Holding device for membrane chromatography unit

Abstract

The present invention relates to a holding device (100) for use with at least one membrane chromatography unit (110a, 110a', 110b). The holding device (100) is suitable for use on a tabletop and, in various embodiments, is relatively lightweight and can be manually lifted. The holding device (100) includes a holding housing (120) for holding and aligning at least one membrane chromatography unit (110a, 110a', 110b). The holding device (100) also includes a pressing mechanism (130) for applying pressure to the at least one membrane chromatography unit (110a, 110a', 110b) when it is held within the holding housing.

Description

[Technical Field]

[0001] The present invention relates generally to a retention device for use with a membrane chromatography unit, for example, a press-type device can be provided to align and ensure a precise sealing arrangement between one or more modular chromatography units mounted within the device in a serial fluidic arrangement. [Background technology]

[0002] Many areas of medicine and biology require the separation of various biological or pharmaceutical components. For example, in bioprocessing applications, it may be necessary to separate various vaccine components (e.g., mRNA, DNA) or other protein-based targets (e.g., monoclonal antibodies) from other components extracted as output from a bioreactor.

[0003] One well-known method for separating such target components is the use of a chromatography-based system or process. For example, various commercially available chromatography systems and products, such as the A (note: umlaut A) KTA™ Pure Chromatography System, are available from Cytiva™ Life Sciences, Uppsala, Sweden (see, e.g., www.cytivalifesciences.com). Available products also include, for example, various Fibro™ PrismA protein A chromatographic affinity units that can be used for fast recirculation cycle chromatography in research and process development applications.

[0004] The use of modular chromatography units / modules is also known to provide scalability, for example, the use of KTA™ systems and Sartorius™ cassettes housed in holders (Sartobind™, Sartoflow™, Sartocube™, etc.).

[0005] While the use of such systems, for example employing "stackable" single-use tangential flow cassettes therein, allows for the provision of expandable and reconfigurable systems for filtration and the like, improvements to such systems remain desirable in the art. For example, systems that are easier to use and can operate at higher pressures / flow rates, etc. are desirable.

[0006] SUMMARY OF THE INVENTION Accordingly, the present invention is provided to address various shortcomings of prior art systems and devices. Summary of the Invention

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

[0008] For example, in a first aspect, the present invention provides a holding device for housing at least one chromatography unit, the holding device may be suitable for use on a benchtop and comprises a holding enclosure for holding and aligning the at least one chromatography unit, and a pressing mechanism for applying pressure to the at least one chromatography unit held within the holding enclosure.

[0009] By providing a retention device according to this aspect of the invention, a powerful, compact retention device can be provided that is easy to clean, quick to assemble, and can also be operated at high flow rates.

[0010] Additionally, certain embodiments of the present invention may provide a lightweight holding housing that enhances portability and ease of use, for example, when used on a benchtop to separate biological or pharmaceutical components in a clean / sterile environment. [Brief explanation of the drawings]

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

[0012] [Figure 1] 1 is a diagram showing a tabletop holder 100 including a membrane chromatography unit according to an embodiment of the present invention. [Figure 2] 2 is a diagram showing the tabletop holder of FIG. 1 with all membrane chromatography units removed according to an embodiment of the present invention. FIG. [Figure 3] 3 is an exploded view of the tabletop holder device shown in FIG. 2.

[0023] FIG. [Figure 4] 2 is a view showing the tabletop holder 100 of FIG. 1 with the casing parts of the press mechanism removed. FIG. [Figure 5] FIG. 2 is a cross-sectional view of the tabletop holder 100 of FIG. [Figure 6] 6A-6C show a tie rod clamp assembly that can be used in embodiments of the tabletop support device such as those shown in FIGS. 1-5. [Figure 7] 6 shows a tie rod clamp assembly that may additionally or alternatively be used in embodiments of the tabletop support device such as those depicted in FIGS. 1-5. FIG. DETAILED DESCRIPTION OF THE INVENTION

[0013] 1 shows a tabletop holder 100 having membrane chromatography units 110a, 110a', and 110b according to one embodiment of the present invention. Optionally, the holder 100 may be configured to be relatively lightweight, making it suitable for use on a tabletop.

[0014] For example, various embodiments may be provided in which the weight or mass excluding the membrane chromatography unit is less than 100 kg, less than 70 kg, preferably less than 50 kg, and more preferably less than 40 kg (e.g., about 35 kg to about 38 kg, about 5 kg or about 10 kg to about 40 kg, or about 15, 20, 30, 34, 35 to about 35 kg, or about 38 kg). Furthermore, various embodiments may be provided that have a relatively compact size. For example, the size or volume may be about 500 to about 700 mm (length), about 200 to about 500 mm (depth), and about 300 to about 500 mm (height).

[0015] As such, various embodiments of the present invention are easier to use than prior art devices / systems, for example manual lifting / handling / manipulation (either with or without mechanical assistance using pulleys / hoists / levers / guides, etc.) can be more easily performed by either one person / operator or multiple people working as a team.

[0016] 1, the holding housing 120 holds and aligns 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 front / rear membrane chromatography units 110a, 110a' or central membrane chromatography units 110b. The membrane chromatography units 110a, 110a', 110b are preferably Fibro ReadyToProcess™ membrane chromatography units available from Cytiva™ Life Sciences, Uppsala, Sweden.

[0017] Each of the front and rear membrane chromatography units 110a, 110a' is provided with a handle 182. These may be provided as part of a pre-assembled cassette package having a predetermined total volume. Such a pre-assembled cassette package may be operable at a relatively high flow rate (e.g., when subjected to a pressure of about 8-10 bar, or about 10 bar).

[0018] An inlet 184 is provided on the outer portion of the front membrane chromatography unit 110a, and an outlet 186 is provided on the outer portion of the rear membrane chromatography unit 110a'. When the central membrane chromatography unit 110b is installed, a fluid channel exists between the inlet 184 and the outlet 186 that passes through both the front / rear membrane chromatography units 110, 110a' and the central membrane chromatography unit 110b. When the central membrane chromatography unit 110b is not installed, once pressed into the holding housing, a fluid channel exists between the inlet 184 and the outlet 186 that passes through both the front / rear membrane chromatography units 110a, 110a'.

[0019] A pressing mechanism 130 is further provided to apply pressure to at least one of the membrane chromatography units 110a, 110a', 110b when the membrane chromatography units 110a, 110a', 110b are held in the holding housing 120. The holding housing 120 is further designed to automatically align the one or more membrane chromatography units 110a, 110a', 110b such that the fluid connection ports of the one or more membrane chromatography units 110a, 110a', 110b match and are sealed under pressure from the pressing mechanism 130.

[0020] 1, the pressing mechanism 130 is manually operable. However, this is not a requirement, and various alternative pressing mechanisms may be used as desired. Furthermore, the pressing mechanism 130 is preferably operable to apply a force of up to about 25 kN (e.g., about 23 kN) to any one or more of the membrane chromatography units 110a, 110a', and 110b disposed therein.

[0021] Various membrane chromatography units 110a, 110a', 110b, or assembled packages thereof may be provided. For example, capacities of 20 ml, 40 ml, 60 ml, ..., 120 ml, 140 ml, 160 ml, etc. may be used. Such membrane chromatography units 110a, 110a', 110b, or assembled packages thereof may be operated under pressures of, for example, 0 bar to 10 bar. The use of higher pressure operation (e.g., about 8 bar to 10 bar, less than 10 bar, or greater than about 10 bar) can be used to provide higher flow rates and thereby improve the productivity of the overall process.

[0022] Although multiple configurations of membrane chromatography units are shown in Figure 1, those skilled in the art will recognize that it is also possible to provide a holding device in which all of the internal membrane chromatography units used therein are substantially identical.

[0023] FIG. 2 shows the tabletop support device 100 of FIG. 1 without any internal membrane chromatography unit, according to one embodiment of the present invention. The tabletop support device 100 has a footprint or volume of 688 mm in length L, 455 mm in depth D, and 380 mm in height H. The press mechanism 130 includes a hydraulic unit 132, which in this example is a hand pump, a pressure gauge 134, and a shutoff / check valve 136. The shutoff / check valve 136 allows oil to flow in one direction through the press mechanism 130 until a desired pressure (e.g., a nominal 190 bar) is reached. Furthermore, the shutoff / check valve 136 prevents oil from flowing in the reverse direction until the valve is opened to retract the tabletop support device 100.

[0024] The press mechanism 130 is connected to the holding housing 120 within the housing's front frame portion 140. The holding housing 120 also includes a rear frame portion 142 joined to the front frame portion 140 via a base tray 158 disposed therebetween. The base tray 158 may be provided to function as a spill tray and / or may be made from multiple pieces, e.g., as a split base, for ease of manufacturing. A pair of first legs 146 are provided on the base tray 158, and a pair of second legs 146 are provided on the front frame portion 140 to together support the holding device 100 during operation.

[0025] Additionally, the rear frame portion 142 and the front frame portion 140 are connected by a pair of handles 154 arranged substantially parallel to one another and extending generally parallel to the central axis of the support device 100 along the length axis (L). Such handles 154 allow for manual lifting of the support device. However, other embodiments may be provided that include, for example, one or more handles / attachment points / eyelets to assist in manual or manual lifting of the support device.

[0026] A pair of tie rods 144 are also provided, extending generally parallel to the central axis of the support device 100 along the length axis (L). The tie rods 144 are held in a fixed relationship between the rear frame 142 and the front frame 140 within the support housing 120 by a plurality of tie rod clamp assemblies 156, 256 (the arrangement of which is shown in more detail in FIG. 3). The tie rods 144 support a rear force beam 150 adjacent to the rear frame 142 in a fixed relationship therebetween. The tie rods 144 also support a front force beam 148 adjacent to the front frame 140 in a movable relationship therebetween. Both the rear force beam 150 and the front force beam 148 are respectively fitted with force plates 152 that engage with each of the membrane chromatography units 110a, 110a', and 110b when the membrane chromatography units 110a, 110a', and 110b are inserted into the support device and pressurized.

[0027] A piston-connected actuator rod 160 passes through the front frame 140 and couples the press mechanism 130 to the front force beam 148. Thus, actuation of the press mechanism 130 causes the front force beam 148 to slide along the tie rods 144 so that a force can be applied to any membrane chromatography units 110a, 110a′ disposed between the force plates 152.

[0028] FIG. 3 shows an exploded view of the tabletop support device 100 shown in FIG. 2. The front frame 140 is provided with a pair of legs 146, as well as a base tray 158. The legs 146 may include respective base rubber feet, plain washers (e.g., Form A ISO 7089 4.3-A4), fasteners, etc. A press mechanism 130, including at least one casing piece 166 (e.g., a removable panel to allow for a complete assessment, verification of equipment specifications, operation, and safety information, etc.), fits onto the front frame 140 and is retained therein by respective fasteners 168. In various embodiments, an interlocking mechanism (not shown) is provided to inhibit operation of the press mechanism 130 if the casing piece 166 is missing or insufficiently secured.

[0029] The front frame 140 and the rear frame 142 are connected to a base tray 158. Optionally, the base tray 158 may function as a drip tray to capture any leaking hydraulic fluid. Alternatively, or in addition, a separate drip tray (not shown) may be provided. The base tray 158 may be comprised of multiple sections. Guide rails 188 are also present on the base tray 158. The guide rails 188 extend along the longitudinal axis (L) of the holding device 100. The guide rails 188 are keyed to align with notches in the alternating membrane chromatography units 110a, 110a', and 110b. The base tray 158 and the guide rails 188, in cooperation with the force plate 152, provide a frame that properly aligns the membrane chromatography units 110a, 110a', and 110b when installed within the holding device 100. In certain embodiments, the guide rails 188 or similar (e.g., grooves) may be asymmetrically shaped and / or positioned to prevent incorrect insertion of the membrane chromatography units 110a, 110a', 110b within the holding device 100.

[0030] A pair of tie rods 144 are provided. Each tie rod 144 has four longitudinally spaced circumferential grooves 162, respectively. These circumferential grooves 162 are preferably semicircular in cross section and connectable to respective tie rod clamp assemblies 156, 256 (see FIGS. 6 and 7). Two tie rod clamp assemblies 156, 256 connected to each tie rod 144 nearest the press mechanism 132 are used to releasably secure each tie rod 144 to the front frame 140. Two additional tie rod clamp assemblies 156, 256 also releasably connect each tie rod 144 proximal to the rear frame 142. For each tie rod 144, the tie rod clamp assemblies 156, 256 secure the tie rod 144 within the retention device 100 at the front frame 140, thereby preventing fore-and-aft movement of the tie rod 144. The center-most tie rod clamp assembly 156, 256 functions as a "shipping clamp" that restrains the front force beam 148 and the rear force beam 150 as the front force beam 148 moves. The final tie rod clamp assembly 156, 256 proximal to the rear force beam 150 is used to set the size of the compression zone by providing a "backstop" for the force plate 152. The tie rod clamp assemblies 156, 256 are quick-release operated for ergonomics and clamping security. This arrangement therefore provides the retention device 100 with a high-rigidity, high-strength framework that can be installed within a decorative enclosure.

[0031] Also depicted in Figure 3 are various additional fasteners, fasteners 168, grommets 164, bushings 170 that may be used in the assembly of the retention device 100. The function of these will be apparent to one skilled in the art and will not be described further herein, but may include one or more of hex socket head bolts, hex socket flat CS head bolts (e.g., M10X20-A4), hex socket button head bolts (e.g., M4X10-A2), hex socket pan head bolts (e.g., M5X8-A4-70), nuts, bolts, etc.

[0032] In this embodiment, the front force beam 148, the rear force beam 150, the force plate 152, and the tie rods 144 are preferably made of a solid material. For example, steel (e.g., stainless steel, such as EN 1.4404 stainless steel, EN 1.4462 stainless steel, etc.) materials can be used for these (and other) components. In this example, the tie rods 144 are 19 mm in diameter, preferably made of EN 1.4462 stainless steel, thereby providing a substantial weight advantage (compared to conventional presses that use 25 mm beams with substantially square cross-section cutouts).

[0033] In this embodiment, holding apparatus 100 has a weight or mass of 35 kg and a footprint / volume of 688 mm (length L), 455 mm (depth D), and 388 mm (height H), making it suitable for use on a benchtop. For example, a prototype of holding apparatus 100 has a total mass of approximately 37-38 kg, of which 18 kg consists of the load-bearing elements (front force beam 148, rear force beam 150, force plate 152, tie rod 144, tie rod clamp assemblies 156, 256), 8.5 kg consists of the press mechanism 130, and 11 kg consists of the remaining components.

[0034] 4 shows the tabletop support apparatus 100 of FIG. 1 with the casing part 166 of the press mechanism 130 removed. The press mechanism 130 may include an interlock mechanism connected to the casing part 166, which inhibits operation of the press mechanism 130 in the absence of the casing part 166. As shown in FIG. 4, the tabletop support apparatus 100 may be mounted on a support carriage 190. Such a support carriage 190 is optionally provided as an accessory and allows the tabletop support apparatus 100 to be more easily moved.

[0035] Figure 5 shows a cross-sectional view of the tabletop support device 100 of Figure 1. As noted above, the embodiment described herein is a relatively lightweight tabletop version of the support device 100. However, those skilled in the art will appreciate that the present invention is not limited solely to the tabletop version of the support device 100.

[0036] Figure 6 illustrates a tie rod clamp assembly 156 that may be used in an embodiment of a support such as the tabletop support 100 illustrated in Figures 1-5. The tie rod clamp assembly 156 includes a first tie rod clamping portion 172 and a second tie rod clamping portion 174. The first tie rod clamping portion 172 and the second tie rod clamping portion 174 are both substantially semi-annular in shape and are joined by a pivot attachment 180.

[0037] Each of the first tie rod clamping portion 172 and the second tie rod clamping portion 174 includes a respective radially inwardly directed semi-annular tie rod engagement rim 178. The rims are preferably arcuate and semi-cylindrical. The tie rod engagement rim 178 itself has a substantially semi-circular cross section. The provision of such semi-circular cross-section engagement rims 178 allows embodiments of the present invention to utilize higher forces than prior art systems (e.g., reducing the induced localized stress buildup associated with angular notches, etc.).

[0038] When the first tie rod clamping portion 172 and the second tie rod clamping portion 174 are combined in an annular (closed) position, a pivotable fastening mechanism 176 is attached to the second tie rod clamping portion 174 and configured to engage with the first tie rod clamping portion 172.

[0039] Thus, when the tie rod clamp assembly 156 is in the open position, the tie rod engaging rim 178 may be positioned adjacent to the groove 162 of the tie rod 144. At this time, the first tie rod clamping portion 172 and the second tie rod clamping portion 174 may be assembled in an annularly arranged (closed) position, and at this time, the fastening mechanism may be engaged to lock the tie rod clamping assembly 156 to the tie rod 144.

[0040] FIG. 7 illustrates a tie rod clamp assembly that may additionally or alternatively be used in embodiments of a support such as the tabletop support 100 shown in FIGS. 1-5.

[0041] The tie rod clamp assembly 256 includes a first tie rod clamping portion 272 and a second tie rod clamping portion 274. Both the first tie rod clamping portion 272 and the second tie rod clamping portion 274 are substantially semi-annular in shape and are joined by a first pivot attachment 280. Each of the first tie rod clamping portion 272 and the second tie rod clamping portion 274 includes a respective radially inwardly directed semi-annular tie rod engaging rim 278. The rims are preferably arcuate and semi-cylindrical in shape. The tie rod engaging rim 278 itself has a substantially semi-circular cross section. Such a tie rod clamping assembly can provide a larger contact area between components to withstand higher pressures than conventional systems.

[0042] When the first tie rod clamping portion 272 and the second tie rod clamping portion 274 are assembled in an annular (closed) position, a pivotable fastener mechanism 276 is attached to the second tie rod clamping portion 274 by a second pivot attachment 282 and is configured to engage the first tie rod clamping portion 172. The pivotable fastener mechanism 276 comprises a substantially bolt-shaped component having a shaft portion connected to a head portion. The shaft portion is coupled near its end to the second pivot attachment 282, and the head portion is configured to fit within a recess in the first tie rod clamping portion 272 when in the closed position.

[0043] In this application, the terms "weight" and "mass" are used interchangeably. Further, for the avoidance of doubt, the contents of all previously mentioned documents, products, etc. are hereby incorporated by reference in their entirety to the maximum extent permissible.

[0044] Thus, various compact and relatively lightweight embodiments of the present invention are provided. These may additionally or alternatively provide improved ease of use, ease of cleaning, and suitability for use in clean / sterile environments. Such embodiments may also provide increased retention forces with only a manual pump. For example, retention forces may be increased by 5-10 times compared to conventional devices. For example, various embodiments may provide compression forces of up to 20 kN (e.g., about 20 kN to about 23 kN, or about 23 kN) in a compression zone maintained at 5% or less vacuum for 16 hours or more. Such embodiments are also useful in cleanroom environments, and may be resistant to cleaning compounds such as up to 0.5% chlorine compounds, up to 35% hydrogen peroxide HO, 2% Virkon, and 10% Decon 90.

[0045] Additionally, various embodiments provide pre-assembled cassette packages for a predetermined total volume. The use of such pre-assembled cassette packages within the holding device of the present invention provides various advantages. For example, it not only reduces setup time, but also eliminates the need for fluid manifolds / connectors, etc., within the components of the holding device itself (by using various non-fluidic components, unlike various prior art systems). Therefore, various embodiments of the present invention may also be easier to clean than certain prior art systems. The inlets / outlets of the various cassette packages may be configured to align with other associated bioprocessing equipment (e.g., column positions in an A (umlaut) KTA ready™ chromatography system) for ease of connection / attachment.

[0046] Additionally, various embodiments have an ergonomic design for ease of use. Guide features to facilitate alignment of the consumable membrane chromatography units / modules may also preferably be provided to further enhance ease of use.

[0047] Embodiments may be provided in which one or more sensors are provided. For example, one or more sensors may be provided for one or more of the following purposes: To detect the presence of at least one chromatography unit / module; To provide an indicator / alarm / lock function if the user attempts to pressurize the device without a module or with under- and / or over-pressure; To detect the correct movement of the press mechanism or parts connected to it, for example to detect the presence of foreign objects and / or twisted / damaged tie bars. An automated (or semi-automated) system may be provided that can apply a predetermined pressure / force within a target range, for example as a fixed value or based on the number or type of modules used / detected.

[0048] Further embodiments are contemplated in which components, such as tie rods, are formed using at least one substantially hollow component to further reduce the weight or mass of the device. Accordingly, various embodiments of the present invention may provide a retention device having a force-to-weight ratio of at least about 0.05, 0.07, 0.1, 0.2, 0.25, 0.5, 0.7, or 1 kN / kg, or from about 0.1 or about 0.25 kN / kg to about 0.3, 0.4, or about 0.5 kN / kg, or even from about 0.1, 0.2, or 0.25 kN / kg to about 0.5 kN / kg, 0.7 kN / kg, or about 1 kN / kg.

[0049] Additionally, contemplated embodiments include holding devices with one or more wheels, skids, and the like, which may be lockable / retractable / detachable, etc., to further facilitate movement of the instrument within the laboratory / production facility. Various "suitcase-like" embodiments are envisioned, such as a device with one or more wheels at one end and a handle at the opposite end.

[0050] Further, for example, while the embodiments described herein depict the use of a manually operated pump, one skilled in the art will appreciate that alternative variations are possible. For example, various embodiments may be provided having one or more electric, powered hydraulic, etc. pumps therein, optionally with a control system operable to ensure that no overpressure or underpressure occurs. Many other possible variations will be apparent to those skilled in the art.

[0051] Thus, various aspects and embodiments of the present invention have been described. However, the present invention is not to be regarded as limited to the above-described embodiments, but can be varied within the scope of the appended claims, as will be readily apparent to those skilled in the art. [Explanation of symbols]

[0052] 100 Holding device 110a Forward membrane chromatography unit 110a' Rear membrane chromatography unit 110b Central membrane chromatography unit 120 Retaining housing 130 Press Mechanism 134 Pressure gauge 136 Check valve 140 Front of frame 142 Rear of frame 144 tie rod 146 Legs 148 Force Beam 150 rear force beam 152 Force Plate 154 Handle 156 Tie rod clamp assembly 158 Base Tray 160 Piston connecting actuator rod 162 Groove 164 Grommet 166 Casing parts 168 Fasteners 170 Bush 172 First tie rod clamp 174 Second tie rod clamp part 176 Fastening mechanism 178 Engagement Rim 180 pivot attachment 182 Handle 184 Inlet 186 Outlet 188 frames 188 Guide Rail 190 Support trolley 256 Tie rod clamp assembly 272 First tie rod clamp 274 Second tie rod clamp part 276 Fastening mechanism 278 Engaging Rim 280 First Pivot Attachment 282 Second Pivot Attachment

Claims

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

2. the holding housing (120) comprises a frame (152, 158, 188) for holding and aligning the at least one membrane chromatography unit (110a, 110a', 110b) in a serially fluidly connected arrangement; The holding device (100) of claim 1.

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

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

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

6. further comprising a rear force beam (150); A holding device (100) according to any one of claims 1 to 5.

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

8. the at least one movable force beam (148) and / or the rear force beam (150) are made of a solid material; A holding device (100) according to claim 7.

9. further comprising one or more casing components (166); Optionally, at least one of said casing parts (166) comprises an interlocking mechanism; A holding device (100) according to any one of claims 1 to 8.

10. The weight or mass excluding any membrane chromatography units (110a, 110a', 110b) is less than 100 kg, less than 70 kg, preferably less than 50 kg, more preferably less than 40 kg, for example, from about 5 kg or 10 kg to about 40 kg, or from about 15 kg to about 35 kg; A holding device (100) according to any one of the preceding claims.

11. The weight or mass of the portion of the frame (152, 158) is less than 70 kg, for example, from about 15 kg to about 25 kg; A holding device (100) according to claim 10.

12. having an occupied size or volume of about 500 to about 700 mm (length), about 200 to about 500 mm (depth), and about 300 to about 500 mm (height); A holding device (100) according to any one of the preceding claims.

13. having an occupied size or volume of about 700 mm (length), about 400 mm (depth), and about 400 mm (height); A holding device (100) according to claim 12.

14. The press mechanism (130) i) applying a force of up to about 25 kN; and / or ii) heating at least one membrane chromatography unit (110a, 110a', 110b) at about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 bar (10 ５ pressures above about 2, 3, 4, 5, 6 or 7 bar (10 ５ Pa) to about 8, 9, 10, 11, or 12 bar (10 ５ Pressure of about 8 bar (10 ５ Pa) to 10 bar (10 ５ Pa), or about 10 bar (10 ５ and operable to pressurize at a pressure up to A holding device (100) according to any one of the preceding claims.

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

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

17. further comprising one or more wheels, skids, etc. A holding device (100) according to any one of the preceding claims.

18. A tie rod clamp assembly (156, 256) for use in a retention device (100) according to any one of claims 1 to 17, comprising: a first tie rod clamping portion (172, 272) rotatably coupled to a second tie rod clamping portion (174, 274); at least one pivotable fastening mechanism (176, 276) for restraining rotational movement of the first tie rod clamping portion (172, 272) relative to the second tie rod clamping portion (174, 274) about the first pivot attachment (180, 280); Tie rod clamp assembly (156, 256).

19. The first tie rod clamping portion (172, 272) and the second tie rod clamping portion (174, 274) each include a tie rod engaging rim (178, 278); 20. The tie rod clamp assembly (156, 256) of claim 18.

20. the tie rod engaging rim (178, 278) has a substantially semicircular cross section and / or a substantially arcuate, semicylindrical shape; 20. The tie rod clamp assembly (156, 256) of claim 19.

21. the pivotable fastener mechanism comprises a substantially bolt-shaped or T-shaped component comprising a shaft portion connected to a head portion; A tie rod clamp assembly (256) according to any one of claims 18 to 20.

22. The shaft portion is coupled near its end to the second pivot attachment (282), and the head portion is configured to fit within a recess in the first tie rod clamp portion (272) when in the closed position.

22. The tie rod clamp assembly (256) of claim 21.

23. A chromatography unit (110a, 110a', 110b) for use in a holding device (100) according to any one of claims 1 to 17, comprising: the casing includes at least one key feature, such as a notch or protrusion, for keyed engagement with a guide rail (188) or other inverted key feature of the retention device (100); Chromatography units (110a, 110a', 110b).

24. The chromatography units (110a, 110a', 110b) are at least one handle (182); It is a single-use device, provided pre-sterilized (e.g., by gamma irradiation); It is stackable and and / or providing one or more quickly removable seals / covers (e.g., film covers) on the fluid ports; 24. A chromatography unit (110a, 110a', 110b) according to claim 23.

25. 25. An assembled cassette package comprising a plurality of chromatography units (110a, 110a', 110b) according to claim 23 or 24, the first chromatography unit (110a) and the second chromatography unit (110a') have a fluid inlet and a fluid outlet, respectively; Pre-assembled cassette package.

26. The first chromatography unit (110a) and the second chromatography unit (110a') are each provided with a handle (182).

26. The assembled cassette package of claim 25.

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

28. Before step ii), the method further comprises the step of placing the holding device (100) on a workbench or tabletop.

28. The method of claim 27.

29. said step ii) of placing at least one chromatography unit (110a, 110a', 110b) in said holding device (100) comprises placing a pre-assembled cassette package of a predetermined volume in said holding device (100); 29. The method of any one of claims 27 or 28.

30. The step iii) of pressurizing the at least one chromatography unit (110a, 110a', 110b) may be performed by pressurizing the at least one membrane chromatography unit (110a, 110a', 110b) to about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 bar (10 ５ pressures above about 2, 3, 4, 5, 6 or 7 bar (10 ５ Pa) to about 8, 9, 10, 11, or 12 bar (10 ５ Pressure of about 8 bar (10 ５ Pa) to 10 bar (10 ５ Pa), or about 10 bar (10 ５ Pressurizing the mixture at a pressure of up to 1000 kJ / cm² (up to 1000 kJ / cm²) 30. The method according to any one of claims 27 to 29.

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