Bioprocessing system

Abstract

A method (1000) and a bioprocessing system are disclosed. The bioprocessing system comprises a plurality of bioprocessing stations (100) each configured to perform a respective bioprocessing operation on a feed comprising a mixed liquid and a sample. The system further comprises a liquid supply arrangement (200) comprising a valve arrangement (210), a conduit (220), a mixing arrangement (230) and a controller (240). The mixing arrangement (230) is configured to supply at least a first solution component and a second solution component to the conduit (220), thereby forming a mixed liquid. The valve arrangement (210) is operable to selectively supply the mixed liquid to each of the bioprocessing stations (100), and the controller (240) is configured to control operation of the mixing arrangement (210) for each bioprocessing station (100) such that the mixed liquid comprises a predetermined set of properties associated with the bioprocessing operation of the bioprocessing station (100).

Description

Technical Field

[0001] This disclosure relates to the manufacture of biopharmaceutical products, and more specifically to bioprocessing systems and methods for performing one or more bioprocessing operations on a feed. Background Technology

[0002] Bioprocessing operations, such as filtration and chromatography, play a crucial role in the biopharmaceutical industry. Bioprocessing operations are commonly used to separate and purify proteins, vaccines, and other components from complex bioreactor mixtures. The target material, i.e., the product of interest to be separated or purified, can be provided in a liquid stream or feed comprising a mobile phase through which the target material passes through the bioprocessing system. The mobile phase typically comprises a mixed liquid (such as a buffer solution) with well-defined properties suitable for the relevant bioprocessing operation, such as pH and conductivity.

[0003] Biopharmaceutical processing places high demands on biosafety and cleanliness to prevent loss of biological integrity (e.g., through the release of harmful chemicals into the environment) and product contamination by particulate matter and microorganisms. Therefore, biopharmaceutical manufacturing requires relatively complex and expensive cleanroom facilities.

[0004] Many bioprocessing systems involve single-use components to reduce the need for cleaning and sterilization. Some single-use components are available as disposable flow kits, which have disposable tubing that carries the liquid flow to the bioprocessing component performing the bioprocessing operation. The flow kit can be replaced between each bioprocessing operation or sample batch.

[0005] The usual efforts to reduce costs and improve production require improved technologies to make more efficient use of biological treatment equipment and facilities. Summary of the Invention

[0006] According to a first aspect of this disclosure, a biological treatment system is provided for separating a target material from one or more impurities in a feed. The system includes a plurality of biological treatment stations, each configured to perform a corresponding biological treatment operation on the feed. The plurality of biological treatment stations are interconnected such that the outlet of a first biological treatment station is connected to the inlet of a next biological treatment station. The system also includes a liquid supply device comprising a valve arrangement, a conduit, a mixing arrangement, and a controller, wherein the mixing arrangement is configured to supply at least a first solution component and a second solution component to the conduit to form a mixed liquid. The valve arrangement is fluidly connected to the conduit and operable to selectively supply the mixed liquid to each of the biological treatment stations. The controller is configured to control the operation of the mixing arrangement for each biological treatment station such that the mixed liquid has a predetermined set of characteristics associated with the biological treatment operation of that biological treatment station. At least two of the plurality of biological treatment stations (e.g., all of them) can be configured to perform different biological treatment operations on the feed (e.g., continuously / in series as at least part of the overall separation process).

[0007] According to a second aspect, a method is provided for separating a target material from one or more impurities in a feed. The method includes: supplying the feed to a plurality of biological treatment stations as outlined above in conjunction with the first aspect; mixing at least a first solution component and a second solution component in a mixing arrangement to form a mixed liquid; and selectively supplying the mixed liquid to each of the plurality of biological treatment stations. For each of the plurality of biological treatment stations, the mixing arrangement is operated to provide the mixed liquid with a predetermined set of characteristics associated with the biological treatment operation performed by said biological treatment station.

[0008] This liquid supply device enables the direct supply of mixed liquids, such as buffer solutions, to a bioprocessing station without any intermediate storage or manual handling. Conventional preparation of mixed liquids typically requires numerous operations, including manual handling and transfer of raw materials, solution preparation, mixing, and cleaning of the equipment involved. Once prepared, a place is needed to store the mixed liquid until it is used in the bioprocessing operation. Therefore, conventional preparation and handling of mixed liquids is often a time-consuming and logistically challenging process, requiring not only planning but also sufficient facility space. This disclosure provides a solution in which mixed liquids can be alternatively delivered to a bioprocessing station on demand and directly. Each mixed liquid can be prepared from water for injection (WFI) and one or more single-component stock solutions, and the liquid supply device can be operated to prepare mixed liquids with a predetermined set of properties matching the requirements associated with a specific bioprocessing operation. The outlet of the liquid supply device can be directly connected to one or more bioprocessing stations to supply mixed liquids on demand without the need for intermediate storage or manual transport. This method of preparing mixed liquids can be referred to as online conditioning. In some instances, each biological processing station in a biological processing plant can be configured to request and receive mixed liquids from a mixing liquid device.

[0009] These bioprocessing stations can be interconnected, such that the outlet of the first bioprocessing station connects to the inlet of the next bioprocessing station. Therefore, bioprocessing stations can be arranged in a cascade configuration, where feed containing biological target compounds and / or impurities can undergo several bioprocessing steps uninterruptedly as it passes continuously through the bioprocessing station. For example, several chromatographic and / or filtration devices can be connected in series within the bioprocessing system. Traditionally, purification process flows are often interrupted due to manual changes to buffers and / or chromatographic equipment within the system, and due to some steps (such as adjustment of chromatographic media and certain filtration / purification steps) being performed in separate containers or devices outside the chromatographic system. Using the currently disclosed bioprocessing systems requires less human intervention and can reduce processing time compared to operating previously known bioprocessing systems.

[0010] The valve arrangement allows the liquid supply unit to supply the mixed liquids required for their respective biological treatment operations to two or more biological treatment stations within a biological treatment plant. Each biological treatment station can be provided with a mixed liquid having a set of characteristics associated with that particular biological treatment station. Therefore, a single liquid supply unit can be used to supply one or more types of mixed liquids to multiple biological treatment stations or connected / co-located production facilities, thus making more efficient use of the liquid supply unit.

[0011] Furthermore, the mixing liquid device can be used to drive the flow of mixed liquids through the biological treatment system, thereby eliminating the need for a dedicated pump in each biological treatment station and simplifying the design of the biological treatment station. Removing the mixing liquid pump from the biological treatment station saves space and simplifies the electrical infrastructure, as no power supply is required for the mixing liquid pump in the biological treatment station.

[0012] The liquid supply device may include a control sensor arrangement comprising sensors such as pH sensors, conductivity sensors, or flow sensors to control corresponding characteristics of the mixed liquid supplied to the biological treatment plant. This reduces the need for sensors within the biological treatment plant. The sensors can be used as the control sensor arrangement, configured to output signals indicating the characteristics of the mixed liquid, and these signals can be used as feedback to control the operation of the mixing arrangement of the liquid supply device.

[0013] In some instances, each bioprocessing station in a bioprocessing plant may include an inlet valve arrangement to control the supply of mixed liquids or samples to the bioprocessing station. The inlet valve arrangement may be configured, for example, to bypass bioprocessing components (such as chromatography columns or filters) when the mixed liquid does not have the desired properties or during a cleaning step, and to guide the mixed liquid and sample to the bioprocessing component to initiate bioprocessing operations.

[0014] In another example, each biological treatment station in a biological treatment plant may include a release valve arrangement configured to control the release of feed or mixed liquid from the biological treatment station. The release valve arrangement may, for example, be operable to direct the feed to a waste outlet or to the inlet of another biological treatment station.

[0015] Valve arrangements can be used to control fluid flow through a biological treatment station during different phases of a biological treatment operation, such as equilibration, column loading, elution, and regeneration (in the case where the biological treatment component is, for example, a chromatography column). In one example, an inlet valve arrangement can be operated to supply a mixed liquid to the biological treatment station during the equilibration, elution, and regeneration phases, and to supply a sample to the biological treatment station during the sample loading phase. In another example, a release valve arrangement can be operated to release output from the biological treatment station to a waste outlet during the equilibration, sample loading, and regeneration phases, and to release output to the next biological treatment station in the series during the elution phase.

[0016] According to a third aspect, a biological processing system is provided, operable to perform multiple biological processing operations on a liquid stream comprising a mixed liquid carrying a sample. The biological processing system includes: a biological processing component operable to perform at least one of the biological processing operations on the liquid stream; a pump unit operable to drive the flow of the mixed liquid through a piping system to the biological processing component; and a sample supply source operable to add a sample to the flow of the mixed liquid at a location between the pump unit and the biological processing component, thereby forming the liquid stream. The piping system is a disposable piping system configured to be replaced between each of the multiple biological processing operations, and the pump unit is a reusable pump unit operable to be reused for each of the multiple biological processing operations.

[0017] According to a fourth aspect, a piping system is provided for a biological treatment system as outlined above in conjunction with the third aspect. The piping system includes: a mixed liquid inlet configured to be coupled to a pump unit; an outlet configured to be coupled to a biological treatment component; a conduit configured to deliver a flow of the mixed liquid from the pump unit to the biological treatment component; and a sample inlet configured to supply a sample to the flow of the mixed liquid, the sample inlet being disposed between the mixed liquid inlet and the outlet. The piping system is a disposable piping system configured to be interchangeable between each of a plurality of biological treatment operations.

[0018] Single-use or disposable piping systems are generally understood as piping systems designed for a single batch or a single production cycle. After use, the piping system can be discarded rather than cleaned and sterilized for reuse. The piping system can be pre-sterilized to eliminate the need for complex and time-consuming processes on-site and may include one or more sterile filters, barriers, or connectors placed at the inlet of the piping system to maintain its sterility before use. Using each piping system only once reduces the risk of cross-contamination between batches and the time required for cleaning, sterilization, and validation of reusable equipment. Typically, piping systems can be formed from relatively inexpensive plastic derivatives or other materials suitable for single use. Therefore, upfront costs can be reduced compared to investing in permanent stainless steel systems.

[0019] Therefore, reusable pump units refer to pump units designed to be used multiple times in the same or different production batches or cycles. Although the initial investment may be higher, reusable pump units are more cost-effective over a longer period due to their long-term use. Furthermore, reusable pump units generate less waste compared to disposable pump units, making them a more environmentally sustainable option.

[0020] The third and fourth aspects outlined above allow for the combination of the benefits of single-use components with those of reusable components. While single-use tubing systems reduce the need for cleaning and sterilizing these parts, reusable pump units reduce the cost and waste of single-use materials. By adding the sample downstream of the pump unit (i.e., between the pump unit and the bioprocessing component), the risk of the pump unit coming into contact with the sample is reduced. This contrasts with conventional bioprocessing systems where the pump unit, or at least the pump head, is included in a single-use flow kit and thus needs to be replaced with the rest of the flow kit. By separating the pump unit from the sample-containing portion of the liquid flow, the need to replace the pump unit between different bioprocessing operations or sample batches is reduced.

[0021] To further reduce the risk of the pump unit coming into contact with the sample, a protective valve can be placed between the pump unit and the location where the sample is supplied to the mixed liquid. The protective valve can be operable to prevent the sample from reaching the pump.

[0022] Furthermore, by separating the pump unit from the disposable piping system, the pump unit can be located in a separate location that maintains a lower cleanliness level than the area where the biological treatment operation is performed. The biological treatment components can, for example, be located in the treatment area maintaining a first cleanliness level, and the pump unit can be located in the service area maintaining a second, lower cleanliness level. In this way, the footprint of the equipment located in the treatment area can be reduced, and the cost of maintaining a higher cleanliness level can be correspondingly lowered.

[0023] It will be appreciated that the biological treatment system of the third aspect may include one or more biological treatment components that may be cascaded in a configuration similar to that discussed above in conjunction with the first and second aspects. Furthermore, the biological treatment station according to the first aspect may include or be used with the piping system of the fourth aspect as outlined above.

[0024] As used in this disclosure, the term "bioprocessing station" generally refers to a processing unit that includes at least one of a chromatographic column, a filter, and a mixer. However, other bioprocessing components or devices are also possible. Bioprocessing operations performed by a chromatographic column, filter, or mixer may be referred to as unit operations.

[0025] Target material can be understood as the product of interest to be separated or purified. Target materials can include, for example, biological target materials such as proteins, vaccine components, antibodies, and biomolecules. Target materials are typically provided as a sample, comprising the target material and one or more impurities.

[0026] The target material is carried by a mobile phase, which typically comprises a mixed liquid that drives the target material through the biological treatment system.

[0027] In the context of this disclosure, "feed" is generally understood as the input / output of a bioprocessing component. Therefore, depending on the actual bioprocessing operation, the feed may or may not include the target material and any impurities.

[0028] The mixed liquid can typically be a buffer solution or a buffer solution. A buffer solution can be prepared from one or more buffering substances, such as a first buffering substance and a second buffering substance mixed with water for injection. In this case, the liquid supply device can be referred to as a buffer feedstock blending system.

[0029] The term "conduit" can generally be understood as a portion of a conduit that connects two elements in a flow path or flow loop. Typically, a conduit forms a section of conduit that delivers a mixed liquid to a biological treatment component. This section may include a single tube or several tubes of different diameters connected in series or parallel.

[0030] A biological treatment station may include a base unit (also referred to as a carriage) to which at least one of the biological treatment components and piping systems can be releasably mounted. The base unit may be a standalone modular unit that can be transported and integrated into a larger treatment system. In some instances, the base unit may include one or more valve arrangements described above, such as protection valves, inlet valves, or relief valves. The valve arrangement may, for example, include a valve actuator capable of being operated to releasably engage conduits of the piping system (e.g., the conduits discussed above in conjunction with the fourth aspect) to form a pinch valve controlling the flow of the mixed liquid through the piping system.

[0031] A biological processing system may include one or more sensor arrays operable to output signals indicative of the properties of a mixed liquid or liquid flow passing through the system. The sensor array may include at least one of a pH sensor, a conductivity sensor, and a sample sensor. In some instances, the sensor array may be positioned upstream of a location where a sample is added to the flow of the mixed liquid and configured to measure at least one of the pH and conductivity levels of the mixed liquid. In some instances, the sensor array is arranged in a disposable piping system, and in some instances, it is arranged in a reusable section associated with a pump unit.

[0032] In some instances, a sensor is provided that is operable to generate a signal indicating the concentration or amount of a sample in a liquid stream. Examples of such sensors include UV sensors configured to measure a specific target material in a liquid stream. The sensor may be positioned upstream of the processing unit to measure the concentration or amount of the target material supplied to the processing unit, or downstream of the processing unit to measure the concentration or amount of the target material leaving (or bypassing) the processing unit.

[0033] In some instances, sensors for measuring sample concentration are included in disposable tubing systems, while pH and conductivity sensors are located in reusable sections of the biological processing system.

[0034] Biological processing operations typically require cleanroom environments with relatively high biosafety and cleanliness levels to prevent product contamination by particulate matter and microorganisms. Maintaining a certain level of cleanliness is generally cost-related, and costs tend to increase with increasing cleanliness levels. To reduce the volume of highly controlled areas and thus lower the cost of maintaining such high cleanliness, cleanroom facilities typically include different areas maintained at different cleanliness levels. For the purposes of this disclosure, cleanroom areas maintained at higher cleanliness levels may be referred to as processing areas, while cleanroom areas maintained at lower cleanliness levels may be referred to as service areas. More generally, these corresponding areas may be referred to as first areas and second areas, respectively maintained at a first cleanliness level and a second cleanliness level.

[0035] In some instances, multiple biological treatment stations according to the first and second aspects can be arranged in the treatment area, while a hybrid layout can be arranged in the service area. In other instances, pump units according to the third and fourth aspects can be arranged in the service area, while piping systems and treatment components can be arranged in the treatment area. By moving some components of the system (such as the hybrid layout or pump units) to a less clean area, the floor space required for equipment in a cleaner area can be reduced. This, in turn, makes it possible to reduce the volume of the cleaner area.

[0036] In another aspect, a method for reconfiguring a biological processing system according to the third aspect is provided. In this method, the biological processing system is reconfigured between two consecutive biological processing operations. The reconfiguration includes disconnecting a first piping system from the pump unit, the biological processing component, and the sample supply source, and connecting a second piping system to the pump unit, the biological processing component, and the sample supply source. Each of the first and second piping systems is configured similarly to the piping system according to the fourth aspect, thus enabling operation to deliver a flow of mixed liquid from the pump unit to the biological processing component. Attached Figure Description

[0037] Further features and advantages of the above aspects will become apparent from the following description of preferred embodiments, which are given by way of example only, with reference to the accompanying drawings.

[0038] Figure 1 A schematic diagram of a biological treatment system based on an example is shown.

[0039] Figure 2 A schematic diagram of a biological treatment system based on another example is shown.

[0040] Figure 3 This is a flowchart outlining a method for operating a biological treatment system based on an example.

[0041] Figure 4a A schematic diagram of a biological treatment system based on an example is shown.

[0042] Figure 4b It is used for, for example Figure 4a The piping system of the biological treatment system shown.

[0043] Figure 5a The piping system installed on the base unit is shown.

[0044] Figure 5b A biological treatment system according to an example is shown, wherein a base unit is arranged in a treatment area and a mixing liquid pump unit is arranged in a service area. Detailed Implementation

[0045] Figure 1 This is a schematic diagram of an example biological treatment system capable of operating to separate a target material from one or more impurities in a feed. The system includes multiple biological treatment stations 100, each configured to perform a corresponding biological treatment operation on the feed. These biological treatment stations are interconnected such that the outlet 112 of a first biological treatment station 110 is connected to the inlet 121 of the next biological treatment station 120. In other words, Figure 1 The biological treatment stations 110, 120, and 130 shown can be arranged in a cascaded manner, wherein the output from one of these stations is fed to the inlet of the next station.

[0046] In this exemplary configuration, a sample containing the target material and one or more contaminants (e.g., provided by a bioreactor mixture) is fed from sample supply source 20 to sample inlet 111 of first bioprocessing station 110. Here, the sample is mixed with a mixed liquid (such as a buffer solution), which is prepared by liquid supply device 200 and used to drive the sample through the bioprocessing components of bioprocessing station 110. Therefore, liquid supply device 200 can operate without the use of any dedicated mixed liquid pump (such as...). Figure 4a and Figure 5b In the case of the pump unit 320 shown, the flow of the mixed liquid and the sample is driven. The mixed liquid may have a first set of characteristics associated with the biological treatment operation, such as pH and conductivity levels, and is supplied to the first biological treatment station 110 via the mixed liquid inlet 113. The output of the first biological treatment station 110 can then be supplied from the feed outlet 112 of the first biological treatment station 110 to the feed inlet 121 of the second biological treatment station 120, where it is mixed with a mixed liquid having a second set of characteristics prepared by the mixing arrangement structure 210 and supplied to the second biological treatment station 120 via the mixed liquid inlet 123. Subsequently, the output from the second biological treatment station 120 is supplied from the feed outlet 122 of the second biological treatment station 120 to the feed inlet 131 of the third biological treatment station 130. In the third biological treatment station 130, the feed is mixed with a mixed liquid having a third set of characteristics prepared by the mixing arrangement structure 210 and supplied to the third biological treatment station 130 via the mixed liquid inlet 133. Figure 1 As shown, the output from the third biological treatment station 130 can be discharged from the discharge port 132 to the storage tank 30. It should be understood that, in the context of this disclosure, the output from each of the biological treatment stations 110, 120, and 130 will be referred to as "feed".

[0047] The liquid supply device 200 is operable to supply the biological treatment station 100 with the mixed liquid required for the corresponding biological treatment operations performed by the biological treatment station 100. The liquid supply device 200 is fluidly connected to Figure 1 Each of the biological treatment stations 100 indicated in the diagram includes a valve arrangement 210 configured to selectively supply the mixed liquid to each of the biological treatment stations. (As will be combined...) Figure 2 As discussed in further detail, the valve arrangement structure 210 is operable to sequentially supply the biological treatment station 100, i.e., one at a time, or two or more simultaneously. The liquid supply device 200 also includes a conduit 220 connecting the valve arrangement structure 210 to a mixing arrangement structure 230 configured to supply at least a first solution component and a second solution component to the conduit 210 to form a mixed liquid. The first and second solution components can be retrieved from their respective component supply sources 10. In one example, the mixed liquid is a buffer solution formed from a first solution component as an acidic buffer component, a second solution component as an alkaline buffer component, and water for injection (WFI). The buffer solution can be prepared, for example, from a weak acid and a weak base, a weak acid and a strong base, or a weak base and a strong acid. Exemplary buffers that can be prepared using the liquid supply device 200 include phosphate, acetate, citrate, Tris buffer, and bis-Tris buffer. It should be understood that additional inlets may be provided, such as... Figure 1 As shown and combined Figure 2 Further detailed discussion is needed.

[0048] Figure 1 One configuration is shown in which a liquid supply device 200 supplies a single production layout, i.e., a production line comprising multiple interconnected bioprocessing stations 100 for producing a specific product or target material. However, it should be understood that the liquid supply device 200 disclosed herein can be arranged to supply two or more production lines, each comprising multiple interconnected bioprocessing stations 100 for producing a corresponding product or target material. Therefore, a single liquid supply device 200 according to this disclosure can be operated to supply a mixed liquid to two or more production lines.

[0049] A controller 240 is provided to control the operation of the liquid supply device 200, and more specifically, to control the operation of the mixing arrangement structure 230, such that the mixed liquid includes a predetermined set of characteristics associated with the biological treatment operations performed by the biological treatment station supplied with the mixed liquid. These characteristics typically refer to pH and conductivity, which can be determined and adjusted by changing the relative proportions of the solution components mixed by the mixing arrangement structure 230.

[0050] These characteristics can be based on the control sensor arrangement structure ( Figure 1 The sensor signal (not shown) is used to determine and is used as correction feedback for the controller 240 to help achieve, for example, the desired pH level or conductivity level.

[0051] The controller 240 can also be arranged to control the operation of the valve arrangement 210 to determine which biological treatment station 100 will be supplied with the mixed liquid. The controller 240 is communicatively connected to the mixing arrangement 230 and the valve arrangement 210, for example, via a wired or wireless connection.

[0052] Figure 2 This is a schematic diagram of a biological treatment system based on an example, which can be connected with... Figure 1 The biological treatment system in the example is configured similarly. The exemplary system includes multiple biological treatment stations 100, including a capture station 110, a normal flow filtration (NFF) station 120, and a purification station 130. Figure 2 The document also discloses an additional biological treatment station, namely a virus inactivation station 140 arranged between the capture station 110 and the NFF station 120. Each of these exemplary biological treatment stations will be discussed in more detail below.

[0053] Starting from capture station 110, this can be... Figure 2The diagram illustrates the first part of a downstream process performed by multiple bioprocessing stations 100. In this station, target materials can be purified from complex mixtures typically derived from bioreactors or fermentation broths. Capture steps can be designed to separate the target material or product of interest (such as proteins, antibodies, or enzymes) from most impurities present in the crude mixture. Bioprocessing operations typically involve the selective binding of target molecules to media such as resins in a chromatography column.

[0054] A sample containing the target material is provided in a target supply source 20, which may be a mixer or tank connected to the sample inlet 111 of the capture station 110. A sample pump 21 is provided to drive the flow of the sample to an inlet valve 116, which is operable to control the release of the sample and the mixed liquid from the mixed liquid inlet 113 to a biological processing unit 115, which in this example is a chromatography column 115. The output from the chromatography column 115 is supplied to a release valve 117, which is operable to selectively release the output feed to either a waste outlet 114 or a feed outlet 112.

[0055] The feed outlet 112 of the capture station 110 is connected to a virus inactivation station 140, which includes a first mixer and a second mixer for exposing the target material to a pH treatment to inactivate the virus. The output from the capture station 110 can be supplied first to the first mixer 141, where the target material is exposed to acid, and then to the second mixer 142, where the target material is neutralized by alkali. The acid and alkali can be supplied by, for example... Figure 2 The corresponding disposable containers 143, 144 shown are provided, or are provided by the liquid supply device 200.

[0056] The output from the virus inactivation station 140 can then be supplied to the feed inlet 121 of the NFF station 120 for filtration. The feed inlet 121 is connected to an inlet valve 126, which is operable to mix the target material in the feed with the liquid mixture received at the mixed liquid inlet 123 of the NFF station 120 and release the feed to a biological treatment unit 125, which in this case may be a depth filter 125. The output from the depth filter 125 can then be supplied to a release valve 127, which is operable to release the feed to either the waste outlet 124 or the mixer 128.

[0057] The output of mixer 128 can be supplied to the feed inlet 131 of purification station 130, which can be configured to perform further purification and refinement of the target material to meet desired quality specifications. Therefore, purification station 130 may include a chromatographic column designed to remove any remaining impurities, such as host cell proteins, DNA, viruses, or target material-related impurities, such as aggregates or variants of the target material. Similar to capture station 110 and NFF station 120, purification station 130 may include an inlet valve 136 operable to adjust and control the flow of the target material from feed inlet 131 and the mixed liquid from mixed liquid inlet 133 to bioprocessing unit 135. A feed pump 22 may also be provided to drive the feed flow from feed inlet 131 to bioprocessing unit 135. Additionally, a release valve 137 may be provided to receive the output from bioprocessing unit 135 to waste outlet 134 or feed outlet, which may then be connected to mixer 138.

[0058] As indicated above, one or more of the biological treatment stations 110, 120, 130, and 140 may be fluidly connected to the liquid supply device 200 for supplying the mixed liquid to be used in the biological treatment operations performed by the biological treatment stations. In this example, each of the capture station 110, NFF station 120, and purification station 130 may be connected to the liquid supply device 200 via a corresponding conduit. These biological treatment stations and their corresponding biological treatment operations are described to illustrate the benefits of the liquid supply device 200 and its online status. It should be understood that the liquid supply device 200 and the plurality of biological treatment stations 110 may be used in other configurations to perform other types of biological treatment operations.

[0059] The liquid supply device 200 includes a mixing arrangement structure 230 operable to receive solution components and mix them into a mixed liquid having predetermined properties, such as pH levels and / or conductivity within a predetermined range. In this example, the mixing arrangement structure 230 includes multiple inlets 10 for receiving respective solution components or buffer components. The inlets can be configured to receive solution components such as: a first inlet 11 receiving an acidic buffer, a second inlet 12 receiving an alkaline buffer, a third inlet 13 receiving a WFI, a fourth inlet 14 receiving a salt, and a fifth inlet 15 receiving one or more additives. Each inlet 11-15 can be connected to a corresponding pump 231, 232, 233, 234, 235 to drive the corresponding solution component to flow through the conduit 220 to form a mixed liquid or a set of properties. Thus, one pump (pump 233) can be a WFI pump, while the other pumps (pumps 231, 232, 234, 235) can be reservoir solution pumps. In this example, the pumps can be diaphragm pumps. However, other types of pumps using different operating principles are also possible.

[0060] Sensors, such as pH sensor 342 and conductivity sensor 344, can be arranged to measure the corresponding properties of the mixed liquid and generate sensor outputs to controller 240.

[0061] Valve arrangement 210 is configured to receive the mixed liquid from conduit 220 and distribute the mixed liquid to one or more of the biological treatment stations 110, 120, and 130. For this purpose, valve arrangement 210 includes a capture outlet 211 connected to a mixed liquid inlet 113 of capture station 110, an NFF outlet 212 connected to a mixed liquid inlet 123 of NFF station 120, and a purification outlet 213 connected to a mixed liquid inlet 133 of purification station 130. Furthermore, a waste outlet 214 is provided to discard the mixed liquid, for example, if any characteristic of the mixed liquid falls outside its acceptable range.

[0062] It should be noted that Figure 2 This is a simplified representation of a biological treatment system, and any of the biological treatment stations 110, 120, 130, 140 and the liquid supply device 200 may include additional features and functions not depicted in the drawings.

[0063] Now refer to Figure 3 Flowchart 1000 describes Figure 2 The illustrated sequence of operations for the biological processing system is an exemplary sequence of operations. This illustrated sequence of operations pertains to a purification process involving a chromatographic column and should be considered illustrative rather than limiting of the scope of the inventive concepts and embodiments disclosed herein.

[0064] In the first processing step S110, the liquid supply device 200 balances the capture column 115 of the capture station 110 by supplying a mixed liquid prepared from an acidic buffer, a basic buffer, a salt, and WFI to the mixed liquid inlet 113 of the capture station 110. The mixed liquid passes through the capture column 115 and is released to the waste outlet 114 by the release valve 117. Balancing is typically performed to establish the correct pH and ionic strength in the stationary phase, thereby making the stationary phase suitable for the conditions required by the specific chromatographic technique used.

[0065] Subsequently, the sample is loaded into the capture column 115 via S120. The sample may be filtrate pumped from the mixer 20 by the sample pump 21. The sample flow may be directed to the capture column 115 by means of an inlet valve 116, which may be arranged to open the flow path between the sample pump 21 and the capture column 115 and simultaneously close the flow path to the mixed liquid inlet 113 to prevent backflow toward the liquid supply device 200. The sample may be supplied to the capture column 115 by means of the sample pump 21 that drives the sample flow through the inlet valve 116. During the loading of the capture column 115, the release valve 117 may be operated to direct the output from the capture column 115 to the waste outlet 114.

[0066] In the next step, the liquid supply device 200 can be used to elute the capture column 115 in S130 and allow the target material to be collected by the inactivation station 140. During the elution process S130, the mixed liquid forms an eluent (such as a solvent or buffer), which disrupts the interaction between the target material and the stationary phase of the capture column 115, thereby allowing the target material (also referred to as the eluent) to be eluted from the column. In this step, the inlet valve 116 is operated to open the flow path between the mixed liquid inlet 113 and the capture column 115, and the release valve 117 is operated to open the flow path from the outlet of the capture column 115 to the feed outlet 112 connected to the inactivation station 140.

[0067] After elution S130, the capture column S140 can be regenerated to remove any remaining target material and impurities and restore column 115 to its initial state. Regeneration may include supplying a buffer solution to the capture column 115 via a liquid supply device 200, which is then passed to waste outlet 114. A virus inactivation process S150 may be performed as a separate process, which may be carried out simultaneously with or separately from the regeneration step S140, wherein the eluent is exposed to acid added to a first incubation mixer 141 of the inactivation station 120. The inactivation process S150 may also include transferring a low-pH eluent to a second incubation mixer 142, wherein the eluent is incubated and neutralized by alkali added from a single-use container 144.

[0068] Following regeneration S140 of the capture column 115, the depth filter 125 of the NFF station 120 can be equilibrated S160 by a buffer solution provided by the liquid supply device 200. Equilibration S160 can be performed simultaneously with at least a portion of the virus inactivation process S150, or at a time separate from the virus inactivation process S150. The depth filter 125 is typically equilibrated S160 by passing the buffer solution through the filter to wet it and remove any air and impurities that may be present. The buffer solution can be provided as a mixed liquid from the NFF outlet 212 of the liquid supply device 200 and transferred to the waste outlet 124 via the release valve 127.

[0069] The neutralized eluent can then be filtered in S170 as it is supplied from the second incubator mixer 142 via the feed inlet 121 to the depth filter 125 and further to the NFF mixer 128. During filtration S170, the inlet valve 126 can be arranged to open the flow path of the eluent and close the flow path of the mixed liquid to prevent backflow of the eluent toward the liquid supply device 200. Similarly, the release valve 127 can be operated to close the flow path to the waste outlet 124 and open the flow path to the feed outlet 122.

[0070] In this example, the liquid supply device 200 is operated to equilibrate the purification column 130 (S180) while filtering the eluent (S170) through the NFF station 120. Equilibration (S180) can be similar to equilibration (S110) of the capture column 115, and can therefore include supplying a buffer solution to the mixed liquid inlet 133 of the purification station 130 and allowing the buffer solution to pass through the purification column 115 to the waste liquid outlet 134.

[0071] The filtration process S170 (in which the eluent is filtered by the depth filter 125) can be completed by the rinsing process S190, in which the inlet valve 123 is operated to open the flow path between the liquid supply device 200 and the depth filter 125, thereby allowing the mixed liquid prepared by the liquid supply device 200 to rinse the filter and drive any remaining eluent in the depth filter 125 toward the NFF mixer 128.

[0072] The eluent can then be fed from the NFF mixer 128 to the feed inlet 131 of the refining column 135 for loading the refining column 135 in S200. Loading can be carried out with the assistance of a feed pump 22, which drives the feed through inlet valve 136 to the refining column 135. During this operation, inlet valve 136 can be arranged to close the flow path between the mixture inlet 133 and the refining column 135 to prevent the eluent from flowing toward the liquid supply device 200. During loading S200, release valve 137 can be operated to release the output from the refining column 135 to waste outlet 134.

[0073] exist Figure 3 In the final step of method 1000, the liquid supply device 200 can be used to elute the purification column 135 in step S210 and allow the target material to be collected by the mixer 138. The elution can be similar to the elution in step S130 of the capture column 115 described above.

[0074] Some or all of the above-described processing steps can be controlled by controller 240, which can therefore be configured to cause liquid supply device 200 to supply the required mixed liquid to the corresponding biological treatment station, and to control the operation of one or more of pumps 21, 22 and one or more of valves 116, 117, 126, 127, 136, 137 to guide the mixed liquid and target material flow through the biological treatment system. Controller 240 may include circuitry configured to perform controller functions, wherein the circuitry may include a processor, such as a central processing unit, CPU, microcontroller, or microprocessor, configured to execute program code. The program code may, for example, be configured to perform an evaluation function to evaluate pH or conductivity levels based on signal outputs from pH sensor 342, conductivity sensor 344, or a sample sensor (not shown), the sample sensor being arranged to measure the concentration of the target material in the feed. The controller 240 may also include a memory, which may be one or more of a buffer, flash memory, hard disk drive, removable media, volatile memory, non-volatile memory, random access memory (RAM), or other suitable devices. In a typical arrangement, the memory may include non-volatile memory for long-term data storage and volatile memory used as system memory for the circuitry. The memory can exchange data with the circuitry via a data bus. Accompanying control lines and an address bus may exist between the memory and the circuitry.

[0075] The processing functions of controller 240 can be embodied in the form of executable logic routines (e.g., lines of code, software programs, etc.), which are stored on a non-transitory computer-readable medium (memory) of controller 240 and executed by circuitry. Furthermore, the processing functions of controller 240 can be a standalone software application or part of a software application. The described functions can be considered as a method configured to be executed by a processing unit (e.g., a processor of circuitry). Moreover, while the described functions can be implemented in software, such functionality can also be executed via dedicated hardware or firmware, or some combination of hardware, firmware, and / or software.

[0076] Figure 4a This is a schematic diagram of a biological processing system capable of operating to perform multiple biological processing operations on a liquid stream including a mixed liquid carrying a sample or target material. The system includes a biological processing component 310, which can be connected to the above-mentioned reference... Figures 1 to 3 Any of the biological processing components discussed are configured similarly. Thus, biological processing component 310 can be a chromatographic column for performing chromatographic operations, a filtration device for performing filtration operations, or a virus inactivation incubator for inactivating any viruses present in the eluent.

[0077] The system also includes a pump unit 320 for driving the flow of the mixed liquid through the piping system 400 to the biological treatment component 310. The mixed liquid (which may be, for example, a buffer solution) can be similar to a combination Figures 1 to 3 The mixed liquid discussed is used to drive the target material through the biological treatment system. The mixed liquid can be supplied from the mixed liquid supplier 10, such as a storage tank or a disposable container.

[0078] Pump unit 320 can be operated to drive a flow of the mixed liquid through the system toward the location or junction where the sample is added to conduit 430. The sample can be supplied from sample supply source 422, which may include sample pump 446 arranged to drive a flow of sample from mixer 20 or disposable container 20 and add the sample to the mixed liquid to form a liquid flow feed to bioprocessing unit 310. The sample supply source is arranged to add the sample to conduit 430 at the portion between pump unit 320, which drives the flow of the mixed liquid, and bioprocessing unit 310. By adding the sample downstream of pump unit 320, the risk of sample contact with pump unit 320 is reduced, and pump unit 320 can therefore be reused between different sample batches. To further reduce the risk of contact between pump unit 320 and the sample, a protective valve 350 can be added between the sample supply point and pump unit 320. Protective valve 350 can be operated to close the flow path to the pump unit while the sample is being pumped into conduit 430. In some instances, samples are added as close as possible to the bioprocessing unit 310 to reduce the length of the flow path between the sample pump 466 and the bioprocessing unit 310.

[0079] The piping system 400 that guides the sample flow from the sample supply source 442 to the bioprocessing unit 310 and further to the inlet 450 downstream of the bioprocessing unit 310 can be a disposable piping system, comprising one or more conduits configured to be replaced between processing operations or sample batches. Alternatively, the pump unit 320 can be reused for several bioprocessing operations or sample batches since it has not yet come into direct contact with the sample. By separating the pump unit 320 and the sample from each other, it is possible to position the pump unit 320 in a location physically separate from the portion of the bioprocessing system exposed to the sample. In one example, the pump unit 320 and the bioprocessing unit 310 can be arranged in a separate area of ​​a cleanroom facility, where the pump unit 320 can be located in a less clean area of ​​the cleanroom to save floor space in the clean area. Examples of this configuration are... Figure 5b As shown in the image.

[0080] One or more sensors can be arranged to measure various characteristics of the liquid flowing through the system, such as the mixed liquid pumped by pump unit 320, the liquid flow supplied to biological treatment unit 310 via component inlet 422, and the output from biological treatment unit 310 at component outlet 424. Figure 4a In the example shown, pH sensor 342 and conductivity sensor 344 can be arranged upstream of the sample supply point (i.e., in the reusable part of the system), while sample sensors (such as UV sensors capable of operating to measure the concentration or amount of target material in the feed discharged from the bioprocessing unit 310) can be arranged downstream of the bioprocessing unit 310 (in the disposable part of the system).

[0081] It should be understood that Figure 4a The schematic diagram in the figure is a simplified version with one or more components and features omitted. For example, additional sensors, valves, air traps, filters, etc., may be provided, which are not depicted in this figure.

[0082] Pumps used to drive flow through a biological treatment system (such as sample pump 446 and pump unit 320 for mixing liquids) can be of various types and depend on flow rate and pressure requirements as well as the specific system configuration. In some instances, peristaltic pumps can be used, where a flexible tube (such as conduit 430) is compressed and released in a controlled manner to move the fluid forward. In other instances, diaphragm pumps can be utilized, which use a flexible diaphragm that moves back and forth to produce the pumping action. In still other instances, piston pumps are used, where the movement of a piston within a chamber generates pressure to drive the fluid.

[0083] Now refer to Figure 4b The discussion focuses on disposable components of system 300, namely the tubing system 400 that guides the mixed liquid and sample through at least a portion of the biological treatment system. The tubing system 400 may also be referred to as a flow kit and can be supplied as a consumable or single-use component. The tubing system 400 can thus be configured for a specific biological treatment operation or sample batch and replaced after the biological treatment operation or sample batch has been completed. Before starting a new biological treatment operation or sample batch, the tubing system 400 can be replaced with a clean, preferably pre-sterilized, tubing system.

[0084] Figure 4b An example of such a piping system 400 is illustrated. The piping system 400 includes a plurality of inlets 410, 444 and outlets 422, 424, 450, between which a flow path is formed by conduits arranged to guide liquid between various components and processing steps of the biological treatment system. In this example, the piping system 400 includes an inlet branch comprising a conduit 430 having a mixing liquid inlet 410 configured to connect to… Figure 4a The pump unit 320 shown, or more specifically, is coupled to a protective valve 350 that protects the pump unit 320 and sensors 342, 344 from contact with the sample. The piping system 400 also includes a sample inlet 440 configured to supply a sample to a mixed liquid flow in the conduit 430. The sample flow provided at the sample inlet 440 can be driven by a sample pump 446, which can therefore be integrated into the disposable piping system 400 and replaced along with the rest of the piping system 400. The sample pump 446 may, for example, include a disposable pump head that can be connected to a reusable pump body or drive unit. The sample flow can be added at a location in the conduit downstream of the mixed liquid inlet 410, thus downstream of the pump unit 320 and sensors 342, 320.

[0085] The conduit 430 can be arranged to direct a liquid flow including a sample carried by the mixed liquid flow to a processing unit inlet 422. The processing unit inlet 422 is configured to connect to an inlet of the bioprocessing unit 310 to supply the sample to that bioprocessing unit. The piping system 400 also includes an outlet branch including a processing unit outlet 424 configured to connect to an outlet of the bioprocessing unit 310 to receive output from the bioprocessing unit 310 and direct that output to a feed outlet 450, which may include a manifold having multiple outlets. In this example, a bypass path 425 may be provided between the processing unit inlet 422 and the bioprocessing unit outlet 424 to allow bypassing the bioprocessing unit.

[0086] Additionally, one or more sensors can be integrated into the disposable piping system 400. Figure 4b In, similar to Figure 4a The sample sensor 460 shown is arranged in the outlet branch.

[0087] The individual fluid lines or conduits forming the flow paths of the piping system 400 can be flexible to facilitate handling and installation, and can be configured with pinch valves to open and close the flow paths during operation of the biological treatment system 300. The conduits can be formed from elastomeric materials, including one or more of silicone rubber, thermoplastic elastomers, or thermoplastic rubbers.

[0088] As previously mentioned, piping system 400 can be housed in a pre-sterilized sealed container or bag. To maintain sterility, one or more inlets / outlets may be provided with a barrier of sterile filters that can be removed or destroyed during installation of piping system 400, or may be provided with connectors that allow for sterilization of installation-related connection points (e.g., via steam).

[0089] Figure 5aThis is a schematic diagram of the piping system 400 when attached to the base unit 500 or the slider. The base unit can form a separate modular unit that can be transported (e.g., by means of wheels 502 provided for this purpose) and integrated into a larger processing system. In the context of this disclosure, the base unit 500 can correspond to the combination as described above. Figures 1 to 3 The biological treatment station under discussion.

[0090] The base unit 500 includes a housing with a plurality of valve actuators 508, 510, 512, 514 to 517 configured to releasably engage a portion of a conduit in the piping system 400 to form a pinch valve controlling flow through the piping system. Each valve actuator may be arranged to cooperate with a housing or valve body to define a passage through which the conduit can pass, and wherein the valve actuator may be moved relative to the housing to reduce the cross-section of the passage, thereby clamping the conduit and closing it. Deactivation of the valve actuator subsequently causes the conduit to resiliently return to its initial open state, thus allowing fluid to flow through it.

[0091] The valve actuator can be operated independently by controller 240, which can be located in base unit 500 or elsewhere. In some instances, controller 240 can be distributed among several nodes or include multiple sub-modules, which can be arranged in each valve actuator or elsewhere.

[0092] The base unit 500 may also include a user interface or human-machine interface (HMI) that allows an operator to interact with and control the operation of the biological treatment system.

[0093] The base unit 500 can also be arranged to provide the power required to drive, for example, the sample pump 446.

[0094] exist Figure 5a In the illustrated example, the base unit 500 and the mounted piping system 400 form a first inlet valve 508 upstream of the sample supply point and a second inlet valve 510 downstream of the sample supply point, wherein the sample supply source 442 adds the sample to the mixed liquid stream. A processing unit inlet 422 and a processing unit outlet 424 are coupled to a processing unit, which in this example is a chromatographic column 310, and a processing unit outlet 512 is formed downstream of the processing unit 310. Furthermore, a bypass valve 511 forms a bypass path 425 extending between the processing unit inlet 422 and the processing unit outlet 424 to allow bypassing the processing unit 310. The manifold including multiple outlets 450 can be engaged by multiple outlet valve actuators to allow controlled release of the output feed to, for example, a waste outlet or a subsequent treatment station, as combined with... Figures 1 to 3The discussion focuses on four different outlets 451 to 454, each controlled by a corresponding pinch valve 514 to 517.

[0095] A conduit or tubing forming an inlet branch 430 for conveying the mixed liquid and sample to the processing unit 310, and an outlet branch 431 for conveying the output from the processing unit 310 to the inlet outlet 450, can be configured for single use, as discussed above. This may also include a sample pump 446.

[0096] This configuration, which adds the sample downstream of pump unit 320, allows pump unit 320 to be configured for multiple uses. In other words, pump unit 320 does not need to be replaced along with piping system 400. Advantageously, this further allows pump unit 320 to be arranged in a different location than the rest of the biological treatment system, or at least in a different location than biological treatment component 310 or base unit 500.

[0097] Figure 5b An example of this configuration is shown, in which the base unit 500 carrying the bioprocessing component 310 is arranged in a first zone 610, and the pump unit 320 is arranged in a second zone 620, distinct from the first zone 610. The first zone 610 and the second zone 620 can form part of a cleanroom facility designed to prevent particulate and microbial contamination of biopharmaceutical products processed by the bioprocessing system. In this example, the first zone 610 can be maintained at a relatively high cleanliness level or grade, such as ISO 7, while the second zone 620 can be maintained at a lower cleanliness level. The first zone 610 can also be referred to as the processing zone, and the second zone 620 can also be referred to as the service zone. The first zone 610 and the second zone 620 can be separated from each other by a wall, and the mixed liquid passes through the wall via a straight-through connection to which the mixed liquid inlet 410 of the piping system 400 can be releasably coupled. Advantageously, this configuration allows for the separation of processing equipment and material supply streams. More specifically, the mixed liquid supply source 10 and pump unit 320 can be located in a less clean service area 620, while the biological treatment component 310 can be kept in a highly controlled treatment area 610. Furthermore, one or more sensors, such as a pH sensor 342 and a conductivity sensor 344, can be arranged in the service area 620.

[0098] It should be understood that similar configurations can be applied to the above combinations. Figures 1 to 3The liquid supply device 200 under discussion. In other words, the liquid supply device 200, or a portion thereof (such as a mixed arrangement 230 for supplying one or more solution components to conduits 220), may be arranged in a second region 620, while one or more of the plurality of biological treatment stations 100 may be arranged in a first region 610. In some instances, the liquid supply device 200 may be operable to supply multiple production lines, each comprising a plurality of interconnected biological treatment stations 100. The multiple production lines may be arranged in the same treatment region 610 or in separate treatment regions. In one example, a hub and spoke arrangement is envisioned, wherein the liquid supply device 200 is arranged in the hub and supplies multiple production lines forming the spokes.

[0099] Therefore, various embodiments of the invention enable the efficient provision of online-regulated fluids for various unit operations (e.g., for different operations such as filtration, chromatography, etc., where the effluent from one carriage can be used as input to the next carriage to provide continuous downstream purification). Various feeds can also be provided in a closed loop, allowing for further provision of fully automated systems. Advantageously, embodiments of the invention can also provide online regulation for different unit operations and / or for different concentrations, gradient distributions, etc. (e.g., buffer fluids) required at different times. An additional benefit of certain embodiments of the invention is that the required stock of reserve solutions is reduced, thereby lowering storage requirements and associated logistical complexities.

[0100] Furthermore, advantageously, embodiments of the invention enable buffer preparation to be carried out in unregulated areas (e.g., outside of cleanrooms). This improves logistics and associated sustainability aspects (e.g., by reducing the amount of single-use packaging, etc., that would otherwise be required to produce buffer solutions in cleanrooms).

[0101] The above embodiments should be understood as illustrative examples of the present invention. It should be understood that any feature described with respect to any embodiment can be used alone or in combination with other described features, and can also be used in combination with one or more features of any other embodiment, or in any combination of any other embodiment. Furthermore, equivalents and modifications not described above may be employed without departing from the scope of the invention as defined in the appended claims.

Claims

1. A biological treatment system for separating a target material from one or more impurities in a feed, the system comprising: Multiple biological treatment stations (100), each configured to perform a corresponding biological treatment operation on the feed, are interconnected such that the outlet (112) of the first biological treatment station is connected to the inlet (121) of the next biological treatment station. A liquid supply device (200) includes a valve arrangement structure (210), a conduit (220), a mixing arrangement structure (230), and a controller (240); wherein The mixing arrangement structure is configured to supply at least a first solution component and a second solution component to the conduit, thereby forming a mixed liquid; The valve arrangement is fluidly connected to the conduit and is operable to selectively supply the mixed liquid to each of the biological treatment stations in the biological treatment station; and The controller is configured to control the operation of the mixed arrangement structure for each biological treatment station, such that the mixed liquid has a predetermined set of characteristics associated with the biological treatment operation of the biological treatment station.

2. The system of claim 1, wherein each of the plurality of biological processing stations comprises a biological processing component (115, 125, 135) as at least one of a chromatography column, a filter, and a mixer.

3. The system according to any one of the preceding claims, wherein the target material is a biological target material.

4. The system according to any one of the preceding claims, wherein the first solution component is a first buffer substance, the second solution component is a second buffer substance, and wherein the mixed liquid is a buffer solution.

5. The system according to any one of the preceding claims, wherein the liquid supply device further comprises a control sensor arrangement (250) configured to output a signal indicating the characteristics of the mixed liquid, and wherein the controller is configured to control the operation of the mixing arrangement at least in part based on the signal from the control sensor arrangement.

6. The system according to any one of the preceding claims, wherein each of the plurality of biological treatment stations includes an inlet valve arrangement (116) configured to control the supply of feed and mixed liquid to the biological treatment station.

7. The system according to any one of the preceding claims, wherein each of the plurality of biological treatment stations includes a release valve arrangement (117) configured to control the release of feed and mixed liquid from the biological treatment station.

8. The system according to any one of the preceding claims, wherein the plurality of biological treatment stations are adapted to be arranged in a treatment area maintaining a first level of cleanliness, and wherein the mixed arrangement is adapted to be arranged in a service area maintaining a second level of cleanliness, the second level being lower than the first level.

9. A method (1000) for separating a target material from one or more impurities in a feed, the method comprising: The feed is supplied to multiple biological treatment stations, each configured to perform a corresponding biological treatment operation on the feed, and the multiple biological treatment stations are interconnected such that the outlet of the first biological treatment station is connected to the inlet of the next biological treatment station. At least a first solution component and a second solution component are mixed in a mixed arrangement structure to form a mixed liquid; The mixed liquid is selectively supplied to each of the plurality of biological treatment stations; as well as For each of the plurality of biological treatment stations: The mixed arrangement structure is operated to provide the mixed liquid having a set of predetermined characteristics associated with the biological treatment operations performed by the biological treatment station.

10. The method (1000) according to claim 9, wherein the biological treatment operation in at least one of the plurality of biological treatment stations includes an equilibration phase, a sample loading phase, an elution phase, and a regeneration phase.

11. The method (1000) according to claim 10, wherein the method comprises: The inlet valve arrangement is configured to supply the mixed liquid to the biological treatment station during the balancing phase, the elution phase, and the regeneration phase, and to supply the sample to the biological treatment station during the sample loading phase.

12. The method (1000) according to claim 10 or 11, wherein the method comprises: The operation involves a release valve arrangement to release the output from the biological treatment station to a waste outlet during the balancing phase, the sample loading phase, and the regeneration phase, and to release the output to the next of the plurality of biological treatment stations during the elution phase.

13. The method (1000) according to any one of claims 9 to 12, wherein the plurality of biological treatment stations are arranged in the treatment area of ​​the cleanroom facility, and the hybrid arrangement is arranged in a service area for supplying materials to the plurality of biological treatment stations, the service area being separated from the treatment area by a wall.

14. A biological processing system (300) operable to perform multiple biological processing operations on a liquid stream including a mixed liquid carrying a sample, the biological processing system comprising: A biological treatment unit (310) is operable to perform at least one of the biological treatment operations on the liquid flow; A pump unit (320) operable to drive a flow of the mixed liquid to the biological treatment unit via a piping system (400); and A sample supply source (442) is operable to add the sample to the flow of the mixed liquid at a location between the pump unit and the biological processing component, thereby forming the liquid flow; The piping system is a disposable piping system configured to be replaced between each of the plurality of biological treatment operations; and The pump unit is a reusable pump unit that can be operated to be reused for each of the plurality of biological treatment operations.

15. The biological treatment system of claim 14, further comprising a base unit (500) operable to releasably engage with the piping system.

16. The biological treatment system of claim 15, wherein the base unit includes a valve actuator (510) operable to releasably engage a conduit of the piping system to form a pinch valve controlling the flow of the mixed liquid through the piping system.

17. The biological treatment system according to any one of claims 14 to 16, the biological treatment system further comprising a sensor (342, 344) arranged upstream of the location where the sample is added to the flow of the mixed liquid, the sensor being at least one of a pH sensor and a conductivity sensor.

18. The biological processing system according to any one of claims 14 to 17, the biological processing system further comprising a sample pump (446) operable to supply the sample to the flow of the mixed liquid.

19. The biological treatment system according to any one of claims 14 to 18, the biological treatment system further comprising a protection valve (350) operable to prevent the sample from reaching the pump unit.

20. The biological treatment system according to any one of claims 14 to 19, wherein the biological treatment component is adapted to be arranged in a treatment area maintaining a first level of cleanliness, and wherein the pump unit is adapted to be arranged in a service area maintaining a second level of cleanliness, the second level being lower than the first level.

21. The biological processing system according to claim 20, which is dependent on claim 17, wherein the sensor is adapted to be arranged in the service area.

22. The biological treatment system according to any one of claims 14 to 21, wherein the biological treatment component is at least one of the following: a filter, a chromatography column, and a purification membrane.

23. A piping system (400) for a biological treatment system, the biological treatment system being operable to perform multiple biological treatment operations on a liquid stream including a mixed liquid carrying a sample, the piping system comprising: Mixed liquid inlet (410), the mixed liquid inlet being configured to be connected to a pump unit of the biological treatment system; Processing component inlet (422), the processing component inlet being configured to connect to the biological processing component of the biological processing system; A conduit (430) configured to deliver a flow of the mixed liquid from the pump unit to the biological treatment component; and A sample inlet (440) is configured to supply the sample to the flow of the mixed liquid, the sample inlet being disposed between the mixed liquid inlet and the processing component inlet; The piping system is a disposable piping system configured to be replaced between each of the plurality of biological treatment operations.

24. The piping system of claim 23, further comprising a sterile connector disposed at each of the mixed liquid inlet, the processing component inlet, and the sample inlet to maintain the sterility of the piping system prior to use.

25. The piping system of claim 23 or 24, wherein the piping system is configured to be removably attached to a base unit including a valve actuator.

26. The piping system of claim 25, wherein the conduit is adapted to releasably engage with the valve actuator to form a pinch valve for controlling the flow of the mixed liquid through the piping system.

27. The tubing system according to any one of claims 23 to 26, wherein the conduit is formed of an elastomeric material, the elastomeric material comprising one or more of the following: silicone rubber, thermoplastic elastomers and / or thermoplastic rubber.

28. The piping system according to any one of claims 23 to 27, the piping system further comprising a sensor (460) operable to generate a signal indicating the concentration of the sample in the liquid flow.

29. The piping system according to any one of claims 23 to 28, the biological treatment system further comprising a protection valve (350) operable to prevent the sample from reaching the pump unit.

30. A method for reconfiguring a biological treatment system, the biological treatment system being operable to perform multiple biological treatment operations on a liquid stream including a mixed liquid carrying a sample, the biological treatment system comprising: A biological treatment unit, operable to perform at least one of the biological treatment operations on the liquid stream; A pump unit, operable to drive a flow of the mixed liquid to the biological treatment component; and A sample supply source operable to add the sample to the stream of the mixed liquid, thereby forming the liquid stream; The method includes performing the following operations between two consecutive biological treatment operations in the plurality of biological treatment operations: Disconnect the first piping system from the pump unit, the biological processing component, and the sample supply source; as well as Connect the second piping system to the pump unit, the biological processing component, and the sample supply source; Each of the first piping system and the second piping system is operable to deliver the flow of the mixed liquid from the pump unit to the biological treatment component.

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