Fluid pumping and bioreactor system

• US 10,294,450 B2
• Filed: 10/07/2016
• Issued: 05/21/2019
• Est. Priority Date: 10/09/2015
• Status: Active Grant

• Current Assignee: Deka Products Limited Partnership
• Original Assignee: Deka Products Limited Partnership
• Inventors: Kamen, Dean, Demers, Jason A., Morgan, Frederick, Moreau, Timothy D., Tracey, Brian D., Ware, Matthew, van der Merwe, Dirk A., Lanigan, Richard J., Baker, Michael A., Blumberg, Jr., David
• Primary Examiner(s): Ware, Deborah K
• Application Number:
  US15/288,900
• Publication Number:
  US 20170101618A1
• Time in Patent Office: 956 Days
• CPC Class Codes: A61L 27/3683 subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• 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 23/40 Manifolds; Distribution pieces fluid transfer means B01L3/563
• CPC Class Codes: C12M 23/42 Integrated assemblies, e.g. cassettes or cartridges
• CPC Class Codes: C12M 25/14 Scaffolds; Matrices in general C12N5/0068
• CPC Class Codes: C12M 29/00 Means for introduction, extraction or recirculation of materials, e.g. pumps pumps per se F04B
• CPC Class Codes: C12M 41/48 Automatic or computerized control automatic analysis G01N35/00
• CPC Class Codes: C12N 5/0602 Vertebrate cells

Abstract

A fluid pumping and bioreactor system including at least two cassettes, at least one storage reservoir, at least one bioreactor, at least one manifold including valve modules, and tubing to connect the cassettes to the storage reservoir and the bioreactor. The cassettes can include pumps, valves, and fluid conduits and can be communicatively connected to the at least one manifold. The bioreactor can include an adapter and fluid conduits extending through the adapter from the exterior of the bioreactor to the interior of the bioreactor. System and method for generating a tissue for transplant by decellularizing and recellularizing a supplied tissue.

Claims

1. A set for decellularizing tissue comprising:

at least one reservoir including a plurality of ports, the plurality of ports including at least one mix port and at least one pump port;

at least one bioreactor including at least one bioreactor port, the at least one bioreactor surrounding the tissue;

at least one pump cassette, the pump cassette including at least one pump, at least one reservoir port fluidically connecting the at least one pump cassette to the at least one reservoir at the at least one pump port, the at least one pump cassette including at least one bioreactor interface port fluidically connecting the at least one pump cassette to the at least one bioreactor at the at least one bioreactor port, the at least one pump cassette including at least one first fluid bus and at least one pump cassette valve, the at least one pump cassette valve managing the routing of a first fluid from the at least one reservoir through the at least one pump to the at least one bioreactor interface port;

at least one mix cassette including at least one dilution port, the at least one dilution port fluidically coupling the at least one mix cassette with a medium, the at least one mix cassette include at least one reservoir port fluidically coupling the at least one mix cassette with the at least one reservoir, the at least one mix cassette including at least one solution port fluidically coupling the at least one mix cassette with at least one second fluid, the at least one mix cassette including at least one mix pump, the at least one mix cassette including at least one second fluid bus, the at least one mix cassette including at least one mix cassette valve managing the routing of the at least one second fluid from the at least one solution port through the at least one mix pump to the at least one reservoir port, the at least one mix pump mixing together a plurality of the at least one second fluid; and

tubing enabling the fluidic connections at least among the at least one first fluid bus and the at least one second fluid bus.

2. The set as in claim 1 wherein the at least one reservoir further comprises:

at least one vent port, at least one overflow port, and at least one level sensor sensing the amount of material in the at least one reservoir.

3. The set as in claim 1 wherein the at least one pump cassette further comprises:

at least one waste port fluidically coupling the at least one pump cassette to at least one waste receptacle.

4. The set as in claim 1 wherein the at least one pump cassette further comprises:

at least one loop line port enabling heating of a fluid circulating in the at least one pump cassette.

5. The set as in claim 4 wherein the at least one first fluid bus and the at least one pump cassette valve manage flow from the at least one reservoir through the at least one loop line port.

6. The set as in claim 1 wherein the at least one bioreactor comprises:

an adapter including a first face and an second face opposing the first face;

an enclosure including a first section and a second section, the first section including a first side and a second side, the enclosure including a liquid-tight seal between the first section and the first face, the enclosure including at least one enclosure pass-through, the enclosure including a liquid-tight seal between at least a portion of the second section and at least a portion of the first section;

a first fluid line operably coupled to the adapter, the first fluid line coupling the at least one enclosure pass-through and the adapter; and

a second fluid line disposed on the second face, the second fluid line fluidically coupled with the first fluid line, the first fluid line coupled with the second fluid line forming a closed fluid path.

7. The set as in claim 1 further comprising:

a flexible sheet covering the at least one pump, the flexible sheet covering at least one mix cassette valve.

8. The set as in claim 7 further comprising:

a controller generating at least one controller command; and

at least one valve module, each of the at least one valve modules, having at least one pressure bus, each of the at least one valve modules having at least one valve operably communicating with the pressure bus, each of the at least one valve modules having an outlet port, the outlet port being associated with each of the at least one mix cassette valve, the outlet port operably communicating with the flexible sheet, the at least one valve module including a first module having a first module processor, the first module processor receiving the at least one controller command, the first module processor generating, based on the controller command, at least one second module command addressed to at least one second module, the at least one second module having a second module processor receiving the at least one second module command and generating, based on the at least second module command, at least one valve command governing fluid flow through the at least one mix cassette valve of the at least one second module, the at least one mix cassette valve controlling pressure applied to the flexible sheet via the outlet ports, the at least one controller command metering the fluid flow to the tissue and the bioreactor, the tissue being decellularized based on the fluid flow.

9. The set as in claim 7 further comprising:

a controller generating at least one controller command; and

at least one first valve module and at least one second valve module, each of the at least one first and second valve modules having at least one pressure bus and at least one mix cassette valve, the at least one mix cassette valve operably communicating with the pressure bus, each of the at least one mix cassette valves being associated with an outlet port, the outlet port operably communicating with the flexible sheeting, the first valve module having a first module processor, the first module processor receiving the at least one controller command, the first module processor generating, based on the controller command, at least one module command addressed to the at least second module, the at least one second valve module having a second module processor receiving the at least one second module command and generating, based on the at least one second module command, a plurality of valve commands, the plurality of valve commands governing fluid flow through the at least one mix cassette valve of the at least one second valve module, the at least one mix cassette valve controlling pressure applied to the flexible sheet via the outlet ports, the at least one controller command metering the fluid flow to the tissue, the tissue being recellularized based on the fluid flow.

10. The set as in claim 7 further comprising:

a recipe including recipe steps; and

a graphical user interface (GUI) receiving GUI input,

wherein the controller accesses the recipe steps, the GUI input, and at least one default value, the controller forming directions based on arbitrating the at least one default value, the recipe steps, and the GUI input, the controller executing the directions to engineer the tissue, the tissue including donor tissue.

11. The set as in claim 10 wherein the controller comprises updating the GUI and updating the recipe steps.