CN116685825A - Art cooling rod - Google Patents

Abstract

Process heat exchange bars for cooling or heating a liquid in a process vessel. The rod may have a linear form and extend downwardly through the upper wall of the process vessel to near the lower bottom. The stem defines a circulating flow path for the heat exchange medium internally, including an outer jacket and a flow divider having a central through bore and an outer helical groove. The heat exchange medium passes down through the central through hole and then flows back up through the spiral groove formed between the flow divider and the outer jacket, and vice versa. By modifying the configuration of the heat exchange bars and the flow rate and temperature of the heat exchange medium, precise heating or cooling of the process fluid can be achieved. The component may be injection molded of a polymer, is generally transparent, and has a high heat transfer coefficient.

Description

Art cooling rod

Technical Field

The present disclosure relates to heat exchange elements for chemical and biological processes.

Background

Various chemical and biological processes in the laboratory environment can generate heat. For example, continuous filtration of the process media can rapidly raise the temperature of the media, leading to deleterious results, particularly for fragile biological cells growing in the culture dish. A standard technique for reducing the temperature of the process contents is to place the reactor or vessel in an ice bath. However, this presents a number of challenges, the most important of which is the accurate and consistent adjustment of the amount of cooling. The process sometimes also requires the addition of a regulated amount of heat.

There remains a need for a rapid heat exchange solution for chemical and biological processes to accurately and consistently regulate the amount of cooling or heating.

Disclosure of Invention

A process cooling element, described as a rod, may be inserted into a bioreactor or other reactor vessel to regulate temperature. The method of using the process cooling element includes immersing a rod into the liquid in the process vessel, the rod extending at least 1 foot into the bottom of the vessel to enable heat transfer with a small amount of liquid in the vessel. A manifold extending from the container has a fluid inlet connector and a fluid outlet connector. The cooling element includes an outer jacket and an inner flow diverter extending from the manifold to a closed distal end of the outer jacket. The flow divider has a central through bore, one or more outer helical grooves contacting the inner jacket wall and defining one or more helical fluid passages of a length equal to the length of the flow divider. The method includes flowing a cooling fluid into the inlet connector, the cooling fluid passing downwardly through the central through bore and then upwardly through the spiral fluid passageway to the outlet connector. The flow direction may be reversed such that the inlet becomes the outlet. The outer jacket and shunt are desirably formed of a polymer, sometimes transparent, with a high heat transfer coefficient; it may be greater than 0.50W/mk@23c or even greater than 0.90W/mk@23c.

A first embodiment of the apparatus disclosed herein includes a fluid process heat exchange lever for heating or cooling a fluid in a process vessel. The first embodiment has an elongate polymeric outer jacket extending along an axis defining a closed distal end and an open proximal end, and a lumen defined within the outer jacket. A manifold connected to the proximal end of the outer jacket and having two connectors providing fluid communication with the lumen; the first connector is offset from the centerline by the manifold and the second connector is positioned along the centerline and aligned with the outer jacket shaft. An elongate polymer shunt is positioned within the lumen. The shunt extends from the manifold to a point spaced from the closed distal end such that a distal space is formed in the lumen between the shunt and the closed distal end. The shunt has a central bore extending the length of the shunt and in fluid communication with the second connector to fluidly connect the second connector and the distal space. The flow splitting section also has an outer surface defined by at least one helical groove extending the length of the flow splitter and having an outer diameter approximately equal to the inner diameter of the outer jacket for contact therewith. The at least one helical groove defines at least one helical groove spaced radially inward from the outer jacket, the helical groove forming at least one helical fluid path between the shunt and the outer jacket fluidly connecting the first connector and the distal space. The heat exchange rod is configured such that fluid flowing into the second connector passes distally through the bore to the distal space and returns proximally from the distal space to the first connector through the at least one helical fluid passage, and fluid flowing into the first connector passes distally through the at least one helical fluid passage to the distal space and returns proximally from the distal space to the second connector through the bore. Thus, the fluid flowing through the heat exchange bars is suitable for heating or cooling the fluid within the process vessel. Furthermore, two parallel spiral grooves may be formed in the flow divider, which define two parallel spiral grooves. The elongate collet may be linear and tubular with the closed distal end being hemispherical.

A second embodiment of the apparatus disclosed herein includes substantially identical fluid process heat exchange bars for heating or cooling a fluid in the process vessel described above. However, the outer surface of the shunt is not defined by at least one helical groove, but rather by ribs extending the length of the shunt, with an outer diameter approximately equal to the inner diameter of the outer jacket for contact therewith. The ribs define at least one fluid passage between the flow divider and the outer jacket that fluidly connects the first connector and the distal space, and the heat exchange fluid flows through the at least one fluid passage.

In any of the embodiments described herein, the outer jacket and the flow splitter can be injection molded of a polymer having a heat transfer coefficient of at least 0.50W/mk@23c or at least 0.90W/mk@23c. The polymer may be transparent and may be a polypropylene-based resin.

In any of the embodiments described herein, the apparatus may further comprise a process vessel adapted to contain a fluid, the process vessel having an upper wall, wherein the heat exchange rod is mounted on the upper wall of the process vessel such that the closed distal end of the outer jacket extends downwardly to the bottom end of the main portion of the process vessel for immersion in the fluid within the process vessel. The process vessel may be a flask having a larger main portion and an upwardly inclined shoulder region forming an upper wall, the heat exchange bars being mounted through holes formed in the upper wall such that the closed distal end of the outer jacket extends downwardly to the bottom end of the main portion of the process vessel.

Drawings

FIG. 1 is a perspective view of an exemplary process cooling bar;

FIG. 2 shows a longitudinal cross-sectional view of a process cooling bar;

FIG. 3 is an exploded view of a process cooling bar;

FIG. 4 illustrates a process vessel having an exemplary process cooling bar mounted through its upper wall with a sealing sleeve;

FIG. 5 is an enlarged view of the upper wall of the process vessel showing an alternative mounting arrangement for the process cooling bars, FIG. 6 is a vertical cross-sectional view therethrough;

FIG. 7 is an enlarged view of the upper wall of the process vessel showing a three-clip mounting assembly for the process cooling lever, FIG. 8 is an exploded vertical cross-section therethrough;

FIG. 9 is an enlarged view of the upper wall of the process vessel showing a threaded mounting arrangement for the process cooling bars, and FIG. 10 is a vertical cross-sectional view therethrough; and

FIG. 11 is a cross-sectional view of an exemplary flask with an internal mixer with its blades recorded to rotate about its lower bottom and showing an exemplary process cooling bar placed therein.

Detailed Description

A rod-shaped process cooling element is described that can be inserted into a bioreactor or other reactor vessel to regulate temperature. The primary application of the cooling bar is to reduce the temperature of the media, but it should be understood that the beneficial properties of the cooling bar are also applicable to increasing the temperature of the process media and thus, more broadly, heat exchange elements or bars are disclosed. Furthermore, the cooling element is preferably shaped as an elongated linear rod, but may be adapted to other shapes, such as a curved rod or an irregular shape reflecting the shape of the container in which it is used. Furthermore, the size of the process cooling bars may vary depending on the cooling capacity required, although a single cooling bar is shown in the example application, multiple cooling bars may be used. Finally, the preferred materials for the cooling bars are described, but should not be considered limiting unless explicitly required.

A particularly useful application for the process heat exchange element is to heat and thus dilute a liquid, such as a manufactured medicament, during the filling step. That is, the heat exchange element may be placed in close proximity to a filling needle lowered into a process vessel containing a liquid drug. The effective heating of the liquid immediately adjacent the filling needle thins the liquid, thereby facilitating withdrawal from the container. Another application is in ultrafiltration of various media. Some filters used in bioreactors tend to accumulate retentate and warm up through an increase in the resistance of fluid flowing therethrough. Heating can damage the valuable medium and place the heat exchange element in the fluid.

Fig. 1 is a perspective view of an exemplary process cooling bar 20, and fig. 2 shows the exemplary process cooling bar in longitudinal section. In the exemplary embodiment, cooling rod 20 includes a hollow housing or jacket 22 having a closed end 24 and a hub or manifold 26 secured to the open end of the housing opposite the closed end. The manifold 26 provides mounting and internal passages for a first connector 28 and a second connector 30. The outer jacket 22 may be tubular and linear defining a longitudinal axis having a closed end 24 formed by a hemispherical cap. The manifold 26 has a generally cylindrical configuration and is sealingly attached around the outside of the open end of the jacket 22, as shown in a section of fig. 2. Adhesives or thermal bonding may be used to join the parts. The first connector 28 extends radially from the manifold 26, while the second connector 30 extends axially along the longitudinal axis and is centered. The two connectors 28, 30 may be formed as conventional barbed hoses.

Referring to the exploded view of fig. 3, the elongated shunt 32 fits snugly within the interior wall 34 of the tubular jacket 22 and extends substantially the entire length thereof. The flow splitter 32 defines a spiral rib or groove 36 having a flat outer dimension that is approximately the same as the diameter of the inner wall 34. The helical groove 36 is sized and pitch-wise arranged such that there are two parallel grooves extending the length of the flow splitter 32. Recessed helical grooves 38 are formed between the grooves 36 that define a helical fluid channel 40 within the inner wall 34.

The axial second connector 30 defines a central throughbore 42 centered about a longitudinal axis that is in fluid communication with a central bore 44 through the flow splitter 32. The bore 44 extends the length of the shunt 32 between the manifold 26 and a plenum 46 defined between the distal end of the shunt and the inner wall of the hemispherical cap 24. Pressurized fluid flowing into the through bore 42 of the connector 30 passes downwardly through the bore 44 as indicated by the arrow until it reaches the plenum 46.

The helical groove 38 opens to the bottom end of the flow divider 32 so that the pressurized fluid within the plenum 46 travels up the groove. Eventually, the fluid reaches the top of the flow splitter 32 and enters an annular space 47 defined within the outer jacket 22 and the manifold 26. An outlet fluid passage 48 formed in the first radial connector 28 communicates with the annular space 47 through a short axial passage 50 in the manifold 26. Of course, it should be appreciated that pressurized fluid may enter through the first connector 28 and pass downwardly through the helical groove 38 and upwardly through the central bore 44 to reverse flow. Either way, a constant flow of cooling (or heating) fluid may be circulated through the process cooling bar 20. Although not shown, the heat exchange medium may be circulated through a cooler or heater external to the heat exchange rod 20 and placed near the process vessel.

As shown in fig. 3, the first connector 28 may be an article molded separately from the manifold 26. The second connector 30 may also be separate, but is desirably molded as a one-piece manifold as shown in the section of fig. 2.

Fig. 4 illustrates a process vessel 60 having an exemplary process cooling rod 20 mounted through its upper wall 62. In the illustrated embodiment, the process vessel 60 is a large flask having a generally cylindrical main portion 61 and an upwardly sloped shoulder region that forms an upper wall 62. The container 60 continues upwardly into the neck region 64 causing the upper mouth to be closed by the cap 66. In some applications, the lid 66 may be replaced with a stirring assembly.

For sterility, a sleeve or other type of sealing boot 68 may be secured between the cooling rod 20 and a hole 69 through the upper wall 62. The sealing sleeve 68 may be removable or the cooling rod 20 may be assembled (glued or welded) with the process vessel 60 using the sealing sleeve 68 and sold as a unit providing a built-in option for cooling or heating the process fluid within the vessel. The boot seal 68 may be an elastomer or a more rigid polymer that is bonded or welded to the cooling rod 20 and the bore through the upper wall 62.

The cooling rod 20 extends downwardly into the process vessel 60 until the closed end cap 24 is adjacent the bottom 70 of the vessel. In one embodiment, the length of the cooling rod 20 is configured such that when installed through the sealing sleeve 68, the closed end cap 24 extends to within 1 inch of the bottom 70 of the container 60. In this way, the cooling bars 20 even reach a low level of fluid at the bottom end of the vessel, as shown, and begin to exchange heat therewith.

Although not shown, the inflow and outflow tubular fluid conduits are then connected to the first and second connectors 28, 30, protruding 30 from the manifold 26 to initiate cooling (or heating) flow through the cooling bar 20. As will be appreciated by those skilled in the art, the temperature and flow rate of the fluid through the cooling rod 20 may be varied to accurately regulate the temperature of the fluid within the container 60.

Fig. 5 is an enlarged view of the upper wall 62 of the process vessel 60 showing an alternative mounting arrangement for the process cooling bars 20. Fig. 6 is a vertical cross-sectional view of an alternative mounting arrangement showing the tubular jacket 22 of the cooling rod 20 passing downwardly through the aperture in the upper wall 62. A circular flange 80 is formed at the lower end of the manifold 26, which is secured to the upper wall 62 by adhesive or bonding/welding. This mounting arrangement allows for a more permanent connection that can be assembled by the manufacturer for shipping and sale of the process vessel 60 with the mounting cooling pole 20.

Fig. 7 is an enlarged view of the upper wall 62 of the process vessel 60 showing a three-clamp mounting assembly 90 for the process cooling lever 20. Fig. 8 shows an exploded view of the assembly 90, which includes an upper flange 92 and a lower flange 94, which together sandwich a resilient pad 94. The upper flange 92 is shown as being formed as an integral part of the manifold 26 of the cooling bar 20, although of course it could be formed separately and sealed thereto. The lower flange 94 is connected to a downwardly oriented tubular sleeve 98. The tubular sleeve 98 passes downwardly through the aperture in the upper wall 62 and may be sealed or otherwise adhered or secured thereto. As shown, the lower surface of the upper flange 92 and the upper surface of the lower flange 94 have circular grooves that mate with circular ribs at the top and bottom ends of the resilient pad 94.

Although not shown, conventionally, three tri-band mounting assemblies are temporarily secured together using external mechanical clamps to achieve a sanitary airtight seal. For example, sanitary fittings Limited liability company in Mascogo, wishttps:// sanitaryfittings.us/product-category/fittings/clamp-fittings/clampsA number of different such fixtures are provided, which are incorporated herein by reference.

The tri-band mounting assembly 90 can facilitate the installation and removal of the process cooling pole 20, or alternative devices such as sampling instruments. Instead, a cover may be attached to the lower flange 94 to close the opening.

Fig. 9 is an enlarged view of the upper wall 62 of the process vessel 60 showing the threaded mounting arrangement for the process cooling rod 20, and fig. 10 is a vertical cross-sectional view therethrough. In this assembly, male threads 100 formed at the lower end of the cooling rod manifold 26 mate with female threads in a mounting sleeve 102. Sleeve 102 in turn extends downwardly through an aperture in upper wall 62 and may be sealed or otherwise bonded or fastened thereto. The mating threads may be PG threads, such as PG13.5 with a thread angle of 80 degrees, commonly used for probes such as pH electrodes, dissolved Oxygen (DO) probes or temperature and conductivity probes, or standard NPT threads, tapered or straight. This simple mounting structure again enables easy attachment and detachment of the process cooling bar 20, or alternative devices such as sampling instruments, or plugs may be attached to the mounting sleeve 102 to close the openings.

Fig. 11 is a cutaway perspective view of an exemplary flask or vessel 120 that forms part of a process reactor and mixing system with which process cooling bars 20 may be integrated. The container 120 includes a large main portion with vertical side walls 122 that may be reinforced with ribs or other stiffening features and may contain dimples (not shown) on the opposite side as the handle. The upwardly sloping shoulder region or upper wall 126 opens into an upper opening 128 to which a lid (not shown) may be secured to seal the contents of the container. In some processes, the cap may include downwardly extending ports and tubes for introducing or removing fluid from the interior of the container 120, such as described in U.S. patent 10,260,036 to Shor et al, the contents of which are expressly incorporated herein by reference. The container 120 may be provided in a volume of 500 ml to 50 l and made of PET or polycarbonate.

Fig. 11 shows an internal mixer 130 with vanes 132 to rotate about a vertical axis above the lower bottom 129 of the vessel. The mixer 130 is desirably rotated beneath and outside the vessel 120 by an external magnetic drive (not shown and sometimes referred to as an agitator plate). For example, mixer 130 may contain two diametrically opposed rare earth or ceramic magnets facing base 129, and the magnetic drive may also have a rotating electromagnet or rotating rare earth magnet (not shown). The magnetic drive is able to rotate the mixer by virtue of being close to the mixer 130.

As described above, the cooling rod 20 extends downwardly into the process vessel 120 until the closed end cap 24 is proximate the bottom 129 of the vessel 120. In one embodiment, the length of the cooling rod 20 is set such that when installed through the top wall 126, the closed end cap 24 extends to within 1 inch of the bottom 129 of the container 120. In this way, the cooling bar 20 can reach even very low levels of fluid at the bottom end of the container to initiate heat exchange therewith. In addition, the cooling bars 20 reach the fluid surrounding the mixer 130 for efficient simultaneous heat transfer and fluid agitation.

The spiral configuration of the flow splitter 32 maximizes the surface area of the outer spiral cooling channels. Advantageously, the entire cooling rod 20 is made of plastic. For example, all components may be made of transparent polycarbonate, which will allow for taking video or still images of the flow while flowing. Preferably, the material is a) non-reactive, b) having as high a heat transfer coefficient as possible, c) easy to manufacture and d) recyclable plastic. Stainless steel and other non-reactive metals may work, although they are not considered disposable.

One exemplary material for use with the cooling bar 20 assembly is a highly thermally conductive plastic, known as thermo-Tech, available from priwan of elv lake ohio. The Therma-Tech polymer formulation is a polypropylene-based resin. A specific formulation of the product of Priwan under the name X TT-10279-002-04EI Natural (EM 1003511360) has the following physical properties:

features (e.g. a character)	Method	Value/unit
			Specific gravity	ASTM D792	1.37
Tensile strength at break	ASTM D638	3573psi
			Elongation at break	ASTM D638	3.0％
Flexural modulus	ASTM D790	354,000psi
			Bending strength at bending	ASTM D790	6000psi
Thermal Conductivity (TC) -in-plane	ASTM E1461	1.15W/mK
			Thermal Conductivity (TC) -through plane	ASTM E1461	0.98W/mK

Advantageously, the heat transfer rate of the thermo-Tech polypropylene is 40% higher than that of polycarbonate. The polycarbonate generally has a heat transfer rate of between 0.19 and 0.22W/mK@23C. Thus, preferably, the polymer used has a heat transfer rate of at least 0.50W/mk@23c, more preferably at least 0.90W/mk@23c.

Terms such as top, bottom, left side and right side are used herein, although the fluid manifold may be used in various positions such as upside down. Accordingly, some descriptive terms are used for relative terms rather than absolute terms.

Throughout the description, the embodiments and examples shown should be considered as exemplars, rather than limitations on the apparatus and procedures disclosed or claimed. Although many of the examples presented herein involve specific combinations of method acts or system elements, it should be understood that these acts and these elements may be combined in other ways to achieve the same objectives. Acts, elements and features that are only associated with one embodiment are not intended to be excluded from a similar role in other embodiments.

As used herein, "plurality" refers to two or more. As used herein, a "set" of items may include one or more of such items. The use of ordinal terms such as "first," "second," "third," etc., in the claims to modify a claim element does not by itself connote any priority, ranking, or order of one claim element relative to another, nor does it connote a temporal order in which acts of a method are performed, but rather merely serves as a label to distinguish one claim element having a particular name from another element having a same name (but for use of the ordinal term) to distinguish the claim elements.

Claims (15)

1. An apparatus comprising a fluid process heat exchange lever for heating or cooling a fluid in a process vessel, comprising:

an elongate polymeric outer jacket extending along an axis defining a closed distal end and an open proximal end, a lumen defined within the outer jacket;

a manifold connected to the proximal end of the outer jacket, the manifold having two connectors providing fluid communication with the lumen, a first connector offset from a centerline through the manifold, and a second connector positioned along the centerline and aligned with the outer jacket axis; and

an elongate polymeric shunt positioned within the lumen, the shunt extending from the manifold to a point spaced from the closed distal end such that a distal space is formed in the lumen between the shunt and the closed distal end, the shunt having a central bore extending the length of the shunt and in fluid communication with the second connector to fluidly connect the second connector and the distal space, the shunt further having an outer surface defined by at least one helical groove extending the length of the shunt and having an outer diameter approximately equal to the inner diameter of the outer jacket for contact therewith, the at least one helical groove defining at least one helical groove spaced radially inward from the inner diameter of the outer jacket, the helical groove forming at least one helical fluid path between the shunt and the outer jacket fluidly connecting the first connector and the distal space,

wherein the heat exchange rod is configured such that fluid flowing into the second connector passes distally through the bore to the distal space and from the distal space back proximally to the first connector through the at least one helical fluid passage, and fluid flowing into the first connector passes distally through the at least one helical fluid passage to the distal space and from the distal space back proximally to the second connector, the fluid flowing through the heat exchange rod, and thus being adapted to heat or cool the fluid within the process vessel.

2. The apparatus of claim 1, wherein at least the outer jacket and the flow splitter are injection molded from a polymer having a heat transfer coefficient of at least 0.50W/mk@23c.

3. The apparatus of claim 2, wherein at least the outer jacket and the flow splitter are injection molded from a polymer having a heat transfer coefficient of at least 0.90W/mk@23c.

4. A device according to any one of claims 2-3, wherein the polymer is transparent.

5. The device of any one of claims 2-4, wherein the polymer is a polypropylene-based resin.

6. A device according to any preceding claim, wherein there are two parallel helical grooves formed in the shunt which define two parallel helical grooves.

7. The device of any one of the preceding claims, wherein the elongate collet is linear and tubular and the closed distal end is hemispherical.

8. The apparatus of any one of the preceding claims, further comprising a process vessel adapted to contain a fluid, the process vessel having an upper wall, wherein the heat exchange rod is mounted on the upper wall of the process vessel such that the closed distal end of the outer jacket extends downwardly to the bottom end of the main portion of the process vessel for immersion in the fluid within the process vessel.

9. The apparatus of claim 8, wherein the process vessel is a flask having a large main portion and an upwardly inclined shoulder region, wherein the upwardly inclined shoulder region forms an upper wall, and the heat exchange rod is mounted through an aperture formed in the upper wall such that the closed distal end of the outer jacket extends downwardly to the bottom end of the main portion of the process vessel.

10. The apparatus of claim 9, wherein the heat exchange rod is removably mounted through an aperture formed in the upper wall using a tri-band assembly or a threaded connection.

11. The device according to claim 9, wherein the heat exchange rod is fixed to the upper wall by means of an adhesive or bonding/welding.

12. The apparatus of any one of claims 8-11, wherein the process vessel heat exchange bars are assembled into a single retail unit and transported and sold therewith.

13. The apparatus of any one of claims 8-12, wherein the process vessel comprises a mixer having blades located directly above the lower bottom of the vessel and rotating about a vertical axis.

14. The apparatus of claim 13, wherein the mixer comprises a magnet facing the lower base so as to be rotatable by an external magnetic drive.

15. The apparatus of any one of claims 13-14, wherein the outer jacket of the heat exchange rod has a length sufficient to extend downwardly into the process vessel such that the closed distal end is proximate the lower bottom of the vessel and adjacent the mixer.