Patent Description:
3D printing is an additive form of manufacturing where an object is built up from multiple layers of a printing material. There are a wide range of printing materials that can be used. Typically these materials need to be cured in some manner, whether by cooling a heated portion of the printing material, ultra-violet curing, heat curing, etc..

In biomedical and/or tissue engineering applications, the printing material may be a biologically compatible compound and is often chemically cured by chemical cross-linking. 3D bioprinting can be used for various purposes including, for example, to construct tissue scaffolds. The application of the chemical cross-linker to the printing material can be difficult to control and can result in poor printing results.

<CIT> of Aspect Biosystems Ltd discloses systems and methods for printing a fiber structure. The print head of <CIT> is configured to displace one or more input materials with a buffer solution at the proximal end of the dispensing channel to terminate the fiber structure with a clean tail end.

An additional, alternative and/or an improved print head for use in 3D bioprinting is desirable.

In accordance with the present disclosure there is provided a misting attachment system for use in a material deposition process, the misting attachment comprising: a receiver for receiving a deposition head for a 3D printing process having an exit nozzle through which a material can be deposited; a mist delivery channel in proximity to the exit nozzle of the deposition head when present, the mist delivery channel arranged to supply a flow of across-linker or suspension of particles around the material being deposited through the deposition head; and a mist extraction channel in proximity to the exit nozzle of the deposition head when present, the mist extraction channel arranged to extract a flow of excess cross-linker or suspension of particles from around the material being deposited; an ultrasonic atomizer within a misting chamber connected to the mist delivery channel for providing the atomized cross-linker or suspension of particles; an air pump connected to the misting chamber to supply the flow of atomized cross-linker or suspension of particles; and a vacuum pump connected to the mist extraction channel to provide suction for extracting excess cross-linker or suspension of particles.

In a further embodiment of the misting attachment, the mist delivery channel substantially surrounds the exit nozzle of the deposition head when present.

In a further embodiment of the misting attachment, the cavity of the mist delivery channel has an opening arranged at a downward angle promoting <NUM>° laminar flow of the atomized cross-linker or suspension of particles around the exit nozzle of the deposition head when present.

In a further embodiment of the misting attachment, the extraction channel substantially surrounds the exit nozzle of the print head when present.

In a further embodiment, the misting attachment further comprises an extraction profile on a surface of the attachment between the extraction channel and the exit nozzle of the print head when present.

In a further embodiment of the misting attachment, the extraction profile has an arcuate profile surrounding the exit nozzle of the print head when present.

In a further embodiment of the misting attachment, the receiver is adapted to be releasably secured to the print head.

In a further embodiment of the misting attachment, the print head comprises one of a syringe, and a dispensing needle.

In a further embodiment of the misting attachment, the deposition head comprises a droplet deposition head.

In a further embodiment of the misting attachment, the extraction channel is spaced apart down stream from the mist delivery channel by a predetermined distance to expose material droplets deposited from the deposition head to the cross-linker or suspension of particles for a sufficient amount of time.

In a further embodiment of the misting attachment, the mist delivery channel supplies the flow of atomized cross-linker or suspension of particles <NUM>° around the material being deposited by the deposition head.

In a further embodiment, the misting attachment further comprises a plurality of mist delivery channels arranged circumferentially around the exit nozzle.

In a further embodiment of the misting attachment, each of the plurality of mist delivery channels are in fluid communication with each other.

In a further embodiment, the misting attachment further comprises a supply connection port for connecting the mist delivery channel to the supply of atomized cross-linker or suspension of particles.

3D bioprinting of materials can use a chemical cross-linking agent that hardens the printed material after being extruded from the print head. A print head attachment is described further below that allows the cross-linker to be supplied as a mist to the extruded printing material and any excess cross-linker extracted from around the print head. Extracting excess cross-linker helps prevent or reduce print errors that can result from a buildup of excess cross linker around the printing area. The print head attachment can be attached to existing print heads without requiring significant changes to the 3D printer.

<FIG> depicts components of a 3D bioprinter incorporating a 3D print head attachment system. The 3D bioprinter <NUM> has a print head assembly that includes a print head <NUM> and a print head attachment <NUM>. The print head assembly may be secured to an XY positioning assembly <NUM> by a print head mount <NUM>. A printing material can be controllably extruded <NUM> from the print head <NUM> onto a print stage <NUM> to additively form a printed object <NUM>. The print stage <NUM> may be connected to a Z positioning assembly <NUM> to raise/lower the print stage <NUM> as the object <NUM> is printed. It will be appreciated that the XY positioning assembly <NUM> and the Z positioning assembly <NUM> provide relative movement between the print stage <NUM> and the print head <NUM>. Although depicted as moving the print head in the XY direction and the print stage in the Z direction, the positioning assemblies may be connected in various arrangements to provide the relative movement between the print head and print stage.

The print head may be provided by, for example a syringe, a Luer-Lock dispensing needles, etc. The print head may be controlled by various means including pneumatically by a compressed air source <NUM>, mechanically by a motor or other types of actuators. The print head may be filled with a print material that is extruded, or otherwise deposited, on the print stage to form the object. The printing material may be selected from a wide range of materials that are cured, or hardened, by contact with another chemical, referred to as a cross-linker. The particular cross-linker used may vary depending upon the printing material used. For example, the printing material may be sodium alginate, chitosan, collagen, agarose, or other compatible biomaterial and/or hydrogels. The cross-linker may include, for example, calcium chloride (calcium ion), genipin, aldehydes or other chemicals capable of cross-linking the printing material.

As depicted in <FIG>, the print head attachment <NUM> may be fit over, or attached to, the print head <NUM> so that the print material exiting the print head at an exit nozzle of the print head passes through the print head attachment. Although depicted as exiting the print head <NUM> within the print head attachment, it is possible for the exit nozzle of the print head may extend past a bottom of the print head attachment. The temperature of the print material being extruded may be controlled, for example temperatures may range between <NUM>° - <NUM>° C. The temperature of the print material may change the material's viscosity for improved control over the printability as well as control of the diffusion of crosslinking ions.

The print head attachment <NUM> comprises a mist delivery channel <NUM> that supplies a mist of the chemical cross-linker around the extruded print material <NUM>. The mist delivery channel <NUM> may be connected to a mist supply port <NUM> that allows the mist delivery channel to be connected to a mist supply source <NUM>, for example by a tube or tubing. The mist supply source <NUM> may comprises a tank holding the cross-linker solution. An ultrasonic atomizer <NUM> may be used to generate a mist of cross-linker droplets <NUM>. An air pump <NUM> may be used to supply a flow of the mist of cross-linker to the mist delivery channel <NUM>. The droplets generated may vary in size, however for calcium chloride used to cross-link sodium alginate a diameter of approximately <NUM> - <NUM> microns in size may be used. Similarly, various flow rates of the cross-linker mist may be provided by the air pump <NUM> at a rate of about <NUM>/min (air and droplets mixed). The mist of cross linker is supplied to the mist delivery channel <NUM> that supplies the cross-linker to around the extruded print material. The mist delivery channel is located in proximity to the exit nozzle of the print head when present so that the mist delivery channel supplies a flow of atomized cross-linker around the printing material extruded through the print head. The mist delivery channel <NUM> may have an exit opening to promote laminar flow of the cross-linker mist about the extruded print material.

In order to prevent excess cross-linker from contacting the printed object or possibly pooling on the print stage, the print head attachment further includes an extraction channel <NUM> that extracts excess cross-linker from the print area. The extraction channel <NUM> may have an extraction connection port <NUM> that can be connected to a vacuum pump <NUM> to provide sufficient suction to extract the excess cross-linker which may be collected in a waste tank <NUM>, or possibly resupplied to the cross-linker solution tank <NUM>. Although the extraction flow rate may vary, a flow rate of about <NUM>-<NUM>/min may be sufficient to extract enough excess cross-linker to prevent or reduce pooling of the cross-linker. The extraction channel enables even removal of the excess cross-linker without disrupting the interaction between the cross-linker and the extruded print material.

<FIG> depicts an illustrative 3D print head attachment. The print head attachment <NUM> was described above as having mist delivery channel with a single opening in proximity to the extruded material. It is desirable to promote flow of the cross-linker around the entirety of the extruded print material and as such a plurality of mist openings may be provided in proximity to the extruded material. The print head attachment <NUM> comprises a body <NUM>, which may be formed from various materials including both plastics and metals. The body <NUM> comprises a receiver opening <NUM> for receiving the print head. The receiver opening <NUM> may secure the attachment to the print head, for example by a friction fit, or an additional securing mechanism (not depicted) may be used. The particular shape of the receiver may depend upon the shape and size of print head used, however it generally comprises an opening into which the print head can be received that continues through the body to allow the print material to be extruded from the print head onto to the print stage.

The body may include a mist connector <NUM> for securing tubing to in order to supply the mist of cross-linker. The mist connector <NUM> may be connected to a mist delivery channel <NUM> surrounding the receiver opening in the body <NUM>. A plurality of delivery openings <NUM>0a, 210b may be connected to the delivery channel about the receiver opening in order to supply the mist of cross-linker around extruded print material. The print head attachment may further comprise an extraction connector <NUM> for connecting the attachment to a vacuum pump. The extraction connector <NUM> may be connected to an extraction channel <NUM> surrounding the receiver opening <NUM>. A plurality of extraction openings 216a, 216b may be connected to the extraction channel about the receiver opening <NUM> in order to extract excess cross-linker from the print area.

<FIG> depicts the 3D print head attachment of <FIG> in use. Elements of the print head attachment described above with reference to <FIG> are not labelled in <FIG> for clarity of the drawing. As depicted, print head, which may be a syringe filled with the printing material, is received within the receiver opening <NUM> in the attachment body <NUM> and is secured to the attachment. The print head controllably extrudes print material <NUM> to form a desired shape. Atomized cross-linker flows through the connection port <NUM>, into the delivery channel <NUM> and out of the delivery openings <NUM>0a, 210b. The flow of cross linker depicted by arrows 222a, 222b flows out of the openings and surrounds the extruded print material <NUM> causing cross links to be formed. Excess cross linker is extracted by a vacuum pump connected to the extraction connection port <NUM>. The excess cross linker is extracted through the plurality of extraction openings 216a, 216b in the extraction channel <NUM>.

<FIG> depicts a further illustrative 3D print head attachment. The print head attachment described above with regard to <FIG> may provide acceptable printing results, however the mist delivery channel and openings as well as the extraction channel and openings may not provide desired printing results. The print head attachment described further below with reference to <FIG> and <FIG> has an improved shape of the mist delivery channel for promoting the laminar flow of the cross-linker mist <NUM>° about the extruded print material. Similarly, the print head attachment has an improved shape of the mist extraction channel to reduce disruption of the laminar flow of the cross-linker mist about the extruded print material while still removing the excess cross-linker from the print area.

The print head attachment <NUM> may be formed as a single unitary piece of material having various channels and openings formed within it. The print head attachment may be formed using various manufacturing techniques including 3D printing and injection molding. The particular shape and size of the print head attachment may be varied according to the particular print head the attachment is designed for.

The print head attachment <NUM> has a receiver opening <NUM> into which a print head, such as a syringe can be received. The receiver opening <NUM> continues through the body as cylindrical body opening <NUM> for receiving a portion of the print head. The receiver opening and body opening may continue through a conical opening portion <NUM> for receiving a portion of the print head, such as a cone-tip needle attachment. The exit nozzle of the print head may extend through the conical opening and through an exit opening <NUM>. The exit nozzle of the print head may extend fully through the exit opening <NUM>, or it may remain within the exit opening <NUM>, or even within the conical opening <NUM>.

The print head attachment <NUM> comprises a mist delivery channel <NUM>. The delivery channel may be formed about a vertical axis of the body to provide a continuous <NUM>° channel. The delivery channel <NUM> is connected to a delivery connection port <NUM> that allows a tube or hose to be connected to the print head attachment for providing a flow of cross-linker mist into the delivery channel <NUM>. The delivery channel <NUM> is in proximity to the exit nozzle of the print head when it is present, and supplies a flow of atomized cross-linker around the printing material extruded through the print head. The delivery channel <NUM> is depicted as having a substantially continuous opening <NUM> that substantially surrounds the exit opening <NUM>, however, it is possible to provide a plurality of discreet openings surrounding the exit opening <NUM>. The delivery channel <NUM> may have a cross sectional profile that descends downward at an angle of between <NUM> - <NUM> ° toward the delivery opening <NUM> to impart downward movement to the mist flow and promote laminar flow about the extruded print material. As depicted, the channel profile may have an enlarged upper chamber with the connection port <NUM> located towards a top of the enlarged upper chamber, which may help provide a better flow of cross-linker out of the delivery opening <NUM>.

The print head attachment <NUM> further comprises a mist extraction channel <NUM> that extracts excess cross-linker from the print area. Similar to the delivery channel, the extraction channel <NUM> may be formed about the vertical axis of the body to provide a continuous <NUM>° channel. The extraction channel <NUM> is arranged in proximity to the exit nozzle of the print syringe when present to extract a flow of excess cross-linker from around the extruded printing material. The extraction channel <NUM> may have a substantially continuous extraction opening <NUM> that that substantially surrounds the exit opening <NUM>, however, it is possible to provide a plurality of discreet extraction openings surrounding the exit opening <NUM>. The extraction opening may be spaced apart circumferentially from the exit opening <NUM>. The bottom surface of the attachment between the extraction opening <NUM> and the exit opening <NUM> may have an arcuate profile <NUM> for helping with the extraction of excess cross linker from the print area. An extraction connection port <NUM> is connected to the extraction channel and allows a vacuum pump to be connected in order to extract the excess cross linker.

<FIG> depicts a cross section of the print head attachment of <FIG>. A print head <NUM> is received within the opening <NUM>, cylindrical body opening <NUM>, conical opening <NUM>, and through the exit opening <NUM>. As depicted, the exit nozzle of the print head extends past the exit opening, however the exit nozzle may remain within the print head attachment. The print head is controlled to extrude the printing material <NUM> onto a printing platform <NUM>. As the printing material is extruded through the exit nozzle of the print head, the printing material is contacted with a flow of cross-linker mist, depicted by arrow <NUM>. The mist of cross-linker is supplied through the connection port <NUM> into the delivery channel <NUM> and out the delivery opening <NUM> located in proximity to the nozzle exit. The shape of the delivery channel <NUM> helps to promote a laminar flow of the cross-linker mist down and around the printing material as it is extruded. The excess cross-linker mist that remains in the print area is extracted by the extraction channel <NUM> as depicted by arrows <NUM> through the extraction opening <NUM>. The extraction profile <NUM> at the bottom of the print head attachment may help to extract the excess cross-linker without disturbing the flow of the cross-linker around the extruded printing material.

A print head attachment system as described above can be easily connected to existing print heads. The print heads may print an object by extruding a filament of a printing material. The extruded filament may have a wide range of sizes, such as for example between about <NUM> microns and about <NUM> microns. The print material may include various compounds or materials including for example, living cells, micro particles, nano particles, etc. The print head attachment can improve the printing results when printing with print materials that are exposed to cross-linkers or other coating particles. The cross-linker may be delivered in the form of atomized mist droplets. The print head attachment may be used with sodium alginate as the print material, using calcium chloride (CaCl<NUM>) as the crosslinking agent to form a solid thermoset elastomer, calcium alginate. The print head attachment may be used with other print materials and crosslinking agents. Ultrasonic atomization of the cross linker creates a fine mist of droplets externally from the attachment that can be delivered to the attachment using forced airflow. The droplets of crosslinking agent are provided into a cavity that is designed to promote <NUM>° laminar flow of mist about the needle tip that is focused directly on the extruded biomaterial. Excess droplets of the cross linker may be removed with an external vacuum pump. The attachment may fit directly onto common bioprinting equipment such as syringes and Luer-Lock dispensing needles. Mist removal may be enabled via a cavity that features a narrow channel to promote even removal of the excess mist to reduce the disruption of interaction between droplets of the crosslinking agent and the print material being extruded. The extraction flow rate may be set at between <NUM>-<NUM>/min. Droplets of the cross linking agent may be generated in the diameter range of <NUM>-<NUM> microns using an ultrasonic atomizing system and forced into the print head at ~<NUM>/min (air and droplets, mixed) by an air pump. The temperature of the printing material may be controlled, for example within a temperature range of between <NUM> - <NUM>, which may change viscosity of the printing material for improved printability and may enable improved diffusion of crosslinking ions. The attachment may fit directly onto common bioprinting equipment such as syringes and Luer-Lock dispensing needles.

<FIG> shows photographs of a 3D printed cylindrical constructs. One cylindrical construct <NUM> was printed with <NUM> wt% sodium alginate using <NUM> wt% CaCl<NUM> mist with a flow rate of <NUM>/min from a misting attachment in accordance with the current disclosure. A second cylindrical construct <NUM> was printed with <NUM> wt% sodium alginate using <NUM> wt% CaCl<NUM> mist from a misting attachment in accordance with the current disclosure. Both cylindrical constructs exhibited strong layer adhesion.

<FIG> shows photographs of 3D printing results with and without mist removal using a misting attachment in accordance with the current disclosure. All other parameters of the printing remained the same and used <NUM> wt% sodium alginate and <NUM> wt% CaCl<NUM> mist. As can be seen in the comparison between print results depicted in panels (a) and (e), panels (b) and (f) and panels (c) and (g), the use of the mist removal during printing results in a higher quality print. Although not wishing to be bound by theory, it is believed that the higher quality print results are, at least in part, a result of no or little liquid accumulation on the print stage when using the mist removal as can be seen in comparison of panels (d) and (h). The print head attachment and system has been described above with particular reference to supplying an atomized mist of a cross-linker around extruded print material. The same print head attachment and system may also be used with materials other than cross-linkers. For example, the mist drops may contain the cross-linker as described above, or may contain suspensions of other particles and liquids such as a coating to be applied to the extruded material. The particles may be the cross-linker as described above, or may be other particles such as a coating to be applied to the extruded material. The coating particles may provide various functionality such as a lubricant, an adhesive, a colorant, or other particles provide desired functionality. Further, the atomized mist supplied around the print material may include a combination of particles such as cross-linkers and coatings. The attachment may be used in various applications including fabricating tissue constructs using biocompatible polymers including sodium alginate in fabricating vascular and liver tissue, collagen in fabricating skin tissue and agarose and chitosan for various tissue engineering applications. Further, the above has described the print head attachment with respect to its use with extrusion based 3D printing. As described further below, a similar attachment may be used with other deposition processes in addition to, or as an alternative to, extrusion based 3D printing.

Droplet-based deposition techniques can be used both as a 3D printing techniques as well as for other applications, including in pharmaceutical development, high-throughput chemical processes, etc. Droplet based deposition techniques may be used for 3D bioprinting and enables precise deposition of biocompatible polymers and living cells, which may be referred to as bioinks, to fabricate complex in-vitro tissue models.

Existing systems crosslink bioink droplets after printing to form rigid structures; however, crosslinkinking after printing may result in too rapid gelation of the droplets as a result of too much crosslinker or too slow gelation of the droplets. Too rapid or too slow gelation can lead to poor adhesion or shape fidelity, respectively. Furthermore, improper gelation can inhibit cell proliferation. The fabrication of complex tissue and organ constructs by, for example, depositing living tissue spheroids may be limited by the rate and extent of fusion the deposited spheroids, which in turn may depend upon the gelation rate. A misting attachment similar to that described above may be used to facilitate the crosslinking of printed bioink droplets before deposition onto the print stage, offering controllable proper gelation of the bioink.

<FIG> depicts a misting attachment for a droplet-based deposition process. The misting attachment <NUM> is similar to the print head attachment described above. The misting attachment <NUM> may be attached to, or otherwise coupled to, a droplet deposition head <NUM> that deposits drops of material <NUM> onto a surface (not shown). The misting attachment <NUM> comprises a mist delivery channel <NUM> that delivers a supply of mist of crosslinker, or other suspensions of particles, around the droplets as they pass through the attachment. The mist delivery channel <NUM> may be connected to a delivery port <NUM> that can be used to provide a flow of the mist, whether it is a crosslinker, which could be atomized, or other suspensions of particles. The attachment <NUM> further comprises a mist extraction channel <NUM> through which excess mist can be extracted. The extraction channel <NUM> may be connected to an extraction port <NUM> that can provide a vacuum to extract the excess mist. The mist may enter a channel through which material droplets are deposited, as depicted by arrows <NUM> and then be extracted away from the droplets <NUM> as they are deposited as depicted by arrows <NUM>.

<FIG> depict simulation results of mist concentration within a misting attachment in accordance with the misting attachment of <FIG>. As depicted, the mist concentration is high in a path that the deposited droplets pass <NUM> prior to being extracted through the mist extraction channel. The concentration of the mist below the attachment is relatively low. The length between the mist delivery channel and the mist extraction channel can be set so that the material droplets are exposed to the mist for an appropriate length of time. The appropriate length of time may depend upon the material being deposited, the misting agent, as well as the desired properties, such as gelation amount, coating amount, etc. for a particular application. In addition to the length between the mist delivery channel and the mist extraction channel, the flow rate and concentration of the mist may also be varied to adjust exposure levels to a desired or appropriate amount.

The misting attachment may direct the flow of mist to provide even, <NUM>-degree contact with the droplets as they are deposited. The geometry of the attachment may provide a uniform mist concentration on the centerline of the attachment, or through the path of the deposited droplets. The mist flowrate and concentration may be adjusted to modify the extent of exposure which may adjust the crosslinking rate. Adjusting the flowrate and concentration may be used to control the mechanical properties of the deposited materials. The temperature of the bioink may be adjusted (<NUM> - <NUM>) to improve diffusion of the crosslinker mist if desired.

The crosslinker, or the suspended particles, may be collected within the attachment device to prevent accumulation of liquid on the print stage. The geometry of the outlet channel may prevent disruption to the printed droplets as they exit the attachment.

The misting attachment for droplet-based deposition techniques may be used in a variety of applications, including for example, fabricating tissue spheroids for in-vitro tissue and organ regeneration, printing or otherwise manufacturing biocompatible beads for drug delivery, coating bioprinted droplets with functional substances (i.e. conductive, hydrophilic, hydrophobic).

<FIG> depicts a porous scaffold printed using the misting attachment described above with reference to <FIG>. The droplet based printing process used a <NUM> wt% sodium alginate with a crosslinking misting agent of <NUM> wt% CaCl<NUM>. As depicted the scaffold exhibits high shape fidelity and has good co-droplet adhesion.

Claim 1:
A misting attachment system (<NUM>) for use in a material deposition process comprising:
a misting attachment (<NUM>, <NUM>, <NUM>, <NUM>) comprising:
a receiver (<NUM>, <NUM>) for receiving a deposition head for a 3D printing process having an exit nozzle through which a material can be deposited;
a mist delivery channel (<NUM>, <NUM>, <NUM>, <NUM>) in proximity to the exit nozzle of the deposition head when present, the mist delivery channel arranged to supply a flow of a cross-linker or suspension of particles around the material being deposited through the deposition head; and
a mist extraction channel (<NUM>, <NUM>, <NUM>, <NUM>) in proximity to the exit nozzle of the deposition head when present, the mist extraction channel arranged to extract a flow of excess cross-linker or suspension of particles from around the material being deposited;
an ultrasonic atomizer (<NUM>) within a misting chamber connected to the mist delivery channel for providing the atomized cross-linker or suspension of particles;
an air pump (<NUM>) connected to the misting chamber to supply the flow of atomized cross-linker or suspension of particles; and
a vacuum pump (<NUM>) connected to the mist extraction channel to provide suction for extracting excess cross-linker or suspension of particles.