EP-4735859-A1 - 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.

Inventors

• FRIGÅRD, Tuomo
• SALOMONSSON, Inger
• ROCH, Patricia
• ESTMER NILSSON, CAMILLA
• FRANCOIS, Tim
• ROSENGREN, LARS

Assignees

• Cytiva Sweden AB

Dates

Publication Date

20260506

Application Date

20240627

Claims (20)

1. 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. 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. 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. 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. 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. 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. 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. 8. The sampling module according to any one of the preceding claims, wherein the sampling module is an aseptic system.
9. 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. 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. 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. 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. 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 system
14. 14. 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 system
15. 15. 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. 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. 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. 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. 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. 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.

Description

SAMPLING MODULE FOR A BIOPROCESS PURIFICATION SYSTEM TECHNICAL FIELD 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. BACKGROUND 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. A further object of embodiments of the present invention is to provide a sampling module for sampling a product stream of a bioproce