Modular culture chamber and virus inactivation method

Abstract

A culture chamber that can be provided in a modular form to provide flexibility in the flow rate and / or residence time of a product stream is disclosed. An assembly comprising such a culture chamber for the purification of biomolecules is also disclosed, as well as a method for the purification of biomolecules, and in particular a method for inactivating viruses in a culture chamber or a plurality of culture chambers arranged in series.

Description

Technology Field

[0001] The present disclosure relates to the cultivation of a fluid having a wide range of residence times and flow rates. More particularly, embodiments of the cultivation chamber and the method for culturing the fluid help ensure that inline virus inactivation is achieved and that the flow path is set to produce a narrow residence time distribution (RTD) of fluid particles. Background Technology

[0002] Large-scale production and economic feasibility related to the purification of therapeutic proteins, particularly monoclonal antibodies, are becoming increasingly important issues in the biopharmaceutical industry. Therapeutic proteins are typically produced in mammalian or bacterial cells engineered to produce the protein of interest. However, once produced, the protein of interest must be separated from various impurities, such as host cell proteins (HCPs), endotoxins, viruses, and DNA.

[0003] In a typical purification process, the cell culture harvest undergoes a purification step to remove cell debris. The purified cell culture harvest containing the protein of interest undergoes one or more chromatography steps, which may include an affinity chromatography step or a cation exchange chromatography step. To ensure the viral safety of the therapeutic candidate and to comply with regulatory obligations, a viral removal unit operation is implemented in the purification process. These steps include protein A and ion exchange chromatography, filtration, and low pH / chemical inactivation.

[0004] Virus inactivation is generally performed after a chromatographic step (e.g., after affinity chromatography or cation exchange chromatography). In a typical large-scale purification process, a chromatographic elution pool containing the protein of interest is collected in a large tank or storage system and undergoes a long-term virus inactivation step / process with mixing, which may take about 30 minutes to 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 a holding tank is used to store materials between unit operations and to facilitate any necessary solution adjustments between steps. Typically, the material is collected in a single tank where it is adjusted to achieve target inactivation conditions. This can be achieved by adding acid to achieve a low pH target level or 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 specific incubation time. The purpose of this transfer is to eliminate the risk of droplets on the walls of the first tank that may not have reached target inactivation conditions and may contain viral particles. By transferring the material to a different tank, this risk is reduced.

[0006] Several virus inactivation techniques are known in the art, including exposing protein solutions to specific temperatures, pH levels, or radiation, and exposing them to specific chemical agents such as detergents and / or salts. One virus inactivation process involves a large holding tank in which the material is maintained under inactivation conditions, such as exposure to low pH and / or detergent, for a given time, e.g., 60 minutes. This static holding step becomes a bottleneck in moving toward continuous processing.

[0007] However, the virus inactivation kinetics indicate that the inactivation time may vary, suggesting that processing time can be significantly reduced (or increased), that static holding tanks for virus inactivation can be eliminated, and that the method may be more suitable for continuous processing.

[0008] Recently, there has been a demand for continuous processes in which unit operations are linked together and manual solution adjustments are minimized. To facilitate this, efforts are being made to develop in-line processing methods that enable in-line virus deactivation and other in-line solution adjustments. In continuous or semi-continuous flow systems, it may be desirable to provide a method for maintaining a narrow residence time distribution in a continuous flow system.

[0009] Past practices for virus inactivation involved introducing the liquid to be inactivated into a low pH solution (e.g., pH 3.6 or lower), homogenizing it if necessary, and then keeping it in a resting state for the required period. Subsequently, virus inactivation is achieved by bringing the entire volume of the liquid containing the virus into bulk contact with the low pH fluid for a fixed dead processing time.

[0010] Continuous or semi-continuous processing is required to be performed while satisfying a minimum retention time to ensure effective inactivation of the virus without interruption and without long retention times under low pH conditions that could damage products (e.g., proteins) contained in the liquid. Such new systems require careful consideration of retention time, fluid flow characteristics (laminar vs. non-laminar), and system / hardware requirements for achieving these retention times and flow characteristics.

[0011] Conventional systems include continuous virus inactivation (WO2002038191, EP1339643B1, EP1464342B1, EP1914202A1 and EP1916224A1), all incorporated herein by reference, which use light irradiated from a spirally wound tube with centrifugal force acting on a fluid, and coil flow inverters (CFI) (WO2015 / 135844A1), in which a tube is spirally wound around a coil axis with a large number of turns, in which the number of turns and the angle of the bend help determine and improve the residence characteristics of the flow (as the fluid moves along the chamber tubing, not all of its particles flow at the same speed due to viscosity effects, which is particularly evident near the tubing wall where the resulting velocity profile along the tube cross-section results in a distribution of residence times of the flow particles). Such systems are rigid and are not designed to allow flexibility regarding changes in the need for virus inactivation in various biopharmaceutical product manufacturing processes.

[0012] Therefore, a specific objective is to achieve uniform mixing under predictable conditions with the narrowest residence time distribution (RTD) of the fluid, equipped with the ability to use different flow rates and residence times for continuous virus inactivation at low pH settings. A new modular culture chamber that can be configured for a wide range of residence times and flow rates will represent an advancement(s) in the industry.

[0013] In a continuous or semi-continuous flow system, it may be desirable to provide a method for maintaining a narrow residence time distribution accordingly. Particularly for protein purification, it may be desirable to provide a continuous or semi-continuous flow system for biomolecular purification. means of solving the problem

[0014] The problem of the prior art is solved by the embodiments disclosed herein, which relate to culture chambers that can be provided in a modular form to provide flexibility in the flow rate and / or residence time of a product stream while narrowing the dispersion of the residence time distribution. An assembly comprising such culture chambers for the purification of biomolecules is also disclosed, as well as a method for the purification of biomolecules and, in particular, a method for virus inactivation in a culture chamber or a plurality of culture chambers arranged in a serial modular form.

[0015] In a specific embodiment, a culture chamber is disclosed, and the culture chamber comprises: a culture chamber housing comprising an inlet port for receiving fluid, an outlet port for dispensing fluid, and an internal cavity; a spiral coil disposed within the internal cavity and fluidly communicating with the inlet port and the outlet port; the culture chamber has an upper outer surface having a first contour and a lower outer surface having a second contour, wherein the upper outer surface may be disengaged or interconnected with the culture chamber having the lower outer surface having the second contour, and the lower outer surface may be disengaged or interconnected with the culture chamber having the upper surface having the first contour.

[0016] In a specific embodiment, the culture chamber accommodates a spiral or coiled tube. The chamber may have an inlet port fluidly communicating with one end of the coiled tube and an outlet port fluidly communicating with the other end of the coiled tube. Each port may be closed by an aseptic connection to form a closed system.

[0017] In certain embodiments, a plurality of culture chambers may be vertically stacked and unlockably interlocked. In some embodiments, the stackable culture chambers may be interconnected; they may be fluidly connected to or arranged to be fluidly connected to each other, for example, configured such that the outlet of a first culture chamber is fluidly connected to or arranged to be fluidly connected to the inlet of a second culture chamber. In some embodiments, the outlet of a second culture chamber is configured such that it is fluidly connected to or arranged to be fluidly connected to the inlet of a third culture chamber, and so on.

[0018] In certain embodiments, the helical coil may have regions having different orientations within a single culture chamber. In some embodiments, the helical coil may be stacked vertically within a single culture chamber (i.e., if the base of the culture chamber is in the xy plane, it may be stacked in the z-direction).

[0019] In a specific embodiment, a coiled tube is configured within the culture chamber to minimize the footprint 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, the method comprising the steps of: obtaining an eluent by performing a chromatographic process (e.g., affinity chromatography such as protein A chromatography) or an ion exchange chromatography process on the fluid sample; introducing a virus inactivating agent into the eluent; and continuously introducing the eluent into a culture chamber comprising a helical flow channel and allowing the eluent to flow within the flow channel for a time sufficient for inactivating the virus. In certain embodiments, the chromatographic process is performed in a continuous or semi-continuous mode. The eluent from the affinity chromatography process may be a real-time elution from a column entering a system having all of the pH gradient, conductivity gradient, concentration gradient, etc., or an eluent pool that is subsequently inactivated after homogenization.

[0021] In some embodiments, different process steps are connected to operate in a continuous or semi-continuous manner. In some embodiments, the virus inactivation method constitutes a process step of a continuous or semi-continuous purification process as described herein, wherein the sample flows continuously to the next step of the process, which is generally a pass-flow purification process step, from, for example, a protein A affinity chromatography step or an ion-exchange chromatography step to a virus inactivation step.

[0022] In some embodiments, the virus inactivation process step is performed continuously or semi-continuously, that is, the eluent 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 using a fluid flow path contained within a culture chamber, and thereafter, in some embodiments, the virus-inactivated eluent may be collected in a storage container until the next process step is performed, or in some embodiments, may be supplied directly and continuously to the next downstream process step.

[0023] The method and apparatus described herein can achieve virus inactivation in a continuous or semi-continuous manner, and can provide significant flexibility in flow rate and residence time due to the modular format. Brief explanation of the drawing

[0024] FIG. 1 is a perspective view of a culture chamber according to a specific embodiment. FIG. 1a is a perspective view of a culture chamber base and cover in an open position, in which a spiral coil is disposed within the internal cavity of the chamber, according to a specific embodiment. FIG. 1b is another perspective view of a culture chamber base and cover in an open position, in which a spiral coil is disposed within the internal cavity of the chamber according to a specific embodiment. FIG. 1c is another perspective view of a culture chamber base and cover in an open position, in which a spiral coil is disposed within the internal cavity of the chamber, according to a specific embodiment. FIG. 1d is another perspective view of a culture chamber base and cover in an open position, in which a spiral coil is disposed within an internal cavity, according to a specific embodiment. FIG. 2 is an exploded view of the culture chamber of FIG. 1, in which the inner chamber includes a spiral coil according to a specific embodiment. FIG. 3 is a top view of the inner chamber of the culture chamber of FIG. 2 according to a specific embodiment. FIG. 4 is a top view of a spiral coil configured to be placed inside a culture chamber according to a specific embodiment. FIG. 5 is a perspective view of a culture chamber accommodating two layers of spiral coils according to a specific embodiment. FIG. 6 is a perspective view of an inclined helical coil according to a specific embodiment. FIG. 7 is a top view of a culture chamber illustrating an internal cavity having an inclined spiral coil that optimally utilizes the space within the internal cavity according to a specific embodiment. FIGS. 8A and FIGS. 8B are perspective views of a modular assembly assembled on a movable cart. FIG. 9 is an additional perspective view of a modular assembly on a movable cart according to a specific embodiment. FIG. 10 is a schematic diagram of a stackable cylindrical modular assembly according to a specific embodiment. FIG. 11 is a bottom perspective view of a culture chamber according to a specific embodiment. Specific details for implementing the invention

[0025] By referring to the accompanying drawings, the components, processes, and devices disclosed herein may be more fully understood. The drawings are merely schematic representations based on convenience and easy description of the contents of the disclosure and are not intended to indicate the relative size and dimensions of the devices and their components, or to define or limit the scope of exemplary embodiments.

[0026] Although specific terms are used in the following description for clarity, these terms are intended to refer only to specific structures of embodiments selected for illustration in the drawings and are not intended to define or limit the scope of the disclosure. In the drawings and the following description, similar numerical representations should be understood to refer to components of similar function.

[0027] Unless otherwise clearly stated in the context, the singular forms (“a,” “an,” and “the”) include plural objects.

[0028] As used in the specification, various devices and parts may be described as "comprising" other components. As used herein, the terms "comprising," "comprising," "having," "having," "able to," and "containing," and variations thereof, are intended to be open-ended transitional phrases, terms, or words, and do not exclude the possibility of additional components.

[0029] The terms “viral inactivation” or “inactivation of viruses” refer to treating a sample containing one or more viruses in such a way that one or more viruses are no longer able to replicate or become inactive. In the methods described herein, the terms “virus” and “of viruses” may be used interchangeably. Viral inactivation may be achieved by physical means, e.g., heat, ultraviolet light, ultrasonic vibration, or by chemical means, e.g., pH change or the addition of chemicals (e.g., detergents). Viral inactivation is a process step generally used during most mammalian protein purification processes, particularly in the case of purifying therapeutic proteins from mammalian-derived expression systems. In the methods described herein, viral inactivation is performed within a fluid flow channel. It will be understood that the failure to detect one or more viruses in a sample using standard analyses known in the art and those described herein indicates the complete inactivation of one or more viruses after treating the sample with one or more viral inactivating agents. Virus inactivating agents as used herein may include changes in solution conditions (e.g., pH, conductivity, temperature, etc.) or detergents, salts, acids (e.g., molar concentration of acetic acid to achieve pH 3.6 or 3.7), polymers, solvents, small molecules, drug molecules, or other suitable entities that interact with one or more viruses in a sample, or combinations thereof, or physical means (e.g., exposure to UV light, vibration, etc.) that cause exposure to the virus inactivating agent to render one or more viruses inactive or unable to replicate.In a specific embodiment, the virus inactivating agent is a pH change, wherein the virus inactivating agent is mixed with a sample containing a target molecule (e.g., an eluent from a protein A binding and elution chromatography step) in, for example, a static mixer and then directed into a flow channel.

[0030] The term “continuous process” as used herein comprises a process for purifying a target molecule, comprising two or more process steps (or unit operations) such that the output from one process step flows directly to the next process step within the process without interruption, wherein the two or more process steps may be performed simultaneously for at least part of their duration. In other words, in the case of a continuous process, as long as a portion of the sample always moves through the process steps, there is no need to complete a process step before the next process step begins.

[0031] Similarly, a "semi-continuous process" may include an operation performed in a continuous mode for a set period, wherein one or more unit operations are periodically interrupted. For example, the interruption of feed loading enables the completion of another rate-limiting step during a continuous capture operation.

[0032] Now, referring to FIGS. 1 through 4, a culture chamber (10) according to a specific embodiment is illustrated. In the illustrated embodiment, the culture chamber (10) has a cover (12) and a base (14). The cover (12) and the base (14) may be configured to interlock in a sealing relationship to surround an internal culture chamber cavity (16) (Fig. 2). In some embodiments, the cover (12) may be hinged to the base (14). A pair of openings (17a, 17b) are provided within the culture chamber to accommodate an inlet end (18a) and an outlet end (18b) of a spiral coil (20). In the illustrated embodiment, the openings (and the inlet end (18a) and 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 understand that the arrangement of the spiral coil (20) within the culture chamber (10) can be changed so that the inlet end (18a) and outlet end (18b) are located on different sides of the culture chamber (10). In this embodiment, one suitable inner diameter of the spiral tube (20) is 9.6 mm and the tube length is 28.08 m.

[0033] In a specific embodiment, the top or uppermost surface or face (12a) of the cover (12) may have a contour configured to engage with a corresponding contour of the bottom surface or face (not shown) of the base (14') of another culture chamber (10'), so that a plurality of culture chambers (10) can be easily stacked and locked together. For example, in the illustrated embodiment, the cover (12) has a perimeter edge (12b) that is lower in height than the top or uppermost surface (12a). The perimeter edge (12b) may accommodate a corresponding perimeter flange (14a) (Fig. 11) extending downward or axially from the base (14') so that the flange is seated within the recess to allow two culture chambers (10) to be engaged in a stacked relationship or locked together. In some embodiments, the top and bottom surfaces are each configured so that they can be easily removed from each other after being locked together.

[0034] Now, referring to FIG. 4, an embodiment of a spiral coil (20) suitable for use within a culture chamber (10) is illustrated. Preferably, the spiral coil (20) is made of a gamma-sterilizable material. For example, circular plastic tubing, such as tubing made of silicone, may be suitable for the spiral coil (20). In the illustrated embodiment, the spiral coil (20) is arranged so that an optimal fluid flow path can be obtained within the culture chamber (10). To this end, the spiral coil comprises: a first region (20a) positioned in the "y" direction; a second region (20b) positioned in the "x" direction perpendicular or substantially perpendicular to the first region (20a); and a third region (20c) positioned in the "x" direction perpendicular or substantially perpendicular to the second region (20b) (and accordingly parallel or substantially parallel to the first region (20a)). and has a fourth region (20d) that is perpendicular to or substantially perpendicular to the third region (20c) (and accordingly parallel to or substantially parallel to the second region (20b)). A particular region includes a coil transition portion that changes direction when transitioning from one coil region to the next coil region. 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 between them. Accordingly, each of the regions (20a, 20b, 20c, and 20d) is fluidly connected to form a continuous fluid flow path. The coil thus configured can be neatly placed within the internal cavity of the culture chamber (10) as shown in FIG. 3.

[0035] The number of windings within the helical coil (20) and the diameter of the helical coil (20) may each be changed and are determined at least partially by the desired residence time of the sample in the flow path formed by the helical coil (20). Suitable design parameters include about 15 to 21 windings, a tube inner diameter of about 3.2 to 9.6 mm (1 / 8" to 3 / 8"); and a winding core diameter of 40 to 105 mm. Preferably, there are at least 5 windings. In certain embodiments, the residence time must be sufficient time to allow virus inactivation at an effective pH to inactivate the virus (e.g., at least about 30 minutes at a maximum pH of 3.6). Those skilled in the art will understand that exposing a product sample to a sufficiently low pH for a long period to inactivate the virus can degrade the product, and accordingly, the embodiments disclosed herein allow for easy adjustment of the residence time and flow through the coil(s) in one or more culture chamber(s) (10) to optimize virus inactivation. Generally, the flow is laminar (e.g., Reynolds number less than 2000) within the spiral coil, but the turbulent flow regime does not negatively affect the efficiency of the culture chamber (the flow may also be turbulent in other parts of the system). pH can be verified, for example, using sampling and offline sensors.

[0036] FIG. 1a illustrates an embodiment of a culture chamber (10), wherein the area forming the internal cavity is not entirely occupied by the spiral coil (20). In the illustrated embodiment, the spiral coil (20) is positioned within the lower right quadrant of the internal cavity closest to the openings (17a and 17b) in order to minimize the straight length of the spiral tube (20). In this embodiment, the suitable tube ID is 4.8 mm and the suitable tube length is 11.99 m.

[0037] FIG. 1b illustrates another embodiment of the culture chamber (10), wherein the area forming the internal cavity is also not completely occupied by the spiral coil (20). In the illustrated embodiment, the spiral coil (20) is positioned within the lower right and upper left quarters of the internal cavity to minimize the straight length of the spiral tube (20), with the lower right area being closest to the openings (17a and 17b). In this embodiment, the suitable tube ID is 4.8 mm and the suitable tube length is 23.99 m.

[0038] FIG. 1c illustrates another embodiment of the culture chamber (10), wherein the area forming the internal cavity is not entirely occupied by the spiral coil (20). This embodiment is similar to that of FIG. 1a, except that the footprint of the culture chamber (10) itself is larger (e.g., 130 mm height versus 65 mm height of the culture chamber in FIG. 1a), and accordingly, the inner diameter of the spiral tube (20) may be larger. In the illustrated embodiment, the spiral coil (20) is positioned within the lower right quarter of the internal cavity closest to the openings (17a and 17b) to minimize the straight length of the spiral tube (20). In this embodiment, the suitable tube ID is 6.4 mm, and the suitable tube length is 20.49 m.

[0039] FIG. 1d illustrates another embodiment of the culture chamber (10), wherein the area forming the internal cavity is not entirely occupied by the spiral coil (20). This embodiment is similar to that of FIG. 1b, except that the footprint of the culture chamber (10) itself is larger and, accordingly, the inner diameter of the spiral tube (20) may be larger. In the illustrated embodiment, the spiral coil (20) is positioned within the upper left and lower right quarters of the internal cavity closest to the openings (17a and 17b) to minimize the straight length of the spiral tube (20). In this embodiment, the suitable tube ID is 6.4 mm and the suitable tube length is 40.98 m.

[0040] In certain embodiments, a plurality of culture chambers may be arranged in series such that the outlet of the first culture chamber supplies into the inlet of the second culture chamber, and so on. Thus, a modular assembly may be constructed (e.g., FIG. 8a and FIG. 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 decrease the residence time and / or flow rate by removing one or more culture chambers from the assembly. In certain embodiments, the connections between the culture chambers are aseptic connections (e.g., ASEPTIQUIK) that ensure a completely closed system. ® It is a connecting part. An assembly of modular culture chambers can be supported on a cart (50) or other (Figs. 8a and 8b) that can be moved between locations. The cart (50) can provide lateral access to the user, thereby facilitating setup.

[0041] As is best seen in FIG. 9, a modular assembly of fluidly connected culture chambers may include culture chambers of different sizes. For example, in the illustrated embodiment, there are 24 culture chambers with a spiral coil (20) configuration of FIG. 1c and 12 culture chambers with a spiral coil (20) configuration of FIG. 1d.

[0042] Alternatively or additionally, by using a culture chamber (10) equipped with a spiral coil having a larger inner diameter, a larger flow rate and / or a longer residence time can be achieved. Similarly, by using a culture chamber equipped with a spiral coil having a smaller inner diameter, a smaller flow rate and / or a shorter residence time can be achieved.

[0043] In some embodiments, a modular assembly may be formed in which 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 may be formed in which the helical coil length and / or diameter in one or more culture chambers of the assembly differs from the helical length and / or coil diameter in one or more other culture chambers of the assembly. In some embodiments, the modular assembly may be formed of a plurality of culture chambers that are fluidly connected or can be connected, wherein at least one culture chamber among the plurality of culture chambers has a helical tube length that is twice the helical tube length in another culture chamber among the plurality of culture chambers.

[0044] Therefore, residence time and flow rate flexibility can be achieved without the need to change the external dimensions of the culture chamber (10).

[0045] The flow rate and tubing length may be selected to target a specific residence time. In the case of a virus inactivation application example, the residence time may be selected to be sufficient to achieve virus inactivation within the flow channel, preferably with some safety factor. For example, in an embodiment where a residence time of 30 minutes is sufficient for virus inactivation, design parameters may be selected so that the bulk of particles passes through the chamber within about 36 minutes, with a fastest residence time of about 32 minutes and a slowest residence time of about 45 minutes. The minimum residence time may also vary depending on regulatory guidelines regarding acceptable safety factors for virus inactivation.

[0046] Suitable nominal residence times include, without limitation, 10 minutes, 15 minutes, 20 minutes, 25 minutes, 30 minutes, 35 minutes, 40 minutes, 45 minutes, 50 minutes, 55 minutes, and 60 minutes.

[0047] As illustrated in FIG. 5, in some embodiments, the internal cavity of the culture chamber (10') is sufficiently deep and has a volume sufficient to accommodate, for example, two or more vertical layers of spiral coils (20). In some embodiments, such a culture chamber (10') can be used with the culture chamber (10) as illustrated in FIG. 8b.

[0048] In some embodiments, to reduce the height of the culture chamber (10), the spiral coil (20) may be formed in an inclined configuration as shown in FIG. 6. Suitable inclination angles range from about 30° to about 60°. While this increases the overall width of the culture chamber, the footprint of the culture chamber (10') or chambers can be minimized as the spiral coil occupies as much internal space as possible within the culture chamber. One suitable arrangement of the inclined spiral coil is shown in FIG. 7.

[0049] In addition, in an additional embodiment, the culture chamber (10) may be in the form of a cylinder, in which a spiral coil flow path is coiled around a cylinder core. Such cylinders may be stacked as shown in FIG. 10 and arranged in series in a manner similar to the cassette-like embodiment of FIG. 1.

Claims

Claim 1 A culture chamber comprising: a culture chamber housing comprising a base, a cover configured to engage with said base in a sealing relationship, an inlet port for receiving fluid, an outlet port for distributing said fluid, and an internal cavity formed by said base and said cover; and a spiral coil disposed within said internal cavity and fluidly communicating with said inlet port and said outlet port; wherein the cover of said culture chamber has an upper outer surface having a first contour to form a recess and a perimeter edge having a height lower than that of said upper outer surface. The base has a lower outer surface having a second contour and a perimeter flange extending downward or axially from said base, said upper outer surface engaging disengageably with a culture chamber having said lower outer surface having the second contour, said lower outer surface engaging disengageably with a culture chamber having said upper surface having the first contour, and said perimeter flange is seated within said recess to allow two culture chambers to engage in a stacking relationship or lock into each other. Claim 2 In claim 1, a culture chamber in which the spiral coil is inclined. Claim 3 A culture chamber according to claim 1, wherein the spiral coil has a first region disposed within the internal cavity in a first direction and a second region disposed within the internal cavity in a second direction substantially perpendicular to the first direction. Claim 4 A modular assembly comprising first and second culture chambers configured to be fluidly connected to each other, wherein the first culture chamber comprises a first culture chamber housing, the first culture chamber housing comprising: a first base, a first cover configured to engage with the first base in a sealing relationship, a first inlet port for receiving fluid, a first outlet port for distributing said fluid, and a first internal cavity formed by the first base and the first cover; a first spiral coil disposed within the first internal cavity and fluidly connected to the first inlet port and the first outlet port; and a second culture chamber comprising a second culture chamber housing, the second culture chamber housing comprising: a second base, a second cover configured to engage with the second base in a sealing relationship, a second inlet port for receiving fluid, a second outlet port for distributing said fluid, and a second internal cavity formed by the second base and the second cover. A modular assembly comprising: a second spiral coil disposed within the second internal cavity and fluidly communicating with the second inlet port and the second outlet port; wherein the first cover of the first culture chamber has an upper outer surface having a first contour to form a recess and a perimeter margin lower than the upper outer surface, and the second base of the second culture chamber has a lower outer surface having a second contour and a perimeter flange extending downward or axially from the second base, wherein the upper outer surface can be disengagedly interconnected with the lower outer surface, and the perimeter flange is seated within the recess to allow the two culture chambers to be interlocked in a stacked relationship or mutually locked. Claim 5 A modular assembly according to claim 4, wherein when the first and second culture chambers are interconnected, the first spiral coil is configured to be in fluid communication with the second spiral coil. Claim 6 A method for inactivating one or more viruses in a sample containing a target molecule, wherein the method comprises the step of flowing the sample within a spiral coil disposed within an internal cavity of a culture chamber while continuously exposing the sample to an inactivation condition during a process for purifying the target molecule, wherein the culture chamber comprises a base and a cover, wherein the cover has an upper outer surface having a first contour to form a recess and a perimeter edge having a height lower than that of the upper outer surface. The base has a lower outer surface having a second contour and a perimeter flange extending downward or axially from the base, wherein the base and the cover form an internal cavity, wherein the upper outer surface can be disengaged with the culture chamber having the lower outer surface having the second contour, wherein the lower outer surface can be disengaged with the culture chamber having the upper surface having the first contour, and wherein the perimeter flange is seated within the recess to allow two culture chambers to be engaged in a stacked relationship or mutually locked. Claim 7 A method according to claim 6, further comprising the steps of: performing a protein A affinity chromatography process on the sample to obtain an eluent; introducing a virus inactivating agent into the eluent; and continuously transferring the eluent to the helical coil and allowing the eluent to flow within the helical coil for a sufficient time to inactivate the virus. Claim 8 A method according to claim 6, further comprising the steps of: performing an ion exchange chromatography process on the sample to obtain an eluent; introducing a virus inactivating agent into the eluent; and continuously transferring the eluent to the spiral coil and allowing the eluent to flow within the spiral coil for a time sufficient to inactivate the virus.

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