Modular culture chamber and virus inactivation method

Abstract

A culture chamber is disclosed which can be provided in a modular form to provide flexibility in terms of the flow rate and / or residence time of a product stream. Also disclosed are an assembly comprising such a culture chamber for purifying biomolecules and a method for purifying biomolecules, in particular a method for inactivating viruses in a culture chamber or in a plurality of culture chambers arranged in series.

Description

Background Art

[0001] The present disclosure relates to the cultivation of fluids with a wide range of residence times and flow rates. More specifically, embodiments of cultivation chambers and methods for cultivating fluids facilitate achieving online viral inactivation and ensuring that flow paths are set to produce narrow residence time distributions (RTDs) of fluid particles.

[0002] Large-scale production and economics surrounding the purification of therapeutic proteins, especially monoclonal antibodies, are increasingly important issues for the biopharmaceutical industry. Therapeutic proteins are typically produced in mammalian or bacterial cells that have been engineered to produce the protein of interest. However, once produced, the protein of interest needs to be separated from various impurities, such as host cell proteins (HCPs), endotoxins, viruses, DNA, etc.

[0003] In a typical purification process, the cell culture harvest is subjected to a clarification step to remove cell debris. The clarified cell culture harvest containing the protein of interest is then subjected to one or more chromatography steps, which may include affinity chromatography steps or cation exchange chromatography steps. In order to ensure the viral safety of the therapeutic candidate drug and comply with regulatory requirements, a viral removal unit operation is implemented into the purification process. Such steps include Protein A and ion exchange chromatography, filtration, and low pH / chemical inactivation.

[0004] Virus inactivation is typically performed after a chromatography step (e.g., after affinity chromatography or after cation exchange chromatography.) In a typical large-scale purification process, the chromatography elution pool containing the protein of interest is collected in a large tank or reservoir and subjected to a lengthy virus inactivation step / process with mixing, which may take from about 30 minutes to about several hours to achieve complete inactivation of any viruses that may be present in the elution pool.

[0005] In monoclonal antibody (mAb) processing, for example, a series of independent unit operations are performed in batch mode, where storage tanks are used to store materials between unit operations and facilitate any necessary solution adjustments between steps. Typically, the material is collected in one tank where it is adjusted to achieve target inactivation conditions. This can be achieved by adding acid to achieve a target level of low pH, or it can be achieved by adding detergent in a detergent-based inactivation process. Next, the material is transferred to a second tank where it is maintained under inactivation conditions for a specified incubation time. The purpose of the transfer is to eliminate the risk that droplets on the walls of the first tank may not have achieved the target inactivation conditions and may contain viral particles. By transferring the material to different tanks, this risk can be reduced.

[0006] Several viral inactivation techniques are known in the art, which include exposing protein solutions to specific temperatures, pH or radiation and exposure to certain chemical agents (e.g., detergents and / or salts). One viral inactivation process involves large tanks where the material is held for a given time (e.g., 60 minutes) under inactivation conditions (e.g., low pH and / or exposure to detergents). This static holding step is an obstacle to moving toward continuous processing.

[0007] However, the virus killing kinetics suggest that the inactivation time may be different, suggesting that the processing time can be significantly shortened (or extended), static storage tanks for virus inactivation can be eliminated, and the method may be more suitable for continuous processing.

[0008] Recently, it has been desirable to have a continuous process where unit operations are linked together and manual solution adjustments are reduced to a minimum. To aid in this, efforts are being made to develop online processing methods to achieve online viral inactivation and other online solution adjustments. In a continuous or semi-continuous flow system, it would be desirable to provide a method to maintain a narrow residence time distribution in a continuous flow system.

[0009] Past practice for virus inactivation includes introducing the liquid to be inactivated into a low pH solution (e.g., at a pH of 3.6), homogenizing if necessary, and then standing for a desired period of time. Virus inactivation is then performed by contacting the entire volume of liquid containing the virus with the bulk low pH fluid and within a fixed dead treatment time.

[0010] Continuous or semi-continuous processing requires uninterrupted viral inactivation with minimum residence times to ensure effective viral inactivation without prolonged residence time in low pH conditions that could damage products contained in the fluid (e.g., proteins). These new systems require careful consideration of residence time, flow characteristics of the fluid (laminar vs. non-laminar), and system / hardware requirements to achieve residence time and flow characteristics.

[0011] Prior systems include using irradiated light in a spirally wound tube and coil flow inverter (CFI) with centrifugal force acting on the fluid to continuously inactivate viruses (WO2002038191, EP1339643B1, EP1464342B1, EP1914202A1 and EP1916224A1), the tube is spirally wound around the coil axis with multiple turns, wherein the number of turns and the bending angle help determine and improve the retention characteristics of the flow (as the fluid flows along the chamber pipe, due to the viscosity effect, all of its particles do not flow at the same speed, especially near the tube wall, where the velocity distribution generated along the cross section of the tube causes the residence time distribution of the flowing particles) (WO2015 / 135844A1), all of which are incorporated herein by reference. These systems are rigid and are not designed to allow flexibility for different virus inactivation requirements in various biopharmaceutical production processes.

[0012] Therefore, having the narrowest fluid residence time distribution (RTD) under predictable conditions and being able to use different flow rates and residence times for uniform mixing in continuous virus inactivation in a low pH setting are specific goals. A new modular culture chamber that can be configured for a wide range of residence times and flow rates would represent a technological advance in the art.

[0013] In a continuous or semi-continuous flow system it would therefore be desirable to provide a method of maintaining a narrow residence time distribution.It would be desirable to provide a continuous or semi-continuous flow system for the purification of biomolecules, in particular for the purification of proteins. Summary of the invention

[0014] The problems of the prior art have been solved by the embodiments disclosed herein, which relate to a culture chamber that can be provided in a modular form to provide flexibility in terms of the flow rate and / or residence time of the product flow while narrowing the dispersion of the residence time distribution. Also disclosed are assemblies comprising such a culture chamber for purifying biomolecules, and methods for biomolecule purification, in particular methods for inactivating viruses in a culture chamber or in a plurality of culture chambers arranged in series in a modular form.

[0015] In certain embodiments, a culture chamber is disclosed, comprising: a culture chamber shell, the shell comprising an inlet port for receiving a fluid, an outlet port for distributing the fluid, and an inner cavity; a spiral coil, which is positioned in the inner cavity and is fluidly connected to the inlet port and the outlet port; wherein the culture chamber has a top outer surface and a bottom outer surface, the top outer surface has a first contour, and the bottom outer surface has a second contour, wherein the top outer surface can be releasably mated or interconnected with a culture chamber having a bottom outer surface having the second contour, and the bottom outer surface can be releasably mated or interconnected with a culture chamber having a top surface having the first contour.

[0016] In certain embodiments, the culture chamber accommodates a spiral tube or coil. The culture chamber may have an inlet port in fluid communication with one end of the coil and an outlet port in fluid communication with the other end of the coil. Each port may be closed by a sterile connector to form a closed system.

[0017] In some embodiments, multiple culture chambers can be vertically stackable and releasably interlocked. In some embodiments, the stackable culture chambers are interconnectable; they are in fluid communication with each other or can be placed in fluid communication with each other, for example, the outlet of the first culture chamber is in fluid communication with the inlet of the second culture chamber or is configured to be in fluid communication with the inlet of the second culture chamber. In some embodiments, the outlet of the second culture chamber is in fluid communication with the inlet of the third culture chamber or is configured to be in fluid communication with the inlet of the third culture chamber, and so on.

[0018] In some embodiments, the spiral coils may have regions of different orientations in a single culture chamber. In some embodiments, the spiral coils may be stacked vertically in a single culture chamber (ie, stackable in the z direction with the base of the culture chamber in the xy plane).

[0019] In certain embodiments, the coils are organized within the culture chamber to minimize the floor space of the culture chamber.

[0020] In certain embodiments, a method for inactivating one or more viruses that may be present in a fluid sample containing a target molecule (e.g., an antibody or an Fc region containing a protein) is provided, comprising subjecting the fluid sample to a chromatography process (e.g., affinity chromatography, such as protein A chromatography) or an ion exchange chromatography process to obtain an eluent; introducing a viral inactivator into the eluent; continuously introducing the eluent into a culture chamber comprising a spiral flow channel, and allowing the eluent to flow in the flow channel for a time sufficient to inactivate the virus. In certain embodiments, the chromatography process is performed in a continuous or semi-continuous mode. The eluent from the affinity chromatography process can be a real-time eluent from a column entering the system with a gradient of all its pH values, conductivity, concentration, etc., or can be a pool of eluents that are subsequently inactivated after homogenization.

[0021] In some embodiments, different process steps are connected to be operated in a continuous or semi-continuous manner. In some embodiments, the virus inactivation methods as described herein constitute a process step in a continuous or semi-continuous purification process, wherein the sample continuously flows from, for example, a protein A affinity chromatography step or an ion exchange chromatography step to a virus inactivation step to the next step in the process, which is typically a flow-through purification process step.

[0022] In some embodiments, the virus inactivation process step is performed continuously or semi-continuously, i.e., the eluate from a previous process step (e.g., a previous binding and elution chromatography step (e.g., protein A affinity chromatography)) flows into the virus inactivation step, which adopts a fluid flow path contained in the culture chamber, and then in some embodiments, the virus inactivated eluate can be collected in a storage container until the next process step is performed, or in some embodiments, can be directly and continuously supplied to the next downstream process step.

[0023] The methods and apparatus described herein are capable of achieving viral inactivation in a continuous or semi-continuous manner, which, due to its modular format, can provide considerable flexibility in flow rates and residence times. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 is a perspective view of a culture chamber according to certain embodiments;

[0025] Figure 1A is a perspective view of a culture chamber base and lid in an open position according to certain embodiments, wherein a helical coil is positioned within an interior cavity of the chamber;

[0026] Figure 1B is another perspective view of a culture chamber base and lid in an open position, wherein a helical coil is positioned within an interior cavity of the chamber, according to certain embodiments;

[0027] Figure 1C is another perspective view of a culture chamber base and lid in an open position according to certain embodiments, wherein a helical coil is positioned within an interior cavity of the chamber;

[0028] Figure 1D is another perspective view of a culture chamber base and lid in an open position according to certain embodiments, wherein a helical coil is positioned within the interior cavity;

[0029] Figure 2 According to some embodiments Figure 1 An exploded view of a culture chamber of , wherein the interior chamber contains a spiral coil;

[0030] Figure 3 According to some embodiments Figure 2 A top view of an interior chamber of a culture chamber;

[0031] Figure 4 is a top view of a helical coil configured for placement within a culture chamber according to certain embodiments;

[0032] Figure 5 is a perspective view of a culture chamber housing two layers of spiral coils according to certain embodiments;

[0033] Figure 6 is a perspective view of an oblique helical coil according to certain embodiments;

[0034] Figure 7 is a top view of a culture chamber according to certain embodiments, showing that an inner cavity with an oblique spiral coil optimizes the use of space in the inner cavity;

[0035] Fig. 8A and Figure 8B is a perspective view of modular components being assembled on a movable cart;

[0036] Fig. 9 is another perspective view of modular components on a mobile cart according to certain embodiments;

[0037] Fig.10 is a schematic diagram of a stackable cylindrical modular assembly according to certain embodiments; and

[0038] Fig.11 is a bottom perspective view of a culture chamber according to certain embodiments. DETAILED DESCRIPTION

[0039] A more detailed understanding of the components, processes, and devices disclosed herein may be obtained by referring to the accompanying drawings, which are merely schematic representations based on convenience and ease of illustrating the present disclosure, and are therefore not intended to indicate relative sizes and dimensions of devices or their components and / or to define or limit the scope of the exemplary embodiments.

[0040] Although specific terms are used in the following description for the sake of clarity, these terms are only intended to refer to the specific structure of the embodiments selected for illustration in the drawings, and are not intended to define or limit the scope of the present disclosure. In the drawings and the following description, it will be understood that the same number designation refers to components with the same function.

[0041] The singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0042] As used in this patent specification, various devices and components may be described as "comprising" other components. As used herein, the terms "include," "comprising," "having," "having," "may," "containing," and variations thereof are intended to be open-ended transitional phrases, terms, or words that do not exclude the possibility of additional components.

[0043] The term "virus inactivation" or "inactivation of viruses" refers to treating a sample containing one or more viruses in a manner such that the one or more viruses are no longer able to replicate or are inactivated. In the methods described herein, the terms "virus" and "viral" can be used interchangeably. Virus inactivation can be achieved by physical means (e.g., heat, ultraviolet light, ultrasonic vibration) or using chemical means (e.g., pH changes or additions of chemicals (e.g., detergents)). Virus inactivation is typically a process step used in most mammalian protein purification processes (particularly in the case of purification of therapeutic proteins from mammalian-derived expression systems). In the methods described herein, virus inactivation is performed in a fluid flow channel. It is understood that the failure to detect one or more viruses in a sample using standard assays known in the art and the assays described herein indicates complete inactivation of one or more viruses after treating the sample with one or more virus inactivators. As used herein, a viral inactivator may include a change in solution conditions (e.g., pH, conductivity, temperature, etc.) or the addition of detergents, salts, acids (e.g., acetic acid having a molar concentration to obtain a pH of 3.6 or 3.7), polymers, solvents, small molecules, drug molecules, or any other applicable entities, etc., or any combination thereof, or physical means (e.g., exposure to ultraviolet light, vibration, etc.) that interact with one or more viruses in a sample, such that exposure to the viral inactivator renders one or more viruses inactive or unable to replicate. In a specific embodiment, the viral inactivator is a pH change, wherein the viral inactivator is mixed with a sample containing a target molecule (e.g., an eluate from a protein A binding and elution chromatography step), for example, in a static mixer and then directed to a flow channel.

[0044] As used herein, the term "continuous processing" includes processes for purifying a target molecule that include two or more process steps (or unit operations) such that the output from one process step flows directly into the next process step of the process without interruption, and two or more process steps can be performed simultaneously for at least a portion of their duration. In other words, in the case of continuous processing, one process step does not need to be completed before starting the next process step, as long as a portion of the sample is always moved through the process steps.

[0045] Likewise, "semi-continuous processing" may encompass operations performed in a continuous mode for a set period of time, wherein one or more unit operations are periodically interrupted, e.g., loading feed is stopped to allow other flow-limiting steps to complete during continuous capture operations.

[0046] Now turn to Figure 1-4, a culture chamber 10 according to some embodiments can be seen. In the illustrated embodiment, the culture chamber 10 has a lid 12 and a base 14. The lid 12 and the base 14 can be configured to cooperate in a sealed relationship to enclose an inner cavity 16 ( Figure 2 ). In some embodiments, the lid 12 may be hinged to the base 14. A pair of apertures 17a, 17b may be provided in the culture chamber to accommodate the inlet end 18a and the outlet end 18b of the spiral coil 20. In the illustrated embodiment, the apertures (and the inlet end 18a and the outlet end 18b of the spiral coil 20) are positioned on the same side of the culture chamber 10, but those skilled in the art will appreciate that the arrangement of the spiral coil 20 in the culture chamber 10 may be modified so that the inlet end 18a and the outlet end 18b are positioned on different sides of the culture chamber 10. In this embodiment, a suitable inner diameter of the spiral tube 20 is 9.6 mm and the tube length is 28.08 m.

[0047] In some embodiments, the top or uppermost surface or face 12a of the cover 12 can have a profile configured to match a corresponding profile of a bottom surface or face (not shown) of a base 14' of another culture chamber 10', so that multiple culture chambers 10 are easily stackable and interlocked. For example, in the illustrated embodiment, the cover 12 has a peripheral edge 12b that is lower in height than the top or uppermost surface 12a. The peripheral edge 12b can receive a corresponding peripheral flange 14a ( Fig.11 ), the peripheral flange extends downward or axially from the base 14 'so that the flange is seated in the recess, thereby allowing two culture chambers 10 to fit or interlock in a stacked relationship. In some embodiments, the corresponding configurations of the top and bottom surfaces allow them to be easily removed relative to each other after interlocking.

[0048] Now turn to Figure 4, shows one embodiment of a spiral coil 20 suitable for use in a culture chamber 10. Preferably, the spiral coil 20 is made of a gamma-sterilizable material. For example, a round plastic pipe such as a pipe made of silicone is suitable for the spiral coil 20. In the illustrated embodiment, the spiral coil 20 is arranged to achieve an optimal fluid flow path in the culture chamber 10. To this end, the spiral coil has a first region 20a positioned along the "y" direction; a second region 20b positioned along the "x" direction that is orthogonal or substantially orthogonal to the first region 20a; a third region 20c positioned along the "x" direction that is orthogonal or substantially orthogonal to the second region 20b (and therefore parallel or substantially parallel to the first region 20a); and a fourth region 20d that is orthogonal or substantially orthogonal to the third region 20c (and therefore parallel or substantially parallel to the second region 20b). Certain regions include coil transition portions that change direction when transitioning from one coil region to the next coil region. Thus, the first region 20a has a coil transition portion 20a' that transitions from the first region 20a to the second region 20b; the second region 20b has a coil transition portion 20b' that transitions from the second region 20b to the third region 20c; and the third region 20c has a coil transition portion 20c' that transitions from the third region 20c to the fourth region 20d. The spiral coil 20 includes an inlet end 18a and an outlet end 18b and a continuous fluid flow path therebetween. Thus, each of the regions 20a, 20b, 20c, and 20d is fluidically connected, thereby defining a continuous fluid flow path. As shown in FIG. Figure 3 As shown, the coil thus configured can be neatly positioned within the inner cavity of the culture chamber 10 .

[0049] The number of turns in the spiral coil 20 and the diameter of the spiral coil 20 can each vary and are determined at least in part by the desired residence time of the sample in the flow path defined by the spiral coil 20. Suitable design parameters include about 15-21 turns, a tube inner diameter of about 3.2-9.6 mm (1 / 8"-3 / 8"); and a winding core diameter of 40-105 mm. Preferably, there are at least 5 windings. In certain embodiments, the residence time should be sufficient to inactivate viruses at an effective pH (e.g., a maximum pH of 3.6) for more than at least about 30 minutes. Those skilled in the art understand that exposing a product sample to a sufficiently low pH for an extended period of time to inactivate viruses can deteriorate the product, and therefore the embodiments disclosed herein enable easy adjustment of the residence time and flow through the coils in one or more culture chambers 10 to optimize viral inactivation. Typically, the flow in the spiral coil is laminar (e.g., Reynolds number <2000), although turbulent conditions do not negatively affect the efficiency of the culture chamber (the flow can even be turbulent in other parts of the system). For example, sampling and offline sensors can be used to verify the pH value.

[0050] Figure 1A An embodiment of the culture chamber 10 is shown in which the area defining the lumen is not completely occupied by the helical coil 20. In the embodiment shown, the helical coil 20 is positioned in the lower right quadrant of the lumen, closest to the apertures 17a and 17b, in order to minimize the linear length of the helical tube 20. In this embodiment, the applicable tube inner diameter is 4.8 mm, and the applicable tube length is 11.99 m.

[0051] Figure 1B Another embodiment of the culture chamber 10 is shown, in which the area defining the lumen is also not completely occupied by the helical coil 20. In the embodiment shown, the helical coil 20 is positioned in the lower right and upper left quadrants of the lumen, with the lower right region being closest to the apertures 17a and 17b, in order to minimize the linear length of the helical tube 20. In this embodiment, the applicable tube inner diameter is 4.8 mm, and the applicable tube length is 23.99 m.

[0052] Figure 1C Yet another embodiment of the culture chamber 10 is shown, in which the area defining the lumen is not completely occupied by the helical coil 20. This embodiment is similar to Figure 1A The embodiment is different in that the cultivation chamber 10 itself occupies a larger space (for example, the height is 130 mm for Figure 1A The height of the culture chamber is 65 mm), and therefore the inner diameter of the spiral tube 20 may be larger. In the embodiment shown, the spiral coil 20 is positioned in the lower right quadrant of the lumen, closest to the apertures 17a and 17b, so as to minimize the linear length of the spiral tube 20. In this embodiment, the applicable tube inner diameter is 6.4 mm, and the applicable tube length is 20.49 m.

[0053] Figure 1D Another embodiment of the culture chamber 10 is shown, in which the area defining the lumen is not completely occupied by the helical coil 20. Figure 1B The embodiment of the present invention is similar to that of the embodiment of the present invention, except that the occupancy space of the culture chamber 10 itself is different, and therefore the inner diameter of the spiral tube 20 can be larger. In the embodiment shown, the spiral coil 2 is positioned in the upper left and lower right quadrants of the lumen, closest to the apertures 17a and 17b, so as to minimize the linear length of the spiral tube 20. In this embodiment, the applicable tube inner diameter is 6.4 mm, and the applicable tube length is 40.98 m.

[0054] In some embodiments, multiple culture chambers may be arranged in series, such that the outlet of a first culture chamber feeds the inlet of a second culture chamber, etc. Thus, modular assemblies (e.g., Fig. 8A and Figure 8B), thereby providing the user with the flexibility to increase the residence time and / or flow rate by adding one or more culture chambers to the assembly, or to reduce the residence time and / or flow rate by removing one or more culture chambers from the assembly. In certain embodiments, the connection between the culture chambers is a sterile connection (e.g., Connectors) ensure a completely closed system. The components of the modular culture chamber can be supported on a cart 50 or the like ( Fig. 8A and Figure 8B ), the cart can be moved from one location to another. The cart 50 can provide a side entrance to the user for easy setup.

[0055] like Fig. 9 As best seen in FIG. 1 , a modular assembly of fluidically connected culture chambers may include culture chambers of varying sizes. For example, in the embodiment shown, a modular assembly of 24 culture chambers having Figure 1C The spiral coil 20 structure of the culture chamber and 12 with Figure 1D The culture chamber is constructed of a spiral coil 20.

[0056] Alternatively or additionally, a higher flow rate and / or longer residence time can be obtained by using a cultivation chamber 10 with a helical coil having a larger inner diameter. Likewise, a lower flow rate and / or shorter residence time can be obtained by using a cultivation chamber with a helical coil having a smaller inner diameter.

[0057] In some embodiments, a modular assembly can be formed wherein the helical coil length and / or diameter (inner diameter) in all culture chambers of the modular assembly is the same. In some embodiments, a modular assembly can be formed wherein the helical coil length and / or diameter in one or more culture chambers of the assembly is different from the helical length and / or coil diameter in one or more other culture chambers of the assembly. In some embodiments, a modular assembly can be formed of a plurality of culture chambers that are fluidly connected or connectable wherein the helical tube length of at least one of the plurality of culture chambers is twice the length of the helical tube in another of the plurality of culture chambers.

[0058] Thus, without changing the outer dimensions of the cultivation chamber 10, residence time and flow rate flexibility can be achieved.

[0059] The flow rate and the length of the pipe can be selected so as to target a specific residence time. For viral inactivation applications, the residence time can be selected to be sufficient to achieve viral inactivation in the flow channel, preferably with some safety factor. For example, in an embodiment where a residence time of 30 minutes is sufficient to inactivate the virus, the design parameters can be selected so that most particles will pass through the chamber in about 36 minutes, wherein the fastest particles stay in the chamber for about 32 minutes and the slowest stay for about 45 minutes. The shortest residence time may also depend on regulatory guidance on acceptable safety factors for viral inactivation.

[0060] Applicable nominal dwell times include, but are not limited to, 10 minutes, 15 minutes, 20 minutes, 25 minutes, 30 minutes, 35 minutes, 40 minutes, 45 minutes, 50 minutes, 55 minutes and 60 minutes.

[0061] like Figure 5 As shown, in some embodiments, the inner cavity of the culture chamber 10' is deep enough, for example, having a sufficient volume to accommodate two or more vertical layers of spiral coils 20. In some embodiments, as shown in FIG. Figure 8B As shown, such a culture chamber 10 ′ can be used in combination with the culture chamber 10 .

[0062] In some embodiments, in order to reduce the height of the culture chamber 10, the spiral coil 20 can be formed as follows: Figure 6 The inclined configuration shown. Suitable inclination angles vary from about 30° to about 60°. Although this increases the overall width of the culture chamber, the footprint of one or more culture chambers 10' can be minimized by having the spiral coil occupy as much interior space within the culture chamber as possible. Figure 7 A suitable oblique helical coil arrangement is shown in FIG.

[0063] In yet another embodiment, the culture chamber 10 may be in the form of a cylinder in which the spiral coil flow path is wound around a cylindrical core. Fig.10 shown stacked and are similar to Figure 1 The box-like embodiments are arranged in series.

Claims

1. A culture chamber for virus inactivation, comprising: A culture chamber housing, comprising: a base; a cover, the cover being configured to mate with the base in a sealed relationship; an inlet port for receiving a fluid, an outlet port for dispensing the fluid, and an inner cavity, the inner cavity being defined by the base and the cover; a helical coil, the helical coil being positioned in the inner cavity and being in fluid communication with the inlet port and the outlet port; wherein the cover of the culture chamber has a top outer surface and a peripheral edge, the top outer surface having a first profile, the height of the peripheral edge being lower than the top outer surface to form a recess, and the base of the culture chamber has a bottom outer surface and a peripheral flange, the bottom outer surface having a second profile, and the peripheral flange extending downwardly or axially from the base, wherein the top outer surface is capable of releasably mating with a culture chamber having a bottom outer surface having the second profile, and the bottom outer surface is capable of releasably mating with a culture chamber having a top outer surface having the first profile, so that the peripheral flange can be seated in the recess, thereby allowing two culture chambers to mate or interlock in a stacked relationship to be in fluid communication with each other.

2. The culture chamber according to claim 1, wherein: The helical coil is inclined.

3. The culture chamber according to claim 1, wherein: The helical coil has a first region positioned within the lumen along a first direction and a second region positioned within the lumen along a second direction substantially orthogonal to the first direction.

4. A modular assembly for virus inactivation, the modular assembly comprising a first culture chamber and a second culture chamber configured to be in fluid communication with each other, the first culture chamber comprising a first culture chamber housing, the first culture chamber housing comprising: First base; a first cover configured to mate with the first base in a sealing relationship; a first inlet port for receiving a fluid, a first outlet port for dispensing the fluid, and a first inner cavity, the first inner cavity being defined by the first base and the first cover; a first helical coil, the first helical coil being positioned in the first inner cavity and being in fluid communication with the first inlet port and the first outlet port; the second culture chamber comprising a second culture chamber housing, the second culture chamber housing comprising: a second base; a second cover, the second cover being configured to mate with the second base in a sealed relationship; a second inlet port for receiving a fluid, a second outlet port for dispensing the fluid, a second inner cavity, the second inner cavity being defined by the second base and the second cover; and a second helical coil, the second helical coil being positioned in the second inner cavity and being fluidly connected to the second inlet port and the second outlet port; wherein the first cover of the first culture chamber has a top outer surface and a first peripheral edge, the top outer surface having a first profile, the height of the first peripheral edge being lower than the top outer surface to form a recess, and the second base of the second culture chamber has a bottom outer surface and a second peripheral flange, the bottom outer surface having a second profile, the second peripheral flange extending downwardly or axially from the base, wherein the top outer surface is capable of releasably interconnecting with the bottom outer surface so that the second peripheral flange can be seated in the recess, thereby allowing the first culture chamber and the second culture chamber to mate or interlock in a stacked relationship.

5. The modular assembly of claim 4, wherein: The first helical coil is configured to be in fluid communication with the second helical coil when the first and second culture chambers are interconnected.

6. A method for inactivating one or more viruses in a sample containing a target molecule, wherein: The method includes flowing the sample in a spiral coil positioned in an interior cavity of a culture chamber while continuously exposing the sample to inactivation conditions during a process for purifying the target molecule, the culture chamber having a lid and a base, the lid having a top outer surface and a peripheral edge, the top outer surface having a first contour, the peripheral edge being lower in height than the top outer surface to form a recess, the base having a bottom outer surface and a peripheral flange, the bottom outer surface having a second contour, the peripheral flange extending downwardly or axially from the base, wherein the lid and the base together define the interior cavity, the top outer surface being releasably matable with a culture chamber having a base whose bottom outer surface has the second contour, and the bottom outer surface being releasably matable with a culture chamber having a lid whose top surface has the first contour so that the peripheral flange can be seated in the recess, thereby allowing two culture chambers to mate or interlock in a stacked relationship to be fluidically connected to each other.

7. The method of claim 6, wherein: The method also includes: subjecting the sample to a protein A affinity chromatography process to obtain an eluate; introducing a virus inactivating agent into the eluate, and continuously transferring the eluate to the spiral coil, and allowing the eluate to flow in the spiral coil for a time sufficient to inactivate the virus.

8. The method of claim 6, wherein: The method further comprises: subjecting the sample to an ion exchange chromatography process to obtain an eluate; introducing a virus inactivating agent into the eluate, and continuously transferring the eluate to the spiral coil, and allowing the eluate to flow in the spiral coil for a time sufficient to inactivate the virus.

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