Chromatography device

Abstract

A chromatography device (1; 101) comprising:-at least one chromatographic material unit (3) wherein the chromatographic material unit comprises a convection-based chromatographic material; -at least one fluid distribution system (7) configured to distribute fluid into and out of the at least one chromatographic material unit (3); an inlet (15); -at least one inlet fluid channel (17a, 17b) connecting the inlet (15) to each chromatographic material unit (3) via a fluid distribution system (7); an outlet (19); and-at least one outlet fluid channel (21) connecting an outlet (19) to each chromatographic material unit (3) via a fluid distribution system (7), said chromatographic device (1; 101) are overmolded by plastic or elastomer and sealed together such that at least the inlet (15) and the outlet (19) are open.

Description

Technical Field

[0001] The present invention relates to a chromatography device comprising a convection-based chromatography material and to a method for producing such a chromatography device. Background Art

[0002] Historically, conventional packed bed chromatography using porous beads has been an extremely powerful separation tool. In systems based on porous beads, the binding event between the target molecule / impurity and the solid phase depends on diffusion into the porous beads. Therefore, there is a strong correlation between the interaction and residence time of the molecules and the solid phase of the system based on porous beads and the flow rate thus applied. Thus, the binding capacity decreases as the residence time shortens. This type of chromatography may be referred to as a chromatography based on diffusion. Chromatographic matrices based on diffusion include any matrix consisting of particles and substantially showing diffusion limitations of mass transfer, because the rate of the adsorption process and the desorption process is determined by the diffusion rate of (multiple) substances diffusing into and diffusing out of the particles due to the diffusion coefficient of (multiple) substances, and the diffusion coefficient depends to a very large extent on the size or molecular weight of the substance and the accessibility of the pores in the particles in terms of their size, structure, and depth.

[0003] As an alternative to the system based on porous beads, monoliths or films can be used. The flow through such materials and the mechanism for making molecules interact with the solid phase is convective, rather than diffusion, and their binding capacity is therefore much less sensitive to flow than the system based on porous beads. These materials can be operated at a flow rate much higher than the material based on porous beads. In (membrane) adsorption chromatography, in contrast to gel permeation chromatography, there is a combination of the composition of the fluid (for example, a single molecule, an association or a particle) to the surface of the solid in contact with the fluid, without the need to transport in the pores by diffusion, and molecules can approach the active surface of the solid phase by convective transport. The advantage of membrane adsorber relative to packed chromatographic columns is that membrane adsorber is suitable for running with much higher flow rates. This is also referred to as chromatograms based on convection. Chromatographic matrix based on convection includes any matrix as follows: wherein, between the inflow and the effluent of the matrix, a hydraulic pressure difference is applied to force the matrix to be perfused, thereby realizing that (multiple) substances are basically convectively transported into the matrix or convectively transported out from the matrix, which is realized very quickly at high flow rates.

[0004] Convection-based chromatography and membrane adsorbers are described, for example, in US20140296464A1, US20160288089A1, US2019308169A1, and US2019234914A1, which are hereby incorporated by reference in their entirety.

[0005] However, one problem with membrane adsorbers is that the total surface area of ​​the solid support accessible for interaction with the target molecule may be smaller compared to porous beads. Therefore, the binding capacity may also be reduced. This is due to the fact that the porous bead structure provides a high surface area inside the bead. In order to increase the surface area and capacity of membrane adsorbers based on convection, and to compensate for the lack of area provided by the diffusion pores, the size of the convective pores of the convective matrix may be reduced. However, as a result, the resistance to flow will increase.

[0006] Therefore, high flow rates through a chromatography device comprising a high capacity convective matrix will require a chromatography device and design that can withstand high operating pressures. Summary of the invention

[0007] It is an object of the present invention to provide an improved chromatography device comprising a convection-based chromatography material.

[0008] It is a further object of the present invention to provide a chromatography device which allows high flow rates and withstands high operating pressures.

[0009] This is achieved according to the independent claims by a chromatography device and by a method for producing a chromatography device.

[0010] According to one aspect of the present invention, there is provided a chromatographic device, the chromatographic device comprising: - at least one chromatography material unit, wherein the chromatography material unit comprises a convection-based chromatography material; - at least one fluid distribution system configured to distribute fluid into and out of at least one chromatography material unit; -Entrance; - at least one inlet fluid channel connecting the inlet to the respective chromatography material unit via the fluid distribution system; - export; and - at least one outlet fluid channel connecting the outlet to the respective chromatography material unit via a fluid distribution system, wherein at least parts of the chromatography device are overmoulded by plastic or elastomer and sealed together leaving at least the inlet and outlet open.

[0011] According to another aspect of the present invention, there is provided a method for producing a chromatography device according to above, the method comprising the following steps: - arranging the at least one chromatography material unit in a chromatography device; - Overmoulding at least some parts of the chromatography device by plastic or elastomer and sealing together, leaving at least the inlet and outlet open.

[0012] Hereby, a chromatography device is achieved which can withstand high operating pressures. Overmoulding will provide suitable strength to the device and the use of convection based chromatography materials allows for high flow rates through the chromatography device.

[0013] Furthermore, the chromatography device according to the invention can be manufactured as a single-use product and can be used without an external stabilizing support.

[0014] In one embodiment of the present invention, the chromatography device further comprises a shell in which at least one chromatography material unit is arranged, the shell comprising the inlet, the outlet, the at least one inlet fluid channel and the at least one outlet fluid channel, wherein the shell comprises at least a top plate and a bottom plate, the at least one chromatography material unit is arranged between the top plate and the bottom plate, and the chromatography device can withstand an operating pressure of at least 10 bar or at least 15 bar after overmolding.

[0015] In one embodiment of the present invention, the chromatography device comprises at least one box, wherein each box comprises a fluid distribution system and a chromatography material unit, wherein the chromatography material unit is sandwiched between a distribution device and a collection device of the fluid distribution system, and wherein the at least one box is arranged in the housing.

[0016] In one embodiment of the invention, the chromatography device comprises at least two cassettes, wherein each cassette is overmolded, and wherein at least two cassettes (5) are arranged in a housing.

[0017] In one embodiment of the invention, the housing comprises one inlet fluid channel between each dispensing device and the inlet in the cassette, and wherein said inlet fluid channels are equal in length and size.

[0018] In one embodiment of the present invention, the chromatography device comprises two chromatography material units, and wherein the housing further comprises a center plate, and wherein one chromatography material unit is arranged between the top plate and the center plate, and wherein one chromatography material unit is arranged between the center plate and the bottom plate, wherein the center plate comprises an inlet and an outlet, and wherein the top plate, the center plate and the bottom plate comprise cooperating connection means, which allow correct connection of the housing so that the fluid channels arranged in the top plate, the bottom plate and the center plate correctly cooperate.

[0019] In one embodiment of the present invention, each chromatography material unit comprises at least one adsorption membrane.

[0020] In one embodiment of the present invention, the adsorption membrane is a polymer nanofiber membrane.

[0021] In one embodiment of the present invention, each chromatographic material unit comprises: at least one adsorption membrane sandwiched between at least one top spacer layer and at least one bottom spacer layer; or at least two adsorption membranes stacked on top of each other and separated from the spacer layers and sandwiched between at least one top spacer layer and at least one bottom spacer layer.

[0022] In one embodiment of the invention, said fluid distribution system and said housing for each of said at least one chromatography material unit are made of plastic or silicone and wherein said chromatography device is a single-use chromatography device.

[0023] In one embodiment of the present invention, the fluid distribution system comprises a distribution device, the distribution device comprising a plate arranged to be adjacent to the inlet surface of the chromatography material unit, wherein the plate comprises a number of openings for distributing the fluid supply provided from the inlet of the chromatography device to the chromatography material unit, wherein the total area of ​​the openings in the plate is smaller than the remainder of the area of ​​the plate or less than 20% of the remainder of the area of ​​the plate or less than 10% of the remainder, wherein the openings are connected to the distribution device inlet via one or more fluid conduits provided in the distribution device.

[0024] In one embodiment of the present invention, the fluid distribution system comprises a collecting device, the collecting device comprising a plate arranged to be adjacent to the outlet surface of the chromatography material unit, wherein the plate comprises a number of openings for collecting fluid from the chromatography material unit, wherein the total area of ​​the openings in the plate is smaller than the remainder of the area of ​​the plate or less than 20% of the remainder of the area of ​​the plate or less than 10% of the remainder, wherein the openings are connected to the collecting device outlet via one or more fluid conduits provided in the collecting device.

[0025] In one embodiment of the invention the total volume of the inlet and outlet fluid channels in the chromatography device including the fluid conduits in at least one fluid distribution system of the chromatography device is less than 20% or less than 10% of the volume of the chromatography material in the chromatography material unit.

[0026] In one embodiment of the present invention, the method further comprises the following steps: - arranging the individual chromatography material units together with the fluid distribution system in a cartridge, wherein the chromatography material units are sandwiched in the individual cartridges between a distribution device and a collection device of the fluid distribution system; - overmolding each cartridge; and - The at least one box is arranged in a housing of the chromatography device, the housing comprising the inlet, the outlet, the at least one inlet fluid channel and the at least one outlet fluid channel, and the housing comprises at least a top plate and a bottom plate, and the at least one box is arranged between the top plate and the bottom plate.

[0027] In one embodiment of the present invention, the method further comprises the following steps: - Overmolding the housing with the at least one cartridge arranged therein such that at least an inlet and an outlet are open. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 is an exploded view of a chromatography device according to one embodiment of the present invention.

[0029] Figure 2 Yes Figure 1 A cross section of the same chromatography device shown in FIG.

[0030] Figure 3 Yes Figure 1 and Figure 2 A perspective view of the same chromatography device shown in FIG. 1 when assembled.

[0031] Figure 4 is a cross-section of a chromatography device according to another embodiment of the present invention.

[0032] Figure 5a and Figure 5b is a perspective view showing the front and rear of a dispensing system according to one embodiment of the present invention.

[0033] Figure 6 A flow chart showing a method according to an embodiment of the present invention is shown. DETAILED DESCRIPTION

[0034] exist Figure 1-3 Detailed Description of the Invention A chromatography device 1 according to an embodiment of the present invention is shown in FIG. Figure 1 An exploded view of the chromatography device 1 is shown, and Figure 2 The chromatographic device 1 is shown in cross section when assembled. Figure 3 1 is a perspective view of the chromatographic device 1 when assembled. The chromatographic device 1 comprises at least one chromatographic material unit 3. Figure 2 3. The chromatographic material unit 3 is seen in FIG. The chromatographic material unit 3 comprises a convection-based chromatographic material. As discussed above, the convection-based chromatographic material may be, for example, an adsorption membrane, wherein the flow through such a material is convective rather than diffusive. The adsorption membrane may be, for example, a polymer nanofiber membrane, such as, for example, cellulose, cellulose acetate and cellulose fibers, which have been treated to act as an adsorbent. The adsorption membrane may alternatively be a monolithic material or a conventional membrane made by emulsification.

[0035] Optionally, the adsorption film includes polymer nanofibers. The polymer nanofibers may have an average diameter from 10nm to 1000nm. For some applications, polymer nanofibers with an average diameter from 200nm to 800nm ​​are appropriate. Polymer nanofibers with an average diameter from 200nm to 400nm may be suitable for certain applications. Optionally, polymer nanofibers are provided in the form of one or more non-woven sheets each including one or more polymer nanofibers. Optionally, the adsorbent chromatographic medium is formed by one or more non-woven sheets each including one or more polymer nanofibers. The non-woven sheet including one or more polymer nanofibers is a pad of one or more polymer nanofibers oriented substantially randomly for each nanofiber, that is, the non-woven sheet is not prepared so that one or more nanofibers adopt a specific pattern. Optionally, the chromatographic material unit includes one or more spacer layers. The spacer layer may be provided to increase structural integrity to the adsorbent chromatographic medium. In particular, the spacer layer may be mechanically more rigid than the non-woven sheet of nanofibers. The spacer layer can help reduce the deformation of the adsorbent chromatographic medium during the manufacture and / or use of the chromatographic system to keep the channel formed with the flow path open. Ideally, the spacer layer should be incompressible or incompressible to a great extent to allow the alternating layering of compressible polymer nanofibers to allow the porosity of the stack to maintain a higher flow rate than the situation where the compressible nanofibers are stacked alone. The format and composition of the spacer material are not particularly limited, but should be more porous than the nanofiber layer and have a minimum thickness to reduce the dead volume in the stack. Suitable material will be 10-120 (grams per square meter) of non-woven polypropylene.

[0036] exist Figure 1-3 In the embodiment of the present invention shown in FIG. Figure 2 In this embodiment, the chromatographic material units 3 are each arranged in a box 5. These boxes can be Figure 1 However, the number of cassettes 5 and the number of chromatography material units 3 provided in the chromatography device 1 may vary within the scope of the invention. Only one or more than two chromatography material units 3 may be provided in the chromatography device 1 .

[0037] Furthermore, the chromatography device 1 comprises at least one fluid distribution system 7, which is configured to distribute fluid into and out of at least one chromatography material unit 3. A fluid distribution system 7 is provided for each chromatography material unit 3, and, therefore, in Figure 1-3In the embodiment shown in, two fluid distribution systems 7 are provided. In this embodiment, each fluid distribution system 7 comprises a distribution device 9a and a collecting device 9b. A chromatographic material unit 3 is sandwiched between the distribution device 9a and the collecting device 9b of the fluid distribution system 7. In this embodiment, the distribution device 9a and the collecting device 9b are exactly the same, but this is not necessary. Thus, in this embodiment, each box 5 comprises a fluid distribution system 7 and a chromatographic material unit 3 in the form of a distribution device 9a and a collecting device 9b. In another embodiment, the fluid distribution system 7 can be provided separately from the box 5 or integrated into the housing 13 of the chromatographic device 1, for example as a separate unit.

[0038] The chromatographic device 1 comprises a housing 13, in which at least one chromatographic material unit 3 is arranged. Figure 1-3 In the embodiment shown in, the two boxes 5 are arranged in the housing 13. The housing 13 includes an inlet 15 for receiving a fluid supply and at least one inlet fluid channel 17a, 17b that connects the inlet 15 to each chromatographic material unit 3 via a fluid distribution system 7. In this embodiment, there are two inlet fluid channels 17a, 17b. In addition, the housing 13 includes an outlet 19 for transferring fluid effluent from the chromatographic device 1 and at least one outlet fluid channel 21 that connects the outlet 19 to each chromatographic material unit 3 via a fluid distribution system 7. In this embodiment, there is only one common outlet fluid channel 21. However, the flow direction through the chromatographic device 1 can also be changed so that the inlet is the outlet, and the inlet fluid channel is the outlet fluid channel, and vice versa. In this embodiment, the housing 13 includes at least a top plate 25 and a bottom plate 27, and the at least one chromatographic material unit 3 is arranged between the top plate 25 and the bottom plate 27.

[0039] According to the present invention, at least some parts of the chromatographic device 1 are overmolded and sealed together by plastic or elastomer, so that at least the inlet 15 and the outlet 19 are open. In one embodiment, each box 5 can be overmolded before they are provided in the housing 13. In addition, the housing 13 itself may also be overmolded after it has been assembled. In addition, instead of overmolding, providing a compressive force by the assembly can be used to produce an airtight seal between each box 5 and different parts of the housing 13 to complete the device. Alternatively, at least one chromatographic material unit 3 can be each provided in the housing 13 together with a fluid distribution system 7, and then, the entire assembly is overmolded in a single overmolding process. Overmolding is a process for producing a seal and for providing stability to the device. The fluid distribution system and the chromatographic material unit can be sealed together by an overmolding process, and the box can be sealed to the housing by an overmolding process. Plastic or elastomer can be used to seal the parts together in the overmolding. Polyolefins can be used, for example, for overmolding and / or elastomeric materials that will act as gaskets between mating parts. In some embodiments of the invention, the material used for overmolding is the same as the material used to make at least some of the parts such as the housing. This can be suitable and provide a good seal. Overmolding is used to form an airtight seal between the chromatographic material unit, the box, and the housing member, and in doing so, overmolding can also be used to help achieve additional mechanical strength of the assembled unit for operation at higher pressures. In some embodiments of the invention, overmolding can be in the following form: 1) a thermoplastic polymer having a similar property to the housing to help form a strong bond caused by heating during the overmolding process, for example, both are polypropylene random copolymers; and / or 2) an elastomeric material that can be bonded to the chromatographic material unit material and also form a seal with the housing under compression. The possibility of using different colors for overmolding and housing provides the possibility of visually verifying the success of overmolding.

[0040] The chromatographic device 1 is designed to withstand an operating pressure of at least 10 bar or at least 15 bar. The dimensions of the housing 13 and the overmolding are adapted so as to achieve a stable chromatographic device that can withstand such an operating pressure without any external support. In addition, a construction with separate boxes (which can also be overmolded) each comprising a chromatographic material unit provides a stable chromatographic device. For example, in some embodiments of the present invention, the top plate 25 and the bottom plate 27 of the housing 13 can be at a surface area of ​​1200 mm 2 With 9600mm 2In some embodiments of the invention, the sacrificial peripheral area around the perimeter of the chromatography material unit 3 is considered to be a sacrificial area to allow the plastic to properly embed the chromatography material unit during overmolding. Such a sacrificial peripheral area may, for example, be in the interval of 0.5-1.5 mm. In embodiments of the invention in which the adsorption membranes are separated from each other by spacer layers and sandwiched between the spacer layers as will be described in more detail below, these spacer layers may be made of a material that can melt and fuse during overmolding, and, thereby, the sacrificial areas of the spacer layers will melt and fuse and, together with the overmolding material, create a sealing area between each layer of the adsorption membrane. In some embodiments of the invention, an injection temperature for overmolding in the interval of 200°C-260°C or in the interval of 220°C-240°C may be used. Temperatures in these intervals are suitable for the overmolding process because the chromatography device will be effectively overmolded and sealed without the risk of negatively affecting the chromatographic properties of the chromatography material.

[0041] In such Figure 1-3 In the embodiment shown in, the housing 13 includes an inlet fluid channel 17a, 17b between the inlet 15 and the distribution device 9a for each in the box 5. The inlet fluid channels 17a, 17b are equal in length and size. This is important in order to ensure uniform fluid supply distribution in the chromatographic device 1. In this embodiment of the invention, the outlet fluid channel 21 of the housing 13 is a common outlet fluid channel 21 that connects the outlet 19 to the collecting device 9b for two boxes 5. However, the positions of the inlet 15 and the outlet 19 are switchable.

[0042] In this embodiment in which the chromatographic device 1 comprises two chromatographic material units 3, the housing 13 further comprises a central plate 29. Thus, one chromatographic material unit 3 is arranged between the top plate 25 and the central plate 29, and one chromatographic material unit 3 is arranged between the central plate 29 and the bottom plate 27. In this embodiment, the central plate 29 comprises an inlet 15 and an outlet 19. In addition, the top plate 25, the central plate 29 and the bottom plate 27 comprise cooperating connection means 31a, 31b, 31c, which allow the correct connection of the housing 13 so that the fluid channels 17a, 17b arranged in the top plate 25, the bottom plate 27 and the central plate 29 are correctly matched. In this example, the inlet fluid channels 17a, 17b are arranged in all three of the top plate 25, the central plate 29 and the bottom plate 27. Therefore, these plates need to be correctly connected for the inlet fluid channels 17a, 17b to be correctly matched. The outlet fluid channel 21 is only arranged in the central plate 29. However, as described above, the direction of flow through the chromatographic device may be changed.

[0043] In some embodiments, the chromatography material unit 3 according to the present invention may include at least two adsorption membranes 41 stacked on top of each other, separated from each other by a spacer layer 43, and sandwiched between one or more top spacer layers 45a and one or more bottom spacer layers 45b. However, in another embodiment, only one adsorption membrane is provided. Figure 2 An example of a chromatography material unit having four stacked adsorption membranes 41 is seen in . In this embodiment, two top spacer layers 45a and two bottom spacer layers 45b are provided. The spacer layers 43, the top spacer layers 45a and the bottom spacer layers 45b may, for example, be polypropylene non-woven layers, and they may suitably have substantially the same surface area as the adsorption membrane 41. In addition, they may, for example, have a non-woven basis weight range of between 10gsm and 120gsm. The function of the spacer layers 43, 45a, 45b is that they provide bed support for the membrane 41. Suitably, the spacer layers 43, 45a, 45b are incompressible, while the adsorption membrane 41 is suitably compressible. As discussed above, the adsorption membrane 41 may, for example, be a polymer nanofiber membrane. Suitable dimensions of the adsorption membrane 41 may, for example, be between 1200mm 2 With 135000mm 2 The surface area between.

[0044] The chromatography device 1 according to the invention is suitably a single-use chromatography device. The housing 13 and the fluid distribution system 7 may for example be made of plastic or silicone. The chromatography device 1 may be sterilized or disinfected, for example by gamma radiation, and provided with sterile connectors.

[0045] The total volume of the inlet fluid channels 17a, 17b and the outlet fluid channels 21 in the chromatographic device 1 including the fluid conduits in at least one fluid distribution system 7 of the chromatographic device 1 is suitably less than 20% of the volume of the chromatographic material in the chromatographic material unit 3 or less than 10% of the volume. Thus, the chromatographic device 1 will have a small hold-up volume, which is particularly advantageous in applications where the sample circulates multiple times on the chromatographic unit (which is often the case in a membrane adsorber). Alternatively or in addition, in some embodiments of the present invention, the total volume of the fluid conduits provided in the fluid distribution system may be less than 20% of the total volume of the inlet fluid channels and the outlet fluid channels in the chromatographic device including the fluid conduits in the fluid distribution system or less than 10% of the total volume.

[0046] Figure 4 is a cross section of a chromatography device 101 according to another embodiment of the present invention. Figure 1-3The same reference numbers as in the embodiment shown in . In this embodiment, the chromatography device 101 includes only one chromatography material unit 3 arranged in one box 5. Therefore, only one fluid distribution system 7 is provided. The chromatography material unit 3 is sandwiched between the distribution device 9a and the collection device 9b of the fluid distribution system 7 as described above. The chromatography device 101 includes a housing 13. The housing includes a top plate 25 and a bottom plate 27, but does not include a center plate. The inlet 15 is arranged in the top plate 25, and the outlet 19 is arranged in the bottom plate 27. The box 5 is arranged in the housing 13, and the top plate 25 and the bottom plate 27 are connected to each other, so that the inlet fluid channel 17 connects the inlet 15 to the chromatography material unit 3 via the fluid distribution system 7, and the outlet fluid channel 21 connects the outlet 19 to the chromatography material unit 3 via the fluid distribution system 7. The chromatography material unit 3 and the fluid distribution system 7 can be connected in the same manner as described above for Figure 1-3 The exemplary embodiment shown in the drawings is designed in the same manner as described.

[0047] The cassette 5 and / or the housing 13 may be overmoulded as described above in order to provide a robust chromatography device 101 .

[0048] exist Figure 5a and Figure 5b An embodiment of a fluid distribution system 7 that can be used in the present invention is shown in FIG. The fluid distribution system 7 may include a distribution device 9a and a collection device 9b, and the distribution device 9a and the collection device 9b may be identical. One of them is in Figure 5a is shown from the front and is Figure 5b 9a and the collecting device 9b. However, the distributing device 9a and the collecting device 9b do not necessarily have to be identical. In this embodiment of the fluid distributing system 7, the distributing device 9a comprises an inlet surface 53a (at the bottom) arranged adjacent to the chromatographic material unit 3. Figure 2 and Figure 4 The plate 51 comprises a plurality of openings 55 for distributing a fluid supply provided from the inlet 15 of the chromatographic device 1; 101 to the chromatographic material unit 3, wherein the total area of ​​the openings 55 in the plate 51 is smaller than the remaining part of the area of ​​the plate 51 or less than 20% of the remaining part of the area of ​​the plate or less than 10% of the remaining part, wherein the openings 55 are connected to the distribution device inlet 57a (in the distribution device 9a) via one or more fluid conduits 59 provided in the distribution device 9a. Figure 2 and Figure 4 ). Figure 5a and Figure 5bIn the embodiment shown in , there are more than one fluid conduit 59 provided, however, in another embodiment, one cavity may be provided as a single fluid conduit for transferring liquid to a number of openings distributed on the plate. The plate 51 is arranged so that it abuts the inlet surface 53a of the chromatography material unit 3 and thereby also provides structural support for the chromatography material unit 3, so that the dimensional integrity and chromatographic function of the chromatography material unit 3 and the entire device are not compromised. Due to the large support area of ​​the plate 51 facing the chromatography material unit 3, the integrity of the chromatography material unit 3 and the chromatography device 1 is maintained. A large support area is provided because the combined size of the openings 55 is relatively small and because lateral distribution of the fluid in the distribution devices 9a, 9b is not provided at the surface of the distribution device facing the chromatography material unit 3 (at Figure 5a ), but instead is provided in the distribution device or on the other side of the distribution device 9a, 9b (in Figure 5b ).

[0049] The collecting device 9b may be identical, ie comprising an outlet surface 53b arranged adjacent to the chromatographic material unit 3 (at Figure 2 and Figure 4 The plate 51 comprises a plurality of openings 55 for collecting fluid from the chromatography material unit 3, wherein the total area of ​​the openings 55 in the plate 51 is smaller than the remaining area of ​​the plate or less than 20% of the remaining area of ​​the plate or less than 10% of the remaining area of ​​the plate, wherein the openings 55 are connected to the collecting device outlet 57b (at the collecting device 9b) via one or more fluid conduits 59 provided in the collecting device 9b. Figure 2 and Figure 4 (see in ).

[0050] Figure 6 A flow chart of a method for producing a chromatography device according to the above text is shown according to one embodiment of the present invention. The method steps are described in order below: S1: The at least one chromatographic material unit 3 is arranged in the chromatographic device 1; 101. In some embodiments of the present invention, each chromatographic material unit 3 can be arranged in a box 5 together with a fluid distribution system 7, wherein the chromatographic material unit 3 is sandwiched between a distribution device 9a and a collection device 9b of the fluid distribution system 7 in each box 5. In some embodiments of the present invention, the at least one box 5 can be arranged in a housing 13 of the chromatographic device 1; 101, the housing comprising the inlet 15, the outlet 19, the at least one inlet fluid channel 17a, 17b and the at least one outlet fluid channel 21, and the housing 13 at least comprises a top plate 25 and a bottom plate 27, and the at least one box 5 is arranged between the top plate 25 and the bottom plate 27.

[0051] S2: Overmolding at least some parts of the chromatography device 1; 101 so that at least the inlet 15 and the outlet 19 are open. In some embodiments of the present invention, each box can be overmolded. In addition, in some embodiments of the present invention, the housing 13 can be overmolded with the box 5 arranged in the housing 13 so that at least the inlet 15 and the outlet 19 are open.

Claims

1. A chromatographic device (1; 101), including: - at least one chromatography material unit (3), wherein the chromatography material unit comprises a convection-based chromatography material, wherein the convection-based chromatography material is an adsorption membrane; - at least one fluid distribution system (7) configured to distribute fluid into and out of the at least one chromatography material unit (3); - entrance (15); - at least one inlet fluid channel (17a, 17b) connecting the inlet (15) to a respective chromatography material unit (3) via the fluid distribution system (7); - an exit (19); and at least one outlet fluid channel (21) connecting the outlet (19) to a respective chromatography material unit (3) via the fluid distribution system (7), Each chromatographic material unit (3) comprises at least two adsorption membranes (41), wherein the at least two adsorption membranes (41) are stacked one above the other, separated from each other by a spacer layer (43), and sandwiched between at least one top spacer layer (45a) and at least one bottom spacer layer (45b). Therein, at least some parts of the chromatography device (1; 101) are overmolded by plastic or elastomer and sealed together so that at least the inlet (15) and the outlet (19) are open.

2. The chromatographic device according to claim 1, wherein The chromatography device (1; 101) further comprises a shell (13) in which the at least one chromatography material unit (3) is arranged, the shell (13) comprises the inlet (15), the outlet (19), the at least one inlet fluid channel (17a, 17b) and the at least one outlet fluid channel (21), wherein the shell (13) comprises at least a top plate (25) and a bottom plate (27), the at least one chromatography material unit (3) is arranged between the top plate (25) and the bottom plate (27), and the chromatography device (1; 101) can withstand an operating pressure of at least 10 bar or at least 15 bar after the overmolding.

3. The chromatographic device according to claim 2, wherein The chromatography device (1; 101) comprises at least one box (5), wherein each box (5) comprises a fluid distribution system (7) and a chromatography material unit (3), wherein the chromatography material unit (3) is sandwiched between a distribution device (9a) and a collection device (9b) of the fluid distribution system (7), and wherein the at least one box (5) is arranged in the housing (13).

4. The chromatographic device according to claim 3, wherein The chromatography device (1; 101) comprises at least two cassettes (5), wherein each cassette (5) is overmoulded, and wherein the at least two cassettes (5) are arranged in the housing (13).

5. The chromatographic device according to claim 3 or 4, wherein The housing (13) comprises an inlet fluid channel (17a, 17b) between each of the fluid distribution systems (7) in the cassette (5) and the inlet (15), and wherein the inlet fluid channels (17a, 17b) are equal in length and size.

6. The chromatographic device according to any one of claims 2 to 5, wherein The chromatography device (1; 101) comprises two chromatography material units (3), and wherein the housing (13) further comprises a central plate (29), and wherein one chromatography material unit (3) is arranged between the top plate (25) and the central plate (29), and wherein one chromatography material unit (3) is arranged between the central plate (29) and the bottom plate (27), wherein the central plate (29) comprises the inlet (15) and the outlet (19), and wherein the top plate (25), the central plate (29) and the bottom plate (27) comprise cooperating connection means (31a, 31b, 31c), and wherein the cooperating connection means (31a, 31b, 31c) allow the housing (13) to be correctly connected so that the fluid channels arranged in the top plate, the bottom plate and the central plate are correctly matched.

7. The chromatographic device according to claims 1-6, wherein The adsorption membrane is a polymer nanofiber membrane.

8. A chromatographic device according to any one of the preceding claims, wherein The fluid distribution system (7) and the housing (13) for each of the at least one chromatography material unit (3) are made of plastic or silicone, and wherein the chromatography device (1; 101) is a single-use chromatography device.

9. A chromatographic device according to any one of the preceding claims, wherein The fluid distribution system (7) comprises a distribution device (9a), the distribution device (9a) comprising a plate (51) arranged adjacent to an inlet surface (53a) of the chromatography material unit (3), wherein the plate (51) comprises a plurality of openings (55) for distributing a fluid supply provided from the inlet (15) of the chromatography device (1; 101) to the chromatography material unit (3), wherein the total area of ​​the openings (55) in the plate (51) is smaller than the remaining area of ​​the plate (51) or smaller than 20% of the remaining area of ​​the plate (51) or smaller than 10% of the remaining area, wherein the openings (55) are connected to a distribution device inlet (57a) via one or more fluid conduits (59) provided in the distribution device (9a).

10. A chromatographic device according to any one of the preceding claims, wherein The fluid distribution system (7) comprises a collecting device (9b), the collecting device (9b) comprising a plate (51) arranged adjacent to an outlet surface (53b) of the chromatography material unit (3), wherein the plate (51) comprises a plurality of openings (55) for collecting fluid from the chromatography material unit (3), wherein the total area of ​​the openings (55) in the plate (51) is smaller than the remaining area of ​​the plate (51) or smaller than 20% or smaller than 10% of the remaining area of ​​the plate (51), wherein the openings (55) are connected to a collecting device outlet (57b) via one or more fluid conduits (59) provided in the collecting device (9b).

11. A chromatographic device according to any one of the preceding claims, wherein The total volume of the inlet fluid channels (17a, 17b) and the outlet fluid channels (21) in the chromatography device (1; 101) including the fluid conduits (59) in the at least one fluid distribution system (7) of the chromatography device is less than 20% of the volume of the chromatography material in the chromatography material unit (3) or less than 10% of the volume.

12. A method for producing a chromatography device (1; 101) according to any one of the preceding claims, comprising the following steps: - arranging the at least one chromatography material unit (3) in the chromatography device (1; 101); - At least parts of the chromatography device (1; 101) are overmoulded and sealed together by plastic or elastomer, leaving at least the inlet (15) and the outlet (19) open.

13. The method according to claim 12, further comprising the steps of: - each chromatography material unit (3) is arranged together with a fluid distribution system (7) in at least one box (5), wherein the chromatography material unit (3) is sandwiched between a distribution device (9a) and a collection device (9b) of the fluid distribution system (7) in each box (5); - overmolding each box (5); and - The at least one box (5) is arranged in the shell (13) of the chromatography device (1; 101), the shell (13) includes the inlet (15), the outlet (19), the at least one inlet fluid channel (17a, 17b) and the at least one outlet fluid channel (21), and the shell (13) includes at least a top plate (25) and a bottom plate (27), and the at least one box (5) is arranged between the top plate (25) and the bottom plate (27).

14. The method according to claim 13, further comprising the steps of: - Overmolding the housing (13) with the at least one cartridge (5) arranged in the housing (13) such that at least the inlet (15) and the outlet (19) are open.

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