Freeze-drying

Abstract

To improve the efficiency and shorten the freeze-drying time of a freeze-dried substance without affecting the ability of the freeze-dried substance to be used later. The system includes a first plate having a first surface and a second plate having a second surface opposite the first surface. The second plate has channels for circulating a fluid. The system further includes a plate movement system operable to increase and decrease the space between the first surface and the second surface. In some embodiments, the first plate includes a second layer that constitutes the first surface.

Description

[Technical field]

[0001] This application claims priority to U.S. Provisional Patent Application No. 62 / 009,629, entitled "Freeze-Drying," filed June 9, 2014, U.S. Provisional Patent Application No. 62 / 010,027, entitled "Freeze-Drying Container," filed June 10, 2014, and U.S. Provisional Patent Application No. 62 / 142,146, entitled "Freeze-Drying Container," filed April 2, 2015, the entireties of which are expressly incorporated herein by reference. [Background technology]

[0002] Freeze-drying is a process used to preserve and increase the shelf life of materials such as biological materials, foods, and drugs. Freeze-drying is accomplished by first freezing the material to solidify it, and then exposing it to a low pressure environment (below atmospheric pressure) to sublimate one component of the material. Typically, the one component is a liquid at standard temperature and pressure, such as water. Summary of the Invention [Problem to be solved by the invention]

[0003] Depending on the type of material and the volume being lyophilized, the process can take several days to complete. There is a need to improve the efficiency and reduce the time for lyophilization of materials without affecting the ability of the lyophilized material to be used at a later time.

[0004] The present invention has been made with the above considerations and others in mind, but the subject matter described herein is not intended to limit the scope of the present invention to certain applications. [Means for solving the problem]

[0005] This section is intended to describe aspects of some embodiments of the invention in a simplified form and is not intended to identify key or critical elements of the claimed invention, nor is it intended to limit the scope of the claims.

[0006] Some embodiments relate to a container for freeze-drying, storing, and infusing blood components. In some embodiments, the container comprises a first wall comprising a flexible polymeric material and a second wall joined to the first wall to define an interior volume of the container. In some embodiments, the second wall is made of a gas-permeable material that allows gas to move from the interior to the exterior of the container. In some embodiments, the container has a second chamber (or second portion) in which freeze-dried materials are stored after processing.

[0007] Other embodiments relate to a method of freeze-drying a multi-component liquid. In some embodiments, the method includes the steps of: holding the multi-component liquid in a container; exposing the multi-component liquid to a first pressure that is less than atmospheric pressure; and allowing at least one component of the multi-component liquid to evaporate for a predetermined period of time. After evaporation, the multi-component liquid is frozen to form a solid. In some embodiments, the multi-component liquid is shaped (e.g., pressed with a compressive force) during freezing; and the solid is exposed to a second pressure that is less than the first pressure; and allowing a portion of the solid to sublimate; and allowing one component of the solid to desorb from the solid.

[0008] Yet another embodiment relates to a system for freeze-drying a multi-component liquid. The system embodiment includes a first plate having a first surface and a second plate having a second surface opposite the first surface. The second plate has channels for circulating a fluid. The system further includes a plate motion system operable to increase and decrease the space between the first surface and the second surface. In some embodiments, the first plate includes a second layer that comprises the first surface. In some embodiments, the second layer is an infrared emitter for adding energy to the material to be freeze-dried.

[0009] Non-limiting and non-exhaustive embodiments are described with reference to the accompanying drawings. [Brief description of the drawings]

[0010] [Figure 1] FIG. 1 is a diagram of a first embodiment of an apparatus for freeze-drying a substance. [Diagram 2] FIG. 2 is a diagram of a second embodiment of an apparatus for freeze-drying a substance. [Diagram 3] FIG. 3 is a diagram of an embodiment of a shelving system. [Figure 4] FIG. 4 is a view of the shelf system of FIG. 3 with the plates moved relative to the state of FIG. [Diagram 5] FIG. 5 is a diagram of a second embodiment of a shelving system. [Figure 6] FIG. 6 is a view of the shelf system of FIG. 5 with the plates moved relative to the state of FIG. [Figure 7] FIG. 7 is a diagram of one embodiment of a mechanism for moving two plates of the shelving system that is part of the system shown in FIGS. [Figure 8] 8A and 8B are diagrams of a first embodiment of a two plate configuration used as part of a shelving system. [Figure 9] FIG. 9 is a diagram of a second embodiment of a two plate configuration used as part of a shelving system. [Figure 10] FIG. 10 is a diagram of a third embodiment of a two plate configuration used as part of a shelving system. [Figure 11] FIG. 11 is a diagram of a container used to hold materials for freeze-drying. [Figure 12] FIG. 12 is an exploded view of a container similar to that of FIG. [Figure 13] FIG. 13 is a cross-sectional view of the vessel of FIG. 12 for holding a fluid. [Figure 14] FIG. 14 is a cross-sectional view of a three-walled container according to one embodiment. [Figure 15] FIG. 15 is a cross-sectional view of a three-walled container according to the second embodiment. [Figure 16] FIG. 16 is a diagram of a container used to contain materials for and after lyophilization, according to an embodiment. [Figure 17] 17A-17C are cross-sectional views of the container shown in FIG. [Figure 18] 18A and 18B are diagrams of a container used to contain materials for and after lyophilization, according to another embodiment. [Figure 19] 19A-19C are diagrams of containers used to contain materials for and after lyophilization, according to other embodiments. [Figure 20] 20A-20C are diagrams of a container used to contain materials for and after lyophilization, according to yet another embodiment. [Figure 21] FIG. 21 is a diagram of one embodiment of a system for storing and filling multiple containers with biological fluids for subsequent lyophilization. [Figure 22] FIG. 22 is a diagram of one embodiment of a system for storing, reducing the volume of, and filling multiple containers with a biological fluid for subsequent freeze-drying. [Figure 23] FIG. 23 is a diagram of one embodiment of a system for storing biological fluids, reducing pathogens in the fluids, and filling multiple containers with the biological fluids for subsequent lyophilization. [Figure 24] FIG. 24 is a diagram of one embodiment of a system for storing a biological fluid, reducing the volume of the biological fluid, reducing pathogens in the reduced volume fluid, and filling multiple containers with the biological fluid for subsequent freeze-drying. [Diagram 25] FIG. 25 is a diagram of a bag containing fluid for treatment and a vibration table for agitating the fluid while irradiating the fluid with light from a light source, according to an embodiment. [Figure 26]FIG. 26 is a diagram of an apparatus for reducing or inactivating pathogens and microorganisms, according to an embodiment. [Figure 27] FIG. 27 is a diagram of a process for lyophilizing, containing, reconstituting, storing and infusing blood components according to one embodiment. [Figure 28] FIG. 28 is a flow chart of a process for freeze-drying a material, according to one embodiment. [Figure 29] FIG. 29 is a flow chart of a process for reducing pathogens in a material and lyophilizing the material according to one embodiment. [Diagram 30] FIG. 30 is a diagram of one embodiment of a system for freeze-drying a material using IR radiation. [Diagram 31] FIG. 31 is a diagram of another embodiment of a system for freeze-drying a material using IR radiation. [Diagram 32] FIG. 32 is a flow chart of a process for freeze-drying a material using IR radiation, according to one embodiment. [Diagram 33] FIG. 33 is a diagram of one embodiment of a computer system that may be used to implement the embodiments. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011] The principles of the present invention will be further understood with reference to the embodiments illustrated in the following detailed description and the accompanying drawings. Although specific features are illustrated and described in detailed embodiments, it should be understood that the present invention is not limited to the embodiments described below.

[0012] DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0023] Reference is now made in detail to the embodiments illustrated in the accompanying drawings. Wherever possible, the same reference numbers are used in the drawings and the description to refer to the same parts.

[0013] FIG. 1 illustrates a first embodiment of an apparatus 100 for freeze-drying a substance (e.g., in the form of a liquid, solid, or a combination thereof) according to the present invention. As illustrated in FIG. 1, the apparatus 100 includes a chamber 104, a housing 108, a shelf system 112, and an interface 116. The housing 108 houses, among other things, a vacuum system, a temperature control system, and a control system. The vacuum system creates a low pressure environment (e.g., below atmospheric pressure) in the chamber 104. The temperature control system controls the temperature of the shelf system 112. The control system controls various functions of the apparatus 100 and may include a computer system (comprising one or more processors). An operator can input data, parameters, and other information and control the functions of the apparatus 100 by using a user interface 116. In one embodiment, the user interface 116 allows an operator to create and execute a custom process for freeze-drying having multi-step programmable cycles.

[0014] In embodiments, the material to be freeze-dried is placed on the shelf system 112 within the chamber 104. A vacuum system then brings the environment within the chamber 104 to a first pressure (a pressure less than atmospheric pressure). In some embodiments, the first pressure is selected based on evaporation of a component of the material to be freeze-dried in a liquid state. After the chamber 104 reaches the first pressure, at least a portion of the first component evaporates from the material. Evaporation occurs for a first period of time or until a predetermined amount of the first component has evaporated from the material.

[0015] After a portion of the first component has evaporated, the remaining material is cooled and the remaining liquid freezes and becomes a solid. In embodiments, the evaporation is part of the freezing step. As can be appreciated, in some embodiments, the evaporation cools the remaining material to such an extent that the liquid freezes and becomes a solid. In other embodiments, the freezing may involve cooling using other mechanisms in addition to or instead of evaporation.

[0016] The vacuum system brings the environment within the chamber 104 to a second pressure. In embodiments, the second pressure is less than the first pressure. Under the second pressure, a second portion of the first component sublimes from the material. In some embodiments, sublimation may include sublimation of other components of the material.

[0017] In some embodiments, after sublimation, the material is maintained at the second pressure for an additional period of time to desorb one or more components from the material that were previously absorbed or adsorbed by the material.

[0018] As described in more detail below, in embodiments, the shelf system 112 has features that deliver / add or remove energy to the material being lyophilized. The addition or removal of energy may occur during one or more of the steps described above. For example, the shelf system 112 may be used to add energy to the material to cause evaporation of components from the material. The shelf system 112 may also be used to remove energy from the system to cool the material and freeze-solidify liquid within the material. In embodiments, the shelf system 112 may be used to add energy to the material during the sublimation step.

[0019] 2 shows a second embodiment of an apparatus 200 for freeze-drying a material in accordance with the present invention. Apparatus 200 has similar features as apparatus 100 and includes a chamber 204 housed within a housing 208. Apparatus 200 further includes a shelving system 212 and a user interface 216. In an embodiment, apparatus 200 has similar functionality and operates similarly to apparatus 100. Apparatus 100 and apparatus 200 are described solely for the purpose of illustrating that the present invention may be practiced in any freeze-drying apparatus or freeze-drying system and are not limited to any particular design or system configuration.

[0020] Various configurations are described below as part of embodiments of a freeze-drying device (e.g., device 100 or device 200) or freeze-drying system. However, the invention is not so limited. Various steps of the freeze-drying process may be performed by different structures, devices, or systems. As a non-limiting example, in some embodiments, the evaporation, freezing, and sublimation steps (described above) are each performed by three separate devices. In other embodiments, one or more devices may have various functions, allowing more than one step of the freeze-drying process to be performed in a single device.

[0021] As an example, the evaporation step may be performed in an apparatus that performs the freezing step. The evaporation provides cooling of the material during the freezing step, as described below with respect to Figure 29. After evaporation and freezing, the material is transferred to an apparatus that sublimes a component of the material.

[0022] In some embodiments, the liquid components are evaporated from the substance in the first device, the substance is then transferred to a second device and frozen, and after freezing, the substance is returned to the first device for lyophilization.

[0023] In other embodiments, an evaporation step is not performed as part of the process. In one apparatus, the material is frozen and transferred to a second apparatus for sublimation. As noted above, the invention is not limited to performing the process in any one apparatus. It may include steps performed in multiple apparatus.

[0024] FIG. 3 illustrates one embodiment of a shelving system 300 for use in a freeze-drying process / apparatus, such as apparatus 100 or apparatus 200 described above. Shelving system 300 includes a plate 304 that defines a shelf 320. Plate 304 provides a surface for placement of the material to be freeze-dried. Depending on the type of material to be freeze-dried, the material may be held in a container, such as a tray, bag, bottle, etc., and the container is placed on plate 304. FIG. 3 illustrates a container placed on plate 304. The container contains the material to be freeze-dried. Shelving system 300 further includes end plates 308. In an embodiment, end plates 308 are fixed, as will be described in more detail below.

[0025] Additionally, the shelving system 300 includes a motion control system 312 that is used to vary the distance between the plates 304. As described in more detail below, the distance between the plates 304 can be varied so that the material to be lyophilized is shaped by being compressed during the freezing step of the lyophilization process. In an embodiment, the motion control system 312 is configured to move the plates 304 closer together and farther apart.

[0026] 4 illustrates the shelving system 300 with the plates 304 moved to, for example, a fully compressed position to compress the material during the freeze-drying process, particularly during the freezing step of the process. As shown in FIG. 4, the end plates 308 are maintained in the same position as shown in FIG. 3, but each plate 304 is elevated such that the first plate (directly below the end plate 308) has the least amount of movement and the seventh plate (furthest from the end plate 308) has the most movement. In the compressed position shown in FIG. 4, pressure is applied to each container on the plates 304, compressing the containers and material. That is, a compressive force is applied to the containers and material therein. As will be explained in more detail below, the application of pressure, e.g., compressing the containers, provides several benefits to the freeze-drying process and is used in several embodiments.

[0027] As will be appreciated, the motion control system 312 includes a number of different components that are used to move the plate 304. For example, the motion control system 312 may include a computer system, such as a controller, including a processor, memory, input devices, output devices, communication devices, or combinations thereof. The motion control system 312 may also include other subsystems, such as hydraulic, pneumatic, or mechanical motion systems, including one or more motors, actuators, pumps, compressors, cylinders, pistons, piping, valves, bladders, sensors, regulators, or combinations thereof.

[0028] System 300 further includes a thermal fluid system 316 that circulates a thermal fluid through at least a portion of shelf 320 to control the temperature of at least a portion of plates 304, and therefore the temperature of materials placed on plates 304 for lyophilization. Thermal fluid system 316 is used to remove or add energy to plates 304 of shelf 320 during various steps of the lyophilization process.

[0029] 5 is a diagram of another embodiment of a shelving system 500 for use in a freeze-drying process / apparatus, such as apparatus 100 or apparatus 200 described above. Shelving system 500 includes a shelf 520 that provides a surface for placement of the material to be freeze-dried. The material is held in a container, such as a tray, bag, bottle, etc., which is placed on a first plate 504 of shelf 520. Shelving system 500 further includes a second plate 508 that is part of shelf 520. Second plate 508 is positioned above first plate 504 so as to face first plate 504. Shelving system 500 further includes a motion control system 512. In an embodiment, motion control system 512 is used to vary the distance between first plate 504 and second plate 508 of the shelf. As will be described in more detail below, varying the distance between first plate 504 and second plate 508 can provide pressure to the material being freeze-dried. In some embodiments, the motion control system 512 is configured to move the first plate 504 toward and away from the fixed second plate 508. In other embodiments, the second plate 508 may be moved toward and away from the fixed first plate 504. In yet other embodiments, the motion control system 512 may be configured to move the first plate 504 and the second plate 508 toward and away from each other.

[0030] Motion control system 512 may include any system suitable for moving plates 504 and / or plates 508 on shelves 520. In some embodiments, motion control system 512 may include components similar to motion control system 312 (FIG. 3) including a computer system, such as a controller, including a processor, memory, input devices, output devices, communication devices, or combinations thereof. System 512 may also include other subsystems, such as hydraulic, pneumatic, or mechanical motion systems including one or more motors, actuators, pumps, compressors, cylinders, pistons, piping, valves, bladders, sensors, regulators, or combinations thereof.

[0031] Figure 6 shows the shelving system 500 of Figure 5 with the plates 504, 508 of the shelf 520 moved to compress the material during the freeze-drying process, particularly during the freezing step of the process. In Figure 6, the second plate 508 has been moved downwardly towards the first plate 504. In the position shown in Figure 6, pressure is applied to each container placed on the first plate 504 by the application of pressure by the second plate 508. Such application of pressure and / or molding to the material as it is being frozen is believed to improve the efficiency of the freeze-drying process and is used in some embodiments.

[0032] System 500 further includes a thermal fluid system 516, similar to thermal fluid system 316. Thermal fluid system 516 circulates a thermal fluid within at least a portion of shelves 520 to control the temperature of at least a portion of plates 504, 508, and thus the temperature of materials placed on plates 504, 508 for lyophilization. Thermal fluid system 516 is used to remove or add energy to shelves 520 during various steps of the lyophilization process, as described in more detail below.

[0033] The above description of the shelf system 300, 500 is provided for the purpose of illustrating some features of certain embodiments of the invention. An embodiment of the invention may include features not described above but that are within the scope of the invention. For example, the number of plates in the system may vary. In some embodiments, the number of plates (e.g., 304, 504) for holding the material to be freeze-dried may be more than 2, or more than 3, or more than 4, or more than 5, or more than 6. In other embodiments, the number of plates (e.g., 304, 504) for holding the material to be freeze-dried may be less than 12, or less than 11, or less than 10, or less than 9, or less than 8. In one embodiment, the number of plates (e.g., 304, 504) for holding the material to be freeze-dried is 7.

[0034] In other embodiments, the plate (e.g., 304, 504) holding the material to be freeze-dried has other features. For example, the plate may have a raised edge around the perimeter, which keeps any leaking material on the plate and allows for easy cleaning. The plate may also be connected to the motion control system (312, 512) and / or the thermal fluid system (316, 516) using any suitable connector, such as connectors, tubing, fittings, pipes, adapters, etc. In one embodiment, the plate is connected (e.g., using quick-fit fittings) for easy removal from the motion control system (312, 512) and / or the thermal fluid system (316, 516), which allows for easy cleaning.

[0035] FIG. 7 shows an embodiment of a system 700 having two plates and a mechanism for moving the plates, which is part of the shelf system 300 or 500 shown in FIGS. 3-6. A first plate 704 is positioned above a second plate 708 with a surface 712 facing a surface 716 of the second plate. As shown in FIG. 7, a space 720 is formed between the two surfaces 712, 716 in which the material to be lyophilized is placed, and the space 720 can be increased or decreased by the movement of one or more plates 704, 708 as indicated by arrows 724. The decrease in the space 720 compresses the material to be lyophilized during one or more steps of the lyophilization process. The space 720 is increased to release the pressure. Alternatively, the space 720 is increased when the material to be lyophilized is positioned on the plate 708.

[0036] In embodiments, any mechanism can be used for moving one or more of plates 704, 708. Figure 7 illustrates one example of a mechanism for moving plates 704 and / or plates 708 to increase or decrease the size of space 720. In the embodiment illustrated in Figure 7, support member 728 is attached to allow plates 704, 708 to move toward and away from one another.

[0037] The support member 728 includes an outer support 732 and an inner support 736. For example, the outer support 732 is a hollow tube and the inner support 736 is a shaft disposed within the hollow tube. In some embodiments, one of the plates 704 or 708 is attached to the outer support 732 and the other is attached to the inner support 736. The plates 704, 708 are attached to the support member 728 by any suitable mechanism. Non-limiting examples of such mechanisms include the use of an L-bracket, such as L-bracket 740. Additionally, in some embodiments, the plates 704, 708 are attached to the respective portions of the support member 728 using fasteners such as screws, nuts, bolts, washers, or combinations thereof.

[0038] 7, outer support 732 has an opening 744 that allows an L-bracket 740 to be attached to inner support 736 and allows the L-bracket 740 to move vertically. One of the plates 704, 708 is attached to the L-bracket 740, and the movement of the L-bracket 740 allows the space 720 to be increased or decreased.

[0039] In an embodiment, at least a portion of support member 728 is connected to a motion control system, such as motion control system 312 (FIGS. 3 and 4) or motion control system 512 (FIGS. 5 and 6). As described above, the motion control system is used to control the spacing of space 720, increasing space 720 during placement of material and some steps in the freeze-drying process, and decreasing space 720 during some steps of compressing the material being freeze-dried.

[0040] The support member 728 and bracket 740 are one example of a mechanism for moving the plates 704, 708. In other embodiments, different components are used as part of different mechanisms for moving the plates 704, 708. Non-limiting examples include brackets, rails, fasteners, bearings, bushings, shafts, tubes, plates, welds, or combinations thereof.

[0041] Plates 704, 708 in FIG. 7 are shown as only one embodiment of a plate structure that may be part of a shelving system, such as shelving system 300 or shelving system 500 shown in FIGS. 3-6. Other embodiments may utilize different structures or designs. As noted above, other embodiments may have different mechanisms for varying the spacing of space 720 between plates 704 and 708. Other shelving systems may include more than the two support members 728 shown in FIG. 7. For example, four or more support members may be positioned near the four corners of plates 704, 708. This is by way of example only, and other embodiments are within the scope of the present invention.

[0042] Figures 8A and 8B are diagrams of a first embodiment of a two-plate structure 800 for use as part of a shelving system, such as system 300 shown in Figures 3 and 4. The structure 800 has a first plate 804 and a second plate 808. The first plate 804 has a side 812 that faces a side 816 of the second plate 808. The two opposing sides 812, 816 form a space 820 between the sides.

[0043] In an embodiment, plates 804 and 808 have a similar structure. Plate 804 has a first layer 828, which in an embodiment is made of a thermally conductive material. First layer 828 has channels 824 for the passage of a thermal fluid. The thermal fluid is used to control the temperature of first layer 828 by heating or cooling first layer 828.

[0044] Plate 804 further includes an interface 832 between first layer 828 and second layer 836. Interface 832 includes an insulating material, which allows the temperature of first layer 828 to differ from the temperature of second layer 836. In other embodiments, interface 832 may alternatively or additionally include properties that aid in adhesion between first layer 828 and second layer 836.

[0045] In one embodiment, the second layer 836 includes an IR emitting material, such as a ceramic material, a metallic material, an intermetallic material, and / or a composite material. In some embodiments, the material is an infrared (IR) emitter that emits infrared energy. In such an embodiment, the second layer 836 may have embedded elements for heating the layer 836 to facilitate IR emission from the surface 812. For example, the second layer 836 may include electrodes, heating elements, sensors (e.g., thermocouples), and / or combinations thereof. As described in more detail below, the IR energy emitted from the surface 812 by the second layer 836 is used in performing several steps of the freeze-drying process. As shown in the embodiment of Figures 8A and 8B, the plate 808 has a similar structure to the plate 804, such as having a first layer 848, a second layer 856, a boundary 852, and channels 844 for circulating a thermal fluid.

[0046] In embodiments, plate structure 800 is used in a shelf system 300 (FIGS. 3 and 4) as part of a freeze-drying apparatus that includes other components, such as a vacuum system, that creates a low pressure environment around at least the shelf of shelf system 300. In these embodiments, plates 804, 808 form part of shelf 320 and are connected to shelf motion system 312 and thermal fluid system 316.

[0047] In operation, the shelf system 300 (including the plate structure 800) is placed in a vacuum chamber (e.g., 104 or 204) that is used to create a low pressure (lower than atmospheric pressure) environment around at least the shelves 320 (e.g., plates 804, 808) of the system 300. The shelf motion system 312 then increases the space 820 and places a container 840 (containing a substance 860, which in some embodiments is a liquid such as a biological liquid) on the surface 816 of the plate 808. The system 312 then moves one or more of the plates 804 and / or 808, decreasing the space 820 and slightly compressing the container 840 (as shown in FIGS. 8A and 8B). The thermal fluid system 316 then circulates a thermal fluid through the channels 844 of the plate 808, cooling the first layer 848 of the plate 808 and thus the substance 860 in the container 840.

[0048] Without being bound by theory, it is believed that compressing the material to be freeze-dried (e.g., material 860 in container 840) during the freezing step can shape the material to a more uniform cross-section. A more uniform cross-section increases the efficiency of removing a component (e.g., ice) from material 860 during the subsequent sublimation step. That is, reducing thickness variation can provide a more uniform rate of advancement of the sublimation front of material 860 during sublimation.

[0049] After the substance 860 freezes, the environment surrounding the shelf 320 is subjected to a low pressure to promote sublimation of at least one component of the substance 860. The shelf motion system 312 then increases the volume of the space 820 in preparation for the sublimation step. Additionally, a thermal fluid is circulated through the channel 844 to apply thermal energy to the substance 860 in the container 840 (through the first layer 848 made of a thermally conductive material) to promote sublimation of a component in the substance 860.

[0050] As mentioned above, in some embodiments, the second layer 836 comprises an IR emitter. In these embodiments, activating the IR emitter directs IR energy to the substance 860 in the container 840. The IR energy provides additional energy to sublimate a component from the substance 860. In these embodiments, the addition of both thermal energy (from the thermal fluid circulating through the channels 844) and IR energy (from the IR emitter in the second layer 836 of the plate 804) can complete the sublimation step more quickly.

[0051] In some embodiments, after sublimation, material 860 is maintained at low pressure while energy (heat and / or IR) is continued to be added. In some embodiments, this is done to remove said components or any other components that are chemically bonded to other components in material 860. As an example, water of hydration is removed in this step.

[0052] After the constituents are removed from material 860 by sublimation, the environment surrounding shelf 320 is brought to atmospheric pressure and material 860 (and container 840) is removed from plate 808 for storage or further processing.

[0053] As will be appreciated, structure 800 allows a plate (e.g., plate 804 or plate 808) to be used to process material both below and above the plate. For example, as described above, second layer 836 has an IR emitter and adds energy to the material placed below it. However, first layer 828 is used to cool the material placed above first layer 828, freeze liquids in the material to a solid, and add thermal energy to the material (e.g., by circulating a thermal fluid through channels 824). Similarly, second layer 856 of plate 808 is used as an IR emitter for material placed below second layer 856, and, as described above, first layer 848 is used to cool material 860, freeze liquids in the material, and add thermal energy in a sublimation step.

[0054] FIG. 8B is a diagram of another embodiment of the plate structure 800. In this embodiment, the plate 808 has features shaped to hold the container and / or the material to be freeze-dried. As shown in FIG. 8B, the plate 808 has an edge 864 that corresponds to at least a portion of the shape of the container 840. The edge 864 defines where the container 840 is placed on the plate 808. In some embodiments, the edge 864 is also useful when pressing the container 840 with the plate 804. The edge 864 can keep the container 840 from moving when it is pressed by the plate 804. It is also used as a mold for the material being freeze-dried during the freezing step.

[0055] In some embodiments, the rim 864 only partially surrounds the container. For example, the rim may be provided on two or three sides of the container, or may be discontinuous, surrounding some portions of the container and not others.

[0056] The above description of the use of plate structure 800 in shelving system 300 is provided for illustrative purposes only. The plate structure 800 and the freeze-drying process utilizing shelving system 300 may include additional steps not described above. The above description is not intended to be exhaustive, but rather to illustrate some of the features of plate structure 800.

[0057] 9 illustrates a second embodiment of a two plate structure 900 for use as part of a shelving system, for example, as part of shelf 320 (FIGS. 3 and 4) in system 300. Structure 900 has several similar features to structure 800 described above. Structure 900 has a first plate 904 and a second plate 908. First plate 904 has a side 912 that faces a side 916 of second plate 908. The two facing sides 912, 916 define a space 920 between the faces.

[0058] As shown in FIG. 9, surface 916 includes several features (e.g., ridges 960). These features provide a surface with improved heat and / or mass transfer surface area. In an embodiment, this is achieved by providing macrostructures. For example, ridges 960, 964 provide structure to the surface of the material during the freezing step of the freeze-drying process. Without being bound by theory, it is believed that improving the heat and / or mass transfer surface area of ​​the material facilitates sublimation (of a component of the material being freeze-dried) during the sublimation step. Although surface 912 is shown with ridges 964 and surface 916 with ridges 960, surfaces 912, 916 may have other types of structures to provide surface areas with improved heat and mass transfer properties. As a non-limiting example of such structures, surface 916 may have a pattern (random or regular) of hemispherical depressions and / or hemispherical protrusions of the same or different sizes.

[0059] In one embodiment, the size, shape, or location of the features is determined by considerations. For example, for features on surface 916, the shape is determined by factors that affect the transfer of thermal energy to the material being freeze-dried, such as the rigidity of the container in which the material is contained. The rigidity of the container will affect the contact between the material to be freeze-dried and surface 916, which will affect the transfer of thermal energy.

[0060] In an embodiment, each plate 904, 908 has a similar structure. In other embodiments, they may have different structures. Plate 904 has a first layer 928, which in an embodiment is made of a thermally conductive material. The first layer 928 has channels 924 for the passage of a thermal fluid. The temperature of the first layer 928 is controlled by heating or cooling the first layer 928 using the thermal fluid.

[0061] Plate 904 further includes an interface 932 between first layer 928 and second layer 936. Interface 932 includes an insulating material, which allows the first layer 928 to have a different temperature than the second layer 936. In other embodiments, interface 932 may alternatively or additionally include properties that aid in adhesion between first layer 928 and second layer 936.

[0062] In one embodiment, the second layer 936 comprises an IR emitting material. In some embodiments, the material is an infrared emitter that emits infrared (IR) energy. In such an embodiment, the second layer 936 has an embedded electrode that heats the layer 936 and a surface 912 that emits IR energy. The IR energy is used in performing some steps of the freeze-drying process. As shown in the embodiment of FIG. 9, the plate 908 has a similar structure to the plate 904, such as having a first layer 948, a second layer 956, a boundary 952, and channels 944 for circulating a heating fluid.

[0063] Figure 10 shows a third embodiment of a two-plate structure 1000 for use as part of a shelving system (e.g., shelf 520) of system 500 shown in Figures 5 and 6. Structure 1000 has a first plate 1004 and a second plate 1008. First plate 1004 has a side 1012 that faces a side 1016 of second plate 1008. The two opposing sides 1012, 1016 define a space 1020 between them. The space 1020 is where the material to be freeze-dried is placed.

[0064] In an embodiment, the plates 1004 and 1008 have different structures. The plate 1004 has a first layer 1028, which in an embodiment is made of a thermally conductive material. The first layer 1028 has channels 1024 for circulating a thermal fluid. The plate 1004 further has a boundary 1032 between the first layer 1028 and the second layer 1036. The boundary 1032 includes a thermally insulating material, which allows the temperature of the first layer 1028 to be different from that of the second layer 1036. In other embodiments, the boundary 1032 may alternatively or additionally have properties that aid in the adhesion of the first layer 1028 to the second layer 1036.

[0065] In one embodiment, the second layer 1036 comprises an IR emitting material. In some embodiments, the material is an infrared emitter that emits infrared (IR) energy. In such embodiments, the second layer 1036 may have embedded elements for generating and emitting IR energy. For example, the second layer 1036 may have electrodes, heating elements, sensors (e.g., thermocouples), and / or combinations thereof. The IR energy emitted by the second layer 1036 is used in performing several steps of the freeze-drying process.

[0066] As shown in the embodiment of Figure 10, the plate 1008 has a layer 1040. In an embodiment, the layer 1040 is made of a thermally conductive material. The layer 1040 has channels 1044 that provide a path for circulating a thermal fluid. The thermal fluid is used to control the temperature of the layer 1040 and the material to be freeze-dried placed on the surface 1016 by heating or cooling the first layer 1040.

[0067] In embodiments, the plate structure 1000 is used in a shelf system 500 (FIGS. 5 and 6) as part of a freeze-drying apparatus that includes other components such as a vacuum system that creates a low pressure (subatmospheric) environment around the shelf system 500. In these embodiments, the plates 1004, 1008 form part of a shelf 520 and are connected to a shelf motion system 512 and a thermal fluid system 516.

[0068] In operation, the shelf system 500 having the plate structure 1000 (as part of the shelf 520) operates similarly to the shelf system 300 having the plate structure 800 described above. The plate structure 1000 as part of the shelf 520 is placed in a vacuum chamber that is used to create a low pressure (e.g., below atmospheric pressure) environment around at least the shelf 520 of the system 500. The shelf motion system 512 then increases the space 1020 and places a container (containing the material to be freeze-dried (e.g., biological liquid)) on the surface 1016 of the plate 1008. The system 512 then moves one or more of the plates 1004 and / or the plate 1008, decreasing the space 1020 and compressing the container containing the material to form a layer of material of approximately uniform thickness. The thermal fluid system 516 then circulates a thermal fluid through the channels 1044 of the plate 1008 to cool the layer 1044 of the plate 1008 and, therefore, the material to be freeze-dried.

[0069] As discussed above, it is believed (without being bound by theory) that compressing the material to be freeze-dried during the freezing step can result in a more uniform cross-section of the material. This more uniform cross-section is believed to increase the efficiency of removing a component (e.g., ice) from the material during the subsequent sublimation step. That is, by reducing thickness variation, the rate at which sublimation proceeds through the material can be made uniform, making the sublimation step more efficient and shorter in duration.

[0070] In other embodiments, during the freezing step, the material to be lyophilized is molded or shaped, for example, on its surface. For example, as described above, a structure can be imprinted onto the material to increase its surface area (see, for example, FIG. 9). In other embodiments, the material is molded based on the shape of a shelf or the shape of a container that contains the material.

[0071] After the substance disposed on surface 1016 is frozen, the shelf 520 (having plate structure 1000) is placed in a low pressure environment to promote sublimation of at least one component of the substance, and shelf motion system 512 increases volume 1020 in preparation for the sublimation step. Additionally, a thermal fluid is circulated through channels 1044 to apply thermal energy to the substance to promote sublimation of a component in the substance.

[0072] As mentioned above, in some embodiments, the second layer 1036 is a layer comprising an IR emitter. In these embodiments, activating the IR emitter directs IR energy to the material on the surface 1016. The IR energy provides additional energy to sublimate a component from the material. In these embodiments, the addition of both thermal energy (from the thermal fluid circulating through the channels 1044) and IR energy (from the IR emitter in the second layer 1036 of the plate 1004) can complete the sublimation step more quickly.

[0073] In some embodiments, the sublimation step is performed using IR energy only. As described above, the IR emitters in the second layer 1036 add energy to the frozen material. In some of these embodiments, the material to be freeze-dried is cooled using a thermal fluid circulating through the channels 1044. Without being bound by theory, it is believed that in the freeze-drying process, sublimation of the material occurs at the surface of the material. Thus, when thermal energy is applied to the bottom surface of the material to be freeze-dried (e.g., using the plate structure shown in FIG. 10), the energy must be transferred to the top surface where sublimation occurs. However, as heat is transferred through the material, it increases the temperature of the material at certain points, which results in the melting of certain components (e.g., ice) at those points, making it even more difficult for the thermal energy to be transferred to the top surface of the material.

[0074] Thus, in some embodiments, the material is sublimated using only IR energy. Furthermore, to avoid melting, thermal energy is removed from the bottom surface of the material to cool the material and avoid melting. For example, referring to FIG. 10, the material is placed in the space 1020 for sublimation. IR emitters in the second layer 1036 are used to apply IR energy to the material, sublimating a component of the material from the top surface of the material facing the second layer 1036. To avoid possible melting, a thermal fluid in the channel 1044 is circulated at a temperature that removes energy (e.g., acts as a heat sink) to keep the material cool and avoid melting. These are examples of processes that can be performed using the plate structure shown in FIG. 10. In other embodiments, processes having different steps can be performed using the plate structure shown in FIG. 10.

[0075] In some embodiments, after sublimation, the material is maintained at low pressure (e.g., below atmospheric pressure) while energy (heat and / or IR) is continued to be added. In some embodiments, this is done to remove said component or any other components that are chemically bonded to other components in the material. As an example, water of hydration is removed in this step.

[0076] After the components (eg, adsorbed components) are removed from the material by sublimation, the environment surrounding shelf 520 is brought to atmospheric pressure and the material is removed from plate 1008 for storage or subsequent processing.

[0077] Although the above description of plate structures 800, 900, 1000 has been given with respect to an embodiment incorporating the plate structures in a freeze-drying device or system (e.g., device 100 or device 200), the invention is not so limited. In other embodiments, plate structures 800, 900, 1000 may be part of different devices used in parts of the freeze-drying process that are not performed in a single device. As non-limiting examples, the evaporation and freezing steps described above may be performed in devices having one or more of the features of plate structures 800, 900, 1000. Also, the sublimation step may be performed in other devices that include the same or different features of plate structures 800, 900, 1000 described above or that do not include the features of the plate structures.

[0078] As another example, a process may only include a freezing step and a sublimation step. The freezing step may be performed in an apparatus that includes one or more features of plate structures 800, 900, 1000 or other features that, for example, shape the material during freezing. The sublimation step may be performed in other apparatus that includes the same or different features of plate structures 800, 900, 1000 or does not include the features of plate structures 800, 900, 1000.

[0079] As yet another example, the freezing step may include providing a surface for the material with improved heat and mass transfer properties, and such a step may be performed in a separate apparatus. In these embodiments, the features of plate structure 900 are used in the apparatus. The previous and subsequent steps may be performed in one or more different apparatus.

[0080] Additionally, although certain features have been described in the above description, other embodiments may include other structures, processes, and steps within the scope of the present invention. As a non-limiting example, the freeze-drying process involves sterile materials that need to be kept sterile. In these embodiments, the apparatus has features that maintain the sterility of, for example, the shelving system, plates, or other structures used in the freeze-drying process. Such sterility is maintained using various systems. Non-limiting examples of such systems include UV (ultraviolet) irradiation systems, microwave systems, cleaning systems, steam systems, pressure systems, additional vacuum systems, filtration systems, and / or combinations thereof. As an example, a UV irradiation system with UV lamps or UV-LEDs is utilized to sterilize components of the freeze-drying apparatus or system and maintain a sterile environment for the materials being freeze-dried that need to be kept sterile.

[0081] Figure 11 shows one embodiment of containers 1100A, 1100B used to contain materials for freeze-drying. As shown in Figure 11, containers 1100A, 1100B are positioned on plates 1104, 1108 that are part of a shelf system of a freeze-drying apparatus, such as apparatus 100 or apparatus 200.

[0082] FIG. 12 is an exploded view of a container 1200 having similar features to containers 1100A, 1100B. Container 1200 has a first wall 1204, a second wall 1208, and three port connectors 1212, 1216, 1220. As shown in FIG. 12, the three port connectors 1212, 1216, 1220 are positioned between the first wall 1204 and the second wall 1208. The port connectors are used to connect to other containers to fill container 1200 with material to be lyophilized, to add liquid to container 1200 to reconstitute the lyophilized material, and / or to remove material (e.g., reconstituted lyophilized material) from container 1200. Port connectors 1212, 1216, 1220 do not have to be positioned between first wall 1204 and second wall 1208. For example, one or more of the port connectors 1212 , 1216 , 1220 may be integrated into one of the walls 1204 , 1208 .

[0083] In some embodiments, the first wall 1204 is made of a material that is permeable to at least some gases. For example, the first wall 1204 is made of a material that is highly permeable to water vapor and has low permeability (i.e., waterproof) to liquid water. In yet other embodiments, the first wall 1204 is made of a biocompatible material. Non-limiting examples of materials that may be used for the first wall 1204 include flashspun high density polyethylene (HDPE) and polytetrafluoroethylene (PTFE). In one embodiment, the first wall 1204 comprises a nonwoven fabric that includes fibers made from flashspun HDPE. In other embodiments, the first wall 1204 is made by casting a copolymer, such as a polyethylene copolymer, a vinyl copolymer, an acrylic copolymer, a polypropylene copolymer, or an amide copolymer, onto a substrate (e.g., a woven or nonwoven fabric). In one particular embodiment, the first wall 1204 is made by casting an acrylic copolymer onto a nylon nonwoven fabric.

[0084] The first wall 1204 may be made from a material produced by a particular process. For example, as described above, the material may be produced by a spinning process, including but not limited to flash spun, spunbond, dry-laid, wet-laid, melt-blowing, spunlace, etc. These processes produce nonwoven fabrics. Alternatively, the process may be used to produce fibers that are further processed, for example, by drawing or weaving. Other examples of such materials include polymers or copolymers that are formed into substrates such as woven or nonwoven fabrics. In producing the material for the first wall 1204, any of these processes may be used to produce the material for the first wall 1204 with the desired properties, gas permeability, tensile strength, waterproofness, etc.

[0085] In certain embodiments, the first wall 1204 has a water vapor transmission rate of greater than about 15 metric perms (unless otherwise noted below, perms are metric perms), or greater than about 20 perms, or greater than about 25 perms, or greater than about 30 perms, or greater than about 35 perms. In other embodiments, the water vapor transmission rate of the first wall 1204 is greater than about 50 perms, or greater than about 75 perms, or greater than about 100 perms, or greater than about 150 perms, or greater than about 200 perms. In some embodiments, the first layer 1204 has a water vapor transmission rate in the range of about 10 perms to about 70 perms, such as between about 15 perms to about 65 perms, or between about 20 perms to about 60 perms. In other embodiments, the first layer 1204 has a water vapor transmission rate in the range of about 50 perm to about 1000 perm, such as between about 100 perm to about 750 perm, or between about 200 perm to about 500 perm. Also, in some embodiments, the first layer 1204 has a water resistance (i.e., hydrostatic head) of greater than about 100 cm, or greater than about 150 cm, or greater than about 200 cm, or greater than about 250 cm. In some embodiments, the first layer 1204 has a water resistance rate in the range of about 50 cm to about 400 cm, such as between about 100 cm to about 350 cm, or between about 150 cm to about 300 cm. In some embodiments, the first layer 1204 has a combination of any of the above water vapor transmission rates and any of the above water resistance rates. In some embodiments, the first wall 1204 is made of a material including a nonwoven fabric formed from polymeric fibers produced by a spinning process. In other embodiments, the first wall 1204 is made from materials including copolymers formed into nonwoven fabrics. These materials are manufactured to have the water vapor transmission rates and water resistance values ​​described above.

[0086] In certain embodiments, the wall 1208 is made of any suitable material, including polymers. In some embodiments, the wall 1208 is made of a transparent or light-transmitting material. Non-limiting examples of such materials include polycarbonate, acrylic, polystyrene, polysulfone, polyethylene, polyolefin, polypropylene, polyvinyl chloride, or combinations thereof. Transparent or light-transmitting materials are useful in embodiments in which the material within the container 1200 undergoes a pathogen reduction process using photosensitizers and illumination. In these embodiments, the container 1200 can be used as an irradiation container. In certain embodiments, the wall 1208 is biocompatible at temperatures and pressures typical of the freeze-drying process. In certain embodiments, the wall 1208 comprises a polyolefin material.

[0087] In some embodiments, the wall 1208 is a single sheet when the container 1200 is a bag. In other embodiments, the wall 1208 provides depth to the material contained in the container 1200. In these embodiments, the wall 1208 takes the form of a tray.

[0088] Figure 13 is a cross-sectional view of container 1200 showing volume 1240. As shown in Figure 13, wall 1204 is joined to wall 1208 at one or more joints 1224. Thus, in addition to the above-mentioned properties of walls 1204, 1208, the walls are made of materials that are compatible with each other such that they can be joined together to form container 1200. Walls 1204, 1208 are joined together using one or more suitable techniques. Non-limiting examples of such techniques include heat sealing, ultrasonic welding, RF welding, solvent bonding, laser welding, adhesive bonding, and / or combinations thereof.

[0089] In one embodiment, container 1200 is used to freeze-dry a biological fluid (plasma 1244, e.g., human plasma) held within volume 1240, as shown in Figure 13. In this embodiment, wall 1204 is made of a material with a water vapor transmission rate of greater than about 35 perm and a water resistance of greater than about 100 cm, so that upon sublimation of ice, water vapor can easily pass through layer 1204 while liquid plasma cannot escape from volume 1240. Waterproofing is also useful when reconstituting the plasma with an aqueous solution.

[0090] In addition to other features of the container 1200, the container can keep the freeze-dried material sterile. That is, both walls 1204 and 1208 provide a barrier against pathogens, bacteria, or other microorganisms to prevent contamination of the material within the container 1200. This feature is particularly useful when the freeze-dried material is a biological liquid that will later be injected into a patient. The ability to maintain a sealed, sterile environment within the container 1200 eliminates the need to ensure sterility of the material environment during freeze-drying. That is, the equipment used in the freeze-drying process does not need to be sterilized before performing various steps. This eliminates the need for expensive vacuum, filter, or other systems used in clean room environments. In these embodiments, the container 1200 maintains a closed system for freeze-drying and further processing (e.g., storage, rehydration, and use of the rehydrated material).

[0091] FIG. 14 is a cross-sectional view of an embodiment of a three-walled container 1400 having a volume 1440 for containing a biological liquid, such as, for example, plasma 1444 (e.g., human plasma). As shown in FIG. 14, the container 1400 has a third wall 1404, a first wall 1408, and a second wall 1412. As shown in FIG. 14, the third wall 1404 is positioned above and adjacent to the first wall 1408. In one embodiment, the third wall 1404 serves as a protective layer for the first wall 1408, among other functions. The provision of the third wall 1404 prevents damage to the first wall 1408 that may occur during handling of the container 1400. In addition, direct contact of hands or other objects with the first wall 1408 is avoided.

[0092] In some embodiments, the third wall 1404 and the second wall 1412 are made of similar materials. In some embodiments, the materials are the same as those described for the wall 1208. The third wall 1404 and the second wall 1412 may be made of any suitable material, including polymers. In some embodiments, the third wall 1404 and the second wall 1412 are made of a transparent or light-transmitting material. Non-limiting examples of such materials include polycarbonate, acrylic, polystyrene, polysulfone, polyethylene, polyolefin, polypropylene, polyvinyl chloride, or combinations thereof. Transparent or light-transmitting materials are useful in embodiments in which the material in the container 1400 undergoes a pathogen reduction process using photosensitizers and illumination. In these embodiments, the container 1400 can be used as an irradiation container. In some embodiments, the wall 1404 is biocompatible at temperatures and pressures typical of the freeze-drying process. In some embodiments, the third wall 1404 and the wall 1412 comprise a polyolefin material. In one embodiment, the walls 1404, 1408 are made of different materials.

[0093] In some embodiments, the first wall 1408 is made of a material that is permeable to at least some gases. For example, the first wall 1408 is made of a material that is highly permeable to water vapor and has low permeability (i.e., waterproof) to liquid water. In yet other embodiments, the first wall 1408 is made of a biocompatible material. Examples of materials that may be used for the first wall 1408 include flashspun high density polyethylene (HDPE) and polytetrafluoroethylene (PTFE). In one embodiment, the first wall 1408 comprises a nonwoven fabric that includes fibers made from flashspun HDPE. In other embodiments, the first wall 1408 is made by forming a copolymer, such as a polyethylene copolymer, a vinyl copolymer, an acrylic copolymer, a polypropylene copolymer, or an amide copolymer, on a substrate (e.g., a woven or nonwoven fabric). In one embodiment, the first wall 1408 is made by forming an acrylic copolymer on a nylon nonwoven fabric.

[0094] In certain embodiments, the first wall 1408 has a water vapor transmission rate of greater than about 15 perm, or greater than about 20 perm, or greater than about 25 perm, or greater than about 30 perm, or greater than about 35 perm. In some embodiments, the first wall 1408 has a water vapor transmission rate in the range of about 10 perm to about 700 perm, such as between about 20 perm to about 650 perm, or between about 30 perm to about 600 perm. Also, in some embodiments, the first wall 1408 has a water resistance (i.e., hydrostatic head) of greater than about 100 cm, or greater than about 150 cm, or greater than about 200 cm, or greater than about 250 cm. In some embodiments, the first wall 1408 has a water resistance in the range of about 50 cm to about 400 cm, such as between about 100 cm to about 350 cm, or between about 150 cm to about 300 cm. In some embodiments, the first wall 1408 has a combination of any of the water vapor transmission rates above and any of the water resistance rates above.

[0095] 14, first wall 1408 is attached to both wall 1404 and wall 1412 at one or more joints 1424. Thus, in addition to other properties, the walls are made of materials that are compatible with one another such that they can be joined together to form container 1400. Walls 1404, 1408, 1412 are joined together using one or more suitable techniques. Non-limiting examples of such techniques include heat sealing, ultrasonic welding, RF welding, solvent bonding, laser welding, adhesive bonding, and the like.

[0096] In one embodiment, the container 1400 is used to freeze-dry a biological fluid, such as plasma 1444. In this embodiment, the wall 1408 is made of a material with a water vapor transmission rate of greater than about 75 perm and a water resistance of greater than about 100 cm, so that during the sublimation step (e.g., sublimation of ice), water vapor passes through the wall 1408 and enters the volume 1448. The wall 1404 has one or more openings, so that gas (e.g., water vapor) can escape from the volume 1448 to the outside environment. The waterproof nature of the wall 1408 prevents water vapor that would condense in the volume 1448 from escaping into the volume 1440 and rehydrating the freeze-dried plasma.

[0097] Figure 15 is a cross-sectional view of a three-walled container 1500 having a volume 1540 for containing a biological fluid, such as, for example, plasma 1544. As shown in Figure 15, the container 1500 has a third wall 1528, a first wall 1504, and a second wall 1508. As shown in Figure 15, the third wall 1528 is positioned above and adjacent to the first wall 1504.

[0098] In some embodiments, the second wall 1508 is made of a material similar to that described for the wall 1208 (FIGS. 12 and 13). The second wall 1508 may be made of any suitable material, including polymers. In some embodiments, the second wall 1508 is made of a transparent or light-transmitting material. Non-limiting examples of such materials include polycarbonate, acrylic, polystyrene, polysulfone, polyethylene, polyolefin, polypropylene, polyvinyl chloride, or combinations thereof. Transparent or light-transmitting materials are useful in embodiments in which the material within the container 1500 undergoes a pathogen reduction process using photosensitizers and illumination. In these embodiments, the container 1500 can be used as an irradiation container. In some embodiments, the second wall 1508 is biocompatible at temperatures and pressures typical of the freeze-drying process. In some embodiments, the third wall 1528 comprises a polyolefin material.

[0099] In some embodiments, the third wall 1528 and the first wall 1504 are made of a material that is permeable to at least some gases. For example, the third wall 1528 and the first wall 1504 are made of a material that is highly permeable to water vapor and has low permeability (i.e., waterproof) to liquid water. Additionally, in other embodiments, the third wall 1528 and the first wall 1504 may be made of a biocompatible material. Examples of materials used for the third wall 1528 and the first wall 1504 include flash-spun high density polyethylene (HDPE) and polytetrafluoroethylene (PTFE). In one embodiment, the third wall 1528 and the first wall 1504 comprise a nonwoven fabric that includes fibers made from flash-spun HDPE. In other embodiments, the third wall 1528 comprises a polymer formed into a nonwoven fabric.

[0100] In certain embodiments, the third wall 1528 and the first wall 1504 have a water vapor transmission rate of greater than about 45 perms, or greater than about 60 perms, or greater than about 75 perms, or greater than about 90 perms, or greater than about 105 perms. In some embodiments, the third wall 1528 and the first wall 1504 have a water vapor transmission rate in the range of about 50 perms to about 900 perms, such as between about 100 perms to about 850 perms, or between about 150 perms to about 800 perms. Also, in some embodiments, the third wall 1528 and the first wall 1504 have a water resistance (i.e., hydrostatic head) of greater than about 75 cm, or greater than about 125 cm, or greater than about 175 cm, or greater than about 225 cm. In some embodiments, the third wall 1528 and the first wall 1504 have a water resistance in the range of about 25 cm to about 500 cm, such as between about 50 cm to about 400 cm, or between about 100 cm to about 300 cm. In some embodiments, the third wall 1528 and the first wall 1504 have a combination of any of the water vapor transmission rates above and any of the water resistance rates above.

[0101] 15, the first wall 1504 (and in some embodiments, the third wall 1528) is joined to the wall 1508 at one or more joints 1524. Thus, in addition to other properties, the first wall 1504 and the second wall 1508 are made of mutually compatible materials such that they can be joined together to form the container 1500. The walls 1528, 1504, 1508 are joined together using one or more suitable techniques, in various combinations. Non-limiting examples of such techniques include heat sealing, ultrasonic welding, RF welding, solvent bonding, laser welding, adhesive bonding, and / or combinations thereof, etc.

[0102] In some embodiments, the third wall 1528 and the first wall 1504 are made of the same or similar materials and / or materials having similar properties. Non-limiting examples of such properties include thickness, tear strength, toughness, water vapor transmission rate, water resistance, etc. However, in other embodiments, the third wall 1528 and the first wall 1504 may have different properties. For example, in some embodiments, the third wall 1528 may be thicker than the first wall 1504 to further add robustness to the container 1500. In other embodiments, the third wall 1528 may have a higher water vapor transmission rate. In this case, water vapor that passes through the first wall 1504 can more easily pass through the third wall 1528 to the surrounding environment. In yet other examples, the third wall 1528 may be more waterproof or provide a more effective barrier against microorganisms. In this case, water is prevented from seeping into the volume 1540, and the sterility of the volume 1540 is maintained.

[0103] Although not shown, in some embodiments, container 1500 may have a fourth wall above third wall 1528. The fourth wall is provided as an additional layer of protection. Similar to third layer 1404 of container 1400, the fourth layer prevents damage to third wall 1528 that may occur when handling container 1500 and also prevents hands or other objects from directly contacting third wall 1528.

[0104] 16-17C show an embodiment of a container 1600 used to contain and store materials for freeze-drying and after freeze-drying. FIG. 16 is a front view of the container 1600. FIGS. 17A-17C are various cross-sectional views of the container 1600 taken along line AA (shown in FIG. 16). In some embodiments, the container 1600 is used to freeze-dry biological fluids such as whole blood or blood components. However, embodiments of the invention are not so limited. Freeze-drying and storage of any substance, liquid or solid, may be performed using embodiments of the container 1600.

[0105] As shown in Figure 16, container 1600 has a first chamber 1604 and a second chamber 1608. As described below, in the embodiment shown in Figures 16-17C, first chamber 1604 is used in the freeze-drying of a material and second chamber 1608 is used to contain and store the freeze-dried material until it is rehydrated for use. Other embodiments may have different constructions, designs or components with a first chamber for containing the material during freeze-drying and a second chamber for containing the material after freeze-drying.

[0106] The first chamber 1604 has a port 1612. A substance such as blood or a blood component (e.g., human plasma) enters the first chamber 1604 via the port 1612. The second chamber 1608 has a port 1616. Hydration water enters the second chamber 1608 via the port 1616. The second chamber 1608 also has a port 1620. Rehydrated substances exit the second chamber 1608 via the port 1620 (e.g., rehydrated blood components such as plasma exit the second chamber via port 1620 for infusion into the patient).

[0107] 17A-17C, the first chamber 1604 has a first wall 1624 and a second wall 1628. The second wall is joined to the first wall to define an interior volume 1632 of the first chamber 1604. As described above, the first chamber 1604 is used to contain a substance during lyophilization. The substance for lyophilization is contained within volume 1632.

[0108] In certain embodiments, the first wall 1624 is made from a flexible polymeric material. In some embodiments, the first wall 1624 is made from a transparent or translucent polymeric material. Non-limiting examples of such materials include polycarbonate, acrylic, polystyrene, polysulfone, polyethylene, polyolefin, polypropylene, polyvinyl chloride, or combinations thereof.

[0109] 16, second wall 1628 has region 1656 that has a gas permeability greater than the gas permeability of first wall 1624. Because first chamber 1604 is used to contain a substance during lyophilization, region 1656 is provided to allow gas (e.g., water vapor) to escape from volume 1632 during lyophilization.

[0110] In certain embodiments, region 1656 is made from a material that is relatively permeable to gases, such as water vapor, and strong enough to hold materials without leaking. In some embodiments, region 1656 is made from one or more of the following materials: flash spun high density polyethylene (HDPE), polytetrafluoroethylene (PTFE), acrylic formed into a woven or nonwoven fabric, amide formed into a woven or nonwoven fabric, and / or combinations thereof.

[0111] 16, for example, occupying more than half of wall 1628. In other embodiments, the entire wall 1628 is made from a material that is permeable to gases, such as water vapor. In such embodiments, there is no region 1656, and instead the entire wall 1628 provides an area for gas (e.g., water vapor) to escape from volume 1632. In still other embodiments, multiple regions 1656 of the same or different sizes may be provided as part of wall 1628.

[0112] The remainder of wall 1628 (and in some embodiments, wall 1624) may be made from any suitable material. In some embodiments, wall 1628 and / or wall 1624 may be made from a flexible polymeric material. Examples of flexible polymeric materials used for portions of wall 1628 and wall 1624 include, but are not limited to, polycarbonate, acrylic, polystyrene, polysulfone, polyethylene, polyolefin, polypropylene, polyvinyl chloride, or combinations thereof.

[0113] As described above, the container 1600 includes a second chamber 1608. The second chamber 1608 includes a first wall 1636 joined to a second wall 1640 to define an interior volume 1644. In certain embodiments, the second chamber 1608 is configured to store a substance (e.g., whole blood or a blood component) after lyophilization. Thus, the walls 1636, 1640 are made from a flexible polymeric material that is robust and can withstand long storage and significant handling. In some embodiments, the walls 1636, 1640 are made from a transparent or light-transmitting polymeric material. Non-limiting examples of such materials include polycarbonate, acrylic, polystyrene, polysulfone, polyethylene, polyolefin, polypropylene, polyvinyl chloride, or combinations thereof.

[0114] In addition to the first and second chambers 1604, 1608, the container 1600 includes a passageway 1648, shown as 1648A, 1648B, and 1648C in Figures 17A, 17B, and 17C, respectively. Volumes 1632 and 1644 are in communication (e.g., fluid communication) through passageway 1648, but are also sealed from communication between volumes 1632 and 1644 by seal 1652.

[0115] 17A shows passageway 1648A sealed by seal 1652. In this embodiment, there is no communication (e.g., fluid communication) between volume 1632 and volume 1644. This embodiment is used when the material in chamber 1604 is being freeze-dried. Seal 1652 prevents the material (e.g., liquid or solid) from entering volume 1644. By keeping the material in volume 1632, the freeze-drying process is more efficient because wall 1628 (defining volume 1632) provides area 1656 for gas (e.g., water vapor) to escape.

[0116] Seal 1652 may be formed using any suitable material, mechanism, or process. Non-limiting examples of seals for use as seal 1652 include welds, adhesives, frangibles, clamps, joints, and / or combinations thereof. Seal 1652 may be formed by mechanical fastening, welding (e.g., radio frequency, ultrasonic, induction, laser, etc. welding), heat sealing, adhesive bonding, or other means. In an embodiment, seal 1652 may be opened to allow communication between volume 1632 and volume 1644.

[0117] FIG 17B shows passage 1648B open to allow communication between volume 1632 and volume 1644. Similarly, FIG 17C shows passage 1648C in an open state to allow communication between volume 1632 and volume 1644. FIG 17B and FIG 17C show two different embodiments with different amounts of passage 1648 open. Although the amount of opening is different, both embodiments allow material to flow from volume 1632 to volume 1644. Depending on the type of seal, passage 1648 is opened to different amounts.

[0118] The embodiment shown in Figures 17B and 17C is used after the freeze-drying process is completed. The freeze-dried material in volume 1632 is transferred to volume 1644 via pathway 1648B or pathway 1648C. After the transfer of the material, pathway 1648B or pathway 1648C is resealed to prevent the material from returning to volume 1632. In some embodiments, first chamber 1604 may be removed after the freeze-dried material is transferred to volume 1644 and pathway 1648B or pathway 1648C is sealed. As an example, seal 1652 is formed by welding wall 1636 and wall 1640 together, and then wall 1624 and wall 1628 are cut to separate first chamber 1604 from second chamber 1608.

[0119] Below, a process according to an embodiment of the invention for freeze-drying and storing whole blood or blood components (e.g., plasma) is described. However, the invention is not so limited and may be used to freeze-dry and store other substances. In the following description, reference is made to certain features of the container 1600 shown in Figures 16-17C, but the invention is not limited to being embodied by any particular structure. In other embodiments, different features may be utilized.

[0120] In one embodiment, a plasma fraction in a liquid state is placed in a container, such as container 1600. In particular, the plasma fraction is loaded into chamber 1604 via port 1612. Chamber 1604 provides a sterile barrier and also allows for the lyophilization of the plasma while allowing water vapor to escape through the walls (e.g., region 1656).

[0121] After the liquid plasma is loaded into chamber 1604, container 1600 is placed in an apparatus for freeze-drying materials, such as apparatus 100 (FIG. 1) or apparatus 200 (FIG. 2), and the liquid plasma is subjected to a freeze-drying process.

[0122] During freeze-drying of plasma, a seal such as seal 1652 is present in passageway 1648, preventing communication between the volumes of chamber 1604 and chamber 1608. That is, there is no fluid communication between volume 1632 and volume 1644.

[0123] After lyophilization of the plasma, container 1600 is removed from the freeze-drying apparatus. Seal 1652 is removed / opened to allow communication through pathway 1648. The lyophilized plasma is transferred from volume 1632 to volume 1644. Seal 1652 is then closed or resealed. In some embodiments, after resealing pathway 1648 or as part of the resealing process of pathway 1648, chamber 1604 is removed from chamber 1608.

[0124] In some embodiments, chamber 1608 is constructed of materials that are robust and can withstand the rigors of significant handling (e.g., backpack transport in a military environment, handling during mobile use such as in an air ambulance (helicopter or vehicle)) and thus allows the freeze-dried plasma to be stored in chamber 1608 for a relatively long period of time until it is ready for use (e.g., rehydrated and ready to be infused into a patient).

[0125] In some embodiments, before the lyophilized plasma is used, a rehydration liquid is transferred to chamber 1608 through port 1616. After a period of time to hydrate the plasma (e.g., less than 5 minutes), the rehydrated plasma is infused into the patient through port 1620.

[0126] In embodiments where container 1600 is used to freeze-dry, store, and infuse plasma, the two chambers 1604, 1608 and the rest of the container are maintained sterile and as a closed system throughout the processes of filling, freeze-drying, transfer between chambers, storage, and use.

[0127] 18A and 18B are front views of another container 1800 according to an embodiment of the present invention. In the embodiment shown in Figures 18A and 18B, the container 1800 has a single chamber 1804 having an interior volume 1808. The container 1800 has a first portion 1804A (e.g., a top portion) and a second portion 1804B (e.g., a bottom portion).

[0128] The container 1800 has a first wall (not shown) and a second wall 1828. The second wall 1828 and the first wall are joined to define the interior volume 1808 of the chamber 1804. In certain embodiments, the first wall is made from a flexible polymeric material. In some embodiments, the first wall is made from a transparent or translucent polymeric material. Non-limiting examples of such materials include polycarbonate, acrylic, polystyrene, polysulfone, polyethylene, polyolefin, polypropylene, polyvinyl chloride, or combinations thereof.

[0129] 18A, the top of wall 1828 has a gas permeable region 1856 that allows gases, such as water vapor, to escape from volume 1808. The bottom of wall 1828 does not include a gas permeable region.

[0130] Region 1856 has a gas permeability that is greater than the permeability of the first wall and the remainder of second wall 1828. Region 1856 is provided to allow gas (e.g., water vapor) to escape from volume 1808 during lyophilization.

[0131] In certain embodiments, region 1856 is made from a material that is relatively permeable to gases such as water vapor and has sufficient strength to hold the freeze-dried material without leakage. In some embodiments, region 1856 is made from one or more of the following materials: flash-spun high density polyethylene (HDPE), polytetrafluoroethylene (PTFE), acrylic formed into a woven or nonwoven fabric, amide formed into a woven or nonwoven fabric, and / or combinations thereof. The remaining portion of wall 1828 is made from any suitable material. In certain embodiments, a portion of second wall 1828 is made from a flexible polymeric material. Examples of flexible polymeric materials used for portions of wall 1828 include, but are not limited to, polycarbonate, acrylic, polystyrene, polysulfone, polyethylene, polyolefin, polypropylene, polyvinyl chloride, or combinations thereof.

[0132] For embodiments using container 1800, the material to be freeze-dried is transferred into volume 1808 via one or more of ports 1816 and / or 1820. After the material is freeze-dried, the freeze-dried material is moved manually or automatically (e.g., by a mechanical system) into chamber 1804 so that the majority of the freeze-dried material is located in bottom portion 1804B. After the freeze-dried material has been moved to bottom portion 1804B, bottom portion 1804B is separated from top portion 1804A, as shown in FIG.

[0133] As part of or prior to the process of separating the top 1804A and bottom 1804B, a seal 1860 is formed at the top of the bottom 1804B. The seal 1860 maintains the lyophilized material in a sterile environment throughout the process of separating the bottom 1804B from the top 1804A. In an embodiment, the seal 1860 is formed by any suitable sealing device. Non-limiting examples of devices that may be used to form the seal 1860 and separate the bottom 1804B from the top 1804A include, but are not limited to, ultrasonic welding devices, laser welding devices, RF welding devices, radio frequency welding devices, induction welding devices, hot bar welding devices, pulse welding devices, hot gas welding devices, infrared welding devices, and / or microwave welding devices.

[0134] In some embodiments, the base 1804B is constructed to be robust and to withstand the rigors of significant handling (e.g., backpack transport in a military environment, handling in mobile use such as transport air vehicles (helicopters and vehicles)) such that the lyophilized material is stored in the base 1804B until it is to be used.

[0135] In some embodiments, before the lyophilized material in bottom portion 1804B is used, rehydration liquid is transferred to bottom portion 1804B through one or more ports 1816 and / or port 1820. After a period of time has passed to hydrate the material, the material is transferred out of bottom portion 1804B via one or more ports 1816 and / or port 1820 for use.

[0136] 19A-19C are side views of another embodiment of a container 1900 used to contain a lyophilized material and to store the material after lyophilization. The container 1900 has a first chamber 1904 and a second chamber 1908. As described below, in one embodiment, the first chamber 1904 is used during lyophilization of the material and the second chamber 1908 is used to store the lyophilized material after lyophilization.

[0137] The first chamber 1904 includes a port 1912 through which a substance (e.g., plasma, whole blood, other blood components) is introduced into the first chamber 1904. The first chamber 1904 further includes a first wall 1916 that is joined to a second wall 1920 via a side wall 1924 to define an interior volume of the first chamber 1904. In some embodiments, the side wall 1924 or a portion thereof may be part of the first wall 1916 or the second wall 1920. For example, in some embodiments, the first wall 1916 and / or the second wall 1920 may be formed from a sheet having a size that allows it to be folded to form the side wall 1924 or a portion thereof. In other embodiments, the wall 1920 may be in the form of a tray having a side wall 1924. In one embodiment, the side wall 1924 extends between and around the perimeter of the first wall 1916 and the second wall 1920 .

[0138] As shown in Figures 19A and 19B, the sidewall 1924 has folds 1928A, 1928B, 1928C that allow the sidewall 1924 to be folded and unfolded. Figure 19A shows the sidewall 1924 in a folded position, reducing the interior volume of the chamber 1904. Figure 19B shows the sidewall 1924 in an unfolded position, increasing the interior volume of the chamber 1904.

[0139] As shown in Figure 19B, chamber 1904 is connected to chamber 1908 via passageway 1932. In Figure 19A, clip 1936 is positioned to close and / or seal passageway 1932 to prevent communication between chamber 1904 and chamber 1908.

[0140] Returning to the chamber 1904, the walls 1920 and / or sidewalls 1924 are made from a flexible polymeric material. In some embodiments, the walls 1920 and / or sidewalls 1924 are made from a transparent or translucent polymeric material. Non-limiting examples of such materials include polycarbonate, acrylic, polystyrene, polysulfone, polyethylene, polyolefin, polypropylene, polyvinyl chloride, or combinations thereof.

[0141] The wall 1916 comprises a gas-permeable material. That is, the wall 1916 comprises a material that has a permeability to gas (e.g., water vapor) that is greater than the permeability of the wall 1920. Because the chamber 1904 is used to contain the material during lyophilization, a permeable material is used to allow gas (e.g., water vapor) to escape the chamber 1904 during lyophilization. In some embodiments, the entire wall 1916 may be made from a gas-permeable material. In other embodiments, only some areas of the wall 1916 may comprise a permeable material, similar to the wall 1828 of the container 1800 (FIG. 18A).

[0142] The permeable material used for the walls 1916 is made from a material that has a relatively high permeability to gases such as water vapor and is strong enough to hold materials without leaking. In some embodiments, the walls 1916 are made from one or more of the following materials: flash spun high density polyethylene (HDPE), polytetrafluoroethylene (PTFE), acrylic formed into a woven or nonwoven fabric, amide formed into a woven or nonwoven fabric, and / or combinations thereof.

[0143] In certain embodiments, the wall 1916 has a water vapor transmission rate of greater than about 65 perm, or greater than about 85 perm, or greater than about 105 perm, or greater than about 125 perm, or greater than about 145 perm. In some embodiments, the wall 1916 has a water vapor transmission rate in the range of about 70 perm to about 825 perm, such as between about 95 perm to about 775 perm, or between about 120 perm to about 725 perm. Also, in some embodiments, the wall 1916 has a water resistance (i.e., hydrostatic head) of greater than about 70 cm, or greater than about 85 cm, or greater than about 100 cm, or greater than about 115 cm. In some embodiments, the wall 1916 has a water resistance in the range of about 20 cm to about 525 cm, such as between about 25 cm to about 500 cm, or between about 30 cm to about 475 cm. In some embodiments, the wall 1916 has a combination of any of the water vapor transmission ratings above and any of the water resistance ratings above.

[0144] In embodiments where only a portion of the wall 1916 is of a transparent material, the remaining portion may be made of any suitable material. Examples of flexible polymeric materials used for the portion of the wall 1916 include, but are not limited to, polycarbonate, acrylic, polystyrene, polysulfone, polyethylene, polyolefin, polypropylene, polyvinyl chloride, or combinations thereof.

[0145] As described above, the container 1900 includes a chamber 1908. The chamber 1908 includes a first wall 1940. The first wall 1940 is joined to a second wall 1944 to define an interior volume of the chamber 1908 (see FIGS. 19B and 19C). In certain embodiments, the chamber 1908 is configured to store a substance (e.g., whole blood or a blood component) after lyophilization. Thus, the walls 1940, 1944 are made of a flexible polymeric material that is robust and can withstand long storage and significant handling. In some embodiments, the walls 1940, 1944 are made of a transparent or light-transmitting polymeric material. Non-limiting examples of such materials include polycarbonate, acrylic, polystyrene, polysulfone, polyethylene, polyolefin, polypropylene, polyvinyl chloride, or combinations thereof.

[0146] The chamber 1908 further includes a port 1948. In certain embodiments, the port 1948 is used to remove material from the chamber 1908. In one embodiment, the freeze-dried material in the chamber 1908 is rehydrated in the chamber 1908 and removed from the chamber 1908 via the port 1948. As an example, freeze-dried plasma is stored in the chamber 1908. After adding a rehydration liquid to the freeze-dried plasma, the rehydrated plasma is injected into the patient via the port 1948. In other embodiments, the chamber 1908 includes more than one port. For such embodiments, the port 1948 is used to input a rehydration fluid to rehydrate the freeze-dried plasma, and another port is used to inject the rehydrated plasma into the patient.

[0147] In Figure 19A, the chamber 1908 is rolled up and therefore does not take up as much space as it does in its unrolled state as shown in Figure 19B. By being able to roll up the chamber 1908 (Figure 19A), for example, the container 1900 can take up less shelf space in a freeze-drying apparatus (e.g., 100 or 200). If the chamber 1908 could not be rolled up, the container 1900 would take up shelf space that could be used to freeze-dry additional materials.

[0148] In addition to the chambers 1904, 1908, the vessel 1900 further includes a passageway 1932. The passageway 1932 allows communication (e.g., fluid communication) between the volumes 1904 and 1908, while also being capable of being sealed by a seal to block communication between the volumes 1904 and 1908.

[0149] 19A shows passageway 1932 sealed by clip 1936. In this embodiment, there is no communication (e.g., fluid communication) between volume 1904 and volume 1908. This embodiment is used when the material in chamber 1904 is being freeze-dried. Clip 1936 prevents the material (e.g., liquid or solid) in chamber 1904 from entering the volume of chamber 1908. By keeping the material in volume 1904, the freeze-drying process is more efficient because wall 1916 includes a gas-permeable material that allows gas (e.g., water vapor) to escape. If material were allowed to migrate into chamber 1908, any gas would have to migrate into chamber 1904 and escape through wall 1916, which would prolong the freeze-drying process.

[0150] In other embodiments, any suitable material, mechanism, or process may be used to form a seal between chamber 1904 and chamber 1908 in place of clip 1936. Non-limiting examples of seals used in place of clip 1936 include welds, adhesives, frangibles, bonds, and / or combinations thereof. Formation of a seal between chamber 1904 and chamber 1908 may include mechanical fastening, welding (e.g., radio frequency, ultrasonic, induction, laser, etc. welding), heat sealing, adhesive bonding, and / or other means.

[0151] 19B shows clip 1936 removed, opening pathway 1932 and allowing communication between volumes 1904 and 1908. After the material is lyophilized in chamber 1904, clip 1936 is removed, opening pathway 1932. With pathway 1932 open, the lyophilized material is transferred from chamber 1904 to chamber 1908 for long term storage.

[0152] After the lyophilized material has been transferred to chamber 1908, chambers 1904 and 1908 are resealed to close the communication between the two chambers. As shown in Figure 19C, chamber 1904 is separated from chamber 1908 with seal 1952 sealing chamber 1908. Chamber 1908 is then used to store the lyophilized material for a relatively long period of time (e.g., about 2 years).

[0153] When the container 1900 is used, the substance to be freeze-dried (in one embodiment, the substance is plasma) is transferred to the volume 1904 via the port 1912. As a result of the plasma being introduced into the chamber 1904, the side wall 1924 is expanded in volume by folds 1928A-C (see chamber 1904 in FIG. 19B). With the chamber 1908 still in a rolled up state (see chamber 1908 in FIG. 19A), the container 1900 is placed in a freeze-drying device, such as device 100 (FIG. 1) or device (FIG. 2), and the plasma is freeze-dried. As described above, the freeze-drying process includes exposing the substance and container 1900 to an environment at a first pressure below atmospheric pressure, freezing, and sublimating a component of the substance. Gases evolved during the sublimation process escape the chamber 1904 through the gas-permeable material of the wall 1916.

[0154] After the material has been lyophilized, the lyophilized material is moved manually or automatically (e.g., by a mechanical system) from chamber 1904 to chamber 1908. In particular, clip 1936 is first removed to provide communication between chamber 1904 and chamber 1908. The lyophilized material is then moved into chamber 1908. Chamber 1908 is then sealed and chamber 1904 is separated from chamber 1908, as shown in FIG. 19C.

[0155] As part of or prior to the process of separating chambers 1904 and 1908, a seal 1952 is formed at the end of chamber 1908. Seal 1952 maintains the lyophilized material in a sterile environment throughout the process of separating chambers 1904 and 1908. In one embodiment, seal 1952 is formed by any suitable sealing device. Non-limiting examples of devices that may be used to form seal 1952 and separate chambers 1904 and 1908 include, but are not limited to, ultrasonic welding devices, laser welding devices, RF welding devices, radio frequency welding devices, induction welding devices, hot bar welding devices, pulse welding devices, hot gas welding devices, infrared welding devices, and / or microwave welding devices.

[0156] 20A-20C are side views of another embodiment of a container 2000 that can be used to contain a lyophilized material and to store the material after lyophilization. Container 2000 has a first chamber 2004 and a second chamber 2008. As described below, in one embodiment, chamber 2004 is used during the lyophilization of the material and chamber 2008 is used to store the lyophilized material until it is ready to be rehydrated and used.

[0157] The first chamber 2004 has a port 2012 through which a substance (e.g., plasma, whole blood, other blood components) is introduced into the first chamber 2004. The first chamber 2004 further has a first wall 2016 that is joined to a second wall 2020 to define the interior volume of the first chamber 2004. In some embodiments, the wall 2020 may be deep relative to the substance contained in the chamber 2004. In such an embodiment, the wall 2020 is in the shape of a tray.

[0158] As shown in Fig. 20B, chamber 2004 is connected to chamber 2008 via passageway 2032. In Fig. 20A, clip 2036 is positioned to close and / or seal passageway 2032 to prevent communication between chambers 2004 and 2008.

[0159] Returning to the chamber 2004, the walls 2020 are made from a flexible polymeric material. In some embodiments, the walls 2020 are made from a transparent or translucent polymeric material. Non-limiting examples of such materials include polycarbonate, acrylic, polystyrene, polysulfone, polyethylene, polyolefin, polypropylene, polyvinyl chloride, or combinations thereof.

[0160] The wall 2016 comprises a gas-permeable material. The wall 2016 comprises a material having a permeability to gas (e.g., water vapor) greater than that of the wall 2020. Because the chamber 2004 is used to contain the material during lyophilization, a permeable material is used to allow gas (e.g., water vapor) to escape the chamber 2004 during lyophilization. In some embodiments, the entire wall 2016 may be made from a gas-permeable material. In other embodiments, only some areas of the wall 2016 may be formed from a permeable material, similar to the wall 1828 of the container 1800 (FIG. 18A).

[0161] The permeable material used for the walls 2016 is made from a material that has a relatively high permeability to gases such as water vapor and is strong enough to hold materials without leaking. In some embodiments, the walls 2016 are made from one or more of the following materials: flash spun high density polyethylene (HDPE), polytetrafluoroethylene (PTFE), acrylic formed into a woven or nonwoven fabric, amide formed into a woven or nonwoven fabric, and / or combinations thereof.

[0162] In some embodiments, the wall 2016 has a water vapor transmission rate of greater than about 135 perm, or greater than about 150 perm, or greater than about 165 perm, or greater than about 180 perm, or greater than about 195 perm. In some embodiments, the wall 2016 has a water vapor transmission rate in the range of about 115 perm to about 725 perm, such as between about 130 perm to about 700 perm, or between about 145 perm to about 675 perm. Also, in some embodiments, the wall 2016 has a water resistance (i.e., hydrostatic head) of greater than about 80 cm, or greater than about 90 cm, or greater than about 100 cm, or greater than about 110 cm. In some embodiments, the wall 2016 has a water resistance in the range of about 20 cm to about 500 cm, such as between about 30 cm to about 450 cm, or between about 40 cm to about 400 cm. In some embodiments, the wall 2016 has a combination of any of the water vapor transmission ratings above and any of the water resistance ratings above.

[0163] In embodiments where only a portion of wall 2016 is of a transparent material, the remaining portion is made of any suitable material. Examples of flexible polymeric materials used for portions of wall 2016 include, but are not limited to, polycarbonate, acrylic, polystyrene, polysulfone, polyethylene, polyolefin, polypropylene, polyvinyl chloride, or combinations thereof.

[0164] As described above, the container 2000 includes a chamber 2008. The chamber 2008 includes a first wall 2040. The first wall 2040 is joined to a second wall 2044 to define an interior volume of the chamber 2008 (see FIG. 20B). In certain embodiments, the chamber 2008 is configured to store a substance (e.g., whole blood or a blood component) after lyophilization. Thus, the walls 2040, 2044 are made from a flexible polymeric material that is robust and can withstand long storage and significant handling. In some embodiments, the walls 2040, 2044 are made from a transparent or light-transmitting polymeric material. Non-limiting examples of such materials include polycarbonate, acrylic, polystyrene, polysulfone, polyethylene, polyolefin, polypropylene, polyvinyl chloride, or combinations thereof.

[0165] Chamber 2008 further includes a port 2048. In certain embodiments, port 2048 is used to remove material from chamber 2008. In one embodiment, freeze-dried material in chamber 2008 is rehydrated in chamber 2008 and removed from chamber 2008 via port 2048. As an example, freeze-dried plasma is stored in chamber 2008. After adding rehydration liquid to the freeze-dried plasma, the rehydrated plasma is injected into a patient via port 2048. In other embodiments, chamber 2008 includes more than one port. For such embodiments, port 2048 is used to input rehydration fluid to rehydrate the freeze-dried plasma, and another port is used to inject the rehydrated plasma into a patient.

[0166] In Fig. 20A, chamber 2008 is rolled up and therefore does not take up as much space as it does in its unrolled state as shown in Fig. 20B. By being able to roll up chamber 2008 (Fig. 20A), for example, container 2000 can take up less shelf space in a freeze-drying apparatus (e.g., Fig. 1 or Fig. 2). If chamber 2008 could not be rolled up, container 2000 would take up shelf space that could be used to freeze-dry additional materials.

[0167] In addition to the chambers 2004, 2008, the vessel 2000 further includes a passageway 2032. The passageway 2032 allows communication (e.g., fluid communication) between the volumes 2004 and 2008, while also being capable of being sealed by a seal to block communication between the volumes 2004 and 2008.

[0168] 20A shows passageway 2032 sealed by clip 2036. In this embodiment, there is no communication (e.g., fluid communication) between volume 2004 and volume 2008. This embodiment is used when the material in chamber 2004 is being freeze-dried. Clip 2036 prevents the material (e.g., liquid or solid) in chamber 2004 from entering the volume of chamber 2008. By keeping the material in volume 2004, the freeze-drying process is more efficient because wall 2016 comprises a gas permeable material that allows gas (e.g., water vapor) to escape.

[0169] In other embodiments, any suitable material, mechanism, or process may be used to form a seal between chamber 2004 and chamber 2008 in place of clip 2036. Non-limiting examples of seals used in place of clip 2036 include welds, adhesives, frangibles, bonds, and / or combinations thereof. Formation of a seal between chamber 2004 and chamber 2008 may include mechanical fastening, welding (e.g., radio frequency, ultrasonic, induction, laser, etc. welding), heat sealing, adhesive bonding, or other means.

[0170] 20B shows clip 2036 removed, opening pathway 2032 and allowing communication between volumes 2004 and 2008. After the material is lyophilized in chamber 2004, clip 2036 is removed, opening pathway 2032. With pathway 2032 open, the lyophilized material may be transferred from chamber 2004 to chamber 2008 for long term storage.

[0171] After the lyophilized material has been transferred to chamber 2008, chambers 2004 and 2008 are resealed to close the communication between the two chambers. As shown in Fig. 20C, chamber 2004 is separated from chamber 2008 with seal 2052 sealing chamber 2008. Chamber 2008 is then used to store the lyophilized material for a relatively long period of time (e.g., about 2 years).

[0172] 21 shows one embodiment of a system 2100 for filling a container with a biological fluid. In one embodiment, the system 2100 is used to pool blood or blood components that are subsequently freeze-dried. In one embodiment, the system 2100 is used to pool human plasma. In the following, an embodiment for pooling plasma is described, although in other embodiments, other biological fluids may be pooled.

[0173] The system 2100 has multiple ports 2104 to which multiple containers (e.g., bags) containing plasma can be connected. In one embodiment, the plasma is from different donors, with each bag containing plasma being from a single donor. In some embodiments, the plasma is selected based on the donor's blood type. For example, the plasma is from multiple donors of one blood type or compatible blood types. In one embodiment, multiple specific blood types may be selected from multiple donors to create a universal blood type. In one embodiment, plasma from donors with blood types A, B, and AB may be used to create a universal plasma that can be infused into patients of any blood type.

[0174] After connection to port 2104, the plasma passes through a filter 2108 to remove certain components or contaminants. In one embodiment, filter 2108 is configured to remove cells, such as white blood cells, from the plasma. Although only one filter 2108 is shown in system 2100, in other embodiments, system 2100 may have a series of multiple filters to filter the above-mentioned components or different components or contaminants from the plasma.

[0175] After filtering, the plasma is pooled together in a container 2112. In one embodiment, the container 2112 is a bag capable of containing a relatively large volume of plasma (e.g., at least the volume of plasma in the multiple containers connected to the multiple ports 2104). While contained in the container 2112, the plasma is agitated and mixed. In such an embodiment, the system 2100 further includes features to perform the agitation. Non-limiting examples of such features include rollers, motors, ultrasonic transducers, power sources, etc.

[0176] In certain embodiments, system 2100 uses gravity to create a flow of plasma from various components of system 2100 to various components. In other embodiments, pumps are used to pump the plasma from various components of system 2100 to various components. In the embodiment shown in FIG. 21, pump 2116 is used to move plasma from container 2112 to container 2120. In other embodiments, pumps may be used in other components of the system. For example, a pump may be used to move plasma from filter 2108 to container 2112.

[0177] Container 2120 can be any container suitable for holding plasma, but in some embodiments, the container is similar to container 1200 (FIGS. 12 and 13), container 1600 (FIGS. 17A-18B), container 1800 (FIGS. 18A and 18B), container 1900 (FIGS. 19A-19C), and / or container 2000 (FIGS. 20A-20C). As described in more detail below, system 2100 is used with container 2120 in a process for pooling a biological fluid (e.g., plasma), lyophilizing the fluid to a solid, storing the solid, reconstituting the solid back into the biological fluid, and using the biological fluid with a patient.

[0178] 22 shows a second embodiment of a system 2200 used to pool biofluids and fill containers. System 2200 has similar features to system 2100, but also has several other features. Like system 2100, system 2200 has multiple ports 2204 to which multiple containers (e.g., bags) containing plasma can be connected. In one embodiment, the plasma is from different donors, with each bag containing plasma being from a single donor. As mentioned above, the plasma is selected based on the donor's blood type to create a plasma of one blood type or a universal plasma that can be infused to patients of any blood type.

[0179] From port 2204, the plasma flows through filter 2208, which is similar to filter 2108 and is used to remove certain components (e.g., cells such as white blood cells) or contaminants from the plasma. In other embodiments, system 2200 may have a series of multiple filters to filter the above-mentioned components or different components or contaminants from the plasma.

[0180] After filtering, the plasma is pooled together in a container 2212. In one embodiment, the container 2212 is a bag. The system 2200 further includes components for performing agitation of the plasma. Non-limiting examples of such components include rollers, motors, ultrasonic transducers, power sources, etc.

[0181] System 2200 further includes a pump 2216, which is used to move the plasma from container 2212 to filter 2220. In other embodiments, pumps may be used in other parts of the system. For example, a pump may be used to move the plasma from filter 2208 to container 2212.

[0182] Filter 2220 is used to concentrate the plasma by removing water and salts from the plasma. In one embodiment, filter 2220 is a hollow fiber membrane filter that removes water, salts, and small molecular weight molecules from the plasma. The water, salts, and molecules from filter 2220 are collected in container 2228 and stored for later use or discarded. Although only one filter 2220 is shown in system 2200, in other embodiments, system 2200 may have a series of multiple filters that remove at least water or other components from the plasma.

[0183] Pump 2232 is used to move the plasma from filter 2220 to container 2236. Container 2236 can be any container suitable for holding concentrated plasma, but in some embodiments, the container is similar to container 1200 (FIGS. 12 and 13), container 1600 (FIGS. 16-17C), container 1800 (FIGS. 18A and 18B), container 1900 (FIGS. 19A-19C), and / or container 2000 (FIGS. 20A-20C). System 2200 is used with a container in a process for pooling a biological fluid (e.g., plasma), lyophilizing the fluid to a solid, storing the solid, converting the solid back to the biological fluid, and using the biological fluid on a patient.

[0184] 23 shows an embodiment of a system 2300 for filling a container with a biological fluid. System 2300 is similar to system 2100 described above, but with the additional feature of reducing pathogens. In an embodiment, system 2300 is used to pool blood or blood components and reduce pathogens in the blood or blood components prior to freeze-drying. In one embodiment, system 2200 is used to pool human plasma and reduce pathogens. Although an embodiment in which plasma is pooled and pathogens are reduced is described below, in other embodiments, other biological fluids may be pooled.

[0185] The system 2300 has multiple ports 2304 to which multiple containers (e.g., bags) containing plasma can be connected. In some embodiments, the plasma is from different donors, with each bag containing plasma being from a single donor. In some embodiments, the plasma is selected based on the donor's blood type. For example, the plasma is from multiple donors of one blood type or compatible blood types. In one embodiment, multiple specific blood types may be selected from multiple donors to create a universal blood type. In some embodiments, plasma from donors with blood types A, B, and AB may be used to create a universal plasma that can be infused into patients of any blood type.

[0186] After connection to port 2304, the plasma passes through filter 2308 to remove some components or contaminants. After filtering, the plasma is pooled together in container 2312. In one embodiment, container 2312 is a bag that can contain a relatively large volume of plasma (e.g., at least the volume of plasma in the multiple containers connected to the multiple ports 2304). While contained in container 2312, the plasma is agitated and mixed. In such an embodiment, system 2300 further includes features to perform the agitation. Non-limiting examples of such features include rollers, motors, ultrasonic transducers, power sources, etc.

[0187] In some embodiments, system 2300 utilizes gravity to generate a flow of plasma from various components of system 2300. In other embodiments, pumps are utilized to pump the plasma from various components of system 2300. For example, pump 2316 is used to move plasma from container 2324 to container 2320.

[0188] System 2300 further includes a container 2324 containing a photosensitizer for use in reducing pathogens in the plasma pooled in container 2312. In one embodiment, container 2324 contains an endogenous photosensitizer. A non-limiting example of such a sensitizer includes a flavin, such as riboflavin.

[0189] Container 2312 is made from a material that is transparent or at least translucent to the wavelengths of light used in the pathogen reduction process, hi some embodiments, container 2312 is made from a flexible polymeric material that is transparent or at least translucent to light in the wavelength range of about 250 nm to about 600 nm.

[0190] After the plasma is pooled in the container 2312, the photosensitizer is mixed with the plasma in the container 2312. The system 2300 may further include a member for agitating the plasma and the photosensitizer. Non-limiting examples of such members include rollers, motors, ultrasonic transducers, power sources, etc.

[0191] After the photosensitizer is mixed with the plasma in container 2312, the plasma is exposed to a light source, such as light source 2328. In some embodiments, light source 2328 is at a wavelength that interacts with the photosensitizer, thereby reducing pathogens in the plasma. Examples and detailed descriptions of pathogen reduction for use in embodiments, including combinations of wavelengths of light and photosensitizers, are provided in U.S. Patent Nos. 6,548,241, 6,258,577, and 6,277,337, the entireties of which are expressly incorporated herein by reference.

[0192] After illumination by light source 2328, the pathogen-reduced plasma is transferred (by pump 2316) to container 2320 for subsequent freeze-drying. Container 2320 may be any suitable container for holding the pathogen-reduced plasma. In certain embodiments, the container may be similar to container 1200 (FIGS. 12 and 13), container 1600 (FIGS. 16C-17C), container 1800 (FIGS. 18A and 18B), container 1900 (FIGS. 19A-19C), and / or container 2000 (FIGS. 20A-20C).

[0193] 24 shows an embodiment of a system 2400 for filling a container with a biological fluid. System 2400 is similar to system 2200 described above, but with the additional feature of reducing pathogens. In an embodiment, system 2400 is used to pool blood or blood components and reduce pathogens in the blood or blood components prior to freeze-drying. In one embodiment, system 2400 is used to pool human plasma and reduce pathogens.

[0194] From port 2404, the plasma flows through filter 2408, which is similar to filter 2208 and is used to remove certain components (e.g., cells such as white blood cells) or contaminants from the plasma. In other embodiments, system 2400 may have a series of multiple filters to filter the above-mentioned components or different components or contaminants from the plasma.

[0195] After filtering, the plasma is pooled together in a container 2412. In one embodiment, the container 2412 is a bag. The system 2400 further comprises a member for performing agitation of the plasma. Non-limiting examples of such members include rollers, motors, ultrasonic transducers, power sources, etc.

[0196] System 2400 further includes a pump 2416, which is used to move the plasma from container 2412 to filter 2420. In other embodiments, pumps may be used in other parts of the system. For example, a pump may be used to move the plasma from filter 2408 to container 2412.

[0197] Filter 2420 is used to concentrate the plasma by removing water and salts from the plasma. In one embodiment, filter 2420 is a hollow fiber membrane filter that removes water, salts, and small molecular weight molecules from the plasma. The water, salts, and molecules from filter 2420 are collected in a container 2428 and stored for later use or discarded. Although only one filter 2420 is shown in system 2400, in other embodiments, system 2400 may have a series of multiple filters that remove at least water or other components from the plasma.

[0198] The pump 2432 is used to move the plasma from the filter 2420 to the container 2440. After the plasma is moved to the container 2440, the photosensitizer contained in the container 2444 is mixed with the plasma in the container 2440. The system 2400 may further include a member for agitating the plasma and the photosensitizer. Non-limiting examples of such members include a roller, a motor, an ultrasonic transducer, a power source, and the like.

[0199] Container 2440 is made from a material that is transparent or at least translucent to the wavelengths of light used in the pathogen reduction process, hi some embodiments, container 2440 is made from a flexible polymeric material that is transparent or at least translucent to light with wavelengths ranging from about 275 nm to about 625 nm.

[0200] After the photosensitizer is mixed with the plasma in container 2440, the plasma is exposed to a light source, such as light source 2448. In some embodiments, light source 2448 is at a wavelength that interacts with the photosensitizer, thereby reducing pathogens in the plasma. Examples and detailed descriptions of pathogen reduction for use in embodiments, including combinations of wavelengths of light and photosensitizers, are provided in U.S. Patent Nos. 6,548,241, 6,258,577, and 6,277,337, the entireties of which are expressly incorporated herein by reference.

[0201] After illumination by light source 2448, the pathogen-reduced plasma is pumped by pump 2432 to container 2436 for subsequent lyophilization. Any suitable container for holding the pathogen-reduced plasma may be used for container 2436. In certain embodiments, the container may be similar to container 1200 (FIGS. 12 and 13), container 1600 (FIGS. 16-17C), container 1800 (FIGS. 18A and 18B), container 1900 (FIGS. 19A-19C), and / or container 2000 (FIGS. 20A-20C).

[0202] In systems 2300, 2400, light source (2328, 2448) may include other components and features in addition to the light source. For example, in FIG. 25, system 2500 is shown being used as light source 2328 (FIG. 23) and / or light source 2448 (FIG. 24). As shown in FIG. 25, system 2500 includes light source 2504 and agitator 2508 (e.g., a vibrating table). The agitator 2508 agitates the fluid in vessel 2518 (in some embodiments, vessel 2312 or vessel 2440) while the fluid is being irradiated by light source 2504.

[0203] FIG. 26 illustrates another embodiment of an apparatus 2600 (e.g., a pathogen reduction apparatus used as part of a light source (2328, 2448)). As shown in FIG. 26, the apparatus 2600 includes a light source 2608 on an openable door 2616. When the door 2616 is opened, a container having a fluid is placed on a table 2612. In one embodiment, the table 2612 includes a window in which a second light source 2604 is positioned to illuminate the fluid in the container. By closing the door 2616, the fluid in the container is illuminated by both the light sources 2604, 2608. In one embodiment, the table 2612 vibrates to agitate the fluid in the container before, after, or during illumination of the light sources 2604, 2608.

[0204] In some embodiments, systems 2100, 2200, 2300, 2400 (or portions of the systems) may be provided as disposable sets that are operatively coupled to permanent components of the system (e.g., light sources). For example, in some embodiments, ports, filters, and vessels may be manufactured as disposable sets with tubing that connects to the various components of the system. Permanent components, such as pumps and / or light sources, are operatively coupled to disposable components.

[0205] FIG 27 illustrates a process 2700 for freeze-drying, storing, reconstituting, storing, and infusing a biological fluid (in FIG 27, plasma). Process 2700 may be performed using a suitable container, such as a bag having the characteristics described above for container 1200 (FIGS. 12 and 13), container 1600 (FIGS. 16-17C), container 1800 (FIGS. 18A and 18B), container 1900 (FIGS. 19A-19C), and container 2000 (FIGS. 20A-20C). In the following, the process for plasma is described using a container referred to as bag 1200, although other embodiments are not limited thereto.

[0206] In step 2704, bag 1200 is filled with plasma. In one embodiment, bag 1200 is filled using a plasma pooling system such as systems 2100, 2200, 2300, and / or 2400. In step 2708, the plasma in bag 1200 is freeze-dried in bag 1200 using an apparatus comprising one or more features of plate structure 800 (FIGS. 8A and 8B), plate structure 900 (FIG. 9), and / or plate structure 1000 (FIG. 10). The freeze-drying process includes steps described below with respect to flowchart 2800, including, but not limited to, evaporating liquid from the plasma while subjecting the plasma to a first pressure (e.g., less than atmospheric pressure), freezing the remaining plasma under pressure to create frozen plasma, and sublimating a portion of the frozen plasma while subjecting the frozen plasma to a second pressure.

[0207] In FIG. 27, a container such as container 1200 is used, but in other embodiments, different containers may be used. By way of example, containers such as container 1600 (FIGS. 16, 17C), container 1800 (FIGS. 18A and 18B), container 1900 (FIGS. 19A-19C), and / or container 2000 (FIGS. 20A-20C) are used. In such embodiments, one chamber (or one portion) of the container is used for freeze-drying the plasma. After freeze-drying, the freeze-dried plasma is transferred to a second chamber or portion of the container, and the first chamber (or first portion) is separated.

[0208] In step 2712, the bag 1200 containing the freeze-dried plasma is packaged for storage. The packaging process may have various steps and utilize various packaging materials. In process 2700, a sleeve 2740 is placed on the bag 1200 to provide strength and typically remains attached to the bag 1200 during subsequent process steps. The sleeve 2740 may be made of any suitable material, such as a polymer. In one embodiment, the sleeve 2740 is made of a flexible, transparent or translucent polymer. Examples of such polymers include polycarbonate, acrylic, polystyrene, polysulfone, polyethylene, polyolefin, polypropylene, polyvinyl chloride, or combinations thereof.

[0209] The bag 1200 and sleeve 2740 are placed within a foil bag 2744. The foil bag 2744 provides additional protection and extends the viability of the freeze-dried plasma within the bag 1200. The metallized foil bag 2744 is light-tight, waterproof, has a desiccant, and is vacuum-packed. This extends the shelf life of the freeze-dried plasma. The use of the flexible bag 1200, flexible sleeve 2740, and flexible foil bag 2744 results in a flexible product that can be easily stored and transported, for example, in a backpack. In one embodiment, freeze-drying the plasma with packaging provides the plasma with a shelf life of at least two years.

[0210] A bag 2748 containing reconstitution fluid can be packaged with bag 1200 in foil bag 2744. If desired, the lyophilized plasma in bag 1200 is reconstituted with the fluid in bag 2748 (see step 2716 of FIG. 27). Bag 2748 is connected to bag 1200 to allow the reconstitution fluid to flow into bag 1200. After a short period of time (e.g., within 2 minutes), and in some embodiments after further agitation, the reconstituted plasma is ready for infusion into the patient in step 2720.

[0211] In another embodiment, in step 2724, the reconstituted plasma is transferred to bag 2748 for re-storage in step 2728. In this embodiment, bag 2748 has characteristics such as a material that allows the liquid to be stored for a period of time. In some embodiments, lyophilization of the plasma and use of bag 2748 allows the reconstituted plasma to be stored for at least one day before infusion from bag 2748 to the patient in step 2720.

[0212] With reference to FIG. 28, a flowchart 2800 for a process for freeze-drying a material according to an embodiment is described. Below, a particular apparatus for performing the steps of the flowchart 2800 is described, but the embodiment is not limited thereto. For example, some steps are described as being performed by a processor and other steps are described as being performed by one or more features of a freeze-drying apparatus. This is for illustrative purposes only, and the flowchart 2800 is not limited to being performed by any particular apparatus, feature, or component. In an embodiment, the flowchart 2800 may be performed by a freeze-drying apparatus such as the apparatus 100, 200 having one or more features of the plate structures 800, 900, 1000 described above in FIGS. 8A and 8B, 9, and 10.

[0213] Additionally, any material, including biological fluids, such as blood, blood components, may be freeze-dried by the process illustrated in flowchart 2800. In a particular embodiment, blood plasma is freeze-dried by the process illustrated in Figure 28, but by way of example only. Although flowchart 2800 is described with respect to biological fluids (e.g., blood plasma), this is for illustrative purposes only and is not intended to limit the scope of application of flowchart 2800 to freeze-drying other materials.

[0214] Flowchart 2800 begins with step 2804. In one embodiment, flowchart 2800 includes an optional pathogen reduction step 2806. One embodiment of a pathogen reduction process is described below with reference to flowchart 2900 of FIG.

[0215] After the optional pathogen reduction process (step 2806), the liquid (or other freeze-dried material) is retained in the container in step 2808. In some embodiments, the container is configured to be used to hold liquid prior to or during freeze-drying, to store freeze-dried material for relatively long periods of time, and also to reconstitute freeze-dried material, and in some embodiments, to administer the reconstituted material to a patient. In one embodiment, the container has one or more of the features described above for container 1200. In other embodiments, container 1600, 1800, 1900, or 2000 is used where one chamber (or one portion) of the container is used for freeze-drying and the other chamber (or other portion) is used for storage of the freeze-dried material. In some embodiments, step 2808 includes substeps such as placing the container on a shelf of a freeze-drying device such as device 100, 200.

[0216] Returning to flowchart 2800, proceed from step 2808 to step 2812, which involves exposing the container and liquid to a first pressure. In some embodiments, the pressure is generated by a freeze-drying device. The first pressure is subatmospheric and varies depending on the substance (e.g., liquid) being freeze-dried. In embodiments in which the plasma comprises water, the first pressure is less than about 100 Torr absolute, or less than about 75 Torr, or less than about 50 Torr, or less than about 25 Torr. In other embodiments, the first pressure is less than about 5×10 -2 Torr or approximately 1×10 -1 Torr or approximately 5×10 -1 Torr, or greater than about 1 Torr, or greater than about 1 Torr, or greater than about 5 Torr, or greater than about 10 Torr. In still other embodiments, the first pressure is in the range of about 40 Torr to about 0 Torr, or in the range of about 30 Torr to about 1 Torr, or in the range of about 20 Torr to about 2 Torr, or in the range of about 15 Torr to about 3 Torr. These are some example ranges of the first pressure, and in other embodiments, different pressures may be used.

[0217] Step 2812 proceeds to optional step 2816, where liquid is evaporated from the material being lyophilized. In embodiments where the material is plasma, the liquid evaporated is water. Because the material is at subatmospheric pressure, only a relatively small amount of energy is required to evaporate the liquid from the material. The energy can be provided, for example, by a thermal fluid circulating within the plates of the shelf or by an IR emitter that is part of the shelf of the freeze-drying apparatus.

[0218] In some embodiments, step 2816 is performed to reduce the volume of the liquid to be lyophilized. Without wishing to be bound by theory, it is believed that by performing step 2816 to reduce the volume of liquid, the subsequent sublimation step may occur more quickly and / or more efficiently.

[0219] Step 2816 is followed by step 2820, where the liquid is cooled and frozen to a solid to form a frozen formulation. In some embodiments, a thermal fluid circulating within the plates of the shelf removes energy and cools the liquid, freezing it to a solid. In some embodiments, step 2820 optionally includes multiple sub-steps. For example, sub-step 2824 is a step of evaporating a portion of the liquid. The evaporation cools the liquid to a degree that it freezes to a solid. In some embodiments, sub-step 2824 may be performed as part of step 2816 described above.

[0220] Additionally, in some embodiments, sub-step 2828 is performed to shape, for example, by pressing, the container and the liquid therein. Without wishing to be bound by theory, it is believed that pressing (or otherwise shaping) the container and the liquid (or other material) therein as part of the freezing step 2820 may form a more uniform cross-section as the liquid (or other material) cools and freezes. Thus, it is believed that a more uniform cross-section may increase the efficiency of removing ice-like components from the frozen formulation during the subsequent sublimation step. That is, reducing the variability in thickness may allow the material to sublimate at a similar rate, improving the efficiency of the process.

[0221] In some embodiments, pressure is applied using shelving system 300 or shelving system 500 described with respect to Figures 3-6. In other embodiments, pressure to compress the substance may be provided by a different system, such as a flexible balloon or bladder that can be filled with a fluid. The balloon or bladder is positioned above the substance to be freeze-dried. The balloon or bladder is filled with a fluid (e.g., gas or liquid) and the balloon or bladder expands, compressing the liquid as it is being frozen. This is merely one example of another embodiment, and any method can be used to apply pressure to the container and liquid to shape the container and / or the substance (e.g., liquid).

[0222] In step 2832, the container and frozen formulation are subjected to a second pressure. In certain embodiments, the pressure is generated by a freeze-drying device. The second pressure is subatmospheric and less than the first pressure. The pressure depends on the substance being freeze-dried. In embodiments where the substance comprises water, the second pressure is about 5×10 -1 Less than Torr, or about 1×10 -1 Less than Torr, or about 5×10 -2 Less than Torr, or about 1×10 -2 In another embodiment, the second pressure is less than about 1×10 -4 Torr or approximately 5×10 -4 Torr or approximately 1×10 -3 Torr or approximately 5×10 -3 Torr or approximately 1×10 -2 These are some example ranges for the second pressure, in other embodiments, different pressures may be used.

[0223] After step 2832, in step 2836, a portion of the frozen formulation (e.g., the solid formed from the residual liquid in step 2820) is sublimated. To sublimate material from the frozen formulation, energy is required. This energy is provided, for example, by a thermal fluid circulating in the plates of the shelf. In some embodiments, step 2836 includes a substep 2840 of applying infrared energy by an IR emitter that is part of the shelf of the freeze-drying apparatus. For embodiments in which the shelf is a plate structure similar to plate structures 800, 900, IR energy is applied from the top and thermal energy from the thermal fluid is applied from the bottom. The flowchart then ends at step 2844.

[0224] Although flowchart 2800 has been described enumerating steps in a particular order, the invention is not so limited. In other embodiments, the steps may be performed in a different order, or in parallel, or at different times (e.g., before or after another step). Also, as noted above, flowchart 2800 includes optional steps / sub-steps. However, any steps listed above that are not designated as optional should not be considered essential to the invention, and such steps may be performed in some embodiments and not in other embodiments.

[0225] In some embodiments, portions of flowchart 2800 may be performed as part of a customized freeze-drying process executed on a freeze-drying apparatus or system. For example, an operator may use an application executing on a computer system (e.g., computer system 3300 described below) to create a custom process having one or more steps of flowchart 2800, which is then executed on the freeze-drying apparatus or system to freeze-dry the material. In some embodiments, once created, the custom process can be executed with the push of a button.

[0226] 29 illustrates a flowchart 2900 of a process for freeze-drying a material according to another embodiment. Particular devices for performing steps of flowchart 2900 are described below, but the embodiments are not limited thereto. For example, some steps are described as being performed by a pathogen reduction device and other steps are described as being performed by one or more features of a freeze-drying device. This is for illustrative purposes only, and flowchart 2900 is not limited to being performed by any particular device, feature, or component. In one embodiment, flowchart 2900 may be performed by a freeze-drying device, such as devices 100, 200.

[0227] Additionally, any material, including biological fluids, such as blood, blood components, may be freeze-dried by the process illustrated in flowchart 2900. In a particular embodiment, plasma is freeze-dried by the process illustrated in Figure 29, but by way of example only. Although flowchart 2900 is described with respect to biological fluids (e.g., plasma), this is for illustrative purposes only and is not intended to limit the scope of application of flowchart 2900 to freeze-drying other materials.

[0228] Flowchart 2900 begins at step 2904 and proceeds to step 2908. In step 2908, the liquid is pooled in a container. In some embodiments, a system such as systems 2400, 2500 is used to pool multiple units, e.g., plasma, in a larger container. In some embodiments, step 2908 includes agitating the pooled liquid in the container to mix the pooled liquid. Agitation may use a mechanism to agitate the liquid, non-limiting examples of which include a pump, vibrator, aerator, roller, motor, ultrasonic transducer, power source, etc.

[0229] After step 2908, proceed to step 2912 and add a pathogen reduction composition. In one embodiment, the pathogen reduction composition is an endogenous photosensitizer, such as a flavin, including riboflavin. In other embodiments, the pathogen reduction composition can be other compositions. For example, the pathogen reduction composition can include surfactants, buffers, salts, pH adjusters, solvents, etc.

[0230] In step 2916, the liquid containing the pathogen reduction composition is illuminated with light. Step 2916 involves the use of any suitable system that includes a light source. The light source illuminates the liquid containing the pathogen reduction composition with a wavelength necessary to reduce pathogens in the liquid. In some embodiments, a system such as system 2500 is used to both agitate the liquid and illuminate with the light source. In other embodiments, a pathogen reduction device such as device 2600 shown in FIG. 26 is used to both agitate the liquid and illuminate with the light source. Agitation involves the use of a mechanism to agitate the liquid. Non-limiting examples of such mechanisms include pumps, vibrators, aerators, rollers, motors, ultrasonic transducers, power sources, etc.

[0231] After step 2916, the liquid is freeze-dried by any suitable freeze-drying process 2920. For example, in some embodiments, flowchart 2900 proceeds to flowchart 2800 described above, where the pathogen-reduced liquid is freeze-dried. In other embodiments, the freeze-drying process may involve flowchart 3200, described below with respect to FIG. 32. Flowchart 2900 then ends at step 2936.

[0232] Figures 30 and 31 show embodiments of a system for freeze-drying a material using primarily IR (infrared) energy. As described above with respect to plate structures 800, 900, 1000 and flow chart 2800 (Figure 28), the present invention provides a freeze-drying process that involves using IR energy in addition to or instead of thermal energy. System 3000 (Figure 30) and system 3100 (Figure 31) are examples of systems that may be used in embodiments that utilize primarily IR energy in the sublimation step of the freeze-drying process. Thus, the following description will be given assuming that the material has been frozen by other features of system 3000 or system 3100 or in a different system or different apparatus (e.g., systems 100, 200 using plate structures 800, 900, and / or 1000).

[0233] FIG. 30 illustrates a system 3000 for sublimating a substance in a container 3004 as part of a freeze-drying process. In some embodiments, the container 3004 has two walls that are joined together to define an interior volume in which the substance to be freeze-dried is placed. The material used for the walls of the container 3004 is made of a material that is relatively permeable to gases such as water vapor and strong enough to hold the substance without leaking. In some embodiments, the walls of the container 3004 are made of one or more of the following materials: flash-spun high density polyethylene (HDPE), polytetrafluoroethylene (PTFE), acrylic formed into a woven or non-woven fabric, amide formed into a woven or non-woven fabric, and / or combinations thereof.

[0234] The container 3004 with the frozen substance therein is placed on a shelf 3008 configured to dissipate gas that travels through the container 3004. In one embodiment, the shelf 3008 is provided with a number of holes to allow gas to escape from the container 3004. In other embodiments, the shelf 3008 is made from a screen structure or other porous structure that allows gas to dissipate from the container 3004.

[0235] Additionally, system 3000 includes IR emitters 3012, 3016. As shown in Figure 30, IR emitters 3012, 3016 are positioned to irradiate IR energy on both sides of container 3004. As discussed above, sublimation occurs on the surface of the material. With the configuration shown in Figure 30, sublimation occurs simultaneously on two sides, decreasing the overall freeze-drying time of the material.

[0236] FIG. 31 illustrates another embodiment of a system 3100 for sublimating a substance in a container (3108, 3112, 3116, 3120) as part of a freeze-drying process. Similar to the container 3004, the containers 3108, 3112, 3116, 3120 have two walls that are joined together to define an interior volume in which the substance to be freeze-dried is placed. The material used for the walls of the containers 3108, 3112, 3116, 3120 is made from a material that is relatively permeable to gases such as water vapor and strong enough to hold the substance without leaking. In some embodiments, the walls of the containers 3108, 3112, 3116, 3120 are made from one or more of the following materials: flash-spun high density polyethylene (HDPE), polytetrafluoroethylene (PTFE), acrylic formed into a woven or non-woven fabric, amide formed into a woven or non-woven fabric, and / or combinations thereof.

[0237] The system 3100 includes a hanger portion 3104 on which containers 3108, 3112, 3116, 3120 having frozen substances therein are hung. The hanger portion 3104 is configured with various hooks or other features for holding the containers 3108, 3112, 3116, 3120 vertically.

[0238] The system 3100 includes IR emitters 3124, 3128, 3132, 3136, 3140. As shown in Figure 31, the IR emitters 3124, 3128, 3132, 3136, 3140 are positioned to irradiate IR energy onto both sides of the containers 3108, 3112, 3116, 3120. As discussed above, sublimation occurs on the surface of the material. With the configuration shown in Figure 31, sublimation occurs simultaneously on two sides, decreasing the overall freeze drying time of the material.

[0239] 32 shows a flowchart 3200 of a process for freeze-drying a material according to an embodiment. In the following, specific apparatus is described for carrying out the steps of flowchart 3200, but the embodiments are not limited thereto.

[0240] Flowchart 3200 begins at step 3204 and proceeds to step 3208 where a substance is held in a container. In some embodiments, the substance is a liquid such as blood or a blood component. In one embodiment, the substance is human plasma. In some embodiments, the container for storing the substance has walls comprising a material that is relatively permeable to gases such as water vapor and has sufficient strength to hold the substance during the process. Non-limiting examples of materials that may be used include those made from one or more of flash spun high density polyethylene (HDPE), polytetrafluoroethylene (PTFE), acrylic formed into a woven or nonwoven fabric, amide formed into a woven or nonwoven fabric, and / or combinations thereof.

[0241] In some embodiments, step 3208 involves transferring material from one container to another, for example, in a human plasma embodiment, step 3208 involves pooling multiple units of plasma, transferring the plasma to multiple containers, and retaining the plasma in the multiple containers.

[0242] After step 3208, flowchart 3200 proceeds to step 3212, where the substance is frozen. In some embodiments, step 3212 involves the use of a shelf having a plate structure including features of plate structure 800 (FIGS. 8A and 8B), plate structure 900 (FIG. 9), or plate structure 1000 (FIG. 10). For example, step 3208 involves placing the container on the shelf. The shelf has paths for circulating a thermal fluid to cool the substance and freeze the liquid within the substance in step 3212.

[0243] Step 3212 may include other substeps. For example, in one embodiment, step 3212 includes substep 3216 of shaping (e.g., pressing) the container and material during freezing. Shaping is accomplished using one or more shelving systems, such as system 300 (FIG. 3) or system 500 (FIG. 5) using plate structure 800 (FIGS. 8A and 8B), plate structure 900 (FIG. 9), and / or plate structure 1000 (FIG. 10). In other embodiments, step 3212 may involve other steps or other structures (e.g., forms, fabrics, stamps) that shape the material during freezing.

[0244] From step 3212, flowchart 3200 proceeds to step 3220, where the material is subjected to a pressure less than atmospheric pressure. The pressure depends on the material to be freeze-dried. For embodiments in which the material includes water, the pressure is about 5×10 -1 Less than Torr, or about 1×10 -1 Less than Torr, or about 5×10 -2 Less than Torr, or about 1×10 -2 In another embodiment, the second pressure is less than about 1×10 -4 Torr or approximately 5×10 -4 Torr or approximately 1×10 -3 Torr or approximately 5×10 -3 Torr or approximately 1×10 -2 Torr. These are some example ranges of the second pressure, and in other embodiments, different pressure ranges may be used. In some embodiments, step 3220 is performed using a freeze-drying apparatus, such as apparatus 100 (FIG. 1) and / or apparatus 200 (FIG. 2).

[0245] From step 3220, the flow chart proceeds to step 3224, where IR energy is applied to the material. In some embodiments, step 3224 may involve applying IR energy to only one side of the container. In other embodiments, step 3224 may involve applying IR energy to more than one side of the container. Step 3224 is performed in a system that provides IR energy. Non-limiting examples of such systems include system 3000 (FIG. 30) and / or system 3100 (FIG. 31). Other examples of structures that may be used to apply IR energy include plate structure 800 (FIGS. 8A and 8B), plate structure 900 (FIG. 9), or plate structure 1000 (FIG. 10).

[0246] As part of step 3224, IR energy is applied to effect a change in the material. For example, application of IR energy causes a component 3228 of the material (e.g., ice) to sublime. Further application of IR energy not only sublimates the component, but also removes components absorbed or adsorbed by the material (e.g., water of hydration) (step 3232). Flowchart 3200 ends at step 3236.

[0247] FIG. 33 illustrates example components of a basic computer system 3300 on which an embodiment of the present invention may be implemented. For example, system 100 (FIG. 1) or system 200 (FIG. 2) may include some features of the basic computer system 3300 illustrated in FIG. 33. The computer system 3300 has an output device 3304 and an input device 3308. The output device 3304 may include one or more displays, such as CRT, LCD, and / or plasma displays, among others. The output device 3304 may also include a printer, speakers, etc. The input device 3308 may include, but is not limited to, a keyboard, a touch input device, a mouse, a voice input device, a scanner, etc.

[0248] In embodiments of the invention, basic computer system 3300 may include one or more processors 3312 and memory 3316. In some embodiments, processor 3312 may be a general-purpose processor operable to execute processor-executable instructions stored in memory 3316. Processor 3312 may include a single processor or multiple processors in embodiments of the invention. Further, in embodiments, each processor may be a single-core or multi-core processor having one or more cores for individually loading and executing instructions. Processors may include general-purpose processors, application specific integrated circuits (ASICs), field programmable gate arrays (FPGAs), and other integrated circuits in embodiments.

[0249] Memory 3316 may include any storage medium for short-term or long-term storage of data and / or processor-executable instructions. Memory 3316 may include, for example, random access memory (RAM), read-only memory (ROM), or electrically erasable programmable read-only memory (EEPROM). Other storage media may include, for example, CD-ROM, tape, digital versatile disk (DVD), or other optical storage devices, tape, magnetic disk drives, magnetic tape, other magnetic storage devices, etc.

[0250] Storage 3328 may be any long term data storage device or component. Storage 3328 may include one or more of the devices listed above in connection with memory 3316. Storage 3328 may be permanent or removable.

[0251] The computer system 3300 also includes a communications device 3336. The communications device 3336 enables the system 3300 to communicate with a network (e.g., a wide area network, a local area network, a storage area network, etc.). The communications device 3336 may include a number of devices such as modems, hubs, network interface cards, wireless network interface cards, routers, switches, bridges, gateways, wireless access points, etc.

[0252] The components of the computer system 3300 are connected by a system bus 3340, as shown in Figure 33. However, in other embodiments, the components of the system 3300 may be connected by multiple buses.

[0253] Those skilled in the art will recognize that various modifications and variations can be made to the methods and structures of the present invention without departing from the scope of the present invention. Therefore, it is to be understood that the present invention is not limited to the specific embodiments described above. Rather, the present invention is intended to cover all such modifications and variations within the scope of the following claims and their equivalents.

[0254] While embodiments and applications of the present invention have been shown and described, it is to be understood that the invention is not limited to the arrangements and instrumentalities shown and described. Various modifications, changes, and the like apparent to those skilled in the art can be made in the arrangement, operation, and other details of the method and system of the present invention without departing from the scope of the invention.

Claims

1. 1. A container for freeze-drying and storing freeze-dried blood components, comprising: a first chamber extending in a first direction and a second direction perpendicular to the first direction, a first wall having a first permeability to water vapor; a first chamber having a second wall joined to the first wall to define an interior volume of the first chamber, the second wall having at least a portion of an area having a second permeability to water vapor that is greater than the first permeability; a flow channel located at an end of the first chamber in the second direction, the flow channel having a width in the first direction substantially equal to a width of a longest portion of the first chamber in the first direction; a second chamber fluidly connected to the first chamber via the flow passage, The third wall, a second chamber having a fourth wall joined to the third wall and defining an interior volume of the second chamber; a seal portion provided in the flow path, isolating the second chamber from the first chamber and capable of opening to communicate between the first chamber and the second chamber through the flow path; the first wall, the third wall, and the fourth wall are formed of a polymeric material having the first permeability to water vapor; The container, wherein the seal is capable of isolating the second chamber from the first chamber again after opening.

2. 2. The container of claim 1, The container, wherein the sealing portion comprises one or more clamps, welds, and breakable portions, or a combination thereof, and when re-isolated, maintains the second chamber sealed even when the first and second walls are severed from the third and fourth walls.

3. 3. The container according to claim 1 or 2, The first chamber further comprises a first port for introducing the blood component into the interior volume of the first chamber.

4. The container according to any one of claims 1 to 3, The second chamber further comprises a second port for introducing a rehydration fluid into the interior volume of the second chamber.

5. 5. The container of claim 4, The second chamber further comprises a third port for removing the rehydrated blood component from the interior volume of the first chamber.

6. The container according to any one of claims 1 to 5, wherein at least a portion of the second wall is made of a nonwoven fabric.

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