Cell suspension supply device

Abstract

The present invention relates to a device for supplying a cell suspension to an instrument for processing cells, the device comprising at least one interior space 16 for holding the suspension, the interior space 16 being at least partially surrounded by a wall 15. The device further comprises at least one inlet port 2 having at least one first opening 3 for introducing the suspension into the interior space 16, and at least one outlet port having at least one second opening for removing the suspension from the interior space 16. The inlet port 2 further comprises at least one barrier element 6 bordering the first opening 3 on the side furthest from the wall 15 and partially disposed between the first opening 3 and the interior space 16.

Description

[Technical Field]

[0001] The present invention relates to an apparatus for supplying a cell suspension to an instrument for processing cells, the apparatus comprising at least one interior space for holding the suspension, the interior space being at least partially surrounded by a wall, the apparatus further comprising at least one inlet port having at least one first opening for introducing the suspension into the interior space, and at least one outlet port having at least one second opening for removing the suspension from the interior space. [Background technology]

[0002] US 2019 / 0169572 A1 discloses a cell therapy product manufacturing system including an automated bioreactor and electroporation unit, in which cell culture flows from the bioreactor to the electroporation unit and back again. The system also includes several disposable consumables, such as a cell engineering cassette, an electroporation cartridge, two electroporation reservoirs, and two connecting tubing sets. The electroporation reservoirs include weldable inlet and outlet tubing with Luer-lock connection ends, a cell inlet port in the reservoir housing connected to an external inlet reservoir tubing for sterile cell transfer to the reservoir, an additional port for Luer-lock substrates on the reservoir inlet tubing, and a vent filter on the cap for air release during volume transfer. However, because the cell inlet port for each reservoir is located in a central position in the reservoir housing, the cell suspension falls from a relatively high height into the reservoir's interior space, resulting in each droplet colliding with the surface of the reservoir housing and / or liquid already present in the reservoir. As a result, the cells are subjected to significant stress when transferred to the reservoir, reducing their viability. Summary of the Invention

[0003] An object of the present invention is to provide an apparatus for supplying a cell suspension to a cell processing device, which allows for gentle and highly conservative supply of cells, thereby increasing cell viability.

[0004] This object is achieved by the device described above, further comprising at least one barrier element in the inlet port, the barrier element being adjacent to the first opening on the side furthest from the wall and partially disposed between the first opening and the internal space. The barrier element is thus positioned so that the cell suspension introduced into the internal space flows gently along the inner surface of the wall, thereby preventing the suspension from falling from the first opening into the internal space and colliding with any surface. When the cell suspension is introduced into the inlet port, the barrier element deflects the suspension toward the wall, slowing its flow and allowing the suspension to flow slowly along the wall from the first opening into the internal space. As a result, the cells are not exposed to mechanical stress, significantly improving cell yield. Furthermore, unpredictable cell loss is avoided, thereby improving the reproducibility of test results and product yield.

[0005] In an advantageous embodiment of the present invention, the wall includes at least one recess, and the barrier element and the recess together form a cavity that flows into the internal space. The barrier element and the recess are therefore arranged and designed so that a cell suspension introduced into the inlet port is deflected by the barrier element toward the recess, slowing its flow. In this way, the suspension accumulates in the cavity and flows slowly from the cavity along the wall into the internal space. This further reduces the exposure of cells to mechanical stress.

[0006] In a further advantageous embodiment of the invention, the inlet port is arranged in an area close to the wall and the recess is arranged in an area close to the first opening. Such an arrangement reduces the distance between the first opening and the recess and between the first opening and the wall, thereby further reducing the exposure of the cells to mechanical stress. This particular arrangement makes the device according to the invention easier to manufacture.

[0007] In another advantageous embodiment of the invention, the inlet port further comprises a tubular channel arranged between the first opening and at least one third opening designed to be connectable to at least one first hose. In a further advantageous embodiment of the invention, the outlet port further comprises a tubular channel arranged between the second opening and at least one fourth opening designed to be connectable to at least one second hose. Thus, the device according to the invention can be easily connected to containers / reservoirs and / or other devices of a cell processing / engineering system. For example, the tubular channels of the inlet port and / or outlet port can be designed as male fittings with a Luer taper connection, thereby standardizing the connection of the device with other parts of a cell processing / engineering system.

[0008] In this way, the device according to the invention can be used as a reservoir for a cell suspension and optionally substrates such as DNA, RNA, proteins or other biologically active molecules, from which the cells and optionally substrates can be delivered to a cell processing / engineering system, such as a large volume cell transfection instrument.

[0009] The inlet port may be part of a cap-like element designed to cover the interior space. The cap-like element may be (reversibly) attached to the wall surrounding the interior space, e.g., by a snap-action connection. Alternatively or additionally, the cap-like element may be (irreversibly) attached to the wall surrounding the interior space, e.g., by an adhesive bond or a welded connection. The cap-like element may also be part of the wall, i.e., the cap-like element and the wall are molded as one part / piece. Furthermore, the cap-like element may comprise at least a portion of the wall surrounding the interior space of the device according to the invention.

[0010] In an advantageous embodiment of the invention, the cap-like element may comprise at least one retainer for holding at least one magnetic element (for example a stirring bar).

[0011] In a further advantageous embodiment of the invention, the transition area between the wall and the outlet port is uniformly formed, which allows the cell suspension to be completely removed from the interior space with almost no residue, thus minimizing the loss of treated cells.

[0012] The walls and / or the internal space can have any kind of shape / form. For example, the walls and / or the internal space can have a spherical, cubic, cylindrical or prismatic shape, or a box-like or rectangular block shape. Preferably, the internal space is elongated and vertically or at least inclined, with the inlet and outlet ports located at both ends of the internal space. For example, the device according to the present invention may be configured with an elongated tube including an inlet port at one distal end of the tube and an outlet port at the other distal end of the tube. In a preferred embodiment of the present invention, the cell suspension is forced by gravity from the inlet port to the bottom of the internal space and / or the outlet port.

[0013] In an advantageous embodiment of the invention, the outlet port is located at the center point of the bottom of the interior space. The outlet port may also be located at the deepest point of the interior space, preferably with a steep drop in the bottom. These measures allow the cell suspension to be removed without residue, minimizing the loss of valuable cells.

[0014] The device according to the present invention is essentially specially optimized for maximum content recovery, meaning that even very small volumes of cell suspension, less than 1 ml, can be filled into the internal space of the device and then completely removed from it, a complete cell removal that cannot be achieved using conventional reservoirs such as bags.

[0015] The walls of the device according to the invention may be made of a synthetic material such as medical grade polycarbonate (Makrolon 2458), which in a preferred embodiment may be coated (at least on the inner surface of the wall) and / or essentially modified to obtain certain beneficial properties, such as hydrophobic properties that allow even small volumes of cell suspension (e.g., less than 1 ml) to be completely removed from the interior space of the device.

[0016] In a further advantageous embodiment of the present invention, the bottom area of ​​the internal space has a flat, circular area for receiving and guiding a magnetic element (e.g., a stirring rod). This allows the cell suspension to be thoroughly stirred during processing, ensuring smooth and consistent movement of the magnetic element. This avoids uneven mixing of the cells and the generation of turbulence in the suspension, further reducing the exposure of the cells to mechanical stress.

[0017] The device according to the present invention may further comprise at least one vent port having at least one fifth opening for balancing pressure within the interior space. The vent port may comprise a vent valve and / or a filter element, such as a sterile membrane filter, to avoid contamination of the cell suspension within the interior space.

[0018] In a further advantageous embodiment of the invention, the device according to the invention, preferably when held by a support device as described below, comprises at least one recess and / or protrusion on at least the outer surface of the wall and / or cap-like element for fixing the position of the device.

[0019] Furthermore, a support device for holding the device according to the present invention is provided, which is composed of at least one base element for holding the device and at least one attachment element, the attachment element having magnetic means for holding at least one magnetic element housed in the device. The attachment element preferably functions as a kind of trap for the magnetic element used to stir the cell suspension or biological / chemical solution within the interior space of the device according to the present invention. When the device containing the magnetic element is fixed to the support device so as to be guided along the magnetic means, the magnetic element is held by the magnetic means and fixed to the wall of the device, thereby keeping it away from the outlet port of the device. This feature ensures residue-free removal of the suspension / solution, which would otherwise hinder removal of the suspension or solution from the device, further reducing the loss of valuable material.

[0020] The magnetic means may be an integral part of the support device, or may be a separate member that can be attached (reversibly or irreversibly) to the support device.

[0021] The mounting element may further comprise at least one protrusion or recess for securing the device, where the protrusion and / or recess of the mounting element correspond to the recess and / or protrusion of the wall and / or cap-like element of the device, respectively, so that the device can be easily and reliably secured to the supporting device in a specific position that is useful for a specific application.

[0022] As used herein, "cell suspension" refers to a fluid containing a liquid (e.g., water, saline, cell culture medium, etc.) in which cells are suspended. The cells may be higher eukaryotic cells, such as human or animal cells, microorganisms, such as bacteria or yeast, or biologically active organelles or vesicles. The liquid may further include a substrate (e.g., DNA, mRNA, protein, or other biologically active molecule) that is mixed with the suspended cells.

[0023] The invention will now be explained in further exemplary detail with reference to the drawings. [Brief explanation of the drawings]

[0024] [Figure 1] 1 shows a schematic view of a preferred embodiment of a part (cap) of a device according to the invention: a) perspective view, b) top view. [Figure 2] 2 shows a schematic view of the rear side of the part (cap) shown in FIG. 1: a) top view, b) close-up of the barrier element. [Figure 3] 2 shows a longitudinal section through part of the wall of the part (cap) shown in FIG. 1 and of a preferred embodiment of the device according to the invention. [Figure 4] 1 shows a schematic view of a preferred embodiment of another part (body, wall) of a device according to the invention: a) perspective view; b) top view. [Figure 5] The cross section of the part (body, wall) shown in Figure 4 cut open vertically. a) Whole part b) Bottom part (enlarged view) [Figure 6] 1 shows a schematic view of a preferred embodiment of a support device for holding a device according to the invention, a) perspective view, b) longitudinal section. DETAILED DESCRIPTION OF THE INVENTION

[0025] 1 and 2 show a part of a device according to the present invention, namely a cap-like element 1 designed to cover the internal space of the device. The cap-like element 1 has an inlet port 2 including a first opening 3 for introducing a cell suspension into the internal space of the device (see FIGS. 3 to 5). The inlet port 2 further includes a tubular channel 4 arranged between the first opening 3 and at least one third opening 5 designed to be connectable to at least one first hose (not shown). The inlet port 2 also includes a barrier element 6, which deflects the suspension toward the wall of the device (see FIG. 3), slowing the suspension's flow rate and allowing the suspension to flow slowly along the wall from the first opening 3 into the internal space. The barrier element 6 is arranged at the first opening 3 and borders the first opening 3 on the side furthest from the wall. The barrier element 6 is partially arranged between the first opening 3 and the internal space. As a result, the barrier element 6 is positioned so that the cell suspension introduced into the internal space flows gently along the inner surface of the wall, effectively preventing the suspension from falling into the internal space from the first opening 3 and from colliding with the bottom of the device or with the surface of the suspension already present in the internal space. When the cell suspension is introduced into the inlet port 2, the barrier element 6 deflects the suspension toward the wall, slowing its flow and allowing the suspension to flow slowly along the wall from the first opening 3 into the internal space, preventing the cells from being exposed to mechanical stress. To shorten the distance the suspension flows, the inlet port 2, and particularly the first opening 3, are positioned in an area close to the wall of the device.

[0026] The cap-like element 1 further comprises a vent port 7, which includes a fifth opening 8, for pressure balancing within the interior space. The vent port 7 further comprises a tubular channel 9 arranged between the fifth opening 8 and at least one sixth opening 10, which is designed to be able to connect, for example, to a filter element, in order to avoid contamination of the cell suspension within the interior space.

[0027] The cap-like element 1 also includes a protrusion 13 for fixing the position of the device according to the invention when it is held by a support device as preferably shown in Figure 6. Furthermore, the underside of the cap-like element 1 is provided with at least one retainer 11 for holding at least one magnetic element.

[0028] The cap-like element 1 can be reversibly attached to the wall surrounding the interior space by snap action means 12. Alternatively, the cap-like element 1 can be irreversibly attached to the wall surrounding the interior space by adhesive bonding means, in which case a suitable adhesive can be applied to the adhesive track 14 before the cap-like element 1 is pressed against the wall surrounding the interior space.

[0029] FIG. 3 shows a longitudinal cross-section of the cap-like element 1 shown in FIGS. 1 and 2 , including a portion of the wall 15 of the device according to the present invention. As can be seen from FIG. 3 , the barrier element 6 is positioned so that the suspension is deflected toward the wall 15 surrounding the internal space 16 of the device and flows along the inner surface of the wall 15 into the internal space 16. For this purpose, the barrier element 6 is positioned at the first opening 3 and borders the first opening 3 on the side farthest from the wall 15. The barrier element 6 is partially positioned between the first opening 3 and the internal space 16 to prevent the suspension from falling directly into the internal space 16. This prevents droplets of the suspension from colliding with the bottom of the device or the surface of the suspension already present there, thereby minimizing exposure of cells to mechanical stress. In contrast, when a cell suspension is introduced into the inlet port 2, the suspension is deflected toward the wall 15 by the barrier element 6, slowing its flow rate and allowing the suspension to flow slowly along the wall 15 from the first opening 3 into the internal space 16. In order to reduce the distance that the suspension must travel, the inlet port 2, and in particular the first opening 3, is located in an area close to the wall 15.

[0030] The wall 15 includes a recess 17 that, together with the barrier element 6, forms a cavity 18 that flows into the internal space 16. The barrier element 6 and the recess 17 are thus arranged and designed so that the cell suspension introduced into the inlet port 2 is deflected by the barrier element 6 toward the recess 17, slowing its flow. The suspension therefore accumulates in the cavity 18 and flows slowly from the cavity 18 along the wall 15 into the internal space 16. As a result, the exposure of the cells to mechanical stress can be further reduced. The recess 17 is preferably located in an area close to the inlet port 2 and the first opening 3.

[0031] The cap-like element 1 further comprises a vent port 7 having a fifth opening 8 for pressure balancing within the interior space. The vent port 7 further comprises a tubular channel 9 arranged between the fifth opening 8 and at least one sixth opening 10 designed to be connectable to, for example, a filter element to avoid contamination of the cell suspension within the interior space. Moreover, the cap-like element 1 comprises at least one retainer 11 on its underside for holding at least one magnetic element (e.g., a stirring rod).

[0032] 4 and 5 show a part of the device according to the invention, namely a wall 20 (body) enclosing an internal space 21 of the device according to the invention. To cover the internal space 21, a cap-like element 1 as shown in FIGS. 1 to 3 may be attached to an upper region 22 of the wall 20. Both the wall 20 and the internal space 21 have an elongated shape and a vertical orientation, with an inlet port (not shown here) and an outlet port 23 arranged at either end of the internal space 21. The outlet port 23 is arranged at a bottom 24 of the internal space 21 and comprises a second opening 25 for removing the suspension from the internal space 21. The outlet port 23 further comprises a tubular channel 29 arranged between the second opening 25 and a fourth opening 19 designed to be connectable to at least one second hose (not shown).

[0033] The wall 20 further includes a recess 26 that, together with a barrier element (not shown), forms a cavity that flows into the internal space 21. The barrier element and recess 26 are thus positioned and designed so that the cell suspension introduced into the inlet port is deflected by the barrier element toward the recess 26, slowing its flow. Therefore, the suspension accumulates in the cavity and flows slowly from the cavity along the wall 20 into the internal space 21. As a result, exposure of the cells to mechanical stress can be further reduced. The recess 26 is preferably positioned in an area close to the inlet port and the first opening.

[0034] In addition, the wall 20 is provided with a projection 27 for fixing the position of the device according to the invention when it is held by a support device such as that shown in FIG.

[0035] As can be seen from FIG. 5 , the outlet port 23 is located at the center of the bottom 24 and at the deepest point of the internal space 21, and the wall 20 slopes down sharply in the bottom area 24. This advantageous structure allows the cell suspension to be removed from the internal space 21 without residue, minimizing the loss of valuable cells. The transition area 28 between the wall 20 and the outlet port 23 is uniformly shaped, i.e., without any irregularities, borders, or edges, ensuring a smooth transition from the internal space 21 to the outlet port 23. This measure allows the cell suspension to be completely removed from the internal space with almost no residue. Furthermore, unnecessary mechanical stress can be prevented when the cells are removed from the internal space 21.

[0036] 6 shows a preferred embodiment of a support device 30 for holding a device 33 according to the present invention, comprising at least one base element 31 and at least one mounting element 32. The mounting element 32 comprises magnetic means 34 for holding at least one magnetic element 35 housed in the interior space 36 of the device 33. In this embodiment, the magnetic means 34 is a separate member that can be reversibly attached to the mounting element 32 of the support device 30. The magnetic means 34 is integrated with a plastic member 37, which is provided with means for attaching it to the mounting element 32. As a result, the magnetic means 34 and thus the mounting element 32 act as a trap for the magnetic element 35, and when the device 33 is fixed to the support device 30 so as to be guided along the magnetic means 34, the magnetic element 35 is held by the magnetic means 34 and fixed to the wall 38 in the upper region of the device 33. As a result, the magnetic element 35 is kept away from the outlet port 39 of the device 33 so as not to interfere with the removal of the cell suspension from the interior space 36 of the device 33.

[0037] Furthermore, the mounting element 32 comprises a recess 40 for fixing the device 33, said recess 40 corresponding to a protrusion 41 on the wall 38 of the device 33. By this means, the device 33 can be fixed to the support device 30 in a specific position that is useful for a specific application.

Claims

1. 1. A device for supplying a cell suspension to an instrument for processing cells, the device comprising at least one internal space (16, 21) for holding the suspension, the internal space (16, 21) being at least partially surrounded by walls (15, 20), the device further comprising at least one inlet port (2) with at least one first opening (3) for introducing the suspension into the internal space (16, 21) and at least one outlet port (23) with at least one second opening (25) for removing the suspension from the internal space (16, 21), the inlet port (2) further comprising at least one barrier element (6), the at least one barrier element (6) abutting the first opening (3) on a side furthest from the walls (15, 20) and being partially disposed between the first opening (3) and the internal space (16, 21), 1. A device according to claim 1, wherein the wall (15, 20) has at least one recess (17, 26) and the barrier element (6), the recess (17, 26) forming a cavity (18) flowing into the internal space (16, 21), and the inlet port (2) and the first opening (3) are arranged in an area close to the wall (15, 20).

2. The device described in claim 1, wherein the recesses (17, 26) are arranged in an area close to the first opening (3).

3. 3. The device according to claim 1 or 2, wherein the inlet port (2) further comprises a tubular channel (4) arranged between the first opening (3) and at least one third opening (5) designed to be connectable to at least one first hose.

4. 4. The device according to claim 1, wherein the outlet port (23) further comprises a tubular channel (29) arranged between the second opening (25) and at least one fourth opening (19) designed to be connectable to at least one second hose.

5. 5. The device according to any one of claims 1 to 4, wherein the inlet port (2) is part of a cap-like element (1) designed to cover the interior space (16, 21).

6. 6. The device according to claim 5, wherein the cap-like element (1) further comprises at least one retainer (11) for holding at least one magnetic element.

7. 7. The device of any one of claims 1 to 6, wherein the transition area (28) between the wall (20) and the outlet port (23) is uniformly shaped.

8. 8. The device according to any one of claims 1 to 7, wherein the outlet port (23) is located at the center point of the bottom area (24) of the interior space (21).

9. 9. The device of any one of claims 1 to 8, wherein the outlet port (23) is located at the deepest point of the interior space (21).

10. 9. The device according to claim 8, wherein the bottom area (24) of the interior space (21) has a flat, circular region for receiving and guiding a magnetic element.

11. 11. The device according to any one of the preceding claims, further comprising at least one vent port (7) having at least one fifth opening (8) for balancing pressure within the interior space (16, 21).

12. 12. Device according to any of the preceding claims, wherein the outer surface of the wall (15, 20) is provided with at least one recess and / or protrusion (13, 27) for fixing the position of the device.

13. A device as described in claim 5 or 6, wherein the outer surface of the cap-like element (1) has at least one recess and / or protrusion (13, 27) for fixing the position of the device.

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