Modular culture chamber and virus inactivation method

Abstract

Culture chambers are disclosed that can be provided in a modular format to provide flexibility in flow rate and / or residence time of product streams. Assemblies including such culture chambers for the purification of biomolecules are disclosed, as are methods for biomolecule purification and, in particular, for virus inactivation in a single culture chamber or multiple culture chambers arranged in series.

Description

[Technical field]

[0001] The present disclosure relates to culturing fluids having a wide range of residence times and flow rates. More specifically, embodiments of the culture chamber and method for culturing the fluids help ensure that the flow paths are configured to achieve in-line viral inactivation and create a narrow residence time distribution (RTD) of the fluid particles. [Background technology]

[0002] Large-scale production and economics surrounding the purification of therapeutic proteins, particularly monoclonal antibodies, have become increasingly important issues for the biopharmaceutical industry. Therapeutic proteins are generally produced in either 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 medium harvest undergoes a clarification step to remove cell debris. The clarified cell culture medium harvest containing the protein of interest then undergoes one or more chromatography steps, including affinity or cation exchange chromatography steps. To ensure the viral safety of therapeutic candidates and meet regulatory requirements, a viral clearance unit operation is incorporated into the purification process. Such steps include protein A and ion exchange chromatography, filtration, and low pH / chemical inactivation.

[0004] Viral inactivation is usually 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 prolonged viral 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, with holding tanks 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 the target inactivation conditions. This may be by the addition of acid to achieve a low pH target level, or by the addition of detergent in a detergent-based inactivation process. The material is then transferred to a second tank where it is kept at the inactivation conditions for a defined incubation time. The purpose of the transfer is to eliminate the risk of droplets on the walls of the first tank that have not reached the 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, or radiation, exposure to specific chemicals such as detergents and / or salts. One virus inactivation process involves large holding tanks where material is held at inactivating conditions such as low pH and / or exposure to detergents for a predetermined period of time, e.g., 60 minutes. This static holding step is a bottleneck toward continuous processing.

[0007] However, viral kill kinetics indicate that inactivation times can vary, suggesting that processing times could be significantly shortened (or increased) and static holding tanks for viral inactivation could be eliminated, making the method more suitable for continuous processing.

[0008] In recent years, it has become desirable to have a continuous process in which unit operations are linked together and manual solution adjustments are minimized. To facilitate this, efforts have been made to develop in-line processing methods that allow in-line viral inactivation as well as other in-line solution adjustments. In continuous or semi-continuous flow systems, it would be desirable to provide a method to maintain a narrow residence time distribution in the continuous flow system.

[0009] Past practice for virus inactivation has involved introducing the liquid to be inactivated into a low pH solution (e.g., pH less than 3.6), homogenizing if necessary, and then allowing to stand for the required period of time. Virus inactivation is then performed by contacting the entire volume of the virus-containing liquid with the bulk low pH fluid for a fixed non-moving treatment time.

[0010] Continuous or semi-continuous processing requires that viral inactivation be performed non-stop and in the context of meeting minimum residence times to ensure effective inactivation of viruses without long residence times at low pH conditions that could damage products contained in the liquid (such as proteins). These new systems require careful consideration of residence times, fluid flow characteristics (laminar vs. non-laminar), and system / hardware requirements to achieve the residence times and flow characteristics.

[0011] Conventional systems include continuous virus inactivation using irradiated light in a spirally wound tube with centrifugal forces acting on the fluid (WO 2002 / 038191, EP 1339643, EP 1464342, EP 1914202, and EP 1916224), and coil flow inverters (CFIs) where the tube is spirally wound a number of turns around the coil axis where the number of turns and bend angle help determine and improve the flow retention characteristics (as the fluid extends along the chamber tube, viscous effects mean that not all of its particles flow at the same rate, as shown especially near the tube wall with a resultant velocity profile along the tube cross section that leads to a distribution of residence times for the flowing particles) (WO 2015 / 135844), all of which are incorporated herein by reference. These systems are rigid and not designed to allow for flexibility for the various virus inactivation demands in various biopharmaceutical manufacturing processes. [Prior art documents] [Patent documents]

[0012] [Patent Document 1] International Publication No. 2002 / 038191 [Patent Document 2] European Patent No. 1339643 [Patent Document 3] European Patent No. 1464342 [Patent Document 4] European Patent Application Publication No. 1914202 [Patent Document 5] European Patent Application Publication No. 1916224 [Patent Document 6] International Publication No. 2015 / 135844 Summary of the Invention [Problem to be solved by the invention]

[0013] Therefore, homogeneous mixing under predictable conditions with the narrowest residence time distribution (RTD) of fluids with the ability to use different flow rates and residence times in continuous virus inactivation at low pH settings is a specific objective. The new modular culture chamber that can be configured for a wide range of residence times and flow rates represents an advancement in the art.

[0014] It would therefore be desirable to provide a method for maintaining a narrow residence time distribution in a continuous or semi-continuous flow system.It would be desirable to provide a continuous or semi-continuous flow system for biomolecule purification, particularly for protein purification. [Means for solving the problem]

[0015] The problems of the prior art are addressed by the embodiments disclosed herein, which relate to culture chambers that can be provided in a modular format to provide flexibility in flow rates and / or residence times of product streams while narrowing the variance of the residence time distribution. Assemblies including such culture chambers for the purification of biomolecules are disclosed, as are methods for biomolecule purification and in particular for virus inactivation in one culture chamber or multiple culture chambers arranged in series in a modular format.

[0016] In certain embodiments, a culture chamber is disclosed comprising a culture chamber housing, the housing comprising an inlet port for receiving a fluid, an outlet port for dispensing a fluid, and an internal cavity, and a helical coil disposed within the internal cavity and in fluid communication with the inlet port and the outlet port, the culture chamber having a top outer surface having a first contour and a bottom outer surface having a second contour, the top outer surface capable of releasably mating or interconnecting with a culture chamber having a bottom outer surface having the second contour, and the bottom outer surface capable of releasably mating or interconnecting with a culture chamber having a top surface having the first contour.

[0017] In certain embodiments, the culture chamber contains a spiral or coiled tube. The chamber may have an inlet port in fluid communication with one end of the coiled tube and an outlet port in fluid communication with the other end of the coiled tube. Each port may be closed by a sterile connector to form a closed system.

[0018] In certain embodiments, the multiple culture chambers may be vertically stackable and releasably connectable. In some embodiments, stackable culture chambers are connectable. They may be in fluid communication or arranged in fluid communication with one another, for example, an outlet of a first culture chamber is in fluid communication or configured to be arranged in fluid communication with an inlet of a second culture chamber. In some embodiments, an outlet of a second culture chamber is in fluid communication or configured to be arranged in fluid communication with an inlet of a third culture chamber, etc.

[0019] In certain embodiments, the spiral coils may have regions with different orientations within a single culture chamber, hi some embodiments, the spiral coils may be stacked vertically within a single culture chamber (i.e., stackable in the z-direction, where the base of the culture chamber lies in the xy-plane).

[0020] In certain embodiments, the coiled tubing is organized inside the culture chamber to minimize the footprint of the culture chamber.

[0021] In certain embodiments, a method is provided 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 protein), comprising the steps of 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 eluate, introducing a virus inactivating agent into the eluate, and continuously introducing the eluate into a culture chamber including a spiral flow path and allowing the eluate to flow through the flow path for a time sufficient to inactivate the viruses. In certain embodiments, the chromatography process is performed in a continuous or semi-continuous mode. The eluate from the affinity chromatography process may be a real-time elution from a column that enters the system with all of its pH, conductivity, concentration, etc. gradients, or it may be a pool of elution that undergoes inactivation after homogenization.

[0022] In some embodiments, the different process steps are connected to be operated continuously or semi-continuously. In some embodiments, the virus inactivation method as described herein constitutes a process step in a continuous or semi-continuous purification process, where the sample flows continuously, for example, from a Protein A affinity chromatography step or an ion exchange chromatography step to a virus inactivation step and then to the next step of the process, which is usually a flow-through purification process step.

[0023] In some embodiments, the viral inactivation process step is performed continuously or semi-continuously, i.e., eluate from a previous process step, such as a previous bind and elute chromatography step (e.g., Protein A affinity chromatography), flows into the viral inactivation step using a fluid flow path contained in the culture chamber, and then, in some embodiments, the viral inactivation eluate may be collected in a storage vessel until the next process step is performed, or in some embodiments, may be continuously fed directly to the next downstream process step.

[0024] The methods and devices described herein can achieve viral inactivation in a continuous or semi-continuous manner, and the modular format can provide great flexibility in flow rates and residence times. [Brief description of the drawings]

[0025] [Figure 1] FIG. 2 is a perspective view of an incubation chamber according to certain embodiments. [Figure 1A] FIG. 13 is a perspective view of a culture chamber base and cover in an open position with a helical coil disposed within the interior cavity of the chamber, according to certain embodiments. [Figure 1B] FIG. 13 illustrates another perspective view of the culture chamber base and cover in an open position with a helical coil disposed within the interior cavity of the chamber, according to certain embodiments. [Figure 1C] FIG. 13 illustrates yet another perspective view of the culture chamber base and cover in an open position with a helical coil disposed within the interior cavity of the chamber, according to certain embodiments. [Figure 1D] FIG. 13 illustrates yet another perspective view of a culture chamber base and cover in an open position with a helical coil disposed within the interior cavity, according to certain embodiments. [Diagram 2] FIG. 2 is an exploded view of the culture chamber of FIG. 1 having an inner chamber including a helical coil according to certain embodiments. [Diagram 3] FIG. 3 is a top view of the inner chamber of the culture chamber of FIG. 2 in accordance with certain embodiments. [Figure 4] FIG. 1 illustrates a top view of a helical coil configured for placement inside a culture chamber in accordance with certain embodiments. [Diagram 5] FIG. 1 is a perspective view of a culture chamber housing containing a two-layer helical coil according to certain embodiments. [Figure 6] FIG. 2 is a perspective view of a diagonal helical coil in accordance with certain embodiments. [Figure 7]FIG. 13 is a top view of a culture chamber showing an interior cavity having a diagonal helical coil that optimally utilizes the space within the interior cavity in accordance with certain embodiments. [Figure 8A] FIG. 1 is a perspective view of the modular assembly assembled on a movable cart. [Figure 8B] FIG. 1 is a perspective view of the modular assembly assembled on a movable cart. [Figure 9] FIG. 13 is a further perspective view of a modular assembly on a mobile cart in accordance with certain embodiments. [Figure 10] FIG. 1 is a schematic diagram of a stackable cylindrical modular assembly according to certain embodiments. [Figure 11] FIG. 2 is a bottom perspective view of a culture chamber according to certain embodiments. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0026] A more complete understanding of the components, processes, and devices disclosed herein can be obtained by reference to the accompanying drawings, which are merely schematic diagrams based on convenience and ease in illustrating the present disclosure, and are therefore not intended to illustrate relative sizes and dimensions of the devices or components thereof, and / or to define or limit the scope of the example embodiments.

[0027] Although specific terminology is used in the following description for clarity, these terms are intended to refer only to the particular structures 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 should be understood that like numeric designations refer to components of similar function.

[0028] The singular forms "a," "an," and "the" include plural referents unless the content clearly dictates otherwise.

[0029] As used herein, various devices and components may be described as "comprising" other components. As used herein, the terms "comprise," "include," "having," "has," "can," "contain," and variations thereof, are intended to be open-ended transitional phrases, terms, or words that do not exclude the possibility of additional components.

[0030] The term "virus inactivation" or "viral inactivation" refers to the treatment of a sample containing one or more viruses in such a way that the one or more viruses can no longer replicate or are inactive. In the methods described herein, the terms "virus" and "viral" may be used interchangeably. Viral inactivation may be achieved by physical means, such as heat, ultraviolet light, ultrasonic vibration, or by chemical means, such as using a pH change or the addition of chemicals (e.g., detergents). Viral inactivation is typically a process step used during most mammalian protein purification processes, especially when purifying therapeutic proteins from mammalian-derived expression systems. In the methods described herein, viral inactivation is performed within the fluid flow path. It is understood that the inability to detect one or more viruses in a sample with standard assays known in the art and the assays described herein indicates complete inactivation of one or more viruses following treatment of the sample with one or more viral inactivating agents. As used herein, a virus inactivating agent may include a change in solution conditions (e.g., pH, conductivity, temperature, etc.) or the addition of a detergent, salt, acid (e.g., acetic acid with a molar concentration to achieve a pH of 3.6 or 3.7), polymer, solvent, small molecule, drug molecule, or any other suitable entity, etc., or any combination thereof, that interacts with one or more viruses in the sample, or physical means (e.g., exposure to UV light, vibration, etc.) such that exposure to the virus inactivating agent renders one or more viruses inactive or non-replicative. In certain embodiments, the virus inactivating agent is a pH change, and the virus inactivating agent is mixed with a sample containing the target molecule (e.g., eluate from a Protein A binding and elution chromatography step), for example in a static mixer, and then directed to the flow path.

[0031] As used herein, the term "continuous process" includes a process for purifying a target molecule that includes two or more process steps (or unit operations) that can be performed simultaneously for at least a portion of their duration, such that the output from one process step flows directly into the next process step in the process without interruption. In other words, for a continuous process, a process step does not need to be completed before the next process step is initiated, as long as a portion of the sample is constantly moving through the process steps.

[0032] Similarly, a "semi-continuous process" may encompass operation of one or more unit operations carried out in a continuous mode for a set period of time with periodic interruptions, such as stopping the loading of feed to allow for completion of other rate-limiting steps during continuous capture operations.

[0033] 1-4, a culture chamber 10 according to certain embodiments can be seen. In the illustrated embodiment, the culture chamber 10 has a cover 12 and a base 14. The cover 12 and base 14 may be configured to mate in a sealing relationship to enclose an interior 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 may be provided within the culture chamber to accommodate the inlet end 18a and the outlet end 18b of the spiral coil 20. In the illustrated embodiment, the openings (as well as the inlet end 18a and the outlet end 18b of the spiral coil 20) are located on the same side of the culture chamber 10, however, one skilled in the art will appreciate that the placement of the spiral coil 20 within the culture chamber 10 can be modified such that the inlet end 18a and the outlet end 18b are located on different sides of the culture chamber 10. One suitable inner diameter of the spiral tube 20 in this embodiment is 9.6 mm and the tube length is 28.08 m.

[0034] In certain embodiments, the top or uppermost surface 12a of the cover 12 may have a contour configured to engage with a corresponding contour of a bottom surface or face (not shown) of a base 14' of another culture chamber 10' such that multiple culture chambers 10 can be easily stacked and connected together. 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) that extends downwardly or axially from the base 14' such that the flange seats within a recess to allow the two culture chambers 10 to mate or connect in a stacked relationship. In some embodiments, the respective configurations of the top and bottom surfaces are such that they can be easily detached from one another after connection.

[0035] Returning now to FIG. 4, one embodiment of a helical coil 20 suitable for use within the culture chamber 10 is shown. Preferably, the helical coil 20 is made of a material that can be gamma sterilized. For example, circular plastic tubing, such as silicone tubing, is suitable for the helical coil 20. In the illustrated embodiment, the helical coil 20 is arranged to allow for optimal fluid flow paths within the culture chamber 10. To this end, the helical coil has a first region 20a arranged in the "y" direction, a second region 20b arranged in the "x" direction that is orthogonal or nearly orthogonal to the first region 20a, a third region 20c arranged in the "x" direction that is orthogonal or nearly orthogonal to the second region 20b (and thus parallel or nearly parallel to the first region 20a), and a fourth region 20d that is orthogonal or nearly orthogonal to the third region 20c (and thus parallel or nearly parallel to the second region 20b). Certain regions include coil transitions that change direction as they transition from one coil region to the next. Thus, the first region 20a has a coil transition portion 20a' transitioning from the first region 20a to the second region 20b, the second region 20b has a coil transition portion 20b' transitioning from the second region 20b to the third region 20c, and the third region 20c has a coil transition portion 20c' transitioning from the third region 20c to the fourth region 20d. The helical coil 20 includes an inlet end 18a, an outlet end 18b, and a continuous fluid flow path therebetween. Thus, each of the regions 20a, 20b, 20c, and 20d are in fluid communication and define a continuous fluid flow path. A coil configured in this manner can be neatly positioned within the interior cavity of the culture chamber 10, as shown in FIG. 3.

[0036] The number of turns in the helical coil 20 and the diameter of the helical coil 20 can each vary and are determined at least in part by the desired residence time of the sample within the flow path defined by the helical coil 20. Suitable design parameters include about 15-21 turns, an inner tube diameter of about 3.2-9.6 mm (1 / 8''-3 / 8''), and a core diameter of 40-105 mm. Preferably, there is a minimum of 5 turns. In certain embodiments, the residence time should be sufficient to allow for viral inactivation at a pH effective to inactivate the virus (e.g., a maximum pH of 3.6 for at least about 30 minutes. One of skill in the art will appreciate that exposing a product sample to a pH low enough to inactivate the virus for too long may degrade the product, and thus the embodiments disclosed herein allow for easy adjustment of residence time and flow through the coils in one or more culture chambers 10 to optimize viral inactivation. Typically, flow is laminar in the helical coils (e.g., Reynolds number <2000), but turbulent conditions do not have a detrimental effect on culture chamber efficiency (in other parts of the system, flow may be turbulent). pH can be verified, for example, using sampling and offline sensors.

[0037] 1A shows an embodiment of the culture chamber 10 in which the area defining the interior cavity is not completely occupied by the helical coil 20. In the illustrated embodiment, the helical coil 20 is positioned in the lower right quadrant of the interior cavity, closest to openings 17a and 17b, to optimize the linear length of the helical tube 20. In this embodiment, the appropriate tube ID is 4.8 mm and the appropriate tube length is 11.99 m.

[0038] 1B shows another embodiment of the culture chamber 10 in which the areas defining the interior cavity are also not completely occupied by the helical coil 20. In the illustrated embodiment, the helical coil 20 is positioned in the lower right and upper left quadrants of the interior cavity, with the upper right region closest to the openings 17a and 17b to optimize the linear length of the helical tube 20. In this embodiment, the appropriate tube ID is 4.8 mm and the appropriate tube length is 23.99 m.

[0039] 1C shows yet another embodiment of the culture chamber 10 in which the area defining the internal cavity is not completely occupied by the helical coil 20. This embodiment is similar to the embodiment of FIG. 1A, except that the culture chamber 10 itself has a larger footprint (e.g., 130 mm height versus 65 mm height for the culture chamber in FIG. 1A), and thus the inner diameter of the helical tube 20 is larger. In the illustrated embodiment, the helical coil 20 is positioned in the lower right quadrant of the internal cavity, closest to the openings 17a and 17b, to optimize the linear length of the helical tube 20. In this embodiment, the appropriate tube ID is 6.4 mm and the appropriate tube length is 20.49 m.

[0040] FIG. 1D shows yet another embodiment of the culture chamber 10 in which the area defining the interior cavity is not completely occupied by the helical coil 20. This embodiment is similar to the embodiment of FIG. 1B, except that the culture chamber 10 itself has a larger footprint, and therefore the inner diameter of the helical tube 20 is larger. In the illustrated embodiment, the helical coil 20 is positioned in the upper left and lower right quadrants of the interior cavity, closest to the openings 17a and 17b, to optimize the linear length of the helical tube 20. In this embodiment, the appropriate tube ID is 6.4 mm and the appropriate tube length is 40.98 m.

[0041] In certain embodiments, multiple culture chambers may be arranged in series, such as with the outlet of a first culture chamber feeding into the inlet of a second culture chamber. Thus, modular assemblies can be constructed (e.g., Figs. 8A and 8B), providing the user with the flexibility to increase residence time and / or flow rate by adding one or more culture chambers to the assembly, or to decrease 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 sterile connections (e.g., ASEPTIQUIK® connectors) that ensure a completely closed system. The assembly of modular culture chambers may be supported on a cart 50 or the like that may be movable from location to location (Figs. 8A and 8B). The cart 50 may provide side access for ease of setup.

[0042] As best seen in Figure 9, a modular assembly of fluidly connected culture chambers can include culture chambers of different sizes. For example, in the illustrated embodiment, there are 24 culture chambers having the helical coil 20 configuration of Figure 1C and 12 culture chambers having the helical coil 20 configuration of Figure 1D.

[0043] Alternatively, or in addition, a culture chamber 10 having a helical coil with a larger inner diameter can be used to achieve higher flow rates and / or longer residence times. Similarly, a culture chamber having a helical coil with a smaller inner diameter can be used to achieve lower flow rates and / or shorter residence times.

[0044] In some embodiments, modular assemblies may be formed in which all of the helical coil lengths and / or diameters (inner diameters) within the culture chambers of the modular assembly are the same. In some embodiments, modular assemblies may be formed in which all of the helical coil lengths and / or diameters within one or more culture chambers of the assembly are different from the helical lengths and / or coil diameters within one or more other culture chambers of the assembly. In some embodiments, a modular assembly may be formed of a plurality of fluidly connected or connectable culture chambers in which at least one culture chamber of the plurality has a helical tube length that is twice the helical tube length of another culture chamber of the plurality.

[0045] Thus, flexibility in residence time and flow rate is achieved without having to modify the exterior dimensions of the culture chamber 10.

[0046] The flow rate and tube length may be selected to target a particular residence time. In virus inactivation applications, the residence time may be selected as a time sufficient to achieve virus inactivation in the flow path, preferably with some safety factor. For example, in an embodiment where a residence time of 30 minutes is sufficient for virus inactivation, the design parameters may be selected so that the majority of particles pass through the chamber in about 36 minutes, with the fastest residence time in the chamber being about 32 minutes and the slowest being about 45 minutes. The minimum residence time may also depend on regulatory guidance regarding acceptable safety factors for virus inactivation.

[0047] Suitable nominal residence 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.

[0048] 5, in some embodiments, the interior cavity of the culture chamber 10' is sufficiently deep, e.g., has a sufficient volume to accommodate two or more vertical layers of helical coils 20. In some embodiments, such a culture chamber 10' can be used in conjunction with culture chamber 10, as shown in FIG.

[0049] In some embodiments, to reduce the height of the culture chamber 10, the helical coil 20 may be formed in a diagonal configuration as shown in FIG. 6. A suitable skew angle ranges from about 30° to about 60°. This increases the overall width of the culture chamber, but allows the helical coil to occupy as much of the interior space within the culture chamber as possible, thereby minimizing the footprint of the culture chamber 10′ or chamber. One suitable arrangement of a diagonal helical coil is shown in FIG. 7.

[0050] In a further embodiment, the culture chamber 10 may be in the form of a cylinder, with a helical coil flow path wrapped around a cylindrical core. Such cylinders may be stackable, as shown in Figure 10, or may be arranged in series, similar to the cassette-like embodiment of Figure 1.

Claims

1. A chamber for inactivating one or more viruses in a sample containing a target molecule, comprising: With the base, a cover configured to mate with the base in a sealing relationship; an inlet port for receiving a fluid; an outlet port for dispensing a fluid; an interior cavity collectively defined by said base and said cover; a chamber housing comprising: a helical coil disposed within the internal cavity and in fluid communication with an inlet port and an outlet port; Equipped with A chamber, wherein the cover of the chamber has a top outer surface having a first contour and a peripheral edge having a lower height than the top outer surface to form a recess, and the base of the chamber has a bottom outer surface having a second contour and a peripheral flange extending downwardly or axially from the base, the top outer surface being releasably matable with a chamber having a bottom outer surface having the second contour and the bottom outer surface being releasably matable with a chamber having a top outer surface having the first contour, the peripheral flange seated in the recess to allow two chambers to mate or interlock in a stacked relationship.

2. The chamber of claim 1 , wherein the helical coil is tapered.

3. 2. The chamber of claim 1, wherein the helical 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 generally perpendicular to the first direction.

4. A modular assembly for inactivating one or more viruses in a sample containing a target molecule, comprising first and second chambers configured in fluid communication with each other, the first chamber comprising a first chamber housing: A first base; a first cover configured to mate in sealing relation with the first base; a first inlet port for receiving a fluid; a first outlet port for dispensing a fluid; a first interior cavity collectively defined by the first base and the first cover; a first helical coil disposed within the first internal cavity in fluid communication with a first inlet port and a first outlet port; Equipped with The second chamber comprising a second chamber housing, A second base; a second cover configured to mate in sealing relation with the second base; a second inlet port for receiving a fluid; and a second outlet port for dispensing a fluid; and a second interior cavity collectively defined by the second base and the second cover; a second helical coil disposed within the second internal cavity in fluid communication with a second inlet port and a second outlet port; Equipped with a first cover of the first chamber having a top outer surface with a first contour and a first peripheral edge having a height less than the top outer surface to form a recess, and a second base of the second chamber having a bottom outer surface with a second contour and a second peripheral flange extending downwardly or axially from the second base, the top outer surface being releasably interconnectable with the bottom outer surface, and the second peripheral flange being seated in the recess to enable the first and second chambers to mate or interlock in a stacked relationship, a modular assembly.

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 chambers are interconnected.

6. 1. A method for inactivating one or more viruses in a sample containing a target molecule, the method comprising: flowing the sample through a helical coil disposed within an internal cavity of a chamber while continuously exposing the sample to inactivation conditions during a process of purifying the target molecule, the chamber having a cover and a base, the cover having a top outer surface having a first contour and a peripheral edge having a height less than the top outer surface to form a recess, the base having a bottom outer surface having a second contour and a peripheral flange extending downwardly or axially from the base, the cover and the base collectively defining the internal cavity, the top outer surface releasably matable with a chamber having a base having a bottom outer surface with the second contour, the bottom outer surface releasably matable with a chamber having a cover having a top surface with the first contour, the peripheral flange seated in the recess to allow two chambers to mate or be joined in a stacked relationship.

7. 7. The method of claim 6, further comprising the steps of subjecting the sample to a Protein A affinity chromatography process, thereby obtaining an eluate; introducing a virus inactivating agent into the eluate; and continuously transferring the eluate to the helical coil and allowing the eluate to flow through the helical coil for a time sufficient to inactivate the viruses.

8. 7. The method of claim 6, further comprising the steps of subjecting the sample to an ion exchange chromatography process, thereby obtaining an eluate; introducing a virus inactivating agent into the eluate; and continuously transferring the eluate to the helical coil and allowing the eluate to flow through the helical coil for a time sufficient to inactivate the viruses.

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