This invention relates to a device for freezing, transporting and thawing fluids, in particular sterile fluids, solutions and suspensions for the chemical, biotechnological, pharmaceutical and food industry, of the type defined in claim 1 and a method of thawing such fluids as defined in claim 10.
Increasing globalisation of production processes used for production in the chemical, pharmaceutical and biotechnological industry but also in the food industry have placed more and more demands on the logistics involved in storing and transporting product stages, e.g. from cell cultures, for downstream processing. In order to deal with this problem, it has become increasingly necessary to freeze smaller or larger batches of liquid intermediate and/or end products and transport the frozen batches. Various devices suitable for this purpose are known from the prior art, which comprise a container with a freeze-thaw unit, by means of which batches of a few to several hundred litres can be frozen.
For example, patent specification U.S. Pat. No. 5,524,706 discloses a device with an upright cylindrical container with a funnel-shaped base with a central outlet orifice. The container wall and base are of a double-skin design and coolant flows through them during the freezing process. In order to ensure gentle and uniform freezing, a plurality of cooling elements is provided in the container. The cooling elements are hollow cylinders, the diameters and lengths of which are adapted to one another so that they are disposed concentrically with one another and extend through the container interior respectively from a top region, which predefines the maximum filling level, to approximately the base. The distance of the cooling elements from the container base and of the cooling elements from one another is the same overall. Coolant can be fed in and out of top-end pipes connecting all the cooling elements via a single inlet pipe and outlet pipe on the top face of the lid. For thawing purposes, an appropriately warm medium is fed through the cooling elements and once the container contents have completely thawed, the container is emptied via the central bottom outlet orifice in the region of the deepest point of the container. Since the cooling elements disclosed in U.S. Pat. No. 5,524,706 occupy a large part of the container volume and have a very large surface area, freezing and thawing is quick and gentle and does not require additional process steps. For economic reasons, however, it is very desirable to reduce the size of the cooling elements massively in order to save on costs and increase the usable volume of the container.
The applicant has developed a freezing and transport device for which the freezing process was quantified in terms of temperatures and phase transitions on the basis of time and location. The device, known under the brand name FreezeContainer®, is illustrated in
For thawing purposes, a warm medium is fed through the container wall, container base and the cooling coil. The thawing process is preferably assisted by shaking the container lightly.
The closed container is filled with fluids, in particular sterile fluids, solutions and suspensions for the chemical, biotechnological, pharmaceutical and food industry, hereafter referred to as product, from the top via an inlet pipe mounted in the cover. The inlet pipe opens exactly above a central outlet orifice at the deepest point of the base so that the product can be drawn off through the base outlet or via the inlet pipe once it has completely thawed.
In order to increase the already high degree of functional versatility and process adaptability still further, it is desirable to be able to pump the product in circulation during thawing, which is not possible with the existing device.
Accordingly, the objective of this invention is to propose a device for freezing, transporting and thawing fluids, in particular sterile fluids, solutions and suspensions for the chemical, biotechnological, pharmaceutical and food industry, which does not have the disadvantages of the known devices and which permits a maximum amount of operating options. Another objective of the invention is to propose a device and a method whereby the frozen product can be thawed more rapidly and gently than in the past whilst simultaneously facilitating mixing of the thawed substrate.
These objectives are achieved by a device as defined in claim 1 and a method as defined in claim 10, by means of a heated immersion pipe which thaws at an early stage and therefore enables thawed and preferably pre-heated product to be pumped in circulation, i.e. drawn off and recirculated, during the entire thawing process. The disadvantages of the known methods are avoided and more rapid thawing is achieved.
The new device proposed by the invention has at least one immersion pipe which has an active thermal connection to the heat exchanger elements at least across a part-region of its longitudinal extension, which preferably extends from approximately a deepest point of the container as far as a maximum filling level. The maximum filling level is the filling level to which the container can be filled with product to be frozen and then thawed on a controlled basis. It is primarily defined by the position of the heat exchanger elements, making allowance for the expansion in volume caused by changes in density. In the case of the embodiments described below, it is between a top container edge and top portions of the heat exchanger elements. The immersion pipe is preferably in direct contact with at least one heat exchanger element and can be passively heated. During thawing, liquefied product can be drawn off from at least one heatable immersion pipe, which in turn preferably extends through the container interior from above and opens above a deepest point of the base. The heatable immersion pipe has an advantage over the known devices, in which the inlet pipe is disposed freely in the container interior and hence freely in the frozen product, because the frozen product thaws very rapidly in the interior of the immersion pipe and the process of drawing off the thawed liquid product is blocked only during an initial phase of the thawing process. Whilst it is being drawn off, the thawed product is also gently heated as it passes through the heated immersion pipe so that it can be discharged at a temperature significantly above freezing point, preferably from above, onto parts of the product still frozen and accelerates the thawing process. In a preferred embodiment of the invention, return pipes are provided on the internal face of the container lid for this purpose.
Heating the thawed product in the immersion pipe as it is drawn off offers a significant advantage over drawing it off from an outlet orifice in the base. In the case of a device of the type known from U.S. Pat. No. 5,524,706, the thawed product is drawn off through the bottom outlet and the product is at a temperature that is only just above freezing point. When this cold product is pumped through the filler neck onto the still frozen product, this barely accelerates the thawing process. In the case of the invention, the product pumped onto the still frozen parts is now pre-heated, which significantly speeds up the thawing process. Furthermore, drawing off the thawed product through the outlet orifice in the base is technically a disadvantage in terms of conductance.
Another advantage of the new device resides in the fact that the distance which the liquid product must travel as it is being pumped out of the container can be kept very short because it does not have to be directed from the outlet in the base to the inlet in the lid of the container. This obviates the need for undesirable pipes on the outside of the container on the one hand and discharging and emptying as well as pumping conveniently take place from the top of the new device on the other hand, because all connectors can be disposed in the lid or at least in a top region of the container.
Preferred embodiments of the stirrer proposed by the invention will be described below with reference to the appended drawings. Of these:
a shows a longitudinal section through a freeze-thaw container based on the prior art with a cooling element in the interior of the container and a base outlet;
b is a side view of the container illustrated in
a is a longitudinal section through a container of a device based on an embodiment of the invention, in which a cooling element and an immersion pipe are illustrated although not in section;
b is a view from above at an angle showing an immersion pipe based on one embodiment, actively co-operating with a cooling coil, where only the parts which lie in the interior of a container are illustrated;
a is a view from below at an angle showing a lid of a device illustrated in
b is a side view of the lid and cooling, immersion and return elements illustrated in
a is a longitudinal section illustrating a freeze-thaw container B designed by the applicant. As explained above, this container is known from the prior art under the name of FreezeContainer. The container B can be closed and sealed by means of a top lid BD. Together with a bottom base BB and a side wall BS, the lid BD defines an interior I of the container B, in which a cooling coil KS is disposed. As indicated in
The geometry of the cooling coil KS is designed to produce an optimum sequence of temperatures and phase transitions in time and locally in the container interior I and is connected to a plurality of vertically extending portions EV, which are each mutually connected via top, respective bottom horizontal portions EH. Whilst the top and bottom horizontal portions EH respectively lie more or less in one plane, a vertical portion EZ disposed centrally in the container extends farther down into the container to just short of a deepest point. This ensures that the region directly above a central outlet orifice A in the container base BB is thawed early during the thawing process. This has proved to be of particular advantage because it is very difficult to provide heat exchanger elements in the region of the base outlet. The top horizontal part-pieces EHO facing the lid BD extend in a region just below the maximum filling level FH of the container B, respectively define the maximum filling level. The vertical part-pieces at the beginning and at the end of the cooling coil extend through the container lid BD and are respectively connected to a coolant inlet ZM and to the cooling pipe KL and thus indirectly to the outlet AM.
The freeze-thaw container B illustrated in
b is a side view of the freeze-thaw container B illustrated in
The container B is preferably filled with the product to be frozen through the inlet pipe ZR in the closed state, i.e. with the lid fitted. Once the desired filling level is reached, an appropriate inlet valve at the upper end of the inlet pipe is closed and the cooling process initiated by circulating cold medium through the cooling circuit which, in addition to the cooling coil and the container wall and container base, additionally comprises at least one pump, not illustrated in the drawing, and a cooling unit or coolant reservoir, also not illustrated in the drawing, until the product in the container interior has been completely frozen on a controlled basis and the minimum temperature desired for storage or transport has been reached. In this state, the product, which is also disposed in the interior of the inlet pipe ZR, is frozen and the latter blocked. For thawing purposes, a warm medium is circulated through the circuit and in order to accelerate the thawing process, the container, which is mounted on a base stand P, is lightly shaken. The deeply extending, central vertical piece EZ ensures that the region above the central outlet orifice is thawed relatively quickly. Although the inlet pipe ZR opens exactly into this region, the thawed product can not be drawn down until the entire volume of the inlet pipe has thawed. As briefly explained above, this is not achieved until practically all the product has thawed. Thawed product can be drawn off relatively early during the thawing process through the bottom central outlet orifice A, which communicates via an outlet pipe AL with an outlet connector AA in an end face of the base stand P. However, since the known container does not have any means of recirculating this liquefied product, it can not be pumped back round. Furthermore, the product contained above the bottom central outlet orifice A is still very cold and would barely have the effect of assisting the thawing process if it were recirculated through the container interior.
During pumping, the disposition of the immersion pipe and cooling coil and/or other heating elements ensures that the lumen of the immersion pipe thaws very quickly after the start of circulating warm medium through the circuit. The thawed product, which in turn collects at the deepest point of the container, can be drawn off upwards through the immersion pipe 60 at an early point during the thawing process. The second, extremely advantageous effect is that the still very cold liquefied product is heated as it is conveyed through the central part-piece 63 because warm medium is flowing round its entire circumference.
The central part-piece 63 of the immersion pipe preferably forms the inner wall of the hollow cylindrical part-piece 51 of the cooling coil so that the immersion pipe and cooling coil are integrally connected to one another in a “pipe in pipe” arrangement and the immersion pipe is integrated in the region of the cooling element that is directly thermally active. A lowermost part-piece 63′ of the immersion pipe is no longer surrounded by the vertical part-piece 51 of the cooling coil and extends down out of it by a few centimetres. The lowermost part-piece 63′ can be very easily adapted to the size of the container 10 by cutting it to a length that will ensure that the bottom opening of the immersion pipe still lies at the desired short distance of preferably 5 mm but at least 1 mm from the container base or lies in the base via a bottom outlet orifice, including in the warm state (e.g. during thawing and pumping). For example, existing devices can be retro-fitted with the combination of cooling element and immersion pipe proposed by the invention, as illustrated in
The immersion pipe and cooling coil may also be manufactured in two pieces and inserted one in the other so that the immersion pipe wall comes into contact with an internal wall of the central part-piece 51. The one-piece design may be used for containers that will be used more than once because it is significantly easier to clean.
The thawing process and the drawing-off of thawed product will be described below with reference to
As indicated in
The combination of removing and pre-heating thawed product with an immersion element 60 proposed by the invention and recirculating it via the direct return line 70 at an early point in time at which a major part of the product in the interior 11 of the container 10 is still frozen leads to rapid and gentle thawing.
Instead of running the immersion pipe through the central part-piece of the cooling coil as described above, it is run in an alternative arrangement, as illustrated in
In other embodiments, the immersion pipe surrounds the cooling coil so that the immersion pipe lies on the outside in the “pipe in pipe” construction and is cooled or heated by the internally lying part-piece of the cooling coil. These embodiments are less preferred in terms of heat conduction. The same applies to embodiments in which the immersion pipe and a co-operating part-piece of the cooling coil are designed as mutually abutting half-pipes, since this also results in poorer flow dynamics.
The inventive idea of placing an immersion pipe in active communication with heat exchanger elements is not restricted to the elements specifically described and illustrated in the drawings so far and instead, can be used with a plurality of other elements. Freeze-thaw elements with heat exchangers disposed in a spiral shape may be placed in active communication with an immersion pipe for drawing off and pre-heating product, as well as plate-shaped or star-shaped heat exchanger elements.
The decisive factor is that a thermal connection exists between the heat exchanger element and at least the portion of the immersion pipe which lies in the region of the frozen product, namely approximately from the deepest point of the container as far as the maximum filling level, respectively where it is filled with it in the frozen state. A direct contact between the immersion element and the heat exchanger element based on the “pipe in pipe” design and the “pipe in wall” design described above is not absolutely necessary but is of advantage.
The technical teaching of the invention may also be used for disposable devices, which are becoming increasingly popular as they are particularly economic in the CIP/SIP sector due to reduced costs. In the case of such “single-use” devices, the entire device may be made from appropriate plastics in a genuine disposable version. In another embodiment, the thermally passive parts, in other words essentially the base, lid and wall of the container and the immersion pipe, may be made from plastic as “disposables”, whilst the heat exchanger elements are made from metal and are removed from the container after use, cleaned and re-used.
In another embodiment, the immersion pipe, which essentially corresponds to that illustrated in
For the electrical variant, heating wires, coils and other elements are preferably disposed in the wall of the immersion pipe isolated from the product and environment. For the inductive variant, at least major portions of the immersion pipe are preferably made from ferromagnetic material. Since a voltage source is necessary for electrically heating the immersion pipe and an appropriately strong magnetic source is needed for inductive heating, both variants are used under specific conditions only.
Number | Date | Country | Kind |
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737/06 | May 2006 | CH | national |
Filing Document | Filing Date | Country | Kind | 371c Date |
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PCT/CH2007/000214 | 5/2/2007 | WO | 00 | 2/24/2009 |