EP3141846A1

EP3141846A1 - Cryogenic coldstore for the preservation of chemical, pharmaceutical & biological materials

Info

Publication number: EP3141846A1
Application number: EP15002623.5A
Authority: EP
Inventors: Tim Wigfall
Original assignee: Linde GmbH
Current assignee: Linde GmbH
Priority date: 2015-09-08
Filing date: 2015-09-08
Publication date: 2017-03-15

Abstract

The invention relates to a method for cooling one of: a chemical, a pharmaceutical or a biological material (6), wherein a liquid cryogen (C) or a gaseous phase (C') derived therefrom is passed (e.g. from a container (2)) to a heat exchanger (4) that is arranged in a compartment (5) in which said material (6) is arranged in order to cool said material (6), wherein the liquid cryogen (C) or gas (C') takes up heat in said heat exchanger (4) such that a warmer gaseous phase (C") of the cryogen (C) is generated which is guided out of the compartment (5) and re-used in the gaseous phase in another application (9). Further, the invention relates to a corresponding system (1).

Description

The invention relates to a method and a system for cooling chemical, pharmaceutical and biological materials.
There are many applications where products, raw materials or biological samples need to be preserved and stored until they are required. One such preservation process is by freezing which results in the inhibition of unwanted chemical and biological degradation reactions. The effectiveness of the freezing of materials as a means of preservation and storage is generally influenced by both the rate at which the material is frozen and the terminal temperature at which it is finally held. The fine chemical, pharmaceuticals and biochemical industries often have especially precious and sensitive specialist materials and products to store. Other general trends and characteristics within these industries include:

common place use of inert gas atmospheres for product quality and Fire/explosion prevention during production and storage activities;
- a concern for and operating licences pertaining to environmental performance including: emissions to atmosphere, carbon foot print, and energy conservation and reduction, noise emissions etc;
- quality assurance, reliability, reproducibility are of major importance and are likely to form part of many drug production licensing, storage and distribution conditions; and
- increasing activity in the use of biological processes and materials for the synthesis of chemicals and pharmaceuticals (need for storage of biological seed cultures etc).

Traditionally there has been widespread use of mechanically refrigerated systems for the storage of many raw materials and end products. Such systems have many draw backs including:

the use of expensive, environmentally damaging and often toxic cooling media such as : CFC's , HCFCs, Ammonia etc.;
significant power requirements and poor energy conversion efficiencies;
high maintenance costs and poor reliability due to the inherent number of continuously moving components required, leaks and losses of cooling agents etc.;
limited cooling capacity and terminal storage temperatures (typically unable to reach temperatures below -40 °C).

Based on the above, the problem underlying the present invention is to provide a method and a system for cooling the above-stated materials which allows the user to cool said materials in an energy and cost efficient way.
This problem is solved by a method having the features of claim 1 as well as a system having the features of claim 7. Preferred embodiments of these aspects of the invention are stated in the corresponding sub claims and are described below.
According to claim 1, a method for cooling one of: a chemical, a pharmaceutical or a biological material is disclosed, wherein a liquid cryogen or a cold gas derived from a liquid cryogen (e.g. a gaseous phase of the liquid cryogen) is passed (e.g. from a container) to a heat exchanger that is arranged in a compartment in which said material is arranged in order to cool said material, wherein liquid cryogen or cold gas removes heat from its surroundings and the resultant warmer gas exiting the heat exchanger is preferably entirely clean and preferably with some further temperature and pressure conditioning is then re-used in the gaseous phase in another application.
In other words, material samples are particularly preserved in specially designed cryogenically cooled storage equipment. The equipment proposed is preferably to be cooled via indirect heat exchange, most preferably but not necessarily exclusively using a cryogenic liquid such as liquid Nitrogen. However, the benefit of the invention over and above the advantages of general cryogenic freezing (i.e. high levels of cooling capability, the maintenance of a safe breathable atmosphere (or and additional gas modified inerted atmosphere if storage conditions are enhanced and safe access controls are in place), reliability due to few moving parts, potentially very low terminal temperatures, quiet, low power requirement and small footprint - is that in this particular application, the pure cold cryogen exhaust gas is conditioned for re-use, e.g. as an ambient temperature gas supply.
According to a preferred embodiment of the present invention said further application is one of:

purging of a further compartment, component or material with the gaseous phase of the cryogen,
inerting of a further compartment, component or material with the gaseous phase of the cryogen when the gaseous phase is an inert gas,
or, when the gaseous phase comprises oxygen or is formed by oxygen, using the gaseous phase for respiration of a human or an animal (for example in hospitals where patients require e.g. cardio vascular support).

Here, in a preferred embodiment of the method and system according to the invention, the cryogen might be nitrogen - for which there is very often an existing demand for gaseous nitrogen for process uses such as purging and inerting etc.
In another embodiment of the present invention, the cryogen could be liquid oxygen, which might be particularly beneficial in hospitals, where biological samples need preservation and gaseous oxygen is required for patient support/respiration (e.g. of human or animal patients).
In either instance the proposed method or system has significant cost, operational, environmental, quality assurance and power consumption benefits over and above the conventionally refrigerated cold store systems.
If the customer already has a requirement for the "cryogen derived gas" then it will most probably be brought to site as a liquid and then vaporised using either ambient heat or other more costly heat sources (e.g. steam etc). The benefit of the proposed system is that the cooling requirement can potentially be met using this "waste" cold energy - thus being very beneficial in terms of reducing power/carbon footprint and potentially no additional running cost.
Furthermore, according to a preferred embodiment of the method according to the invention, compartment air may be circulated along the heat exchanger in order to cool said air and therewith said material arranged in said compartment. In a corresponding system, such a circulation may be achieved by means of at least one fan that is configured to move air along the heat exchanger.
According to a further aspect of the present invention, a system for cooling chemical, pharmaceutical or biological material, is provided, which system is particularly used in the method according to the invention.
According to claim 7, this system comprises a container for storing a liquid cryogen, a compartment for accommodating said material to be cooled, a heat exchanger arranged in said compartment and in fluid connection with said container so that liquid cryogen can be guided (e.g. from said container) into said heat exchanger, a conduit means being in fluid connection with the heat exchanger, which conduit means is configured to guide a gaseous phase of the cryogen (e.g. evaporated in the heat exchanger) out of said compartment, a further compartment and particularly a component arranged therein, the further compartment being in fluid connection with said conduit means so that said gaseous phase can be guided into said further compartment, preferably in order to purge said further compartment or said component arranged therein or in order to render said further compartment or said component arranged therein inert.
According to a preferred embodiment of the system according to the invention, said further compartment or component is one of or formed by one of an enclosure, a chemical reactor, a product drier (e.g. a centrifuge), or a chemical storage tanks etc.
Particularly, a flammable atmosphere and/or a solvent is present in said further compartment and/or component. Such a flammable (e.g. organic) solvent or gas may be one of e.g. xylene, toluene, acetone, or hydrogen etc.
According to an embodiment of the system according to the invention, the system comprises a further heat exchanger arranged in said compartment and in fluid connection with said container so that liquid cryogen or a gaseous phase derived from the liquid cryogen can be guided from said container into said further heat exchanger in order to cool said material.
The system then preferably further comprises a further conduit means being in fluid connection with the further heat exchanger, which further conduit means is configured to guide a gaseous phase of the cryogen from the further heat exchanger out of said compartment, the further compartment being in fluid connection with said further conduit means so that said gaseous phase can be guided into said further compartment in order to purge said further compartment or a component arranged in said further compartment or in order to render said further compartment or a component arranged in said further compartment inert
According to a further embodiment of the system according to the invention, the system is configured to alternately defrost the two heat exchangers and to use the heat exchanger that is not being defrosted for cooling said material in said compartment. Using the method according to the invention, the preservation/degradation of a material can be greatly influenced by the rate at which it is cooled, and the terminal temperatures at which it is then stored. Due to the formidable cooling capacity of cryogenic liquids, a cryogenic based cooling and storage solution offers greatly enhanced flexibility, controllability and terminal temperatures vs traditional mechanically refrigerated systems. Cryogenic cooling systems also offer very precise temperature control capability and potential terminal storage temperatures of -196 °C vs -40 °C for mechanical systems. Further, because they involve a compression stage, mechanical systems are often prone to noise and vibration. Many production facilities and hospitals have over time been surrounded by housing developments around their perimeters, and therefore neighborhood nuisance noise is often of great concern. On the other hand, cryogenic gases are typically natural, non polluting components derived from air and as such are not polluting when released back into the atmosphere - where as many chemically derived cooling fluids: CFC's, HCFC's etc contain chlorine atoms that become atmospheric ozone depleting radicals. Ammonia is another common refrigerant and is both highly toxic and flammable.
Further features and advantages of embodiments of the present method and system according to the invention shall be described below with reference to the Figure, wherein

Fig. 1 shows a schematical view of a method/system according to the invention.

Fig. 1 shows a system 1 and method for cooling chemical, pharmaceutical or biological material 6. The system 1 comprises a container 2 for storing a liquid cryogen C such as e.g. nitrogen or oxygen, a compartment 5 for accommodating said material 6 to be cooled, a heat exchanger 4 arranged in said compartment 5 and in fluid connection with said container 2. The system 1 further comprises a conduit means 7 being in fluid connection with the heat exchanger 4, which conduit means 7 is adapted to guide a gaseous phase C" of the cryogen from the heat exchanger 4 out of said compartment 5 where the gaseous cryogen C" can be re-used in another application 9. In beforehand the pressure and/or temperature of said gaseous phase C" may be adjusted so that it is suitable for the further application 9.
Particularly, the cryogen C may me guided into the heat exchanger 4 (or into the further heat exchanger 4', see below) in the liquid phase, Then, the cryogen C evaporates in the heat exchanger when cooling the material 6/compartment 5 to form the gaseous phase C". However, the cryogen C may also be guided into the heat exchangers 4 (and optionally heat exchanger 4') in the gaseous phase C' (i.e. as a cold gas) which then takes up heat in the heat exchanger 4 (and optionally heat exchanger 4'). The then warmer gaseous phase C" is then re-used in said other application 9. In other words, the heat exchangers 4, 4' can be operated with a liquid cryogen C or with a cold gas C" derived from the liquid cryogen C.
Now, the gaseous phase C" as generated in the heat exchanger 4 (and particularly also 4') may be used for purging or inerting a further compartment 10, or for purging or inerting a component or material 11, e.g. arranged in said further compartment 10. When the gaseous phase C" is used for inerting it preferably forms an inert gas, e.g. such as nitrogen.
However, the cryogen C may also be oxygen. Here, the gaseous phase C" may be used in the further compartment 10 for providing respiration, e.g. to a human 11 or animal 11 or for supporting a biological sample 11.
When the method according to the invention is conducted using the system 1, cryogen C is piped from the container 2 via conduit 3 into the heat exchanger 4 (or into heat exchanger 4', see below), where the cryogen C takes up heat stored in the compartment 5, particularly in the air or atmosphere therein, and in said material 6. Thus, said material 6 is cooled while the cryogen C is evaporated yielding a gaseous phase C" which is then guided via conduit means 7 towards its further use 9 described herein. Alternatively, as described above, the cryogen C may be evaporated to form a gold gas C' which is then guided into the heat exchanger 4 (or 4'). Cooling in the compartment 5 can be supported by circulating the air or atmosphere in the compartment 5 using a rotating fan 12 as indicated in Fig. 1
Whenever a moist atmosphere is cooled below zero degrees, then water from the atmosphere will condense and then freeze on cold surfaces, such as the surface of heat exchanger 4. If such ice build-ups were left to develop unchecked, then the ice could reach such an amount as to mechanically break, or insulate the heat exchangers so as to seriously and detrimentally affect cooling performance. Ice buildup and fouling would not be of concern if cooling were only to be required for short periods of time (e.g. 24hrs for batch processes) - in which case the ice could be defrosted naturally under normal ambient conditions when cooling was not required. However, coldstores often have to be operated continuously over extended periods of time
Therefore, as indicated in dashed lines in Fig. 1, the system or method according to the invention may use a further heat exchanger 4' arranged in said compartment 5 and in fluid connection with said container 2 so that liquid cryogen C or a gaseous phase C' derived from the liquid cryogen C can be guided (e.g. from said container 2) into said further heat exchanger 4'. For this, a further conduit means 7' may be in fluid connection with the further heat exchanger 4', which further conduit means 7' is configured to guide a gaseous phase C" of the cryogen C from the further heat exchanger 4' out of said compartment 5 into a further compartment 10 being in fluid connection with said further conduit means 7' so that said gaseous phase C" can be guided into said further compartment 10 in order to purge or render said further compartment 10 or a component 11 or material 11 arranged in said further compartment 10 inert.
Further, each heat exchanger 4, 4' is preferably mounted within an (e.g. open) container 4a. 4b when in use (hence allowing cold air to circulate throughout the coldstore or compartment 5). When ice buildup on the heat exchanger 4 reached a determined amount, cooling to the heat exchanger 4 would be isolated, its container 4a would be closed to isolate it from the general compartment 5 and the temperature raised within the container 4a to melt the ice and remove water. The melting of the ice could be done by: electric heater contained within the enclosure/container 4a, or using heated inert gas passed within the heat exchanger 4, or a combination of both. Whilst one heat exchanger 4 was being de-iced, the second heat exchanger 4' would be used to maintain cooling within the compartment 5 (and vice-versa).

Claims

Method for cooling one of: a chemical, a pharmaceutical or a biological material (6), wherein a medium comprising a liquid cryogen (C) and/or a gaseous phase (C') derived from a liquid cryogen (C) is passed to a heat exchanger (4) that is arranged in a compartment (5) in which said material (6) is arranged in order to cool said material (6), wherein said medium removes heat from its surroundings such that a resultant warmer gaseous phase (C") of the cryogen (C) is generated which is guided out of the compartment (5) and re-used in the gaseous phase in another application (9).
Method according to claim 1, characterized in that the temperature and/or pressure of said generated gaseous phase (C") is adjusted before re-using said gaseous phase in said other application (9).
Method according to claim 1 or 2, characterized in that the liquid cryogen (C) is one of: liquid nitrogen, or liquid oxygen.
Method according to one of the preceding claims, characterized in that said further application (9) is one of:
- purging of a further compartment (10), component (11) or material (11) with the gaseous phase (C") of the cryogen,

- inerting of a further compartment (10), component (11) or material (11) with the gaseous phase (C") of the cryogen (C) when the gaseous phase is an inert gas, preferably where flammable atmospheres/solvents are present in an enclosure, a chemical reactor, a product drier, a centrifuge, or a chemical storage tank, or preferably where materials are stored that are sensitive to spoilage due to contact or reaction with oxygen molecules,

- using the gaseous phase, preferably comprising oxygen, for respiration (9) of a human (11) or an animal (11).
Method according to one of the preceding claims, characterized in that compartment air or atmosphere is circulated along the heat exchanger (4) in order to cool said air or atmosphere and therewith said material (6) arranged in said compartment (5).
Method according to one of the preceding claims, characterized in that a further heat exchanger (4') is used, wherein the two heat exchangers (4, 4') are alternately defrosted, wherein the heat exchanger (4', 4) which is not being defrosted is used to cool said material (6) in said compartment (5).
System (1) for cooling a chemical, pharmaceutical or biological material (6), comprising: a container (2) for storing a liquid cryogen (C), a compartment (5) for accommodating said material (6) to be cooled, a heat exchanger (4) arranged in said compartment (5) and in fluid connection with said container (2) so that liquid cryogen (C) or a gaseous phase (C') derived from the liquid cryogen (C) can be guided into said heat exchanger (4), a conduit means (7) being in fluid connection with the heat exchanger (4), which conduit means (7) is configured to guide a gaseous phase (C") of the cryogen (C) from the heat exchanger (4) out of said compartment (5), and a further compartment (10) being in fluid connection with said conduit means (7) so that said gaseous phase (C") can be guided into said further compartment (10) in order to purge said further compartment (10) or a component (11) arranged in said further compartment (10), or in order to render said further compartment (10) or a component (11) arranged in said further compartment (10) inert.
System according to claim 7, characterized in that a flammable atmosphere and/or solvent is present in said further compartment and/or component.
System according to claim 7 or 8, characterized in that said further compartment or said component is formed by one of: a chemical reactor, a product drier, a centrifuge, a chemical storage tank.
System according to one of the claims 7 to 9, characterized in that the system comprises a further heat exchanger (4') arranged in said compartment (5) and in fluid connection with said container (2) so that liquid cryogen (C) or a gaseous phase (C') derived from the liquid cryogen (C) can be guided from into said further heat exchanger (4').
System according to claim 10, characterized in that the system is configured to alternately defrost the two heat exchangers (4, 4') and to use the heat exchanger that is not being defrosted for cooling said material (6) in said compartment.