Automated devices, systems, and methods for the fabrication of tissue

Abstract

Described herein are improvements to bioprinting technology that facilitate automation of tissue and organ fabrication processes.

What is claimed is: 
     
         1 . An automated bioprinter comprising:
 a. a printer head comprising one or more cartridges, each cartridge comprising contents selected from: bio-ink, support material, and a combination thereof; and for each cartridge:
 i. an actuation means that vertically positions the cartridge relative to a receiving surface to produce a particular three-dimensional geometry in the dispensed contents of the cartridge, the actuation means operating independently from other actuation means; and 
 ii. a deposition orifice; 
   b. a receiving surface for receiving dispensed contents of a cartridge; and   c. a calibration means comprising a three-dimensional calibration system, the system comprising at least two lasers, a sensor fixed to the receiving surface for determining the position of the deposition orifice; and a sensor fixed to the printer head for determining the position of the receiving surface; whereby the system calculates a print height, the print height comprising the distance between the deposition orifice and the receiving surface;   whereby a construct is bioprinted without stopping the bioprinter to manually replace one or more cartridges or to manually adjust the positioning of the printer head or the positioning of one or more of the cartridges.   
     
     
         2 . The automated bioprinter of  claim 1 , wherein the three-dimensional calibration system creates a topographical map of the receiving surface. 
     
     
         3 . The automated bioprinter of  claim 1 , wherein the three-dimensional calibration system creates a topographical map of the deposition orifice. 
     
     
         4 . The automated bioprinter of  claim 1 , wherein the three-dimensional calibration system monitors the print height during deposition of the contents of a cartridge. 
     
     
         5 . The automated bioprinter of  claim 1  further comprising at least one die, each die controlling
 a. simultaneous deposition of a plurality of constructs in parallel and arranged in a pattern, each construct having a particular three-dimensional geometry; 
 b. deposition of a single construct having a particular three-dimensional geometry; or 
 c. a combination thereof. 
 
     
     
         6 . The automated bioprinter of  claim 1  further comprising one or more multiaxial nozzles for controlling the deposition of one or more constructs having a particular three-dimensional geometry, wherein each multiaxial nozzle has dual or greater concentric flow capability with at least two independent inputs for at least two different materials and at least two independent outputs for the preparation of a multiaxial tube with a core layer and a mantle layer and optionally one or more intermediate layers in between the core and mantle layers, any two adjacent layers having different composition of materials with respect to each other and the materials being selected from bio-ink, support material, and a combination thereof. 
     
     
         7 . The automated bioprinter of  claim 6 , wherein each of the one or more multiaxial nozzles further comprises a means to independently regulate the flow of each of the at least two different materials through the at least two independent outputs. 
     
     
         8 . The automated bioprinter of  claim 7 , wherein the means to independently regulate the flow of each of the at least two different materials through the at least two independent outputs allows for continuous extrusion or sputter extrusion. 
     
     
         9 . The automated bioprinter of  claim 6 , wherein one of the at least two different materials is removed after bioprinting to create one or more voids. 
     
     
         10 . The automated bioprinter of  claim 1 , wherein at least one cartridge further comprises a means to adjust and/or maintain the temperature of the cartridge. 
     
     
         11 . An automated bioprinter comprising
 a. a printer head comprising at least three cartridges, wherein:
 i. at least one cartridge comprises a capillary tube containing bio-ink; 
 ii. at least one cartridge comprises a needle containing bio-ink; 
 iii. at least one cartridge is configured for ink-jet printing; and 
 iv. each cartridge comprises contents selected from bio-ink, support material, and a combination thereof; and 
   b. a receiving surface for receiving dispensed contents of a cartridge;   whereby a construct is bioprinted without stopping the bioprinter to manually replace one or more cartridges or to manually adjust the positioning of the printer head or the positioning of one or more of the cartridges.   
     
     
         12 . The automated bioprinter of  claim 11 , wherein the needle is in communication with a bio-ink reservoir, bio-ink deposition is by pneumatic displacement, and the bio-ink is a liquid or semi-solid composition. 
     
     
         13 . The automated bioprinter of  claim 11 , wherein the capillary tube deposits bio-ink through a positive displacement mechanism, and the bio-ink is a solid or semi-solid composition. 
     
     
         14 . The automated bioprinter of  claim 11  further comprising a calibration means comprising a three-dimensional calibration system, the system comprising at least two lasers, a sensor fixed to the receiving surface for determining the position of a deposition orifice; and a sensor fixed to the printer head for determining the position of the receiving surface; whereby the system calculates a print height, the print height comprising the distance between the deposition orifice and receiving surface. 
     
     
         15 . The automated bioprinter of  claim 11  further comprising at least one die, each die controlling
 a. simultaneous deposition of a plurality of constructs in parallel and arranged in a pattern, each construct having a particular three-dimensional geometry; 
 b. deposition of a single construct having a particular three-dimensional patterned geometry; or 
 c. a combination thereof. 
 
     
     
         16 . The automated bioprinter of  claim 11  further comprising one or more multiaxial nozzles for controlling the deposition of one or more constructs having a particular three-dimensional geometry, wherein each multiaxial nozzle has dual or greater concentric flow capability with at least two independent inputs for at least two different materials and at least two independent outputs for the preparation of a multiaxial tube with a core layer and a mantle layer and optionally one or more intermediate layers in between the core and mantle layers, any two adjacent layers having different composition of materials with respect to each other and the materials being selected from bio-ink, support material, and a combination thereof. 
     
     
         17 . An automated bioprinter comprising at least one die, each die controlling
 a. simultaneous deposition of a plurality of constructs in parallel and arranged in a pattern, each construct having a particular three-dimensional geometry;   b. deposition of a single construct having a particular three-dimensional patterned geometry; or   c. a combination thereof;   whereby the single construct or plurality of constructs are bioprinted without stopping the bioprinter to manually replace or to manually adjust the positioning of one or more components of the bioprinter.   
     
     
         18 . The automated bioprinter of  claim 17 , wherein the die is permanently fixed. 
     
     
         19 . The automated bioprinter of  claim 17 , wherein the die is reversibly fixed. 
     
     
         20 . The automated bioprinter of  claim 17 , wherein the die controls simultaneous deposition of 2-384 constructs in parallel and arranged in a pattern. 
     
     
         21 . The automated bioprinter of  claim 17 , wherein the die is connected to one or more chambers for containing a uniform layer of bio-ink, support material, or a combination thereof. 
     
     
         22 . The automated bioprinter of  claim 17 , wherein the die controls simultaneous deposition of a plurality of materials in parallel. 
     
     
         23 . The automated bioprinter of  claim 22 , wherein the die comprises an input port for each material. 
     
     
         24 . The automated bioprinter of  claim 17 , wherein each construct in the plurality of constructs has the same three-dimensional geometry. 
     
     
         25 . The automated bioprinter of  claim 17 , wherein each of the constructs in the plurality of constructs is in contact with one another to form a single construct. 
     
     
         26 . An automated bioprinter comprising one or more multiaxial nozzles for controlling the deposition of one or more constructs having a particular three-dimensional geometry, wherein each multiaxial nozzle has dual or greater concentric flow capability with at least two independent inputs for at least two different materials and at least two independent outputs for the preparation of a multiaxial tube with a core layer and a mantle layer and optionally one or more intermediate layers in between the core and mantle layers, any two adjacent layers having different composition of materials with respect to each other and the materials being selected from bio-ink, support material, and a combination thereof; whereby the one or more constructs are bioprinted without stopping the bioprinter to manually replace or to manually adjust the positioning of one or more components of the bioprinter. 
     
     
         27 . The automated bioprinter of  claim 26 , wherein each of the one or more multiaxial nozzles further comprises a means to independently regulate the flow of each of the at least two different materials through the at least two independent outputs. 
     
     
         28 . The automated bioprinter of  claim 27 , wherein the means to independently regulate the flow of each of the at least two different materials through the at least two independent outputs allows for continuous extrusion or sputter extrusion. 
     
     
         29 . The automated bioprinter of  claim 26 , wherein one of the at least two different materials is removed after bioprinting to create one or more voids. 
     
     
         30 . The automated bioprinter of  claim 26 , wherein one or more of the multiaxial nozzles are coaxial nozzles.