NZ774792B2

NZ774792B2 - Fluid pumping and bioreactor system

Info

Publication number: NZ774792B2
Application number: NZ774792A
Authority: NZ
Inventors: Michael A Baker; David Blumberg Jr; Jason A Demers; Dean Kamen; Richard J Lanigan; Timothy D Moreau; Frederick Morgan; Brian D Tracey; Der Merwe Dirk A Van; Matthew Ware
Original assignee: Deka Products Limited Partnership
Filing date: 2016-10-07
Publication date: 2025-05-01

Abstract

method for generating a tissue for transplant comprising: accessing, by a controller, a recipe including recipe steps; receiving, by the controller, GUI input from a graphical user interface (GUI); accessing, by the controller, the recipe steps, the GUI input, and at least one default value; forming, by the controller, at least one controller command based on arbitrating the at least one default value, the recipe steps, and the GUI input; executing, by the controller, the at least one controller command to generate the tissue for transplant through iteratively decellularizing and recellularizing the biological specimen; covering at least one pumping chamber and at least one fluid valve of at least one pump cassette with a flexible sheet; housing donor tissue in the at least one bioreactor, the at least one bioreactor being in fluid communication with the at least one pump cassette; receiving, by at least one valve module processor, the at least one controller command from the controller; generating, by the at least one valve module processor, at least one valve module command based on the at least one controller command, the at least one valve module command being addressed to at least one valve module; receiving, by the at least one valve module, the at least one valve module command; generating, by the at least one valve module, a plurality of the at least one valve module commands based on the at least one valve module command, the plurality of the valve module commands governing fluid flow by managing states of a plurality of valves of the at least one valve module, the at least one valve controlling pressure applied to the flexible sheet via outlet ports; and engineering the tissue into transplantable tissue using the fluid flowing into and out of the at least one bioreactor, the flowing being based on the at least one controller command. The method allows for decellularization/recellularization procedures to be performed on a large scale with speed, efficiency, precision, repeatability, versatility, and flexibility.

Claims

What is claimed is:

1. A method for generating a tissue for transplant comprising: accessing, by a ller, a recipe ing recipe steps; ing, by the controller, GUI input from a graphical user ace (GUI); accessing, by the controller, the recipe steps, the GUI input, and at least one default value; forming, by the controller, at least one controller command based on arbitrating the at least one default value, the recipe steps, and the GUI input; executing, by the ller, the at least one controller command to generate the tissue for transplant through iteratively decellularizing and recellularizing the biological specimen; covering at least one pumping chamber and at least one fluid valve of at least one pump cassette with a flexible sheet; housing donor tissue in the at least one bioreactor, the at least one bioreactor being in fluid communication with the at least one pump cassette; receiving, by at least one valve module sor, the at least one controller command from the ller; generating, by the at least one valve module processor, at least one valve module command based on the at least one controller command, the at least one valve module command being addressed to at least one valve module; receiving, by the at least one valve module, the at least one valve module command; generating, by the at least one valve module, a plurality of the at least one valve module commands based on the at least one valve module command, the plurality of the valve module commands governing fluid flow by managing states of a plurality of valves of the at least one valve module, the at least one valve controlling pressure applied to the flexible sheet via outlet ports; and ering the tissue into transplantable tissue using the fluid flowing into and out of the at least one bioreactor, the flowing being based on the at least one controller command.

2. The method as in claim 1 further comprising: applying a first protocol to the ularizing; and applying a second protocol to the recellularizing.

3. The method as in claim 1 further comprising: introducing at least one agent to the biological specimen for a pre-selected amount of time; introducing a cell culture to the biological specimen.

4. The method as in claim 3 wherein the at least one agent comprises: at least one of solutions, media, fluids, and biological agents.

5. The method as in claim 2 wherein the second protocol comprises: expanding and differentiating a population of cells; and introducing the expanded and differentiated cells to the biological specimen.

6. The method as in claim 5 wherein the differentiating comprises: in vitro differentiation of endothelial cells and smooth muscle cells.

7. The method as in claim 6 wherein the introducing ses: ing the endothelial cells and the smooth muscle cells.

8. The method as in claim 7 n the ing comprises: administering endothelial cells and the smooth muscle cells in alternating fashion.

9. The method as in claim 1 further comprising: preparing the biological specimen by decellularizing the biological specimen a plurality of times.

10. The method as in claim 1 further comprising: decellularizing the iteratively ularized and ularized biological specimen a plurality of times.

11. The method as in claim 3 further comprising: amending the biological specimen by removing an undesired ent using the at least one agent; and rinsing the amended biological specimen.

12. The method as in claim 3 further comprising: perfusing the at least one agent may through an anatomical passageway of the ical specimen.

13. The method as in claim 3 further comprising: bathing the biological en in the at least one agent.

14. The method as in claim 3 further comprising: mechanically agitating the biological specimen; and regulating temperature of the biological specimen.

15. The method as in claim 3 wherein recellularization comprises: introducing the cell culture to the decellularized biological specimen.

16. The method as in claim 15 wherein introducing cells ses: perfusing the cells through an anatomical passageway of the biological specimen

17. The method as in claim 15 wherein introducing cells comprises: bathing the biological specimen in the cells.

18. The method as in claim 15 wherein introducing cells comprises: ing different types of the cells through an anatomical passageway of the biological specimen.

19. The method as in claim 15 further sing: simulating pulsatile blood flow through the biological specimen.

20. The method as in claim 1 further comprising: ng, by the controller, the GUI based at least on a status of the tissue for lant; and updating, by the controller, the recipe based at least on the status.

21. The method as in claim 1 comprising: continually managing, by the controller, a valve state of at least one fluid valve in a fluid path according to the at least one controller command, the continually-managed valve state continually adjusting the fluid path, the fluid path ing a conduit for fluid containing at least one agent, a cell culture, and at least one solution, the fluid enabling the decellularization and the recellularization; enabling, by the controller, pumping water through the continually-adjusted fluid path past at least one of the at least one fluid valve to at least one mix cassette, an amount of the water being based on the at least one controller command; enabling, by the controller, pumping the fluid through the ually-adjusted fluid path past at least one of the at least one fluid valve to the at least one mix cassette, characteristics of the fluid being based at least on the at least one controller command; enabling, by the controller, mixing the water and the fluid in the at least one mix cassette to form media, a mixing amount of the mixing being based at least on the at least one controller command; enabling, by the controller, pumping the media through the ually-adjusted fluid path to at least one oir based at least on the at least one controller d; enabling, by the controller, pumping the media through the continually-adjusted fluid path from the at least one reservoir to at least one ctor based at least on the at least one controller command, the media becoming a used media in the at least one bioreactor; and enabling, by the ller, pumping the used media through the continually-adjusted fluid path from the at least one bioreactor to a drain based at least on the at least one controller command.

22. The method as in claim 21 further comprising: filtering the water; deaerating the water; and if a water amount of the water exceeds a pre-selected threshold, g at least part of the water.

23. The method as in claim 1 wherein the at least one pump cassette comprises a pneumatically controlled cassette.

24. The method as in claim 1 n the at least one mix cassette comprises a pneumatically controlled cassette.

25. The method as in claim 1 wherein at least one of the at least one pump cassette comprises a disposable cassette.

26. The method as in claim 1 wherein at least one of the at least one mix cassette comprises a disposable cassette.

27. The method as in claim 1, substantially as herein described or exemplified. wmw w momv - (mg. 302‘ ”Emwwuqmvw Gear I”VEFNH momw warm (om? _w_\N ) I .