Holding device for membrane chromatography unit

Abstract

The invention relates to a holding device (100) for accommodating at least one membrane chromatography unit (110a), (110a '), (110b). The retention device (100) may be suitable for use on a table top, and in various embodiments are relatively lightweight and may be manually lifted. The holding device (100) comprises a holding housing (120) for holding and aligning at least one membrane chromatography unit (110a), (110a '), (110b). The holding device (100) further comprises a pressing mechanism (130) for applying a pressure to the at least one membrane chromatography unit (110a), (110a '), (110b) when the at least one membrane chromatography unit (110a), (110a'), (110b) is held in the holding housing (120).

Description

Technical Field

[0001] The present invention generally relates to a holding device for use with a membrane chromatography unit. For example, a press-based device can be provided for aligning one or more modular chromatography units arranged in a series fluid arrangement and ensuring a proper sealing configuration between these modular chromatography units. Background Art

[0002] In many fields of medicine and biology, there is a need to separate various biological and / or pharmaceutical components. For example, in bioprocessing applications, it may be necessary to separate various vaccine components (mRNA, DNA, etc.) or other protein-based targets (monoclonal antibodies, etc.) from other components obtained as an output from a bioreactor.

[0003] One well-known way to separate such target components is to use chromatography-based systems and processes. For example, various commercially available chromatography systems and products (such as pure chromatography systems) can be obtained from Cytiva in Uppsala, Sweden TM Life Sciences (see, for example, www.cytivalifesciences.com). The available products also include, for example, various Fibro TM PrismA Protein A Chromatography Affinity Units, which can be used for fast cycle chromatography in research and process development applications.

[0004] It is also known to use modular chromatography units / modules to provide scalability. For example, using systems or Sartorius cartridges (Sartobind TM , Sartoflow TM , Sartocube TM , etc.) set in a holder. TM

[0005] Although using such systems (e.g., those employing "stackable" single-use tangential flow cartridges) allows for providing scalable and reconfigurable systems for filtration, etc., there is still a desire in the art to improve such systems. For example, systems that are easier to use and can operate at higher pressures / flow rates, etc., are desirable.

[0006] Therefore, the present invention is provided to overcome various drawbacks of the prior art systems and devices. Summary of the Invention

[0007] Accordingly, various aspects and embodiments of the present invention as defined by the appended claims are provided.

[0008] ​For example, in a first aspect, the present invention provides a holding device for accommodating at least one membrane chromatography unit. The holding device is suitable for use on a workbench and includes a holding housing for holding and aligning at least one membrane chromatography unit and a pressing mechanism for applying pressure to at least one membrane chromatography unit when the at least one membrane chromatography unit is held in the holding housing.

[0009] By providing the holding device according to this aspect of the present invention, a robust and compact holding housing can be provided, which is easy to clean, quick to construct and operable at high flow rates.

[0010] In addition, certain embodiments of the present invention may also provide a lightweight holding housing, which has improved portability and ease of use when the holding housing is to be used on a workbench, for example, in a clean / sterile environment for separating biological and / or pharmaceutical components. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] The present invention will now be described in more detail with reference to the drawings, in which:

[0012] Figure 1 A benchtop holding device including a membrane chromatography unit according to an embodiment of the present invention is shown;

[0013] Figure 2 A benchtop holding device according to an embodiment of the present invention is shown, Figure 1 in which there are no membrane chromatography units;

[0014] Figure 3 A disassembled view of the benchtop holding device is shown; Figure 2 in which the housing component of the pressing mechanism is removed;

[0015] Figure 4 A benchtop holding device is shown, Figure 1 in which the housing component of the pressing mechanism is removed;

[0016] Figure 5 A cross-sectional view of the benchtop holding device taken through Figure 1 is shown;

[0017] Figure 6 A tie bar clamp assembly that can be used in an embodiment of the benchtop holding device as shown in Figures 1 to 5 is shown; and

[0018] Figure 7 A tie bar clamp assembly is shown, which can alternatively or additionally be used in an embodiment of the benchtop holding device as shown in Figures 1 to 5 is shown. DETAILED DESCRIPTION

[0019] Figure 1Shown is a benchtop holding device 100 according to an embodiment of the present invention, which includes membrane chromatography units 110a, 110a', 110b. The holding device 100 may optionally be configured to be relatively lightweight, thus making it suitable for use on a benchtop.

[0020] For example, various embodiments may be provided that, in the absence of any membrane chromatography units, have a weight / mass of less than 100 kg, less than 70 kg, preferably less than 50 kg, more preferably less than 40 kg, such as about 35 kg to 38 kg, from about 5 kg or 10 kg to about 40 kg, or from about 15 kg, 20 kg, 30 kg or 34 kg, 35 kg to about 35 kg or 38 kg. Additionally, various embodiments with relatively compact dimensions may also be provided. For example, having a footprint of dimensions from about 500 mm to about 700 mm (length), from about 200 mm to about 500 mm (depth), and from about 300 mm to about 500 mm (height).

[0021] Thus, various embodiments of the present invention are more readily available than prior art devices / systems. For example, manual lifting / carrying / manipulation (with mechanical assistance (such as using pulleys / lifters / levers / guides, etc.) or without assistance) can be more easily facilitated by a single person / operator or more than one person as a team.

[0022] As Figure 1 shown, a holding housing 120 is provided for holding and aligning at least one membrane chromatography unit 110a, 110a', 110b therein. In this embodiment, the membrane chromatography units 110a, 110a', 110b take different forms depending on whether they are end front membrane chromatography units 110a / end rear membrane chromatography units 110a' or central membrane chromatography units 110b. The membrane chromatography units 110a, 110a', 110b are preferably Fibro ReadyToProcess membrane chromatography units obtainable from Cytiva Life Sciences, Uppsala, Sweden. TM Life Sciences TM membrane chromatography units.

[0023] Each of the front membrane chromatography unit 110a and the rear membrane chromatography unit 110a' is provided with a respective handle 182. These may be provided as part of a pre-assembled cartridge package having a pre-defined total internal volume. Such a pre-assembled cartridge package may be capable of operating at relatively high flow rates (e.g., when subjected to a pressure of about 8 bar to 10 bar or up to about 10 bar).

[0024] The inlet 184 is provided on the outer portion of the front membrane chromatography unit 110a, and the outlet 186 is provided on the outer portion of the rear membrane chromatography unit 110a'. In the case where any central membrane chromatography unit 110b is provided, a fluid channel exists between the inlet 184 and the outlet 186, and this fluid channel passes through both the end front membrane chromatography unit 110a / end rear membrane chromatography unit 110a' and any such central membrane chromatography unit 110b. In the case where no central membrane chromatography unit 110b is provided, a fluid channel is provided between the inlet 184 and the outlet 186, and once the front membrane chromatography unit 110a and the rear membrane chromatography unit 110a' are pressed together in the holding housing 120, this fluid channel passes through both the front membrane chromatography unit 110a and the rear membrane chromatography unit 110a'.

[0025] A pressing mechanism 130 is also provided, and the pressing mechanism 130 is used to apply pressure to at least one of the membrane chromatography units 110a, 110a', 110b when at least one of the membrane chromatography units 110a, 110a', 110b is held in the holding housing 120. The holding housing 120 is also designed to automatically align one or more of the membrane chromatography units 110a, 110a', 110b such that their fluid connection ports match and are sealed under the pressure applied by the pressing mechanism 130.

[0026] In Figure 1 an embodiment, the pressing mechanism 130 is manually operable. However, this is not a necessary requirement, and various alternative pressing mechanisms can be used as required. Additionally, preferably, the pressing mechanism 130 can be operated to apply a force of up to about 25 kN (e.g., about 23 kN) on any of the membrane chromatography units 110a, 110a', 110b provided therein.

[0027] Various membrane chromatography units 110a, 110a', 110b or their assembled packages can be provided. For example, volumes of 20 mL, 40 mL, 60 mL, … 120 mL, 140 mL, 160 mL, etc. can be used. For example, such membrane chromatography units 110a, 110a', 110b or their assembled packages can be operated at 0 bar to 10 bar. High-pressure operation (e.g., at about 8 bar to 10 bar or up to about 10 bar or more bar) can be used to provide a faster flow rate in order to increase the overall process productivity.

[0028] Although Figure 1 multiple forms of membrane chromatography units are shown therein, those skilled in the art will realize that a holding device can also be provided in which all of the membrane chromatography units to be used therein are substantially the same.

[0029] Figure 2 showing in accordance with an embodiment of the present invention Figure 1Tabletop holding device 100, in which there is no membrane chromatography unit in the tabletop holding device 100. The holding device 100 has a size / volume footprint of 688 mm (length L), 455 mm (depth D), and 388 mm (height H). The pressing mechanism 130 includes a hydraulic unit 132, which, in this embodiment, includes a manual pump, a pressure gauge 134, and a shut-off / check valve 136. The shut-off / check valve 136 allows oil to flow through it in one direction until the desired pressure (e.g., nominal 190 bar) is reached using the pressing mechanism 130. The shut-off / check valve 136 further prevents oil from flowing in the reverse direction until it is opened to retract the tabletop holding device 100.

[0030] The pressing mechanism 130 is connected to the holding housing 120 in the front frame part 140 of the holding housing 120. The holding housing 120 further includes a rear frame part 142, which is connected to the front frame part 140 by means of a base tray 158, which is arranged between the rear frame part 142 and the front frame part 140. The base tray 158 can be arranged to act as an overflow tray and / or can be made of multiple segments, for example as a split base, for ease of manufacture. A first pair of feet 146 is arranged on the base tray 158, and a second pair of feet 146 is arranged on the front frame part 140 for supporting the holding device 100 together when in use.

[0031] The rear frame part 142 and the front frame part 140 are further connected by a pair of handles 154 arranged substantially parallel to each other, which extend generally parallel to the central axis of the holding device 100 along the length axis (L). Such handles 154 allow the holding device 100 to be lifted manually. However, alternative embodiments can be provided, for example, which include one or more handles / attachment points / holes / etc., for example to assist in the manual lifting or manually activated lifting of the holding device 100.

[0032] A pair of tie rods 144 is also provided, which are arranged generally parallel to the central axis of the holding device 100 along the length axis (L). The tie rods 144 are maintained in a fixed relationship within the holding housing 120 between the rear frame part 142 and the front frame part 140 by means of a plurality of tie rod clamp assemblies 156, 256 ( Figure 3This arrangement is shown in more detail). Tie rod 144 supports the rear force beam 150 adjacent to the rear portion 142 of the frame in a fixed relationship between the tie rod 144 and the rear force beam 150. Tie rod 144 also supports the front force beam 148 adjacent to the front portion 140 of the frame in a movable relationship between the tie rod 144 and the front force beam 148. Both the rear force beam 150 and the front force beam 148 are provided with corresponding force plates 152 attached thereto, and when the membrane chromatography units 110a, 110a', 110b are inserted into the holding device 100 under pressure, the corresponding force plates 152 engage the corresponding membrane chromatography units 110a, 110a', 110b.

[0033] The piston-connected actuator rod 160 connects the pressing mechanism 130 to the front force beam 148 through the front frame 140. Thus, actuation of the pressing mechanism 130 causes the front force beam 148 to translate slidably along the tie rod 144 such that force can be applied to any of the membrane chromatography units 110a, 110a', 110b disposed between the force plates 152.

[0034] Figure 3 shown Figure 2 An exploded view of the benchtop holding device 100 is shown. The front portion 140 of the frame is provided with a pair of feet 146, and so is the base tray 158. The feet 146 may include corresponding base rubber feet, flat washers (e.g., Form A ISO7089 4.3 - A4), fasteners, etc. The pressing mechanism 130 including at least one housing member 166 (e.g., a panel which may be removable to enable full evaluation, verification of equipment specifications, operation, supportive safety information, etc.) fits into the front portion 140 of the frame and is held in the front portion 140 of the frame by corresponding fasteners 168. In various embodiments, an interlocking mechanism (not shown) may be provided such that operation of the pressing mechanism 130 is prohibited in case any of the housing members 166 is missing or not properly secured.

[0035] The front frame portion 140 and the rear frame portion 142 are connected to the base tray 158. Optionally, the base tray 158 can act as a drip tray to capture hydraulic fluid in case of any leakage. Alternatively or additionally, a separate drip tray (not shown) can be provided. The base tray 158 can be formed in multiple segments. Guide rails 188 are also present on the base tray 158. The guide rails 188 extend along the length axis L of the holding device 100. The guide rails 188 are keyed in shape to cooperate with complementary notches provided in the membrane chromatography units 110a, 110a', 110b. This enables the base tray 158 and the guide rails 188 to cooperate with the force plate 152 to provide a frame that aligns the membrane chromatography units 110a, 110a', 110b in the correct orientation when they are placed into the holding device 100. In some embodiments, the guide rails 188 or the like (e.g., grooves) can be asymmetrically shaped and / or positioned to further help prevent misinsertion of the membrane chromatography units 110a, 110a', 110b into the holding device 100.

[0036] A pair of tie rods 144 are provided. Each tie rod 144 includes four respective circumferential grooves 162 that are longitudinally separated from each other. These circumferential grooves 162 are each preferably semi-circular in cross-section and are adapted to connect to corresponding tie rod clamp assemblies 156, 256 (see Figure 6 and Figure 7 ). The two tie rod clamp assemblies 156, 256 that are closest to the pressing mechanism 132 and connected to each tie rod 144 are used to releasably secure the respective tie rod 144 to the front frame portion 140. The other two tie rod clamp assemblies 156, 256 are also capable of being releasably connected to each tie rod 144 at a location near the rear frame portion 142. For each tie rod 144, the two tie rod clamp assemblies 156, 256 secure the tie rod 144 to the holding device 100 at the front frame portion 140 to prevent forward / backward movement of the tie rod 144. The most central tie rod clamp assemblies 156, 256 act as "transport clamps" that restrain the front force beam 148 and the rear force beam 150 when the front force beam 148 moves. The outermost tie rod clamp assemblies 156, 256 near the rear force beam 150 are used to set the size of the compression zone by providing a "rear stop" for the force plate 152. For ergonomics and fastening safety, the tie rod clamp assemblies 156, 256 can be operated in a quick-release manner. Thus, such an arrangement provides a holding device 100 with a high-stiffness, high-strength skeleton that can be disposed within an aesthetic exterior.

[0037] In Figure 3Also depicted are various additional fixing components, fasteners 168, grommets 164, and bushings 170 used in the assembly of the holding device 100. Since the functions of these components are considered to be clear to those skilled in the art, they are not described further here, except to say that they may include one or more of the following: socket head cap screws, socket head flat countersunk screws (e.g., M10X20 - A4), socket head round head screws (e.g., M4X10 - A2), socket head pan head screws (e.g., M5X8 - A4 - 70), nuts, bolts, etc.

[0038] In this embodiment, the front force beam 148, the rear force beam 150, the force plate 152, and the tie rod 144 are preferably made of solid material. For example, steel (e.g., stainless steel, such as EN1.4404 stainless steel, EN1.4462 stainless steel, etc.) materials can be used for these (and other) components. In this example, the tie rod 144 is made to have a diameter of 19 mm, preferably made of EN1.4462 stainless steel (compared with some conventional presses that use a 25 - mm beam with a notch having a substantially square cross - section), thus providing a significant weight advantage.

[0039] In this embodiment, the holding device 100 has a weight / mass of approximately 35 kg and a size / volume footprint of 688 mm (length L), 455 mm (depth D), and 388 mm (height H), thus making it suitable for table - top use. For example, a prototype of the fabricated holding device 100 has a total mass of approximately 37 kg to 38 kg, of which 18 kg includes the load - bearing elements (front force beam 148, rear force beam 150, force plate 152, tie rod 144, and tie rod clamp assemblies 156, 256), 8.5 kg includes the pressing mechanism 130, and 11 kg includes the remainder.

[0040] Figure 4 Shown Figure 1 is the table - top holding device 100 from which the housing component 166 of the pressing mechanism 130 has been removed. The pressing mechanism 130 may include an interlocking mechanism connected to the housing component 166, and then the absence of the housing component 166 causes the operation of the pressing mechanism 130 to be prohibited. As Figure 4 shown in, the table - top holding device 100 can be set on a support trolley 190. Such a support trolley 190 is optionally provided as an accessory to enable the table - top holding device 100 to be moved more easily.

[0041] Figure 5 Shown through Figure 1Cross-sectional view of the tabletop holding device 100. As described above, the embodiments discussed herein are relatively lightweight tabletop versions of the holding device 100. However, those skilled in the art will recognize that the present invention is not limited to the tabletop variant of the holding device 100.

[0042] Figure 6 Shows a tie rod clamp assembly 156 used in an embodiment of a holding device (such as the tabletop holding device 100 shown in Figures 1 to 5 ). The tie rod clamp assembly 156 includes a first tie rod clamp portion 172 and a second tie rod clamp portion 174. The first tie rod clamp portion 172 and the second tie rod clamp portion 174 are each substantially semi-circular in shape and are joined together by a pivot attachment 180.

[0043] Each of the first tie rod clamp portion 172 and the second tie rod clamp portion 174 includes a respective radially inwardly facing semi-circular tie rod engaging edge 178. The edge is preferably arcuate and semi-cylindrical. The tie rod engaging edge 178 itself is substantially semi-circular in cross-section. Compared with prior art systems, the provision of such a semi-circular cross-sectional engaging edge 178 advantageously enables embodiments of the present invention to use greater forces (e.g., because it can reduce any induced local stress accumulation associated with notches and the like of angular shapes).

[0044] A pivotable snap mechanism 176 is attached to the second tie rod clamp portion 174 and is configured to engage the first tie rod clamp portion 172 when the first tie rod clamp portion 172 and the second tie rod clamp portion 174 are brought together in an annular arrangement (closed) position.

[0045] Thus, when the tie rod clamp assembly 156 is in the open position (as shown in Figure 6 ), the tie rod engaging edge 178 can be placed adjacent to the groove 162 of the tie rod 144. Then, the first tie rod clamp portion 172 and the second tie rod clamp portion 174 can be brought together into an annular arrangement (closed) position, and the snap mechanism 176 can then be engaged to lock the tie rod clamp assembly 156 to the tie rod 144.

[0046] Figure 7 Shows a tie rod clamp assembly 256, which can be used additionally or alternatively in an embodiment of a holding device (such as the tabletop holding device 100 shown in Figures 1 to 5 ).

[0047] The tie bar clamp assembly 256 includes a first tie bar clamp portion 272 and a second tie bar clamp portion 274. The first tie bar clamp portion 272 and the second tie bar clamp portion 274 are each substantially semi-circular in shape and are joined together by a first pivot attachment 280. Each of the first tie bar clamp portion 272 and the second tie bar clamp portion 274 includes a respective radially inwardly facing semi-circular tie bar engaging edge 278. The edge is preferably arcuate and semi-cylindrical in shape. The tie bar engaging edge 278 itself is substantially semi-circular in cross-section. Such a tie bar clamp assembly can provide a greater surface contact area between components, enabling them to withstand higher pressures than conventional systems.

[0048] The pivotable latch mechanism 276 is attached to the second tie bar clamp portion 274 by way of a second pivot attachment 282 and is configured to engage the first tie bar clamp portion 272 when the first tie bar clamp portion 272 and the second tie bar clamp portion 274 are brought together in an annular arrangement (closed) position, as shown. The pivotable latch mechanism 276 includes a substantially bolt-shaped member that includes a shaft portion connected to a head portion. The shaft portion is coupled to the second pivot attachment 282 near the end thereof, and the head portion is configured to reside in a recessed portion of the first tie bar clamp portion 272 when in the closed position.

[0049] In the present application, the terms "weight" and "mass" have been used interchangeably. Additionally, for the avoidance of doubt, the content of all or any of the previously mentioned documents, products, etc. is hereby incorporated herein by reference in its entirety to the maximum extent permitted.

[0050] Accordingly, various compact and relatively lightweight embodiments of the present invention can be provided. Improved ease of use, ease of cleaning, and suitability for use in a clean / sterile environment can also be provided or alternatively provided. Such embodiments can further allow the use of only a manually operated pump to apply an increased holding force. For example, compared to conventional equipment, an increase in the holding force that can be applied of five to ten times can be achieved. For example, various embodiments can provide a compressive force of about 20 kN (e.g., from about 20 kN to about 23 kN, or about 23 kN) to a compression zone that is held at a decompression of 5% or less for more than 16 hours. Such embodiments are also useful in a cleanroom environment and can be made resistant to cleaning compounds such as, for example: up to 0.5% chlorine compound, up to 35% hydrogen peroxide (H2O2), 2% Virkon, 10% Decon 90, etc.

[0051] In addition, in various embodiments, a pre-assembled cartridge package may be provided that is set with a pre-defined total internal volume. Using such a pre-assembled cartridge package within the holding device of the present invention provides various advantages. For example, not only is the setup time reduced, but it is also not necessary to provide fluid manifolds / connectors, etc. within the components of the holding device itself (i.e., by using various components without fluid paths, different from various prior art systems). Thus, various embodiments of the present invention can be made easier to clean than some prior art systems. For ease of connection / installation, the various inlets / outs of the cartridge package can also be configured to align with other related bioprocessing equipment (e.g., with ready TM the column position of a chromatography system).

[0052] In addition, various embodiments have an ergonomic design in which all controllers, etc. are easily accessible. Guide features for easily aligning the disposable membrane chromatography units / modules used therein may also preferably be provided to further contribute to ease of use.

[0053] Embodiments may also be provided in which one or more sensors are provided. For example, one or more sensors may also be provided for one or more of the following purposes: detecting the presence of at least one chromatography unit / module; providing an indicator / alert / locking function if the user attempts to pressurize the device without any modules in the device; providing underpressure and / or overpressure sensing; detecting the correct movement of a pressing mechanism or parts connected thereto, e.g., in order to detect any foreign objects and / or kinked / damaged ties, etc. present. Thus, an automated (or semi-automated) system can be provided in which a predetermined pressure / force can be applied within a target range, e.g., as a fixed value, or based on the number or type of modules used / detected.

[0054] Additional embodiments are envisioned in which parts thereof (such as ties, etc.) can be formed using at least one substantially hollow component to further reduce the weight / mass of the device. Thus, various embodiments of the present invention can provide a holding device having a force generation to weight ratio of at least about 0.05 kN / kg, 0.07 kN / kg, 0.1 kN / kg, 0.2 kN / kg or 0.25 kN / kg, 0.5 kN / kg, 0.7 kN / kg or 1 kN / kg, from about 0.1 kN / kg or about 0.25 kN / kg to about 0.3 kN / kg, 0.4 kN / kg or about 0.5 kN / kg, or from about 0.1 kN / kg, 0.2 kN / kg or 0.25 kN / kg to about 0.5 kN / kg, 0.7 kN / kg or about 1 kN / kg.

[0055] Additional envisioned embodiments also include a holding device that includes one or more wheels, sliders, or the like. These may be lockable / retractable / removable, etc., to further facilitate moving the device within a laboratory / production facility. For example, various "suitcase-like" embodiments may be envisioned, where the device is provided with one or more wheels at one end thereof and a handle at its opposite end.

[0056] In addition, for example, while the embodiments described herein depict the use of a manually operated pump, those skilled in the art will understand that alternative variations will be possible. For example, various embodiments may be provided that have one or more electric, power hydraulic, etc. pumps, which are optionally provided with a control system operable to ensure that overpressure / underpressure does not occur. Many other possible modifications will also be obvious to those skilled in the art.

[0057] Accordingly, various aspects and embodiments of the invention have been described. However, the invention will not be considered limited to the embodiments described above, but may vary within the scope of the appended claims, as will be readily apparent to those skilled in the art.

Claims

1. A holding device (100) for holding at least one membrane chromatography unit (110a, 110a', 110b), the holding device (100) comprising: A holding housing (120) for holding and aligning at least one membrane chromatography unit (110a, 110a', 110b); And A pressing mechanism (130) for applying pressure to the at least one membrane chromatography unit (110a, 110a', 110b) when the at least one membrane chromatography unit (110a, 110a', 110b) is held in the holding housing (120).

2. The holding device (100) according to claim 1, wherein, The holding housing (120) includes a frame (152, 158, 188) for holding and aligning the at least one membrane chromatography unit (110a, 110a', 110b) in a fluid configuration connected in series.

3. The holding device (100) according to claim 1 or 2, further comprising at least one movable force beam (148) for compressing the at least one membrane chromatography unit (110a, 110a', 110b).

4. The holding device (100) according to claim 3, wherein, The at least one movable force beam (148) is slidably mounted on at least one tie rod (144).

5. The holding device (100) according to claim 4, wherein, Each respective tie rod (144) is held within the holding housing (120) by at least one tie rod clamp assembly (156, 256).

6. The holding device (100) according to any one of the preceding claims, further comprising a rear force beam (150).

7. The holding device (100) according to any one of claims 3 to 6, wherein, The at least one movable force beam (148) and / or the rear force beam (150) is free of fluid paths.

8. The holding device (100) according to claim 7, wherein, The at least one movable force beam (148) and / or the rear force beam (150) is formed of solid material.

9. The holding device (100) according to any one of the preceding claims, further comprising therein one or more housing parts (166), and optionally therein, At least one of the housing components (166) includes an interlocking mechanism.

10. The holding device (100) according to any one of the preceding claims, having a weight / mass of less than 100 kg, less than 70 kg, preferably less than 50 kg, more preferably less than 40 kg, such as from about 5 kg or 10 kg to about 40 kg, or from about 15 kg to about 35 kg, in the absence of any membrane chromatography unit (110a, 110a', 110b).

11. The holding device (100) according to claim 10, wherein, The frame (152, 158) portion / the frame (152, 158) portion has a weight / mass of less than 70 kg, such as from about 15 kg to about 25 kg.

12. The holding device (100) according to any one of the preceding claims, having a size / volume footprint of from about 500 mm to about 700 mm (length), from about 200 mm to about 500 mm (depth), and from about 300 mm to about 500 mm (height).

13. The holding device (100) according to claim 12, wherein, The size / volume footprint is about 700 mm (length), about 400 mm (depth), and about 400 mm (height).

14. The holding device (100) according to any one of the preceding claims, wherein, The pressing mechanism (130) is operable to: i) apply a force of up to about 25 kN; and / or ii) pressurize at least one of the membrane chromatography units (110a, 110a', 110b) therein to a pressure greater than about 2 bar, 3 bar, 4 bar, 5 bar, 6 bar, 7 bar, 8 bar, 9 bar, 10 bar, 11 bar or 12 bar, from about 2 bar, 3 bar, 4 bar, 5 bar, 6 bar or 7 bar to about 8 bar, 9 bar, 10 bar, 11 bar or 12 bar, from about 8 bar to 10 bar, or up to about 10 bar.

15. The holding device (100) according to any one of the preceding claims, wherein, The pressing mechanism (130) is manually operable.

16. The holding device (100) according to any one of the preceding claims, further comprising at least one handle (154), attachment point, eyelet or the like.

17. The holding device (100) according to any one of the preceding claims, further comprising one or more wheels, sliders or the like.

18. A tie-down clamp assembly (156, 256) for use in a holding device (100) according to any one of the preceding claims, the tie-down clamp assembly (156, 256) comprising: a first tie-down clamp portion (172, 272) rotatably coupled to a second tie-down clamp portion (174, 274); and at least one pivotable snap mechanism (176, 276) for prohibiting rotational movement of the first tie-down clamp portion (172, 272) relative to the second tie-down clamp portion (174, 274) about a first pivot attachment (180, 280).

19. The tie rod clamp assembly (156, 256) according to claim 18, wherein, The first tie-down clamp portion (172, 272) and the second tie-down clamp portion (174, 274) include corresponding tie-down engagement edges (178, 278).

20. The tie rod clamp assembly (156, 256) according to claim 19, wherein, The tie-down engagement edges (178, 278) are substantially semi-circular in cross-section and / or substantially arcuate and semi-cylindrical in shape.

21. The tie rod clamp assembly (256) according to any one of claims 18 to 20, wherein, The pivotable snap mechanism (276) includes a substantially bolt-shaped or T-shaped member, the substantially bolt-shaped or T-shaped member including a shaft portion connected to a head portion.

22. The tie bar clamp assembly (256) according to claim 21, wherein, The shaft portion is coupled to the second pivot attachment (282) near an end thereof, and the head portion is configured to reside in a recessed portion of the first tie-down clamp portion (272) when in a closed position.

23. A chromatography unit (110a, 110a', 110b) for use in a holding device (100) according to any one of claims 1 to 17, the chromatography unit (110a, 110a', 110b) including at least one keying feature, such as a notch or a protrusion, in its housing for keying engagement with a guide rail (188) or other complementary keying features of the holding device (100).

24. The chromatography unit (110a, 110a', 110b) according to claim 23, wherein, The chromatography unit (110a, 110a', 110b) includes at least one handle (182), the chromatography unit (110a, 110a', 110b) is a single-use product, the chromatography unit (110a, 110a', 110b) is provided pre-sterilized (e.g., by gamma radiation), and the chromatography unit (110a, 110a', 110b) is stackable and / or is provided with one or more quick-removable seals / covers (e.g., film-based caps) at its fluid ports.

25. A pre-assembled cassette package comprising a plurality of chromatographic units (110a, 110a', 110b) as defined in claim 23 or 24, wherein, Its first chromatography unit (110a) and second chromatography unit (110a') include corresponding ports of a fluid inlet port and a fluid outlet port.

26. The pre-assembled cassette package according to claim 25, wherein, The first chromatography unit (110a) and the second chromatography unit (110a') are provided with corresponding handles (182).

27. A method for separating biological components from a fluid mixture, comprising: i) providing a holding device (100) as defined in any one of claims 1 to 17; ii) installing at least one chromatography unit (110a, 110a', 110b) in the holding device (100); iii) pressurizing the at least one chromatography unit (110a, 110a', 110b); and iv) using the pressurized at least one chromatography unit (110a, 110a', 110b) to separate biological components from a fluid mixture.

28. The method according to claim 27, further comprising placing the holding device (100) on a work surface or tabletop before step ii).

29. The method according to claim 27 or 28, wherein, Step ii) of installing at least one chromatography unit (110a, 110a', 110b) in the holding device (100) includes installing a pre-assembled cartridge having a pre-determined internal volume in the holding device (100).

30. The method according to any one of claims 27 to 29, wherein Step iii) of pressurizing the at least one chromatography unit (110a, 110a', 110b) includes pressurizing the at least one chromatography unit (110a, 110a', 110b) to a pressure greater than about 2 bar, 3 bar, 4 bar, 5 bar, 6 bar, 7 bar, 8 bar, 9 bar, 10 bar, 11 bar or 12 bar, from about 2 bar, 3 bar, 4 bar, 5 bar, 6 bar or 7 bar to about 8 bar, 9 bar, 10 bar, 11 bar or 12 bar, from about 8 bar to 10 bar, or up to about 10 bar.

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