Bioprocess system and related entities and methods

Abstract

The present disclosure relates to a bioprocess system (1) for tangential flow filtration and related entities and methods. The system (1) comprises at least a fluid circuit (10) including tubing (13), provided at an outer side of an apparatus (2) and defining at least a recirculation circuit of the fluid circuit (10), a recirculation vessel (4) for containing fluid, a vessel holder (9) attached to the apparatus (2) and holding the vessel (4) at an elevated level of the apparatus (2), a filter (5) for tangential flow filtration, a pump (11) downstream the vessel (4) and for pumping fluid along the fluid circuit, an upper fluid junction J1 including at least one inlet path for governing supply of fluid and a retentate path including a pressure control valve (16) for controlling pressure in the filter downstream the filter (5), and a lower fluid junction J2 downstream the pump (11) and including at least a junction inlet path, a filter connection path fluidly connecting to the filter (5) and a drain path for draining fluid.

Description

BIOPROCESS SYSTEM AND RELATED ENTITIES AND METHODS TECHNICAL FIELD

[0001] The present invention relates to a bioprocess system and related entities / components and methods. Specifically, the invention relates to a fluid junction for being mounted to a bioprocess apparatus, use of the fluid junction, a sensor configured for being mounted to a bioprocess apparatus, use of the sensor, a fluid kit configured for being mounted to a bioprocess apparatus, use of the kit, a vessel holder for the bioprocess apparatus, use of the vessel holder, a filter holder adaptor for the bioprocess apparatus, use of the filter holder adaptor, a method for pump calibration of the bioprocess system and a corresponding control unit, a method for testing a filter of the bioprocess system and a corresponding control unit, a method for permeate flow meter calibration of the bioprocess system and a corresponding control unit, the bioprocess apparatus, the use of the bioprocess system.BACKGROUND OF THE INVENTION

[0002] Tangential flow filtration (TFF), also called cross flow filtration, is an established bioprocess method for filtration of fluid. Typically, the fluid is expensive so that waste of fluid which occurs upon processing / filtration shall be reduced. Often, small manufacturing volumes are of interest.

[0003] There is a need to improve bioprocesses, in particular TFF, with respect to individual entities of the system, an apparatus, the system in its entirety, and methods applied in relation to the bioprocess, in particular in view of waste reduction, small scale manufacturing, automation and / or performance.SUMMARY OF THE INVENTION

[0004] The present invention relates to the system of claim 1. Accordingly, a bioprocess system for tangential flow filtration is provided, wherein the system comprises at least a fluid circuit including tubing, is provided at an outer side of an apparatus of the system and defines at least a recirculation circuit of the fluid circuit; a recirculation vessel (also referred to as tank) for containing fluid; a vessel holder attached to the apparatus and holding the vessel at an elevated level of theapparatus; a plurality of filter ports for fluid connection to a filter for tangential flow filtration, a pump downstream the vessel and for pumping fluid along the fluid circuit; an upper fluid junction including at least one inlet path for supply of fluid via an inlet section of the fluid circuit, and a retentate path including a pressure control valve for controlling pressure in the filter downstream the filter in a recirculation circuit of the fluid circuit; a lower fluid junction downstream the pump and including at least a junction inlet path, a filter connection path fluidly connecting to the filter and a drain path for draining fluid. The recirculation circuit includes and fluidly connects the vessel, the filter, the upper and lower fluid junctions by way of the tubing. The system is configured to facilitate drainage of fluid from the inlet path to the drain path in a drain section of the fluid circuit. Optionally, a total length of the tubing in the recirculation circuit is less than 1 m (1000 mm), further optionally less than 0.9 m (900 mm), even further optionally less than 0.8 m (800 mm). Alternatively, or additionally, optionally, a total volume of fluid receivable by the tubing in the recirculation circuit is less than about 10 ml, further optionally less than about 8 ml. Optionally, the system includes the filter, which is fluidly connected to the recirculation circuit.

[0005] The idea underlying this aspect of the invention is a bioprocess system allowing for reduced waste of fluid. In particular, the fluid volume held or retained by the system is reduced. In other words, the hold-up volume is reduced. This may be achieved by reducing the length of the tubing in the recirculation circuit, and / or the volume of fluid received by the tubing in the recirculation circuit, so that less fluid remains in the tubing. Existing systems may have longer tubing. According to the invention, the total tubing of the recirculation circuit may be reduced for about at least 50, more preferably at least 100, even more preferably at least 115 mm, and corresponding fluid volume may be reduced. This aspect of the invention therefore offers in particular improvements as to performance.

[0006] At the same time, the system allows for a small scale, i.e. small dimensions. The system may be of bench top scale; in particular, the system may be configured for being placed on top of a bench. The vessel is held by a vessel holder attached to the apparatus, which renders the system more expedient in terms of space savings and location of the vessel relative to the apparatus, in particular as to the height at which the vessel is located.

[0007] The system may be configured for fluid flow rates of about 0.5 l / min. The inner diameter of the tubing, i.e., tubes, may be about 3.2 mm or more precisely3.175 mm. The tubing may be flexible. In particular, the tubing may be made of silicone or Thermoplastic Elastomer (TPE).poos] The vessel may contain about 1 I fluid. The end product collected e.g. via the drain path may be about 15 ml.

[0009] The upper fluid junction may be located higher than the lower fluid junction and at least in parts higher than the vessel. The vessel may be located higher than the lower fluid junction. The fluid junctions are built in cooperation with sets of valve, respectively.

[0010] The filter is a filter configured for TFF, optionally a TFF cassette. The filter may be held by a filter holder. The filter holder is configured for holding the filter, in particular the TFF cassette, optionally by sandwiching the filter between opposing holder parts.

[0011] Optionally, the bioprocess system of claim 1 is the system of claim 53.

[0012] The present invention relates to the fluid junction of claim 2. Accordingly, a fluid junction for being mounted to a bioprocess apparatus is provided, optionally as part of a fluid kit, to form part of a fluid circuit of a bioprocess system, optionally for tangential flow filtration. The junction at least comprises at least four ports each for fluid connection to a respective tube forming part of the fluid circuit. The at least four ports include an inlet port for fluid connection in the fluid circuit downstream of a pump of the fluid circuit; a filter connection port for fluid connection to a filter in the fluid circuit upstream of the filter; a drain port for fluid connection in the fluid circuit for draining fluid (optionally draining of retentate; out of the fluid circuit); and a bypass port for (fluid connection in the fluid circuit for establishing fluid flow) bypassing the filter connection port and / or the drain port. The fluid junction further includes a fluid junction passageway for flowing fluid through the junction, wherein the fluid junction passageway includes an inlet-filter connection passageway fluidly connecting the inlet port and the filter connection port and including an inlet passageway at the inlet port and a filter connection passageway at the filter connection port; a drain passageway fluidly connecting the inlet port to the drain port, and a bypass passageway fluidly connecting the inlet port and the bypass port for (fluid connection in the fluid circuit for establishing fluid flow) bypassing the filter connection port and / or the drain port.

[0013] The fluid junction is not limited to TFF but may be used for other bioprocess applications. The junction may be a single-use, disposable entity, but is not limited in this regard.

[0014] The fluid junction may be regarded as a manifold. In the fluid junction, fluid paths in the fluid passageways cross each other and / or are branched.

[0015] The idea underlying this aspect of the invention is improved flow of fluid through the junction. This may be achieved by the at least four ports and respective passageways. In particular, the bypass port and the bypass passageway may support more dedicated and optimized fluid paths, e.g. when mounted to the apparatus. For example, the bypass port may be configured for connection to a bypass flow path bypassing the filter. This may allow for additional fluid paths and methods on the basis of such paths, e.g. for priming, preparing and or calibrating. Hence, the at least four ports of the junction may improve the versatility of a system using the junction.

[0016] An axis defining the orientation of the port may be perpendicular to a surface from which the port extends / protrudes. Alternatively or additionally, the axis may run in the direction of an overlap between the port and a corresponding tube. All ports and / or axes may be in the same plane, e.g. parallel to a housing / chassis of the apparatus, when mounted to the apparatus.

[0017] One or more of the ports, optionally all ports have a protruding male part for receiving tubing at an outer side of the male part. The male part may protrude from a main body of the junction.

[0018] One or more, preferably all of the passageways extend straight in the junction. The outer geometry of the junction is not limited. For milling purposes, straight flow paths as may be preferable. Alternatively or additionally, one or more, preferably all passageways may be configured as internal cavities (e.g. milled out from the e.g. solid main body) within the junction. Hence, the passageways may be formed within a main body from which the male ports protrude.

[0019] Optionally, the drain port is positioned such that an angle y between the inlet port axis defined by the inlet port, and a drain port axis defined by the drain port is more than 90° and less than 160°, further optionally between 120 and 140°. Alternatively or additionally, an angle [3 between the filter connection port axis defined by the filter connection port, and the drain port axis defined by the drain port is less than 120°, further optionally less than 100°. Alternatively or additionally, the inlet passageway is angled relative to the drain passageway at the angle y, and / or the outlet passageway is angled relative to the drain passageway at the angle [3. Alternatively or additionally, the inlet and filter connection ports are positioned such that an angle a between an inlet port axis defined by the inlet port,and a filter connection port axis defined by a filter connection port is more than 90° and less than 160°, optionally between 120 and 140°. Alternatively or additionally, the inlet passageway and the filter connection passageway are angled relative to each other at the angle a.

[0020] Optionally, the junction is a non-symmetrical junction, in particular in the sense that the angles a, y, [3 differ from each other.

[0021] The junction may be seen as including a Y-junction, including the inlet, filter connection and drain ports. Alternatively or additionally, the junction may be regarded as L-shaped. Further optionally, the junction may be regarded as double L-shaped: The inlet passageway and the bypass passageway are L-shaped relative to each other; and / or the filter connection passageway and the drain passageway are at least substantially L-shaped relative to each other.

[0022] In use, in particular when mounted to an apparatus, the positions of the ports and / or the passageways of the junction may be such that both the inlet and drain passageways direct fluid downwards to support drainage of fluid by means of gravity. Alternatively or additionally, during use, the drain passageway is not vertical, but angled relative to the direction of gravity, so as to support exchange of fluid received in the drain passageway during fluid flow when the drain port is closed (more correctly, when a valve downstream the drain port is closed). Hence, the drain passageway extends downwards but may not be vertical to reduces nonconcentrated fluid residual remainders upstream the valve for closing the drain port.

[0023] Optionally, at least the inlet passageway and the filter connection passageway intersect at an intersection, further optionally at which the inlet passageway and the filter connection passageway are angled relative to each other at the angle a. Further optionally, also the drain passageway intersects the inlet-filter connection passageway at the intersection, even further optionally wherein the drain passageway is angled at the angle [3 relative to the filter connection passageway at the intersection and / or the drain passageway is angled at the angle y relative to the inlet passageway at the intersection.

[0024] This may in particular be realized if the passageways are straight, and not bent, so that the orientation of the ports and passageways is identical.

[0025] Optionally, the bypass passageway and the inlet passageway intersect upstream the intersection. Alternatively, or additionally, optionally the bypass passageway and the inlet-filter connection passageway are perpendicular to eachother. This may support flow of fluid. Specifically, the bypass port / passageway and the inlet port / passageway may be perpendicular to each other, also where the respective passageways intersect.

[0026] Optionally, the junction further comprises a pressure sensor fluidly connected to the passageway, wherein the junction is configured such that the pressure sensor is configured to measure the pressure of fluid in the passageway, optionally upstream the intersection. This may allow to reduce tubing and hence hold-up volume, as the junction and the pressure sensor are combined. In particular, tubing connecting the junction and the pressure sensor can be saved.

[0027] Optionally, the pressure sensor protrudes in a direction other than the at least four ports, further optionally in a direction orthogonal to the at least four ports. This may save space.

[0028] Accordingly, the pressure sensor faces away from the bioprocess apparatus when mounted to the apparatus. This supports space-saving. The pressure sensor may be located on top of the main body of the junction and / or may protrude from the main body.

[0029] The invention is also directed to the use of the fluid junction of the invention, for a fluid kit and / or a bioprocess apparatus forming part of a fluid circuit of a bioprocess system, optionally for tangential flow filtration. The use comprises establishing a fluid connection with the fluid circuit by connecting the inlet port of the fluid junction with an inlet tube of tubing of the fluid circuit, the filter connection port of the fluid junction with a filter connection tube of the tubing of the fluid circuit, and the drain port of the fluid junction with a drain tube of the tubing of the fluid circuit, such that the inlet port axis and / or the inlet passageway are inclined relative to the horizontal, when the fluid junction is mounted to the apparatus, optionally wherein the drain port axis is angled relative to the vertical, when the fluid junction is mounted to the apparatus. This may support drainage of fluid through the junction. The inclination may be such that the drainage of fluid is supported.

[0030] The present invention relates to the sensor of claim 9. Accordingly, the sensor is configured for being mounted to a bioprocess apparatus, optionally of the invention and / or as part of a fluid kit, optionally of the invention, to form part of a fluid circuit of a bioprocess system, optionally of the invention, optionally for tangential flow filtration. The sensor comprises a sensor inlet and a sensor outlet for fluid connection to the fluid circuit, wherein a sensor passageway fluidly connects the inlet and outlet for flowing fluid of the fluid circuit through the sensor;a conductivity measurement unit extending into the sensor passageway for determination of the conductivity of fluid flowing through the sensor passageway; and a pressure measurement unit for determination of the pressure of fluid flowing through the sensor passageway.

[0031] The sensor is not limited to TFF, but may be used for other bioprocess applications. The sensor may be a single-use, disposable entity, but is not limited in this regard.

[0032] The idea underlying this aspect of the invention is to provide a sensor configured for both conductivity measurement (of the electrical conductivity of the fluid) and pressure measurement. Hence the sensor may be seen as a combined sensor combining electrical conductivity and pressure measurements. Compared to separate conductivity and pressure sensors connected with tubing, the tubing length may be reduced, thus reducing hold-up volume.

[0033] Both the conductivity measurement unit and the pressure measurement unit share at least a part of the sensor passageway of the fluid path for measurement. Hence, basically the same part of the fluid circuit may be used for both measurements. Put differently, electrical conductivity of fluid and pressure of fluid flow may be measured / determined at substantially the same location. For example, both measurement units may be arranged such that they substantially measure at a common measurement region of the fluid circuit and / or share the measurement region within the fluid passageway. In one example, the measurement may take place at the same location seen in the flow direction, so that both measurement units measure substantially neither up- nor downstream relative to each other.

[0034] Optionally, the pressure measurement unit and the conductivity measurement unit are located at different sides of the passageway, further optionally angled relative to each other or at opposite sides of the sensor passageway. This may support saving space and using space around the sensor effectively. When located at opposite sides, both measurement units may be located perpendicular to the housing of the apparatus when the sensor is mounted to the apparatus. Optionally, when the sensor is connected to tubing, the sensor may be extend to different sides of the tubing, further optionally be angled relative to each other or at opposite sides of the tubing.

[0035] Optionally, the sensor inlet and the sensor outlet define a sensor inlet axis and a sensor outlet axis, respectively, wherein the sensor inlet axis and the sensoroutlet axis are offset by an offset and parallel to each other, and / or the sensor passageway includes a step forming a cavity, optionally into which the conductivity measurement unit protrudes and / or at which the pressure measurement unit measures the pressure.

[0036] The cavity in the passageway may avoid or at least reduce trapping of air (compared to an upper dead-end cavity) and stay / remainders of fluid (compared to a lower dead-end cavity). The step may be formed by the offset to form the cavity in the sensor passageway. The step may be an upward step, seen in the flow direction.

[0037] The invention is also directed to the use of the sensor of the invention, for a fluid kit and / or a bioprocess apparatus forming part of a fluid circuit of a bioprocess system, optionally for tangential flow filtration. The use comprises establishing a fluid connection with the fluid circuit by connecting the sensor inlet and the sensor outlet to tubing of the fluid circuit.

[0038] The present invention relates to the fluid kit of claim 13. Accordingly, the fluid kit, optionally single-use / disposable, is configured for being mounted to a bioprocess apparatus, optionally of the invention, to form a fluid circuit of a bioprocess system for tangential flow filtration. The kit comprises at least a recirculation vessel for receiving fluid of the fluid circuit, a pump unit for cooperation with re-useable pump drive means for pumping fluid through the fluid circuit, and tubing fluidly connecting the vessel and the pump unit, the tubing including at least one supply port for supply of fluid, filter ports for fluid connection to a filter for tangential flow filtration, and at least one outlet port for fluid drainage or collection.

[0039] The idea underlying this aspect of the invention is to improve avoidance of contamination and / or support automation of processes related to tangential flow filtration and also to reduce tube length.

[0040] The entire kit may be disposable after a single use and may be configured for a single-use only. Thus, the kit may help to avoid cleaning of tubing, thus avoiding cleaning chemicals. Also, the kit may help to meet hygienic / cleaning requirements and to support avoiding contamination of the bioprocess the kit is used for.

[0041] Optionally, the kit is sterile / aseptic. The tubing may be closed for the kit to be aseptic / sterile. The kit may be configured for GPM purposes.

[0042] The pump (including the single-use pump unit and the re-useable pump drive means) may be referred to as main pump and / or feed pump.

[0043] The pump may include a membrane pump, optionally with three chambers. The cooperation between the single-use pump unit and the re-useable pump drive means includes mechanical engagement, so as to transfer the oscillation by the pump drive means to the single-use pump unit. The single-use pump unit may include one or more pump chambers, e.g. three chambers.

[0044] The vessel may be substantially cylindrical and / or may contain a magnetic stirrer.

[0045] A tube length between the vessel and the pump unit may be less than 300 mm; and / or between the filter and the recirculation vessel may be less than 400 mm. Additionally or alternatively, the volume of fluid received by the tubing between the vessel and the pump unit may be less than 3 ml; and / or between the filter and the recirculation vessel may be less than 3 ml.

[0046] Optionally, the recirculation vessel has a bottom and at least one wall arising from the bottom, wherein the bottom includes at least one inclined bottom region which is inclined relative to a plane perpendicular to the at least one wall of the vessel and / or relative to the horizontal when the recirculation vessel is mounted to the bioprocess apparatus.

[0047] The bottom of the recirculation vessel may be sloped, optionally the entire bottom (which may be a circular bottom). The angle of the slope / inclination relative to a horizontal may be about 5°. This may support drainage of fluid from the vessel.

[0048] Optionally, the bottom of the recirculation vessel includes a vessel outlet and the bottom comprises an indentation fluidly connecting to the vessel outlet, further optionally the indentation being included in the inclined bottom region. The indentation may be a depression in the bottom of the vessel. It may be lower than the bottom. The indentation helps to facilitate drainage of fluid towards the vessel outlet, i.e. towards the drain port.

[0049] Optionally, the kit includes a fluid bypass path directly connecting the bypass valve to a drain port, such that the kit is configured to establish a fluid path bypassing the filter (ports).

[0050] By way of the bypass path, it may be possible to bypass the filter (more specifically the junction connection to the filter) for prim ing and / or for initial pumping of fluid. The bypass path may allow to establish a higher flow rate of fluid in the fluid circuit than the filter can withstand.

[0051] Optionally, the pump unit is located downstream the vessel, when the kit is used for filtration. This may support drainage of fluid from the vessel.

[0052] Optionally, the kit comprises a junction of the invention, optionally downstream of the pump unit, when the kit is used for filtration, and / or at least one sensor of the invention, optionally downstream of the filter ports when the kit is used for filtration. This may improve advantages even further, in particular as regards the reduction of fluid hold-up volume.

[0053] Optionally, a tube length between the pump unit and the junction is less than 120 mm, further optionally about 100 mm. A volume of fluid received by the tubing may be less than 1 ml.

[0054] The kit may comprise the upper and lower fluid junctions.

[0055] The invention is also directed to the use of the kit with a bioprocess apparatus for forming a fluid circuit of a bioprocess system for tangential flow filtration. The use comprises fluidly connecting the at least one inlet port with a fluid supply, the at least one outlet port with fluid collection means, and the filter ports with a filter, and engaging the pump unit with the re-useable pump drive means of the apparatus.

[0056] The present invention relates to the vessel holder of claim 20. Accordingly, a vessel holder for a bioprocess apparatus for tangential flow filtration is provided. The holder is configured for holding a (optionally recirculation) vessel as part of a fluid circuit of the apparatus and for being attached to the apparatus. The holder includes mounting means for mounting the vessel holder to an outer housing of the apparatus, a receiving portion, optionally substantially circular, for receiving at least a bottom of the vessel, and a load cell below and / or included in the receiving portion and configured to measure the weight of the vessel (including its content, i.e. the fluid), when the vessel is received by the receiving portion.

[0057] The vessel holder is not limited to TFF, but may be used for other bioprocess application. The vessel holder is not limited to receiving and holder a single-use vessel.

[0058] The idea underlying this aspect of the invention is that the vessel is held by the holder mounted directly to the apparatus and, at the same time, allows to measure the weight of the fluid contained in the vessel. This may be achieved by the holder holding the vessel attached / mounted to the apparatus and including a load cell, in particular at a level above the bottom of the apparatus. This may save space.

[0059] Due to the integration of load cell into the vessel holder, the vessel may be positioned in an upper part of the fluid circuit to support drainage of fluid by gravity.In particular, the vessel does not need to be placed on a bench top (external to the apparatus), but may may be elevated and mounted to the apparatus via the vessel holder directly mounted to the apparatus.

[0060] The holder may comprise mounting means are for attaching / fixing the holder to the apparatus.

[0061] The holder may be 3D printed.

[0062] The holder may extend substantially in the horizontal direction when mounted to the apparatus. The holder may protrude from the apparatus, optionally to the front, when mounted to the apparatus.

[0063] The receiving portion may be configured to hold / support the vessel, optionally from below / beneath the vessel or its bottom. The receiving portion may be regarded as a receptable.

[0064] The load cell is configured to measure the weight of the fluid received in vessel. Thus, the amount of fluid received in the vessel may be determined.

[0065] The receiving portion and the mounting means of the holder are substantially in the same (elevated) plane.

[0066] The holder may include mounting means for mounting the holder to the apparatus at an elevated level (i.e. above the bench top), so that the vessel does not need to be located on the bottom or supported by another entity external to the apparatus for the vessel to be at an elevated level (i.e. above the bench top level). The vessel holder may be configured as a cantilever protruding from the apparatus.

[0067] Optionally, the load cell is at least partially circular and / or is donut-shaped. This may support efficient use of space available below a vessel having a circular cross-section.

[0068] Optionally, the holder includes a magnet impeller drive for magnetically agitating a magnetic stirrer in the vessel for mixing fluid in the vessel. This may allow for using space below the vessel effectively.

[0069] Further optionally, the magnet impeller drive is located in the middle of the receiving portion and is even further optionally surrounded by the load cell. This may be preferably in terms of space.

[0070] Optionally, the magnet impeller drive protrudes from the load cell in a length direction of the wall of the vessel and / or in a direction opposite to gravity, when the vessel holder is mounted to the apparatus. The upper side of the impeller drive may have a protruding / elevated magnetic surface for interaction with the magnetic stirrer of the vessel. The magnetic surface may be higher than the load cell whenthe holder is mounted to the apparatus. This may help to locate the vessel within the vessel holder.

[0071] Optionally, the holder includes a cantilever portion connecting the receiving portion and the mounting means of the holder. Further optionally, the cantilever portion has a substantially trapezoidal shape and / or is angled such that the mounting means is inclined relative to a tangential to the wall of the vessel parallel to an outer side of a housing of the apparatus, when the vessel is received in the vessel holder and the vessel holder is mounted to the apparatus.

[0072] Hence, the holder may be directly attachable to apparatus via the cantilever portion. The cantilever portion may protrude from the housing of the apparatus, optionally horizontally, when the holder is mounted to the apparatus. The cantilever portion is configured to place the vessel sideways (e.g. further to the left), as cantilever portion is not symmetrical. Here, the angled configuration means no orthogonal configuration.

[0073] Optionally, the holder comprises a tube fixation configured to at least partially fix tubing (fluidly connecting to the vessel) to the holder, optionally to the cantilever portion. This may help to avoid perturbations due to tube movement, as the load cell is very sensitive to perturbations.

[0074] Further optionally, the tube fixation includes at least one slot, optionally two, for holding and receiving a section of the tubing, optionally wherein the tube fixation protrudes from the remaining cantilever portion upwards, when the holder is mounted to the apparatus. This may specifically help to avoid perturbations.

[0075] The invention is also directed to the use of the vessel holder of the invention for a bioprocess applications, in particular for tangential flow filtration. The use comprises attaching the mounting means of the vessel holder to the apparatus, optionally to an outer side of the apparatus.

[0076] The present invention relates to the filter holder adaptor / adapter of claim 29. Accordingly, a filter holder adaptor configured for (establishing) attachment of a filter holder (for) a filter cassette to a bioprocess apparatus for tangential flow filtration is provided. The filter holder adaptor includes at least one apparatus-side adaptor, optionally detachably, attachable to the apparatus, the apparatus-side adaptor comprising apparatus-side engagement means, and at least one filter-side adaptor, optionally detachably, attachable to the filter holder (for) compressing and / or holding the filter material of the filter, the filter-side adaptor comprising filterside engagement means. The apparatus-side engagement means and the filter-side engagement means are configured for mechanical engagement with each other, and the apparatus-side adaptor and the filter-side adaptor are configured such that mechanically engaging the apparatus-side engagement means and the filter-side engagement means attaches the filter holder to the apparatus, when the apparatus-side adaptor and the filter-side adaptor are attached to the apparatus and the filter holder, respectively.

[0077] The idea underlying this aspect of the invention is swift and / or secure mounting of the filter cassette to the apparatus. In existing systems, the filter is assembled so as to yield a filter-filter holder combination and, at the same time, the filter combination is mounted to the apparatus. By way of the invention, it is possible to first assemble the filter and the filter holder to yield the filter combination, and to secondly mount the filter combination to the apparatus. This ensures that the filter is tightly held by the filter holder when dis / mounting, which avoids leakage of the filter when mounting the filter (holder) to or dismounting from the apparatus. Hence, the filter holder adaptor facilitates attachment of a filter to an outer housing / chassis of the apparatus.

[0078] Mounting of the filter cassette holder to the apparatus is achievable manually by way of the filter holder adaptor of the invention: Mounting / attachment is possible by the user’s hands, without tools, such as screw drivers. As such the filter holder is attachable / detachable to the apparatus without tools.

[0079] The filter may be a filter cassette. An off the shelf filter (cassette) holder may be used for the filter.

[0080] The apparatus-side adaptor may be configured as a bar / bracket.

[0081] Optionally two (identical) apparatus-side adaptors, more optionally underneath each other when attached to the apparatus, are provided.

[0082] Optionally, the filter-side adaptor is attachable to a substantially planar jaw of the filter holder, further optionally by means of mechanical attachment means, and / or includes a substantially planar frame or plate for lying against the jaw of the filter holder. The plate may have cut-outs to form a frame-like structure. The plate or frame aligns to the filter holder.

[0083] Attachment may be achieved by means of fasteners (screws), which are other fasteners than the ones for compressing the filter material within the filter holder.

[0084] Optionally, the apparatus-side adaptor includes at least one bar / bracket and / or the apparatus-side engagement means includes at least one recess,optionally formed in the bar / bracket, for receiving the filter-side engagement means. The recess may be open in a direction of a plane defined by the frame, when the filter-side adaptor and the apparatus-side adaptor are in engagement.

[0085] The recess may be a slot and / or may be open, i.e. at an edge of the apparatus-side engagement means. Specifically, the recess may be open at the top of recess.

[0086] The recess may have inclined walls to facilitate insertion of a counterpart into the recess.

[0087] The apparatus-side adaptor may be fastened to the apparatus (its housing), e.g. by means of screws.

[0088] The apparatus-side adaptor may be bracket- or bar-shaped. The elongation of the bracket / bar may be substantially parallel to the horizontal, when the filter holder adaptor is attached to the apparatus.

[0089] Optionally, the filter-side engagement means includes a protrusion for being received by the apparatus-side engagement means, further optionally wherein the protrusion protrudes in a direction perpendicular to a plane defined by the filterside adaptor.

[0090] The protrusion may be configured as a knob and / or may serve as a hook. The protrusion may have head / enlarged end.

[0091] Optionally, the apparatus-side adaptor comprises an inclined wall which faces away from the filter-side adaptor and is inclined relative to the vertical and / or the filter-side adaptor, such that the distance of the inclined wall relative to the filter-side adaptor increases in the direction opposite to gravity, when the filter-side engagement means and the apparatus-side engagement means are in engagement. This supports (self) strengthening of the engagement.

[0092] The inclination may be about 5° towards the filter-side adaptor in the direction of gravity, when the adaptor is in use. The inclination helps to fasten the filter-side adaptor to apparatus-side holder, as filter-side adaptor thickens in the direction towards the apparatus (being a symmetrical apparatus-side adaptor), in the direction of gravity. The protrusion may have an enlarged head which represents a counterpart for the inclination.

[0093] Optionally, the at least one apparatus-side engagement means, optionally the recess, is offset from a middle / centerof the apparatus-side adaptor, when seen in a length direction of the apparatus-side adaptor means. Two recesses which are both offset may be provided in the (single, each) apparatus-side adaptor means.

[0094] The length direction may be the horizontal direction, when the apparatusside engagement means is mounted to the apparatus.

[0095] Optionally, the apparatus-side adaptor includes a first and an opposite second side, wherein each of the first and second sides is configured to face towards the apparatus, when the filter is attached to the apparatus.

[0096] The apparatus-side adaptor may be configured turneable / two-sided so as to adapt a left-right location for different filters, when looking at the front of the apparatus. For example, if connectors for the filter need more space, by turning the apparatus-side adaptor accordingly, the appropriate distance sideways, i.e. along the front of the apparatus, of the filter (cassette holder) can be selected.

[0097] Also, the offset may help to avoid an inappropriate placement of the filter. Two recesses each offset relative to the centre / middle of the apparatus-side adaptor may be provided. This configuration allows for a configuration of the filter in which the engagement position of the apparatus-side and filter-side engagement means is adaptable by the offset recess and the turnable / two-sided use of the adapter.

[0098] The present invention is also directed to the use of the filter holder adaptor of the present invention, for a filter and an apparatus for tangential flow filtration, the filter being held by a filter holder. The use comprises attaching the apparatusside adaptor to the apparatus, and / or attaching the filter-side adaptor to the filter holder. Optionally, the use comprises engaging the apparatus-side engagement means and the filter-side engagement means with each other.

[0099] The present invention relates to the method for pump calibration of claim 38. Accordingly, the method for pump calibration of a bioprocess system, optionally of the present invention, for tangential flow filtration is provided, the system including at least a vessel for containing fluid, a pump, optionally including a pump unit and a pump drive means, for pumping fluid along a fluid filtration circuit of the bioprocess system, a filter for filtration of fluid by means of tangential flow of fluid across the filter in the fluid filtration circuit, and a fluid collection port for collecting drained fluid (optionally for draining waste or for draining / collection of permeate). The following steps are performed, at least: Providing fluid in the vessel; establishing a fluid calibration circuit bypassing the filter; flowing fluid from the vessel to the collection port by pumping fluid at a predetermined default flow rate by means of the pump along the fluid calibration circuit; measuring the amount of fluid in the vessel at at least two different points in time within the time period duringwhich fluid is flown along the calibration circuit at the predetermined default flow rate, to obtain a measured flow rate representative of the fluid flow; comparing the measured flow rate and the predetermined default flow rate for calibration of the pump to obtain a calibrated flow rate of the pump, and calibrating the pump based on the calibrated flow rate.

[0100] The idea underlying this aspect of the invention is automation of pump calibration, in particular in the context of single-use entities. Optionally, entities are single-use entities, further optionally those of the kit of the invention. Here, the pump needs to be calibrated for each use, i.e. for each kit. However, the calibration of the pump is not limited to single-use entities.

[0101] For an automated calibration, the filter needs to be bypassed. By bypassing / deviating the filter, a fluid circuit without fluid flowing through filter is obtained. The bypass allows to bypass the filter for priming and preparing. Specifically, a flow rate higher than a flow rate the filter can withstand is possible.

[0102] Calibration serves to compensate for the deviation between the default flow rate and the measured (“real”) flow rate, e.g. by a setting factor. The method facilitates calibration of the pump, which is, in existing systems, carried out by means of a flow meter, in the retentate circuit. Hence, the calibration method of the present invention renders a flow meter in retentate circuit for calibration of the pump void. This contributes to a reduction of hold-up volume. Hence, the bioprocess system / apparatus is free of a flow meter at front, i.e. in the retentate flow path.

[0103] The method is a control method, wherein method steps are controlled accordingly.

[0104] The pump may be referred to as main pump and / or feed pump.

[0105] The fluid calibration circuit does not need to be closed, but may be open.

[0106] The default flow rate may be the non-calibrated / theoretical flow rate as indicated by pump before calibration. The predetermined default flow rate may be fixed, and may optionally be constant during calibration. The amount of fluid per pump run is determined. Hence, the flow rate as a function of the pump speed is determined.

[0107] Optionally, the amount of fluid in the vessel is determined by gravimetric measurement, optionally by means of a load cell of a vessel holder of the present invention, wherein the vessel is supported by the vessel holder.

[0108] The present invention is also directed to a control unit configured to carry out (controlling) the method of the invention.

[0109] The present invention relates to the method for testing (the integrity of) a filter of claim 41. Accordingly, a method for testing a filter of a bioprocess system, optionally of the present invention, for tangential flow filtration is provided. The system at least includes a transfer pump for pumping fluid in a fluid test (testing) circuit, a filter for filtration of fluid by means of tangential flow of fluid across the filter, a pressure sensor in fluid communication with the filter, optionally included in the sensor of the present invention, a retentate outlet port fluidly connecting to the filter in the fluid test circuit, wherein the filter retentate outlet port is downstream the filter during filtration, and further filter ports fluidly connecting to the filter and the fluid filtration circuit during filtration. The following steps are performed, at least: Providing the further filter ports in a closed state and the filter retentate outlet port in an open state; establishing the fluid test circuit by fluidly connecting at least the transfer pump and the filter via the retentate outlet port; supplying gas (e.g. air) to the fluid test circuit by means of the transfer pump, when the fluid test circuit has been established and the further filter connections are closed, so as to pressurize the system until a target pressure is reached; measuring the pressure in the filter directly or indirectly (or at least the pressure indicative of the pressure in the filter) by means of the pressure sensor to obtain a measured pressure, after the target pressure has been reached and supply of gas was stopped; monitoring the measured pressure over time during a time interval, in particular a decay of the pressure over time, so as to obtain a pressure decay rate; and identifying a test result from the pressure decay rate.

[0110] The idea underlying this aspect of the invention is automation of testing for filter integrity, in particular in the context of single-use entities. Optionally, the entities are single-use entities, further optionally those of the kit of the invention. In this case, the testing needs to be done for each use, i.e. for each kit and / or filter. The testing of the filter is, however, not limited to single-use entities.

[0111] The method allows to detect leakage of gas from the circuit. Hence, the integrity of filter in fluid circuit is tested. The method represents a pressure hold test or pressure drop test. A pressure drop / decay indicates leakage of gas (air).

[0112] The filter may be a filter cassette or another filter for tangential flow filtration.

[0113] The further filter ports are closed by closing the valves adjacent to the further filter ports. The connections are sealed, in particular gas-tight. Also other remaining valves are opened / closed to pressurize upstream side on the pressure.

[0114] The transfer pump may be a peristaltic pump. An air filter on the transfer side of the circuit is used to pass the gas / air through transfer pump into the system.

[0115] The test involves pressurizing the system with gas (air) until a target pressure is reached. Upstream pressure of the filter is monitored for changes due to gas diffusion through the filter. Before conducting the test, it may be ensured that the filter (membrane) is properly wetted and fluid is drained out of the filter.

[0116] The method may include one or more of the following steps: Start the transfer pump to slowly increase the pressure to the target pressure. Upon reaching the target pressure, close the valves to isolate the pressure source. Monitor the pressure decay over the specified time. A properly functioning membrane system maintains the pressure with a very slow rate of decay. After completion of the test, relieve the pressure in the system by opening relevant valves.

[0117] The method is a control method, wherein method steps are controlled accordingly. The present invention is also directed to a control unit configured to carry out (controlling) the method of the invention.

[0118] The present invention relates to the method for calibration of the permeate flow meter (a flow meter in the permeate circuit) of claim 44. Accordingly, a method for permeate flow meter calibration of a bioprocess system, optionally of the present invention, for tangential flow filtration is provided. The system includes at least a vessel for containing fluid, a pump, optionally including a pump unit and a pump drive means, for pumping fluid along a fluid filtration circuit of the bioprocess system, a filter for filtration of fluid by means of tangential flow of fluid across the filter in the fluid filtration circuit, the flow meter downstream the filter for measuring the flow of permeate, and a fluid collection port for collection of fluid. The following steps are performed, at least: Providing fluid in the vessel, establishing the fluid filtration circuit including the filter, flowing fluid from the vessel to the collection port along the fluid filtration circuit by pumping fluid by means of the pump, wherein fluid downstream the filter flows through the flow meter at an indicated flow rate indicated by the flow meter; measuring the amount of fluid in the vessel at at least two different points in time within the time period during which fluid is flown along the fluid filtration circuit to obtain a measured flow rate representative of the fluidflow; comparing the measured flow rate and the indicated flow rate of the flow meter to obtain a calibrated flow rate of the flow meter, and calibrating the flow meter based on the calibrated flow rate.

[0119] The idea underlying this aspect of the invention is automation of calibration of the flow meter in the permeate circuit, in particular in the context of single-use entities. Optionally, entities are single-use entities, further optionally those of the kit of the invention. Here, the calibration needs to be done for each use, i.e. for each kit. The testing of the filter is, however, not limited to single-use entities.

[0120] The bypass allows for deviation of the filter, so that a fluid circuit without fluid flowing through filter is obtained for the calibration.

[0121] The fluid circuit does not need to be closed, but may be open. The supply path may be closed, so that no fluid is supplied to vessel. Thus, changes in the fluid level in vessel are attributable to the calibration process. Accordingly, the fluid level in the vessel decreases during the calibration process.

[0122] The calibration may serve to compensate for the deviation between the (default) flow rate indicated by the flow meter and measured flow rate, e.g. by setting factor in the permeate flow meter. The amount of fluid flown along the circuit is measured, e.g. by way of the load cell.

[0123] The method is a control method, wherein method steps are controlled accordingly. The present invention is also directed to a control unit configured to carry out (controlling) the method of the invention.

[0124] The pump may be referred to as main pump and / or feed pump.

[0125] Optionally, the amount of fluid in the vessel is determined by gravimetric measurement, further optionally by means of a load cell of a vessel holder of the present invention, wherein the vessel is supported by the vessel holder.

[0126] The present invention relates to the bioprocess apparatus of claim 47. Accordingly, a bioprocess apparatus (configured to form a fluid circuit of a bioprocess system) for tangential flow filtration (through a filter) is provided. The apparatus comprises at its outer side, a vessel holder for holding a recirculation vessel (optionally single use vessel) containing fluid, optionally the vessel holder of the present invention, wherein the vessel holder is attached to the apparatus, an upper set of valves including at least one pinch valve for governing (controlling) supply of fluid and a pressure control valve for controlling pressure in the filter downstream the filter, wherein the upper set of valves is located at least in parts higher than the vessel holder, pump drive means, optionally of a membrane pump,for engagement / cooperation with a disposable pump unit to form a pump for pumping fluid along the fluid circuit, wherein the pump is, in the fluid circuit, downstream the vessel, a lower set of valves including at least two pinch valves for governing (controlling) fluid flow downstream the pump, wherein at least one of the valves of the lower set of valves is located lower than the pump drive means, and wherein the upper set of valves is located higher than the lower set of valves.

[0127] The idea underlying this aspect of the invention is improvement of the performance of TFF and / or reduction of wasted fluid, i.e. of hold-up volume. In particular, the positions of the entities support drainage of fluid from the upper set of valves, though the vessel and to the lower set of valves. This may reduce the distance and hence tubing used for the circuit.

[0128] The apparatus may be configured for a single-use / disposable fluid kit of the invention and / or a filter holder adaptor if the invention being mounted to the apparatus.

[0129] The upper set of valves may define the location of the intersecting tubes at the highest position / level of the recirculation part of the fluid circuit. Specifically, the upper set of valves may be located higher than the vessel holder and / or the vessel inlet port, so as to support drainage of fluid toward the vessel.

[0130] The vessel does not need to be located on a lab bench or on a separate entity, but directly attached, via vessel holder, to the front of the apparatus. The holder may hold the vessel at an at an elevated level above a lab bench, e.g. in an upper half of the apparatus.

[0131] The lower set of valves allows for directing fluid flow along the filter or towards collection means.

[0132] The entities as defined in claim 47 may be located at the front of the apparatus, i.e. in the retentate fluid circuit. The apparatus may be free of a flow meter at the front, i.e. in the retentate fluid circuit.

[0133] To make the apparatus relatively small, further entities may be located at one or two side surfaces of apparatus. For example, at a (right) side of the apparatus: the flow meter for determination of permeate flow rate may be located; hence, at least in parts, the permeate fluid circuit may be located this side. At a (left) side (optionally opposite to the other side), the transfer pump and / or fluid supply ports may be located.

[0134] The apparatus does not need to comprise the single-use kit of the invention and / or a filter.

[0135] Optionally, at least one, optionally all, of the valves of the upper and lower sets of valves include a tube guidance, optionally a valve cavity, for receiving a part of the tubing and guiding the tubing via the tube guidance in a predetermined direction. The tube guidance of at least one valve of the upper and lower sets of valves may be inclined relative to the horizontal, when the apparatus is installed on site, such that tubing received by the at least one valve is inclined relative to the horizontal accordingly. Optionally, all pinch valves of the apparatus include such guidance.

[0136] The tube guidance may be configured to capture a part of the tubing, in particular by surrounding the tubing along its circumference. Tube guidance may support a slope / inclination of tube, including bending of tube.

[0137] Optionally, the lower set of valves includes the at least one valve having the inclined tube guidance, optionally such that the at least one valve is arranged for fluid connection to a fluid junction of the present invention, wherein the at least one valve is downstream of the filter port.

[0138] Optionally, the lower set of valves includes a bypass valve establishing a fluid bypass path (including the bypass tube) bypassing the filter. Providing a bypass valve for a corresponding bypass path may allow for e.g. calibration of various entities, which requires bypassing of the filter. Accordingly, the bypass valve / line allows for automatic calibration.

[0139] Optionally, the apparatus includes a vessel holder of the present invention, optionally detachably mounted to the apparatus for holding the vessel. The vessel holder may be exchanged, and dedicated vessel holders for different vessels may selectively be attached to the apparatus.

[0140] Optionally, the apparatus includes a control unit of the invention, in particular of claim 40, 43 and / or 46. The control unit may also be referred to as control circuitry. The control unit may be a common control unit configured to carry out the steps of the various method claims.

[0141] A bioprocess system of the invention, optionally the bioprocess system of claim 1 , may include the bioprocess apparatus of the invention and the kit of the invention and optionally the filter holder adaptor of the invention, optionally including a filter holder for holding a filter for tangential flow filtration, further optionally also the filter for tangential flow filtration.

[0142] The present invention is also directed to the use of the bioprocess system of the invention for tangential flow filtration. The use comprises flowing fluid thoughthe fluid circuit, wherein fluid is contained in the vessel, pumped by the pump and flown through the filter, wherein permeate fluid passes through the filter and retentate fluid is returned / recirculated to the vessel.

[0143] Detailed embodiments and further advantages and features related to the present invention are described in the following, wherein these examples shall not be regarded as limiting the invention.BRIEF DESCRIPTION OF THE DRAWINGSFig. 1 (a) shows a front view of a system of an embodiment of the invention. Fig. 1(b) shows, from the left side, a perspective view of a system of an embodiment of the invention.Fig. 1(c) shows, from the right side, a perspective view of a system of an embodiment of the invention.Fig. 2(a) shows a front view of an apparatus of an embodiment of the invention.Fig. 2(b) shows a (left) side view of an apparatus of an embodiment of the invention.Fig. 2(c) shows a (right) side view of an apparatus of an embodiment of the invention.Fig. 2(d) shows a sectional perspective view of a pinch valve of an apparatus of an embodiment of the invention.Fig. 3 shows a perspective view of a fluid kit of an embodiment of the invention.Fig. 4(a) shows a perspective view of a junction connected to tubing, of an embodiment of the invention.Fig. 4(b) shows a perspective view of a junction of an embodiment of the invention.Fig. 4(c) shows a cross-sectional view of a junction of an embodiment of the invention.Fig. 5(a) shows a front view of a system of an embodiment of the invention. Fig. 5(b) indicates, for Fig. 5(a), the fluid flow path during filtration.Fig. 5(c) indicates, for Fig. 5(a), a fluid flow path for priming of the pump. Fig. 5(d) indicates, for Fig. 5(a), the fluid flow path for pump calibration.Fig. 5(e) indicates, for Fig. 5(a), the fluid flow path for filter integrity testing. Fig. 5(f) indicates, for Fig. 5(a), the fluid flow path for retentate collection.Fig. 5(g) indicates, for Fig. 5(a), in Fig. (g)(i) the fluid flow path for flow meter calibration at the front side, and in Fig. (g)(ii) the remaining fluid flow path for flow meter calibration at the right side.Fig. 6(a) shows a perspective view of a sensor of an embodiment of the invention.Fig. 6(b) shows a cross-sectional view of a sensor of an embodiment of the invention.Fig. 7(a) shows a sectional perspective view of a vessel holder of an embodiment of the invention.Fig. 7(b) shows a top view of a vessel holder of an embodiment of the invention.Fig. 7(c) shows a cross-sectional view of a vessel holder including a vessel, of an embodiment of the invention.Fig. 7(d) shows a perspective view of a vessel holder including a vessel, of an embodiment of the invention.Fig. 7(e) shows a perspective view of a vessel holder including a vessel, of an embodiment of the invention.Fig. 8(a) shows a perspective view of a disassembled filter holder adaptor and a filter holder, of an embodiment of the invention.Fig. 8(b) shows a perspective view of an assembled filter holder adaptor including a filter holder, of an embodiment of the invention.Fig. 8(c) shows, from a side, a perspective view of a filter holder adaptor of an embodiment of the invention.Fig. 8(d) shows, from a side, a detailed perspective view of a filter holder adaptor of an embodiment of the invention.DETAILED DESCRIPTION

[0144] Fig. 1(a) shows a front view of a bioprocess system 1 for tangential flow filtration. The system 1 comprises a bioprocess apparatus 2, a fluid kit 3, and a filter 5.

[0145] The apparatus 2 includes feet 24 for placing the apparatus 2 on a bench top. The system 1 comprises at least a fluid circuit 10 including tubing 13 for flowing fluid. More specifically, the fluid circuit 10 is provided outside a housing / chassis of the apparatus 2.

[0146] As retentate / recirculation circuit forming a part of the fluid circuit 10 is provided at a front surface of the apparatus 2, as shown in Fig. 1 (a),

[0147] Part of the recirculation circuit is an upper fluid junction J1 including at least one fluid inlet path via a supply section 10g of the fluid circuit 10 for supply of fluid, and a retentate path including recirculation sections 10a-10f of the fluid circuit 10, including a pressure control valve 16 for controlling pressure in the filter 5 downstream the filter 5. Hence, in the upper fluid junction J1 , freshly supplied fluid (via section 10g) and recirculated retentate (via section 10d) merge, and flow into the recirculation vessel 4 (via sections 103, 10f). The upper fluid junction J1 includes an upper set of valves V1. The upper fluid junction J1 may include an intersection / branch, here including four branches.

[0148] Part of the recirculation circuit is also the recirculation vessel 4 containing and storing fluid.

[0149] A vessel holder 9 is attached to the apparatus 2 and holds the vessel 4 at an elevated level of the apparatus 2 above the level of the feet 24. Specifically, the vessel stores fluid freshly supplied and recirculated retentate, supplied via the section 10f of the fluid circuit.

[0150] Part of the recirculation circuit is a pump 11 , so-called main pump, provided downstream the vessel 4 and pumps fluid along the fluid circuit 10.

[0151] Part of the recirculation circuit is also a lower fluid junction J2 provided downstream the pump 11. The lower fluid junction J2 includes a junction inlet path (here the section 10b) fluidly connecting the pump 11 and the junction 7, a filter connection path connecting the junction 7 and the filter 5, and a drain path including a drain section 10h of the fluid circuit 10 for draining fluid from the junction 7. The lower fluid junction J2 includes a lower set of valves V2. The lower fluid junction J1 includes the junction 7.

[0152] The recirculation circuit includes and fluidly connects the vessel 4, the filter 5, the upper J1 and lower J2 fluid junctions by way of the tubing.

[0153] Fig. 1 (a) further shows part of the upper fluid junction J1 three pinch valves 17 and a control valve 16. Between the pressure control valve 16 and the filter 5, a sensor 8 is provided. The upper fluid junction J1 is connected, via the pressure sensor 7e to the vessel 4. The vessel 4 is fluidly connected to the pump 11 , which fluidly connects to the junction 7. The junction 7 forms, together with the three pinch valves 17, the lower fluid junction J2.

[0154] Further, the apparatus 2 comprises the secondary supply ports 14a, b, c, d for supply of fluid, for example for priming. Each of the secondary supply ports 14a, b, c, d connects to the fluid circuit via a pinch valve 17 and sideways. Outlet ports 15 extends downwards and includes a drain port 15a, a collection port 15b and a permeate port 15c.

[0155] The system 1 is configured to facilitate drainage of fluid from the inlet path in a supply section 10g to a drain path in the drain section 10h, as shown in Fig.1(a). Fluid is flown through the fluid circuit 10, wherein fluid is contained in the vessel 4, pumped by the pump 11 and flown through the filter 5, wherein permeate fluid passes through the filter 5 and retentate fluid returns to the vessel 4.

[0156] Example lengths and volumes of the system 1 of the present invention are summarized in the following table, wherein Fig. 1(a) indicates the respective sections a to f in the fluid circuit 10, and Fig. 3 indicates the respective sections a to f in the tubing 13, wherein the sections in the fluid circuit 10 are formed by the respective section of the fluid 13.

[0157] A total length of the tubing 13 in the recirculation circuit 10a-1 Of is less than 1000 mm, optionally less than 900 mm, further optionally less than 800 mm. A total volume of fluid receivable by the tubing 13 in the recirculation circuit 10a-10f is less than 10 ml, optionally less than 8 ml.

[0158] A tube length between the vessel 4 and the pump 11 may be less than 300 mm and / or a volume received by the tube length may be less than 3 mm (section 10a of the circuit and / or tube 13a of the tubing). Additionally or alternatively, a tube length between the filter 5 and the recirculation vessel 4 may be less than 300 mm and / or a volume received by the tube length may be less than 3 mm (sections 10c and 10d of the circuit and / or tubes 13c and 13d of the tubing).

[0159] Optionally, a tube length between the pump 11 and the lower fluid junction J2 (namely the junction 7, as described below) is less than 120 mm, further optionally about 100 mm and / or volume of fluid received by the tubing may be less than 1 ml (see section 10b of the circuit and / or tube 13b of the tubing).

[0160] Fig. 1 (b) shows, from the left side, a perspective view of the system 1. Here, the fluid circuit upstream the recirculation circuit is located. Primary supply ports 20a, b, c are located for the supply of fluid to be filtered. A pinch valve 17 is provided for each primary supply port 20a, b, c. The primary supply ports 20a, b, c are fluidly connected to the transfer pump 12, via an air sensor 22. The transfer pump 12 is connected to the supply section 10g of the fluid circuit 10.

[0161] Fig. 1 (c) shows, from the right side, a perspective view of the system 1. Here, the permeate circuit is located. A sensor 8, a flow meter 18, a flow cell 19and a pressure control valve 16 are fluidly connected and form part of the permeate circuit, and are fluidly connected to the drain ports 15, the latter located at the front side.

[0162] Fig. 2(a) to 2(c) show the apparatus 2, wherein no fluid kit 3 is mounted to the apparatus 2. The tubing 13 of the kit 3 to be mounted to the apparatus 2 is indicated in dashed lines in Fig. 2(a) to 2(c). The apparatus 2 is configured to form a fluid circuit 10 of a bioprocess system 1 for tangential flow filtration through the filter 5, once the kit 3 and the filter 5 have been mounted to the apparatus 2 to form the system 1.

[0163] Fig. 2(a) shows a front view of the bioprocess apparatus 2. The apparatus 2 comprises, at its outer side, in particular at its front, the vessel holder 9 for holding a recirculation vessel (not shown in Fig. 2(a)), wherein the vessel holder 9 is attached to the apparatus 2.

[0164] The apparatus 2 comprises an upper set of valves V1 including three pinch valves 17 for governing supply of fluid and a pressure control valve 16 for controlling pressure in the filter 5 downstream the filter 5. The upper set of valves V1 is located at least in parts higher than the vessel holder 9.

[0165] The apparatus 2 comprises pump drive means 11 b of a membrane pump 1 for engagement with a disposable pump unit 11a (not shown in Fig. 2(a)) to form the pump 11 for pumping fluid along the fluid circuit. The pump drive means 11b and, thus, the pump 11 is, in the fluid circuit, downstream the vessel 4.

[0166] The apparatus 2 comprises a lower set of valves V2 including three pinch valves 17 for governing fluid flow downstream the pump 11. The three valves of the lower set of valves V2 are located lower than the pump drive means 11 b. The upper set of valves V1 is located higher than the lower set of valves V2.

[0167] The lower set of valves V2 includes, as one of the three valves 17, a bypass valve establishing a fluid bypass path (through the bypass tube 13d’, as shown in Fig. 3) bypassing the filter 5.

[0168] The apparatus 2 includes the vessel holder 9, which is detachably mounted to the apparatus 2 and holds the vessel 4. The vessel holder 9 is described in connection with Fig. 7 in more detail below.

[0169] A connector 23 for a sensor 8, which is described in detail in connection with Fig. 6, is provided at the apparatus 2. A plurality of (pinch) valves 17 is provided.

[0170] A number of the valves 16, 17 are inclined. Tube guidance 17a, as explained in more detailed in connection with Fig. 2(d), may be inclined accordingly, namely downwards in the flow direction. For example, the (downwards) inclination of the pressure control valve 16 in the upper set of valves V1 downstream the filter port 21a (see Fig. 5(a)) may be between 5 and 15 °, optionally about 8 to 12°, relative to the horizontal H, as indicated in Fig. 2(a).

[0171] The (downwards) inclination of the valve 17 of the lower set of valves V2 downstream the drain port 7c of the junction 7 (as indicated in Fig. 4(b) and 4(c)) may be about 30 to 50°, optionally between 38 and 42° relative to the vertical V. The (downwards) inclination of the valve 17 of the lower set of valves V2 downstream the filter connection port 7b of the junction 7 (as indicated in Fig. 4(b) and 4(c)) may be about 60 to 80°, optionally between 65 and 70° relative to the vertical V.

[0172] Fig. 2(b) shows, from the left side, a perspective view of the apparatus 2. The air sensor 22 and the transfer pump 12 are provided at the apparatus 2, as well as pinch valves 17.

[0173] Fig. 2(c) shows, from the right side, a perspective view of the apparatus 2. A sensor connector 23 for the sensor 8, the flow meter 18 and a connector 23 for the flow cell 19 are provided.

[0174] Fig. 2(d) shows a sectional perspective view of a pinch valve 17 of the apparatus 2. The valve 17, i.a. of the upper V1 and lower V2 sets of valves, includes a tube guidance 17a, as shown in Fig. 2(d). The tube guidance 17a is formed as a cavity, for receiving a part of the tubing (not shown in Fig. 2(d)) and guiding the tubing via the tube guidance 17a in a predetermined direction Di?a. The tube guidance 17a, i.e. the direction Di7a, of the valve 17 may be inclined relative to the horizontal H, when the valve is mounted to the apparatus 2. Hence, the tubing received by the valve 17 is inclined relative to the horizontal H, in the direction Di7a, in line with the tube guidance 17a. A piston 17b presses against the tubing so as compress the tubing received in the tube guidance 17a to stop fluid flow. Upon control of the movement of the piston 17b, the valve 17 is opened and closed.

[0175] Fig. 3 shows a perspective view of a single-use fluid kit 3. The kit 3 is to be disposed after a single use. The kit 3 is configured for being mounted to the bioprocess apparatus 2, shown in Fig. 2 above, to form a fluid circuit 10 of a bioprocess system 1 for tangential flow filtration, as shown in Fig. 1 and 5.

[0176] The kit 3 comprises the single-use recirculation vessel 4 receiving fluid of the fluid circuit 10, the single-use pump unit 11a for cooperation with re-useable pump drive means 11 b of the apparatus 2 for pumping fluid through the fluid circuit 10, filter ports 21, 21a for fluid connection to the filter (not shown in Fig. 3) for tangential flow filtration, and tubing 13 fluidly connecting the vessel 4, the pump unit 11a and the filter ports 21, 21a for flowing fluid in the fluid circuit. The tubing 13 includes three primary supply port 20a, b, c and three secondary supply ports 14a-d for supply of fluid, and three outlet ports 15a, b, c for fluid drainage or collection.

[0177] The vessel 4 of the kit 3 is described in more detail in connection with Fig.7 and the vessel holder 9.

[0178] The kit 3 includes a bypass tube 13d’ directly connecting the bypass valve (of the apparatus 2, not shown in Fig. 3) to the collection port 15b, such that the kit 3 is configured to establish a fluid path bypassing the filter port 21. The pump unit 11 a is located downstream the vessel 4, when the kit 3 is mounted to the apparatus 2 and used for filtration.

[0179] The kit 3 includes two sensors 8, which are described in more detail in Fig.6. One of the sensors 8 is provided downstream of the filter ports 21 and another one of the sensors 8 is provided in the permeate circuit, when the kit 3 is used for filtration. The two sensors 8 and the flow cell 19 (including a pH and UV sensor) are part of the kit 3.

[0180] The kit 3 comprises the fluid junction 7 which is described in more detail in Fig. 4. The junction 7 is located downstream the pump unit 11a, when the kit 3 is mounted to the apparatus 2 and used for filtration.

[0181] The kit 3 is to be used with the bioprocess apparatus 2 for forming a fluid circuit 10 of the bioprocess system 1. Specifically, the at least one inlet port 20a, b, c is connected to a fluid supply, the at least one outlet port 15a, b, c is connected to fluid collection means, and the filter ports 21 , 21a are connected to the filter 5. The pump unit 11a is engaged with the re-useable pump drive means 11b of the apparatus 2.

[0182] The kit 3 is configured to facilitate drainage of fluid from an inlet path in a supply tube 13g of the tubing 13 to a drain path in a drain tube 13h of the tubing, optionally the drain tube 13c’. Tube sections 13a-f corresponding to sections 10a-f of the fluid circuit 10 are provided in the tubing 13 of the kit 3. In the context of the junction 7, the junction inlet tube 13a’ (corresponding to the tube section 13b),the filter connection tube 13b’, the drain tube 13c’ (corresponding to the drain tube 13h), and bypass tube 13d’ are provided in the kit 3, see also the description in connection with Fig. 4(a).

[0183] In particular, the kit 3 of Fig. 3 includes at least the primary supply ports 20a-c, the supply tube 13g, the junction J1 , the vessel 4, the pump unit 11a, the junction 7, the bypass tube 13’, the outlet ports 15, the filter ports 21, 21a, the sensors 8, the flow cell 19, and the corresponding tubes 13a-f.

[0184] The tubing 13 of the kit 3 comprises the tube parts 13a-f, as described above in connection with Fig. 1(a) and the above table. Further, the tube parts 13a’ to 13d’ are referred to in connection with the kit 3.

[0185] Fig. 4(a) shows a perspective view of the fluid junction 7 connected to tubing, of an embodiment of the invention. Fig. 4(b) shows a perspective view of the fluid junction 7. Fig. 4(c) shows a cross-sectional view of the fluid junction 7. The fluid junction 7 is part of the fluid kit 3 and forms part of the fluid circuit 10 of the bioprocess system 1.

[0186] The junction 7 comprises four ports 7a, 7b, 7c, 7d, connected to respective tubes 13a’, 13b’, 13c’, 13d’, as shown in Fig. 4(a). The junction 7 includes an inlet port 7a for fluid connection in the fluid circuit downstream of the pump 11 of the fluid circuit, a filter connection port 7b for fluid connection in the fluid circuit upstream of the filter 5, a drain port 7c for fluid connection in the fluid circuit for draining fluid, and a bypass port 7d for fluid connection in the fluid circuit for establishing fluid flow bypassing the filter connection port 7b and / or the drain port 7c.

[0187] The fluid junction 7 further includes a fluid junction passageway 7f for flowing fluid through the junction 7. As shown in Fig. 4(c), the fluid junction passageway 7f includes an inlet-filter connection passageway 7f-ab fluidly connecting the inlet port 7a to the filter connection port 7b. The inlet-filter connection passageway 7f-ab includes an inlet passageway 7f-a at the inlet port 7a and a filter connection passageway 7f-b at the filter connection port 7b. A drain passageway 7f-c fluidly connects the inlet ports 7a to the drain port 7c. A bypass passageway 7f-d fluidly connects the inlet port 7a and the bypass port 7d for fluid connection in the fluid circuit for establishing fluid flow bypassing the filter connection port 7b and / or the drain port 7c.

[0188] As shown in Fig. 4(b) and 4(c), the drain port 7c is positioned such that an angle y between the inlet port axis a?a defined by the inlet port 7a, and a drain portaxis a?c defined by the drain port 7c is more than 90° and less than 160°, optionally between 120 and 140°.

[0189] An angle [3 between the filter connection port axis a?b defined by the filter connection port 7b and the drain port axis a?c defined by the drain port 7c is less than 120°, optionally less than 100°.

[0190] The inlet passageway 7f-a is angled relative to the drain passageway 7f-c at the angle y. The filter connection passageway 7f-b is angled relative to the drain passageway 7f-c at the angle [3.

[0191] The inlet and filter connection ports 7a, 7b are positioned such that an angle a between an inlet port axis a?a defined by the inlet port 7a, and a filter connection port axis a?b defined by filter connection port 7b is more than 90° and less than 160°, optionally between 120 and 140°. The inlet passageway 7f-a and the filter connection passageway 7f-b are angled relative to each other at the angle a.

[0192] As shown in Fig. 4(c), the inlet passageway 7f-a and the filter connection passageway 7f-b intersect at an intersection 7g. Here, the inlet passageway 7f-a and the filter connection passageway 7f-b are angled relative to each other at the angle a.

[0193] The drain passageway 7f-c intersects the inlet-filter connection passageway 7f-ab at the intersection 7g. The drain passageway 7f-c is angled at the angle [3 relative to the filter connection passageway 7f-b at the intersection 7g. The drain passageway 7f-c is angled at the angle y relative to the inlet passageway 7f-a at the intersection 7g. When the junction 7 is mounted to the apparatus 2, the direction P faces away from the apparatus 2.

[0194] The bypass passageway 7f-d and the inlet passageway 7f-a intersect upstream the intersection 7g. The bypass passageway 7f-d and the inlet-filter connection passageway 7f-ab are perpendicular to each other.

[0195] As shown in Fig. 4(a) and 4(b), the junction 7 comprises a pressure sensor 7e, which is fluidly connected to the passageway 7f. The junction 7 is configured such that the pressure sensor 7e is configured to measure the pressure of fluid in the passageway 7f, optionally upstream the intersection 7g. The pressure sensor 7e protrudes in a direction P other than the at least four ports 7a, 7b, 7c, 7d and orthogonal to the at least four ports, as shown in Fig. 4(b).

[0196] As shown in Fig. 4(a), when using the junction 7 in the kit 3, a fluid connection with the fluid circuit is established by the inlet port 7a of the fluid junction connected with a junction inlet tube 13a’ of tubing 13 of the fluid circuit, the filterconnection port 7b of the fluid junction with the filter connection tube 13b’ of the tubing 13 of the fluid circuit, the drain port 7c of the fluid junction with the drain tube 13c’ of the tubing 13 of the fluid circuit, and the bypass port 7d with the bypass tube 13d’.

[0197] The passageway 7f is configured as an internal cavity (e.g. milled out from a solid main body 7h) within the junction 7. Hence, the passageway 7f may be formed within the main body 7h from which the ports 7a, 7b, 7c, 7d protrude. The ports 7a, 7b, 7c, 7d are male ports.

[0198] In one embodiment, the inlet port axis a?a and the inlet passageway 7f-a are inclined relative to the horizontal H, as indicated in Fig. 4(c). The drain port axis a?c is angled relative to the vertical V, when the fluid junction 7 is mounted to the apparatus 2, as indicated in Fig. 4(c). This supports drainage and flow of fluid. The bypass port axis a?d may but does not have to be vertical, when the fluid junction 7 is mounted to the apparatus 2. The same or substantially same inclination may be identified for the corresponding valves 17 downstream the junction 7 and their respective tube guidance 17a.

[0199] Fig. 5(a) shows a front view of the system 1 of an embodiment of the invention, as shown in Fig. 1 (a). In particular, the filter ports 21, 21a are connected to the filter 5, so as to include the filter 5 in the fluid circuit.

[0200] Fig. 5(b) indicates with arrows, for the system 1 shown in Fig. 5(a), the fluid flow path in the fluid circuit during filtration. Fluid is provided via the transfer pump 12, from the primary supply ports 20a, b, c, as shown in Fig. 1(b), to the upper fluid junction J1. Here, fluid flows into the vessel 4, then out of the vessel 4 through the pump 11 to the junction 7. Fluid passes through the filter connection port (7b, as shown in Fig. 7) into the filter 5. Permeate passes through the filter 5 into the permeate circuit, which is mainly located at the right side of the apparatus 2, as shown in Fig. 1(c). Permeate drains via the permeate port 15c. Retentate recirculates via the filter port 21a through the pressure control valve 16 into the vessel 4, in the recirculation circuit.

[0201] Fig. 5(c) indicates with arrows, for the system shown in Fig. 5(a), the fluid flow path during priming of the pump. Fluid is flown from one of the secondary supply ports 14a-d through the pump 11 , via the bypass port (7d, as show in Fig.4) and the bypass tube 13d’ to the collection port 15b.

[0202] Fig. 5(d) indicates with arrows, for the system shown in Fig. 5(a), the fluid flow path during pump calibration. For pump calibration, fluid is flown from thevessel 4 by the pump 11 via the bypass port (7d, as show in Fig. 4) and the bypass path through the bypass tube 13d’ to the collection port 15b.

[0203] Specifically, fluid is provided in the vessel 4, a fluid calibration circuit bypassing the filter 5 is established, fluid is flown from the vessel 4 to the collection port 15b by pumping fluid at a predetermined default flow rate by means of the pump 11 along the fluid calibration circuit. The amount of fluid in the vessel 4 at at least two different points in time within the time period during which fluid is flown along the calibration circuit at the predetermined default flow rate is measured, to obtain a measured flow rate representative of the fluid flow. The measured flow rate and the predetermined default flow rate for calibration of the pump are compared, to obtain a calibrated flow rate of the pump. Finally, the pump 11 is calibrated based on the calibrated flow rate.

[0204] The amount of fluid in the vessel 4 over time is determined by gravimetric measurement, namely by means of the load cell 9a of the vessel holder 9, as described in Fig. 7 in more detail. The vessel 4 is supported by the vessel holder 9.

[0205] Fig. 5(e) indicates with arrows, for the system 1 shown in Fig. 5(a), the fluid flow path during filter integrity testing. Specifically, filter ports 21b, c, d are provided in a closed state and the filter retentate outlet port 21a is provided in an open state. The fluid test circuit is established by fluidly connecting at least the transfer pump 12 and the filter 5 via the retentate outlet port 21a. Gas (here: air) is supplied to the fluid test circuit by means of the transfer pump 12, when the fluid test circuit has been established and the further filter ports 21 b, c, d are closed, so as to pressurize the system, in particular the fluid test circuit, until a target pressure is reached within the filter 5. The pressure in the filter 5 is measured directly or indirectly for the filter 5, by means of a pressure sensor (e.g. such as 7e or 8b included as in other entities) next to the filter 5 in the fluid test circuit (upstream during filtration), so as to obtain a measured pressure, after the target pressure has been reached and supply of gas has been stopped. Measuring the pressure includes measuring the pressure indicative of the pressure in the filter, e.g. the pressure outside the filter 5. The measured pressure is monitored over time during a time interval, in particular a decay of the pressure over time is monitored, so as to obtain a pressure decay rate. The test result is identified based on the pressure decay rate and indicates whether the testing was successful.

[0206] Fig. 5(f) indicates with arrows, for the system 1 of Fig. 5(a), the fluid flow path during retentate collection. From the junction J1, along a first path, fluid drains to the vessel 4, then out of the vessel through the pump 11 to the junction 7, via the inlet port (7a, as shown in Fig. 7). along a first path, fluid drains via the filter 5 to filter connection port (7b, as shown in Fig. 7) of the junction 7. In the junction 7, the first and second paths merge, and fluid drains via the drain port 7c of the junction 7 to the drain port 15a.

[0207] Fig. 5(g) indicates with arrows, for the system 1 of Fig. 5(a), in Fig. (g)(i) the fluid flow path during permeate flow meter calibration at the front side of the apparatus 2, and in Fig. (g)(ii) the remaining fluid flow path during permeate flow meter calibration, at the right side of the apparatus 2. The entities indicated in Fig. (g)(ii) correspond to the entities shown in Fig. 1(c).

[0208] Specifically, fluid is provided in the vessel 4 and the fluid filtration circuit including the filter 5 is established. Fluid is flown from the vessel 4 to the collection port 15b along the fluid filtration circuit by pumping fluid by means of the pump 11. Fluid downstream the filter 5 flows through the flow meter 18 at an indicated flow rate indicated by the flow meter. The amount of fluid in the vessel 4 is measured at at least two different points in time within the time period during which fluid is flown along the fluid filtration circuit to obtain a measured flow rate representative of the fluid flow. The measured flow rate and the indicated flow rate of the flow meter are compared to obtain a calibrated flow rate of the flow meter. The flow meter is calibrated based on the calibrated flow rate.

[0209] The amount of fluid in the vessel 4 is determined by gravimetric measurement, namely by means of the load cell 9a of a vessel holder 9, as described in connection with Fig. 7. The vessel 4 is supported by the vessel holder 9.

[0210] Fig. 6(a) shows a perspective view of a sensor 8. Fig. 6(b) shows a cross-sectional view of the sensor 8. The sensor 8 is to be mounted to the bioprocess apparatus 2, namely as part of the fluid kit 3.

[0211] As shown in Fig. 6(b), the sensor 8 comprises a sensor inlet 8d and a sensor outlet 8e for fluid connection to the fluid circuit 10. The sensor passageway 8c is configured for flowing fluid and fluidly connects the sensor inlet 8d and sensor outlet 8e for flowing fluid of the fluid circuit 10 through the sensor 8. The sensor 8 comprises a conductivity measurement unit 8a extending into the sensor passageway 8c for determination of the electrical conductivity of fluid flowingthrough the sensor passageway 8c. The sensor further comprises a pressure measurement unit 8b for determination of the pressure of fluid flowing through the sensor passageway 8c.

[0212] The pressure measurement unit 8b and the conductivity measurement unit 8a are located at different sides of the sensor passageway 8c, namely at opposite sides of the sensor passageway 8c.

[0213] The sensor inlet 8d and the sensor outlet 8e define a sensor inlet axis csd and a sensor outlet axis cse, respectively. The sensor inlet axis csd and the sensor outlet axis cse are offset by an offset o and parallel to each other. The sensor passageway 8c includes a step 8f, which forms a cavity 8g, into which the conductivity measurement unit 8a protrudes and at which the pressure measurement unit 8b measures the pressure.

[0214] For use, a fluid connection with the fluid circuit 10 is established by connecting the sensor inlet 8d and the sensor outlet 8e to tubing of the fluid circuit 10.

[0215] Fig. 7(a) shows a sectional perspective view of the vessel holder 9. Fig.7(b) shows a top view of the vessel holder 9. Fig. 7(c) shows a cross-sectional view of the vessel holder 9 including the vessel 4. Fig. 7(d) shows a perspective view of the vessel holder 9 including the vessel 4. Fig. 7(e) shows a perspective view of the vessel holder 9 including the vessel 4. The holder 9 supports the vessel 4, which may be part of a fluid circuit 10 of the apparatus 2. The holder 9 is, as shown in Fig. 1(a), attached to the apparatus 2.

[0216] With continued reference to Fig. 7, the holder 9 comprises mounting means 9e for mounting the vessel holder 9 to an outer housing of the apparatus 2. Further, the holder 9 includes a receiving portion 9f, which is substantially circular and receives a bottom of the vessel 4. The holder 9 further includes the load cell 9a below and included in the receiving portion 9f. The load cell 9a measures the weight of the vessel 4 (including the fluid contained in the vessel), when the vessel 4 is received by the receiving portion 9f. The load cell 9a is at least partially circular and is donut-shaped.

[0217] The holder 9 includes a magnet impeller drive 9b for magnetically agitating a magnetic stirrer 4d in the vessel 4 for mixing of fluid in the vessel 4. The magnet impeller drive 9b is located in the middle of the receiving portion 9f and is surrounded by the load cell 9a. The magnet impeller drive 9b protrudes from theload cell 9a in a length direction l_4f of the wall 4f of the vessel and in a direction opposite to gravity, when the vessel holder 9 is mounted to the apparatus 2.

[0218] Fig. 7(a) shows a surface 9c for contact with the bottom of the vessel 4. The surface 9c covers the magnet impeller drive 9b.

[0219] The holder 9 includes a cantilever portion 9d connecting the receiving portion 9f and the mounting means 9e of the holder. The cantilever portion 9d has a substantially trapezoidal shape and is angled such that the mounting means 9e is inclined relative to a tangential to the cylindrical wall 4f of the vessel 4 parallel to an outer side of a housing of the apparatus 2, when the vessel 4 is received in the vessel holder 9 and the vessel holder 9 is mounted to the apparatus 2.

[0220] As shown in Fig. 7(d) and Fig. 7(e), the holder 9 further comprises a tube fixation 9g configured to at least partially fix tubing fluidly connecting the vessel 4 to the holder 9, to the cantilever portion 9d. The tube fixation 9g further includes two slots 9h for holding and receiving the respective tubing. With reference to Fig.3, the tube 13f to which the inlet 4c is connected, and the tube 13a to which the outlet 4b of the vessel 4 is connected are received by a slot 9g. The tube fixation 9g protrudes from the remaining cantilever portion 9d upwards, when the holder is mounted to the apparatus 2.

[0221] With reference to the vessel 4, Fig. 7(a) and 7(c) show that the recirculation vessel 4 has a bottom (region 4a) and a cylindrical wall 4f arising from the bottom. The bottom includes an inclined bottom region 4a which is inclined relative to a plane perpendicular to the wall 4f of the vessel 4 and relative to the horizontal H when the recirculation vessel 4 is mounted to the bioprocess apparatus 2.

[0222] The bottom of the recirculation vessel 4 includes a vessel outlet 4b and the bottom comprises an indentation 4e fluidly connecting to the vessel outlet 4b. As shown in Fig. 7(c), the indentation 4e is included in the inclined bottom region 4a. As shown in Fig. 7(d) and 7(e), the vessel 4 further includes a vessel inlet 4c for supplying the vessel 4 with fluid. Specifically, the vessel inlet 4c is to connected with the section 13f of the tubing 13, and the vessel outlet 4b is to be connected with the section 13a of the tubing 13 (wherein Fig. 7 (d) and 7(e) do not show the tubing 13; see Fig. 3 in connection with the tube sections 13).

[0223] Fig. 8(a) shows a perspective view of a disassembled filter holder adaptor 6 and a filter holder 25 (with no filter 5 being provided between filter holder jaws 25b). Fig. 8(b) shows a perspective view of an assembled filter holder adaptor 6 mounted to the filter holder 25. Fig. 8(c) shows, from a side, a perspective viewof the filter holder adaptor 6 without filter holder 25. Fig. 8(d) shows, from a side, a detailed perspective view of the filter holder adaptor 6.

[0224] The filter holder adaptor 6 attaches the filter holder 25 holding a filter 5 (not shown in Fig. 8) to the bioprocess apparatus 2. The filter holder adaptor 6 includes at least one apparatus-side adaptor 6c, which is detachably attachable to the apparatus 2. The apparatus-side adaptor 6c is for attachment to the apparatus 2 and comprises apparatus-side engagement means 6d. The filter holder adaptor 6 further includes at least one filter-side adaptor 6b, which is detachably attachable to the filter holder 25. The filter holder 25 compresses and holds the filter material of the filter 5 (not shown in Fig. 8).

[0225] The filter-side adaptor 6b comprises filter-side engagement means 6e. The apparatus-side engagement means 6d and the filter-side engagement means 6e are configured for mechanical engagement with each other. The apparatus-side adaptor 6c and the filter-side adaptor 6b are configured such that mechanically engaging the apparatus-side engagement means 6d and the filter-side engagement means 6e attaches the filter holder 5 to the apparatus 2, when the apparatus-side adaptor 6c and the filter-side adaptor 6b are attached to the apparatus 2 and the filter holder 25, respectively.

[0226] The filter-side adaptor 6b is attachable to a substantially planar jaw 25b of the filter holder 25, by means of mechanical attachment means 6a, and includes a substantially planar frame or plate 6b for lying against the jaw 25 of the filter holder 25. Specifically, the filter holder 25, in particular its jaw 25b, comprises holes 25a for receiving the mechanical attachment means 6a for fastening the filter-side adaptor to the filter holder 25. As shown in Fig. 8(a), the mechanical attachment means 6a are screws, and the holes 25a are screw holes.

[0227] The filter-side engagement means includes a protrusion 6e which is received by the apparatus-side engagement means 6d, see Fig. 8(b). The protrusion 6e protrudes in a direction perpendicular to a plane (e.g. the plane defined by the horizontal H and the vertical V) defined by the filter-side adaptor 6c, e.g. the horizontal direction H. The apparatus-side adaptor 6c includes at least one bracket / bar 6c and least one recess 6d formed in the bracket / bar 6c. The recess 6d receives the filter-side engagement means 6e. As shown in Fig. 8(a), the recess 6d is open in a direction Led (the vertical direction V) of a plane defined by the bar / bracket 6c, when the filter-side adaptor 6b and the apparatus-side adaptor 6c are in engagement.

[0228] Example dimensions of the bar 6c are about 70 x 40 x 25 mm. An example length of the protrusion 6e (in the horizontal direction H) is less than 30 mm, about 22 mm.

[0229] As shown in Fig. 8(c), the apparatus-side adaptor 6c comprises an inclined wall 6f which faces away from the filter-side adaptor 6b and is inclined relative to the vertical V and the filter-side adaptor 6c. The wall 6f is inclined towards the filterside adaptor 6b when seen in the direction opposite to gravity, i.e. in the direction V, as indicated in Fig. 8(c). Put differently, the wall 6f inclined away from the filterside adaptor 6b, when seen in the direction of gravity. As a result, the distance of the inclined wall 6f relative to the filter-side adaptor 6b increases in the direction opposite to gravity, when the filter-side engagement means 6e and the apparatusside engagement means 6d are in engagement.

[0230] The angle of inclination is about 5° in Fig. 8(c). The protrusion 6e has the enlarged head, and the inclination facilitates engagement between the head and the apparatus-side adaptor 6c, when the filter-side adaptor 6b is brought into engagement with the apparatus-side adaptor, from above.

[0231] The apparatus-side engagement means, namely the recess 6d, is offset from a middle of the apparatus-side adaptor 6c, when seen in a length direction Lee of the apparatus-side adaptor means 6c.Fig. 8(d) shows that the recess 6e has a top opening 8g; hence, the recess 6e is open in an upper direction (opposite to gravity, when installed at the apparatus 2).

[0232] As shown in Fig. 8(d), the apparatus-side adaptor 6c includes a first 6h and an opposite second 6i side, wherein each of first and second sides is configured to face towards the apparatus 2, when the filter 5 is attached to the apparatus 2. In Fig. 8(d), the first side 6h faces towards the apparatus 2, as the second side 6i faces towards the filter holder 25.

[0233] In use, the filter holder 25 holding the filter 5 is attached to the filter-side adaptor 6b, and the apparatus-side adaptor 6c is attached to the apparatus 2. Then, the apparatus-side engagement means 6d and the filter-side engagement means 6e are engaged with each other.

[0234] Various aspects and embodiments of the present invention thus provide a bioprocess apparatus means, that may be used with a single-use fluid flow kit means, to provide a bioprocess apparatus means for optimizing the amount of fluid that can be recovered from a TFF process.

[0235] The detailed description of the invention is provided with respect to the embodiments depicted in the drawings. Various variations and alternatives may occur to the skilled person, based on the summary of the invention and the detailed description provided herein. These variations and alternatives are part of the invention in so far as they are covered by the appended claims and equivalents thereof.

[0236] With reference to the above, the term horizontal (H) as used herein may refer to a horizontal axis of the bioprocessing apparatus 2, e.g., when the apparatus is arranged to perform a bioprocessing operation and / or when the apparatus is arranged to rest on the apparatus feet 24. When discussing the horizontal for a respective component, the horizontal axis may be relative to a view, i.e. , face or side, of the bioprocessing apparatus 2 which the respective component is attached to or arranged to be attached to.

[0237] With reference to the above, the term vertical (V) as used herein may refer to a vertical axis of the bioprocessing apparatus 2, e.g., when the apparatus is arranged to perform a bioprocessing operation and / or when the apparatus is arranged to rest on the apparatus feet 24.

[0238] Vertical and Horizontal axes defining the term Horizontal (H) and Vertical (V) are illustrated relative to the bioprocessing system 1 and bioprocessing apparatus 2 in Figs. 1a-c, and 2a.

[0239] As illustrated in Figs 1a-c, the term Horizontal may be relative to a view or side of the bioprocessing apparatus 2.

[0240] Fig. 1a may illustrate a front view or front side of the bioprocessing apparatus 2. Fig. 1b may illustrate a left view or left side of the bioprocessing apparatus 2. Fig. 1c may illustrate a right view or right side of the bioprocessing apparatus 2.

[0241] With reference to the above, one or more features described in connection with any particular embodiment(s) may be combined with one or more features of one or more other embodiments, in any suitable manner.REFERENCE SIGNS1 bioprocess system2 bioprocess apparatus3 fluid kit4 recirculation vessel4a inclined bottom region4b vessel outlet4c vessel inlet4d magnetic stirrer4e indentation4f wall5 filter (cassette)6 filter holder adaptor6a fastener6b filter-side adaptor6c apparatus-side adaptor6d apparatus-side engagement means6e filter-side engagement means6f inclined wall of apparatus-side adaptor6g top opening of apparatus-side engagement means 6h first side6i second side7 junction7a inlet port7b filter connection port7c drain port7d bypass port7e pressure sensor7f, 7f--ab, 7f-a, 7f-b, 7f-c, 7f-d junction passageways7g intersection7h main body8 sensor8a conductivity measurement unit8b pressure measurement unit8c fluid sensor passageway8d sensor inlet8e sensor outlet8f step8g cavity9 vessel holder9a load cell9b magnet impeller drive9c surface9d cantilever portion9e mounting means9f receiving portion9g tube fixation9h slot for tube10 fluid circuit10a section a of the fluid circuit10b section b of the fluid circuit10c section c of the fluid circuit10d section d of the fluid circuit10e section a of the fluid circuit10f section f of the fluid circuit10g section g of the fluid circuit (supply section)10h section h of the fluid circuit (drain section)11 pump11a pump unit11b pump drive means12 transfer pump13 tubing13a-f tube sections corresponding to sections 10a-f of the fluid circuit 13g supply tube13h drain tube13a’ junction inlet tube13b’ filter connection tube13c’ drain tube13d’ bypass tube14a, b, c, d secondary supply ports15 outlet port15a drain port15b collection port15c permeate port16 pressure control valve17 pinch valve17a tube guidance17b piston18 flow meter19 flow cell20a, b, c primary supply ports21 filter port21a retentate outlet port22 air sensor23 sensor connector24 apparatus feet25 filter holder25a filter holder engagement means (screw holes)25b filter holder jaw25c filter holder fastener / screwV1 upper set of valvesV2 lower set of valvesJ1 upper fluid junctionJ2 lower fluid junctiona, [3, Y angles at junctiona?a, a?b, a?c junction port axis (inlet port axis, outlet port axis, drain port axis) asd, ase sensor port axis (sensor inlet axis, sensor outlet axis) o offset of sensor passagewaysLee length direction of apparatus-side adaptorl_4f length direction of wall of vesselLed direction of opening of recessDi7a direction of tube guidanceP direction in which pressure sensor protrudesG direction of gravityH horizontal V vertical

Claims

CLAIMS:

1. A bioprocess system (1 ) for tangential flow filtration, the system (1 ) comprising at leasto a fluid circuit (10) including tubing (13), provided at an outer side of an apparatus (2) of the system (1 ) and defining at least a recirculation circuit of the fluid circuit,o a recirculation vessel (4) for containing fluid,o a vessel holder (9) attached to the apparatus (2) and holding the vessel (4) at an elevated level of the apparatus (2),o a plurality of filter ports (21 ) for fluid connection to a filter (5) for tangential flow filtration, optionally the system including the filter (5), o a pump (11 ) downstream the vessel and for pumping fluid along the fluid circuit (10),o an upper fluid junction (J1 ) including at least one inlet path for supply of fluid via a supply section (10g) of the fluid circuit (10), and a retentate path including a pressure control valve (16) for controlling pressure in the filter (5) downstream the filter (5) in a recirculation circuit (10a-10f) of the fluid circuit (10),o a lower fluid junction (J2) downstream the pump (11 ) and including at least one junction inlet path, a filter connection path fluidly connecting to the filter (5) and a drain path for draining fluid via a drain section (1 Oh) of the fluid circuit,wherein the recirculation circuit (10) includes and fluidly connects the vessel (4), the plurality of filter ports (21), the upper (J1) and lower (J2) fluid junctions and optionally the filter (5), by way of the tubing, and the system (1) is configured to facilitate drainage of fluid from the inlet path to the drain path, whereina total length of the tubing in the recirculation circuit is less than 1 m, optionally less than 0.9m, further optionally less than 0.8 m,and / ora total volume of fluid receivable by the tubing in the recirculation circuit is less than about 10 ml, optionally less than about 8 ml.

2. A fluid junction (7) for being mounted to a bioprocess apparatus (2),44optionally as part of a fluid kit (3), to form part of a fluid circuit (10) of a bioprocess system (1 ), optionally for tangential flow filtration, wherein the junction (7) at least comprises at least four ports (7a, 7b, 7c, 7d) each for fluid connection to a respective tube (13a’, 13b’, 13c’, 13d’) forming part of the fluid circuit (10), the at least four ports includingo an inlet port (7a) for fluid connection in the fluid circuit downstream of a pump (11 ) of the fluid circuit,o a filter connection port (7b) for fluid connection in the fluid circuit upstream of a filter (5),o a drain port (7c) for fluid connection in the fluid circuit for draining fluid, ando a bypass port (7d) for bypassing the filter connection port (7b) and / or the drain port (7c), whereinthe fluid junction further includes a fluid junction passageway (7f) for flowing fluid through the junction, wherein the fluid junction passageway (7f) includes an inlet-filter connection passageway (7f-ab) fluidly connecting the inlet port (7a) and the filter connection port (7b) and including an inlet passageway (7f-a) at the inlet port (7a), and a filter connection passageway (7f-b) at the filter connection port (7b), a drain passageway (7f-c) fluidly connecting the inlet port (7a) to the drain port (7c), and a bypass passageway (7f-d) fluidly connecting the inlet port (7a) and the bypass port (7d) for bypassing the filter connection port (7b) and / or the drain port (7c).

3. The fluid junction of claim 2, whereino the drain port (7c) is positioned such that an angle y between the inlet port axis (a?a) defined by the inlet port (7a), and a drain port axis (a?c) defined by the drain port (7c) is more than 90° and less than 160°, optionally between 120 and 140°, and / or an angle [3 between the filter connection port axis (a?b) defined by the filter connection port (7b) and the drain port axis (a?c) defined by the drain port (7c) is less than 120°, optionally less than 100°, and / oro the inlet passageway (7f-a) is angled relative to the drain passageway (7f-c) at the angle y, and / or the filter connection45passageway (7f-b) is angled relative to the drain passageway (7f-c) at the angle [3and / oro the inlet and filter connection ports (7a, 7b) are positioned such that an angle a between an inlet port axis (a?a) defined by the inlet port (7a), and a filter connection port axis (a?b) defined by filter connection port (7b) is more than 90° and less than 160°, optionally between 120 and 140°,and / oro the inlet passageway (7f-a) and the filter connection passageway (7f-b) are angled relative to each other at the angle a.

4. The fluid junction of claim 2 or 3, wherein at least the inlet passageway (7f-a) and the filter connection passageway (7f-b) intersect at an intersection (7g), optionally at which the inlet passageway (7f-a) and the filter connection passageway (7f-b) are angled relative to each other at the angle a, andoptionally also the drain passageway (7f-c) intersecting the inlet-filter connection passageway (7f-ab) at the intersection (7g), further optionally wherein the drain passageway (7f-c) is angled at the angle [3 relative to the filter connection passageway (7f-b) at the intersection (7g) and / or the drain passageway (7f-c) is angled at the angle y relative to the inlet passageway (7f-b) at the intersection (7g).

5. The fluid junction of claim 4, wherein the bypass passageway (7f-d) and the inlet passageway (7f-a) intersect upstream the intersection (7g) and / or the bypass passageway (7f-d) and the inlet-filter connection passageway are perpendicular to each other.

6. The fluid junction of any of the preceding claims 2 to 5, further comprising a pressure sensor (7e) fluidly connected to the passageway (7f), wherein the junction is configured such that the pressure sensor (7e) is configured to measure the pressure of fluid in the passageway (7), optionally upstream the intersection (7g).

467. The fluid junction of claim 6, wherein the pressure sensor (7e) protrudes in a direction (P) other than the at least four ports (7a, 7b, 7c, 7d), optionally in a direction orthogonal to the at least four ports.

8. Use of the fluid junction (7) of any of the preceding claims 2 to 7 for a fluid kit (3) and / or a bioprocess apparatus (2) forming part of a fluid circuit of a bioprocess system (1 ), optionally for tangential flow filtration, wherein the use comprises establishing a fluid connection with the fluid circuit by connecting the inlet port (7a) of the fluid junction with a junction inlet tube (13a’) of the tubing (13) of the fluid circuit, the filter connection port (7b) of the fluid junction with a filter connection tube (13b’) of the tubing (13) of the fluid circuit, the drain port (7c) of the fluid junction with a drain tube (13c’) of the tubing (13) of the fluid circuit, and the bypass port (7d) of the fluid junction with a bypass tube (13d’) of the tubing (13) of the fluid circuit, such that the inlet port axis (a?a) and / or the inlet passageway (7f-a) are inclined relative to the horizontal (H), when the fluid junction (7) is mounted to the apparatus (2), optionally wherein the drain port axis (a?c) is angled relative to the vertical (V), when the fluid junction (7) is mounted to the apparatus (2).

9. A sensor (8) configured for being mounted to a bioprocess apparatus (2), optionally as part of a fluid kit (3), to form part of a fluid circuit (10) of a bioprocess system (1 ), optionally for tangential flow filtration, wherein the sensor (8) compriseso a sensor inlet (8d) and a sensor outlet (8e) for fluid connection to the fluid circuit (10), wherein a sensor passageway (8c) fluidly connects the sensor inlet (8d) and outlet (8e) for flowing fluid of the fluid circuit (10) through the sensor (8),o a conductivity measurement unit (8a) extending into the sensor passageway (8c) for determination of the conductivity of fluid flowing through the sensor passageway (8c), ando a pressure measurement unit (8b) for determination of the pressure of fluid flowing through the sensor passageway (8c).

10. The sensor of claim 9, wherein the pressure measurement unit (8b) andthe conductivity measurement unit (8a) are located at different sides of the sensor passageway (8c), optionally angled relative to each other or at opposite sides of the sensor passageway (8c).

11. The sensor of claim 9 or 10, wherein the sensor inlet (8d) and the sensor outlet (8e) define a sensor inlet axis (csd) and a sensor outlet axis (cse), respectively, wherein the sensor inlet axis (csd) and the sensor outlet axis (cse) are offset by an offset (o) and parallel to each other, and / or the sensor passageway (8c) includes a step (8f) forming a cavity (8g), optionally into which the conductivity measurement unit (8a) protrudes and / or at which the pressure measurement unit (8b) measures the pressure.

12. Use of the sensor (8) of any of the preceding claims 9 to 11 , for a fluid kit (3) and / or a bioprocess apparatus (2) forming part of a fluid circuit of a bioprocess system (1 ), optionally for tangential flow filtration, wherein the use comprises establishing a fluid connection with the fluid circuit (10) by connecting the sensor inlet (8d) and the sensor outlet (8e) to tubing of the fluid circuit (10).

13. A single-use fluid kit (3) configured for being mounted to a bioprocess apparatus (2) to form a fluid circuit (10) of a bioprocess system (1 ) for tangential flow filtration, wherein the kit comprises at leasto a recirculation vessel (4) for receiving fluid of the fluid circuit (10), o a disposable pump unit (11 a) for cooperation with a pump drive means (11 b) for pumping fluid through the fluid circuit (10),o tubing (13) fluidly connecting at least the vessel (4) and the pump unit (11a), the tubing including at least one supply port (20a, b, c; 14a-d) for supply of fluid, filter ports (21 , 21a) for fluid connection to a filter (5) for tangential flow filtration, and at least one outlet port (15a, b, c) for fluid drainage and / or collection.

14. The kit of claim 13, wherein the recirculation vessel (4) has a bottom and at least one wall (4f) arising from the bottom, wherein the bottom includes at least one inclined bottom region (4a) which is inclined relative to a planeperpendicular to the at least one wall (4f) of the vessel (4) and / or relative to the horizontal (H) when the recirculation vessel (4) is mounted to the bioprocess apparatus (2).

15. The kit of claim 13 or 14, wherein the bottom of the recirculation vessel (4) includes a vessel outlet (4b) and the bottom comprises an indentation (4e) fluidly connecting to the vessel outlet (4b), optionally the indentation (4e) included in the inclined bottom region (4a).

16. The kit of any of the preceding claims 13 to 15, wherein the kit (3) includes a bypass tube (13d’) directly connecting the bypass valve (17) to a collection port (15b), such that the kit is configured to establish a fluid path bypassing the filter ports (21 , 21a).

17. The kit of any of the preceding claims 13 to 16, wherein the pump unit (11a) is located downstream the vessel (4), when the kit is used for filtration.

18. The kit of any of the preceding claims 13 to 17, wherein the kit (3) comprises a junction (7) of any of the preceding claims 2 to 7, optionally downstream of the pump unit (11a), when the kit is used for filtration, and / or at least one sensor (8) of any of the preceding claims 8 to 10, optionally downstream of the filter ports (21 , 21a) when the kit is used for filtration.

19. Use of the kit (3) of any of the preceding claims 12 to 18, with a bioprocess apparatus (2) for forming a fluid circuit (10) of a bioprocess system (1) for tangential flow filtration, wherein the use comprises fluidly connecting the at least one inlet port with a fluid supply, the at least one outlet port with fluid collection means, and the filter ports (21, 21a) with a filter (5), and engaging the pump unit (11a) with the re-useable pump drive means (11 b) of the apparatus (2).

20. A vessel holder (9) for a bioprocess apparatus (2) for tangential flow filtration, the holder (9) configured for holding a recirculation vessel (4) as49part of a fluid circuit (10) of the apparatus (2) and for being attached to the apparatus (2), wherein the holder (9) includeso mounting means (9e) for mounting the vessel holder (9) to an outer housing of the apparatus (2),o a receiving portion (9f), optionally substantially circular, for receiving at least a bottom of the vessel (4), ando a load cell (9a) below and / or included in the receiving portion (9f) and configured to measure the weight of the vessel (4), when the vessel (4) is received by the receiving portion (9f).

21. The vessel holder of claim 20, wherein the load cell (9a) is at least partially circular and / or is donut-shaped.

22. The vessel holder of claim 20 or 21 , further including a magnet impeller drive (9b) for magnetically agitating a magnetic stirrer (4d) in the vessel (4) for mixing of fluid in the vessel (4).

23. The vessel holder of claim 22, wherein the magnet impeller drive (9b) is located in the middle of the receiving portion (9f) and is optionally surrounded by the load cell (9a).

24. The vessel holder of claim 22 or 23, wherein the magnet impeller drive (9b) protrudes from the load cell (9a) in a length direction (l_4f) of the wall (4f) of the vessel and / or in a direction opposite to gravity, when the vessel holder is mounted to the apparatus (2).

25. The vessel holder of any of the preceding claims 20 to 24, wherein the holder includes a cantilever portion (9d) connecting the receiving portion (9f) and the mounting means (9e) of the holder, optionally wherein the cantilever portion (9d) has a substantially trapezoidal shape and / or wherein the cantilever portion (9d) is angled such that the mounting means (9e) is inclined relative to a tangential to the wall (4f) of the vessel parallel to an outer side of a housing of the apparatus (2), when the vessel (4) is received in the vessel holder (9) and the vessel holder (9) is mounted to the apparatus (2).5026. The vessel holder of any of the preceding claims 20 to 25, wherein the holder (9) further comprises a tube fixation (9g) configured to at least partially fix tubing fluidly connecting to the vessel (4) to the holder (9), optionally to the cantilever portion (9d).

27. The vessel holder of claim 26, wherein the tube fixation (9g) further includes at least one slot (9h), optionally two, for holding and receiving a section of the tubing, optionally wherein the tube fixation (9g) protrudes from the remaining cantilever portion upwards, when the holder is mounted to the apparatus (2).

28. Use of the vessel holder (9) of any of the preceding claims 20 to 27 for a bioprocess, optionally tangential flow filtration, wherein the use comprises attaching the mounting means (9e) of the vessel holder (9) to the apparatus (2), optionally to an outer side of the apparatus.

29. A filter holder adaptor (6) configured for establishing attachment of a filter holder (25) holding a filter cassette (5) to a bioprocess apparatus (2) for tangential flow filtration, wherein the filter holder adaptor (6) includes o at least one apparatus-side adaptor (6c), optionally detachably, attachable to the apparatus (2), the apparatus-side adaptor (6c) comprising apparatus-side engagement means (6d),o at least one filter-side adaptor (6b), optionally detachably, attachable to the filter holder (25) compressing and / or holding the filter material of the filter (5), the filter-side adaptor (6b) comprising filter-side engagement means (6e), whereino the apparatus-side engagement means (6d) and the filter-side engagement means (6e) are configured for mechanical engagement with each other, and the apparatus-side adaptor (6c) and the filter-side adaptor (6b) are configured such that mechanically engaging the apparatus-side engagement means (6d) and the filter-side engagement means (6e) attaches the filter holder (5) to the apparatus (2), when the apparatus-side adaptor (6c) and the filter-side adaptor (6b) are attached to the apparatus (2) and the51filter holder (25), respectively.

30. The filter holder adaptor (6) of claim 29, wherein the filter-side adaptor (6b) is attachable to a substantially planar jaw (5b) of the filter holder (25), optionally by means of mechanical attachment means, and / or includes a substantially planar frame or plate (6b) for lying against the jaw (25b) of the filter holder (5).31.The filter holder adaptor (6) of claim 29 or 30, wherein the apparatus-side adaptor (6c) includes at least one bracket (6c) and / or the apparatus-side engagement means includes at least one recess (6d), optionally formed in the bracket (6c), for receiving the filter-side engagement means (6e), more optionally the recess (6d) being open in a direction (Led) of a plane defined by the filter-side adaptor (6b), when the filter-side adaptor (6b) and the apparatus-side adaptor (6c) are in engagement.

32. The filter holder adaptor of any of the preceding claims 29 to 31 , wherein the filter-side engagement means (6e) includes a protrusion (6e) for being received by the apparatus-side engagement means (6d), optionally wherein the protrusion (6e) protrudes in a direction perpendicular to a plane defined by the filter-side adaptor (6b).

33. The filter holder adaptor of any of the preceding claims 29 to 32, wherein the apparatus-side adaptor (6c) comprises an inclined wall (6f) which faces away from the filter-side adaptor (6c) and is inclined relative to the vertical and / or the filter-side adaptor (6b), such that the distance of the inclined wall (6f) relative to the filter-side adaptor (6b) increases in the direction opposite to gravity, when the filter-side engagement means (6e) and the apparatus-side engagement means (6d) are in engagement.

34. The filter holder adaptor of any of the preceding claims 29 to 33, wherein the at least one apparatus-side engagement means, optionally the recess (6d), is offset from a middle of the apparatus-side adaptor (6c), when seen in a length direction (Lee) of the apparatus-side adaptor means (6c).5235. The filter holder adaptor of any of the preceding claims 29 to 34, wherein the apparatus-side adaptor (6c) includes a first (6h) and an opposite second (6i) side, wherein each of first and second sides is configured to face towards the apparatus (2), when the filter (5) is attached to the apparatus (2).

36. Use of the filter holder adaptor (6) of any of the preceding claims 29 to 35 for a filter (5) and an apparatus (2) for tangential flow filtration, the filter (5) being held by a filter holder (25), wherein the use comprises attaching the apparatus-side adaptor (6c) to the apparatus (2), and / or attaching the filter-side adaptor (6b) to the filter holder (25).

37. The use of claim 36, wherein the use comprises engaging the apparatusside engagement means and the filter-side engagement means with each other.

38. A method for pump calibration of a bioprocess system (1) for tangential flow filtration, the system including at least a vessel (4) for containing fluid, a pump (11 ), optionally including a pump unit (11 a) and a pump drive means (11 b), for pumping fluid along a fluid filtration circuit (10) of the bioprocess system (1), a filter (5) for filtration of fluid by means of tangential flow of fluid across the filter (5) in the fluid filtration circuit (10), and a collection port (15b) for draining fluid, wherein the following steps are performed:o providing fluid in the vessel (4),o establishing a fluid calibration circuit bypassing the filter (5), o flowing fluid from the vessel (4) to the collection port (15b) by pumping fluid at a predetermined default flow rate by means of the pump (11 ) along the fluid calibration circuit,o measuring the amount of fluid in the vessel (4) at at least two different points in time within the time period during which fluid is flown along the calibration circuit at the predetermined default flow rate, to obtain a measured flow rate representative of the fluid flow, o comparing the measured flow rate and the predetermined default flow rate for calibration of the pump to obtain a calibrated flow rate53of the pump, ando calibrating the pump based on the calibrated flow rate.

39. The method of claim 38, wherein the amount of fluid in the vessel (4) is determined by gravimetric measurement, optionally by means of a load cell (9a) of a vessel holder (9) of any of the preceding claims 20 to 27, wherein the vessel (4) is supported by the vessel holder (9).

40. A control unit configured to carry out controlling the method of any of the preceding claims 38 to 39.

41. A method for testing a filter (5) of a bioprocess system (1 ) for tangential flow filtration, the system (1) at least including a transfer pump (12) for pumping fluid in a fluid test circuit, a filter (5) for filtration of fluid by means of tangential flow of fluid across the filter (5), a pressure sensor (7e, 8b) in fluid communication with the filter (5), optionally included in the sensor (8) of any of the preceding claims 9 to 11 , a retentate outlet port (21a) fluidly connecting to the filter (5) in the fluid test circuit, wherein the filter retentate outlet port (21a) is downstream the filter (5) during filtration, and further filter ports (21 ) fluidly connecting to the filter (5) and the fluid filtration circuit during filtration, wherein the following steps are performed:o providing the further filter ports (21 b, c, d) in a closed state and the filter retentate outlet port (21a) in an open state,o establishing the fluid test circuit by fluidly connecting at least the transfer pump (12) and the filter (5) via the retentate outlet port (21a),o supplying gas to the fluid test circuit by means of the transfer pump (12), when the fluid test circuit has been established and the further filter connections are closed, so as to pressurize the fluid test circuit until a target pressure is reached,o measuring the pressure indicative of the pressure in the filter (5) by means of the pressure sensor (7e, 8b) to obtain a measured pressure, after the target pressure has been reached and supply of gas was stopped, ando monitoring the measured pressure over time during a time interval,54in particular a decay of the pressure over time, so as to obtain a pressure decay rate ando identifying a test result based on the pressure decay rate.

42. The method of claim 41 , wherein the fluid supplied by to fluid test circuit is air.

43. A control unit configured to carry out controlling the method of any of the preceding claims 41 and 42.

44. A method for calibrating a permeate flow meter (18) of a bioprocess system (1) for tangential flow filtration, the system including at least a vessel (4) for containing fluid, a pump (11), optionally including a pump unit (11 a) and a pump drive means (11 b), for pumping fluid along a fluid circuit (10) of the bioprocess system (1 ), a filter (5) for filtration of fluid by means of tangential flow of fluid across the filter (5) in the fluid filtration circuit (10), the flow meter (18) downstream the filter for measuring the flow of permeate, and a collection port (15b) for collection of fluid, wherein the following steps are performed:o providing fluid in the vessel (4),o establishing the fluid circuit including the filter (5),o flowing fluid from the vessel (4) to the collection port (15b) along the fluid circuit by pumping fluid by means of the pump (11 ), wherein fluid downstream the filter (5) flows through the flow meter (18) at an indicated flow rate indicated by the flow meter,o measuring the amount of fluid in the vessel (4) at at least two different points in time within the time period during which fluid is flown along the fluid circuit to obtain a measured flow rate of the fluid flow,o comparing the measured flow rate and the indicated flow rate to obtain a calibrated flow rate of the flow meter, ando calibrating the flow meter based on the calibrated flow rate.

45. The method of claim 44, wherein the amount of fluid in the vessel (4) is determined by gravimetric measurement, optionally by means of a load55cell (9a) of a vessel holder (9) of any of the preceding claims 20 to 27, wherein the vessel (4) is supported by the vessel holder (9).

46. A control unit configured to carry out controlling the method of any of the preceding claims 44 and 45.

47. A bioprocess apparatus (2) configured to form a fluid circuit (10) of a bioprocess system (1 ) for tangential flow filtration through a filter (5), the apparatus (2) comprising, at its outer side,o a vessel holder (9) for holding an optionally single-use recirculation vessel (4) containing fluid, wherein the vessel holder (9) is attached to the apparatus (2),o an upper set of valves (V1 ) including at least one pinch valve (17) for governing supply of fluid and a pressure control valve (16) for controlling pressure in the filter (5) downstream the filter (5), wherein the upper set of valves (V1) is located at least in parts higher than the vessel holder (9),o pump drive means (11 b), optionally of a membrane pump (11 ), for cooperation with a disposable pump unit (11 a) to form a pump (11 ) for pumping fluid along the fluid circuit, wherein the pump (11 ) is, in the fluid circuit, downstream the vessel (4),o a lower set of valves (V2) including at least two pinch valves (17) for governing fluid flow downstream the pump (11), wherein at least one of the valves of the lower set of valves (V2) is located lower than the pump drive means (11 b), ando wherein the upper set of valves (V1 ) is located higher than the lower set of valves (V2).

48. The apparatus of claim 47, wherein at least one of the valves of the upper (V1) and lower (V2) sets of valves includes a tube guidance (17a), optionally a cavity, for receiving a part of the tubing and guiding the tubing via the tube guidance (17a) in a predetermined direction (Di7a), and the tube guidance of at least one valve of the upper (V1 ) and lower (V2) sets of valves is inclined relative to the horizontal (H), when the apparatus (2) is installed on site, such that tubing received by the at least one valve is56inclined relative to the horizontal (H) accordingly.

49. The apparatus of claim 48, wherein the lower set of valves (V2) includes the at least one valve having the inclined tube guidance (17a), optionally such that the at least one valve is arranged for fluid connection to a fluid junction (7) of any of the preceding claims 2 to 7, wherein the at least one valve is downstream of the filter connection port (7b).

50. The apparatus of any of the preceding claims 47 to 49, wherein the lower set of valves (V2) includes a bypass valve establishing a fluid bypass path bypassing the filter (5).51.The apparatus of any of the preceding claims 47 to 50, wherein the vessel holder (8) is the vessel holder of any of the preceding claims 20 to 27, optionally detachably mounted to the apparatus (2) for holding the vessel (4).

52. The apparatus of any of the preceding claims 47 to 51 , further including the control unit of claim 40, 43 and / or 46.

53. A bioprocess system (1), optionally of claim 1, including the bioprocess apparatus (2) of any of the preceding claims 47 to 52, the kit (3) of any of the preceding claims 13 to 18 and / or the filter holder adaptor (6) of any of the preceding claims 29 to 35, optionally a filter (5) for tangential flow filtration, further optionally the filter (5) being held by a filter holder (25).

54. Use of the bioprocess system (1 ) of claim 1 or 53 for tangential flow filtration, wherein the use comprises flowing fluid though the fluid circuit (10), wherein fluid is contained in the vessel (4), pumped by the pump (11 ) and flown through the filter (5), wherein permeate fluid passes through the filter (5) and retentate fluid returns to the vessel (4).57

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