Medical device system and method for producing a dose - Patents.com

Abstract

1. A medical device system comprising: a first container and a second container, the first container including a first container outer body defining a first interior space connected to a first opening of the first container, and a first container-side valve configured to actuate from a normally closed position to the first interior space to an actuated position when the second container is connected to the first container, and the second container including a second container outer body defining a second container interior space and a stem fluidly connected to the second container interior space, the first container-side valve configured to contact the stem when the second container is connected to the first container, and the stem configured to actuate the first container-side valve from the normally closed position to the actuated position.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No. 63 / 294,851, filed December 30, 2021, U.S. Provisional Application No. 63 / 294,853, filed December 30, 2021, U.S. Provisional Application No. 63 / 294,854, filed December 30, 2021, and U.S. Provisional Application No. 63 / 435,196, filed December 23, 2022, the entire contents of each of which are incorporated herein by reference. [Background technology]

[0002] FIELD OF THE DISCLOSURE The present disclosure relates generally to medical device systems and methods for creating a dose of a pharmaceutical product. The pharmaceutical product may include a cell-based pharmaceutical product. Summary of the Invention [Problem to be solved by the invention]

[0003] A need has been identified to provide improvements to the process for creating doses of cell-based formulation products, including, but not limited to, creating doses of the formulation product having a consistent volume and cell concentration that meets a predetermined target concentration, as well as minimizing or eliminating the risk of contamination of the formulation product in various environments, such as an operating room or off-site locations away from an operating room, without access to a clean environment, such as a biosafety cabinet or clean room. [Means for solving the problem]

[0004] In a first embodiment, a medical device system is described. The medical device system includes a first container and a second container, the first container including a first container outer body defining a first interior space connected to a first opening of the first container, and a first container-side valve configured to operate from a normally closed position to a working position to relatively increase flow through the first opening of the first container to the first interior space when the second container is connected to the first container, and the second container including a second container outer body defining a second container interior space and a stem fluidly connected to the second container interior space, the first container-side valve configured to contact the stem when the second container is connected to the first container, and the stem configured to operate the first container-side valve from the normally closed position to the working position.

[0005] In a first embodiment, the second container interior space extends along a longitudinal direction, and at a first end of the second container interior space along the longitudinal direction, the width of the second container interior space decreases toward the first end opening of the second container interior space, and the stem is fluidly connected to the first end opening of the second container interior space and extends along the longitudinal direction.

[0006] In a first embodiment, the stem is connected to the second container outer body so as to be immovable relative to the second container interior space.

[0007] In a first embodiment, the first container further comprises a sheath defining a sheath interior space, with at least a portion of the first container outer body configured for removably insertion into the sheath interior space.

[0008] In a first embodiment, a first container side valve is configured to be connected to a first end of the sheath, and a first container outer body is configured to be positioned within the sheath internal space so as to contact the first container side valve so as to relatively increase flow into the first internal space through the first opening of the first container when the first container side valve is actuated from a normally closed position to an actuated position.

[0009] In a first embodiment, the first container further comprises a sheath cap configured to be removably connected to the second end of the sheath, the first container outer body being enclosed within the sheath by the sheath cap.

[0010] In a first embodiment, the sheath cap includes a vent configured to release air displaced from the first interior space and a filter disposed within the vent.

[0011] In a first embodiment, the first container further includes a plunger seal disposed within the first internal space of the first container outer body, the plunger seal configured to receive a force to move the plunger seal within the first internal space to change the volume of space within the first internal space between the plunger seal and the first container-side valve.

[0012] In a first embodiment, the sheath cap defines a through hole for venting gas within the interior space of the first container outer body.

[0013] In a first embodiment, the medical device system further comprises a plunger, the plunger configured to be removably connected to the plunger seal.

[0014] In a first embodiment, the first container further comprises a plunger seal disposed within the first internal space, the plunger seal configured to receive a force to move the plunger seal within the first internal space to change a volume of space within the first internal space between the plunger seal and the first container-side valve.

[0015] In a first embodiment, the medical device system further includes a plunger configured to apply a force to the plunger seal to move the plunger seal within the first interior space to change a volume of space within the first interior space between the plunger seal and the first container-side valve.

[0016] In a first embodiment, the medical device system further includes a movable body disposed within a first internal space of the first container outer body, the movable body configured to move within the first internal space between the plunger seal and the first container side valve.

[0017] In a first embodiment, the moveable body comprises a stainless steel body.

[0018] In a first embodiment, the movable body is configured to move within the first interior space by a magnetic force acting from outside the first container.

[0019] In a first embodiment, the medical device system further comprises a movable body disposed within the first interior space of the first container outer body and configured to move within the first interior space.

[0020] In a first embodiment, the movable body defines one or more through holes connecting a first side of the movable body facing the first container-side valve and a second side of the movable body opposite the first side of the movable body.

[0021] In a first embodiment, the first container further comprises a valve cap configured to be removably connected to the first container-side valve, preventing direct contact of the first container-side valve from outside the valve cap.

[0022] In a second embodiment, a medical device system is described. The medical device system includes a first container and a second container, the first container including a first container outer body defining a first interior space connected to a first opening of the first container, a first container-side valve configured to operate upon connection of the second container to the first container from a normally closed position that relatively reduces flow through the first opening of the first container into the first interior space to an actuated position that relatively increases flow through the first opening of the first container into the first interior space, a sheath defining a sheath interior space and configured for at least a portion of the first container outer body to be removably inserted into the sheath interior space, and a second end of the sheath configured to removably connect to the first container. and a sheath cap configured to enclose the outer body within the sheath, and optionally further comprising a plunger seal disposed within the first internal space, the plunger seal configured to receive a force to move the plunger seal within the first internal space to change a volume of the space within the first internal space between the plunger seal and the first container-side valve; the second container comprising a second container outer body defining a second container internal space and a stem fluidly connected to the second container internal space, wherein upon connection of the second container to the first container, the first container-side valve is configured to contact the stem, and the stem is configured to actuate the first container-side valve from a normally closed position to an actuated position.

[0023] In a third embodiment, a medical device system is described, the medical device system comprising a first container and a second container, the first container comprising a first container outer body defining a first interior space connected to a first opening of the first container, a first container-side valve configured to actuate upon connection of the second container to the first container from a normally closed position that relatively reduces flow through the first opening of the first container into the first interior space to an actuated position that relatively increases flow through the first opening of the first container into the first interior space, and a sheath-side valve defining a sheath interior space, wherein at least a portion of the first container outer body is removably disposed within the sheath interior space. the second container comprises a second container outer body defining a second container interior space and a stem fluidly connected to the second container interior space, the second container outer body comprising a second connection structure configured to be connected to the first connection structure of the sheath to connect the second container to the first container, and upon connection of the second container to the first container, the first container-side valve is configured to contact the stem, and the stem is configured to actuate the first container-side valve from a normally closed position to an actuated position.

[0024] In a fourth embodiment, a medical device system is described. The medical device system includes a first container and a second container, the first container including a first container outer body defining a first interior space connected to a first opening of the first container, a first container-side valve configured to actuate upon connection of the second container to the first container from a normally closed position that relatively reduces flow through the first opening of the first container into the first interior space to an actuated position that relatively increases flow through the first opening of the first container into the first interior space, and optionally further including a plunger seal disposed within the first interior space. the plunger seal is configured to receive a force to move the plunger seal within the first internal space to change a volume of the space within the first internal space between the plunger seal and the first container-side valve, the second container comprising a second container outer body defining a second container internal space and a stem fluidly connected to the second container internal space, and upon connection of the second container to the first container, the first container-side valve is configured to contact the stem and the stem is configured to actuate the first container-side valve from a normally closed position to an actuated position.

[0025] In a fifth embodiment, an apparatus is described, the apparatus comprising a first container, the first container comprising a first container outer body, a first container body disposed within the first container outer body and defining a first interior space connected to a first opening of the first container, and a first container-side valve configured to actuate from a normally closed position that relatively reduces flow through the first opening of the first container into the first interior space to an actuated position that relatively increases flow through the first opening of the first container into the first interior space when a second container is connected to the first container outer body.

[0026] In a fifth embodiment, the second container is provided with a second container-side valve, and when the second container is connected to the first container outer body, the first container-side valve contacts the second container-side valve.

[0027] In a fifth embodiment, when the second container is connected to the first container outer body, the first container side valve is configured to be contacted and actuated by the second container side valve from a normally closed position to an actuated position.

[0028] In a fifth embodiment, the second container comprises a second container outer body defining a second container body internal space connected to the first opening of the second container, the second container side valve is configured to operate from a normally closed position that relatively reduces the flow through the first opening of the second container into the second container body internal space to an actuated position that relatively increases the flow through the first opening of the second container into the second container body internal space when the second container is connected to the first container outer body, the first container side valve is configured to be contacted by the second container side valve and actuated from the normally closed position to the actuated position when the second container is connected to the first container outer body, and the second container side valve is configured to actuate from the normally closed position to the actuated position to connect the second container body internal space to the first internal space.

[0029] In a fifth embodiment, the second container-side valve includes a valve stem, and when the second container is connected to the first container outer body, the first container-side valve is configured to be contacted by the valve stem and actuated from a normally closed position to an actuated position, and the second container-side valve is configured to actuate from the normally closed position to the actuated position to connect the internal space of the second container body to the first internal space via the valve stem.

[0030] In a sixth embodiment, a medical device system is described. The medical device system includes a first container and a second container, the first container including a first container outer body, a first container body disposed within the first container outer body and defining a first interior space connected to a first opening of the first container, and a first container-side valve configured to operate from a normally closed position that relatively reduces flow through the first opening of the first container into the first interior space to an actuated position that relatively increases flow through the first opening of the first container into the first interior space when the second container is connected to the first container outer body.

[0031] In a sixth embodiment, the second container is provided with a second container-side valve, and when the second container is connected to the first container outer body, the first container-side valve contacts the second container-side valve.

[0032] In a sixth embodiment, when the second container is connected to the first container outer body, the first container side valve is configured to be contacted and actuated by the second container side valve from a normally closed position to an actuated position.

[0033] In a sixth embodiment, the second container comprises a second container outer body defining a second container body internal space connected to the first opening of the second container, the second container side valve is configured to operate from a normally closed position that relatively reduces the flow from the second container body internal space through the first opening of the second container to an actuated position that relatively increases the flow from the second container body internal space through the first opening of the second container when the second container is connected to the first container outer body, the first container side valve is configured to be contacted by the second container side valve and actuated from the normally closed position to the actuated position when the second container is connected to the first container outer body, and the second container side valve is configured to actuate from the normally closed position to the actuated position to connect the second container body internal space to the first internal space.

[0034] In a sixth embodiment, the second container-side valve includes a valve stem, and when the second container is connected to the first container outer body, the first container-side valve is configured to be contacted by the valve stem and actuated from a normally closed position to an actuated position, and the second container-side valve is configured to actuate from the normally closed position to the actuated position to connect the internal space of the second container body to the first internal space via the valve stem.

[0035] In a seventh embodiment, a process for operating a medical device system is described. The process includes a first container and a second container, the first container including a first container outer body, a first container body disposed within the first container outer body and defining a first interior space connected to a first opening of the first container, and a first container-side valve, the process includes aligning the first container and the second container, and connecting the second container to the first container outer body, the first container-side valve being configured to operate from a normally closed position that relatively reduces flow through the first opening of the first container into the first interior space to an actuated position that relatively increases flow through the first opening of the first container into the first interior space when the second container is connected to the first container outer body.

[0036] In a seventh embodiment, the second container is provided with a second container-side valve, and the process includes a step of contacting the first container-side valve with the second container-side valve in the step of connecting the second container to the first container outer body.

[0037] In a seventh embodiment, the process includes a step of contacting a first container-side valve with a second container-side valve, whereby the second container-side valve actuates the first container-side valve from a normally closed position to an actuated position.

[0038] In a seventh embodiment, the second container comprises a second container outer body defining a second container body internal space connected to the first opening of the second container, and the process includes a step of actuating the second container side valve from a normally closed position that relatively reduces the flow from the second container body internal space through the first opening of the second container to an actuated position that relatively increases the flow from the second container body internal space through the first opening of the second container when connecting the second container to the first container outer body, thereby connecting the second container body internal space to the first internal space.

[0039] In a seventh embodiment, the second container side valve includes a valve stem, and the process includes a step of contacting the valve stem with the first container side valve to actuate the first container side valve from a normally closed position to an actuated position, and actuating the second container side valve from the normally closed position to an actuated position, thereby connecting the interior space of the second container body to the first interior space via the valve stem, when connecting the second container to the first container outer body.

[0040] In a seventh embodiment, the process further comprises pre-filling the first interior space of the first container with a cell delivery solution.

[0041] In a seventh embodiment, the process further comprises filling the second container body interior space with a mixture comprising a plurality of cells and a washing solution.

[0042] In a seventh embodiment, the process further includes a step of, after connecting the second container body internal space to the first internal space, applying centrifugal force to the medical device system to move the plurality of cells from the second container body internal space through the second container side valve in the actuated position and the first container side valve in the actuated position to the first internal space.

[0043] In an eighth embodiment, an apparatus is described. The apparatus includes a first container, the first container including a first container outer body, a first container body disposed within the first container outer body and defining a first internal space connected to a first opening of the first container, a first container-side valve configured to operate from a normally closed position that relatively reduces the flow through the first opening of the first container into the first internal space to an operating position that relatively increases the flow through the first opening of the first container into the first internal space when a second container is connected to the first container outer body, and a movable body disposed within the first internal space of the first container body and configured to move within the first internal space by a force applied from outside the first container.

[0044] In an eighth embodiment, the movable body comprises a magnet configured to move within the first interior space by a magnetic force acting from outside the first container.

[0045] In an eighth embodiment, the moveable body defines one or more through holes extending between a first surface of the moveable body and a second surface of the moveable body opposite the first surface.

[0046] In an eighth embodiment, the second container is provided with a second container-side valve, and when the second container is connected to the first container outer body, the first container-side valve contacts the second container-side valve.

[0047] In an eighth embodiment, when the second container is connected to the first container outer body, the first container side valve is configured to be contacted and actuated by the second container side valve from a normally closed position to an actuated position.

[0048] In an eighth embodiment, the second container comprises a second container outer body defining a second container body internal space connected to the first opening of the second container, the second container side valve is configured to operate from a normally closed position that relatively reduces the flow through the first opening of the second container into the second container body internal space to an actuated position that relatively increases the flow through the first opening of the second container into the second container body internal space when the second container is connected to the first container outer body, the first container side valve is configured to be contacted by the second container side valve and actuated from the normally closed position to the actuated position when the second container is connected to the first container outer body, and the second container side valve is configured to actuate from the normally closed position to the actuated position to connect the second container body internal space to the first internal space.

[0049] In an eighth embodiment, the second container-side valve includes a valve stem, and when the second container is connected to the first container outer body, the first container-side valve is configured to be contacted by the valve stem and actuated from a normally closed position to an actuated position, and the second container-side valve is configured to actuate from the normally closed position to the actuated position to connect the internal space of the second container body to the first internal space via the valve stem.

[0050] In a ninth embodiment, a medical device system is described. The medical device system includes a first container and a second container, the first container includes a first container outer body, a first container body disposed in the first container outer body and defining a first internal space connected to a first opening of the first container, a first container side valve configured to operate from a normally closed position that relatively reduces the flow through the first opening of the first container to the first internal space to an operating position that relatively increases the flow through the first opening of the first container to the first internal space when the second container is connected to the first container outer body, and a movable body disposed in the first internal space of the first container body and configured to move within the first internal space by a force applied from the outside of the first container.

[0051] In a ninth embodiment, the medical equipment system further comprises a first container mixing module having an external magnet, and the movable body comprises a magnet configured to move within the first internal space by a magnetic force applied by the external magnet of the first container mixing module.

[0052] In a ninth embodiment, the moveable body defines one or more through holes extending between a first surface of the moveable body and a second surface of the moveable body opposite the first surface.

[0053] In a ninth embodiment, the second container is provided with a second container-side valve, and when the second container is connected to the first container outer body, the first container-side valve contacts the second container-side valve.

[0054] In a ninth embodiment, when the second container is connected to the first container outer body, the first container side valve is configured to be contacted and actuated by the second container side valve from a normally closed position to an actuated position.

[0055] In a ninth embodiment, the second container comprises a second container outer body defining a second container body internal space connected to the first opening of the second container, the second container side valve is configured to operate from a normally closed position that relatively reduces the flow from the second container body internal space through the first opening of the second container to an actuated position that relatively increases the flow from the second container body internal space through the first opening of the second container when the second container is connected to the first container outer body, the first container side valve is configured to be contacted by the second container side valve and actuated from the normally closed position to the actuated position when the second container is connected to the first container outer body, and the second container side valve is configured to actuate from the normally closed position to the actuated position to connect the second container body internal space to the first internal space.

[0056] In a ninth embodiment, the second container-side valve includes a valve stem, and when the second container is connected to the first container outer body, the first container-side valve is configured to be contacted by the valve stem and actuated from a normally closed position to an actuated position, and the second container-side valve is configured to actuate from the normally closed position to the actuated position to connect the internal space of the second container body to the first internal space via the valve stem.

[0057] In a tenth embodiment, a process for operating a medical device system is described. The process includes a first container and a second container, the first container including a first container outer body, a first container body disposed within the first container outer body and defining a first internal space connected to a first opening of the first container, a first container-side valve, and a movable body disposed within the first internal space of the first container body, the process including the steps of aligning the first container and the second container, connecting the second container to the first container outer body, the first container-side valve configured to operate from a normally closed position that relatively reduces the flow through the first opening of the first container to the first internal space to an operating position that relatively increases the flow through the first opening of the first container to the first internal space when connecting the second container to the first container outer body, and applying a force to the movable body from the outside of the first container to move the movable body within the first internal space.

[0058] In a tenth embodiment, the movable body is provided with a magnet, and applying a force to the movable body includes applying a magnetic force to the magnet of the movable body from outside the first container to move the movable body within the first internal space.

[0059] In a tenth embodiment, the moveable body defines one or more through holes extending between a first surface of the moveable body and a second surface of the moveable body opposite the first surface.

[0060] In a tenth embodiment, the second container is provided with a second container-side valve, and the process includes a step of contacting the first container-side valve with the second container-side valve in the step of connecting the second container to the first container outer body.

[0061] In a tenth embodiment, the process includes a step of contacting a first container-side valve with a second container-side valve, whereby the second container-side valve actuates the first container-side valve from a normally closed position to an actuated position.

[0062] In a tenth embodiment, the second container comprises a second container outer body defining a second container body internal space connected to the first opening of the second container, and the process includes a step of actuating the second container side valve from a normally closed position that relatively reduces the flow from the second container body internal space through the first opening of the second container to an actuated position that relatively increases the flow from the second container body internal space through the first opening of the second container when connecting the second container to the first container outer body, thereby connecting the second container body internal space to the first internal space.

[0063] In a tenth embodiment, the second container side valve includes a valve stem, and the process includes the steps of contacting the valve stem with the first container side valve to actuate the first container side valve from a normally closed position to an actuated position, and actuating the second container side valve from the normally closed position to an actuated position, thereby connecting the interior space of the second container body to the first interior space via the valve stem, when connecting the second container to the first container outer body.

[0064] In a tenth embodiment, the process further comprises pre-filling the first interior space of the first container with a cell delivery solution.

[0065] In a tenth embodiment, the process further comprises filling the second container body interior space with a mixture comprising a plurality of cells and a washing solution.

[0066] In a tenth embodiment, the process further includes a step of, after connecting the second container body internal space to the first internal space, applying centrifugal force to the medical device system to move the plurality of cells from the second container body internal space through the second container side valve in the actuated position and the first container side valve in the actuated position to the first internal space.

[0067] In an eleventh embodiment, an apparatus is described. The apparatus includes a first container, the first container including a first container outer body, a first container body disposed within the first container outer body and defining a first interior space connected to a first opening of the first container and a second opening of the first container, and a first container-side valve configured to operate from a normally closed position that relatively reduces the flow through the first opening of the first container into the first interior space to an operating position that relatively increases the flow through the first opening of the first container into the first interior space when a second container is connected to the first container outer body, the apparatus further including a plunger seal disposed within the first container body between the first opening and the second opening, the plunger seal configured to receive a force to move the plunger seal within the first container body to change the volume of the space within the first interior space between the first opening and the plunger seal.

[0068] In an eleventh embodiment, the device further comprises a plunger removably connected to the plunger seal and configured to transmit a force to move the plunger seal within the first container body to change the volume of space within the first interior space between the first opening and the plunger seal.

[0069] In an eleventh embodiment, the second container is provided with a second container-side valve, and when the second container is connected to the first container outer body, the first container-side valve contacts the second container-side valve.

[0070] In an eleventh embodiment, when the second container is connected to the first container outer body, the first container side valve is configured to be contacted and actuated by the second container side valve from a normally closed position to an actuated position.

[0071] In an eleventh embodiment, the second container comprises a second container outer body defining a second container body internal space connected to the first opening of the second container, the second container side valve is configured to operate from a normally closed position that relatively reduces the flow through the first opening of the second container into the second container body internal space to an actuated position that relatively increases the flow through the first opening of the second container into the second container body internal space when the second container is connected to the first container outer body, the first container side valve is configured to be contacted by the second container side valve and actuated from the normally closed position to the actuated position when the second container is connected to the first container outer body, and the second container side valve is configured to actuate from the normally closed position to the actuated position to connect the second container body internal space to the first internal space.

[0072] In an eleventh embodiment, the second container side valve has a valve stem, and when the second container is connected to the first container outer body, the first container side valve is configured to be contacted by the valve stem and actuated from a normally closed position to an actuated position, and the second container side valve is configured to actuate from the normally closed position to the actuated position to connect the internal space of the second container body to the first internal space via the valve stem.

[0073] In a twelfth embodiment, a medical device system is described. The medical device system includes a first container and a second container, the first container includes a first container outer body, a first container body disposed within the first container outer body and defining a first interior space connected to a first opening of the first container and a second opening of the first container, a first container side valve configured to operate from a normally closed position to relatively reduce a flow through the first opening of the first container into the first interior space to an actuated position to relatively increase a flow through the first opening of the first container into the first interior space when the second container is connected to the first container outer body, and a plunger seal disposed within the first container body between the first opening and the second opening, the plunger seal configured to receive a force to move the plunger seal within the first container body to change a volume of a space within the first interior space between the first opening and the plunger seal.

[0074] In a twelfth embodiment, the medical device system further comprises a plunger removably connected to the plunger seal and configured to transmit a force to move the plunger seal within the first container body to change the volume of space within the first interior space between the first opening and the plunger seal.

[0075] In a twelfth embodiment, the second container is provided with a second container-side valve, and when the second container is connected to the first container outer body, the first container-side valve contacts the second container-side valve.

[0076] In a twelfth embodiment, when the second container is connected to the first container outer body, the first container side valve is configured to be contacted and actuated by the second container side valve from a normally closed position to an actuated position.

[0077] In a twelfth embodiment, the second container comprises a second container outer body defining a second container body internal space connected to the first opening of the second container, the second container side valve is configured to operate from a normally closed position that relatively reduces the flow from the second container body internal space through the first opening of the second container to an actuated position that relatively increases the flow from the second container body internal space through the first opening of the second container when the second container is connected to the first container outer body, the first container side valve is configured to be contacted by the second container side valve and actuated from the normally closed position to the actuated position when the second container is connected to the first container outer body, and the second container side valve is configured to actuate from the normally closed position to the actuated position to connect the second container body internal space to the first internal space.

[0078] In a twelfth embodiment, the second container-side valve includes a valve stem, and when the second container is connected to the first container outer body, the first container-side valve is configured to be contacted by the valve stem and actuated from a normally closed position to an actuated position, and the second container-side valve is configured to actuate from the normally closed position to the actuated position to connect the internal space of the second container body to the first internal space via the valve stem.

[0079] In a thirteenth embodiment, a process for operating a medical device system is described. The process includes a first container and a second container, the first container including a first container outer body, a first container body disposed within the first container outer body and defining a first interior space connected to a first opening of the first container and a second opening of the first container, a first container valve, and a plunger seal disposed within the first container body between the first openings, the process including aligning the first container and the second container, and connecting the second container to the first container outer body, the first container outer body being connected to a first opening of the first container and a second opening of the first container. The method includes the steps of: operating the container-side valve from a normally closed position, which relatively reduces flow through the first opening of the first container into the first internal space, to an actuated position, which relatively increases flow through the first opening of the first container into the first internal space, when connecting the second container to the first container outer body; and applying a force to move a plunger seal within the first container body to change the volume of space in the first internal space between the first opening and the plunger seal.

[0080] In a thirteenth embodiment, the process further includes the steps of connecting a plunger to a plunger seal and transmitting a force from the plunger to the plunger seal to move the plunger seal within the first container body to change the volume of space within the first interior space between the first opening and the plunger seal.

[0081] In a thirteenth embodiment, the second container is provided with a second container-side valve, and the process includes a step of contacting the first container-side valve with the second container-side valve in the step of connecting the second container to the first container outer body.

[0082] In a thirteenth embodiment, the process includes a step of contacting a first container-side valve with a second container-side valve, whereby the second container-side valve actuates the first container-side valve from a normally closed position to an actuated position.

[0083] In a thirteenth embodiment, the second container comprises a second container outer body defining a second container body internal space connected to the first opening of the second container, and the process includes a step of actuating the second container side valve from a normally closed position that relatively reduces the flow from the second container body internal space through the first opening of the second container to an actuated position that relatively increases the flow from the second container body internal space through the first opening of the second container when connecting the second container to the first container outer body, thereby connecting the second container body internal space to the first internal space.

[0084] In a thirteenth embodiment, the second container side valve includes a valve stem, and the process includes a step of contacting the valve stem with the first container side valve to actuate the first container side valve from a normally closed position to an actuated position, and actuating the second container side valve from the normally closed position to an actuated position, thereby connecting the internal space of the second container body to the first internal space via the valve stem, when connecting the second container to the first container outer body.

[0085] In a thirteenth embodiment, the process further comprises pre-filling the first interior space of the first container with a cell delivery solution.

[0086] In a thirteenth embodiment, the process further comprises filling the second container body interior space with a mixture comprising a plurality of cells and a washing solution.

[0087] In a thirteenth embodiment, the process further includes a step of, after connecting the second container body internal space to the first internal space, applying centrifugal force to the medical device system to move the plurality of cells from the second container body internal space through the second container side valve in the actuated position and the first container side valve in the actuated position to the first internal space.

[0088] In a fourteenth embodiment, an apparatus is described, comprising: a first container connected to a second container, the second container comprising a second container outer body defining a second container interior space and a stem fluidly connected to the second container interior space, the first container comprising the first container outer body defining a first interior space connected to a first opening of the first container, and a first container-side valve configured to be actuated from a normally closed position that relatively reduces flow through the first opening of the first container into the first interior space to an actuated position that relatively increases flow through the first opening of the first container into the first interior space when the second container is connected to the first container.

[0089] In a fourteenth embodiment, the first container further comprises a sheath defining a sheath interior space, and at least a portion of the first container outer body is configured for removably insertion into the sheath interior space.

[0090] In a fourteenth embodiment, the first container side valve is configured to be connected to a first end of the sheath, and the first container outer body is configured to be positioned within the sheath internal space so as to contact the first container side valve so as to relatively increase flow into the first internal space through the first opening of the first container when the first container side valve is actuated from a normally closed position to an actuated position.

[0091] In a fourteenth embodiment, the first container further comprises a sheath cap configured to be removably connected to the second end of the sheath, and the first container outer body is enclosed within the sheath by the sheath cap.

[0092] In a fourteenth embodiment, the sheath cap includes a vent configured to release air displaced from the first interior space, and a filter disposed within the vent.

[0093] In a fourteenth embodiment, the first container further includes a plunger seal disposed within the first internal space of the first container outer body, the plunger seal configured to receive a force to move the plunger seal within the first internal space to change the volume of space within the first internal space between the plunger seal and the first container side valve.

[0094] In a fourteenth embodiment, the sheath cap defines a through hole for releasing gas within the interior space of the first container outer body.

[0095] In a fourteenth embodiment, the plunger is configured to be removably connected to the plunger seal.

[0096] In a fourteenth embodiment, the first container further comprises a plunger seal disposed within the first internal space, the plunger seal configured to receive a force to move the plunger seal within the first internal space to change the volume of space within the first internal space between the plunger seal and the first container-side valve.

[0097] In a fourteenth embodiment, the device further comprises a plunger configured to apply a force to the plunger seal to move the plunger seal within the first internal space and change a volume of space within the first internal space between the plunger seal and the first container-side valve.

[0098] In a fourteenth embodiment, the device further includes a movable body disposed within a first internal space of the first container outer body, the movable body configured to move within the first internal space between the plunger seal and the first container side valve.

[0099] In a fourteenth embodiment, the moveable body comprises a stainless steel body.

[0100] In a fourteenth embodiment, the movable body is configured to move within the first internal space by a magnetic force acting from outside the first container.

[0101] In a fourteenth embodiment, the movable body defines one or more through holes connecting a first side of the movable body facing the first container-side valve and a second side of the movable body opposite the first side of the movable body.

[0102] In a fourteenth embodiment, the first container further comprises a valve cap configured to be removably connected to the first container side valve, preventing direct contact of the first container side valve from outside the valve cap.

[0103] In a fifteenth embodiment, a process for creating a cell solution for delivery is disclosed. The process includes receiving a cell preparation product (e.g., a suspension of cells in a cryoprotectant) and separating the cells from the cryoprotectant with a cell wash, optionally into a "cell delivery solution", to generate a cell solution for delivery to a subject / patient. In some variations, the "cell delivery solution" is contained in the first container before the cells are introduced into the first container. The addition of cells to the cell delivery solution results in the creation of a "cell solution for delivery", which is the final cell preparation for injection / delivery to a patient. It should be understood that the device disclosed herein can be used to create a cell (e.g., other macromolecule)-free solution for injection into a patient.

[0104] In a sixteenth embodiment, an apparatus is disclosed that provides a means (e.g., an automated means) for washing a cell preparation product (e.g., a cell product containing cells and a cryopreservative) with a washing solution and delivering the cells to a cell delivery solution to create a cell solution for delivery.

[0105] Further features as well as the structure and operation of various embodiments are described in detail below with reference to the accompanying drawings, where like reference numbers indicate identical or functionally similar elements. [Brief description of the drawings]

[0106] [Figure 1]1 illustrates a medical device system according to one embodiment including a first container, a second container, a second container loading module, and a dose loading module. [Diagram 2] 1 illustrates features of a first container according to one embodiment. [Diagram 3] 1 illustrates features of a first container according to one modified embodiment. [Figure 4] 1 illustrates a process for assembling a first container according to one embodiment. [Diagram 5] 1 illustrates features of a second container according to one embodiment. [Figure 6] 1 illustrates a first container and a second container in an unconnected and connected state according to one embodiment. [Figure 7] 1 illustrates a process for assembling a second container according to one embodiment. [Figure 8] 1 illustrates features of a second container loading module according to one embodiment. [Figure 9] 1 illustrates a process for preparing a cell solution for delivery according to one embodiment. [Figure 10] 1 illustrates a medical device system according to one embodiment including a first container, a second container, a second container loading module, and a dose loading module. [Figure 11] 1 illustrates a first container and a second container in an unconnected and connected state according to one embodiment. [Figure 12] 1 illustrates a moveable body for use with a first container according to one embodiment. [Figure 13A] 1 illustrates an example of a moveable body according to one embodiment. [Figure 13B] 1 illustrates an example of a moveable body according to one embodiment. [Figure 13C] 1 illustrates an example of a moveable body according to one embodiment. [Figure 13D] 1 illustrates an example of a moveable body according to one embodiment. [Figure 14] 1 illustrates a first vessel mixing module according to one embodiment. [Figure 15]1 illustrates a medical device system according to one embodiment including a first container, a second container, a second container loading module, and a dose loading module. [Figure 16] 1 illustrates a first container and a second container in an unconnected and connected state according to one embodiment. [Figure 17] 1 illustrates a first container with a plunger head and plunger seal according to one embodiment. [Figure 18] 1 illustrates a delivery device according to one embodiment that applies a force to a plunger to advance a plunger seal. [Figure 19] 1 illustrates a delivery device according to one embodiment that applies a force to a plunger to advance a plunger seal. [Figure 20] 1 illustrates a first container of a medical device system according to one embodiment. [Figure 21] 1 illustrates a sheath and a first container-side valve according to one embodiment. [Figure 22] 1 illustrates a sheath cap according to one embodiment. [Diagram 23] 1 illustrates a second container according to one embodiment. [Figure 24] 1 illustrates a medical device system including a first container and a second container according to one embodiment. [Diagram 25] 13 illustrates different configurations of a first container during preparation of a dose according to one embodiment. [Figure 26] 1 illustrates a medical device system according to one embodiment. [Figure 27] 1 illustrates a first container of a medical device system according to one embodiment. [Figure 28] 27 illustrates a dose tube of the first container of FIG. 26 according to one embodiment. [Figure 29] 1 illustrates an alternative dose tube retention mechanism according to one embodiment. [Diagram 30] 1 illustrates a second container of a medical device system according to one embodiment. [Diagram 31] Two connection locations between a first container and a second container are shown. [Diagram 32] 1 illustrates a sheath cap according to one embodiment. [Diagram 33] 1 illustrates a loading adapter according to one embodiment. [Diagram 34] 1 illustrates a delivery device guided by a loading adapter according to one embodiment. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0107] 1 illustrates an example of a medical device system 10 for performing dose preparation according to one embodiment. The medical device system 10 may include a first container 100 (also referred to as a dose preparation tube), a second container 200 (also referred to as a irrigation tube), a second container loading module 300, and a dose loading module 400.

[0108] First container (dose producing tube) Next, a first container 100, which is an apparatus, will be described with reference to Fig. 2. The first container 100 may include a first tube body 104. The first tube body 104 may extend along a first tube body axis A between a first end of the first tube body 104 and a second end of the first tube body 104.

[0109] The first tube body 104 may define a first interior space 106. The first interior space 106 may be connected to a first opening 104A at a first end of the first tube body 104.

[0110] The volume of the first internal space 106 is not particularly limited. For example, the volume of the first internal space 106 may be selected based on the target dose volume of the dose to be produced. As an example, the volume of the first internal space 106 may be selected to hold the target dose volume and further account for some additional dead volume (e.g., about 50 μl).

[0111] In some embodiments, the target dose volume is at least about 1 microliter, at least about 2 microliters, at least about 3 microliters, at least about 4 microliters, at least about 5 microliters, at least about 6 microliters, at least about 7 microliters, at least about 7.2 microliters, at least about 7.4 microliters, at least about 7.6 microliters, at least about 7.8 microliters, at least about 8 microliters, at least about 8.1 microliters, at least about 8.2 microliters, at least about 8.3 microliters, at least about 8.4 microliters, at least about 8.5 microliters, at least about It may be 8.6 microliters, at least about 8.7 microliters, at least about 8.8 microliters, at least about 8.9 microliters, at least about 9 microliters, at least about 9.5 microliters, at least about 10 microliters, at least about 11 microliters, at least about 12 microliters, at least about 13 microliters, at least about 14 microliters, at least about 15 microliters, at least about 20 microliters, at least about 30 microliters, at least about 100 microliters, at least about 1 mL, at least about 10 mL, at least about 100 mL, at least about 500 mL, or at least about 800 mL.

[0112] In some embodiments, the target dose volume is about 1000 mL or less, about 800 mL or less, about 500 mL or less, about 100 mL or less, about 10 mL or less, about 1 mL or less, about 100 microliters or less, or about 90 microliters or less, or about 80 microliters or less, or about 70 microliters or less, or about 60 microliters or less, or about 50 microliters or less, or about 40 microliters or less, or about 30 microliters or less, or about 20 microliters or less, or about 15 microliters or less, or about 12 microliters or less, or about 10 microliters or less, or about It may be 9.9 microliters or less, or about 9.8 microliters or less, or about 9.7 microliters or less, or about 9.6 microliters or less, or about 9.5 microliters or less, or about 9.4 microliters or less, or about 9.3 microliters or less, or about 9.2 microliters or less, or about 9.1 microliters or less, or about 9 microliters or less, or about 8.8 microliters or less, or about 8.2 microliters or less, or about 8 microliters or less, or about 7 microliters or less, or about 6 microliters or less, or about 5 microliters or less.

[0113] In some embodiments, the target dose volume can be about 150 microliters, about 1.8 microliters, or about 2.0 microliters.

[0114] Combinations of the above ranges are also possible. For example, in some embodiments, the target dose volume is about 100 microliters to about 1 mL, or 1 mL to about 1000 mL, or about 10 mL to about 800 mL, or about 100 mL to about 500 mL, or about 1 microliter to about 100 microliters, or about 2 microliters to about 60 microliters, or about 3 microliters to about 30 microliters, or about 4 microliters to about 20 microliters, or about 5 microliters to about 18 microliters, or about 6 microliters to about 16 microliters, or about 7 microliters to about 14 microliters, or about 8 microliters to about 10 microliters, or about 8.5 microliters to about 9.5 microliters, or about 8.9 microliters to about 9.1 microliters, or about 9 microliters to about 9.1 microliters.

[0115] As an example, the first tube body 104 may include a first container outer body 108 and a first container body 110 disposed within the first container outer body 108 .

[0116] The material for forming the first container outer body 108 is not particularly limited. Examples of materials for forming the first container outer body 108 may include materials with low leachability and / or extractability, such as cyclic olefin polymers, cyclic olefin copolymers, perfluoroalkoxyalkanes, ethylene tetrafluoroethylene, cyclic block copolymers, polyethylene, polypropylene, and polycarbonate. The material for forming the first container may be selected based on the possible manufacturing method, such as injection molding.

[0117] The first container outer body 108 may have a shape or structure for directly or indirectly connecting the first container 100 to the second container 200. A surface of the first container outer body 108 may include a first portion 112 of a connecting or coupling mechanism for directly or indirectly connecting the first container 100 to the second container. The connecting or coupling mechanism is not particularly limited. As an example, the first portion 112 of the connecting or coupling mechanism may include one portion of a threaded connection, while the second container 200 may include another portion of a threaded connection that is detachably connected to the portion of the threaded connection to connect the second container 200 to the first container 100. The one portion of the threaded connection may be one of a male thread (as shown in FIG. 2) and a female thread, and the other portion of the threaded connection provided on the second container 200 may be the other of the male thread and the female thread.

[0118] The first container outer body 108 may have a shape or structure that enables the first container 100 to fit within a centrifuge compartment when attached to the second container 200, as described in further detail below.

[0119] The first container body 110 may be disposed within the first container outer body 108 along the first tube body axis A. The first container body 110 may define a first interior space 106. The first container body 110 may be open-ended proximate a first end of the first tube body 104 to connect the first interior space 106 to a first opening 104A of the first tube body 104. The first container body 110 may be closed-ended proximate a second end of the first tube body 104.

[0120] The dimensions of the first container body 110 are not particularly limited. For example, the length of the first container body 110 along the first tube body axis A and the inner diameter of the first container body 110 perpendicular to the first tube body axis A may be selected based on the target dose volume of the dose to be produced.

[0121] The first container body 110 may be formed as a unitary structure or as an assembly of multiple structures. The material for forming the first container body 110 is not particularly limited. The material for forming at least the inner surface and any other cell contacting surfaces of the first container body 110 may be a biocompatible material, such as a biocompatible polymer. The material for forming the first container body 110 may be selected to minimize cell attachment to the inner surface and any other cell contacting surfaces of the first container body 110. Examples of materials constituting the first container body 110 may include resins, such as polypropylene and polycarbonate.

[0122] With reference to FIG. 1, the medical device system 10 may include a first flow path control module 124 for controlling flow between the second container 200 and the first container 100 .

[0123] 1 and 2, the first vessel 100 may include a first portion of a first flow path control module 124. The first portion of the first flow path control module 124 is configured to be actuated from a normally closed position to an actuated position and to be deactuated from the actuated position to the normally closed position. In the normally closed position, flow into and out of the first interior space 106 through the first opening 104A is reduced or completely restricted compared to the actuated position. In the actuated position, flow into and out of the first interior space 106 through the first opening 104A is increased compared to the normally closed position.

[0124] There are no particular limitations on the structure and shape of the first portion of the first flow path control module 124. An example of the first portion of the first flow path control module 124 will be described in detail below.

[0125] The first flow path control module 124 may include a valve system. A first portion of the first flow path control module 124 may include a first container-side valve 126. The first container-side valve 126 may be provided at a first end of the first tube body 104. The first container-side valve 126 may include a first valve housing 128 attached to the first container outer body 108. Although the first container-side valve 126 is described as a separate structure from other portions of the first container 100, such as the first container outer body 108, portions of the first container-side valve 126, such as the first valve housing 128, may be formed as a unitary structure with the first container outer body 108.

[0126] The exterior surface of the first valve housing 128 may have a shape or structure for directly or indirectly connecting the first container-side valve 126 of the first container 100 to a third container. The exterior surface of the first valve housing 128 may include a first portion of a connection or coupling mechanism for directly or indirectly connecting the first container 100 to a third container. An example of a first portion of a connection or coupling mechanism may include one portion of a threaded connection, while the third container may include another portion of a threaded connection that detachably connects the third container to the first container-side valve 126 of the first container 100. The third container may include a medical device, such as a syringe, for receiving a dose of the cell solution for delivery from the first container 100 and delivering the dose to a subject. The third container may include a connector to a medical device that can transfer the dose from the first container 100 to the medical device, such as a syringe.

[0127] The inner surface of the first valve housing 128 may define a first valve housing interior space 130 that communicates with the first opening 104A of the first tube body 104. The first container-side valve 126 may include a first seal 132 disposed in the first valve housing interior space 130 of the first valve housing 128. The first seal 132 is configured to provide a normally closed position and an actuated position of the first container-side valve 126. The structure of the first seal 132 is not particularly limited. One example of the first seal 132 is a self-sealing seal.

[0128] A first seal 132 may be disposed in the first valve housing interior space to control flow through the open end of the first container body 110 into the first interior space 106. For example, the open end of the first container body 110 may extend along the first tube body axis A into the first valve housing interior space 130 and abut the first seal 132.

[0129] The first seal 132 may have a normally closed position that relatively reduces or completely restricts flow through the first seal 132. The normally closed position of the first seal 132 may be a sealing position of a self-sealing seal.

[0130] The first seal 132 may be actuated from a normally closed position to an actuated position. The actuated position of the first seal 132 allows for a relatively increased flow through the first seal 132 and the open end of the first container body 110 into the first interior space 106 of the first container body 110 (and the first tube body 104). For example, the first seal 132 may be actuated from the normally closed position to the actuated position by deforming a self-sealing seal to provide a flow path through the first seal 132. The first seal 132 may be actuated by a valve stem, as described below.

[0131] The first seal 132 may be made of a resilient material such as rubber, silicone rubber, flexible plastic, or other elastomeric polymer.

[0132] With reference to FIG. 2, the first container outer body 108 can have a shape or structure for connecting a first portion of the first flow path control module 124 to the first container outer body 108 .

[0133] To aid in assembly of the first container 100, the first container outer body 108 may be provided in multiple pieces. For example, the first container outer body 108 may include a first outer body portion 108A and a second outer body portion 108B. The first outer body portion 108A and the second outer body portion 108B may be sequentially disposed along the first tube body axis A such that the first outer body portion 108A is disposed near a first end of the first tube body 104 and the second outer body portion 108B is disposed near a second end of the first tube body 104 along the first tube body axis A.

[0134] The second outer body portion 108B can define an interior space extending along the first tube body axis A. For example, the second outer body portion 108B can have a tubular inner surface that defines the interior space of the second outer body portion 108B. The interior space of the second outer body portion 108B can be dimensioned such that the first container body 110 can be disposed therein. The first container body 110 can be connected to the tubular inner surface of the second outer body portion 108B, for example, by press-fitting the first container body 110 into the tubular inner surface of the second outer body portion 108B and / or by, for example, gluing the cylindrical outer surface of the first container body 110 to the tubular inner surface of the second outer body portion 108B.

[0135] The first outer body portion 108A and the second outer body portion 108B may have shapes or configurations that cooperate to connect the first container outer body 108 to the first container side valve 126.

[0136] The first outer body portion 108A can define an interior space extending along the first tube body axis A. For example, the first outer body portion 108A can have a tubular inner surface that defines the interior space of the second outer body portion 108B. The first valve housing 128 can have a cylindrical outer surface having an outer diameter that matches an inner diameter of the tubular inner surface of the first outer body portion 108A such that the first valve housing 128 is coaxially disposed in the interior space defined by the tubular inner surface of the first outer body portion 108A. The first valve housing 128 can be connected to the tubular inner surface of the first outer body portion 108A, for example, by press-fitting the first valve housing 128 into the tubular inner surface of the first outer body portion 108A and / or by, for example, gluing the cylindrical outer surface of the first valve housing 128 to the tubular inner surface of the first outer body portion 108A.

[0137] The exterior surface of the first valve housing 128 may include a first valve housing flange 128A. The first outer body portion 108A may include a first clamping surface 108A1, and the second outer body portion 108B may include a second clamping surface 108B1. Further, the first clamping surface 108A1 and the second clamping surface 108B1 may be separated by a gap that may position the first valve housing flange 128A to be sandwiched by the first clamping surface 108A1 and the second clamping surface 108B1. Furthermore, the first outer body part 108A and the second outer body part 108B may have corresponding surfaces that can be connected by press-fitting and / or adhesively, for example, with the first valve housing flange 128A sandwiched between the first clamping surface 108A1 and the second clamping surface 108B1, thereby making it possible to connect the first container outer body 108 to the first container-side valve 126. In this connected state, when the first seal 132 is actuated from the normally closed position to the actuated position, flow can occur from the second container 200 to the first interior space 106 of the second outer body part 108B, or from the first interior space 106 of the second outer body part 108B to the third container.

[0138] Although the first container 100 has been described above as including multiple separate parts, such as the first outer body portion 108A, the second outer body portion 108B, the first valve housing 128, and the first container body 110, two or more of the multiple separate parts may be provided as a unitary structure.

[0139] The dimensions of the first container 100 are not particularly limited. For example, the length of the first container 100 along the first tube body axis A and the outer diameter of the first container 100 perpendicular to the first tube body axis A can be selected so that the first container 100 can be placed in a centrifuge compartment together with a second container, as described below.

[0140] First vessel (dose producing tube) - improved Next, referring to FIG. 3, an improved embodiment of the first container 100 will be described. The improved embodiment of the first container 100 is similar to the first container 100 described above. In the improved embodiment, a portion of the second outer body portion 108B of the first container outer body 108 and a portion of the first container body 110 as described above may be replaced with a malleable material. The malleable material may be selected to be compressed to reduce the volume of the first internal space. As an example, the malleable material may include fluorinated ethylene propylene, a polyimide material such as Kapton®, polyvinyl chloride, polypropylene, silicone, polyurethane, or any suitable material.

[0141] Process for Assembling the First Container (Dose Making Tube) 4, the process for assembling the first container 100 will now be described.

[0142] The process for assembling the first container 100 may include a step S102 of placing a first seal 132 in a first valve housing interior space 130 of a first valve housing 128 of a first container-side valve 126.

[0143] The process for assembling the first container 100 may include a step S104 of connecting the first container body 110 to a tubular surface of the second outer body portion 108B, for example by pressing the first container body 110 into the tubular inner surface of the second outer body portion 108B and / or by gluing the cylindrical outer surface of the first container body 110 to the tubular inner surface of the second outer body portion 108B.

[0144] The process for assembling the first container 100 may include step S106 of connecting the first container-side valve 126 to the first container body 110. Step S106 may include disposing the first seal 132 on the first container body 110 such that when the first seal 132 is actuated from a normally closed position to an actuated position, the actuated position of the first seal 132 allows for a relatively increased flow through the first seal 132 and the open end of the first container body 110 into the first interior space 106 of the first container body 110.

[0145] The first container side valve 126 may be connected to the first container body 110 by connecting the first valve housing flange 128A of the first valve housing 128 to the second clamping surface 108B1 of the second outer body portion 108B.

[0146] The process for assembling the first container 100 may include a step S108 of connecting the first outer body portion 108A to the second outer body portion 108B. For example, corresponding surfaces of the first outer body portion 108A and the second outer body portion 108B may be connected, for example, by a press fit and / or adhesive. When connecting the first outer body portion 108A to the second outer body portion 108B, the first valve housing flange 128A may be clamped between the first clamping surface 108A1 and the second clamping surface 108B1.

[0147] The process for assembling the first container 100 may include a step S110 of loading a predetermined amount of cell delivery solution into the first interior space 106 of the first container body 110. The cell delivery solution may be loaded into the first interior space 106 via the first container side valve 126 that is actuated from a normally closed position to an actuated position. The predetermined amount of cell delivery solution loaded into the first interior space 106 may be selected based on the target dose volume to be created. For example, the predetermined amount of cell delivery solution may be selected to be the same as the volume of the first interior space 106. By selecting the predetermined amount of cell delivery solution to be the same as the volume of the first interior space 106, further loading of cells from the second container 200 into the first interior space 106 may displace the same or substantially the same amount of cell delivery solution, such that the first interior space 106 with the cells and cell delivery solution (considered to be the dose created together) occupies the entire or substantially the entire first interior space 106. In another example, the predetermined amount of cell delivery solution may be selected such that the predetermined amount of cell delivery solution, along with the predetermined amount of cells loaded into the first interior space 106 from the second container 200, occupies all or substantially all of the first interior space 106.

[0148] As used herein, a cell delivery solution may be any solution added to unwashed cells (directly to thawed cells) or washed cells so that the cells can be administered to a subject. The cell delivery solution may contain no, or only minimal or trace amounts of cryoprotectant and / or cell washing fluid that preserved and / or washed the cells prior to contact with the cell delivery solution, and that was not completely removed from the container after a supernatant discarding process that may be performed after an optional container centrifugation step that can optionally form a cell pellet or concentrated cell solution. This supernatant discarding process reduces the concentration and / or removes components, such as cryoprotectants, that are undesirable for delivery of the preserved sample to a subject. The cell delivery solution may be used to reconstitute the cell solution for delivery after thawing the cells prior to administration for clinical use.

[0149] As used herein, a cell wash solution is any solution added to a container containing cells and cryoprotectant after the container is removed from a sub-0°C environment. As used herein, the term "cryoprotectant" refers to a substance used to reduce or eliminate cell damage caused by the freezing and thawing process, which inevitably involves ice crystal formation and ionic and osmotic imbalances when cells and / or tissues are stored at temperatures below 0°C. Cryoprotectants are not limited to specific substances, so long as they can reduce cell damage during storage below 0°C. Examples include, but are not limited to, permeating cryoprotectants such as dimethyl sulfoxide (DMSO), glycerol, propylene glycol, ethylene glycol, and the like, or non-permeating cryoprotectants such as sucrose, carboxymethylcellulose salts, carboxymethylcellulose (CMC), monosaccharides, disaccharides, and the like.

[0150] The process for assembling the first container 100 has been described as including steps S102-S110 performed in the order described above. However, steps S102-S110 may be performed in a different order.

[0151] The above-described process for assembling the first container 100 may be performed in a sterile environment (e.g., a biosafety cabinet) or a near-sterile environment to eliminate or minimize contamination of the first interior space 106 after the first container 100 is fully assembled.

[0152] Second container (washing tube) Returning to FIG. 1, the medical instrument system 10 may include a second container 200 (also referred to as a irrigation tube).

[0153] 5, the second container 200, i.e., the apparatus, may include a second tube body 204. The second tube body 204 may extend along a second tube body axis C between a first end 204A of the second tube body 204 and a second end 204B of the second tube body 204.

[0154] The dimensions of the second container 200 are not particularly limited. For example, the length of the second container 200 along the second tube body axis C and the outer diameter of the second container 200 perpendicular to the second tube body axis C can be selected so that the second container 200 with the first container 100 connected thereto can fit within a centrifuge compartment.

[0155] The second tube body 204 may include a second vessel outer body 208. The second vessel outer body 208 may have a shape or configuration that allows the second vessel 200 to fit within a centrifuge compartment when connected to the first vessel 100, as described in more detail below.

[0156] The material for forming the first and / or second container outer body 208 is not particularly limited. Examples of materials for forming the second container outer body 208 may include low leachable and / or low extractable materials, such as cyclic olefin polymers, cyclic olefin copolymers, perfluoroalkoxy alkanes, ethylene tetrafluoroethylene, cyclic block copolymers, polyethylene, silicone, polypropylene, and polycarbonate. The material for forming the first and / or second container may be selected based on the possible manufacturing method, such as injection molding.

[0157] As envisaged herein, any components that will come into contact with the solution, particularly any components of the first and second containers, may be low leachable and / or low extractable materials.

[0158] Referring to FIG. 5, the second container outer body 208 may include a first portion 208A, a second portion 208B, and a third portion 208C arranged in the above-mentioned order from the first end 204A of the second tube body 204 to the second end 204B of the second tube body 204. The first portion 208A and the second portion 208B may be formed as a single structure. The first portion 208A and the second portion 208B may define the second interior space 206 between the first opening (i.e., also the first end 204A) and the second opening. Furthermore, the third portion 208C may be a separate structure connected to the second portion 208B. The third portion 208C may be connected to the second portion 208B such that a portion of the third portion 208C is disposed in the second interior space 206.

[0159] The first portion 208A of the second container outer body 208 may have a shape or structure for directly or indirectly connecting the second container 200 to the first container 100, as described above. A surface of the first portion 208A of the second container outer body 208 may include a second portion of a connecting or coupling mechanism for directly or indirectly connecting the second container 200 to the first container 100. As an example, an inner surface of the first portion 208A of the second container outer body 208 may include female threads (as shown in FIGS. 5 and 6 ) configured to connect to male threads (as shown in FIGS. 2 and 6 ) of the first portion 112 of the first container outer body 108.

[0160] 5, the third portion 208C of the second container outer body 208 can define the second container body interior space 212. The third portion 208C can extend along the second tube body axis C between a first end of the third portion 208C and a second end of the third portion 208C. The third portion 208C can define a first opening 212A along the second tube body axis C between the first end 204A of the second tube body 204 and the second end 204B of the second tube body 204. The third portion 208C can define a second opening 212B along the second tube body axis C closer to the second end 204B of the second tube body 204 than the first opening 210A of the second container body 210.

[0161] The volume of the second container body interior space 212 is not particularly limited. For example, the volume of the second container body interior space 212 may be selected based on the target dose volume of the dose to be created in the first container 100 and the volume of the therapeutic substance in the wash buffer to be loaded into the second container body interior space 212. In some embodiments, the therapeutic substance to be delivered is a cell or other particle having a specific diameter. However, it should be understood that the therapeutic substance is not limited to a cell or particle. In any case discussed below, "cells" may be replaced with any other therapeutic substance as needed.

[0162] In some embodiments, the cell is a cell derived from a pluripotent stem cell (PSC), or a precursor or progenitor cell thereof. The PSC may be an embryonic stem cell or an induced pluripotent stem cell. In some aspects, the cell is a PSC. In some embodiments, the cell is a dopaminergic neuronal cell, or a precursor or progenitor cell thereof, and in some embodiments, may be an iPSC-derived dopaminergic neuronal cell, or a precursor or progenitor cell thereof. However, it should be understood that the type of cell is not particularly limited. Mesenchymal stem cells, hematopoietic stem cells, embryonic or induced pluripotent stem cells, red blood cells, platelets, chondrocytes, skin cells, immune cells (e.g., tumor infiltrating lymphocytes, virally reconstituted T cells, dendritic cells, regulatory T cells, macrophages), neural crest stem cells, neurons, glia, smooth muscle, cardiac tissue, chondrocytes, bone cells, glial-restricted progenitor cells, astrocytes, oligodendrocytes, neuroblasts, megakaryoblasts, megakaryocytes, monoblasts, monocytes, macrophages, myeloid dendritic cells, proerythroblasts, erythroblasts, normoblasts, reticulocytes, platelets, myeloblasts, progranulocytes, neutrophilic myelocytes, neutrophilic bands, neutrophils, eosinophilic myelocytes, eosinophilic bands, eosinophils Other types of cells may be treated, such as basophilic myelocytes, basophilic band cells, basophils, lymphoid progenitor cells, pre-NK cells, NK lymphoblasts, NK cells, thymocytes, T lymphoblasts, T cells, plasmacytoid dendritic cells, pre-B cells, B lymphoblasts, B cells, plasma cells, osteoblasts, chondrocytes, myoblasts, myotubes, fibroblasts, adipocytes, mesoderm, ectoderm, primordial germ cells, sperm, oocytes, definitive endoderm, myeloid progenitor cells, microglial cells, myeloid cells, cardiac cells (e.g., cardiomyocytes such as atrial or ventricular cardiomyocytes), progenitor or precursor cells thereof, or any other suitable type of cell.

[0163] The third portion 208C may have a shape or structure for directing the displacement of cells in the wash buffer by the centrifugal force applied by the centrifuge toward the first opening 212A of the third portion 208C. The shape or structure of the third portion 208C is not particularly limited. For example, the third portion 208C may include a first portion 212C, a second portion 212D, and a third portion 212E arranged in the above-mentioned order along the second tube body axis C from the second opening 212B of the third portion 208C and the first opening 212A of the third portion 208C. The first portion 212C may have a cylindrical shape with a first diameter. The second portion 212D may be a cone shape with a varying diameter, the varying diameter decreasing from the first diameter to the second diameter along the second tube body axis C in a direction from the second opening 212B toward the first opening 212A. The third portion 212E may be cylindrical in shape having a second diameter.

[0164] 5, the second container 200 may include a cover 230 configured to connect to the third portion 208C and cover the second opening 212B of the third portion 208C. The cover 230 and the second tube body 204 each have a portion of a connection or coupling mechanism for directly or indirectly connecting the cover 230 to the second tube body 204. As an example, the third portion 208C may include one portion of a threaded connection, while the cover 230 may include another portion of a threaded connection that detachably connects the cover 230 to the second container outer body 208. One portion of the threaded connection may be one of male threads (as shown in the figure) and female threads, while the other portion of the threaded connection provided on the cover 230 may be the other of male threads and female threads (as shown in the figure).

[0165] Referring to FIG. 5, the second container 200 may include a second flow path control module 232 disposed on the cover 230. The second flow path control module 232 may include a luer valve that can be actuated from a normally closed position to an actuated position to allow flow into the second container body interior space 212 and can be deactuated from an actuated position to a normally closed position to reduce and eliminate flow into the second container body interior space 212. The number of second flow path control modules 232 may be numerous. For example, there may be two or more second flow path control modules 232. In some embodiments, one second flow path control module can be used to introduce cell washing solution into the second container and another second flow path control module can be used to evacuate air.

[0166] 5, the second container 200 may include a second portion of the first flow path control module 124. The second portion of the first flow path control module 124 is configured to be actuated from a normally closed position to an actuated position and deactuated from the actuated position to the normally closed position. In the normally closed position, flow from the second container body 210 through the first opening 212A of the third portion 208C is relatively reduced or completely restricted. In the actuated position, flow from the third portion 208C through the first opening 212A is increased compared to the normally closed position.

[0167] As described above, the first flow path control module 124 may include a valve system. A second portion of the first flow path control module 124 may include a second container-side valve 220. The second container-side valve 220 may be provided in the second portion 208B of the second container outer body 208, as described below.

[0168] The second container-side valve 220 may include a valve cap 222 , a valve stem 224 , and a second seal 226 .

[0169] The valve cap 222 may include a cylinder 222A and a mounting surface 222B. The cylinder 222A may be disposed in the second portion 208B of the second container outer body 208. The inner surface of the second portion 208B of the second container outer body 208 is sized to limit movement of the cylinder 222A to a predetermined range of movement along the second tube body axis C in a direction from the first end 204A of the second tube body 204 toward the second end 204B of the second tube body 204.

[0170] The valve stem 224 can be connected to the mounting surface 222B at an intermediate portion of the valve stem 224 along the length of the valve stem 224. A first portion 224A of the valve stem 224 on the side of the mounting surface 222B facing the third portion 208C of the second container outer body 208 is exposed while being radially surrounded by the cylinder 222A of the valve cap 222, and a second portion 224B of the valve stem 224 on the side of the mounting surface 222B facing the first end 204A is also exposed. The valve stem 224 is connected to the cylinder 222A by the mounting surface 222B such that when the cylinder 222A moves along a predetermined range of the second tube axis C, the valve stem 224 also moves along the second tube axis C. A portion of the valve stem 224 including a first end of the valve stem 224 may have a taper that reduces an outer diameter of the portion of the valve stem 224 in a direction toward the first end of the valve stem 224. A portion of the valve stem 224 including a second end of the valve stem 224 may have a taper that reduces an outer diameter of the portion of the valve stem 224 in a direction toward the second end of the valve stem 224. The taper of the portion of the valve stem 224 including the first and second ends of the valve stem 224 may improve the ability of the valve stem 224 to actuate the first seal 132 and the second seal 226, as described in more detail below.

[0171] The second seal 226 may be positioned to connect to the third portion 212E of the third section 208C of the second container outer body 208. The second seal 226 is configured to provide a normally closed position and an actuated position for the second container-side valve 220. One example of the second seal 226 is a self-sealing seal.

[0172] The second seal 226 has a normally closed position that relatively reduces or completely restricts flow through the second seal 226. The second seal 226 can be actuated from the normally closed position to an actuated position. The actuated position of the second seal 226 allows for a relatively increased flow through the second seal 226. For example, the second seal 226 can be actuated from the normally closed position to an actuated position by deforming the self-sealing seal to provide a flow path through the second seal 226. The second seal 226 can be actuated by the valve stem 224 as described below.

[0173] With reference to FIG. 6, actuation of the first container valve 126 and the second container valve 220 by the valve stem 224 through the connection between the first container 100 and the second container 200 will be described.

[0174] As described above, the first container outer body 108 can include male threads and the first portion 208A of the second container outer body 208 can include female threads. The first container 100 and the second container 200 can be connected by aligning the first tube body axis A and the second tube body axis C, rotating the first container 100 relative to the second container 200 to engage the male threads of the first container outer body 108 with the female threads of the first portion 208A of the second container outer body 208, and advancing the first container-side valve 126 toward the second container-side valve 220. As the first container-side valve 126 continues to advance toward the second container-side valve 220, the tapered portion of the valve stem 224 closest to the first seal 132 advances past the first valve housing 128 and contacts the first seal 132, actuating it from the normally closed position to the actuated position.

[0175] As the male threads of the first container outer body 108 continue to engage with the female threads of the first portion 208A and the first container valve 126 advances toward the second container valve 220, the first valve housing 128 of the first container valve 126 can come into contact with the valve cap 222. For example, the first valve housing 128 can come into contact with the mounting surface 222B of the valve cap 222. A force in a direction toward the second container 200 of the first container 100 resulting from the advancement of the first container valve 126 toward the second container valve 220 can be transmitted from the first valve housing 128 to the valve cap 222 to move the valve cap 222 with the valve stem 224 attached thereto toward the second seal 226 along a predetermined range of the second tube body axis C in the direction of the second end 204B of the second tube body 204. When the valve cap 222 moves toward the second seal 226, the tapered portion of the first portion 224A of the valve stem 224 contacts the second seal 226 to actuate the valve from the normally closed position to the actuated position. When the valve cap 222 moves to the end of a predetermined range closest to the second end 204B of the second tube body 204, the tapered portion of the valve stem 224 contacts the first seal 132 and the second seal 226, respectively, to actuate the first container-side valve 126 and the second container-side valve 220, and form a flow path from the second interior space 206 of the second tube body 204 to the first interior space 106 of the first tube body 104.

[0176] Referring to FIG. 6, the deactivation of the first container valve 126 and the second container valve 220 due to the decoupling of the first container 100 and the second container 200 will be described.

[0177] The first container 100 and the second container 200 can be separated by rotating the first container 100 in the opposite direction relative to the second container 200 to disengage the male threads of the first container outer body 108 from the female threads of the first portion 208A of the second container outer body 208, thereby retracting the first container valve 126 from the second container valve 220. As the first container valve 126 continues to retract from the second container valve 220, the tapered portion of the second portion 224B of the valve stem 224 that actuated the first container valve 126 retracts away from the first seal 132, deactivating the first seal 132 from an actuated position to a normally closed position, thereby reducing or completely eliminating flow through the first seal 132 of the first container valve 126.

[0178] Process for Assembling the Second Vessel (Washing Pipe) 7, the process for assembling the second container 200 will now be described.

[0179] The process for assembling the second container 200 may include a step S202 of placing the valve cap 222 and the valve stem 224 connected to the valve cap 222 in the second portion 208B of the second container outer body 208. The valve cap 222 and the valve stem 224 may be inserted through a second opening of a single structure including the first portion 208A and the second portion 208B to be placed in the second interior space 206. The valve cap 222 and the valve stem 224 may be placed in the second interior space 206 such that the first portion 224A of the valve stem 224 faces the third portion 208C of the second container outer body 208 and the second portion 224B of the valve stem 224 faces the first opening 104A of the second tube body 204.

[0180] The process for assembling the second container 200 may include the step S204 of placing the second seal 226 on the third portion 212E of the third region 208C of the second container outer body 208.

[0181] The process for assembling the second container 200 may include a step S206 of connecting the third portion 208C of the second container outer body 208 to the second portion 208B such that a portion of the third portion 208C is disposed in the second interior space 206. For example, the third portion 208C may be connected to the second portion 208B such that the third portion 212E (with the second seal 226 disposed in the third portion 212E) and a portion of the second portion 212D of the third portion 208C are disposed in the second interior space 206.

[0182] The third portion 208C can be connected to the second portion 208B to define a predetermined range of travel for the cylinder 222A of the second container-side valve 220. Furthermore, the second container-side valve 220 is in a normally closed position when the third portion 208C is connected to the second portion 208B.

[0183] The process for assembling the second container 200 may include a step S208 of connecting a cover 230 having a second flow path control module 232 disposed on the cover 230 to a third portion 208C of the second container outer body 208 to cover the second opening 212B of the second container body interior space 212. The above-described process for assembling the second container 200 may be performed in a sterile environment (e.g., a biosafety cabinet) to minimize or eliminate contamination of the second container body interior space 212 and the second interior space 206 after the second container 200 is fully assembled.

[0184] Second Container Loading Module Referring to FIG. 1 , the medical instrument system 10 can include a second container loading module 300 for loading a plurality of cells and a cell washing solution into the second container body interior space 212 of the second container 200 .

[0185] The second container loading module 300 will be described with reference to FIG. 8. The second container loading module 300 may include a flow regulator 302, an adapter 304, and a cell vial 308. The cell vial 308 may hold a mixture of a predetermined number of cells and a cryoprotectant. The flow regulator 302 may fluidly connect a source of wash fluid to the adapter 304. The adapter 304 may fluidly connect the flow regulator 302 to the cell vial 308. The adapter 304 may separately fluidly connect the cell vial 308 to the second container 200.

[0186] The flow regulator 302 can regulate the flow of wash fluid through the adapter 304 to the cell vial 308 at, for example, one drop per second (approximately 50 microliters) to prevent osmotic shock to the cells contained in the cell vial 308.

[0187] The adapter 304 can fluidly direct the wash solution, the flow rate of which is regulated by the flow regulator 302, to the cell vial 308. Furthermore, the adapter 304 can be directly or indirectly connected to the second flow path control module 232 to fluidly direct the mixture of cells, cryoprotectant, and wash solution from the cell vial 308 through the second flow path control module 232 to the second container body interior space 212 of the third portion 208C of the second container outer body 208.

[0188] As an alternative to the second vessel loading module 300, the solution of cells can be placed directly into the second vessel body interior space 212 of the second vessel 200, and a washing solution can be provided to the second vessel body interior space 212 of the second vessel 200 before or after the solution of cells is placed into the second vessel body interior space 212 of the second vessel 200. The mixture of the solution of cells and the washing solution in the second vessel 200 is then centrifuged to transfer a portion of the cells to the first vessel 100, as described below.

[0189] As yet another alternative, the solution of cells can be placed directly into the first container 100, which is then centrifuged.

[0190] Process for preparing a cell solution for delivery A process for preparing a cell solution for delivery, such as a cell-based cell solution for delivery, is described with reference to FIG.

[0191] The process for preparing a cell solution for delivery may include a step S302 of regulating the flow of a wash fluid from a source of wash fluid to a cell vial 308 (see, e.g., FIG. 8 ) holding a mixture of cells and cryoprotectant by a flow regulator 302. The wash fluid may serve to wash cells that have been cryopreserved in the cryoprotectant. Regulating the wash fluid may serve to prevent osmotic shock to the cells contained in the cell vial 308.

[0192] The process for preparing a cell solution for delivery may include step S304 of fluidly directing a mixture of cells, cryoprotectant, and washing solution from a cell vial 308 through a second flow path control module 232 to a second container body interior space 212 of a third portion 208C of the second container outer body 208.

[0193] The process for preparing the cell solution for delivery may include a step S306 of connecting the first container 100 and the second container 200. Connecting the first container 100 and the second container 200 may include aligning the first tube body axis A and the second tube body axis C, and rotating the first container 100 relative to the second container 200 to engage the male threads of the first container outer body 108 with the female threads of the first portion 208A of the second container outer body 208, and advancing the first container side valve 126 toward the second container side valve 220. As the first container side valve 126 continues to advance toward the second container side valve 220, the tapered portion of the valve stem 224 closest to the first seal 132 advances past the first valve housing 128 and contacts the first seal 132 to actuate it from the normally closed position to the actuated position.

[0194] As the male threads of the first container outer body 108 continue to engage with the female threads of the first portion 208A and the first container valve 126 advances toward the second container valve 220, the first valve housing 128 of the first container valve 126 can come into contact with the valve cap 222. For example, the first valve housing 128 can come into contact with the mounting surface 222B of the valve cap 222. A force in a direction toward the second container 200 of the first container 100 resulting from the advancement of the first container valve 126 toward the second container valve 220 can be transmitted from the first valve housing 128 to the valve cap 222 to move the valve cap 222 with the valve stem 224 attached thereto toward the second seal 226 along a predetermined range of the second tube body axis C in the direction of the second end 204B of the second tube body 204. When the valve cap 222 moves toward the second seal 226, the tapered portion of the first portion 224A of the valve stem 224 contacts the second seal 226 to actuate the valve from the normally closed position to the actuated position. When the valve cap 222 moves to the end of a predetermined range closest to the second end 204B of the second tube body 204, the tapered portion of the valve stem 224 contacts the first seal 132 and the second seal 226, respectively, to actuate the first container-side valve 126 and the second container-side valve 220, and form a flow path from the second interior space 206 of the second tube body 204 to the first interior space 106 of the first tube body 104.

[0195] Please note that prior to connection of the first container 100 and the second container 200, the first interior space 106 of the first container 100 is pre-loaded with a predetermined amount of cell delivery solution in accordance with step S110, as described above.

[0196] The predetermined amount of cell delivery solution loaded into the first interior space 106 may be selected based on the target dose volume to be created. For example, the predetermined amount of cell delivery solution may be selected to be the same as the volume of the first interior space 106. By selecting the predetermined amount of cell delivery solution to be the same as the volume of the first interior space 106, further loading of cells from the second container 200 into the first interior space 106 can displace the same or substantially the same amount of cell delivery solution, such that the first interior space 106 with the cells and cell delivery solution (together considered the created dose) occupies the entire or substantially the entire first interior space 106. In another example, the predetermined amount of cell delivery solution may be selected such that the predetermined amount of cell delivery solution, together with the predetermined amount of cells loaded into the first interior space 106 from the second container 200, occupies the entire or substantially the entire first interior space 106.

[0197] The process for preparing a cell solution for delivery may include a step S308 of applying a centrifugal force to the connected first container 100 and second container 200. Step S308 may include loading the connected first container 100 and second container 200 into a centrifuge in an orientation such that at least a portion of the cells in the second container 200 move radially outward of the spin axis from the second container 200 to the first container 100 during the spinning action of the centrifuge along the spin axis. After step S306, the first container side valve 126 and the second container side valve 220 are each in an actuated position, so that at least a portion of the cells in the second container 200 move from the second container body internal space 212, through the second seal 226 in an actuated position, through the valve stem 224, through the first seal 132 in an actuated position, and into the first internal space 106 defined by the first container body 110 to form a dose of cell solution for delivery.

[0198] In step S308, the centrifuge can be controlled to operate for at least a predetermined length of time, at a predetermined speed, or both, to ensure that a sufficient number of cells are separated from the cryoprotectant and washing solution in the first container 100 and transferred to the first interior space 106 of the first container body to produce a dose having a cell concentration that meets a predetermined target concentration and volume.

[0199] The above-described process for preparing a cell solution for delivery may be modified to include other steps. For example, after step S304 of directing the mixture of cells, cryoprotectant, and washing solution from the cell vial 308 to the second container body internal space 212 and before performing step S306 of connecting the first container 100, the process for preparing a cell solution for delivery may include a step of applying centrifugal force to the mixture of cells, cryoprotectant, and washing solution contained in the second container 200 to separate the cells from the cryoprotectant and washing solution. The cells separated from the cryoprotectant and washing solution may be formed as a pellet mainly in a portion of the second container body internal space 212 in the third portion 212E of the third portion 208C of the second container outer body 208. After forming a pellet of cells in the third portion 212E of the third portion 208C of the second container outer body 208, a step S306 of applying centrifugal force is performed to transfer the cells from the second container 200 to the first container 100 through the first flow path control module 124 having the first container side valve 126 in the operating position and the second container side valve 220 in the operating position. By performing a step of applying centrifugal force to the mixture of cells, cryoprotectant, and washing solution contained in the second container 200 before performing step S308, the amount of cryoprotectant and washing solution transferred to the first container 100 in step S308 can be minimized, and the number of cells transferred to the first container 100 in step S308 can be increased, thereby increasing the possibility that the cell concentration of the dose created in the first container 100 will meet the predetermined target concentration.

[0200] The process of preparing the cell solution for delivery may include, after step S308, step S310 of disconnecting the first container 100 from the second container and deactivating the first container valve 126 and the second container valve 220. The first container 100 and the second container 200 may be disconnected by disengaging the male threads of the first container outer body 108 from the female threads of the first portion 208A of the second container outer body 208 by rotating the first container 100 in the opposite direction relative to the second container 200 to retract the first container valve 126 from the second container valve 220. As the first container-side valve 126 continues to retract from the second container-side valve 220, the tapered portion of the second portion 224B of the valve stem 224 that actuated the first container-side valve 126 retracts away from the first seal 132, deactivating the first seal 132 from an actuated position to a normally closed position, thereby reducing or completely eliminating flow through the first seal 132 of the first container-side valve 126.

[0201] Upon completion of step S310, the dose of cells comprising a mixture of cells and cell delivery solution is sealed in the first interior space 106 of the first container body 110 by the first container valve 126, which is in a normally closed position.

[0202] According to some embodiments of a process for preparing a cell solution for delivery, cells originally cryopreserved in a cryoprotectant (i.e., a cell preparation product) and held by a cell vial 308 are washed and transferred from the cell vial 308 to the second container 200 and then to the first container 100 in a flow path that minimizes or eliminates the risk of contamination of the cells through contact with the external environment. Thus, the cell solution for delivery can be considered sterile or nearly sterile.

[0203] 10 illustrates an example of a medical device system 10 for performing dose preparation according to one embodiment. The medical device system 10 may include a first container 100 (also referred to as a dose preparation tube), a second container 200 (also referred to as a irrigation tube), a second container loading module 300, a mobile body 400, and a first container mixing module 500.

[0204] The medical equipment system 10 shown in Figure 10 is similar to the medical equipment system 10 shown in Figure 1, but further includes a movable body 400 and a first container mixing module 500. The features of the first container 100, the second container 200, and the second container loading module 300 shown in Figure 10 are similar to the features of the first container 100, the second container 200, and the second container loading module 300 described above with reference to Figures 1 to 9.

[0205] movable body 11, 12, and 13A to 13D show the movable body 400 disposed in the first internal space 106 of the first container 100. As shown in FIG.

[0206] 12 and 13A-13D, a description will be given of a movable body 400 that may be used with the first container 100. For ease of explanation, a description will be given of a single movable body 400. However, multiple movable bodies 400 are also contemplated.

[0207] The movable body 400 may have a shape or structure that allows the movable body 400 to move in the first internal space 106 of the first container body 110 due to an external force. The movement of the movable body 400 is not particularly limited. In one example, the movable body 400 may have a shape or structure that allows the movable body 400 to move parallel to or on the first tube body axis A in the first container body 110. The range of movement of the movable body 400 parallel to or on the first tube body axis A may include a movement between both ends of the first container body 110 or a shorter range. In another example, the movable body 400 may have a shape or structure that allows the movable body 400 to rotate around the first tube body axis A in the first container body 110. In one example, the movable body 400 may have a shape or structure that allows the movable body 400 to both move parallel to or on the first tube body axis A within the first container body 110, and rotate around the first tube body axis A.

[0208] The movable body 400 may be configured to move in the range of movement by an external force. The external force is not particularly limited. In one example, the movable body 400 may be configured to move by manually or mechanically moving the first container 100 relative to the movable body 400. In another example, the movable body 400 may be configured to move by a magnetic force.

[0209] The movable body 400 may include a movable body housing 402 and one or more magnets 404 (or magnetic materials) disposed in the movable body housing 402. As described herein, the magnetic materials may be suitable substitutes for magnets. For example, if the movable body disclosed herein is a magnetic material, movement of the magnetic material may be achieved using magnets external to the devices disclosed herein.

[0210] A first example of a movable body 400 will be described with reference to FIG. 13A.

[0211] In a first example, the movable body housing 402 may extend along a length axis B between a first end 402A of the movable body housing 402 and a second end 402B of the movable body housing 402. The maximum diameter of the movable body housing 402 along the length axis B may be selected to be smaller than the minimum diameter of the first interior space 106 along the first tube body axis A.

[0212] An outer diameter of a first portion of the movable body housing 402 provided between the first end 402A of the movable body housing 402 and the second end 402B of the movable body housing 402 may be smaller than an outer diameter of a second portion of the movable body housing 402 between the first end 402A of the movable body housing 402 and the first portion of the movable body housing 402. An outer diameter of the first portion of the movable body housing 402 may be smaller than an outer diameter of a third portion of the movable body housing 402 between the second end 402B of the movable body housing 402 and the first portion of the movable body housing 402.

[0213] At least a portion of the outer surface of the moveable body housing 402 may be formed as a cylindrical shaft having a helical groove 406 .

[0214] Additionally, the movable body housing 402 can house a magnet 404. The magnet 404 can be housed within the movable body housing 402 such that the magnetic polarity of the magnet 404 is aligned with or oriented parallel to the length axis B of the movable body housing 402 such that a magnetic force applied to the magnet 404 can be transferred to the movable body housing 402 to move the movable body 400 parallel to or along the first tube body axis A within the first container body 110.

[0215] A second example of the movable body 400 will be described with reference to FIG. 13B.

[0216] In a second example, the movable body housing 402 may extend along a length axis B between a first end 402A of the movable body housing 402 and a second end 402B of the movable body housing 402. The maximum diameter of the movable body housing 402 along the length axis B may be selected to be smaller than the minimum diameter of the first interior space 106 along the first tube body axis A.

[0217] The movable body housing 402 may include an inner cylinder 408 extending along a length axis B and an outer cylinder 410 extending along the length axis B. The inner cylinder 408 and the outer cylinder 410 may be coaxial along the length axis B.

[0218] The moveable body housing 402 may further include a plurality of blades 412 connecting the inner cylinder 408 and the outer cylinder 410. The plurality of blades 412 may be circumferentially spaced apart from one another about the length axis B. The plurality of blades 412 may be circumferentially spaced apart from one another in an equidistant manner about the length axis B. The plurality of blades 412 may be arranged to have rotational symmetry about the length axis B.

[0219] The magnet 404 may be housed within the inner cylinder 408 of the movable body housing 402 such that the magnetic polarity of the magnet 404 is oriented parallel or substantially parallel to the length axis B of the movable body housing 402 such that a magnetic force applied to the magnet 404 can be transferred to the movable body housing 402 to move the movable body 400 along the first tube body axis A within the first container body 110. Depending on the magnetic force applied to the magnet 404, the movable body 400 may move parallel to or along the first tube body axis A, may move in rotation about the first tube body axis A, or both.

[0220] The movable body 400 may be positioned within the first container body 110 such that a portion of the inner cylinder 408 protrudes past the outer cylinder 410 along the longitudinal axis B toward the first opening 104A of the first tube body 104, and is closer to the first opening 104A of the first tube body 104 than the outer cylinder 410.

[0221] In such an arrangement, the side of the movable body 400 closer to the second opening 104B of the first tube body 104 may have a concave shape. Furthermore, the side of the movable body 400 closer to the first opening 104A of the first tube body 104 may have a convex shape, and the side of the first container-side valve 126 facing the side of the movable body 400 having the convex shape may have a concave shape that matches the convex shape of the movable body 400. The matching shapes of the first container-side valve 126 and the movable body 400 can increase the range of movement of the movable body 400 in the first internal space 106 of the first container body 110 along the first tube body axis A.

[0222] A third example of a movable body 400 will be described with reference to FIG. 13C.

[0223] In a third example, the movable body housing 402 may extend along a length axis B between a first end 402A of the movable body housing 402 and a second end 402B of the movable body housing 402. A maximum diameter of the movable body housing 402 along the length axis B may be selected to be smaller than a minimum diameter of the first interior space 106 along the first tube body axis A.

[0224] The moveable body housing 402 may include an inner disk 414 , a number of outer rings, and a number of connectors connecting the multiple outer rings to each other and to the inner disk 414 .

[0225] The inner disc 414 may be arranged such that a length axis B passes through a center of the inner disc 414. The plurality of outer rings may include an outer ring 416 and an inner ring 418. A diameter of the outer ring 416 may be larger than a diameter of the inner disc 414. A diameter of the inner ring 418 may be larger than a diameter of the outer ring 416. The inner disc 414, the outer ring 416, and the inner ring 418 may be arranged coaxially along the length axis B. The inner disc 414, the outer ring 416, and the inner ring 418 may be arranged in a stepped manner. The inner disk 414 may be disposed on a first plane along the length axis B, the inner ring 418 may be disposed on a second plane along the length axis B, and the outer ring 416 may be disposed on a third plane along the length axis B, the first, second, and third planes being perpendicular to the length axis B, and the second plane being located between the first and third planes.

[0226] The plurality of connectors may include a first pair of connectors 420 and a second pair of connectors 422. The first pair of connectors 420 may be disposed on a fourth plane along with a length axis B. The second pair of connectors 422 may be disposed on a fifth plane along with a length axis B, the fifth plane being orthogonal to the fourth plane.

[0227] One connector of the first pair of connectors 420 may be configured to connect the inner disc 414, the outer ring 416, and the inner ring 418 in one direction provided on the fourth plane, and the other connector of the first pair of connectors 420 may be configured to connect the inner disc 414, the outer ring 416, and the inner ring 418 in the other direction provided on the fourth plane, the two directions on the fourth plane being axially symmetric with respect to the fifth plane.

[0228] One connector of the second pair of connectors 422 may be configured to connect the inner disc 414, the outer ring 416, and the inner ring 418 in one direction provided on the fifth plane, and the other connector of the second pair of connectors 422 may be configured to connect the inner disc 414, the outer ring 416, and the inner ring 418 in the other direction provided on the fifth plane, the two directions on the fifth plane being axially symmetric with respect to the fourth plane.

[0229] When the movable body 400 is viewed along the longitudinal axis B, multiple gaps are defined between the outer ring 416 and the inner ring 418 by portions of the outer ring 416 and the inner ring 418 that are not connected by the first pair of connectors 420 and the second pair of connectors 422, and multiple gaps are defined between the inner ring 418 and the inner disk 414 by portions of the inner ring 418 and the inner disk 414 that are not connected by the first pair of connectors 420 and the second pair of connectors.

[0230] The plurality of magnets 404 may be housed in the first pair of connectors 420 and the second pair of connectors 422. A first magnet of the plurality of magnets 404 may be housed in one connector of the first pair of connectors 420 such that the magnetic polarity of the first magnet is aligned or oriented parallel to one direction provided on the fourth plane. A second magnet of the plurality of magnets 404 may be housed in the other connector of the first pair of connectors 420 such that the magnetic polarity of the second magnet is aligned or oriented parallel to another direction provided on the fourth plane. A third magnet of the plurality of magnets 404 may be housed in one connector of the second pair of connectors 422 such that the magnetic polarity of the third magnet is aligned or oriented parallel to one direction provided on the fifth plane. A fourth magnet of the plurality of magnets 404 may be housed in the other connector of the second pair of connectors 422 such that the magnetic polarity of the fourth magnet is aligned or parallel to the other direction provided on the fifth plane. The magnetic polarity of each of the first to fourth magnets 404 transmits a magnetic force applied to the magnet 174 to the movable body housing 402 to allow the movable body 400 to move within the first container body 110 along the first tube body axis A. Depending on the magnetic force applied to the magnet 404, the movable body 400 may move parallel to or along the first tube body axis A, may move to rotate around the first tube body axis A, or both.

[0231] The movable body 400 may be positioned within the first container body 110 such that the inner disk 414 is positioned closer to the first opening 104A of the first tube body 104 than the inner ring 418, and the outer ring 416 is positioned closer to the second opening 104B of the first tube body 104 than the inner ring 418.

[0232] In such an arrangement, the side of the movable body 400 closer to the first opening 104A of the first tube body 104 can have a convex shape, and the side of the first container-side valve 126 facing the convex side of the movable body 400 can have a concave shape that matches the convex shape of the movable body 400. The matching shapes of the first container-side valve 126 and the movable body 400 can increase the range of movement of the movable body 400 in the first interior space 106 of the first tube body 104 along the first tube body axis A.

[0233] A fourth example of a movable body 400 will be described with reference to FIG. 13D.

[0234] In a fourth example, the movable body housing 402 may extend along a length axis B between a first end 402A of the movable body housing 402 and a second end 402B of the movable body housing 402. A maximum diameter of the movable body housing 402 along the length axis B may be selected to be smaller than a minimum diameter of the first interior space 106 along the first tube body axis A.

[0235] The movable body housing 402 defines two or more through holes or passages extending between the first end 402A and the second end 402B. As shown in FIG. 13D, each of the two or more through holes extends between the first end 402A and the second end 402B along an axis parallel or oblique to the length axis B. Furthermore, the axes of each of the two or more through holes can intersect such that as the movable body 400 moves along the first tube body axis A, fluid flows passing through the two or more through holes between the first end 402A and the second end 402B are directed toward each other to promote mixing.

[0236] The movable body 400 may be formed as a solid body from a material such as stainless steel with two or more holes defined therethrough. The movable body 400 may be moved within the first container body 110, for example, by turning the first container body 110 and allowing the weight of the movable body 400 to move by gravity along the first tube body axis A. Other materials that are sufficiently dense and heavy to allow gravity mixing are also contemplated.

[0237] With reference to FIG. 14, a first vessel mixing module 500 may include one or more external magnets 502 and one or more movement guides 504 .

[0238] The movement guide 504 may be connected to one or both of the first container 100 and the one or more external magnets 502. Furthermore, the movement guide 504 may move the first container 100 relative to the one or more external magnets 502 to guide the magnetic polarity of the one or more external magnets 502 to act on the one or more magnets 404 of the movable body 400 to move the movable body 400 within the first interior space 106. As described above, the movement of the movable body 400 in the first interior space 106 may include the movement of the movable body 400 parallel to the first tube body axis A within the first container body 110 or the movement of the movable body 400 on the first tube body axis A as well as the rotation of the movable body 400 on the first tube body axis A. The movement of the movable body 400 within the first interior space 106 causes the cells in the pellet to mix with the cell delivery matrix to create a dose.

[0239] In one example, the first container mixing module 500 may include a stand 506 on which the first container body 110 is removably disposed and / or attached. Further, the movement guide 504 is disposed relative to the stand 506 on which the first container body 110 is removably disposed and / or attached, and guides the external magnet 502 relative to the first container body 110 to guide the magnetic polarity of the external magnet 502 so as to act on one or more magnets 404 of the movable body 400 to move the movable body 400 within the first internal space 106.

[0240] The first container mixing module 500 may include an actuator 508 and a controller 510. The controller 510 may control the actuator 508 to move the external magnet 502 guided by the movement guide 504 to guide the magnetic polarity of the external magnet 502 to act on one or more magnets 404 of the movable body 400 to move the movable body 400 within the first internal space 106.

[0241] 9 , the process for preparing the cell solution for delivery may include placing and / or mounting the first container 100 into which the cells have been transferred (in step S308) on a stand 506. Additionally, the process may include moving the external magnet 502 manually or by a controller 510 and actuator 508 to act on one or more magnets 404 of the movable body 400 to move the movable body 400 within the first interior space 106.

[0242] Movement of the one or more magnets 404 can reduce the level of settling of the cells within the first interior space 106 and can promote suspension of the cells in the cell delivery solution as a heterogeneous mixture.

[0243] 15 shows an example of a medical device system 10 for performing dose preparation according to one embodiment. The medical device system 10 may include a first container 100 (also referred to as a dose preparation tube), a second container 200 (also referred to as a irrigation tube), a second container loading module 300, and a dose loading module 600.

[0244] The medical equipment system 10 shown in Figure 15 is similar to the medical equipment system 10 shown in Figure 1, but further includes a dose loading module 600. The features of the first container 100, the second container 200, and the second container loading module 300 shown in Figure 10 are similar to the features of the first container 100, the second container 200, and the second container loading module 300 described above with reference to Figures 1 to 9.

[0245] Dose Loading System 17-19, a dose loading module 600 for loading a dose, created by mixing the cells in the first container 100 with a cell delivery matrix, into a cell delivery device is described.

[0246] The first container outer body 108 can have a shape or structure that allows the first container 100 to receive a plunger of a plunger system (described in further detail below), such that the plunger moves relative to the first container 100 to reduce the volume of the first interior space 106 between the plunger seal 140 and the first opening 104A of the first tube body 104. As an example, the first container outer body 108 can define a through hole 114 for receiving the plunger. The through hole 114 can be provided at a second end of the first tube body 104.

[0247] The first container outer body 108 may have a shape or structure for directly or indirectly connecting the first container 100 to the cover 116. The cover 116 may be detachably connected to the first container outer body 108 to cover the through hole 114. For example, the cover 116 may be connected to the first container 100 and may connect the first container 100 to the second container 200. The first container 100 and the cover 116 may have a shape or structure that allows the first container 100 and the cover 116 to be contained within a centrifuge compartment when connected to each other. The first container outer body 108 may include a first portion 118 of a connection or coupling mechanism for directly or indirectly connecting the first container 100 to the cover 116. As an example, the first container outer body 108 may include one portion of a threaded connection. The cover 116 may include a second portion 120 of a connecting or coupling mechanism for directly or indirectly connecting the cover 116 to the first container 100. As an example, the cover 116 may include another portion of a threaded connection that removably connects the cover 116 to the first container 100. One portion of the threaded connection provided on the first container outer body 108 may be one of male threads (as shown in the figures) and female threads, while the other portion of the threaded connection provided on the cover 116 may be the other of male threads and female threads (as shown in the figures).

[0248] The first container body 110 may be disposed within the first container outer body 108 along the first tube body axis A. The first container body 110 may define a first interior space 106. The first interior space 106 defined by the first container body 110 may be connected to a first opening 104A at a first end of the first tube body 104. Furthermore, the first interior space 106 defined by the first container body 110 may be connected to a second opening 104B at a second end of the first tube body 104. For example, the first interior space 106 may be connected to a second opening 104B at a second end of the first tube body 104 so as to communicate with a through hole 114 for receiving a plunger. For example, communication between the first internal space 106 and the through hole 114 may be configured to allow the distal end of the plunger to move through the through hole 114 and into the first internal space 106, as described in further detail below.

[0249] The dimensions of the first container body 110 are not particularly limited. For example, the length of the first container body 110 along the first tube body axis A and the inner diameter of the first container body 110 in a direction perpendicular to the first tube body axis A may be selected so that a portion of the plunger system can be moved within the first container body 110 to change the volume of the first interior space 106.

[0250] The dose loading module 600 may include a plunger system 136. The plunger system 136 may be configured to form a seal with the inner surface of the first container body 110 to reduce or prevent flow past the second opening 104B and the through-hole 114 of the first tube body 104. The shape and structure of the plunger system 136 are not particularly limited.

[0251] As an example, the plunger system 136 may include a plunger head 138 and a plunger seal 140. The plunger head 138 and the plunger seal 140 may be provided as a unitary structure or as separate structures.

[0252] The plunger head 138 may be disposed within the first container body 110. Additionally, a plunger seal 140 may be attached to the plunger head 138 to form a seal with an inner surface of the first container body 110 to reduce or prevent flow past the second opening 104B of the first tube body 104 and the through hole 114. Additionally, the plunger head 138 and the plunger seal 140 attached to the plunger head 138 may be configured to advance within the first interior space 106 of the first container body 110 toward the first opening 104A of the first tube body 104 and retract within the interior space 106 of the first container body 110 toward the second opening 104B of the first tube body 104 while maintaining a seal with the inner surface of the first container body 110, upon application of a force thereto. When the plunger head 138 and the plunger seal 140 advance, the volume of the first internal space 106 between the plunger seal 140 and the first opening 104A decreases, while when the plunger head 138 and the plunger seal 140 retract, the volume of the first internal space 106 between the plunger seal 140 and the first opening 104A increases.

[0253] As an example, the plunger system 136 may include a plunger 142. The plunger 142 may be in the form of a wire configured to be inserted through the through hole 114 of the first tube body 104. The plunger head 138, plunger seal 140, and plunger 142 may be provided as a unitary structure or as separate structures. The distal end of the plunger 142 can be inserted through the through hole 114 of the first tube body 104 to directly or indirectly transmit a force applied to the plunger 142 to the plunger head 138 and the plunger seal 140 to advance the plunger head 138 and the plunger seal 140 toward the first opening 104A of the first tube body 104 in the first internal space 106 within the first container body 110 and to retract the plunger head 138 and the plunger seal 140 toward the second opening 104B of the first tube body 104 in the first internal space 106 defined by the first container body 110.

[0254] In the embodiment shown in S in which the first container 100 has a plunger head 138 and plunger seal 140 disposed in the first interior space 106, the third outer body portion 108C of the first container outer body 108 can define a through hole 114 through which the plunger 142 can pass to transmit force to the plunger head 138 and plunger seal 149 to move the plunger head 138 and plunger seal 140.

[0255] In the embodiment shown in Figures 2 and 3, in which the first container 100 does not have a plunger head 138 and plunger seal 140 disposed in the first internal space 106, the first container outer body 108 may include a surface that does not define a through hole 114 and seals the end of the first internal space 106 opposite the end of the first internal space 106 at which the first container side valve 126 is provided.

[0256] Referring to FIG. 4, a process for assembling the first container 100 may include placing a plunger head 138 having a plunger seal 140 attached thereto into the first container body 110 to form a seal with the inner surface of the first container body 110.

[0257] The process for assembling the first container 100 may include, after positioning the plunger head 138 and plunger seal 140 within the first container body 110, connecting the third outer body portion 108C to the second outer body portion 108B, for example by a press fit, adhesive, and / or threaded connection, to provide access to the plunger head 138 through the through hole 114 defined by the third outer body portion 108C.

[0258] The dose loading module 600 may further include a third container 602. The third container 602 may include a male luer 604 and a Tuohy-Borst adaptor 606 fluidly connected to the male luer 604.

[0259] The male luer 604 may include one portion of a threaded connection that removably connects the male luer 604 to another portion of a threaded connection on the exterior surface of the first valve housing 128, thereby providing a path for flow from the first interior space 106 to a Tuohy-Borst adapter 606. The Tuohy-Borst adapter 606 is configured to receive a distal end of a needle 608 of a dose delivery device.

[0260] The stand 506 can hold the plunger 142 of the plunger system 136 so that the distal end of the plunger 142 is guided into the through hole 114 of the first tube body 104 arranged on the stand 506 and contacts the plunger head 138 of the plunger system 136.

[0261] The dose loading module 600 may further include a delivery device 610. The delivery device 610 may be disposed on the stand 506 of the first container mixing module 500. As shown in Figs. 18 and 19, the delivery device 610 may apply a force to the plunger 142 of the plunger system 136 to advance the plunger head 138 and the plunger seal 140 toward the first container-side valve 126 to reduce the volume of the first internal space 106. The reduction in the volume of the first internal space 106 causes the flow of the dose in the first internal space 106 through the path formed by the connection between the first container-side valve 126 and the male luer 604 to load the dose or a portion of the dose into the dose delivery device through the distal end of the needle 608 disposed in the Tuohy-Borst adaptor 606.

[0262] The delivery device 610 may include a lead screw 612 and a delivery wheel 614. The delivery wheel 614 may be connected to the plunger 142. Furthermore, the delivery wheel 614 may be movably connected to the threads of the lead screw 612. Rotation of the delivery wheel 614 causes the delivery wheel 614 to move along the longitudinal axis of the lead screw 612, moving the plunger 142 to advance the plunger head 138 and the plunger seal 140 toward the first container-side valve 126, decreasing the volume of the first interior space 106. As described above, the decrease in the volume of the first interior space 106 causes the flow of the dose in the first interior space 106 through the path formed by the connection between the first container-side valve 126 and the male luer 604, thereby loading the dose or a portion of the dose into the dose delivery device through the distal end of the needle 608 disposed in the Tuohy-Borst adaptor 606.

[0263] The delivery device 610 may further include an actuator 616 and a controller 618. The controller 618 may control the actuator 616 to rotate the delivery wheel 614 to move the delivery wheel 614 along the longitudinal axis of the lead screw 612, thereby moving the plunger 142 to advance the plunger head 138 and the plunger seal 140 toward the first container-side valve 126 and reduce the volume of the first interior space 106. As described above, the reduction in the volume of the first interior space 106 causes the flow of the dose in the first interior space 106 through the path formed by the connection between the first container-side valve 126 and the male luer 604 to load the dose or a portion of the dose into the dose delivery device through the distal end of the needle 608 disposed in the Tuohy-Borst adaptor 606.

[0264] 20-25 show an example of a medical device system 10 (see FIG. 24) for performing dose preparation according to one embodiment. The medical device system 10 may include a first container 100 (also referred to as a dose preparation tube) and a second container 200 (also referred to as a irrigation tube) that is removably connected to the first container 100.

[0265] First container (dose producing tube) Next, the first container 100, which is an apparatus, will be described with reference to Fig. 20. The first container 100 may include a first container outer body 108. The first container outer body 108 may extend along a first tube body axis A between a first end of the first container outer body 108 and a second end of the first container outer body 108.

[0266] The first container outer body 108 may define a first interior space 106. The first interior space 106 may be connected to a first opening 104A at a first end of the first container outer body 108 and a second opening 104B at a second end of the first container outer body 108.

[0267] The volume of the first container outer body 108 is not particularly limited. For example, the volume of the first internal space 106 may be selected based on the target dose volume of the dose to be produced. For example, the volume of the first internal space 106 may be about 1.8 mL or 2.0 mL.

[0268] The material for forming the first container outer body 108 is not particularly limited. Examples of materials for forming the first container outer body 108 may include materials with low leachability and / or extractability, such as cyclic olefin polymers, cyclic olefin copolymers, perfluoroalkoxyalkanes, ethylene tetrafluoroethylene, cyclic block copolymers, polyethylene, polypropylene, and polycarbonate. The material for forming the first container may be selected based on the possible manufacturing method, such as injection molding.

[0269] The first container 100 may further include a first container valve 140 and a sheath 150 .

[0270] 20 and 21 , the sheath 150 may define a sheath interior space 152 into which at least a portion of the first container outer body 108 may be removably inserted. The sheath interior space 152 may be connected to a first opening 150A at a first end of the sheath 150 and a second opening 108B at a second end of the sheath 150. In some embodiments, the sheath provides or maximizes sterile conditions or means for protecting the contents of the first and / or second container from contamination.

[0271] In some embodiments, the sheath 150 comprises a sterilizable material. Non-limiting examples of sterilizable materials include polycarbonate, polystyrene, nylon, polyethylene, cyclic olefin copolymer, CoPC, and acrylic.

[0272] The first container side valve 140 may be connected to the sheath 150 at a first opening 150A of the sheath 150. In a configuration in which the first container outer body 108 is inserted into the sheath interior space 152, the first opening 108A of the first container outer body 108 communicates with the first container side valve 140.

[0273] The first container-side valve 140 may include a valve housing 142 connected to the sheath 150 at a first opening 150A of the sheath 150. The first container-side valve 140 may further include a seal 144 disposed within the valve housing 142. The seal 144 is configured to provide a normally closed position and an actuated position (see FIG. 24 ) of the first container-side valve 140. The structure of the seal 144 is not particularly limited. One example of the seal 144 is a self-sealing seal.

[0274] A seal 144 may be disposed within the valve housing 142 to control flow into the first interior space 106 through the first opening 150A of the sheath 150 and the first opening 108A of the first container outer body 108.

[0275] The seal 144 may have a normally closed position that relatively reduces or completely restricts flow through the seal 144. The normally closed position of the seal 144 may be the sealing position of a self-sealing seal.

[0276] The seal 144 can be actuated from a normally closed position to an actuated position. The actuated position of the seal 144 allows for a relatively increased flow into the first interior space 106 through the seal 144 and the first opening 150A of the sheath 150 and the first opening 108A of the first container outer body 108. For example, the seal 144 can be actuated from the normally closed position to the actuated position by deforming the self-sealing seal to provide a path for flow through the seal 144 (see FIG. 24 ). The seal 144 can also be actuated by a valve stem, which will be described below.

[0277] The seal 144 may be made of a resilient material such as rubber, silicone rubber, flexible plastic, or other elastomeric polymer.

[0278] The first container-side valve 140 may further include a valve cap 146 configured to be removably connected to the valve housing 142 to removably cover the seal 144 to prevent exposure or contact.

[0279] 20 to 22, the first container 100 may further include a sheath cap 160 that is detachably connected to the sheath 150. The sheath cap 160 may include a sheath cap body 162 that is detachably connected to the sheath 150. The sheath 150 and the sheath cap body 162 may have a connection mechanism. For example, a male thread structure may be provided on the outer surface of the sheath 150, and a female thread structure that receives the male thread structure to connect the sheath 150 to the sheath cap 160 may be provided on the sheath cap body 162.

[0280] The sheath cap 160 may further include a packing 164, which is a mechanical gasket having a circular cross section. The packing 164 may be seated in a groove inside the sheath cap body 162. When the sheath 150 is connected to the sheath cap 160, the packing 164 is compressed between the sheath 150 and the sheath cap body 162 to form a seal at the interface between the sheath 150 and the sheath cap body 162. In this way, when the sheath 150 is connected to the sheath cap 160, the first container outer body 108 is completely enclosed within the sheath interior space 152, and the first container outer body 108 may be prevented from being exposed to the environment.

[0281] The sheath cap 160 may further include a vent 166. The vent 166 (or valve) may be disposed within the first interior space 106 for releasing air dislodged from the first interior space 106, as described in detail below. The sheath cap 160 may further include a filter 168 that allows unidirectional air flow from the first interior space 106 to prevent exposure of the first container outer body 108 to the environment.

[0282] 20, the first container 100 may further include a plunger seal 170 disposed in the first interior space 106 of the first container outer body 108 so as to contact the inner surface of the first container outer body 108. For example, the plunger seal 170 may be inserted into the first interior space 106 from the second opening 108B of the first container outer body 108. The plunger seal 170 is configured to change the volume of the space in the first interior space 106 between the plunger seal 170 and the first container-side valve 140 when a force is applied to move the plunger seal 170 in the first interior space 106. As the plunger seal 170 moves toward the first container-side valve 140, the space in the first interior space 106 between the plunger seal 170 and the first container-side valve 140 decreases. As the plunger seal 170 moves away from the first container-side valve 140, the space in the first interior space 106 between the plunger seal 170 and the first container-side valve 140 increases. Additionally, as the plunger 170 moves away from the first container-side valve 140, air pushed out of the second opening 108B by the plunger 170 can be released through the vent 166 via the filter 168.

[0283] 20, the first container 100 may further include a movable body 400. The movable body 400 may be disposed in the space in the first internal space 106 between the plunger seal 170 and the first container-side valve 140. The movable body 400 may have the structure described above with reference to FIGS. 13A to 13D.

[0284] 20 and 25, the first container 100 may further include a plunger 172. The plunger 172 may be removably connected to the plunger seal 170. When the plunger 172 is connected to the plunger seal 170, the plunger 172 is configured to transmit a force to the plunger seal 170, thereby moving the plunger seal 170 within the first interior space 106 of the first container outer body 108.

[0285] 20 and 25, the first container 100 may further include a first container outer body flange 110. The first container outer body flange 110 may be removably attached to the first container outer body 108. The first container outer body flange 110 may be configured to support a user's finger or may be configured to fit a syringe pump. Pressure applied between the plunger 172 and the first container outer body flange 110 applies a force to the plunger seal 170, causing the plunger seal 170 to move within the first interior space 106 of the first container outer body 108.

[0286] Second container (washing tube) Next, the second container 200 will be described with reference to FIGS.

[0287] The second container 200 may include a second container outer body 202 , a second container stem 204 , and a second container cover 206 .

[0288] The second container outer body 202 may define a second interior space 204. The second interior space 204 may be connected to a first opening 202A at a first end of the second container outer body 202 and a second opening 202B at a second end of the second container outer body 202. The first opening 202A and the second opening 202B may be disposed along the second container outer body axis C.

[0289] The volume of the second container outer body 202 is not particularly limited. For example, the volume of the second internal space 204 may be selected based on the target dose volume of the dose to be produced. The volume of the second internal space 204 may be, for example, about 50 mL or about 300 mL.

[0290] The second container cover 208 may be provided to be removably connected to the second container outer body 202 to cover the first opening 202A of the second container 200. Further, the second container stem 206 may be provided to be connected to the second container outer body 202 at the second opening 202B of the second container outer body 202, or may be integrally formed with the second container outer body 202 to provide the second opening 202B of the second container outer body 202.

[0291] The inner surface of the second container outer body 202 that defines the second interior space 204 can have a portion having a conical shape. The conical shape can have a varying diameter that decreases along the second container outer body axis C in a direction from the first opening 202A of the second container outer body 202 toward the second opening 202B of the second container outer body 202. The conical shape of the second interior space 204 can help direct the flow of fluid toward the second container stem 206, as described below.

[0292] The materials for forming the second container outer body 202, the second container side stem 206, and the second container cover 208 are not particularly limited. Examples of materials for forming the second container outer body 202, the second container side stem 206, and the second container cover 208 may include materials with low leachability and / or extractability, such as cyclic olefin polymers, cyclic olefin copolymers, perfluoroalkoxyalkanes, ethylene tetrafluoroethylene, cyclic block copolymers, polyethylene, polypropylene, and polycarbonates. The materials for forming the second container outer body 202 may be selected based on possible manufacturing methods, such as injection molding.

[0293] With reference to FIG. 24, the system 10 may further include a connector 210 configured to removably connect the second container 200 to the first container 100 .

[0294] When the second container 200 is connected to the first container 100 via the connector 210, the second container stem 206 is positioned to actuate the first container valve 140 from the normally closed position to an actuated position, relatively increasing flow through the seal 144 by communication between the second interior space 204 and the first interior space 106. For example, as shown in FIG. 24, the second container stem 206 is positioned by the connector 210 to urge the seal 144 of the first container valve 140 from the normally closed position to an actuated position, thereby communicating between the first interior space 106 of the first container outer body 108 and the second interior space 204 of the second container 200.

[0295] Process for preparing cell solutions for delivery A process for preparing a cell solution for delivery will be described with reference to Figures 24 and 25. The process may include a series of steps including the construction of a first container 100 as shown from left to right in Figure 25.

[0296] The process for preparing a cell solution for delivery may include preparing a first container 100 as shown in FIG. 25. The first container 100 may be in an assembled state in which the first container outer body 108 is at least partially disposed in the sheath inner space 152, the first container valve 140 is attached to the first opening 108A of the first container outer body 108, the valve cap 146 is connected to the first container valve 140, and the sheath cap 160 is connected to the sheath 150. The first container 100 may be pre-filled with a cell delivery solution. In this assembled state, contamination of the first container outer body 108, particularly the first inner space 106, may be minimized. Furthermore, the first container may be transported in this assembled state to a location for preparing a cell solution for delivery.

[0297] The process for preparing the cell solution for delivery may then proceed to connecting the second container 200 to the first container as shown in Figure 24. In this step, the valve cap 146 may be separated from the valve housing 142 to expose the seal 144 of the first container valve 140. Furthermore, the second container 200 may be connected to the first container 100 via an intermediate structure such that the second container stem 206 contacts the seal 144 to bias the seal 144 from the normally closed position to the actuated position, thereby relatively increasing the flow through the seal 144 due to communication between the second interior space 204 and the first interior space 106.

[0298] The process for preparing the cell solution for delivery may then proceed with introducing or providing a mixture of the wash solution, cells, and cryoprotectant into the second interior space 204 of the second container 200. The mixture may be introduced or provided directly into the second interior space 204 or may be introduced through one or more openings in the second container cover 208.

[0299] The process for preparing the cell solution for delivery may then proceed to a step of applying centrifugal force to the connected first container 100 and second container 200. This step may include loading the connected first container 100 and second container 200 into a centrifuge in an orientation such that, during the spinning motion of the centrifuge along the spin axis, at least a portion of the cells in the second container 200 move radially outwardly of the spin axis from the second interior space 204 of the second container 200 through the second container stem 206 and the seal 144 of the first container valve 140 that has been actuated by the container stem 206 from a normally closed position to an actuated position, into the first interior space 106 of the first container 100. The portion of the cells that move from the second container 200 to the first interior space 106 of the first container 100 by centrifugation becomes part of the cell solution for delivery prepared and disposed in the first interior space 106 of the first container 100. As the cells move from the second container 200 to the first internal space 106, the plunger 170 moves away from the first container side valve 140, allowing air pushed out of the second opening 108B by the plunger 170 to be released through the vent 166 via the filter 168.

[0300] The process for preparing the cell solution for delivery may then proceed to the steps of removing the first container 100 and the second container 200 from the centrifuge, disconnecting the second container 200 from the first container 100, and connecting the valve cap 146 to the valve housing 142 to cover the seal 144 to prevent contamination of the cell solution for delivery brought to the first interior space 106 through the first container side valve 140.

[0301] Additionally, a mixer that may be optionally provided in the first interior space 106 of the first container 100 may be operated in the manner described above to mix the contents of the first container (e.g., a cell delivery solution or a cell solution for delivery).

[0302] The process for preparing the cell solution for delivery may then proceed with the step of separating the sheath cap 160 from the sheath 150 as shown in FIG.

[0303] The process for preparing the cell solution for delivery may then proceed to the step of connecting the plunger 172 to the plunger seal 170 and connecting the first container outer body flange 110 to the first container outer body 108, as shown in FIG. 25.

[0304] The process for preparing the cell solution for delivery may then proceed with the step of withdrawing the first container outer body 108 from the sheath interior space 152 of the sheath 150. As the first container outer body 108 is withdrawn from the sheath interior space 152 of the sheath 150, the first container outer body 108 is decoupled from the first container side valve 140, as shown in Figure 25. This step may be performed in a clean (e.g., sterile) environment to minimize contamination of the cell solution for delivery through the first opening 108A of the first container outer body 108.

[0305] At any time after at least a portion of the cells have been moved into the first interior space 106 of the first container 100 by centrifugal force, a step can be performed in which the movable body 400 is moved within the first interior space 106 to mix the cell solution for delivery and to uniformly distribute the cells. This step can be repeated as necessary.

[0306] Upon completion of the above steps, the cell solution for delivery is prepared and loaded into the first interior space 106 of the first container 100. The cell solution for delivery can then be delivered to a subject. For example, the first container 100 can be held by hand or mounted in a syringe pump. Then, by applying pressure between the plunger 172 and the first container outer body flange 110, a force is applied to the plunger seal 170, causing the plunger seal 170 to move within the interior space 106 and expel the cell solution for delivery from the interior space 106 through the first opening 108A. The expelled cell solution for delivery can be delivered to a subject through a needle directly or indirectly connected to the first opening 108A of the first container 100.

[0307] In some embodiments, the devices disclosed herein have some or all of the features shown in FIGS. 20-24, and optionally FIG.

[0308] 26 shows an example of a medical device system 1000 for performing dose preparation according to one embodiment. The medical device system 1000 may include a first container 2000 (also referred to as a dose preparation tube) and a second container 3000 (also referred to as a irrigation tube) that is removably connected to the first container 2000.

[0309] First container (dose producing tube) Next, the first container 2000, which is an apparatus, will be described with reference to Figures 27 and 28. The first container 2000 may include a first container tube 2020, a sheath 2040, and a holding structure 2060.

[0310] The first container pipe 2020 may include a first container pipe body 2022 and a first container-side valve 2024 attached to the first container body 2022. The first container-side valve 2024 and the first container body 2022 define a first interior space 2026 extending in a longitudinal axis of the first container pipe 2020. The first container-side valve 2024 may include a first container-side valve body 2028 attached to the first container body 2022 and a first container-side valve seal 2030 disposed within the first container-side valve body 2028. The first container-side valve body 2028 defines a first opening of the first container 2000 that communicates with the first interior space 2026.

[0311] The first container-side valve seal 2030 is configured to be in a normally closed position that relatively reduces flow through the first container-side valve 2024 into the first interior space 2026. For example, in the normally closed position, the first container-side valve seal 2030 can block or block flow through the first opening of the first container 2000 into the first interior space 2026. The first container-side valve seal 2030 is further configured to actuate from the normally closed position to an actuated position that relatively increases flow through the first opening of the first container 2000 into the first interior space 2026 when the first container 2000 is connected to the second container 3000. The actuation of the first container-side valve 2024 is described in more detail below.

[0312] Although the first container-side valve 2024 has been described as including a valve body and a valve seal, the first container-side valve 2024 may include other structures that restrict flow into the first interior space 2026 and that are actuated upon connection of the first container 2000 and the second container 3000. For example, the first container-side valve 2024 may include a valve body and a membrane (or barrier) that blocks flow into the first interior space 2026, and be actuated by piercing the membrane to allow flow into the first interior space 2026.

[0313] The first container 2000 may also include a moveable body, such as the moveable body shown in Figures 13A-13D.

[0314] Returning to FIG. 27, the sheath 2040 and retention structure 2060 will now be described in detail.

[0315] The sheath 2040 can include a sheath body 2042 that defines an interior space and an opening to the interior space. The interior space of the sheath body 2042 can be dimensioned to receive the first container tube 2020.

[0316] The retaining structure 2060 can be attached to the sheath body 2042 to retain the first container tube 2020 within the internal space of the sheath body 2042. The retaining structure 2060 can be a collar provided at an opening leading to the internal space of the sheath body 2042, as shown in FIG. 27. The collar can include a flexible tapered structure that narrows as the collar extends from the opening of the sheath body 2042 toward the internal space of the sheath body 2042 along the longitudinal axis of the first container 2000. When the first container tube 2020 passes through the opening of the sheath body 2042 and moves toward the internal space of the sheath body 2042, the first container tube 2020 flexibly expands the collar in a radial direction of the longitudinal axis of the first container 2000, allowing the first container tube 2020 to move into and be positioned within the internal space of the sheath body 2042. With the first container tube 2020 disposed within the interior space of the sheath body 2042, the collar returns to its tapered shape to retain the first container tube 2020 within the interior space of the sheath body 2042. For example, the tapered collar abuts the first container tube 2020 and prevents movement of the first container tube 2020 along the longitudinal axis of the first container 2000 from the interior space of the sheath body 2042 toward the opening of the sheath body 2042.

[0317] The retention structure 2060 is not limited to the collar shown in FIG 27. For example, the retention structure 2060 may include a retention cap as shown in FIG 29. The retention cap can be removably attached to the sheath body 2042 to enclose the first container tube 2020 within the interior space of the sheath body 2042. In FIG 29, the retention cap and sheath body 2042 are shown as being removably attached by a bayonet connection.

[0318] Additionally, the sheath 2040 can include a sheath body connection mechanism 2044 configured to connect the first container 2000 to the second container 3000, as described in detail below. As an example, the sheath body connection mechanism 2044 can include one of male or female threads that connect to corresponding female or male threads provided on the second container 3000.

[0319] Second container (washing tube) Next, the second container 3000 which is an apparatus will be described with reference to FIG.

[0320] The second container 3000 may include a second container outer body 3002 extending along a longitudinal axis of the second container 3000. The second container outer body 3002 defines a second interior space 3004 having a first opening 3004A and a second opening 3004B at opposite ends of the second interior space 3004 along the longitudinal axis.

[0321] The volume of the second container outer body 202 is not particularly limited. For example, the volume of the second interior space 204 may be selected based on the target dose volume of the dose to be produced.

[0322] There is no particular limitation on the material forming the second container outer body 202, the second container side stem 206, and the second container cover 208. Examples of materials for forming the second container outer body 202, the second container side stem 206, and the second container cover 208 include resins such as polypropylene and polycarbonate.

[0323] The second container 3000 may include a second container stem 3006 at the second opening 3004B.

[0324] The second container 3000 may include a second container cover 3008 configured to be removably connected to the second container outer body 3002 so as to cover the first opening 3004A of the second container outer body 3002.

[0325] The second container cover 3008 may define one or more openings for accessing the second interior space 3004. For example, the second container cover 3008 may define a first opening through which a mixture of washing solution, cells, and cytoprotectant may be provided to the second interior space 3004. The second container cover 3008 may further define a second opening through which air displaced by the mixture of washing solution, cells, and cryoprotectant may escape from the second interior space 3004. Additionally, the second opening may provide access to sample the mixture provided to the second interior space 3004 and adjust the volume and / or concentration of the mixture provided to the second interior space 3004.

[0326] The inner surface of the second container outer body 3002 that defines the second interior space 3004 can have a portion having a conical shape. The conical shape can have a varying diameter that decreases along the longitudinal axis of the second container 3000 in a direction from the first opening 3004A of the second container outer body 3002 toward the second opening 3004B of the second container outer body 3002. The conical shape of the second interior space 3004 can help direct the flow of fluid toward the second container stem 3006, as described below.

[0327] The second container 3000 may further include a second container connection mechanism 3010 configured to connect the second container 3000 to the first container 2000. In one example, the second container connection mechanism 3010 may include a tubular extension extending from the second container outer body 3002 away from the second container stem 3006. An inner surface of the tubular extension may be provided with corresponding female or male threads that threadably mate with the male or female threads of the sheath body connection mechanism 2044 to connect the second container 3000 to the first container 2000.

[0328] Although a threaded connection has been described for connecting the first container 2000 and the second container 3000, other types of connections can be provided. For example, a ratchet connection can be provided that allows the first container 2000 to be pushed towards the container 3000 in a stepwise manner.

[0329] 31 shows two connection positions of the first container 2000 and the second container 3000. In the first connection position, the first container 2000 is connected to the second container 3000 by the sheath body connection mechanism 2044 and the second container connection mechanism 3010, for example by rotating the first container 2000 relative to the second container 3000 so that the first container side valve seal 2030 abuts the second container side stem 3006. Positioning the first container side valve seal 2030 to abut the second container side stem 3006 can reduce or prevent flow from the second interior space 3004 through the second container side stem 3006.

[0330] In the second connection position, the first container 2000 is connected to the second container 3000 by the sheath body connection mechanism 2044 and the second container connection mechanism 3010, for example by further rotating the first container 2000 relative to the second container 3000, such that the second container stem 3006 moves past its position in the first connection position and actuates the first container valve 2024 from a normally closed position to an actuated position by penetrating the first container valve seal 2030. In the second connection position, the second interior space 3004 of the second container 3000 communicates with the first interior space 2026 of the first container 2000, allowing flow from the second interior space 3004 to the first interior space via the second container stem 3006.

[0331] In some embodiments, the devices disclosed herein have some or all of the features shown in Figures 26-34 with an optional magnetic system for moving the mixer that is manually operated or automatically operated by an attached device.

[0332] Sheath Cap 32, the medical device system 1000 may include a sheath cap 2046. The sheath cap 2046 may be removably connected to the sheath 2040 to enclose the first container tube 2020 within the interior space of the sheath 2040. In one example, the sheath cap 2046 may be provided with corresponding female or male threads that connect the sheath cap 2046 to the male or female threads of the sheath body connection mechanism 2044 of the sheath 2040. The sheath cap 2046 may be connected to the sheath 2040 to isolate the first container tube 2020 from the outside environment.

[0333] Loading Adapter 33 and 34 , the medical instrument system 1000 can include a loading adapter 4000. The loading adapter 4000 can include a loading adapter body 4002 defining a guide space 4004, which can extend along a longitudinal axis of the loading adapter body 4002. Additionally, the loading adapter 4000 can include a loading adapter connector 4006.

[0334] In one example, the loading adapter connector 4006 can be provided at one end of the loading adapter body 4002 along a longitudinal axis of the loading adapter body 4002. The loading adapter connector 4006 can be configured to removably connect to the first container tube 2020 and to separate the first container tube 2020 from the sheath 2040.

[0335] In one example, the loading adapter connector 4006 can include a connection mechanism, such as male or female threads, that can be removably connected to corresponding female or male threads on the exterior surface of the first container side valve body 2028. Additionally, the loading adapter connector 4006 can include one or more fingers. In operation, the longitudinal axis of the loading adapter body 4002 is aligned with the longitudinal axis of the sheath body 2042. The loading adapter connector 4006 is then placed within the collar, flexibly expanding the collar radially of the longitudinal axis of the first container 2000. The loading adapter 4000 is then rotated along its longitudinal axis to thread the male or female threads of the loading adapter connector 4006 into the corresponding female or male threads of the first container side valve body 2028 to connect the loading adapter 4000 to the first container tube 2020. The loading adapter 4000 is then separated from the sheath 2040 while still spreading the collar radially about the longitudinal axis of the first container 2000 to facilitate withdrawal of the first container tube 2020 from the interior space of the sheath body 2042.

[0336] 34, in an arrangement in which the loading adapter 4000 is connected to the first container tube 2020, the guide space 4004 of the loading adapter 4000 can guide the distal end of the device to the first container-side valve 2024 to facilitate the transfer of the dose created in the first internal space 2026 to the device. The distal end of the device may include a needle or pipette tip. The guide space 4004 can help protect the needle from damage as it approaches the first container 2000. Additionally, the guide space 4004 can help to more precisely guide the needle toward a designated point on the first container-side valve seal 2030.

[0337] Process for preparing a cell solution for delivery The process for preparing a cell solution for delivery will now be described with reference to Figures 26-34.

[0338] A process for preparing a cell solution for delivery may include providing a first container 2000 as shown in Figure 28 held by a collar within a sheath 2040 as shown in Figure 27. The first container 2000 may be pre-filled with the cell delivery solution.

[0339] The process for preparing the cell solution for delivery may further include connecting the first container 2000 to the second container 3000 such that the first container valve seal 2030 abuts the second container stem 3006 in the first connection position shown in Figure 31. Positioning the first container valve seal 2030 abuts the second container stem 3006 may reduce or prevent flow from the second interior space 3004 through the second container stem 3006.

[0340] The process for preparing the cell solution for delivery may then further include introducing or providing a mixture of the washing solution, cells, and cryoprotectant into the second interior space 3004 of the second container 3000.

[0341] The process for preparing the cell solution for delivery may further include placing the first container 2000 and the second container 3000 in the second connection position shown in Fig. 31 by, for example, rotating the first container 2000 relative to the second container 3000 such that the second container stem 3006 moves past its position in the first connection position and actuates the first container valve 2024 from a normally closed position to an actuated position by penetrating the first container valve seal 2030. In the second connection position, the second interior space 3004 of the second container 3000 communicates with the first interior space 2026 of the first container 2000, allowing flow from the second interior space 3004 to the first interior space 2026 via the second container stem 3006.

[0342] The process for preparing the cell solution for delivery may further include applying a centrifugal force to the connected first and second containers 2000 and 3000. This may include loading the connected first and second containers 2000 and 3000 into a centrifuge in an orientation such that upon spinning of the centrifuge along the spin axis, at least a portion of the cells in the second container 3000 move radially outwardly of the spin axis from the second interior space 3004 of the second container 3000 through the second container stem 3006 and the seal 2030 of the first container valve 2024 actuated by the second container stem 3006 to the first interior space 2026 of the first container 2000. A portion of the cells moved from the second container 3000 to the first internal space 2026 of the first container 2000 by centrifugation become part of the cell solution for delivery that is created and placed in the first internal space 2026 of the first container 2000.

[0343] The process for preparing the cell solution for delivery may further include the steps of disconnecting the first container 2000 from the second container 3000 and connecting the sheath cap 2046 to the sheath 2040 to enclose the first container tube 2020 within the interior space of the sheath 2040. In this state, the first container tube 2020 containing the cell solution for delivery may be stored for later use or transportation. Additionally, a mixer that may be optionally provided in the first interior space 2026 of the first container 2000 may be operated in the manner described above to mix the cell solution for delivery.

[0344] The process for preparing the cell solution for delivery may further include the steps of disconnecting the sheath cap 2046 from the sheath 2040 and withdrawing the first container tube 2020 from the interior space of the sheath body 2042 using the loading adapter 4000.

[0345] The process for preparing the cell solution for delivery may further include guiding a needle or pipette through the guide space 4004 of the loading adapter 4000 to penetrate the first container side valve seal 2030, thereby allowing a portion of the cell solution for delivery to be drawn into the needle or pipette.

[0346] The terms used herein are for the purpose of describing particular embodiments only and are not intended to be limiting of the present invention. As used herein, the singular forms "a," "an," and "the" are intended to include the plural forms unless otherwise clear from the context. It will be further understood that the terms "comprises" and / or "comprising," as used herein, specify the presence of stated features, integers, steps, operations, elements, and / or components, but do not exclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and / or groups thereof.

[0347] Where there are elements described as means-plus-functions or step-plus-functions in the following claims, the corresponding structures, materials, acts, and equivalents of all elements described as means-plus-functions or step-plus-functions are intended to include any structures, materials, or acts that perform the function in combination with other claimed elements as specifically recited in the claims. The description of the present invention has been presented for purposes of illustration and description and is not intended to be exhaustive or to limit the invention to the disclosed form. Numerous modifications and variations will be apparent to those skilled in the art without departing from the scope and spirit of the invention. The embodiments have been selected and described to best explain the principles and practical applications of the invention and to enable those skilled in the art to understand the invention in various embodiments with various modifications suitable for the particular use envisaged. [Explanation of symbols]

[0348] 10 Medical device system, 100 First container, 104 First tube body, 104A First opening, 104B Second opening, 106 First internal space, 108 First container outer body, 108A First outer body part, 108A1 First clamping surface, 108B Second outer body part, 108B1 Second clamping surface, 108C Third outer body part, 110 First container body, 112 First part (of connection mechanism), 114 Through hole, 116 Cover, 118 First part (of connection mechanism), 120 Second part (of connection mechanism), 124 First flow path control module, 126 First container side valve, 128 First valve housing, 128A First valve housing flange, 130 First valve housing internal space, 132 First seal, 136 Plunger system, 138 Plunger head, 140 Plunger seal, 142 Plunger, 144 Seal, 146 Valve cap, 149 Plunger seal, 150 Sheath, 150A First opening, 152 Sheath interior space, 160 Sheath cap, 162 Sheath cap body, 164 Packing, 166 Vent, 168 Filter, 170 Plunger seal, 172 Plunger, 174 Magnet, 200 Second container, 202 Second container outer body, 202A First opening, 202B Second opening, 204 Second tube body, 204A First end, 204B Second end, 206 Second interior space, 208 Second container outer body, 208A First section, 208B Second section, 208C Third section, 210 Second container body, 210A, first opening, 212, container body interior space, 212A, first opening, 212B, second opening, 212C, first part, 212D, second part, 212E, third part, 220, second container side valve, 222, valve cap, 222A, cylinder, 222B, mounting surface, 224, valve stem, 224A, first part, 224B, second part, 226, second seal, 230, cover, 232, second flow path control module, 300, second container loading module, 302, flow regulator, 304, adapter, 308, cell vial, 400, movable body, 402, movable body housing, 402A, first end, 402B, second end, 404, magnet, 406, groove, 408, inner cylinder, 410, outer cylinder, 412Blade, 414 Inner disc, 416 Outer ring, 418 Inner ring, 420 Connector, 422 Connector, 500 First container mixing module, 502 External magnet, 504 Movement guide, 506 Stand, 508 Actuator, 510 Controller, 600 Dose loading module, 602 Third container, 604 Male luer, 606 Tuohy-Borst adapter, 608 Needle, 610 Delivery device, 1000 Medical device system, 2000 First container, 2020 First container tube, 2022 First container tube body, 2024 First container side valve, 2026 First interior space, 2028 First container side valve body, 2030 First container side valve seal, 2040 Sheath, 2042 Sheath body, 2044 Sheath body connection mechanism, 2046 Sheath cap, 2060, retention structure, 3000, second container, 3002, second container outer body, 3004, second internal space, 3004A, first opening, 3004B, second opening, 3006, second container side stem, 3008, second container cover, 3010, second container connection mechanism, 4000, loading adapter, 4002, loading adapter body, 4004, guide space, 4006, loading adapter connector, A, tube body axis, B, length axis, C, second tube body axis

Claims

1. 1. A system for performing dose creation, comprising: a first container comprising a first container tube, a sheath, and a retention structure for retaining the first container tube within the sheath, the first container comprises a first container pipe body and a first container valve defining a first interior space, the first container valve defining a first opening communicating with the first interior space of the first container, the first container valve comprising a first container valve seal configured to be actuated from a normally closed position that relatively reduces flow through the first opening of the first container into the first interior space to an actuated position that relatively increases flow through the first opening of the first container into the first interior space; the sheath includes a sheath body and a sheath body connection mechanism, the sheath body defining a sheath interior space configured to contain at least a portion of the first container tube; the retention structure is attachable to the sheath body and releasably retains the first container tube at least partially within the sheath interior space of the sheath body. a first container; a second container comprising a second container outer body, a second container stem, and a second container connection mechanism; the second container outer body defining a second interior space, the second interior space having a first opening at a first end of the second interior space; the second container stem is fluidly connected to the second container outer body and includes the first opening at the first end of the second interior space; the second container connection mechanism is configured to removably connect the second container to the first container; a second container; and Equipped with the second container connection mechanism is configured to interact with the sheath body connection mechanism to connect the first container to the second container; the first container is movable relative to the second container between a first connected position in which the first interior space is not in flow communication with the first opening in the second container stem and a second connected position in which the second container stem actuates the first container-side valve from the normally closed position to the actuated position.

2. The second internal space extends along the longitudinal direction, a width of the second interior space along the longitudinal direction decreasing toward a first end of the second interior space; The system of claim 1 , wherein the second vessel stem is fluidly connected to the first end of the second interior space and extends along the longitudinal direction.

3. The system of claim 1 , wherein the second container stem is connected to the second container outer body so as to be immovable relative to the second interior space.

4. 2. The system of claim 1, wherein the first container further comprises a sheath cap configured to be removably connected to the second end of the sheath, the first container tube being enclosed within the sheath by the sheath cap.

5. a movable body disposed within the first interior space of the first container tube; The system of claim 1 , wherein the movable body is configured to move within the first interior space.

6. The system of claim 5 , wherein the movable body is configured to move within the first interior space by a magnetic force acting from outside the first container.

7. The system of claim 1 , wherein the first container is configured to be removably connected to the second container.

8. The system of claim 1 , wherein in the first connected position, the second container stem is configured to abut the first container valve seal.

9. The system of claim 1 , wherein the first container moves relative to the second container through interaction of the sheath body connection mechanism and the second container connection mechanism.

10. The system of claim 1 , wherein the second container connection mechanism and the sheath body connection mechanism comprise mating threads configured to facilitate rotation of the first container relative to the second container.

11. The system of claim 1 , wherein the second container connection mechanism comprises a tubular extension extending from the second container outer body.

12. the retaining structure includes a collar provided at the sheath opening and inserted into the sheath interior space; the collar has a flexible tapered structure that narrows along a longitudinal axis of the first container away from the sheath opening toward the sheath interior space; 2. The system of claim 1, wherein the collar is configured to flex radially and abut the first container tube to prevent movement of the first container tube out of the sheath interior space.

13. 10. The system of claim 1, wherein the second container further comprises a second container cover connected to the second container outer body and configured to cover a second opening of the second container outer body.

14. The second container cover comprises: providing a mixture into the second interior space; Releasing air from the second interior space; accessing the second interior space to sample the mixture provided therein; adjusting the volume and / or concentration of the mixture supplied to the second internal space; 14. The system of claim 13, comprising a plurality of openings for providing at least one of the group consisting of:

15. a loading adapter comprising a loading adapter body and a loading adapter connector at one end of the loading adapter body; The system of claim 1 , wherein the loading adapter connector is configured to removably connect to the first container tube and to separate the first container tube from the sheath.

16. 1. A process for preparing a dose mixture for delivery, comprising: Providing a first container and a second container, the first container comprises a first container tube, a sheath, and a retaining structure, the first container tube comprises a first container tube body and a first container-side valve defining a first interior space, the first container-side valve defining a first opening of the first container and having a first container-side valve seal configured to operate between a closed position and an actuated position; the sheath includes a sheath body and a sheath body connecting mechanism, the sheath body configured to contain at least a portion of the first container tube, the retaining structure attached to the sheath body and at least partially retaining the first container tube within an interior space of the sheath; the second container comprises a second container outer body, a second container stem, and a second container connection mechanism, the second container outer body having a first opening at a first end of a second interior space, the second container stem connected to the second container outer body and including the first opening at the first end of the second interior space, and the second container connection mechanism configured to removably connect the second container to the first container; Steps and - loading the mixture containing a plurality of parts and a cleaning solution into the second interior space; A process comprising:

17. connecting the second container to the first container; in response to connecting the second container to the first container, the second container stem actuating the first container-side valve from the normally closed position to the actuated position; 17. The process of claim 16, further comprising:

18. 17. The process of claim 16, wherein the first container and the second container are provided in an interconnected state, and in the interconnected state, the second container connection mechanism is connected to the sheath body connection mechanism, thereby attaching the first container to the second container and the second container stem abutting the first container-side valve seal to prevent flow into the interior of the first container through the second container stem.

19. The process comprises:

17. The process of claim 16, comprising actuating a second vessel from the closed position, which relatively reduces flow through the first opening of the second vessel, to the actuated position, which relatively increases flow from the second interior space through the first opening of the second vessel, placing the second interior space in communication with the first interior space.

20. 17. The process of claim 16, further comprising the step of applying centrifugal force to the first container and the second container after connecting the internal space of the second container with the first internal space to move a plurality of cells from the second internal space to the first internal space.

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