing means 110 can also be introduced into the closed environment 20. The extrusion printing means 110 is known and will not be described further. For example, the extrusion printing means 110 comprises a plurality of extruders. If the extruders have motors housed in the environment 20, each motor is installed in a box-like housing provided with a sealing gasket and connected to the outside (to the environment 20) by a tubular cable passage 21. Alternatively, the motors are arranged directly outside the environment 20.

[0068] By way of non-limiting example, the extrusion printing means 110 can include a hot / cold syringe, hot / cold filament, inkjet, heat transfer / insulation platform, suction device / blower, blower and plasma, laser, cutter or blade, light or LED (polymerization / sterilization), camera, leveler.

[0069] A printing platform 120 can be incorporated above the working surface 3. Preferably, the printing platform 120 can be flat, as shown in Figure 6, or hemispherical in shape. Alternatively, as shown in Figure 10b, the printing platform 120 can be connected to a rotation system 122 on which the material is placed. This embodiment allows the formation of arteries.

[0070] The printing bed 120 is preferably of the refrigerated type and is configured to reach temperatures as low as -34°C in 20 seconds. This is preferably done in four stages: Peltier, liquid cooled, Peltier, liquid cooled.

[0071] Alternatively, the print platform 120 is of the heated type.

[0072] Alternatively, the print platform 120 can be provided with a removable customized (shaped, gridded) surface.

[0073] Alternatively, the print platform 120 can be equipped with sliding rollers.

[0074] Alternatively, the print platform 120 can include a tank with a screen and a projector.

[0075] Alternatively, the print platform 120 can include a tank containing the powder.

[0076] Preferably, the underwater 3D bioprinter 100 includes a control unit 130 that controls the extrusion printing means 110.

[0077] The overall air filtering structure (sterilizable printers, environmental control systems) allows for the use of more exotic materials (e.g. multi-component filaments that can produce vapors toxic to humans).

[0078] In one embodiment, the print platform 120 contains one or more materials for the development of a print product, and in such a case, the print platform 120 includes members or tools 121 for moving or adapting the one or more materials.

[0079] The member 121 may be, for example, a roller, a flattening system, a laminating system, an extruder cleaning or calibration system.

[0080] Figure 7a shows two rollers with blades and laser / inkjet above. Figure 7b shows a tank with a screen and projector above. Figure 7c shows a tank containing powder and with blades and laser / inkjet above. Figure 7d shows the cleaning and drying system (cleaning fluid enters from the left and air enters from the right). Figure 7e shows the needle leveling and positioning sensor. The needle is vertical and from top to bottom we can see the non-contact sensor, cutting blade and waste pan.

[0081] In one embodiment, the underwater 3D bioprinter 100 includes a culture medium 140. The culture medium 140 can contain cells.

[0082] The extruder 110 can be used to perform the medium exchange. A single extruder 110 can be used selectively to withdraw from and introduce into the medium 140.

[0083] With at least two extruders 110, the medium 140 can be continuously circulated. This slow but continuous process prevents the medium 140 from becoming contaminated.

[0084] Preferably, the underwater 3D bioprinter 100 comprises a stimulation system 150 acting on the culture medium 140. The illustrated stimulation system 150 is optical, alternatively, the stimulation system can be thermal, electrical, electromagnetic, etc.

[0085] In a preferred embodiment, the underwater 3D bioprinter 100 comprises a biochemical reactor (bioreactor) 160 in the form of a rotatable tube containing a structure dedicated to cell growth containing culture medium 140.

[0086] In one embodiment, the underwater 3D bioprinter 100 includes a microscope 170 for observing the cells in the culture medium 140 .

[0087] The dynamometer that is the subject of the present invention is generally designated 200 and is described below.

[0088] The dynamometer 200 comprises a modular system 1 and at least a first gripper 210 mounted on the support head 10 of the modular system 1 and a second gripper 220 mounted on the working surface 3. The dynamometer 200 comprises a detection system 230 arranged between the working surface 3 and the second gripper 220.

[0089] The weighing machine that is the subject of the present invention is designated by the reference numeral 300 and will now be described.

[0090] The weighing machine 300 comprises the described modular system 1. The weighing machine 300 comprises at least one plate 310 arranged above a detection system 320 mounted on the working surface 3 of the modular system 1. The weighing machine comprises a cover 330 mounted on the support head 10 of the modular system 1 to protect it from interaction with the laminar flow.

[0091] The features of the modular system of the present invention and the underwater 3D bioprinter comprising the modular system are apparent from this specification, as are the advantages thereof.

[0092] In particular, the proposed configuration of the modular system means that there are no axes of movement above the print platform. The X and Y axes are below the print area, while the Z axis is to the side. Thus, the modular system itself is a single-axis system moved by a motor located in a housing equipped with a specific sealing gasket for sterilization. It is installed in a development environment that contains only those components strictly essential for the system's mechanical function, while the remaining components can remain outside the environment thanks to tubular cable passages. This ensures sterilization inside the autoclave.

[0093] Furthermore, the components of the upright structure (Z-axis) are made of self-lubricating materials to prevent friction from generating particles that can get into the printed product, and are suitable for placement in an autoclave, allowing for complete sterilization.

[0094] Furthermore, the proposed modular system is versatile and can be easily converted into multiple devices that include additional components that share the same structure as the modular system itself.

[0095] The resulting 3D bioprinter from the modular system is therefore submersible and sterilizable. [Prior art documents] [Patent documents]

[0096] [Patent Document 1] International Publication No. 2020 / 252624

Claims

1. A modular system (1) insertable into a closed environment (20), such as a tank containing a fluid, said modular system (1) comprising: a base portion (2) having an operating surface (3) movable along a plane of operation defined by a first direction (X) and a second direction (Y) inclined relative to each other; an upright structure (9) that is constrained to one side of the base portion (2) and extends from the one side; a support head (10) for supporting a tool or accessory, Furthermore, the upright structure (9) a guide means (11) for guiding the support head (10) along a third direction (Z) intersecting the plane of motion; a sliding means (14) for sliding the support head (10) along the guide means (11); at least one motor (M) operatively acting on said sliding means (14); a box-shaped housing (15) for housing the motor (M), the box-shaped housing having a sealing gasket; The modular system (1) further comprises at least one tubular body (21) forming a tubular cavity for electrical wires connected to the motor (M).

2. 2. The modular system (1) according to claim 1, wherein said guiding means (11) and said sliding means (14) are made of PTFE or nylon or EPDM or stainless steel inox or medical grade inert material.

3. 10. A modular system (1) according to any of the preceding claims, wherein the guiding means (11) comprises two posts spaced apart from one another and a support (12) on which the head (10) is mounted, the support (12) being arranged between the posts (11) and constrained to be slidable along said posts, and the sliding means (14) comprising a nut connected to a corresponding threaded portion of the support (12).

4. 10. A modular system (1) according to any of the preceding claims, wherein the upright structure (9) is mounted rotatably relative to the base part (2) and is capable of closing the top of the base part.

5. The base part (2) is A plate portion (6), a first guide means (4) for guiding the plate portion (6) along the first direction (X); and a second guide means (5) for guiding the plate portion (6) along the second direction (Y), 10. A modular system (1) according to any of the preceding claims, wherein the working surface (3) is a surface of the plate portion (6).

6. 6. A modular system (1) according to claim 5, wherein said plate (6) is mounted to said first guide means (4), and said first guide means (4) is further mounted to said second guide means (5).

7. 10. The modular system (1) according to any of the preceding claims, wherein the base (2) and the upright structures (9) are provided with a coating having a roughness of less than 0.5 μm.

8. The modular system (1) according to any of the preceding claims, an extrusion printing means (110) mounted on the support head (10) of the modular system (1); a printing table (120) mounted on the working surface (3); A control unit (130) of the extrusion printing means (110); An underwater 3D bioprinter (100) comprising:

9. 9. The underwater 3D bioprinter (100) of claim 8, wherein the printing bed (120) can be flat, hemispherical, or connected to a rotation system (122).

10. 10. The underwater 3D bioprinter (100) of claim 8 or 9, wherein the printing bed (120) is of a refrigeration type configured to reach temperatures as low as -34°C in 20 seconds.

11. 9. The underwater 3D bioprinter (100) of claim 8, wherein the underwater 3D bioprinter comprises a culture medium (140) and a stimulation system (150) for stimulating the culture medium (140), and the extrusion printing means (110) comprises one or more extruders configured to remove / introduce a medium from / to the culture medium (140).

12. 12. The underwater 3D bioprinter (100) of claim 11, wherein the underwater 3D bioprinter comprises a rotatable tubular biochemical reactor (150), the biochemical reactor (150) containing the culture medium (140).

13. 13. The underwater 3D bioprinter (100) of any one of claims 8 to 12, wherein the printing bed (120) contains one or more materials for creating a printed product, and the printing bed (120) further comprises members or tools (121) for moving or adapting the one or more materials.

14. A modular system (1) according to any one of claims 1 to 7, at least a first gripper (210) mounted on the support head (10) of the modular system (1); a detection system (230) mounted on the working surface (3) of the modular system (1); at least a second gripper (220) attached to said detection system (230); A dynamometer (200) comprising:

15. A modular system (1) according to any one of claims 1 to 7, a detection system (320) mounted on the working surface (3) of the modular system (1); a plate portion (310) disposed above the detection system (320); a cover (330) attached to the support head (10) of the modular system (1) to protect it from interaction with laminar flow; A weighing machine (300) comprising:

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