Abstract:
A lid assembly is provided for covering and sealing a lyophilizer tray that contains a material for freeze-drying into a product in a lyophilizer chamber. The tray has an opening defined by a peripheral lip. The lid assembly includes a first lid disposable to seal around the lip of the tray, second lid disposed on the first lid, and a filter paper disposed therebetween. The first lid includes an opening. The second lid covers the opening and includes a hole over the opening. The filter paper is disposed over the opening between the first and second lids for inhibiting the product from escaping the tray through the hole while permitting water vapor to pass therethrough. With a lyophilization stopper to seal the hole, the tray containing the product can be protected from environmental humidity even after removal from the chamber.

Description:
STATEMENT OF GOVERNMENT INTEREST 
     The invention described was made in the performance of official duties by one or more employees of the Department of the Navy, and thus, the invention herein may be manufactured, used or licensed by or for the Government of the United States of America for governmental purposes without the payment of any royalties thereon or therefor. 
    
    
     BACKGROUND 
     The invention relates generally to lyophilization accessories. In particular, the invention relates to a high efficiency particulate air (HEPA) filtered, sealable lid for a bulk lyophilization tray. 
     Freeze drying involves four stages: pre-treating, freezing, primary drying and secondary drying. Pretreatment of a sample material can include increasing concentration, increasing surface area, and reducing vapor pressure. The freezing process involves cooling the material below its thermodynamic triple point (i.e., the lowest temperature in which solid and liquid phases coexist). In the primary drying phase, the pressure is reduced to a few millibars by a partial vacuum and the material is heated to sublime the water therein, thereby removing the ice. The secondary drying phase removes the unfrozen water from the material, often with reduced pressures. Afterwards, the vacuum can be disengaged with inert gas, such as nitrogen, before sealing the freeze dried material, referred to herein as a product. 
     Bulk freeze drying (lyophilization) uses a tray to contain and transfer frozen material, such as biological organisms, pharmaceuticals, or other materials, to and from a freeze dryer (lyophilizer) before, during and after the freeze drying process. These trays are open, stainless steel trays designed to fit specifically in a particular freeze dryer, but the dimensions can be modified to fit any bulk lyophilization tray for any make or model freeze dryer. As the material dries, some particulates therefrom may be prone to escape from the lyophilizer tray, resulting in reduced product yield. 
     Moreover, when vacuum is released from the inside of the lyophilizer, some of the product may tend to dissipate into the air due to turbulence of air rushing into the inside of the lyophilizer. This can result in contamination of the lyophilizer and loss of product. Following the freeze drying process and disengagement of the vacuum, the tray containing the product is removed from the freeze dryer and directly exposed to environmental humidity, which could be detrimental to the product. There is currently no conventional item that protects the material and equipment that does not interfere with the freeze drying process. 
     Several solutions have been posed to address these issues for bulk lyophilizers. For example, a single-use tray is marketed where the operator first fills the tray with some quantity of material to be dried through a hole in the top, which is sealed with a screw-on cap before placing the tray into the freeze dryer. Once the material is dry and the vacuum disengaged, the tray is removed from the freeze dryer. The operator then cuts the entire top off the tray to access the lyophilized material, which makes the trays single use only. These trays do not enable an operator to seal the trays inside of the lyophilizer and thus, potentially expose the material to environmental humidity. Also, Lyoguard® trays do not fit in benchtop models of lyophilizers and decrease visibility of product. 
     An alternate solution employs bags with a heat sealer to contain lyophilized material. The bags permit vapor to escape, but decelerate the lyophilization process. The bag wraps the entire tray and, thus, prevents intimate contact between the tray and the shelf, which is required to maintain efficient temperature control to the product. Conventionally, this involves a manual process, yielding inconsistent results. Furthermore, these bags are one-time-use only. Thus, there is a need for a reusable device that can be used with standard lyophilizers to protect the material and equipment before, during and after the freeze drying process, as well as provide improved safety protection of operators from contamination. 
     SUMMARY 
     Conventional tray lids yield disadvantages addressed by various exemplary embodiments of the present invention. In particular, various exemplary embodiments provide a lyophilization tray lid for containing material within a bulk lyophilization tray container during the freeze drying process and then seal the dried material (i.e., product) within the tray container to protect that material from humidity upon removal of the tray and product from the freeze dryer. The lyophilization tray lid covers the tray container and enables vapors to exit therefrom during lyophilization while containing the product. 
     In exemplary embodiments, the tray lid can utilize the built-in stoppering function of the lyophilizer to press stoppers into holes in the lid, thereby sealing the tray while remaining inside the freeze dryer chamber. When the tray container containing the product is removed from the chamber, the product is protected from environmental humidity. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       These and various other features and aspects of various exemplary embodiments will be readily understood with reference to the following detailed description taken in conjunction with the accompanying drawings, in which like or similar numbers are used throughout, and in which: 
         FIG. 1  is a perspective view of an exemplary lyophilizer tray lid assembly; 
         FIG. 2  is a perspective view of the exemplary lyophilizer tray lid disposed on a lyophilizer tray container; and 
         FIG. 3  is an exploded perspective view of the exemplary lyophilizer tray lid and tray container components. 
     
    
    
     DETAILED DESCRIPTION 
     In the following detailed description of exemplary embodiments of the invention, reference is made to the accompanying drawings that form a part hereof, and in which is shown by way of illustration specific exemplary embodiments in which the invention may be practiced. These embodiments are described in sufficient detail to enable those skilled in the art to practice the invention. Other embodiments may be utilized, and logical, mechanical, and other changes may be made without departing from the spirit or scope of the present invention. The following detailed description is, therefore, not to be taken in a limiting sense, and the scope of the present invention is defined only by the appended claims. 
     One aspect of the disclosed embodiments provides an exemplary lid assembly for covering a tray that includes a primary lid; at least one opening formed through the primary lid; at least one secondary lid disposed to cover the opening; holes formed in the secondary lid; and a filter paper disposed between the primary lid and the secondary lid. The filter paper inhibits escape of material from the tray through the holes. In another aspect of the present disclosure, the lid assembly further includes a gasket material disposed between the secondary lid and the primary lid to hold the filter paper in position; and fasteners disposed to removably secure the secondary lid to the primary lid. 
     Yet another aspect of the exemplary embodiments provides a method for containing a product in a lyophilization tray before, during and after lyophilization. This method includes disposing a product to be freeze dried into the lyophilizer tray; placing a lid assembly over the lyophilizer tray; disposing lyophilization stoppers atop the holes prior to inserting the tray and lid into the freeze dryer chamber; lyophilizing the product in a lyophilization chamber; releasing the vacuum inside the chamber upon lyophilization completion; and pressing the stoppers into the corresponding holes to seal the material inside the tray. 
     The lid assembly includes a primary lid, at least one opening formed through the primary lid, at least one secondary lid disposed to cover the opening, holes formed in the secondary lid, and filter paper disposed between the primary lid and the secondary lid. These and other features, aspects and advantages of various exemplary embodiments will become better understood with reference to the following drawings, description and claims. 
     The present disclosure relates generally to a lyophilization tray lid assembly that can contain material within a bulk lyophilization tray during the freeze drying process, and then seal the dried material within the tray container to protect that material from humidity once the tray and product are removed from the freeze dryer. The lyophilization tray lid assembly covers the tray container and enables vapors to exit the tray while containing the product. 
     The tray lid assembly can utilize the built-in stoppering function of the freeze dryer to press stoppers into holes in the lid assembly, thereby sealing the tray container while remaining inside the freeze dryer chamber. Upon removal of the tray container containing the product from the chamber, the product is protected from environmental humidity. 
       FIG. 1  shows a perspective view of a lyophilizer tray lid assembly  10 , which includes a primary lid  12  with a peripheral groove  26  that forms a continuous channel on the lid&#39;s distal side. At least one secondary lid  14  (with two units depicted) is disposed on the proximal side of the primary lid  12 . Both lids  12  and  14  constitute rectangular shaped thin-shell plates (i.e., thickness at least one order of magnitude less than the lateral sides). The secondary lid  14  includes holes  16  (with eight arrayed) penetrating therethrough to reveal filter paper  18  underneath. 
     A gasket  20  containing the filter paper  18  is disposed between the lids  12  and  14 , which are secured together by screws  22  (or alternative fasteners) that penetrate through the secondary lid  14  and into the primary lid via cavities in mutual alignment.  FIG. 2  shows a perspective view of the tray lid assembly  10  disposed on a lyophilizer tray container  24  that houses the sample material to be freeze-dried. A stopper  28  covers each hole  16  on the secondary lid  14 . 
       FIG. 3  shows an exploded perspective view of the lyophilization container assembly. The tray container  24  includes a peripheral lip at its top opening. The groove  26  of the primary lid  12  receives the lip (shown by lower dash alignment lines) after a sample for freeze drying is disposed within the tray container  24 . The primary lid  12  includes at least one opening  30  (corresponding to the array of holes  16  of each secondary lid  14 ). Although a single rectangular opening  30  is depicted for the corresponding secondary lid  14 , other geometries and quantities can be considered without departing from the scope of the invention. 
     The gaskets  20  are disposed on the primary lid  12  aligned so as to enable the filter paper  18  on the gasket  20  to cover the corresponding opening  30  in the primary lid  12 . The filter paper  18  enables water vapor to escape from the tray container  24  while restricting particulate material from passing therethrough. The secondary lids  14  are disposed over their corresponding gaskets  20  onto the primary lid  12 . The holes  16  in the secondary lids  14  are arranged so as to be disposed within the perimeter of the opening  30 , albeit separated therefrom by the filter paper  18 . The screws  22  insert sequentially into corresponding cavities at the peripheries of the secondary lid  14 , gasket  20  and the primary lid  12  (shown by mezzanine dash alignment lines). The stoppers  28  can be inserted into their corresponding holes  16  (shown by upper dash alignment lines). 
     Referring again to  FIGS. 1 ,  2  and  3 , the lyophilizer tray lid assembly  10  can include the primary lid  12  and the secondary lids  14  that contain the plurality of holes  16  formed therethrough. The primary lid  12  can include openings  30  cut therein over which the secondary lids  14  are correspondingly positioned. The openings  30  are formed through the primary lid  12  in an array larger than the footprint of the holes  16  in the secondary lids  14  and smaller than the length and width of the secondary lids  14 . While the openings  30  are shown as rectangular shaped in  FIG. 3 , the openings  30  can be formed in various geometric and non-geometric shapes, provided that each opening  30  aligns with its corresponding hole  16  of the secondary lids  14 . 
     Filter paper  18  can be disposed on a bottom or distal side (i.e., facing the tray) of the secondary lid  14  to cover the openings  30 . Typically, one unit of filter paper  18  can completely cover each opening  30  of the primary lid  12 . However, multiple pieces of filter paper  18  can be stacked upon each other, provided that the filter paper  18  covers the entirety of openings  30  without gaps that would enable product to escape from the tray container  24  sealed by the lyophilizer tray lid assembly  10 . The filter paper  18  can be an HEPA filter paper sheet, and can be sized to cover the opening  30  of the primary lid  12 . 
     The gasket  20  can be disposed between the secondary lid  14  and the primary lid  12 . The gasket  20  can help ensure a seal between the secondary lid  14  and the primary lid  12  as well as hold the filter paper  18  in position. The gasket  20  can be shaped to fit on the primary lid  12 , surrounding the opening  30  of the primary lid  12 . Typically, the gasket  20  is sized to match the length and width of the secondary lid  14 . The gasket  20  can be disposed above or below the filter paper  18 . In some embodiments, two gaskets  20  can be used to sandwich the filter paper  18  therebetween. 
     A plurality of fasteners, such as the screws  22  can be used to secure the secondary lid  14  onto the primary lid  12 . Of course, other fasteners may be employed to position and retain the secondary lid  14  on the primary lid  12 . The screws  22  enable an operator to separate the secondary lid  14  from the primary lid  12  to, for example, replace the filter paper  18  with a clean piece of filter paper. The tray lid assembly  10  fits onto the lyophilizer tray container  24 . The tray lid assembly  10  can be formed in various shapes and sizes, depending on the shape and size of the particular tray container  24 . 
     The primary lid  12  can include a groove  26  cut about a bottom or distal side outer periphery thereof to help properly position the lid assembly  10  onto the lyophilizer tray container  24 . Stoppers  28  can be designed to fit into the holes  16  of the secondary lids  14 . The stoppers  28  preferably should be lyophilization style stoppers that enable passage of lyophilized vapors out of the tray container  24  while seated atop the holes  16 , for example. The stoppers  28  can be disposed inside of the lyophilizer (not shown) and can be pressed into the holes  16  of the secondary lid  14  via an automatic stoppering function of the lyophilizer for sealed containment. 
     Therefore, an operator is not required to remove the lyophilizer tray container  24  (and, therefore, the product therewithin) from the lyophilizer without having the product sealed within a container. The primary lid  12  and the secondary lid  14  can be formed from a clear transparent material, enabling the operator to visualize the material therewithin, or alternatively an opaque material. In some embodiments, an auxiliary orifice can be disposed through the primary lid  12  to enable a temperature probe to be inserted into the lyophilizer tray container  24  and then sealed with a pliable material, such as putty. 
     While the drawings show two secondary lids  14  fitting over two corresponding openings  30  in the primary lid  12 , a single secondary lid  14  or else more than two secondary lids  14  can be used within the scope of the present invention. Typically, the number of secondary lids  14  can be determined based on the size and shape of the lyophilizer tray container  24 , where larger tray containers would typically include more openings  30  in the primary lid  12  and, thus, more secondary lids  14 . Similarly, the number of holes  16  in each secondary lid  14  and the corresponding number of stoppers  28  can vary from the eight each depicted in the drawings, without departing from the inventive scope of the embodiments. 
     While certain features of the embodiments of the invention have been illustrated as described herein, many modifications, substitutions, changes and equivalents will now occur to those skilled in the art. It is, therefore, to be understood that the appended claims are intended to cover all such modifications and changes as fall within the true spirit of the embodiments.