Chromatography system and couplings for it

Abstract

Chromatography column unit comprising at least one chromatography column (13) and at least one male part (20), wherein at least one male part (20) protrudes at one end of the chromatography column (13), wherein the outer surface of the male part (20) is designed in such a way that it receives a fluid hose (30) on an inner surface of the fluid hose, the male part has an open end for coupling with the fluid hose (30), and the chromatography column unit is arranged such that a clamping force applied against the fluid tube (30) forces the fluid tube (30) against the male part (20) to form a fluid-tight coupling.

Description

TECHNICAL AREA

[0001] The present invention relates to chromatography systems, such as liquid chromatography systems, in particular, but not exclusively, a versatile system in laboratory or “tabletop” format that allows convenient reconfiguration for different chromatographic methods and convenient automated use, and also relates to reconnectable fluid hose couplings for connecting hoses and the like belonging to such devices or systems. BACKGROUND

[0002] Reusable fluid hose couplings, meaning couplings that can be repeatedly removed and reattached while maintaining a fluid seal for flexible tubular lines such as garden hoses and plastic pipe installations, are well-known. However, their ease of connection and / or hygiene are questionable, especially when the same designs are used in chromatography systems, where hygienic couplings are required and where much higher fluid pressures, for example, 20 bar or more, are often present. Typical installation fittings used for chromatography systems have multiple components, including metal springs and O-rings, and therefore have dead ends or O-ring grooves where unwanted contaminants, such as pathogens, can accumulate during use. These dead ends and grooves are difficult to disinfect.Furthermore, the use of metal parts is problematic when attempting to disinfect such a coupling arrangement by gamma irradiation. Additionally, the use of screw threads or specialized tools is impractical when speed and ease of connection and disconnection are critical criteria.

[0003] A barbed hose coupling arrangement of the prior art is shown in US8662542, but this coupling requires tools for assembly and is not intended for quick release.

[0004] Liquid chromatography is a well-known method for separating mixtures of molecules, for example, proteins in liquid samples. The proteins are typically suspended in a fluid and passed through a chromatographic separation medium along with a buffer solution. The different sample molecules in the mixture move through the chromatographic medium at different speeds, leading to their separation. This separation can be completed by a fractionation step, in which the mobile phase can be directed into different containers, for example, through an outlet valve of the chromatography system.

[0005] Furthermore, with chromatography systems, especially benchtop experimental equipment, it is often necessary to clean the equipment, which includes connecting tubing, during use and then disassemble the tubing network to reassemble it in a different configuration for another experiment. Therefore, dedicated disinfection equipment is impractical, and rapid cleaning, disconnection, and reconnection are required. Such a device is disclosed in US 8821718, which is hereby incorporated by reference into the present text, wherein interchangeable modular components of a chromatography system can be connected to one another via external fluid lines, which would benefit from an improved means for such connection. BRIEF SUMMARY OF THE INVENTION

[0006] One object of embodiments of the invention is to provide a chromatography system, in particular a liquid chromatography system, comprising detachable fluid couplings that can be quickly reconnected without the need to screw on fluid lines or to require space around each fluid line to perform such actions. A further object of the present invention is to provide a chromatography system that has one or more of the following features: enhanced functionality, for example the ability to be used for both conventional batch and continuous chromatography; the ability to be used in a wider range of applications; no significantly larger overall dimensions or higher manufacturing costs; and ease of use.

[0007] A further objective of embodiments of the present invention is to provide a coupling that is easy to clean and has as few dead ends or other spaces as possible where contaminants can accumulate. A further objective of embodiments of the invention is to provide a coupling that can be connected and disconnected quickly and without the use of tools, if necessary.

[0008] According to one aspect of the invention, a chromatography system is provided in accordance with the claims set forth in the present text.

[0009] According to a further aspect of the invention, a detachable coupling as defined in further claims set forth in the present text is provided, wherein the coupling can be used as part of a coupling arrangement, for example in a chromatography system such as a benchtop chromatography system, in which modular components can be rearranged in a support frame, for example as is most suitable for a particular experimental setup, and in which the arranged modular components can be connected to each other by fluid hoses, wherein the hoses have opposite ends, each end comprising one of the coupling arrangements according to the invention for fluidically coupling respective modular components.

[0010] Further preferred aspects of the invention are described in the dependent claims set forth in the present text.

[0011] Further advantages and benefits of the present invention will become readily apparent to the person skilled in the art upon studying the following detailed description. DRAWINGS

[0012] The invention will now be described in more detail with reference to the attached drawings, wherein: Fig. 1 shows an exploded view of the coupling components; Fig. Figure 2 shows the coupling of Fig. 1 in a fluidically connected state on average; Fig. Figure 3 shows the same coupling in cross-section in a solvable state; Fig. Figure 4 shows a coupling arrangement in cross-section, which enables the coupling of Fig. 1 completely in a fluidically sealed state; Fig. Figure 5 shows a sectional view through the coupling arrangement of Fig. 4, but rearranged into a solvable state; Fig. Figures 6 a, b and c show a modification of the coupling arrangement above. Fig. Figures 7a, b, c and d show variations of a coupling arrangement; Fig. Figure 8 shows a chromatography system in which several coupling arrangements are used; Fig. Figure 9 shows a coupling release tool; Fig. 10, Fig. 11 and Fig. Figure 12 shows embodiments of the invention which include a bayonet connection; Fig. Figures 13 to 16 show one variant of components of a coupling; Fig. Figure 17 shows a pictorial representation of a chromatography system; Fig. Figure 18 shows a schematic representation of the in Fig. 17 chromatography systems shown; and Fig. 19, Fig. 20 and Fig. 21 show variations of the in the Fig. 17 and Fig. Chromatography system shown in 18. Fig. Figure 22 illustrates a first version of a state-of-the-art modular component equipped with four ports; Fig. Figure 23 illustrates a modular component equipped with four ports; Fig. 24a and Fig. Figure 24b shows cross-sectional views of two variants of a converter; Fig. Figure 25a shows a second version of a modular component of the prior art, which is equipped with three ports; Fig. Figure 25b shows a screw connection for the modular component of Fig. 25a. Fig. 26a and Fig. 26b shows cross-sectional views of adapters; Fig. Figure 27 shows an alternative converter; Fig. 28a and Fig. Figure 28b shows a cross-sectional view of a nozzle with a hose attached; Fig. 29a and Fig. Figure 29b shows cross-sectional views of alternative sealing bead configurations. Fig. Figures 30a-30c show cross-sectional views of one embodiment of the sealing configuration. DETAILED DESCRIPTION

[0013] Good Manufacturing Practice (GMP) establishes guidelines for bioprocessing procedures which, if followed, require cleanliness standards. Advantageously, these standards are more easily achieved with the proposed device, for example, if fluid paths in the system, at least in one embodiment, have a continuous flow path without significant stagnation sections, thus enabling complete cleaning without having to disconnect the fluid lines. Embodiments of the proposed system provide a small-scale hygienic chromatography system suitable for both GMP and non-GMP applications. The system's large usable flow and pressure ranges make it suitable for the production of technical batches and scalability studies, as well as for the small-scale production of GMP-quality material.The high accuracy and large flow range of the pumps enable precise gradient formation, covering a wide range of chromatography column sizes and delivering more reproducible results.

[0014] In various configurations, a modular design enables extended functionality for diverse applications. Interactive control software allows for real-time modifications and rapid detection of unexpected deviations. Its compact, tabletop design saves laboratory space. The system allows for in-situ column packing, meaning the ability to compress chromatography media within the column, or within each column when using two or more, while connected to the system, without the need to disconnect fluid lines before performing chromatographic procedures.

[0015] Fig. Figure 1 shows an exploded view of an embodiment of a detachable coupling 100 according to one embodiment. The coupling 100 comprises two parts: a cylindrical inner component in the form of a clamping piece 110 for receiving a fluid hose and a cylindrical locking slip-on sleeve 130 with an inner through-hole 132 for the sliding reception of the clamping piece 110. A fluid hose (not shown) extends in use along an axis T and within a central bore 112 within the clamping piece 110, the bore being sized to fit precisely around the hose. The clamping piece 110 has a clamping flange 114 formed on a cylindrical central section 116 and several reboundable and circumferentially arranged fingers 118 extending from the central section 116 to a distal end 120 of the clamping piece 110.

[0016] The clamping element 110 engages in a sliding fit within a through-opening 132 of the slip-on sleeve 130, allowing the slip-on sleeve 130 to be mounted over and around the fingers 118 and the central section 116 of the clamping element 110. The slip-on sleeve 130 can be moved along the fingers 118 and the central section 116 to selectively deflect or release the fingers 118, with the deflection causing the hose to grip, as described in more detail below. Movement of the slip-on sleeve 130 is assisted by a slip-on sleeve flange 134 at a distal end of the slip-on sleeve, which extends from a body 136 of the slip-on sleeve and can be pulled or pushed by hand. The slip-on sleeve has a distal end 140. The fingers 118 widen outwards towards the distal end 120 of the clamping piece.This means that if the opening 132 has a generally constant inner diameter, moving the slip-on sleeve 130 in one direction from the clamping flange 114 to the distal end 120 of the clamping piece 110 causes the inner diameter of the opening 132 to abut outer surfaces of the fingers 118 and force them inwards to create a hose clamping effect.

[0017] Fig. Figure 2 shows the coupling of 100 from Fig. Figure 1 shows the hose clamp in a section. Here, the distal end 140 of the slip-on sleeve 130 and the distal end 120 of the clamping piece 110 were brought into alignment by manually repositioning the slip-on sleeve flange 134 relative to the clamping piece flange 114. In this position, the inner surface of the opening 132 and an outer surface of the fingers form complementary surfaces that abut each other, thereby causing the fingers 118 to deflect inwards in the direction of axis T. This deflection forces an adjacent section of hose (not shown) inwards inside the clamping piece, for example, to compress, squeeze, or clamp the hose. The coupling is released by moving the slip-on sleeve and its flange in the direction of arrow R.

[0018] Fig. Figure 3 shows the coupling 100 again in section, but arranged in a hose release position. Here, the slip-on sleeve 130 has been shifted towards R towards a distal end of the clamping piece, but is prevented from sliding off the clamping piece by the clamping piece flange 114 and / or a step 138 in both the opening 132 and the bore 112, one or both of which form an end stop. In this position, the fingers 118 are relaxed and spring outwards to eliminate or reduce any pushing, compressing, or clamping action on the hose. The in Fig. The position shown in Figure 3 is achieved by moving the slip-on sleeve 130 and its flange 134 in the direction of arrow R ( Fig. 2) relative to the clamping piece 110.

[0019] Fig. Figure 4 shows a section through a coupling arrangement 10 comprising a male part, in this case in the form of a connector stub 20, wherein the male part has a widening, for example a sealing bead, a raised section, or a barb, 22, which can be positioned inside a fluid hose 30 beyond an open end of the hose 30 as a sliding fit. The hose 30 is held on the stub 20 by compressing the hose 30. The coupling 100 surrounds the hose 30 and ensures that the hose can be releasably compressed onto the stub 20 in the manner described above, especially with regard to Fig. Figure 2 describes how the coupling arrangement 10 is designed to detachably hold the hose 30 on the nozzle 20. This figure clearly shows that the fingers 118 compress the hose 30 behind the widening 22, thereby assisting in holding the hose on the nozzle and effectively locking it in place. The coupling arrangement 10 can supply fluid to or withdraw fluid from the module 1. In this embodiment, the module 1 is a chromatography system requiring a detachable fluid coupling that is easy to clean and in which contaminants cannot accumulate. In another embodiment, the fluid pressure at the module 1 could be measured or adjusted via the fluid hose 30, requiring only one fluidic connection. Therefore, fluid flow within the hose 30 is not essential.

[0020] Fig. 5 shows the same cut as in Fig. 4. However, in this view, the coupling arrangement 10 is located in the Fig. 3 release positions shown. During use, the [part] jams according to Fig. 4. The positioned coupling 100 secures the hose 30 to the nozzle 20, and when the slip-on sleeve flange 134 is pulled in the direction of arrows R, the compression force acting on the hose is released. This release allows the slip-on sleeve flange 134, the slip-on sleeve 130, and the clamping piece 110 to slide along the hose in the direction of arrow R. Fig. 5. As described above, the clamping piece has one or more stops (clamping piece flange 114 and / or step 138) that prevent the slip-on sleeve from being pulled off the clamping piece, thus allowing the clamping piece to be retracted with the flange 134. In this retracted position, the hose 30 can be easily pulled off the fitting 20. Connecting or reconnecting the hose 30 to the fitting is carried out in the reverse order of the steps above. This means that the hose 30 is pushed over the fitting 20, the clamping flange 114 is pushed in the direction opposite to the arrow R and, as soon as the distal end 120 of the clamping piece is firmly in contact with the module 1, the slip-on sleeve flange 134 is pushed into its final position to deflect the fingers 118 against an outer surface of the hose and thus clamp the hose onto the fitting 20.

[0021] The coupling 100 is preferably formed from only two molded plastic parts. As can be seen from the drawings, the outer surface of the slip-on sleeve 130 is smooth; that is, the slip-on sleeve flange 134 is a continuous annular structure projecting from the annular body 136, and the slip-on sleeve flange and an outer surface of the slip-on sleeve on which the slip-on sleeve flange is formed have a continuously curved profile without sudden changes in direction. This reduces the risk of contamination of the coupling during use, and the coupling can be easily cleaned. Additionally, the user can hold each side of the slip-on sleeve flange with two fingers, one on each side of the slip-on sleeve body 136, and pull it in the direction of arrow R ( Fig. 5) At the same time, the user can exert a counterforce to this tensile force with his thumb by supporting his thumb on the clamping flange 114, which is opposite the two fingers.

[0022] Care must be taken to ensure that the hose 30 is essentially fully seated on the fitting 20. For this purpose, the clamp 110 and the slip-on sleeve 130 can be made of transparent plastic. Furthermore, the fitting can be a different color than the hose to provide a visual indicator if the hose does not completely cover the fitting, as some of the fitting's color will be visible. A variation of the one described in the Fig. The embodiment shown in 1 to 5 is in the Fig. 6a, Fig. 6b and Fig. 6c shown, where: Fig. Figure 6a shows a modified nozzle 20' having rebound projections 24, for example rebound arms, extending outwards; Fig. Figure 6b shows a hose 30 that is fully pushed into its final position on the fitting 20'. When the hose is fully seated in its final position on the fitting, the arms 24 move inwards. Only then can the clamping fingers 118 be pushed over the hose, as Fig. Figure 6c shows that the slip-on sleeve 130 is ready to be pushed over the fingers to clamp the hose as described above. If the nozzle 20' is not fully inserted into the hose 30, the clamping piece 110 cannot pass the arms 24.

[0023] Fig. 7a, Fig. 7b and Fig. Figure 7c shows a cross-sectional modification 105 of the coupling arrangement. In this embodiment, the slip-on sleeve 130 was Fig. 1 is replaced by a locking plate 230, which has several through-holes 232, each of which receives a clamping piece 110. The locking plate includes projections 234 that replace the flange 134 shown in the previous figures. The centers of the through-holes are aligned with the centers of several male parts projecting from a module 1, so that multiple connections can be made in a single operation.

[0024] In Fig. Figure 7a shows how the locking plate 230 is brought to the module 1, with the clamping pieces 110 being inserted into the through-openings 232 and the hoses 30 inside the clamping pieces 110 already pushed over the male parts, such as the nozzles 20. Fig. Figure 7b shows the same coupling arrangement as in Fig. 7a is shown, except that the locking plate 230 and the clamping pieces 110 are pushed in the direction of the arrow R to a front side of the module 1, such that the clamping pieces lie over the nozzle 20 and the ends of the hoses 30. Fig. Figure 7c shows another view of the coupling arrangement of Fig. 7a, where the locking plate 230 is now extended even further in the direction of arrow R in Fig. 7b has been moved. In Fig. 7c the locking plate clamps the fingers 118 of the clamping pieces 110 around the hoses 30 in the manner described above.

[0025] Fig. Figure 7d shows a further modification of the coupling arrangement, wherein locking slip-on sleeves 230' are each mounted on a locking plate 231 by means of a flexible mounting bracket, in this case a spherical mounting bracket 233, which allows each slip-on sleeve 230' to rotate about a center point of the mounting bracket 233, thereby providing tolerance for a certain degree of misalignment or dimensional errors in the male parts of the module. The locking plate could, of course, also be made of a flexible material to provide a similar degree of tolerance. Fig. Although Figure 7a illustrates two couplings, other linear or two-dimensional arrangements of couplings could also be used, corresponding to a configuration of the male parts 20. For example, a grouping of 4 couplings could be used, corresponding to the one shown in Figure 7a. Fig. The square arrangement of male parts shown in Figure 8 fits. The couplings do not need to lie in the same plane. The couplings do not need to have generally parallel axes if a certain degree of flexibility is given, such as with reference to Fig. 7d described. To simplify handling, the hoses 30 can have a single coupling 100 at one end and can be joined together at an opposite end in a multiple coupling 105 in the manner of a distributor.

[0026] Fig. Figure 8 shows a chromatography system 11 comprising a support frame 80 which includes conventional modular fluid processing components in the form of interchangeable modules, such as: 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.

[0027] Other modules can also be used. The modules can be connected in any suitable way using a fluid hose 30, which has couplings 100 at each end, of which only one is shown for clarity. The couplings 100 could be replaced by several hoses and couplings 105 of the type shown in the Fig. The couplings shown in 7a, b, c or d can be replaced to speed up connecting and disconnecting them. For simplicity, each of the valves 14 has the same male part design, meaning that the same design of the locking plate 230 could be used for each valve.

[0028] Fig. Figure 9 shows a release tool 200 having a forked end 210 suitable for engaging each side of a flange 134 or projection 234 in order to pull or push it outwards from a module 1 or 12 to 18 when there is not enough space to pull it with the fingers.

[0029] An alternative embodiment of the coupling 300 is described in the Fig. 10, Fig. 11 and Fig. 12 shown. In this embodiment, a locking slip-on sleeve 330 surrounds ( Fig. 10) a cylindrical inner component in the form of a clamping piece 310, which has fingers 318 of the type described above, which in turn surround the fluid hose 30. The coupling 300 can be actuated in largely the same way as the couplings 100 and 105 described above. That is, to create a fluid-tight coupling, the hose 30 is pushed over a male part 20 projecting from a module 1, then the clamping piece is pushed over the hose until its distal end 340 abuts or abuts the module 1, and then the slip-on sleeve is moved towards the module to initiate the clamping of the fingers 318 of the clamping piece 310. This position is in Fig. 11 shown.

[0030] It can be seen that the distal end 340 comprises a pair of bayonet-like openings for receiving complementary locking pins 27, which are supported by a shoulder 25 extending from the module 1 around the male part 20. In this embodiment, the final locking position of the slip-on sleeve 330 is only reached when it is inserted further towards the module 1 into the Fig. The final locking position shown in Figure 12 was reached by moving a distal end 340 of the slip-on sleeve linearly and rotationally over and along the shoulder 25, such that the bayonet openings 345 engage the pins 27. This further clamps the fingers 318 onto the hose 30, and the slip-on sleeve 330 (and the coupling 300) is attached to the module 1 and held in position by the pins 27.

[0031] The in the Fig. 10, Fig. 11 and Fig. The anchoring shown in Figure 12 is based on the essentially linear locking movement of a locking slip-on sleeve mentioned above; that is, a small rotational movement is required to secure the slip-on sleeve 330 in its position and apply a clamping force. This rotational movement can be facilitated by using wings 334 extending from the slip-on sleeve 330 instead of the flange mentioned above.

[0032] Fig. Figures 13 to 16 show in detail sections of another clamping piece 410 and another slip-on sleeve 430 that could be used in couplings 100, 105, or 300. In this variant, the clamping of the fingers, in this case the fingers 418, can be achieved by a rotational movement of the slip-on sleeve 430 around the clamping piece 410, either as an alternative to the sliding movement of the slip-on sleeve 430, as described above, or in addition to this sliding movement.

[0033] More precisely, an inner surface of the slip-on sleeve 430 has locking projections 432 that act on tapered sections 431 of the fingers 418 when the slip-on sleeve is rotated relative to the fingers. The circumferentially extending ramps 431 each act as a cam and, during use, are pressed inwards towards the hose 30 by their respective locking projections when the slip-on sleeve is rotated, in this example in the direction of arrow R. This causes the fingers 418 to be pressed around the hose 30 by the Fig. 13 and Fig. 14 shown position in the Fig. 15 and Fig. The clamping position shown in Figure 16, in which the detent projections come to rest in complementary recesses 433, is compressed. The rotary movement used for locking is 120 degrees or less and is preferably about 90 degrees or less when three or more circumferentially arranged fingers are used.

[0034] Experiments have shown that the couplings 100, 105, and 300 described above, for use with a hose having an outer diameter of approximately 3 to 10 mm, are capable of sealing the hose at the coupling at internal fluid pressures of at least 10 bar or higher, such as 15, 20, 25, or 30 bar or more, as will be discussed in more detail later. Embodiments of the couplings have been successfully verified by extensive leak tests at 30 bar. These couplings provide a fluid-tight connection of a hose around a male part, which can be connected and disconnected by an essentially purely linear movement of the locking slip-on sleeve 130 or the locking plate 230, without the need for twisting or screwing any parts. In this way, the couplings can be positioned closer together than conventional screw couplings, since no space is required for rotational movements."Essentially linear" in the context of this text means a rotational movement of 120 degrees or less, for example 90 degrees or less, less than 45 degrees, less than 30 degrees, less than 15 degrees, less than 5 degrees or almost no rotation at all.

[0035] Various slip-on sleeve elements in different embodiments have been described, all of which have the same functionality in the detachable connection, namely the described features: locking slip-on sleeve 130, locking plate 230, locking slip-on sleeve 230', locking slip-on sleeve 330, and slip-on sleeve 430. One of these is non-cylindrical (locking plate 230), and the others are cylindrical. The slip-on sleeve element comprises at least one projection, for example, a slip-on sleeve flange 134 or wing 334, which extends outwards from the opening and is such that the slip-on sleeve can be moved manually between the first and second positions.

[0036] The inner component was developed in conjunction with the Fig. 1-7 is described as a clamping piece 110, which may be provided with an end stop section, such as a clamping piece flange 114 and / or a step 138. The clamping piece flange 114 extends outwards and is sized to facilitate manual movement of the coupling. Furthermore, "spring-loaded deflectable section" is a term used to describe the deflectable fingers 118, which are connected to the Fig. 1-7 were described, and fingers 418, which are associated with the Fig. 13-16 were described, is equivalent.

[0037] Fig. Figure 17 shows a chromatography apparatus 400 according to one aspect of the invention. The apparatus comprises, for example, individual modular components 51 to 75, as listed below, at least some of which can be detached from an opening-provided front plate 420 of a support frame 410 of the apparatus 400 and mounted thereon in a single, generally vertical plane, such that the fluid connections required between the modular components can be established solely on the front surface 420. In practice, the detachable modular components have no more than two standard sizes, which can be repositioned on the plate 420 as needed to meet the requirements of a different process.Each modular component has a communication link via a serial bus and a power connection, so its physical position is irrelevant for a controller located, for example, in the support frame 410 or at a spatially separate location. This allows the modular components to be considered modular and therefore repositionable and / or interchangeable.

[0038] The in Fig. Chromatography apparatus 17 shown has the following modular components: 51 Control panel 52 pH monitor 53 Outlet valve 1-3, port 1 can be used for waste 54 Exhaust valve 4-6 55 Conductivity Monitor 56 Exhaust valve 7-9 57 Conductivity monitor in front of the column 58 Column valve unit, which includes a pressure sensor before and after the column 59 bottles for pump rinsing solution 60 Inlet valve A1-A3 61 Inlet valve A4-A6 62 Inlet valve B1-B3 63 Inlet valve B4-B6 64 Fixed rubber feet 65 Adjustable Feet 66 System pump A 67 System pump B 68 Flow restrictor, which includes a system pressure switch 69 modular mixer components 70 Mixing valve 71 Air trap valve that includes an air sensor 72 Air trap 73 ON / OFF switches 74 holders for line filters (typical filter capsule shown) 75 UV monitor

[0039] Modular components can be omitted or repositioned, as explained above. It is clear that some modular components can be replaced by other modular components, or that the empty space created by an omitted modular component can be covered with a cover plate (see, for example, Figure 76 in...). Fig. 20). If necessary, more than one of the modular components with the same number can be used.

[0040] Fluidic connections between the fluid-processing modular components of the device, that is, all the modular components listed above except modular components 51, 64, 65 and 73, and external modular components, for example sample input reservoirs, buffer fluid reservoirs, chromatography columns and fraction collection equipment, all of which are in Fig. 17 not shown, are formed via fluid lines, in this case in the form of plastic hoses, which can be easily coupled to and uncoupled from corresponding ports of the fluid-processing modular components in any desired configuration, for example using a coupling described above.

[0041] Fig. Figure 18 shows a possible liquid connection configuration between the modular main components of the chromatography apparatus 400, which in this case are connected to two chromatography columns 700 and 800, although the apparatus allows any practical connection between modular components and additional parts, such as multiple columns and liquid reservoirs. Reconfigurable liquid connections are indicated by dash-dash lines 580.

[0042] The core component of the device 400 is the column valve unit 58, which in this case has a design as disclosed in pending application GB 1715399.0, filed on September 22, 2017, and hereby incorporated into the present text by reference. The valve unit 58 allows multiple switching of the flow direction to permit flow in one or both columns 700 / 800 in either direction (upward or downward in the drawing). The user can select between upward and downward flow or can choose to bypass one or both columns. The flow can be directed into the waste section or to the next component in the flow path.The columns can also be connected in series, each column comprising a chamber with variable volume for receiving chromatographic separation media and an adapter that is movable to increase or decrease each volume, and wherein the column valve unit 58 is in fluid communication with each adapter and can be selectively actuated to move each adapter independently or together by means of fluid pressure changes in order to change each volume and in use to bring about compression or compression relief of the media within each column volume.

[0043] The column valve unit 58 includes pressure sensors upstream and downstream of the column and further includes a fluid inlet 510 configured to receive an input fluid. The input fluid can, for example, be 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 provided output fluid can typically be the resulting fluid after the received input fluid has passed through one or more columns of the chromatography apparatus 400. The valve unit 100 further 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.The valve unit 58 further comprises a coupling valve arrangement which is configured to direct fluid between a selection from the fluid inlet 510, the fluid outlet 520, the first pair of fluid ports 531 and 532 and the second pair of fluid ports 541 and 542 in response to one or more control signals.

[0044] Furthermore, 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 compress the contents of the columns, a process also known as column packing. This packing process can be automated. It has been found that column diameters between approximately 25 and 250 mm can be packed with such a system. The columns can be pre-packed, but then purged and reconsolidated with the aid of pressure sensors in the valve unit 58, which measure the back pressure resulting from the pressure within the columns, and according to known protocols, such as those described in W02007045491, the disclosure of which is hereby incorporated into the present text by reference.

[0045] The remaining System 400 includes: Inlet valve groups A and B, 60, 61, 62 and 63, suitable for the provision of selectable liquids, including sample-containing liquids, buffer solutions and cleaning fluids; The inlet valves supply two system pumps, each featuring a pair of pistons and associated one-way valves, delivering a variable flow rate of 0-600 ml per minute (max. 1200 ml / min) with high volume and high flow resolution, thus ensuring accurate flow rates. This accuracy allows for good repeatability of results across a wide range of column diameters. The pumps supply a flow restrictor 68 in series, which comprises a system pressure monitor, a mixing valve 70, and a mixing module 69, before the pumped liquid is diverted to the column valve unit 58; entrained air can escape via an air trap valve 71 and a vent 72, the vent also having an air outlet from columns 700 and 800. The air trap can be constructed according to pending application GB1713993, filed on April 5, 2017, the disclosure of which is hereby incorporated into the present text by reference; Once liquids reach the column valve unit 58, they can be routed according to the arrangement described in pending application GB 1715399.0, filed on 22 September 2017, thereby enabling numerous chromatography modes to be carried out: from simple batch processes in which a straightforward chromatographic separation process is carried out using only a single column, to processes more similar to commercial processes on a larger scale in which two or more columns can be used, with one being prepared for use while the other is used for separation; The output from the one or more chromatography columns is routed through port 520 to a conductivity monitor 55, a UV light absorption monitor 75, and a pH monitor 52. From there, depending on the signals from the three monitors, the output is directed to a suitable storage container, thereby collecting separated fractions in a suitable container 501. Discharges from the column washing process can be collected in a waste container 500. the dash-dot-dash lines 610 in Fig. Component 18 constitutes a system bus that transports signals and power to and from the aforementioned modular components to and from a controller 600. It is understood that control and monitoring signals can be transmitted wirelessly according to known protocols, thus eliminating the need for a communication bus. The chromatography system 400 also includes a display screen 530. Software running on the controller displays several symbols on the screen 530 and allows the user to manipulate the symbols on the screen by dragging and dropping them to create a row of symbols representing a user-defined chromatography control procedure, thereby simplifying operation. The user-defined chromatography control procedure comprises a continuous chromatography process in which the two or more chromatography columns are used by selective valve opening in the column valve unit 58.

[0046] Fig. 19, Fig. 20 and Fig. Figures 21 show the system, which is connected to hoses for various configurations, with only some of the components shown in these figures. Fig. The 17 illustrated modular components remain in place and the openings left by the removed modular components are covered with cover plates 526, which are screwed over the opening to prevent accidental ingress of liquid into the support frame 410.

[0047] Fig. Figure 19 shows a System 400' with a modular component configuration suitable for controlled environments where systems are custom-built in a production plant. The system is delivered assembled, calibrated, and performance-tested and is suitable for operation in GMP environments. Fig. Figure 20 shows a System 400'' from which some modular components have been removed, and Fig. Figure 21 shows a System 400''' with more modular components, similar to Fig. 20, where typical hose connections 580 are shown.

[0048] In operation, modular components are easily removed or added to the system, and installation is completed with a single-click activation in the software, which can recognize each modular component. The software enables comprehensive operational control, adaptable to specific requirements, as well as preventive maintenance. In addition to the modular components described above, modular input / output communication components can be used to connect to analog and / or digital external sensors or other equipment, such as automatic fraction collection devices. The wide flow rate and pressure ranges allow for more than 40-fold scaling of columns with inner diameters ranging from 25 to 250 mm. Thanks to this broad range, the device is suitable for bridging the transition to GMP environments.

[0049] The packing (and repacking) of chromatography columns using the system described above can be fully controlled by the Controller 600, initiated via the Control Panel 51. The Controller 600 can display the Screen 530 ( Fig. 18) to support the visualization of the packing process and its progress. The control software includes an accessible column packing log. Column packing logs can therefore be defined, created, and updated via the software for traceability and quality assurance purposes. Furthermore, the log can be used to monitor column performance and provide statistics on usage, separation efficiency, and packing intervals.

[0050] The display screen can provide process visualization, giving the operator a quick overview of system function, progress through operating steps, and alarms, displaying only the required amount of information at each step. The process visualization always shows the active flow path to minimize operator error. Changes can be made in real time by selecting the relevant process on the visualization screen, for example, by selecting or dragging icons. Graphical user interfaces are provided for control of certain sections, such as the column valve unit 58.

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

[0052] The system described and illustrated above is designed for hygienic environments. For example, the support frame 410 is flat or curved and, except at the edges of the end faces, has no joints, gaps, or significant cavities, making it easy to wipe clean and reducing the risk of dust and liquid inclusions. The pH monitor 52 has in-line calibration, and the column valve unit 58 allows for in-process column packing, enabling a closed flow path through the various operations. This means that no interruptions in the fluid path are necessary during one or more chromatography column packing / regeneration stages and throughout the entire separation operation.

[0053] Fig. Figure 22 illustrates a prior art modular component 810 equipped with four ports 811, each designed to be connected to a prior art fluidic connection 812. Due to the size of the coupling 813 required to attach the fluidic connection 812 to the port 811, the couplings must be arranged at different heights. This is a bulky solution that also requires space around the modular component to facilitate the assembly / disassembly of the fluidic connections 812 at the respective port 811.

[0054] Fig. Figure 23 illustrates a modular component 820 with four ports 821, each having a hose 822 connected at one end to a detachable coupling 100 (as in connection with the Fig. (described in sections 1-6) is equipped with a hose that is connected to each respective port 821. A second end of one of the hoses is connected to a converter 823 with a further detachable coupling 100 to allow the attachment of a fluidic connection that is not suitable for direct connection to port 821. The converter 823 is used in conjunction with the Fig. 24a and Fig. 24b is described in more detail. The result of using detachable couplings when connecting the fluidic connection to the modular component is a less bulky design, as the ports can be positioned closer together. Furthermore, the detachable coupling is easier to disinfect, assemble / disassemble, and replace if necessary.

[0055] Fig. Figure 24a shows a cross-sectional view of a converter 823, which has a body 830, a flange 831, a through-hole 832, and a nozzle 833 integrally formed with the body 830. In this embodiment, the converter 823 is manufactured from a single piece of material, such as plastic, metal, etc. In this example, the flange 831 is designed for use in a Tri-Clamp (TC) coupling, and the nozzle 833 is designed to accommodate a hose fitted with a resealable coupling 100 (not shown).

[0056] Fig. Figure 24b shows a cross-sectional view of an alternative converter 823', which is related to the one used in conjunction with Fig. The converter described in 24a is similar except for one exception.

[0057] The converter 823' comprises two parts, wherein the body 830 and the flange 831 are made from a single piece of material, for example plastic, and the nozzle 833' is made from a different material, for example metal.

[0058] Fig. Figure 25a shows a modular component 910 of the prior art with three threaded holes as ports 911. Hoses 912 are attached to the respective ports 911, each of which is equipped with a screw connector 913. Fig. Figure 25b shows a screw connector 913 comprising an end flange 914, which is attached to a first end of the hose 912 and is designed to provide a seal when positioned in the threaded hole 911, and which includes a body having a threaded section 915 and a handle section 916 designed to be used when the screw connector 913 is attached to the modular component 910. Due to the space required for attaching the screw connector 913 to the modular component 910, this design is more efficient compared to using a detachable coupling, as shown in Figure 25b. Fig. 23 shown, quite bulky.

[0059] When a fluid hose is connected to a port using a screw connector, tightening the connector to a threaded hole causes the hose to twist unintentionally (approximately 2-3 turns). This is particularly problematic when connecting short fluid hoses, for example, 10-30 cm long, which are prone to kinking. Furthermore, a separate O-ring may be required to achieve the desired pressure and fluid seal.

[0060] To take advantage of the benefits of the resealable coupling 100, adapters can be inserted into the threaded holes of the modular component 910.

[0061] Fig. Figure 26a shows a cross-sectional view of an adapter 915 comprising a body 920, a threaded section 921, a through-hole 922, and a nozzle 923 integrally formed with the body 930. In this embodiment, the adapter 920 is manufactured from a single piece of material, such as plastic, metal, etc. The threaded section 921 is designed to be inserted into the threaded hole of a modular component, with the body 920 serving as a handle section, and the nozzle 923 is designed to accommodate a hose fitted with a resealable coupling 100 (not shown).

[0062] Fig. Figure 26b shows a cross-sectional view of an alternative adapter 915', which is used in conjunction with Fig. The adapter described in 26a is similar except for one exception. The converter 915' comprises two parts, wherein the body 920 and the threaded section 921 are made from a single piece of material, for example plastic, and the nozzle 923' is made from a different material, for example metal.

[0063] Fig. Figure 27 shows a cross-sectional view of an alternative converter 925, which has a body 930, a section with a threaded hole 931, a through hole 932, and a nozzle 933 integrally formed with the body 930. In this embodiment, the converter 925 is manufactured from a single piece of material, such as plastic, metal, etc. The threaded hole 931 is designed in this example to receive a screw connector, as in conjunction with Fig. 25b described. The fitting 933 is designed to accommodate a hose equipped with a resealable coupling 100 (not shown). It should be noted that the fitting can be manufactured separately from a different material than the body and the section with the threaded hole.

[0064] One advantage of the detachable coupling arrangement 10 is that it has no thread, which means it can be disinfected and requires less maintenance. A simple widening 22 (that is, a sealing bead, barb, or protrusion) on a spigot 20 extending from the front of a panel is much easier to disinfect than a conventional screw connector with very limited access to the threaded hole, as in the Fig. 25a and Fig. 25b illustrates.

[0065] Another advantage is that, unlike what is associated with Fig. As illustrated in Figure 22, no flange is required, and it is therefore possible to manually cut the hose to size before connecting it using the detachable coupling 100. Because the contact size of the hose's inner diameter is in the same range as the outer diameter of the sealing bead 22 on the fitting 20, it is easy to replace a hose if necessary, with the contact size of the hose's inner diameter preferably being less than ±10% of the fitting's outer diameter.

[0066] Another advantage is that neither an O-ring nor a gasket is required, resulting in less maintenance and a more robust solution compared to state-of-the-art solutions. The seal is achieved by bringing the hose material into direct sealing contact with the sealing bead 22. This, however, requires the hose to possess a certain degree of flexibility and deformation. The resealable coupling allows for a minimal number of connections between different materials and parts, improving the possibility of disinfecting the fluidic connection when necessary. A further advantage is the ease of installation of the resealable coupling assembly, for example, with a one-handed snap-fit ​​connection for low-pressure applications.

[0067] Converter connections, as in connection with the Fig. 24a, Fig. 24b and Fig. The adapters described in section 27 can be used to make connections to other ports, for example, TC ports. Threaded adapters, as described in connection with the Fig. 26a and Fig. 26b described, can be used to repair old equipment with threaded holes (see Fig. 25a) to upgrade to connections suitable for the use of detachable coupling when attaching hoses.

[0068] As described above, nozzles 20 can be positioned closer together than in the case of screw or TC connections. This would allow for shorter internal flow paths in the modular components, such as valves, and the use of detachable coupling arrangements can reduce the size of fluidic components with internal flow paths. This, in turn, affects the overall chromatography system, which requires a smaller footprint relative to its flow capacity.

[0069] Fig. 28a and Fig. Figure 28b shows a cross-sectional view of a fitting with and without a hose attached. It is important to emphasize that the dimensions of the hose (inner diameter DI) and the fitting (outer diameter D2) are crucial for achieving a proper seal and preventing the formation of pockets between the hose 30 and the open end 281 of the fitting 280, as biological material residues can accumulate in such pockets. The elastic modulus of the hose provides the necessary deformation to allow it to be pushed over the sealing bead 282, which is located in close proximity to the open end 821. The shape of the sealing bead is important for achieving the desired functionality with the following key aspects: - Disinfectability, as the direct sealing creates a pocket-free design that avoids pockets in which biological material could accumulate, - an upper pressure limit to keep the hose attached to the fitting.

[0070] As mentioned above, other important parameters are: - the elastic modulus of the fluid hoses - the inner diameter of the fluid hoses and the outer diameter of the fitting.

[0071] In some embodiments, the sealing bead has a rounded design with a radius R and a height h from the center of the fitting. The radius extends to the open end of the fitting and forms an angle that allows the hose to slide over the sealing bead onto the fitting with a force sufficiently low for a normal operator, without the hose bending under pressure as it slides over the sealing bead. The rounded section may begin at a radius similar to the inner radius of the hose, and the height is determined by the hose's modulus of elasticity and the pressure limits for the connection.

[0072] In the Fig. 28a, Fig. 29a and Fig. Figure 29b shows other forms of the sealing bead. Arrows F1-F3 in Fig. Figure 28b schematically illustrates the forces acting when sealing and locking the hose end 30 to the fitting 280. In one embodiment, such as the connector 100 shown above, the clamping piece is designed to exert the hose clamping pressure on the fitting side of the center point of the sealing bead, as shown by F2 in Fig. 28b indicated. In one embodiment, the fluid sealing force FI between the hose and the front end of the sealing bead near the open end of the fitting is achieved essentially by the elasticity of the hose. The seal is achieved without pockets if the sealing bead is positioned in the immediate vicinity of the open end, that is, if there is no flat section at the open end of the fitting.

[0073] By applying the locking pressure of essentially F2 behind the center of the sealing bead, essentially the entire available clamping force is used to hold the hose on the sealing bead. The pressure limit depends on the height of the sealing bead, the clamping force, the inclination of the sealing bead, and the coefficient of friction between the hose and the fitting. However, all surfaces should be as smooth as possible to improve disinfectability. In alternative embodiments, part of the available clamping force can be applied to the end section 281 of the fitting 280 to further secure the seal between the fitting and the hose. In the disclosed embodiment 100, the fingers 118 of the clamping element 110 are designed such that they apply a clamping force only in the vicinity of the sealing bead 282, but leave some space to the hose at the lower end of the fitting in the clamped position.In this way, the clamping force is less dependent on dimensional deviations in the various components (fitting, hose, clamping piece, and slip-on sleeve), since the clamping force also includes a spring load on 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 sliding the slip-on sleeve 130 over the clamping piece 110 into the hose clamping position, thereby displacing the fingers 118 so that they bear against the hose. The force required to lock the clamp by sliding the slip-on sleeve 130 should be adjusted to be a reasonable force for the operator, while simultaneously avoiding the need for an excessively high release force to loosen the clamp.

[0074] Fig. Figure 28b shows a situation in which the fluid hose 30 is mounted over the sealing bead 282 and the length of the nozzle 280, and schematically illustrates the locking pressure on the hose exerted on the nozzle side of the center point of the sealing bead. The fluid sealing force FI between the hose and the front end of the sealing bead near the open end of the nozzle is achieved essentially by the elasticity of the hose. The seal is achieved without pockets when the sealing bead is positioned in close proximity to the open end, that is, when there is no flat section at the open end of the nozzle.

[0075] Applying the locking pressure F2 behind the center of the sealing bead essentially utilizes the entire available clamping force to hold the hose on the sealing bead. The pressure limit depends on the height of the sealing bead, the clamping force, the angle of the sealing bead, and the coefficient of friction between the hose and the fitting. However, all surfaces should be as smooth as possible to improve disinfection. Furthermore, sharp corners can unintentionally create pockets where biological material could become trapped. Therefore, sharp corners should be avoided to improve disinfection.

[0076] It may be desirable to apply an additional sealing force F3 at the base of the fitting (the rear side opposite the open end) to increase the sealing pressure limit. In one embodiment, at least 80% of the clamping force is applied behind the center point of the sealing bead (designated F2). In another embodiment, a contact pressure or a lower pressure is applied at or near the base of the fitting to stabilize the connection.

[0077] The clamping force can be provided using a detachable coupling, as described above. Other types of couplings, such as hose clamps or eccentric couplings, are also possible, provided they provide a suitable amount of clamping force, as described above. The length of the chosen connector must be selected based on the length of the nozzle to avoid leverage.

[0078] Fig. 29a and Fig. Figure 29b shows cross-sectional views of alternative sealing bead configurations. Fig. Figure 29a shows a fitting 290 with a first alternative sealing bead 292, which has a non-uniform contour. The trailing edge 291 of the sealing bead slopes more rapidly from the center of the sealing bead to the outer surface of the fitting. This improves the pressure limit of the connection. Furthermore, the leading edge of the sealing bead 292 is in line with the open end of the fitting, as indicated by reference numeral D3. This increases the pressure limit of the connection compared to the Fig. 28a and Fig. The force required to fit the fluid hose (not shown) is described in section 28b.

[0079] Fig. Figure 29b shows a nozzle 295 with a second alternative sealing bead 297, which has a non-uniform contour. The trailing edge 296 of the sealing bead is curved with a radius r2 from the center of the sealing bead to the outer surface of the nozzle. The contour from the center of the sealing bead to the open end of the nozzle is curved with a radius r1, where r1 is larger than r2.

[0080] Furthermore, the front end of the sealing bead 297 is in line with the open end of the nozzle, as indicated by reference numeral D4, which in this example is larger than D3. This indicates that the force required to fit the fluid hose (not shown) is lower compared to that required in conjunction with Fig. The stub described in 29a is smaller.

[0081] In general terms, the present invention relates to a novel connector concept for chromatography systems, wherein the conventional fluidic screw connectors, as in the Fig. 25a and Fig. Figure 25b shows an example of how the existing connector can be replaced by a significantly more convenient nozzle-type connector. In this design, the tubing used to connect components in the chromatography system is simply pushed onto a nozzle and then secured by a releasable clamp that exerts a radial clamping force on the outer circumference of the tubing. As mentioned, the nozzle is preferably equipped with a sealing bead to allow the connector concept to be used within the required pressure ranges. Surprisingly, it has been verified that it is possible to design a connector that provides a leak-proof fluidic connection at internal pressures exceeding the 20 bar range required in liquid chromatography, and even going beyond 30 bar, while simultaneously significantly improving ease of use for the operator.The procedure for connecting a tube to a port in a chromatography system according to the embodiments described herein simply comprises the steps of sliding the tube end over the port, positioning the 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 the embodiments described herein simply comprises the steps of releasing the connector clamp to release the locking force, optionally removing the releasable connector clamp from the tube end, and pulling the tube end off the port.A significant advantage of the disclosed embodiments is that the steps of sliding and attaching the locking clamp do not require any rotational movement that could transmit a rotational movement to the tubing, thus preventing the tubing from being rotated relative to the male part during the attachment step. As mentioned, this prevents the tubing from twisting and forming kinks that could restrict fluid flow or even damage the tubing segment. Compared to conventional chromatography systems with connectors that require flanged tubing, for example, tubing with an inner diameter of 1 to 10 mm, the present system also offers the advantage that the fluid path can be customized by adding the step of cutting the tubing segment to an optimal length before connecting the path. Leakage test of the connector.

[0082] Embodiments of the present connector / chromatography system were subsequently verified to provide leak-proof connections over the desired pressure range for liquid chromatography. In one embodiment, the upper pressure limit for operation of the chromatography system is 20 bar, and to verify proper sealing at 20 bar, the connectors were periodically tested for leaks at 30 bar. During the tests, the threshold for detecting a leak was set at 1 µl / min at 20 bar per connector in the tested flow path. The successful tests were performed under the following conditions: • Leakage test at 20 bar over a temperature range of 4-40 °C. • 6000 repeated connections and disconnections, leak test at 30 bar every 500 cycles (performed for two different dimensions) • Static leak test for 12 months at 40 °C, leak test at 30 bar once a week. • Tensile test 0-20 N 10000 cycles, leak test at 30 bar before and after each cycle.

[0083] As mentioned previously, it was surprisingly found that this could be achieved while simultaneously noticeably improving ease of use compared to conventional connections.

[0084] In addition to the leak tests described above, salt creep tests were performed in which a mobile phase of 2.5 M (NH4)2SO4 was circulated in the system overnight (approximately 12 hours) at a dynamic pressure of 1.5 MPa. The system was then visually inspected for salt creep around the connectors, valves, and other modules. It was verified that the connectors and the chromatography system passed the test without any visible salt creep.

[0085] Fig. Figures 30a-30c show the interaction of the nozzle 20, the hose 30, and the clamping piece 110 and its fingers 118 according to one embodiment. Fig. Figure 30a shows the hose end 310 above the fitting, with the dashed lines indicating the relationship between the inner diameter of the hose and the fitting elements. As can be seen, the fitting base is slightly wider than the inner diameter of the hose, and the sealing bead 22 is significantly wider but has a rounded leading edge to allow the hose to be pushed onto the fitting. Fig. 30b the hose end was pushed onto the fitting (beyond the part shown), and the clamping piece 110 was placed around the hose end and actuated in a locked position to clamp the hose securely. The clamping piece 110 is in Fig.Figure 30c discloses in greater detail, showing that the fingers 118 are provided with a clamping section 350 to clamp the tubing in the region of the center of the sealing bead 22 of the nozzle 20. In one embodiment, the inner diameter of the tubing is 3.2 mm and the outer diameter is 4.8 mm, while the base diameter of the nozzle is 3.25 mm and the sealing bead is 3.45 mm, which, together with the clamping force of the clamp 10, ensures a leak-free connection. The tubing used in liquid chromatography systems of this type is generally made of a sufficiently rigid material to withstand the pressures that occur and can, for example, be made of FEP (fluoroethylene propylene) plastic.

[0086] According to one embodiment, a component 12-18; 810; 910 for a chromatography system 11 is disclosed. The component (which may be modular) comprises one or more ports, each port being accessible via a nozzle 20; 923, 923' for receiving a first end of a fluid tube 30; 812; 912. The first end can be sealed around the nozzle by a releasable coupling 100, 105, 300 outside the tube end, and the coupling has a releasable clamping action that can be actuated by a sliding movement of a slip-on sleeve element 130, 230, 230', 330, 430 of the coupling along the end of the fluid tube.

[0087] The nozzle (20) can be an integral part of component 12-18. Furthermore, the nozzle 923; 923' can be arranged on an adapter 915; 915' configured to connect to the port of component 910. In some embodiments, the port is a threaded hole 911, and the adapter 915, 915' comprises a corresponding threaded section 921, a body 920, and a nozzle 923; 923'.

[0088] In some embodiments, the adapter 915 is manufactured from a single piece of material, which may be plastic or metal.

[0089] In some embodiments, the nozzle 923' is made of a first material, and the body 920 and the threaded section 921 are made of a second material, wherein the first material may be a metal and the second material may be plastic.

[0090] According to one embodiment, a detachable coupling 100 is disclosed, which is designed to hold a fluid hose to a nozzle. The coupling comprises: • a cylindrical inner component 110; 310; 410 configured to receive a fluid hose 30, the inner component comprising a resiliently deflectable section 118; 418 designed to push an outer surface of the hose towards the nozzle; and • a slip-on sleeve element 130 with an inner through-opening 132 for sliding reception of the inner component, wherein the opening and the resiliently deflectable section have complementary surface designs which, in a first position of the slip-on sleeve element mounted on the inner component, provide the resilient deflection in use and, in a second, different position, prevent an effect against the outer surface of the fluid hose.

[0091] The slip-on sleeve element includes at least one projection extending outwards from the opening and of such a size that the slip-on sleeve can be moved by hand between the first and second positions.

[0092] In some embodiments, the inner component 110 further comprises an end stop section 138; 114 which can interact with the slip-on sleeve element to prevent or inhibit the slip-on sleeve element from sliding down from the inner component in at least one direction.

[0093] In some embodiments, the slip-on sleeve element can slide on the inner component from the first position, where the deflection takes place, to the second position, where the slip-on sleeve element rests against the end stop section.

[0094] In some embodiments, the slip-on sleeve flange 134 is formed at one end of the slip-on sleeve element, with the end stop section being formed at one end of the inner component. The slip-on sleeve flange 134 and the end stop section can be moved close to each other into the second position by manual actuation, and the slip-on sleeve element can be pushed further into the first position by manual actuation, with the slip-on sleeve flange 134 being spaced apart from the end stop section.

[0095] In some embodiments, the section is a clamping flange 114 that extends outwards and is sized to facilitate manual handling of the coupling. In some embodiments, the slip-on sleeve flange 134 is a continuous annular structure that projects from the body 136 of the slip-on sleeve.

[0096] In some embodiments, the slip-on sleeve flange 134 and an outer surface of the slip-on sleeve element on which the slip-on sleeve flange is formed have a continuously curved profile without sudden changes in direction.

[0097] In some embodiments, the resiliently deflectable section 118; 418 of the inner component 110; 310; 410 comprises several circumferentially arranged fingers that can deflect inwards towards the hose during use. In some embodiments, the slip-on sleeve element 330 further comprises bayonet openings 345 that interact with complementary locking pins 27 to detachably attach the coupling to a module 1.

[0098] According to one embodiment, a converter 823; 823'; 925 for connecting one end of a first fluid hose 822 to one end of a second fluid hose is disclosed. The converter comprises a nozzle 833; 833'; 933 for receiving the end of the first fluid hose 822, wherein the end of the first fluid hose can be sealed around the nozzle by a releasable coupling 100, 105, 300 outside the hose end. The coupling has a releasable clamping action that can be actuated by a sliding movement of a slip-on sleeve element 130, 230, 230', 330, 430 of the coupling along the end of the fluid hose.

[0099] In some embodiments, the converter 823; 823' further comprises a body 830 and a flange 831 or a body 930 and a section with a threaded hole 931 which is provided to be connected to the end of the second fluid hose.

[0100] In some embodiments, the converter 823 is manufactured from a single piece of material, which may be plastic or metal.

[0101] In some embodiments, the nozzle 833' is made of a first material, and the body 830 and the flange 831, or the body 930 and the section with the threaded hole 931, are made of a second material. The first material may be a metal, and the second material may be plastic.

[0102] According to one embodiment, a chromatography system 11 is disclosed, comprising several components 12-18; 810; 910, as described above, which can be fluidically connected to one another by fluid hoses 30. The components comprise one or more nozzles 20 for receiving a respective end of the fluid hose 30, wherein the end of the fluid hose can be sealed around the nozzle by a releasable coupling 100, 105, 300, as described above, the coupling having a releasable clamping action that can be actuated by a sliding movement of a slip-on sleeve element 130, 230, 230', 330, 430 of the coupling along the end of the fluid hose.

[0103] In some embodiments, the sliding movement is generally a movement in the direction of a particular component, and the clamping effect can be released by moving away from that component.

[0104] In some embodiments, the multiple components 12-18 are modular components whose position in a support frame 80 can be rearranged, and the fluid hose 30 comprises multiple lengths of fluid hoses, each having opposite ends and provided at each end with one of the couplings 100, 105, 300, which together in use permit a generally sealed fluid flow or fluidic connection between the respective modular components.

[0105] In some embodiments, the sliding motion is only a linear motion, or is an essentially linear motion with a rotational movement of 120 degrees or less.

[0106] In some embodiments, the chromatography system is a chromatography system that is formed from several components.

[0107] In some embodiments, the chromatography system further includes a converter, as described above.

[0108] According to one embodiment, a chromatography system is provided comprising several fluid handling components which can be fluidically connected to one another by fluid hoses 30 to form a chromatography fluid flow path, wherein the fluid handling components comprise one or more fluid ports with a nozzle extending from a component end face and serving to receive a respective end of the fluid hose, such that the end of the fluid hose seals around the nozzle, and serving to receive a releasable locking clamp for applying a radial locking force to an outer surface of the hose end to lock the end of the fluid hose onto the nozzle, wherein the connection is leak-proof at an internal pressure of at least 10 bar, preferably 15, 20, 25 or 30 bar.

[0109] The invention is not to be interpreted as being limited by the embodiments described above. Rather, it is readily apparent to a person skilled in the art that it can be varied within the scope of protection of the appended claims. QUOTES INCLUDED IN THE DESCRIPTION

[0000] This list of documents cited by the applicant was automatically generated and is included solely for the reader's convenience. The list is not part of the German patent or utility model application. The DPMA accepts no liability for any errors or omissions. Cited patent literature

[0000] US 8662542

[0003] US 8821718

[0005] GB 1715399 [0042, 0045] GB 1713993

[0045]

Claims

[1] Chromatography column unit comprising at least one chromatography column (13) and at least one male part (20), wherein at least one male part (20) protrudes at one end of the chromatography column (13), wherein the outer surface of the male part (20) is designed in such a way that it receives a fluid hose (30) on an inner surface of the fluid hose, the male part has an open end for coupling with the fluid hose (30), and the chromatography column unit is arranged such that a clamping force applied against the fluid tube (30) forces the fluid tube (30) against the male part (20) to form a fluid-tight coupling. [2] Chromatography column unit according to claim 1, wherein the at least one male part (20) is a first male part (20) and a second male part (20), wherein the first male part (20) projects at a first end of the chromatography column (13) and the second male part (20) projects at a second end of the chromatography column (13). [3] Chromatography column unit according to claim 2, wherein the first male part of the chromatography column projects upwards and the second male part of the chromatography column projects downwards. [4] Chromatography column unit according to claim 1, 2 or 3, wherein the at least one male part has a widening (22, 282) which is arranged near the open end, such that the fluid tube (30) is in fluid-tight engagement with the widening (22, 282) around the outer surface of the at least one male part (20). [5] Chromatography column unit according to one of the preceding claims, wherein the at least one male part is designed as a nozzle (20). [6] Chromatography column unit according to one of the preceding claims, wherein the at least one male part is configured to receive a fluid tube (30) having an inner diameter between 1 and 10 mm.

Images