WO2024098119A1

WO2024098119A1 - A detachable printhead for a bioprinter and a bioprinter

Info

Publication number: WO2024098119A1
Application number: PCT/AU2023/051148
Authority: WO
Inventors: Aidan O'mahony; Zachary ARTIST; Andrew Sexton; Jason LEAVENS; Gilbert ALEMANA
Original assignee: Inventia Life Science Pty Ltd
Priority date: 2022-11-11
Filing date: 2023-11-13
Publication date: 2024-05-16

Abstract

A detachable printhead for a bioprinter is disclosed, the detachable printhead 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, in fluid communication with the dispensing system, supported by the body; and a coupling for attaching to the fixed portion of the bioprinter, the coupling including an interface for operating the dispensing system.

Description

A DETACHABLE PRINTHEAD FOR A BIOPRINTER AND A BIOPRINTER

FIELD

[0001] The present disclosure relates to a detachable printhead suitable for a bioprinter. This disclosure also relates to a bioprinter associated with the detachable printhead.

CROSS-REFERENCE TO RELATED APPLICATION

[0002] This application claims priority to Australian provisional patent application number 2022903386 which is incorporated by reference in its entirety.

BACKGROUND

[0003] A hospital is a fast-moving environment. Health professionals often have to move between different patients and utilise various instruments within a short period of time. Contamination of instruments, surfaces and poor hygiene of patients or health professionals can all lead to the spread of disease and infections.

[0004] Therefore, sterilisation and sanitisation of instruments plays an important role in preventing the spread of infection and disease in hospitals. Sterile devices are particularly important in wound care.

[0005] Any reference to or discussion of any document, act or item of knowledge in this specification is included solely for the purpose of providing a context for the present invention. It is not suggested or represented that any of these matters or any combination thereof formed at the priority date part of the common general knowledge, or was known to be relevant to an attempt to solve any problem with which this specification is concerned.

SUMMARY

[0006] In one form, a detachable printhead for a bioprinter is disclosed, the detachable printhead 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, in fluid communication with the dispensing system, supported by the body; and a coupling for attaching to the fixed portion of the bioprinter, the coupling including an interface for operating the dispensing system.

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

[0008] In an embodiment, the body comprises an internal body and the reservoirs are arranged on the outer surface of the internal body. In an embodiment, each reservoir is part of a reservoir assembly, the reservoir assembly also being part of the dispensing system.

[0009] In an embodiment, the body, preferably the internal body, includes a central void for receiving a corresponding extending portion of the fixed portion. In an embodiment, the central void is circular in cross section.

[0010] In an embodiment, the body has a central axis perpendicular to a coupling face of the coupling. In an embodiment, the central void has a centre point located on the central axis. In an embodiment, the centre point is on a void axis and the void axis and central axis are colinear.

[0011] In an embodiment, the body has an outer body, wherein the outer body substantially surrounds the dispensing system. The outer body may be at least partially transparent at least in some areas. In an embodiment, the outer body is at least partially transparent in an area which enables fluid levels of one or more of the reservoirs to be inspected.

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

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

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

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

[0016] In an embodiment, the or each reservoir have at least one inlet and at least one outlet. In an embodiment, the at least one inlet are arranged at an end of the reservoir closest to the coupling. In an embodiment, the at least one outlet are arranged at an end of the reservoir furthest from the coupling. The or each reservoir has a reservoir axis parallel to the central axis which represents a centre of the internal volume. In an embodiment, the at least one outlet is spaced apart from the reservoir axis towards the central axis. Keeping the reservoir outlet as close as possible to the central axis enables the size of the bottom surface of the detachable printhead to be minimised. Minimising the size of the bottom surface of the detachable printhead allows for each droplet dispensing valve (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 an embodiment, the one or more reservoirs are generally cylindrical in shape over the majority of their length. In an embodiment, the one or more reservoirs have a tapered section towards the or each outlet, wherein the taper is away from the reservoir axis towards the central axis.

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

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

[0020] In an embodiment, there are 2, 4, 6, 8, 10, 12, 14, 16 or more reservoirs. Whilst even numbered reservoirs are specifically mentioned, it is envisaged that the detachable printhead may comprise an odd number of reservoirs. For example, in an embodiment, there is a single reservoir. In an embodiment, the one or more reservoirs are installed individually. [0021] In an embodiment, each reservoir has a cap attached to an inlet of the reservoir. In an embodiment, the cap may be used to seal fluid in the reservoir. The cap is adapted to allow gas into the reservoir while not allowing fluid to leave through the first end of the reservoir. In an embodiment, the cap comprises an pneumatic connector, such that a gas, for example air, can be provided to the reservoir. In an embodiment, the reservoir is capable of being pressurised by virtue of the pneumatic connections and other inlets I outlets. In an embodiment, the cap comprises one or more filters. In an embodiment, the or each filter is hydrophobic and, as such, mitigates fluid from passing through the filter.

[0022] The coupling is adapted to removably attach a detachable printhead to a fixed portion of the bioprinter. That is, the coupling is operated, without the use of tools and, therefore, is hand operated, when detaching or attaching to the fixed portion.

[0023] In an embodiment, the coupling is capable of providing a suitable connection for the interface for operating the dispensing system. In one embodiment, the coupling comprises a retention ring which rotates about the interface to engage with the fixed portion. In one embodiment, the retention ring is arranged to pull the detachable printhead onto the fixed position as the retaining ring is rotated. In one embodiment, the retention ring provides a quick release mechanism to engage with the fixed portion. In one embodiment, the quick release mechanism comprises a lug and slot style coupling. That is, at least one lug or slot is provided on the coupling which engages with a respective at least one lug or slot on the fixed portion. In an embodiment, each lug or slot is arranged to pull the detachable printhead onto the fixed position as the retaining ring is rotated.

[0024] In an embodiment, the retaining ring has a screw thread which corresponds to an appropriate screw thread on the fixed portion and the detachable printhead is pulled onto the fixed position as the retaining ring is rotated.

[0025] In an embodiment, the retaining ring comprises a recess for a locking pin. In an embodiment, when the retaining ring has been rotated sufficiently, the recess is capable of receiving a corresponding locking pin.

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

[0027] In an embodiment, the interface includes a plurality of dispensing electrical connections capable of a interfacing with fixed portion dispensing connection, the dispensing electrical connections providing electrical signals to one or more dispensing valves of the dispensing system. In an embodiment, the central void comprises the plurality of dispensing electrical connections. In an embodiment, the plurality of dispensing electrical connections are situated at the end of the central void.

[0028] In an embodiment, the interface includes a pneumatic connector for each reservoir. In an embodiment, a reservoir cap comprises 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 a pneumatic connector for multiple reservoirs. For example, the pneumatic interface may involve directing a single pressure source to one or more reservoirs.

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

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

[0032] In an embodiment, the sample droplets are pneumatically ejected from the reservoir out of the dispensing valve. In a preferred embodiment, the dispensing valves are microvalves.

[0033] In an alternative embodiment, the dispensing system is an extrusion system. [0034] In an embodiment, the printing area is a wound in a subject, such as an animal or human patient. In an embodiment, the wound is a wound in the subject's skin, and the fluid dispensed by the dispensing system forms a gel over the wound.

[0035] In an embodiment, the detachable printhead is disposable. In an embodiment, the detachable printhead is re-usable. In an embodiment, the detachable printhead is sterilisable.

[0036] In an embodiment, the detachable printhead may comprise a distance sensor.

[0037] In an embodiment, the detachable printhead may have a window. The window may be a passage through the detachable printhead or a transparent substrate. In an embodiment, the window enables a distance sensor beam to travel through the detachable printhead. In an embodiment, the distance sensor is remote from the detachable printhead.

[0038] In a further form, a bioprinter is disclosed, the bioprinter comprising a fixed portion, capable of receiving one or more detachable printheads, wherein each detachable printhead comprises a body; a dispensing system, supported by the body; one or more reservoirs, for holding one or more biomaterials, in fluid communication with the dispensing system, supported by the body; and a coupling for attaching to the fixed portion of the bioprinter, the coupling including an interface for operating the dispensing system, the bioprinter further comprising systems to control the interface and operate the dispensing system of the detachable printhead.

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

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

[0041] In an embodiment, the fixed portion is movable to position the one or more detachable printheads.

[0042] In an embodiment, the fixed portion may include a switch, wherein the switch allows the user to override any automated printing and manually operate the bioprinter and/or allows the bioprinter to be operated in a mode which allows manual guiding of the position of the bioprinter.

[0043] In an embodiment, the fixed portion may include a distance sensor, wherein the distance sensor provides the distance between the detachable printhead and a printing area. In an embodiment, the fixed portion includes a shaft for insertion into a corresponding void in the detachable printhead. In an embodiment, the shaft is configured to allow a distance sensor measurement to be taken through the centre of the shaft. In an alternative embodiment, the shaft is configured to allow a camera to operate through the centre of the shaft. In an alternative embodiment, the shaft is configured to allow both a camera and distance sensor to operate through the centre of the shaft. In an embodiment, the shaft comprises fixed portion electrical dispensing connections, for controlling corresponding dispensing valves in the detachable printhead.

[0044] In an embodiment, the fixed portion includes a connection portion. In an embodiment, the connection portion includes a pneumatic interface capable of providing a pneumatic connection with pneumatic connectors of the detachable printhead. In an alternative embodiment, the pneumatic interface includes an integrated pressure distribution function, wherein a single pressure source may be directed to one or more reservoirs.

[0045] In an embodiment, the body comprises an internal body and the reservoirs are arranged on the outer surface of the internal body. In an embodiment, each reservoir is part of a reservoir assembly, the reservoir assembly also being part of the dispensing system.

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

[0047] In a further form, a bioprinting system is disclosed, the bioprinting system comprising a bioprinter as previously described and further comprising a robotic arm for manipulating the bioprinter.

[0048] In an alternative form, a bioprinting system is disclosed, the bioprinting system comprising a bioprinter as previously described and further comprising a gantry robot for manipulating the bioprinter.

[0049] In a further form, a method for using a bioprinter is disclosed, the method including the steps of: attaching a detachable printhead to a fixed portion of the bioprinter, the detachable printhead comprising a body, a dispensing system, supported by the body, and a coupling for attaching to the fixed portion of the bioprinter, the coupling including 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.

[0050] In an embodiment, the method further includes the step of using a sterile drape.

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

BRIEF DESCRIPTION OF THE DRAWINGS

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

[0053] Figure 1 illustrates an isometric view of a bioprinter according to an embodiment including a detachable printhead, fixed portion and robotic arm;

[0054] Figure 2 illustrates front and side views of a printhead assembly according to an embodiment including a detachable printhead and a fixed portion;

[0055] Figure 3 is a front view of a detachable printhead, according to an embodiment;

[0056] Figure 4 is a cross-sectional view of the detachable printhead of Figure 3;

[0057] Figure 5 is an exploded parts view of the detachable printhead of Figure 3;

[0058] Figure 6 is an isometric view of a single reservoir and dispensing valve from the detachable printhead of Figure 3;

[0059] Figure 7 is a cross-sectional side view of a single reservoir and single dispensing valve from the detachable printhead of Figure 3;

[0060] Figure 8 is a cross-sectional perspective view of the detachable printhead of Figure 3; [0061] Figure 9 illustrates perspective views of the connection portion for an 8 reservoir variation of the detachable printhead, from a top perspective view;

[0062] Figure 10 illustrates perspective views of the connection portion for a 16 reservoir variation of the detachable printhead, from a top perspective view;

[0063] Figure 11 is a perspective view of the fixed portion according to an embodiment;

[0064] Figure 12 is an exploded parts view of the fixed portion according to an embodiment;

[0065] Figure 13 is a perspective view of the mount assembly according to an embodiment;

[0066] Figure 14 is a perspective view of the connection portion of the fixed portion according to an embodiment;

[0067] Figure 15 is an exploded parts view of the mount assembly according to an embodiment of the present invention;

[0068] Figure 16 is a side view of the locking clip of the locking mechanism according to an embodiment;

[0069] Figure 17 is a cross-sectional perspective view from the bottom of the shaft of the fixed portion of Figure 3, according to an embodiment;

[0070] Figure 18 is a perspective view of the bayonet end cap from the bottom of the shaft shown in Figure 17;

[0071] Figure 19 is a cross-sectional front view from the bottom of the printhead assembly of Figure 2, showing the detachable printhead and fixed portion in connection;

[0072] Figure 20 is a perspective view of a bioprinting system according to an embodiment;

[0073] Figure 21 is a block diagram of a bioprinting system according to an embodiment;

[0074] Figure 22 is perspective view of an alternative embodiment of a detachable printhead;

[0075] Figure 23 illustrates an isometric view of a bioprinter according to an embodiment showing the fixed portion and robotic arm, with four detachable printheads of the embodiment shown in Figure 22 individually attached to the fixed portion;

[0076] Figure 24 illustrates an embodiment of the pneumatic interface, showing an integrated pressure distribution manifold;

[0077] Figure 25 shows the pneumatic interface of Figure 24 coupled to a detachable printhead according to an embodiment;

[0078] Figure 26 illustrates an alternative embodiment of the locking mechanism;

[0079] Figure 27 shows a side view of a bioprinter according to an embodiment including a detachable printhead and gantry robot; and

[0080] Figure 28 is a perspective view of the front and rear casing according to an embodiment;

DETAILED DESCRIPTION

[0081] Figures 1 and 2 show a bioprinter 10 according to one embodiment. In this embodiment, the bioprinter 10 has a fixed portion 30, a detachable printhead 20, a robotic arm 40 and a mounting base 45. The fixed portion 30 is attached to the robotic arm 40 in a manner which requires one or more tools to remove. The detachable printhead 20 is attached to the fixed portion 30 in a manner which does not require any tools. That is, 'detachable', as used herein, describes the ability for the printhead to be detached and reattached without the use of tools. The detachable printhead 20 has a central axis 35, which is generally perpendicular to a coupling face 307 of a connection portion 300 (see Fig. 11 and 12) of the fixed portion 30.

[0082] A bioprinter having a robotic arm and the general concept of a printhead attached to a robotic arm is disclosed in W02021/108870A1 , which is incorporated by reference in its entirety. As disclosed therein, the bioprinter has a robotic arm with six axes of rotation and the robotic arm 40 as disclosed in this specification has similar functionality. In other embodiments, alternative mechanical manipulation devices may be utilised with the fixed portion 30 and corresponding detachable printhead 20. For example, the bioprinter 10 may include a detachable printhead 3020 that is manipulated by a gantry robot (see Figure 27). [0083] The fixed portion 30 can be removably attached to the bioprinter 10 with specialist tools and considerable time. It is intended to be used with multiple disposable and/or reusable detachable printheads 20. Therefore, the fixed portion 30 can be considered to be a permanent fixture of the bioprinter 10 while the one or more detachable printheads 20 are more readily attached and removed during use of the bioprinter in a simple manner and, preferably, through hand operation. In other embodiments, the fixed portion 30 can be permanently attached to the bioprinter 10.

[0084] The fixed portion 30 is movable in all the previously discussed arrangements. That is, the fixed portion 30 is part of the bioprinter 10 which requires to manipulate the detachable printheads 20, which are on the fixed portion 30.

Detachable Printhead

[0085] Figures 3 to 5, Figure 8 illustrate various views of the detachable printhead 20 for a bioprinter 10, according to one embodiment. Figures 22 and 23 illustrate an alternative embodiment of the detachable printhead 1020 for a bioprinter 1010.

[0086] The detachable printhead 20 is capable of receiving biomaterials and cells required for printing a liquid to a site of a subject. In an embodiment, the detachable printhead 20 is a single use detachable printhead, meaning that it is designed to be disposed of after a single use. In this manner, the single use detachable printhead can be prepared for use in a sterile environment minimising, and preferably eliminating, any contamination. The single use detachable printhead can simply be removed from its sterile wrapping or container, attached to the fixed portion 30 and loaded with biomaterials with minimal opportunity for contamination before being removed and disposed of after the printing operation.

[0087] Biomaterials, in the context of this description, includes bio-inks, activators, cells (and in particular a cell suspension) or other relevant fluids and/or materials related to a bioprinting system. Where reference is made to printing bioinks or activators, these may be replaced by other appropriate biomaterials and, indeed, may contain other appropriate biomaterials. For example, the cell suspension may be present in the bio-ink or activator. [0088] In other embodiments, the detachable printhead 20 is a sterilisable detachable printhead which can be reused. In one embodiment, the sterilisable detachable printhead can be reused a predefined number of times according to a particular sterilising method. For example, the predefined number may be up to 10 times. The limit to the predefined number is related to the effect that the use and repeated application of the sterilisation process has on key components of the sterilisable detachable printhead, such as seals, valves, tubes and the like.

[0089] The detachable printhead 20 has a body 25 and a dispensing system 180. The detachable printhead 20 is removably attachable to a fixed portion 30 of the bioprinter 10.

[0090] The dispensing system 180 is supported by the body 25, which may comprise multiple portions of the detachable printhead 20.

[0091] The detachable printhead 20 has a coupling 200 for attaching to the fixed portion 30 of the bioprinter 10. The coupling 200 includes an interface for operating the dispensing system 180. The dispensing system 180, coupling 200 and interface will be described in more detail below.

[0092] The detachable 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. Whilst even numbered reservoirs are specifically mentioned, it is envisaged that the detachable printhead 20 may comprise an odd number of reservoirs. For example, an embodiment can comprise a single reservoir.

[0093] Figure 22 shows a single detachable printhead 1020 in an alternative embodiment. The detachable printhead 1020 comprises a single reservoir 1110 supported by a body 1025. Figure 23 provides an illustration of four detachable printheads 1020 of this embodiment removably attached to the fixed portion 1030 of the bioprinter 1010.

[0094] The ability to utilise an individual detachable printhead with a single dispensing system (or module) provides the user with the option to tailor the number of dispensing systems or modules to the specific application that the bioprinter 10 is being used for. The user can also align the type of dispensing systems or modules with the specific application. This inbuilt flexibility, along with the use of detachable printheads, provides advantages in flexibility and cost reduction as the configuration can be planned and changed based on the application.

[0095] Figure 3 depicts a detachable printhead 20 with a reservoir assembly 100 with eight reservoirs 1 10 located around a central axis 35. In an alternative embodiment, the reservoir assembly 100 may include 16 reservoirs 110. In an alternative embodiment, the reservoir assembly 100 may include a single (1 ) reservoir 1 10. However, in other embodiments, the reservoir assembly 100 may include a different number of reservoirs 110. The one or more reservoirs are arranged around a central axis 35. However, other embodiments are not limited to this configuration and the reservoir assembly 100 could be conceived to have reservoirs arranged in a line, a pyramid, a rectangular arrangement, a cluster or any reasonable configuration which still allows the reservoirs to hold and dispense fluid from the detachable printhead 20. For example, the one or more reservoirs may be arranged in a rectangular array. A rectangular array provides advantages due to the option to align more than two dispensing valves on a single printhead pass. It also reduces the design complexity of the bioprinter 10. In addition, to an embodiment with a specific arrangement of reservoirs in a detachable printhead 20, other embodiments may have multiple detachable printheads in a specific arrangement. For example, the detachable printhead 1020 of Figure 22 is a single reservoir embodiment and can be arranged, as shown in Figure 23, in a line of multiple detachable printheads, achieving a similar output to the embodiment of multiple reservoirs arrange in a line in a single printhead.

[0096] Figures 6 and 7 illustrate a single reservoir assembly 100 including a reservoir 1 10 attached to an inlet valve 130, a reservoir cap 120, having 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 particulates, a disc filter 139 and a dispensing valve 150. In this manner, each reservoir has at least one inlet for receiving fluids (including the biomaterials and, where required, other fluids, such as a gas to pressurise the reservoir) and an outlet for dispensing the bioprinting fluid, as well as an internal volume for holding fluids. The filter 137 is optional depending on the purity of the air source and other filtration that may be present. For example, the disc filter 139 may be provide sufficient filtration and also provides an additional advantage in mitigating back flow from the reservoir 110. The disc filter 139 may also be hydrophobic to assist in preventing any unintentional fluid flow. Furthermore, whilst this pneumatic connector 135 includes an o-ring 136, it may be that other suitable components and structures can be used to made a suitable pneumatic connector.

[0097] Each reservoir 110 may contain a respective fluid or liquid. Alternatively, the more than one reservoir 110 may contain the same fluid or liquid. The reservoirs 110 include a first end 112, at which the reservoir cap 120, including the pneumatic connector 135, and inlet valve 130 are generally situated, and a second end 115, having an outlet which is connected to the dispensing valve 150. The reservoirs 110 may have a cylindrical cross-section. However, in other embodiments, the reservoirs may have other cross-sections, such as elliptical, or other shapes, such as spherical or rectangular.

[0098] As shown in Figures 6 and 7, the second end 115 of a reservoir is tapered, reducing the cross-section of the reservoir towards the outlet 138. The second end 115 may be tapered away from a reservoir axis 142 of the reservoir 110, such that the outlet 138 is off-centre. The placement of the outlet 138 at an off-centre position towards the central axis 35 (regardless of the shape of the reservoir) at the second end 115 of the reservoir 110 assists in minimising the overall diameter of the detachable printhead 20 at the point at which printing actually occurs at the detachable printhead base 190. That is, it is advantageous to have individual dispensing valves of the detachable printhead 20 as close as possible to each other. By orientating the reservoirs 110 circumferentially around the central axis 35 and, additionally, having the outlets 38 of the reservoirs offset towards the central axis 35, the distance between dispensing valves is minimised.

[0099] The inlet valve 130 is adapted for insertion of a fluid into the reservoir, as is discussed in detail in earlier application WO2021 /108870A1 . The inlet valve 130 may be a check valve and/or a one-way valve, however, any valve that would enable the filling of the reservoir and the retaining of the fluid within the reservoir would be appropriate.

[00100] Fluids may be manually loaded by the user with a syringe, through the inlet valve 130, and directly into the reservoir 110. However, the fluid may be loaded through other means, such as, a cartridge system or an automatic loading system.

[00101] The reservoir 110 may be at least partially transparent. The reservoir 110 can also be transparent or opaque. Transparency has the advantage of allowing the operators of the bioprinting system to easily see the contents of the reservoirs 110 and, in particular, the amount of bioprinting fluid is in a particular reservoir.

[00102] Each reservoir is in fluid communication with a dispensing valve 150. The dispensing valve 150 may be a microvalve 150. In an embodiment, the microvalve is a solenoid valve.

[00103] Each dispensing valve 150 forms part of the dispensing system 180 of the detachable printhead, along with the reservoir assembly 100 and respective fluid connections. The dispensing system 180 is a droplet dispensing system. The dispensing system is configured to print droplets from the one or more reservoirs onto a substrate. In an embodiment, the fluid is pneumatically ejected from the reservoir 110 out of the dispensing valve 150, which is electronically controlled.

[00104] An embodiment of the coupling 200 is shown in Figure 5, in an exploded view. The coupling 200 includes a gasket 210, support ridges 225, retention plate 230, retention ring 240 and the internal body 170. The internal body 170 includes a central void 172 which receives a corresponding shaft 305 (see Figure 11 ) of the fixed portion 30. The retention plate 230 is attached to the internal body 170 through the use of one or more screws 220, and the retention ring 240 is held between the retention plate 230 and the internal body 170. Other embodiments are not limited to the use of screws, and any other means that would retain the parts together in the assembly would be considered as being covered by this disclosure. The gasket 210 assists in providing a fluidic seal between the reservoir caps of the reservoir assembly which protrude through the retention plate 230 and gasket 210, so that they can connect with appropriate fluidic connections on the fixed portion 30. The gasket 210 is optional in some embodiments and the fluidic seal is provided by the pneumatic connectors 135.

[00105] The detachable printhead 20 has an outer body 160. The outer body 160 may be moulded around the reservoir assembly 100 and attached to an inner body 170. The outer body 160 may at least partially transparent. The outer cover may have a textured lower portion. This textured portion allows a surgeon or other operator to grip and manoeuvre the detachable printhead 20.

[00106] The detachable printhead 20 may have a base portion 190, attached to the internal body 170 through the use of one or more screws 191 , having an opening 192 to enable a distance sensor to travel through the centre of the detachable printhead 20 (to be discussed in more detail below). The screws 191 may also take the form of pins or any other feature that may assist in aligning and/or attaching the detachable printhead 20.

[00107] The number of reservoirs may be selected to enable the printing of two materials that require two nozzles each. In an example, the two nozzles might separately contain a bio-ink and an activator for each material. The use of two nozzles (or 4, 6, 8, etc.) increases the printing speed of the printing assembly. However, the invention is not limited to this arrangement and an uneven number of nozzles could be utilised for printing and still be covered by the present disclosure.

[00108] In an embodiment, the detachable printhead 20 contains 8 reservoir assemblies 100 configured in a circular pattern. This configuration enables the dispensing valves to be equidistant from the distance sensor (located centrally) to improve the printing robustness when printing on an uneven surface. This arrangement also minimises the size of the detachable printhead 20 in the region closest to the printing surface, so that the bioprinter is easy to manoeuvre around the printing surface and reach more difficult locations.

Bioprinter

[00109] Figures 1 and 2 illustrate a bioprinter 10 which includes a fixed portion 30 and a detachable printhead 20. The detachable printhead 20 is removably attached to the fixed portion 30. As discussed previously, the bioprinter may comprise the fixed portion 30 and detachable printhead 20 or it may also comprise a mechanical manipulation device, such as a robotic arm 40 or a gantry robot 560.

[00110] An example including a gantry robot 560 is depicted in Figure 27. Figure 27 shows the detachable printhead 3020 mounted on an XY gantry robot 560, which includes two axes. The detachable printhead 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.

[00111] The bioprinter 10 includes an interface for operating the dispensing system 180 of the detachable printhead 20. As can be expected, the interface has two components, the detachable printhead interface and the fixed portion interface. In this embodiment, the fixed portion interface enables the pneumatic and electrical connection of the detachable printhead 20 to the rest of the bioprinter. The fixed portion 30 may contain other parts, such as hardware components. These hardware components may include a distance sensor 350, a camera, a control button or enable switch 450, a control system (including relevant interface to operate the bioprinter), or parts designed to provide safety or manoeuvrability advantages.

[00112] Figures 11 and 12 shows an embodiment of the fixed portion 30. The fixed portion 30 includes a front casing 410 and rear casing 420 that cover the internal components of the fixed portion 30. Figures 11 and 28 show different designs of the front casing 410 and rear casing 420 being different embodiments. The invention is not intended to be limited to the shape depicted in these two figures and could include other designs that still fit the purpose of covering the internal components of the fixed portion 30. In this embodiment, a seal 425 runs around the border of the rear casing 420. A robot mount 430 is provided for connecting the fixed portion 30 to the robotic arm 40.

[00113] The embodiment shown in Figure 11 provides a switch 450 on the fixed portion 30. The switch 450 activates a mode in which the robotic arm 40 can be hand guided by the user. This switch 450 allows the user to hand guide the bioprinter for a variety of reasons. For example, the switch 450 can enable an override mode, to override the automated printing and move the bioprinter 10 across more difficult surfaces or navigate harder to access areas of a surface. Alternatively, the switch 450 may allow a pre-printing mode to be entered in which the area to be printed is manually defined and the control system then controls the bioprinter to print in the areas defined during the pre-printing mode.

[00114] Further embodiments may include this switch in other locations of the bioprinter 10, such as on the detachable printhead 20, and the switch 450 may be removed in other embodiments.

[00115] The control system, and associated hardware, may include functions to control the dispensing valves in the detachable printhead 20.

[00116] Figures 11 to 15 illustrate various aspects of a connection portion 300, which is attached to one or both of the front and rear casing 410, 420 by screws 302. The connection portion 300 provides mechanical support to the detachable printhead 20 and enables the user to manipulate the bioprinter 10 without damaging any of the connections between the fixed portion 30 and the detachable printhead 20. [00117] Figure 11 shows the connection portion 300 in an exploded view. The connection portion 300 includes a shaft 305. This shaft 305 is intended to fit within the internal body 170 of the detachable printhead 30, and aids in providing support through the middle of the reservoir assembly 100. The shaft 305 may also provide an indexing function. Indexing aids in ensuring that the detachable printhead 30 is aligned correctly to the mating surfaces, such as the base 190. While these functions have been discussed in relation to the shaft 305, the invention is not limited to this and it is envisaged that other features could be utilised to provide the indexing function, such as the use of pins 193. The alternative features may be used independently or in conjunction with the use of a shaft.

[00118] Figure 13 shows the connection portion 300 in a position ready to be used with the detachable printhead 20.

[00119] The shaft 305 is attached to the mount assembly 310, which is shown in more detail in Figures 14 and 15. The shaft 305 is depicted in Figures 11 and 15 as being substantially extended from the mount assembly 310, however, alternative embodiments may depict the shaft 305 as shorter such as in Figures 12 and 13. The mount assembly 310 contains tubing 330 that facilities gas lines for bringing gas to the interface of the fixed portion 30.

[00120] The mount assembly 310 may comprise a distance sensor 350. In an embodiment, the distance sensor 350 is an optical distance sensing device, such as an optical sensing beam 355 based distance sensor 350. The distance sensor 350 is attached to the mount assembly 310 by on a mount 340. The distance sensor 350 is used to register the distance between the base 190 of the printhead and a printing substrate or subject. This assists the control system in safely and easily maintaining the required distance from the substrate.

[00121] The printing surface may be the surface of a subject, for example, the surface of a patient's skin. It is also envisaged that the distance sensor 350 may be disposed outside and coupled to the bioprinter 10. The distance sensor 350 may be an ultrasonic sensor, an optical sensor, a camera (or cameras), an inductive sensor, a capacitive sensor, a photoelectric sensor, a contact sensor that physically contacts the surface of a patient's skin, or any other suitable sensor known in the art that is capable of monitoring the distance between the base 190 of the detachable printhead 20 and the printing surface. The printing surface may be the wound of a subject. [00122] The mount assembly 310 may include a camera. The camera may be included instead of distance sensor 350 or in addition to the distance sensor 350 and, indeed, may function as the distance sensor 350.

[00123] In some embodiments, a window 375 is provided to enable the optical sensing beam 355, such as a laser, of the distance sensor 350 to exit the detachable printhead 20. It is also envisaged that the distance sensor 350 may be any other suitable means known in the art that can be used as a visual aid to position the bioprinter 10. The window 375 may not be required in other embodiments.

[00124] The mount assembly 310 includes a connector 345 for the distance sensor 350. A gasket 320 is provided to provide a seal with the remainder of the fixed portion 30 and the mount assembly 310.

[00125] In an embodiment, having an optical distance sensor 350 enables the sensor 350 mounted on remotely from the remote end of the shaft 305. In this instance, the shaft 305 allows the light to pass through its centre, preferably because it is hollow, and through the opening 192 of the detachable printhead 20 to register the distance between the subject and the base 190 of the detachable printhead 20, without the sensor being in the detachable printhead 20.

[00126] Alternative embodiments do not include an internal body 170 in the detachable printhead 20 and/or a shaft 305 provided by the connection portion 300. Further alternative embodiments include the distance sensor 350 in the detachable printhead 20.

[00127] Figures 13 and 15 illustrate the mount assembly 310 and its interaction with the coupling of the detachable printhead 20. The mount assembly 310 comprises a locking mechanism 360 and, together, they are adapted to removably attach a detachable printhead 20 and a fixed portion 30 (such as a fixed printhead 30) of the bioprinter. The mount assembly 310 is designed to enable a simple and reliable attachment process. The mount assembly 310 is designed to couple the detachable printhead 20 with the fixed portion 30 mechanically, whilst also bringing the interface(s) of the fixed portion 30 into contact with the interface of the detachable printhead 20, to provide electrical and pneumatic connections. [00128] The operation of the mount assembly 310 and retention ring 240 will be described below in relation to the fixed portion 30 and detachable printhead 20, however, other embodiments can utilise other mechanisms to detachably connect the detachable printhead 20 to other fixed parts, arms or portions of the bioprinter.

[00129] The retention ring 240 is moveable relative to the detachable printhead 20 circularly. That is, it can rotate about the internal body 170 without separating from that body 170. The mount assembly 310 comprises a plurality of pneumatic receiving portions 315 forming part of a pneumatic interface of the fixed portion interface. The plurality of pneumatic connectors 135 of the reservoir assemblies 110 protrude from the gasket 210 of the coupling 200, and form part of the detachable printhead interface. The pneumatic receiving portions 315 are spaced accordingly to receive the pneumatic connectors 135 of the detachable printhead 20.

[00130] The plurality of pneumatic receiving portions allows individual sources of pressure to align with individual reservoirs. This arrangement allows for the one or more reservoirs to receive different pressures at the same time, providing greater flexibility in the capability of the dispensing system.

[00131] 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.

[00132] In this embodiment, a single pressure source is provided to multiple reservoirs through the pneumatic interface 552, i.e. the pneumatic interface directs a single pressure source to one or more reservoirs. The pneumatic interface has a pneumatic receiving portion on one side to receive input from a pressurised air supply. However, in this embodiment, a manifold 550 is created within the pneumatic interface so that the direction of the flow of pressure can be manipulated within the manifold. Manifold valves 548 control the air supply to manifold outlets 554 which, when connected to a detachable printhead 20, are configured so that the single pressure source can direct pressure towards the inlets of multiple reservoirs.

[00133] An advantage of this embodiment is that an increase in the number of reservoirs does not necessarily involve an increase in the number of pressure sources. However, the invention is not limited to this and it is envisaged that multiple pressure sources could be implemented while still utilising a pneumatic interface such as the one described. Further advantages can be found in the ability to scale up the arrangement with a larger number of reservoirs without the need to accommodate the space for multiple pressure sources in the arrangement.

[00134] The mount assembly 310 comprises a plurality of ramp protrusions 317, or lugs, arranged around its circumference. The retention ring 240 has matching slots on its inner surface, which are strengthened by support ridges 225 so that the slot can act against the ramp protrusions to securely attach the detachable printhead 20 to the fixed portion 30. Importantly, this coupling mechanism allows the interface components of the detachable printhead 20 to connected without any rotation of those components. Only the retention ring 240 requires to be rotated.

[00135] The coupling mechanism is not limited to the use of the above examples and other designs may be implemented to securely attach the detachable printhead 20 to the fixed portion 30. For example, a cam and lever mechanism could be arranged to provide mechanical coupling between the detachable printhead and the fixed portion. The use of a cam 555 and lever 558 is shown in Figure 26. The cam 555 and lever 558 are used in combination to pull the detachable printhead onto the fixed portion.

[00136] In use, the detachable printhead 20 is located onto the shaft 305 and the pneumatic connectors 135 are pushed into the pneumatic receiving portions 315. At this point the retention ring 240 is rotated such that the slots on its inner surface engage with the ramp protrusions 317. Due to the protrusions having a predefined ramp size, the detachable printhead 20 is brought towards the fixed portion 30 to a predefined relative location.

[00137] Additionally, to prevent accidental release, the mount assembly 310 includes a locking mechanism 360 which incorporates a biased locking pin 365. The retention ring 240 comprises a locking recess (not shown) on its inner surface and the pin 365 of the locking mechanism engages with the locking recess when the retention ring 240 has been rotated to a predefined position. This prevents the retention ring 240 from being rotated without biasing the pin 365 away from the support ridges 225 with the locking mechanism 360. [00138] In addition, the shaft 305 comprises an end cap 370 which comprises a series of electrical connectors which provide electrical signals to dispensing valves 150 of the detachable printhead 20 (see Figures 9, 10, 15, 17 and 18).

[00139] Figure 9 shows a detachable electrical interface 255, forming part of the detachable printhead interface, and comprising dispensing electrical connections 260, in the form of pogo-pins, on one side of a substrate and header connectors 270 on the other side of the substrate. A pair of dispensing connections 260 are connected to a header 270 which is in turn connected to a dispensing valve 150. The detachable electrical interface 255 is positioned in the internal body 170 where it would be contacted with the end of the shaft 305, when attached to the fixed portion 30. Figure 10 shows an alternative embodiment of the detachable electrical interface where 16 reservoir assemblies 110 are used instead of 8.

[00140] The shaft 305 of the fixed portion 30 includes, in the end cap 370, a fixed portion electrical interface as part of the fixed portion interface. The fixed portion electrical interface comprises dispensing connections 380 and header connectors 390. The dispensing connections 380 are arranged to coordinate with the detachable dispensing connections 260 such that when the shaft 305 is inserted into the internal body 170, the control system has electrical connections to the dispensing valves 150 and can operate the dispensing valves 150 as required.

[00141] Figure 19 illustrates where the detachable printhead 20 is removably attached to the fixed portion 30. That is, the shaft 305 is fully inserted into the internal body 170 and both pneumatic and electrical connections have been made. Also shown is the optical sensing beam 355 from the distance sensor 350.

Bioprinting Platform

[00142] The detachable printhead 20 may be used as part of a drop-on- demand bioprinter. The drop-on-demand bioprinter deposits biomaterials onto a substrate. The bioprinter may also use patient cells. In an embodiment, the substrate can be the site of an injury of a patient.

[00143] The bioprinter 10 may be attached to a mobile base 50. The mobile base 50 houses subsystem components that enable the bioprinter 10 to function and which have, in general, been described as part of the fixed portion 30. The mobile base 50 enables the mobility of the platform from various locations within the facilities, such as a hospital. The mobile base 50 may contain the functions such as printing pneumatics, a robotic controller, braking if the bioprinter is movable, along with computer parts and electronics. The robotic arm 40 is attached to the fixed portion 30 and enables the movement of the bioprinter 10. This movement provides space around the substrate along with providing the precision required to deposit the treatment to the substrate. In an embodiment, the robotic arm 40 is the Kuka LBR MED which is certified for use as a component in a medical device. However, the invention is not limited to the use of this robotic arm, and alternatives may be utilised. For example, while a robotic arm is discussed in this example, it is envisaged that a gantry robot could be utilised to provide the manipulation of the detachable printhead 3020.

[00144] The various components that are utilised by the bioprinter 10 may be housed in any desired manner. For example, they may be attached to or located on/within a static structure or may be attached to or located on/within a mobile structure, such as a trolley. Figure 20 shows an embodiment in which the mobile base 50 is a trolley. The robotic arm 40 is attached to the trolley 50 via the mounting base 45 of the robotic arm 40. The trolley 50 allows movement of the bioprinting system 60 to a desired location, making the bioprinting system 60 portable such that, for example, the bioprinting system 60 can be moved between medical locations. The trolley 50 also may comprise control systems and graphic user interfaces for operation of the bioprinter 10. This embodiment demonstrates the self-contained nature of the bioprinting system 60, That is, the bioprinting system 60 can be moved to the location it is required on the trolley 50 whilst having all systems required to operate the bioprinter 10. According to other embodiments, the robotic arm 40 could be mounted on another surface or at a fixed location. Figure 1 shows the robotic arm 40, fixed portion 30 and detachable printhead 20 when not attached to the trolley 50.

[00145] In an embodiment, the detachable printhead 20 consists of the dispensing valves, reservoirs, check valves and the electrical and mechanical components and fittings necessary to house and control these components. In this embodiment, the sensing and the remaining electronics are housed in the fixed portion 30. However, alternative embodiments, where the components are located in another part of the bioprinter 10, are envisaged. This includes, but is not limited to, configurations where the check valves are located in the fixed portion or the reservoirs are located in the fixed portion.

Printing Method

[00146] According to an embodiment, the bioprinter 10 prints a fluid or a gel using a drop-on-demand method. In this method, at least one reservoir 110 is primed with a bio-ink and at least one reservoir 110 is primed with an activator. One or more reservoirs 110 are arranged in a reservoir assembly 100 within a detachable printhead 20. The detachable printhead 20 is removably attached to a fixed portion 30 and locked into place using a locking mechanism. When connected together, a connection portion 300 provides a shaft 305 through the internal body 170 of the detachable printhead 30. The detachable printhead 20 and the fixed portion 30 form a bioprinter 10.

[00147] 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 within the fixed portion 30, is configured to monitor the distance between the base 190 of the detachable printhead 20 and a printing surface. The printing surface may be the surface of a subject, for example, a wound on the surface of a patient's skin.

[00148] To form a fluid or gel using the drop-on-demand method described above, it will be appreciated that, using current technology biomaterials, a minimum of two reservoirs 110 included in the detachable printhead 20 will often be required. Multiple reservoirs 110 can be utilised to improve printing speed or where insufficient biomaterials can be held in the minimum reservoirs required. However, in some embodiments, only one reservoir is required.

[00149] Additional reservoirs could be used to add additional materials to increase the biological complexity of the structures that are created.

[00150] In this instance, multiple reservoirs may be primed with bio-ink and that multiple reservoirs 110 may be primed with an activator. In this case, for example, when all the bio-ink has been dispensed from one reservoir 110, bio-ink will be dispensed from another reservoir 110. This will reduce the need to pause the printing regime to re-prime a reservoir 110. It is also envisaged that the reservoirs 110 may be primed with different types of liquids. If the reservoirs 110 are primed with different liquids, the bioprinter 10 may be able to form a gel having layers of different materials, layers that include different cells and/or medicaments, and/or different liquids printed/deposited between each layer of the gel.

[00151] It is important that all portions of the bioprinting system that are likely to be in contact with the patient or any of the other clinical users are sterile. This includes the steps that are outlined above, as well as any steps involved in detaching and/or replacing the detachable printhead from the bioprinter.

[00152] This can be achieved through the use of a sterile drape. A sterile drape can be used to ensure that the portions or parts of the bioprinting system that may touch the patient or the user are protected from doing so in an unsafe manner. All embodiments described herein may be configured to be compatible with the use of a sterile drape.

[00153] Sterile draping can be carried out by installing the sterile drape onto the bioprinting system initially with a sterile adapter on the fixed portion of the bioprinter. The sterile detachable printhead can then be attached to the sterile adapter. Use of a sterile adaptor to ensure the sterility of surgical tools and robots is common practice.

[00154] Sterile draping may also be achieved by installing the sterile drape and the sterile printhead simultaneously. While the following method is discussed as being completed by two users, this method can be completed by a single user or more than two users. Typically, the method is carried out by one or two users.

[00155] The robotic arm can be straightened and moved to a position that provides plenty of room to manoeuvre around it for the draping process. A first user inserts the detachable printhead into the sterile drape, before attaching the drape below the lock ring and above the check or one-way valves through the use of sterile tape. This placement can allow the reservoirs to be more easily seen in some embodiment.

[00156] While the first user keeps the detachable printhead in place, the second user attaches the fixed printhead to the detachable printhead. The first user then inverts the sterile drape over the detachable printhead and fixed portion. A preliminary system pressure check may be performed following this step. The second user then pulls the sterile drape along the robotic arm. Straps may be attached to the sterile drape and robotic arm to limit the movement of excess draping material. [00157] Other methods to maintain a sterile process and environment may be employed in conjunction with the bioprinting method outlined above.

[00158] With this in mind, the printhead may assist in providing a number of non-obvious advantages. For example:

• The detachable printhead provides for easy sterilisation of the bioprinter between printing surfaces as the detachable printhead can be removed from the rest of the printhead assembly and processed before use.

• The sterilised detachable may be used a predetermined number of times without need for disposal.

• Embodiments of the detachable printhead are designed to be disposable after single use which reduces the sterilisation risk between patients.

• The detachable printhead facilitates the optimisation of the coupling of fluidic components to reduce dead volume, hence minimise potential cell wastage

• The detachable printhead enables the configurability of the printhead for a user's application by enabling the maximum loaded sample volume, type of dispensing technology and number of dispensing modules to be varied independently of the bioprinting system.

• The detachable printhead enables the user to load a fluid sample into a detached printhead in a sterile environment, such as a bio safety cabinet, before installing the printhead on the system to enable the use of the bioprinting system in a non-sterile setting without risking contamination.

• The detachable printhead improves the ease of with which cleaning and servicing can be conducted, and is inherently replaceable in the event of a component failure.

• In one of the desired embodiments, the size and configuration of the reservoir assembly has been designed to minimise the size of the detachable printhead in the region that is close to the patient. This makes it easier to manoeuvre the detachable printhead around a patient and print on difficult-to-access parts of the body.

In one of the desired embodiments, the use of the switch allows for additional user control over the speed and positioning of the printing. • In one of the desired embodiments, the detachable printhead is configured to enable a distance sensor to be housed in the fixed portion so that the, relatively, expensive, high precision sensing components are not in the detachable printhead, which may be single use or may be restricted in the number of times it can be used.

• In one of the desired embodiments, the shaft of the connection portion of the fixed portion reinforces the coupling of the detachable printhead and enables safe manipulation of the printhead/system without putting mechanical stress on the interface (such as the pneumatic and electrical connections).

• The bioprinter, and therefore the detachable printhead, is non-contact which reduces the potential for contamination and disturbance of a print area, such as a wound.

[00159] Referring now to Figure 21 , a schematic diagram of the bioprinting system 60 is shown. Where elements of the schematic diagram have been previously described, like reference numerals are used to refer to those elements in this Figure as have been previously used herein.

[00160] In preparation for printing, biomaterials 510 and autologous biologic material 512 are prepared and loaded via inlet valve 130 into reservoirs 110.

[00161] A mobile base, or trolley, 50 houses a system control 502 and pneumatics 504. The pneumatics 504 provides the necessary elements to provide a gas, normally air, supply to the fixed portion 30 and, ultimately, the detachable printhead 20. Various sensors provide feedback 506 to the system control 502. From this information, and from other data and settings provide via a system interface, such as a graphical user interface, the system control 502 operates the bioprinter in the form of moving the robotic arm 40 and printing via the detachable printhead 20. The distance sensor 350 provides feedback as to the distance of the detachable printhead 20 from a wound site of a patient 508. The detachable printhead prints the biomaterials, being the prepared biomaterials 510 and autologous biologic material 512, onto a printing area, being the wound site of the patient 508 in this example. The nature of the biomaterials used allows for a three dimensional biological print which has significant advantages for wound healing. [00162] Many characteristics of the printhead architecture described are specific to bioprinting, i.e. the creation of 3D biological constructs with cells, and are not directly transferable to or from other printing technologies. For instance, the design of the reservoirs and their working volumes have been optimised to handle precious fluids such as patient cells at volume ranges and losses specific to bioprinting applications. One such example is that the working range of volumes compatible with the described detachable printhead architecture spans from 5 pL to 50 mL.

[00163] The types of materials that the described printhead architecture must support include a suite of materials of interest for scientists and clinicians engaging in research or clinical care. These types of materials include cells, tissue, bio-ink, crosslinking agents, growth media, growth factors, buffers/cell buffers, and manufactured (ie Laminin, Fibrinogen, Collagen) and point of care platelets rich plasma, serum) biological fluid products.

[00164] The materials and volumes supported by the described printhead architecture are deposited via printing parameters and processes that have been optimised for the creation of 3D biological constructs. These result in the generation of droplets in a working range of 1 nL to 200 nL with high biological viability.

[00165] The creation of 3D biological constructs using droplets of the specified volume range, of the specified fluids detailed above, is achieved by parameterisation of the following features of the printhead design and printing process: back pressure; dispensing nozzle orifice diameter; dispensing valve opening time; dispensing nozzle orifice surface energy; fluid path dead volume; fluid viscosity; fluid surface tension; fluid particle size distribution; process duration; and droplet deposition accuracy.

[00166] It will be appreciated by persons skilled in the art that numerous variations and/or modifications may be made to the invention as shown in the specific embodiments without departing from the spirit or scope of the invention as broadly described. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive.

[00167] Although the invention has been described with reference to the embodiments above, it will be appreciated by persons skilled in the art that the invention may be embodied in many other forms. It will be appreciated by persons skilled in the art that numerous variations and/or modifications may be made to the technology as shown in the specific embodiments without departing from the spirit or scope of technology as broadly described. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive.

[00168] In this specification, adjectives such as left and right, top and bottom, hot and cold, first and second, and the like may be used to distinguish one element or action from another element or action without necessarily requiring or implying any actual such relationship or order. Where context permits, reference to a component, an integer or step (or the alike) is not to be construed as being limited to only one of that component, integer, or step, but rather could be one or more of that component, integer or step.

[00169] In this specification, the terms ‘comprises’, ‘comprising’, ‘includes’, ‘including’, or similar terms are intended to mean a non-exclusive inclusion, such that a method, system or apparatus that comprises a list of elements does not include those elements solely, but may well include other elements not listed.

[00170] Throughout this specification, the term 'consisting of means consisting only of.

[00171] Unless the context requires otherwise or specifically stated to the contrary, integers, steps, or elements of the technology recited herein as singular integers, steps or elements clearly encompass both singular and plural forms of the recited integers, steps or elements.

[00172] In the context of the present specification the terms 'a' and 'an' are used to refer to one or more than one (ie, at least one) of the grammatical object of the article. By way of example, reference to 'an element' means one element, or more than one element.

[00173] In the context of the present specification the term 'about' means that reference to a figure or value is not to be taken as an absolute figure or value, but includes margins of variation above or below the figure or value in line with what a skilled person would understand according to the art, including within typical margins of error or instrument limitation. In other words, use of the term 'about' is understood to refer to a range or approximation that a person or skilled in the art would consider to be equivalent to a recited value in the context of achieving the same function or result. [00174] The above description relating to embodiments of the present disclosure is provided for purposes of description to one of ordinary skill in the related art. It is not intended to be exhaustive or to limit the disclosure to a single disclosed embodiment. As mentioned above, numerous alternatives and variations to the present disclosure will be apparent to those skilled in the art from the above teaching. Accordingly, while some alternative embodiments have been discussed specifically, other embodiments will be apparent or relatively easily developed by those of ordinary skill in the art. The present disclosure is intended to embrace all modifications, alternatives, and variations that have been discussed herein, and other embodiments that fall within the spirit and scope of the above description.

Item List:

Claims

Claims:

1 . A detachable printhead for a bioprinter, the detachable printhead 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, in fluid communication with the dispensing system, supported by the body; and a coupling for attaching to the fixed portion of the bioprinter, the coupling including an interface for operating the dispensing system.

2. A detachable printhead according to claim 1 , wherein the body comprises an outer body and wherein the outer body substantially surrounds the dispensing system.

3. A detachable printhead according to claim 2, wherein the outer body is at least partially transparent at least in some areas.

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

5. A detachable printhead according to claim 4, wherein the body comprises an internal body and the reservoirs are arranged on the outer surface of the internal body.

6. A detachable printhead according to any one of the preceding claims, wherein the body includes a central void for receiving a corresponding extending portion of the fixed portion, preferably, the central void is circular in cross section.

7. A detachable printhead according to any one of the preceding claims, wherein the body has a central axis perpendicular to a coupling face of the coupling.

8. A detachable printhead according to claim 7, wherein the central void has a centre point located on the central axis, preferably, the centre point is on a void axis and the void axis and central axis are colinear.

9. A detachable printhead 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 about the central axis, preferably, the two or more reservoirs are arranged in a circle around a reservoir axis, and further preferably, the reservoir axis and central axis are colinear.

10. A detachable printhead according to any one of the preceding claims, 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 is adapted to allow insertion of a fluid into the reservoir and, further preferably, the inlet valve may be a check valve and/or a one-way valve.

11. A detachable printhead according to any one of the preceding claims, wherein the coupling is capable of providing a suitable connection for the interface for operating the dispensing system.

12. A detachable printhead according to any one of the preceding claims, wherein the coupling is adapted to removably attach a detachable printhead to a fixed portion of the bioprinter.

13. A detachable printhead according to any one of the preceding claims, wherein the interface includes a plurality of dispensing electrical connections capable of a interfacing with fixed portion dispensing connection, the dispensing electrical connections providing electrical signals to one or more dispensing valves of the dispensing system.

14. A detachable printhead according to claim 13, wherein the central void comprises the plurality of dispensing electrical connections, preferably, the plurality of dispensing electrical connections are situated at the end of the central void.

15. A detachable printhead according to any one of the preceding claims, wherein the interface includes a pneumatic connector for one or more reservoirs.

16. A detachable printhead according to any one of the preceding claims, wherein the interface includes an integrated pressure distribution function in which a single pressure source is directed to one or more reservoirs.

17. A detachable printhead according to any one of the preceding claims, wherein the dispensing system is a droplet dispensing system.

18. A detachable printhead according to claim 16 or claim 17, wherein the droplets are pneumatically ejected from the reservoir out of the dispensing valve, and, preferably, wherein the dispensing valves are microvalves.

19. A detachable printhead according to any one of claims 1 to 15, wherein the dispensing system is an extrusion system.

20. A detachable printhead according to any one of claims 16 to 19, wherein the printing area is a wound in a subject, such as an animal or human patient, preferably, the wound is a wound in the subject's skin, and, further preferably, the fluid dispensed by the dispensing system forms a gel over the wound.

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

22. A detachable printhead according to any one of claims 1 to 20, wherein the detachable printhead is re-usable.

23. A detachable printhead according to any one of claims 1 to 22, wherein the detachable printhead is sterilisable.

24. A detachable printhead according to any one of claims 1 to 23, wherein the detachable printhead comprises a distance sensor and/or a camera.

25. A bioprinter comprising a fixed portion, capable of receiving one or more detachable printheads, wherein each detachable printhead comprises a body; a dispensing system, supported by the body; one or more reservoirs, for holding one or more biomaterials, in fluid communication with the dispensing system, supported by the body; and a coupling for attaching to the fixed portion of the bioprinter, the coupling including an interface for operating the dispensing system, the bioprinter further comprising systems to control the interface and operate the dispensing system of the detachable printhead.

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

27. A bioprinter according to claim 25, wherein one or more detachable printheads are individually attached to the fixed portion of the bioprinter.

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

29. A bioprinter according to any one of claims 25 to 28, wherein the fixed portion includes a distance sensor, wherein the distance sensor provides the distance between the detachable printhead and a printing area.

30. A bioprinter according to claim 25 or claim 26, wherein the fixed portion includes a shaft for insertion into a corresponding void in the detachable printhead.

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

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

33. A method for using a bioprinter is disclosed, the method including the steps of: attaching a detachable printhead to a fixed portion of the bioprinter, the detachable printhead comprising a body, a dispensing system, supported by the body, and a coupling for attaching to the fixed portion of the bioprinter, the coupling including 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.