Medical contact shock freezer

Abstract

A medical contact shock freezer (10, figure 1) for fast freezing a plurality of individual bags containing a medical liquid (e.g. blood plasma) comprises a first pair of freezing plates comprising a f

Description

[1] This invention relates to a medical contact shock freezer and methods for fast freezing a plurality of individual bags containing a medical liquid, notably blood plasma. [2] Blood plasma bags are commonly used to store, transport and dispense blood plasma and comprise flexible plastics walls which may be made of polyethylene, polypropylene or plasticized PVC. In order to ensure plasma quality, once the plasma has been obtained, for example by plasmapheresis, it is desirable for the plasma contained within a filled, sealed plasma bag to be completely frozen to a temperature of -30°C or less within a short time period. The step of rapidly freezing the plasma, for example from its collection temperature or from room temperature to -30°C, is facilitated by use of a contact shock freezer in which a plurality of plasma bags are pressed between cooling plates which are chilled by a circulating coolant. Once frozen, the plasma bags are transferred to a medical storage freezer which may be maintained at a temperature of -30°C, -50 °C or below. [3] Contact shock freezers require a high refrigeration power in order to rapidly remove a significant quantity of heat from the sealed plasma bags. Consequently, contact shock freezers have typically been based on refrigeration circuits which use large, high power semi-hermetic compressors and large quantities of refrigerants. An alternative approach for a contact shock freezer of blood plasma bags is disclosed in WO 2023 / 285652 A1 which uses a cascade refrigeration circuit comprising a first stage refrigerant circulating in a first stage refrigeration circuit, a second stage refrigerant circulating in second stage refrigeration circuit and an inter-stage heat exchanger. The second stage refrigerant passes through each of a pair of freezing plates to freeze plasma bags clamped between the freezing plates. [4] The power requirements for storage freezers to which the shock frozen plasma bags are transferred is significantly lower and the cooling circuits for such medical storage freezers are thus designed accordingly. [5] In accordance with one of its aspects, the present invention provides a medical contact shock freezer in accordance with claim 1. Other aspects are defined in other independent claims. The dependent claims define preferred or alternative features. [6] In one of its aspects, the present invention is based upon the realisations that: - a practical way to improve the rapid freezing of blood plasma in individual blood plasma bags from room temperature to -30°C using a contact shock freezer is to separate freezing of the blood plasma into at least two different cooling phases comprising i) a first cooling phase during which bags of liquid blood plasma are frozen to an intermediate frozen product temperature by operating the freezing plates at a first cooling phase temperature, for example about -20°C and ii) a second cooling phase during which the temperature of the frozen blood plasma is further reduced to a lower temperature, for example -30°C, by operating the freezing plates at a lower, second cooling phase temperature, for example about -40°C; - that such separation of the cooling cycle can be used to optimise the combination of freezing time and power required for freezing; - that one advantageous way of implementing such a cooling cycle is i) to use a high first phase refrigerant mass flow rate during the first cooling phase, the combination of the high refrigerant mass flow rate and the “intermediate” first cooling phase temperature being effective to rapidly reduce the temperature of the blood plasma from room temperature to an “intermediate” frozen blood plasma temperature, for example a first phase frozen blood plasma temperature of about -15 °C, and ii) to subsequently use a lower, second phase refrigerant mass flow rate during the second cooling phase, the combination of the lower, second phase refrigerant mass flow rate and the lower second cooling phase temperature being effective to further reduce the temperature of the frozen blood plasma from the “intermediate” temperature to a required final temperature, for example a final temperature of about -30 °C; - that one particularly advantageous way of implementing this is by using a single stage vapour compression refrigeration circuit (as opposed to a cascade refrigeration circuit), notably using a single speed compressor, and an expansion valve which can provide at least a first throttling effect and a second (greater) throttling effect. [7] As used herein, the term contact shock freezer means a freezing device which is configured to clamp individual bags containing a liquid medical product, notable blood plasma, between a pair of freezing plates such that the surfaces of the bags are flattened prior to and during a freezing process; this increases the contact area and improves heat transfer. Sufficient force may be applied to clamp the bags between the freezing plates such that a pressure which is >0.1 bar or >0.2 bar and / or <0.5 bar is generated in the medical liquid within the bags. [8] During the first cooling phase, the initially liquid medical product is frozen to an “intermediate” temperature, for example about -15°C, and during the second cooling phase the temperature of the medical product is further reduced to a desired end temperature, for example about -30°C. As used herein, the terminology “first cooling phase” and “second cooling phase” indicates separate, distinct cooling phases in which the configuration and / or operating conditions of the cooling circuit are different. For example, the mass flow rate of the refrigerant in the refrigeration circuit may be greater during the first cooling phase than during the second cooling phase. Thus, switching between the “first cooling phase” and the “second cooling phase” involves a change in the configuration and / or operating conditions of the cooling circuit. [9] Preferably, the amount of heat removed from the medical product during the first cooling phase is greater than the amount of heat removed from the medical product during the second cooling phase. For example, particularly where the liquid medical product is blood plasma, with respect to the total amount of heat removed from the medical product in reducing its temperature from a) its initial temperature when first arranged between the first and second freezing plates at the start of the first cooling phase and b) its second cooling phase product temperature (i.e. its temperature at the end of the second cooling phase when the medical product has reached a desired temperature at which it will be removed from the contact shock freezer for subsequent storage), at least 75% of the heat is removed during the first cooling phase and no more than 25% of the heat is removed during the second cooling phase, and preferably at least 80% of the heat is removed during the first cooling phase and no more than 20% of the heat is removed during the second cooling phase.

[10] Particularly where the liquid medical product is blood plasma: - the first cooling phase product temperature (i.e. the temperature of the medical product at the end of the first cooling phase) is preferably in the range -5 °C to -20 °C, more preferably in the range -10° C to -18°C; and - the second cooling phase product temperature is preferably in the range -30 °C to -50 °C, more preferably in the range -30° C to -35°C. This provides an advantageous way of reaching the desired end temperature.

[11] Particularly where the liquid medical product is blood plasma: - during the first cooling phase, the first and second freezing plates may be operated at a first cooling phase freezing plate temperature in the range -5 °C to -25°C; and - during the second cooling phase, the first and second freezing plates may be operated at a second cooling phase freezing plate temperature in the range -35 °C to -55°C, preferably at a second cooling phase freezing plate temperature in the range -35°C to -45°C. This is arranged by appropriate configuration of the evaporation temperature of the refrigerant (i.e. the temperature of the refrigerant immediately after the expansion valve in the refrigeration circuit) during the first cooling phase and during the second cooling phase. The evaporation temperature of the refrigerant will generally be the same as the temperature of the refrigerant at the entry to the evaporator in the refrigeration circuit (allowing for some heat losses). Therefore, the temperature of the refrigerant at the entry to the evaporator can be used as an indication of the evaporation temperature of the refrigerant.

[12] One advantageous configuration involves arranging for the first cooling phase refrigerant mass flow rate (ie. the mass flow rate of the refrigerant during the first cooling phase) to be greater than that during the second cooling phase; this facilitates a high rate of heat transfer from the medical product during the first cooling phase. As used herein the term “refrigerant mass flow rate” means the mass of the refrigerant per second that is circulated through the refrigeration circuit by the compressor. Preferably, the refrigerant mass flow rate i) is constant during the first cooling phase and ii) is constant during the second colling phase (but lower than during the first cooling phase). If the refrigerant mass flow rate is not constant during the first cooling phase or during the second cooling phase then the average refrigerant mass flow rate during the respective cooling phase(s) should be considered.

[13] It is preferable for the first freezing plates to form part of the first vapour refrigeration circuit and for the second freezing plates to form part of a second (separate) vapour refrigeration circuit so that i) the first refrigeration circuit evaporator comprises the first freezing plate (but not the second freezing plate) and ii) the second refrigeration circuit evaporator comprises the second freezing plate (but not the first freezing plate). This separation, with each of the first and second freezing plates being cooled by its own, individual and dedicated cooling circuit, allows the first and second refrigeration circuits to provide, in combination, a desirable amount of refrigeration power using readily available components for the refrigeration circuits. This is unlike the refrigeration circuits used in currently commercialised contact shock freezer which use a single, high power refrigeration circuit to cool a pair of freezing plates. Preferably, each refrigeration circuit of the medical contact shock freezer has a Plasma Bag Refrigeration Power of at least 6.5 kg per hour, preferably at least 7.5 kg per hour. As used herein, the term “Plasma Bag Refrigeration Power” means the amount of blood plasma per hour that the refrigeration circuit can cool from +20°C to -30°C when the blood plasma is provided, in the usual way, in plasma bags which are clamped between the first and second freezing plates. For example, an arrangement in which identical first and second refrigeration circuits which, when operating together can cool 7.5 kg of blood plasma evenly distributed in 30 plasma bags from +20 °C to -30 °C in 30 minutes has a total Plasma Bag Refrigeration Power of 15 kg per hour with each of the refrigeration circuits having a Plasma Bag Refrigeration Power of 7.5 kg per hour. The Plasma Bag Refrigeration Power should be assessed in respect of the contact shock freezer when operated in its usual way, notably when operated in accordance with operation guidance provided by its manufacturer.

[14] The medical contact shock freezer is preferably configured to freeze at least 12 individual 350 ml plasma bags, each containing 250ml of blood plasma from 25°C to -30 °C in 60 minutes or less, preferably 45 minutes or less. This allows for commercial operation. One of the challenges in providing devices and methods for rapid freezing of blood plasma is to allow for freezing of a large number of plasma bags within a short freezing time using simple, relatively low power equipment.

[15] Each bag to be frozen may contain a quantity of medical liquid, notably blood plasma, which is >150 ml, >200 ml or >250 ml and / or <1000 ml, <850 ml, <500 ml or <450 ml or <350 ml. Each bag may have a nominal volume of 500 ml; in this case, each bag may contain about 250 ml of medical liquid, notably blood plasma, for example from a whole blood donation of 500 ml. Each bag may have a nominal volume of 1000 ml; in this case, each bag may contain about 850 ml of medical liquid, notably blood plasma, for example from plasmapheresis.

[16] It is particularly surprising that the refrigeration circuit(s) of the contact shock freezer can be configured using a hydrocarbon refrigerant, notably R290 (propane); hydrocarbon refrigerants are more environmentally friendly but generally less efficient that the refrigerants traditionally used in high power contact shock freezer refrigeration circuits. Thus, the present invention provides, in one of its aspects, a surprising way of providing a contact shock freezer which uses an environmentally friendly hydrocarbon refrigerant, notably in a quantity of less than 400g per refrigeration circuit, preferably less than 300g per refrigeration circuit and more preferably less than 200g per refrigeration circuit which avoids the need for large refrigerant quantities and mitigates risks associated with flammability. The use of a hydrocarbon refrigerant avoids the need to use refrigerant gasses in a contact shock freezer whose use is less desirable or outlawed, for example CFCs (ChloroFluoroCarbons), HCFCs (HydroChloroFluoroCarbons) and HFCs (HydroFluoroCarbons). The use of R290 (propane) as the refrigerant is particularly preferred notably for its refrigerant properties combined with its availability (which facilitates replacement if this becomes necessary). Nevertheless, the refrigerant may be a mixed refrigerant comprising at least 80 wt% R290 (propane); a mixed refrigerant comprising at least 80 wt% R290 (propane) and at least 5 wt% R600a (isobutane), for example a mixed refrigerant comprising about 80 wt% R290 (propane) and about 10 wt% R600a (isobutane); a mixed refrigerant comprising at least 80 wt% R290 (propane) and at least 5 wt% R170 (Ethane), for example a mixed refrigerant comprising about 90 wt% R290 (propane) and about 10 wt% R170 (Ethane); R1270 (propylene); a mixed refrigerant comprising at least 80 wt% R1270 (propylene); a mixed refrigerant comprising at least 80 wt% R1270 (propylene) and at least 5 wt% R600a (isobutane), for example a mixed refrigerant comprising about 90 wt% R1270 (propylene) and about 10 wt% R600a (isobutane); a mixed refrigerant comprising at least 80 wt% R1270 (propylene) and at least 5 wt% R170 (ethane), for example a mixed refrigerant comprising about 90 wt% R1270 (propylene) and about 10 wt% R170 (ethane). As used herein, reference to a refrigerant by its “R” number, for example R290 (propane) means “refrigerant grades” of the materials i.e., grades (which are generally less than 100% pure) which are intended for and used for refrigeration applications. For example, R290 (propane) preferably and generally has a purity of at least 97.5 %.

[17] The expansion valve of each vapour compression refrigeration circuit is preferably an expansion valve which is switchable between a first cooling phase configuration in which it provides a first throttling effect and a second cooling phase configuration in which it provides a second, greater throttling effect. As used herein the term “throttling effect” is the resistance to flow of the refrigerant provided by the expansion valve so that, for a refrigerant provided at an inlet to the expansion valve at the same pressure and temperature, the greater the throttling effect of the expansion valve, the lower the mass flow rate of refrigerant through the expansion value will be. Thus, increasing the throttling effect of the expansion valve (with the refrigerant provided at the inlet to the expansion valve at the same pressure and temperature) decreases the evaporation temperature of the refrigerant. Thus, in preferred configurations, i) during the first cooling phase the expansion valve is configured to provide a first throttling effect and ii) during the second cooling phase the expansion valve is configured to provide a second, greater throttling effect. This can be used such that i) during the first cooling phase there is a high mass flow rate of the refrigerant which provides for a high heat transfer rate to rapidly remove heat from the medical product (but with a first phase refrigerant evaporation temperature that is higher than the desired final temperature of the medical product) and ii) during the second cooling phase the evaporation temperature of the refrigerant is lower than the first phase refrigerant evaporation temperature and sufficiently low to cool the medical product to its desired final temperature (but the mass flow rate of the refrigerant is lower during the second cooling phase so that the heat transfer rate from the medical product is also lower during the second cooling phase). It is particularly preferable to operate this arrangement using a single speed compressor (as opposed to a variable speed compressor); single speed compressors are compact, readily available and highly reliable and their use as part of the refrigeration circuit disclosed provides an advantageous way of achieving the advantages disclosed herein.

[18] One particularly advantageous way of configuring the expansion valve is using a first capillary tube which provides the first throttling effect, a second capillary tube which provides the second throttling effect and a switching valve, notably in which the switching valve has - a first cooling phase configuration in which the first capillary tube is connected to its refrigeration circuit and, -a second cooling phase configuration in which the first capillary tube is disconnected from its refrigeration circuit and the second capillary tube is connected to its refrigeration circuit. This implements the desired configuration of the expansion valve using simple, reliable and readily available components. The lengths and internal diameters of the first and second capillary tubes may selected from configuration consisting of i) the internal diameter of the first capillary tube being larger than the internal diameter of the second capillary tube; ii) the length of the first capillary tube being less than the length of the second capillary tube; and, iii) the internal diameter of the first capillary tube being larger than the internal diameter of the second capillary tube and the length of the first capillary tube being less than the length of the second capillary tube. Each of these configurations can provide a configuration in which the second throttling effect is greater than the first throttling effect. It is particularly preferred for the first and second capillary tubes to have the same internal diameter and for the length of the first capillary tube to be less than the length of the second capillary tube; this simplifies the components required. The first and second capillary tubes may be arranged in series in the refrigeration circuit; alternatively, they may be arranged in parallel. When the first and second capillary tubes are arranged in series in the refrigeration circuit, a bypass for the second capillary tube is preferably provided, notably operable by valve (preferably a solenoid valve) so that, during the first cooling phase the refrigerant flows through the first capillary tube but bypasses the second capillary tube and during the second cooling phase, the refrigerant flow through both the first and the second capillary tubes. When the first and second capillary tubes are arranged in parallel in the refrigeration circuit, a) a valve is preferably provided, notably a solenoid valve, to prevent flow of the refrigerant through the first capillary tube during the second cooling phase (so that, during the second cool phase, the entire flow of the refrigerant is through the second capillary tube) and b) during the first cooling phase either i) a valve, notably a solenoid valve, may prevent flow of the refrigerant through the second capillary tube or ii) a portion of the refrigerant may flow through the first capillary tube and another portion of the refrigerant may flow through the second capillary tube with the portions being recombined at the outlet of the expansion valve.

[19] The expansion valve may be configured such that, if the refrigerant is R290 (propane) supplied to the expansion valve at an inlet pressure of 10 bar and an inlet temperature of 25 °C, - the first throttling effect provides the R290 (propane) with a outlet pressure of less than 3 bars and an outlet temperature of less than -18 °C; and - the second throttling effect provides the R290 (propane) with a outlet pressure of less than 1.5 bars and an outlet temperature of less than - 30 °C. This provides a particularly advantageous set of conditions, notably when the medical product is blood plasma. For example, the refrigeration circuit may be arranged using R290 (propane) as the refrigerant with a condensing temperature of 25 °C and a condensing pressure of 10 bars, a first phase evaporation temperature of -20 °C at 2.4 bars and a second phase evaporation temperature of -40 °C at 1.1 bars.

[20] Each compressor may be a three phase compressor; in general three phase compressors are used in contact shock freezers to provide high compressor power. Surprisingly, each compressor of the contact shock freezer disclosed herein may be a single phase compressor, preferably a single speed and single phase compressor whilst still providing a commercially useful freezing power, notably such that each refrigeration circuit has a Plasma Bag Refrigeration Power of at least 6.5 kg per hour. The use of a single phase compressor simplifies the arrangement by allowing the contact shock freezer to be operated using a single phase electricity supply; when the compressor is a single speed and single phase compressor reliable, readily available compressors can be used.

[21] The first pair of freezing plates may comprise an upper freezing plate and a lower freezing plate, with the upper freezing plate being arranged above the lower freezing plate. This provides a convenient arrangement, notably where each of the upper and lower freezing plates are horizontal or substantially horizontal.

[22] The contact shock freezer may comprise a single pair of freezing plates. Alternately, the contact shock freezer may comprise two (and only two) pairs of freezing plates.

[23] Preferably, one of the freezing plates of a pair of freezing plates is immobile and does not move during normal operation of the contact shock freezer with the other freezing plate of the pair being a moveable freezing plate; this provides a mechanically advantageous arrangement. An arrangement in which the contact shock freezer comprises: a first pair of upper and lower freezing plates and a second pair of upper and lower freezing plates, the first pair being arranged above the second pair; in which the first pair of upper and lower freezing plates comprises an immobile lower freezing plate and a moveable upper freezing plate; and in which the second pair of upper and lower freezing plates comprises an immobile upper freezing plate and a moveable lower freezing plate; and notably in which the lower freezing plate of the first pair of freezing plates and the upper freezing plate of the second pair of freezing plates are provided by a single, integrated freezing plate, provides a compact and convenient arrangement for providing two pairs of freezing plates to enable simultaneous freezing of a large number of individual bags whilst minimising the footprint of the shock freezer and facilitating loading and unloading.

[24] The first and second pairs of freezing plates are preferably arranged with one pair above the other. Preferably, the refrigeration circuit(s) of each pair of freezing plates are independently operable, that is to say, that one pair of freezing plates can be operated without the other. This enables each pair of the two pairs of freezing plates to be operated independently, for example in the event of the capacity of one pair of freezing plates being sufficient for the number of bags it is desired to freeze simultaneously. Where independently operable first and second pairs of freezing plates are provided, the components and configuration of the refrigeration circuit(s) for each pair of freeing plates are preferably identical or substantially identical; this facilitates assembly and maintenance. Thus, the disclosure herein in relation to the components, configuration and arrangement of one of the pairs of freezing plates applies equally to the equivalent components, configuration and arrangement of the other pair of freezing plates.

[25] Each pair of freezing plates is preferably substantially horizontal; this facilitates loading and unloading of the individual bags, for example by arranging the individual bags of medical liquid to be frozen on a heat conductive tray and loading the tray carrying the individual bags between the freezing plates when in their loading position. Thus, to facilitate loading and unloading, the freezing plates are preferably arranged at an angle of less to 30° to the horizontal. An improvement in the freezing cycle can be obtained by arranging the freezing plates at a small angle to the horizontal, for example at an angle of at least 2° or at least 3° with respect to the horizontal; this helps to mitigate against unintentional inclusion of air in the bags. An angle of between 3° and 10°, notably 5°, to the horizontal provides an advantageous effect combined with a configuration which facilitates loading and unloading of the bags.

[26] The or each pair of freezing plates may define an operating surface, that is to say a surface at which individual bags can be arranged for freezing, which has an area >0.25 m2, >0.3 m2, >0.4 m2, >0.5 m2, >0.55 m2, >0.7 m2 or >0.8 m2 and / or <1.4 m2, <1.3 m2 <1.2 m2 or <1 m2. For example, the or each pair of freezing plates may define an operating surface which has: - a width that is >0.4m, >0.5, >0.6m, >0.7m, >0.8m or >0.9m and / or <1.6m, <1.5m, <1.2m or less than 1.1m; and / or - a depth that is >0.5m, >0.6m and / or <1.1 m, <1 m or <0.9m. Such dimensions facilitate loading of the bags by an operator. The or each pair of freezing plates may be configured and / or dimensioned to simultaneously freeze >9 bags, >12 bags, >16 bags, >21 bags or >30 bags and / or <50, <48, <40 or <32 bags, notably 500 ml nominal volume bags. For example, the or each pair of freezing plates may be configured and / or dimensioned to simultaneously freeze 3, 4, 5, 6, 7 8 or 9 rows of bags arranged across its width with 3 or 4 bags in each row arranged along its depth, notably bags having a nominal volume of 500 ml. Particularly in the case of bags containing between 150 ml and 355 ml of medical liquid to be frozen, individual bags may be stacked one on another to form i) a first layer of bags, each bag in the first layer having a lower side which is in contact with the contact surface of a lower freezing plate of a pair of freezing plates and ii) a second layer of bags, each bag in the second layer having a lower side which sits on an upper side of a bag in the first layer of bags and an upper side which, in the freezing position, is in contact with the contact surface of an upper freezing plate of the pair of freezing plates. Preferably, each bag has an outlet from which the medical liquid will be extracted, and the outlet is arranged facing the rear of the shock freezer.

[27] The time required to attain a core temperature of the medical liquid in the bags of -30 °C is preferably <60 minutes, more preferably <50 minutes or even more preferably <45 minutes, notably when the freezing plates are fully loaded with bags to be frozen at an initial temperature of 20 °C, notably bags each containing >200 ml or >250 ml and / or <1000 ml or <850 ml of blood plasma. Preferably, such a freezing performance is achieved with an initial temperature which is >25°C, >30°C or >32°C and / or <35°C.

[28] The movement of the freezing plate(s) from the loading position to the freezing position is preferably a linear movement, notably a vertical linear movement, without rotation of either freezing plate. This facilitates accurate clamping of the plurality of bags between the plates. Preferably, the freezing plates are parallel in their freezing position and remain parallel during movement between the loading and the freezing position. This further facilitates accurate clamping of the plurality of bags. The use of parallel and preferably planer freezing plates is also advantageous when it is desired for the shock freezer to be useable in a configuration having two layers of bags arranged between a pair of freezing plates. Preferably, the angle of each freezing plate to the horizontal is fixed, that is to say this angle does not change; each freezing plate may be fixed in rotation so that it cannot rotate. At least one of the upper and lower freezing plates of a pair of freezing plates may be associated with a linear drive to affect its movement from the loading to the freezing position, for example one or more pneumatic or hydraulic cylinders, notably a pair of spaced cylinders, for example arranged at opposite sides of the freezing plate. The movement may be guided by a linear guide arrangement, for example comprising a linear guide arranged at each of the left and right sides of the freezing plate. Each linear guide may comprise a pair of, preferably vertical, tubular guide elements which together guide the movement.

[29] In accordance with a further aspect, the present invention provides a method of fast freezing a plurality of individual bags of liquid blood plasma to provide frozen blood plasma, the method comprising: - clamping the plurality of individual bags of liquid blood plasma between a first freezing plate and a second freezing plate of a medical contact shock freezer, notably a medical contact shock freezer as disclosed herein, the medical contact shock freezer comprising a first vapour compression refrigeration circuit configured to circulate a first refrigeration circuit refrigerant, preferably a hydrocarbon refrigerant, sequentially through a first refrigeration circuit compressor, a first refrigeration circuit condenser, a first refrigeration circuit expansion valve, a first refrigeration circuit evaporator and back to the first refrigeration circuit compressor; - operating the first vapour compression refrigeration circuit in a first cooling phase to reduce the temperature of the liquid blood plasma to provide frozen blood plasma at a first cooling phase blood plasma temperature by operating the first and second freezing plates at a first cooling phase freezing plate temperature in the range -5 °C to -25°C, preferably in the range -15 °C to -25°C; and - subsequently operating the first vapour compression refrigeration circuit in a second cooling phase to reduce the temperature of the frozen blood plasma from the first cooling phase blood plasma temperature to a lower, second cooling phase blood plasma temperature by operating the first and second freezing plates at a second cooling phase freezing plate temperature in the range -35 °C to -50°C, preferably in the range -35 °C to -45°C.

[30] Aspects disclosed herein in relation to one specific aspect of the invention may be used according to any other aspect to the invention.

[31] An embodiment of the invention will now be described, by way of example only, with reference to the accompanying drawings, of which: Fig 1 is a schematic view of a medical contact shock freezer; Fig 2 is a schematic circuit diagram of a first and second refrigeration circuit; and Fig 3 is a schematic circuit diagram of a third and fourth refrigeration circuit.

[32] The medical contract shock freezer 10 shown in Fig 1 comprises upper 111 and lower 211 freezing plates of a first pair of freezing plates 11 and upper 311 and lower 411 freezing plates of a second pair of freezing plates 12 , each pair of freezing plates having the same footprint (for example about 1 m wide by about 0.8 m deep) with the first pair of freezing plates 11 being arranged above the second pair of freezing plate 12 within the same footprint. The lower freezing plate 211 of the first pair of freezing plates and the upper freezing plate 311 of the second pair of freezing plates are provided by a single, immobile, structure in which each of the freezing plates 211, 311 is integrated. Each of the freezing plates 111, 211,311,411 is arranged at an angle of 5° to the horizontal sloping downwards from the rear of the contact shoch freezer to the front.

[33] Fig 1 shows the freezing plates 111, 211, 311, 411 in their loading position in which sufficient separation is provided between the freezing plates of each pair to allow a heat conductive tray carrying individual bags of blood plasma (for example a heat conductive tray carrying fifteen individual bags, each containing 250 ml of blood plasma arranged in five rows in the width direction and three rows in the depth direction of the contact shock freezer) to be loaded between each pair of freezing plates prior to freezing. The loading position is also used during removal of the frozen plasma bags from between each pair of freezing plates subsequent to the freezing operation. In order to clamp the plasma bags between their respective freezing plates for the freezing operation, the moveable freezing plate 111 of the first pair of freezing plates is moved vertically, linearly downwardly by vertically arranged hydraulic cylinders to clamp plasma bags between the first pair of freezing plates and the moveable freezing plate 411 of the first pair of freezing plates is moved vertically, linearly upwards by vertically arranged hydraulic cylinders to clamp plasma bags between the second pair of freezing plate. These movements are reversed to move from the freezing position to the loading position.

[34] The contact shock freezer is configured to operate: i) in a first cooling phase during which its refrigeration circuit(s) are operated so that its refrigerant(s) are circulated in a steady state to provide a first cooling phase evaporation temperature of, for example, -20°C and ii) in a subsequent second cooling phase during which its refrigeration circuit(s) are operated so that its refrigerant(s) are circulated in a steady state to provide a lower, second cooling phase evaporation temperature of, for example, -40°C. The first cooling phase is used to reduce the temperature of blood plasma from room temperature or collection temperature (generally about 20°C to 25°C) to a temperature below freezing, for example about -15°C, and the second cooling phase is used to further reduce the temperature of the blood plasma from this intermediate temperature to a lower temperature, typically -30°C, at which the frozen blood plasma can be introduced into a storage freezer.

[35] Fig 2 schematically shows i) a first refrigeration circuit 100 which includes the first refrigeration circuit evaporator 111 provided by the first freezing plate and ii) a second refrigeration circuit 200 which includes the second refrigeration circuit evaporator 211 provided by the second freezing plate.

[36] The first refrigeration circuit is configured to circulate a first refrigeration circuit refrigerant sequentially through a first refrigeration circuit compressor 101, a first refrigeration circuit condenser 104 which is preferably a finned condenser cooled by air circulation generated by a condenser fan 105, a first refrigeration circuit filter dryer 106, a first refrigeration circuit expansion valve 107, the first refrigeration circuit evaporator 111, a first refrigeration circuit 2-phase separator 112 and back to the first refrigeration circuit compressor 101. The first refrigeration circuit compressor is associated with an oil separator 102 and a pressostat 103.

[37] The first refrigeration circuit expansion valve 107 comprises i) a first capillary tube 108 having, for example, an internal diameter of 1mm and a length of 0.5m, ii) a second capillary tube 109 having, for example, an internal diameter of 1mm and a length of 1.4m and iii) a switching valve 110, for example a solenoid valve. In the first cooling phase configuration, the switching valve 110 connects the first capillary tube 108 to the first refrigeration circuit 100 so that the refrigerant circulated through the first refrigeration circuit by the first refrigeration circuit compressor 101 flows through the first capillary tube 108. In the first cooling phase some of the refrigerant also flows through the second capillary tube 109. Due to a higher flow resistance of the second capillary tube 109, the mass flow rate of the portion of the refrigerant that flows through the first capillary tube it greater than that of the portion that flows through the second capillary tube. Expansion of the refrigerant by passage though the expansion valve 107 during the first cooling phase results in a first cooling phase evaporation temperature of the refrigerant, i.e. the temperature of the refrigerant immediately after expansion valve 107 (in this case once the flows through the first 108 and second 109 capillary tubes are recombined) of, for example -20 °C. At the end of the first cooling phase the solenoid valve 110 is switched so that it disconnects the first capillary tube 108 from the refrigeration circuit 100 and prevents refrigerant from the compressor 101 passing through the first capillary tube 108. As a result, all of the refrigerant circulated by the compressor 101 is directed through the second capillary tube 109. The second capillary tube has a greater throttling effect than the first capillary tube, for example due to having the same internal diameter but a greater length; consequently, during the second cooling phase the second cooling phase evaporation temperature of the refrigerant (i.e. the temperature of the refrigerant immediately after the expansion valve 107) is lower than during the first cooling phase, for example it is about -40 °C and the mass flow rate of the refrigerant in the refrigeration circuit during the second cooling phase is lower than during the first cooling phase.

[38] The second vapour compression refrigeration circuit 200 has the same configuration as the first refrigeration circuit 100; its components are the same as the equivalent components of the first refrigeration circuit 100 and it operates in the same way.

[39] The first 100 and second refrigeration circuits 200 are operated together so that the first refrigeration circuit 100 removes heat from the first evaporator plate 111 of the pair of freezing plates 11 and the second refrigeration circuit removes heat from the second evaporator plate 211 of the pair of freezing plates 11. Thus, each refrigeration circuit includes only one of the freezing plates 111,211. It is advantageous for the direction of flow 113 of the first refrigeration circuit refrigerant through the first freezing plate 111 to be in the opposite direction to the direction of flow 213 of the second refrigeration circuit refrigerant through the second freezing plate 211. This helps to ensure that each plasma bags clamped between the plates 111, 211 has the same or a very similar cooling rate during freezing, irrespective of the position of a particular plasma bag in an array of plasma bags.

[40] One preferred configuration for such a system uses the parameters set out in Table 1 for the first refrigeration circuit: Table 1 compressor Single speed R290 compressor, 220-240 V 50Hz, 1.25 hp refrigerant R290 (propane) first capillary tube Copper, 0.5m long, internal diameter 1mm second capillary tube Copper, 1.5m long, internal diameter 1mm first cooling phase evaporation temperature of the refrigerant - 20°C second cooling phase evaporation temperature of the refrigerant - 40 °C with the same parameters being used for the second refrigeration circuit. These first and second refrigeration circuits together provide a heat removal capacity during the first cooling phase of 1450 W, a heat removal capacity during the second cooling phase of 550 W and are capable of reducing the temperature of 7.5kg of blood plasma form 25°C to -30 °C in 28 5 minutes.

[41] Fig 3 schematically shows i) a third refrigeration circuit 300 which includes the third refrigeration circuit evaporator 311 provided by the third freezing plate and ii) a fourth refrigeration circuit 400 which includes the fourth refrigeration circuit evaporator 411 provided by the second freezing plate. These are configured and operate in the same way at the first 10 100 and second 200 refrigeration circuits.

[42] Reference numbers 10 medical contract shock freezer 11 first pair of freezing plates 12 second pair of freezing plates 100 first refrigeration circuit 101 first refrigeration circuit compressor 102 oil separator 103 pressostat 104 condenser 105 condenser fan 106 filter dryer 107 expansion valve 108 first capillary tube 109 second capillary tube 110 switching valve 111 evaporating plate 112 2-phase separator 113 direction of flow of refrigerant through evaporating plate 200 second refrigeration circuit 201 second refrigeration circuit compressor 202 oil separator 203 pressostat 204 condenser 205 condenser fan 206 filter dryer 207 expansion valve 208 first capillary tube 209 second capillary tube 210 switching valve 211 evaporating plate 212 2-phase separator 213 direction of flow of refrigerant through evaporating plate 300 third refrigeration circuit 301 third refrigeration circuit compressor 302 oil separator 303 pressostat 304 condenser 305 condenser fan 306 filter dryer 307 expansion valve 308 first capillary tube 309 second capillary tube 310 switching valve 311 evaporating plate 312 2-phase separator 313 direction of flow of refrigerant through evaporating plate 400 fourth refrigeration circuit 401 fourth refrigeration circuit compressor 402 oil separator 403 pressostat 404 condenser 405 condenser fan 406 filter dryer 407 expansion valve 408 first capillary tube 409 second capillary tube 410 switching valve 411 evaporating plate 412 2-phase separator 413 direction of flow of refrigerant through evaporating plate

Claims

1. A medical contact shock freezer configured for fast freezing a plurality of individual bags of a liquid medical product, notably liquid blood plasma, to provide a frozen medical product, notably frozen blood plasma, the contact shock freezer comprising:- a first pair of freezing plates comprising a first freezing plate and a second freezing plate configured so that the individual bags of the liquid medical product can be clamped between the first pair of freezing plates; and- a first vapour compression refrigeration circuit configured to circulate a first refrigeration circuit refrigerant, preferably a hydrocarbon refrigerant, sequentially through a first refrigeration circuit compressor, a first refrigeration circuit condenser, a first refrigeration circuit expansion valve, a first refrigeration circuit evaporator and back to the first refrigeration circuit compressor;in which the first refrigeration evaporator comprises the first freezing plate;in which the first vapour compression refrigeration circuit is configured to operate in a first cooling phase and in a subsequent second cooling phase;in which the first cooling phase comprises reducing the temperature of the liquid medical product to provide the frozen medical product at a first cooling phase product temperature, the first cooling phase comprising circulating the first refrigeration circuit refrigerant through the first vapour compression refrigeration circuit at a first cooling phase refrigerant mass flow rate to provide a first cooling phase evaporation temperature of the first refrigerant; and in which the subsequent second cooling phase comprises further reducing the temperature of the frozen medical product from the first cooling phase product temperature to a lower, second cooling phase frozen product temperature, the second cooling phase comprising circulating the first refrigeration circuit refrigerant through the first vapour compression refrigeration circuit at a second cooling phase refrigerant mass flow rate to provide a second cooling phase evaporation temperature of the first refrigerant; andin which the second cooling phase evaporation temperature of the first refrigerant is lower than the first cooling phase evaporation temperature of the first refrigerant.

2. A medical contact shock freezer in accordance with claim 1, whereinthe first cooling phase refrigerant mass flow rate of the first refrigerant is greater than the second cooling phase refrigerant mass flow rate of the first refrigerant.

3. A medical contact shock freezer in accordance with claim 1 or claim 2,in which the first refrigeration circuit evaporator comprises the first freezing plate but not the second freezing plate;and in which the medical contact shock freezer further comprises:- a second vapour compression refrigeration circuit configured to circulate a second refrigeration circuit refrigerant, preferably a hydrocarbon refrigerant, sequentially through a second refrigeration circuit compressor a second refrigeration circuit condenser, a second refrigeration circuit expansion valve, a second refrigeration circuit evaporator and back to the second refrigeration circuit compressor;in which the second refrigeration circuit evaporator comprises the second freezing plate but not the first freezing plate;in which the second vapour compression refrigeration circuit is configured to operate in the first cooling phase and in the subsequent second cooling phase;in which the first cooling phase comprises circulating the second refrigeration circuit refrigerant through the second vapour compression refrigeration circuit at a first cooling phase refrigerant mass flow rate to provide a first cooling phase evaporation temperature of the second refrigerant; andin which the subsequent second cooling phase comprises circulating the second refrigeration circuit refrigerant through the second vapour compression refrigeration circuit at a second cooling phase refrigerant mass flow rate to provide a second cooling phase evaporation temperature of the second refrigerant; andin which the second cooling phase evaporation temperature of the second refrigerant is lower than the first cooling phase evaporation temperature of the second refrigerant.

4. A medical contact shock freezer in accordance with claim 3, whereinthe first cooling phase refrigerant mass flow rate of the second refrigerant is greater than the second cooling phase refrigerant mass flow rate of the second refrigerant.

5. A medical contact shock freezer configured for fast freezing a plurality of individual bags of a liquid medical product, notably liquid blood plasma, to provide a frozen medical product, notably frozen blood plasma, notably a contact shock freezer in accordance with any preceding claim, wherein the medical contact shock freezer comprises:- a first pair of freezing plates comprising a first freezing plate and a second freezing plate configured so that the individual bags can be clamped between the first pair of freezing plates; and- a first vapour compression refrigeration circuit configured to circulate a first refrigeration circuit refrigerant, preferably a hydrocarbon refrigerant, sequentially through a first refrigeration circuit compressor, preferably a single speed compressor, a first refrigeration circuit condenser, a first refrigeration circuit expansion valve, a first refrigeration circuit evaporator and back to the first refrigeration circuit compressor;in which the first refrigeration evaporator comprises the first freezing plate;in which the first refrigeration circuit expansion valve is switchable between a first cooling phase configuration in which it provides a first throttling effect and a second cooling phase configuration in which it provides a second throttling effect,and in which the second throttling effect of the first refrigeration circuit expansion valve is greater than the first throttling effect of the first refrigeration circuit expansion valve.

6. A medical contact shock freezer in accordance with claim 1 or claim 5,in which the first refrigeration circuit evaporator comprises the first freezing plate but not the second freezing plate;and in which the medical contact shock freezer further comprises:- a second vapour compression refrigeration circuit configured to circulate a second refrigeration circuit refrigerant, preferably a hydrocarbon refrigerant, sequentially through a second refrigeration circuit compressor, preferably a single speed compressor, a second refrigeration circuit condenser, a second refrigeration circuit expansion valve, a second refrigeration circuit evaporator and back to the second refrigeration circuit compressor;in which the second refrigeration circuit evaporator comprises the second freezing plate but not the first freezing plate;in which the second refrigeration circuit expansion valve is switchable between a first cooing phase configuration in which it provides a first throttling effect and a second cooling phase configuration in which it provides a second throttling effect,and in which the second throttling effect of the second refrigeration circuit expansion valve is greater than the first throttling effect of the second refrigeration circuit expansion valve.

7. A medical contact shock freezer in accordance with claim 5 or claim 6,in which each expansion valve comprises a first capillary tube which provides the first throttling effect, a second capillary tube which provides the second throttling effect and a switching valve, notably in which the switching valve hasa first cooling phase configuration in which the first capillary tube is connected to its refrigeration circuit and preferably the second capillary tube is disconnected from its refrigeration circuit, anda second cooling phase configuration in which the first capillary tube is disconnected from its refrigeration circuit and the second capillary tube is connected to its refrigeration circuit.

8. A medical contact shock freezer in accordance with claim 7, in which for each expansion valve the lengths and internal diameters of the first and second capillary tubes are selected from configuration consisting of i) the internal diameter of the first capillary tube being larger than the internal diameter of the second capillary tube; ii) the length of the first capillary tube being less than the length of the second capillary tube; and, preferably, iii) the internal diameter of the first capillary tube being larger than the internal diameter of the secondcapillary tube and the length of the first capillary tube being less than the length of the second capillary tube.

9. A medical contact shock freezer in accordance with any preceding claim, in whicheach refrigeration circuit refrigerant is a hydrocarbon refrigerant, preferably R290 (propane); andeach refrigeration circuit preferably comprises less than 200g, more preferably less than 155 g of its refrigerant.

10. A medical contact shock freezer in accordance with any preceding claim, in which each refrigeration circuit has a Plasma Bag Refrigeration Power of at least 6.5 kg per hour, preferably at least 7.5 kg per hour.

11. A medical contact shock freezer in accordance with any of claims 5 to 10, in which when applied to R290 (propane) at an inlet pressure of 10 bar and an inlet temperature of 25 °C,- the first throttling effect provides the R290 (propane) with a outlet pressure of less than 3 bars and an outlet temperature of less than -18 °C; and- the second throttling effect provides the R290 (propane) with a outlet pressure of less than 1.5 bars and an outlet temperature of less than - 30 °C.

12. A medical contact shock freezer in accordance with any of claims 5 to 10, in which when applied in a steady state to R290 (propane) at an inlet pressure of 10 bar and an inlet temperature of 25 °C,- the first throttling effect provides the R290 (propane) with a first phase evaporation temperature in the range -25°C to -10 °C, preferably in the range -25°C to -15 °C; and- the second throttling effect provides the R290 (propane) with a second phase evaporation temperature in the range -35°C to -50 °C, preferably in the range -35°C to -45 °C.

13. A medical contact shock freezer in accordance with any preceding claim, in which each compressor is a single phase compressor, preferably a single speed and single phase compressor, and notably in which each refrigeration circuit has a Plasma Bag Refrigeration Power of at least 6.5 kg per hour14. A medical contact shock freezer in accordance with any preceding claim, in which the medical shock freezer further comprises:- a second pair of freezing plates comprising a third freezing plate and a fourth freezing plate configured so that the individual bags can be clamped between the second pair of freezing plates; and- a third vapour compression refrigeration circuit configured to circulate a third refrigerationcircuit refrigerant, preferably a hydrocarbon refrigerant, sequentially through a third refrigeration circuit compressor, preferably a single speed compressor, a third refrigeration circuit condenser, a third refrigeration circuit expansion valve, a third refrigeration circuit evaporator and back to the third refrigeration circuit compressor;in which the third refrigeration evaporator comprises the third freezing plate but not the fourth freezing plate;in which the third refrigeration circuit expansion valve is switchable between a first cooling phase configuration in which it provides a first throttling effect and a second cooling phase configuration in which it provides a second throttling effect,and in which the second throttling effect of the third refrigeration circuit expansion valve is greater than the first throttling effect of the third refrigeration circuit expansion valve;and in which the medical contact shock freezer further comprises:- a fourth vapour compression refrigeration circuit configured to circulate a fourth refrigeration circuit refrigerant, preferably a hydrocarbon refrigerant, sequentially through a fourth refrigeration circuit compressor, preferably a single speed compressor, a fourth refrigeration circuit condenser, a fourth refrigeration circuit expansion valve, a fourth refrigeration circuit evaporator and back to the fourth refrigeration circuit compressor;in which the fourth refrigeration circuit evaporator comprises the fourth freezing plate but not the third freezing plate;in which the fourth refrigeration circuit expansion valve is switchable between a first cooling phase configuration in which it provides a first throttling effect and a second cooling phase configuration in which it provides a second throttling effect,and in which the second throttling effect is greater than the first throttling effect.

15. A medical contact shock freezer in accordance with any preceding claim in which each refrigeration circuit is configured such that in the first cooling phase configuration the freezing plate of each refrigeration circuit operates at a temperature within the range -15°C to -25°C, preferably within the range -18°C to -22°C.

16. A medical contact shock freezer in accordance with any preceding claim in which each refrigeration circuit is configured such that in the second cooling phase configuration the freezing plate of each refrigeration circuit operates at a temperature within the range -35 °C to -45°C, preferably within the range -38°C to -42°C.

17. A medical contact shock freezer in accordance with any preceding claim, in which each pair of freezing plates is arranged at an angle of between 2° and 10° to the horizontal.

18. A medical contact shock freezer in accordance with any preceding claim, in which each pair of freezing plates comprises a fixed freezing plate and a movable freezing plate and inwhich movement between the loading and freezing position of each pair of freezing plates consists of a linear, vertical displacement of the moveable freezing plates.

19. A method of fast freezing a plurality of individual bags of liquid blood plasma to provide frozen blood plasma, the method comprising:- clamping the plurality of individual bags of liquid blood plasma between a first freezing plate and a second freezing plate of a medical contact shock freezer, notably a medical contact shock freezer in accordance with any preceding claim, the medical contact shock freezer comprising a first vapour compression refrigeration circuit configured to circulate a first refrigeration circuit refrigerant, preferably a hydrocarbon refrigerant, sequentially through a first refrigeration circuit compressor, a first refrigeration circuit condenser, a first refrigeration circuit expansion valve, a first refrigeration circuit evaporator and back to the first refrigeration circuit compressor;- operating the first vapour compression refrigeration circuit in a first cooling phase to reduce the temperature of the liquid blood plasma to provide frozen blood plasma at a first cooling phase blood plasma temperature by operating the first and second freezing plates at a first cooling phase freezing plate temperature in the range -5 °C to -25°C,; and- subsequently operating the first vapour compression refrigeration circuit in a second cooling phase to reduce the temperature of the frozen blood plasma from the first cooling phase blood plasma temperature to a lower, second cooling phase blood plasma temperature by operating the first and second freezing plates at a second cooling phase freezing plate temperature in the range -35 °C to -45°C.

20. A method in accordance with claim 19, in which the method comprises;- operating the medical contact shock freezer in the first cooling phase for a duration in the range 15 to 35 minutes; and- subsequently operating the medical contact shock freezer in the second cooling phase for a duration in the range 5 to 15 minutes.A

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