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EP-4735814-A1 - FREEZE-DRYING SYSTEMS AND METHODS

EP4735814A1EP 4735814 A1EP4735814 A1EP 4735814A1EP-4735814-A1

Abstract

Freeze-drying systems and methods. Such a system includes a phased array RF system configured to emit electromagnetic waves into a process chamber via an antenna array to form an electromagnetic field in the process chamber. The phased array RF system varies the electromagnetic field distribution in the chamber, for example, by randomly varying over time a phase-shift between two or more separate RF signals emitted into the process chamber from separate antennas of the antenna array.

Inventors

  • PEROULIS, DIMITRIOS
  • ALEXEENKO-PEROULIS, Alina
  • STRONGRICH, ANDREW DAVID
  • DARWISH, Ahmad Naif

Assignees

  • Purdue Research Foundation

Dates

Publication Date
20260506
Application Date
20240620

Claims (15)

  1. 1. A freeze-drying system comprising: a process chamber configured for freeze-drying a product; and a phased array RF system configured to emit electromagnetic waves into the process chamber via an antenna array to form an electromagnetic field in the process chamber having an electromagnetic field distribution, wherein the phased array RF system is configured to vary the electromagnetic field distribution in the chamber.
  2. 2. The freeze-drying system of claim 1, wherein the phased array RF system varies the electromagnetic field distribution randomly or pseudo-randomly over time.
  3. 3. The freeze-drying system of claim 1, wherein the phased array RF system comprises a plurality of phase shifters that phase shift a plurality of RF signals to generate a corresponding plurality of phase-shifted RF signals that have different phases from each other, wherein the phase-shifted RF signals are delivered to the antenna array to form the electromagnetic waves.
  4. 4. The freeze-drying system of claim 3, wherein the varying of the electromagnetic field distribution is caused by phase shifting of the RF signals by the phase shifters.
  5. 5. The freeze-drying system of claim 4, wherein the phased array RF system comprises a controller configured to control variation of the phase shifting.
  6. 6. The freeze-drying system of claim 5, wherein the controller is configured to cause the antenna array to vary phases of the focused RF energy emitted into the process chamber.
  7. 7. The freeze-drying system of claim 5, wherein the controller is configured to cause the antenna array to emit focused RF energy inside the freeze-dryer.
  8. 8. The freeze-drying system of claim 7, wherein the controller is configured to cause the antenna array to generate non-focused RF energy in addition to the focused RF energy.
  9. 9. The freeze-drying system of claim 1, wherein the phased array RF system is mounted to an exterior of the process chamber.
  10. 10. The freeze-drying system of claim 9, further comprising a door configured to permit access into the process chamber, wherein the phased array RF system is coupled to the door.
  11. 11. A method of freeze-drying a product, the method comprising: maintaining a product in a frozen condition inside a process chamber, wherein in the frozen condition, the product includes a frozen solvent; lowering the pressure of the process chamber to induce sublimation of the frozen solvent; heating the product during the sublimation with an electromagnetic field formed by electromagnetic waves emitted from an antenna array, wherein the electromagnetic field has an electromagnetic field distribution within the process chamber; and varying the electromagnetic field distribution inside of the process chamber over time during the sublimation.
  12. 12. The method of claim 11, wherein the step of varying comprises varying the electromagnetic field distribution randomly or pseudo-randomly over time.
  13. 13. The method of claim 11, wherein the step of varying comprises: generating a plurality of separate RF signals; phase shifting at least one of the RF signals such that at least two of the separate RF signals are out of phase with each other; and varying the phase shifting over time to form different and varying electromagnetic field distributions inside the process chamber.
  14. 14. The method of claim 13, wherein the antenna array comprises at least two antennas, wherein each of the at least two separate RF signals is emitted by respective separate one of the at least two antennas.
  15. 15. The method of claim 11, further comprising at least one of: freezing the product inside the process chamber prior to the heating; regulating pressure in the process chamber with a ballast gas during the sublimation; and desorbing remaining liquid from the product after the sublimation by raising the temperature of the product and maintaining a vacuum within the process chamber.

Description

FREEZE-DRYING SYSTEMS AND METHODS CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims the benefit of provisional U.S. Patent Application No. 63/524,382 filed June 30, 2023, the contents of which are incorporated herein by reference. BACKGROUND OF THE INVENTION [0002] The invention generally relates to systems, components, and/or processes for freeze-drying items using electromagnetic energy, and, in some nonlimiting embodiments, to freeze-drying biopharmaceutical products. [0003] Freeze-drying (also referred to as lyophilization) is a process of removing water from a material and has been used to preserve perishable materials, extend shelf life, and/or make a material more convenient for transport. Freeze-drying works by freezing the material, then reducing the pressure and adding heat to allow the frozen water in the material to sublimate. A benefit of freeze-drying is that it can reduce drying times of the material by up to 30% over other conventional drying processes, such as passive or active air and/or thermal drying processes. [0004] Typically, conventional freeze-drying methods include three phases. In the first phase (the freezing phase), the material is cooled below its triple point to ensure sublimation occurs. For biological materials, this initial freezing phase is accomplished rapidly to prevent cell wall damage caused by large ice crystals that form during slower freezing processes. In the second phase (the primary drying (sublimation) phase), the pressure in and around the material is reduced and the product is warmed slightly to sublimate the ice (frozen water) in the material, yielding water vapor. This phase typically removes about 95% of the frozen water. In the third phase (the secondary drying (adsorption) phase), ionically-bound water molecules are removed from the material by raising the temperature further above that in the sublimation phase while maintaining a vacuum. This adsorption phase breaks the bonds between the material and remaining water molecules and results in the material having a porous structure. Typically, the freeze-drying process ends by breaking the vacuum using an inert gas before sealing the material, and typically achieves a residual moisture of about 1-5%. [0005] Freeze-drying can be used to stabilize biomaterials, including but not limited to highly sensitive pharmaceutical drugs and biological products, prior to long-term storage. Freeze-drying of biologic materials, such as biopharmaceuticals, has gained significant interest in recent years due to the high demand for product stabilization, and has become widely used in the pharmaceutical industry because it permits the processing of thermolabile products in sterile conditions. Further, there is rising demand for lyophilized injectable medicines and molecular diagnostics. Unfortunately, freeze-drying is a very time-consuming industrial processes with a relatively low energy efficiency typically of less than 10%. [0006] To address these limitations, some methods of freeze-drying have been investigated that also use various forms of electromagnetic energy. For example, radio frequency (RF)/microwave-based lyophilization has been investigated because it significantly accelerates such processes relative to typical conventional freeze-drying processes. However, most existing microwave-assisted lyophilization systems operate in the common industrial, science, and medical (ISM) band of about 2.45 GHz, which usually results in high batch inhomogeneity due to hot spots generated inside the dryer. It also typically results in a longer drying time since ice absorption to RF energy is significantly lower than 18 GHz. Pulsed electric field (PEF) freeze-drying methods have also been investigated because it can intensify the dehydration process when freeze-drying biologies. However, PEF-assisted methods can lead to damage or death of cells in biologic materials due to the formation of pores that also appear to result in the reduced drying times. [0007] Some previous approaches to RF-assisted freeze-drying utilize a metallic Faraday chamber ("RF chamber" or "RF box") containing mechanical stirrers and a radiator (antenna) to be placed inside the freeze-dryer. However, such a metallic chamber inside the freeze-dryer does not allow product stoppering. Hence, the dried products are exposed to humid air, increasing the products’ residual moisture content. Moreover, using a fully metallic encapsulated RF chamber prevents the visual inspection of the products during freeze-drying. In addition, the utilized mechanical stirrers are large, limiting the number of vials containing the biopharmaceuticals that can be placed inside the RF box during drying. Since the mechanical stirrers need to be moving for effective uniformity, motors are attached to the RF box inside the freeze-dryer. This constitutes another drawback of previous approaches. Finally, integrating temperature sensor probes inside the vials is inconve