Devices, systems, and methods for the fabrication of tissue

• US 8,931,880 B2
• Filed: 08/15/2013
• Issued: 01/13/2015
• Est. Priority Date: 10/21/2010
• Status: Active Grant

• Current Assignee: Organovo Inc. (Organovo Holdings, Inc.)
• Original Assignee: Organovo Inc. (Organovo Holdings, Inc.)
• Inventors: Murphy, Keith, Dorfman, Scott, Smith, Nathan, Bauwens, Larry, Sohn, Ian, McDonald, Tim, Leigh-Lancaster, Chris, Law, Richard Jin
• Primary Examiner(s): Vo, Anh T. N.
• Application Number:
  US13/968,313
• Publication Number:
  US 20140012407A1
• Time in Patent Office: 516 Days
• Field of Search: 347/5, 347/8, 347/20, 347/37, 347/84, 347/85, 347/103, 347/198, 347/19, 424/572, 427/2.1, 427/2.24, 427/8, 435/395, 435/397, 604/289, 700/98, 700/118
• US Class Current: 347/20
• CPC Class Codes: B01L 3/0268 using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries
• CPC Class Codes: B28B 1/001 Rapid manufacturing of 3D objects by additive depositing, agglomerating or laminating of material selective deposition modelling of metallic powder B22F10/00; rapid manufacturing of 3D objects in general and in particular of plastics B29C64/00
• CPC Class Codes: B29C 31/045 moving along predetermined circuits or distributing the material according to predetermined patterns
• CPC Class Codes: B29C 64/106 using only liquids or viscous materials, e.g. depositing a continuous bead of viscous material
• CPC Class Codes: B29C 64/112 using individual droplets, e.g. from jetting heads
• CPC Class Codes: B29C 64/20 Apparatus for additive manufacturing; Details thereof or accessories therefor
• CPC Class Codes: B29C 64/209 Heads; Nozzles
• CPC Class Codes: B29C 64/245 Platforms or substrates support structures intended to be sacrificed after manufacture B29C64/40
• CPC Class Codes: B29C 64/295 Heating elements
• CPC Class Codes: B29C 64/386 Data acquisition or data processing for additive manufacturing
• CPC Class Codes: B29C 64/393 for controlling or regulating additive manufacturing processes
• CPC Class Codes: B29C 64/40 Structures for supporting 3D objects during manufacture and intended to be sacrificed after completion thereof
• CPC Class Codes: B33Y 30/00 Apparatus for additive manufacturing; Details thereof or accessories therefor
• CPC Class Codes: B33Y 50/02 for controlling or regulating additive manufacturing processes
• CPC Class Codes: B33Y 70/00 Materials specially adapted for additive manufacturing
• CPC Class Codes: B41J 2/04501 Control methods or devices therefor, e.g. driver circuits, control circuits
• CPC Class Codes: B41J 2/04503 aiming at compensating carriage speed
• CPC Class Codes: B41J 2/04505 aiming at correcting alignment
• CPC Class Codes: B41J 2/04526 controlling trajectory
• CPC Class Codes: B41J 2/04553 detecting ambient temperature
• CPC Class Codes: B41J 2/04563 : detecting head temperature; Ink temperature
• CPC Class Codes: B41J 2/17503 : Ink cartridges
• CPC Class Codes: B41J 2/1752 : Mounting within the printer
• CPC Class Codes: B41J 3/407 : for marking on special material
• CPC Class Codes: C12M 21/08 : for producing artificial tissue or for ex-vivo cultivation of tissue prostheses A61F2/00, grafts A61L27/00
• CPC Class Codes: C12M 33/00 : Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus chemical or physical laboratory apparatus in general B01L, devices for taking cell samples A61B10/0045, withdrawing or distributing predetermined quantities of fluid B01L99/00
• CPC Class Codes: C12N 5/0062 : General methods for three-dimensional culture

Abstract

Described herein are bioprinters comprising: one or more printer heads, wherein a printer head comprises a means for receiving and holding at least one cartridge, and wherein said cartridge comprises contents selected from one or more of: bio-ink and support material; a means for calibrating the position of at least one cartridge; and a means for dispensing the contents of at least one cartridge. Further described herein are methods for fabricating a tissue construct, comprising: a computer module receiving input of a visual representation of a desired tissue construct; a computer module generating a series of commands, wherein the commands are based on the visual representation and are readable by a bioprinter; a computer module providing the series of commands to a bioprinter; and the bioprinter depositing bio-ink and support material according to the commands to form a construct with a defined geometry.

Claims

1. A three-dimensional bioprinter comprising:

a. one or more printer heads, wherein a printer head comprises a means for receiving and holding at least one cartridge, wherein a cartridge comprises at least one deposition orifice and contents comprising a bio-ink, wherein the bio-ink comprises solid or semi-solid aggregates of living cells;

b. a means for calibrating a position in space of the at least one cartridge or the at least one deposition orifice utilizing a laser and a laser detector;

c. a means for extruding the contents of the at least one cartridge by application of pressure, utilizing a piston;

d. a receiving surface for receiving the extruded contents of the at least one cartridge; and

e. a programmable computer processor communicatively connected to the means for calibrating and the means for extruding, the programmable computer processor for positioning the one or more printer heads in three dimensions and regulating the extrusion of the contents of the at least one cartridge.

2. The bioprinter of claim 1, further comprising a means for applying a wetting agent, utilizing a sprayer or a pipette, to one or more of:

a. the receiving surface;

b. the at least one deposition orifice;

c. the bio-ink; and

d. the extruded contents of the at least one cartridge;

wherein the wetting agent is applied at one or more time points selected from;

before the bio-ink is extruded by the bioprinter, substantially concurrently with extruding, and after the bio-ink is extruded by the bioprinter.

3. The bioprinter of claim 1, wherein the means for calibrating the position of the at least one cartridge or the at least one deposition orifice calibrates along an x-axis, a y-axis, and a z-axis, utilizing one or more lasers and the laser detector.

4. The bioprinter of claim 1, wherein the computer processor is programmable by:

a. a graphical user interface that is capable of receiving input of a visual representation of a desired tissue construct; and

b. generating a series of commands, wherein the commands are based on the visual representation inputted via the graphical user interface.

5. The bioprinter of claim 4, wherein the visual representation comprises identification of one or more elements of a desired tissue construct as one or more of:

a. the bio-ink; and

b. a specific composition of the bio-ink.

6. The bioprinter of claim 1, wherein the one or more printer heads, the at least one cartridge, or the at least one deposition orifice are moved relative to the receiving surface, utilizing the laser and the laser detector, to produce a desired tissue construct of a particular three-dimensional geometry inputted via the graphical user interface in the extruded contents of the at least one cartridge.

7. The bioprinter of claim 1, wherein the receiving surface is moved relative to the one or more printer heads, the at least one cartridge, or the at least one deposition orifice, utilizing the laser and the laser detector, to produce a desired tissue construct of a particular three dimensional geometry inputted via the graphical user interface, in the extruded contents of the at least one cartridge.

8. The bioprinter of claim 1, wherein the solid or semi-solid aggregates of living cells are substantially elongate.

9. The bioprinter of claim 8, wherein the solid or semi-solid aggregates of living cells are substantially in the form of cylinders or ribbons.

10. The bioprinter of claim 1, wherein the solid or semi-solid aggregates of living cells cellular aggregates are substantially spheroid.