Direct Contact Spray Freezing System

Abstract

The direct contact spray freezing system includes a freezing tower having an internal chamber, in which the bulk product is delivered in the form of droplets that fall vertically into the internal chamber of the freezing tower. A coolant fluid is also delivered that contacts the droplets in the internal chamber and can be directly frozen, converting the droplets into frozen particles that collect at the bottom of the tower. The coolant fluid is delivered in the form of a subcooled cryogenic mist composed of coolant fluid microparticles through which the droplets pass vertically. Each of the coolant fluid microparticles is substantially smaller than the droplets delivered to the internal chamber of the freezing chamber, thereby maintaining the structural integrity of the droplets that are formed and preventing the vertical trajectory of the droplets from being significantly affected during freezing.

Description

[Technical Field]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This application claims priority under relevant portions of 35 U.S.C. § 119 and 35 U.S.C. § 120 to U.S. Patent Application No. 63 / 447,388, filed February 22, 2023, entitled "DIRECT CONTACT SPRAY FREEZING SYSTEM," the entire contents of which are incorporated herein by reference.

[0002] This application relates generally to the field of freeze drying, and more particularly to a direct contact spray freezing system for use in freeze drying equipment. [Background technology]

[0003] Freeze-drying or lyophilization is a process that removes a solvent or suspension medium, typically water, from a product. This disclosure uses water as an exemplary solvent, but other solvents, such as (but not limited to) alcohol, can also be removed in the freeze-drying process.

[0004] The freeze-drying process for removing water involves freezing the water in the product to form ice, sublimating the ice under vacuum, and directing the water vapor toward a condenser, where it condenses as ice and is subsequently removed from the condenser. Freeze-drying is particularly useful in the pharmaceutical industry because product integrity can be preserved during the freeze-drying process, maintaining and ensuring product stability for relatively long periods of time. Freeze-dried products are typically, but not necessarily, biological materials.

[0005] Pharmaceutical freeze-drying is often an aseptic process requiring sterile conditions within the freeze-drying chamber. For these bulk products, it is important to ensure that all components of the freeze-drying system that come into contact with the product are sterile.

[0006] Most bulk freeze-drying under sterile conditions is performed in freeze-dryers designed for vials, with the bulk product being placed in multiple trays sized and configured to hold the vials. In one example of a bulk freeze-drying system 100 shown in FIG. 1, batches of product 102 are placed in freeze-drying trays 104 within a freeze-drying chamber 106. Freeze-dryer shelves 108 are used to support the trays 104 and transfer heat between the trays 104 and the product 102 as needed by the process. Heat-transfer fluid flowing through conduits within the shelves 108 is used to remove or add heat.

[0007] Under vacuum, the frozen product 102 heats slightly, causing the ice within the product to sublimate. The water vapor resulting from the sublimation of the ice flows through a passageway 110 into a condensing chamber 112 containing a condensing coil or other surface 114 maintained below the condensation temperature of the water vapor. A coolant is passed through the coil 114, removing heat and causing the water vapor to condense as ice on the coil.

[0008] Both the freeze-drying chamber 106 and the condensation chamber 112 are maintained under vacuum during the process by a vacuum pump 116 connected to the exhaust of the condensation chamber 112. Non-condensable gases contained within the chambers 106, 112 are removed by the vacuum pump 116 and exhausted at a high-pressure outlet 118.

[0009] Tray dryers are designed for drying sterile vials and are not optimized to handle bulk products. The product must first be manually loaded into the tray, freeze-dried, and then manually removed from the tray. Furthermore, handling the tray is difficult and creates a risk of liquid spillage. Heat transfer resistance between the product and the tray and between the tray and the shelf sometimes causes irregular heat transfer. The dried product must be removed from the tray after processing, resulting in product handling losses.

[0010] Because the aforementioned bulk processes are performed on large quantities of product, agglomeration into a "cake" often occurs, thus necessitating milling to achieve a suitable powder and uniform particle size. Cycle times can be longer than necessary due to the resistance of large chunks of product to heat and poor heat transfer characteristics between multiple trays, products, and shelves.

[0011] Subsequently, spray freeze drying was proposed, in which a liquid substance is sprayed into a low-temperature, low-pressure environment and the falling particles are exposed to radiant heat to sublimate the water in the frozen particles (see, for example, Patent Document 1). This process is limited to materials that can rapidly remove water while the particles are suspended in air, and is less efficient in low-temperature environments because a radiant heater is required.

[0012] Spray freezing of products by spraying them with liquid nitrogen (LN2) or cryogenic gas has been proposed, along with atmospheric freeze-drying using a drying gas such as nitrogen. An example of this type of process is shown in U.S. Patent No. 5,623,999. The frozen particles are collected in a drying vessel having a bottom fitted with a porous metal filter plate. The drying gas passes over the product, creating a partial pressure of water vapor from the product above the dry drying gas, causing sublimation and / or evaporation of the water contained in the product. Such a process is not well suited to aseptic processing, since both the cryogenic gas and the drying gas must be sterile. This process can also consume large amounts of nitrogen. Atmospheric drying is typically slower than vacuum drying of an equivalent amount of powder.

[0013] The use of spray product nozzles in spray-freezing towers, as described in U.S. Patent Nos. 5,999,149 and 5,999,523, is inefficient because a significant amount of frozen product tends to collect on the interior surface of the tower housing. One technique, described in U.S. Patent No. 5,999,523, generates a stream of droplets within the freezing tower in which a coolant fluid is dispensed into the tower within cavities formed in the sidewalls of the freezing tower and circulated against the product in indirect contact therewith. There is an ongoing and widespread need in the art to improve the process of aseptic freezing of liquid products for freeze-drying. There is a further long-felt need to provide a direct-contact spray-freezing system that eliminates wasted frozen product and produces repeatable, uniformly sized frozen particles or beads for drying purposes. [Prior art documents] [Patent documents]

[0014] [Patent Document 1] U.S. Patent No. 3,300,868 [Patent Document 2] U.S. Patent No. 7,363,726 [Patent Document 3] U.S. Patent No. 9,052,138 [Patent Document 4] U.S. Patent No. 11,148,463 Summary of the Invention [Means for solving the problem]

[0015] Thus, according to one aspect of the present invention, there is provided a direct contact spray freezing system comprising a freezing tower having an interior chamber and at least one means for delivering a bulk product in the form of droplets to the interior chamber of the freezing tower, wherein at least one means is provided for delivering a refrigerant fluid capable of contacting and directly freezing the droplets within the interior chamber of the freezing tower, the droplets being converted into frozen particles that collect in a lowermost portion of the freezing tower, and the refrigerant fluid is delivered in the form of a subcooled cryogenic mist composed of refrigerant fluid microparticles, each of which is substantially smaller than the droplets delivered to the interior chamber of the tower housing.

[0016] The coolant fluid microparticles have an average size small enough so as not to interfere with the structural integrity of the droplets when in direct contact with them or significantly affect the trajectory of the falling liquid particles as the particles fall under gravity through the subcooled cryogenic mist. According to at least one embodiment, the ratio of the average droplet size to the average coolant particle size should preferably be at least 2:1. According to at least one embodiment, the average size of each droplet is about 600 microns and the average size of each coolant fluid microparticle is about 10 microns to about 100 microns.

[0017] In at least one embodiment, the coolant fluid and droplets are each delivered to an upper portion of the freezing tower. In at least one version, the means for delivering the coolant fluid includes means for sterilizing the coolant fluid prior to delivery to the freezing tower.

[0018] The means for delivering the bulk product to the freezing tower can include a droplet generator having one or more vibrating nozzles and configured to generate droplets that fall vertically from the one or more vibrating nozzles under gravity.

[0019] In at least one version, the means for delivering bulk product in droplet form further comprises a liquid reservoir and one or more hollow tubular members disposed between the liquid reservoir and the one or more vibrating nozzles, the tubular members configured for single product or single use. According to at least one embodiment, means are further provided for maintaining the bulk product in the product reservoir at a predetermined pressure (and temperature) prior to delivery to the one or more vibrating nozzles.

[0020] According to at least one embodiment, the means for delivering the bulk product further includes means for initially cooling the bulk product to a predetermined temperature prior to delivering the bulk product as droplets to the inner chamber of the freezing tower.

[0021] Preferably, the means for delivering the coolant fluid comprises one or more coolant nozzles configured to generate a subcooled cryogenic mist of coolant fluid microparticles, the coolant fluid may be liquid nitrogen, and the interior chamber of the freezing tower is maintained at ambient pressure.

[0022] In at least one embodiment, the means for delivering coolant fluid for the systems described herein further includes one or more additional coolant nozzles configured to condition the internal chamber to a predetermined temperature prior to delivery of the droplets.

[0023] According to another aspect, a process for freezing a liquid material in a direct-contact spray freezing system is provided, the process comprising: delivering a bulk product material in the form of droplets that are released into an internal chamber of a freezing tower; and providing a refrigerant fluid in the form of a subcooled cryogenic mist through which the droplets pass vertically through the internal chamber of the freezing tower, directly freezing the droplets into frozen particles. The subcooled cryogenic mist is composed of a plurality of refrigerant fluid microparticles that directly contact the droplets, and because the size of the refrigerant particles is substantially smaller than the size of each droplet, the structural integrity of the droplets is not compromised and the trajectory of each vertically passing droplet is not affected to the extent that the droplets are directed into contact with the internal wall of the freezing tower. According to at least one version, the average size of the droplets delivered to the interior of the freezing tower is at least two times larger than the average size of the refrigerant particles in the refrigerant mist. In at least one embodiment, either the refrigerant fluid or the refrigerant fluid and the liquid product are sterilized prior to delivery.

[0024] In at least one embodiment, the droplets are ejected from one or more vibrating nozzles at a frequency that allows each droplet to be ejected under gravity.

[0025] In at least one version, the process further includes filtering excess refrigerant fluid from the frozen particles, which are collected in a bottom portion of the freezing tower.

[0026] Preferably, the freezing tower is maintained at ambient pressure during the freezing process, and the bulk product is maintained at a constant pressure (and temperature) before delivering the liquid to the interior of the freezing tower.

[0027] In at least one embodiment, the process further includes preconditioning or conditioning the interior chamber of the freezing tower to a predetermined temperature prior to delivery of the droplets. In an exemplary version, conditioning the interior chamber of the freezing tower further includes monitoring an exhaust temperature of the freezing tower and comparing the exhaust temperature to a predetermined threshold temperature, and delivery of the droplets is initiated only when the exhaust temperature has cooled to or below the predetermined threshold temperature. According to at least one version, the aforementioned portion of the process further includes opening one or more additional coolant nozzles when the monitored exhaust temperature has not reached the predetermined threshold temperature, and isolating and closing one or more additional coolant nozzles when the predetermined threshold temperature is reached.

[0028] At least one of the coolant fluid or the coolant fluid and bulk product is sterilized before being delivered to the interior chamber of the freezing tower. Preferably, filtered gas is used to sterilize either the coolant fluid or the coolant fluid and bulk product. Preferably, the coolant fluid can be liquid nitrogen and the filtered gas can be nitrogen gas. Additionally, the freezing tower itself can be periodically sterilized between uses using steam or other means. [Effects of the Invention]

[0029] An advantage of the freezing tower described herein is increased efficiency as less frozen product adheres to the interior side walls of the freezing chamber.

[0030] Another advantage is that the formed and frozen product beads are consistent in terms of their overall size from formation to the point of collection.

[0031] Yet another advantage is that in the direct contact spray system described herein, the heat exchange coefficient is significantly improved, resulting in shorter duration and reduced size of the equipment (freezing tower).

[0032] Yet another advantage is that the spray freezing systems described herein allow for sterility of the cooling fluid and liquid product, as well as the freezing tower and associated components.

[0033] These and other features and advantages will become readily apparent from the following detailed description which is to be read in conjunction with the accompanying drawings. [Brief explanation of the drawings]

[0034] [Figure 1] FIG. 1 is a diagram of a conventional bulk freeze-drying system. [Figure 2] 1 is a schematic diagram of a direct contact spray freezing system according to an embodiment of the present invention. [Figure 3] FIG. 3 is a schematic diagram of the direct contact spray freezing system of FIG. 2, illustrating the conditioning process of the freezing tower prior to dispensing of the liquid product. [Figure 4A] FIG. 4 is a partial top cross-sectional view of the direct contact spray freezing system of FIGS. 2 and 3. [Figure 4B] FIG. 4B is a partial cross-sectional side view of a droplet generator of the direct contact spray freezing system of FIGS. 2, 3 and 4A. [Figure 5] FIG. 5 is a schematic diagram of the direct contact spray freezing system of FIGS. 2-4, illustrating the freezing of droplets according to an embodiment of the present invention. [Figure 6] 1 is a flowchart of an exemplary process for directly freezing droplets with a coolant fluid, according to an aspect of the present invention. [Figure 7] 1 illustrates a direct contact spray freezing system according to another exemplary embodiment, in accordance with aspects of the present invention. [Figure 8] 1 illustrates another alternative embodiment of a direct contact spray freezing system in accordance with aspects of the present invention. [Figure 9] 10 illustrates yet another alternative embodiment of a direct contact spray freezing system in accordance with aspects of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0035] The following description relates to an exemplary embodiment of a spray freezing system in which controlled-size droplets of product fall under the influence of gravity and directly contact a subcooled cryogenic mist formed from a cooling or coolant fluid, such as liquid nitrogen. The system described herein is designed so that the structural integrity and trajectory of the vertically falling droplets are not significantly affected as they pass through the subcooled cryogenic mist.

[0036] The processes and apparatus may be advantageously used for freezing and drying pharmaceuticals that require aseptic or sterile processing, such as injectables. However, the methods and processes may also be used in processing materials that do not require aseptic processing, but require moisture removal while maintaining structure and require a dry product in powder form. For example, ceramic / metal products used in superconductors or to form nanoparticles or microcircuit heat sinks may be produced using the techniques disclosed herein.

[0037] The systems and methods described herein may be performed, in part, by industrial controllers and / or computers used in conjunction with the processing equipment described herein. The equipment is controlled by one or more plant logic controllers (PLCs), such as controller 390 shown in FIGS. 2, 3, and 5, which control the opening and closing of various valves as discussed herein and also contain the processing logic for the valves, motors, etc. Interface with the PLC is provided via a PC. The PC loads and executes well-defined recipes into the PLC. The PLC uploads historical data from its execution to the PC for storage. The PC may also be useful for manual control of devices / apparatus that operate specific steps for freezing.

[0038] PLCs and PCs may include a central processing unit (CPU) and memory, as well as an input / output (I / O) interface connected to the CPU via a bus. The PLC is connected to processing equipment via the I / O interface to receive data from sensors that monitor various conditions of the processing equipment, such as temperature, position, speed, flow rate, etc. The PLC is further connected to operate devices that are part of the processing equipment.

[0039] The memory may also include random access memory (RAM) and read-only memory (ROM). The memory may also include removable media such as a disk drive, a tape drive, or a combination thereof. The RAM functions as a data memory that stores data used during program execution in the CPU and is used as a work area. The ROM functions as a program memory that stores one or more programs containing steps to be executed by the CPU. The programs may reside on the ROM, be stored on removable media, or on any other non-volatile computer-usable medium within a PLC or PC, or may be computer-readable instructions stored for execution by the CPU or other processor (including ASIC) to perform the methods disclosed herein.

[0040] A first exemplary embodiment is shown in Figures 2-6 of an exemplary direct contact spray freezing system 200. Briefly, the spray freezing system 200 is defined by a freezing vessel or freezing tower 204, a liquid product delivery subsystem 240 for delivering bulk product in liquid form to the boundary of the freezing tower 204, and a refrigerant fluid delivery subsystem 280 for delivering a refrigerant fluid to the boundary of the freezing tower 204. Each of the foregoing will now be described in more detail.

[0041] First, the freezing tower 204 is defined by a structure having a defined, vertically extending interior cavity (also referred to herein as a chamber) 208, which further includes an inner peripheral sidewall 212 and an outer peripheral sidewall 216, each of which further includes an upper portion 220 and a lower portion 224. According to at least one version, the cavity can be formed between the inner sidewall 212 and the outer sidewall 216. Preferably, the freezing tower 204 is well insulated, such as by vacuum insulation or other suitable techniques, within the aforementioned cavity between the inner peripheral sidewall 212 and the outer peripheral sidewall 216 to maintain a sufficiently cool environment within the defined interior chamber 208 for the delivered coolant fluid and product, as will be described in more detail below, maximizing the duration that the coolant fluid (liquid nitrogen) microdroplets exist as a liquid before evaporation due to heat leaks.

[0042] The upper or top portion 220 of the freezing tower 204 is configured to hold one or more vertically disposed nozzles 324, which form a portion of the oscillating droplet generator 320. The lower portion 224 of the freezing tower 204, according to this exemplary embodiment, is defined by a hollow frusto-conical configuration including an inwardly tapering bottom wall 228 having a product opening or port 234 formed in the bottom-most portion of the tower 204. As discussed later in this discussion, the design of the bottom portion 224 of the freezing tower 204 can be appropriately modified for the purposes of collecting the formed frozen product material and / or evaporating excess refrigerant fluid.

[0043] Product delivery subsystem 240 is defined by a product source or reservoir 244 coupled to an oscillating droplet generator 320 including a corresponding number of droplet nozzles 324 via one or more connecting passages or conduits 248 and one or more valves 252, such as gate valves. According to this particular embodiment, a total of four vertically extending droplet nozzles 324 are separately coupled to product reservoir 244 by respective passages 248 and valves 252, as shown in spaced apart relationship in FIG. 4A . Each droplet nozzle 324 is preferably configured to receive the same flow rate from product reservoir 244, and flow monitoring of each flow path / passage 248 can be monitored via a flow meter (not shown). Furthermore, each fluid flow path can be hard pipe or, alternatively, can utilize connectable tubing configured for single use or single product use.

[0044] 4B , in this embodiment, vibration drive motor 328 is connected via an extension 329, such as a connecting rod, that leads from drive motor 328 to nozzle disk 330, to which droplet nozzles 324 are attached through openings formed in disk 330. According to embodiments described herein, nozzle disk 330 is made of metal. Each fluid flow path from the product reservoir is directly connected to a corresponding droplet nozzle 324 by a flexible element that does not interfere with the vibration of vibrating nozzle disk 330 as driven by vibration drive motor 328. According to one version, nozzle disk 330 is connected to a flexible diaphragm 334 to create a physical barrier between the nozzle tip in the sterile environment / space 336 of freezing tower 204 and the tubing / vibration drive motor 328 in the non-sterile space. Product delivered to each droplet nozzle 324 is forced through an orifice by pressure and separated from the nozzle tip by the vibration of the nozzle body and gravity, generating individual droplets or product beads. A typical drive frequency is in the range of approximately 2000 Hz. Product bead size may be varied by controlling the vibration rate and orifice size of each droplet nozzle 324. A typical nozzle diameter for producing 600 μm beads is on the order of approximately 150 microns. In summary, the vibrating droplet generator 320 produces uniform product droplets with a relatively tight and narrow size distribution, which are forced to fall downward under gravity along a vertical trajectory toward the bottom of the freezing tower 204. Controlled and predictable production of product droplets is important in the drying and packing of bead material.

[0045] According to this particular embodiment, the product delivery subsystem 240 further includes a chiller 250 coupled to the product reservoir 244 via respective inlet and outlet passages 254, 256. The outlet passage 256 further includes a valve 258, and the chiller 250 is configured to maintain the stored bulk product at a controlled temperature prior to delivering the product to the freezing tower 204. Additionally, according to this embodiment, a dry gas, such as nitrogen gas (N), can be provided from a suitable source 262 and directed to the product reservoir 244 via a passage or conduit 264 as regulated by a valve 268, the gas first passing through a filter 266 positioned intermediate the gas source 262 and the product reservoir 244 to produce a sterilizing gas. According to this embodiment, the bulk product is temporarily stored in the product reservoir 244. Sterile nitrogen, i.e., nitrogen gas passed through filter 266, is delivered to product reservoir 244 to pressurize the container to ensure a consistent supply of stored bulk product liquid solution and delivery of the liquid product to vibrating droplet generator 320. As mentioned above, product reservoir 244 may optionally be in communication with an external cooling device, such as chiller 250, to maintain the liquid product within a specified non-freezing temperature range before entering freezing tower 204.

[0046] The coolant delivery system 280 according to this exemplary embodiment includes one or more coolant nozzles 284 connected via conduits or passages 288, 289 from a coolant fluid source 292, which, according to this particular embodiment, contains liquid nitrogen (LN2), controlled by a shut-off valve 294. The one or more coolant nozzles 284 are located in the upper portion 220 of the freezing tower 204 below the oscillating droplet generator 320, creating an air pocket therebetween, although it is understood that the location of these latter nozzles can be appropriately varied within the chamber 208. The created air pocket is intended to keep the droplet nozzles 324 warmer, thus preventing the bulk product from freezing prior to delivery. Alternatively, a nozzle heater (not shown) can be provided in place of the created air pocket. However, it is understood that the use of a nozzle heater can adversely affect the controlled product temperature, and the temperature may not remain constant. According to yet another alternative, a separate gas line (not shown) can be provided between the coolant nozzle 289 and the oscillating nozzle 324 to create a positive pressure against the oscillating nozzle 324 .

[0047] According to this embodiment, the coolant fluid must be rendered sterile (i.e., sterilized) before being injected into the freezing tower 204. To accomplish this, a dry gas (nitrogen gas, N2) is further provided from a source 296 and directed through a filter 298 via a passageway or fluid conduit 300 to produce a sterile gas, the flow of which is regulated by a valve 302. The sterile gas and coolant fluid are each directed via their respective passageways 300, 289 to an intermediately disposed heat exchanger 304 to condense the gas into its liquid form. In this embodiment, the gas travels through a coil of the heat exchanger 304 that is submerged in liquid nitrogen. The submerged coil isolates the sterile gas from the non-sterile liquid while also allowing heat exchange to occur. Gases resulting from the evaporation of the coolant fluid from source 292 are removed from heat exchanger 304 via passage 308 to vent 312, where the sterilized coolant fluid (LN2) is directed via passage 288 to freezing tower 204, more specifically to cooling nozzle 284.

[0048] According to this exemplary embodiment, prior to introducing the product droplets into the inner chamber 208 of the freezing tower 204, it is preferable to precondition the processing atmosphere within the chamber 208. This preconditioning of the chamber 208 is preferably performed to establish stable and homogeneous conditions throughout the volume of the inner chamber 208, thus ensuring the quality of the freezing process prior to the injection of the droplets. More specifically, preconditioning minimizes product loss at the beginning of the freezing process, improving overall product yield. Furthermore, during preconditioning, air is vented through the passageway 288, advantageously removing oxygen from the freezing tower 204 and reducing humidity. A stable temperature is achieved, and the inner chamber 208 is effectively filled with sterile LN, stabilizing the operation of the coolant nozzle 284. This processing step also improves the consistency of the overall freezing process.

[0049] This adjustment is achieved by spraying the same sterile liquid nitrogen used for freezing through nozzle 284 and one or more additional nozzles 340, which may have a higher flow rate than nozzle 284, to pre-cool the internal chamber 208 in a reasonable amount of time. This spraying is shown schematically in FIG. 3 as 346. A passageway 288 extends from the coolant nozzle 284 to an additional nozzle 340 (shown in FIG. 4B), which also includes a shut-off valve 344. The additional nozzle 340 is actively controlled by measuring the exhaust temperature of the freezing tower 204. When the temperature of the freezing tower 204 falls below a predetermined threshold, the additional nozzle 340 is shut off via valve 344, and the flow of liquid nitrogen continues only through nozzle 284. As this nitrogen evaporates on the warm surfaces of the freezing tower 204, it purges air from the freezing system 200. The evaporated nitrogen and entrained air can be vented from the freezing tower 204 through a process vent 348, the latter of which is shown schematically in FIG. 3. Once this conditioning is complete, the freezing of droplets 350 passing vertically through the subcooled cryogenic mist 354 can begin, as shown schematically in FIG.

[0050] Freezing of the falling droplets occurs through direct contact between the droplets and the coolant fluid. To achieve this type of freezing, it is necessary to generate a subcooled cryogenic mist 354 or fog of tiny coolant fluid (LN2) particles. According to this exemplary embodiment, the subcooled cryogenic mist 354 is generated by one or more cooling nozzles 284 located below the oscillating droplet generator 324 in the freezing tower 204, thereby transferring the heat of vaporization from the liquid nitrogen (LN2) to the warm product. Furthermore, this collision between each droplet 350 and the coolant fluid (LN2) particles must be such that the size and velocity of the liquid nitrogen microdroplets do not significantly affect the structural integrity of the product droplets (i.e., do not break or explode the droplets) as they contact each other, nor affect the trajectory of the falling droplets by deflecting vertically passing droplets toward or contacting the inner peripheral sidewall 212 of the freezing tower 204. The subcooled cryogenic mist 354 or fog is generated using a hydraulic atomizing nozzle capable of atomizing liquid nitrogen, such as a Spraying Systems Co. Fine Spray Nozzle, 1 / 4" M Series, or other appropriately designed atomizing nozzle. This atomizing nozzle is capable of producing coolant fluid microdroplets of 10-100 microns in size, compared to a nominal 600 micron product droplet size.

[0051] Thus, the average size of each droplet 350 (e.g., 600 microns) is significantly larger than the average size of each coolant fluid (LN2) microdroplet in the formed subcooled cryogenic mist 354 (approximately 10-100 microns). It is understood that other suitable ratios, preferably at least 2:1 (droplet size:coolant fluid microparticle size), are desirable so as not to disrupt the integrity or trajectory of the falling product droplets as they pass through the subcooled cryogenic mist 354 as produced by the cooling nozzle 284.

[0052] An exemplary process 400 is shown in Figure 6, and portions of this process are further illustrated sequentially in Figures 2, 3, and 5. More specifically, with respect to the actual process, the cycle initially begins at step 400, where the coolant fluid (liquid nitrogen) supply condenser is preconditioned at step 404, and bulk product is delivered under pressure from the product reservoir 344 to the vibrating droplet generator 320. The sterile liquid nitrogen produced through the heat exchanger 304 (step 408) enters the freezing tower 204, more specifically the inner chamber 208, and exits through the cooling nozzle 284 at a first (low) flow rate (step 412). At step 416, a second branch of the liquid nitrogen passes through the first coolant nozzle 284 and valve 344 toward the second coolant nozzle 340. The exhaust temperature of the freezing tower 204 is monitored in real time and compared to a threshold or target temperature or temperature range (step 420). If the monitored temperature is warmer than the threshold temperature, coolant fluid is sprayed into chamber 208 by each of nozzles 284, 340, the latter preferably having a higher flow rate than first coolant nozzle 284. If the monitored exhaust temperature drops below the threshold or target temperature, valve 344 is closed and controller 390 initiates oscillating droplet generator 320 to begin dispensing droplets through oscillating (droplet) nozzle 324 (step 432). The liquid product droplets come into gravity-directed contact with the atomized coolant fluid microparticles of the formed subcooled cryogenic mist 354 (FIG. 5) and begin freezing (step 436).

[0053] As described in this and other embodiments, the orientation of the coolant fluid atomizing nozzles may be in any manner that produces a dense field or mist of fine droplets for the product droplets to pass vertically through, which may include spraying with the nozzles angled upward, downward, or somewhat horizontally.

[0054] As mentioned above, the droplets are frozen in their downward passage through the formed mist of liquid nitrogen. In the bottom portion 224 of the freezing tower 204, the frozen product beads can be separated from any residual and unvaporized liquid nitrogen. According to one version, this can be done using an inclined screen or membrane (not shown) with a mesh size configured to retain the particles and move them toward a collection nozzle or port, while the unvaporized coolant fluid (LN2) can fall through the inclined screen to the bottom of the freezing tower 204. This unvaporized liquid nitrogen can then be removed from the bottom of the freezing tower 204 or, alternatively, heated to vaporize within the tower. The vaporized liquid nitrogen can be vented at the top or bottom of the freezing tower. To maintain a sterile environment, the vent path needs to filter the air / nitrogen through a sterile filter system (0.2 microns or greater). The overall shape / configuration of the lower or bottom portion of the freezing tower 204 can be appropriately modified to provide the aforementioned features.

[0055] Alternatively, as shown in Figures 2, 3, and 5, a jacket formed on the bottom portion 224 of the freezing tower 204 can be used to remove unvaporized coolant fluid (liquid nitrogen). A cavity unique to only the tapered bottom wall 228 of the bottom portion 224 of the freezing tower 204 can receive a circulating heat transfer fluid, such as silicone oil, which can be used to vaporize excess coolant fluid (LN2) and vent it from the freezing tower 204 via vent 348. Collected frozen product beads are retained in product vent 234, which is isolated from the rest of the freeze-drying system by valve 356 or other similar means. In the manner discussed herein or other variations, the frozen product beads can be extracted from the freezing tower 204 and subjected to freeze-drying in an attached freeze dryer (not shown), or removed from the freezing tower into an insulated container (not shown) and placed in a separate freeze dryer. The freezing tower 204 is configured and ported therein so that the interior chamber 208 can be sterilized after use using steam or other means.

[0056] Other suitable configurations are described in the following embodiments. As will be apparent from the discussion, the specific positioning of the product nozzles and coolant nozzles in the freezing tower is not necessarily limited to that described in the previous embodiments. For example, according to another exemplary embodiment in FIG. 7 , a direct contact spray freezing system 500 is shown. The system 500 includes a vertically oriented freezing vessel or tower 502 having an inner peripheral sidewall 504 and a bottom wall 508 that define a freezing chamber 510. The freezing chamber 510 further includes an outer sidewall 506, which is spaced apart from the inner sidewall to form a cavity 505 between the inner sidewall 504 and the outer sidewall 506. The system 500 also includes a vibrating prilling head 512 disposed in a top or upper portion 514 of the freezing tower 502 and having one or more product nozzles 516. The prilling head 512 is connected to a product source 518, such as a liquid product in bulk form, by a fluid product passageway or conduit 520, which provides fluid communication between the product source 518 and the prilling head 512. The prilling head 512 includes a vibrating unit 522 that generates product droplets or beads 524 having a nominally fixed diameter, which are then sequentially sheared from the product nozzle 516 to form a stream of droplets that fall under gravity toward the bottom of the freezing chamber 510. The prilling head can be designed, for example, like that of the previously described vibrating droplet generator 320 of FIG. 2.

[0057] According to one aspect of the present invention, system 500 includes at least one cooling nozzle (first cooling nozzle 526) connected to a cooling fluid source 528, such as liquid nitrogen, by a cooling fluid conduit 530 that provides fluid communication between the cooling fluid source 528 and first cooling nozzle 526. Although not shown in this embodiment or subsequent embodiments (FIGS. 7-9), each of the cooling fluid and liquid product may be sterilized as described above before delivery to freezing tower 502. First cooling nozzle 526 is configured to atomize the cooling fluid (LN2), and according to this embodiment, spray liquid nitrogen vertically downward into freezing chamber 510 to form a cryogenic fog or mist 532 of small liquid nitrogen particles (liquid nitrogen microdroplets 534). Product beads 524 sheared from one or more product nozzles 516 fall through the formed liquid nitrogen mist 532 and come into direct contact with one or more liquid nitrogen microdroplets 534. This contact utilizes the heat of vaporization of the liquid nitrogen to cool the warm product beads 524, thereby freezing the product beads 524. The product beads 524 fall downward through the mist 532 a sufficient distance, and the subcooled cryogenic mist 532 has a sufficient density of liquid nitrogen microdroplets 534 to ensure sufficient contact between the product beads 524 and the liquid nitrogen microdroplets 534 to freeze each of the falling product beads 524.

[0058] Liquid nitrogen contacting product beads 524 is vaporized, and the resulting liquid nitrogen gas is vented from chamber 510 through a vent port located in the top portion of the freezing tower, according to this particular embodiment. Liquid nitrogen that is not vaporized also falls downward onto a liquid nitrogen separation device, but the frozen product beads 524 are captured by a product separation screen, which is located in the lower portion of freezing chamber 510.

[0059] As with the previous embodiment, the size and velocity of the liquid nitrogen microdroplets 534 are configured such that neither the structure of the product beads 524 nor their vertical fall trajectories are significantly adversely affected, thereby ensuring that the integrity of the product beads is maintained. That is, the product beads 524 are not fragmented, broken, or otherwise damaged due to contact with the much smaller liquid nitrogen microdroplets 534. In this embodiment, the optimal ratio of product bead diameter to liquid nitrogen microdroplet diameter is at least 6:1, although literally any ratio of 2:1 or greater will provide the necessary integrity.

[0060] In one embodiment, the first cooling nozzle 526 may be a hydraulic spray nozzle suitable for spraying liquid nitrogen. For example, the first cooling nozzle 526 may be capable of producing liquid nitrogen microdroplets 534 having a diameter of approximately 10-100 microns, compared to a product bead diameter of approximately 600 microns. The first cooling nozzle 526 may be, for example, a type sold by Spraying Systems, Inc. (Glendale Heights, Illinois) and designated as a Fine Spray nozzle, 1 / 4 inch M series, although an equivalent nozzle may also be used.

[0061] The first cooling nozzle 526 may be located in any section or region of the freezing tower 502 and oriented in any direction suitable for generating a relatively high-density field of liquid nitrogen microdroplets 534 within the freezing chamber 510. This positioning may include positioning at least one cooling nozzle so that the liquid nitrogen microdroplets 534 are directed upward, downward, or into or out of at least one horizontally positioned nozzle. Alternatively, multiple nozzles may be used, positioned along the periphery of the sidewall of the freezing tower 502 and oriented horizontally or tilted downward into the freezing chamber 510. By way of example, FIG. 7 illustrates an embodiment including a first cooling nozzle 526 and a second cooling nozzle 538, both configured to spray liquid nitrogen microdroplets 534 vertically. The second cooling nozzle 538 may be supplied by an associated cooling fluid source via an associated cooling fluid conduit. Alternatively, the first cooling nozzle 526 and the second cooling nozzle 538 may be supplied via a common cooling fluid source. The first cooling nozzle 526 is positioned to spray liquid nitrogen microdroplets 534 into the freezing chamber 510 in a first vertical direction 540 (e.g., downward), and the second cooling nozzle 538 is positioned to spray liquid nitrogen microdroplets 534 into the chamber 510 in a second vertical direction 542 opposite the first vertical direction 540 (i.e., upward), forming a subcooled cryogenic mist 532.

[0062] According to one or more embodiments of the present invention, a cooling fluid (LN2) separator device or arrangement within the freezing chamber 510 enables separation of unvaporized liquid nitrogen from the product beads 524. The following is an exemplary arrangement for separating liquid nitrogen from the product beads 524. It is understood that other methods, devices, or arrangements may be used to separate the liquid nitrogen from the product beads. The bottom wall 508 of the freezing tower 502 is sloped in a first slope direction 544. The product separation screen 546 is located above the bottom wall 508 and slopes in a second slope direction 548 opposite the slope direction of the first slope direction 544. The product separation screen 546 receives both the frozen product beads 524 and any liquid nitrogen that is not vaporized by contact with the product beads 524. The product separation screen 546 is sized with an appropriate mesh to separate the frozen product beads 524 from the smaller liquid nitrogen microdroplets 534. The product separation screen 546 captures the frozen product beads 524, which then travel under gravity through a product removal outlet 550. The frozen product beads 524 are then received by a freeze-drying chamber, such as the aforementioned freeze-drying chamber 110 of the freeze-drying system 100 shown in Figure 1, and freeze-dried to form the freeze-dried product. Alternatively, the frozen product beads 524 can be collected in an insulated container (not shown) to be placed in a separate freeze-dryer (not shown).

[0063] The liquid nitrogen that is not vaporized flows through product separator screen 546 and onto sloped bottom wall 508. In one embodiment, the liquid nitrogen then flows by gravity through liquid nitrogen outlet 552, thereby removing the liquid nitrogen from the bottom of freezing tower 502. In another embodiment, a heating element 554 is mounted below bottom wall 508. The heating element serves to heat bottom wall 508, and therefore the liquid nitrogen, to vaporize the liquid nitrogen collected at bottom wall 508 into liquid nitrogen gas. The gas is then vented from chamber 510 via vent port 536.

[0064] A cool environment is created within chamber 510 due to the atomization of liquid nitrogen within the chamber as it forms mist 532 of liquid nitrogen microdroplets 534. According to one aspect of the invention, an insulating jacket 558 is positioned within cavity 505 to provide insulation to maintain the cool environment. This jacket 558 functions to maximize the duration of liquid nitrogen microdroplets 534 as a liquid before vaporization occurs due to a heat leak in freezing tower 502. In another embodiment, a vacuum is created within cavity 505 between inner sidewall 506 and outer sidewall 508 to provide vacuum insulation to further maintain a cool environment.

[0065] 8 illustrates another alternative embodiment for positioning the cooling nozzles. Similar parts are labeled with the same reference numerals for clarity. In this embodiment, third and fourth cooling nozzles 560, 562 are aligned with one another and constructed and arranged to spray liquid nitrogen into the chamber 510 in a substantially horizontal direction. In this embodiment, the third cooling nozzle 560 is positioned to spray liquid nitrogen droplets 534 into the chamber 510 in a first horizontal direction 566 (e.g., toward the fourth cooling nozzle 562), and the fourth cooling nozzle 562 is positioned to spray liquid nitrogen droplets 534 into the chamber 510 in a second horizontal direction 568 opposite the first direction 566 (i.e., toward the third cooling nozzle 560) to form a mist 532. Alternatively, the third and fourth cooling nozzles 560, 562 may be offset relative to one another to form a staggered or offset arrangement, such as where the third cooling nozzle 560 is positioned above the horizontal axis 564 and the fourth cooling nozzle 562 is positioned below the horizontal axis 564. Additionally, at least one additional cooling nozzle may be added that sprays liquid nitrogen microdroplets 534 in a horizontal direction.

[0066] FIG. 9 illustrates a further embodiment for positioning the cooling nozzles, in which liquid nitrogen microdroplets 534 are sprayed by the cooling nozzles in both horizontal and vertical directions. Again, like parts are designated by the same reference numerals throughout this description. In this particular embodiment, first and second cooling nozzles 526, 538 are configured to spray liquid nitrogen microdroplets 534 in first and second vertical directions 540, 542, respectively, and third and fourth cooling nozzles 560, 562 are configured to spray liquid nitrogen microdroplets 534 in first and second horizontal directions 566, 568, respectively, to form mist 532. The positioning, arrangement, and number of the cooling nozzles may be appropriately modified to optimize the formation of mist 532 or the location of mist 532 within chamber 510 of freezing tower 502. For example, each of the cooling nozzles may be independently movable horizontally or vertically relative to the chamber 510 to optimize the formation of mist 532 within chamber 510. Additionally, the spray angles of any or all of the cooling nozzles described herein may be independently adjustable.

[0067] While the present invention has been described with reference to particular variations and illustrative diagrams, those skilled in the art will recognize that the present invention is not limited to the variations or diagrams described. Furthermore, where the above methods and steps show certain events occurring in a certain order, those skilled in the art will recognize that the order of certain steps may be changed, and that such changes are in accordance with variations of the present invention. Furthermore, some of the steps may be performed simultaneously in a parallel process, where possible, or may be performed sequentially as described above. Therefore, to the extent there are variations of the present invention that are within the spirit of the present disclosure or equivalent to the invention found in the claims, it is intended that this patent cover those variations as well.

[0068] To the extent that a claim recites the phrase "at least one of" in reference to multiple elements, this is intended to mean at least one or more of the listed elements, and not limited to at least one of each element. For example, "at least one of element A, element B, and element C" is intended to refer to element A only, or element B only, or element C only, or any combination thereof. "at least one of element A, element B, and element C" is intended to be unlimited to at least one of element A, at least one of element B, and at least one of element C.

[0069] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting. As used herein, the singular forms "a," "an," and "the" are intended to include the plural forms as well, unless the context clearly dictates otherwise. It is further understood that the terms "comprise" (and any form of "comprise," such as "comprises" and "comprising"), "have" (and any form of "have," such as "has" and "having"), "include" (and any form of "include," such as "includes" and "including"), and "contain" (and any form of "contain," such as "contains" and "containing") are open-ended linking verbs. Consequently, a method or device that "comprises," "has," "includes," or "contains" one or more steps or elements includes, but is not limited to, those one or more steps or elements. Similarly, a method step or device element that "comprises," "has," "includes," or "contains" one or more features includes, but is not limited to, those one or more features. Furthermore, a device or structure configured in a certain way is configured in at least that way, but may also be configured in ways not listed. Unless otherwise specified or limited, the terms "connected," "supported," and "coupled," as well as variations thereof, are used broadly and encompass direct and indirect mounting, connecting, supporting, and coupling. Furthermore, the terms "connected" and "coupled" are not necessarily limited to physical or mechanical couplings or connections.

[0070] Corresponding structure, materials, acts, and equivalents of all means or step-plus-function elements in the following claims are intended to include, where present, any structure, material, or act for performing a function in combination with other claimed elements as specifically claimed. The description set forth herein has been presented for purposes of illustration and description, but is not intended to be exhaustive or limited to the disclosed form. Many modifications and variations will be apparent to those skilled in the art without departing from the scope and spirit of the present disclosure. The embodiments have been chosen and described to best explain the principles and practical application of one or more aspects described herein, and also in accordance with the appended claims to enable those skilled in the art to understand one or more aspects described herein with various modifications suited to the particular use contemplated for the various embodiments. Additional embodiments include any of the embodiments described above and any of the embodiments shown in any drawings or other materials accompanying this application, where one or more of the components, functionality, or structures are exchanged for, replaced by, or augmented by one or more of the components, functionality, or structures of the different embodiments described above.

[0071] This detailed description uses examples to disclose the invention, including the best mode, and also enables any person skilled in the art to practice the invention, including making and using any devices or systems and performing any incorporated methods. The patentable scope of the invention is defined by the claims, and may include other examples that occur to those skilled in the art. Such other examples are intended to be within the scope of the claims if they have structural elements that do not differ from the literal words of the claims, or if they include equivalent structural elements that do not differ substantially from the literal words of the claims. As stated above, it is understood that other suitable variations and modifications will be readily apparent to and appreciated by those skilled in the art upon reading the foregoing detailed description, and will be further understood from the following appended claims. [Explanation of symbols]

[0072] 100 Freeze Drying System 102 Frozen products 104 Trays (multiple) 106 Freeze-drying chamber 108 Freeze Dryer Shelf 110 Passage 112 Condensation Chamber 114 Condensing coils or other surfaces 116 Vacuum Pump 118 High pressure outlet 200 Direct Contact Spray Freezing System 204 Freezing Tower 208 Cavity or Chamber 212 Inner sidewall, freezing tower 216 Outer wall, freezing tower 220 Upper part, freezing tower 224 Lower part, freezing tower 228 Inwardly tapered bottom wall 234 Product openings or ports 240 Product Delivery Subsystem 244 Product reservoir or source 248 Passages or conduits 250 Chiller 252 Valve 254 Passages or fluid conduits 256 Passages or fluid conduits 262 Sterilization gas source 264 Passages or fluid conduits 266 filters 268 Valve 280 Coolant Fluid Delivery Subsystem 284 Coolant nozzle 288 Passages or conduits 289 Passages or conduits 292 Coolant fluid source 294 Valve 296 Gas Source 298 filters 300 Passages or conduits 302 Valve 304 Heat exchanger 308 Passages or conduits 312 Vent 320 Vibrating Droplet Generator 324 Droplet Nozzle 328 Vibration Drive Motor 329 Extensions or connecting rods 330 nozzle disc 334 Flexible Diaphragm 336 Sterile space 340 additional coolant nozzles 344 Valve 346 Coolant Fluid Spray Preconditioning 348 Process Vent 350 droplets, liquids 354 Sub-cooled cryogenic mist 356 Valve 390 Controller 400 processes 402 Step 404 Step 408 Steps 412 steps 416 steps 420 steps 424 steps 428 steps 432 steps 436 steps 500 Direct Contact Spray Freezing System 502 Freezing container or freezing tower 504 Inner side wall 505 cavity 506 Peripheral side wall 508 bottom wall 510 Freezing Chamber 512 vibratory prilling head 514 Top part 516 at least one product nozzle 518 Product Source 520 Passages or conduits 522 vibration unit 524 Product droplets or beads 526 cooling nozzle (first) 528 Cooling Fluid Source 530 Cooling Fluid Conduit 532 Subcooled cryogenic mist 534 Cooling fluid microdroplets or microparticles 536 Ventilation port 538 Second Cooling Nozzle 540 First Vertical 542 Second Vertical 544 First Inclination 546 Product Separation Screen 548 Second tilt direction 550 Product removal outlet 552 Cooling fluid outlet 554 Heating Element 558 insulation jacket 560 Third Cooling Nozzle 562 Fourth Cooling Nozzle 564 horizontal axis 566 First Horizontal 568 Second Horizontal

Claims

1. 1. A direct contact spray freezing system comprising: a freezing tower having an interior chamber; at least one means for delivering bulk product in droplet form to the interior chamber of the freezing tower; at least one means for delivering a coolant fluid capable of contacting the droplets in the interior chamber of the freezing tower and directly freezing the droplets; wherein the liquid droplets are converted into frozen particles that are collected in a lowermost portion of the freezing tower, and the coolant fluid is delivered in the form of a subcooled cryogenic mist composed of coolant fluid microparticles, each of which is substantially smaller than the liquid droplets delivered to the interior chamber.

2. The direct contact spray freezing system of claim 1 , wherein the coolant fluid and the droplets are each delivered to an upper portion of the freezing tower.

3. 3. The direct contact spray freezing system of claim 1 or 2, wherein the means for delivering the coolant fluid includes means for sterilizing the coolant fluid prior to delivery.

4. 4. The direct contact spray freezing system of claim 1, wherein the means for delivering the bulk product to the freezing tower comprises a droplet generator having one or more vibrating nozzles and configured to generate droplets that fall vertically from the one or more vibrating nozzles under gravity.

5. 5. The direct contact spray freezing system of claim 4, wherein the coolant fluid microparticles have an average size small enough that when in direct contact with the droplets of the bulk product, they do not substantially interfere with the structural integrity and vertical fall trajectory of the droplets of the bulk product.

6. 6. The direct contact spray freezing system of claim 5, wherein the ratio of the average size of the droplets to the average size of the coolant fluid microparticles is at least 2:

1.

7. 6. The direct contact spray freezing system of claim 5, wherein the average size of each droplet is about 600 microns and the average size of each coolant fluid microparticle is about 100 microns.

8. 8. The direct contact spray freezing system of claim 4, wherein the means for delivering the bulk product in the form of droplets further comprises a liquid reservoir and one or more hollow tubular members disposed between the liquid reservoir and the one or more vibrating nozzles, the tubular members configured for a single product or single use.

9. 10. The direct contact spray freezing system of claim 8, including means for maintaining the bulk product at a predetermined pressure prior to delivery to the one or more vibrating nozzles.

10. 10. The direct contact spray freezing system of any one of claims 1 to 9, wherein the means for delivering the bulk product further comprises means for initially cooling the bulk product to a predetermined temperature before delivering the bulk product as droplets to the interior chamber of the freezing tower.

11. 11. The direct contact spray freezing system of claim 1, wherein the means for delivering the coolant fluid comprises one or more coolant nozzles configured to generate a subcooled cryogenic mist of coolant fluid microparticles.

12. 12. The direct contact spray freezing system of claim 11, wherein the means for delivering the coolant fluid further comprises one or more additional coolant nozzles configured to condition the internal chamber to a predetermined temperature prior to delivery of the droplets.

13. A direct contact spray freezing system according to any one of claims 1 to 12, wherein the coolant fluid is liquid nitrogen.

14. 14. The direct contact spray freezing system of any one of claims 1 to 13, wherein the interior chamber of the freezing tower is maintained at ambient pressure.

15. 1. A process for freezing a liquid material in a direct contact spray freezing system, said process comprising: delivering bulk product material in the form of droplets that are discharged into an interior chamber of a freezing tower; providing a coolant fluid in the form of a subcooled cryogenic mist through which said droplets pass vertically through said interior of said freezing tower and directly freezing said droplets into frozen particles; Including, The subcooled cryogenic mist comprises a plurality of coolant fluid microparticles configured to directly contact the vertically falling droplets, the coolant fluid microparticles being substantially smaller in size such that the structural integrity and trajectory of each vertically passing droplet are not significantly affected.

16. 16. The process of claim 15, wherein the average size of the droplets delivered to the interior of the freezing tower is at least two times larger than the average size of the refrigerant fluid microparticles of the subcooled cryogenic mist.

17. 17. The process of claim 15 or 16, wherein the droplets are emitted from one or more vibrating nozzles at a frequency that allows each droplet to be emitted under gravity.

18. 18. The process of any one of claims 15 to 17, further comprising filtering excess coolant fluid from the frozen particles collected in a bottom portion of the freezing tower.

19. The process of any one of claims 15 to 18, wherein the freezing tower is maintained at ambient pressure during the freezing process.

20. 20. The process of any one of claims 15 to 19, wherein the bulk product is maintained at a constant pressure before delivering the liquid to the interior of the freezing tower.

21. 21. The process of any one of claims 15 to 20, further comprising the step of first cooling the bulk product to a predetermined temperature before delivering the droplets to the inner chamber of the freezing tower.

22. 22. The process of any one of claims 15 to 21, further comprising adjusting the internal chamber of the freezing tower to a predetermined temperature prior to delivery of the droplets.

23. 23. The process of claim 22, wherein adjusting the internal chamber of the freezing tower further comprises monitoring an exhaust temperature of the freezing tower and comparing the exhaust temperature to a predetermined threshold temperature, and wherein delivery of the droplets is initiated only when the exhaust temperature has cooled to or below the predetermined threshold temperature.

24. 24. The process of claim 23, wherein the adjusting step further comprises the steps of opening one or more additional coolant nozzles when the monitored exhaust temperature has not reached the predetermined threshold temperature, and isolating and closing the one or more additional coolant nozzles when the predetermined threshold is reached.

25. 25. The process of any one of claims 15 to 24, wherein one of the coolant fluid and the bulk product is each sterilized before being delivered to the interior chamber of the freezing tower.

26. 26. The process of claim 25, wherein filtered gas is used to sterilize the coolant fluid and the bulk product.

27. 27. The process of claim 26, wherein the filtered gas is nitrogen gas.

28. The process of any one of claims 15 to 27, wherein the coolant fluid is liquid nitrogen.

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