Sampling module for a bioprocess purification system

Abstract

A sampling module 130 for sampling a product stream of a bioprocess purification system 100, 110, and a method for controlling a sampling module 130 are disclosed. The sampling module 130 comprises a controllable sampling valve unit 170 and a fluid coupling network 180, the sampling module 130 being configured to be fluidly couplable to a bioprocess purification system 100, 110 and a bioanalytical system 120, the sampling module 130 being controllable to sample a product stream of the bioprocess purification system 100, 110, wherein the sampling module 130 is configured to: obtain a fluid sample, wherein the fluid sample is obtained by providing a fluid path from the bioprocess purification system 100, 110 to the fluid coupling network 180 via the controllable sampling valve unit 170, and provide the fluid sample, wherein the fluid sample is provided to the bioanalytical system 120 by providing a fluid path from the fluid coupling network 180 to the bioanalytical system 120, wherein the sampling module 130 is a closed system such that the fluid sample is prevented from contact with the environment surrounding the sampling module 130.

Description

[0001] SAMPLING MODULE FOR A BIOPROCESS PURIFICATION SYSTEM

[0002] TECHNICAL FIELD

[0003] The present invention relates to a sampling module being controllable to sample a product stream of a bioprocess purification system. The invention further relates to a method for controlling the sampling module, and to a control unit for controlling the sampling module.

[0004] BACKGROUND

[0005] The term bioprocess refers to a series of techniques and methods used to produce biological products, such as drugs, enzymes, proteins, nucleotides, oligonucleotides, VP (viral particles), AAV’s (adeno associated virus) or nanoparticles, using living organisms or their components. Bioprocesses involve the use of microorganisms, animal or plant cells, or other biological systems to produce and modify products, often through genetic engineering, fermentation, or other techniques. Bioprocesses range from small scale processes, e.g. performed for experimental or bioanalytical purposes in a laboratory, to large scale industrial manufacturing. Bioprocesses are used in a wide range of industries, including pharmaceuticals, biotechnology, food production, and agriculture.

[0006] The initial stages of the bioprocess, also referred to as the upstream phase, typically involve culturing or growing the organism or cells that produce the desired product. This may involve selecting and optimizing the growth conditions, such as temperature, pH, and nutrients, to ensure maximum productivity and yield. The upstream phase may also include genetic engineering and fermentation, which can be used to modify and improve the organism's ability to produce the desired product.

[0007] The upstream phase is typically followed by purification and processing of the product produced during the upstream phase. This purification and processing is referred to as the downstream phase. The goal of the downstream phase is to isolate and purify the desired product from the complex mixture of other components produced in the upstream phase. The downstream phase, or bioprocess purification system, often involves a series of separation and purification steps, such as filtration, chromatography, and crystallization, to obtain a highly pure and concentrated product.

[0008] Overall, the upstream and downstream phases of a bioprocess are both critical to the success of the process, as they are interdependent and each affects the quality and yield of the final product. By optimizing both phases of the process, high yields of high- quality products that are suitable for use in various applications can be obtained.

[0009] In bioprocesses, sampling of the product streams may be performed in the upstream phase as well as in the downstream phase. Periodic sampling of the fluid in the bioreactor in the upstream phase is often performed, e.g. to monitor and control the conditions and levels of nutrients needed for cell growth. Sampling in the downstream process, or bioprocess purification system, may also be performed in order to monitor e.g. progress and efficiency of various separation and purification steps.

[0010] Conventionally, sampling of a product stream in a bioprocess purification system is performed manually, typically performed from fractions in a fraction collector or from a holding tank between process steps. Manual sampling can be time consuming and expensive and increases the risk of introducing errors due to sample handling and also the risk of the product stream becoming contaminated. Automated sampling systems often suffer the disadvantage of wasting a relatively large volume of fluid each time a fluid sample is obtained. Furthermore, the existing sampling methods are typically too slow for monitoring and controlling the purification and processing of the product in the downstream phase.

[0011] There is therefore a need for improved methods and devices for sampling of product streams in the downstream phase of a bioprocess. There is also a need for improved methods and devices for sampling of product streams in a bioprocess purification system which allows for samples to be obtained as sampling points throughout the process, based on either known or unknown attributes, e.g. impurities, of the product stream.

[0012] OBJECTS OF THE INVENTION An object of embodiments of the present invention is to provide a solution which mitigates or solves the drawbacks and problems described above.

[0013] A further object of embodiments of the present invention is to provide a sampling module and a method for sampling a product stream of a bioprocess purification system, which allows for monitoring and controlling the purification and processing steps in the downstream phase.

[0014] A further object of embodiments of the present invention is to provide a sampling module and a method for sampling a product stream of a bioprocess purification system that reduces or minimizes the risk of contamination of the fluid sample or the product stream.

[0015] A further object of embodiments of the present invention is to provide a sampling module for sampling a product stream of a bioprocess purification system, wherein said sampling module can be integrated in new bioprocess systems or retrofitted in existing bioprocess systems.

[0016] SUMMARY OF THE INVENTION

[0017] The above objects are achieved by the subject matter described herein. Further advantageous implementation forms of the invention are further defined herein.

[0018] According to a first aspect of the invention, the above mentioned and other objects are achieved by a sampling module for sampling a product stream of a bioprocess purification system, the sampling module comprising a controllable sampling valve unit and a fluid coupling network, the sampling module being configured to be fluidly couplable to a bioprocess purification system and a bioanalytical system, the sampling module being controllable to sample a product stream of the bioprocess purification system, wherein the sampling module is configured to: obtain a fluid sample, wherein the fluid sample is obtained by providing a fluid path from the bioprocess purification system to the fluid coupling network via the controllable sampling valve unit, and provide the fluid sample, wherein the fluid sample is provided to the bioanalytical system by providing a fluid path from the fluid coupling network to the bioanalytical system, wherein the sampling module is a closed system such that the fluid sample is prevented from contact with the environment surrounding the sampling module.

[0019] An advantage of embodiments according to the first aspect is that the risk of contamination of the fluid sample or the product stream of the bioprocess purification system is reduced or minimized. A further advantage is that the volume of the fluid sample drawn from the product stream of the bioprocess purification system is reduced. Yet a further advantage of embodiments according to the first aspect is that the sampling can be automated, which allows for monitoring, and optionally also controlling, the progress and efficiency of various separation and purification steps of the bioprocess purification system. This may also allow for more specific analysis as more data points can be analyzed.

[0020] According to a second aspect of the invention, the above mentioned and other objects are achieved by a method for controlling a sampling module as defined with reference to the first aspect to sample a product stream of a bioprocess purification system, the method comprising: obtaining a fluid sample from the bioprocess purification system, wherein the step of obtaining the fluid sample comprises controlling a flow of fluid from the bioprocess purification system to the fluid coupling network via the controllable sampling valve unit, and providing the fluid sample, wherein the step of providing the fluid sample comprises providing the fluid sample from the fluid coupling network to the bioanalytical system.

[0021] According to a third aspect of the invention, the above mentioned and other objects are achieved by a control unit (CU) for a sampling module being controllable to sample a product stream of a bioprocess purification system, the control unit comprising: processing circuitry, a memory comprising instructions executable by the processing circuitry, causing the processing circuitry to perform the method according to the first aspect.

[0022] According to a fourth aspect of the invention, the above mentioned and other objects are achieved by a bioprocess system comprising a bioprocess purification system, a bioanalytical system, and a sampling module according to the first aspect. Advantages of embodiments according to the second to fourth aspect are at least the same as for the first aspect. Further applications and advantages of embodiments of the invention will be apparent from the following detailed description.

[0023] BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Fig. 1 shows a bioprocess system comprising a bioprocess purification system, a bioanalytical system, and a sampling module according to one or more embodiments of the present application.

[0025] Fig. 2 shows details according to one or more embodiments of the bioprocess system.

[0026] Fig. 3 shows details according to one or more embodiments of the bioprocess system.

[0027] Fig. 4 shows details according to one or more embodiments of the bioprocess system.

[0028] Fig. 5 shows a control unit according to one or more embodiments of the present application.

[0029] A more complete understanding of embodiments of the invention will be afforded to those skilled in the art, as well as a realization of additional advantages thereof, by a consideration of the following detailed description of one or more embodiments. It should be appreciated that like reference numerals are used to identify like elements illustrated in one or more of the figures.

[0030] DETAILED DESCRIPTION

[0031] An “or" in this description and the corresponding claims is to be understood as a mathematical OR which covers “and” and “or”, and is not to be understood as an XOR (exclusive OR). The indefinite article “a” in this application and claims is not limited to “one” and can also be understood as “one or more”, i.e. , plural. In the present application, a “bioprocess” generally denotes a chemical process which involves organisms or biochemically active substances derived from such organisms. The term “bioprocessing system” refers to a system for carrying out a bioprocess or parts thereof. The bioprocess may be carried out in a “bioreactor”. Examples of bioreactors include single use reactors, high throughput bioreactors, glass bioreactors and stainless steel reactors. Examples of process modes used in the bioreactors include perfusion culturing, fed batch culturing and batch culturing.

[0032] In the present application, the term “bioprocess purification system” generally denotes a system comprising one or more separation and purification step(s), such as filtration and chromatography step(s), configured to purify and concentrate a product stream comprising one or more products obtained from a bioprocess.

[0033] In the present application, the term “bioanalytical system” denotes equipment for analyzing the composition or chemical or physical or biological properties of a sample of a product stream of the bioprocess purification system. The bioanalytical system comprises one or more bioanalytical instruments.

[0034] In the present application, the term “sampling module” refers to a device being configured to be fluidly couplable to a bioprocess purification system and a bioanalytical system, the sampling module being controllable to obtain a fluid sample of a product stream of the bioprocess purification system and to provide the sample to the bioanalytical system for analysis.

[0035] In the present application, the term “controllable valve unit” denotes an arrangement or apparatus being configured to allow or prevent fluid, received from an inlet of the controllable valve unit to an outlet of the controllable valve unit. The controllable valve unit typically comprises one or more controllable valve(s), an actuator unit and control logics, which control logics are capable of receiving a control signal and control the actuator unit to move the valve to an open operational state where fluid is fully allowed to flow from the inlet to the outlet, to a closed operational state where fluid is prevented from flowing from the inlet to the outlet or optionally to an intermediate operational state where a reduced flow is allowed from the inlet to the outlet. In all the embodiments described herein changes of operational states of the controllable valve(s) are made in response to a received control signal. In one example a control unit sends a control signal indicative of a desired operational state to a controllable valve.

[0036] In the present application, the term “fluid coupling network” denotes an arrangement for providing fluid paths to / from a bioprocess purification system to a bioanalytical system, such as a mass spectrometer or a high-performance liquid chromatography system. In its most basic form, the fluid coupling network consists of an arrangement for providing a fluid path from the bioprocess purification system or from an inlet of the sampling module being fluidly couplable to the bioprocess purification system to an inlet of the controllable valve unit, and from an outlet of the controllable valve unit to the bioanalytical system or to an outlet of the sampling module being fluidly couplable to the bioanalytical system.

[0037] In the present application the term “fluid path” denotes an assembly of components configured to / for conveying a fluid, e.g. conduits fluidly coupled to one or more fluid valves. The fluid path typically comprises one or more conduits connecting fluid inlets and fluid outlets and any intermediate equipment, such as pumps, valves, flow diverters, mixers, pressure restrictors, ventilators, sensors, etc.

[0038] In the present application, the term “buffer source” denotes an arrangement for providing buffer fluid, e.g. containers and / or pumps arranged to provide the buffer fluid. Buffer fluid may e.g. include Phosphate, Acetate, TRIS, Citrate, HEPES, Acetonitrile, Methanol, Formic acid, Tri-Fluoroacetic acid TFA, salts and / or Additives (detergents).

[0039] In the present application, the term “clean in place source” or “CIP source” denotes an arrangement for providing CIP fluid, e.g. containers and / or pumps arranged to provide the CIP fluid. Examples of CIP fluids are Oxidizing agents (NaCIO, peracetic acid, H2O2), Organic solvents (IPA, EtOH), Acids (HNO3, HAc), Bases (NaOH) and Steam.

[0040] In the present application the term “waste port” or simply “waste” denotes an arrangement for receiving fluid, such as a drain, a container or other receptacle. The waste port may e.g. comprise a valve or a check valve that is control led / switched to an open / closed operational state.

[0041] In the present application the term “conduit reservoir" denotes an arrangement for holding the sample from the bioprocess purification system, e.g. a looped conduit, a container, a tube, a syringe, or an air trap. An important feature of the “conduit reservoir" is that it is arranged to allow cleaning by letting a fluid flow through the entire reservoir. By using a reservoir with substantially the same cross-section area, the entire reservoir is effectively cleaned. This is e.g. the case for the variable sample volume reservoir Superloop™ from Cytiva. In other words, preferably the “conduit reservoir" is a “looped conduit reservoir", allowing cleaning fluid to flow through and clean the reservoir.

[0042] The method of the present application comprises obtaining a fluid sample from the bioprocess purification system, wherein the step of obtaining the fluid sample comprises controlling a flow of fluid from the bioprocess purification system to the fluid coupling network via the controllable sampling valve unit. As mentioned in the background section, conventional sampling of a bioprocess purification system is a manual procedure. It is time consuming and may contaminate the product stream in the bioprocess purification system. The sampling typically allows measurement of characteristics, such as the composition or chemical or physical or biological properties, of a sample of a product stream of the bioprocess purification system. The present application improves the sampling process by providing a sampling module comprising a controllable sampling valve unit and a fluid coupling network, and a method for controlling the sampling module. A fluid sample is obtained, optionally held in a conduit reservoir, and then provided, optionally via a sample preparation system and / or a sample storage unit, to a bioanalytical system, typically for determining characteristics of the fluid sample. The sampling module is a closed system such that the fluid sample is prevented from contact with the environment surrounding the sampling module.

[0043] Fig. 1 shows a bioprocessing system 100 comprising a bioprocess purification system (BPS) 110, a bioanalytical system (BAS) 120, and a sampling module 130 according to one or more embodiments of the present application. In some embodiments, the bioprocess purification system 110 is a chromatography system, or a filtration system.

[0044] The bioanalytical system 120 is preferably a bioanalytical system capable of automatically determining a characteristic of a sample provided from the sampling module, and preferably also capable of forwarding a signal corresponding to the determined characteristic back to the sampling module 130 or the bioprocess purification system 110. In some embodiments, the bioanalytical system 120 is a bioanalytical system based on a bioanalytical technique selected from the group consisting of mass spectrometry (MS), high-performance liquid chromatography (HPLC), ultra-performance liquid chromatography (LIPLC), liquid chromatography-mass spectrometry (LC-MS), capillary electrophoresis (CE), capillary electrophoresis-mass spectrometry (CE-MS), surface plasmon resonance (SPR), ELISA, flow cytometry, or a combination thereof.

[0045] The sampling module 130 is configured to be fluidly couplable to the bioprocess purification system 110, and the bioanalytical system 120. The sampling module 130 may further be configured to be fluidly couplable to one or more buffer source(s) 140, one or more clean in place (CIP) source(s) 150, and / or one or more waste containers 160 or waste port(s) 162. In an exemplary embodiment the application of Fig. 1 is implemented using controllable valves fluidly coupled by using conduits or tubing. The skilled person understands how the various components described herein may be combined and connected in order to achieve desired functionality of the sampling module 130. For example, the skilled person understands how pumps, valves, tubing, conduits, and liquid sources should be combined and connected in order to achieve transport of fluid from one point to another.

[0046] The sampling module 130 is controllable to sample or to provide a fluid sample from the bioprocess purification system 110. In some embodiments, the sampling module 130 is configured to be connectable to a control unit (CU) 200 for controlling the sampling module 130. In some embodiments, the method for controlling the sampling module 130 is a computer implemented method. In some embodiments, the control unit 200 is configured to perform the inventive method. In some embodiments, the control unit 200 is configured to communicate with the bioprocess purification system 110 and / or the bioanalytical system 120. For example, in some embodiments, the control unit 200 is configured to initiate the inventive method based on a signal from the bioprocess purification system 110.

[0047] The sampling module 130 comprises a controllable sampling valve unit 170 being configured to allow or prevent fluid flow from the bioprocess purification system 110 to a fluid coupling network 180. The controllable sampling valve unit 170 has an inlet 172 and an outlet 174.

[0048] The fluid coupling network 180 in Fig. 1 consists of a fluid path from an inlet 132 of the sampling module 130 being fluidly couplable to the bioprocess purification system 110 to an inlet of the controllable valve unit 172, and from an outlet 174 of the controllable valve unit to an outlet 134 of the sampling module 130 being fluidly couplable to the bioanalytical system 120.

[0049] The controllable sampling valve unit 170 may comprise a single valve, referred to as the inlet valve, or it may comprise a system of two or more interconnected valves. The inlet valve may be used alone or in combination with other valves and devices, particularly with one or more conduit reservoirs for sample volume definition, to achieve complex fluid control sequences.

[0050] In one or more embodiments, the controllable sampling valve unit 170 comprises an inlet valve selected from the group consisting of a rotary valve, a membrane valve, a pinch valve, a switch valve or a static flow diverter. In large scale bioprocess purification systems a switch valve or a static flow diverter may advantageously be used. In small scale bioprocess purification systems a rotary valve or a membrane valve may advantageously be used. Rotary or membrane valves are preferred in small scale bioprocess purification systems because they are typically very fast, thereby allowing for small sample volumes to be obtained quickly and with high precision.

[0051] A rotary valve is an apparatus for selectively controlling fluid flow in a fluid coupling network where precise fluid control is required. The rotary valve typically comprises a rotatable cylindrical body having a plurality of ports arranged in a circumferential pattern around the periphery of the body, and a rotor rotatably disposed within the cylindrical body. The rotor has a plurality of channels extending radially therethrough, each channel being in communication with one of the ports. The rotary valve is adapted to be coupled to a fluid coupling network and is operated by rotating the cylindrical body to align the desired port with an inlet or outlet of the fluid coupling network. The rotor is also rotated to selectively block or permit fluid flow through the channels, thereby controlling the flow of fluid. The cylindrical body and rotor may be fabricated from any suitable material, such as stainless steel, aluminum, or plastic, and may be coated with a suitable material to enhance its chemical resistance or reduce friction. The valve may be designed for manual or automated operation, and may be controlled by control unit, such as a computer or other suitable device.

[0052] A membrane valve is an apparatus for selectively controlling fluid flow in a fluid coupling network where precise fluid control is required. The membrane valve comprises a valve body having an inlet and an outlet, and a flexible membrane disposed within the valve body. The membrane is arranged to selectively block or permit fluid flow between the inlet and the outlet. The membrane valve is adapted to be coupled to a fluid coupling network and is operated by applying a pressure differential across the membrane. When the pressure differential is applied, the membrane deflects and selectively blocks or permits fluid flow through the valve. The valve body and membrane may be fabricated from any suitable material, such as plastic, stainless steel, or glass, and may be coated with a suitable material to enhance its chemical resistance or reduce friction. The membrane may be supported by a support structure, such as a mesh or perforated plate, to enhance its mechanical stability. The valve may be designed for manual or automated operation and may be controlled by control unit, such as a computer or other suitable device.

[0053] A pinch valve is an apparatus for selectively controlling fluid flow in a fluid coupling network where precise fluid control is required. The valve comprises a valve body having an inlet and an outlet, and a flexible tube disposed within the valve body. The tube is arranged to selectively block or permit fluid flow between the inlet and the outlet. The pinch valve is adapted to be coupled to a fluid coupling network and is operated by compressing the tube at a desired location to selectively block fluid flow through the valve. The tube may be compressed using any suitable mechanism, such as a manual clamp, a solenoid, or a pneumatic actuator. The valve body and flexible tube may be fabricated from any suitable material, such as plastic, silicone, or rubber, and may be coated with a suitable material to enhance its chemical resistance or reduce friction. The tube may be reinforced with a suitable material, such as a braided mesh or wire, to enhance its mechanical stability. The valve may be designed for manual or automated operation and may be controlled by control unit, such as a computer or other suitable device.

[0054] A switch valve is an apparatus for selectively switching between two or more fluid paths in a fluid coupling network where precise fluid control is required. The valve comprises a valve body having an inlet and two or more outlets, and a switching mechanism disposed within the valve body. The switching mechanism may comprise any suitable mechanism for selectively directing fluid flow between the inlet and the outlets, such as a rotary valve, a sliding piston, or a solenoid valve. The valve body and switching mechanism may be fabricated from any suitable material, such as plastic, stainless steel, or glass, and may be coated with a suitable material to enhance its chemical resistance or reduce friction. The switch valve is adapted to be operated by selectively directing fluid flow between the inlet and the outlets using the switching mechanism. The valve may be designed for manual or automated operation, and may be controlled by a control unit, such as a computer or other suitable device.

[0055] A static flow diverter is an apparatus for selectively dividing fluid flow, e.g. during chromatographic separation processes. The diverter comprises a valve body having an inlet and two or more outlets, and a stationary mechanism disposed within the valve body. The stationary mechanism may comprise any suitable mechanism for selectively dividing fluid flow between the outlets, such as a splitter, a baffle, or a flow divider. The valve body and stationary mechanism may be fabricated from any suitable material, such as plastic, stainless steel, or glass, and may be coated with a suitable material to enhance its chemical resistance or reduce friction. The static flow diverter is adapted to be coupled to a fluid flow process, such as in a chromatographic separation column, and is operated by directing fluid flow from the inlet through the stationary mechanism to the outlets. The diverter may be designed for manual or automated operation, and may be controlled by a control unit, such as a computer or other suitable device. The static flow diverter may be used in combination with other valves and devices to achieve complex fluid control sequences, and may be designed to accommodate different types of fluid flow processes, such as chromatographic separation columns. The stationary mechanism may be configured to provide different flow ratios between the outlets, depending on the volume of fluid sample to be diverted for analysis.

[0056] The inlet valve may be used alone or in combination with other valves and devices to achieve complex fluid control sequences.

[0057] The sample volume of the fluid sample can be defined by opening and closing the inlet valve of the controllable sampling valve unit 170.

[0058] Advantages of embodiments of the present application include that the volume of the fluid sample drawn from the product stream of the bioprocess purification system is reduced, and that the sampling time is reduced, which allows for monitoring, and optionally also controlling, the progress and efficiency of various separation and purification steps of the bioprocess purification system.

[0059] The sample volumes are preferably as small as possible, while still being large enough to provide a representative sample and to allow for the bioanalytical system 120 to measure / determine the desired characteristics of the fluid sample. Depending on the scale of the bioprocessing system and bioprocess purification system being sampled, the sample volume of the fluid sample may be in the range of 0.1 pl - 50 ml.

[0060] In some embodiments, the sample volume of the fluid sample is 1 ml or more. This is typically the case in large scale bioprocess purification systems. By large scale bioprocess purification systems in the present application is meant bioprocess purification systems having a product stream flow rate of more than 150 ml / minute. In such large scale bioprocess purification systems, the sample volume of the fluid sample is preferably in the range of 0.1 - 50 ml, and more preferably in the range of 1 - 50 ml. Although, the sample volume may in some cases be lower also in large scale bioprocess purification systems, such as in the range of 0.1 pl - 100 pl. In some embodiments, the sample volume of the fluid sample is significantly smaller than 1 ml. This is typically the case in small scale bioprocess purification systems, such as analytical or laboratory scale bioprocess purification systems. By small scale bioprocess purification systems in the present application is meant bioprocess purification systems having a product stream flow rate of 150 ml or less, such as in the range of 0.01 -150 ml / min. In such small scale bioprocess purification systems, the sample volume of the fluid sample is preferably in the range of 0.1 - 100 pl, preferably 0.5 - 20 pl, and more preferably 1 - 10 pl.

[0061] The controllable sampling valve unit 170 and the sample volume are preferably selected such that the step of obtaining the fluid sample can be performed quickly.

[0062] In some embodiments, the controllable sampling valve unit 170 and the sample volume are selected such that the step of obtaining a fluid sample is completed in 60 seconds or less, preferably in 5 seconds or less, more preferably in 2 seconds or less, and more preferably in 1 second or less. In some embodiments, the step of obtaining a fluid sample is completed in 0.01 -60 seconds, preferably in 0.01 -5 seconds, more preferably in 0.01 - 2 seconds, and more preferably in 0.01 -1 seconds.

[0063] In some embodiments, the controllable sampling valve unit 170 and the sample volume are preferably selected such that the steps of obtaining and providing a fluid sample are both completed in 60 seconds or less, preferably in 30 seconds or less, more preferably in 20 seconds or less, and more preferably in 10 seconds or less.

[0064] The sampling module 130 is a closed system such that the fluid sample is prevented from contact with the environment surrounding the sampling module 130. The term “closed system” as used herein denotes a system wherein the product and product contact surfaces are not exposed to the immediate room environment. This reduces or minimizes the risk of contamination of the fluid sample or the product stream of the bioprocess purification system. In some embodiments, the sampling module 130 is an aseptic system. The term “aseptic” refers to a system or process that is free of microbial contamination. Aseptic techniques and processes are used to prevent the introduction of microorganisms into the sampling module and into the bioprocess purification system and to maintain the sterility of the system throughout the sampling process.

[0065] The sampling module 130 may in some embodiments be provided with a housing and be arranged as an integrated unit.

[0066] The sampling module 130 may in some embodiments be provided as an assembly of components, e.g. loose valves and conduits.

[0067] In a typical sampling cycle of the bioprocess purification system 110, the bioprocessing system 100 is configured to control the sampling module 130, using the control unit 200, to obtain a fluid sample from the bioprocess purification system 110, wherein the step of obtaining the fluid sample comprises controlling a flow of fluid from the bioprocess purification system 110 to the fluid coupling network 180 via the controllable sampling valve unit 170.

[0068] The bioprocessing system 100 is then configured to control the sampling module 130, using the control unit 200, to provide the fluid sample, wherein the step of providing the fluid sample comprises providing the fluid sample from the fluid coupling network 180 to the bioanalytical system 120.

[0069] In some embodiments, the step of obtaining a fluid sample is completed in 5 seconds or less, more preferably in 2 seconds or less, and more preferably in 1 second or less. In some embodiments, the step of obtaining a fluid sample is completed in 0.01-60 seconds, preferably in 0.01 -5 seconds, more preferably in 0.01 -2 seconds, and more preferably in 0.01 -1 seconds.

[0070] In some embodiments, the steps of obtaining and providing a fluid sample are both completed in 60 seconds or less, preferably in 30 seconds or less, more preferably in 20 seconds or less, and more preferably in 10 seconds or less.

[0071] In some embodiments, the method further comprises repeating the steps of obtaining and providing a fluid sample. In some embodiments, the method comprises repeating the steps of obtaining and providing a fluid sample at least 5 times, preferably at least 10 times, and more preferably at least 15 times within a period of 5 minutes.

[0072] The sampling module of the present application can be used for monitoring, and optionally also controlling, the progress and efficiency of various separation and purification steps of the bioprocess purification system. Obtaining, and optionally also providing, the sample quickly allows for a series of samples to be collected, and in some embodiments also analyzed, in a short period of time.

[0073] In some embodiments, the steps of obtaining and providing a fluid sample, and analyzing the sample to determine a characteristic of the sample, are completed in 120 seconds or less, preferably in 60 seconds or less, more preferably in 30 seconds or less, and more preferably in 20 seconds or less.

[0074] To ensure that fluid paths, when providing / transporting the fluid sample from the controllable sampling valve unit 170, are not comprising / containing unwanted fluids, such as air, such section / s of fluid paths are filled with buffer fluid from a buffer source via a buffer port of the sampling module 130. In one embodiment, the sampling module 130 is further configured / controlled to be fluidly couplable to a buffer source 140 via a buffer port 142 of the sampling module 130. In one embodiment, the sampling module 130 is further configured / controlled to fill a section of the fluid coupling network 180 by controlling a flow of buffer fluid from the buffer source 140 to the bioanalytical system 120 via the fluid coupling network 180. In other words, the sampling module 130 is configured / controlled to provide a fluid path from the buffer source 140 to a port 134 couplable to the bioanalytical system 120. This step prepares the fluid coupling network 180 for providing the fluid sample by ensuring that the fluid paths of the section of the fluid coupling network 180 is filled with buffer fluid, and not unwanted fluids, such as air. To ensure that the entire sample has been provided from the controllable sampling valve unit 170, the controllable sampling valve unit 170 may in a further embodiment be rinsed by using buffer fluid. In one embodiment, the fluid coupling network 180 is further configured / controlled to rinse the controllable sampling valve unit 170 by controlling a flow of buffer fluid from the buffer source to the bioanalytical system 120 via the controllable sampling valve unit 170 and the fluid coupling network 180. In other words, the fluid coupling network 180 is configured / controlled to provide a fluid path from the buffer source to the bioanalytical system 120 via the controllable sampling valve unit 170.

[0075] To prepare the sampling module 130 for the next fluid sampling cycle, a cleaning fluid or clean in place, CIP, fluid is allowed to flow through the fluid coupling network 180. In one embodiment, the sampling module 130 is further configured / controlled to be fluidly couplable to a clean in place, CIP, source 150 via a CIP port 152 of the sampling module 130. The sampling module 130 is further configured / controlled to clean the section of the fluid coupling network 180 by controlling a flow of cleaning fluid from the CIP source 150 to the bioanalytical system 120 via the fluid coupling network 180. In other words, the sampling module 130 is configured / controlled to provide a fluid path from the CIP source 150 to the waste port 162 or waste container 160. Additionally, in one embodiment, the sampling module 130 is further configured / controlled to clean the controllable sampling valve unit 170 by controlling a flow of cleaning fluid from the CIP source 150 to a waste port 162 via the controllable sampling valve unit 170. In an exemplary embodiment the application of Fig. 1 is implemented using controllable valves fluidly coupled using conduits or tubing.

[0076] Fig. 2 shows a bioprocessing system 100 as described with reference to Fig. 1 , the sampling module 130 further being configured to be fluidly couplable to at least one conduit reservoir 176,176’ for defining the sample volume of the fluid sample. In some embodiments, the sampling module 130 is further configured to be fluidly couplable to two or more conduit reservoirs 176, 176' for defining the sample volumes of two or more fluid samples, wherein a first fluid sample is obtained by providing a fluid path from the bioprocess purification system 110 to the fluid coupling network 180 via the controllable sampling valve unit 170 and a first conduit reservoir 176, and wherein the sample volume of the first fluid sample is defined by the first conduit reservoir 176, and wherein a second fluid sample is obtained by providing a fluid path from the bioprocess purification system 110 to the fluid coupling network 180 via the controllable sampling valve unit 170 and a second conduit reservoir 176’, and wherein the sample volume of the second fluid sample is defined by the second conduit reservoir 176’.

[0077] In a typical sampling cycle of the bioprocess purification system 110, the bioprocessing system 100 is configured to control the sampling module 130, using the control unit 200, to obtain a fluid sample from the bioprocess purification system 110, wherein the step of obtaining the fluid sample comprises controlling a flow of fluid from the bioprocess purification system 110 to the fluid coupling network 180 via the controllable sampling valve unit 170 and the conduit reservoir 176,176’, and wherein the sample volume of the fluid sample is defined by the conduit reservoir 176,176’. The conduit reservoir 176,176’ may be a looped conduit, which can be selected / configured to have an inner diameter and / or length to contain a particular fluid sample volume required to measure / determine characteristics of the fluid sample. An advantage of this is that the volume may be adapted by cutting a conduit, such as a tubing, to a length matching the required sample volume. An important feature of the conduit reservoir 176,176’ is that it is arranged to allow cleaning by letting a fluid flow through the entire reservoir.

[0078] The bioprocessing system 100 is then configured to control the sampling module 130, using the control unit 200, to provide the fluid sample, wherein the step of providing the fluid sample comprises providing the fluid sample from the fluid coupling network 180 to the bioanalytical system 120.

[0079] The sampling module 130 may be configured to obtain and provide one fluid sample at the time, or it may be configured to first obtain two or more fluid samples and then provide said samples simultaneously or sequentially to the bioanalytical system 120 for analysis.

[0080] For first obtaining two or more fluid samples and then providing said samples simultaneously or sequentially to the bioanalytical system 120 for analysis, the fluid samples may be stored in separate conduit reservoirs 176,176’ or in a sample storage unit (not shown in Fig. 2) pending analysis. In some embodiments the sampling module 130 is further configured to be fluidly couplable to two or more conduit reservoirs 176,176’ for defining the sample volumes of two or more fluid samples. The step of obtaining the fluid sample comprises: obtaining a first fluid sample by controlling a first flow of fluid from the bioprocess purification system 110 to the fluid coupling network 180 via the controllable sampling valve unit 170 and a first conduit reservoir 176, and wherein the sample volume of the first fluid sample is defined by the first conduit reservoir 176, and obtaining a second fluid sample by controlling a second flow of fluid from the bioprocess purification system 110 to the fluid coupling network 180 via the controllable sampling valve unit 170 and a second conduit reservoir 176’, and wherein the sample volume of the second fluid sample is defined by the second conduit reservoir 176’.

[0081] The conduit reservoirs 176,176’ can be rinsed and cleaned independently of each other.

[0082] To ensure that fluid paths, when providing / transporting the fluid sample from the conduit reservoirs 176,176’, are not comprising / containing unwanted fluids, such as air, such section / s of fluid paths are filled with buffer fluid from a buffer source 140. In one embodiment, the sampling module 130 is further configured / controlled to fill a section of the fluid coupling network 180 by controlling a flow of buffer fluid from the buffer source 140 to the bioanalytical system 120 via the fluid coupling network 180. In other words, the sampling module 130 is configured / controlled to provide a fluid path from the buffer source 140 to a port couplable 134 to the bioanalytical system 120. This step prepares the fluid coupling network 180 for providing the fluid sample by ensuring that the fluid paths of the section of the fluid coupling network 180 is filled with buffer fluid, and not unwanted fluids, such as air. To ensure that the entire sample has been provided from the conduit reservoir 176,176’, the conduit reservoir may in a further embodiment be rinsed by using buffer fluid. In one embodiment, the fluid coupling network 180 is further configured / controlled to rinse the conduit reservoir 176, 176’ by controlling a flow of buffer fluid from the buffer source 140 to the bioanalytical system 120 via the conduit reservoir 176,176’ and the fluid coupling network 180. In other words, the fluid coupling network 180 is configured / controlled to provide a fluid path from the buffer source 140 to the bioanalytical system 120 via the conduit reservoir 176,176’. To prepare the sampling module 130 for the next fluid sampling cycle, a cleaning fluid or clean in place, CIP, fluid is allowed to flow through the fluid coupling network 180. In one embodiment, the sampling module 130 is further configured / controlled to be fluidly couplable to a clean in place, CIP, source 150 via a CIP port 152 of the sampling module. The sampling module 130 is further configured / controlled to clean the section of the fluid coupling network 180 by controlling a flow of cleaning fluid from the CIP source 150 to the bioanalytical system 120 via the fluid coupling network 180 to the waste port 162 or waste container 160. Additionally, or alternatively, in one embodiment, the sampling module 130 is further configured / controlled to clean the conduit reservoir 176,176’ by controlling a flow of cleaning fluid from the CIP source 150 to a waste port 162 via the conduit reservoir 176,176’.

[0083] The sample volume of the first and the second sample may be the same or different. The same sample volume may be preferred when a direct comparison of the two samples is desired. In other cases, different sample volumes may be preferred. For example, where there is a large variation in the analyte concentration in the product stream, a larger sample volume may be collected using a first conduit reservoir when sampling a fraction of the product stream having a low analyte concentration, and a smaller sample volume may be collected using a second conduit reservoir when sampling a fraction of the product stream having a high analyte concentration.

[0084] The embodiment of Fig. 2 is described as having one or two conduit reservoirs 176, 176’, however, embodiments having more than two conduit reservoirs, are also contemplated. For example, an array of 2-50 conduit reservoirs, 2-25, or 2-10 conduit reservoirs may be useful for monitoring e.g. progress and efficiency of various separation and purification steps.

[0085] Fig. 3 shows a bioprocessing system 100 as described with reference to Fig. 2, the sampling module 130 further being configured to be fluidly couplable to a sample preparation system 300, wherein the step of providing the fluid sample comprises providing the fluid sample from the fluid coupling network 180 to the sample preparation system 300, treating the fluid sample in the sample preparation system 300, and providing the treated fluid sample to the bioanalytical 120 system via the fluid coupling network 180.

[0086] In one or more embodiments, the treatment in the sample preparation system 300 is selected from dilution, desalting, buffer exchange, pH adjustment, enzymatic treatment, concentration, filtration, capture, heating, and labelling, or a combination thereof.

[0087] In a more specific embodiment of the bioprocessing shown in Fig. 3, the bioprocess purification system 110 is a chromatography column for protein purification, the bioanalytical system 120 is a mass spectrometer, and the sample preparation system 300 is a desalting system comprising a desalting column. The desalting column may for example be a hydrophobic interaction chromatography column capable of immobilizing analytes present in the fluid sample. The sampling module 130 is further configured to be fluidly couplable to a buffer source 140 containing a buffer for washing the immobilized sample on the column, and configured to be fluidly couplable to an eluent source 310 via an eluent port 312, said eluent source containing an eluent capable of eluting the washed sample from the column and providing the treated fluid sample to the bioanalytical system 120 via the fluid coupling network 180.

[0088] Fig. 4 shows a bioprocessing system 100 as described with reference to Fig. 3, the sampling module 130 further being configured to be fluidly couplable to the bioanalytical system 120 via a sample storage unit (SSU) 400, wherein the step of providing the fluid sample comprises providing the fluid sample to the sample storage unit 400 before providing the fluid sample to the bioanalytical system 120. A sample storage unit is useful e.g. in embodiments where the bioanalytical technique is more time consuming than the sampling cycle, such that the analysis of the obtained samples forms a bottleneck for how fast the obtained samples can be provided to the bioanalytical system 120. The sample storage unit 400 then acts as an intermediate storage for the samples pending analysis. The sample storage unit 400 may for example be provided in the form of an array of wells or conduits. The sample storage unit 400 may be used as an alternative to conduit reservoirs 176,176’ or as a complement to conduit reservoirs. According to one or more embodiments of the present application, a sample tracking module is arranged to keep track of the fluid sample. In some embodiments, the sample tracking module is configured to track the status of at least one particular sample. In some embodiments, the sample tracking module is configured to display the tracked status of the at least one particular sample in a user interface. In some embodiments, the tracked status of the at least one particular sample comprises chemical or physical information retrieved from sensors or analytical devices, of a fraction or pool where the sample is taken from. In addition, the retrieved information is connected to the fraction ID, the starting time point and the ending time point of the fraction, the bioprocess phase of the sample etc., wherein the fraction ID is configured to identify the ID number of the fraction and the bioprocess phase comprises in which phase of the bioprocess the sample is taken. Also, the retrieved information is connected to the sample ID, which is further connected to any secondary data tracking system, e.g. batch or project or candidate construct (LIMS). According to some embodiments, the sample tracking module may be a module arranged in the control unit 200. According to some other embodiments, the sample tracking module may be a separate module communicatively coupled with the control unit 200, the sampling module 130 and the bioanalytical system 120.

[0089] Fig. 5 shows the control unit 200 according to one or more embodiments of the present application. The control unit (CU) 200 may be in the form of a computer, e.g. an Electronic Control unit, a server, an on-board control unit, a stationary computing device, a laptop control unit, a tablet control unit, a handheld control unit, a wrist-worn control unit, a smart watch, a smartphone or a smart TV. The control unit 200 may comprise processing circuitry 212 communicatively coupled to a communications interface, e.g. a transceiver 204, configured for wired or wireless communication. The control unit may further comprise at least one optional antenna (not shown in figure). The antenna may be coupled to the transceiver 204 and is configured to transmit and / or emit and / or receive wired or wireless signals in a communication network, such as Wi-Fi, Bluetooth, 3G, 4G, 5G etc. In one example, the processing circuitry 212 may be any of a selection of a processor and / or a central processing unit and / or processor modules and / or multiple processors configured to cooperate with each other. Further, the control unit 200 may further comprise a memory 215 communicatively coupled to the processing circuitry 212. The memory 215 may e.g. comprise a selection of a hard RAM, disk drive, a floppy disk drive, a flash drive or other removable or fixed media drive or any other suitable memory known in the art. The memory 215 may contain instructions executable by the processing circuitry to perform any of the steps or methods described herein. The processing circuitry 212 may be communicatively coupled to a selection of any of the transceiver 204 and the memory 215. The control unit 200 may be configured to send / receive control signals directly to / from any of the above-mentioned units or to external nodes or to send / receive control signals via a wired and / or wireless communications network. The wired / wireless transceiver 204 and / or a wired / wireless communications interface may be configured to send and / or receive data values or parameters as a signal to or from the processing circuitry 212 to or from other external nodes. In an embodiment, the transceiver 204 communicates directly to external nodes or via the wireless communications network. In one or more embodiments the control unit 200 may further comprise an input device 217, configured to receive input or indications from a user and send a user input signal indicative of the user input or indications to the processing circuitry 212. In one or more embodiments the control unit 200 may further comprise a display 218 configured to receive a display signal indicative of rendered objects, such as text or graphical user input objects, from the processing circuitry 212 and to display the received signal as objects, such as text or graphical user input objects. In one embodiment the display 218 is integrated with the user input device 217 and is configured to receive a display signal indicative of rendered objects, such as text or graphical user input objects, from the processing circuitry 212 and to display the received signal as objects, such as text or graphical user input objects, and / or configured to receive input or indications from a user and send a user-input signal indicative of the user input or indications to the processing circuitry 212. In a further embodiment, the control unit 200 may further comprise and / or be coupled to one or more additional sensors (not shown in the figure) configured to receive and / or obtain and / or measure physical properties pertaining to the bioprocessing system 100 or bioprocess purification system 110 and send one or more sensor signals indicative of the physical properties to the processing circuitry 212. An example of such an additional sensor may be a sensor, such as a UV sensor, arranged in the bioprocess purification system 110 and configured to measure a property of the fluid in the product stream. In a further embodiment, the control unit 200 may further be coupled to the bioanalytical system 120 and configured to receive and / or obtain a signal indicative of properties pertaining to an analyzed sample, and send one or more signals indicative of the properties to the processing circuitry 212. In one or more embodiments, the processing circuitry 212 is further communicatively coupled to the input device 217 and / or the display 218 and / or the additional sensors. In embodiments, the communications network communicate using wired or wireless communication techniques that may include at least one of a Local Area Network (LAN), Metropolitan Area Network (MAN), Global System for Mobile Network (GSM), Enhanced Data GSM Environment (EDGE), Universal Mobile Telecommunications System, Long term evolution, High Speed Downlink Packet Access (HSDPA), Wideband Code Division Multiple Access (W-CDMA), Code Division Multiple Access (CDMA), Time Division Multiple Access (TOMA), Bluetooth®, Zigbee®, Wi-Fi, Voice over Internet Protocol (VoIP), LTE Advanced, IEEE802.16m, WirelessMAN- Advanced, Evolved High-Speed Packet Access (HSPA+), 3GPP Long Term Evolution (L TE), Mobile WiMAX (IEEE 802.16e), Ultra Mobile Broadband (UMB) (formerly Evolution-Data Optimized (EV-DO) Rev. C), Fast Low-latency Access with Seamless Handoff Orthogonal Frequency Division Multiplexing (Flash-OFDM), High Capacity Spatial Division Multiple Access (iBurst®) and Mobile Broadband Wireless Access (MBWA) (IEEE 802.20) systems, High Performance Radio Metropolitan Area Network (HIPERMAN), Beam-Division Multiple Access (BDMA), World Interoperability for Microwave Access (Wi-MAX) and ultrasonic communication, etc., but is not limited thereto. Moreover, it is realized by the skilled person that the control unit 200 may comprise the necessary communication capabilities in the form of e.g., functions, means, units, elements, etc., for performing the present solution. Examples of other such means, units, elements and functions are: processors, memory, buffers, control logic, encoders, decoders, rate matchers, de-rate matchers, mapping units, multipliers, decision units, selecting units, switches, interleavers, de-interleavers, modulators, demodulators, inputs, outputs, antennas, amplifiers, receiver units, transmitter units, DSPs, MSDs, TCM encoder, TCM decoder, power supply units, power feeders, communication interfaces, communication protocols, etc. which are suitably arranged together for performing the present solution. Especially, the processing circuitry of the present application may comprise one or more instances of a processor, processor modules and multiple processors configured to cooperate with each other, Central Processing Unit (CPU), a processing unit, a processing circuit, a processor, an Application Specific Integrated Circuit (ASIC), a microprocessor, a Field-Programmable Gate Array (FPGA) or other processing logic that may interpret and execute instructions. The expression “processing circuitry” and / or “processing means” may thus represent a processing circuitry comprising a plurality of processing circuits, such as, e.g., any, some or all of the ones mentioned above. The processing means may further perform data processing functions for inputting, outputting, and processing of data comprising data buffering and device control functions, such as call processing control, user interface control, or the like. It is understood that all the embodiments described with reference to Figs. 1 -5 may be combined in any combination without departing from the present application.

[0090] Finally, it should be understood that the invention is not limited to the embodiments described above, but also relates to and incorporates all embodiments within the scope of the appended claims.

Claims

CLAIMS:

1. A sampling module for sampling a product stream of a bioprocess purification system, the sampling module comprising a controllable sampling valve unit and a fluid coupling network, the sampling module being configured to be fluidly couplable to a bioprocess purification system and a bioanalytical system, the sampling module being controllable to sample a product stream of the bioprocess purification system, wherein the sampling module is configured to: obtain a fluid sample, wherein the fluid sample is obtained by providing a fluid path from the bioprocess purification system to the fluid coupling network via the controllable sampling valve unit, and provide the fluid sample, wherein the fluid sample is provided to the bioanalytical system by providing a fluid path from the fluid coupling network to the bioanalytical system, wherein the sampling module is a closed system such that the fluid sample is prevented from contact with the environment surrounding the sampling module.

2. The sampling module according to claim 1 , wherein the controllable sampling valve unit comprises an inlet valve selected from the group consisting of a rotary valve, a membrane valve, a pinch valve or a switch valve and a static flow diverter, preferably selected from the group consisting of a rotary valve and / or a membrane valve.

3. The sampling module according to any one of the preceding claims, further being configured to be fluidly couplable to at least one conduit reservoir for defining the sample volume of the fluid sample, wherein the fluid sample is obtained by providing a fluid path from the bioprocess purification system to the fluid coupling network via the controllable sampling valve unit and the conduit reservoir, and wherein the sample volume of the fluid sample is defined by the conduit reservoir.

4. The sampling module according to any one of the preceding claims, further being configured to be fluidly couplable to two or more conduit reservoirs for defining the sample volumes of two or more fluid samples,wherein a first fluid sample is obtained by providing a fluid path from the bioprocess purification system to the fluid coupling network via the controllable sampling valve unit and a first conduit reservoir, and wherein the sample volume of the first fluid sample is defined by the first conduit reservoir, and wherein a second fluid sample is obtained by providing a fluid path from the bioprocess purification system to the fluid coupling network via the controllable sampling valve unit and a second conduit reservoir, and wherein the sample volume of the second fluid sample is defined by the second conduit reservoir.

5. The sampling module according to any one of the preceding claims, wherein the sample volume of the fluid sample is in the range of 0.1 pl - 50 ml.

6. The sampling module according to claim 5, wherein the sample volume of the fluid sample is 1 ml or more, preferably in the range of 0.1 - 50 ml, and more preferably in the range of 1 - 50 ml.

7. The sampling module according to claim 5, wherein the sample volume of the fluid sample is in the range of 0.1 - 100 pl, preferably 0.5 - 20 pl, and more preferably 1 - 10 pl.

8. The sampling module according to any one of the preceding claims, wherein the sampling module is an aseptic system.

9. The sampling module according to any one of the preceding claims, further being configured to be fluidly couplable to a sample preparation system, wherein the fluid sample is provided to the bioanalytical system by providing a fluid path from the fluid coupling network to the sample preparation system and by providing a fluid path from the sample preparation system to the to the bioanalytical system via the fluid coupling network.

10. The sampling module according to claim 9, wherein the treatment in the sample preparation system is selected from dilution, desalting, buffer exchange, pH adjustment,enzymatic treatment, concentration, filtration, capture, heating, and labelling, or a combination thereof.11 . The sampling module according to any one of the preceding claims, further being configured to be fluidly couplable to a sample storage unit, wherein the fluid sample is provided to the bioanalytical system by providing a fluid path from the fluid coupling network to the sample storage unit and by providing a fluid path from the sample storage unit to the to the bioanalytical system via the fluid coupling network.

12. The sampling module according to any one of the preceding claims, the sampling module being configured to be connectable to a control unit (CU) for controlling the sampling module.

13. The sampling module according to claim 12, the control unit (CU) being configured to communicate with the bioprocess purification system and / or the bioanalytical system14. The sampling module according to any one of claims 12-13, the control unit (CU) being configured to initiate the obtaining of a fluid sample based on a signal from the bioprocess purification system15. The sampling module according to any one of the preceding claims, wherein the bioprocess purification system is a chromatography system or a filtration system.

16. The sampling module according to any one of the preceding claims, wherein the bioanalytical system is based on a bioanalytical technique selected from the group consisting of mass spectrometry (MS), high-performance liquid chromatography (HPLC), ultra-performance liquid chromatography (UPLC), liquid chromatography-mass spectrometry (LC-MS), capillary electrophoresis (CE), capillary electrophoresis-mass spectrometry (CE-MS), surface plasmon resonance (SPR), ELISA, flow cytometry, or a combination thereof.

17. A method for controlling a sampling module according to any one of claims 1 -16 to sample a product stream of a bioprocess purification system, the method comprising:obtaining a fluid sample from the bioprocess purification system, wherein the step of obtaining the fluid sample comprises controlling a flow of fluid from the bioprocess purification system to the fluid coupling network via the controllable sampling valve unit, and providing the fluid sample, wherein the step of providing the fluid sample comprises providing the fluid sample from the fluid coupling network to the bioanalytical system.

18. The method according to claim 17, the sampling module further being configured to be fluidly couplable to a at least one conduit reservoir for defining the sample volume of the fluid sample, wherein the step of obtaining the fluid sample comprises controlling a flow of fluid from the bioprocess purification system to the fluid coupling network via the controllable sampling valve unit and the conduit reservoir, and wherein the sample volume of the fluid sample is defined by the conduit reservoir.

19. The method according to claim 17, the sampling module further being configured to be fluidly couplable to two or more conduit reservoirs for defining the sample volumes of two or more fluid samples, wherein the step of obtaining the fluid sample comprises: obtaining a first fluid sample by controlling a first flow of fluid from the bioprocess purification system to the fluid coupling network via the controllable sampling valve unit and a first conduit reservoir, and wherein the sample volume of the first fluid sample is defined by the first conduit reservoir, and obtaining a second fluid sample by controlling a second flow of fluid from the bioprocess purification system to the fluid coupling network via the controllable sampling valve unit and a second conduit reservoir, and wherein the sample volume of the second fluid sample is defined by the second conduit reservoir.

20. The method according to any one of the claims 17-19, wherein the sample volume of the fluid sample is in the range of 0.1 pl - 50 ml.21 . The method according to claim 20, wherein the sample volume of the fluid sample is 1 ml or more, preferably in the range of 0.1 - 50 ml, and more preferably in the range of 1 - 50 ml.

22. The method according to claim 20, wherein the sample volume of the fluid sample is in the range of 0.1 - 100 pl, preferably 0.5 - 20 pl, and more preferably 1 - 10 pl.

23. The method according to any one of claims 17-22, the sampling module further being configured to be fluidly couplable to a sample preparation system, wherein the step of providing the fluid sample comprises providing the fluid sample from the fluid coupling network to the sample preparation system, treating the fluid sample in the sample preparation system, and providing the treated fluid sample to the bioanalytical system via the fluid coupling network.

24. The method according to claim 23, wherein the treatment in the sample preparation system is selected from dilution, desalting, buffer exchange, pH adjustment, enzymatic treatment, concentration, filtration, capture, heating, and labelling, or a combination thereof.

25. The method according to any one of claims 17-24, the sampling module further being configured to be fluidly couplable to a sample storage unit, wherein the step of providing the fluid sample comprises providing the fluid sample to the sample storage unit before providing the fluid sample to the bioanalytical system.

26. The method according to any one of claims 17-25, wherein the step of obtaining a fluid sample is completed in 60 seconds or less, preferably in 5 seconds or less, more preferably in 2 seconds or less, and more preferably in 1 second or less.

27. The method according to any one of claims 17-26, wherein the steps of obtaining and providing a fluid sample are completed in 60 seconds or less, preferably in 30 seconds or less, more preferably in 20 seconds or less, and more preferably in 10 seconds or less.

28. The method according to any one of claims 17-27, the method further comprising repeating the steps of obtaining and providing a fluid sample.

29. The method according to claim 28, comprising repeating the steps of obtaining and providing a fluid sample at least 5 times, preferably at least 10 times, and more preferably at least 15 times within a period of 5 minutes.

30. The method according to any one of claims 17-29, wherein the method for controlling the sampling module is a computer implemented method.31 . A control unit (CU) for a sampling module being controllable to sample a product stream of a bioprocess purification system, the control unit comprising: processing circuitry, a memory comprising instructions executable by the processing circuitry, causing the processing circuitry to perform the method according to any of claims 17- 30.

32. A bioprocessing system comprising a bioprocess purification system, a bioanalytical system, and a sampling module according to any one of claims 1 -16.

33. The bioprocessing system according to claim 32, further comprising a control unit (CU) according to claim 31 .

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