Detachable printer head for bioprinter and bioprinter

Abstract

A detachable printer head for a bioprinter is disclosed, the detachable printer head comprising: a body removably attachable to a fixed portion of the bioprinter; a dispensing system supported by the body; one or more reservoirs for holding one or more biomaterials, the reservoirs being in fluid communication with the dispensing system and supported by the body; and a coupling device for attachment to the fixed portion of the bioprinter, the coupling device comprising an interface for operating the dispensing system.

Description

[Technical Field]

[0001] The present disclosure relates to a detachable printer head suitable for a bioprinter, and also to a bioprinter associated with the detachable printer head.

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to Austrian Provisional Patent Application No. 2022903386, the entire contents of which are incorporated herein by reference. [Background technology]

[0003] Hospitals are fast-paced environments. Healthcare workers are often required to move between different patients and use various facilities in a short space of time. Contamination of equipment or surfaces, and poor hygiene by patients or healthcare workers can all contribute to the spread of disease and infection.

[0004] Sterilization and disinfection of equipment therefore plays a vital role in preventing the spread of infection and disease within a hospital. Sterile devices are particularly important in wound care.

[0005] Any reference or mention in this specification to documents, acts, or items of knowledge is included solely for the purpose of providing a context for the present invention, and nothing is being suggested or represented that any of these items, or combinations thereof, formed part of the general public knowledge at the priority date, or that any of these items, or combinations thereof, were known to be relevant to attempting to solve any of the problems to which this specification is addressed. Summary of the Invention

[0006] In one form, a detachable printer head for a bioprinter is disclosed, the detachable printer head comprising: a body removably attachable to a fixed portion of the bioprinter; a dispensing system supported by the body; one or more reservoirs for holding one or more biomaterials, the reservoirs being in fluid communication with the dispensing system and supported by the body; and a coupling device for attachment to the fixed portion of the bioprinter, the coupling device comprising an interface for operating the dispensing system.

[0007] In one embodiment, the dispensing system includes one or more reservoirs for holding one or more biomaterials. The one or more reservoirs have an interior volume for holding a fluid. In one embodiment, there is a single reservoir. In another embodiment, there are two or more reservoirs.

[0008] In one embodiment, the body comprises an inner body and the reservoirs are disposed on an outer surface of the inner body, hi one embodiment, each reservoir is part of a reservoir assembly, which is also part of the dispensing system.

[0009] In one embodiment, the body, preferably the inner body, comprises a central cavity for receiving a corresponding extension of the fixing part, hi one embodiment, the central cavity is annular in cross section.

[0010] In one embodiment, the body has a central axis that is perpendicular to the coupling surface of the coupling device. In one embodiment, the central cavity has a center point located on the central axis. In one embodiment, the center point is on the cavity axis, and the cavity axis and the central axis are collinear.

[0011] In one embodiment, the body comprises an outer body, the outer body substantially enclosing the dispensing system. The outer body may be at least partially transparent in at least some areas. In one embodiment, the outer body is at least partially transparent in areas where the fluid level in one or more reservoirs is inspected.

[0012] In one embodiment, the one or more reservoirs are arranged around a central axis. In one embodiment, the one or more reservoirs are arranged in a circle centered on the reservoir axis. In one embodiment, the reservoir axis and the central axis are collinear. In an alternative embodiment, the one or more reservoirs are arranged in a rectangular array.

[0013] In one embodiment, one or more reservoirs are individually located within the dispensing system.

[0014] In an alternative embodiment, the one or more reservoirs are attached to a stationary portion of the bioprinter. In one embodiment, the one or more reservoirs are arranged about a central axis. In one embodiment, the one or more reservoirs are arranged in a circle centered about the reservoir axis. In one embodiment, the reservoir axis and the central axis are collinear. In an alternative embodiment, the one or more reservoirs are arranged in a rectangular array.

[0015] In an alternative embodiment, one or more reservoirs are individually attached to a stationary portion of the bioprinter.

[0016] In one embodiment, the or each reservoir has at least one inlet and at least one outlet. In one embodiment, the at least one inlet is located at the end of the reservoir closest to the coupling device. In one embodiment, the at least one outlet is located at the end of the reservoir furthest from the coupling device. The or each reservoir has a reservoir axis parallel to a central axis that indicates the center of the interior volume. In one embodiment, the at least one outlet is located spaced apart from the reservoir axis in a direction toward the central axis. Maintaining the reservoir outlet as close as possible to the central axis allows the size of the base of the detachable printer head to be minimized. Minimizing the size of the base of the detachable printer head allows droplet dispensing valves (discussed below) to be as close as possible to each other. This, in turn, allows for more accurate printing and ease of use.

[0017] In one embodiment, the one or more reservoirs are generally cylindrical in shape over most of their length, hi one embodiment, the one or more reservoirs have a tapered section towards the or each outlet, the taper being in a direction away from the reservoir axis and towards the central axis.

[0018] In one embodiment, each of the one or more reservoirs includes an inlet valve connected to at least one of the reservoir inlets. In one embodiment, the inlet valve is adapted to allow insertion of a fluid into the reservoir. In one embodiment, the inlet valve may be a check valve and / or a one-way valve.

[0019] In one embodiment, one or more reservoirs may be at least partially transparent. One or more reservoirs may be transparent. Alternatively, one or more reservoirs may be opaque.

[0020] In one embodiment, there are 2, 4, 6, 8, 10, 12, 14, 16, or more reservoirs. Although an even number of reservoirs is specifically mentioned, it is contemplated that a removable print head may have an odd number of reservoirs. For example, in one embodiment, there is a single reservoir. In one embodiment, one or more reservoirs are individually located.

[0021] In one embodiment, each reservoir has a cap attached to the reservoir inlet. In one embodiment, the cap can be used to seal the fluid within the reservoir. The cap is adapted to allow gas to be introduced into the reservoir but prevent fluid from exiting through the first end of the reservoir. In one embodiment, the cap includes a pneumatic connector, e.g., allowing gas, e.g., air, to be supplied to the reservoir. In one embodiment, the reservoir can be pressurized thanks to the pneumatic connection and other inlets / outlets. In one embodiment, the cap includes one or more filters. In one embodiment, the or each filter is hydrophobic, thereby, e.g., reducing fluid from passing through the filter.

[0022] The coupling device is adapted to removably attach the detachable printer head to the fixed part of the bioprinter, i.e., the coupling device is operated without the use of tools and is therefore manually operated when removing from or attaching to the fixed part.

[0023] In one embodiment, the coupling device can provide a suitable connection for an interface to operate the dispensing system. In one embodiment, the coupling device includes a retaining ring that rotates about the interface to engage the fixed portion. In one embodiment, the retaining ring is arranged to retract the removable printer head into the fixed position when the retaining ring is rotated. In one embodiment, the retaining ring provides a quick release mechanism for engaging with the fixed portion. In one embodiment, the quick release mechanism includes a coupling device in the form of a protrusion and slot. That is, at least one protrusion or slot is provided on the coupling device that engages with at least one respective protrusion or slot on the fixed portion. In one embodiment, each protrusion or slot is arranged to retract the removable printer head into the fixed position when the retaining ring is rotated.

[0024] In one embodiment, the retaining ring has screw threads that correspond to appropriate screw threads on the fixed portion, and the removable print head is pulled into the fixed position when the retaining ring is rotated.

[0025] In one embodiment, the retaining ring includes a recess for a locking pin, which, in one embodiment, can receive a corresponding locking pin when the retaining ring is rotated sufficiently.

[0026] In an alternative embodiment, a cam and lever mechanism provides a mechanical coupling between the removable printer head and the fixed portion, in this embodiment the cam and lever mechanism is arranged to pull the removable printer head onto the fixed portion.

[0027] In one embodiment, the interface comprises a plurality of dispensing electrical connections that can interface with the dispensing connections of the fixed portion. The dispensing electrical connections provide electrical signals to one or more dispensing valves of the dispensing system. In one embodiment, the central cavity comprises a plurality of dispensing electrical connections. In one embodiment, the plurality of dispensing electrical connections are located at ends of the central cavity.

[0028] In one embodiment, the interface includes a pneumatic connector for each reservoir, hi one embodiment, the reservoir cap includes the pneumatic connector.

[0029] In an alternative embodiment, the pneumatic interface includes an integrated pressure distribution function. In this embodiment, a single pressure source may provide pneumatic connections for multiple reservoirs. For example, the pneumatic interface may include directing a single pressure source to one or more reservoirs.

[0030] In one embodiment, the dispensing system may be a droplet dispensing system. In one embodiment, the droplet dispensing system may include one or more dispensing valves. In one embodiment, the one or more dispensing valves are in fluid communication with at least one outlet of the or each reservoir. In one embodiment, the dispensing valves are electrically actuated. In one embodiment, the dispensing valves may be microvalves. In one embodiment, the microvalves may be solenoid valves.

[0031] In one embodiment, the dispensing system is configured to print onto the print area. In one embodiment, the droplet dispensing system prints droplets of fluid onto the print area.

[0032] In one embodiment, the sample droplets are pneumatically expelled from the reservoir and out of the dispense valve. In a preferred embodiment, the dispense valve is a microvalve.

[0033] In an alternative embodiment, the dispensing system is a dispensing system.

[0034] In one embodiment, the print area is a wound on a subject, such as an animal or human patient. In one embodiment, the wound is a wound in the skin of the subject, and the fluid dispensed by the dispensing system forms a gel that covers the wound.

[0035] In one embodiment, the detachable printer head is disposable. In one embodiment, the detachable printer head is reusable. In one embodiment, the detachable printer head is sterilizable.

[0036] In one embodiment, the detachable printer head may include a distance sensor.

[0037] In one embodiment, the detachable printer head may have a window. The window may be a passageway through the detachable printer head or a transparent substrate. In one embodiment, the window allows the distance sensor beam to travel through the detachable printer head. In one embodiment, the distance sensor is separate from the detachable printer head.

[0038] In a further aspect, a bioprinter is disclosed comprising a fixed portion capable of receiving one or more detachable printer heads, each detachable printer head comprising a body, a dispensing system supported by the body, one or more reservoirs for holding one or more biomaterials, the reservoirs being in fluid communication with the dispensing system and supported by the body, and a coupling device for attachment to the fixed portion of the bioprinter, the coupling device comprising an interface for operating the dispensing system, the bioprinter further comprising a system for controlling the interface and for operating the dispensing system of the detachable printer head.

[0039] In one embodiment, the dispensing system includes one or more reservoirs. Preferably, each reservoir is part of a reservoir assembly. In one embodiment, the reservoir assembly is also part of the dispensing system.

[0040] In one embodiment, one or more detachable printer heads are individually attached to a fixed portion of the bioprinter.

[0041] In one embodiment, the fixed portion is movable to position one or more removable printer heads.

[0042] In one embodiment, the fixed portion may comprise a switch that allows a user to disable automatic printing and manually operate the bioprinter and / or cause the bioprinter to operate in a mode that allows manual guidance of the bioprinter's position.

[0043] In one embodiment, the fixed portion may include a distance sensor, where the distance sensor provides the distance between the detachable printer head and the print zone. In one embodiment, the fixed portion includes a shaft for insertion into a corresponding cavity in the detachable printer head. In one embodiment, the shaft is configured to allow the distance sensor to measure through its center. In an alternative embodiment, the shaft is configured to allow a camera to operate through its center. In an alternative embodiment, the shaft is configured to allow both a camera and a distance sensor to operate through its center. In one embodiment, the shaft includes a dispense electrical connection on the fixed portion for controlling a corresponding dispense valve in the detachable printer head.

[0044] In one embodiment, the fixed portion comprises a connecting portion. In one embodiment, the connecting portion comprises a pneumatic interface capable of providing a pneumatic connection with a pneumatic connector in the detachable print head. In an alternative embodiment, the pneumatic interface comprises an integrated pressure distribution function, where a single pressure source can be directed to one or more reservoirs.

[0045] In one embodiment, the body comprises an inner body and the reservoirs are disposed on an outer surface of the inner body, hi one embodiment, each reservoir is part of a reservoir assembly, which is also part of the dispensing system.

[0046] In an alternative embodiment, one or more reservoirs are individually attached to a stationary portion of the bioprinter.

[0047] In a further aspect, a bioprinting system is disclosed that includes the bioprinter described above and further includes a robotic arm for maneuvering the bioprinter.

[0048] In an alternative aspect, a bioprinting system is disclosed that includes the bioprinter described above and further includes a gantry robot for maneuvering the bioprinter.

[0049] In a further aspect, a method for using a bioprinter is disclosed, the method comprising: attaching a detachable printer head to a fixed portion of the bioprinter, the detachable printer head comprising a body, a dispensing system supported by the body, and a coupling device for attachment to the fixed portion of the bioprinter, the coupling device comprising an interface for operating the dispensing system; controlling the bioprinter to move across the printing surface; forming a fluid or gel on the printing surface; Includes.

[0050] In one embodiment, the method further comprises using a sterile drape.

[0051] Further features and advantages of the present disclosure will become apparent from the following detailed description.

[0052] Embodiments will now be described, by way of example only, with reference to the accompanying drawings, in which: [Brief explanation of the drawings]

[0053] [Figure 1] FIG. 1 shows an isometric view of a bioprinter according to an embodiment, comprising a detachable printer head, a fixed part, and a robotic arm. [Figure 2] FIG. 2 shows front and side views of a printhead assembly according to an embodiment, including a removable printhead and a fixed portion. [Figure 3] FIG. 3 is a front view of a detachable printer head according to an embodiment. [Figure 4] FIG. 4 is a cross-sectional view of the detachable printer head of FIG. [Figure 5] FIG. 5 is a partial exploded view of the detachable printer head of FIG. [Figure 6] FIG. 6 is an isometric view of a single reservoir and dispense valve of the detachable printhead of FIG. [Figure 7] FIG. 7 shows a side cross-sectional view of a single reservoir and a single dispense valve from the detachable printer head of FIG. [Figure 8] FIG. 8 shows a perspective cross-sectional view of the detachable printer head of FIG. [Figure 9] FIG. 9 shows a perspective view of the connections for the eight reservoir variation of the detachable printhead from a top perspective view. [Figure 10] FIG. 10 shows a perspective view of the connections for the 16 reservoir variation of the detachable printhead from a top perspective view. [Figure 11] FIG. 11 is a perspective view of a fixing portion according to an embodiment. [Figure 12] FIG. 12 is a partial exploded view of a fixed portion according to an embodiment. [Figure 13] FIG. 13 is a perspective view of a mounting assembly according to an embodiment. [Figure 14]FIG. 14 is a perspective view of a connecting portion of a fixed portion according to an embodiment. [Figure 15] FIG. 15 is a partial exploded view of a mounting assembly according to an embodiment of the present invention. [Figure 16] FIG. 16 is a side view of a locking clip of a locking mechanism according to an embodiment. [Figure 17] 17 is a cross-sectional perspective view from the bottom of the shaft of the fixed portion of FIG. 3, according to an embodiment. [Figure 18] 18 is a perspective view of the bayonet end cap from the bottom of the shaft shown in FIG. 17. [Figure 19] FIG. 19 is a bottom front cross-sectional view of the printhead assembly of FIG. 2, showing the detachable printhead and fixed portion connected together. [Figure 20] FIG. 20 is a perspective view of a bioprinting system according to an embodiment. [Figure 21] FIG. 21 is a block diagram of a bioprinting system according to an embodiment. [Figure 22] FIG. 22 is a perspective view of an alternative embodiment of a detachable printer head. [Figure 23] FIG. 23 shows an isometric view of a bioprinter according to an embodiment showing the stationary part and the robotic arm, with the four detachable printer heads of the embodiment shown in FIG. 22 individually attached to the stationary part. [Figure 24] FIG. 24 shows an embodiment of a pneumatic interface showing an integrated pressure distribution manifold. [Figure 25] FIG. 25 shows the pneumatic interface of FIG. 24 coupled to a detachable printer head according to an embodiment. [Figure 26] FIG. 26 shows an alternative embodiment of the locking mechanism. [Figure 27] FIG. 27 shows a side view of a bioprinter according to an embodiment including a detachable printer head and a gantry robot. [Figure 28]FIG. 28 is a perspective view of the front casing and the rear casing according to the embodiment. DETAILED DESCRIPTION OF THE INVENTION

[0054] 1 and 2 illustrate a bioprinter 10 according to one embodiment. In this embodiment, the bioprinter 10 includes a fixed portion 30, a detachable printer head 20, a robotic arm 40, and a mounting base 45. The fixed portion 30 is attached to the robotic arm 40 in a manner that requires one or more tools for removal. The detachable printer head 20 is attached to the fixed portion 30 in a manner that does not require any tools. That is, as used herein, the term "detachable" refers to the printer head's ability to be removed and reattached without the use of tools. The detachable printer head 20 has a central axis 35 that is generally perpendicular to the mating surface 307 (see FIGS. 11 and 12 ) of the connecting portion 300 of the fixed portion 30.

[0055] A bioprinter having a robotic arm and the general concept of a printer head attached to the robotic arm is disclosed in International Publication No. WO 2021 / 108870, the entire disclosure of which is incorporated herein by reference. As disclosed therein, the bioprinter has a robotic arm with six axes of rotation, and the robotic arm 40 disclosed herein has similar functionality. In other embodiments, alternative mechanical steering devices may be utilized with the fixed portion 30 and corresponding detachable printer head 20. For example, the bioprinter 10 may include a detachable printer head 3020 that is steered by a gantry robot (see FIG. 27).

[0056] Fixed portion 30 can be removably attached to bioprinter 10 by a specialist using tools and a considerable amount of time. It is intended for use with multiple disposable and / or reusable detachable printer heads 20. Thus, fixed portion 30 may be considered a permanent, fixed part of bioprinter 10, while one or more detachable printer heads 20 are more easily attached and detached in a simple manner, preferably manually, during use of the bioprinter. In other embodiments, fixed portion 30 may be permanently attached to bioprinter 10.

[0057] The fixed portion 30 is movable in all of the configurations discussed above, i.e., it is the portion of the bioprinter 10 that is required to steer the detachable printer head 20 that resides on the fixed portion 30.

[0058] (detachable printer head) Figures 3-5 and 8 show various views of a detachable printer head 20 for a bioprinter 10 according to one embodiment. Figures 22 and 23 show an alternative embodiment of a detachable printer head 1020 for a bioprinter 1010.

[0059] The detachable printer head 20 can receive the biomaterial and cells necessary to print the fluid at the site of interest. In one embodiment, the detachable printer head 20 is a disposable detachable printer head, meaning that it is designed to be disposed of after use. In this manner, the disposable detachable printer head can be prepared for use in a sterile environment, minimizing and preferably eliminating contamination. The disposable detachable printer head only needs to be removed from its sterile packaging or container, attached to the fixed portion 30, and loaded with biomaterial, minimizing the chance of contamination before removal and when disposed of after the printing operation.

[0060] In the context of this specification, biomaterials include bioinks, activators, cells (particularly cell suspensions), or other related fluids and / or materials associated with a bioprinting system. Where reference is made to bioinks or activators, these may be substituted with, and indeed may include, other suitable biomaterials. For example, a cell suspension may be present in a bioink or activator.

[0061] In another embodiment, the detachable printer head 20 is a reusable, sterilizable, detachable printer head. In one embodiment, the sterilizable, detachable printer head can be reused a predetermined number of times according to a particular sterilization method. The predetermined number can be, for example, up to 10 times. The predetermined number limit relates to the effect that the use and repeated application of the sterilization process has on key components of the sterilizable, detachable printer head, such as seals, valves, tubing, and the like.

[0062] The detachable printer head 20 includes a body 25 and a dispensing system 180. The detachable printer head 20 is removably attachable to the fixed portion 30 of the bioprinter 10.

[0063] The dispensing system 180 is supported by a body 25, which may include multiple portions of the removable printer head 20.

[0064] The detachable printer head 20 has a coupling device 200 for attachment of the bioprinter 10 to the fixed part 30. The coupling device 200 provides an interface for operating the dispensing system 180. The dispensing system 180, the coupling device 200, and the interface are described in more detail below.

[0065] The removable printhead 20 includes a reservoir assembly 100. The reservoir assembly includes one or more reservoirs 110. There may be 2, 4, 6, 8, 10, 12, 14, 16, or more reservoirs. While an even number of reservoirs is specifically mentioned, it is contemplated that the removable printhead 20 may include an odd number of reservoirs. For example, one embodiment may include a single reservoir.

[0066] Figure 22 shows an alternative embodiment of a single detachable printer head 1020. The detachable printer head 1020 includes a single reservoir 1110 supported by a body 1025. Figure 23 provides an example of four detachable printer heads 1020 of this embodiment removably attached to a fixed portion 1030 of the bioprinter 1010.

[0067] The ability to utilize individual detachable printer heads with a single dispensing system (or module) provides the user with the option to tailor the number of dispensing systems or modules to the particular application in which the bioprinter 10 is being used. The user can also tailor the type of dispensing system or module depending on the particular application. This built-in flexibility, along with the use of detachable printer heads, offers advantages in flexibility and cost savings, as the configuration can be planned and changed based on the application.

[0068] FIG. 3 illustrates a removable printhead 20 having a reservoir assembly 100 with eight reservoirs 110 arranged about a central axis 35. In an alternative embodiment, the reservoir assembly 100 may include sixteen reservoirs 110. In an alternative embodiment, the reservoir assembly 100 may include a single reservoir 110. However, in other embodiments, the reservoir assembly 100 may include a different number of reservoirs 110, with one or more reservoirs arranged about the central axis 35. However, other embodiments are not limited to this configuration, and it is contemplated that the reservoir assembly 100 may have reservoirs arranged in a linear, pyramidal, rectangular, clustered, or any other reasonable configuration that still allows the reservoirs to hold and dispense fluid from the removable printhead 20. For example, one or more reservoirs may be arranged in a rectangular array. A rectangular array offers the advantage of having the option of aligning more than two dispense valves on a single printer head path, which also reduces the design complexity of the bioprinter 10. Furthermore, for embodiments with a specific reservoir arrangement in the detachable printer head 20, other embodiments may have multiple detachable printer heads in a specific arrangement. For example, the detachable printer head 1020 of FIG. 22 is a single reservoir embodiment, and multiple detachable printer heads arranged in a row, as shown in FIG. 23, can achieve a similar output to an embodiment with multiple reservoirs arranged linearly within a single printer head.

[0069] 6 and 7 show a single reservoir assembly 100, including a reservoir 110 attached to an inlet valve 130, a reservoir cap 120, and a pneumatic connector 135, which in this embodiment includes an O-ring 136, a filter 137 (in the form of a frit in this embodiment) for removing particles, a disk filter 139, and an outlet valve 150. Thus, each reservoir has at least one inlet for receiving fluid (including biomaterial and, optionally, other fluids, such as gas for pressurizing the reservoir), an outlet for dispensing bioprinting fluid, and an interior volume for holding the fluid. The filter 137 is optional, depending on the purity of the air supply and other filtration components that may be present. For example, a disk filter 139 can provide sufficient filtration and also offer the added benefit of mitigating backflow from the reservoir 110. Additionally, the disc filter 139 may be hydrophobic to help prevent unintended fluid flow. Additionally, while this pneumatic connector 135 includes an O-ring 136, other suitable components and structures may be used to create a suitable pneumatic connector.

[0070] Each reservoir 110 may contain a respective fluid or liquid. Alternatively, more than one reservoir 110 may contain the same fluid or liquid. The reservoirs 110 have a first end 112 at which a reservoir cap 120 includes a pneumatic connector 135 and typically includes an inlet valve 130, and a second end 115 having an outlet connected to an outlet valve 150. The reservoirs 110 may have a cylindrical cross-section, although in other embodiments the reservoirs may have other cross-sections, such as an oval or other shape, such as round or rectangular.

[0071] As shown in FIGS. 6 and 7 , the reservoir second end 115 is tapered, with the cross-sectional area of ​​the reservoir decreasing toward the outlet 138. The second end 115 tapers away from the reservoir axis 142 of the reservoir 110, and the outlet 138 is off-center. Locating the outlet 138 at the second end 115 of the reservoir 110 off-center toward the central axis 35 (regardless of reservoir shape) helps minimize the overall diameter of the removable printhead 20 at the point where printing actually occurs at the removable printhead base 190. That is, it is advantageous to have the individual dispense valves of the removable printhead 20 as close to each other as possible. By circumferentially arranging the reservoir 110 about the central axis 35 and having the reservoir outlets 38 offset relative to the central axis 35, the distance between the dispense valves is minimized.

[0072] The inlet valve 130 is adapted to insert fluid into the reservoir, as discussed in detail in the aforementioned WO 2021 / 108870. The inlet valve 130 may be a check valve and / or a one-way valve, although any valve that allows for filling of the reservoir and retention of fluid within the reservoir would be suitable.

[0073] Fluid can be loaded manually by a user with a syringe through inlet valve 130 and directly into reservoir 110. However, fluid may also be loaded through other means, such as a cartridge system or an automated loading system.

[0074] Reservoirs 110 can be at least partially transparent. Reservoirs 110 can also be transparent or opaque. Transparency has the advantage of allowing an operator of the bioprinting system to easily see the contents of reservoirs 110, and in particular, the amount of bioprinting fluid that is in a particular reservoir.

[0075] Each reservoir is in fluid communication with a dispense valve 150. The dispense valve 150 may be a microvalve 150. In one embodiment, the microvalve is a solenoid valve.

[0076] Each dispense valve 150, together with the reservoir assembly 100 and respective fluid communication, forms part of the dispense system 180 of the removable print head. The dispense system 180 is a droplet dispense system configured to print droplets from one or more reservoirs onto a substrate. In one embodiment, fluid is pneumatically expelled from the reservoirs 110 out of the dispense valve 150, which is electronically controlled.

[0077] FIG. 5 shows an embodiment of a coupling device 200 in an exploded view. The coupling device 200 includes a gasket 210, a support ridge 225, a retainer plate 230, a retainer ring 240, and an inner body 170. The inner body 170 includes a central cavity 172 that receives a corresponding shaft 305 (see FIG. 11 ) of the fixed portion 30. The retainer plate 230 is attached to the inner body 170 through the use of one or more screws 220, and the retainer ring 240 is held between the retainer plate 230 and the inner body 170. Other embodiments are not limited to the use of screws, and other means of holding the parts of the assembly together are contemplated as covered by this disclosure. The gasket 210 serves to provide a fluid seal between the retainer plate 230 and the reservoir caps of the reservoir assembly that protrude through the gasket 210 so that they can be connected with appropriate fluid communication on the fixed portion 30. Gasket 210 is optional in some embodiments, and the fluid seal is provided by pneumatic connector 135 .

[0078] The removable printer head 20 has an outer body 160. The outer body 160 is formed around the reservoir assembly 100 and may be said to be attached to an inner body 170. The outer body 160 may be at least partially transparent. The outer cover may have a textured lower portion. This textured portion allows a surgeon or other operator to grasp and manipulate the removable printer head 20.

[0079] The removable printer head 20 may have a base portion 190 that is attached to the inner body 170 through the use of one or more screws 191 and has an opening 192 that allows a distance sensor to travel through the center of the removable printer head 20 (discussed in more detail below), and the screw 191 may take the form of a pin or other feature that may aid in aligning and / or attaching the removable printer head 20.

[0080] The number of reservoirs can be selected to allow printing of two materials, each requiring two nozzles. In one example, two nozzles can contain a separate bioink and activator for each material. The use of two (or four, six, eight, etc.) nozzles increases the printing speed of the printing assembly. However, the invention is not limited to this configuration, and an odd number of nozzles can be utilized for printing and still be covered by the present disclosure.

[0081] In one embodiment, the detachable printer head 20 includes eight reservoir assemblies 100 arranged in a circular pattern. This configuration allows the dispense valves to be equidistant from the distance sensor (located in the center), improving printing robustness when printing on uneven surfaces. This arrangement also minimizes the size of the detachable printer head 20 in the area closest to the printing surface, allowing the bioprinter to easily maneuver around the printing surface and reach more difficult locations.

[0082] (bioprinter) 1 and 2 show a bioprinter 10 that includes a fixed portion 30 and a detachable printer head 20. The detachable printer head 20 is removably attached to the fixed portion 30. As discussed above, a bioprinter may include a fixed portion 30 and a detachable printer head 20, or it may also include a mechanical steering device such as a robotic arm 40 or a gantry robot 560.

[0083] An example including a gantry robot 560 is shown in Figure 27. Figure 27 shows a removable printer head 3020 mounted on a two-axis XY gantry robot 560. The removable printer head 3020 is positioned on a first track 562 in the X axis. The Y axis is depicted as a second track 564 in Figure 27.

[0084] The bioprinter 10 includes an interface for operating the dispensing system 180 of the detachable printer head 20. As can be expected, the interface has two components: the detachable printer head and a fixed portion interface. In this embodiment, the fixed portion interface allows the pneumatic and electrical connections of the detachable printer head 20 to be connected to the rest of the bioprinter. The fixed portion 30 may include other parts, such as hardware components. These hardware components may include a distance sensor 350, a camera, control buttons or enable switches 450, a control system (including associated interfaces for operating the bioprinter), or parts designed to provide safety or operability advantages.

[0085] 11 and 12 show an embodiment of the fixed portion 30. The fixed portion 30 includes a front casing 410 and a rear casing 420 that encase the internal components of the fixed portion 30. FIGS. 11 and 28 show different designs of the front casing 410 and rear casing 420, which are different embodiments. The present invention is not intended to be limited to the shapes shown in these two figures and may include other designs that still meet the purpose of encasing the internal components of the fixed portion 30. In this embodiment, a seal 425 runs around the perimeter of the rear casing 420. A robot mount 430 is provided for connecting the fixed portion 30 to a robot arm 40.

[0086] The embodiment shown in FIG. 11 includes a switch 450 on the fixed portion 30. The switch 450 activates a mode in which the robotic arm 40 can be manually guided by a user. This switch 450 allows a user to manually guide the bioprinter for a variety of reasons. For example, the switch 450 can enable an override mode, disabling automatic printing, to move the bioprinter 10 across more difficult surfaces or navigate across more difficult-to-access surface areas. Alternatively, the switch 450 can enable a pre-print mode in which the area to be printed is manually defined, and then the control system controls the bioprinter to print in the area defined during the pre-print mode.

[0087] Further embodiments may include this switch in other locations on bioprinter 10, such as on removable printer head 20. Additionally, switch 450 may be eliminated in other embodiments.

[0088] The control system and associated hardware may include functionality for controlling the dispensing valves in the detachable printer head 20 .

[0089] 11-15 show various embodiments of the connecting portion 300, which is attached to one or both of the front casing 410 and the rear casing 420 by screws 302. The connecting portion 300 provides mechanical support for the detachable printer head 20 and allows the user to manipulate the bioprinter 10 without damaging any of the connections between the fixed portion 30 and the detachable printer head 20.

[0090] FIG. 11 shows the connecting portion 300 in an exploded view. The connecting portion 300 includes a shaft 305. The shaft 305 is intended to fit within the inner body 170 of the removable print head 30 and helps provide support through the central portion of the reservoir assembly 100. The shaft 305 may also provide an indexing function. Indexing helps ensure that the removable print head 30 is properly aligned with respect to the mating surface, for example, with respect to the base 190. While these functions have been discussed with reference to the shaft 305, the invention is not so limited, and it is contemplated that other features may be utilized to provide the indexing function, such as the use of pins 193. Alternative features may be utilized independently of or in conjunction with the use of a shaft.

[0091] FIG. 13 shows the connecting portion 300 in a position ready for use with a detachable printhead 20.

[0092] Shaft 305 is attached to a mounting assembly 310, which is shown in more detail in Figures 14 and 15. Although shaft 305 is depicted in Figures 11 and 15 as extending substantially from mounting assembly 310, alternative embodiments may show shaft 305 as being shorter, as shown in Figures 12 and 13. Mounting assembly 310 includes tubing 330 that facilitates a gas line for bringing gas to the interface of fixed portion 30.

[0093] The mounting assembly 310 may include a distance sensor 350. In one embodiment, the distance sensor 350 is an optical distance sensing device, such as a distance sensor 350 based on an optical sensing beam 355. The distance sensor 350 is attached to the mounting assembly 310 by a mount 340. The distance sensor 350 is used to measure the distance between the print head base 190 and the print substrate or object to be printed on. This helps the control system to safely and easily maintain the required distance from the substrate.

[0094] The printing surface may be a surface of the subject, such as the surface of the patient's skin. It is also contemplated that a distance sensor 350 may be externally disposed and coupled to the bioprinter 10. The distance sensor 350 may be an ultrasonic sensor, an optical sensor, a camera(s), an inductive sensor, a capacitive sensor, a photoelectric sensor, a contact sensor that physically contacts the surface of the patient's skin, or any other suitable sensor known in the art that can monitor the distance between the base 190 of the detachable printer head 20 and the printing surface. The printing surface may be a wound on the subject.

[0095] Mounting assembly 310 may include a camera, which may be provided in place of or in addition to distance sensor 350, and may in fact function as distance sensor 350.

[0096] In some embodiments, a window 375 is provided to allow the optical sensing beam 355 of the distance sensor 350, for example, a laser, to exit the detachable printer head 20. It is contemplated that the distance sensor 350 may be any other suitable means known in the art that can be used as a visual aid for positioning the bioprinter 10. The window 375 may not be necessary in other embodiments.

[0097] The mounting assembly 310 includes a connector 345 for a distance sensor 350. A gasket 320 is provided to provide a seal between the remainder of the fixed part 30 and the mounting assembly 310.

[0098] In one embodiment, having an optical distance sensor 350 allows the sensor 350 to be mounted at a location away from the distal end of the shaft 305. In this example, the shaft 305 is preferably hollow so that light can pass through its center and through the opening 192 in the detachable printer head 20 to measure the distance between the object and the base 190 of the detachable printer head 20. It is not necessary that the sensor be located within the detachable printer head 20.

[0099] An alternative embodiment does not include the inner body 170 in the detachable printer head 20 and / or does not include the shaft 305 provided by the connecting portion 300. A further alternative embodiment includes a distance sensor 350 in the detachable printer head 20.

[0100] 13 and 15 show the mounting assembly 310 and its interaction with the coupling device of the detachable printer head 20. The mounting assembly 310 includes a locking mechanism 360, which together are adapted to removably mount the detachable printer head 20 and the fixed portion 30 (e.g., the fixed printer head 30) of the bioprinter. The mounting assembly 310 is designed to enable a simple and reliable mounting process. The mounting assembly 310 is designed to mechanically couple the detachable printer head 20 with the fixed portion 30, while also contacting the interface of the fixed portion 30 with the interface of the detachable printer head 20 to provide electrical and pneumatic connections.

[0101] Although the operation of the mounting assembly 310 and retaining ring 240 is described below in connection with the fixed portion 30 and the detachable printer head 20, other embodiments may utilize other mechanisms to detachably attach the detachable printer head 20 to other fixed portions, arms or portions of the bioprinter.

[0102] The retaining ring 240 is circumferentially movable relative to the removable printhead 20; that is, it can rotate around the inner body 170 without becoming separated from the body 170. The mounting assembly 310 includes a plurality of pneumatic receiving portions 315 that form part of the pneumatic interface of the fixed portion interface. A plurality of pneumatic connectors 135 of the reservoir assembly 110 protrude from the gasket 210 of the coupling device 200 and form part of the removable printhead interface. The pneumatic receiving portions 315 are appropriately spaced to receive the pneumatic connectors 135 of the removable printhead 20.

[0103] Multiple air pressure receiving portions allow for individual pressure sources to be aligned with individual reservoirs, allowing one or more of the reservoirs to be simultaneously subjected to different pressures, providing additional flexibility in the capabilities of the dispensing system.

[0104] In an alternative embodiment, the pneumatic interface is formed from an integrated pressure distribution manifold 550. This embodiment is shown in Figures 24 and 25.

[0105] In this embodiment, a single pressure source is provided to multiple reservoirs through pneumatic interface 552. That is, the pneumatic interface can direct a single pressure source to one or more reservoirs. This pneumatic interface has an air pressure receiving portion on one side for receiving input from a pressurized air supply. However, in this embodiment, a manifold 550 is created within the pneumatic interface, and the direction of pressure flow can be manipulated within the manifold. Manifold valve 548 controls the air supply to manifold outlet 554, which is configured to allow a single pressure source to direct pressure to the inlets of multiple reservoirs when manifold outlet 554 is connected to removable printhead 20.

[0106] An advantage of this embodiment is that an increase in the number of reservoirs does not necessarily entail an increase in the number of pressure sources. However, the invention is not limited in this respect, and it is contemplated that multiple pressure sources may be implemented while still utilizing a pneumatic interface such as that described above. A further advantage is found in the ability to expand the construct with a greater number of reservoirs without having to provide space for multiple pressure sources within the same construct.

[0107] Mounting assembly 310 includes a plurality of ramp-like protrusions 317 or projections disposed around its circumference. Retaining ring 240 has corresponding slots on its inner surface, reinforced by support ridges 225, that act against the ramp-like protrusions to securely mount removable printhead 20 to fixed portion 30. Importantly, this coupling mechanism allows the interface components of removable printhead 20 to be connected without rotation of those components; only retaining ring 240 requires rotation.

[0108] The coupling mechanism is not limited to use in the above example, and other designs can be implemented to fixedly attach the removable printer head 20 to the fixed part 30. For example, a cam or lever mechanism can be arranged to provide a mechanical coupling between the removable printer head and the fixed part. The use of a cam 555 and a lever 558 is shown in FIG. 26. The cam 555 and the lever 558 are used in combination to pull the removable printer head onto the fixed part.

[0109] In use, the removable printer head 20 is placed on the shaft 305 and the pneumatic connector 135 is pressed into the pneumatic receiving portion 315. At this point, the retaining ring 240 is rotated so that the slots on its inner surface engage the ramp-like protrusions 317, which have a predetermined ramp size, thereby bringing the removable printer head 20 toward the fixed portion 30 into a predetermined relative position.

[0110] Additionally, to prevent accidental release, the mounting assembly 310 includes a locking mechanism 360 incorporating a biased locking pin 365. The retaining ring 240 includes a locking recess (not shown) on its inner surface, and the locking mechanism's pin 365 engages the locking recess when the retaining ring 240 is rotated to a predetermined position. This prevents the retaining ring 240 from rotating unless the locking mechanism 360 is used to bias the pin 365 away from the support ridge 225.

[0111] Additionally, shaft 305 includes an end cap 370 that includes a series of electrical connectors that provide electrical signals to dispensing valve 150 of removable printhead 20 (see Figures 9, 10, 15, 17, and 18).

[0112] 9 shows a detachable electrical interface 255 that forms part of the detachable printhead interface and that includes dispense electrical connections 260 in the form of pogo pins on one side of a substrate and a header connector 270 on the other side of the substrate. A pair of dispense connections 260 are connected to the header 270, which in turn is connected to the dispense valve 150. The detachable electrical interface 255 is disposed within the inner body 170, where it contacts the end of the shaft 305 when attached to the fixed part 30. FIG. 10 shows an alternative embodiment of the detachable electrical interface in which sixteen reservoir assemblies 110 are used instead of eight.

[0113] The shaft 305 of the fixed part 30 includes a fixed part electrical interface within the end cap 370 as part of the fixed part interface. The fixed part electrical interface includes a spout connection 380 and a header connector 390. The spout connection 380 is arranged to cooperate with the detachable spout connection 260 so that when the shaft 305 is inserted into the inner body 170, the control system has an electrical connection to the spout valve 150 and can operate the spout valve 150 as required.

[0114] 19 shows the detachable printer head 20 removably attached to the fixed part 30, i.e., the shaft 305 is fully inserted into the inner body 170 and both pneumatic and electrical connections are made. The optical sensing beam 355 from the distance sensor 350 is also shown.

[0115] (Bioprinting Platform) The detachable printer head 20 may be used as part of a drop-on-demand bioprinter that deposits biomaterial onto a substrate. The bioprinter may also use cells from the patient. In one embodiment, the substrate may be a wound site on the patient.

[0116] The bioprinter 10 may be mounted to a portable base 50. The portable base 50 houses the subsystem components that enable the bioprinter 10 to function and that have generally been described as part of the fixed portion 30. The portable base 50 allows portability of the platform from various locations within a facility, such as a hospital. The portable base 50 may include features such as printing air pressure, a robotic controller, and braking equipment if the bioprinter is mobile, as well as computer and electronic components. The robotic arm 40 is mounted to the fixed portion 30 and allows movement of the bioprinter 10. This movement provides space around the substrate and the precision needed to deposit a therapeutic agent onto the substrate. In one embodiment, the robotic arm 40 is a Kuka LBR MED, which is approved for use as a component of a medical device. However, the present invention is not limited to the use of this robotic arm, and alternatives may be utilized. For example, while a robotic arm is discussed in this example, it is contemplated that a gantry robot may also be utilized to provide steering of the removable printer head 3020.

[0117] The various components utilized by bioprinter 10 may be stored in any desired manner. For example, they may be mounted or located on / in a static structure or on / in a portable structure, such as a trolley. FIG. 20 illustrates an embodiment in which portable base 50 is a trolley. Robotic arm 40 is attached to trolley 50 via mounting base 45 of robotic arm 40. Trolley 50 allows bioprinting system 60 to be moved to a desired location, making bioprinting system 60 portable, e.g., allowing bioprinting system 60 to be moved between medical locations. Trolley 50 may also include a control system and a graphic user interface for operation of bioprinter 10. This embodiment illustrates the self-contained nature of bioprinting system 60. That is, bioprinting system 60 can be placed on trolley 50 and moved to a required location while containing all the systems necessary to operate bioprinter 10. According to other embodiments, the robotic arm 40 may be mounted on other surfaces or in a fixed position. Figure 1 shows the robotic arm 40, fixed portion 30, and removable printer head 20 when not attached to the trolley 50.

[0118] In one embodiment, the detachable printer head 20 consists of the dispensing valve, reservoir, check valve, electrical and mechanical components, and the necessary fittings to house and control these components. In this embodiment, the remaining electronics for sensing are housed within the fixed portion 30. However, alternative embodiments are contemplated in which these components are located within other portions of the bioprinter 10. This includes, but is not limited to, configurations in which the check valve is located within the fixed portion or the reservoir is located within the fixed portion.

[0119] (Printing method) According to one embodiment, the bioprinter 10 prints fluids or gels using a drop-on-demand method. In this method, at least one reservoir 110 is filled with a bioink and at least one reservoir is filled with an activator. The one or more reservoirs 110 are disposed within a reservoir assembly 100 within the detachable printer head 20. The detachable printer head 20 is removably attached to the fixed portion 30 and locked in place using a locking mechanism. When connected together, the connecting portion 300 provides a shaft 305 that passes through the inner body 170 of the detachable printer head 30. The detachable printer head 20 and the fixed portion 30 form the bioprinter 10.

[0120] In this embodiment, the robotic arm 40 is controlled to move the bioprinter 10 to each of the intended points where material is to be deposited on the printing surface. A distance sensor 350 found in the fixed part 30 is configured to monitor the distance between the base 190 of the detachable printer head 20 and the printing surface. The printing surface may be the surface of a target, for example, a wound on the surface of a patient's skin.

[0121] It will be appreciated that with current state-of-the-art biomaterials, a minimum of two reservoirs 110 contained within the detachable printer head 20 are often required to form a fluid or gel using the drop-on-demand method described above. Multiple reservoirs 110 may be utilized to improve printing speed or may be necessary when insufficient biomaterial can be held in the smallest reservoir. However, in some embodiments, a single reservoir is all that is required.

[0122] Additional reservoirs can be used to add additional materials to increase the biological complexity of the structures created.

[0123] In this example, multiple reservoirs can be filled with bioink and multiple reservoirs 110 can be filled with activator. For example, in this example, when all of the bioink has been dispensed from one reservoir 110, bioink is dispensed from the other reservoirs 110. This can reduce the need to stop the printing regime and refill the reservoirs 110. It is also contemplated that the reservoirs 110 may be filled with different types of liquids. If the reservoirs 110 are filled with different liquids, the bioprinter 10 can form a gel having layers of different materials, layers containing different cells and / or drugs, and / or different liquids printed / layered between each layer of the gel.

[0124] It is important that all parts of the bioprinting system that may come into contact with either the patient or other medical users are sterile, including the steps outlined above and steps involving removing and / or replacing the detachable printer head from the bioprinter.

[0125] This can be achieved through the use of sterile drapes. Sterile drapes can be used to ensure that parts and portions of the bioprinting system that may come into contact with the patient or user are prevented from contacting the patient or user in an unsafe manner. All embodiments described herein can be configured to be compatible with the use of sterile drapes.

[0126] Sterile draping can be performed by first placing a sterile drape onto the bioprinting system using a sterile adapter on the fixed part of the bioprinter. A sterile, detachable printer head can then be attached to the sterile adapter. It is common practice to use sterile adapters to ensure sterility of surgical tools and robots.

[0127] Sterile draping can also be achieved by simultaneously attaching a sterile drape and a sterile printer head. Although the following method is discussed as being completed by two users, the method may be completed by one user or more than two users. Typically, the method is performed by one or two users.

[0128] The robotic arm can be moved into a position that is straightened out and provides ample space for manipulation around it for the draping process. The first user inserts the detachable printer head into the sterile drape before attaching the drape under the locking ring and over the check valve or one-way valve through the use of sterile tape. This arrangement can allow for easier viewing of the reservoir in some embodiments.

[0129] A first user holds the detachable printer head in place while a second user attaches the printer head to the detachable printer head. The first user then inverts the sterile drape over the detachable printer head and the fixed portion. A preliminary system pressure check can be performed following this step. The second user then pulls the sterile drape along the robotic arm. Straps can be attached to the sterile drape and the robotic arm to limit movement of excess drape material.

[0130] Sterilization processes and other methods for maintaining the environment may be used in conjunction with the bioprinting methods outlined above.

[0131] With this in mind, the printer head can help provide many unstated advantages, such as: The detachable printer head provides for easy sterilization of the bioprinter between printing surfaces, as the detachable printer head can be removed from the rest of the printer head assembly and disposed of before use. The sterile detachable portion can be used a predetermined number of times without having to be disposable. The detachable printer head embodiment is designed to be disposable after use, reducing the risk of disinfection between patients. The detachable printer head facilitates optimizing the coupling of fluidic components to reduce dead volume, thus minimizing possible cell waste. The detachable printer head allows the maximum load sample volume, type of dispensing technology, and number of dispensing modules to be changed independently of the bioprinting system, thereby giving the user the ability to configure the printer head for their application. The detachable printer head allows the user to load a fluid sample into the detached printer head in a sterile environment, such as a biosafety cabinet, before installing the printer head into the system, allowing the bioprinting system to be used in a non-sterile setting without risking contamination. Removable printheads improve the ease of cleaning and maintenance, and are replaceable in the event of component failure. In one preferred embodiment, the size and configuration of the reservoir assembly has been designed to minimize the size of the detachable printer head in the area close to the patient, making it easier to manipulate the detachable printer head around the patient and print on hard-to-access areas of the body. In one preferred embodiment, the use of switches allows additional user control over the speed and positioning of the print. In one preferred embodiment, the detachable printer head is configured to allow the distance sensor to be housed within the fixed portion, so that relatively expensive, highly accurate sensing components are not located within the detachable printer head, which may be disposable or have a limited number of uses. In one preferred embodiment, the shaft of the connecting portion of the fixed portion strengthens the coupling of the detachable printer head and allows for safe manipulation of the printer head / system without introducing mechanical stress on the interface (e.g., pneumatic and electrical connections). The bioprinter, and therefore the detachable printer head, is non-contact, which reduces the possibility of contamination and disturbance of the print area, such as a wound.

[0132] 21, there is shown a schematic diagram of a bioprinting system 60. Where elements of the schematic diagram have been described above, like reference numerals are used in this figure to refer to those elements already used herein.

[0133] In preparation for printing, biomaterial 510 and autologous biological material 512 are prepared and loaded into reservoir 110 via inlet valve 130.

[0134] The portable base or trolley 50 houses a system controller 502 and a pneumatic device 504. The pneumatic device 504 provides the necessary elements to supply gas, typically air, to the fixed portion 30 and ultimately to the detachable printer head 20. Various sensors provide feedback 506 to the system controller 502. From this information, and from other data and settings provided via a system interface, such as a graphical user interface, the system controller 502 operates the bioprinter to move the robotic arm 40 and print via the detachable printer head 20. A distance sensor 350 provides feedback on the distance from the wound site of the patient 508 to the detachable printer head 20. The detachable printer head prints biomaterial, which is prepared biomaterial 510 and autologous biological material 512, onto the print area, which in this example is the wound site of the patient 508. The nature of the biomaterials used allows for three-dimensional bioprinting, which offers significant advantages for wound healing.

[0135] Many features of the printer head architecture described above are specific to bioprinting, i.e., the generation of three-dimensional biological structures using cells, and are not directly transferable to or from other printing technologies. For example, the design of the reservoir and its working volume has been optimized for processing precious fluids, such as patient cells, with volume ranges and losses specific to bioprinting applications. One such example is that the range of working volumes compatible with the described detachable printer head architecture spans from 5 μL to 50 mL.

[0136] The material types that the above-described printer head architecture must support include a range of materials of interest to scientists and clinicians engaged in research or clinical care. These material types include cells, tissues, bioinks, crosslinkers, growth media, growth factors, buffers / cell buffers, and manufactured biological fluid products (i.e., laminin, fibrinogen, collagen, and point-of-care platelet-rich plasma, serum).

[0137] Materials and volumes supported by the printer head architecture are deposited via printing parameters and processes optimized to generate three-dimensional biological structures, resulting in droplets in the 1 nL to 200 nL working range with high biological viability.

[0138] The generation of three-dimensional biological structures using droplets of a specified volume range of the specified fluid detailed above is achieved by parameterizing the following features of the printer head design and printing process: back pressure, diameter of the orifice of the ejection nozzle, opening time of the ejection valve, surface energy of the orifice of the ejection nozzle, dead volume of the fluid path, fluid viscosity, surface tension of the fluid, particle size distribution of the fluid, process duration, and droplet deposition accuracy.

[0139] Those skilled in the art will appreciate that numerous changes and / or modifications to the invention as shown in the specific embodiments may be made without departing from the spirit or scope of the invention as broadly described, and the present embodiments are therefore to be considered in all respects as illustrative and not restrictive.

[0140] While the present invention has been described with reference to the above embodiments, those skilled in the art will recognize that the present invention may be embodied in many other forms. Those skilled in the art will recognize that numerous changes and / or modifications may be made to the techniques shown in the specific embodiments without departing from the spirit or scope of the technology broadly described. The present embodiments, therefore, are to be considered in all respects as illustrative and not restrictive.

[0141] As used herein, adjectives such as left and right, up and down, hot and cold, first and second, and the like, may be used to distinguish one element or act from another, but do not necessarily require or imply such an actual relationship or order. Where the context permits, a reference to a component, integer, or step (or the like) should not be construed as being limited to only one of that component, integer, or step, but may be one or more of that component, integer, or step.

[0142] As used herein, the words "comprise," "comprising," "include," "including," and similar terms are intended to mean an open-ended inclusion, such that a method, system, or device that contains recited elements does not contain only those elements, but can also contain other unrecited elements.

[0143] Throughout this specification, the term "consisting of" means consisting solely of.

[0144] Unless the context requires otherwise or unless expressly stated to the contrary, any integer, step, or technical element described herein as a singular integer, step, or technical element expressly includes both the singular and plural forms of the described integer, step, or technical element.

[0145] In the context of this specification, the words "a" and "an" may be used to refer to one or to more than one (i.e., to at least one) of the grammatical objects of the document. By way of example, a reference to "an element" means one element or more than one element.

[0146] In the context of this specification, the term "about" means that reference to a number or value should not be construed as an absolute number or value, but rather includes a margin of variation above and below that number or value consistent with what one of ordinary skill in the art would understand according to the art. This margin of variation includes within the margin of typical error or equipment limitations. In other words, the use of the term "about" is understood to refer to a range or approximation of values ​​that one of ordinary skill in the art would consider equivalent to the stated value in the context of achieving the same function or result.

[0147] The above description related to embodiments of the present disclosure is provided for purposes of explanation to those skilled in the art. This description is not intended to be exhaustive, and is not intended to limit the present disclosure to the single embodiment disclosed. As noted above, various alternatives and modifications to the present disclosure will be apparent to those skilled in the art in light of the above teachings. Thus, while several alternative embodiments have been specifically discussed, other embodiments will be apparent or relatively easily developed by those skilled in the art. The present disclosure is intended to encompass all modifications, substitutions, and variations discussed herein, as well as other embodiments that fall within the spirit and scope of the above description. [Explanation of symbols]

[0148] 10 Bioprinter 20 Detachable Printer Head 25 Body 30 Fixed part 35 Center axis 40 Robot Arm 45 Mounting base for robot arm 50 Portable base 60 Bioprinting System 100 Reservoir Assembly 110 Reservoir 112 first end 115 Second end 120 Reservoir Cap 130 Inlet valve 135 Pneumatic Connector 136 O-ring 137 filters 138 Exit 139 Disc Filter 142 Reservoir axis 150 Outlet valve 160 outer body 170 inner body 172 Central cavity 180 Dispensing System 190 Detachable printer head base 191 Screw 192 Aperture 193 pins 200 Coupling device 210 Removable printer head gasket 220 Screw 225 Support Ridge 230 Maintenance Plate 240 Maintenance Ring 255 Detachable Printer Head Electrical Interface 260 Outlet connection 270 Header Connector 300 Connection part 302 attachment screw 305 shaft 307 Bonding surface 310 Mounting Assembly 315 Acceptance Section 317 Ramp-shaped protrusion of fixed part 320 Fixed part gasket 330 Tubing 340 Distance sensor mounting part 345 Connector 350 distance sensor 355 Sensing Beam 360 Locking Mechanism 365 Lock Pin 370 End Cap Components 375 windows 380 Fixed pouring connection 390 Fixed Header Connector 410 front casing 420 rear casing 425 Fixed part seal 430 Robot mounting part 450 Switch 502 System control unit 504 Pneumatic equipment 506 Feedback 508 patients 510 Biomaterials 512 Autologous Biological Materials 548 Manifold Valve 550 Integrated Pressure Distribution Manifold 552 Pneumatic Interface 554 Manifold outlet 555 Cam 558 Lever 560 Gantry Robot 562 First Track 564 Second Track 1010 Bioprinter 1020 Detachable Printer Head 1025 Body 1030 Fixed part 1040 Robot Arm 1045 Mounting base for robot arm 1110 Reservoir 2020 Detachable Printer Head 3020 Detachable Printer Head

Claims

1. A detachable printer head for a bioprinter, the detachable printer head comprising: a body removably attachable to a fixed portion of the bioprinter; a dispensing system supported by the body; one or more reservoirs for holding one or more biomaterials, the reservoirs being in fluid communication with the dispensing system and supported by the body; and a coupling device for attachment to the fixed portion of the bioprinter, the coupling device comprising an interface for operating the dispensing system.

2. 10. The detachable printhead of claim 1, wherein the body comprises an outer body, the outer body substantially enclosing the dispensing system.

3. 3. The removable printhead of claim 2, wherein the outer body is at least partially transparent in at least some areas.

4. 4. A detachable printer head according to any one of claims 1 to 3, wherein the dispensing system comprises one or more reservoirs, and preferably each reservoir is part of a reservoir assembly, the reservoir assembly also being part of the dispensing system.

5. 5. The removable printhead of claim 4, wherein the body comprises an inner body, and the reservoir is disposed on the outer surface of the inner body.

6. 6. A detachable printer head as claimed in any one of claims 1 to 5, wherein the body comprises a central cavity for receiving a corresponding extension of the fixed part, preferably the central cavity being annular in cross section.

7. 7. A detachable printer head according to claim 1, wherein the body has a central axis perpendicular to a coupling surface of the coupling device.

8. 8. The removable printer head of claim 7, wherein the central cavity has a center point located on the central axis, and preferably the center point is on the cavity axis, and the cavity axis and the central axis are collinear.

9. 9. A detachable printer head according to claim 7 or 8, when dependent on claims 3 to 6, wherein there are two or more reservoirs, and the two or more reservoirs are arranged around the central axis, preferably the two or more reservoirs are arranged in a circle around the reservoir axis, and more preferably the reservoir axis and the central axis are collinear.

10. 10. A detachable printer head according to any one of claims 1 to 9, wherein each of the one or more reservoirs includes an inlet valve connected to at least one of the reservoir inlets, preferably the inlet valve being adapted to allow insertion of fluid into the reservoir, and more preferably the inlet valve may be a check valve and / or a one-way valve.

11. A detachable printer head according to any one of claims 1 to 10, wherein the coupling device is capable of providing a suitable connection to the interface for operating the dispensing system.

12. 12. A detachable printer head according to any one of claims 1 to 11, wherein the coupling device is adapted to removably attach the detachable printer head to a fixed part of the bioprinter.

13. 13. A detachable printer head as claimed in any one of claims 1 to 12, wherein the interface comprises a plurality of dispensing electrical connections that can interface with fixed portion dispensing connections, the dispensing electrical connections providing electrical signals to one or more dispensing valves of the dispensing system.

14. 14. A detachable printer head as claimed in claim 13, wherein said central cavity comprises said plurality of electrical outlet connections, preferably said plurality of electrical outlet connections being located at ends of said central cavity.

15. A detachable printer head according to any preceding claim, wherein the interface comprises a pneumatic connector for one or more reservoirs.

16. 16. A detachable printhead as described in any one of claims 1 to 15, wherein the interface includes an integrated pressure distribution feature in which a single pressure source is directed to one or more reservoirs.

17. A detachable printer head according to any one of claims 1 to 16, wherein the dispensing system is a droplet dispensing system.

18. 18. A detachable printer head as claimed in claim 16 or 17, wherein droplets are pneumatically expelled from the reservoir out of the dispense valve, and preferably the dispense valve is a microvalve.

19. A detachable printer head according to any one of claims 1 to 15, wherein the dispensing system is a jetting system.

20. 20. A detachable printer head as claimed in any one of claims 16 to 19, wherein the print area is a wound in a subject such as an animal or human patient, preferably the wound is a wound in the skin of the subject, and more preferably the fluid dispensed by the dispensing system forms a gel covering the wound.

21. 21. A detachable printer head according to any one of claims 1 to 20, wherein the detachable printer head is disposable.

22. A detachable printer head according to any one of claims 1 to 20, wherein the detachable printer head is reusable.

23. 23. A detachable printer head according to any one of claims 1 to 22, wherein the detachable printer head is sterilizable.

24. A detachable printer head according to any one of the preceding claims, wherein the detachable printer head is equipped with a distance sensor and / or a camera.

25. 1. A bioprinter comprising a fixed portion capable of receiving one or more detachable printer heads, each detachable printer head comprising: a body; a dispensing system supported by the body; one or more reservoirs for holding one or more biomaterials, the reservoirs being in fluid communication with the dispensing system and supported by the body; and a coupling device for attachment to the fixed portion of the bioprinter, the coupling device comprising an interface for operating the dispensing system; the bioprinter further comprising a system for controlling the interface and for operating the dispensing system of the detachable printer head.

26. 26. The bioprinter of claim 25, wherein the dispensing system comprises the one or more reservoirs, and preferably each reservoir is part of a reservoir assembly, the reservoir assembly also being part of the dispensing system.

27. 26. The bioprinter of claim 25, wherein one or more detachable printer heads are individually attached to the fixed portion of the bioprinter.

28. 28. A bioprinter according to any one of claims 25 to 27, wherein the fixed part is movable to position the one or more detachable printer heads.

29. 29. A bioprinter according to any one of claims 25 to 28, wherein the fixed part comprises a distance sensor, the distance sensor providing the distance between the detachable printer head and a printing area.

30. 27. A bioprinter according to claim 25 or 26, wherein the fixed part comprises a shaft for insertion into a corresponding cavity in the detachable printer head.

31. 31. A bioprinting system comprising the bioprinter of any one of claims 25 to 30 and a robotic arm for maneuvering the bioprinter.

32. 31. A bioprinting system comprising the bioprinter of any one of claims 25 to 30 and a gantry robot for maneuvering the bioprinter.

33. A method for using a bioprinter is disclosed, the method including the steps of attaching a detachable printer head to a fixed portion of the bioprinter, the detachable printer head comprising a body, a dispensing system supported by the body, and a coupling device for attachment to the fixed portion of the bioprinter, the coupling device comprising an interface for operating the dispensing system; controlling the bioprinter to move across a printing surface; and forming a fluid or gel on the printing surface.

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