Introduction:

The long-term preservation of suspension of cells by freezing and stroage at cryogenic temperatures is a well-established technique. A wide variety of single cell types in addition to multicellular structures and organisms may be kept indefinitely through suspension in a cryopreservation fluid with subsequent freezing at a controlled rate of temeprature reduction. The cryogenic storgae vessels in which the cell suspensions are frozen are typically stored for extended preriods in a vacuum-insulated tank that is refigerated by liquid nitrogen, although mechnical refrigeration systems may also be applied. Cell suspensions that are preserved by such methods may also be transported to remote locations while maintaining cryogenic temperature conditions of -196 to -150c by means of vacuum-insulated flasks wherein liquid nitrogen, as a refigerant to maintain temperature, has been introduced into an adsorbent material. Such a container is often refered to as a “dry-shipped”. Alternatively, if shortterm tempperature shifts to a range of -80C to 50C are not exceedingy deleterious to cell viability, an insulated container using dry-ice as a refigeerant may be applied. Upon arrival at the destination the frozen cell suspension may be transferred to a local extended-term storage system, or may be recovered from the refigerated shipping system and used directoy. Prior to use, frozen cell suspension must be tahwed and retrieved fromt eh storage vessel. (WO 2019/2900145). 

Types of Cryogenic Storage Devices/Vessels:

Feezing Bag:

A common type of cyrogenic storage vessel is a flexible-wall storage bag also referred to as a “feezing bag”, a “cryopreservation storage bag” or a “cryostorage bag”. Common procedrues for cryostorage bag usage include the filling of the bag to a selected volume, after which, the tubing extension is often heat sealed at a location enar to the ports and the remainder of the tubing assembly is severed and disposed. In some cases, a suer will elave a short extension of tubing attached to the port area with intermitten seals such that, post thawing, segments of cell solutions may be isolated for varous testing pruposes. The edge of the bag opposite to the port edge may comprise an extension of the sealed region in which may be located a slot by which the bag may be suspended on a hanging apparatus.(WO 2019/2900145)

As a result of the flexible properties and fragile design of cryostorage bags, various procedures are generally followed and limits applied when preparing and feezing these types of crysorage vessels. For example, to control the thickness of the cryostorage bag vessel, the bags are typically limited in fill volume, and frozen in an orientation such that the major planar surfaces of the bag are perpendicular to the gravitions force vector (also referred to as a “falt” orientation). In some instances, the filled bags may be frozen while being stored wihtin a rigid cassette in order to limit and control the thickness of the frozen cryostorage bag and contents. However, despite efforts taken during the feezing process, the natural expansion of the aqueous solution in the flexible cryostorage bag resutls in uneven surface variations, dimensions, and solution thickness. (WO 2019/2900145).

Storage/Shipping cassette:

For some procedrues, a cryostorage bag is encloded within a storage or shipping cassette as part of a freezing process. eous solution in the flexible cryostorage bag resutls in uneven surface variations, dimensions, and solution thickness. (WO 2019/2900145

Biolife Solutions (US 17/046,502, published as US Patent Application No: 20210137787 and WO2019/200145) discloses a storage system which is configured to work with commercially available cryostorage bags which includes a protective interface cusion having an upper and lower half configured to receive a cryostorage bag. The upper and/or lower halves can include one or more recesses which achieve a desired shape or configuation of a solution in the cryostorage bag during and following a freezing process. The uper and/or lower halves may futher include one or more openings to provide access to the bag ports or bag port extension tubing. The upper and lower halves include one or more cutouts and/or recesses formed on an interior surface of the halves, wherein these features act as a mold to acheive a desired shape or configuation of a solution in the cryostorage bag during and folloiwng a feezing prcoess. Portions of the cryostrage bag expand into the one or more cutouts and/or recesses as the liquides of the cryostorage bag solidify during the freezing process. Upon subsequent removal of the protective interface cushion device, the resultant and desired shape or configuation of the cryostorage bag and its contents may assist in storing the cryostorage bag. In some instances, the resultant and desired shape or configuation of the cryostorage bag and its contents is utilized to process the contents of the cyrostroage bag, suchh as to provide optimized interaction with external thawing instrument equipment and/or components. Following the freezing prcoess, the one or more cutouts and/or recesses in the upper and lower halves of the protective interfact cusion device provide cushioning to the frozen contents and protect fragile elements of the cryostorage bag, such as the heat-sealed seams, as well as prevent undersirable movement or shifting of the cryostorage bag relative to the protective interface cusion device and other elements of the storage system. In some embodiments, the protective interface cusion device includes a thermoinsulative material configured to absorb impact, shock and acceleration forces at crogenic temepratures. The protective interface cusion device may include a fibrous synthetic polymer material, as at cryogenic temperatures, polymeric fibers may remain sufficiently flexible to sustain a compressible cusioning effect. In some embodiments, the storage system further includes a protective shell casette including a first and second half, each half having an interior surface for receiving and housing at least a portion of the protective interface cusion device and bag. In some embodiments, the protective interface cusion devide is provided without an overflow region, and is further configured to limit the total volume of fill volume of the cryostroage bag. In place of an overflow region the protective interface cusion device includes an expanded or enlarged exclusion region. The volume limitations and external pressrues provdied by the exclusion region displaces the entire liquid contents of the bag into the fill volume. Thus, liquid contents are not reliant on gravity for displacement into the fill volume. Accordingly the protective interface cusion device is compantbile for freezing in a variety of orientations. 

Sartorius Stedim North American Inc. (US 2012/0017609) disclsoes a system for use in feezing, storing and thawing biophamraceutical materials which incluedes a fexible sterile container for holding the biopharmacetucial material and a holder which is more rigid and fiedly connected to the container means. The flexible container 10 may be formed of a laminated film which includes a plurality of layers. The sterile, flexible container 10 may be configured (e.g., shaped and dimensioned) to be received in, and integrally connected to a supporting strcuture, such as a frame or holder. The container 10 may can include one or more ports or conduits to allow filling or draining of biopharmaceutical materials. A typical process is that one or mroe of the cotainers is integrally formed or fixedly connected to a holder.