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

• US 9,315,043 B2
• Filed: 07/10/2015
• Issued: 04/19/2016
• Est. Priority Date: 07/31/2013
• Status: Active Grant

• Current Assignee: Organovo Inc. (Organovo Holdings, Inc.)
• Original Assignee: Organovo Inc. (Organovo Holdings, Inc.)
• Inventors: Murphy, Keith, Lin, Frank, Gorgen, Vivian, Platt, Clay, Rapoport, Harry Scott, Damle, Samir, Joshi, Vaidehi, Presnell, Sharon C., Pentoney, Stephen Jr.
• Primary Examiner(s): Hindenlang, Alison L
• Application Number:
  US14/796,910
• Publication Number:
  US 20150314613A1
• Time in Patent Office: 284 Days
• US Class Current: 1/1
• CPC Class Codes: A61F 2/00 Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents as cosmetic articles, see the relevant subclasses, e.g. wigs, hair pieces, A41G3/00, A41G5/00; artificial nails A45D31/00; dental prostheses A61C13/00; materials for prostheses A61L27/00; artificial hearts A61M60/00; artificial kidneys A61M1/14
• CPC Class Codes: A61F 2240/00 Manufacturing or designing of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
• 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 64/182 in parallel batches
• CPC Class Codes: B29C 64/393 for controlling or regulating additive manufacturing processes
• CPC Class Codes: B29K 2033/08 Polymers of acrylic acid esters, e.g. PMA, i.e. polymethylacrylate
• CPC Class Codes: B29K 2071/02 Polyalkylene oxides, e.g. PEO, i.e. polyethylene oxide, or derivatives thereof
• CPC Class Codes: B29K 2995/0056 Biocompatible, e.g. biopolymers or bioelastomers
• CPC Class Codes: B29L 2031/40 Test specimens ; Models, e.g. model cars mannequins B29L2031/7028; Probes
• CPC Class Codes: B29L 2031/7532 Artificial members, protheses
• CPC Class Codes: B33Y 10/00 Processes of additive manufacturing
• 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: B33Y 80/00 Products made by additive manufacturing
• CPC Class Codes: B41J 2/04 generating single droplets or particles on demand
• 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 25/00 Means for supporting, enclosing or fixing the microorganisms, e.g. immunocoatings
• 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: C12M 33/12 : by pressure
• CPC Class Codes: C12M 41/00 : Means for regulation, monitoring, measurement or control, e.g. flow regulation controlling or regulating chemical, physical or physicochemical processes B01J19/0006; heating or cooling apparatus for laboratory use B01L7/00; electro optical investigation of individual particles, flow cytometers G01N15/14; automatic analysis G01N35/00; controlling or regulating in general G06N
• CPC Class Codes: G05B 19/27 : using an absolute digital measuring device
• CPC Class Codes: G05B 2219/49023 : 3-D printing, layer of powder, add drops of binder in layer, new powder

Abstract

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

Claims

1. A bioprinter comprising one or more coaxial nozzles with an N-value of two or more configured to control the deposition of materials to form one or more constructs having a pre-determined three-dimensional geometry, wherein each coaxial nozzle has concentric flow wherein each coaxial nozzle comprises at least two independent inputs for at least two different materials and at least two independent outputs configured to prepare a coaxial tube comprising a core layer and a mantle layer, any two adjacent layers having a different composition of materials with respect to each other, and the materials being selected from a bio-ink, or a combination of bio-ink and support material, wherein the bio-ink comprises living cells.

2. The bioprinter of claim 1, wherein each of the one or more coaxial 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.

3. The bioprinter of claim 2, 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, wherein sputter extrusion is the stopping and starting of the flow through at least one of the at least two independent outputs.

4. The bioprinter of claim 2, wherein the means to independently regulate the flow of each of the at least two different materials produces a flow rate for at least one of the materials of about 0.1 to about 1 ml/min.

5. The bioprinter of claim 1, wherein one of the at least two different materials is removed after bioprinting to create one or more voids.

6. The bioprinter of claim 1, wherein the one or more coaxial nozzles has an N-value of three or more.

7. The bioprinter of claim 6, comprising three independent inputs for three different materials and three independent outputs for the preparation of a coaxial tube with a core layer, a mantle layer, and an intermediate layer, the intermediate layer between the core layer and the mantle layer.

8. The bioprinter of claim 1, wherein the one or more coaxial nozzles are configured to produce a core layer that is about 150 μ

m in diameter and a mantle layer that is about 500 μ

m in diameter.

9. The bioprinter of claim 1, comprising four independent inputs for four different materials and four independent outputs configured to prepare a coaxial tube with a core layer, a mantle layer, and at least two intermediate layers.

10. The bioprinter of claim 1, configured to prepare any of the one or more constructs with a three-dimensional geometry that is a cylinder, hollow cylinder, polygon, sheet, or sphere.

11. The bioprinter of claim 1, wherein the bio-ink, or the bio-ink and the support material are a solid or semi-solid.

12. The bioprinter of claim 1, wherein the bioprinter deposits the materials by application of pressure to extrude the materials though an orifice.