Chromatography system and connector thereof

Abstract

Chromatographic systems are disclosed that include a plurality of fluid processing members fluidly interconnected by a fluid tube to form a bioprocess fluid flow path, the fluid processing members including two or more fluid ports, where at least one of the fluid processing members has at least one fluid port, and the fluid processing members are fluidly interconnected by the fluid tube to form the bioprocess fluid flow path. And at least one fluid port having a male portion protruding from the front surface of the at least one fluid handling member, the male portion being arranged to receive a first end of a fluid tube thereon, the fluid tube is arranged to be coupled to a respective fluid port by applying a radial locking force on an outer surface of a first end of the fluid tube to lock the first end of the fluid tube on the male portion.

Description

Technical Field

[0001] The present invention relates to chromatography systems, such as liquid chromatography systems, and particularly but not exclusively to laboratory or 'bench top' sized systems of a general purpose nature which allow convenient reconfiguration and convenient automated use for different chromatographic procedures, and to reconnectable fluid tubing couplings for connecting tubing etc. associated with such apparatus or systems. Background Art

[0002] Reconnectable fluid pipe couplings, i.e. couplings that can be disassembled and replaced multiple times but still provide a fluid seal for flexible pipes (such as garden hoses and plastic pipes) at each reconnection, are known. However, their ease of connection and / or sanitation issues are questionable, especially if the same design is used in a chromatography system, where sanitary couplings are required and higher fluid pressures (e.g., up to 20 Bar or more) are typically encountered. Typical pipe fittings used in chromatography systems have multiple components including metal springs and O-rings, resulting in dead corners or O-ring grooves, which can accumulate harmful contaminants, such as pathogens, during use. These dead corners and grooves are very difficult to clean. In addition, the use of metal parts is problematic when attempting to sterilize such coupling components by gamma irradiation. In addition, it is undesirable to use threads or special tools when seeking speed and ease of connection or disconnection.

[0003] One prior art barb lock pipe coupling arrangement is shown in US8662542, but this coupling requires tools for assembly and is not intended to be easily released.

[0004] Liquid chromatography is a well-known procedure for separating mixtures of molecules, for example for separating proteins in a liquid sample. Proteins are usually suspended in a fluid and pushed through a chromatographic separation medium along with a buffer solution. The various sample molecules in the mixture travel through the chromatographic medium at different speeds, causing them to separate. This separation can be accomplished by a fractionation step, in which the mobile phase can be directed to different containers, for example, through an outlet valve of the chromatographic system.

[0005] In addition, in chromatography systems, especially bench-top experimental equipment, it is often necessary to clean the equipment, including the interconnected tubes in use, and then remove the tube arrangement so that the tubes can be reconnected in different configurations to accommodate different experiments. Therefore, dedicated disinfection equipment is inconvenient and requires rapid cleaning, along with rapid disconnection and reconnection. One such device is disclosed in US8821718, incorporated herein by reference, in which interchangeable modular components of a chromatography system can be interconnected by external fluid conduits and would benefit from improved means of such interconnection. Summary of the invention

[0006] Embodiments of the present invention aim to provide a chromatography system, particularly a liquid chromatography system, comprising a releasable fluid coupling that can be quickly reconnected without twisting or twisting the fluid conduits and without requiring space around each fluid conduit to perform such actions. It is also an object of the present invention to provide a chromatography system having one or more of the following features: enhanced functionality, such as being able to operate in conventional batch chromatography and continuous chromatography; being able to be used in a wider range of applications; not significantly increasing the overall size or manufacturing cost; and being simple to operate.

[0007] Another object of embodiments of the present invention is to provide an easily cleanable coupling with no or limited dead spots or other spaces where contaminants can accumulate. Another object of embodiments of the present invention is to provide a coupling that can be quickly connected and released without the use of tools if necessary.

[0008] According to one aspect of the present invention there is provided a chromatography system according to the claims herein.

[0009] According to another aspect of the invention, there is provided a releasable connector as defined in the other claims herein, which can be used as part of a connector assembly, for example in a chromatography system (such as a benchtop chromatography system), wherein modular components can be, for example, rearranged on a support to best suit a particular experimental setup, and the arranged modular components can be interconnected by fluid tubes having opposite ends, each end comprising one of the connector assemblies of fluid connectors for the corresponding modular components according to the invention.

[0010] Further preferred aspects of the invention are described in the dependent claims herein.

[0011] Further advantages and benefits of the present invention will be apparent to those skilled in the art based on the following detailed description. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] The present invention will now be described in more detail with reference to the accompanying drawings, in which: Figure 1 An exploded view showing a coupling component; Figure 2 The cross section shows the fluid connection state. Figure 1 Connecting parts; Figure 3 showing the same coupling in cross section in a releasable state; Figure 4 Shown in cross section Figure 1 A coupling assembly of a coupling, all of which are in a fluid-tight state; Figure 5 Shown through Figure 4 A cross-sectional view of a coupling assembly of the embodiment of the present invention, but reconfigured to be releasable; Figure 6a , b and c show variations of the above coupling assembly; Figure 7a , b, c and d show variations of the coupling assembly; Figure 8 A chromatography system employing a plurality of coupling assemblies is shown; Fig. 9 A coupling release tool is shown; Fig.10 , Fig.11 and Fig.12 An embodiment of the present invention including a bayonet locking feature is shown; Figures 13 to 16 Variations of the components of the coupling are shown; Fig.17 is a schematic diagram of the chromatography system; Fig.18 Show Fig.17 A schematic diagram of the chromatography system shown in ; and Fig.19 , Fig. 20 and Fig.21 Show Fig.17 and Fig.18 The configuration of the chromatography system is shown in FIG. Fig. 22 A first form of prior art modular component is shown having four ports; Fig.23 A modular component is shown with four ports; Fig.24a and Figure 24b Cross-sectional views showing two variants of the converter; Fig.25a A second form of prior art modular component is shown with three ports; Fig.25b Shown for Fig.25a Threaded connectors for modular components. Fig.26a and Figure 26b showing a cross-sectional view of the adapter; Fig. 27 An alternative converter is shown; Fig.28a and Fig.28b showing a cross-sectional view of the spigot with the tube installed; Fig.29a and Fig.29b A cross-sectional view showing an alternative sealing ridge configuration. Figures 30a-30c A cross-sectional view of one embodiment of a sealing configuration is shown. DETAILED DESCRIPTION

[0013] Good Manufacturing Practice (GMP) specifies guidelines for bioprocessing procedures, and if the guidelines are followed, cleanliness standards are required. Advantageously, it is easier to achieve the standards using the proposed equipment, for example, wherein the fluid path in the system has a continuous flow path in at least one configuration, without substantial stagnant sections, thereby providing complete cleaning without the need to remove the fluid conduit. An embodiment of the proposed system provides a sanitary small-scale chromatography system suitable for both GMP and non-GMP work. The wide flow and pressure range of the system's functionality makes it suitable for both technical batch production and scale-up research, as well as small-scale production of GMP-grade materials. The high precision and flow range of the pump enable accurate gradient formation, covering a wide range of chromatographic column sizes and more reproducible results.

[0014] In embodiments, the modular structure provides enhanced functionality for different uses. Interactive control software allows changes to be made in real time and allows for quick identification of unexpected deviations. The small benchtop size frees up laboratory space. The system allows for in-situ column packing, i.e., the ability to compress a column while connected to the system, or to compress the chromatographic media in each column when two or more columns are used, without the need to disconnect any fluid conduits prior to performing a chromatographic procedure.

[0015] Figure 1 An exploded view of an embodiment of a releasable coupling 100 according to one embodiment is shown. The coupling 100 comprises two parts: a cylindrical inner member in the form of a collet 110 for receiving a fluid tube, and a cylindrical locking collar 130 having an internal through hole 132 for slidably receiving the collet 110. The fluid tube (not shown) will extend along the axis T in use and within a central opening 112 in the collet 110 which is sized to fit closely around the tube. The collet 110 has a collet flange 114 formed on a cylindrical middle portion 116, and a plurality of resiliently deflectable and circumferentially arranged fingers 118 extending from the middle portion 116 of the collet 110 to a distal end 120.

[0016] The collet 110 is a sliding fit in the through hole 132 of the collar 130, and thus the collar 130 can be mounted on and around the fingers 118 and the middle portion 116 of the collet 110. The collar 130 can be manipulated along the fingers 118 and the middle portion 116 to selectively deflect or relax the fingers 118, as described in more detail below, the deflection causing the tube to be clamped. Manipulation of the collar 130 is aided by a collar flange 134 at the distal end of the collar, which extends from the body 136 of the collar, and the collar can be manually pulled or pushed. The collar has a distal end 140. The fingers 118 flare outwardly toward the distal end 120 of the collet, and it will be appreciated that if the aperture 132 has a substantially constant inner diameter, sliding the collar 130 in a direction from the collet flange 114 to the distal end 120 of the collet 110 will cause the inner diameter of the aperture 132 to abut the outer surface of the fingers 118 and push them inwardly to provide a tube clamping action.

[0017] Figure 2 Shown in cross section Figure 1 The coupling 100 is shown in a tube clamping position. Here, the distal end 140 of the collar 130 and the distal end 120 of the collet 110 are manipulated into alignment by manually repositioning the collar flange 134 relative to the collet flange 114. In this position, the inner surface of the orifice 132 and the outer surface of the fingers form complementary surfaces that abut and thereby cause the fingers 118 to deflect inwardly toward the axis T to push inwardly an adjacent portion of a tube (not shown) within the collet, e.g., compress, or squeeze or clamp the tube. Manipulation of the collar and its flange in the direction of arrow R achieves release of the coupling.

[0018] Figure 3 The coupling 100 is again shown in cross section, but arranged in a tube release position. Here, the collar 130 has slid in the direction R towards the distal end of the collet, but is prevented from sliding out of the collet by the collet flange 114 and / or steps 138 (one or each of which forms a stop) in both the aperture 132 and the opening 112. In this position, the fingers 118 are released and resiliently rebound outwardly to stop or reduce any pushing / compression / gripping action on the tube. Figure 3 The position shown in FIG. 1 is obtained by moving along arrow R ( Figure 2 ) is achieved by manipulating the collar 130 and its flange 134 relative to the orientation of the chuck 110.

[0019] Figure 4A cross-sectional view of a coupling assembly 10 is shown, which includes a male portion, in this embodiment in the form of a connector socket 20, having a widened portion, such as a sealing ridge, bead or barb 22, which can be placed within a flexible fluid tube 30, beyond the open end of the tube 30 as a push fit. The tube 30 is retained to the socket 20 by compressing the tube 30 onto the socket 20. The coupling 100 surrounds the tube 30 and is primarily described above. Figure 2 The described manner releasably compresses the tube onto the socket 20 to releasably hold the tube 30 to the socket 20. In this figure, it is clear that the finger 118 compresses the tube 30 behind the widened portion 22, thereby assisting in fixing the tube to the socket and effectively locking the tube to the socket 20. The connector assembly 10 can supply fluid to or remove fluid from the module 1, which in this embodiment is a chromatography system that requires a releasable fluid connector that can be easily cleaned and will not carry contamination. In another embodiment, the fluid pressure at the module 1 can be measured or adjusted via the fluid tube 30, and therefore only fluid communication is required. It follows that fluid flow in the tube 30 is not required.

[0020] Figure 5 Shown with Figure 4 Same cross section, but in this view the coupling assembly 10 is in the released position, as shown in FIG. Figure 3 In use, according to Figure 4 The positioned coupling 100 clamps the tube 30 in place on the socket 20 and releases the compression on the tube when the collar flange 134 is pulled in the direction of arrow R. This release allows the collar flange 134, collar 130 and collet 110 to move in a Figure 5 134 along the tube. As described above, the chuck has one or more stops (chuck flange 114 and / or step 138) that prevent the collar from detaching from the chuck and thereby allow the chuck to be withdrawn together with the flange 134. In this withdrawn position, the tube 30 can be easily pulled out of the socket 20. Connecting or reconnecting the tube 30 to the socket is performed by the reverse steps of the steps mentioned above. That is, the tube 30 is assembled over the socket 20, the chuck flange 114 is pushed in the direction opposite to the arrow R, and once the distal end 120 of the chuck is firmly against the module 1, the collar flange 134 is pushed back into place so that the fingers 118 are deflected against the outer surface of the tube to clamp the tube on the socket 20.

[0021] The coupling 100 is preferably formed of only two plastic molded parts. From the figure, it can be seen that the outer surface of the collar 130 is smooth, that is, the collar flange 134 is a continuous annular structure upright from the annular body 136, and the outer surface of the collar flange and the collar on which the collar flange is formed has a continuously curved profile without abrupt changes in direction. Therefore, the chance of contaminating the coupling during use is reduced, and the coupling can be easily cleaned. In addition, the user's two fingers can be used, with one finger on each side of the collar flange on each side of the collar body 136 to pull it in the direction of arrow R ( Figure 5 ). At the same time, the user's thumb can be used to react to such pulling forces by resting the thumb against the clamp flange 114 opposite the two fingers.

[0022] It is important to ensure that the tube 30 is substantially completely fitted onto the socket 20. To this end, the collet 110 and the collar 130 may be formed of a clear plastic. Additionally, the socket may be a different color than the tube to provide a visual color indication, wherein if any of the socket's color is visible, the tube is not completely overlapped with the socket. Figure 6a , Figure 6b and Figure 6c Show Figures 1 to 5 A variation of the embodiment shown in , wherein: Figure 6a A modified socket 20' is shown having an outwardly extending resilient protrusion 24, such as a resilient arm; Figure 6b The tube 30 is shown pushed back completely onto the socket 20'. When the tube is completely against the socket, the arm 24 moves inwardly before allowing the collet fingers 118 to be pushed onto the tube, as shown in FIG. Figure 6c 1 , in preparation for pressing the collar 130 onto the fingers for clamping the tube in place as described above. The collet 110 will not pass through the arm 24 when the spigot 20 ′ is not fully inserted into the tube 30 .

[0023] Figure 7a , Figure 7b and Figure 7c A variation 105 of a coupling assembly is shown in cross section. In this embodiment, Figure 1 The collar 130 has been replaced by a locking plate 230 having a plurality of through holes 232, each of which receives the collet 110. The locking plate includes a protrusion 234 which replaces the flange 134 shown in the previous figures. The centers of the through holes are aligned with the centers of the plurality of male parts protruding from the module 1, so that multiple connections can be made in one operation.

[0024] exist Figure 7a In FIG. 2 , it can be seen that a locking plate 230 is provided to the module 1 , wherein the collet 110 is assembled in the through hole 232 and inside the collet 110 , the tube 30 has been fitted on a male part, such as the socket 20 . Figure 7b Shown with Figure 7a1 , but with the locking plate 230 and the collet 110 pushed to the front surface of the module 1 in the direction of arrow R so that the collet overlies the socket 20 and the end of the tube 30 . Figure 7c Show Figure 7a Another view of the coupling assembly, but now with the locking plate 230 along Figure 7b Push further in the direction of arrow R. Figure 7c In the embodiment of the present invention, the locking plate is used to clamp the fingers 118 of the collet 110 around the tube 30 in the manner as described above.

[0025] Figure 7d A further variation of the coupling assembly is shown in which the locking collars 230' are each mounted to a locking plate 231 by means of a flexible mounting, in this case a spherical mounting 233, which allows each collar 230' to rotate about the centre of the mounting 233 and thereby provide tolerance for a degree of misalignment or dimensional error in the male part on the module. The locking plate could of course be formed of a flexible material to provide similar tolerance. The two couplings are Figure 7a As shown in FIG. 1 , other linear arrays or two-dimensional arrays of truncations may also be used to match the configuration of the male portion 20, for example, an array of four couplings may be used to match Figure 8 The square male portion arrangement shown in FIG. 2 is not necessarily in the same plane. If a certain degree of flexibility is provided, the couplings do not necessarily have substantially parallel axes, for example, with reference to FIG. Figure 7d For ease of use, the tube 30 may have a single coupling 100 at one end and may be brought together at the opposite end of a plurality of couplings 105 in a manifold manner.

[0026] Figure 8 A chromatography system 11 is shown comprising a support 80 comprising conventional fluid handling modular components in the form of interchangeable modules, such as: Pump 12; Chromatographic column 13; Various valves 14; pH monitor 15; Conductivity monitor 16; a mixer 17; and UV monitor 18.

[0027] Other modules may be used. The modules may be connected in any suitable manner using fluid pipes 30 having couplings 100 at each end, only one of which is shown for convenience. Couplings 100 may be provided by Figure 7a , b, c or d shown in the type of multiple tubes and connectors 105 instead, to speed up the connection and release of the connector. For convenience, each valve 14 has the same male part configuration, which means that the same configuration of the locking plate 230 can be used for each valve.

[0028] Fig. 9 A release tool 200 is shown having a forked end 210 adapted to engage each side of a flange 134 or protrusion 234 to pull it outwardly away from the module 1 or 12 to 18, or to push it if there is no room for finger pulling.

[0029] exist Fig.10 , Fig.11 and Fig.12 An alternative embodiment of the coupling 300 is shown in FIG. In this embodiment, the locking collar 330 ( Fig.10 ) surrounds a cylindrical inner member in the form of a collet 310 having fingers 318 of the type described above, which in turn surround the fluid tube 30. The coupling 300 can be operated in much the same manner as the couplings 100 and 105 described above, in that, to form a fluid-tight coupling, the tube 30 is pushed through the male portion 20 protruding from the module 1, the collet is then slid over the tube until its distal end 340 is adjacent or abutting the module 1, and the collar is then moved toward the module to begin tightening the fingers 318 of the collet 310. This position is Fig.11 Shown in.

[0030] It will be noted that the distal end 340 includes a pair of bayonet-type openings for receiving complementary locking pins 27 supported by bosses 25 extending from the module 1 around the male portion 20. In this embodiment, the bayonet openings 345 receive the pins 27 by manipulating the distal end 340 of the collar on and along the bosses 25 in a linear and rotational manner until it is pushed further toward the module 1. Fig.12 In the final locked position shown in FIG. 3 , the final locked position of the collar 330 is reached. The fingers 318 are thereby further clamped to the tube 30 and the collar 330 (and the coupling 300) are fixed to the module 1 , held in place by the pins 27 .

[0031] Fig.10 , Fig.11 and Fig.12 The insert shown in , relies on the basic linear locking movement of the locking collar just mentioned above, i.e., some twisting is used to fix the collar 330 in place and apply the clamping force. By using wings 334 extending from the collar 330 instead of the flange mentioned above, twisting can be made easier.

[0032] Figures 13 to 16Portions of another collet 410 and collar 430 are shown in detail that may be used with coupling 100, 1050 or 300. In this variation, clamping of the fingers (in this case fingers 418) may be achieved by twisting of the collar 430 about the collet 410, either as an alternative to sliding movement of the collar 430 (in the manner described above), or in addition to the sliding movement.

[0033] In more detail, the inner surface of the collar 430 has detents 432 which act on the tapered portion 431 of the finger 418 when the collar is twisted relative to the finger. The circumferential ramps 431 act as cams respectively, and in this example, when the collar is twisted in the direction of arrow R, the circumferential ramps 431 are pushed inwardly toward the tube 30 by the corresponding detents. Thus, the finger 418 is moved around the tube 30 from the inner surface to the outer surface of the finger 418 in use. Fig.13 and Fig.14 The positions shown in the figure are compressed to Fig.15 and Fig.16 4, where the pawl rests in the complementary recess 433. The amount of twist for locking is less than 120 degrees, and preferably less than about 90 degrees if three or more circumferentially arranged fingers are used.

[0034] Experiments show that the couplings 100, 105 and 300 described above for use with a tube having an outer diameter of about 3 to 10 mm can seal the tube at the coupling, wherein the internal fluid pressure is at least 10 bar or higher, such as 15, 20, 35 or 30 bar or higher, as will be discussed in more detail below, and the embodiment of the coupling has been successfully verified by a wide range of leak tests of 30 bar. The coupling provides a liquid-tight connection of the tube around the male part, which can be connected and released by the basic linear movement of the locking collar 130 or the locking plate 230 without twisting or threaded connection parts. Therefore, due to the space to avoid twisting, the couplings can be spaced closer to each other than conventional threaded couplings. Substantially linear herein refers to rotations below 120 degrees, such as below 90 degrees, less than 45 degrees, less than 30 degrees, less than 15 degrees, less than 5 degrees or almost no rotation.

[0035] Collar elements have been described in different embodiments, each having the same function in a releasable coupling, namely the described features: locking collar 130, locking plate 230, locking collar 230', locking collar 330 and collar 430. One is non-cylindrical (locking plate 230) while the others are cylindrical. The collar elements include at least one protrusion, such as collar flange 134 or wing 334, extending outwardly away from an aperture having a size that allows manual manipulation of the collar between a first position and a second position.

[0036] Combination Figure 1-7 describes the internal member as a clamp 110, which may be provided with a stop portion, such as a clamp flange 114 and / or a step 138. The clamp flange 114 extends outwardly and has a size that facilitates manual manipulation of the coupling. In addition, the elastically deflectable portion is equivalent to the combination Figure 1 -7 The deflectable finger 118 and the combination described Figure 13-16 The terminology of finger 418 is described.

[0037] Fig.17 A chromatography device 400 is shown according to aspects of the invention. The device includes, but is not limited to, individual modular components 51 to 75 as listed below, at least some of which can be detached from a perforated front panel 420 of a support 410 of the device 400 and mounted thereto in a substantially vertical plane so that required liquid connections between modular components can only be made at the front 420. In practice, the detachable modular components have no more than two standard sizes and can be repositioned on the panel 420 to suit different procedures if necessary. Each modular component has a serial bus communication connection and a power supply connection so that its physical location is unimportant to a controller located in the support 410 or remotely located. Thus, the modular components can be considered modular and thus repositionable and / or interchangeable.

[0038] Fig.17 The chromatographic apparatus shown in has the following modular components: 51 Control Panel 52 pH Monitor 53 Outlet valves 1-3, port 1 can be used for waste 54 outlet valve 4-6 55 Conductivity Monitor 56 outlet valve 7-9 57 Pre-column conductivity monitor 58 column valve unit including pre-column and post-column pressure sensors 59 Bottle for pump flushing fluid 60 Inlet valve A1-A3 61 Inlet valve A4-A6 62 Inlet valve B1-B3 63 Inlet valve B4-B6 64 Fixed rubber feet 65 Adjustable feet 66 System Pump A 67 System Pump B 68 Flow Restrictor, Including System Pressure Monitor 69 Mixer Modular Components 70 Mixing valve 71 Air trap valve, including air sensor 72 Air Trap 73 On / Off button 74 Inline filter holder (typical filter capsule shown) 75 UV monitor.

[0039] As explained above, modular components may be omitted or repositioned. It will be apparent that some modular components may be replaced by other modular components, or that the spaces left by omitted modular components may be filled with cover plates (see, for example, FIG. Fig. 20 76). More than one modular component with the same number may be used if necessary.

[0040] The fluid handling modular components of the device (i.e., all the modular components listed above except modular components 51, 64, 65 and 73) and external modular components (e.g., sample input reservoirs, buffer reservoirs, chromatography columns and fraction collection devices, all of which are not in the Fig.17 The fluid interconnection between the components (shown in the drawings) is via a fluid conduit in this case in the form of a flexible plastic tube, which can be easily connected and disconnected with corresponding ports of the fluid handling modular components in any desired configuration, for example using couplings as previously described.

[0041] Fig.18 One possible configuration of liquid interconnections between the main modular components of the chromatography device 400 is shown, in this case the device is connected to two chromatography columns 700 and 800, but the device allows any workable interconnection between the modular components and additional parts (such as multiple columns) and liquid reservoirs. The reconfigurable liquid interconnection is represented by a short chain of dashed lines 580.

[0042] The core of device 400 is column valve unit 58, in which case column valve unit 58 has a structure disclosed in pending application GB 1715399.0 filed on September 22, 2017, and the application is incorporated herein by reference. Valve unit 58 provides multiple switching of flow to allow flow in one or two posts 700 / 800 in either direction (upward or downward in the figure). The user can select upstream or downstream, or choose to bypass one or two posts. Flow can be directed to the next member in waste or flow path. Posts can also be connected in series, each post includes a chamber for accommodating a variable volume of chromatographic separation medium and an adapter that can be moved to increase or reduce each volume, and wherein column valve unit 58 is fluidly connected to each adapter, and by means of a change in fluid pressure, can be selectively operated to move each adapter independently or jointly, thus changing each volume, and causing compression or relieving compression of the medium in each column volume in use.

[0043] The column valve unit 58 includes a pressure sensor before and after the column, and also includes a fluid inlet 510 configured to receive an input fluid. The input fluid may be, for example, a chemical sample suspended in a buffer composition. The column valve unit 58 also includes a fluid outlet 520 configured to provide an output fluid from the valve unit. The output fluid provided may generally be a resulting fluid after the received input fluid passes through one or more columns of a chromatographic device 400. The valve unit 100 also includes a first pair of fluid ports 531 and 532 configured to be coupled to the first column 700 and a second pair of fluid ports 541 and 542 configured to be coupled to the second column 800. The valve unit 58 also includes a connection valve assembly, which is configured to guide fluid between the fluid inlet 510, the fluid outlet 520, the first pair of fluid ports 531 and 532, and the second pair of fluid ports 541 and 542 in response to one or more control signals.

[0044] In addition, the valve has a port 550 which can be used to change the volume of hydraulic cylinders 710 and 810 as part of columns 700 and 800, for example to provide compression of the column contents, also known as column packing. The packing process can be automated. It has been found that with such a system, diameters of about 25 to 250 mm can be filled in this way. The column can be pre-filled, but flushed and re-consolidated according to known procedures, such as described in WO2007045491, the disclosure of which is incorporated herein by reference.

[0045] The remaining system 400 includes: Inlet valve groups A and B, 60, 61, 62 and 63, adapted to provide selectable liquids, including liquids containing oil samples, buffer solutions and cleaning fluids; The inlet valves supply two system pumps, where each pump has a pair of pistons and associated non-return valves, providing a variable flow rate between 0-600 ml per minute (maximum 1200 ml / min) with high flow and flow resolution, allowing accurate flow rates to be maintained. This accuracy ensures good result reproducibility over a wide range of column diameters; Before the pumped liquid is transferred to the column valve unit 58 , the pump is supplied in series with a flow restrictor 68 , which comprises a system pressure monitor, a mixer valve 70 and a mixer module 69 .

[0046] Any entrained air may escape via the air trap valve 71 and the air trap exhaust 72 which also has air flowing out of the columns 700 and 800. The air trap may be constructed in accordance with co-pending application GB1713993 filed on 5 April 2017, the disclosure of which is incorporated herein by reference; Once the liquid reaches the column valve unit 58, it can be delivered according to the arrangement described in the co-pending application GB1715399.0 filed on 22 September 2017, and a variety of chromatography modes can thereby be performed, from simple batch work with only one column for a direct chromatographic separation process to procedures that more closely replicate large-scale commercial procedures, where two or more columns may be used, one ready for use while the other is used for separation; The output of the chromatography column is passed through port 520 to: conductivity monitor 55, UV absorbance monitor 75 and pH monitor 52 and directed to appropriate storage containers depending on the signals from the three monitors and the separated fractions are thereby collected in appropriate containers 501. Column washes may be collected in waste container 500; Figure 2 In the long chain dotted line 610 represents system bus, and this system bus transmits signal and power supply to and from above-mentioned modular component, to and from controller 600.It will be appreciated that control and monitoring signal can be sent wirelessly according to known protocol, without communication bus.Chromatographic system 400 also comprises display screen 530.The software running on controller will show multiple icons on screen 530, and allows user to manipulate the icon on screen to drag and drop icon to form a series of icons representing user-defined chromatographic control method, with ease of use.The chromatographic control method defined by user comprises the continuous chromatography that uses described two or more chromatographic columns by selectively opening valve in described column valve unit 58.

[0047] Fig.19 , Fig. 20 and Fig.21 The systems connected to the pipes are shown for various configurations, wherein only the Fig.17 Some of the modular components cited in the figure are removed, and the openings left by the removed modular components are covered by sealing plates 526 and screwed into appropriate positions above the openings to prevent liquid from accidentally entering the support member 410.

[0048] exist Fig.19 In the embodiment, the system 400' has a construction of modular components suitable for a regulated environment where the system is custom built in a factory. The system is delivered installed, calibrated and performance tested and is suitable for working in a GMP environment. Fig. 20 A system 400" is shown with some modular components removed, and Fig.21 Shown is a system 400"' with more modular components in place, similar to Fig.17 , and a typical tubular interconnect 580 is shown.

[0049] In use, modular components are very easy to remove or add to the system, and installation is completed by one-click activation in the software that can identify each modular component. The software can provide comprehensive and customizable operational control and preemptive maintenance. In addition to the modular components described above, the input and output communication modular components can also be used to dock with analog and / or digital external sensors or other devices (such as automatic fraction collection devices). The wider flow rate and pressure range allows the column with an internal diameter range of 25 to 250 mm to be scaled more than 40 times. This wide range makes the device suitable for transition to a GMP environment.

[0050] The filling (and refilling) of a chromatography column using the system described above can be fully controlled by a controller 600 activated by the control panel 51. The controller 600 can drive the display screen 530 ( Fig.18 ) to help visualize the filling process and progress. The control software includes a column filling log that can be accessed. Therefore, the column filling log can be defined, generated and updated from the software for traceability and quality assurance purposes. In addition, the log can be used to monitor column performance and provide statistics on usage, separation performance and filling intervals.

[0051] The display screen can provide process visualization, which can quickly provide the operator with an overview of system functions, the progress of operating steps and alarms, while providing only the required amount of information for each step. The active flow path is always shown in the process visualization to minimize user errors. Real-time changes can be made by selecting the appropriate process on the visualization screen, for example, by selecting or dragging an icon on the screen. Control, graphical interfaces are provided for specific sections (such as column valve unit 58).

[0052] Use pre-programmed steps, but modify these and save them as user-defined steps for added customization.

[0053] The system described and shown above is designed for a sanitary environment. For example, the support 410 is flat or curved, with no connectors, gaps or significant concavities except at the edges of the face, which makes wiping easy and reduces the chance of dust and liquid trapping. The pH monitor 52 has an inline calibration, and the column valve unit 58 provides in-process column filling, so a closed flow path can be used throughout the operation, meaning that there is no need to interrupt the flow path during the filling / regeneration phase of one or more chromatographic columns and throughout the separation operation.

[0054] Fig. 22A prior art modular component 810 is shown, which is provided with four ports 811, each port being adapted to be connected to a prior art fluid connection 812. Due to the size of the couplings 813 required to secure the fluid connections 812 to the ports 811, the couplings must be arranged at different heights. This is a cumbersome solution and also requires space to be provided around the modular component to facilitate the installation / removal of the fluid connections 812 with the corresponding ports 811.

[0055] Fig.23 A modular component 820 is shown having four ports 821, each port having a tube 822 having a releasable coupling 100 (eg, in combination with a tube 822) at a first end thereof. Figure 1 -6), the releasable coupling 100 is connected to each corresponding port 821. The second end of one of the tubes is connected to the converter 823 through another releasable coupling 100 to provide an accessory for fluid connection that is not suitable for direct connection to the port 821. Fig.24a and Figure 24b The converter 823 is described in more detail. When connecting the fluid connection to the modular component, the result of using a releasable coupling is a smaller design because the ports can be positioned closer to each other. Likewise, the releasable coupling is easier to clean, install / remove and replace when necessary.

[0056] Fig.24a A cross-sectional view of a converter 823 is shown having a body 830, a flange 831, a through hole 832, and a socket 833 integral with the body 830. In this embodiment, the converter 823 is made of a single piece of material, such as plastic, metal, etc. In this example, the flange 831 is adapted for use in a tri-clamp (TC) coupling, and the socket 833 is adapted to receive a tube provided with a releasable coupling 100 (not shown).

[0057] Figure 24b A cross-sectional view of an alternative converter 823' is shown, which is similar to the combination of Fig.24a The converter 823' is described with one exception. The converter 823' comprises two parts, with the body 830 and flange 831 being made of a single piece of material (eg, plastic), and the socket 833' being made of another material (eg, metal).

[0058] Fig.25a A prior art modular component 910 is shown having three threaded holes as ports 911. Tubes 912, each provided with a threaded connector 913, are fixed to the corresponding ports 911. Fig.25bA threaded connector 913 is shown, which includes an end flange 914 that is fixed to the first end of the tube 912 and is adapted to provide a seal when arranged in the threaded hole 911, and a body having a threaded portion 915 and a gripping portion 916 designed to be used when fixing the threaded connector 913 to the modular component 910. Fig.23 As shown in FIG, due to the space required to secure the threaded connector 913 to the modular member 910, this design is relatively cumbersome compared to using a releasable coupling.

[0059] When a threaded connector is used to connect a fluid tube to a port, there is unintended rotation (about 2-3 turns) of the fluid tube when the threaded connector is secured to the threaded hole. This is particularly a disadvantage when securing short fluid tubes (e.g., 10-30 cm long), where the tube experiences kinking behavior. In addition, a separate O-ring may be required to create the required pressure and fluid seal.

[0060] To benefit from the advantages provided by the resealable coupling 100 , an adapter may be introduced into a threaded hole of the modular component 910 .

[0061] Fig.26a A cross-sectional view of an adapter 915 is shown having a body 920, a threaded portion 921, a through hole 922, and a socket 923 integral with the body 920. In this embodiment, the adapter 920 is made of a single piece of material, such as plastic, metal, etc. In this example, the threaded portion 921 is adapted to be introduced into a threaded hole of a modular component using the body 920 as a gripping portion, and the socket 923 is adapted to receive a tube having a resealable coupling 100 (not shown).

[0062] Figure 26b A cross-sectional view of an alternative adapter 915' is shown, which is similar to the adapter combined with Fig.26a The adapter is described with one exception. The converter 915' comprises two parts, with the body 920 and the threaded portion 921 being made of a single piece of material (eg, plastic), and the socket 923' being made of another material (eg, metal).

[0063] Fig. 27 A cross-sectional view of an alternative converter 925 is shown having a body 930, a portion with a threaded hole 931, a through hole 932, and a socket 933 integral with the body 830. In this embodiment, the converter 925 is made of a single piece of material, such as plastic, metal, etc. The threaded hole 931 in this example is adapted to receive a connector such as a connector that is coupled to the body 830. Fig.25b The socket 933 is adapted to receive a tube provided with a resealable coupling 100 (not shown). It should be noted that the socket may be manufactured separately from the body and the portion having the threaded hole using a different material.

[0064] An advantage of the releasable coupling assembly 10 is that it has no threads, which means that it is easy to clean and requires less maintenance. Fig.25a and Fig.25b As shown in Figure 1, by providing a simple widening 22 (ie sealing ridges, barbs or beads) on the socket 20 extending from the front of the panel it is made easier to clean compared to conventional threaded connectors which have very limited access to the threaded hole.

[0065] Another advantage is that, combined with Fig. 22 Compared to the one shown, no flange is required and therefore it is possible to manually cut the tube before connecting it using the releasable connector 100. Therefore, it is easy to replace the tube when necessary because the resting size of the inner diameter of the tube is in the same range as the outer diameter of the sealing ridge 22 on the socket 20, which is preferably less than ±10% of the outer diameter of the socket.

[0066] Another advantage is that no O-rings or gaskets are required, which means less maintenance and a more robust solution compared to prior art solutions. The seal is achieved using tubing that is in direct sealing engagement with the sealing ridge 22. However, this requires the tubing to have a certain degree of flexibility and deformation properties. The resealable coupling provides a minimum number of connections / couplings between different materials and parts, which improves the possibility of clean fluid connections when required. Another advantage is that the resealable coupling assembly is easy to attach, such as a one-handed snap fit for low pressure applications.

[0067] As combined Fig.24a , Figure 24b and Fig. 27 As described, a converter connector can be used to provide a connection to other connectors (e.g., a TC connector). Fig.26a and Figure 26b As described, threaded adapters can be used to replace older equipment with threaded holes (see Fig.25a ) is upgraded to a connector suitable for use with a releasable coupling when attaching a tube.

[0068] As described above, the sockets 20 can be arranged closer together than if a screw-type connector or TC connector were provided. This will allow shorter internal flow paths in modular components (e.g., valves), whereby the use of releasable coupling components can reduce the size of fluidic components having internal flow paths. This, in turn, will affect the entire chromatography system and reduce the footprint relative to flow capacity.

[0069] Fig.28a and Fig.28bCross-sectional views of the spigot are shown without and with the tube installed. It should be emphasized that the size of the tube (inner diameter D1) and the size of the spigot (outer diameter D2) are important to create a proper seal and avoid the creation of a cavity between the tube 30 and the open end 281 of the spigot 280, in which deposits of biological material residues can be trapped. The elastic modulus of the tube will provide the necessary deformation of the tube to allow it to pass through the sealing ridge 282 located proximate to the open end 821. The shape of the sealing ridge is very important to achieve the desired function in key aspects: - Cleanability, since direct sealing creates a cavity-free construction, avoiding cavities in which biological material could be trapped, - Hold the tube to the upper pressure limit of the spigot.

[0070] As mentioned above, other important parameters are: - Elastic modulus of the fluid tube -Inner diameter of the fluid pipe and outer diameter of the socket In some embodiments, the sealing ridge has a rounded design with a radius R and a height h from the center of the socket. The radius extends to the open end of the socket and provides an angle to allow the tube to be slid over the sealing ridge onto the socket using a force low enough for an ordinary operator, and the tube does not bend under pressure when sliding over the sealing ridge. The starting radius of the rounded section can be similar to the inner radius of the tube, and the height is determined by the elastic modulus of the tube and the pressure limit of the connector.

[0071] Other shapes of sealing ridges are Fig.28a , Fig.29a and Fig.29b Shown in. Fig.28b The arrows F1-F3 in the diagram schematically indicate the forces involved in sealing and locking the tube end 30 onto the spigot 280. In one embodiment, such as illustrated by connector 100 above, the collet is arranged to apply a tube clamping pressure on the spigot side of the midpoint of the sealing ridge, as indicated by Fig.28b In one embodiment, the basic fluid sealing force F1 between the tube and the front end of the sealing ridge close to the open end of the spigot is obtained mainly by the elasticity of the tube. When the sealing ridge is positioned immediately adjacent to the open end, sealing is achieved without any voids, i.e., there is no flat section at the open end of the spigot.

[0072] By applying a locking pressure of substantially F2 behind the midpoint of the sealing ridge, substantially all of the available clamping force is used to hold the tube on the sealing ridge. The pressure limit depends on the height of the sealing ridge, the clamping force, the slope of the sealing ridge, and the coefficient of friction between the tube and the socket. However, all surfaces should be as smooth as possible for cleaning. In an alternative embodiment, a portion of the available clamping force may be applied to the end section 281 of the socket 280 to further secure the seal between the socket and the tube. In the disclosed embodiment 100, the fingers 118 of the chuck 110 are designed so that they only apply a specific clamping force near the sealing ridge 282, leaving space for the tube at the lower end of the socket when in the clamped position. In this way, since the clamping force will involve the spring loading of the fingers 118 around the clamped position, the clamping force is less dependent on the dimensional changes in the different components (socket, tube, chuck and collar). In the disclosed embodiment, the available clamping force is determined by the force applied by the operator when pushing the collar 130 over the collet 110 into the tube clamping position, whereby the fingers 118 are displaced to abut the tube, and the force required to lock the clamp by pushing the collar 130 should be adapted to be a reasonable force for the user while avoiding requiring too much release force to release the clamp.

[0073] Fig.28b The situation when the fluid tube 30 is installed on the sealing ridge 282 and the length of the socket 280 is shown, and the locking pressure applied to the tube on the socket side at the midpoint of the sealing ridge is schematically indicated. The fluid sealing force F1 between the tube and the front end of the sealing ridge close to the open end of the socket is achieved by the elasticity of the tube. When the sealing ridge is positioned immediately adjacent to the open end, sealing is achieved without any voids, that is, there is no flat section at the open end of the socket.

[0074] By applying a locking pressure of F2 behind the midpoint of the sealing ridge, substantially all of the available clamping force is used to hold the tube on the sealing ridge. The pressure limit depends on the height of the sealing ridge, the clamping force, the slope of the sealing ridge, and the coefficient of friction between the tube and the socket. However, all surfaces should be as smooth as possible to facilitate cleaning. In addition, sharp corners can accidentally create cavities in which biological material can be trapped, and therefore sharp corners should be avoided for cleaning.

[0075] It may be necessary to provide additional sealing force F3 at the bottom of the spigot (opposite the open end) to increase the sealing pressure limit. In one embodiment, at least 80% of the clamping force is applied behind the midpoint of the sealing ridge (indicated by F2). In one embodiment, abutment or less pressure is applied at or near the bottom of the spigot to stabilize the connection.

[0076] A releasable coupling as described above may be used to provide the clamping force. Other types of couplings are possible, provided they provide the appropriate amount of clamping force as described above, such as hose clamps, eccentric couplings. The length of the selected connector must be selected based on the length of the socket to avoid leverage.

[0077] Fig.29a and Fig.29b A cross-sectional view showing an alternative sealing ridge configuration. Fig.29a 2 shows a spigot 290 having a first alternative sealing ridge 292 with a non-uniform profile. The rear edge 291 of the sealing ridge drops more rapidly from the midpoint of the sealing ridge to the outer surface of the spigot. This improves the pressure limit of the connection. In addition, the front end of the sealing ridge 292 is in line with the open end of the spigot, as indicated by reference numeral D3. In combination with Fig.28a and Fig.28b This will increase the force required to install the fluid tube (not shown) compared to the socket described.

[0078] Fig.29b A spigot 295 is shown having a second alternative sealing ridge 297 with a non-uniform profile. The rear edge 296 of the sealing ridge curves at a radius r2 from the midpoint of the sealing ridge to the outer surface of the spigot. The profile from the midpoint of the sealing ridge to the open end of the spigot curves at a radius r1, which is greater than r2.

[0079] In addition, the front end of the sealing ridge 297 is aligned with the open end of the socket as indicated by reference numeral D4, which in this example is greater than D3, indicating that the sealing ridge 297 is aligned with the open end of the socket as indicated by reference numeral D4. Fig.29a The force required to install a fluid tube (not shown) is compared to the socket described.

[0080] In general, the present invention relates to a novel connector concept for a chromatography system, wherein Fig.25a and Fig.25bConventional threaded fluid connector shown can be replaced by a more convenient socket type connector, wherein only the tube for interconnecting member in the chromatographic system needs to be simply pushed onto the socket, and then fixed onto the socket by a releasable fixture, radial clamping force is applied to the outer periphery of the tube. As mentioned, the socket is preferably provided with a sealing ridge so that the connector concept can be used within the required pressure range. Surprisingly confirmed, it is possible to design such connectors to provide leak-proof fluid connection under the internal pressure (20bar, and even up to more than 30bar) exceeding the range required by liquid chromatography, while still significantly improving the ease of use for the operator. According to the program of the port in the chromatographic system connected to the pipe of its embodiment, only the following steps are involved: the pipe end is pushed through the socket, the releasable connector fixture is positioned around the pipe end, and the locking force is applied by actuating the connector fixture. Similarly, according to the program of the port disconnection for the pipe in the chromatographic system of its embodiment, only the following steps are involved: the connector fixture is actuated to release the locking force, the releasable connector fixture is optionally removed from the pipe end, and the pipe end is pulled out from the socket. A major advantage of the disclosed embodiments is that the steps of pushing and applying the locking clamp do not require a twisting motion that would transfer rotational motion to the tube so that the tube does not rotate relative to the male portion during the applying step. As mentioned, this prevents the tube from twisting and forming kinks, which could restrict fluid flow, or even damage the tube segment. In addition, compared to conventional chromatography systems with connectors that require flanged tubing, for example, tubing with an inner diameter of 1 to 10 mm, the present system provides the benefit of allowing customization of fluid paths by adding the step of cutting the tubing segments to optimal lengths prior to interconnecting the paths.

[0081] Connector leak test.

[0082] Embodiments of the present connector / chromatography system have been verified to provide leak-proof connections within the expected pressure range of the liquid chromatograph. In one embodiment, the upper operating pressure limit of the chromatography system is 20 Bar, and to verify the correct sealing at 20 Bar, the connector is regularly tested for leaks at 30 Bar. In the test, the limit value for determining leakage was set to 1 μl / min at 20 Bar for each connector in the flow path tested. Successful testing was performed under the following conditions: Leak test at 20 Bar in the temperature range of 4-40°C.

[0083] 6000 repetitive connections and disconnections, leak tested at 30 Bar every 500 cycles (performed on two different sizes) • Static leak testing at 40°C for 12 months, with weekly leak testing at 30 Bar.

[0084] • Tensile test 0-20N, 10000 cycles, leak test at 30 bar before and after each cycle As mentioned previously, it was surprisingly found that this could be achieved whilst providing such improved ease of use compared to conventional connections.

[0085] In addition to the leak test above, a salt creep test was performed by circulating a mobile phase of 2.5M (NH4)2SO4 in the system overnight (about 12 hours) with a back pressure of 1.5 MPa. Afterwards, the system was visually inspected for salt creep around connectors, valves, and other modules. The connectors and chromatographic system were confirmed to pass the test with no visible salt creep.

[0086] Figures 30a-30c The interaction between the socket 20, the tube 30 and the collet 110 and its fingers 118 is shown according to one embodiment. Fig.30a In FIG, the tube end 310 is shown above the spigot, with the dashed line indicating the relationship between the inner diameter of the tube and the spigot elements. As can be seen, the spigot bottom is slightly wider than the inner diameter of the tube, and the sealing ridge 22 is significantly wider but has a rounded front edge for allowing the tube to be pushed onto the spigot. Fig.30b In the embodiment shown, the tube end has been pushed onto the spigot (beyond the portion that was pulled out), and the collet 110 has been applied around the tube end and actuated in the locked position to clamp the tube. Fig.30c 1, wherein it can be seen that the fingers 118a are provided with a clamping section 350 for clamping the tube in the central area of ​​the sealing ridge 22 of the socket 20. In one embodiment, the tube has an inner diameter of 3.2 mm and an outer diameter of 4.8, while the socket bottom diameter is 3.25 and the sealing ridge 3.45, which together with the locking force from the clamp 10 provide a leak-free connection. The tubes used in this type of liquid chromatography system are generally tubes of a material that is sufficiently rigid to comply with the pressures involved, and may be made of, for example, fluorinated ethylene propylene (FEP) plastic.

[0087] According to one embodiment, a component 12-18; 810; 910 for a chromatography system 11 is disclosed. The component (which may be modular) includes one or more ports, each of which is accessible via a socket 20; 923, 923', which is used to receive a first end of a fluid tube 30; 812; 912. The first end can be sealed around the socket by a releasable coupling 100, 105, 300 on the outside of the tube end, and the coupling has a releasable clamping action, which can be actuated by sliding movement of a collar element 130, 230, 230', 330, 430 of the coupling along the end of the fluid tube.

[0088] The socket (20) can be an integral part of the components 12-18. In addition, the socket 923; 923' can be provided on the adapter 915; 915', and the adapter is configured to connect to the port of the component 910. In some embodiments, the port is a threaded hole 911, and the adapter 915, 915' includes a corresponding threaded portion 921, a body 920 and a socket 923; 923'.

[0089] In some embodiments, the adapter 915 is made from a single piece of material, which may be plastic or metal.

[0090] In some embodiments, the socket 923 ′ is made of a first material, and the body 920 and the threaded portion 921 are made of a second material, wherein the first material may be metal and the second material may be plastic.

[0091] According to one embodiment, a removable coupling 100 is disclosed, which is configured to retain a fluid tube to a socket. The coupling comprises: a cylindrical inner member 110; 310; 410 configured to receive the fluid tube 30, said inner member comprising a resiliently deflectable portion 118; 418 arranged to push the outer surface of the tube towards the socket; and - a collar element 130 having an internal through hole 132 for slidably receiving an inner member, the orifice and the resiliently deflectable portion having complementary surface structures which provide for said resilient deflection in use in a first position of the collar element mounted to the inner member and prevent action relative to the outer surface of the fluid tube in a second, different position.

[0092] The collar element includes at least one protrusion extending outwardly away from the aperture, the aperture being sized to allow manual manipulation of the collar between a first position and a second position.

[0093] In some embodiments, the inner member 110 further includes a stop portion 138; 114 to cooperate with the collar element to prevent or inhibit sliding of the collar element away from the inner member in at least one direction.

[0094] In some embodiments, the collar element is slidable on the inner member from a first position in which the deflection is provided to a second position in which the collar element abuts the stop portion.

[0095] In some embodiments, the collar flange 134 is formed at one end of the collar element, wherein the stop portion is formed at one end of the inner member. The collar flange 134 and the stop portion can be brought to the vicinity of the second position by manual manipulation, and the collar element can be further slid to the first position by manual manipulation, where the collar flange 134 is spaced apart from the stop portion.

[0096] In some embodiments, the portion is a collet flange 114 that extends outwardly and is sized to facilitate manual manipulation of the coupling. In some embodiments, the collar flange 134 is a continuous annular structure upstanding from the body 136 of the collar.

[0097] In some embodiments, the collar flange 134 and the outer surface of the collar element on which it is formed have a continuously curved profile without abrupt changes in direction.

[0098] In some embodiments, the resiliently deflectable portion 118; 418 of the inner member 110; 310; 410 comprises a plurality of circumferentially arranged fingers which, in use, can be deflected inwardly toward the tube. In some embodiments, the collar element 330 further comprises a bayonet opening 345 cooperating with a complementary locking pin 27 to releasably secure the coupling to the module 1.

[0099] According to one embodiment, a converter 823; 823'; 925 for connecting an end of a first fluid tube 822 to an end of a second fluid tube is disclosed. The converter comprises a socket 833; 833'; 933 for receiving the end of the first fluid tube 822, wherein the end of the first fluid tube can be sealed around the socket by a releasable coupling 100, 105, 300 on the outside of the tube end. The coupling has a releasable clamping action that can be actuated by a sliding movement of a collar element 130, 230, 230', 330, 430 of the coupling along the end of the fluid tube.

[0100] In some embodiments, the converter 823; 823' further includes a body 830 and a flange 831, or a body 930 and a portion having a threaded hole 931, which is configured to be connected to an end of a second fluid pipe.

[0101] In some embodiments, the converter 823 is made from a single piece of material, where the single piece of material can be plastic or metal.

[0102] In some embodiments, the socket 833' is made of a first material, and the body 830 and the flange 831, or the body 930 and the portion having the threaded hole 931 are made of a second material. The first material may be metal, and the second material may be plastic.

[0103] According to one embodiment, a chromatography system 11 comprising a plurality of components 12-18; 810; 910 as described above is disclosed that can be fluidically interconnected by a fluid tube 30. The components include one or more sockets 20f for receiving respective ends of the fluid tube 30, the fluid tube ends being sealed around the sockets by releasable couplings 100, 105, 300 as described above, the couplings having a releasable clamping action that can be actuated by sliding movement of a collar element 130, 230, 230', 330, 430 of the couplings along the ends of the fluid tubes.

[0104] In some embodiments, the sliding movement is a movement generally towards the respective component, and the clamping action may be releasable by movement away from the component.

[0105] In some embodiments, multiple components 12-18 are modular components that can be rearranged on the support member 80, and the fluid tube 30 includes multiple lengths of fluid tubes, each fluid tube having opposite ends, and a connector 100, 105, 300 is provided at each end, which are used together to allow substantially sealed fluid flow or fluid communication between the corresponding modular components.

[0106] In some embodiments, the sliding motion is only linear motion, or substantially linear motion, wherein the torsional motion is less than 120 degrees.

[0107] In some embodiments, the chromatography system is a chromatography system formed from a plurality of components.

[0108] In some embodiments, the chromatography system further comprises a converter as described above.

[0109] According to one embodiment, a chromatography system is provided, which includes a plurality of fluid handling components that can be fluidically interconnected via a fluid tube 30 to form a chromatography fluid flow path, the fluid handling components including one or more fluid ports having a socket extending from a component face and for receiving a corresponding end of a fluid tube, such that the fluid tube end sealingly surrounds the socket and is for receiving a releasable locking clamp that applies a radial locking force to an outer surface of the tube end to lock the fluid tube end on the socket, wherein the interconnection is leak-proof at an internal pressure of at least 10 Bar (preferably 15, 20, 25 or 30 Bar).

[0110] The invention should not be seen as limited to the embodiments described above, but may be varied within the scope of the appended claims, as is readily apparent to a person skilled in the art.

[0111] Terms: 1. A chromatography system (11), comprising a plurality of components (12-18; 810; 910), the plurality of components being fluidically interconnected via a fluid tube (30), the components comprising one or more ports, each port being accessible via a socket (20; 280; 923, 923'), the socket being adapted to receive a respective end of the fluid tube (30), wherein the socket is provided with an open end, the open end having a sealing ridge (22; 282) proximate to the open end, and the fluid tube end creating a direct seal between the inner wall of the tube and the sealing ridge (22). 2. A chromatography system according to clause 1, characterized in that the direct seal is a cavity-free seal around a sealing ridge of the socket. 3. Chromatographic system according to clause 1 or clause 2, characterized in that the fluid tube is pressurized or can be pressurized to a pressure of up to 20 bar and maintains the seal or the cavity-free seal. 4. A chromatography system according to any one of clauses 1 to 3, characterized in that the multiple components (12-18) are modular components that can be rearranged in a positionable manner on a support (80), and wherein the fluid tube (30) includes multiple lengths of fluid tube, each of which has opposite ends, and a connector (100, 105, 300) is provided at each end, which are used together to allow substantially sealed fluid flow or fluid communication between the corresponding modular components. 5. A chromatography system according to any one of clauses 1 to 4, characterized in that the first end of the fluid tube (30) can be sealed around the socket by a releasable connector (100, 105, 300) outside the tube end, and the connector has a releasable clamping action, which can be actuated by a sliding movement of a ring element (130, 230, 230', 330, 430) of the connector along the end of the fluid tube. 6. Chromatography system according to clause 5, characterized in that the sliding movement is a movement generally towards the corresponding component, and the clamping action can be released by the movement away from the component. 7. The chromatography system according to any one of clauses 5 to 6, characterized in that the sliding motion is only a linear motion, or a substantially linear motion including a torsional motion of less than 120 degrees. 8. The chromatography system according to any one of clauses 5 to 7, wherein the releasable coupling comprises: - a cylindrical inner member (110; 310; 410) configured to receive the fluid tube (30), the inner member comprising a resiliently deflectable portion (118; 418) arranged to push the outer surface of the tube towards the socket; and a collar element (130) having an internal through hole (132) for slidably receiving the inner member, the aperture and the resiliently deflectable portion having complementary surface structures which, in a first position of the collar element mounted to the inner member, provide for the resilient deflection in use and which, in a second, different position, prevent movement relative to an outer surface of the fluid tube, Wherein the collar element further comprises at least one protrusion extending outwardly away from the aperture, the aperture having a size to allow manual manipulation of the collar between the first position and the second position. 9. The chromatography system according to clause 8, characterized in that the internal component (110) further comprises a stop portion (138; 114), which cooperates with the collar element to prevent or inhibit the collar element from sliding away from the internal component in at least one direction. 10. The chromatography system according to clause 9, wherein the collar element is slidable on the inner member from the first position in which the deflection is provided to the second position in which the collar element abuts the stop portion. 11. A chromatography system according to clause 8 or clause 9, characterized in that a ring flange (134) is formed at one end of the ring element, wherein the stop portion is formed at one end of the internal component, wherein the ring flange (134) and the stop portion can be approached to the second position by manual manipulation, and wherein the ring element can be further slid to the first position by manual manipulation, at which the ring flange (134) is separated from the stop portion. 12. The chromatography system according to clause 11, characterized in that the stop portion is a chuck flange (114) extending outwardly and having a size to assist manual manipulation of the coupling. 13. The chromatography system according to any one of clauses 8 to 12, characterized in that the collar flange (134) is a continuous annular structure upstanding from the body (136) of the collar. 14. The chromatography system according to clause 13, characterized in that the collar flange (134) and the outer surface of the collar element on which the collar flange is formed have a continuously curved profile without abrupt changes in direction. 15. A chromatography system according to any one of clauses 8 to 14, characterized in that the elastically deflectable portion (118; 418) of the internal component (110; 310; 410) comprises a plurality of circumferentially arranged fingers which are capable of deflecting inwardly toward the tube during use. 16. The chromatography system according to any one of clauses 8 to 15, characterized in that the collar element (330) further comprises a bayonet opening (345) cooperating with a complementary locking pin (27) for releasably securing the coupling to the module (1). 17. The chromatography system according to any one of clauses 1 to 16, characterized in that the socket (20) is an integral part of each modular component (12-18). 18. The chromatography system according to any one of clauses 1 to 16, characterized in that the socket (923; 923') is provided on an adapter (915; 915'), and the adapter is configured to be connected to a port of the module (910). 19. The chromatography system according to clause 18, characterized in that the port is a threaded hole (911), and the adapter (915, 915') comprises a corresponding threaded portion (921), a body (920) and a socket (923; 923'). 20. The chromatography system according to any one of clauses 18 to 19, characterized in that the adapter (915) is made of a single piece of material. 21. The chromatography system of clause 20, wherein the single piece of material is plastic or metal. 22. The chromatography system according to clause 19, characterized in that the socket (923') is made of a first material, and the body (920) and the threaded portion (921) are made of a second material. 23. The chromatography system of clause 22, wherein the first material is metal and the second material is plastic. 24. A chromatography system according to any one of clauses 1 to 23, characterized in that the chromatography system also includes a converter (823; 823'; 925), which is used to connect the end of a first fluid tube (822) to the end of a second fluid tube, wherein the converter includes a socket (833; 833'; 933), which is used to receive the end of the first fluid tube (822), the end of the first fluid tube can be sealed around the socket by a releasable connector (100, 105, 300) outside the tube end, and the connector has a releasable clamping action, which can be actuated by a sliding movement of a ring element (130, 230, 230', 330, 430) of the connector along the end of the fluid tube. 25. The chromatography system according to clause 24, characterized in that the converter (823; 823') further comprises a body (830) and a flange (831), or a body (930) and a portion with a threaded hole (931), which is configured to be connected to the end of the second fluid tube. 26. Chromatography system according to clause 24 or clause 25, characterized in that the converter (823) is made of a single piece of material. 27. The chromatography system of clause 26, wherein the single piece of material is plastic or metal. 28. The chromatography system according to clause 24, characterized in that the socket (833') is made of a first material, and the body (830) and the flange (831), or the body (930) and the portion with the threaded hole (931) are made of a second material. 29. The chromatography system of clause 28, wherein the first material is metal and the second material is plastic. 30. A chromatography system (11), comprising a plurality of fluid handling components (12-18; 810; 910), the plurality of fluid handling components being capable of being fluidically interconnected via a fluid tube (30) to form a bioprocess fluid flow path, the fluid handling component comprising one or more fluid ports with a socket (20; 923, 923'), the socket extending from a component face and being used to receive a corresponding end of the fluid tube (30) so that the fluid tube end sealingly surrounds the socket, and being used to receive a releasable locking clamp, the releasable locking clamp being used to apply a radial locking force to an outer surface of the tube end so as to lock the end of the fluid tube onto the socket, wherein the interconnection withstands at least 20 bar. 31. A releasable coupling (100) for retaining a fluid tube to a male part in a chromatography system, the coupling comprising: a cylindrical inner member (110) for receiving a fluid tube (30), the inner member comprising a resiliently deflectable portion (118) arranged to urge an outer surface of the tube towards the male part; and a cylindrical collar element (130) having an internal through hole (132) for slidably receiving the inner member, the orifice and the resilient portion having complementary surface structures which provide the resilient deflection in use in a first position of the collar mounted to the inner member and which do not cause the deflection in a second, different position, the coupling being characterized in that the collar comprises at least one protrusion, such as a collar flange (134) or a collar wing (334), extending outwardly away from the orifice, the orifice having a size allowing manual manipulation of the collar between the first position and the second position. 32. A coupling according to clause 31, characterized in that the inner member (110) further comprises a stop portion (138 / 114) which cooperates with the collar to prevent or inhibit sliding of the collar away from the inner member in at least one direction. 33. A coupling according to clause 32, wherein the collar is slidable on the inner member from the first position in which the deflection is provided to the second position in which the collar abuts the stop portion. 34. A connector according to clause 32 or clause 33, characterized in that the ring flange / wing is formed at one end of the ring, wherein the stop portion is formed at one end of the internal member, wherein the ring flange and the stop portion can be approached to the second position by manual manipulation, and wherein the ring can be further slid to the first position by manual manipulation, in which the ring flange is separated from the stop portion. 35. A coupling according to clause 31, wherein the collar flange and the outer surface of the collar on which the flange is formed have a continuously curved profile without abrupt changes in direction. 36. A coupling as claimed in any one of clauses 31 to 35, wherein the resiliently deflectable portion of the inner member comprises a plurality of circumferentially arranged fingers which are deflectable inwardly towards the tube in use. 37. A releasable coupling assembly (10) for retaining a fluid tube to a male portion, the coupling comprising: A flexible fluid tube (30); a male portion (20), the male portion (20) being insertable into the fluid tube; a cylindrical inner member (110) for fitting over the fluid tube, the inner member comprising a resiliently deflectable portion (118) arranged to push an outer surface of the tube onto the male portion; and a cylindrical collar element (130, 230) having an internal through hole (132, 232) for enabling the collar to be slidably mounted on the inner member; wherein the orifice and the resilient portion have complementary surface structures which provide for said resilient deflection in use in a first position of said collar mounted on said inner member, whereby when the inner part is fitted on said tube, said tube is pushed onto said male part by said resiliently deflectable portion, and said complementary surface structures do not cause said deflection in a second position, whereby said tube is not so pushed or is pushed less onto said male part, The coupling is characterized in that the collar includes a collar flange (134, 234) extending outwardly away from the aperture, the aperture being sized to allow manual manipulation of the collar between the first position and the second position. 38. A releasable coupling (100) for retaining a fluid tube to a male part in a chromatography system, the coupling comprising: a cylindrical inner member (110) for receiving a fluid tube (30), the inner member comprising a resiliently deflectable portion (118) arranged to urge an outer surface of the tube towards the male part; and a cylindrical collar element (130) having an internal through hole (132) for slidably receiving the inner member, the orifice and the resilient portion having complementary surface structures which provide the resilient deflection in use in a first position of the collar mounted to the inner member and which do not cause the deflection in a second, different position, the coupling being characterized in that the collar comprises at least one protrusion extending outwardly away from the orifice, such as a collar flange (134) or a collar wing (334), the orifice having a size allowing manual manipulation of the collar between the first position and the second position. 39. The coupling (100) of clause 38, wherein the inner member (110) further comprises a stop portion (138, 114) that cooperates with the collar to prevent or inhibit the collar from sliding away from the inner member in at least one direction. 40. A coupling (100) according to clause 39, characterized in that the collar is capable of sliding on the inner member from the first position in which the deflection is provided to the second position in which the collar abuts the stop portion (138, 114). 41. A connector (100) according to clause 39 or clause 40, characterized in that the ring flange / wing is formed at one end of the ring, wherein the stop portion is formed at one end of the internal component, wherein the ring flange and the stop portion can be approached to the second position by manual manipulation, and wherein the ring can be further slid to the first position by manual manipulation, at which the ring flange is separated from the stop portion. 42. A coupling (100) according to any one of clauses 38 to 41, characterized in that the collar flange and the outer surface of the collar on which the flange is formed have a continuously curved profile without abrupt changes in direction. 43. A coupling (100) according to any one of clauses 38 to 42, characterized in that the resiliently deflectable portion of the inner member comprises a plurality of circumferentially arranged fingers (118) which are deflectable inwardly towards the tube during use. 44. A coupling (100) according to clause 43, characterized in that the finger (118) extends from a middle portion (116) of the cylindrical inner member (110) to a distal end (120) of the cylindrical inner member (110). 45. The coupling (100) of clause 44, wherein the fingers (118) flare outwardly toward the distal end (120). 46. ​​A coupling (100) according to any one of clauses 38 to 45, characterised in that the coupling (100) is formed from two mouldings of plastic material. 47. The coupling (100) according to clause 46, characterized in that the cylindrical inner member (110) and the cylindrical collar element (130) are formed of transparent plastic. 48. A coupling (100) according to any one of clauses 38 to 47, characterized in that the distal end (340) of the cylindrical collar element (330) comprises a pair of bayonet-type openings (345) for receiving complementary locking pins (27). 49. A connector (100) according to any one of clauses 38 to 47, characterized in that the cylindrical collar element (430) includes a pawl (432), and when the cylindrical collar element (430) is twisted relative to the finger (418), the pawl serves as the tapered portion (431) of the finger (418), and the tapered portions (431) each serve as a cam, so that when the cylindrical collar element (430) is twisted, the tapered portion (431) is pushed inward relative to the cylindrical collar element (430) by the corresponding pawl (432) in the cylindrical collar element (430). 50. A coupling (100) according to clause 49, characterized in that the finger (418) comprises a corresponding complementary recess (433) for a corresponding detent (432) to rest therein. 51. A coupling (100) according to any one of clauses 38 to 50, characterized in that the cylindrical collar element (130) is part of a locking plate (230) having a plurality of through holes (232). 52. The coupling (100) according to clause 51, characterized in that the cylindrical collar element (130) is mounted to the locking plate (230) by means of a flexible mounting. 53. A coupling (100) according to clause 52, characterized in that the flexible mounting member is a spherical mounting member (233) which allows the cylindrical collar element (130) to rotate about a center point of the mounting member (233). 54. A releasable coupling assembly (10) for retaining a fluid tube to a male portion, the coupling comprising: A flexible fluid tube (30); a male portion (20), the male portion (20) being insertable into the fluid tube; a cylindrical inner member (110) for fitting over the fluid tube, the inner member comprising a resiliently deflectable portion (118) arranged to push an outer surface of the tube onto the male portion; and a cylindrical collar element (130, 230) having an internal through hole (132, 232) for enabling the collar to be slidably mounted on the inner member; wherein the orifice and the resilient portion have complementary surface structures which provide for said resilient deflection in use in a first position of said collar mounted on said inner member, whereby when the inner part is fitted on said tube, said tube is pushed onto said male part by said resiliently deflectable portion, and said complementary surface structures do not cause said deflection in a second position, whereby said tube is not so pushed or is pushed less onto said male part, The coupling is characterized in that the collar includes a collar flange (134, 234) extending outwardly away from the aperture, the aperture being sized to allow manual manipulation of the collar between the first position and the second position. 55. A coupling (10) according to clause 54, characterized in that the resiliently deflectable portion (118) comprises a plurality of resiliently deflectable and circumferentially arranged fingers. 56. A coupling (10) according to clause 55, characterized in that the finger extends from a middle portion (116) of the cylindrical inner member (110) to a distal end (120) of the cylindrical inner member (110). 57. A coupling (10) according to clause 56, characterized in that the fingers (118) flare outwardly toward the distal end (120). 58. A coupling (100) according to any one of clauses 54 to 57, characterised in that the coupling (100) is formed from two mouldings of plastic material. 59. The coupling (100) according to clause 58, characterized in that the cylindrical inner member (110) and the cylindrical collar element (130) are formed of transparent plastic. 60. A coupling (100) according to any one of clauses 54 to 59, characterized in that the distal end (340) of the cylindrical collar element (330) comprises a pair of bayonet-type openings (345) for receiving complementary locking pins (27). 61. A connector (100) according to any one of clauses 54 to 59, characterized in that the cylindrical ring element (430) includes a pawl (432), and when the cylindrical ring element (430) is twisted relative to the finger (418), the pawl serves as the tapered portion (431) of the finger (418), and the tapered portions (431) each serve as a cam, so that when the cylindrical ring element (430) is twisted, the tapered portion (431) is pushed inward relative to the cylindrical ring element (430) by the corresponding pawl (432) in the cylindrical ring element (430). 62. A coupling (100) according to clause 61, characterized in that the finger (418) comprises a corresponding complementary recess (433) for the corresponding pawl (432) to rest therein. 63. A coupling (100) according to any one of clauses 54 to 62, characterized in that the cylindrical collar element (130) is part of a locking plate (230) having a plurality of through holes (232). 64. A coupling (100) according to clause 63, characterized in that the cylindrical collar element (130) is mounted to the locking plate (230) by means of a flexible mounting. 65. A coupling (100) according to clause 64, characterized in that the flexible mounting member is a spherical mounting member (233) which allows the cylindrical collar element (130) to rotate about a center point of the mounting member (233). 66. A reconfigurable liquid interconnect (580) for connecting to at least one modular component (51-75) in a chromatography device (400), the reconfigurable liquid interconnect (580) comprising a connector (100) according to any one of clauses 54 to 65. 67. A reconfigurable liquid interconnect (580) according to claim 66, characterized in that the modular components (51-75) include one or more of the following: a control panel (51), a pH monitor (52), an outlet valve (53, 54, 56), a conductivity monitor (55), a pre-column conductivity monitor (57), a column valve unit (58) including pre-column and post-column pressure sensors, a bottle (59), an inlet valve (60, 61, 62, 63), a system pump (66, 67), a flow restrictor (68) including a system pressure monitor, a mixer modular component (69), a mixing valve (70), an air trap valve (71) including an air sensor, an air trap (72), a holder for an inline filter (74) and / or a UV monitor (75). 68. The reconfigurable liquid interconnect (580) of clause 66 or clause 67, wherein the reconfigurable liquid interconnect (580) further comprises at least one tube (30) formed of a substantially rigid material. 69. The reconfigurable liquid interconnect (580) of clause 68, wherein the substantially rigid material comprises fluorinated ethylene propylene (FEP) plastic. 70. A converter (823, 823', 925) for connecting the end of a first fluid tube (822) to the end of a second fluid tube, wherein the converter includes a socket (833, 833', 933) for receiving the end of the first fluid tube (822), wherein the end of the first fluid tube (822) can be sealed around the socket (833, 833', 933) by a releasable connector (100, 105, 300) arranged on the outside of the end of the first fluid tube (822), and the releasable connector (100, 105, 300) has a releasable clamping action, and the releasable clamping action can be actuated by a sliding movement of a ring element (130, 230, 230', 330, 430) of the connector along the end of the first fluid tube (822). 71. The converter (823, 823', 925) according to clause 70, characterized in that the releasable coupling assembly (10) comprises: a male portion (20), the male portion (20) being insertable into the first fluid tube (822); a cylindrical inner member (110) for fitting onto the end of the first fluid tube (822), the cylindrical inner member comprising a resiliently deflectable portion (118) arranged to push an outer surface of the end of the first fluid tube (822) onto the male portion (20); The collar element (130, 230) has an internal through hole (132, 232) for enabling the collar element (130, 230) to be slidably mounted on the cylindrical inner member (110). wherein the orifice (132, 232) and the resilient portion (118) have complementary surface structures, the complementary surface structures providing the resilient deflection in use in a first position of the collar element (130, 230) mounted on the cylindrical inner member (110), whereby when the cylindrical inner member (110) is assembled on the fluid tube (822), the fluid tube (822) is pushed onto the male portion (20) by the resiliently deflectable portion (118), and the complementary surface structures do not cause the deflection in a second position, whereby the fluid tube (822) is not pushed or is pushed less onto the male portion (20), the collar element (130, 230) further comprising a collar flange (134, 234) extending outwardly away from the orifice (132, 232), the orifice having a size allowing the collar element (130, 230) to be manually manipulated between the first position and the second position. 72. The converter (823, 823', 925) according to clause 71, characterized in that the elastically deflectable portion (118) comprises a plurality of elastically deflectable and circumferentially arranged fingers. 73. The converter (823, 823', 925) according to clause 72, characterized in that the finger extends from a middle portion (116) of the cylindrical inner member (110) to a distal end (120) of the cylindrical inner member (110). 74. The converter (823, 823', 925) according to clause 73, characterized in that the fingers (118) flare outwardly toward the distal end (120). 75. The converter (823, 823', 925) according to any one of clauses 71 to 74, characterized in that the converter (823, 823', 925) is formed from two plastic material mouldings. 76. The converter (823, 823', 925) according to clause 75, characterized in that the cylindrical inner member (110) and the collar element (130) are formed of transparent plastic. 77. A converter (823, 823', 925) according to any one of clauses 70 to 76, characterized in that the converter (823, 823', 925) also includes a body (830) and a flange (831), or a body (930) and a part with a threaded hole (931), which is configured to be connected to the end of the second fluid pipe. 78. The converter (823, 823', 925) according to any one of clauses 70 to 77, characterized in that the converter (823, 823', 925) is made of a single piece of material. 79. A converter (823, 823', 925) according to any one of clauses 70 to 77, characterized in that the socket (833') is made of a first material, and the body (830) and the flange (831) or the body (930) and the part with the threaded hole (931) are made of a second material. 80. Converter (823, 823', 925) according to clause 78 or clause 79, characterized in that the single piece of material is plastic or metal, or wherein the first material is metal and the second material is plastic. 81. A converter (823, 823', 925) according to any one of clauses 70 to 80, characterized in that the converter (823, 823', 925) has a body (830), a flange (831) and a through hole (832), wherein the socket (833) is integrated with the body (830). 82. The converter (823, 823', 925) according to clause 81, characterized in that the flange (831) is suitable for use in a triple clamp (TC) coupling. 83. A converter (915, 925) according to any one of clauses 70 to 82, characterized in that the converter (915, 925) has a body (920, 930), a threaded portion (921, 931) and a through hole (922, 932), and wherein the socket (923, 933) is integrated with the body (920, 930). 84. A converter (915, 925) according to clause 83, characterized in that the threaded portion (921) is suitable for being introduced into a threaded hole of a modular component using the body (920) as a gripping portion.

Claims

1. A chromatography system (11, 400) comprising a plurality of fluid handling components (12-18, 51-72, 820; 910), the plurality of fluid handling components being capable of being fluidically interconnected via a fluid tube (30, 580, 822) to form a bioprocess fluid flow path, the fluid handling components comprising two or more fluid ports (520, 531, 532, 541, 542, 550, 821), wherein: At least one of the fluid handling components has at least one fluid port, and the at least one fluid port has a male part (20, 20', 280, 290, 295, 833, 833', 923, 923'), the male part protruding from the front surface of the at least one fluid handling component, and the male part is arranged to receive the first end of the fluid tube on the male part, wherein the fluid tube is arranged to be connected to the corresponding fluid port by applying a radial locking force on the outer surface of the first end of the fluid tube to lock the first end of the fluid tube on the male part.

2. The chromatography system according to claim 1, wherein: The interconnections between the plurality of fluid handling components withstand at least 10 bar.

3. The chromatography system according to claim 1 or 2, wherein: The fluid tube is locked to the male portion by a releasable connector.

4. The chromatography system according to claim 3, wherein: The releasable connector comprises: an inner member (110, 310, 410) for receiving the fluid tube, the inner member comprising a resiliently deflectable portion (118, 318, 418) arranged to urge an outer surface of the fluid tube toward the male portion (20, 20', 280, 290, 295, 833, 833', 923, 923'); and A locking member (130, 330, 430) for applying a clamping force on the resiliently deflectable portion (118, 318, 418) thereby applying the radial locking force on the outer surface of the first end of the fluid tube.

5. The chromatography system according to claim 4, wherein: The resiliently deflectable portion (118) of the inner member (110) comprises a plurality of circumferentially arranged fingers which are deflectable inwardly in use.

6. The chromatography system according to claim 4 or 5, wherein: The locking member comprises an internal through hole (132) for receiving the internal member, the orifice and the elastically deflectable portion having complementary surface structures, wherein in the locked position of the releasable connector, the locking member is mounted to the internal member so that the locking member applies the clamping force on the elastically deflectable portion (118, 318, 418), the elastically deflectable portion deflects inwardly and thereby applies the radial locking force on the outer surface of the first end of the fluid tube, and wherein in the released position of the releasable connector, the deflectable portion elastically springs outwardly, thereby releasing the radial locking force on the outer surface of the first end of the fluid tube.

7. The chromatography system according to claim 1 or 2, wherein: The male portion is provided with an open end, the male portion having a widened portion (22, 282) adjacent the open end, wherein the first end of the fluid tube is arranged to sealingly engage the widened portion around the outer surface of the male portion.

8. The chromatography system according to claim 6, wherein: The locking member includes at least one protrusion extending outwardly away from the internal through hole, the at least one protrusion having a size that allows manual manipulation of the locking member between the locking position and the release position.

9. The chromatography system according to claim 4 or 5, wherein: The clamping force is generated by substantially linear movement of the locking member along the inner member.

10. The chromatography system according to claim 9, wherein: The substantially linear movement is a sliding movement of the locking member along the inner member.

11. The chromatography system according to claim 9, wherein: The substantially linear movement is a twisting movement of the locking member about the inner member.

12. The chromatography system according to claim 9, wherein: The clamping force is generated by movement of the locking member along the inner member in an opposite direction toward the open end of the male portion.

13. The chromatography system according to claim 1 or 2, wherein: The fluid tube has an outer diameter of 3 mm to 10 mm.

14. The chromatography system according to claim 1 or 2, wherein: The static dimension of the inner diameter of the fluid tube is less than ±10% of the outer diameter dimension of the male portion.

15. The chromatography system according to claim 7, wherein: The widened portion of the male part includes a sealing ridge (22).

16. The chromatography system according to claim 15, wherein: The fluid tube has an inner diameter of 3.2 mm and an outer diameter of 4.8 mm, and the male portion has a bottom diameter of 3.25 mm and the sealing ridge has a diameter of 3.45 mm.

17. The chromatography system according to claim 1 or 2, wherein: The fluid tube is formed from a substantially rigid material.

18. The chromatography system according to claim 17, wherein The substantially rigid material includes fluorinated ethylene propylene (FEP) plastic.

19. The chromatography system according to claim 1 or 2, wherein: The fluid handling component is at least one of: an outlet valve, an inlet valve, an air trap valve, a column valve, a mixing valve and a pump.

20. The chromatography system according to claim 1 or 2, wherein: The male portion is configured as a socket (20).

21. The chromatography system according to claim 1 or 2, wherein: The fluid port is arranged as a non-threaded hole having the male portion protruding from the front surface of the at least one fluid handling member.

22. The chromatography system according to claim 1 or 2, wherein: The chromatography system is configured for use in a Good Manufacturing Practice (GMP) environment.

23. A chromatography column comprising at least one male portion (20) for connecting the chromatography column to a chromatography system according to any one of claims 1 to 22 via a releasable connector, the at least one male portion of the chromatography column being arranged to protrude from a front surface of the chromatography column.

24. The chromatographic column according to claim 23, wherein The releasable connector comprises: an inner member (110, 310, 410) for receiving a fluid tube, the inner member comprising a resiliently deflectable portion (118, 318, 418) arranged to urge an outer surface of the fluid tube towards the male portion (20; 20', 280, 290, 295, 833, 833', 923, 923'); and A locking member (130, 330, 430) is provided for applying a clamping force on the resiliently deflectable portion (118, 318, 418), thereby applying a radial locking force on the outer surface of the first end of the fluid tube.

25. The chromatographic column according to claim 24, wherein The resiliently deflectable portion of the inner member comprises a plurality of circumferentially arranged fingers which are deflectable inwardly in use.

26. The chromatographic column according to claim 23, wherein The male portion includes a sealing ridge.

27. The chromatographic column according to claim 26, wherein The male portion has a bottom diameter of 3.25 mm and / or the sealing ridge has a diameter of 3.45 mm.

28. The chromatographic column according to claim 24, wherein The male portion is provided with an open end, the male portion having a widened portion (22, 282) adjacent the open end, wherein the first end of the fluid tube is arranged to sealingly engage the widened portion around the outer surface of the male portion.

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