Differential airflow system to facilitate bottom-up freezing of plasma in a compressed bag

Abstract

The present disclosure relates to a method and system for rapidly freezing one or more bags containing biological products, particularly plasma. The present disclosure relates to a method and system for freezing individual bags or multiple bags of plasma, which is accomplished by directing differential airflows over the top and bottom surfaces of horizontally positioned bags to favor bottom-up ice crystal growth. The present disclosure relates to a method and system for freezing a bag in which the bottom of the bag has a heat transfer efficiency ten times greater than the top. The present disclosure relates to a differential airflow system in which at least one fan or blower provides differential airflow over the top and bottom surfaces of the plasma bag. The present disclosure relates to a method for freezing a bag using a differential airflow system, the method comprising the steps of: providing a controlled temperature chamber; disposing the differential airflow system in the controlled temperature chamber; directing cool air from within the controlled temperature chamber toward fins and a support using a fan and a flow conveyor to cool the bag; disposing the bag or a case containing the bag on a support; compressing the bag or case against the support using a compression means; and freezing the bag.

Description

[Technical Field]

[0001] This disclosure relates to a method and system for rapidly freezing one or more bags containing biological products, particularly plasma. In particular, this disclosure relates to a differential airflow system for facilitating bottom-up freezing of plasma in a compressed bag. [Background technology]

[0002] Biological fluids, such as plasma, are typically collected from donors, processed, and stored, usually frozen to minimize degradation until use. Generally, bags are containers chosen for biological fluids and are made from biocompatible materials. Bags can have several forms, capacity options, safety features, and other properties to improve the overall process.

[0003] Freezing is a crucial step in plasma preservation, as fresh, frozen plasma is the primary source of coagulation factors (particularly factor VIII) used in patients with hemorrhagic disorders. Existing medical and scientific literature recommends that plasma should be frozen at -25°C or below to achieve the highest yield of factor VIII, and that a decrease in factor VIII content occurs during freezing when plasma coagulation takes longer than one hour. Therefore, in recent years, several freezers, especially those applied to plasma freezing, have been developed for the purpose of rapidly freezing plasma stored in bags. [Overview of the project] [Problems that the invention aims to solve]

[0004] Many recent methods and devices, commonly known as contact / impact freezers, use cooling plates (cooled by a circulating coolant) to rapidly freeze plasma bags. Some of these feature parallel cooling plates that compress the bags between them, promoting rapid freezing and homogeneous freezing between bags. Some of these devices arrange the cooling plates in a vertical plane, while others recommend a horizontal configuration. However, these geometries may result in formulation loss or reduced factor VIII activity. During freezing, pure ice is formed, plasma solutes are concentrated in the remaining water, and each solute crystallizes when its solubility is exceeded. With existing devices, heat transfer to the bags is greatly facilitated at both side walls of the bags by the compressing cooling plates, thus promoting ice crystal growth from the container walls to the middle section, resulting in heterogeneity in the solute distribution. The solute becomes highly concentrated in the middle of the plasma bag, and the factor VIII molecule is exposed to high concentrations of salt over extended periods, resulting in molecular inactivation and, consequently, loss of factor VIII. Furthermore, direct contact of the plasma bag with the cooling plate can cause deformation and rupture of the bag, and thus lead to loss of the preparation. Several frames and boxes have been described to circumvent this problem, but some of these solutions, especially those made from low-conductivity materials (plastics), reduce heat transfer to the bag and, consequently, increase the freezing time.

[0005] While systems and methods already exist that help improve the plasma freezing process, these systems still fail to solve the problem of factor VIII loss due to freezing heterogeneity (solute distribution). Uncontrolled freezing geometry is one cause of heterogeneity in the solute distribution that occurs in the frozen solution of biologics, because its geometry displaces the solute toward the bottom and center of the container. This has been categorized for various systems, and the ice matrix (cm 3The local composition of solute in a given area shows a variation of over 100% between concentrated areas (typically the bottom or center of the container) and dilute areas (typically the top of the container). Therefore, it is desirable to design a simple and reproducible freezing system for plasma bags that can be used to freeze multiple bags and that can avoid solute heterogeneity. Previous studies have shown that heterogeneity of solute distribution during the freezing process can be reduced by using a controlled freezing geometry, i.e., freezing from bottom to top (see Non-Patent Literature 1: in doi:10.1002 / btpr.1771).

[0006] This disclosure aims to solve the above-mentioned problems by using a differential airflow system to promote bottom-up ice crystal growth during the freezing of plasma bags. Other aspects of this disclosure refer to cases for plasma bags that maintain the integrity of the case and protect from external stresses, as well as maintain heat transfer at the bottom surface of the bag. [Means for solving the problem]

[0007] This disclosure provides a method and system for freezing a plasma bag by using a differential airflow system to promote bottom-up ice crystal growth.

[0008] This disclosure provides a method and system for freezing individual bags or a group of individual bags by performing differential airflow on the upper and bottom surfaces of horizontally positioned bags to facilitate bottom-up ice crystal growth.

[0009] In this disclosure, the differential airflow causes the heat transfer coefficient at the bottom of the bag to be different from that at the top of the bag, and preferentially, to favor a bottom-up freezing geometry, the heat transfer coefficient at the bottom of the bag is 10 times greater than that at the top of the bag.

[0010] In one embodiment, differential airflow on the top and bottom surfaces of the plasma bag is enforced by at least one fan. A fan or a blower may be used, with a fan being preferred.

[0011] In one embodiment, the differential airflow system may include multiple fans, preferably one fan per bag.

[0012] In one embodiment, the fan should be suitable for use in extremely low-temperature environments.

[0013] In one embodiment, the fan speed can be controlled to increase or decrease heat transfer in a manner that is appropriately convenient for the freezing process.

[0014] In one embodiment, the fan speed is controlled such that the heat transfer coefficient at the bottom of the bag is 10 times greater than that at the top.

[0015] In one embodiment, the heat transfer coefficient at the top of the bag is 5 W / (m²). 2 • Below ℃, preferentially 2W / (m 2 The temperature must be less than 20°C, and the heat transfer coefficient at the bottom of the bag must be 20 W / (m²). 2 If it is higher than °C, the priority is 50W / (m 2 It must be higher than (°C).

[0016] In one embodiment, the differential airflow system includes a flow conveyor that drives air from a fan to the bottom surface of a plasma bag.

[0017] In one embodiment, the air in the flow conveyor has a speed in the range of about 1 m / s to about 10 m / s, more preferably in the range of about 2 m / s to about 8 m / s.

[0018] In one embodiment, the flow conveyor is made of a material with low thermal conductivity, such as plastic, polymer, or other material having low thermal conductivity.

[0019] In some embodiments, the differential air flow system comprises a support for receiving the bag. The support is a lattice or solid metal plate.

[0020] In some embodiments, the support may have fins that achieve maximum heat transfer from the air to the support. The fins can have several configurations to ensure maximum heat transfer from the air to the support.

[0021] In some embodiments, the support and the fins can be made of a highly thermally conductive material such as aluminum, stainless steel, copper, or the like.

[0022] In some embodiments, the dimensions of the support can vary to be able to receive one or several bags. The thickness of the support can be from 1 mm to 10 mm.

[0023] In some embodiments, a fan or a plurality of fans are orthogonal to the support and are directly connected to the flow conveyor.

[0024] [[ID=二十一]] [[ID=二十二]] [[ID=二十三]]

[0025] [[ID=二十四]] [[ID=二十五]]<0QQ001QQ>本開示は、バッグが圧迫されるときバッグの頂部における核形成を防止するよう凍結一貫性を向上するため、またバッグの凍結及び保存中に保護するため、バッグを収容するケースを提供する。[[ID=二十六]] [[ID=二十七]]

[0026] [[ID=二十八]] [[ID=二十九]] [[ID=三十]]

[0027] [[ID=三十一]] [[ID=三十二]] [[ID=三十三]]

[0028] It should be noted that there seems to be an error in line 21 where the tag is incorrectly written as <0QQ001QQ>. I have translated it as it is in the current form. Also, the Chinese text in line 25 seems to be a mix-up and might need to be corrected for a more accurate translation.​ In one embodiment, the bottom surface of the case may have an opening or a thin film of a highly thermally conductive material such as aluminum to ensure heat transfer to the bottom of the bag inside the case.

[0029] In one embodiment, the top surface of the case may have an additional layer of a low thermal conductivity material to prevent nucleation at the top of the bag.

[0030] In one embodiment, the heat transfer coefficient at the top of the case obtained by dividing the thermal conductivity of the material by its thickness is 5 W / (m 2 • Below ℃, preferentially 2W / (m 2 It must be less than ℃.

[0031] In one embodiment, the case may be designed to accommodate one or more bags.

[0032] In one embodiment, the differential airflow system includes compression means for compressing the bag or case in order to improve contact between the bottom surface and the support.

[0033] In one embodiment, the compression means is made of a rigid material having low thermal conductivity, such as a plastic, polymer, or other material having high rigidity and low thermal conductivity.

[0034] In one embodiment, the compression means may have a grooved surface that contacts the bag or case in order to minimize heat transfer to the top of the bag. The compression means may have ribs or a corrugated pattern on the surface that contacts the bag or case.

[0035] In one embodiment, the compression means may be mechanically actuated to compress the bag or case against a support. The compression means may also be operated by an automated mechanical actuator.

[0036] In one embodiment, the methods and systems disclosed herein are designed for use in a controlled temperature chamber to freeze individual bags or a group of individual bags containing biological products, particularly plasma.

[0037] In one embodiment, the temperature probe may be located at one or more points in the differential airflow system or within the case.

[0038] In one embodiment, an air velocity probe may be positioned at one or more points in a differential airflow system, preferably in a flow conveyor, to obtain information regarding the airflow velocity at a specific location.

[0039] One aspect of the present disclosure relates to a method for freezing a plasma bag by using a differential airflow system to promote bottom-up ice crystal growth, the method comprising: The steps include preparing the control temperature chamber, The steps include: arranging the differential airflow system within the control temperature chamber; The steps include: cooling the fins and support by sending cold air from the control temperature chamber to them using a fan and a flow conveyor; The steps include: horizontally placing a bag or a case for storing the bag on a support; The steps include compressing the bag or case against the support using a compression means, The step of freezing the bag, It is equipped with.

[0040] In one embodiment, the method and apparatus of the present invention can be used not only for freezing but also for thawing. [Brief explanation of the drawing]

[0041] These and other purposes, features, and advantages of this disclosure will become clear when the following detailed description is read in conjunction with the accompanying drawings. [Figure 1]This exhibits the recovery of factor VIII after freezing two plasma bags at -45°C inside a controlled temperature chamber using a differential airflow system that promotes bottom-up ice crystal growth according to this disclosure. [Figure 2] A schematic diagram of a differential airflow system 200 for a freezing bag 100 is shown, which ensures that the heat transfer efficiency at the bottom 101 of the bag is greater than that at the top 102, making it suitable for bottom-up ice crystal growth. [Figure 3] This disclosure provides a schematic perspective view of a differential airflow system for a bag 100, which uses a fan 300 to achieve differential airflow 200 on the upper 102 and bottom 101 surfaces of the bag 100 placed on a support 500. [Figure 4] This is a cross-sectional perspective view of a differential airflow system having a flow conveyor 400 with an inlet 401, a channel 402, and an outlet 403, which directs outside air from a fan 300 through fins 501 connected to a support 500, maximizing heat transfer from the outside air to the support 500 and, consequently, to the bottom 101 of the bag 100. [Figure 5] This is a cross-sectional perspective view of the differential airflow system according to the present disclosure, showing a support 500 connected to the fin 501 for transferring heat to the bottom of the bag 100. [Figure 6] This disclosure provides a perspective view of a differential airflow system comprising multiple fans 30 for freezing multiple bags 100. [Figure 7A] This is a perspective view from the bottom side of a case 600 that houses a bag 100, the case having an opening 601 at the bottom to promote heat transfer on the bottom surface of the bag. [Figure 7B] This is a perspective view of a case 600 that houses a bag 100, with an additional layer 602 of a low thermal conductivity material on the top of the case, as seen from the top surface. [Figure 8] This is a perspective view of a differential airflow system that freezes multiple bags 100 inside a case 600, having a compression means 700 for compressing the bags. [Figure 9]This is a system breakdown perspective view. [Figure 10] This is a cross-sectional view of the system. [Figure 11] This is a cross-sectional view of the system. [Figure 12] This is a perspective view of the system from the bottom. [Figure 13] This is a perspective view of the system from the top side. [Figure 14] These are systems with different configurations, and 402 is a cross-sectional view showing the airflow channel 200. [Figure 15] This is a perspective view of systems with different configurations. [Modes for carrying out the invention]

[0042] This section describes the purpose of disclosure and the fundamental assumptions of the proposed embodiments.

[0043] As mentioned above, one major limitation in the storage of biological fluids such as plasma is the freezing step. When using existing methods and equipment during freezing, ice grows from the walls of the container toward the middle, and the solute is gradually concentrated in the middle of the plasma bag, exposing factor VIII molecules to high concentrations of salt, resulting in molecular inactivation and, consequently, loss of factor VIII. Therefore, we have found that by applying differential airflow (with different airflow rates) to the top and bottom surfaces of a plasma bag (placed horizontally), and by favoring heat transfer from the bottom, a bottom-up freezing geometry can be achieved, leading to high recovery of factor VIII (see Figure 1). In this disclosure, differential airflow means that the heat transfer coefficient at the bottom of the bag differs from that at the top of the bag, and preferably, the heat transfer coefficient at the bottom of the bag is preferentially 10 times greater than that at the top to favor the bottom-up freezing geometry. When controlling different heat transfer rates, it is not necessary to control to different temperatures, or even to add insulation, in order to achieve a bottom-up freezing geometry. In fact, to obtain different heat transfer rates, it is only necessary to apply differential airflow by blowing more air to the bottom of the bag than to the top. This method greatly simplifies the system described herein compared to existing systems. Any chamber with a controlled temperature can be converted into a highly efficient, low-maintenance plasma freezer.

[0044] Accordingly, this specification discloses a method and system for freezing individual bags 100 or a group of individual bags in a manner conducive to bottom-up ice crystal growth, which is performed by flowing a differential airflow 200 over the upper 102 and bottom 101 surfaces of the horizontally positioned bags. (See Figure 2 for illustrative purposes.)

[0045] Furthermore, a differential air flow system is disclosed that accomplishes the above-described method that is conducive to bottom-up ice crystal growth by flowing a differential air flow 200 over the surfaces of the upper portion 102 and the bottom portion 101 of the plasma bag 100. In a preferred embodiment, the differential air flow 200 at the surfaces of the upper portion 102 and the bottom portion 101 of the plasma bag 100 is imposed by at least one fan 300. In this embodiment, a fan or a blower can be used, and preferably a fan is used. In another embodiment, the differential air flow system can comprise a plurality of fans, and preferably can comprise one fan per bag. In a preferred embodiment, this fan should be suitable for use in cryogenic environments. In another embodiment, the speed of the fan can be controlled to conveniently increase or decrease heat transfer according to the freezing process. In a preferred embodiment, the speed of the fan is controlled such that the heat transfer rate at the bottom of the bag is 10 times greater than that at the top. In another embodiment, the heat transfer rate at the top of the bag should be less than 5 W / (m 2 ·°C), preferably less than 2 W / (m 2 ·°C), and the heat transfer rate at the bottom of the bag should be higher than 20 W / (m 2 ·°C), preferably higher than 50 W / (m 2 ·°C). (See FIGS. 2-8 for illustration of examples.)

[0046] In another embodiment, the differential air flow system comprises a flow conveyor 400 that feeds air from the fan 300 onto the surface of the bottom portion 101 of the plasma bag. In one embodiment, the flow conveyor 400 can have an inlet for outside air 401 from the fan 300, a channel 402 that passes through the bottom of the bag to feed air, and an outlet 403 to the outside air. In a preferred embodiment, the air within the flow conveyor has a speed within the range of about 1 m / s to about 10 m / s, and more preferably about 2 m / s to about 8 m / s. In a preferred embodiment, the flow conveyor is made of a low heat conductor such as a plastic, a polymer or other material having low conductivity. (See FIGS. 4-8 for illustration of examples.)

[0047] In one embodiment, the differential airflow system comprises a support 500 that receives the bag 100. In a preferred embodiment, the support 500 is a grid-like or solid metal plate. In one embodiment, the support 500 may have fins 501 that maximize heat transfer from the outside air to the support 500 and, consequently, to the bottom 101 of the bag. The fins 501 can be attached to the support 500 by screws, any type of adhesive or paste, or by other means to ensure good thermal conductivity. These fins may have several configurations to ensure maximum heat transfer from the outside air to the support. The support and fins can be made of a highly thermally conductive material such as aluminum, stainless steel, copper, or other material. The dimensions of the support may vary, so as to be able to receive one or more bags. The thickness of the support can be 1 mm to 10 mm. The dimensions of the support in a particular configuration should be taken into account the characteristics from the whole system, thereby enabling it to have a well-known global thermal conductivity and thermal inertia. (See Figures 4-8 for illustrative purposes.)

[0048] In another embodiment, the flow conveyor is designed with respect to its supports and fins to maximize heat transfer from the outside air to the bottom of the bag.

[0049] In another embodiment, the fan 300 or more fans are directly connected to the flow conveyor 400 perpendicular to the support. In another embodiment, the fan 300 or more fans can be positioned below the support 500 and the fins 501. In another embodiment, the differential airflow system may have multiple fans, preferably one fan per bag. (See Figures 2-8 for illustrative purposes.)

[0050] One exemplary embodiment of the present disclosure is a case 600 for housing a bag 100, which is intended to improve freeze consistency to prevent nucleation at the top of the bag when the bag is compressed, and to protect the bag during freezing and storage. In a preferred embodiment, the case 600 may have an opening 601 at the bottom to facilitate heat transfer at the bottom plane 101 of the bag. The case may be made of a polymer, cardboard, or other material having low thermal conductivity. In another embodiment, the case may be made of a compressible material so that the case maintains its integrity when uniformly distributed pressure is applied. Preferably, the case is made of a material that maintains its integrity even at low temperatures, e.g., -50°C. In another embodiment, the bottom surface of the case may have an opening or a thin film of a highly thermally conductive material such as aluminum to ensure heat transfer to the bottom of the bag inside the case. In another embodiment, the top surface of the case may have an additional layer 602 of a low thermal conductivity material to prevent nucleation at the top of the bag. In another embodiment, the case may further have embodiments made from any other material having several functionalities. For example, the case may have an additional window to ensure that information in the bag can be reliably read. The case may have a barcode or chip for sample recognition. In one embodiment, the case may be designed in accordance with the bag being used. In another embodiment, the case may be designed to accommodate one or more bags. (See Figure 7 for illustrative purposes.)

[0051] In one embodiment, the heat transfer coefficient at the top of case 600, obtained by dividing the thermal conductivity of the material by the case thickness 602, is 5 W / (m 2 • Below ℃, preferentially 2W / (m 2 The temperature must be less than 0°C. In one embodiment, case 600 is made of corrugated cardboard (0.064 W / m²). 2 When manufactured with an average thermal conductivity of 5°C, the top of case 600 is 5W / (m 2To obtain a heat transfer coefficient of (°C), the thickness must be 1.2 cm. In another embodiment, extruded polystyrene (0.025 W / m 2 When using a material with an average thermal conductivity of ℃ and maintaining the same thickness, W / (m 2 Obtain the heat transfer coefficient (°C).

[0052] In another embodiment, the differential airflow system includes a compression means 700 that compresses the bag 100 or case 600 to increase the surface contact of the bottom 101 with respect to the support 500. In another embodiment, this compression means is made of a rigid material having low thermal conductivity, such as a plastic, polymer, or other material having high rigidity and low conductivity. In a preferred embodiment, the compression means is made of a transparent material. In another embodiment, the compression means 700 may have a grooved surface 701 that contacts the bag or case to minimize heat transfer to the top of the bag. In a preferred embodiment, the compression means may have a rib or corrugated pattern that contacts the bag or case. This pattern allows for good contact to compress the box while reducing heat transfer to the top of the bag and preventing nucleation at the top.

[0053] In another embodiment, the compression means may be mechanically operated to press the bag or case against a support. The compression means has two positions: open and closed. In one embodiment, the open position is set for loading or unloading the bag / case into the differential airflow system, and the closed position is set for pressing the bag / case against the support to allow good heat transfer to the bottom surface of the bag. Furthermore, when the compression means is set to the closed position, all bags achieve the same format, thereby enabling homogeneous and reproducible freezing of multiple bags. In another embodiment, the compression means may also be operated by an automated mechanical actuator.

[0054] In a preferred embodiment, the method and system disclosed herein are designed for use within a controlled temperature chamber. This controlled temperature chamber may or may not have convection, and may be cooled or heated. In short, by using the method and differential airflow system disclosed herein, cold air within the controlled temperature chamber is delivered to the fins and support by fans and flow conveyors to cool them. As the support is cooled, the case containing the bag is placed on the support to facilitate heat transfer from the support to the bottom of the bag. Finally, the case containing the bag is compressed by compression means to increase contact between the bottom of the bag and the support. This method and differential airflow system enable bottom-up ice crystal growth within the plasma bag, while ensuring its homogeneity and integrity.

[0055] In a preferred embodiment, the methods and systems disclosed herein allow the use of an arbitrary controlled temperature chamber for freezing one or more individual bags containing biological products, particularly plasma.

[0056] In a preferred embodiment, the disclosure relates to a method for freezing a plasma bag by using a differential airflow system to promote bottom-up ice crystal growth, the method comprising: The steps include preparing the control temperature chamber, The steps include: placing the differential airflow system inside the control temperature chamber; The steps include: cooling the fins and support by sending cold air from inside the control temperature chamber toward them using a fan and a flow conveyor; A step of horizontally placing a bag or a case for storing a bag on a support, The steps include compressing the bag or case against a support using a compression means, Steps to freeze the bag, It is equipped with.

[0057] In one embodiment, the temperature probe may be located at one or more points in the differential airflow system or within a case. This temperature probe may display a time-temperature profile (curve) during the freezing process. The temperature probe may have a thermocouple, a thermistor, or other common temperature sensing device suitable for use in cryogenic environments.

[0058] In another embodiment, the air velocity probe may be positioned at one or more points in a differential airflow system, preferably on a flow conveyor, to obtain information regarding the airflow velocity at a specific location. The air velocity probe may have an anemometer, a pilot tube, or other common sensing device suitable for use in cryogenic environments.

[0059] In one embodiment, the method and differential airflow system of the present invention can be used not only for freezing but also for thawing.

[0060] In one embodiment, as shown in Figure 9 as an exploded perspective view and in Figures 10 and 11 as cross-sectional views, the present disclosure describes a case for housing a bag 100 that can be used for freezing, transporting, storing and / or thawing. In one embodiment, the case 600 may have a heat transfer plate 604 at the bottom to facilitate heat transfer at the bottom surface 101 of the bag. The heat transfer plate 604 at the bottom surface of the case 600 may be made of a highly thermally conductive material such as aluminum to ensure heat transfer to the inside of the case and to the bottom of the bag.

[0061] In one embodiment, as shown in Figures 9 and 12, the heat transfer plate 603 at the bottom may further have perforated holes 604 to achieve a high heat transfer coefficient at the edges of the bag, thereby ensuring nucleation and uniform bottom-up freezing. Furthermore, the perforated holes allow air to flow into the tubes 605 of the bag, promoting controlled freezing.

[0062] In one embodiment, as shown in Figure 10, the heat transfer plate 603 on the bottom surface is configured to ensure good thermal contact with the bottom and edges of the bag. The heat transfer plate can be shaped or bent according to the shape of the bag 100.

[0063] In one embodiment, as shown in Figure 11, the metal plate functions as a heat transfer plate at the bottom 101 of the bag and is also configured to cover the entire case to physically protect the entire case 600.

[0064] In one embodiment, the case 600 is made of a polymer or material having low thermal conductivity. For example, the case may be made of extruded polystyrene.

[0065] In one embodiment, as shown in Figures 9, 10, and 11, an additional layer 606 of phase change material may be placed on the top surface of the bag 102 to further prevent ice crystal growth at the top of the bag and to promote bottom-up freezing.

[0066] In one embodiment, as shown in Figures 9 and 13, the bottom of the case 600 is configured to accommodate the bag 100 and the piping assembly 605, ensuring that the tubes are secured in place.

[0067] In one embodiment, the case 600 has a top lid 607 that closes the case. The case can also be used as a transport bag.

[0068] In one embodiment, the system may be configured in a stacked configuration, as shown in Figure 14 as a cross-sectional view of the system and Figure 15 as a perspective view. The cases are stacked, allowing multiple cases to be used simultaneously. The stacked cases 600 are configured to have channels 402 for supplying airflow 200 from the bottom of a bag placed in the first case to the bottom of a second case stacked immediately vertically on top of the top of the first case. Figure 14 illustrates how the differential airflow 200 circulates within the stacked system.

[0069] In one embodiment, the stacked configuration of the system has multiple layers, preferably at least two layers, and more preferably at least three layers.

[0070] Whenever the term “bottom of the bag” is used herein, it is intended to refer to the portion of the bag that comes into contact with higher airflow velocities, or to the heat transfer plate or support on which the bag rests.

[0071] Whenever the term “comprising” is used herein, it is intended to indicate the presence of the described feature, entity, step, or component, but not to exclude the presence or addition of one or more other features, entities, steps, components, or groups thereof.

[0072] Unless otherwise specified herein, any particular sequence in the steps described is for illustrative purposes only and can be changed without departing from this disclosure. Therefore, unless otherwise stated, the steps described are unordered, meaning that they may be performed in any convenient or preferred order, whenever possible.

[0073] This disclosure should be viewed as not being in any way restrictive to the embodiments described, and those skilled in the art will foresee many possibilities or modifications thereof.

[0074] The embodiments described above are combinable. The claims further describe embodiments of the present disclosure.

Claims

1. A method for freezing individual bags or multiple bags containing a biological agent to promote bottom-up ice crystal growth, comprising the following steps: The steps include preparing the control temperature chamber, The steps include: arranging a differential airflow system within the control temperature chamber; The steps include placing a bag or a case for storing the bag on a support, The steps of compressing the bag or case against the support, The steps include: sending cold air into the control temperature chamber to obtain a differential airflow for freezing the bag; Equipped with, The differential airflow is achieved by blowing air onto the bottom of the bag such that the air velocity at the bottom of the bag is higher than the air velocity at the top of the bag, thereby promoting bottom-up ice crystal growth. The heat transfer coefficient at the top of the bag is 5 W / (m²). ２ The temperature must be less than 50°C, and the heat transfer coefficient at the bottom of the bag must be 50 W / (m²). ２ A method wherein the temperature must be higher than ℃, and the air blown onto the bottom of the bag has a velocity in the range of approximately 1 m / s to approximately 10 m / s.

2. In the method for freezing a bag according to claim 1, the heat transfer coefficient at the top of the bag is 2 W / (m²). ２ The temperature is less than ℃, and the heat transfer coefficient at the bottom of the bag is 20 W / (m²). ２ A method wherein the temperature is higher than (°C), and the air blown onto the bottom of the bag has a velocity in the range of approximately 1 m / s to approximately 10 m / s.

3. A method for freezing a bag according to any one of claims 1 to 2, wherein the differential airflow is achieved by a fan and a flow conveyor that supply and blow cold air onto the bottom of the bag, the support, or the fins of the support.

4. A method for freezing a bag according to any one of claims 1 to 3, wherein the support is a horizontal configuration or a vertically stacked configuration consisting of at least two layers.

5. An airflow system for freezing individual bags or a group of bags containing a biological agent to promote bottom-up ice crystal growth, using the method according to any one of claims 1 to 4, The system includes a control temperature chamber for arranging the aforementioned airflow system, An airflow system configured to be placed inside a controlled temperature chamber, A bag or case, or a support for holding multiple bags or cases, The aforementioned bag or case, or a compression means for compressing the plurality of bags or cases, Equipped with, The airflow system is configured to supply cold air into the control temperature chamber in order to obtain a differential airflow for freezing the bag. The differential airflow is achieved by blowing air onto the bottom of the bag such that the air velocity at the bottom of the bag is higher than the air velocity at the top of the bag, thereby promoting bottom-up ice crystal growth. The heat transfer coefficient at the top of the bag is 5 W / (m²). ２ The temperature must be less than ℃, and the heat transfer coefficient at the bottom of the bag must be 20 W / (m²). ２ • An airflow system that must be higher than (°C).

6. An airflow system according to claim 5, wherein differential airflow on the upper surface and the bottom surface of the bag is provided by at least one fan.

7. An airflow system according to any one of claims 6, further comprising a controller for controlling the speed of the fan.

8. An airflow system according to claim 6 or 7, further comprising a flow conveyor that drives the air from the fan to the bottom surface of the bag, wherein the air in the flow conveyor has a velocity in the range of 1 m / s to 10 m / s.

9. An airflow system according to any one of claims 5 to 8, wherein the support has a horizontal configuration.

10. An airflow system according to any one of claims 5 to 9, wherein the bag or the case for housing the bag is arranged on the support in a horizontal configuration.

11. An airflow system according to any one of claims 5 to 9, wherein the bag or case for housing the bag is arranged on the support in a vertical stacking configuration, and the airflow system further comprises airflow channels that allow air to flow within each layer such that the bottom of the bag or the bottom of the case is exposed to an airflow of a higher velocity.

12. An airflow system according to any one of claims 5 to 11, wherein the support has fins.

13. An airflow system according to any one of claims 5 to 12, further comprising a case for housing a bag.

14. An airflow system according to any one of claims 5 to 13, wherein the case is made of a polymer, cardboard, or has low thermal conductivity.

15. An airflow system according to any one of claims 5 to 14, wherein the compression means is made of a rigid material having low thermal conductivity, such as plastic or polymer, and the airflow system.

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