System and method for cell and tissue preparation

Patent metadata

Field	Value
Publication number	US-11713442-B2
Application number	US-202016904198-A
Country	US
Kind code	B2
Filing date	Jun 17, 2020
Priority date	Jun 17, 2019
Publication date	Aug 1, 2023
Grant date	Aug 1, 2023

Abstract

Manufacturing system and method for creating multiple tissue constructs from cells. System can include a thaw subsystem (if the cells are provided in a frozen state), an expansion subsystem, a concentration subsystem, and a tissue maturation subsystem. Each of these subsystems is modular and can be reconfigured, and the process can be repeated depending on the specific tissue process being implemented. Multiple tissue types can be combined in multiple bioreactors. The activities of multiple bioreactors can be coordinated and controlled in an automated manner by a supervisor controller. The supervisor controller can receive user input at the start of the process, and can manage the process henceforth, alerting the user if user actions are required.

First claim

What is claimed is:

1. A system for enabling automatic manufacture of tissue comprising:
a thaw subsystem including a thaw station receiving frozen cells in at least one vial and automatically thawing the frozen cells;
a thaw controller controlling the preparing of the cells;
an insulated container and container lid station having a cooling means cooling an environment surrounding the frozen cells in the at least one vial maintaining the frozen cells at a pre-selected temperature range;
a lid gripper and a vial gripper, the lid gripper moving, under control of the thaw controller, the container lid, the vial gripper moving, under control of the thaw controller, the at least one vial;
at least one device locating, under control of the thaw controller, a position of each of the at least one vial;
a decontamination station receiving, from the vial gripper, under control of the thaw controller, the at least one vial of thawed cells, the decontamination station including a means for decontaminating an exterior surface of the at least one vial of thawed cells, thereby forming at least one decontaminated vial of thawed cells;
a puncture station receiving, from the vial gripper, under control of the thaw controller, the at least one decontaminated vial of thawed cells, the puncture station including at least two needles, the at least two needles puncturing, under control of the thaw controller, the at least one decontaminated vial, a first needle of the at least two needles having a first length, a second needle of the at least two needles having a second length, the puncture station including a needle controller puncturing, under control of the thaw controller, the at least one decontaminated vial of thawed cells with the first needle, the first needle extending into the at least one decontaminated vial of thawed cells a first pre-selected distance, the needle controller puncturing, under control of a thaw manager, the at least one decontaminated vial of thawed cells with the second needle, the second needle extending into the at least one decontaminated vial of thawed cells a second pre-selected distance; and
a solution pump pumping, under control of the thaw controller, solution from a solution reservoir through solution tubing and the first needle into the at least one decontaminated vial of thawed cells, the thawed cells being drawn through the second needle, the thawed cells flowing through cell tubing into a cell reservoir, the cells being removed from the at least one decontaminated vial of thawed cells creating at least one waste vial,
wherein the thaw station is configured to receive, from the vial gripper, under control of the thaw controller, the at least one located vial, the thaw station including a thawing device housing the at least one located vial, the thawing device thawing the cells within the at least one vial, the thaw station including a thaw station controller, under control of the thaw controller, the thaw station controller providing a status of the cells to the thaw controller;
an expansion subsystem automatically pumping cells from at least one vial to at least one first bioreactor, the expansion subsystem automatically shutting valves from the at least one vial to the at least one first bioreactor when the cells are moved to the at least one first bioreactor, the expansion subsystem automatically creating a first pre-selected environment promoting expansion of the cells in the at least one first bioreactor, the expansion subsystem automatically pumping the expanded cells from the at least one first bioreactor to a concentrator when the expanded cells have reached a pre-selected density, the expansion subsystem configured to create resuspended cells from concentrated cells;
a concentration subsystem automatically concentrating the expanded cells; and
a maturation subsystem automatically pumping the resuspended cells into at least one second bioreactor when a pre-selected event has occurred, the maturation subsystem automatically creating a second pre-selected environment promoting maturation of the concentrated cells in the at least one second bioreactor based on monitoring sensor data of critical process parameters.

2. The system as in claim 1 wherein the concentration subsystem comprises a centrifugation device.

3. The system as in claim 1 wherein the pre-selected event comprises a detection of a desired concentration.

4. The system as in claim 1 wherein the first pre-selected environment comprises a first growth media, the first growth media being continuously automatically adjusted based on monitoring sensor data of the critical process parameters to maintain first pre-selected levels of growth media characteristics.

5. The system as in claim 1 wherein the second pre-selected environment comprises second growth media, the second growth media being continuously automatically adjusted based on monitoring of sensor data of the critical process parameters to maintain second pre-selected levels of growth media characteristics.

6. The system as in claim 1 further comprising:
an identification station identifying, under control of the thaw controller, each of the at least one vial.

7. The system as in claim 1 wherein the first length comprises a longer length than the second length.

8. The system as in claim 1 wherein the first pre-selected distance comprises a shorter distance than the second pre-selected distance.

9. The system as in claim 1 comprising a gas purge forcing substantially all contents of the at least one decontaminated vial to exit the at least one decontaminated vial.

10. The system as in claim 1 wherein the decontamination station comprises:
a hood retaining decontamination fluids within a pre-selected area surrounding the located at least one vial of thawed cells;
a decontamination pump pumping, under control of the thaw controller, the decontamination fluids into the pre-selected area; and
a nozzle directing the decontamination fluids towards the at least one located vial of thawed cells.

11. The system as in claim 1 wherein the puncture station comprises:
a base gripper maintaining the at least one located vial in place while the needle controller, under control of the thaw controller, removes the first needle and the second needle.

12. The system as in claim 1 further comprising:
a waste system receiving, from the vial gripper, under control of the thaw controller, the at least one waste vial after the needle controller removes the first needle and the second needle, the waste system depositing the at least one waste vial into a waste receptacle.

13. The system as in claim 1 further comprising:
a hood surrounding the puncture station, the hood maintaining a controlled, clean volume surrounding the puncture station.

14. The system as in claim 1 wherein the expansion subsystem comprises:
an expansion controller controlling a flow of cells from a thaw subsystem to the expansion subsystem; and
a bioreactor controller monitoring and modifying the first pre-selected environment.

15. The system as in claim 14 wherein the bioreactor controller comprises:
an agitation controller agitating the cells to encourage attachment of the cells to a surface;
a temperature controller adjusting temperature of the at least one first bioreactor based on a pre-selected desired temperature;
a gas mixing processor adjusting levels of gas in media surrounding the cells, the levels of gas based on pre-selected desired values of characteristics of the media;
a monitoring process sensing values of the characteristics of the media; and
a pump controller moving the med

Assignees

• Deka Products Lp

Inventors

• Andrews Richard E
• Miskell Stephanie M
• Kops Zachary T
• Ferrentino Justin M
• Tilley Michael C
• Capulli Andrew K
• Mcgrath Keira L
• Jacobson Stuart A

Classifications

• C12M41/00

  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 title

• C12M33/00

  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 title

• C12M29/00

  Means for introduction, extraction or recirculation of materials, e.g. pumps (pumps per se F04B) · CPC title

• C12M41/48 Primary

  Automatic or computerized control (automatic analysis G01N35/00) · CPC title

• B01L3/50273

  characterised by the means or forces applied to move the fluids · CPC title