Detachable printing head for bio-printer and bio-printer

Abstract

Disclosed is a removable printhead for a bio-printer, the removable printhead comprising: a body removably attached to a fixed portion of the bio-printer; a dispensing system supported by the body; one or more reservoirs for containing one or more biological materials and in fluid communication with the dispensing system and supported by the body; and a coupling for attachment to a fixed portion of a bio-printer, the coupling comprising an interface for operating the dispensing system.

Description

Technical Field

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

[0002] Cross - Reference to Related Applications

[0003] This application claims the priority of Australian Provisional Patent Application No. 2022903386, the entire content of which is incorporated herein by reference. Background Art

[0004] Hospitals are a fast - paced environment. Healthcare professionals often need to move between different patients and use a variety of instruments in a short period of time. Instrument contamination, surface contamination, and poor hygiene of patients or healthcare professionals can all lead to the spread of diseases and infections.

[0005] Therefore, the sterilization and disinfection of instruments play an important role in preventing nosocomial infections and the spread of diseases. Sterile equipment is particularly important in wound care.

[0006] Any reference or discussion in this specification to any document, act, or item of knowledge is incorporated only for the purpose of providing background to the present invention. It is not implied or represented that any one of these matters, or any combination thereof, formed part of the common general knowledge at the priority date or was known to be relevant to solving any problem addressed in this specification. Summary of the Invention

[0007] In one form, a detachable print head for a bioprinter is disclosed. The detachable print head includes: a body removably attached to a fixed part of the bioprinter; a dispensing system supported by the body; one or more reservoirs for containing one or more biological materials, in fluid communication with the dispensing system and supported by the body; and a coupling for attaching to the fixed part of the bioprinter, the coupling including an interface for operating the dispensing system.

[0008] In one embodiment, the dispensing system includes one or more reservoirs for containing one or more biological materials. The one or more reservoirs have an internal volume for containing fluid. In one embodiment, there is a single reservoir. In another embodiment, there are two or more reservoirs.

[0009] In one embodiment, the body includes an inner body, and the reservoirs are arranged on the outer surface of the inner body. In one embodiment, each reservoir is part of a reservoir assembly that is also part of the dispensing system.

[0010] In one embodiment, the body (preferably the inner body) includes a central void for receiving a corresponding extension of the fixed portion. In one embodiment, the cross-section of the central void is circular.

[0011] In one embodiment, the body has a central axis perpendicular to the coupling surface of the coupling member. In one embodiment, the central void has a central point located on the central axis. In one embodiment, the central point is located on the void axis, and the void axis is collinear with the central axis.

[0012] In one embodiment, the body has an outer body, where the outer body substantially surrounds the dispensing system. The outer body can be at least partially transparent in at least some regions. In one embodiment, the outer body is at least partially transparent in a region where the fluid level of one or more reservoirs can be inspected.

[0013] In one embodiment, one or more reservoirs are arranged around the central axis. In one embodiment, one or more reservoirs are arranged in a circle around a reservoir axis. In one embodiment, the reservoir axis is collinear with the central axis. In an alternative embodiment, one or more reservoirs are arranged in a rectangular array.

[0014] In one embodiment, one or more reservoirs are individually mounted within the dispensing system.

[0015] In an alternative embodiment, one or more reservoirs are attached to the fixed portion of the bioprinter. In one embodiment, one or more reservoirs are arranged around the central axis. In one embodiment, one or more reservoirs are arranged in a circle around a reservoir axis. In one embodiment, the reservoir axis is collinear with the central axis. In an alternative embodiment, one or more reservoirs are arranged in a rectangular array.

[0016] In an alternative embodiment, one or more reservoirs are individually attached to the fixed portion of the bioprinter.

[0017] In one embodiment, the reservoir or each reservoir has at least one inlet and at least one outlet. In one embodiment, at least one inlet is arranged at the end of the reservoir closest to the coupling member. In one embodiment, at least one outlet is arranged at the end of the reservoir farthest from the coupling member. The reservoir or each reservoir has a reservoir axis parallel to the central axis representing the center of the internal volume. In one embodiment, at least one outlet is spaced from the central axis. Keeping the reservoir outlet as close as possible to the central axis can minimize the bottom surface size of the detachable print head. Minimizing the bottom surface size of the detachable print head allows each droplet dispensing valve (discussed below) to be as close to each other as possible. This in turn allows for more precise printing and ease of use.

[0018] In one embodiment, one or more reservoirs are generally cylindrical along most of their length. In one embodiment, one or more reservoirs have a tapered section towards the outlet or each outlet, where the taper is away from the reservoir axis towards the central axis.

[0019] 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 the introduction (insertion) of fluid into the reservoir. In one embodiment, the inlet valve can be a check valve and / or a one-way valve.

[0020] In one embodiment, one or more reservoirs can be at least partially transparent. One or more reservoirs can be transparent. Alternatively, one or more reservoirs can be opaque.

[0021] 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 detachable printhead can include an odd number of reservoirs. For example, in one embodiment, there is a single reservoir. In one embodiment, one or more reservoirs are mounted individually.

[0022] In one embodiment, each reservoir has a cap attached to the inlet of the reservoir. In one embodiment, the cap can be used to seal the fluid in the reservoir. The cap is adapted to allow gas to enter the reservoir while not allowing fluid to leave through the first end of the reservoir. In one embodiment, the cap includes a pneumatic connector such that gas (e.g., air) can be provided to the reservoir. In one embodiment, the reservoir can be pressurized by means of a pneumatic connection and other inlets / outs. In one embodiment, the cap includes one or more filters. In one embodiment, the filter or each filter is hydrophobic, thus slowing down the passage of fluid through the filter.

[0023] The coupling is adapted to removably attach the detachable printhead to a fixed part of the bioprinter. That is, when disassembling or attaching to the fixed part, the coupling can be operated without the use of tools, so the coupling is manually operable.

[0024] In one embodiment, the coupling is capable of providing a suitable connection for an interface to operate a dispensing system. In one embodiment, the coupling includes a retention ring that rotates around the interface to engage with a fixed portion. In one embodiment, the retention ring is arranged to pull a detachable print head to a fixed position when a retaining ring rotates. In one embodiment, the retention ring provides a quick-release mechanism to engage with the fixed portion. In one embodiment, the quick-release mechanism includes a lug and slot coupling. That is, at least one lug or slot is provided on the coupling, which engages with a corresponding at least one lug or slot on the fixed portion. In one embodiment, each lug or slot is arranged to pull the detachable print head to a fixed position when the retaining ring rotates.

[0025] In one embodiment, the retaining ring has threads corresponding to the corresponding threads on the fixed portion, and the detachable print head is pulled to a fixed position when the retaining ring rotates.

[0026] In one embodiment, the retaining ring includes a recess for a locking pin. In one embodiment, when the retaining ring has rotated sufficiently, the recess is capable of receiving a corresponding locking pin.

[0027] In an alternative embodiment, a cam and lever mechanism provides a mechanical coupling between the detachable print head and the fixed portion. In this embodiment, the cam and lever mechanism is arranged to pull the detachable print head to the fixed portion.

[0028] In one embodiment, the interface includes a plurality of dispensing electrical connections that can interface with the dispensing connections on the fixed portion, and the dispensing electrical connections provide electrical signals to one or more dispensing valves of the dispensing system. In one embodiment, the central void includes a plurality of dispensing electrical connections. In one embodiment, the plurality of dispensing electrical connections are located at the ends of the central void.

[0029] In one embodiment, the interface includes a pneumatic connector for each reservoir. In one embodiment, the reservoir lid includes a pneumatic connector.

[0030] In an alternative embodiment, the pneumatic interface includes an integrated pressure distribution function. In this embodiment, a single pressure source can provide pneumatic connectors to multiple reservoirs. For example, the pneumatic interface can involve directing a single pressure source to one or more reservoirs.

[0031] In one embodiment, the dispensing system can be a droplet dispensing system. In one embodiment, the droplet dispensing system can include one or more dispensing valves. In one embodiment, the one or more dispensing valves are in fluid communication with the reservoir or at least one outlet of each reservoir. In one embodiment, the dispensing valve is electrically actuated. In one embodiment, the dispensing valve can be a microvalve. In one embodiment, the microvalve can be a solenoid valve.

[0032] In one embodiment, the dispensing system is configured to print on a printing area. In one embodiment, the droplet dispensing system prints fluid droplets onto the printing area.

[0033] In one embodiment, the sample droplets are pneumatically ejected from the reservoir through the dispensing valve. In a preferred embodiment, the dispensing valve is a microvalve.

[0034] In an alternative embodiment, the dispensing system is an extrusion system.

[0035] In one embodiment, the printing area is a wound of a subject (such as an animal or a human patient). In one embodiment, the wound is a wound on the subject's skin, and the fluid dispensed by the dispensing system forms a gel on the wound.

[0036] In one embodiment, the detachable print head is disposable. In one embodiment, the detachable print head is reusable. In one embodiment, the detachable print head is sterilizable.

[0037] In one embodiment, the detachable print head can include a distance sensor.

[0038] In one embodiment, the detachable print head can have a window. The window can be a channel through the detachable print head or a transparent substrate. In one embodiment, the window enables a distance sensor beam to pass through the detachable print head. In one embodiment, the distance sensor is remote from the detachable print head.

[0039] In another form, a bioprinter is disclosed that includes a fixed portion capable of receiving one or more detachable print heads, where each detachable print head includes: a body; a dispensing system supported by the body; one or more reservoirs for containing one or more biomaterials, in fluid communication with the dispensing system and 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, and the bioprinter further includes a system for controlling the interface and operating the dispensing system of the detachable print head.

[0040] 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.

[0041] In one embodiment, one or more detachable print heads are individually attached to a stationary portion of the bioprinter.

[0042] In one embodiment, the stationary portion is movable to position one or more detachable print heads.

[0043] In one embodiment, the stationary portion may include a switch, where the switch allows a user to override any automatic printing and manually operate the bioprinter, and / or allows the bioprinter to operate in a mode that allows manual guidance of the positioning of the bioprinter.

[0044] In one embodiment, the stationary portion may include a distance sensor, where the distance sensor provides the distance between the detachable print head and the printing area. In one embodiment, the stationary portion includes a shaft that is inserted into a corresponding void in the detachable print head. In one embodiment, the shaft is configured to allow distance sensor measurements through the center of the shaft. In an alternative embodiment, the shaft is configured to allow a camera to operate through the center of the shaft. In an alternative embodiment, the shaft is configured to allow both a camera and a distance sensor to operate through the center of the shaft. In one embodiment, the shaft includes an electrical distribution connection for the stationary portion to control corresponding dispensing valves in the detachable print head.

[0045] In one embodiment, the stationary portion includes a connection portion. In one embodiment, the connection portion includes a pneumatic interface that is capable of providing a pneumatic connection to a pneumatic connector of the detachable print head. In an alternative embodiment, the pneumatic interface includes an integrated pressure distribution function, where a single pressure source can be directed to one or more reservoirs.

[0046] In one embodiment, the body includes an inner body, and the reservoirs are disposed on the outer surface of the inner body. In one embodiment, each reservoir is part of a reservoir assembly that is also part of the dispensing system.

[0047] In an alternative embodiment, one or more reservoirs are individually attached to a stationary portion of the bioprinter.

[0048] In another form, a bioprinting system is disclosed that includes the bioprinter as described above and further includes a robotic arm for manipulating the bioprinter.

[0049] In an alternative form, a bioprinting system is disclosed, which includes the bioprinter as described above and further includes a gantry robot for manipulating the bioprinter.

[0050] In yet another form, a method of using a bioprinter is disclosed, the method comprising the steps of:

[0051] attaching a detachable print head to a fixed part of the bioprinter, the detachable print head including a body, a dispensing system supported by the body, and a coupling for attaching to the fixed part of the bioprinter, the coupling including an interface for operating the dispensing system;

[0052] controlling the bioprinter to move on a printing surface; and

[0053] forming a fluid or gel on the printing surface.

[0054] In one embodiment, the method further includes the step of using a sterile drape.

[0055] Further features and advantages of the present disclosure will become apparent from the following detailed description. BRIEF DESCRIPTION OF THE DRAWINGS

[0056] Embodiments will now be described by way of example only and with reference to the drawings, in which:

[0057] Figure 1 An isometric view of a bioprinter according to one embodiment is shown, the bioprinter including a detachable print head, a fixed part, and an arm;

[0058] Figure 2 A front view and a side view of a print head assembly according to one embodiment are shown, the print head assembly including a detachable print head and a fixed part;

[0059] Figure 3 is a front view of a detachable print head according to one embodiment;

[0060] Figure 4 is Figure 3 a cross-sectional view of the detachable print head of

[0061] Figure 5 is Figure 3 an exploded view of the detachable print head of

[0062] Figure 6 is Figure 3 an isometric view of a single reservoir and dispensing valve of the detachable print head of

[0063] Figure 7 is Figure 3Side cross-sectional view of a single reservoir and a single dispensing valve of a detachable print head;

[0064] Figure 8 is Figure 3 Exploded perspective view of a detachable print head;

[0065] Figure 9 Perspective view showing the connection part of a variant of 8 reservoirs for a detachable print head from a top three-dimensional angle;

[0066] Figure 10 Perspective view showing the connection part of a variant of 16 reservoirs for a detachable print head from a top three-dimensional angle;

[0067] Figure 11 Perspective view of a fixed part according to an embodiment;

[0068] Figure 12 Exploded component view of a fixed part according to an embodiment;

[0069] Figure 13 Perspective view of an installation assembly according to an embodiment;

[0070] Figure 14 Perspective view of the connection part of a fixed part according to an embodiment;

[0071] Figure 15 Exploded component view of an installation assembly according to an embodiment of the present invention;

[0072] Figure 16 Side view of a locking clip of a locking mechanism according to an embodiment;

[0073] Figure 17 is according to an embodiment from Figure 3 Exploded perspective view seen from the bottom of the shaft of a fixed part;

[0074] Figure 18 is from Figure 17 Perspective view of a bayonet end cap seen from the bottom of the shaft shown;

[0075] Figure 19 is from Figure 2 Front cross-sectional view seen from the bottom of a print head assembly, showing a detachable print head and a fixed part in a connected state;

[0076] Figure 20 Perspective view of a bioprinting system according to an embodiment;

[0077] Figure 21 Block diagram of a bioprinting system according to an embodiment;

[0078] Figure 22 Is a perspective view of an alternative embodiment of a detachable print head;

[0079] Figure 23 Shows an isometric view of a bioprinter according to an embodiment, showing the fixed part and the robotic arm, and four Figure 22 The detachable print heads of the embodiment shown are respectively attached to the fixed part;

[0080] Figure 24 Shows an embodiment of a pneumatic interface, which shows an integrated pressure distribution manifold;

[0081] Figure 25 Shows Figure 24 The pneumatic interface of, which is coupled to a detachable print head according to an embodiment;

[0082] Figure 26 Shows an alternative embodiment of a locking mechanism;

[0083] Figure 27 Shows a side view of a bioprinter according to an embodiment, the bioprinter including a detachable print head and a gantry robot; and

[0084] Figure 28 Is a perspective view of a front housing and a rear housing according to an embodiment. Detailed Description

[0085] Figure 1 And Figure 2 Shows a bioprinter 10 according to an embodiment. In this embodiment, the bioprinter 10 has a fixed part 30, a detachable print head 20, a robotic arm 40, and a mounting base 45. The fixed part 30 is attached to the robotic arm 40 in a manner that requires one or more tools to remove. The detachable print head 20 is attached to the fixed part 30 in a manner that does not require any tools. That is, when used herein, "detachable" describes the ability of the print head to be removed and reattached without the use of tools. The detachable print head 20 has a central axis 35, which is generally perpendicular to the coupling surface 307 of the connecting part 300 of the fixed part 30 (see Figure 11 And 12 ).

[0086] A bioprinter having the general concept of a robotic arm and a print head attached to the robotic arm is disclosed in WO2021 / 108870A1, the entire disclosure of which is incorporated herein by reference. As disclosed therein, the robotic arm of the bioprinter has six rotational axes, and the robotic arm 40 disclosed in this specification has a similar function. In other embodiments, alternative mechanical manipulation devices may be used in combination with the fixed part 30 and the corresponding detachable print head 20. For example, the bioprinter 10 may include a detachable print head 3020 manipulated by a gantry robot (see Figure 27 ).

[0087] The fixed part 30 can be detachably attached to the bioprinter 10 by means of a special tool and taking a considerable amount of time. It is designed to be used with a plurality of disposable and / or reusable detachable print heads 20. Therefore, the fixed part 30 can be regarded as a permanent component of the bioprinter 10, while one or more detachable print heads 20 are more easily attached and removed in a simple manner (and preferably by manual operation) during the use of the bioprinter. In other embodiments, the fixed part 30 may be permanently attached to the bioprinter 10.

[0088] In all the previously discussed arrangements, the fixed part 30 is movable. That is, the fixed part 30 is part of the bioprinter 10, and the bioprinter needs to manipulate the detachable print head 20 located on the fixed part 30.

[0089] Detachable print head

[0090] Figures 3 to 5 、 Figure 8 Shows various views of a detachable print head 20 for a bioprinter 10 according to one embodiment. Figure 22 and Figure 23 Shows an alternative embodiment of a detachable print head 1020 for a bioprinter 1010.

[0091] The detachable print head 20 is capable of receiving the biological materials and cells required to print a liquid onto a subject's site. In one embodiment, the detachable print head 20 is a single-use detachable print head, which means it is designed to be discarded after a single use. In this way, the single-use detachable print head can be prepared for use in a sterile environment in order to minimize and preferably eliminate any contamination. The single-use detachable print head can simply be removed from its sterile packaging or container, attached to the fixed part 30 and loaded with biological materials, such that the chance of contamination before removal is minimized and it is discarded after the printing operation.

[0092] In the context of this specification, biomaterials include bioinks, activators, cells (especially cell suspensions), or other relevant fluids and / or materials associated with a bioprinting system. When referring to printing bioinks or activators, they can be replaced by other suitable biomaterials and can actually contain other suitable biomaterials. For example, a cell suspension can be present in a bioink or an activator.

[0093] In other embodiments, the detachable printhead 20 is a sterilizable detachable printhead that can be reused. In one embodiment, the sterilizable detachable printhead can be reused a predetermined number of times according to a specific sterilization method. For example, the predetermined number of times can be up to 10 times. The limit of the predetermined number of times is related to the effects of the use and repeated application of the sterilization process on the critical components (such as seals, valves, pipes, etc.) of the sterilizable detachable printhead.

[0094] The detachable printhead 20 has a body 25 and a dispensing system 180. The detachable printhead 20 is removably attached to a fixed part 30 of the bioprinter 10.

[0095] The dispensing system 180 is supported by the body 25, which may include multiple parts of the detachable printhead 20.

[0096] The detachable printhead 20 has a coupling 200 for attaching to the fixed part 30 of the bioprinter 10. The coupling 200 includes an interface for operating the dispensing system 180. The dispensing system 180, the coupling 200, and the interface will be described in more detail below.

[0097] The detachable printhead 20 includes a reservoir assembly 100. The reservoir assembly includes one or more reservoirs 110. There can be 2, 4, 6, 8, 10, 12, 14, 16 or more reservoirs. Although an even number of reservoirs is specifically mentioned, it is contemplated that the detachable printhead 20 can include an odd number of reservoirs. For example, one embodiment can include a single reservoir.

[0098] Figure 22 A single detachable printhead 1020 in an alternative embodiment is shown. The detachable printhead 1020 includes a single reservoir 1110 supported by a body 1025. Figure 23 A diagram is provided: Four detachable printheads 1020 of this embodiment are removably attached to a fixed part 1030 of the bioprinter 1010.

[0099] The ability to utilize a single detachable printhead with a single dispensing system (or module) provides the user with the option to customize the number of dispensing systems or modules according to the specific application for which the bioprinter 10 is used. The user can also match the type of dispensing system or module to the specific application. This built-in flexibility and the use of detachable printheads offer advantages in terms of flexibility and cost reduction, as the configuration can be planned and changed according to the application.

[0100] Figure 3 Depicted is a detachable printhead 20 having a reservoir assembly 100 with eight reservoirs 110 arranged around a central axis 35. In alternative embodiments, the reservoir assembly 100 can include 16 reservoirs 110. In alternative embodiments, the reservoir assembly 100 can include a single (1) reservoir 110. However, in other embodiments, the reservoir assembly 100 can include a different number of reservoirs 110. One or more reservoirs are arranged around the central axis 35. However, other embodiments are not limited to this configuration, and the reservoir assembly 100 can be conceived as having reservoirs arranged in a straight line, pyramid shape, rectangular arrangement, cluster, or any reasonable configuration that still allows the reservoirs to hold fluid and dispense fluid from the detachable printhead 20. For example, one or more reservoirs can be arranged in a rectangular array. The rectangular array offers advantages due to the option of matching more than two dispensing valves in a single printhead stroke. This also reduces the design complexity of the bioprinter 10. Additionally, in addition to embodiments having reservoirs with a specific arrangement in the detachable printhead 20, other embodiments can have multiple detachable printheads with a specific arrangement. For example, Figure 22 The detachable printhead 1020 is a single reservoir embodiment and can be arranged in a straight line as Figure 23 shown to achieve an output similar to an embodiment having multiple reservoirs arranged in a straight line in a single printhead.

[0101] Figure 6 and Figure 7A single reservoir assembly 100 is shown, which includes a reservoir 110 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 for removing particles (in the form of a frit in this embodiment), a disc filter 139, and a dispensing valve 150. In this way, each reservoir has at least one inlet for receiving fluids (including biological materials and, if needed, other fluids such as a gas for pressurizing the reservoir) and an outlet for dispensing the bio-printing fluid, as well as an internal volume for containing the fluid. 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 provide sufficient filtration and also provides the additional advantage of reducing backflow from the reservoir 110. The disc filter 139 can also be hydrophobic to help prevent any accidental fluid flow. Additionally, although the pneumatic connector 135 includes an O-ring 136, other suitable components and structures can be used to fabricate a suitable pneumatic connector.

[0102] Each reservoir 110 can contain a corresponding fluid or liquid. Alternatively, more than one reservoir 110 can contain the same fluid or liquid. The reservoir 110 includes a first end 112 and a second end 115, the reservoir cap 120 includes a pneumatic connector 135 at the first end, and the inlet valve 130 is generally located at the first end, and the second end has an outlet connected to the dispensing valve 150. The reservoir 110 can have a cylindrical cross-section. However, in other embodiments, the reservoir can have other cross-sections, such as oval, or other shapes, such as spherical or rectangular.

[0103] As Figure 6 and Figure 7 shown, the second end 115 of the reservoir is tapered, and the cross-section of the reservoir decreases towards the outlet 138. The second end 115 can be tapered away from the reservoir axis 142 of the reservoir 110 such that the outlet 138 is eccentric. Arranging the outlet 138 at an eccentric position towards the central axis 35 at the second end 115 of the reservoir 110 (regardless of the shape of the reservoir) helps to minimize the overall diameter at the point where the detachable print head 20 actually performs printing on the detachable print head base 190. That is, it is advantageous to have the dispensing valves of the detachable print head 20 as close to each other as possible. By orienting the reservoir 110 circumferentially around the central axis 35 and additionally offsetting the outlet 38 of the reservoir towards the central axis 35, the distance between the dispensing valves is minimized.

[0104] The inlet valve 130 is adapted to introduce fluid into the reservoir, as discussed in detail in the earlier application WO2021 / 108870A1. The inlet valve 130 can be a check valve and / or a one-way valve. However, any valve that can fill the reservoir and hold the fluid within the reservoir is suitable.

[0105] The fluid can be manually loaded by the user with a syringe through the inlet valve 130 and directly into the reservoir 110. However, the fluid can be loaded in other ways (e.g., through a cartridge system or an automatic loading system).

[0106] The reservoir 110 can be at least partially transparent. The reservoir 110 can also be transparent or opaque. Transparency has the advantage of allowing the operator of the bioprinting system to easily see the contents of the reservoir 110, especially the amount of bioprinting fluid in a particular reservoir.

[0107] Each reservoir is in fluid communication with a dispensing valve 150. The dispensing valve 150 can be a microvalve 150. In one embodiment, the microvalve is an electromagnetic valve.

[0108] Each dispensing valve 150, together with the reservoir assembly 100 and the corresponding fluid connection, forms part of a dispensing system 180 of a detachable print head. The dispensing system 180 is a droplet dispensing system. The dispensing system is configured to print droplets from one or more reservoirs onto a substrate. In one embodiment, the fluid is pneumatically ejected from the reservoir 110 through an electronically controlled dispensing valve 150.

[0109] In Figure 5 an exploded view shows an embodiment of the coupling 200. The coupling 200 includes a gasket 210, a support ridge 225, a retaining plate 230, a retaining ring 240, and an inner body 170. The inner body 170 includes a central void 172 that receives the corresponding shaft 305 of the fixing part 30 (see Figure 11 ). The retaining plate 230 is attached to the inner body 170 by using one or more screws 220, and the retaining ring 240 is held between the retaining plate 230 and the inner body 170. Other embodiments are not limited to using screws, and any other device that can hold the components of the assembly together will be considered to be covered by this disclosure. The gasket 210 helps to provide a fluid seal between the reservoir lid of the reservoir assembly that protrudes through the retaining plate 230 and the gasket 210, such that they can be connected to the fixing part 30 through an appropriate fluid connection. In some embodiments, the gasket 210 is optional, and the fluid seal is provided by a pneumatic connector 135.

[0110] The detachable print head 20 has an outer body 160. The outer body 160 can be molded around the reservoir assembly 100 and attached to the inner body 170. The outer body 160 can be at least partially transparent. The outer cover can have a textured lower portion. This textured portion allows a surgeon or other operator to grip and manipulate the detachable print head 20.

[0111] The detachable print head 20 can have a base 190 that is attached to the inner body 170 using one or more screws 191. The base has an opening 192 to allow a distance sensor to travel through the center of the detachable print head 20 (which will be discussed in more detail below). The screws 191 can also take the form of pins or any other feature that can assist in aligning and / or attaching the detachable print head 20.

[0112] The number of reservoirs can be selected such that two materials can be printed, with each material requiring two nozzles. In one example, the two nozzles can respectively hold bioink and activator for each material. Using two (or 4, 6, 8, etc.) nozzles increases the printing speed of the printing assembly. However, the present invention is not limited to this arrangement, and printing can be performed using an uneven number of nozzles and still be covered by the present disclosure.

[0113] In one embodiment, the detachable print head 20 includes 8 reservoir assemblies 100 configured in a circular pattern. This configuration positions the dispensing valves equidistant from a (center-located) distance sensor to improve the printing robustness when printing on uneven surfaces. This arrangement also minimizes the size of the detachable print head 20 in the area closest to the printing surface, making it easier for the bioprinter to operate around the printing surface and reach more difficult locations.

[0114] Bioprinter

[0115] Figure 1 and Figure 2 shows a bioprinter 10 including a fixed portion 30 and a detachable print head 20. The detachable print head 20 is removably attached to the fixed portion 30. As previously mentioned, the bioprinter can include a fixed portion 30 and a detachable print head 20, or it can also include mechanical manipulation devices such as a robotic arm 40 or a gantry robot 560.

[0116] Figure 27 An example including a gantry robot 560 is shown. Figure 27 shows a detachable print head 3020 mounted on an XY gantry robot 560 including two axes. The detachable print head 3020 is located on a first track 562 on the x-axis. The y-axis is in Figure 27is depicted as the second track 564.

[0117] The bioprinter 10 includes an interface for operating a dispensing system 180 of a detachable print head 20. As expected, the interface has two components, namely, a detachable print head interface and a fixed part interface. In this embodiment, the fixed part interface enables the detachable print head 20 to be pneumatically and electrically connected to the rest of the bioprinter. The fixed part 30 may include other parts, such as hardware components. These hardware components may include a distance sensor 350, a camera, control buttons or an enable switch 450, a control system (including the relevant interfaces for operating the bioprinter), or components designed to provide safety or operability advantages.

[0118] Figure 11 and Figure 12 An embodiment of the fixed part 30 is shown. The fixed part 30 includes a front housing 410 and a rear housing 420 that cover the internal components of the fixed part 30. Figure 11 and Figure 28 Different designs of the front housing 410 and the rear housing 420 are shown as different embodiments. The present invention is not intended to be limited to the shapes shown in these two figures, but may include other designs that are still suitable for the purpose of covering the internal components of the fixed part 30. In this embodiment, a seal 425 extends around the boundary of the rear housing 420. A robotic mount 430 is provided for connecting the fixed part 30 to the robotic arm 40.

[0119] Figure 11 The shown embodiment provides a switch 450 on the fixed part 30. The switch 450 activates a mode in which the robotic arm 40 can be manually guided by the user. This switch 450 allows the user to manually guide the bioprinter for various reasons. For example, the switch 450 can enable an undo mode to undo an automatic print and move the bioprinter 10 across a more difficult surface or navigate to a more inaccessible area of the surface. Alternatively, the switch 450 can allow entry into a pre-print mode, in which the area to be printed is manually defined, and the control system then controls the bioprinter to print in the area defined during the pre-print mode.

[0120] Further embodiments may include this switch at other locations of the bioprinter 10 (such as on the detachable print head 20), and in other embodiments the switch 450 may be removed.

[0121] The control system and related hardware may include functions for controlling the dispensing valves in the detachable print head 20.

[0122] Figures 11 to 15Shows various aspects of the connection portion 300, which is attached to one or both of the front housing and the rear housings 410, 420 by screws 302. The connection portion 300 provides mechanical support for the detachable print head 20 and enables a user to manipulate the bioprinter 10 without damaging any connection between the fixed portion 30 and the detachable print head 20.

[0123] Figure 11 The connection portion 300 is shown in an exploded view. The connection portion 300 includes a shaft 305. The shaft 305 is designed to fit within the inner body 170 of the detachable print head 30 and helps provide support through the middle of the reservoir assembly 100. The shaft 305 may also provide an indexing function. Indexing helps ensure that the detachable print head 30 is correctly aligned to a mating surface, such as the base 190. Although these functions have been discussed with respect to the shaft 305, the present invention is not limited thereto, and it is contemplated that other features (such as using pins 193) may be utilized to provide the indexing function. Alternative features may be used independently or in combination with the use of the shaft.

[0124] Figure 13 Shows the connection portion 300 ready to be used with the detachable print head 20.

[0125] The shaft 305 is attached to the mounting assembly 310, which is shown in more detail in Figure 14 and Figure 15 The shaft 305 is depicted in Figure 11 and Figure 15 as extending substantially from the mounting assembly 310; however, alternative embodiments may depict the shaft 305 as shorter, as shown in Figure 12 and Figure 13 The mounting assembly 310 contains a conduit 330 that provides gas pipeline facilities for delivering gas to the interface of the fixed portion 30.

[0126] 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 record the distance between the base 190 of the print head and the printing substrate or the subject. This helps the control system safely and easily maintain the desired distance from the substrate.

[0127] The printing surface can be the surface of a subject, such as the skin surface of a patient. It is also contemplated that the distance sensor 350 can be provided externally and connected to the bioprinter 10. The distance sensor 350 can 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 skin surface of the patient, or any other suitable sensor known in the art capable of monitoring the distance between the base 190 of the detachable print head 20 and the printing surface. The printing surface can be a wound of the subject.

[0128] The mounting assembly 310 can include a camera. The camera can be included instead of or in addition to the distance sensor 350, and in fact the camera can be used as the distance sensor 350.

[0129] 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 print head 20. It is also contemplated that the distance sensor 350 can be any other suitable device known in the art that can be used as a visual aid for positioning the bioprinter 10. The window 375 may not be required in other embodiments.

[0130] The mounting assembly 310 includes a connector 345 for the distance sensor 350. A gasket 320 is provided to provide a seal with the rest of the fixed part 30 and the mounting assembly 310.

[0131] In one embodiment, having an optical distance sensor 350 enables the sensor 350 to be mounted at a position remote from the distal end of the shaft 305. In this case, the shaft 305 allows light to pass through its center (preferably because it is hollow) and through the opening 192 of the detachable print head 20 to record the distance between the subject and the base 190 of the detachable print head 20 without a sensor within the detachable print head 20.

[0132] In an alternative embodiment, the shaft 305 provided by the inner body 170 and / or the connecting part 300 is not included in the detachable print head 20. In a further alternative embodiment, a distance sensor 350 is included within the detachable print head 20.

[0133] Figure 13 and Figure 15Shows the interaction of the mounting assembly 310 and its couplings with the detachable printhead 20. The mounting assembly 310 includes a locking mechanism 360, and together they are adapted to removably attach the detachable printhead 20 to a fixed portion 30 of the bioprinter (e.g., the fixed printhead 30). The mounting assembly 310 is designed to enable a simple and reliable attachment process. The mounting assembly 310 is designed to mechanically couple the detachable printhead 20 to the fixed portion 30 while also bringing the interface of the fixed portion 30 into contact with the interface of the detachable printhead 20 to provide electrical and pneumatic connections.

[0134] The operation of the mounting assembly 310 and the retaining ring 240 will be described below in conjunction with the fixed portion 30 and the detachable printhead 20. However, other embodiments may utilize other mechanisms to removably connect the detachable printhead 20 to other fixed components, arms, or portions of the bioprinter.

[0135] The retaining ring 240 is movable circularly relative to the detachable printhead 20. That is, it can rotate around the inner body 170 without separating from the body 170. The mounting assembly 310 includes a plurality of pneumatic receivers 315 that form part of the pneumatic interface of the fixed portion interface. A plurality of pneumatic connectors 135 of the reservoir assembly 110 project from the gasket 210 of the coupling 200 and form part of the detachable printhead interface. The pneumatic receivers 315 are thus spaced apart to receive the pneumatic connectors 135 of the detachable printhead 20.

[0136] The plurality of pneumatic receivers allows individual pressure sources to be aligned with individual reservoirs. This arrangement allows one or more reservoirs to receive different pressures simultaneously, thus providing greater flexibility in the capabilities of the dispensing system.

[0137] In an alternative embodiment, the pneumatic interface is formed by an integrated pressure distribution manifold 550. This embodiment is shown in Figure 24 and Figure 25 shown.

[0138] In this embodiment, a single pressure source is provided to a plurality of reservoirs through the pneumatic interface 552, i.e., the pneumatic interface directs the single pressure source to one or more reservoirs. The pneumatic interface has pneumatic receivers on one side to receive input from a compressed air source. However, in this embodiment, a manifold 550 is formed within the pneumatic interface such that the direction of the pressure flow can be manipulated within the manifold. The manifold valve 548 controls the air supply to the manifold outlet 554, which is configured such that when connected to the detachable printhead 20, the single pressure source can direct pressure towards the inlets of the plurality of reservoirs.

[0139] The 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 present invention is not limited thereto, and it is conceivable to implement multiple pressure sources while still utilizing the one pneumatic interface described. A further advantage is the ability to scale up the arrangement with a greater number of reservoirs without having to accommodate space for multiple pressure sources in the arrangement.

[0140] The mounting assembly 310 includes a plurality of ramped protrusions 317 or lugs disposed around its circumference. The retaining ring 240 has mating slots on its inner surface that are reinforced by support ridges 225 such that the slots can act against the ramped 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 be connected without any rotation of these components. Only the retaining ring 240 needs to be rotated.

[0141] The coupling mechanism is not limited to using the above example, and other designs can be implemented to securely attach the detachable printhead 20 to the fixed portion 30. For example, a cam and lever mechanism can be arranged to provide a mechanical coupling between the detachable printhead and the fixed portion. The Figure 26 use of a cam 555 and a lever 558 is shown. The cam 555 and the lever 558 are used in combination to pull the detachable printhead towards the fixed portion.

[0142] In use, the detachable printhead 20 is positioned on the shaft 305, and the pneumatic connector 135 is pushed into the pneumatic receiving portion 315. At this time, the retaining ring 240 is rotated so that the slots on its inner surface engage the ramped protrusions 317. Due to the protrusions having a predetermined ramp size, the detachable printhead 20 is pulled towards the fixed portion 30 to a predetermined relative position.

[0143] Furthermore, to prevent accidental release, the mounting assembly 310 includes a locking mechanism 360 that includes a biased locking pin 365. The retaining ring 240 includes locking recesses (not shown) on its inner surface, and when the retaining ring 240 has been rotated to a predetermined position, the pin 365 of the locking mechanism engages the locking recesses. This prevents the retaining ring 240 from rotating without biasing the pin 365 away from the support ridge 225 through the locking mechanism 360.

[0144] In addition, the shaft 305 includes an end cap 370 that contains a series of electrical connectors that provide electrical signals to the dispensing valve 150 of the detachable printhead 20 (see Figure 9 、 Figure 10 、 Figure 15 、 Figure 17 and Figure 18 ).

[0145] Figure 9Shown is a detachable electrical interface 255, which forms part of a detachable printhead interface and includes distribution electrical connectors 260 in the form of pogo-pins on one side of the substrate and a header connector 270 on the other side of the substrate. A pair of distribution connectors 260 are connected to the header 270, which in turn is connected to the dispensing valve 150. The detachable electrical interface 255 is positioned within the inner body 170 and, when attached to the fixed part 30, will contact the end of the shaft 305. Figure 10 An alternative embodiment of the detachable electrical interface is shown, in which 16 reservoir assemblies 110 are used instead of 8 reservoir assemblies.

[0146] The shaft 305 of the fixed part 30 includes a fixed part electrical interface as part of the fixed part interface within the end cap 370. The fixed part electrical interface includes a distribution connector 380 and a header connector 390. The distribution connector 380 is arranged to cooperate with the detachable distribution connector 260 such that when the shaft 305 is inserted into the inner body 170, the control system establishes an electrical connection with the dispensing valve 150 and can operate the dispensing valve 150 as required.

[0147] Figure 19 Shown is the detachable printhead 20 attached to the fixed part 30 in a removable manner. That is, the shaft 305 is fully inserted into the inner body 170, and both pneumatic and electrical connections have been formed. Also shown is the optical sensing beam 355 from the distance sensor 350.

[0148] Bioprinting platform

[0149] The detachable printhead 20 can be used as part of a drop-on-demand bioprinter. The drop-on-demand bioprinter deposits biological materials onto a substrate. The bioprinter can also use patient cells. In one embodiment, the substrate can be the damaged site of a patient.

[0150] The bioprinter 10 can be attached to a mobile base 50. The mobile base 50 houses subsystem components that enable the bioprinter 10 to operate and that have generally been described as part of the stationary section 30. The mobile base 50 enables the platform to move to different locations within a facility, such as a hospital. The mobile base 50 can include functions such as print pneumatics, a robot controller, brakes (if the bioprinter is movable), and computer components and electronics. The robotic arm 40 is attached to the stationary section 30 and enables the bioprinter 10 to move. This movement provides space around the substrate and provides the precision required to deposit the therapeutic agent onto the substrate. In one embodiment, the robotic arm 40 is a Kuka LBR MED robotic arm that is certified for use as a component in a medical device. However, the present invention is not limited to the use of this robotic arm, and alternatives can be used. For example, although a robotic arm is discussed in this example, it is contemplated that a gantry robot could be utilized to manipulate the detachable print head 3020.

[0151] The various components used by the bioprinter 10 can be housed in any desired manner. For example, they can be attached to or located on / in a static structure, or they can be attached to or located on / in a mobile structure, such as a cart. Figure 20 An embodiment is shown in which the mobile base 50 is a cart. The robotic arm 40 is attached to the cart 50 via the mounting base 45 of the robotic arm 40. The cart 50 allows the bioprinting system 60 to be moved to a desired location, such that the bioprinting system 60 is portable, e.g., such that the bioprinting system 60 can be moved between medical sites. The cart 50 can also include a control system and a graphical user interface for operating the bioprinter 10. This embodiment demonstrates the self - contained nature of the bioprinting system 60, i.e., the bioprinting system 60 can be moved on the cart to the desired location while having all the systems required to operate the bioprinter 10. According to other embodiments, the robotic arm 40 can be mounted on another surface or at a fixed location. Figure 1 The robotic arm 40, the stationary section 30, and the detachable print head 20 are shown when not attached to the cart 50.

[0152] In one embodiment, the detachable print head 20 consists of a dispensing valve, a reservoir, a check valve, and electrical and mechanical components, as well as the fittings required to house and control these components. In this embodiment, the sensing and holding electronics are housed in the stationary section 30. However, alternative embodiments are envisioned in which the components are located in another part of the bioprinter 10. This includes, but is not limited to, configurations in which the check valve is located in the stationary section or the reservoir is located in the stationary section.

[0153] Printing method

[0154] According to one embodiment, the bioprinter 10 uses a drop-on-demand method to print fluids or gels. In this method, at least one reservoir 110 is filled with bioink, and at least one reservoir 110 is filled with an activator. One or more reservoirs 110 are arranged in a reservoir assembly 100 within a detachable print head 20. The detachable print head 20 is removably attached to a fixed part 30 and locked in place using a locking mechanism. When connected together, the connection part 300 provides an axis 305 passing through the inner body 170 of the detachable print head 30. The detachable print head 20 and the fixed part 30 form the bioprinter 10.

[0155] In this embodiment, the robotic arm 40 is controlled to move the bioprinter 10 to each intended point on the print surface where material is to be deposited. A distance sensor 350 located within the fixed part 30 is configured to monitor the distance between the base 190 of the detachable print head 20 and the print surface. The print surface can be the surface of a subject, such as a wound on a patient's skin surface.

[0156] To form fluids or gels using the above drop-on-demand method, it should be understood that when using current state-of-the-art biomaterials, it is generally necessary to include at least two reservoirs 110 in the detachable print head 20. Multiple reservoirs 110 can be used to increase the printing speed or when there is not enough biomaterial to be accommodated in the minimum number of required reservoirs. However, in some embodiments, only one reservoir is needed.

[0157] Additional reservoirs can be used to add additional materials to increase the biological complexity of the created structure.

[0158] In this case, multiple reservoirs can be filled with bioink, and multiple reservoirs 110 can be filled with an activator. In this case, for example, when all the bioink in one reservoir 110 has been dispensed, bioink will be dispensed from another reservoir 110. This will reduce the need to pause the printing regime to refill the reservoir 110. It is also conceivable that the reservoirs 110 can be filled with different types of liquids. If the reservoirs 110 are filled with different liquids, the bioprinter 10 may be able to form gels with different material layers, layers containing different cells and / or drugs, and / or different liquids printed / deposited between each layer of the gel.

[0159] Importantly, all parts of the bioprinting system that may come into contact with the patient or any other clinical user are sterile. This includes the above steps, as well as any steps involving the disassembly and / or replacement of the detachable print head from the bioprinter.

[0160] This can be achieved by using a sterile drape. The sterile drape can be used to ensure that parts or components in the bioprinting system that may come into contact with the patient or user are protected from coming into contact with the patient or user in an unsafe manner. All embodiments described herein can be configured to be compatible with the use of a sterile drape.

[0161] The laying of the sterile drape is initially performed by mounting the sterile drape onto the bioprinting system via a sterile adapter on the fixed part of the bioprinter. Then the sterile detachable print head can be attached to the sterile adapter. It is common practice to use a sterile adapter to ensure the sterility of surgical tools and robots.

[0162] The laying of the sterile drape can also be achieved by simultaneously mounting the sterile drape and the sterile print head. Although the following method is described as being done by two users, this method can be done by one user or more than two users. Generally, this method is performed by one or two users.

[0163] The robotic arm can be straightened and moved to a position that provides sufficient operating space to manipulate the drape laying process around it. The first user inserts the detachable print head into the sterile drape and then attaches the drape to below the locking ring and above the check valve or one-way valve by using sterile tape. In some embodiments, this placement can make the reservoir more visible.

[0164] While the first user holds the detachable print head in place, the second user attaches the fixed print head to the detachable print head. Then the first user flips the sterile drape over the detachable print head and the fixed part. A preliminary system pressure check can be performed after this step. Then the second user pulls the sterile drape along the robotic arm. A strap can be attached to the sterile drape and the robotic arm to restrict the movement of excess drape material.

[0165] Other methods of maintaining a sterile process and environment can be used in combination with the bioprinting methods described above.

[0166] Based on this, the print head can contribute to providing many non-obvious advantages. For example:

[0167] · The detachable print head enables easy sterilization of the bioprinter between print surfaces because the detachable print head can be removed from the rest of the print head assembly and processed before use.

[0168] · The sterilized detachable item can be used a predetermined number of times without being discarded.

[0169] · Embodiments of the detachable print head are designed to be discarded after single use, which reduces the risk of cross-contamination between patients.

[0170] · The detachable print head helps to optimize the connection of fluid components to reduce dead volume, thus minimizing potential cell waste.

[0171] · The detachable print head enables print head configurability for user applications by allowing the maximum loaded sample volume, the type of dispensing technology, and the number of dispensing modules to vary independently of the bioprinting system.

[0172] · The detachable print head allows the user to load fluid samples into the separate print head in a sterile environment (such as a biosafety cabinet) and then install the print head onto the system, enabling the use of the bioprinting system in a non-sterile environment without the risk of contamination.

[0173] · The detachable print head improves the convenience of cleaning and maintenance and is essentially replaceable in the event of component failure.

[0174] · In a desired embodiment, the reservoir assembly is sized and configured to minimize the size of the detachable print head in the vicinity of the patient area. This makes it easier to manipulate the detachable print head around the patient and print on hard-to-reach parts of the body.

[0175] · In a desired embodiment, the use of a switch allows for additional user control of the printing speed and positioning.

[0176] · In a desired embodiment, the detachable print head is configured to accommodate a distance sensor in the fixed part, so that relatively expensive high-precision sensing components are not in the detachable print head, as the detachable print head may be disposable or have a limited number of uses.

[0177] · In a desired embodiment, the shaft of the connecting part of the fixed part strengthens the connection of the detachable print head and enables the safe manipulation of the print head / system without applying mechanical stress to the interfaces (such as pneumatic connections and electrical connections).

[0178] · The bioprinter (and thus the detachable print head) is non-contact, which reduces the possibility of contamination and interference with the printing area (such as a wound).

[0179] Now refer to Figure 21 , a schematic diagram of a bioprinting system 60 is shown. Where elements in the schematic diagram have been previously described, the same reference numerals are used to refer to those elements in this figure as previously used herein.

[0180] When preparing for printing, the biomaterial 510 and the autologous biomaterial 512 are prepared and loaded into the reservoir 110 through the inlet valve 130.

[0181] The mobile base or cart 50 houses the system control unit 502 and the pneumatic unit 504. The pneumatic unit 504 provides the necessary components to supply gas (usually air) to the fixed part 30 and ultimately to the detachable print head 20. Various sensors provide feedback 506 to the system control unit 502. Based on this information and other data and settings provided through a system interface such as a graphical user interface, the system control unit 502 operates the bioprinter in the form of moving the robotic arm 40 and printing through the detachable print head 20. A distance sensor 350 provides feedback on the distance between the detachable print head 20 and the wound site of the patient 508. The detachable print head prints biomaterials (i.e., the prepared biomaterials 510 and autologous biomaterials 512) onto the printing area, which in this example is the wound site of the patient 508. The nature of the biomaterials used allows for the formation of three-dimensional bioprinted bodies, which have significant advantages for wound healing.

[0182] Many features of the described print head architecture are specific to bioprinting, i.e., using cells to create three-dimensional biological constructs and not being directly transferable to other printing technologies. For example, the design of the reservoir and its working volume have been optimized to handle precious fluids such as patient cells, and their volume ranges and losses are specific to bioprinting applications. One such example is that the working volume range compatible with the described detachable print head architecture is from 5 μL to 50 mL.

[0183] The types of materials that the described print 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 artificial (i.e., laminin, fibrinogen, collagen) and point-of-care biologic fluid products such as platelet-rich plasma, serum, etc.

[0184] The materials and volumes supported by the described print head architecture are deposited through print parameters and processes optimized for creating three-dimensional biological constructs. This results in the generation of droplets with a working range of 1 nL to 200 nL and high biologic viability.

[0185] Creating three-dimensional biological constructs using droplets of specific fluids within the above-described specific volume ranges is achieved by parameterizing the following characteristics of the print head design and the 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.

[0186] Those skilled in the art should understand that many variations and / or modifications can be made to the present invention shown in the specific embodiments without departing from the spirit or scope of the present invention as broadly described. Therefore, the embodiments of the present invention should be considered exemplary rather than restrictive in all respects.

[0187] Although the present invention has been described with reference to the above embodiments, those skilled in the art should understand that the present invention can be embodied in many other forms. Those skilled in the art should understand that many variations and / or modifications can be made to the technology shown in the specific embodiments without departing from the spirit or scope of the technology as broadly described. Therefore, the embodiments of the present invention should be considered exemplary rather than restrictive in all respects.

[0188] In this specification, adjectives such as left and right, top and bottom, hot and cold, first and second, etc. 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 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.

[0189] In this specification, the terms "comprising", "including", "having", "containing", or similar terms are intended to mean non-exclusive inclusion, such that a method, system, or device comprising a series of elements not only includes those elements, but may also include other elements not expressly listed.

[0190] In this specification, the term "consisting of" means consisting only of.

[0191] Unless the context otherwise requires or clearly states the contrary, the singular forms of integers, steps, or elements of the technologies described herein clearly encompass the singular and plural forms of the said integers, steps, or elements.

[0192] In the context of this specification, the terms "a" and "an" are used to refer to one or more (i.e., at least one) of the grammatical objects of the article. For example, a reference to "an element" refers to one element or multiple elements.

[0193] In the context of this specification, the term "about" means that a reference to a number or value should not be regarded as an absolute number or value, but rather includes a margin of variation around that number or value according to the understanding of those skilled in the art, including within typical margins of error or instrument limitations. In other words, the use of the term "about" should be understood to refer to a range or approximation that those skilled in the art would consider equivalent to the said value in the context of achieving the same function or result.

[0194] The foregoing description of embodiments of the present disclosure is provided to enable a person skilled in the art to make and use the disclosure. It is not intended to be exhaustive or to limit the disclosure to the single embodiments disclosed. As noted above, many alternatives and variations of the disclosure will be apparent to those skilled in the art from the foregoing teachings. Accordingly, while specific alternative embodiments have been discussed, other embodiments will be apparent or relatively easy to develop for those of ordinary skill in the art. The present disclosure is intended to cover all modifications, alternatives, and variations discussed herein, as well as other embodiments falling within the spirit and scope of the foregoing description. Item list:

[0195]

[0196]

[0197]

[0198]

Claims

1. A detachable print head for a bioprinter, the detachable print head comprising: A body removably attachable to a fixed part of the bio - printer; A dispensing system supported by the body; One or more reservoirs for containing one or more biomaterials, in fluid communication with the dispensing system and supported by the body; And a coupling for attaching to a fixed part of the bio - printer, the coupling including an interface for operating the dispensing system.

2. The detachable print head according to claim 1, wherein, The body includes an outer body, and wherein the outer body substantially surrounds the dispensing system.

3. The detachable print head according to claim 2, wherein, The outer body is at least partially transparent in at least some regions.

4. The detachable print head according to any one of claims 1 to 3, wherein, The dispensing system includes the one or more reservoirs, and wherein, preferably, each reservoir is part of a reservoir assembly which is also part of the dispensing system.

5. The detachable print head according to claim 4, wherein, The body includes an inner body, and the reservoirs are arranged on the outer surface of the inner body.

6. The detachable print head according to any one of the preceding claims, wherein, The body includes a central void for receiving a corresponding extension of the fixed part, preferably, the cross - section of the central void is circular.

7. The detachable print head according to any one of the preceding claims, wherein, The body has a central axis perpendicular to the coupling surface of the coupling.

8. The detachable print head according to claim 7, wherein, The central void has a central point located on the central axis, preferably, the central point is located on the void axis and the void axis is collinear with the central axis.

9. The detachable print head according to claim 7 or 8, when referring to 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 circular pattern around a reservoir axis, and further preferably, the reservoir axis is collinear with the central axis.

10. The detachable print head 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 a plurality of reservoir inlets, preferably, the inlet valve is adapted to allow fluid to be introduced into the reservoir, and further preferably, the inlet valve can be a check valve and / or a one - way valve.

11. The detachable print head according to any one of the preceding claims, wherein, The coupling can provide a suitable connection for the interface for operating the dispensing system.

12. The detachable print head according to any one of the preceding claims, wherein, The coupling is adapted to removably attach a detachable print head to a fixed part of the bio - printer.

13. The detachable print head according to any one of the preceding claims, wherein, The interface includes a plurality of dispensing electrical connections which can interface with fixed - part dispensing connections, the dispensing electrical connections providing electrical signals to one or more dispensing valves of the dispensing system.

14. The detachable print head according to claim 13, wherein, The central void includes the plurality of dispensing electrical connections, preferably, the plurality of dispensing electrical connections are located at the ends of the central void.

15. The detachable print head according to any one of the preceding claims, wherein, The interface includes pneumatic connectors for one or more reservoirs.

16. The detachable print head according to any one of the preceding claims, wherein, The interface includes an integrated pressure - distribution function, wherein a single pressure source is directed to one or more reservoirs.

17. The detachable print head according to any one of the preceding claims, wherein, The dispensing system is a droplet - dispensing system.

18. The detachable print head according to claim 16 or 17, wherein, The droplets are pneumatically ejected from the reservoir through the dispensing valve, and preferably, the dispensing valve is a micro - valve.

19. The detachable print head according to any one of claims 1 to 15, wherein, The dispensing system is an extrusion system.

20. The detachable print head according to any one of claims 16 to 19, wherein, The printing area is a wound of a subject such as an animal or a human patient, preferably, the wound is a wound on the skin of the subject, and further preferably, the fluid dispensed by the dispensing system forms a gel on the wound.

21. The detachable print head according to any one of claims 1 to 20, wherein, The detachable print head is disposable.

22. The detachable print head according to any one of claims 1 to 20, wherein, The detachable print head is reusable.

23. The detachable print head according to any one of claims 1 to 22, wherein, The detachable print head is sterilizable.

24. The detachable print head according to any one of claims 1 to 23, wherein, The detachable print head includes a distance sensor and / or a camera.

25. A bioprinter, comprising a stationary part capable of receiving one or more detachable printheads, wherein, Each detachable print head includes: a body; a dispensing system supported by the body; one or more reservoirs for containing one or more biological materials, in fluid communication with the dispensing system and supported by the body; and a coupling for attachment to a stationary part of the bioprinter, the coupling including an interface for operating the dispensing system, the bioprinter further including a system for controlling the interface and operating the dispensing system of the detachable print head.

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

27. The bioprinter according to claim 25, wherein, One or more detachable print heads are respectively attached to the stationary part of the bioprinter.

28. The bioprinter according to any one of claims 25 to 27, wherein, The stationary part is movable to position the one or more detachable print heads.

29. The bioprinter according to any one of claims 25 to 28, wherein, The stationary part includes a distance sensor, wherein the distance sensor provides the distance between the detachable print head and the printing area.

30. The bioprinter according to claim 25 or 26, wherein, The stationary part includes a shaft for insertion into a corresponding void in the detachable print head.

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 comprising the steps of: Attach a detachable print head to a stationary part of the bioprinter, the detachable print head including a body, a dispensing system supported by the body, and a coupling for attachment to the stationary part of the bioprinter, the coupling including an interface for operating the dispensing system; control the bioprinter to move on a printing surface; and form a fluid or gel on the printing surface.

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