FR3160597A1 - FLUIDIC ASSEMBLY FOR THE PARALLEL TREATMENT OF BIOLOGICAL PARTICLES, ASSOCIATED SYSTEM AND METHOD - Google Patents

Abstract

The invention relates to a fluidic assembly (10) for the at least partially automated processing of biological particles, in particular biological cells, comprising: at least two reagent reservoirs (22); at least two bioprocessors (21) for the at least partially automated processing of the particles in each of the bioprocessors simultaneously, each bioprocessor (22) comprising at least one fluidic inlet (213); a first individual connector (211) for the input of a customized starting material into the bioprocessor; a collective feed connection (25) comprising a liquid flow path fluidly connected to each of the reagent reservoirs (22) and fluidly connected to the fluidic inlet (213) of each bioprocessor (21); and a set of means (31) for ensuring a unidirectional flow between the collective feed connection (25) and each bioprocessor (21). Abstract: Fig. 1

Description

FLUIDIC ASSEMBLY FOR THE PARALLEL TREATMENT OF BIOLOGICAL PARTICLES, ASSOCIATED SYSTEM AND METHOD Field of invention

The invention relates to the field of manufacturing biological products comprising cells, biomolecules and other products containing cells or biomolecules. It is particularly suitable for the manufacturing of personalized biological products, in particular cell and gene therapies. The invention relates to a fluidic assembly, a bioprocessing system comprising such an assembly, and an associated method.

State of the art

With the development of personalized therapeutic approaches such as autologous cell therapy products, the pharmaceutical industry is facing the challenge of manufacturing large numbers of personalized batches of increasingly complex pharmaceutical products. In some cases, these personalized therapies are intended for critically ill patients, which motivates decentralization that can be carried out at the continental, national, regional, or point-of-care level. In other cases, these therapies are intended for large patient populations, which requires scaling up the manufacturing of these personalized products to minimize personnel and facility requirements that could otherwise hamper profitability, scale, or simply represent too risky investments and cause patients to miss out on the opportunity to be treated with the best therapeutic technology available for their condition.

The aim of the invention is to propose a bioprocessing device in which numerous bioprocessors can be used simultaneously and in a desynchronized manner while avoiding cross-contamination between particles from different modules. Another aim of the invention is also to reduce the quantity of reagents used and to reduce the carbon footprint of such a process.

According to one aspect, the invention relates to a fluidic assembly for the at least partially automated treatment of biological particles, in particular biological cells.

The fluidic assembly comprises at least 2 reagent reservoirs and at least 3 bioprocessors for at least partially automated processing of particles in each of the bioprocessors simultaneously. Each bioprocessor comprises at least one fluidic inlet and a first individual connector for inputting a custom starting material into the bioprocessor. The fluidic assembly further comprises a collective supply connection comprising a liquid flow path fluidly connected to each of the reagent reservoirs and fluidly connected to the fluidic inlet of each bioprocessor.

In one embodiment, the fluidic assembly further comprises a set of means for ensuring unidirectional flow between the collective supply connection and each bioprocessor.

In one embodiment, each bioprocessor is configured to implement at least steps of incubating the particles in a liquid medium and replacing all or part of said liquid medium by retaining said particles in the bioprocessor.

In one embodiment, each bioprocessor includes at least one second individual connector for outputting a material from the bioprocessor to a recovery container.

In one embodiment, the fluidic assembly includes at least one fluidic pump and/or fluidic reservoir associated per bioprocessor for moving a liquid from the collective supply connection to the bioprocessor in a manner unsynchronized with the other bioprocessors.

In one embodiment, the bioprocessor further comprises a fluidic outlet fluidly connected to the fluidic inlet.

In one embodiment, the fluidic assembly includes a collective discharge connection including a liquid flow path fluidly connected to the fluidic outlet of each bioprocessor and fluidly connected to a waste container.

In one embodiment, the fluidic assembly further comprises a purge line fluidly connecting the collective supply connection to the waste container, said purge line comprising at least one means for ensuring unidirectional flow from the collective supply connection to the waste container.

In one embodiment, the liquid flow path of the collective discharge connection comprises at least one measuring module for measuring a parameter of a liquid flowing in said liquid flow path of the collective discharge connection.

In one embodiment, the collective feed connection includes a homogenization chamber for mixing the reagents prior to their introduction into one of the bioprocessors.

In one embodiment, each bioprocessor includes a transparent face to allow an acquisition device to acquire an image of the particles in the bioprocessor during incubation.

In one embodiment, each bioprocessor comprises a bioprocessing module fluidly arranged between the fluidic inlet and the fluidic outlet of said bioprocessor for implementing the steps of incubation of the particles and replacement of the liquid medium.

In one embodiment, each bioprocessor comprises a buffer reservoir fluidly connected between the fluidic inlet of the bioprocessor and said bioprocessing module.

According to another aspect, the invention relates to an at least partially automated system for the treatment of biological particles, in particular biological cells, comprising a fluidic assembly according to the invention and a basic device designed to cooperate with said fluidic assembly and in which said fluidic assembly is for single use.

In one embodiment, the system further comprises a set of means for providing unidirectional flow between the collective power connection and each bioprocessor.

In one embodiment, the fluidic assembly comprises a bioprocessing module fluidly arranged between the fluidic inlet and the fluidic outlet of said bioprocessor for implementing the steps of incubation of the particles and replacement of the liquid medium, and characterized in that the system further comprises an acquisition device designed to acquire a signal coming from each bioprocessing module, said bioprocessing modules comprising at least one face allowing said signal to pass.

In one embodiment, the system further comprises a solicitation module configured to cooperate with each bioprocessor to interact with the particles incubated in said bioprocessor and/or to modify the operating conditions of the incubation of said particles in said bioprocessor.

• la sélection d’un bioprocesseur parmi les au moins 3 bioprocesseurs du système ;
• l’identification automatique d’au moins une connectique associée audit bioprocesseur sélectionné ;
• la transmission d’une information à l’utilisateur pour désigner la au moins une connectique identifiée et/ou
• la déblocage automatique de la au moins une connectique identifiée.

In one embodiment, the system comprises hardware and/or material means for implementing the following steps:

• the selection of a bioprocessor from among the at least 3 bioprocessors in the system;
• the automatic identification of at least one connector associated with said selected bioprocessor;
• the transmission of information to the user to designate at least one identified connection and/or
• the automatic unlocking of at least one identified connection.

• l’installation d’un ensemble fluidique selon l’invention dans un dispositif de base dans un dispositif de base pour former un système selon l’invention ;
• la connexion de chaque bioprocesseur à un récipient comprenant le matériau de départ personnalisé par le premier connecteur individuel du bioprocesseur ; ledit matériau de départ comprenant des particules biologiques ;
• le remplacement automatique d’un milieu liquide contenu dans le bioprocesseur par un nouveau milieu liquide fourni à partir d’au moins un des réservoirs de réactifs ;
• une seconde introduction d’un second milieu liquide dans un second bioprocesseur depuis la connexion d’alimentation collective de manière désynchronisée avec la première introduction ;
• l’incubation des particules dans le nouveau milieu liquide de chaque bioprocesseur.

According to another aspect, the invention relates to a method for treating biological particles, in particular biological cells, for the production of at least 3 batches of personalized biological product, implementing the following steps:

• the installation of a fluidic assembly according to the invention in a basic device in a basic device to form a system according to the invention;
• connecting each bioprocessor to a container comprising the customized starting material by the first individual connector of the bioprocessor; said starting material comprising biological particles;
• automatic replacement of a liquid medium contained in the bioprocessor with a new liquid medium supplied from at least one of the reagent reservoirs;
• a second introduction of a second liquid medium into a second bioprocessor from the collective supply connection in a manner desynchronized with the first introduction;
• the incubation of particles in the new liquid medium of each bioprocessor.

Brief description of the figures

Other characteristics and advantages of the invention will emerge from reading the detailed description which follows, with reference to the appended figures, which illustrate:

FIG. 1 : a schematic view of a fluidic assembly according to an embodiment of the invention comprising 3 reagent reservoirs and 3 bioprocessors.

FIG. 2 : a schematic view of a fluidic assembly according to an embodiment of the invention comprising a collective evacuation connection fluidly connecting the bioprocessors to a waste container.

FIG. 3 : a schematic view of a fluidic assembly according to an embodiment of the invention in which the collective evacuation connection comprises a collective measurement module.

FIG. 4 : a schematic view of a fluidic assembly according to an embodiment of the invention comprising a purge pipe.

FIG. 5 : a schematic view of a fluidic assembly according to an embodiment of the invention in which the collective supply connection comprises a homogenization chamber.

FIG. 6 : a schematic view of a biological particle processing system according to one embodiment in which it comprises a mobile optical acquisition device for acquiring images of the particles being incubated by each bioprocessor.

FIG. 7 : a schematic view of a bioprocessor according to an embodiment of the invention in which it comprises a buffer reservoir between the bioprocessing module and the fluidic inlet of said bioprocessor.

FIG. 8 : a schematic view of a bioprocessor according to an embodiment of the invention in which it comprises a second individual connector for the output of a material to a recovery container.

FIG. 9 : a schematic view of a bioprocessor according to an embodiment of the invention in which the means for ensuring a unidirectional flow towards the bioprocessing module are arranged inside the bioprocessor.

FIG. 10 : a schematic view of a processing system according to an embodiment of the invention further comprising a processor associated with a memory for implementing steps in an automated manner.

FIG. 11 : a flowchart of an incubation method according to one aspect of the invention.

FIG. 12 : a flowchart of a connection assistance method according to an embodiment of the invention.

Description of the invention

The invention relates to a system for processing biological particles, in particular for the bioprocessing of particles in parallel for the manufacture of personalized biological products.

The invention may be particularly useful in the field of cell therapy.

In one embodiment, the system comprises a first base device coupled to a single-use fluidic assembly. The fluidic assembly is intended to be in contact with reagent fluids, liquid incubation media, biological particles, etc. As such, the fluidic assembly must be replaced after each use.

The base device and the fluid assembly include cooperation means to cooperate with each other and provide removable connections to facilitate replacement of the fluid assembly.

In this description, "particles" may refer to either a raw material, an intermediate product, a final product or a substrate for the production of the biological product.

The particles may comprise biological cells, cell aggregates, microtissues, or microorgans (e.g., organoids). The particles may comprise viral particles or lipid nanoparticles. The particles may comprise chemically functionalized beads capable of catalyzing chemical reactions such as DNA synthesis, RNA synthesis, or protein synthesis. The particles may comprise microcarriers that promote the growth of adherent cells. In one embodiment, the term "particle" also refers to soluble molecules or biomolecules.

Different types and subtypes of particles can be used in each bioprocessor and during each step of the process.

In one embodiment, the particles have a diameter of less than 1 mm.

An example of a fluidic assembly is now described with reference to the FIG. 1 .

The fluidic assembly 10 comprises at least two, preferably at least three, reagent reservoirs 22. By “reagent reservoir” is meant here reservoirs or containers each intended to accommodate a reagent or a mixture of liquid reagents. The reagent reservoirs 22 preferably comprise bags, for example flexible plastic bags for containing reagents necessary for the particle biotreatment process. The reagent reservoirs may comprise any other container, in particular variable-volume or ventilated containers. The reagent reservoirs may comprise glass bottles such as ventilated glass bottles or syringes.

The fluidic assembly 10 also comprises at least two, preferably at least three bioprocessors 21 fluidly connected to the reagent reservoirs 22.

An example of a bioprocessor is now described with reference to the FIG. 8 .

Each bioprocessor includes a fluidic inlet 213 and a bioprocessing module 214 fluidly connected to the fluidic inlet 213 of the bioprocessor.

The bioprocessing module may comprise a chamber or a microfluidic device designed to implement at least one step of incubating the particles in a liquid medium and/or replacing all or part of this liquid medium by retaining said particles in the bioprocessing module or in the bioprocessor.

Additionally, each bioprocessor includes an individual connector 211.

In one example, the individual connector 211 is connected 102 on the one hand to the bioprocessor 21 or to the bioprocessing module 214, and on the other hand to a personalized raw material and/or to a container intended to comprise a personalized raw material.

By “customized” is meant that the individual connection 211 of each bioprocessor is connected to a raw material and/or a container different from that connected to the individual connections 211 of the other bioprocessors 21. In this way, each bioprocessor 21 is able to receive, via the individual connection 211, a starting material or a raw material which may comprise particles to be incubated in a liquid medium in the bioprocessor 21.

The individual connector 211 is intended for entry into the bioprocessor 21, preferably into the bioprocessing module 214 of a personalized starting material. The starting material may comprise any tissue or particle such as those previously described.

The fluidic assembly 10 further comprises a collective supply connection 25.

The collective supply connection 25 preferably comprises a single flow path intended to transport a liquid from the reagent reservoir(s) 22 to one or more bioprocessors 21.

Preferably, the collective supply connection 25 comprises a single flow path extending in a longitudinal direction from a first end to a second end.

In one embodiment, the first end of the collective supply connection 25 is connected on one side to all the reagent reservoirs 22 and the second end of the collective supply connection 25 is connected to all the bioprocessors 21, preferably to the fluidic inlet 213 of each bioprocessor.

As illustrated in the FIG. 1 , the fluidic assembly comprises, for each bioprocessor, a fluidic connection connecting the fluidic inlet of each bioprocessor 21 to the collective supply connection 25.

In an embodiment illustrated in particular on the FIG. 1 , the collective supply connection 25 comprises on a first longitudinal side, a plurality of bifurcations, each fluidically connected by a fluidic segment to a different reagent reservoir 22 and on a second longitudinal side, a second plurality of bifurcations, each fluidically connected by a fluidic segment to a different bioprocessor 21 (or to a fluidic inlet 213 of a different bioprocessor 21).

Thus, the invention advantageously makes it possible to carry out different incubation steps in parallel by immersing the particles in a liquid medium and replacing the liquid medium with particles while sharing the reagent containers.

Each processing module 21 further comprises at least one individual connector 211. In one embodiment, the individual connector comprises a flow path for transporting a starting material comprising a first end connected to the bioprocessor 21 and a second end comprising a connector.

Preferably, each second end of each individual connector is intended to be connected to a starting material reservoir of the base device 1. As such, a single starting material reservoir may be provided and connected to each individual connector 211. In an alternative example, a plurality of starting material reservoirs are provided and each individual connector 211 is intended to be connected to a different starting material reservoir.

Preferably, the starting material comprises at least particles as defined above.

The system of the invention advantageously allows for parallel and independent bioprocessing operations (i.e., different batches manufactured simultaneously) without the bulk, complexity, and high investment that characterize the use of multiple integrated bioreactors or automated factories. For example, some embodiments may allow for the manufacture of ten customized CAR-T (Chimeric Antigen Receptor T) products in a benchtop system with a minimal number of manual operations.

For example, T cells from different patients may be injected into each bioprocessor 21 using an individual connection 211 of each bioprocessing module 21, and then processed in the bioprocessing modules 21 with activation reagents, transduction reagents, expansion reagents, and medium supplied successively from common reagent reservoirs 22 to obtain multiple customized CAR-T products that may be individually recovered using an individual connection 211 of each bioprocessing module 21.

Unidirectional flow

In one embodiment, the system comprises means for ensuring unidirectional flow between the collective supply connection and the fluidic inlet of each bioprocessor 21.

In one embodiment, the means for providing unidirectional flow comprises a flow direction control module.

One advantage is to provide a means of ensuring unidirectional flow from the collective supply connection 25 into each bioprocessor 21. In this way, cross-contamination of different batches produced in the different bioprocessors 21 through the collective supply connection 25 is avoided while providing the advantages of shared reagent reservoirs 22, including reduced reagent reservoir 22 filling or connecting operations and associated error risks as well as improved damping of dead volumes and fluctuations in reagent consumption over a plurality of batches, reducing reagent waste and, consequently, production costs.

It should be noted that a means of providing unidirectional flow 31 from the collective supply connection 25 into a bioprocessor 21 may operate or be integrated into said bioprocessor as illustrated in FIG. 9 . In this embodiment, the means for ensuring a unidirectional flow 31 is fluidly arranged between the fluidic inlet 213 and the bioprocessing module 214 of the bioprocessor 21.

As illustrated on the FIG. 1 , it can also be fluidically arranged downstream of the first bifurcation of the collective supply connection 25 and upstream of the bioprocessor 21, it can also operate or be integrated at multiple points or along the segment between this bifurcation and in the bioprocessor.

In the context of the invention, a means for ensuring unidirectional flow is a means for ensuring unidirectional flow of a fluid from one end of a fluid segment to the other, preferably with high reliability. The function of a means for ensuring unidirectional flow is to prevent a fluid from flowing through it in the direction opposite to the intended flow direction. Pumps are not always suitable, at least alone, as a means for ensuring unidirectional flow, because, depending on their design, they may not prevent flow from occurring in a direction opposite to the intended flow direction when they are not pumping or when no flow is applied.

Since for one of the applications of the system according to one embodiment, said system is designed for the manufacture of personalized therapeutic products, the failure of a means of ensuring unidirectional flow may result in cross-contamination of one or more personalized products, which may result in a loss of efficacy or a risk to the health of the recipient patients.

In one embodiment, a flow direction control module 31 may comprise a pair or triplet of individual means for providing unidirectional flow connected in series to achieve the required reliability.

For example, each flow direction control module 31 comprises a series of at least two or three pinch valves. The pinch valves advantageously make it possible to pinch the flow path such as a tube until the latter is closed, thus ensuring the closure of the flow passing through said flow path without contact between the valve and the liquid. In one embodiment, each pinch valve is controlled by a controller so as to activate their closing and opening in an automated manner.

In one embodiment, a flow direction control module 31 comprises a passive component inserted into the flow path ensuring the flow of liquid in a single direction. For example, the flow path comprises a check valve, preferably at least two or three check valves arranged in series.

Check valves are advantageously simpler, less expensive and can be included in the pipes or flow paths of the fluidic assembly.

In one embodiment, the check valves are selected from check valves having a strictly positive opening pressure. If the upstream pressure falls below the opening pressure or, if back pressure is exerted (the flow attempts to move from the outlet to the inlet), the check valve closes. The check valve may comprise a valve, a ball, a diaphragm or a disc that is pressed against a seal to close the valve. When the inlet pressure falls below the opening pressure or there is back pressure, the valve closes by gravity, by spring and/or by using the back pressure.

In one embodiment, a flow direction control module 31 comprises a drip chamber. The drip chamber (better known by the English term “drip chamber”) comprises an opening through which the upstream fluid will pass, forming a drop by gravity and/or by positive pressure, and a chamber collecting the drops and comprising a fluid outlet downstream. The flow in a single direction from upstream to downstream is thus ensured and also advantageously makes it possible to prevent the presence of gas in the fluid after it has passed through the drip chamber.

In one embodiment, the fluidic assembly or system includes an aseptic device configured to be integrated with the fluidic assembly to reduce contamination of fluids passing therethrough, particularly at the flow direction control modules 31. More particularly, the aseptic device includes an aseptic barrier that prevents contamination from spreading in the fluidic system while allowing fluid flow through the assembly.

Preferably, such an aseptic device is integrated or designed to be integrated into the flow direction control module(s) 31. For example, an aseptic barrier is integrated between two one-way valves of the flow direction control module 31.

One advantage is to reduce the risk of cross-contamination by the rise of a contaminant from the bioprocessor to the collective power connection.

In one embodiment, the aseptic barrier is positioned to separate the fluid circulating within the fluid assembly from the external environment. This aseptic barrier may be made from a porous material, but impermeable to microbial contaminants, such as bacteria, viruses and fungi.

In another embodiment, the aseptic barrier is configured from a thermal sterilization barrier, such as a heating resistor optionally associated with a thermocouple. In this case, the aseptic device may include a leakage line for the evacuation of hot gases.

In another embodiment, the aseptic barrier comprises a chemical sterilization barrier. For example, the chemical aseptic barrier is designed to be activated by the controlled injection of isopropanol, an effective antimicrobial agent, to eliminate microbial contaminants present in the fluid flow. The chemical aseptic barrier is also equipped with a purging or drying system, allowing its effectiveness to be regenerated after use and before any reuse of the fluid path. This system ensures a continuous process of disinfection and maintenance of sterility throughout the use of the fluid assembly. In one embodiment, a combination of the above-mentioned means can be used for one or more flow direction control modules 31.

Method of use

An example method of using the system according to the invention is now described.

In one embodiment, the method comprises placing the fluidic assembly in the base device of the system according to the invention.

The basic device comprises complementary connection means with removable connection means of the fluidic assembly 10. The installation of the fluidic assembly in the basic device notably comprises the connection of a reservoir of starting material to each bioprocessor 21. In one embodiment, each bioprocessor 21 is connected to a different reservoir of starting material, but it can also be envisaged that the basic device comprises a reservoir of starting material connected to several bioprocessors, for example for the production of the same biological product in several bioprocessors in parallel.

In one embodiment, a starting material is introduced into the bioprocessor via the first individual connector 211 of the bioprocessor. Preferably, the starting material comprises particles as defined above.

Preferably, the starting material comprises particles such as cells suspended in a first liquid medium. In one example, the starting material comprises lymphocyte-enriched plasma such as an apheresis product.

In one embodiment, for each bioprocessor, the first liquid medium in each bioprocessor is replaced with a second liquid medium in an automated manner.

This replacement step preferably comprises the introduction of a second liquid medium into the bioprocessor and the extraction of all or part of the first liquid medium from the bioprocessor. During the extraction of all or part of the first liquid medium, the particles are retained in said bioprocessor. For example, the bioprocessor comprises a membrane designed to selectively retain or allow the flow of particles depending on their size. Such a membrane thus allows the passage of the liquid while preventing the passage of particles through said membrane.

All or part of the first liquid may be expelled through a fluid outlet 215 of the bioprocessor 21 or may be expelled to a waste container of a bioprocessor (not shown).

In one embodiment, the introduction of a second liquid medium is carried out by the introduction of one or more reagents from one or more reagent reservoirs 21 of the system. The liquid is extracted from the reagent reservoir(s) 21, passes through the flow path of the collective supply connection 25 to the bioprocessor.

The liquid may be driven by a fluidic pumping device such as a peristaltic pump. Alternatively, the liquid is driven by pressurizing the reservoir(s) when these include flexible bags such as flexible plastic bags.

In one embodiment, a first set of valves (not shown) make it possible to automatically select the reservoirs from which the liquid is drawn to supply a bioprocessor 21. Similarly, a second set of valves, fluidically arranged between the collective supply connection 25 and each bioprocessor, advantageously make it possible to select the bioprocessor(s) into which the liquid medium must be injected.

The first and/or second set of valves can be controlled by a control module such as a PRO processor.

In one embodiment, a step of incubating the particles in the second liquid medium. As such, the system may comprise temperature control means for controlling the temperature of the liquid medium during the step of incubating the particles.

In one embodiment, a plurality of successive steps of replacing the liquid medium while retaining the particles and incubating said particles in a new liquid medium are implemented until a biological product is obtained.

In a first mode of execution, the recovery of the biological product is performed. The recovery of the biological product can be recovered manually by extracting the bioprocessor from the system.

In a second embodiment, the biological product is automatically extracted from the bioprocessor via the first individual connector 211.

In an alternative embodiment, the biological product is automatically extracted from the bioprocessor via a second individual connector 216 illustrated in the FIG. 8 . The second individual connector 216 is designed to cooperate with a biological product container. Preferably, the biological product is extracted via the second individual connector 216 in suspension in a liquid medium.

Preferably, the second individual connector 216 makes it possible to fluidly connect the biotreatment module 214 to the biological product container. Pumping means can allow the transport of the biological product suspended in a liquid medium to the biological product container.

The second individual connector 216 advantageously allows the recovery of the biological product by reducing the disturbance of the system around the bioprocessor 21, in particular the temperature and the composition of the gases in said bioprocessor 21 and/or more generally in the system.

Advantageously, the method according to the invention thus allows the parallel production of several biological products from one or different starting materials, asynchronously.

Drain connection

In one embodiment, illustrated in the FIG. 7 , each bioprocessor 21 comprises a fluidic outlet 215. The fluidic outlet is fluidically connected to the fluidic inlet 213 of the bioprocessor 21. Preferably, the bioprocessing module 214 is fluidically arranged between the inlet and the fluidic outlet.

The fluid outlet is intended to evacuate from the bioprocessor the liquid medium used for the particle incubation step, particularly in the biotreatment module.

In one embodiment, the fluid assembly comprises a collective discharge connection 26.

The collective discharge connection comprises a flow path extending longitudinally between a first end and a second end. The flow path may comprise tubing and/or conduits formed in a substrate such as a molded plastic part. In one embodiment, the first end of the collective discharge connection is connected to each bioprocessor 21, preferably to the fluid outlet of each bioprocessor 21.

In one embodiment, the second end of the collective discharge connection is fluidically connected or is adapted to be connected to a waste container 23.

One advantage is to eliminate the effluent liquids from each bioprocessor 21 in a shared manner. Such a system thus advantageously makes it possible to reduce the volume of the bioprocessors 21. It also makes it possible to generate an individualized product in the bioprocessor 21 from several incubation steps and several steps of replacing the liquid medium by reducing the manual operations of purging the bioprocessors.

Preferably, each fluid segment between the fluid outlet 215 of the bioprocessor 21 and the collective evacuation connection 26 comprises means for ensuring a unidirectional flow 32 between each bioprocessor 21 and the collective evacuation connection 26. These means for ensuring a unidirectional flow 32 may be similar to those already described between the collective supply connection 25 and each bioprocessor 21.

The means for ensuring a unidirectional flow 32 between each bioprocessor 21 and the collective discharge connection 26 advantageously allow the flow of liquids towards the waste container 23 without risking cross-contamination between the processes taking place in the bioprocessors 21, i.e. without risking that an effluent from one bioprocessor 21 enters another bioprocessor 21 via the collective discharge connection 26.

Collective measurement module

In one embodiment, the flow path of the collective discharge connection 26 comprises at least one measurement module 24. The measurement module 24 comprises at least one sensor. Said sensor 24 is configured to measure a parameter of the fluid present in the flow path of the fluid discharge connection 26.

The measurement module 24 arranged at the fluid discharge connection advantageously makes it possible to measure a parameter of an effluent from each bioprocessor by a single sensor in a shared manner and without it being necessary to carry out manual or robotic operations to take samples.

Indeed, when replacing the liquid medium in the dual processor, the old liquid is expelled through the fluid outlet, to the waste collector 23 via the flow path of the collective evacuation connection 26. Each time the liquid medium in the biotreatment module is replaced, the old liquid medium replaced can thus be analyzed by said measurement module 24.

The measurement module 24 may comprise one or more sensors for measurement and/or detection such as electrodes, microscopy cells and/or cytometry cells.

In one embodiment, the measuring module 24 comprises means for measuring chemical parameters such as pH, dissolved oxygen concentration, dissolved carbon dioxide concentration, glucose concentration, lactate concentration, ammonia concentration, amino acid concentration. In one embodiment, the measuring module 24 comprises means for measuring cellular parameters such as cell concentration, cell dimensions or mass.

In one embodiment, the flow path of the collective discharge connection comprises a measuring chamber. The measuring chamber comprises a portion of the flow path whose cross-section perpendicular to the direction of flow of the fluids is greater than the same cross-section on the other portions of the collective discharge connection. The measuring chamber may further comprise an agitator or means for homogenizing the liquid in said chamber.

In one embodiment, the system 1 is designed to adapt certain parameters to the measurements carried out by the measurement module 24. The measurement module 24 is connected to the processor so as to transmit to the processor PRO information relating to the measurements carried out.

The PRO processor is preferably configured to modify a parameter of the system based on said information. For example, the measurement carried out by the measurement module 24 can trigger an adjustment of the supply of reagent to the bioprocessor, the temperature of the bioprocessing module and/or the incubation time of the particles in the liquid medium.

Purge line

In one embodiment, the fluid assembly comprises a purge line 40. The purge line 40 comprises a fluid flow path extending from the collective supply connection 25 to the collective exhaust connection 26.

Preferably, the purge line does not include any bioprocessor. An advantage is that it allows the liquid from the reagent tanks 22 to flow to the waste container 23.

The purge line 40 advantageously makes it possible to rinse or pre-fill at least part of the collective supply connection 25 with a buffer solution or a reagent contained in one of the reagent reservoirs 22. In this way, it is possible to supply two different bioprocessors 21 with a different reagent. When the rinsing of the collective supply connection is carried out between the two supplies, the risk of contamination of the reagent of the second supply by the reagent of the first supply is reduced. Similarly, pre-filling the purge line 40 with a reagent to be injected to supply into one of the bioprocessors 21 makes it possible to reduce the dilution of said reagent; the precision and efficiency of the operations are thus advantageously improved.

In one embodiment, the purge line 40 further comprises means for providing a unidirectional flow 41 from the collective supply connection 25 to the collective discharge connection 26.

These means for ensuring unidirectional flow 41 may be similar to those already described between the collective power connection 25 and each bioprocessor 21.

The means for ensuring unidirectional flow 41 in the purge line 40 significantly protects against injection of effluent from one bioprocessor 21 into another bioprocessor 21 by flow along the purge line 40 in the prevented direction.

In one embodiment illustrated in the FIG. 4 , the fluidic assembly comprises both a purge line 40 and a measurement module 24. The purge line can, in this case, be used to rinse the measurement module 24 or the measurement chamber. Cross-contamination between successive samples is thus reduced. Calibration measurements can also be carried out in order to compare them with the measurements carried out during the passage of an effluent from a bioprocessor 21.

In one embodiment, one of the reagent reservoirs is provided to contain a calibration liquid for said sensor of the measurement module 24.

Homogenization chamber

In one embodiment illustrated in the FIG. 5 , the collective supply connection 25 comprises, on a portion of its flow path, a homogenization chamber 251. The homogenization chamber has a section (perpendicular to the direction of flow of the fluids) enlarged compared to the section of the rest of the collective supply connection 25.

A first advantage is to allow the successive or simultaneous introduction into said homogenization chamber 251 of at least two reagents from at least two different reagent reservoirs 22. The enlargement of the section will allow a mixture of the two reagents and the introduction into a bioprocessor of a more homogeneous mixture.

In one embodiment, the homogenization chamber comprises a mixer, such as a means for agitating the volume of liquid in said chamber, advantageously making it possible to improve the mixing of the reactants or to allow a higher flow rate through the collective supply connection. An agitation means may comprise an agitator such as a magnetic or mechanical agitator.

In one embodiment, the homogenization chamber 251 includes a fluidic pump such as a peristaltic pump or other pumping means to cause flow through the collective supply connection 26.

In one embodiment, the homogenization chamber 251 comprises a homogenization device comprising a main channel, at least two buffer channels, a collector connected to the main channel by a main conduit and connected to the first buffer channel and to the second buffer channel by respectively a first and a second fluidic segment.

The manifold preferably comprises a flow separation point intended to divide the main conduit into first and second fluid segments. The homogenization device further comprises a pumping unit and a control unit configured to move the multi-component fluid from the main channel to the first or second buffer channel through the manifold and to move the fluid from the first or second buffer channel to the main channel through the manifold. Such a device advantageously makes it possible to improve the homogenization of the flow through the main supply channel comprising at least two different reagents.

Such a device advantageously makes it possible to improve the homogenization of the mixture between at least two reagents derived from two different reagents before their introduction into a bioprocessor 21.

Analysis and solicitation

In one embodiment, illustrated in the FIG. 6 , the system 1 further comprises an acquisition device 50. Preferably, the acquisition device is arranged so as to acquire an image of the particles or a signal from the particles in the bioprocessor 21. More preferably, the acquisition device is designed or arranged to acquire an image or a signal from the particles located in the bioprocessing module 214.

In one embodiment, the bioprocessor 21 and/or the bioprocessing module 214 comprise at least one transparent wall to allow the acquisition device to acquire an image of the particles or a signal from the particles in said bioprocessor and/or in said bioprocessing module 214.

In one embodiment, the bioprocessor comprises an analysis chamber (not shown) comprising at least one transparent wall for image or signal acquisition by the acquisition device 50. The imaging chamber is preferably substantially flat, preferably less than 1 mm thick, more preferably less than 500 µm thick.

The transparent wall is preferably made of a material with high transparency and low autofluorescence, such as glass, quartz or a cycloolefinic polymer of suitable quality.

In one embodiment, the system comprises a guidance device for moving the acquisition device relative to the bioprocessors in an automated manner. Thus, a single acquisition device advantageously makes it possible to carry out acquisitions for each bioprocessor 21, thus pooling the necessary components without manual operation.

In an example illustrated on the FIG. 6 , the acquisition device 50 is mounted movably on a rail 51. The guide device further comprises a motor for controlling the movement of the acquisition device 50 along the rail 50. Other guide devices can be imagined such as a robotic arm or a double rail for freedom of movement of the acquisition device according to two degrees of freedom.

In one embodiment, the acquisition device 50 comprises an image acquisition device such as an optical camera, an optical microscope and/or a spectroscope.

In one embodiment, the acquisition device 50 comprises at least one light source and at least one optical sensor.

In an alternative embodiment, each bioprocessor 21 comprises an acquisition device, thus advantageously allowing simultaneous detection in each bioprocessor.

In one embodiment, the acquisition device comprises a device configured to measure fluorescence such as a fluorimeter or a fluorescence microscope.

In this respect, the particle analysis step comprises a first sub-step of incubating the particles in a liquid medium comprising a fluorescence marker, detecting a fluorescent signal and analyzing said signal. In one embodiment, detecting said signal comprises acquiring an image by a fluorescence microscope and analyzing the acquired image to measure the intensity of the fluorescent signal of a set of particles, for example a set of 10,000 particles, 100,000 particles or more.

In an alternative or cumulative embodiment not shown, the system 1 further comprises a stressing device.

The stressing device is preferably designed to cooperate with at least one bioprocessor 21. The stressing device is designed to interact with the particles in the bioprocessor or to modify the operating conditions.

For example, the biasing device may be configured to heat or cool the bioprocessor particles in the bioprocessing module. In another example, the biasing device may be configured to apply an electric field, an acoustic field, and/or a magnetic field to the particles located in the bioprocessor and/or in the bioprocessing module. In another example, the biasing device is configured to apply thermal control, electroporation, electrophoresis, dielectrophoresis, photoporation, photopheresis, acoustoporation, acoustopheresis, magnetic trapping, magnetopheresis, and/or photolysis.

In one embodiment, in the same way as the acquisition device, the solicitation device is a collective solicitation device, that is to say capable of cooperating with each bioprocessor 21 or each bioprocessing module 214, preferably in an automated manner. The collective solicitation device is preferably mounted movably relative to the bioprocessors so as to be able to cooperate with each bioprocessor.

In an alternative embodiment, the system 1 comprises at least one solicitation device for each bioprocessor 21. This latter mode allows the simultaneous solicitation of several bioprocessors 21, but loses the advantages of sharing the cost and size of a mobile collective solicitation device.

Bioprocessor

In one embodiment illustrated in the FIG. 9 , the bioprocessor comprises a storage compartment 212.

The storage compartment is fluidically arranged between the fluidic inlet 213 of the bioprocessor 21 and the bioprocessing module 214.

The storage compartment 212 is intended to accommodate a liquid medium which will be subsequently or simultaneously injected into the bioprocessing module to serve as a liquid medium for the incubation of the particles at a later stage.

The bioprocessor preferably comprises a liquid pumping interface designed to fill said storage compartment 212 with reagent via the collective supply connection 25 and to convey said reagent in the storage compartment 212 to the bioprocessing module 214 of the bioprocessor 21 at the same time or at a different time.

The storage compartment 212 preferably has a volume suitable for carrying out a complete step of the manufacturing process or for at least 8, 12 or 24 hours of processing. The volume of the reservoir can vary from 10µL to 500mL, and more commonly from 100µL to 200mL.

An advantage is to store in the bioprocessor 21 the liquid medium for the next incubation step. In this way, when replacing the liquid medium in the bioprocessing module 214, the liquid medium present in the storage compartment 212 can directly feed the bioprocessing module. Such a storage compartment 212 allows the reduction of the feeding frequency of the bioprocessors 21 by transferring larger quantities of reagent into the storage compartment 212 and then gradually infusing them into the bioprocessing module 214. This advantageously allows the system to gain flexibility, in particular in the case where two bioprocessors have a need for different reagents simultaneously.

The storage compartment, by reducing the power supply frequency, also makes it possible to reduce the risks of cross-contamination between bioprocessors 21.

In one embodiment, each bioprocessor 21 comprises a second fluidically arranged storage compartment between the bioprocessing module and the fluidic inlet of the bioprocessor. The bioprocessor is thus self-sufficient in reagent for the next two steps of replacing the liquid medium. In each bioprocessor 21, one storage compartment can be used at a given time to execute the current process step in the bioprocessing module and the other storage compartment can be filled in advance from the collective supply connection 25 for the next process step. This embodiment allows the bioprocessor to be filled with the necessary reagents asynchronously (and in advance) and thus helps to avoid conflicts related to simultaneous filling requests to the collective supply connection 25, in particular when processes are executed asynchronously or when a large number of bioprocessors 21 are used.

In one embodiment, the bioprocessors 21 are microfluidic bioprocessors, advantageously increasing the precision and efficiency of the process, in particular by reducing dead volumes and routing volumes.

In one embodiment, the fluidic assembly 10 comprises a microfluidic routing fluidly connecting the bioprocessing module to the collective supply connection via the microfluidic inlet 213 of the bioprocessor 21. Preferably, the microfluidic routing comprises a section diameter of between 30 µm and 800 µm, more preferably between 50 µm and 600 µm.

Preferably, the bioprocessor 21 comprises valves making it possible to close or open the outlet, the inlet and/or the various fluid connections inside the bioprocessor 21, for example between the storage compartment 212 and the bioprocessing module 214.

In an example where the bioprocessor is microfluidic, the bioprocessor includes microfluidic valves. An advantage of microfluidic valves is that they have a very low displaced volume and are highly compact. For example, pneumatic valves such as "Quake" valves or "Doormat" valves can be used.

Preferably, the bioprocessing module 214 comprises one or more microfluidic chambers. At least one dimension of a microfluidic chamber is preferably between 30 µm and 500 µm. These microfluidic chambers have particularly advantageous advection kinetics and diffusion kinetics. The duration, effectiveness and efficiency of the manufacturing of biological products are thus advantageously improved.

In one embodiment, the biotreatment module 214 preferably comprises a membrane capable of selectively retaining or allowing the particles to flow depending on their size. Alternatively, the biotreatment module 214 preferably comprises a sub-module capable of selectively retaining or allowing the particles to flow depending on their size, this module being able to be, for example, a gravity separation module (based on sedimentation), inertial, acoustic, electrophoretic, magnetic. In one embodiment, the biotreatment module 214 preferably comprises a membrane capable of eliminating the gases contained in the biotreatment module 214.

Bioprocessor gas exchange

In an embodiment not shown, each bioprocessor 21 comprises or cooperates with a gas exchanger. The gas exchanger comprises means for exchanging, supplying or removing gases in the liquid medium comprising the particles.

For example, the system 1 comprises at least one gas reservoir such as a carbon dioxide reservoir and/or a dioxygen reservoir and the gas exchanger comprises an inlet connector for fluidically connecting said gas reservoir to the bioprocessor 21 so as to introduce said gas into the liquid incubation medium. Preferably, the bioprocessor comprises a gas outlet connector intended to cooperate with a gas suction means such as a vacuum pump so as to extract gases from the liquid medium from the bioprocessor.

Preferably, the bioprocessor 21 comprises a gas exchanger connected to a circulation loop of a gas mixture (not shown). Said circulation loop comprises said gas reservoir and the system comprises hardware and/or software means (such as a processor associated with a data medium) for controlling said recirculation loop.

Preferably, the gas exchanger comprises a filtration means such as a filter in order to ensure contact between the liquids and particles handled and the gases while avoiding contamination. In one embodiment, the filtration means is a sterile filtration means.

In one embodiment, the filtration means comprises pores whose largest passage dimension is less than or equal to 0.2 µm.

In one embodiment, the filtration means comprises one or more gas permeable membranes, for example platinum crosslinked poly-dimethyl siloxane, bubble tanks and/or mist filters.

Fluidic assembly

In one embodiment, the fluidic assembly 10 is intended to cooperate with the base device. As such, it may include connectors so as to generate a removable connection with the base device. For example, the various reservoirs 22 and bioprocessors 21 may be inserted into receptacles of the base device provided for this purpose.

In one embodiment, the fluidic assembly is intended for single use. Another fluidic assembly can then be mounted in the base device in order to initiate a new operation.

In one embodiment, the various connectors and connection means of the fluidic assembly comprise aseptic connectors. The manufacturing safety and reliability of the fluidic assembly and the system are thus improved.

In one embodiment, the base device and/or fluidic assembly 10 are manufactured from USP grade VI compliant materials and high purity pharmaceutical grade materials.

The manufacturing of the system, the basic device and/or the fluidic assembly is preferably carried out in an environment with controlled air quality such as an ISO 7 environment and in accordance with ISO 13 485 guidelines.

The fluidic assembly 10 is preferably stored in an airtight container to prevent any contamination, for example in a sealed plastic bag. In one embodiment, the fluidic assembly, before its installation in the base device, undergoes a sterilization step such as sterilization by gamma irradiation or any other similar sterilization process.

The system and/or fluidic assembly may advantageously be used for the manufacture of biological products without the need to be in an environment with controlled air quality, or may be used in any space not conventionally used for the manufacture of pharmaceutical products.

Basic system and device

In one embodiment, the basic device comprises a housing configured to receive the fluidic assembly and in particular the bioprocessors 2 and/or the reservoirs.

The basic device preferably comprises means for regulating the temperature inside said housing. In one example, a heating element such as a heating resistor, a heat pump, or Peltier elements are integrated into the basic device for this purpose. The device may further comprise a temperature sensor for controlling said temperature regulating means.

Preferably, the temperature control means are configured to maintain the temperature inside the accommodation within a predetermined target temperature range. The accommodation may comprise a closed enclosure. Preferably, the dimensions of the accommodation are less than 1m or 2m.

In an embodiment not shown, the system further comprises a gas pressure source connected to the collective power connector 25.

Such a source advantageously allows for testing the integrity of the flow path with gas before beginning manufacturing operations and for injecting larger bubbles or volumes of gas into the collective feed connector 25 and into the downstream flow path, which may be a more efficient means of purging the flow path of liquid and/or particles compared to flowing a liquid.

This embodiment is particularly advantageous when the system includes a purge line 40 and a waste container 23, as it is thus advantageously unnecessary to circulate the gas through a bioprocessor 21. The same advantages of purging the flow path with gas can apply inside a bioprocessor 21. In these embodiments, suitable means for removing bubbles that may be generated or injected into the bioprocessors 21 upon resuming the liquid supply are preferably provided to ensure robust operations and avoid any potential interference with the process.

In an alternative embodiment, the second individual connection 216 for the output of the biological product is fluidically connected to the first individual connection 211 of another bioprocessor 21 to serve as starting material for said other bioprocessor 21. An advantage is to connect in series at least two bioprocessors so as to carry out multi-step manufacturing processes continuously, with a small footprint and reducing manual operations.

Automated control

In one embodiment, illustrated in the FIG. 10 , the system includes a CNT control module.

The CNT control module is configured to control the introduction of a liquid from the reagent reservoir 22 to a bioprocessor 21.

Preferably, the control module is configured to control the first set of valves fluidically arranged between the collective supply connection and each reagent reservoir 22 and/or the pumping device making it possible to drive the liquid from the reagent reservoirs 22 to the collective supply connection 25. The control module thus makes it possible to control the injection of one or more reagents into the collective supply connection 25.

Preferably, the CNT control module is also configured to control the second set of valves arranged between the collective supply connection 25 and each bioprocessor 21. The control module thus advantageously allows the bioprocessor 21 to receive the liquid present in the collective supply connection 25.

Preferably, the control module is configured to control the different valves or means of transporting liquid inside each bioprocessor 21, for example to guide the liquid medium between the fluid inlet 213, the storage tank(s) 212, the biotreatment module, the fluid outlet 215, the first individual connector 211 and/or the second individual connector.

The system is thus advantageously capable of managing at least partially in an automated manner the biotreatment of the particles in each bioprocessor 21 simultaneously.

In one embodiment, the CNT control module is connected to the various sensors of the system 1. In particular, the controller can be connected to the measurement module 24, to the temperature sensor of the base device and/or to the acquisition device 50 so as to receive a signal representative of a measurement or an acquisition carried out by one or more of these components.

In one embodiment, the control module is configured to adjust the supply of reagents to the bioprocessing module 214 based on the analysis of the measurements received by the various sensors of the system.

The controller thus advantageously makes it possible to create a feedback loop between the measurements of the measurement module 24 and/or the acquisition device and the supply of reagents to each bioprocessing module 214.

The CNT control module comprises at least one PRO processor and at least one data medium (preferably non-transitory) such as a MEM memory associated with said PRO processor.

The processor is configured to execute a computer program product recorded on the memory to cause the system according to the invention to execute the method or any step of the method previously described in the present description.

In the context of this application, a data carrier is a computer-readable storage medium such as any tangible or non-transitory medium capable of containing or storing a program for use by or in connection with a system, apparatus, or device for executing instructions. More specific examples (a non-exhaustive list) of the computer-readable storage medium may include the following, a hard disk drive, random access memory (RAM), a drive, memory only (ROM), an erasable programmable read-only memory (EPROM or Flash memory), an optical fiber, a portable compact disc read-only memory (CD-ROM), an optical storage device, a magnetic storage device, or any other suitable combination of the foregoing.

Connection assistance

In one embodiment, illustrated in the FIG. 12 , the system includes a connection module.

The connection module preferably comprises software and hardware means for implementing a connection assistance method 1000 described below. Said method aims to secure the connection between the bioprocessor 21 and at least one predetermined connection. For example, the predetermined connection may comprise a connection of the fluidic section connected to the collective supply connection, an individual connector and/or a connection fluidically connected to the evacuation connection.

Preferably, the connection module comprises at least one processor associated with a non-transitory data medium such as a memory on which is stored the computer program product comprising the instructions for executing said method. Preferably, the connection module is similar to the control module previously described. More preferably, the connection module and the control module are the same module.

In one embodiment, each bioprocessor is associated with one or more identified connectors such as a first connector connected to the collective supply connection, a second connector comprising an individual connector and a third connector connected to the exhaust connection.

In one embodiment, said method 1000 comprises the identification 110 of a bioprocessor. Each bioprocessor may comprise an identification means and the system comprises a reader of said identification means. The identification means may comprise an identification code such as a barcode or a radio-identification chip (better known by the English acronym “RFID” for “Radio Frequency Identification”). The system comprises in this mode a barcode reader such as a laser reader or an RFID reader. The assistance module then generates an identifier from the signal generated by the reader which can be associated with a bioprocessor.

In an alternative embodiment, the system comprises a human-machine interface allowing the operator to select or enter information on a bioprocessor. The human-machine interface may comprise any means known to those skilled in the art, such as a mouse, a keyboard, a touch screen, a voice recognition system, etc. For example, the operator wishing to connect a bioprocessor to the system enters an identifier such as a code associated with said bioprocessor via the human-machine interface.

Preferably, the system comprises means of access to a database comprising the list of each bioprocessor (or its identification code) and the connector(s) associated with said bioprocessor.

The database may be stored in a system memory or in a remote memory. In the latter case, the means of access to said database include any telecommunication means such as transmission and reception means allowing remote connection to said memory.

The method comprises a step 120 of identifying at least one connector associated with said identified bioprocessor or associated with said bioprocessor identification code. In one example, a request comprising an identifier associated with the identified bioprocessor is transmitted to said database which, in return, transmits an identifier of at least one connector associated with said identified bioprocessor.

In one embodiment, the method comprises a step 130 of transmitting information to the user. The information comprises the designation of the at least one connection associated with the identified bioprocessor. Preferably, the information can be transmitted visually, audibly, haptically, or a combination of these different ways.

In one embodiment, the system comprises display means for designating the at least one identified connector to be connected to the bioprocessor. The display means may comprise a display screen or more preferably a light means such as a light diode. In one embodiment, the assistance module is configured to, when a bioprocessor is identified, generate the lighting of a light means associated with a connector to be connected to said bioprocessor. For example, the light means is arranged on said connector or near said connector so as to be quickly identified by the user.

In an alternative or cumulative embodiment, the system comprises a connector locking device. The locking device comprises means for locking each connector individually. For example, the system may comprise a plurality of housings where each housing is designed to accommodate an identified connector and perform reversible locking of said connector.

Each housing is controlled by the assistance module which is configured to automatically maintain or release the connection in the housing.

The locking device is configured to release one or more selected connectors while maintaining the mechanical locking of the other connectors.

The blocking means may include any type of blocking such as mechanical, magnetic, electrostatic blocking means or a combination thereof.

In this mode, the module is configured to, when a bioprocessor is identified, release the blocking of the connector associated with said dual processor for its connection to said bioprocessor.

The method 1000 then includes a step 140 of automatic unlocking of the identified connector.

Thus, a user who uses the wrong connector will not be able to manipulate a connector that is not the connector associated with the identified bioprocessor and therefore prevents a connection error.

The user can then connect at least one identified connector to the initially selected bioprocessor.

Claims (9)

Fluidic assembly (10) for the at least partially automated treatment of biological particles, in particular biological cells, comprising:

• at least 2 reagent tanks (22);
• at least 3 bioprocessors (21) for the at least partially automated processing of particles in each of the bioprocessors simultaneously, each bioprocessor (21) comprising at least:
  • a fluid inlet (213);
  • a first individual connector (211) for inputting a personalized starting material into the bioprocessor;
• a collective supply connection (25) comprising a liquid flow path fluidly connected to each of the reagent reservoirs (22) and fluidly connected to the fluidic inlet (213) of each bioprocessor (21).

Fluidic assembly (10) according to claim 1, further comprising a set of means (31) for ensuring a unidirectional flow between the collective supply connection (25) and each bioprocessor (21). Fluidic assembly (10) according to one of claims 1 to 2, comprising at least one fluidic pump and/or a fluidic reservoir associated with a bioprocessor (21) for moving a liquid from the collective supply connection (25) to the bioprocessor (21) in a non-synchronized manner with the other bioprocessors (21). Fluidic assembly (10) according to one of claims 1 to 3, characterized in that the bioprocessor further comprises a fluidic outlet (215) fluidically connected to the fluidic inlet (213) and in that the fluidic assembly comprises a collective evacuation connection (26) comprising a liquid flow path fluidically connected to the fluidic outlet (215) of each bioprocessor (21) and fluidically connected to a waste container (23). Fluidic assembly (10) according to claim 4, characterized in that it further comprises a purge pipe (40) fluidly connecting the collective supply connection (25) to the waste container (23), said purge pipe (40) comprising at least one means (41) for ensuring a unidirectional flow from the collective supply connection (25) to the waste container (23). Fluidic assembly (10) according to claim 4 or claim 5, characterized in that the liquid flow path of the collective discharge connection (26) comprises at least one measuring module (24) for measuring a parameter of a liquid circulating in said liquid flow path of the collective discharge connection (26). Fluidic assembly (10) according to one of claims 4 to 6, in which each bioprocessor (21) comprises:

• a bioprocessing module (214) fluidly arranged between the fluidic inlet (213) and the fluidic outlet (215) of said bioprocessor (21) for implementing the steps of incubation of the particles and replacement of the liquid medium, and
• a buffer reservoir (212) fluidically connected between the fluidic inlet (213) of the bioprocessor (21) and said bioprocessing module (214).

System (1) for at least partially automated processing of biological particles, in particular biological cells, comprising a fluidic assembly (10) according to claim 1 and a base device (12) designed to cooperate with said fluidic assembly and in which said fluidic assembly is single-use and further comprising a set of means (31) for ensuring a unidirectional flow between the collective supply connection (25) and each bioprocessor (21). Method (100) for treating biological particles, in particular biological cells, for the production of at least 3 batches of personalized biological product, implementing the following steps:

• the installation (101) of a fluidic assembly (10) according to claim 1 in a base device in a base device to form a system according to claim 8;
• connecting (102) each bioprocessor (21) to a container comprising the customized starting material by the first individual connector (211) of the bioprocessor (21); said starting material comprising biological particles;
• automatically replacing (103) a liquid medium contained in the bioprocessor with a new liquid medium supplied from at least one of the reagent reservoirs (22);
• a second introduction (104) of a second liquid medium into a second bioprocessor from the collective supply connection in a manner desynchronized with the first introduction;
• the incubation (105) of the particles in the new liquid medium of each bioprocessor.