Chromatography system and couplings for chromatography system

Abstract

To provide a liquid chromatography system, which comprises releasable fluid couplings which can be quickly reconnected.SOLUTION: A releasable coupling 100 comprises a cylindrical inner component 110, a resiliently deflectable portion 118, and a cylindrical collar 130 having an internal through-aperture 132. The internal through-aperture and the resiliently deflectable portion have complementary surface formations. The complementary surface formations provide the resilient deflection in use in a first position with the cylindrical collar attached to the cylindrical inner component, and do not cause the deflection in a second different position. In the releasable coupling, the collar comprises a collar flange 134 extending outwardly away from the aperture of a size allowing manual manipulation of the collar between the first and second positions.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present invention relates to a chromatography system such as a liquid chromatography system, and more particularly, but not limited to, a versatile laboratory or "bench-top" sized system that enables convenient reconfiguration and convenient automatic use for various chromatographic procedures, and a reconnectable fluid tube coupling for connecting tubes associated with such an apparatus or system.

Background Art

[0002] Reconnectable fluid tube couplings, i.e., couplings that can be removed and replaced multiple times but still provide a fluid seal at each reconnection to a flexible tube such as a garden hose or plastic tubing, are known. However, particularly when such a design is employed in a chromatography system where a sanitary coupling is required and is often utilized at much higher fluid pressures, for example up to 20 bar or more, there is room for doubt regarding ease of connection and / or sanitation. Typical pipe fittings used in chromatography systems have multiple components including metal springs and O-rings, and as a result have dead-end ends or O-ring grooves, which can potentially provide a hiding place for unwanted contaminants such as pathogenic bacteria during use. These dead-end ends and grooves are difficult to sanitize. Furthermore, when gamma irradiation is attempted to sanitize such a coupling assembly, the use of metal parts becomes a problem. Additionally, when speed and ease of connection or disconnection are desired, the use of threads or special tools is undesirable.

[0003] One prior art barb lock tube coupling configuration is shown in U.S. Patent No. 8,662,542, but this coupling requires an assembly tool and is not intended to be easily releasable.

[0004] Liquid chromatography is a well-known procedure for separating molecular mixtures, such as separating proteins in a liquid sample. These proteins are typically suspended in a fluid and can be passed through a chromatographic separation medium together with a buffer. The various sample molecules of the mixture are separated by moving through the chromatographic medium at different speeds. This separation may be completed by a fractionation step, in which the mobile phase can be sent to various containers, for example, by an outlet valve of a chromatographic system.

[0005] Also, in a chromatography system, particularly in a desktop laboratory device, it is often necessary to clean the device equipped with interconnecting tubes during use and then disassemble the tube assemblies to reconfigure the tubes into different configurations to accommodate different experiments. Therefore, special sanitizing devices are inconvenient, and quick disconnection and reconnection along with rapid cleaning are required. One such device is disclosed in U.S. Patent No. 8,821,718, which is incorporated herein by reference. In this device, the replaceable modular components of the chromatography system can be interconnected by external fluid conduits and enjoy the benefits of such improved interconnecting means.

Prior Art Documents

Patent Documents

[0006]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

Patent Document 5

Summary of the Invention

Problems to be Solved by the Invention

[0007] One object of an embodiment of the present invention is to provide a chromatographic system, particularly a liquid chromatographic system, comprising a releasable fluid coupling that can be quickly reconnected without involving screwing or twisting operations of fluid conduits or without requiring space around each fluid conduit for such operations. Another object of the present invention is to provide one or more of the following improvements in functionality to the chromatographic system: operable in, for example, conventional batch chromatography and continuous chromatography, usable over a wider range of applications, without a significant increase in overall size or manufacturing cost, and having simple operation.

[0008] Another object of an embodiment of the present invention is to provide a coupling that is more easily cleanable, having no or limited dead ends or other spaces where contaminants can accumulate. Another object of an embodiment of the present invention is to provide a coupling that allows for quick connection and disconnection without the use of tools when necessary.

Means for Solving the Problems

[0009] According to one aspect of the present invention, there is provided a chromatographic system as set forth in the appended claims.

[0010] According to another aspect of the present invention, there is provided a releasable coupling as defined by other appended claims, which can be used as part of a coupling assembly in a chromatographic system, such as a benchtop chromatographic system, and modular components can be rearranged on a support, for example, to best suit a particular experimental setup, and the configured modular components are interconnected by fluid tubes, the tubes having both ends, each end comprising one of the coupling assemblies according to the present invention for fluid connection of the respective modular components.

[0011] Other preferred aspects of the present invention are set forth in the appended dependent claims.

[0012] Additional advantages and benefits of the present invention will become readily apparent to those skilled in the art upon review of the following detailed description.

[0013] The present invention will now be described in more detail with reference to the accompanying drawings.

Brief Description of the Drawings

[0014]

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DETAILED DESCRIPTION OF THE INVENTION

[0015] The Manufacturing and Quality Control Rules for Pharmaceuticals and Quasi-Drugs (GMP, Good Manufacturing Practice) present guidelines for bioprocessing, and cleanliness standards are required when following these. Advantageously, these standards are more easily achieved by using the proposed apparatus. For example, the fluid path in the system has a continuous flow path without significant stagnant portions in at least one configuration, thereby enabling complete cleaning without the need to disassemble fluid conduits. Embodiments of the proposed system provide a hygienic benchtop chromatography system suitable for both GMP operations and non-GMP operations. Due to the functionally wide flow rate range and pressure range of this system, the chromatography system is suitable for both the production of technical batches and scale-up studies and the small-scale production of GMP-grade materials. The high accuracy and large flow rate range of the pump enable accurate gradient formation, thereby accommodating a wide range of chromatography column sizes and more reproducible results.

[0016] In an embodiment, the modular structure realizes high functionality for various uses. The interactive control software enables real-time changes and rapid identification of unexpected deviations. The small benchtop size liberates the lab from space constraints. This system enables in-situ column packing, that is, when a column or two or more columns are used, the chromatographic medium in each column can be compressed without the need to disconnect the fluid conduits while the system is connected and prior to the implementation of chromatographic processing.

[0017] FIG. 1 shows an exploded view of one embodiment of a releasable coupling 100 according to one embodiment. The coupling 100 includes two parts, namely a cylindrical inner component in the form of a collet 110 for receiving a fluid tube, and a cylindrical locking collar 130 having an inner through aperture 132 for slidably receiving the collet 110. In use, a fluid tube (not shown) extends along axis T and into a central bore 112 within the collet 110 sized to slip fit around the tube. The collet 110 has a collet flange 114 formed on a cylindrical intermediate portion 116 and a plurality of elastically deflectable circumferentially disposed fingers 118 extending from the intermediate portion 116 of the collet 110 to a distal end 120.

[0018] The collet 110 is slidably fitted within the through aperture 132 of the collar 130, and thus the collar 130 can be attached over the fingers 118 of the collet 110 and around 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 relax the fingers 118, and this deflection effects gripping of the tube as will be explained in more detail below. The manipulation of the collar 130 is assisted by a collar flange 134 located at the distal end of the collar extending from the body 136 of the collar and which can be manually pushed and pulled. The collar has a distal end 140. The fingers 118 flare outwardly towards the distal end 120 of the collet, and thus, when the aperture 132 has a substantially constant inner diameter, by sliding the collar 130 in the direction from the collet flange 114 of the collet 110 to the distal end 120, the inner diameter portion of the aperture 132 abuts against the outer surface of the fingers 118 and is pushed inwardly so as to effect a tube clamping action.

[0019] Figure 2 shows a cross-section of the coupling 100 of FIG. 1 disposed at the tube clamp fixing position. Here, the distal end 140 of the collar 130 and the distal end 120 of the collet 110 are operated into an aligned state by manual positioning of the collar flange 134 relative to the collet flange 114. At that position, the inner surface of the aperture 132 and the outer surface of the finger form complementary surfaces, and when these surfaces come into contact, the finger 118 is deflected inwardly toward the axis T, biasing the adjacent portion of the tube (not shown) inside the collet inwardly, for example, compressing, squeezing, or clamping the tube. Release of the coupling is achieved by operating the collar and its flange in the direction.

[0020] Figure 3 again shows the coupling 100 in cross-section in a state disposed at the tube release position. Here, the collar 130 is slid in the direction R toward the distal end of the collet, but the collar 130 is prevented from slipping off the collet by one or both of the collet flange 114 and / or the step 138 in both the aperture 132 and the bore 112 forming a stopper. At that position, the finger 118 is relaxed and elastically rebounds outwardly, stopping or relaxing the biasing / compressing / clamping action on the tube. The position shown in FIG. 3 is achieved by operating the collar 130 and the flange 134 in the direction relative to the collet 110 (FIG. 2).

[0021] FIG. 4 shows a cross-section of a coupling assembly 10 with a male part, which in this case is in the form of the connector insertion port 20. This male part has an extension 22, such as a seal ridge, bead, or barb, that can be positioned inside the flexible fluid tube 30 beyond the open end of the tube 30 as a press-fit portion. The tube 30 is held in the insertion port 20 by compressing the tube 30 onto the insertion port 20. The coupling 100 surrounds the tube 30 and provides a releasable compression of the tube against the insertion port 20 in the manner described above mainly in relation to FIG. 2 to releasably hold the tube 30 in the insertion port 20. In this figure, it is clear that the finger 118 assists in holding the tube against the insertion port by compressing the tube 30 deeper into the extension 22 and effectively locks the tube in the insertion port 20. The coupling assembly 10 can supply fluid to or remove fluid from the module 1. In this embodiment, the module 1 is a chromatography system that requires a releasable fluid coupling that can be easily cleaned and does not provide a hiding place for contaminants. In another embodiment, the fluid pressure of the module 1 can be measured or adjusted through the fluid tube 30, so only fluid communication is required. Therefore, fluid flow in the tube 30 is not an essential condition.

[0022] Figure 5 shows the same cross-sectional view as in Figure 4, but in this figure, the coupling assembly 10 is in the released position as shown in Figure 3. In use, the coupling 100 positioned as in Figure 4 clamps the tube 30 in place over the insertion port 20, and when pulled in the direction of the collar flange 134, the compression on the tube is released. This release causes the collar flange 134, collar 130, and collet 110 to be pulled along the tube in the direction of Figure 5. As described above, the collet has stoppers (collet flange 114 and / or step 138), which prevent the collar from coming off the collet, thereby enabling the collet to be pulled out with the flange 134. In this pulled-out position, the tube 30 can be easily removed from the insertion port 20. Connecting or reconnecting the tube 30 to the insertion port 20 is performed by reversing the above-described steps. That is, when the tube 30 is fitted over the insertion port 20, the collet flange 114 is pushed in the opposite direction, and when the distal end 120 of the collet seats firmly against the module 1, the collar flange 134 is pushed to the home position to deflect the fingers 118 against the outer surface of the tube to clamp the tube to the insertion port 20.

[0023] The coupling 100 is preferably formed from only two plastic material moldings. From the drawings, it will be understood that the outer surface of the collar 130 is smooth, i.e., the collar flange 134 is a continuous annular formation standing upright from the annular body 136, and the outer side of the collar where the collar flange and the collar flange are formed thereon has a continuously curved profile without a sharp change in direction. Thus, the likelihood of the coupling being contaminated during use is reduced, and the coupling is easily washable. Further, the user can hold each side of the collar flange and pull the collar flange in the direction (Figure 5) with two fingers with each finger placed on each side of the collar body 136. At the same time, the user can respond to such pulling force by placing the thumb on the collet flange 114 on the opposite side of the two fingers described above.

[0024] It is important to ensure that the tube 30 fits substantially completely over the insertion port 20. For this purpose, the collet 110 and the collar 130 can be formed from a transparent plastic. Further, the insertion port can be of a different color than the tube in order to give a visual color indication that the tube does not completely overlap the insertion port if any of the color of the insertion port is visible. One modification of the embodiment shown in FIGS. 1-5 is shown in FIGS. 6a, 6b, and 6c. FIG. 6a shows a modified insertion port 20' having an elastic protrusion 24 such as an elastic arm extending outwardly, and FIG. 6b shows the tube 30 pushed completely into the home position relative to the insertion port 20'. When the tube is in the completely home position at the insertion port, the arm 24 moves inwardly and only in that case can the collet finger 118 be pushed onto the tube as shown in FIG. 6c, and the collar 130 is in a state where it can be pressed from above the finger to clamp and fix the tube in place as described above. If the insertion port 20' is not completely inserted into the tube 30, the collet 110 does not pass through the arm 24.

[0025] FIGS. 7a, 7b, and 7c show a cross-section of a modified coupling assembly 105. In this embodiment, the collar 130 of FIG. 1 is replaced by a locking plate 230 having a plurality of through apertures 232 each receiving a collet 110. This locking plate is provided with a protrusion 234 that serves as a substitute for the flange 134 shown in the previous figures. The centers of the through apertures are aligned with the centers of a plurality of male parts protruding from module 1 so that a plurality of connections can be realized in one operation.

[0026] In FIG. 7a, it is shown that the locking plate 230 is provided to the module 1 with the collet 110 assembled in the through aperture 232 and the tube 30 pre-fitted inside the collet 110 covering male parts such as the insertion port 20. FIG. 7b shows the same coupling assembly as shown in FIG. 7a, but the locking plate 230 and the collet 110 are pushed in the direction with respect to the front surface of the module 1 such that the collet overlaps the insertion port 20 and the end of the tube 30. FIG. 7c shows another view of the coupling assembly of FIG. 7a, where the locking plate 230 is further pushed in the direction in FIG. 7b. In FIG. 7c, the locking plate serves to clamp and fix the fingers 118 of the collet 110 around the tube 30 in the manner as described above.

[0027] FIG. 7d shows yet another modified form of the coupling assembly, where the locking collars 230´ are each attached to the locking plate 231 by a flexible mount, in this case a spherical mount 233, which allows each collar 230´ to rotate around the center point of the mount 233, thereby providing a tolerance for some alignment error or dimensional error in the male parts on the module. Naturally, the locking plate can be formed from a flexible material to provide a similar tolerance. Two couplings are shown in FIG. 7a, but other linear arrays or two-dimensional arrays of couplings can be used to match the configuration of the male parts 20, for example an array of four couplings can be used to match the square male part configuration shown in FIG. 8. These couplings do not need to be located in the same plane. The couplings do not need to have substantially parallel axes if some degree of flexibility is provided as described with reference to FIG. 7d for example. For ease of use, the tube 30 may have a single coupling 100 at one end and may be integrated at the opposite end in a manifold manner with a plurality of couplings 105.

[0028] FIG. 8 shows a chromatography system 11 including a support portion 80, which a pump 12, a chromatography column 13, various valves 14, a pH monitor 15, a conductivity monitor 16, a mixer 17, and a UV monitor 18 and includes conventional fluid processing modular components in the form of replaceable modules such as these. Other modules can be used. Those modules can be connected in any suitable manner using a fluid tube 30 having couplings 100 at each end, and only one of those couplings 100 is shown for convenience. The coupling 100 can be replaced by a plurality of tubes and couplings 105 of the type shown in FIGS. 7a, 7b, 7c, or 7d to speed up the connection and disconnection of the couplings. For convenience, the valves 14 each have the same male part configuration, i.e., a locking plate 230 of the same configuration can be used for each valve.

[0029] FIG. 9 shows a release tool 200 having a bifurcated end 210 suitable for engagement with each side of a flange 134 or a protrusion 234 to pull the flange 134 or the protrusion 234 outward away from module 1 or modules 12 - 18, or to push the flange 134 or the protrusion 234 if there is no space to pull with a finger.

[0030] An alternative embodiment of coupling 300 is shown in FIGS. 10, 11, and 12. In that embodiment, a locking collar 330 (FIG. 10) surrounds a cylindrical internal component in the form of a collet 310 having fingers 318 of the type described above, and these fingers further surround fluid tube 30. Coupling 300 is operable in substantially the same manner as couplings 100 and 105 described above in that the tube 30 is pushed onto male part 20 projecting from module 1 to achieve a liquid-tight connection, and then the collet is slid on the tube until the distal end 340 of the collet abuts or contacts module 1, and then the collar is moved towards the module to initiate clamping of the fingers 318 of the collet 310. Its position is shown in FIG. 11.

[0031] It will be noted that the distal end 340 comprises a pair of bayonet-type openings for receiving complementary locking pins 27 supported by a boss 25 extending from module 1 around male part 20. In this embodiment, the final locking position of the collar 330 is not achieved until the bayonet openings 345 receive the pins 27 and the distal end 340 of the collar is linearly and rotationally manipulated over and along the boss 25 to be further pushed towards module 1 to the final locked position shown in FIG. 12. Thereby, the fingers 318 are further clamped to the tube 30 and the collar 330 (and coupling 300) is fixed to module 1 with the pins 27 holding it in place.

[0032] The embodiment shown in FIGS. 10, 11, and 12 relies on a substantially linear locking operation of the locking collar described immediately above, i.e., some torsional movement is utilized to fix the collar 330 in place and to apply the clamping force. This torsional movement can be facilitated by the use of wings 334 extending from the collar 330 rather than the flange described above.

[0033] Figures 13 - 16 show in detail another collet 410 and a portion of a collar 430 that can be used with couplings 100, 105, or 300. In this variant, in this case, the clamping of the fingers, which are fingers 418, can be effected by twisting the collar 430 around the collet 410 as an alternative to the sliding movement of the collar 430 in the manner described above or to said sliding movement.

[0034] More specifically, the inner surface of the collar 430 has detents 432 that act on the tapered portion 431 of the fingers 418 when the collar is twisted relative to the fingers. The circumferential ramps 431 each function as a cam that, in use when the collar is twisted in the direction of arrow R in this example, is pushed inwards towards the tube 30 by the respective detent. Thereby, the fingers 418 are compressed around the tube 30 from the positions shown in FIGS. 13 and 14 to the clamped and fixed positions shown in FIGS. 15 and 16 in use, and in that position the detents come to rest in complementary recesses 433. The amount of twisting movement utilized for locking is 120 degrees or less, and preferably about 90 degrees or less, when three or more circumferentially arranged fingers are used.

[0035] The above-described couplings 100, 105, and 300 for use with a tube having an outer diameter of about 3 to 10 mm have been experimentally shown to be capable of sealing the tube with a coupling with an internal fluid pressure of at least 10 bar or more, such as 15, 20, 25, 30 bar or more, and as will be described in more detail, embodiments of these couplings have been duly demonstrated by an extensive leak test at 30 bar. The coupling realizes a liquid-tight connection of the tube around the male part that can be connected and disconnected only by a substantially linear movement of the locking collar 130 or the locking plate 230 without the need for torsional movement or screwing of parts. Therefore, these couplings can be placed closer to each other compared to conventional screw couplings because the space for torsional movement is avoided. As used herein, substantially linear means a rotation of 120 degrees or less, such as 90 degrees or less, less than 45 degrees, less than 30 degrees, less than 15 degrees, less than 5 degrees, or substantially no rotation.

[0036] Various embodiments, each having the same functionality in a releasable coupling, i.e., the locking collar 130, the locking plate 230, the locking collar 230´, the locking collar 330, and the collar 430, which are the features described above, have been described for the collar elements. Some are non-cylindrical (locking plate 230), and others are shaped cylindrically. The collar element comprises at least one protrusion, such as the collar flange 134 or the wing 334, that extends outwardly away from an aperture sized to allow manual operation of the collar between a first position and a second position.

[0037] In connection with FIGS. 1-7, an internal component has been described as a collet 110 that may include stop portions such as a collet flange 114 and / or a step 138. The collet flange 114 extends outwardly and has a size that aids in the manual operation of the coupling. Further, the elastically deflectable portion is equivalent to the deflectable finger 118 described in connection with FIGS. 1-7 and the finger 418 described in connection with FIGS. 13-16.

[0038] FIG. 17 shows a chromatography apparatus 400 according to one aspect of the present invention. The apparatus includes, but is not limited to, individual modular components 51-75 as described below, at least some of which are removable from the apertured front panel 420 of the support 410 of the apparatus 400 and are mounted on the apertured front panel 420 in one substantially vertical plane such that the required liquid communication between the modular components can be achieved only at the front face 420. In practice, these removable modular components have only one reference size and can be repositioned within the panel 420 as appropriate for different processes. Each modular component has a serial bus communication connection and a power connection such that its physical location is of no concern to a controller located, for example, within the support 410 or remotely. Therefore, the modular components can be considered to be modular and thus repositionable and / or replaceable.

[0039] The chromatography apparatus shown in FIG. 17 includes the following modular components, namely 51 Control panel 52 pH monitor 53 Outlet valves 1-3, port 1 can be used for waste 54 Outlet valves 4-6 55 Conductivity monitor 56 Outlet valves 7-9 57 Pre-column conductivity monitor 58 Column valve unit with pre-column and post-column pressure sensors 59 Bottle for pump cleaning solution 60 Inlet valves A1 - A3 61 Inlet valves A4 - A6 62 Inlet valves B1 - B3 63 Inlet valves B4 - B6 64 Fixed rubber feet 65 Adjustable feet 66 System pump A 67 System pump B 68 Flow restrictor with system pressure monitor 69 Mixer module - type component 70 Mixer valve 71 Air trap valve with air sensor 72 Air trap 73 On / Off button 74 Holder for in - line filter (illustrating a typical filter capsule) 75 UV monitor

[0040] The modular components can be omitted or re - positioned as described above. It will be apparent that some modular components can be replaced with other modular components, or the space created by the omitted modular components can be filled with blank plates (see, for example, 76 in Figure 20). It is possible to use two or more modular components with the same reference numeral as required.

[0041] The fluid interconnection between the modular components of the device's fluid operation module, i.e., all the modular components listed above except for the modular components 51, 64, 65, and 73, and external modular components such as a sample input reservoir, a buffer fluid reservoir, a chromatography column, and a fraction collection device, although not all are shown in, for example, FIG. 17, is in this case effected via fluid conduits in the form of flexible plastic tubes, which can be easily coupled and decoupled to the corresponding ports of the modular components of the fluid operation module in any desired configuration, for example, using couplings as described above.

[0042] FIG. 18 shows one possible liquid interconnection configuration between the main modular components of a chromatography device 400 connected to two chromatography columns 700 and 800 in this case, although the device allows for any realizable interconnection between the modular components and additional parts such as multiple columns and a liquid reservoir. The reconfigurable liquid interconnection is indicated by the dash-dotted line 580.

[0043] At the center of the device 400 is located a column valve unit 58, which in this case has a structure as disclosed in the pending UK application No. 1715399.0 filed on September 22, 2017, and is incorporated herein by reference. The valve unit 58 enables a plurality of flow switches to allow flow in one or both of the columns 700 / 800 in each direction (upward and downward in the drawing). The user can select an upward flow or a downward flow, or can select to bypass one or both of the columns. This flow can be sent to waste or to the next component in the flow path. Also, these columns can be connected in series, and each column includes a variable volume chamber for accommodating a chromatographic separation medium and an adapter that is movable to increase or decrease each of the said volumes. The column valve unit 58 is in fluid communication with each adapter and is selectively operable to move each adapter individually or collectively by a fluid pressure change, resulting in a change in each volume, and to cause compression or release of the medium within each column volume during use.

[0044] The column valve unit 58 includes a pre-column pressure sensor and a post-column pressure sensor, and further 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 further includes a fluid outlet 520 configured to provide an output fluid from the valve unit. The output fluid provided can typically be the resultant fluid after passing the received fluid through one or more columns of the chromatographic device 400. The valve unit 58 further 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 further includes a coupling valve assembly configured to send fluid between select ones of 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.

[0045] Furthermore, the valve may be used to change the volume of the hydraulic cylinders 710 and 810, which are part of columns 700 and 800, in order to enable compression of the column contents, also known as column packing, for example. The packing process can be automated. With such a system, column diameters between about 25 and 250 mm can be packed in this way. These columns can be pre-packed, but can be washed and reintegrated with the aid of a pressure sensor in the valve unit 58 that measures the backpressure resulting from the pressure within the column and according to a known protocol as described, for example, in WO 2007 / 045491, the disclosure of which is incorporated herein by reference.

[0046] The remaining system 400 includes inlet valve groups A and B, 60, 61, 62, and 63 suitable for providing selectable liquids including sample-containing liquid, buffer, and wash fluid and is provided with. These inlet valves supply two system pumps, where each of these two system pumps has a pair of pistons and associated one-way valves, thereby realizing a variable flow rate of 0 to 600 ml / min (maximum 1200 ml / min) with a high volume flow and a high flow rate resolution, enabling the maintenance of an accurate flow rate. With such accuracy, good result reproducibility for a wide range of column diameters is possible. These pumps are sequentially supplied to a flow restrictor 68 with a system pressure monitor, a mixer valve 70, and a mixer module 69 before the liquid pumped is delivered to the column valve unit 58. The entrained air can escape through the air trap valve 71 and the air trap vent 72, and this air trap vent 72 further allows air escape from columns 700 and 800. The air trap may be constructed according to the pending UK application No. 1713993 filed on April 5, 2017, the disclosure of which is incorporated herein by reference. When the liquids reach the column valve unit 58, they can be sent according to the configuration described in the pending UK application No. 1715399.0 filed on November 22, 2017. Thus, a number of chromatographic modes can be implemented, from a simple batch operation where a straightforward chromatographic separation process is carried out using only one column, to a process that more closely mimics a larger commercial process where two or more columns, one being available for use while the other is being used for separation, can be used. The output from the chromatographic column passes through port 520 and is sent to the conductivity monitor 55, the UV light absorption monitor 75, and the pH monitor 52. From there, depending on the signals from the three monitors, it is sent into an appropriate storage container, whereby the separated fractions are collected in the appropriate container 501. The column washings can be collected in the waste container 500. The dash-dot line 601 in Figure 2 represents a system bus that carries signals and power from the above-described modular components to and from the controller 600. It will be understood that the control and monitoring of the signals may be wirelessly communicated according to known protocols without the need for a communication bus. Also, the chromatographic system 400 includes a display screen 530. Software executed on the controller displays a plurality of icons on the screen 530 and enables the user to operate the icons on the screen to form a series of icons representing a user-defined chromatographic control method for ease of use. The user-defined chromatographic control method includes a continuous chromatographic process using the two or more chromatographic columns by selective valve openings in the column valve unit 58.

[0047] Figures 19, 20, and 21 show systems connected to tubes for various configurations, and only some of the modular components referred to in Figure 17 remain in place in these drawings. The apertures created by the removed modular components are closed with blank plates 526 screwed into position to cover the apertures to prevent the unintended entry of liquid into the support 410.

[0048] In Figure 19, a system 400' having a configuration of modular components suitable for a customized environment fabricated in a factory. This system is sent, installed, calibrated, performance tested, and is suitable for operation in a GMP environment. Figure 20 shows one system 400'' from which the modular components have been removed, and Figure 21 shows a system 400''' in which additional modular components are in place, showing a typical tube interconnect 580 similar to that of Figure 71.

[0049] In use, the modular components can be easily removed from or added to the system, and installation is completed with a single click operation in software that can recognize each modular component. This software can implement comprehensive and customizable operation control and preemptive maintenance. In addition to the modular components described above, input / output communication modular components can be used to interface with other devices such as analog and / or digital external sensors or automatic fraction collection devices. The wide flow rate and pressure ranges enable scaling by more than 40 times in columns with an inner diameter of 25 - 250 mm. This wide range makes the device suitable for bridging the transition to a GMP environment.

[0050] The packing (and repacking) of the chromatography column using the above system is fully controllable by a controller 600 activated by the control panel 51. The controller 600 is capable of driving a display screen 530 (FIG. 18) to assist in visualizing the packing process and progress. The control software includes accessible column packing records. Thus, the column packing records can be defined, generated, and updated from the software for traceability and quality assurance purposes. Further, the records can be used to monitor column performance and provide statistics regarding usage, separation performance, and packing intervals. The display screen can provide only the desired amount of information at each step by enabling process visualization that quickly gives the operator an overview of the system functions, progress during the operating steps, and warnings. The active flow path is always displayed in this process visualization to minimize user errors. Real-time changes can be made by selecting the appropriate process on the visualization screen, such as selecting or dragging an icon on the screen. The control graphic interface is provided for specific sections such as the column valve unit 58.

[0051] Pre-programmed steps are used, but they can be modified and saved as user-defined steps for additional customization.

[0052] The system described and shown above is designed for a hygienic environment. For example, the support part 410 is flat or curved without joints, gaps, or large concave parts except at the edges of its surface, so it is easy to wipe and less likely to trap dust and liquid. The pH monitor 52 has in-line calibration, and the column valve unit 58 enables in-process column packing, so a closed flow path can be used during operation, that is, no interruption in the flow path is required throughout one or more chromatographic column packing / regeneration stages and throughout the separation operation.

[0053] Figure 22 shows a prior art modular component 810 with four ports 811 configured to be connected to prior art fluid communication parts 812 respectively. Due to the size of the couplings 813 required to fix the fluid communication parts 812 to the ports 811, these couplings have to be arranged at different heights. This is a bulky solution and further requires space to be provided around the modular component to facilitate the attachment / detachment of the fluid communication parts 812 to / from each port 811.

[0054] Figure 23 shows a modular component 820 with four ports 821, each of these ports 821 having a tube 822 with a releasable coupling 100 (as described in relation to FIGS. 1 - 6) attached to the first end thereof. The second end of one of the tubes is connected to a converter 823 with another releasable coupling 100 to enable the attachment of a fluid communication part not suitable for direct connection to the port 821. The converter 823 will be described in more detail in relation to FIGS. 24a and 24b. Using releasable couplings when connecting fluid communication parts to the modular component allows the ports to be positioned closer to each other relative to each other, resulting in a less bulky design. Also, the releasable couplings are more easily sanitized, attached / detached, and replaced as required.

[0055] FIG. 24a shows a cross-sectional view of a converter 823 having a body 830, a flange 831, a through hole 832, and an insertion port 833 integrated with the body 830. The converter 823 is made of a single piece of material such as plastic or metal in this embodiment. The flange 831 is configured to be used in a tri-clamp (TC) coupling in this example, and the insertion port 833 is configured to receive a tube having a releasable coupling 100 (not shown).

[0056] FIG. 24b shows a cross-sectional view of an alternative converter 823' that is similar to the converter described in relation to FIG. 24a except for one exception. The converter 823' includes two parts, the body 830 and the flange 831 are made of a single piece of material such as plastic, and the insertion port 833' is made of another material such as metal.

[0057] FIG. 25a shows a prior art modular component 910 having three threaded holes as ports 911. Tubes 912 each having a screw connector 913 are fixed to the respective ports 911. FIG. 25b shows an end flange 914 fixed to the first end of the tube 912 and configured to form a seal when disposed within the threaded hole 911, and a body having a threaded portion 915 and a grip portion 916 designed to be used when fixing the screw connector 913 to the modular component 910. A screw connector 913 is shown. Because space is required to fix the screw connector 913 to the modular component 910, this design is somewhat bulkier compared to the case where a releasable coupling is used as shown in FIG. 23. When a fluid tube is connected to a port using a screw connector, fixing the screw connector to the threaded hole causes an unintentional rotation (about 2 to 3 rotations) of the fluid tube. This is particularly a drawback when fixing a short fluid tube, for example, 10 to 30 cm long, because the tube takes on a kinked behavior. Additionally, a separate O-ring may be required to create the desired pressure and fluid seal.

[0058] To enjoy the benefits from the advantages obtained by the releasable coupling 100, the adapter may be introduced into the threaded hole of the modular component 910.

[0059] FIG. 26a shows a cross-sectional view of an adapter 915 having a body 920, a threaded portion 921, a through hole 922, and a plug-in port 923 integrated with the body 920. The adapter 915 is made of a single piece of material such as plastic, metal, etc. in this embodiment. The threaded portion 921 is configured to be introduced into the threaded hole of the modular component using the body 920 as a grip portion in this example, and the plug-in port 923 is configured to receive a tube having a releasable coupling 100 (not shown).

[0060] FIG. 26b shows a cross-sectional view of an alternative adapter 915' that is similar to the adapter described in relation to FIG. 26a except for one exception. The adapter 915' includes two parts, the body 920 and the threaded portion 921 are made of a single piece of material such as plastic, etc., and the plug-in port 923' is made of another material such as metal.

[0061] FIG. 27 shows a cross-sectional view of an alternative transducer 925 having a body 930, a portion having a threaded hole 931, a through hole 932, and a plug-in port 933 integrated with the body 930. This transducer 925 is made of a single piece of material such as plastic, metal, etc. in this embodiment. The threaded portion 931 is configured to receive a threaded connector as described in relation to FIG. 25b in this example. The plug-in port 933 is configured to receive a tube having a releasable coupling 100 (not shown). Note that the plug-in port may be manufactured separately from different materials compared to the body and the portion having the threaded hole.

[0062] One advantage of the releasable coupling assembly 10 is that it has no threads, i.e., it can be sterilized and requires less maintenance. A simple extension 22 (i.e., a seal ridge, bead, or bead) at the insertion port 20 extending from the front of the panel is much easier to sterilize compared to conventional screws of connectors with very limited access to the screw holes as shown in FIGS. 25a and 25b.

[0063] Another advantage is that, in contrast to what is shown in connection with FIG. 22, no flange is required, and thus it is possible to manually cut the tube before connecting the tube using the releasable coupling 100. Thus, the static size of the inner diameter of the tube is within the same range as the outer diameter of the sealing ridge 22 of the insertion port 20, and the static size of the inner diameter of the tube is preferably less than ±10% of the outer diameter of the insertion port.

[0064] Another advantage is that no O-ring or gasket is required, i.e., it is a solution with less maintenance and higher robustness compared to prior art solutions. Sealing is achieved by using a tube material that is in direct sealing engagement with the sealing ridge 22. However, this requires the tube to have some flexibility and deformability. The releasable coupling results in a minimum number of connections / joints between various materials and parts, which improves the possibility of sterilizing the fluid communication part as required. Another advantage is that the releasable coupling assembly is easy to attach, for example, to a one-handed snap fit for low-pressure applications.

[0065] As described in connection with FIGS. 24a, 24b, and 27, the transducer connector may be used to provide a connection to other connectors such as, for example, a TC connector. As described in connection with FIGS. 26a and 26b, the screw adapter may be used to upgrade an old device having a screw hole (see FIG. 25a) to a connector configured to use a releasable coupling when attaching a tube. As described above, the insertion ports 20 may be placed closer to each other than when a screw type connector or a TC connector is provided. This allows for a shorter internal flow path in modular components such as valves, for example, and thereby allows the size of fluid components having an internal flow path to be reduced by using a releasable coupling assembly. Further, this affects the entire chromatography system having a low footprint with respect to flow capacity.

[0066] FIGS. 28a and 28b show cross-sectional views of the insertion port with the tube not attached and the tube attached. The tube dimensions (inner diameter D1) and the insertion port dimensions (outer diameter D2) are emphasized as being important to provide a proper seal between the tube 30 and the open end 281 of the insertion port 280 and to avoid the formation of pockets where deposits of residues from biological substances could be trapped. The modulus of elasticity of the tube allows for the deformation of the tube necessary to pass over the sealing ridge 282 provided in the vicinity of the open end 821. The shape of the sealing ridge is important to achieve the desired functionality having the following important aspects. - It is possible to achieve asepsis. This is because a pocketless structure is provided by direct sealing to avoid pockets where biological substances could be trapped. - A pressure limit for holding the tube in the insertion port.

[0067] As described above, other important parameters are as follows. - The modulus of elasticity of the fluid tube. - The inner diameter of the fluid tube and the outer diameter of the insertion port.

[0068] In some of these embodiments, the sealing ridge has a circular design with a radius R and a height h from the center of the insertion opening. This radius extends to the open end of the insertion opening and allows the tube to slide over the sealing ridge using a force low enough for a normal operator and to achieve an angle at which the tube does not bend under pressure when sliding over the sealing ridge. This circular section starts at a radius similar to the inner diameter of the tube. The height is determined by the modulus of elasticity of the tube and the pressure limit value for the connector.

[0069] Other shapes of the sealing ridge are shown in FIGS. 28a, 29a, and 29b. The arrows F1 - F3 in FIG. 28b schematically show the forces involved in the attachment and locking of the tube end 30 onto the insertion opening 280. In one embodiment, for example as illustrated by the connector 100 above, the collet is arranged to apply a tube clamping fixing pressure as shown by F2 in FIG. 28b to the insertion opening side of the midpoint of the sealing ridge. In one embodiment, essentially, the fluid sealing force F1 between the tube and the front end of the sealing ridge near the open end of the insertion opening is mainly achieved by the elasticity of the tube. This sealing is achieved without any pockets when positioning the sealing ridge near the open end, i.e., when there is no flat section at the open end of the insertion opening.

[0070] By applying the locking pressure F2 essentially behind the midpoint of the sealing ridge, essentially all of the available clamping force is utilized to hold the tube against the sealing ridge. The pressure limit value is determined by 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 insertion port. However, all surfaces should be as smooth as possible to be made sanitary. In an alternative embodiment, a portion of the available clamping force may be applied at the end section 281 of the insertion port 280 to further secure the seal between the insertion port and the tube. In the disclosed embodiment 100, the fingers 118 of the collet 110 apply the clamping force only in the vicinity of the sealing ridge 282 and are designed to leave a space for the tube at the lower end of the insertion port when in the clamping position. By doing so, the clamping force is hardly affected by the dimensional variations in the various components (insertion port, tube, collet, and collar). This is because the clamping force is accompanied by the spring load of the fingers 118 around the clamping position. In the disclosed embodiment, the available clamping force is determined by the force applied by the operator when pushing the collar 130 on the collet 110 towards the tube clamping position. Thus, the fingers 118 are displaced to contact the tube, and the force required to lock the clamp by pushing the collar 130 is adapted to be a moderate force for the user, while at the same time avoiding the need for an overly high release force to release the clamp.

[0071] Figure 28b shows the situation when the fluid tube 30 is attached covering the length portions of the sealing ridge 282 and the insertion port 280, and schematically shows the locking pressure on the tube applied to the insertion port side of the midpoint of the sealing ridge. The fluid sealing force F1 between the tube and the front end of the sealing ridge near the open end of the insertion port is achieved by the elasticity of the tube. This seal is achieved without any pockets when positioning the sealing ridge near the open end, i.e., when there is no flat section at the open end of the insertion port.

[0072] By applying a locking pressure F2 behind the midpoint of the sealing ridge, essentially all of the available clamping force is utilized to hold the tube against the sealing ridge. The pressure limit value is determined by 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 insertion opening. However, all surfaces should be as smooth as possible to be biocompatible. Additionally, sharp corners may inadvertently form pockets where biological substances can be trapped, and thus sharp corners should be avoided as much as possible to be biocompatible.

[0073] To increase the sealing pressure limit value, it may be desirable to apply an additional sealing force F3 to the base of the insertion opening (opposite the open end). 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, a contact or lower pressure is applied at or near the position of the base of the insertion opening to stabilize the connection.

[0074] The clamping force may be provided using a releasable coupling as described above. Other types of couplings such as hose clamps, eccentric couplings, etc. are possible when providing an appropriate clamping force as described above. The length of the connector selected must be based on the length of the insertion opening so as to avoid a lever effect.

[0075] Figures 29a and 29b show cross-sectional views of alternative sealing ridge configurations. Figure 29a shows an insertion opening 290 having a first alternative sealing ridge 292 with a non-uniform profile. The trailing edge 291 of the sealing ridge drops more steeply from the midpoint of the sealing ridge to the outer surface of the insertion opening. This improves the pressure limit value of the connection. Additionally, the front end of the sealing ridge 292 is in line with the open end of the insertion opening as indicated by reference numeral D3. This increases the force required for the attachment of a fluid tube (not shown) compared to the insertion opening described in relation to Figures 28a and 28b.

[0076] FIG. 29b shows an insertion port 295 having a second alternative sealing ridge 297 with a non-uniform contour. The trailing edge 296 of the sealing ridge curves with a radius r2 from the midpoint of the sealing ridge to the outer surface of the insertion port. The contour from the midpoint of the sealing ridge to the open end of the insertion port curves with a radius r1, and r1 is greater than r2.

[0077] Furthermore, the front end of the sealing ridge 297 is in line with the open end of the insertion port as indicated by reference numeral D4, and D4 is greater than D3 in this example, which indicates that even the force required for the attachment of a fluid tube (not shown) is less compared to the insertion port described in relation to FIG. 29a.

[0078] Generally, the present invention relates to a novel connector concept for a chromatography system, in which a conventional threaded fluid connector as exemplified in FIGS. 25a and 25b can be replaced by a much more convenient plug-in type connector, and a tube for interconnecting components in a chromatography system is simply pushed into a plug-in opening and then fixed to this plug-in opening by a releasable clamp that applies a radially clamping force to the outer peripheral portion of the tube. As described above, the plug-in opening preferably comprises a sealing ridge so as to be available in the pressure range required by this connector concept. Surprisingly, it has been proven possible to design such a connector that still significantly improves the ease of use for the operator while realizing a fluid connection that does not leak at internal pressures exceeding the required range in liquid chromatography of 20 bar and even up to more than 30 bar. The procedure for connecting a tube to a port in a chromatography system according to these embodiments simply involves pushing the tube end onto the plug-in opening, positioning a releasable connector clamp around the tube end, and applying a locking force by actuating the connector clamp. Similarly, the procedure for disconnecting a tube from a port in a chromatography system according to these embodiments simply involves deactivating the connector clamp to release the locking force, optionally removing the releasable connector clamp from the tube end, and pulling the tube end out freely from the plug-in opening. One major advantage of one of the disclosed embodiments is that the step of applying the locking clamp does not require a torsional movement that can transmit a rotational movement to the tube, whereby the tube is not rotated relative to the male part during the application step. As described above, this prevents the tube from undergoing a torsional movement and forming kinks that can restrict the fluid flow or even break the tube segment.Furthermore, compared to a conventional chromatography system having a connector that requires a flanged tube such as a tube having an inner diameter of, for example, 1 to 10 mm, the present system provides the advantage of enabling customization of the fluid path by adding a step of cutting the tube segment to an optimal length before interconnecting the paths.

[0079] Leak test of the connector. To demonstrate an embodiment of the present connector / chromatography system to achieve leak-proof connection for a desired pressure range for liquid chromatography. In one embodiment, the upper pressure limit of the chromatography system for operation is 20 bar, and the connector was periodically leak tested at 30 bar to demonstrate proper sealing at 20 bar. In this test, the limit for determining leakage was set to 1 μl / min at 20 bar for each connector in the flow path being tested. A normal test was conducted under the following conditions. · Leak test at 20 bar over a temperature range of 4 to 40 °C · 6000 repetitions of connection and disconnection, leak test at 30 bar every 500 cycles (performed for two different dimensions) · Static leak test at 40 °C over 12 months, leak test at 30 bar once a week · 1000 cycles of tensile test with a tension of 0 to 20 N, leak test at 30 bar before and after each cycle

[0080] As described above, surprisingly, it has been found that this can be achieved while providing significantly improved ease of use compared to conventional connections.

[0081] In addition to the above leak tests, a Salt Creep Test was performed by circulating a mobile phase of 2.5 M (NH4)2SO4 in the system overnight (about 12 hours) at a back pressure of 1.5 MPa. Thereafter, a visual inspection was performed regarding salt creeping around the connector, valve, and other modules. It was demonstrated that the connector and the chromatography system passed the test without visible salt creep.

[0082] Figures 30a through 30c illustrate the interaction between the insertion port 20, the tube 30, the collet 110, and the fingers 118 of the collet 110, according to one embodiment. In Figure 30a, the tube end 310 is shown above the insertion port, and the dashed line indicates the relationship between the inner diameter of the tube and the insertion port element. As will be appreciated, the insertion port base is slightly wider than the tube inner diameter, and the sealing ridge 22 is significantly wider but has a circular leading edge so that the tube can be pushed into the insertion port. In Figure 30b, the tube end has been pushed into the insertion port (beyond the portion shown), the collet 110 has been applied around the tube end, and is actuated in the locked position to clamp the tube. The collet 110 is disclosed in more detail in Figure 30c, where it can be seen that the fingers 118 include a clamping section 350 for clamping the tube in the region of the center of the sealing ridge 22 of the insertion port 20. In one embodiment, the tube inner diameter is 3.2 mm, the outer diameter is 4.8 mm, while the insertion port base diameter is 3.25 and the sealing ridge is 3.45, and this sealing ridge, together with the locking force from the clamp 10, provides a leak-free connection. Tubes used in this type of liquid chromatography system generally have tubes of a material rigid enough to withstand the pressures used and can be made, for example, from fluorinated ethen propen (FEP) plastic.

[0083] According to one embodiment, components 12-18, 810, 910 for a chromatography system 11 are disclosed. The components (which may be modular) comprise one or more ports, each port being accessible via an insertion opening 20, 923, 923' for receiving a first end of a fluid tube 30, 812, 912. The first end can be sealed around the insertion opening by a releasable coupling 100, 105, 300 external to the tube end, the coupling having a releasable clamping action operable by sliding of collar elements 130, 230, 230', 330, 430 of the coupling along the end of the fluid tube.

[0084] The insertion opening (20) may be an integral part of components 12-18. Further, the insertion openings 923, 923' may be provided on adapters 915, 915' configured to be coupled to ports of component 910. In some embodiments, the ports are threaded holes 911 and the adapters 915, 915' comprise corresponding threaded portions 921, bodies 920, and insertion openings 923, 923'.

[0085] In some embodiments, adapter 915 is made from a single piece of material, which may be plastic or metal.

[0086] In some embodiments, insertion opening 923' is made from a first material and body 920 and threaded portion 921 are made from a second material, the first material may be metal and the second material may be plastic.

[0087] According to one embodiment, a releasable coupling 100 configured to hold a fluid tube in an insertion opening is disclosed. The coupling comprises - cylindrical inner components 110, 310, 410 configured to receive fluid tube 30, the inner components comprising elastically deflectable portions 118, 418 configured to bias the outer surface of the tube towards the insertion opening, - A color element 130 having an internal through - aperture 132 for slidably receiving an internal component, wherein the aperture and the elastically deflectable portion have complementary surface profiles, and these complementary surface profiles provide the elastic deflection during use at a first position of the color element attached to the internal component and prevent an action on the outer surface of the fluid tube at a second different position, the color element 130 comprises. The color element comprises at least one protrusion extending outwardly away from an aperture sized to enable manual operation of the color between the first position and the second position.

[0088] In some embodiments, the internal component 110 further comprises stop portions 138, 114 that can cooperate with the color element to prevent or impede sliding of the color element away from the internal component in at least one direction.

[0089] In some embodiments, the color element is slidable on the internal component from a first position where deflection is provided to a second position where the color element abuts against the stop portion.

[0090] In some embodiments, a color flange 134 is formed at one end of the color element and the stop portion is formed at one end of the internal component. The color flange 134 and the stop portion are moved manually in the vicinity of the second position, and the color element can be further slid manually to a first position where the color flange 134 is spaced from the stop position.

[0091] In some embodiments, the portion is a collet flange 114 that extends outwardly and has a size to assist in manual operation of the coupling. In some embodiments, the color flange 134 is a continuous annular shape standing upright from the body 136 of the color. In some embodiments, the outer surface of the color element on which the color flange 134 and the color flange are formed has a continuously curved profile without a sharp change in direction.

[0092] In some embodiments, the elastically deflectable portions 118, 418 of the internal components 110, 310, 410 comprise a plurality of circumferentially arranged fingers that are deflectable inwardly towards the tube in use. In some embodiments, the collar element 330 further comprises a bayonet opening 345 that cooperates with a complementary locking pin 27 to removably secure the coupling to module 1.

[0093] According to one embodiment, converters 823, 823', 925 are disclosed for connecting the end of a first fluid tube to the end of a second fluid tube. The converter comprises an insertion port 833, 833', 933 for receiving the end of the first fluid tube, and the end of the first fluid tube is sealable around the insertion port by a removable coupling 100, 105, 300 external to the tube end. The coupling has a releasable clamp fixing operation that is operable by sliding movement of the collar element 130, 230, 230', 330, 430 of the coupling along the end of the fluid tube.

[0094] In some embodiments, the converters 823, 823' further comprise a body 830 and a flange 831, or a body 930 and a threaded hole 931 configured to be coupled to the end of the second fluid tube.

[0095] In some embodiments, the converter 823 is made from a single piece of material, which may be plastic or metal.

[0096] In some embodiments, the insertion port 833' is made from a first material, and the portion having the body 830 and the flange 831, or the body 930 and the threaded hole 931, is made from a second material. The first material may be metal, and the second material may be plastic.

[0097] According to one embodiment, a chromatography system 11 is disclosed that includes a plurality of components 12-18, 810, 910 as described above that can be fluidly interconnected by a fluid tube 30. These components include one or more inlets 20 for receiving respective ends of the fluid tube 30, and the fluid tube ends can be sealed around the inlets by releasable couplings 100, 105, 300 as described above. The couplings have a releasable clamping operation that can be actuated by a sliding operation of the collar elements 130, 230, 230', 330, 430 of the couplings along the ends of the fluid tube.

[0098] In some embodiments, the sliding operation is an operation substantially towards each component, and the clamping operation can be released by an operation away from the component.

[0099] In some embodiments, the plurality of components 12-18 are modular components that can be repositioned on a support 80, and the fluid tube 30 includes a plurality of fluid tubes 30 each having one of the couplings 100, 105, 300 at each end, which provide a substantially sealed fluid flow and fluid communication between the respective modular components in use.

[0100] In some embodiments, the sliding operation is only a linear motion or a substantially linear motion with a torsional motion of 120 degrees or less.

[0101] In some embodiments, the chromatography system is a chromatography system formed from a plurality of components.

[0102] In some embodiments, the chromatography system further includes a transducer as described above.

[0103] According to one embodiment, a chromatography system is provided that includes a plurality of fluid handling components that are fluidly interconnected by a fluid tube 30 to form a chromatography fluid flow path. The fluid handling components include one or more fluid ports having insertion openings extending from a component surface, and these fluid ports are for receiving respective ends of the fluid tube such that the fluid tube ends sealingly surround the insertion openings, and for receiving a releasable locking clamp for applying a radially locking force to the outer surface of the tube ends to lock the fluid tube ends to the insertion openings. The interconnecting portion preferably has leak prevention at an internal pressure of at least 10 bar, such as 15, 20, 25, or 30 bar.

[0104] The present invention should not be regarded as being limited by the above-described embodiments and can be modified within the scope of the appended claims as will be readily apparent to those skilled in the art.

Explanation of Reference Numerals

[0105] 1 Module 10 Coupling Assembly, Clamp 11 Chromatography System 12 Pump, Module, Component 13 Chromatography Column, Module, Component 14 Valve, Module, Component 15 pH Monitor, Module, Component 16 Conductivity Monitor, Module, Component 17 Mixer, Module, Component 18 UV Monitor, Module, Component 20 Connector Insertion Opening, Male Part 22 Extension, Sealing Ridge 24 Elastic Projection, Arm 25 Boss 27 Complementary Locking Pin 30 Tube, Fluid Tube, Tube End 51 Control Panel, Modular Component 52 pH Monitor, Modular Component 55 Conductivity Monitor, Modular Component 58 Column Valve Unit, Modular Component 68 Flow Limiter, Modular Component 69 Mixer Module, Modular Component 70 Mixer Valve, Modular Component 71 Air Trap Valve, Modular Component 72 Air Trap Vent, Modular Component 75 UV Absorption Monitor, Modular Component 80 Support Part 100 Removable Coupling, Coupling, Connector 105 Coupling 110 Collet, Cylindrical Inner Component 112 Central Bore 114 Collet Flange, Stop Part 116 Cylindrical Intermediate Part 118 Finger, Collet Finger, Elastically Deflectable Part 120 Distal End 130 Collar, Cylindrical Locking Collar, Collar Element 132 Internal Through Aperture 134 Collar Flange 136 Body, Collar Body, Annular Body 138 Step, Stop Part 140 Distal End 200 Release Tool 210 Forked End 230 Locking Plate, Collar Element, Collar 230´ Locking Collar, Collar Element 231 Locking Plate 232 Through Aperture 233 Spherical Mount 234 Protrusion 280 Insertion Port 281 Open End, End Section 282 Sealing Ridge 290 Insertion Port 291 Rear Edge 292 Sealing Ridge 295 Insertion Port 296 Rear Edge 297 Sealing Ridge 300 Coupling 310 Collet, Tube End, Cylindrical Inner Component 318 Finger 330 Collar, Locking Collar, Collar Element 334 Wing 340 Distal End 345 Bayonet Opening 350 Clamping Section 400 Chromatography Apparatus, Remaining System, Chromatography System 410 Collet, Cylindrical Inner Component, Support 418 Finger, Elastically Deflectable Portion 420 Front Panel with Aperture, Front Face 430 Collar, Collar Element 431 Tapered Portion, Circumferential Inclination 432 Retainer 433 Complementary Recess 500 Waste Container 501 Container 510 Fluid Inlet 520 Fluid Outlet, Port 526 Blank Plate 530 Display Screen 531 Fluid Port 541 Fluid Port 542 Fluid Port 550 Port 580 Dashed Short Line, Tube Interconnection 600 Controller 601 Dashed Long Line 700 First Column 710 Hydraulic Cylinder 800 Second Column 810 Modular Component, Component 811 Port 812 Fluid communication part 813 Coupling 820 Modular component 821 Port, open end 822 First fluid tube 823 Converter 830 Body 831 Flange 832 Through hole 833 Insertion port 910 Modular component, component 911 Port, threaded hole 912 Tube 913 Threaded connector 914 End flange 915 Threaded part, adapter 915´ Adapter 916 Grip part 920 Body 921 Threaded part 922 Through hole 923 Insertion port 925 Converter 930 Body 931 Threaded hole, threaded part 932 Through hole 933 Insertion port

Claims

1. A chromatography system (11) comprising a plurality of fluid handling components (12-18; 820) that are fluid-interconnected by fluid tubes (30; 822) to form a bioprocess fluid channel, wherein the plurality of fluid handling components each have one or more fluid ports, and at least one of the plurality of fluid handling components has at least one fluid port having a male part (20; 20'; 280; 290; 295), the male part being configured to protrude from the front of at least one fluid handling component, and the male part being connected to the corresponding part of the fluid tube (30; 822). A chromatography system (11) configured to receive the end of a male part, the male part having an open end having an expanded portion (22; 282) near the open end, the first end of the fluid tube configured to engage seamlessly with the expanded portion around the outer surface of the male part, the fluid tube (30; 822) configured to be coupled to the corresponding fluid port by applying a radial locking force to the outer surface of the first end of the fluid tube, thereby locking the first end of the fluid tube to the male part (20; 20'; 280; 290; 295).

2. The chromatography system (11) according to claim 1, wherein the interconnection can withstand at least 15 bar.

3. The chromatography system (11) according to claim 1 or 2, wherein the fluid tube is locked to the male part by a releaseable connector (100, 300).

4. The aforementioned releaseable connectors (100, 300) An internal component (110, 310, 410) for receiving the fluid tube (30; 822), the internal component (110, 310, 410) includes elastically deflectable portions (118, 318, 418) configured to bias the outer surface of the fluid tube (30) toward the respective male parts (20; 20'; 280; 290; 295), A locking component (130, 230, 230', 330, 430) applies a clamping force to the elastically deflectable portion (118, 318, 418), thereby applying a radial locking force to the outer surface of the first end of the fluid tube. A chromatography system (11) according to claim 3, comprising the above.

5. The chromatography system (11) according to claim 4, wherein the elastically deflectable portion (118) of the internal component (110) includes a plurality of circumferentially arranged fingers that can be deflected inward during use.

6. Chromatography system (11) according to claim 4, wherein the locking component comprises internal through-apertures (132, 232) for receiving the internal component, the internal through-apertures and the elastically deflectable portion have complementary surface configurations in the locked position of the releaseable connector, the locking component is attached to the internal component, and as a result, the locking component applies a clamping force to the elastically deflectable portion (118, 318, 418) that deflects inward, thereby applying a radial locking force to the outer surface of the first end of the fluid tube, and in the released position of the releaseable connector, the elastically deflectable portion elastically springs up outward, releasing the radial locking force on the outer surface of the first end of the fluid tube.

7. The chromatography system (11) according to claim 6, wherein the locking component includes at least one projection extending outward from the internal through-aperture, which is sized to allow the locking component to be manually operated between a locked position and an unlocked position.

8. The chromatography system (11) according to claim 4, wherein the clamping force is generated by the movement of the locking component along the inner component toward the fluid handling component.

9. The chromatography system (11) according to claim 1 or 2, wherein the outer diameter of the fluid tube (30; 822) is 3 to 10 mm.

10. The chromatography system (11) according to claim 1 or 2, wherein the static size of the inner diameter of the fluid tube (30; 822) is less than ±10% of the outer diameter of the male part (20; 20'; 280; 290; 295).

11. The chromatography system (11) according to claim 1 or 2, wherein the extension portion (22; 282) is a sealing ridge.

12. Chromatography system (11) according to claim 11, wherein the fluid tube (30) has an inner diameter of 3.2 mm and an outer diameter of 4.8 mm, the male parts (20; 20'; 280; 290; 295) have a base diameter of 3.25 mm, and the sealing ridge (22) has a diameter of 3.45 mm.

13. The chromatography system (11) according to claim 1 or 2, wherein the fluid tube (30) is formed from a rigid material.

14. The chromatography system (11) according to claim 13, wherein the rigid material is made of fluorinated etenpropene (FEP) plastic.

15. The chromatography system (11) 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 mixer valve, and a pump.

16. The chromatography system (11) according to claim 1 or 2, wherein the fluid port is configured as a non-threaded hole having a male part protruding from the front surface of at least one fluid handling component.

17. The chromatography system (11) according to claim 1 or 2, wherein the chromatography system is configured for use in a Good Manufacturing Practice (GMP) environment.

18. A chromatography column (13) comprising at least one male part (20) for connection to a chromatography system via a releasable connector, wherein at least one male part of the chromatography column is configured to protrude from the surface of the chromatography column, the male part is configured to receive a corresponding first end of a fluid tube (30, 822) such that the end of the fluid tube seals around the male part, and the fluid tube (30, 822) is configured to be coupled to a corresponding fluid port of the chromatography system by applying a radial locking force to the outer surface of the tube end to lock the first end of the fluid tube to the male part (20; 20'; 280; 290; 295).

19. The aforementioned releaseable connector is An internal component (110, 310, 410) for receiving the fluid tube, the internal component (110, 310, 410) includes an elastically deflectable portion (118, 318, 418) configured to bias the outer surface of the fluid tube toward the male part (20), A locking component (130, 230, 230', 330, 430) applies a clamping force to the elastically deflectable portion (118, 318, 418), thereby applying a radial locking force to the outer surface of the first end of the fluid tube. A chromatography column (13) according to claim 18, comprising the above.

20. The chromatography column (13) according to claim 19, wherein the elastically deflectable portion of the internal component includes a plurality of circumferentially arranged fingers that can be deflected inward during use.

21. The chromatographic column (13) according to claim 18, wherein the male part is provided with a sealing ridge.

22. The chromatographic column (13) according to claim 21, wherein the male part has a base diameter of 3.25 mm, or the sealing ridge has a diameter of 3.45 mm.

23. The chromatographic column (13) according to claim 20, wherein the male part is provided with an open end having an expanded portion (22, 282) near the open end, and the first end of the fluid tube is configured to seal-engage with the expanded portion surrounding the outer surface of the male part.

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