BACKGROUND

The present teachings relate generally to multi-dimensional printing, and more specifically to printing to enable tissue creation.

Three-dimensional printers have been developed that can use living cells as the printer “ink”. Bioprinters have been used to print miniature and/or replicas of tissues for research purposes. Building structures that incorporate a complete set of elements that keep tissues alive, such as blood vessels and vascular structures to maintain oxygen flow, has been accomplished by combining living cells with special types of plastics and gels that can mimic biological tissues, muscle, and cartilage. As the cells divide and multiply, they secrete a supporting matrix that can maintain the structure's shape. What is needed is a multi-dimensional printer and an associated motion controller that that can dispense material into a biologic printing environment in a pre-designed configuration, where the pre-designed configuration and the biologic environment can promote organized cell division and therefore tissue creation.

Tissue modeling/robotic bioassembly systems can combine tools to design and print volumetric models of biological constructs by extruding a boundary to form a model volumetric object, sketching a 2-dimensional bounded construct on at least two different planes, and connecting the boundaries of the constructs. Such bioassembly systems dispense material through extrusion syringe dispensers adapted for direct-writing of a biomaterial onto a substrate. The dispensing apparatus is a robotic arm that has a robotic arm end effector that grips a syringe barrel. The robotic arm provides movement of a syringe along several axes, and dispenses biomaterials onto a print substrate by non-sequential planar layering, oblique-angle printing, and printing on print substrates having variable surface topographies. What is needed, however, is a system that can provide constrained printing inside a tissue enclosure, and can print multi-dimensional shapes without traditional slicing. What is further needed is a system that can convert a design sketched on a computer user interface to robot commands that can create the design within the tissue enclosure.

SUMMARY

The multi-dimensional printer of the present teachings, stably constructed of low-mass parts, can include a computer numerically controlled system that can enable motors driving delivery systems. The motors can include encoders that can enable achieving arbitrary resolution. The motors can drive ballscrews to enable linear motion of the delivery systems, and the delivery systems can enable printing of a biological material in a pre-selected pattern in a tissue enclosure such as, for example, but not limited to, a petri dish or an enclosed tissue enclosure. The tissue enclosure can accommodate a medium such as, for example, a biological gel, and can further accommodate a vision system such as, for example, a laser micrometer that can detect actual position of a delivery device. The printer can accommodate multiple delivery devices, multiple types of delivery devices, multiple materials, and multiple types of materials.

The motors can be controlled by a motion controller that can accommodate an arbitrary number of actuators, and multiple axes. The motion controller can interface with a processor via, for example, but not limited to, an Ethernet connection, and/or the motion controller can execute on the processor itself. The motion controller can include, among other control types, pass-through commands, control loops, and configurable control loops for multiple inputs. The processor/motion controller, as well as power and safety features, can be housed in an enclosure that can include start, stop, and emergency stop switches.

The system of the present teachings for creating tissue can include, but is not limited to including, at least one positional interface that can receive positional information related to creating the tissue. The positional interface can compute motion information based at least on the positional information. At least one motion controller can compute at least one motion command based at least on the motion information. A multi-dimensional printer can include at least one delivery system, and at least one hardware device. At least one of the hardware devices can receive sensor data, and at least one of the hardware devices can include at least one motor. The printer can drive at least one motor based at least on at least one motion command and the sensor data. The motors can drive at least one delivery system based at least on the sensor data. At least one delivery system can be associated with at least one printing environment, and can create the tissue by delivering at least one material into the at least one printing environment.

The printer can optionally print a three-dimensional structure. The printer can optionally be constructed of low-mass materials. The printer can optionally include a kinematic mount receptacle for the printing environment. The at least one sensor can optionally include a vision system sensing delivery system characteristics of the at least one delivery system. The vision system can provide the delivery system characteristics to the motion controller. The at least one delivery system can optionally include multiple needles of various sizes. The motion controller can optionally include a sensor processor, a group processor, and a node processor. The group processor can manage at least one group, and the at least one group can include at least one node. The at least one node can be associated with at least one actuator. The node processor can manage the at least one actuator, and the sensor processor can manage at least one sensor hardware through at least one sensor driver. The sensor processor can communicate the sensor data to the group processor and the node processor.

The motion controller can optionally include at least one actuator driver driving the at least one actuator, at least one hardware driver that can drive the at least one hardware device, and an error processor that can track errors encountered by the motion controller. The motion controller can optionally include multiple control types.

The method of the present teachings for controlling at least one actuator in any configuration can include, but is not limited to including, linking each of the at least one actuator to at least one sensor, controlling each of the at least one actuator in a control loop, grouping the at least one actuator to accomplish coordinated/synchronized motion, and establishing communications among the at least one actuator. The communications can optionally include a network (CANbus, EtherCAT). The at least one actuator can optionally include a group consisting of rotational motion, linear motion, binary valves, pneumatic compressor, pneumatics valves, and heating element. The at least one sensor can optionally include a group consisting of motor encoder, linear position, pressure sensor, gyroscope, accelerometer, and temperature sensor.

The bioprinting system for printing tissue into a tissue enclosure of the present teachings can include, but is not limited to including, a multi-dimensional printer, a delivery device operably coupled to the multi-dimensional printer, a motion controller commanding the delivery device to print the tissue, and a delivery device locating subsystem returning the delivery device to selected locations within the printed tissue. The delivery device locating subsystem can optionally include a mounting plate including kinematic positioning features, a tissue enclosure being a repository for the printed tissue, the tissue enclosure including kinematic mounting features matably couplable with the kinematic positioning features the mounting features and the positioning features insuring consistent between mounting and remounting of the tissue enclosure, and at least one sensor enabling determining the position of the delivery device within the tissue enclosure. The delivery device locating subsystem can optionally include at least one delivery device fiducial operably coupled with the delivery device.

The at least one sensor can optionally determine the position of the delivery device based at least on the at least one delivery device fiducial. The printer can optionally be constructed of low-mass materials. The at least one sensor can optionally include a vision system sensing delivery system characteristics of the at least one delivery system. The vision system can provide the delivery system characteristics to the motion controller. The motion controller can optionally include a sensor processor, a group processor, and a node processor. The group processor can manage at least one group, and the at least one group including at least one node. The at least one node can be associated with at least one actuator. The node processor can manage the at least one actuator, and the sensor processor can manage at least one sensor hardware through at least one sensor driver. The sensor processor can communicate the sensor data to the group processor and the node processor. The motion controller can optionally include at least one actuator driver driving the at least one actuator, at least one hardware driver driving the at least one hardware device, and an error processor tracking errors encountered by the motion controller. The delivery device can optionally include bi-directional fluid control between the delivery device and the tissue enclosure. The delivery device can optionally accommodate a plurality of input materials, and can include a mixing valve receiving the plurality of input materials. The mixing valve can extrude a single stream of the input materials as the printed tissue.

The system of the present teachings for returning a delivery device of a bioprinter to a specific location in a tissue enclosure after tissue has been printed by the bioprinter, where the bioprinter includes a motion controller, the system can include, but is not limited to including, a kinetic mount means coupling the tissue enclosure with the bioprinter, and a calibration system determining origin coordinates of a reference point of the delivery device within the tissue enclosure. The calibration system can provide the reference point to the motion controller. The system can include a delivery device locating system determining location coordinates of the delivery device as the motion controller commands the delivery device to print the tissue. The kinematic mount means can optionally include mounting features affixed to the tissue enclosure, and positioning features associated with the bioprinter. The mounting features can operably couple with the positioning features to consistently position the tissue enclosure between removal and replacement of the tissue enclosure between printing sessions. The calibration system can optionally include at least one sensor operably coupled with the motion controller. The at least one sensor can enable automatic calibration of the delivery system within the tissue enclosure. The delivery device locating system can optionally include at least one fiducial associated with the delivery device, and at least one sensor sensing the location of the delivery device based on the at least one fiducial.

The method of the present teachings for returning to a specific location in a tissue enclosure after tissue has been printed by a multi-dimensional printer, where the multi-dimensional printer include a delivery device and a motion controller, the method can include, but is not limited to including, coupling the tissue enclosure with the multi-dimensional printer with a kinematic mount means, determining origin coordinates of a reference point of the delivery device within the tissue enclosure, providing the reference point to the motion controller, locating coordinates of the delivery device as the motion controller commands the delivery device to print the tissue, and returning to the delivery device coordinates after the printing of the tissue is complete.

The motion controller can optionally control at least one actuator including linking each of the at least one actuator to at least one sensor, controlling each of the at least one actuator in a PID loop, grouping the at least one actuator to accomplish coordinated/synchronized motion, and establishing communications among the at least one actuator. The communications can optionally include a communications network. The at least one actuator can optionally be selected from a group consisting of rotational motion, linear motion, binary valves, pneumatic compressor, and heating element. The at least one sensor can optionally be selected from a group consisting of motor encoder, linear position, pressure sensor, gyroscope, accelerometer, and temperature sensor.

The bioprinting system of the present teachings for multi-dimensional printing of tissue into a tissue enclosure can include, but is not limited to including, a multi-axis, multi-dimensional printer including a robot controller controlling the motion of the printer, and a delivery device operably coupled with the printer. The delivery device can deliver the tissue. The system can include a tissue enclosure that can include a space for the printed tissue. The tissue enclosure can receive the delivered tissue, and the tissue enclosure can include a plurality of control points that can enable entry of the delivery device. The tissue enclosure can include production line mounting features. The system can include a computer that can access a design of the tissue to be printed. The computer can convert the design to coordinates that the multi-dimensional printer can use to print tissue into the tissue enclosure. The computer can execute computer commands including, but not limited to, accessing parameters associated with the computer commands, and pathing of the design based at least on the parameters. The pathing can produce robot coordinates of the design. The computer can execute commands including transferring the robot coordinates from the computer to the multi-dimensional printer. The system can include a robot controller that can process the robot coordinates including converting the robot coordinates to robot points, an approach vector, an orientation vector, and at least one path, choosing a robot figure for each path based on a desired robot position and range of motion, determining a translation data type based on the approach vector, the orientation vector, and the robot figure, creating at least one motion command based on the translation data type and the robot points, and printing the tissue into the tissue enclosure by commanding the printer based on the at least one motion command.

The method of the present teachings for printing tissue into a tissue enclosure using a robot can include, but is not limited to including, accessing a design of the tissue by a computer, converting the design to robot coordinates that the robot can use to print tissue into the tissue enclosure including, but not limited to including, initializing a multi-axis, multi-dimensional printing system including, but not limited to including, establishing offset parameters for a robot tool, the robot tool enabling printing of the tissue into the tissue enclosure, locating at least one control point used in pathing, and creating at least one path point to be pathed in part space. The pathing can include, but is not limited to including, converting the at least one control point and the at least one path point to robot coordinates, and determining robot orientations. The transferring of the robot coordinates from the computer to the robot can include, but is not limited to including, creating batches of data, setting a pose for the robot for each of the batches, sending the batches to the robot using a communications network protocol, and processing the batches in the robot can include, but is not limited to including, converting the data in each of the batches to robot points, an approach vector, and an orientation vector, choosing a robot figure for each path based on a desired robot position and range of motion, determining a translation data type based on the vector components and the robot figure, and creating a motion command based on the translation data type and the robot points. The method can include executing the motion command to print the tissue in the tissue enclosure.

The method of the present teachings for filling a syringe with a material housed in a container, where the syringe includes a syringe barrel and a plunger, the method can include, but is not limited to including, inserting the syringe barrel into a syringe filler. The syringe barrel can include a plunger end and a coupling end. The syringe filler can include a syringe coupler at a first end of the syringe filler, and a flange at a second end of the syringe filler. The syringe coupler can include a contact end having an opening. The method can include operably coupling the coupling end of the syringe barrel with the syringe coupler, and depressing the flange and the syringe barrel into the container until the material enters the opening and until the material emerges from the syringe plunger end of the syringe barrel.

The method can optionally include removing the plunger from the syringe barrel before inserting the syringe barrel into the syringe filler, and replacing the plunger into the syringe barrel after the syringe barrel is removed from the syringe filler. The material can optionally include a gel-like substance. The method can optionally include homogenizing the material by centrifugation or speed mixing. The syringe coupler can optionally include threading. The threading can matingly couple the syringe barrel with the syringe coupler. The opening size can optionally be based at least on a desired flow rate of the material into the syringe coupler and a desired normal force on the flange required to transfer the material to the syringe barrel.

The syringe filler of the present teachings for filling a syringe barrel with a material, where the syringe barrel includes a plunger end and a coupling end, the syringe filler system can include, but is not limited to including, a filler body including enough space to accept the syringe barrel, and a flange operably coupled with filler body. The flange can enable a substantially normal force to be exerted against the filler body. The substantially normal force can push the syringe filler into a container containing the material. The syringe filler can include a syringe coupler that can include a syringe coupling and a material tube. The syringe coupling can matably connect with the filler body. The material can travel through the material tube from the container to the syringe barrel. The filler body can optionally include a diameter accommodating the size of the syringe barrel and the diameter of the container. The syringe coupler can optionally include at least one protrusion providing at least one seating position for at least one gasket. The at least one gasket can enable the syringe coupler to tightly couple with the container as the syringe coupler moves into the container.

The printing device of the present teachings for printing in a gel-like material can include, but is not limited to including, at least one chassis composed of a base structure and a chassis upright and further comprising a first region and a second region. The first region can be partitioned from the second region through a barrier on base structure of the chassis. The printing device can include at least one primary carriage operatively coupled with the chassis upright and performing a first set of at least one guided motion along at least one fixed path on the plane of the chassis upright. The printing device can include at least one first sub-carriage providing an engaging feature and a pathway operatively coupled with the at least one primary carriage to perform a second set of at least one guided motion. The printing device can include at least one second sub-carriage configured to travel along the pathway of the first sub-carriage to perform a third set of at least one guided motion. The printing device can include at least one delivery system engaged with one of the carriages through a common base plate. The at least one delivery system can perform a resultant motion from combination of first, second and third sets of guided motions. The delivery system can engage one or more printing cartridges at more than one engaging points to exhibit bi-directional material flow in the one or more cartridges. The delivery system can include at least one vessel comprising the gel-like material wherein the printing device prints, the at least one vessel further arrested by a vessel adaptor configured to accommodate vessels of varying dimensions. The printing device can optionally include at least one referencing system. The printing device can optionally include at least one monitoring system that can operate in conjunction with the at least one referencing system.

The method of the present teachings for manufacturing a printing system for printing a specimen in a gel-like material can include, but is not limited to including, providing a chassis with a base structure and an upright body. The base structure can house one or more vessel adaptors to arrest one or more vessels of varying dimensions. The method can include engaging the chassis with at least one primary carriage performing a first set of at least one guided motion along plane of the chassis, and engaging the at least one primary carriage with at least one first sub-carriage comprising an engaging portion and a pathway. The first sub-carriage can provide a second set of at least one guided motion. The method can include engaging the first sub-carriage with a second sub-carriage comprising an engaging portion and a second pathway. The second sub-carriage can perform a third set of at least one guided motion. The method can include engaging at least one delivery assembly with the second sub-carriage. The delivery assembly can include, but is not limited to including, a base plate engaging a lower end of at least one printing cartridge. The base plate engage the at least one delivery assembly with at least one of the carriages such that a combined motion of the first, second and third sets of guided motion is advanced to the delivery assembly. The delivery assembly can include at least one actuating plate engaging at least one plunger end of the printing cartridge such that one or more travel features on the at least one actuating plate can bi-directionally actuate the at least one plunger of the printing cartridge. The at least one actuating plate can be partially engaged with the base plate. The delivery assembly can include at least one printing cartridge that can include a body portion with print material and a delivery needle and a plunger portion that can actuate the print material therein. The at least one printing cartridge can be partially held between the base plate and the at least one actuating plate such that the plunger portion is bi-directionally actuated.

