Reaction apparatus system

Abstract

The present disclosure relates to a reactor vessel system for providing headspace-based condensation, coarsening, and other features. In some embodiments, the present disclosure provides a system for reducing the relative humidity (RH) of exhaust gases prior to or simultaneously with their exit from the system through an exhaust filter.

Description

Description of Related Applications

[0001] This application claims priority to U.S. Provisional Patent Application No. 62 / 799,794, filed on February 1, 2019, which is hereby incorporated by reference in its entirety.

Technical Field

[0002] The present disclosure relates to reaction vessel systems (e.g., reactor systems) for providing headspace-based condensation, coalescing devices, and other features.

Background Art

[0003] The present disclosure relates to devices and methods for the manufacture of chemical and / or biological formulations such as biopharmaceuticals using reaction vessels such as, for example, multi-use (“MU”) and / or disposable container (“DC”, e.g., single-use (“SU”)) systems (“reaction vessel systems”). For example, fermenters or bioreactors typically provide reaction vessels for culturing microorganisms or mammalian, insect, or plant cells to produce such formulations.

Summary of the Invention

Problems to be Solved by the Invention

[0004] Common problems encountered by reaction vessels using such systems include excessive moisture in the exhaust therefrom; excessive stress imposed on the upper portion of disposable containers (“DC”; e.g., continuous film portions and / or seams and / or joints; headspace portions); the need for a separate condensation unit external to the reactor in which a separate DC is housed (e.g., GE's Xcellerex and ThermoFisher's DHX systems) that requires additional tubing and pumps (e.g., exhaust tubing); and / or maintaining the temperature of the reaction mixture within the reactor and / or DC during processing.

Means for Solving the Problems

[0005] The present disclosure provides improved systems and components that solve such problems. The systems described herein, for example, condense fluid from the gas in the headspace (providing a "headspace condenser" or "HC") by making the temperature inside lower than that of the portion of the vessel in which the reaction takes place (thereby reducing the load imposed on the exhaust filter); provide a jacketed sealed holder to remove heat across two zones of the DC and provide additional physical support (e.g., a solid surface that transfers heat so that the temperature in the headspace is reduced) at the top of the DC (e.g., the holder dome), thereby relieving the pressure thereon and / or giving it higher operating pressure performance; directly associate the vessel (e.g., fermenter) with the coarsening unit so that an external condensation unit for the reactor is not required; introduce and / or return the condensing fluid into the reaction mixture (e.g., passively by gravity) to provide both increased efficiency and additional temperature control; use cyclone / mixing / contact forces to cause agglomeration of the condensed vapor particles for additional or alternative removal of the condensing fluid; and / or preferably use an exhaust pump to reduce the pressure to the DC film by drawing the exhaust from the headspace downstream of the sterile barrier; thereby solving such problems. This application also addresses problems related to the use of heat rejection filters and exhaust gases containing moisture. In some embodiments, the exhaust gas is heated by the heat rejection filter as it enters or prior to entering so as to exhibit a lower relative humidity (RH). Other problems and solutions to the same or other problems will be described, described in, and / or derivable from the present disclosure as described below. BRIEF DESCRIPTION OF THE DRAWINGS

[0006]

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Mode for Carrying Out the Invention

[0007] In some embodiments, the present disclosure provides a reaction system comprising, in some embodiments, at least one exhaust line through which exhaust gas exiting from a disposable reaction vessel (DC) passes, the disposable reaction vessel (DC) being in communication with the reaction system; at least one filter through which the exhaust gas passes and exits the system; at least one source of externally heated air; at least one fluid path connecting the at least one source of externally heated air to the at least one exhaust line; and optionally, at least one bacterial filter between the at least one source of externally heated air and the at least one exhaust line, and at least one second fluid path connecting the heated air exiting the bacterial filter to the at least one exhaust line. In some embodiments, the externally heated air has a temperature sufficiently higher than the temperature of the exhaust gas such that when the externally heated air and the exhaust gas are mixed to produce a mixed exhaust gas, the relative humidity of the mixed exhaust gas is lower than that of the exhaust gas. In some embodiments, the relative humidity of the mixed exhaust gas is sufficiently low such that moisture from the mixed exhaust gas does not accumulate on the filter when the mixed exhaust gas exits the system. The present disclosure also provides a method of reducing the relative humidity of exhaust gas within such a reaction system, the method comprising passing the exhaust gas through such a system. Other embodiments will be apparent from the disclosure provided herein.

[0008] The present disclosure relates to multi-use (“MU”) and / or disposable containers (“DC”, e.g., reaction vessel systems such as single-use (“SU”) systems, and methods of using the same, which solve some of the problems recognized in some of the relevant art, some of which are described above. In some embodiments, the system may comprise a reaction tank, a disposable container (e.g., a single-use disposable container (“SUDC”) typically made of a flexible material such as plastic), one or more filters, and / or one or more exhaust devices. These systems may also comprise a jacketed platen, one or more coarsening units in contact with the jacketed platen, one or more additional condensation units, and / or one or more exhaust systems. In some embodiments, the present disclosure provides systems and methods for reducing the relative humidity of an exhaust gas stream generated during a reaction in a disposable reaction vessel before the exhaust gas stream enters a filter that communicates with the external environment of the reaction system.

[0009] In some embodiments, the system includes a single-use disposable container (DC) that forms (e.g., encloses) a headspace ("HS") within the DC that is maintained at a temperature lower than the portion of the DC where the reaction takes place (e.g., the fluid reactant), and / or a condenser directly associated with / contacting the film that forms the headspace, and / or a coarsening device that improves the collection (e.g., gathering) and drainage of liquid from the headspace. In some embodiments, the DC system includes a DC that includes a first zone containing a reaction mixture maintained at a first temperature and a second zone containing an HS maintained at a second temperature lower than the first temperature, the HS having an upper inner surface (adjacent to or opposite the outer surface) and at least one side wall; and may include a coalescer that condenses within the upper inner surface and / or at least one side wall of the HS and collects the fluid exiting therefrom. In some embodiments, the heat exchange device contacts and / or is provided within the HS. In some preferred embodiments, the temperature difference may be about 5 to 10 °C (i.e., the first temperature may be 5 to 10 °C warmer than the second temperature, or conversely, the second temperature may be 5 to 10 °C lower than the first temperature). In some embodiments, such a heat exchange device contacts the side wall and / or the upper inner surface and / or the outer surface of the HS. In most preferred embodiments, the DC is surrounded by a reaction vessel that typically provides support to the DC and other components of the system.

[0010] In certain embodiments in which the systems described herein operate, one or more drying gases (e.g., air, N2, O2, CO2) are introduced into a reaction mixture contained within a DC (first zone) from the bottom (e.g., through a port located at or near the bottom surface or lower surface of the DC), pass through (e.g., toward) the liquid reaction mixture, and move into a second zone (HS). Along this path, the originally dry gas becomes a wet (or humidified or moist) gas (e.g., vapor and / or mist). In some embodiments, the wet gas emerging from the reaction mixture enters the second zone (HS), passes through it, and then passes through a coalescer and then, typically and optionally, a sterilizing filter. In some embodiments, some of the fluid contained in the wet gas is condensed within the second zone HS due to the temperature difference between the first zone containing the reaction mixture and the second zone (HS), and the remaining wet gas passes through and out of the HS and continues to move into the coalescer. Next, the condensate collected within the cooled HS moves passively (e.g., by gravity) so as to return to the reaction mixture (since it is located below the HS within the DC), thereby reducing and / or maintaining the temperature of the reaction mixture at a desired temperature and / or temperature range. The coalescer serves to agglomerate or collect any additional moisture (e.g., within any remaining wet gas) that has exited the HS (or passed across it). This agglomeration may be enhanced, for example, by a further temperature difference between the HS and the coalescer (e.g., a lower temperature than the HS, such as a room temperature environment (e.g., 25°C)), and / or other processes (e.g., cyclone / mixing / contact forces that cause agglomeration of condensed vapor particles). The coalescer may also, if desired, be associated with (e.g., in direct contact with) a heat exchange device, which may be the same as or different from the device that cools the second zone (HS) (i.e., a heat exchange device), and may be further cooled (i.e., actively cooled) to a lower and / or specific temperature, and in some embodiments may be or include a jacketed platen.This system may further include a condensation unit, which may have a temperature even lower than either and / or both of the HS and / or the core lessor.

[0011] For example, in some embodiments, a first region of the reaction vessel (i.e., the portion thereof containing the liquid reaction mixture) may be maintained at an average temperature (i.e., the first temperature) of 35-40 °C, such as 37 °C, while a second region (i.e., the HS) may be maintained at 30-34 °C (i.e., the second temperature) (e.g., 30 °C, 32 °C, 34 °C), and the core lessor may be maintained at a different temperature (e.g., an average temperature of 25 °C, or room temperature; the third temperature is 5-10 °C lower than the second temperature of the second region, and thus 10-15 °C lower than the first temperature of the first region). The temperature of the core lessor may also be affected by the jacketed platen, at least a portion of which is typically placed thereon (see, e.g., FIG. 1B). The optional additional condensation unit described below may provide a lower average temperature to further assist in the condensation of the fluid from the wet gas. "Average temperature" refers to, for example, the average of the temperatures measured in three different regions of the section of interest. Because, as will be understood by those skilled in the art, the temperatures of such different regions will vary during the course of the reaction but will together provide the average temperature. Next, the fluid collected in the lessor passively moves (e.g., by gravity) back into the second region (HS) and / or into the first region (containing the reaction mixture) (this is also passive by gravity), thereby reducing and / or maintaining the temperature of the reaction mixture at the desired temperature and / or temperature range. Next, any residual gas (i.e., the still wet gas) may exit the second region (HS) and / or the core lessor, pass through a filter (e.g., a sterilizing filter), and out of the system through the exhaust port. As described below, in some embodiments, the movement of the gas through the headspace, into the core lessor, and out of the system may be assisted by an exhaust pump, which may include one or more fans in some embodiments.

[0012] In some embodiments, the systems described herein include a reaction vessel. The reaction may occur within the reaction vessel itself or within a container (e.g., a DC) housed within the reaction vessel. The reactions conducted within the systems described herein typically occur within the DC. The reaction vessel may take the form of a reaction chamber, a fermenter, a bioreactor, etc. This reaction vessel is suitable for chemical reactions, microbial fermentations, culturing of cells (e.g., mammalian, insect or plant-based), or other applications. The reaction vessel is typically associated with a heat transfer system that includes a heat transfer device for controlling the temperature of the chemical, pharmaceutical, or biological process occurring within the internal reaction chamber of the vessel. In some embodiments, the heat transfer system provides for the distribution of a heat transfer medium such that heat generated by or required for the process is transferred from or to the reaction mixture. In some embodiments, the reaction vessel includes a jacket and / or a jacketed headplate (e.g., a dimple jacket) that provides a fluid passage through which a heat transfer fluid is circulated. In some embodiments, the reaction vessel may be at least partially surrounded by a fluid passage. The jacketed headplate may also function as a lid for the reaction vessel. The jacketed headplate may also serve to support and / or relieve pressure to the DC (e.g., the top of the DC) housed within the reaction vessel.

[0013] In some embodiments, instead of or in addition to the jacketed platen, a flexible material cover and / or multiple straps (which may consist of such flexible material) may be used to support and / or relieve pressure on a DC (e.g., the upper part of the DC) housed within the reaction vessel. In some embodiments, such flexible material covers and / or straps may be placed on the DC at one or more locations thereon that would not be able to withstand the pressure, as well as at one or more other locations on the DC (e.g., seams in the material forming the DC). The straps may be arranged, for example, in a pattern that traverses the outer surface of the upper part of the DC and that supports and / or reinforces that surface (e.g., passes over the surface one or more times in a back-and-forth manner; a cross pattern). Such straps may be composed of any suitable material, such as, but not limited to, fabric, rubber, plastic, metal, and / or combinations thereof, and may be flexible or inflexible. The flexible material cover and / or straps are typically attached to the reaction vessel at one or more locations thereon (e.g., its inner and / or outer surfaces) using one or more connectors and / or brackets (e.g., tie connectors, pipe grip ties). In some embodiments, each of the one or more straps has at least two ends, and each end is attached (e.g., reversibly attached) to the reaction vessel through a connector and / or bracket across the upper diameter of the reaction vessel such that the strap extends across one or more upper diameters of the DC. In some embodiments, the strap may take the form of a net. In some embodiments, the strap forms a flat strap cargo net that would cover only a portion or all of the upper surface of the DC, or areas of the upper surface that experience increased pressure (e.g., where forces / pressures would concentrate) or exhibit weakness (e.g., seams) compared to other areas not exposed to such pressure and / or exhibit such relative weakness.In some embodiments, the flexible material may be a lightweight nylon fabric (e.g., a "parachute-style" fabric) that is more conformable to the shape of the DC and less elastic than other materials, thereby ensuring proper snug and adequate support. In this way, the DC will be able to withstand greater forces (e.g., increased pressure) resulting from certain reactions occurring in the first region of the DC. A reaction may produce a volume of gas that creates a pressure beyond the capacity of the DC, causing deformation of the DC (e.g., seam breakage); a platen (e.g., a jacketed platen, one or more straps) provides support to the DC, thereby increasing the pressure performance of the system. In some embodiments, it is preferable to use a jacketed platen, a flexible cover, and / or straps to maintain a pressure on the upper surface of the DC greater than 0.1 - 0.2 pounds per square inch (PSI) (about 700 - 1400 Pa). In some embodiments, the flexible support and / or straps can facilitate the installation process in that they can be easily removable / retractable when the DC is installed and / or can be attached over the DC to support the load during the operating phase and operation of the pressure test. In some embodiments, the flexible material and / or straps may include a heat transfer function, such as by including heat transfer fluid passages within the material. In some embodiments, the support may be incorporated into the DC material, such as between multiple layers of the DC material. For example, one or more materials having greater pressure resistance than the DC material (e.g., a membrane) can be inserted or interlaced between two layers of material that together form the upper part of the DC. In some embodiments, including such a flexible material cover and / or multiple straps on or within its upper surface provides sufficient support such that fluid transport to another tank or container can be performed without using the equipment (e.g., a peristaltic pump) conventionally used for the DC. In such embodiments, gas may be introduced into the headspace, thereby increasing the pressure therein and facilitating fluid transport. The pressure difference between multiple tanks controls the rate of liquid transport.Assuming that the receiving tank is at atmospheric pressure and the liquid level in the supply tank is above that of the receiving tank, the higher the pressure in the supply tank (e.g., DC), the faster the transport rate. As long as the pressure is higher than atmospheric pressure, there is no lower limit to the pressure, and the upper limit is determined by the design of the tank and how the DC is supported. In some embodiments, and thus, the fluid in the DC (e.g., "below" the headspace in the DC) can thereby be "pushed out" from the open port into another container (e.g., the fluid will be moved from the DC (e.g., bioreactor) into the harvest tank). Thus, in some embodiments, the systems described herein include a disposable reaction vessel having an upper surface adjacent to a second region including a headspace, and a flexible cover and / or strap adjacent to and / or incorporated into the upper surface thereof. In some embodiments, the flexible cover and / or strap includes at least one heat transfer fluid passage. In some preferred embodiments, the flexible cover and / or strap maintains a pressure on the upper surface of the DC greater than about 0.1 - 0.2 pounds per square inch (PSI) (about 700 - 1400 Pa). Thus, the jacketed platen, flexible material cover, and / or strap provide additional performance, safety, and cost advantages to the system in addition to the heat transfer function.

[0014] The reaction vessels described herein are exemplary but not necessarily composed of metal, typically but not necessarily corrosion-resistant alloys. For example, suitable materials would include, without limitation, sheet / plate stock (and / or, for example, dimple jacket material for a heat transfer system). Suitable exemplary materials include, among others, for example, carbon steel, stainless steel (e.g., 304, 304L, 316, 316L, 317, 317L, AL6XN), aluminum, Inconel® (e.g., "Inconel" 625, Chronin 625, Altemp 625, Haynes 625, Nickelvac 625 and Nicrofer 6020), Incoloy®, Hastelloy (e.g., A, B, B2, B3, B142T, Hybrid-BC1, C, C4, C22, C22HS, C2000, C263, C276, D, G, G2, G30, G50, H9M, N, R235, S, W, X), and Monel®, titanium, Carpenter 20®. However, it will be understood that other materials, without limitation, such as plastics, rubbers, and mixtures of such materials, may also be suitable in addition to or instead of corrosion-resistant alloys. The "mixture" of materials may refer to either the actual mixture itself for forming a composite or the use of various materials within the system (e.g., alloy reactor outer shell structure and rubber baffle members).

[0015] The DC is typically made of a flexible material that is rigid and water-impermeable so that reactions can occur therein without the DC losing its integrity, and the DC can be discarded (e.g., removed from the reaction vessel) after use. The DC is physically supported by the reaction vessel and / or associated components and typically includes and / or is attached to components that can attach the DC to the reaction vessel. The DC is also sealable so that, for example, when filled with fluid, it will not be damaged by the hydrodynamic forces applied thereto and so that a sterilization process can occur therein. In some embodiments, the DC may be made of a flexible, water-impermeable material such as low density polyethylene having a thickness in the range of about 0.1 mm to about 5 mm or other suitable thickness. This material may be configured as a single layer or multiple layers (e.g., a single layer or a bilayer). When the DC comprises multiple layers, it may consist of two or more separate layers that are fixed to each other, for example, by an adhesive. Exemplary materials and arrangements that can be used include, but are not limited to, those described in the specifications of U.S. Patent Nos. 4,254,169; 4,284,674; 4,397,916; 4,647,483; 4,917,925; 5,004,647; and / or 6,083,587; and / or U.S. Patent Application Publication No. 2002 / 0131654A1. The disposable reaction vessel may be manufactured to have any desired size (e.g., 10 liters, 30 liters, 100 liters, 250 liters, 500 liters, 750 liters, 1,000 liters, 1,500 liters, 3,000 liters, 5,000 liters, 10,000 liters, or other desired volume).

[0016] Portions of the system (e.g., the HS, optional additional coarsening unit, optional further condensation unit, and / or sterilization filter) may be connected to each other by welding or other similar processes or using flexible materials such as tubing (e.g., of a type standard in the industry). Such connection techniques will be understood by those skilled in the art.

[0017] The reaction vessel system described herein includes a first zone where the reaction takes place (i.e., the first zone contains the reaction mixture), and a zone (a second zone) that provides a headspace (HS) formed within a vessel (e.g., a DC) positioned above and connected to the first zone (with respect to the flow of gas entering and leaving the system). This second zone (HS) provides a temperature lower than the temperature present in the first zone (e.g., the temperature of the reaction mixture). This lower temperature may be provided passively, for example, by the temperature of the air surrounding the DC or HS, but more typically is provided actively, for example, by using a heat exchange device or a heat transfer system. The heat transfer system described herein may be constructed from any material through which a heat transfer fluid (e.g., a gas and / or a liquid) is transported such that heat is transferred to and / or absorbed from another part of the system by radiation, convection, conduction, or direct contact. In some embodiments, the heat transfer system may provide a fluid path such as a passage through which the heat transfer fluid can flow and / or circulate. The heat transfer system may be made from any suitable material, such as, for example, a dimple jacket material.

[0018] The system described herein (e.g., a reaction system) includes a first zone that is at a high temperature (e.g., 37°C) or maintained at that temperature and contains a reaction mixture (e.g., an active fermentation reaction); and a second zone (i.e., HS) that is at a lower temperature than the first zone (e.g., slightly lower, perhaps 34°C, but in some embodiments at least about 5°C lower) or maintained at that temperature and typically contains only humid gas and condensed fluid during use. The reaction vessel has the second zone. The reaction vessel may provide a continuous surface along the wall or may be separated according to the dimensions of the first and second zones. The reaction vessel may be configured to contain only the first zone, while a separate device is configured to contain the second zone (e.g., physically coupled to the second zone) (e.g., a combination of heat transfer tubes and insulation described herein). In some embodiments, the first and / or second zone (HS) is coupled to a heat transfer system (HTS) that may be the same or different between those zones. In some embodiments, the temperature difference between the first and second zones may be maintained without coupling a heat transfer system to the second zone. However, in some embodiments, each of the first and second zones (HS) is coupled to the same and / or different heat transfer systems. In some embodiments, the heat transfer system is a "jacket" (e.g., a dimple jacket material) through which a heat transfer fluid is circulated to transfer heat between the first and / or second zone and the heat transfer system, as is generally understood in the art. In some embodiments, the first and / or second zone is in contact with (e.g., thereby at least partially surrounded by) the one or more heat transfer systems. In some embodiments, the first and / or second zone may be coupled to a plurality of heat transfer systems. For example, in some embodiments, the second zone may be in contact with a plurality of jacketed heat transfer systems, including, for example, the jacketed platen described above.In some embodiments, there may be multiple sets of heat transfer baffles (e.g., one or more types and / or arrangements in a first zone, and another type or multiple types and / or arrangements in a second zone).

[0019] In some embodiments, the heat exchanger may include, for example, a device taught in any of the specifications of U.S. Patent Nos. 2,973,944 (Etter et al.), 3,986,934 (Muller, H.), 4,670,397 (Wegner et al.), 4,985,208 (Sugawara et al.), 4,460,278 (Tetsuyuki et al.), a Platecoil® system, and / or one or more heat transfer baffles such as those described in the specification of U.S. Patent No. 8,658,419B2 (Knight, C.; ABEC, Inc.). In some embodiments, one or more of the heat transfer systems may include, for example, a first subassembly substantially consisting of a first material joined to a second material to form a first distribution passage, as described in the specification of U.S. Patent No. 8,658,419B2; a second subassembly substantially consisting of a first material joined to a second material to form a second distribution passage; optionally, a closure bar joining the first subassembly and the second subassembly to each other; and a buffer passage between the first subassembly and the second subassembly, wherein the closure bar, if present, sets the width of the buffer passage, and the distribution passage and the buffer passage do not communicate unless a leak opening is formed in the distribution passage. In some embodiments, such a heat transfer baffle may include two or more separate regions through which a heat transfer medium can circulate independently of any other region. In some embodiments, such a heat transfer baffle may be joined to the inner surface of the reaction vessel, and each baffle is joined to at least one heat transfer medium inlet header and at least one heat transfer medium outlet header, and the buffer passage of each baffle is vented to the outside of the vessel. In some embodiments, the heat transfer baffle may be fixedly attached to the inner surface of the reaction vessel at an angle to the inner wall or the radial extent of the reaction vessel, and the angle is selected from the group consisting of about 5°, 10°, 15°, 20°, 25°, 30°, 35°, 40°, 45°, 50°, 55°, 60°, 65°, 70°, 75°, 80°, 85°, and 90°.

[0020] As described above, in some embodiments, the one or more heat exchange systems may include a jacket through which a heat transfer fluid circulates. The jacket may, for example, include a passage through which the heat transfer fluid circulates. In some embodiments, the jacket may be a "dimpled" material. Dimpled jackets are typically attached around a reaction vessel such as a fermenter and may be used as part of a heat transfer system. Dimpled jacket materials may be wound around a reaction vessel in a typical manner and used in the devices described herein. In certain embodiments described herein, dimpled jacket materials may be used within a baffle structure in addition to, or instead of, being wound around a reaction vessel. Dimpled jacket materials are commercially available, and any such materials would be suitable for the uses disclosed herein. Typically, dimpled jacket materials have a substantially uniform pattern of dimples (e.g., indentations, impressions) pressed or formed into a base material (e.g., a metal sheet). Dimpled jacket materials may be manufactured, for example, mechanically ("mechanical dimpled jacket") or by inflation (e.g., inflated resistance spot welding (RSW)). To prepare a mechanical dimpled material, a metal sheet with a substantially uniform array of dimples, each typically containing a center hole, is welded to the base metal through its center hole. Inflated RSW dimpled materials (e.g., inflated HTS or H.T.S.) are typically manufactured by resistance spot welding a series of spots on a thin sheet of metal to a thicker substrate (e.g., metal). The edges of the composite are sealed by welding, and the interior is inflated under high pressure until the thin material forms a pattern of dimples. Mechanical dimpled materials, when used as a jacket, typically have a high pressure rating and a low to medium pressure drop, while RSW dimpled materials typically exhibit a medium pressure rating and a high to medium pressure drop. The heat transfer fluid typically flows between sheets of the dimpled material.Other suitable dimple materials will be available to those skilled in the art and will be suitable for the uses as described herein.

[0021] In some embodiments, a heat transfer system (e.g., one or more baffles and / or jackets) may be present across both the first and second zones (e.g., in contact with both the reaction mixture and the HS). In such embodiments, the heat transfer system may provide for cooling of the reaction mixture to a first temperature (e.g., 35 - 40°C such as 37°C) and cooling of the HS to a second temperature lower than that first temperature (e.g., 5°C or more lower). In some embodiments, such a heat transfer system may be associated with only the first zone or only the second zone (i.e., the HS). In embodiments where the heat transfer system is present only in the first zone, that heat transfer system serves to maintain the reaction mixture present therein at the first temperature. In such embodiments, the second zone (HS) may be maintained at a second temperature lower than the first temperature, with or without the use of a heat exchange system. In some embodiments, the second zone (HS) may be maintained at a second temperature lower than the first temperature using a heat exchange system such as a different baffle and / or jacket than that present in the first zone. In some embodiments, a different heat transfer system (e.g., baffles and / or jackets and / or fluid passages / tubes) may circulate the same or different heat transfer fluids, which may be maintained at the same or different temperatures. For example, the heat transfer fluid circulating through the heat transfer system (e.g., baffle and / or jacket) present in the first zone may be maintained at a first heat transfer fluid temperature that is warmer or colder than that circulating through the heat transfer system present in the second zone (HS).

[0022] In some embodiments, the second zone (headspace) is at least partially surrounded by and in direct contact with a heat transfer system such as one or more fluid passages (e.g., a single pipe or multiple pipes) through which a heat transfer fluid is circulated. The one or more fluid passages are also connected to a source of heat transfer fluid by a suitable material (e.g., pipes). In some of such embodiments, the reaction vessel may only provide physical support for the DC and / or fluid passages and not actually house the fluid passages (e.g., the fluid passages are not located within the walls of the reaction vessel). In some embodiments, the fluid passages may consist of a single or multiple passages (e.g., pipes with suitable heat transfer capabilities) wound around the second zone where the spacing between the passages can be varied as required by the user. In some embodiments, the spacing is constant between each successive level of fluid passages (e.g., when the fluid passages run from the bottom to the top and across horizontally of the second zone), and in other embodiments, the spacing is variable between each successive level. In some embodiments, the spacing may be constant in a particular section of the second zone and variable in other sections of the second zone. In some embodiments, one or more fluid passages may be oriented substantially vertically (i.e., extending from the bottom of the second zone (i.e., closest to the top of the first zone) to the top of the second zone). In some embodiments, the fluid passages may be positioned substantially horizontally as well as substantially vertically. Therefore, in some embodiments, in some embodiments, a particular portion of the second zone is not in direct contact with the fluid passages, and in other embodiments, all or substantially all (i.e., 90% or more) of the second zone is in direct contact with one or more fluid passages. In some embodiments, the fluid passages may be in direct contact with the second zone (headspace) on one side and with insulation on the other side (i.e., the side of the fluid passage farthest from the DC surface). In some of such embodiments, the reaction vessel may enclose the first zone but not the second zone.In some embodiments, one or more fluid passages may be tubular in shape and may be made of a suitable heat-conducting material such as, but not limited to, copper. In some of such embodiments, the coreless is also in direct contact with one or more fluid passages and / or is positioned over an insulating material that covers the fluid passage(s) above the second region but through which heat transfer to the coreless will still be achieved (see, e.g., coreless 1 in FIG. 5). As will be understood by those skilled in the art, other configurations may also be suitable.

[0023] Exemplary heat transfer fluids include, but are not limited to, one or more gases and / or liquids. Suitable exemplary fluids and gases include, but are not limited to, vapor (from top to bottom), warm water and cold water, glycol, heat transfer oil, refrigerant, or other fluids that can be pumped with a desired operating temperature range. For example, it is also possible to utilize multiple types of heat transfer media such that one type of medium is directed to one area of the reaction vessel and another type of medium is directed to a different area of the reaction vessel (e.g., the zone system described above). A mixture of heat transfer fluids (e.g., 30% glycol) may also be desirable.

[0024] As described above, the systems described herein include one or more coalescers for collecting fluid that condenses within the headspace (HS) (i.e., the second zone) and exits therefrom (e.g., moves or migrates). The function of the one or more coalescers is typically primarily to direct (or coarsen) smaller fluid droplets into larger fluid droplets. The gas entering the first zone (e.g., through a sparger) is typically a dry gas that becomes a wet gas (or a vapor, which those skilled in the art would understand to be the gaseous state of a substance co-existing with its liquid) as it moves through the reaction mixture in the first zone. Thus, the gas exiting the first zone and entering the second zone (HS) is a fully saturated humidified gas (i.e., this humidified gas, or vapor, has a relative humidity of 100% ("fully saturated"); "relative humidity" is defined as the relationship between the amount of water vapor present in a gas mixture, measured as milligrams of water vapor per liter of air (mg / L ("water vapor content")), and the "absolute humidity" as defined herein, and the actual mass or pressure (content) of water in air at a particular temperature and the maximum mass or pressure (capacity) of water that air can hold at that particular temperature). In this fully saturated state, upon cooling, the humidified gas transitions (i.e., condenses) to the liquid state. Therefore, due to the cooler temperature provided by the second zone (HS), the humidified gas condenses into its liquid form. In at least some cases, and most often, and thus, most of the remaining humidified gas (i.e., 50, 60, 70, or 80% or more), substantially all (i.e., 90% or more), or all passes through the coalescer. Since the coalescer is at least partially (e.g., in contact) on a jacketed platen that transfers heat to the second zone (HS), the temperature within the coalescer is typically higher than the temperature within the second zone (HS), but still typically cooler than the temperature provided by the first zone (i.e., its temperature will be between those of the first and second zones). Therefore, some degree of condensation will occur within the coalescer.However, the main benefit of the coreless is to provide an increased residence time of the humidified gas as it moves out of the disposable reaction vessel into the environment (e.g., through the exhaust port), and to collect any additional fluid formed from the humidified gas as it moves through and out of the second zone (HS). Thus, the gas that exits the coreless and enters the filter remains as humidified gas. Put another way, the humidified gas is not dehumidified either in the second zone (HS) or in the coreless; any fluid collected simply represents a change in state from humidified gas to liquid. Considering that some of the humidified gas that exits the first zone, enters the second zone, and is condensed therein (and thus some of it enters the coreless) is collected as fluid, a smaller volume of gas (i.e., humidified gas) is processed through the filter. The increased residence time provided by the coreless allows much of the gas that has transitioned to liquid form to be collected therein before encountering the filter. Additionally, note that the filter is typically heated, whereby the gas is dehumidified. Thus, the gas that exits the filter and is discharged into the environment is dehumidified gas.

[0025] Therefore, in some embodiments, moisture (i.e., water, water vapor, or water droplets) is removed from the gas (i.e., exhaust gas) released from the reaction mixture (this gas is typically about 37 °C when exiting the DC) by cooling it, thereby condensing and coalescing the moist air (e.g., reducing the humidity of the exhaust gas or dehumidifying it). In some embodiments, the exhaust gas can be passed through one or more heated exhaust filters to ensure that the exhaust gas has a lower water content when it passes through the exhaust filter, or preferably, can be heated before entering the exhaust filter (which may or may not be heated (e.g., preheated)), thereby accumulating less or not at all on it (or, for example, on the filter material, within it) than on unheated (i.e., higher humidity) exhaust gas. However, in some embodiments, the effectiveness of heating the filter to assist in dehumidifying the exhaust gas can be limited due to the indirect contact between the heat and the exhaust gas, the limited surface area of the filter that can be heated, and the limitation on the temperature to which the filter can be heated. In such situations, the heat that can be transferred to the exhaust filter to raise the temperature of the exhaust gas (e.g., a heated exhaust filter and / or heat introduced when the exhaust gas enters the exhaust filter (heated or unheated exhaust filter)) is insufficient to keep the relative humidity of the exhaust gas ( "RH", the ratio of the partial pressure of water vapor to the equilibrium vapor pressure of water at a given temperature) sufficiently away from the dew point (i.e., below which water droplets begin to condense and dew can form, varying with pressure and humidity of the ambient temperature), such that moisture can accumulate on the filter such that the functionality as a filter becomes inefficient (or even non-functional).As a solution to such problems, in some embodiments, the present disclosure ensures that little or no moisture accumulates on a filter (e.g., an exhaust filter material or membrane) (or at least less moisture than in the unheated exhaust gas), by having "heated outside air" come into direct contact with the exhaust gas (i.e., enter its flow and / or mix with it), and heating the exhaust gas to a temperature well above its dew point (i.e., reducing the RH of the exhaust gas) before it enters the exhaust filter (e.g., contacts the exhaust filter material or membrane). The heated outside air introduced into the exhaust gas (e.g., exhaust gas stream) is at a higher temperature than the exhaust gas (e.g., exhaust gas stream) when it exits the DC (and then, in some embodiments, enters the coreless). When it mixes with the exhaust gas, it has a temperature that raises the temperature of the exhaust gas to a point well above its dew point so that the moisture contained therein does not accumulate on the exhaust filter (e.g., exhaust filter material or membrane), or at least reduces the amount of such moisture that accumulates thereon. Therefore, the heated outside air serves to evaporate the moisture present in the exhaust gas, thereby reducing its RH. For example, for illustrative purposes only, raising the temperature of saturated exhaust gas (i.e., 100% humidity) from 37°C to 40°C reduces its relative humidity (RH) to 88%; raising the temperature of saturated exhaust gas from 37°C to 50°C reduces its RH to 54%; raising the temperature of saturated exhaust gas from 37°C to 60°C reduces its RH to 35%. Raising the temperature of the exhaust gas above 60°C may also be suitable depending on the particular application. The temperature of the exhaust gas can be controlled using heated outside air having a specific temperature. For example, an exhaust gas showing a higher temperature (e.g., 50°C) will require less heated outside air showing a lower temperature (e.g., 40°C), or only heated outside air having a lower temperature, or both, to achieve the same mixing temperature and RH.Therefore, the outside air is usually heated to a temperature higher than the target temperature of the exhaust gas and lower than the temperature of the heated outside air before mixing with the exhaust gas (e.g., introduced into the exhaust) so that the outside air shows a temperature higher than the temperature of the exhaust gas when the mixture exits the DC (and in some embodiments, the core less). For example, one skilled in the art would determine a sufficient volume of heated outside air having a temperature of 60° C. that needs to be introduced into the exhaust gas having a temperature of about 40° C. in order to produce, for example, an exhaust stream (i.e., exhaust gas mixed with heated outside air) having a target temperature setting of 50° C. In some embodiments, the heated outside air can be introduced into the exhaust gas at a temperature higher than what would be necessary to reach the target temperature of a mixture of equal volumes of heated outside air and exhaust gas, and then the heated outside air can be bled into the exhaust gas at a ratio of less than 1:1, thereby raising the temperature of the exhaust gas to the target temperature while using a smaller volume of heated outside air. Heat (e.g., as heated outside air) can be introduced into the exhaust gas at any point during its passage from the DC to the exhaust filter. For example, in embodiments where the reactor system includes a core less, the heat can be introduced as heated outside air at some point after the gas exits the DC and enters the core less, but preferably after the gas exits the core less and before the gas enters the exhaust filter (e.g., at 3A and / or 3B in FIG. 6, or near there). In a preferred embodiment, the external heat is introduced into the exhaust gas stream so that before entering the exhaust filter (see FIG. 6, at 3A, or near there), for example, in contact with the exhaust filter material or membrane, the temperature of the exhaust gas is raised to be well above its dew point and at a lower RH, ensuring that little or no moisture accumulates on the filter (e.g., the exhaust filter material or membrane) (or at least less moisture than in the unheated exhaust gas). In some preferred embodiments, the external heat can be introduced at any suitable point between the core less and the exhaust filter (e.g., at 3 in FIG. 6) into a junction (e.g., a tubular junction).

[0026] In some embodiments, such as those in which the system does not include a coreless, the heated outside air is introduced into the exhaust gas as it exits the DC and before it contacts the exhaust filter (e.g., FIG. 7). As shown in FIG. 7, in some embodiments, the reactor system can include a DC (1) and an exhaust line (2), and the exhaust exits the DC through it and approaches the filter (3) before being discharged into the external environment (4). In this illustrated embodiment, the externally heated air from the source (5) can be introduced into the exhaust at any point as it passes through the exhaust line (2) and / or enters the filter container (3). This is indicated by arrows extending from the source of heated air (5) (e.g., an electric or other air heating unit) to any one or more of several points in the exhaust line (2) and / or to the filter container (3) or the exhaust filter itself immediately before the point where the exhaust gas contacts the exhaust filter. Therefore, in some embodiments, the hot outside air, which can be sterile air but is not necessarily sterile air, can be heated to a temperature higher than the temperature when it exits the DC and introduced (e.g., pumped) into the exhaust gas (e.g., exhaust stream) exiting the DC in order to ensure that the material condenses beyond the sterile boundary and maintain that temperature. In some embodiments, the heated outside air (e.g., which can be sterile air) can be created by passing the air through an electric heater or its equivalent (e.g., 5 in FIG. 7) to create heated outside air at a temperature within the operating capacity of the DC and / or other single-use bioprocess equipment, and then introducing the heated outside air into the exhaust gas (e.g., exhaust gas stream).

[0027] In some embodiments, the externally heated air can be introduced into the exhaust stream (i.e., exhaust gas) by connecting a fluid passageway (e.g., a tube), preferably a fluid passageway that can be opened and closed as needed (e.g., by including a valve such as a ball or air valve), through which the exhaust is moving, to a fluid passageway (e.g., a tube) through which the exhaust is moving. In some embodiments, the heated air can be passed through a filter (e.g., a bacteria filter) before being introduced into the exhaust (e.g., moist) air. In some embodiments, the heated air can be introduced into the exhaust line on the sterile side of the exhaust filter to directly heat the exhaust (e.g., moist) air. In some embodiments, the heated air can be introduced through the non-sterile side of the exhaust filter to heat the exhaust (e.g., moist) air before passing through a hydrophobic bacteria filter (thereby creating sterile heated air). In some embodiments, the exhaust can be directly heated as it passes through a fluid path such as a tube (e.g., 2 (i.e., between the DC and the coreless in FIG. 6) or 3 (i.e., the joint between the coreless and the exhaust filter (e.g., a tubular joint)); 6A and / or 6B in FIG. 8). As shown in FIG. 8, in some embodiments, the externally heated air can flow through an optional but preferred bacteria filter (7) (from a source (5) of externally heated air, through an optional but preferred fluid path 6A connected to the filter (7), through the optional but preferred bacteria filter (7), into the fluid path 6B, and into the filter container (8)). As shown in FIG. 9, in some embodiments, the fluid path (6B) through which the externally heated air is introduced into the exhaust gas stream extends into a filter container (8) that can accommodate a filter (3) therein. The exhaust gas exiting the filter (3), treated as described above, is discharged into the environment as a dehumidified gas (4). Note that these systems for heating the exhaust stream may also be used in systems without a coreless.

[0028] Therefore, in some embodiments, the present disclosure provides a system in the system including at least an exhaust line through which exhaust gas exiting from a disposable reaction vessel (DC) communicates; at least one filter through which the exhaust gas passes and exits the system; at least one source of externally heated air; at least one fluid path connecting at least one source of externally heated air to at least one exhaust line; and optionally but preferably, at least one bacterial filter between at least one source of externally heated air and at least one exhaust line, and at least one second fluid path connecting the heated air exiting from the bacterial filter to at least one exhaust line. In some embodiments, the externally heated air includes or results in air having a temperature sufficiently higher than the temperature of the exhaust gas such that when the externally heated air and the exhaust gas are mixed to produce a mixed exhaust gas, the relative humidity of the mixed exhaust gas is lower than that of the exhaust gas. In some embodiments, the relative humidity of the mixed exhaust gas is sufficiently low (e.g., raising its temperature sufficiently higher than its dew point) such that moisture from the mixed exhaust gas does not accumulate on the filter when the mixed exhaust gas exits the system. The present disclosure also provides a method of reducing the relative humidity of exhaust gas in such a reaction system (e.g., raising its temperature sufficiently higher than its dew point), the method comprising passing the exhaust gas (e.g., as a mixed exhaust gas) through such a system (e.g., as shown in any of FIGS. 6-9).

[0029] The one or more core condensers are typically positioned at the upper part of the reaction vessel, such as at the upper part of the jacketed head plate (see, for example, FIGS. 1B, 1D, 5). Typically, but not necessarily, the one or more core condensers do not provide significant heat exchange and / or condensation. Heat exchange across the upper part of the head space (second zone 5) is typically provided mainly by the jacketed head plate. In some embodiments, the jacketed head plate may transfer heat thereto since one or more core condensers are positioned thereon. The one or more core condensers may have an upper surface and a lower surface. The lower surface of each core condenser is typically in contact with (on) the jacketed head plate over a certain extent of the surface area of the lower surface of the core condenser (e.g., at least about 10, 20, 25%, or more). In some embodiments, the lower surface of each core condenser is in contact with the jacketed head plate over at least any of about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100% of its surface area.

[0030] The one or more corelessers typically include a serpentine and / or sine wave fluid path (a "fluid path" is an area through which fluid can move) that extends across all or substantially all of the corelesser, e.g., more than 50% of its interior. In some embodiments, the one or more corelessers include, or may be, a container (e.g., a flexible container) that includes one or more fluid passages that provide a serpentine and / or sine wave fluid path within the corelesser. As described above, this serpentine and / or sine wave fluid path provides an increased residence time of the humidifying gas and an increased collection of fluid. In some embodiments, the corelesser may be a flexible bag made of (or manufactured from) a material suitable for use within a DC (e.g., a sterilizable flexible water-impermeable material such as low density polyethylene having an appropriate thickness, e.g., from about 0.1 to 5 mm (e.g., 0.2 mm)). In some of such embodiments, the corelesser may be manufactured by using standard techniques in the art to fuse together at least two sheets of such flexible material to provide an internal volume. Similar techniques may be used to fuse together flexible sheets in a manner that provides a continuous fluid path (e.g., a passage) within its interior chamber, such that several windings of serpentine and / or sine wave fluid paths are provided within its internal volume. In some embodiments, the one or more corelessers provide, or may be, a flexible, semi-rigid, or rigid tubular path (e.g., a tube) that cyclone removes gas from the headspace.

[0031] In some embodiments, the corelesser may also include, be connected to, and / or be attached to a device that includes a mesh and / or a packed solid (e.g., a "defoaming device" as described in the specification of U.S. Patent Application Publication No. 2016 / 0272931A1 (Rudolph et al.)). Such a device may be positioned, for example, between the DC and one or more corelessers, between multiple corelessers, within a corelesser, or between a corelesser and any other part of the system described herein (e.g., a filter) such that the humid gas passes through the defoaming device before entering one or more corelessers. In some embodiments, as described in the specification of U.S. Patent Application Publication No. 2016 / 0272931A1, the defoaming device may include a container, the internal volume of which may include a static mixer and / or granules (e.g., a serpentine path) that break down the bubbles (e.g., in the form of air bubbles) entering the defoaming device. The defoaming device typically includes an inlet receiving surface and a discharge surface positioned opposite each other on opposite sides of the chamber. The serpentine path is seen within the chamber between the inlet and discharge surfaces of the defoaming device. The chamber may be in the form of, for example, tubing (e.g., plastic tubing). Each of the gas inlet and discharge surfaces may be made of a material (e.g., a porous and / or mesh material) that serves to hold the granules. The materials forming those surfaces may thus serve to compartmentalize the granules and thereby form the container. In some embodiments, the defoaming device may be housed within a portion of the tubing connected to the DC between the exhaust port at the top of the DC and before the exhaust. In such embodiments, the defoaming device need not necessarily form a completely separate piece of equipment, but instead may be present within one tube through which the wet gas and / or fluid moves from a second zone (HS) through it. In such embodiments, the defoaming device may be formed by positioning the material at both ends of the portion of the tubing that houses the serpentine fluid path. A piece of such material may be positioned within the tube such that it is close to the DC and distal to the exhaust port and may function as a gas flow receiving surface.Another piece of material is positioned within the tube such that it is proximate to the exhaust port and distal to the DC and may function as an exhaust surface. Thereby, the serpentine fluid path is positioned between the gas flow receiving surface and the exhaust surface. In some embodiments, the serpentine fluid path, tubing, materials, and / or DC are made of substantially the same material. Alternatively, the defoaming device may be manufactured and then inserted into, for example, the tubing. In some such embodiments, the wet gas moving from the second zone (HS) encounters the defoaming device (e.g., the defoaming device is positioned between the second zone (HS) and the coalescer and provides a gas outlet) before entering the coalescer. The system may include one or more such devices, for example, one device attached to a single coalescer of the system, multiple devices attached to one or each of the coalescers of the system, and / or a single individual device attached to multiple and / or each of the multiple coalescers of the system. Thus, in some embodiments, the system may include a DC including the second zone (HS), and the wet gas moves from that second zone, through this device, and into the coalescer. As will be appreciated by those skilled in the art, other embodiments may also be suitable.

[0032] As described above, the wet gas (e.g., vapor, mist) passes from the second zone (HS) into the coalescer through one or more fluid passages (e.g., tubes) connecting the second zone (HS) and the coalescer. In some embodiments, such fluid paths may include, for example, screens and / or other additional features (e.g., tubes) such that the nominal cross-sectional area through which the gas moves (e.g., as an exhaust) will not cause a substantial pressure drop. These fluid paths may be, or include and / or be associated with, one or more intake ports and / or exhaust ports.

[0033] Thus, the coreless described herein typically includes one or more fluid paths (e.g., passages) that provide a meandering and / or sinusoidal fluid path throughout or substantially throughout. The coreless is typically also connected to one or more intake ports (e.g., exhaust inlets) and / or one or more exhaust ports (e.g., exhaust outlets). Moist gas (e.g., vapor and / or mist) moves from a second region (headspace) into the coreless through one or more intake ports (e.g., through a path such as associated tubing), and subsequently through the fluid path of the coreless and out through one or more exhaust ports (e.g., through a path such as associated tubing) (e.g., to the outside through an exhaust opening) that may be arranged at various positions therein. As the moist gas moves through the fluid path of the coreless, the fluid condenses on its walls (e.g., in embodiments where the temperature therein is lower than the temperature of the second region), and in some embodiments can then passively return to the DC (i.e., the second region) and into the reaction mixture. In some embodiments, fluid that has not condensed but has only been coarsened (or collected) within the coreless can also passively return to the second region (HS) and / or the first region (e.g., be dropped into the reaction mixture).

[0034] In some embodiments, the coalescers may be arranged as a number of straight or substantially straight sets of main passages connected to each other through serpentine passages or connecting passages. A unit of serpentine passages (e.g., any two or more straight main passages connected by at least one straight main passage or connecting passage) (e.g., 1 in FIG. 6) may be physically connected to each other, although fluid and / or gas may or may not pass between such units. In some embodiments, one or more of such main passages are connected to one or more intake ports from a second zone (headspace) (e.g., connected by tubing in the main passage; e.g., 2 in FIG. 6). An outlet / exhaust port through which non-coarsened fluid passes through it to an exhaust system (e.g., one or more filters (4 in FIG. 6)) is also located within the main passage and is used to connect it to the filter through a suitable path (e.g., tubing (e.g., 3 in FIG. 6)). In some embodiments where the coalescer is positioned horizontally or substantially horizontally on the reactor (e.g., in the headspace, or on the insulation surrounding the headspace), the intake port is positioned closest to the second zone (headspace) (e.g., the bottom of the main passage), and the exhaust port is positioned distally from the second zone (headspace) relative to the intake port (e.g., at the top of the main passage). Thus, fluid moves from the second zone (headspace) through a connector (e.g., tubing) to the coalescer, where the non-coarsened fluid moves through the main passage (e.g., in some embodiments, also through one or more connecting passages) to the exhaust port, through a connector (e.g., tubing) connected to the exhaust system (e.g., filter), and then out of the system to the atmosphere.

[0035] In some embodiments, a number of corelessers can be included in the system (e.g., as in FIG. 1D). Such a number of corelessers may be connected to each other by one or more fluid passages (e.g., pipes) through, for example, one or more intake ports and exhaust ports. In such embodiments, each corelesser may be individually connected to DC and / or to one or another corelesser. When a number of corelessers are included, only one, a plurality, or all of those corelessers may be in contact with the jacketed platen.

[0036] As described above, one or more filters may be included in the system. The filter is of the type typically used in disposable reactor systems such as, for example, a bacterial filter such as a 0.2 micrometer filter (not necessarily required). The filter is typically connected to the HS and / or more typically to the corelesser (e.g., using pipes). To improve the function of the filter, one or more heating elements may be associated therewith (e.g., in contact with the outer surface of the filter) and may serve to dehumidify the saturated gas exiting the corelesser. As described below, the exhaust system may include a vacuum pump for drawing air and / or gas from within the system into an exhaust system that will further improve the useful life of the filter. Therefore, the use of heat and / or vacuum reduces the tendency for fluid to accumulate therein, thereby increasing the functionality of the filter. Accordingly, one or more filters may be used in the systems described herein.

[0037] Typically, the system also includes an exhaust system. The exhaust system may include an exhaust pump such as a vacuum pump. In some embodiments, the tubing may be connected to an exhaust pump downstream of a bacteria barrier filter attached to a reaction vessel (e.g., a DC); the tubing may connect the exhaust pump to an inlet or outlet of a coalescer and a bacteria barrier filter attached to a reaction vessel (e.g., a DC); the exhaust pump includes variable speed control and is operably connected, as needed, to equipment for maintaining the pressure of the reaction vessel (e.g., a DC); a first fan optionally disposed on the coalescer draws exhaust gas from the headspace through a coarsening device and into or through a downstream bacteria barrier; and / or the system includes at least a second fan for recirculating exhaust gas within the condenser headspace and / or the coarsening device. Each such exhaust system removes air and / or gas (dry or wet) from the reaction vessel system. Exemplary exhaust pumps and exhaust systems include, but are not limited to, those described in the specification of U.S. Patent Application Publication No. 2011 / 0207170A1 (Niazi et al.).

[0038] The systems described herein may include, but are not limited to, one or more manual and / or automatic control systems (e.g., not requiring continuous direct human intervention), including one or more remotely-operated control systems. For example, the control system may continuously monitor and adjust one or more conditions (e.g., temperature) occurring within the first and / or second zones to maintain them at a specific value (e.g., a closed-loop system). Using temperature as an exemplary condition, the control system may separately monitor the temperature of the first zone, the second zone (headspace), and / or the core cooler to optimize the temperature of the reaction components within each zone of the system (e.g., by being connected to a thermostat within each that reports the temperature independently to the control system). The temperature can be optimized, for example, by changing the type, temperature, and / or velocity of the heat transfer fluid moving through the heat transfer system, or by increasing or decreasing the temperature of these zones. Such a control system may be used to maintain the temperature of the first zone, for example, at about 37°C and the temperature of the second zone (headspace) at a temperature of about 32°C. Such a control system typically includes one or more general-purpose computers that process such information and include software for manually or automatically adjusting the desired parameters of the reaction as required by a particular process. Thus, the control system may control values such as the flow of heat transfer material to or from the system (e.g., one or more of its heat transfer systems).

[0039] The exemplary DC embodiments described herein are shown in FIG. 1. FIG. 1A shows a disposable reaction vessel 3 therein, a first zone 4, a second zone 5 (i.e., the headspace (“HS”)), a jacketed platen 6 (shown in more detail in FIG. 1B, which may be a third zone where a third heat transfer system is used (e.g., “zone 3” in FIG. 2)), a filter 7, an exhaust pump 8, an air input (e.g., a sparger) 9, a heat exchange device 10 (e.g., a heat exchange jacket surrounding the second zone 5) and / or 11 (e.g., a heat exchange baffle 11 is positioned within the first zone 4, such a baffle may extend into and / or be positioned within the second zone 5 as needed (e.g., as a separate baffle having an independent heat transfer function from those within zone 4)), a core lessor 13 in contact with the jacketed platen 6, an exhaust inlet 14, an exhaust outlet 15, a coarsening liquid 16, a DC loading support assembly 17, and a drive system 18 (e.g., including an impeller) to provide a front view of an exemplary DC system 1 including a reaction tank 2 (typically with a door 2a). An optional port belt (12) may also be included and positioned as needed and / or desired (e.g., as shown in FIG. 1A). Typically, a non-aerated liquid is present within the first zone 4 and an aerated liquid is present within the second zone 5 (HS) along with a wet gas, although some non-aerated liquid may be present within the second zone 5 (HS) (e.g., if the uppermost liquid level of the reaction mixture extends into zone 5 (HS)). The reaction tank may also include a door (2a, see FIG. 2) through which the DC and / or other components of the system are inserted and removed therefrom. The top view given in FIG. 1B further shows the jacketed platen 6, the core lessor 13 in contact with the jacketed platen 6 and including the exhaust inlet 14, the exhaust outlet 15, the coarsening liquid 16, and the DC loading support assembly 17. FIG. 1C gives a side view of this exemplary embodiment. As can be seen from the figure, in this embodiment, the core lessor 13 covers approximately 75% of the upper portion of the second zone 5 (HS) and is in contact with and / or positioned on the jacketed platen 6.DC3 is positioned within the reaction vessel 2, providing a space (the first zone 4) where the reaction (e.g., fermentation) takes place and a headspace (the second zone 5).

[0040] Figures 1D - F provide additional figures of these and other embodiments. Figure 1D provides a view of an embodiment in which a number of coreless are positioned on a jacketed platen. Figure 1E provides a view from above the jacketed platen that covers approximately 75% of the upper surface of the DC, in which the seam within the DC is covered by the jacketed platen, thereby providing additional physical support there. Figure 1F shows a side view of the DC in which the first zone ("zone 1") is maintained at 35 - 40°C and the second zone (HS) is maintained at a lower temperature (shown as "minimum temperature" in this illustration).

[0041] As described above, referring to FIG. 1, the disposable reaction vessel 3 includes a first zone 4 where the reaction takes place and a second zone 5 that provides a headspace (HS). Thus, the first zone 4 typically contains a fluid reaction mixture (e.g., components and products of a biological reaction) that may be agitated (e.g., stirred) by a drive system 18 (e.g., equipped with an impeller). Air (e.g., gas) is typically introduced into the first zone 4 and moves into and / or through the reaction mixture. The second zone 5 (HS) typically extends from the uppermost liquid level of the reaction mixture and the upper part of the DC3 (typically extending up to the upper part of the reaction tank 2 and / or physically supported by the jacketed end plate 6). The first and second zones may also be associated with (e.g., in contact with) at least one heat exchange device 10 and 11 that may be the same or different within each zone. This heat exchange device, individually or together (e.g., when including a single unit spanning the first zone 4 and the second zone 5 (HS)), may serve to maintain the average temperature of the reaction mixture contained within the disposable reaction vessel 3, more particularly, within the first zone 4 and / or the second zone 5 (HS). The heat exchange device is typically arranged to maintain a desired temperature within the first zone 4 and a lower (i.e., colder) temperature within the second zone 5 (HS) in order to induce condensation within the HS. For example, the heat exchange device may maintain the temperature of the first zone 4 at 35 - 40 °C and the temperature of the second zone 5 (HS) at, for example, 30 °C. Since the temperature of the reaction mixture is typically higher than the temperature of the headspace, the heat transfer fluid of a single heat transfer device extending between the first zone 4 and the second zone 5 may maintain different temperatures in these zones. Thus, the cooling effect provided by the heat exchange device may be relative to the temperature of the contents of each zone (e.g., the reaction mixture within the first zone 4 and the air within the second zone 5 (HS)). For example, the temperature of the reaction mixture within the first zone 4 may be reduced from 50 °C to 40 °C by the heat exchange device, while the temperature within the second zone 5 may be reduced from 35 °C to 30 °C by the same heat exchange device.As described above, in some embodiments, different heat exchange devices may be provided in each of the first zone 4 and the second zone 5, and each such device may separately cool each of the respective zones.

[0042] As described above, the heat exchange system may include a jacketed system 10 surrounding the disposable reaction vessel 3 and / or one or more baffle systems (11). The jacketed system may, for example, be incorporated into the tank as part of a tank wall. The jacketed platen 6 positioned at the upper end of the reaction tank may be jacketed as described herein (e.g., using a dimpled sandwich arrangement) and typically covers at least 5% of the upper surface of the second zone 5 (HS). In some embodiments, the jacketed platen 6 may cover more than 5% of the upper surface of the second zone 5 (HS), such as about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the upper surface. In the embodiment shown in FIG. 1, associated with, positioned on, adjacent to, or above the jacketed platen 6 is the core lessor 13. As described above, at least one surface of the core lessor typically contacts the jacketed platen covering a portion (e.g., at least about 25%) of the surface area of the surface of the core lessor. The core lessor 13 includes an exhaust inlet 14 connected to the second zone 5 (HS) through which gas moves from the second zone 5 into the core lessor 13, and an exhaust outlet 15 through which gas (e.g., humidified gas) exits the core lessor 13 and can enter an exhaust system for discharge from the system (e.g., into the environment). The exhaust outlet 15 is typically also connected to a filter 7, which is connected to the exhaust system 8. The coarsened liquid 16 typically exits the second zone 5 (HS) and collects within the core lessor 13. The coarsened liquid 16 may or may not exit the core lessor 13, but typically is not actively removed therefrom. Thus, the coarsened liquid 16 may passively (e.g., by gravity) exit the core lessor 13 into the second zone 5 (HS) and then typically back to the first zone 4. This movement is shown in FIG. 1A by an upward-pointing arrow and a downward-pointing arrow positioned between the second zone 5 and the core lessor 13.In this embodiment, various parts of the system, including but not limited to the second zone 5 (HS), the coreless 13, the filter 7, and the exhaust system 8, are connected using flexible pipes.

[0043] Figures 2A - E show various views of an exemplary reaction vessel that can hold DC therein. For example, as shown in Figure 2A, the reaction vessel may include a stirring assembly, a door fixed by a hinge and a latch assembly, a top head having heat transfer capabilities (i.e., "dimple jacket structure (zone 3) provided by an inflated heat transfer surface (H.T.S.)", i.e., "jacketed platen"), and a DC loading support assembly. Figure 2B gives another view of the reaction vessel, showing dimple heat transfer surfaces associated with the first and second zones (e.g., "dimple jacket (zone 1)" that transfers heat to the first zone 4, and "dimple jacket (zone 2)" and "jacketed platen (zone 3)" that transfers heat to the second zone 5 (HS), and these heat transfer systems may or may not be adjacent to each other). Figure 2C gives a top view of this exemplary reaction vessel and another view of the jacketed platen ("jacketed platen (zone 3)"). Figure 2D shows a view of the reactor on the opposite side of that in Figure 2A (i.e., the door is on the opposite side of the reaction vessel shown in this figure), and also shows dimple heat transfer surfaces associated with zones 1 and 2 (respectively, "dimple H.T.S. (zone 1)" and "dimple H.T.S. (zone 2)"), and a "jacketed platen (zone 3)" that also transfers heat to the second zone 5 (HS). Figure 2D also shows a "4 - inch (about 10 cm) gap" between the heat transfer surfaces of the first and second zones. It should be understood that the length of this gap may vary, and 4 inches (about 10 cm) is only being referred to here as a non - limiting example. Figure 2E also shows a "jacketed platen (zone 3)" similar to that in Figure 2C. It should be understood that each of these explanatory diagrams is only an illustration and may be modified.

[0044] Figure 3 shows an alternative or additional arrangement of the system in which the coalescer-containing coarsening device (19) is at least partially in contact with and / or restricted by one or more heat transfer surfaces (e.g., one or more dimple-jacket type heat transfer units such as 20A and 20B) other than or in addition to the jacketed platen. In such embodiments, one or more heat transfer surfaces cooled by a heat transfer fluid (e.g., water), such as one or more plates (preferably two plates positioned on both sides of the coalescer), which are in contact with the coalescer and cool the interior chamber and its contents when the coalescer expands as a result of the entry of fluid (coalescate) ("C") and humid gas into the coalescer through its gas intake ("I") (e.g., when the coalescer is composed of a flexible material surrounding an interior chamber including only tubes and / or housed within an interior chamber). In these embodiments, as in others described herein, the coalescer provides a tortuous and / or serpentine fluid path through which coalescates and / or wet gas can move. The fluid path may also include one or more meshes and / or solids (such as the defoaming device described above) throughout or a portion thereof. The surface area of the coalescer in these embodiments is typically not in contact with the heat transfer surface over its entire surface area. For example, in some embodiments, the coalescer is in contact with one or more heat transfer surfaces over 50% or less of its surface area (see, e.g., the example shown in Figure 3). As in other embodiments, the contents of the coalescer may be cooled by the ambient temperature of the environment surrounding the coalescer that is not in contact with an active heat transfer system (e.g., one or more plates), and the ambient temperature is typically approximately room temperature (e.g., 25 °C). The contents of the interior chamber are typically humid gas and liquid moving from the headspace (e.g., zone 5). The expansion of the coalescer promotes the discharge of the coarsening liquid into the DC either passively (e.g., by gravity) or actively (e.g., using a pump).The humidified gas continues its movement through the system, passes through the coreless, exits from its exhaust ("O"), then passes through a filter (which may be heated to dehumidify the humidified gas), and exits into the environment through the exhaust outlet. Such movement may be assisted, for example, by the use of an exhaust system as described above, which may include one or more fans.

[0045] The present disclosure provides and describes a system (e.g., a reaction system) comprising a reaction vessel (e.g., a DC); at least one heat exchange system; a jacketed platen positioned on the reaction vessel (e.g., the DC); and one or more corelessas in contact with (e.g., typically positioned on) the jacketed platen and including an internal serpentine fluid path, wherein the disposable reaction vessel can include a first zone that can contain a reaction mixture maintained at a first temperature; the disposable reaction vessel can include a second zone that includes a headspace above the reaction mixture into which humid gas moving from the reaction mixture can move; the second zone can be maintained at a second temperature lower than the first temperature; and the fluid moving from the second zone can coarsen within the serpentine fluid path inside the corelessa. In some embodiments, the system is then at least one disposable reaction vessel including the first and second zones, wherein the first zone contains a reaction mixture and the second zone includes a headspace into which humid gas moves from the first zone; at least one heat transfer system for maintaining the first zone at the first temperature; at least one heat exchange system for maintaining the second zone at a second temperature lower than the first temperature, and the fluid moves from the headspace (i.e., the second zone) and coarsens within the internal fluid path of the corelessa. In some embodiments, the system comprises a reaction tank including a heat transfer system. In some embodiments, the jacketed platen is integral with the reaction tank. In some embodiments, the reaction tank also includes one or more heat transfer baffles. In some embodiments, the jacketed platen physically supports the disposable reaction vessel. In some embodiments, heat transfer is by radiation, convection, conduction, or direct contact, and / or the heat transfer fluid is a gas or a liquid. In some embodiments, the first heat transfer system is associated with the first zone and the second heat transfer system is associated with the second zone. In some embodiments, a third heat transfer system is also provided by the jacketed platen and can be in fluid communication with the first and / or second heat transfer systems.In some embodiments, at least two of the heat transfer systems are adjacent to each other (e.g., interconnected by fluid paths), and at least one of their heat exchange systems is not adjacent to at least one other heat transfer system. In some embodiments, the second and third heat transfer systems are interconnected. In some embodiments, the same type of heat exchange fluid is in each of one or more of their heat exchange systems, while in some embodiments, the heat exchange fluids in each of one or more of those heat exchange systems are different. In a preferred embodiment, the second zone is positioned above the first zone, where "above" is with respect to the direction of flow of the wet gas from the reaction mixture in the first zone into the second zone (e.g., the second zone is physically above the first zone). In some embodiments, the second zone is partially defined by an upper outer surface adjacent to the jacketed platen. As described above, this arrangement allows the disposable reaction vessel to withstand higher pressures than would otherwise be possible. In some embodiments, at least one of the corelessas has an upper surface and a lower surface, and the internal serpentine fluid path is adjacent to either or both of its upper and / or lower surfaces. In some embodiments, at least one of the corelessas is made of at least two pieces of flexible material fused together to form a chamber containing an internal serpentine fluid path. In some embodiments, the internal serpentine fluid path can be defined by the fusion of at least two pieces of flexible material. In some embodiments, the internal serpentine fluid path is defined by a third material housed within the chamber. In some embodiments, at least one anti-foaming device is positioned between the disposable reaction vessel and at least one of the corelessas.In some embodiments, the system comprises: a first subassembly substantially made of a first material typically fabricated as part of the reaction vessel and joined to a second material to form a first distribution passageway; a second subassembly substantially made of a first material joined to a second material to form a second distribution passageway; optionally, a closure bar joining the first and second subassemblies to each other; and a buffer passageway between the first and second subassemblies: optionally including at least one baffle, the closure bar, if present, setting the width of the buffer passageway, and the distribution and buffer passageways not communicating unless a leak opening is formed in the distribution passageway. In some embodiments, at least one such baffle is associated with a first zone and another such baffle is associated with a second zone. As described above, in some embodiments, the system may include a number of corelessers interconnected or not interconnected through one or more fluid pathways and / or at least one anti-foaming device. In some embodiments, at least one corelesser or each corelesser has a bottom surface, with at least about 25% of the surface area of the bottom surface being on a jacketed platen. In some embodiments, the corelesser may include a flexible container including a serpentine fluid pathway; a flexible, semi-rigid, or rigid tubular form for cyclone removal of gas from a headspace; and / or a container including a mesh and / or a packed solid. Typically, the systems described herein include an exhaust pump.In some such embodiments, the tubing can be connected to an exhaust pump downstream of a bacterial barrier filter in fluid communication with a disposable reaction vessel; the tubing can connect the exhaust pump to an inlet or outlet of a bacterial barrier in fluid communication with a coarser and a disposable reaction vessel; the exhaust pump can include variable speed control and / or can be operably connected to equipment for maintaining a DC pressure, as needed; the exhaust system can include at least a first fan, optionally disposed on a coarser, that can draw exhaust gas from a headspace through a coarsening device and into and / or through a downstream bacterial barrier, and / or can include at least one fan for recycling exhaust gas within a condenser headspace and / or a coarsening device, as needed. In some embodiments, the system is in direct contact, at least in part directly, with the exterior of a second zone and is not at least partially positioned within the reaction vessel (e.g., as shown in FIG. 5). Additional embodiments will be apparent to those skilled in the art from the present disclosure.

[0046] In some embodiments, the systems described herein may include, for example, one or more pressure transmitters or sensors, load cells, and / or scales (e.g., weigh scales) in contact with a second zone (e.g., a headspace) that measure the pressure on the walls of a reaction vessel within the second zone due to gases and fluids present therein. In some embodiments, the pressure transmitter may be a diaphragm pressure transmitter or a load cell. The pressure transmitter may include a membrane for detecting the pressure on the walls of the reaction vessel. In some embodiments, the pressure transmitter or load cell is in contact with the outer surface of the reaction vessel (e.g., the membrane of the diaphragm pressure transmitter is in contact with the outer surface of the reaction vessel adjacent to the second zone). In some embodiments, the pressure transmitter monitors (e.g., continuously monitors) (e.g., by receiving and analyzing information regarding the pressure) the pressure within the second zone and communicates with a control system for adjusting the pressure as needed to ensure that the pressure does not exceed the capacity of the reaction vessel (e.g., a disposable reaction vessel) in order to maintain integrity in the presence of that pressure. In some embodiments, the control system uses an exhaust pump to adjust the pressure within the second zone (e.g., by operating the exhaust pump to remove some of the gas, etc. from the second zone). In some embodiments, the control system is automated (e.g., using software). Other embodiments including such pressure transmitters are also contemplated herein, as would be understood by one of ordinary skill in the art.

[0047] In some embodiments, the reaction system comprises a disposable reaction vessel having a wall with an outer and an inner surface surrounding the reaction chamber, the inner surface being directly adjacent to the reaction chamber; and one or more fluid passages (or paths) extending into the reaction chamber through the wall, the fluid passages having a number of fluid outlets and terminating at a closed end. Since the fluid passages terminate at a closed end, the fluid flowing through the fluid passages exits therefrom through the fluid outlets. In some embodiments, the fluid passages are or may include tubing that includes fluid outlets (e.g., holes in the walls of the tubing). In some embodiments, the fluid exits the fluid passages under sufficient pressure to contact the inner surface of the wall, for example, by spraying outwardly toward the inner surface. In some embodiments, the closed end is formed, for example, by a fused wall of the fluid passage or a cap covering the end of the fluid passage. In some embodiments, the fluid outlets are positioned substantially centrally within the reaction chamber relative to the inner surface. In some embodiments, the fluid outlets within the reaction chamber are relatively uniformly distributed along the fluid passages. In some embodiments, the fluid outlets are arranged to distribute the fluid from the fluid passages at various angles and / or away from the fluid passages in substantially all vertical and / or upward and / or substantially all directions. In some embodiments, the reaction chamber is at least partially spherical (e.g., forming a shape such as a dome (e.g., resembling the hollow upper half of a sphere)). In some embodiments, the fluid flowing through the fluid passages is a cleaning liquid. In some embodiments, the flow of fluid into the fluid passages and / or the reaction chamber is regulated by a control system such as an automated control system (e.g., using software). Exemplary reaction systems for which these embodiments may be suitable include, but are not limited to, any of those described herein (e.g., reaction systems including first and second zones (e.g., headspaces)), each of U.S. Patent Nos. 8,658,419 B2, 9,228,165 B2, and / or any of those described in the specifications of U.S. Patent Application Publication No. 2016 / 0272931 A1, each of which is incorporated herein by reference in its entirety.Other embodiments including such fluid passage structures will also be contemplated herein, as would be understood by those skilled in the art.

[0048] For example, acids and bases are periodically added to a reaction system (e.g., a fermenter, a bioreactor, etc.) to adjust the pH between 2.5 and 11 in order to carry out certain processes, such as cell digestion, virus inactivation, or chemical decontamination of the reaction system (e.g., from microorganisms or active agents). In some embodiments, it may be necessary to use strong acids or bases to treat (e.g., clean) the reaction chamber. Those skilled in the art understand that typical materials, such as polyethylene films and polyolefin ports, are compatible (e.g., structurally stable) with solutions having a pH from 2.5 to 11, and there is limited relevant data regarding the pH at which such materials actually cease to function. In the art, there is a need for reaction systems suitable for use in solutions having a pH from 0 to 14. Thus, in some embodiments, one or more of the fluid passages and associated structures (e.g., ports) described above are chemically compatible (e.g., structurally stable) with solutions having a pH from 0 to 14 (herein referred to as "low / high pH compatibility"). Exemplary materials capable of providing such low / high pH compatibility include, for example, mixtures containing a thermoplastic elastomer (e.g., at least about 20% by weight) and a polyolefin (e.g., less than about 50% by weight), and optionally further containing styrene, and / or thermoplastic elastomers (TPEs) such as those described in the specification of U.S. Patent No. 9,334,984 B2 (Siddhamalli et al.). Exemplary low / high pH compatible tubing that can be used as described herein includes commercially available C-Flex® tubing (Saint-Gobain Performance Plastics Corp., including, for example, any of compoundings 374, 082, 072). In some embodiments, the acid or base solution may be held in a low / high pH compatible container (e.g., a glass container) and delivered to the reaction chamber through a low / high pH compatible fluid passage (e.g., tubing made of TPE).The low / high pH compatible fluid passage may extend through a port (e.g., a polyolefin port) made of a low / high pH incompatible material that leads from outside to inside the reaction chamber, or the low / high pH incompatible material (e.g., polyolefin) that constitutes the port may be in the same plane as the end of the port that opens into the reaction chamber so that the high / low pH solution does not come into contact with it. In some embodiments, the polyolefin port may include a disk-shaped surface having a diameter wider than the diameter of the fluid passage (see, e.g., FIG. 4). FIG. 4 shows an exemplary arrangement of a low / high pH compatible fluid passage (e.g., a tube) (1) within a typically larger-diameter tube (2) made of a material that is not low / high pH compatible (i.e., is low / high pH incompatible). In FIG. 4, the low / high pH compatible tube (1) and the low / high pH incompatible tubes (2) are shown in a port structure (3 including port disks 4a and port necks 4b). In some embodiments, the port may include a port disk (4a) and an extended neck (5) that effectively functions as an outer tube (having a diameter larger than the low / high pH compatible fluid passage / tube). This low / high pH compatible tube (1) is typically connected to a source of low or high pH solution that is to be dropped through this low / high pH compatible tube (1) into the reaction chamber. Using this arrangement, a high / low pH solution can be dropped into the reaction chamber and any fluid contained therein (e.g., the reactants remaining after the reaction is complete) without contacting and / or damaging the pH-incompatible components of the reaction system. The fluid contained within the reaction chamber (including that after the addition of the low or high pH solution) is maintained at a pH that is compatible with the material that constitutes the disposable container (e.g., the material surrounding or forming the reaction chamber). Such a compatible pH is typically from about 2.5 to about 11 (e.g., an acceptable setpoint / control point). Making these changes to the system described herein allows a low / high pH solution (i.e., a solution with a pH less than 2.5 or greater than 11) to pass from the source solution into the reaction chamber without the risk of material breakdown due to pH incompatibility.Thus, in some embodiments, the disposable reaction systems described herein include a fluid passageway, and optionally some or preferably all of the tubing leading to the fluid passageway and / or reaction chamber, made of a material that remains structurally intact in the presence of a fluid having a pH between zero and 14. In some embodiments, the material is or includes a thermoplastic elastomer. Such components, and similar components, as well as other arrangements of other low / high pH compatible materials, are contemplated herein, as would be understood by one of ordinary skill in the art.

[0049] One or more low / high pH compatible tubes (e.g., fluid passageways) may be prepared and included in a set of tubing (e.g., a “tube set,” “tube-in-tube” system; see, e.g., the exemplary embodiment shown in FIG. 4) for use in a low / high pH solution delivery system. For example, a first fluid passageway (e.g., a tube) made of a low / high pH compatible material (e.g., the material is stable in the pH range of 0 to 14) may be inserted into or constructed within a second fluid passageway (e.g., a tube) that is not made of a low / high pH compatible material (e.g., the material is not stable in the pH range of 0 to 14) (e.g., overmolded). In some embodiments, such a tube set may be constructed, for example, by building overmolded components (overmolding the inner tube's outer diameter (OD) with the outer tube's inner diameter (ID)), inserting the inner tube into a port (leading to the reaction chamber), and positioning the outer hose over the inner hose and barb (if present). In some embodiments, such a tube set may be constructed, for example, by building overmolded components, inserting an inner tube (e.g., a hose) into a port made of a low / high pH incompatible material such that the outer tube (e.g., a hose) is positioned over the inner tube and barb, filling the annular space with resin, melting it, and achieving flow / seal of the two tubes. Other methods of manufacturing such pH compatible systems are contemplated herein, as would be understood by one of ordinary skill in the art.

[0050] Accordingly, in some embodiments, the present disclosure provides a system comprising a reaction vessel; optionally but preferably at least one heat transfer system; optionally a jacketed platen positioned over the reaction vessel; optionally but preferably a core cooler including an internal serpentine fluid path; at least one exhaust filter; and a heated air source. The reaction vessel can include a first zone containing a reaction mixture maintained at a first temperature; the reaction vessel can include a second zone including a headspace above the reaction mixture into which humid gas moving from the reaction mixture can move; the second zone can be maintained at a second temperature lower than the first temperature; fluid moving from the second zone can, if present, agglomerate within the internal serpentine fluid path of the core cooler; exhaust gas exits the reaction vessel and then exits the system through the exhaust filter; and the heated air source introduces heated air into the exhaust gas after the exhaust gas exits the reaction vessel and before or simultaneously with its exit from the system through the exhaust filter to produce a mixed exhaust gas. In some embodiments of such a system, the heated air source introduces air into the exhaust gas after the exhaust gas exits the reaction vessel and before its exit from the system through the exhaust filter. In some embodiments, the system comprises a core cooler through which the exhaust gas passes, and the heated air source introduces air into the exhaust gas after the exhaust gas exits the core cooler to produce a mixed exhaust gas, which then exits the system through the exhaust filter. In a preferred embodiment, the relative humidity of the mixed exhaust gas is lower than that of the exhaust gas. In some embodiments, a) the reaction vessel is a disposable reaction vessel; b) the system further comprises a reaction vessel including a heat transfer system; c) the system comprises a jacketed platen integral with the reaction vessel in which the reaction system is housed; d) the system comprises a core cooler; the disposable reaction vessel includes a first and a second zone, the first zone containing a reaction mixture and the second zone including a headspace into which humid gas moves from the first zone; the first zone is maintained at a first temperature; the second zone is maintained at a second temperature lower than the first temperature; fluid moving from the headspace agglomerates within the internal fluid passage of the core cooler;e) Heat transfer is effected by radiation, convection, conduction or direct contact, and / or the heat transfer fluid is a gas and / or a liquid; f) The disposable reaction vessel includes a first and a second region, the first region containing the reaction mixture and the second region containing a headspace into which the wet gas moves from the first region, the first heat transfer system being associated with the first region and the second heat transfer system being associated with the second region; g) The system comprises a jacketed platen; the disposable reaction vessel includes a first and a second region, a first heat transfer system associated with the first region, a second heat transfer system associated with the second region, and, optionally, a third heat transfer system provided by the jacketed platen in fluid communication with the first and / or second heat transfer systems, at least two of these heat transfer systems being adjacent to each other, at least one of the heat transfer systems not being adjacent to at least one other heat transfer system, at least two of the heat transfer systems being interconnected by a fluid path, the second and third heat transfer systems being interconnected, and / or the same type of heat transfer fluid being within each heat transfer system; h) The second region is positioned above the first region; i) The system comprises a jacketed platen, the second region being partially defined by an upper outer surface adjacent to the jacketed platen; j) The system comprises a coreless, the coreless having an upper and a lower surface, an internal serpentine fluid path being adjacent to either or both of the upper and / or lower surfaces, the coreless being made from at least two pieces of flexible material fused together to form a chamber containing the internal serpentine fluid path, the internal serpentine fluid path being defined by the fused portion of the at least two pieces of flexible material, and / or the internal serpentine fluid path being defined by a third material housed within the chamber; k) The system comprises a coreless further including at least one anti-foaming device positioned between the disposable reaction vessel and the coreless; l) The system comprises a first sub-assembly substantially consisting of a first material joined to a second material so as to form a first distribution passageway; a second sub-assembly substantially consisting of a first material joined to a second material so as to form a second distribution passageway; and, optionally, a closure bar joining the first sub-assembly and the second sub-assembly to each other;A heat transfer system having at least one baffle with a buffer passage between a first subassembly and a second subassembly, the closure bar, if present, setting the width of the buffer passage, the distribution passage and the buffer passage not communicating unless a leak opening is formed in the distribution passage, and optionally, at least one such baffle is associated with a first zone and another such baffle is associated with a second zone; m) the system comprises a number of corelessers, and optionally, those corelessers are not interconnected through one or more fluid paths, are interconnected through one or more fluid paths, and one or more of the corelessers are associated with at least one defoaming device, and each corelesser has a lower surface in contact with a jacketed platen; n) the system comprises a corelesser including a flexible container having a serpentine fluid path and having a flexible, semi-rigid, or rigid tubular form for cyclone removal of gas from the headspace; and / or a corelesser including a container containing a mesh and / or a packed solid; o) the system comprises an exhaust pump, and optionally, a pipe is connected to the exhaust pump downstream of a bacterial barrier filter in fluid communication with a disposable reaction vessel; a pipe connects the exhaust pump to an inlet or outlet of a bacterial barrier in fluid communication with the corelesser and the disposable reaction vessel; the exhaust pump includes variable speed control and is operably connected to a facility for maintaining a DC pressure, if necessary; a first fan optionally disposed on the corelesser passes exhaust gas from the headspace through the corelesser and draws it into or through a downstream bacterial barrier; and / or at least a second fan for recirculating exhaust gas in a condenser headspace and / or within the corelesser; p) the system comprises a jacketed platen physically supporting the disposable reaction vessel; q) the system comprises a heat transfer system that is in at least some direct contact directly with the outside of the second zone and is not at least partially positioned within the reaction vessel; and / or r) the reaction vessel includes a first zone containing a reaction mixture maintained at a first temperature; a second zone including a headspace above the reaction mixture into which moist gas migrating from the reaction mixture can migrate;And optionally, at least one diaphragm pressure transmitter, load cell, and / or scale including a membrane for detecting the pressure in contact with the reaction vessel, in contact with a second zone, for detecting the pressure exerted on the reaction vessel by the gases and fluids present in the second zone and / or communicating with a control system to adjust the pressure within the second zone in response to information received from the diaphragm pressure transmitter, the outer surface of the reaction vessel in contact with, optionally, the control system continuously monitors the information generated by the system, uses an exhaust pump to adjust the pressure within the second zone and / or is automated. In a preferred embodiment, the reaction vessel included in such a system is a disposable reaction vessel. In some preferred embodiments, the system comprises: a) at least one exhaust line through which exhaust gas exits from a disposable reaction vessel (DC) and passes through; b) an exhaust filter through which the exhaust gas passes and exits the system; c) at least one source of externally heated air; d) at least one fluid path connecting at least one source of externally heated air to at least one exhaust line; and e) optionally, a bacterial filter between at least one source of externally heated air and at least one exhaust line and at least one second fluid path connecting the heated air exiting the bacterial filter to at least one exhaust line. In a preferred embodiment, the externally heated air has a temperature sufficiently higher than the temperature of the exhaust gas such that when the externally heated air and the exhaust gas are mixed to produce a mixed exhaust gas, the relative humidity of the mixed exhaust gas is lower than that of the exhaust gas. In a preferred embodiment, the relative humidity of the mixed exhaust gas is sufficiently low such that moisture from the mixed exhaust gas does not accumulate on the filter when the mixed exhaust gas exits the system. In a preferred embodiment, the present disclosure also provides a method of reducing the relative humidity of the exhaust gas within a reaction system, the method comprising passing the exhaust gas through any such system. In a preferred embodiment, the present disclosure also provides a method of performing a reaction using any such system. Other aspects and embodiments of the present disclosure will also be contemplated by those skilled in the art, as will be understood.;

[0051] Terms such as "about" and "approximately", when attached to a list of numerical values or ranges, refer independently to each individual value in the list or range as if each such individual value were immediately after the term. The term means that the value it refers to is exactly that value, close to that value, or of the same order of magnitude as that value. The term "maintain" with respect to temperature is not intended to indicate that a particular temperature remains the same over any particular period. A temperature "maintained" at a particular level should be understood to vary, for example, by about 1%, 5%, or 10% (e.g., 0.1 - 10%) over time. "Fixedly attached", "attached", or "adjacent" means that at least two materials are joined to each other in a substantially permanent manner. The various components described herein may be joined to each other, for example, using welding, using adhesives, another similar process, and / or using connectors such as tubing. Those components must remain attached to each other during use, and the attachment points (e.g., boundaries, joints) between those components must be able to withstand hydrodynamic and other forces encountered within the reaction vessel and between the components, due to, for example, the pressure generated by the flow of the heat transfer medium and the movement of the contents of the reactor in response to the action of the agitation mechanism. "Optional" or "optionally" means that the subsequently described event or situation may or may not occur, and that the description includes examples where the event or situation occurs and examples where it does not occur. A range may be expressed herein as from about one particular value and / or to about another particular value. When such a range is expressed, another aspect includes from that one particular value and / or to the other particular value. Similarly, when a value is expressed as an approximation using the antecedents "about" or "approximately", it will be understood that that particular value forms another aspect. Further, it will be understood that each endpoint of a range is significant both in relation to and independent of the other endpoint. A range (e.g., 90 - 100%) is intended to include the range itself, as well as each independent value within the range as if each value were individually listed.The term "on" means, unless otherwise specified, "directly on or directly connected to another element" (e.g., two parts of the system described herein). The term "adjacent" may refer to an indirect connection between two elements, such as parts of the system described herein.

[0052] A "fluid path" is a path (e.g., a passageway) within the system described herein through which one or more fluids (e.g., gases or liquids) can move, and / or be transported, and / or be caused to move. "Fluidly connected" or "in fluid communication" refers to at least two parts of the system described herein through which fluid can flow directly and / or indirectly (e.g., fluid can move from a disposable reaction vessel to a coreless, and / or vice versa, such that the disposable reaction vessel and the coreless share a "fluid connection" and are "in fluid communication" with each other). A "fluid path" or "fluid passageway" is a path (e.g., a passageway) through which fluid can flow, as generally understood by those skilled in the art. Other similar terms of this disclosure will be understood by those skilled in the art when read in the appropriate context.

[0053] All documents cited within this disclosure are hereby incorporated by reference in their entirety. Specific embodiments are described herein by way of example only and are in no way intended to limit the scope of the claims. Although specific embodiments are described in relation to preferred embodiments, it will be understood that modifications and variations will occur to those skilled in the art. Accordingly, the appended claims cover all such equivalent variations that fall within the scope of the following claims. Hereinafter, preferred embodiments of the present invention will be described item by item. Embodiment 1 In the system, a. A reaction vessel, b. At least one heat transfer system, c. Optionally, a jacketed platen positioned above the reaction vessel, d. Optionally, a core cooler having an internal serpentine fluid path, e. At least one exhaust filter, and f. A heated air source, are provided, The reaction vessel can include a first zone containing a reaction mixture maintained at a first temperature, The reaction vessel can include a second zone containing a headspace above the reaction mixture into which humid gas moving from the reaction mixture can move, The second zone can be maintained at a second temperature lower than the first temperature, The fluid moving from the second zone can coarsen within the internal serpentine fluid path of the core cooler, if present, The exhaust gas exits the reaction vessel and then exits the system through the exhaust filter, The heated air source is a system that introduces heated air into the exhaust gas after the exhaust gas exits the reaction vessel and before or simultaneously with its discharge from the system through the exhaust filter to produce a mixed exhaust gas. Embodiment 2 The system according to Embodiment 1, wherein the heated air source introduces air into the exhaust gas after the exhaust gas exits the reaction vessel and before its discharge from the system through the exhaust filter. Embodiment 3 The system according to Embodiment 1 or 2, comprising the core cooler through which the exhaust gas passes, wherein the heated air source introduces air into the exhaust gas after the exhaust gas exits the core cooler to produce the mixed exhaust gas, and then the mixed exhaust gas exits the system through the exhaust filter. Embodiment 4 The system according to Embodiment 1 or 2, wherein the relative humidity of the mixed exhaust gas is lower than that of the exhaust gas. Embodiment 5 a) The reaction vessel is a disposable reaction vessel, b) The system further comprises a reaction vessel including a heat transfer system, c) The system comprises a jacketed platen integral with the reaction vessel in which the reaction system is housed. d) The system comprises a core less; the disposable reaction vessel includes a first and a second zone, the first zone containing a reaction mixture, the second zone containing a headspace into which humid gas moves from the first zone; the first zone is maintained at a first temperature; the second zone is maintained at a second temperature lower than the first temperature; the fluid moving from the headspace coarsens within the internal fluid passage of the core less. e) Heat transfer is effected by radiation, convection, conduction or direct contact, and / or the heat transfer fluid is a gas and / or a liquid. f) The disposable reaction vessel includes a first and a second zone, the first zone containing a reaction mixture, the second zone containing a headspace into which humid gas moves from the first zone, a first heat transfer system being associated with the first zone and a second heat transfer system being associated with the second zone; g) The system comprises a jacketed platen; the disposable reaction vessel includes a first and a second zone, a first heat transfer system associated with the first zone, a second heat transfer system associated with the second zone, and, optionally, a third heat transfer system provided by the jacketed platen in fluid communication with the first and / or the second heat transfer system, at least two of the heat transfer systems being adjacent to each other, at least one of the heat transfer systems not being adjacent to at least one other heat transfer system, at least two of the heat transfer systems being interconnected by a fluid path, the second and the third heat transfer systems being interconnected, and / or the same type of heat transfer fluid being within each heat transfer system. h) The second zone is positioned above the first zone. i) The system comprises a jacketed platen, the second zone being partially defined by an upper outer surface adjacent to the jacketed platen. j) The system comprises a core less which has an upper and a lower surface, the internal serpentine fluid passage being adjacent to either or both of the upper and / or the lower surface, the core less being made of at least two pieces of flexible material fused together to form a chamber containing the internal serpentine fluid passage, the internal serpentine fluid passage being defined by the fused portion of the at least two pieces of flexible material, and / or the internal serpentine fluid passage being defined by a third material housed within the chamber. k) The system further comprises a core cooler with at least one defoaming device positioned between the disposable reaction vessel and the core cooler. l) The system comprises at least one baffle having a heat transfer system including a first subassembly substantially consisting of a first material joined to a second material to form a first distribution passageway; a second subassembly substantially consisting of a first material joined to a second material to form a second distribution passageway; optionally, a closure bar joining the first subassembly and the second subassembly to each other; and a buffer passageway between the first subassembly and the second subassembly, the closure bar, if present, setting the width of the buffer passageway, the distribution passageways and the buffer passageway not communicating unless a leak opening is formed in the distribution passageway, and optionally, at least one such baffle is associated with the first zone and another such baffle is associated with the second zone. m) The system comprises a number of core coolers, optionally, the core coolers are not interconnected through one or more fluid paths, are interconnected through one or more fluid paths, one or more of the core coolers are associated with at least one defoaming device, and each core cooler has a lower surface in contact with the jacketed platen. n) The system comprises a core cooler including a flexible container having a serpentine fluid path and having a flexible, semi-rigid, or rigid tubular form for cyclone removing gas from the headspace; and / or a container including a mesh and / or a packed solid. o) The system comprises an exhaust pump, optionally, a pipe is connected to the exhaust pump downstream of a bacterial barrier filter in fluid communication with the disposable reaction vessel; a pipe connects the exhaust pump to an inlet or outlet of a bacterial barrier in fluid communication with the core cooler and the disposable reaction vessel; the exhaust pump includes variable speed control and is optionally operably connected to a facility for maintaining a DC pressure; a first fan optionally disposed on the core cooler draws exhaust gas from the headspace through the core cooler and into or through a downstream bacterial barrier; and / or at least a second fan for recirculating exhaust gas within the condenser headspace and / or within the core cooler. p) The system comprises a jacketed platen that physically supports a disposable reaction vessel. q) The system comprises a heat transfer system that is at least to some extent in direct contact with the exterior of the second zone and is not positioned at least partially within the reaction vessel, and / or r) The reaction vessel comprises a first zone containing a reaction mixture maintained at a first temperature; a second zone above the reaction mixture containing a headspace into which humid gas migrating from the reaction mixture can migrate; and optionally at least one diaphragm pressure transmitter, load cell, and / or scale in contact with the second zone and including a membrane for detecting the pressure in contact with the reaction vessel, for detecting the pressure exerted on the reaction vessel by the gas and fluid present in the second zone, and / or in response to information received from the diaphragm pressure transmitter, communicating with a control system for regulating the pressure within the second zone in contact with the outer surface of the reaction vessel, optionally the control system continuously monitors the information generated by the system, uses an exhaust pump to regulate the pressure within the second zone, and / or is automated. The system according to Embodiment 1. Embodiment 6 The system according to any one of Embodiments 1 to 5, wherein the reaction vessel is a disposable reaction vessel. Embodiment 7 a) At least one exhaust line through which exhaust gas exiting the disposable reaction vessel (DC) passes. b) At least one filter through which the exhaust gas passes and exits the system. c) At least one source of externally heated air. d) At least one fluid path connecting the at least one source of externally heated air to the at least one exhaust line, and e) Optionally, a bacterial filter between the at least one source of externally heated air and the at least one exhaust line, and at least one second fluid path connecting the heated air exiting the bacterial filter to the at least one exhaust line. The system according to any one of Embodiments 1 to 6, comprising. Embodiment 8 The system according to any one of Embodiments 1 to 7, wherein the externally heated air has a temperature sufficiently higher than the temperature of the exhaust gas such that when the externally heated air and the exhaust gas are mixed to produce a mixed exhaust gas, the relative humidity of the mixed exhaust gas is lower than that of the exhaust gas. Embodiment 9 The system according to embodiment 8, wherein the relative humidity of the mixed exhaust gas is sufficiently low such that moisture from the mixed exhaust gas does not accumulate on the filter when the mixed exhaust gas exits the system. Embodiment 10 A method for reducing the relative humidity of exhaust gas in a reaction system, the method comprising the step of passing the exhaust gas through the system according to any one of embodiments 1 to 9. Embodiment 11 A method for performing a reaction using the system according to any one of embodiments 1 to 9.

Explanation of Symbols

[0054] 1 DC system 2 Reaction tank 3 Disposable reaction vessel 4 First area 5 Second area 6 Jacketed platen 7 Filter 8 Exhaust pump 9 Air input, sparger 10 Heat exchanger 11 Heat exchange baffle 13 Coreless 14 Exhaust inlet 15 Exhaust outlet 16 Coarsening liquid 17 DC loading support assembly 18 Drive system 19 Coarsening device

Claims

【Claim 1】 In a system, a. A disposable reaction vessel contained within a reaction tank including at least one heat transfer system, the disposable reaction vessel discharging exhaust gas; b. A core cooler having an internal serpentine fluid path for receiving the exhaust gas discharged from the disposable reaction vessel; c. An exhaust line for passing the exhaust gas from the core cooler to an exhaust filter, the exhaust line receiving the exhaust gas from the core cooler; d. A heated air source for directly introducing heated air having a temperature higher than the temperature of the exhaust gas into the exhaust line to generate a mixed exhaust gas; and e. At least one exhaust filter through which the mixed exhaust gas passes when exiting the system, comprising, the mixed exhaust gas being generated before entering the exhaust filter; a system, a) The system comprises a jacketed platen integral with the reaction tank; b) The system comprises a core cooler; the disposable reaction vessel includes first and second internal regions, the first internal region containing a reaction mixture, the second internal region containing a headspace through which moist gas moves from the first region; the first region is maintained at a first temperature; the second region is maintained at a second temperature lower than the first temperature; fluid moving from the headspace coarsens within the internal fluid passage of the core cooler; c) Heat transfer is effected by radiation, convection, conduction or direct contact, and / or the heat transfer fluid is a gas and / or a liquid; d) The disposable reaction vessel includes first and second internal regions, the first internal region containing a reaction mixture, the second internal region containing a headspace through which moist gas moves from the first internal region, a first heat transfer system being associated with the first internal region and a second heat transfer system being associated with the second internal region; e) The system comprises a jacketed platen; the disposable reaction vessel includes first and second internal regions, a first heat transfer system associated with the first internal region, a second heat transfer system associated with the second internal region, and, optionally, a third heat transfer system provided by a jacketed platen in fluid communication with the first and / or the second heat transfer system, at least two of the heat transfer systems being adjacent to each other, at least one of the heat transfer systems not being adjacent to at least one other heat transfer system, at least two of the heat transfer systems being interconnected by a fluid path, the second and the third heat transfer systems being interconnected, and / or the same type of heat transfer fluid being within each heat transfer system, f) The system comprises a coreless, which has an upper surface and a lower surface, the internal serpentine fluid path being adjacent to either or both of the upper surface and / or the lower surface, the coreless being made of at least two pieces of flexible material fused together to form a chamber containing the internal serpentine fluid path, the internal serpentine fluid path being defined by the fused portion of the at least two pieces of flexible material, and / or the internal serpentine fluid path being defined by a third material housed within the chamber, g) The system comprises a coreless and further comprises at least one anti-foaming device positioned between the disposable reaction vessel and the coreless, h) The system comprises at least one baffle having a heat transfer system comprising a first sub-assembly substantially made of a first material joined to a second material to form a first distribution passageway, a second sub-assembly substantially made of a first material joined to a second material to form a second distribution passageway, optionally a closure bar joining the first sub-assembly and the second sub-assembly to each other, and a buffer passageway between the first sub-assembly and the second sub-assembly, the closure bar, if present, setting the width of the buffer passageway, the distribution passageway and the buffer passageway not communicating unless a leak opening is formed within the distribution passageway, and optionally at least one such baffle being associated with the first region and another such baffle being associated with the second region, i) The system comprises a number of corelessers, which, if necessary, are not interconnected through one or more fluid paths, are interconnected through one or more fluid paths, and one or more of the corelessers are associated with at least one defoaming device, and each corelesser has a lower surface in contact with the jacketed platen; j) The system comprises a corelesser that includes a flexible container having a serpentine fluid path and having a flexible, semi-rigid, or rigid tubular form for cyclone removal of gas from the headspace; and / or a corelesser that includes a container containing a mesh and / or a packed solid; k) The system comprises an exhaust pump, and if necessary, a pipe is connected to the exhaust pump downstream of a bacterial barrier filter that is in fluid communication with the disposable reaction vessel; a pipe connects the exhaust pump to an inlet or outlet of the bacterial barrier that is in fluid communication with the corelesser and the disposable reaction vessel; the exhaust pump includes variable speed control and is operably connected to a facility for maintaining the pressure of DC if necessary; a first fan optionally disposed on the corelesser passes exhaust gas from the headspace through the corelesser and draws it into or through the downstream bacterial barrier; and / or at least a second fan recirculates exhaust gas within the condenser headspace and / or within the corelesser; l) The system comprises a jacketed platen that physically supports the disposable reaction vessel; and / or m) The disposable reaction vessel includes a first internal region containing a reaction mixture maintained at a first temperature; a second internal region including a headspace above the reaction mixture into which humid gas moving from the reaction mixture can move; and, optionally, at least one diaphragm pressure transmitter, load cell, and / or scale in contact with the second region and including a membrane for detecting the pressure in contact with the reaction vessel, for detecting the pressure exerted on the reaction vessel by the gas and fluid present in the second region, and / or for communicating with a control system to adjust the pressure within the second region in response to information received from the diaphragm pressure transmitter, and optionally, the control system continuously monitors the information generated by the system, uses an exhaust pump to adjust the pressure within the second region, and / or is automated, in contact with the outer surface of the reaction vessel, which communicates with the control system to adjust the pressure within the second region in response to information received from the diaphragm pressure transmitter. A system for manufacturing chemical and / or biological agents. **Claim 2** The system according to claim 1, wherein the relative humidity of the mixed exhaust gas is lower than that of the exhaust gas. **Claim 3** A bacterial filter between at least one source of externally heated air and the at least one exhaust line, and at least one second fluid path connecting the heated air exiting the bacterial filter and the at least one exhaust line. The system according to claim 1 or 2, comprising the same. **Claim 4** The system according to any one of claims 1 to 3, wherein the heated air has a temperature sufficiently higher than the temperature of the exhaust gas such that when the externally heated air and the exhaust gas are mixed to produce a mixed exhaust gas, the relative humidity of the mixed exhaust gas is lower than that of the exhaust gas. **Claim 5** The system according to claim 4, wherein the relative humidity of the mixed exhaust gas is low enough that moisture from the mixed exhaust gas does not accumulate on the filter when the mixed exhaust gas exits the system. **Claim 6** A method for reducing the relative humidity of exhaust gas within a reaction system, the method comprising passing the exhaust gas through the system according to any one of claims 1 to 5. **Claim 7** A method for performing a reaction using the system according to any one of claims 1 to 6.

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