Chromatographic system and coupling therefor

Abstract

A chromatography system is disclosed employing a releasable coupling (100) to retain a fluid tube to a port, the coupling comprising a cylindrical inner member (110) for receiving a fluid tube (30), said inner member comprising a resiliently deflectable portion (118) arranged to urge the outer surface of the tube towards the port, and a cylindrical collar (130) having an internal through bore (132) for slidable receipt of the inner member, the bore and resilient portion having complementary surface formations which in a first position of the collar mounted to the inner member provide for said resilient deflection in use, and in a second, different position do not cause said deflection, the coupling being characterised in that the collar comprises a collar flange (134) extending outwardly away from the bore, the bore having a dimension which allows manual manipulation of the collar between the first and second positions. A chromatography system employing said coupling is also disclosed.

Description

Technical Field

[0001] This invention relates to chromatographic systems, such as liquid chromatography systems, and particularly, but not exclusively, to general-purpose laboratory or benchtop-sized systems that allow for easy reconfiguration and convenient automation of different chromatographic programs, as well as reconnectable fluid tubing fittings for connecting tubing and the like associated with such devices or systems. Background Technology

[0002] Reconnectable fluid tubing fittings, which can be disassembled and replaced multiple times but still provide a fluid seal for flexible tubing (such as garden hoses and plastic pipes) upon each reconnection, are known. However, their ease of connection and / or hygiene are questionable, especially if the chromatography system is of the same design, requiring hygienic fittings and typically encountering higher fluid pressures (e.g., up to 20 bar or more). Typical tubing fittings used in chromatography systems have multiple components, including metal springs and O-rings, resulting in dead ends or O-ring grooves that can accumulate harmful contaminants, such as pathogens, during use. These dead ends and grooves are very difficult to clean. Furthermore, the use of metal parts presents problems when attempting to sterilize such fitting assemblies with gamma irradiation. Additionally, the use of threads or special tools is undesirable when speed and ease of connection or disconnection are sought.

[0003] US8662542 shows a prior art barbed locking tube coupling arrangement, but the coupling requires tools for assembly and is not intended to be easy to release.

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

[0005] Furthermore, in chromatography systems, especially benchtop experimental equipment, it is often necessary to clean the equipment, including the interconnecting tubing in use, and then disassemble the tubular setup so that the tubing can be reconfigured for different experiments. Therefore, dedicated sterilization equipment is inconvenient, and rapid cleaning, along with rapid disconnection and reconnection, is required. A such device is disclosed in US8821718, which is incorporated herein by reference, in which interchangeable modular components of the chromatography system can be interconnected via external fluid conduits and will benefit from improved means of such interconnection. Summary of the Invention

[0006] The objective of embodiments of the present invention is to provide a chromatography system, particularly a liquid chromatography system, comprising a releasable fluid coupling that can be quickly reconnected without tightening or twisting the fluid conduits, and without requiring space around each fluid conduit for such actions. A further objective of the present invention is to provide a chromatography system that offers enhanced functionality, such as operability in conventional batch and continuous chromatography; applicability in a wider range of applications; without significantly increasing overall size or manufacturing costs; and ease of operation.

[0007] Another object of embodiments of the present invention is to provide a connector that can be easily cleaned, having no or limited dead ends or other spaces where contaminants can accumulate. Another object of embodiments of the present invention is to provide a connector that can be quickly connected and disconnected without the use of tools, if desired.

[0008] According to one aspect of the invention, a chromatographic system as described herein is provided.

[0009] According to another aspect of the invention, a releasable coupling as defined herein is provided, which can be used as part of a coupling assembly, for example in a chromatography system (such as a benchtop chromatography system), wherein modular components can be rearranged, for example, 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 including one of a coupling assembly of fluid couplings according to the invention for the respective modular component.

[0010] Other preferred aspects of the invention are described herein.

[0011] Further advantages and benefits of the invention will readily become apparent to those skilled in the art in light of the detailed description below. Attached Figure Description

[0012] The invention will now be described in more detail with reference to the accompanying drawings, in which:

[0013] Figure 1 An exploded view of the connecting component is shown;

[0014] Figure 2 The cross-section shows the state of fluid connection. Figure 1 Connecting parts;

[0015] Figure 3 The same coupling in the releasable state is shown in cross-section;

[0016] Figure 4 Shown in cross section including Figure 1 The connecting components of the connecting parts are all in a fluid-sealed state;

[0017] Figure 5 Showing through Figure 4 A cross-sectional view of the connector assembly, but reconstructed into a releasable state;

[0018] Figure 6a b and c show variations of the connector assembly described above;

[0019] Figure 7a b, c, and d show variations of the connecting component assembly;

[0020] Figure 8 This illustrates a chromatography system employing multiple connecting components;

[0021] Figure 9 Show the connector release tool;

[0022] Figure 10 , Figure 11 and Figure 12 An embodiment of the invention, including a bayonet locking feature, is shown;

[0023] Figures 13 to 16 The variations of the connecting components are shown;

[0024] Figure 17 This is a schematic diagram of a chromatography system;

[0025] Figure 18 Show Figure 17 A schematic diagram of the chromatographic system shown in the figure; and

[0026] Figure 19 , Figure 20 and Figure 21 Show Figure 17 and Figure 18 The structure of the chromatographic system is shown in the figure.

[0027] Figure 22 This illustrates a first form of a prior art modular component with four ports;

[0028] Figure 23 A modular component with four ports is shown;

[0029] Figure 24a and Figure 24b Cross-sectional views of two variants of the converter are shown;

[0030] Figure 25a A second form of a prior art modular component with three ports is shown;

[0031] Figure 25b Showing the use of Figure 25a Threaded connectors with modular components.

[0032] Figure 26a and Figure 26b A cross-sectional view of the adapter is shown;

[0033] Figure 27 Alternative converters are shown;

[0034] Figure 28a and Figure 28b A cross-sectional view showing the socket with the installed tube;

[0035] Figure 29a and Figure 29b A cross-sectional view of an alternative sealing ridge construction is shown.

[0036] Figures 30a-30c A cross-sectional view showing one embodiment of the sealing structure. Detailed Implementation

[0037] Good Manufacturing Practices (GMP) specify guidelines for biological processing procedures, and compliance with these guidelines requires cleanliness standards. Advantageously, the proposed equipment makes it easier to meet these standards, for example, where the fluid paths in the system have continuous flow paths in at least one configuration without substantial stagnation, thus providing complete cleanliness without decomposing the fluid conduits. Embodiments of the proposed system provide a hygienic small-scale chromatography system suitable for both GMP and non-GMP operations. The system's wide range of flow and pressure capabilities makes it suitable for both technical batch production and scale-up studies, as well as small-scale production of GMP-grade materials. The pump's high precision and high flow range enable accurate gradient formation, covering a wide range of column sizes and more reproducible results.

[0038] In this embodiment, the modular design provides added functionality for different uses. Interactive control software allows for real-time changes and rapid identification of unexpected deviations. The compact benchtop form factor saves laboratory space. The system allows for in-situ column packaging—the ability to compress columns or use chromatographic media in each of two or more columns while connected to the system—without disconnecting any fluid conduits before performing the chromatographic procedure.

[0039] Figure 1An exploded view of an embodiment of a releasable coupling 100 is shown. The coupling 100 comprises two parts: a cylindrical inner member, in the form of a chuck 110, for receiving a fluid tube; and a cylindrical locking collar 130 having an internal through-hole 132 for slidably receiving the chuck 110. The fluid tube (not shown) extends along an axis T in use and extends within a central opening 112 in the chuck 110, which is sized to fit snugly around the tube. The chuck 110 has a chuck flange 114 formed on a cylindrical intermediate portion 116, and a plurality of resiliently deflectable, circumferentially arranged fingers 118 extending from the intermediate portion 116 of the chuck 110 to a distal end 120.

[0040] The collet 110 slides into the through-hole 132 of the collar 130, and thus the collar 130 can be mounted above and around the fingers 118 and the intermediate portion 116 of the collet 110. The collar 130 can be manipulated along the fingers 118 and the intermediate portion 116 to selectively deflect or loosen the fingers 118, as described in more detail below, which causes the tube to grip. Manipulation of the collar 130 is assisted by a collar flange 134 at the distal end of the collar, which extends from the body 136 of the collar and can be manually pulled or pushed. The collar has a distal end 140. The fingers 118 flare outward toward the distal end 120 of the chuck, so it will be understood that if the orifice 132 has a substantially constant inner diameter, the slippage of the collar 130 along the direction from the chuck flange 114 to the distal end 120 of the chuck 110 will cause the inner diameter of the orifice 132 to abut against the outer surface of the fingers 118 and push it inward to provide tube clamping action.

[0041] Figure 2 Shown in cross section Figure 1 The coupling 100 is arranged in the tube clamping position. Here, the distal end 140 of the collar 130 and the distal end 120 of the collet 110 have been 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 thus cause the fingers 118 to deflect inward toward axis T to push adjacent portions of the tube (not shown) within the collet inward, for example, compressing, squeezing, or clamping the tube. The coupling is released by manipulating the collar and its flange in the direction of arrow R.

[0042] Figure 3The connector 100 is shown again in cross-section, and is arranged, but in the tube release position. Here, the collar 130 has slid along direction R toward the distal end of the chuck, but is prevented from sliding out of the chuck by the chuck flange 114 and / or step 138 (one or each of which forms a stop) in both orifice 132 and opening 112. In this position, the fingers 118 are released and elastically rebound outward to stop or reduce any pushing / compressing / clamping action on the tube. Figure 3 The position shown is indicated by following arrow R ( Figure 2 This is achieved by the directional control collar 130 and its flange 134 relative to the chuck 110.

[0043] Figure 4 A cross-sectional view of a connector assembly 10 is shown, which includes a male portion, in this case in the form of a connector socket 20, having a widened portion, such as a sealing ridge, crimp, or barb 22, which can be positioned within a flexible fluid tube 30, extending beyond the open end of the tube 30 for a push-in fit. The tube 30 is held to the socket 20 by compressing it onto the socket 20. The connector 100 wraps around the tube 30, and as described above, primarily concerns... Figure 2 The described method releasably compresses the tube onto the socket 20 to releasably retain the tube 30 to the socket 20. In this figure, it is clear that the fingers 118 compress the tube 30 behind the widened portion 22, thereby assisting in securing the tube to the socket and effectively locking the tube to the socket 20. The coupling assembly 10 can supply or remove fluid to or from module 1, in this embodiment, which is a chromatography system requiring a releasable fluid coupling that is easily cleaned and will not carry contaminants. In another embodiment, the fluid pressure at module 1 can be measured or adjusted via the fluid tube 30, and therefore only fluid communication is required. Consequently, fluid flow within the tube 30 is not necessary.

[0044] Figure 5 Showing with Figure 4 The same cross-section, but in this view, the connecting assembly 10 is in the released position, as shown. Figure 3 As shown in the diagram. In use, according to... Figure 4 The positioning connector 100 clamps the tube 30 in place on the socket 20, and releases 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 clamp 110 to... Figure 5Arrow R in the diagram indicates retraction 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 disengaging from the chuck and thus allow the chuck to be withdrawn together with flange 134. In this withdrawn position, the tube 30 can be easily pulled out of socket 20. Connecting or reconnecting the tube 30 to the socket is performed by reversing the steps mentioned above. That is, the tube 30 is fitted over socket 20, the chuck flange 114 is pushed in the opposite direction to arrow R, and once the distal end 120 of the chuck is firmly against module 1 in place, the collar flange 134 is pushed back into place so that the fingers 118 deflect against the outer surface of the tube to clamp the tube onto socket 20.

[0045] The connector 100 is preferably formed from only two plastic molded parts. As can be seen from the figure, the outer surface of the collar 130 is smooth; that is, the collar flange 134 is a continuous annular structure erected from the annular body 136, and the collar flange and the outer surface of the collar on which the collar flange is formed have a continuously curved profile without abrupt changes in direction. Therefore, the chance of contamination of the connector during use is reduced, and the connector can be easily cleaned. Additionally, the user can use two fingers, holding 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, by pressing the thumb against the clamp flange 114 opposite to the two fingers, the user's thumb can be used to respond to such pulling forces.

[0046] It is important to ensure that the tube 30 is substantially fully fitted onto the socket 20. For this purpose, the clamp 110 and the collar 130 may be made of transparent plastic. Alternatively, the socket may be a different color from the tube to provide a visual color indication that the tube does not completely overlap with the socket if any color of the socket is visible. Figure 6a , Figure 6b and Figure 6c Show Figures 1 to 5 A variation of the embodiment shown in the figure, wherein: Figure 6a An improved socket 20' is shown, which has an outwardly extending resilient protrusion 24, such as a resilient arm; Figure 6b The tube 30 is shown fully pushed back onto the socket 20'. When the tube is fully against the socket, the arm 24 moves inward before the clamp finger 118 can be pushed across the tube, as shown. Figure 6c As shown, the collar 130 is pressed against the fingers to clamp the tube in place as described above. The clamp 110 will not pass through the arm 24 if the spigot 20' is not fully inserted into the tube 30.

[0047] Figure 7a , Figure 7b and Figure 7cA cross-section of the connector assembly, variant 105, is shown. In this embodiment, Figure 1 The collar 130 has been replaced by a locking plate 230 having a plurality of through holes 232, each through hole 232 receiving a chuck 110. The locking plate includes a protrusion 234 which replaces the flange 134 shown in the previous figures. The center of the through hole is aligned with the center of a plurality of common portions protruding from module 1, allowing multiple connections to be made in a single operation.

[0048] exist Figure 7a In the middle, it can be seen that the locking plate 230 is provided to the module 1, wherein the clamp 110 is assembled in the through hole 232, and inside the clamp 110, the tube 30 is assembled on the male part, such as the socket 20. Figure 7b Showing with Figure 7a The same connector assembly is shown, but the locking plate 230 and the clamp 110 are pushed to the front surface of the module 1 in the direction of arrow R, so that the clamp covers the end of the socket 20 and the tube 30. Figure 7c Show Figure 7a Another view of the connector assembly, but now the locking plate 230 along Figure 7b The direction of arrow R in the image is further pushed. Figure 7c In this case, the locking plate is used to clamp the fingers 118 of the chuck 110 around the tube 30 in the manner described above.

[0049] Figure 7d This illustration shows another variation of the coupling assembly, in which locking collars 230' are mounted on locking plate 231 by means of flexible mounts, in this case spherical mounts 233, which allow each collar 230' to rotate about the center of mount 233, and thus provide tolerance for a certain degree of misalignment or dimensional error in the common parts of the module. The locking plate could, of course, be formed of a flexible material to provide similar tolerance. The two couplings are in... Figure 7a As shown, but other linear or two-dimensional array truncated forms can also be used to match the construction of common part 20, such as an array of four connectors. Figure 8 The arrangement of the square common parts is shown. The connectors do not necessarily have to be in the same plane. If a degree of flexibility is provided, the connectors do not necessarily have substantially parallel axes, for example, as shown in the reference... Figure 7d As described. For ease of use, the pipe 30 may have a single connector 100 at one end and may converge at opposite ends of multiple connectors 105 in a manifold manner.

[0050] Figure 8 A chromatography system 11 is shown, which includes a support 80 comprising conventional fluid handling modular components in the form of interchangeable modules, such as:

[0051] Pump 12;

[0052] Column 13;

[0053] Various valves 14;

[0054] pH monitor 15;

[0055] Conductivity monitor 16;

[0056] Mixer 17; and

[0057] Ultraviolet monitor 18.

[0058] Other modules may be used. The modules can be connected in any suitable manner using a fluid conduit 30, which has a connector 100 at each end; only one is shown for simplicity. The connector 100 may be made of… Figure 7a Multiple pipes and couplings 105 of the type shown in a, b, c, or d are used instead to expedite the connection and release of the couplings. For convenience, each valve 14 has the same common part construction, meaning that the same construction of the locking plate 230 can be used for each valve.

[0059] Figure 9 A release tool 200 is shown, which has a forked end 210 adapted to engage with each side of a flange 134 or a protrusion 234 to pull it outward away from module 1 or 12 to 18, or to push it if there is no space for finger pulling.

[0060] exist Figure 10 , Figure 11 and Figure 12 An alternative embodiment of the connector 300 is shown. In this embodiment, the locking collar 330 ( Figure 10 The coupling 300 surrounds a cylindrical internal component, which is in the form of a clamp 310 having fingers 318 of the type described above, which in turn surround the fluid tube 30. The coupling 300 can operate largely in the same manner as couplings 100 and 105 described above, since, to form a liquid-tight coupling, the tube 30 is pushed past the male portion 20 protruding from the module 1, and then the clamp is slid across the tube until its distal end 340 is adjacent to or abuts the module 1, and then the collar is moved toward the module to begin tightening the fingers 318 of the clamp 310. This position is in Figure 11 As shown in the image.

[0061] Note that the distal end 340 includes a pair of bayonet-type openings for receiving complementary locking pins 27, which are supported by a boss 25 extending from the module 1 around the common part 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 boss 25 in a linear and rotational manner until it is pushed further toward the module 1. Figure 12In the final locking position shown, the collar 330 is reached. This further clamps the finger 318 to the tube 30 and secures the collar 330 (and the connector 300) to the module 1, held in place by the pin 27.

[0062] Figure 10 , Figure 11 and Figure 12 The insert shown relies on the basic linear locking movement of the locking collar mentioned above, i.e., using some torsion to hold the collar 330 in place and apply clamping force. Torsion is made easier by using a wing 334 extending from the collar 330 instead of the flange mentioned above.

[0063] Figures 13 to 16 A portion of another chuck 410 and collar 430 is shown in detail, which can be used with couplings 100, 1050, or 300. In this variation, clamping of the finger (in this case, finger 418) can be achieved by twisting the collar 430 around the chuck 410 as an alternative to sliding movement of the collar 430 (as described above), or as well as the sliding movement.

[0064] More specifically, the inner surface of the collar 430 has a pawl 432 that serves as a guide for the tapered portion 431 of the finger 418 when the collar is twisted relative to the finger. The circumferential bevels 431 function as cams, which, in this example, are pushed inward toward the tube 30 by the corresponding pawls when the collar is twisted in the direction of arrow R during use. Thus, the finger 418, during use, moves around the tube 30 from... Figure 13 and Figure 14 The position shown in the figure is compressed to Figure 15 and Figure 16 The clamping position is shown in the diagram, where the pawl stops in the complementary recess 433. The amount of torsion for locking is less than 120 degrees, and preferably less than about 90 degrees if three or more circumferentially arranged fingers are used.

[0065] Experiments have shown that the couplings 100, 105, and 300 described above, used with pipes having an outer diameter of approximately 3 to 10 mm, are capable of sealing the pipe at the coupling where 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, embodiments of the couplings have been successfully validated through extensive leakage tests at 30 bar. The couplings provide a liquid-tight connection of the pipe around the male portion, which can be engaged and disengaged by a substantially linear movement of the locking collar 130 or locking plate 230 without the need for torsion or threaded connections. Therefore, due to the avoidance of torsion space, the couplings can be spaced closer together than conventional threaded couplings. "Substantially linear" in this document means rotation less than 120 degrees, for example less than 90 degrees, less than 45 degrees, less than 30 degrees, less than 15 degrees, less than 5 degrees, or almost no rotation.

[0066] In different embodiments, collar elements have been described, each collar element having the same function in the 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. Each collar element includes at least one protrusion, such as a collar flange 134 or wing 334, extending outwardly away from an orifice having dimensions that allow manual manipulation of the collar between a first position and a second position.

[0067] Combination Figure 1 -7 describes the internal component as a chuck 110, which may have a stop portion, such as a chuck flange 114 and / or a step 138. The chuck flange 114 extends outward and has dimensions that facilitate manual manipulation of the coupling. Furthermore, the resiliently deflectable portion is equivalent to the engagement. Figure 1 -7 describes the deflectable finger 118 and the combination Figure 13-16 The terminology used to describe finger-like objects 418.

[0068] Figure 17 A chromatographic apparatus 400 according to an aspect of the invention is shown. This apparatus includes, but is not limited to, individual modular components 51 to 75 listed below, at least some of which are detachable from the perforated front panel 420 of the support 410 of the apparatus 400 and mounted thereon in a generally vertical plane, such that required liquid connections between the modular components can only be made at the front 420. In practice, the detachable modular components have no more than two standard sizes, which can be repositioned on the panel 420 to suit different programs if needed. Each modular component has a serial bus communication connection and a power connection, such that its physical location is insignificant to a controller located in the support 410 or remotely. Thus, the modular components can be considered modular and thereby repositionable and / or interchangeable.

[0069] Figure 17 The chromatography apparatus shown has the following modular components:

[0070] 51 Control Panel

[0071] 52 pH monitor

[0072] 53. Outlet valves 1-3, port 1 can be used for waste disposal.

[0073] 54 Outlet valve 4-6

[0074] 55 Conductivity Monitor

[0075] 56 Outlet valve 7-9

[0076] 57. Pre-column conductivity monitor

[0077] 58-pipe valve unit, including pre-pipe and post-pipe pressure sensors.

[0078] 59 Bottles for pump flushing fluid

[0079] 60 Inlet valves A1-A3

[0080] 61 Inlet valves A4-A6

[0081] 62 Inlet valves B1-B3

[0082] 63 Inlet valves B4-B6

[0083] 64 Fixed rubber feet

[0084] 65 Adjustable feet

[0085] 66 System Pump A

[0086] 67 System Pump B

[0087] 68. Current limiters, including system pressure monitors.

[0088] 69 Modular components for mixers

[0089] 70 Mixing Valve

[0090] 71 Air trap valve, including air sensor

[0091] 72 Air Trap

[0092] 73 On / Off Button

[0093] 74. Inline filter retainer (showing a typical filter capsule)

[0094] 75. Ultraviolet monitor.

[0095] As explained above, modular components can be omitted or repositioned. It will be apparent that some modular components can be replaced by others, or the space left by omitted modular components can be filled with end panels (see, for example). Figure 20 (76). If necessary, more than one modular component with the same number may be used.

[0096] The equipment's fluid manipulation modular components (i.e., all modular components listed above except for modular components 51, 64, 65, and 73) and external modular components (e.g., sample inlet reservoirs, buffer reservoirs, chromatographic columns, and fraction collection devices, all of which are not listed in the original text) are all included. Figure 17 The fluid interconnection between (shown in the figure) is carried out via a fluid conduit in the form of a flexible plastic tube in this case. The fluid conduit can be easily connected and disconnected with the corresponding port of the fluid manipulation modular component in any desired configuration, for example, using a connector as previously described.

[0097] Figure 18 This diagram illustrates one possible liquid interconnect configuration between the main modular components of a chromatography apparatus 400, in which the apparatus is connected to two chromatographic columns 700 and 800, but allows for any working interconnects between the modular components and additional parts (such as multiple columns) and the liquid reservoir. Reconfigurable liquid interconnects are indicated by short chain dashed lines 580.

[0098] At the heart of device 400 is column valve unit 58, which in this case has a construction as disclosed in pending application GB1715399.0 filed September 22, 2017, and which is incorporated herein by reference. Valve unit 58 provides multiple flow switching to allow flow in one or both columns 700 / 800 in either direction (upward or downward in the figure). The user can select upward or downward flow, or choose to bypass one or both columns. Flow can be directed to the next component in the waste or flow path. Columns can also be connected in series, each column including a chamber for containing a variable volume of chromatographic separation medium and an adapter movable to increase or decrease each said volume, wherein column valve unit 58 is in fluid communication with each adapter and can be selectively operated to move each adapter independently or jointly by means of changes in fluid pressure, thus changing each volume and causing compression or decompression of the medium within each column volume during use.

[0099] Column valve unit 58 includes pre- and post-column pressure sensors and a fluid inlet 510 configured to receive input fluid. The input fluid may, for example, be a chemical sample suspended in a buffer composition. Column valve unit 58 also includes a fluid outlet 520 configured to provide output fluid from the valve unit. The provided output fluid may typically be the fluid obtained after passing the received input fluid through one or more columns of the chromatography apparatus 400. Valve unit 100 also includes a first pair of fluid ports 531 and 532 configured to be coupled to a first column 700 and a second pair of fluid ports 541 and 542 configured to be coupled to a second column 800. Valve unit 58 also includes a coupling valve assembly configured to guide fluid between the fluid inlet 510, 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.

[0100] Additionally, the valve has a port 550, which can be used to change the volume of hydraulic cylinders 710 and 810, which are part of columns 700 and 800, for example, to provide compression of the column contents, also known as column filling. This filling process can be automated. It has been found that, using such a system, diameters of approximately 25 to 250 mm can be filled in this manner. The column can be pre-filled, but flushed and reconsolidated according to known procedures, such as those described in WO2007045491, the disclosure of which is incorporated herein by reference.

[0101] The remaining 400 systems include:

[0102] Inlet valve assemblies A and B, 60, 61, 62 and 63 are adapted to provide selectable liquids, including liquids containing oil samples, buffer solutions and cleaning fluids;

[0103] The inlet valve supplies two system pumps, each equipped with a pair of pistons and an associated check valve, providing a variable flow rate between 0 and 600 ml / min (maximum 1200 ml / min) with high flow rate and resolution, ensuring accurate flow rate. This accuracy ensures good repeatability of results over a wide range of column diameters.

[0104] Before the pumped liquid is transferred to the column valve unit 58, the pump is supplied in series with the flow limiter 68, which includes a system pressure monitor, a mixer valve 70, and a mixer module 69.

[0105] Any entrained air may escape via air trap valve 71 and air trap outlet 72, which also has air flowing out from columns 700 and 800. The air trap may be constructed according to pending application GB1713993 filed April 5, 2017, the disclosure of which is incorporated herein by reference.

[0106] Once the liquid reaches column valve unit 58, it can be delivered according to the arrangement described in pending application GB1715399.0 filed on September 22, 2017, and thus a variety of chromatographic modes can be performed, from simple batch work of direct chromatographic separation process using only one column to programs that are closer to replicating large-scale commercial procedures, in which two or more columns can be used, one ready for use and the other for separation.

[0107] The column output is transmitted via port 520 to a conductivity monitor 55, an ultraviolet absorbance monitor 75, and a pH monitor 52, and is directed to an appropriate storage container based on signals from these three monitors, thereby collecting the separated fraction in an appropriate container 501. Column wash solution can be collected in waste container 500.

[0108] Figure 2 The long dashed line 610 in the diagram represents the system bus, which transmits signals and power to and from the aforementioned modular components and to and from the controller 600. It will be appreciated that control and monitoring signals can be transmitted wirelessly according to known protocols without a communication bus. The chromatography system 400 also includes a display screen 530. Software running on the controller will display multiple icons on screen 530 and allow the user to manipulate the icons on the screen by dragging and dropping them to form a series of icons representing a user-defined chromatographic control method for ease of use. The user-defined chromatographic control method includes continuous chromatography using two or more columns by selectively opening valves in the column valve unit 58.

[0109] Figure 19 , Figure 20 and Figure 21 The diagrams show systems for pipe connections used in various constructions, with only a few figures retained. Figure 17 Some modular components are referenced in the document, and the openings left by the removed modular components are covered by a sealing plate 526 and screwed into the appropriate position above the opening to prevent liquid from accidentally entering the support 410.

[0110] exist Figure 19 In this system, system 400' features a modular construction suitable for regulatory environments where the system is custom-built in the factory. The system has been delivered for installation, calibration, and performance testing and is suitable for operation in a GMP environment. Figure 20 Figure 521 shows a system 400" with some modular components removed, and Figure 521 shows a system 400"' with more modular components in place, similar to Figure 71, and shows a typical tubular interconnect 580.

[0111] In use, modular components are very easy to remove or add to the system, and installation is completed via one-click activation in the software that recognizes each modular component. This software provides comprehensive and customizable operational control as well as proactive maintenance. In addition to the modular components described above, the input / output communication modular components can also be used to interface with analog and / or digital external sensors or other devices, such as automated fractionation collection units. A wide range of flow rates and pressures allows for scaling of columns with inner diameters ranging from 25 to 250 mm by more than 40 times. This wide range makes the device suitable for transitioning to GMP environments.

[0112] The packing (and repacking) of the chromatographic column using the system described above can be fully controlled by the controller 600 activated by the control panel 51. The controller 600 is capable of driving the display screen 530 ( Figure 18 This helps visualize the filling process and progress. The control software includes accessible column filling records. Therefore, column filling records can be defined, generated, and updated by the software for traceability and quality assurance purposes. Furthermore, these records can be used to monitor column performance and provide statistics on usage, separation performance, and filling intervals.

[0113] The display screen provides process visualization, quickly giving operators an overview of system functionality, operational steps, and alarm progress, with only the necessary amount of information provided for each step. Active flow paths are always shown in the process visualization to minimize user error. 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. Controls, graphical interfaces are provided for specific sections (such as column valve unit 58).

[0114] Use pre-programmed steps, but these can be modified and saved as user-defined steps for adding customization.

[0115] The system described and illustrated above is designed for hygienic environments. For example, the support 410 is flat or curved, with no connecting parts, gaps, or significant concave surfaces at the edges of the surface, which facilitates wiping and reduces the chance of dust and liquid trapping. The pH monitor 52 has inline calibration, and the column valve unit 58 provides column packing during the process, thus enabling a closed flow path throughout operation, meaning that the flow path does not need to be interrupted during the packing / regeneration phases of one or more columns and throughout the entire separation operation.

[0116] Figure 22A prior art modular component 810 is shown, which has four ports 811, each adapted to connect to a prior art fluid connector 812. Due to the size of the coupling 813 required to secure the fluid connector 812 to the port 811, the couplings must be arranged at different heights. This is a cumbersome solution and also requires space around the modular component to facilitate the installation / removal of the fluid connector 812 from the corresponding port 811.

[0117] Figure 23 A modular component 820 with four ports 821 is shown, each port having a tube 822, the tube having a releasable coupling 100 at its first end (as in combination). Figure 1 (As described in -6), the releasable coupling 100 is connected to each corresponding port 821. A second end of one of the tubes is connected to the converter 823 via another releasable coupling 100 to provide an accessory unsuitable for direct connection to the port 821. Figure 24a and Figure 24b The converter 823 is described in more detail. When fluid connections are attached to modular components, the use of releasable couplings results in a smaller design because the ports can be positioned closer together. Similarly, releasable couplings are easier to clean, install / remove, and replace when needed.

[0118] Figure 24a A cross-sectional view of a converter 823 is shown, which has a body 830, a flange 831, a through-hole 832, and a socket 833 integrated with the body 830. In this embodiment, the converter 823 is made of a single material, such as plastic, metal, etc. In this example, the flange 831 is adapted for use in a triple clamp (TC) connector, and the socket 833 is adapted to receive a tube provided with a releasable connector 100 (not shown).

[0119] Figure 24b A cross-sectional view of alternative converter 823' is shown, which is similar to the combined Figure 24a With one exception to the described converter, converter 823' comprises two parts, wherein the body 830 and flange 831 are made of a single material (e.g., plastic), and the socket 833' is made of another material (e.g., metal).

[0120] Figure 25a A prior art modular component 910 with three threaded holes as ports 911 is shown. Tubes 912, each equipped with a threaded connector 913, are fixed to the corresponding ports 911. Figure 25bA threaded connector 913 is shown, comprising an end flange 914 secured to a first end of a tube 912 and adapted to provide a seal when arranged in a threaded hole 911, and a body having a threaded portion 915 and a gripping portion 916 designed for use when securing the threaded connector 913 to a modular member 910. Figure 23 As shown, the design is rather bulky compared to using a releasable coupling due to the space required to secure the threaded connector 913 to the modular component 910.

[0121] When using threaded connectors to attach fluid tubing to a port, there is an unintended rotation of the fluid tubing (approximately 2-3 turns) as the connector is secured to the threaded hole. This is particularly a disadvantage when securing short fluid tubing (e.g., 10-30 cm long), where the tubing undergoes kinking behavior. Furthermore, a separate O-ring may be required to generate the necessary pressure and fluid seal.

[0122] To take advantage of the benefits provided by the resealable coupling 100, an adapter can be introduced into the threaded hole of the modular component 910.

[0123] Figure 26a A cross-sectional view of adapter 915 is shown, which has a body 920, a threaded portion 921, a through hole 922, and a socket 923 integrated with the body 920. In this embodiment, adapter 920 is made of a single material, such as plastic, metal, etc. In this example, the threaded portion 921 is adapted to be inserted into the threaded hole of the modular component using the body 920 as a gripping part, and the socket 923 is adapted to receive a tube with a resealable connector 100 (not shown).

[0124] Figure 26b A cross-sectional view of alternative adapter 915' is shown, which is similar to a combination Figure 26a The described adapter has one exception. The converter 915' comprises two parts, wherein the body 920 and the threaded portion 921 are made of a single material (e.g., plastic), and the socket 923' is made of another material (e.g., metal).

[0125] Figure 27 A cross-sectional view of an alternative converter 925 is shown, which has a body 930, a portion with a threaded hole 931, a through hole 932, and a socket 933 integrated with the body 930. In this embodiment, the converter 925 is made of a single material, such as plastic, metal, etc. The threaded hole 931 in this example is adapted to receive, for example, a coupling. Figure 25b The threaded connector described. The socket 933 is adapted to receive a tube equipped with a resealable coupling 100 (not shown). It should be noted that the socket can be manufactured from different materials compared to the body and portion having threaded holes.

[0126] The advantage of the releasable coupling assembly 10 is that it has no threads, which means it is clean and requires less maintenance. Figure 25a and Figure 25b As shown, the simple widening 22 (i.e., sealing ridge, barb, or curl) on the socket 20 extending from the front of the panel is much easier to clean than conventional threaded connectors with very limited access to the threaded hole.

[0127] Another advantage is that it can be combined with... Figure 22 Compared to the diagram shown, no flange is required, and therefore the tube can be manually cut before connecting it with the releasable connector 100. Thus, since the stationary dimension of the tube's inner diameter is within the same range as the outer diameter of the sealing ridge 22 on the socket 20, the tube can be easily replaced when needed, and the stationary dimension of the tube's inner diameter is preferably less than ±10% of the outer diameter of the socket.

[0128] Another advantage is that no O-rings or gaskets are required, which translates to less maintenance and a more robust solution compared to existing technologies. Sealing is achieved using tubing that directly seals against the sealing ridge 22. However, this requires the tubing to have a degree of flexibility and deformability. Resealable couplings provide a minimal number of connections / fittings between different materials and sections, improving the possibility of clean fluid connections when needed. Another advantage is the ease of attachment of resealable coupling assemblies, such as a one-handed snap-fit ​​fit for low-pressure applications.

[0129] Such as combination Figure 24a , Figure 24b and Figure 27 As described, the converter connector can be used to provide a connection to other connectors (such as TC connectors). (As in combination) Figure 26a and Figure 26b As described, the threaded adapter can be used to connect older devices with threaded holes (see...). Figure 25a Upgraded to a connector suitable for use with releasable couplings when attached to a pipe.

[0130] As described above, the sockets 20 can be arranged much closer together compared to providing spiral or TC connectors. This allows for shorter internal flow paths in modular components (e.g., valves), thereby freeing up the use of coupling assemblies and reducing the size of fluid components with internal flow paths. In turn, this will affect the entire chromatography system and reduce the footprint relative to flow capacity.

[0131] Figure 28a and Figure 28bCross-sectional views are shown with and without the spigot, and with the spigot installed. It should be emphasized that the dimensions of the pipe (inner diameter D1) and the spigot (outer diameter D2) are important for producing a proper seal and preventing cavitation between the pipe 30 and the open end 281 of the spigot 280, in which deposits of biological material residue can be trapped. The elastic modulus of the pipe will provide the necessary deformation of the pipe to allow it to pass through the sealing ridge 282 located immediately adjacent to the open end 821. The shape of the sealing ridge is crucial for achieving the required functionality in key aspects:

[0132] - Cleanability, because the direct seal creates a void-free structure, avoiding cavities that could trap biological material.

[0133] - Keep the tube at the upper pressure limit of the socket.

[0134] As mentioned above, other important parameters are:

[0135] - Elastic modulus of fluid tube

[0136] -Inner diameter of the fluid pipe and outer diameter of the spigot

[0137] In some embodiments, the sealing ridge has a rounded design with a radius R and a height h from the center of the socket. This radius extends to the open end of the socket and provides an angle to allow the tube to slide onto the socket using a sufficiently low force for an average operator, and the tube does not bend under pressure when sliding on the sealing ridge. The initial radius of the rounded section may 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.

[0138] Other shapes of sealing ridges Figure 28a , Figure 29a and Figure 29b As shown in the image. Figure 28b Arrows F1-F3 schematically indicate the forces involved in sealing and locking the tube end 30 onto the socket 280. In one embodiment, such as the connector 100 illustrated above, the clamp is arranged to apply tube clamping pressure on the socket side at the midpoint of the sealing ridge, as by Figure 28b As indicated by F2. In one embodiment, the basic fluid sealing force F1 between the tube and the leading edge of the sealing ridge near the open end of the spigot is obtained primarily by the elasticity of the tube. When the sealing ridge is positioned immediately adjacent to the open end, a seal is achieved without any voids, i.e., there is no flat section at the open end of the spigot.

[0139] By applying a locking pressure of approximately F2 behind the midpoint of the sealing ridge, virtually all 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 spigot. However, all surfaces should be as smooth as possible for easy cleaning. In an alternative embodiment, a portion of the available clamping force may be applied at the end section 281 of the spigot 280 to further secure the seal between the spigot and the tube. In the disclosed embodiment 100, the fingers 118 of the clamp 110 are designed such that they apply a specific clamping force only near the sealing ridge 282, while leaving space for the tube at the lower end of the spigot when in the clamped position. In this way, since the clamping force involves spring loading of the fingers 118 around the clamped position, the clamping force depends less on dimensional variations in the different components (spigot, tube, clamp, and collar). In the disclosed embodiments, the available clamping force is determined by the force applied by the operator when pushing the collar 130 past the chuck 110 into the tube clamping position, thereby displacing the finger 118 adjacent to the tube. The force required to lock the clamp by pushing the collar 130 should be appropriate to be a reasonable force for the user, while avoiding the need for excessive release force to release the clamp.

[0140] Figure 28b The diagram illustrates the configuration when the fluid tube 30 is installed along the length of the sealing ridge 282 and the spigot 280, and schematically indicates the locking pressure applied to the tube on the spigot side at the midpoint of the sealing ridge. The fluid sealing force F1 between the tube and the leading edge of the sealing ridge near the open end of the spigot is achieved through the elasticity of the tube. When the sealing ridge is positioned immediately adjacent to the open end, a seal is achieved without any voids, i.e., there is no flat section at the open end of the spigot.

[0141] By applying a locking pressure of F2 behind the midpoint of the sealing ridge, virtually all 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 easy cleaning. Furthermore, sharp corners can unintentionally create cavities that can trap biological material, and therefore should be avoided for cleaning purposes.

[0142] Additional sealing force F3 may be required at the bottom of the socket (opposite to 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 another embodiment, adjacent or lesser pressure is applied at or near the bottom of the socket to stabilize the connection.

[0143] A releasable coupling as described above can be used to provide clamping force. Other types of couplings are possible, provided they provide the appropriate amount of clamping force as described above, such as hose clamps and eccentric couplings. The length of the selected connector must be chosen based on the length of the socket to avoid leverage.

[0144] Figure 29a and Figure 29b A cross-sectional view of an alternative sealing ridge construction is shown. Figure 29a The image shows a socket 290 with a first alternative sealing ridge 292 having an inconsistent profile. The rear edge 291 of the sealing ridge descends more rapidly from the midpoint of the sealing ridge to the outer surface of the socket. This improves the pressure limit of the connection. Furthermore, the front end of the sealing ridge 292 is aligned with the open end of the socket, as indicated by reference numeral D3. (This is related to the connection / coupling.) Figure 28a and Figure 28b Compared to the described socket, this will increase the force required to install the fluid pipe (not shown).

[0145] Figure 29b The socket 295 is shown, which has a second alternative sealing ridge 297 with an inconsistent profile. The rear edge 296 of the sealing ridge bends from the midpoint of the sealing ridge to the outer surface of the socket with a radius r2. The profile from the midpoint of the sealing ridge to the open end of the socket bends with a radius r1, where r1 is greater than r2.

[0146] Furthermore, the front end of the sealing ridge 297 is aligned with the open end of the socket as indicated by reference numeral D4, where in this example D4 is greater than D3, indicating engagement. Figure 29a Compared to the described connector, the force required to install the fluid tube (not shown).

[0147] Generally, the present invention relates to a novel connector concept for a chromatography system, wherein Figure 25a and Figure 25bThe conventional threaded fluid connector shown can be replaced by a more convenient socket-type connector, in which the tube used for interconnecting components in the chromatography system is simply pushed onto the socket and then secured to the socket by a releasable clamp, applying a radial clamping force to the outer periphery of the tube. As mentioned, the socket preferably has a sealing ridge so that the connector concept can be used within the required pressure range. Surprisingly, it has been confirmed that such connectors can be designed to provide leak-proof fluid connections at internal pressures exceeding those required by liquid chromatography (20 bar, and even up to 30 bar or more), while still significantly improving ease of use for the operator. The procedure for connecting the tube to a port in the chromatography system according to an embodiment involves only the following steps: pushing the tube end through the socket, positioning the releasable connector clamp around the tube end, and applying a locking force by actuating the connector clamp. Similarly, the procedure for disconnecting the tube from a port in the chromatography system according to an embodiment involves only the following steps: actuating the connector clamp to release the locking force, optionally removing the releasable connector clamp from the tube end, and pulling the tube end out of the socket. A key advantage of the disclosed embodiments is that the steps of pushing and applying the locking clamp do not require a torsional motion that would otherwise transmit rotational motion to the tube, thus preventing the tube from rotating relative to the common portion during the application step. As mentioned, this prevents the tube from twisting and forming kinks, which can restrict fluid flow or even damage the tube segment. Furthermore, compared to conventional chromatography systems with connectors requiring flanged tubes, such as tubes with inner diameters of 1 to 10 mm, this system offers the benefit of allowing for customized fluid paths by adding a step of cutting the tube segment to the optimal length before the interconnecting path.

[0148] Connector leakage test.

[0149] Embodiments of this connector / chromatographic system have been validated to provide leak-proof connections within the desired pressure range for liquid chromatography. In one embodiment, the upper operating pressure limit of the chromatographic system is 20 Bar, and to verify proper sealing at 20 Bar, the connector is periodically subjected to a leak test at 30 Bar. During the test, the leakage threshold is set at 1 μl / min per connector at 20 Bar in the test flow path. Successful testing was achieved under the following conditions:

[0150] • Conduct leak tests at 20 Bar within a temperature range of 4-40℃.

[0151] • 6000 repeated connection and disconnect cycles, with a leak test performed at 30 Bar every 500 cycles (performed for two different sizes).

[0152] • Perform static leak testing over a 12-month period at 40°C, followed by weekly leak testing at 30 Bar.

[0153] • Tensile test 0-20N, 10,000 cycles, with leakage test at 30 bar before and after each cycle.

[0154] As mentioned earlier, it was surprising to find that this was achieved while providing such improved ease of use compared to conventional connections.

[0155] In addition to the leak test described above, a salt creep test was performed by circulating a 2.5M (NH4)2SO4 mobile phase in the system overnight (approximately 12 hours) at a back pressure of 1.5 MPa. Following this, the system was visually inspected for salt creep around the connectors, valves, and other modules. The connectors and chromatographic system were confirmed to have passed the test, with no visible salt creep.

[0156] Figures 30a-30c The diagram illustrates the interaction between the socket 20, tube 30, and clamp 110 and its fingers 118 according to one embodiment. Figure 30a In the diagram, tube end 310 is shown above the spigot, with the dashed line indicating the relationship between the tube's inner diameter and the spigot element. As can be seen, the spigot bottom is slightly wider than the tube's inner diameter, and the sealing ridge 22 is significantly wider, but has a rounded front edge to allow the tube to be pushed onto the spigot. Figure 30b In the middle, the tube end has been pushed onto the socket (beyond the pulled-out portion), and the clamp 110 has been applied around the tube end and actuated in the locked position to clamp the tube. Figure 30c The clamp 110 is disclosed in more detail, wherein fingers 118a are provided with a clamping section 350 for clamping the tube in the central region 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 mm, while the socket bottom diameter is 3.25 mm and the sealing ridge diameter is 3.45 mm, which, together with the locking force from the clamp 10, provides a leak-free connection. The tubes used in this type of liquid chromatography system are generally made of sufficiently rigid material to withstand the pressures involved and may be made, for example, from fluorinated ethylene propylene (FEP) plastic.

[0157] According to one embodiment, components 12-18; 810; 910 for a chromatography system 11 are disclosed. The components (which may be modular) include one or more ports, each accessible via sockets 20; 923, 923' for receiving a first end of a fluid tube 30; 812; 912. The first end can be sealed around the socket by releasable couplings 100, 105, 300 external to the tube end, and these couplings have a releasable clamping action actuated by sliding movement of collar elements 130, 230, 230', 330, 430 along the end of the fluid tube.

[0158] The socket (20) may be part of components 12-18. Additionally, sockets 923 and 923' may be provided on adapters 915 and 915', which are configured to connect to a port on component 910. In some embodiments, the port is a threaded hole 911, and adapters 915 and 915' include a corresponding threaded portion 921, a body 920, and sockets 923 and 923'.

[0159] In some embodiments, the adapter 915 is made of a single material, which may be plastic or metal.

[0160] 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.

[0161] According to one embodiment, a detachable connector 100 is disclosed, configured to retain a fluid conduit to a socket. The connector includes:

[0162] - Cylindrical internal components 110; 310; 410 configured to receive fluid conduit 30, said internal components including resiliently deflectable portions 118; 418 arranged to push the outer surface of the conduit toward the socket; and

[0163] - A collar element 130 having an internal through-hole 132 for slidably receiving an internal component, the orifice and the resiliently deflectable portion having complementary surface structures that provide resilient deflection in use in a first position of the collar element mounted to the internal component and prevent movement relative to the outer surface of the fluid tube in a second different position.

[0164] The collar element includes at least one protrusion extending outward away from an orifice having a size that allows manual manipulation of the collar between a first position and a second position.

[0165] In some embodiments, the internal member 110 further includes a stop portion 138; 114 to cooperate with the collar element to prevent or inhibit slippage of the collar element away from the internal member in at least one direction.

[0166] In some embodiments, the collar element is capable of sliding on the inner member from a first position in which it is deflected to a second position in which the collar element abuts the stop portion.

[0167] In some embodiments, a collar flange 134 is formed at one end of the collar element, wherein a stop portion is formed at one end of the internal member. The collar flange 134 and the stop portion can be manually manipulated to bring the collar element to a vicinity of a second position, and the collar element can be manually manipulated to further slide to a first position, where the collar flange 134 is spaced apart from the stop portion.

[0168] In some embodiments, this portion is a collet flange 114 that extends outward and has dimensions that facilitate manual manipulation of the coupling. In some embodiments, a collar flange 134 is a continuous annular structure erected from the collar body 136.

[0169] In some embodiments, the outer surface of the collar flange 134 and the collar element on which the collar flange is formed has a continuously curved profile, wherein there is no abrupt change in direction.

[0170] In some embodiments, the resiliently deflectable portions 118 and 418 of the internal members 110, 310, and 410 include a plurality of circumferentially arranged fingers that, in use, can deflect inward toward the tube. In some embodiments, the collar element 330 further includes a bayonet opening 345 cooperating with a complementary locking pin 27 to releasably secure the coupling to the module 1.

[0171] According to one embodiment, a converter 823; 823'; 925 is disclosed for connecting the end of a first fluid tube 822 to the end of a second fluid tube. 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 can be sealed around the socket by a releasable coupling 100, 105, 300 outside the tube end. The coupling has a releasable clamping action actuated by sliding movement of the coupling's collar elements 130, 230, 230', 330, 430 along the end of the fluid tube.

[0172] In some embodiments, the converter 823; 823' also includes a body 830 and a flange 831, or a body 930 and a portion having a threaded hole 931 configured to connect to the end of a second fluid conduit.

[0173] In some embodiments, the converter 823 is made of a single material, which may be plastic or metal.

[0174] In some embodiments, the socket 833' is made of a first material, and the body 830 and 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.

[0175] According to one embodiment, a chromatographic system 11 comprising a plurality of components 12-18; 810; 910 as described above is capable of fluid interconnection via a fluid conduit 30. The components include one or more sockets 20f for receiving respective ends of the fluid conduit 30, the fluid conduit ends being sealed around the sockets by releasable couplings 100, 105, 300 as described above, the couplings having a releasable clamping action actuated by sliding movement of collar elements 130, 230, 230', 330, 430 of the couplings along the ends of the fluid conduits.

[0176] In some embodiments, the sliding motion is a motion generally toward the corresponding member, and the clamping action is releasable by motion away from said member.

[0177] In some embodiments, the plurality of components 12-18 are modular components capable of being repositioned on the support 80, and the fluid conduit 30 includes a plurality of fluid conduits of multiple lengths, each having opposite ends, and at each end provided a coupling 100, 105, 300, which are used together to allow substantially sealed fluid flow or fluid communication between the respective modular components.

[0178] In some embodiments, the sliding motion is only linear motion, or essentially linear motion, wherein the torsional motion is less than 120 degrees.

[0179] In some embodiments, the chromatographic system is a chromatographic system formed by multiple components.

[0180] In some embodiments, the chromatography system further includes a converter as described above.

[0181] According to one embodiment, a chromatography system is provided comprising a plurality of fluid processing components capable of being fluidly interconnected via fluid conduits 30 to form a chromatographic fluid path. Each fluid processing component includes one or more fluid ports having sockets extending from a component surface for receiving corresponding ends of fluid conduits, such that the fluid conduit ends sealably surround the sockets, and for receiving releasable locking clamps that apply a radial locking force to the outer surface of the conduit ends to lock the fluid conduit ends onto the sockets. The interconnection is leak-proof under an internal pressure of at least 10 Bar (preferably 15, 20, 25, or 30 Bar).

[0182] This invention should not be considered as limited to the embodiments described above, but can be varied within the scope of the appended claims, as will be readily apparent to those skilled in the art.

Claims

1. A releasable coupling (100) for retaining a fluid tube to a common portion of a chromatographic system, the chromatographic system including a plurality of fluid handling components (12-18; 810; 910) fluidly interconnected via the fluid tube (30, 812, 822, 912) to form a bioprocess fluid path, wherein the common portion is configured to protrude from at least one of the plurality of fluid handling components of the chromatographic system for receiving a first end of the fluid tube thereon, wherein the common portion has an open end and a widened portion (22, 282) adjacent to the open end, the coupling comprising: A cylindrical internal member (110, 310, 410) for receiving the fluid tube (30) and completely separated from the male portion by the fluid tube, the internal member including a resiliently deflectable portion arranged to push the outer surface of the fluid tube toward the male portion; as well as A cylindrical locking element (130, 330, 430) has an internal through-hole (132) for receiving the internal component. The orifice and the resiliently deflecting portion have complementary surface structures that provide resilient deflection in use at a first position of the locking element mounted to the internal component, and that the complementary surface structures do not cause the deflection at different second positions. The coupling is configured such that when the distal end (120) of the cylindrical inner member is pushed against the at least one fluid handling member, a clamping force is generated by the movement of the cylindrical locking element along the cylindrical inner member toward the at least one fluid handling member. The clamping force is thus applied to the resiliently deflectable portion (118, 318, 418), thereby pushing the resiliently deflectable portion inward and thereby applying a radial locking force to the outer surface of the first end of the fluid tube.

2. Coupling (100) according to claim 1, characterized in that The internal member (110) further includes a stop portion (138, 114) that cooperates with the locking element to prevent or inhibit the sliding of the locking element away from the internal member in at least one direction.

3. Coupling (100) according to claim 2, characterized in that The locking element is capable of sliding on the internal member from the first position in which the deflection is provided to the second position in which the locking element is adjacent to the stop portion (138, 114).

4. Coupling (100) according to claim 2 or claim 3, characterized in that The locking element includes a collar flange / wing formed at one end of the locking element, wherein a stop portion is formed at one end of the internal member, wherein the collar flange and the stop portion can be manually operated to approach the second position, and wherein the locking element can be further manually operated to slide to the first position, at the first position where the collar flange is spaced apart from the stop portion.

5. Coupling (100) according to claim 4, characterized in that The collar flange and the outer surface of the locking element on which the flange is formed have a continuously curved profile, wherein there is no abrupt change in direction.

6. The coupling (100) according to any one of claims 1 to 3, characterized in that The resiliently deflectable portion of the internal component includes a plurality of circumferentially arranged fingers that are capable of deflecting inward toward the tube during use.

7. Coupling (100) according to claim 6, characterized in that The finger extends from the middle portion (116) of the cylindrical internal member (110) to the distal end (120) of the cylindrical internal member (110).

8. Coupling (100) according to claim 7, characterized in that The fingers open outward toward the distal end (120) of the cylindrical internal member (110).

9. The coupling (100) according to any one of claims 1 to 3, characterized in that The connector (100) is formed from two molded plastic parts.

10. Coupling (100) according to claim 9, characterized in that The cylindrical internal component (110) and the cylindrical locking element (130) are made of transparent plastic.

11. The coupling (100) according to any one of claims 1 to 3, characterized in that The distal end (340) of the cylindrical locking element (330) includes a pair of bayonet-type openings (345) for receiving complementary locking pins (27).

12. The coupling (100) according to any one of claims 1 to 3, characterized in that The cylindrical locking element (430) includes a pawl (432) that, when the cylindrical locking element (430) is twisted relative to the finger, serves as a tapered portion (431) of the finger, each of the tapered portions (431) serving as a cam such that, when the cylindrical locking element (430) is twisted, the tapered portion (431) is pushed inward relative to the cylindrical locking element (430) by the corresponding pawl (432) in the cylindrical locking element (430).

13. Coupling (100) according to claim 12, characterized in that The resiliently deflectable portion includes a corresponding complementary recess (433) for stopping a corresponding pawl (432) therein.

14. The coupling (100) according to any one of claims 1 to 3, characterized in that The cylindrical locking element (130) is part of a locking plate having multiple through holes (232).

15. Coupling (100) according to claim 14, characterized in that The cylindrical locking element (130) is mounted to the locking plate by means of a flexible mounting member.

16. The connector (100) according to claim 15, characterized in that, The flexible mounting element is a spherical mounting element (233) that allows the cylindrical locking element (130) to rotate about the center point of the mounting element (233).

17. The coupling (100) of claim 1, wherein, The locking element includes at least one protrusion extending outward from the orifice, the orifice having dimensions that allow manual manipulation of the locking element between the first position and the second position.

18. The coupling (100) of claim 1, wherein, The locking element includes at least one collar flange (134) or collar wing (334) extending outward away from the orifice, the orifice having dimensions that allow manual manipulation of the locking element between the first position and the second position.

19. A releasable coupling assembly (10) for retaining a flexible fluid tube (30, 812, 822, 912) to a common portion (20) of a chromatographic system, the chromatographic system including a plurality of fluid handling members (12-18; 810; 910) capable of fluidly interconnecting the fluid tube (30, 812, 822, 912) to form a bioprocess fluid path, wherein the common portion is configured to protrude from at least one of the plurality of fluid handling members of the chromatographic system for receiving a first end of the fluid tube thereon, wherein the common portion has an open end and a widened portion (22, 282) adjacent to the open end, the coupling assembly comprising: The flexible fluid tubes (30, 812, 822, 912); The male part (20) can be inserted into the fluid tube; A cylindrical internal component (110) is used to be fitted onto the fluid tube and is completely separated from the male portion by the fluid tube. The internal component includes a resiliently deflectable portion arranged to push the outer surface of the fluid tube onto the male portion. as well as A cylindrical locking element (130, 230) having an internal through hole (132, 232) for mounting the locking element on the internal component. The orifice and the resiliently deflectable portion have complementary surface structures that provide resilient deflection in use in a first position of the locking element mounted on the internal member, whereby, when the internal portion is assembled onto the fluid tube, the fluid tube is pushed onto the male portion by the resiliently deflectable portion, and the complementary surface structures do not cause the deflection in a second position, thereby the fluid tube is not pushed onto the male portion or is pushed onto it less frequently. The coupling assembly is configured such that, when the distal end (120) of the cylindrical inner member is pushed against the at least one fluid handling member, a clamping force is generated by the movement of the cylindrical locking element along the cylindrical inner member toward the at least one fluid handling member. The clamping force is thus applied to the resiliently deflectable portion (118, 318, 418), thereby pushing the resiliently deflectable portion inward and thereby applying a radial locking force to the outer surface of the first end of the fluid tube.

20. The releasable coupling assembly (10) of claim 19, wherein, The elastically deflectable portion includes a plurality of circumferentially arranged, elastically deflectable fingers.

21. The releasable coupling assembly (10) of claim 20, wherein, The finger extends from the middle portion (116) of the cylindrical internal member (110) to the distal end (120) of the cylindrical internal member (110).

22. The releasable coupling assembly (10) according to claim 21, characterized in that, The fingers open outward toward the distal end (120).

23. The releasable coupling assembly (10) according to any one of claims 19 to 22, wherein, The connector (100) is formed from two molded plastic parts.

24. The releasable coupling assembly (10) of claim 23, wherein, The cylindrical internal component (110) and the cylindrical locking element (130) are made of transparent plastic.

25. The releasable coupling assembly (10) according to any one of claims 19 to 22, wherein, The distal end (340) of the cylindrical locking element (330) includes a pair of bayonet-type openings (345) for receiving complementary locking pins (27).

26. The releasable coupling assembly (10) according to any one of claims 19 to 22, wherein, The cylindrical locking element (430) includes a pawl (432) that, when the cylindrical locking element (430) is twisted relative to the resiliently deflectable portion, functions as a tapered portion (431) of a finger, each of the tapered portions (431) functioning as a cam such that, when the cylindrical locking element (430) is twisted, the tapered portion (431) is pushed inward relative to the cylindrical locking element (430) by the corresponding pawl (432) in the cylindrical locking element (430).

27. The releasable coupling assembly (10) of claim 26, wherein, The resiliently deflectable portion includes a corresponding complementary recess (433) for stopping a corresponding pawl (432) therein.

28. The releasable coupling assembly (10) according to any one of claims 19 to 22, wherein, The cylindrical locking element (130) is part of a locking plate having multiple through holes (232).

29. The releasable coupling assembly (10) of claim 28, wherein, The cylindrical locking element (130) is mounted to the locking plate by means of a flexible mounting member.

30. The releasable coupling assembly (10) of claim 29, wherein, The flexible mounting element is a spherical mounting element (233) that allows the cylindrical locking element (130) to rotate about the center point of the mounting element (233).

31. The releasable coupling assembly (10) according to claim 19, characterized in that, The locking element includes a collar flange (134, 234) extending outward away from the orifice, the orifice having dimensions that allow manual manipulation of the locking element between the first position and the second position.

32. A reconfigurable liquid interconnect (580) for connection to at least one modular component in a chromatography apparatus (400), said reconfigurable liquid interconnect (580) comprising a connector assembly (10) according to any one of claims 19 to 31.

33. The reconfigurable liquid interconnect (580) of claim 32, wherein, The modular components include one or more of the following: control panel (51), pH monitor (52), outlet valve (53, 54, 56), conductivity monitor (55), pre-column conductivity monitor (57), column valve unit (58) including pre-column and post-column pressure sensors, bottle (59), inlet valve (60, 61, 62, 63), system pump (66, 67), flow restrictor (68) including system pressure monitor, mixer modular component (69), mixing valve (70), air trap valve (71) including air sensor, air trap (72), retainer (74) for inline filter and / or ultraviolet monitor (75).

34. The reconfigurable liquid interconnect (580) of claim 32 or claim 33, wherein, The reconfigurable liquid interconnect (580) also includes at least one tube (30) formed of a substantially rigid material.

35. The reconfigurable liquid interconnect (580) of claim 34, wherein, The substantially rigid materials include fluorinated ethylene propylene (FEP) plastics.

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