Refrigeration – With indicator or tester – Condition sensing
Reexamination Certificate
1999-12-07
2001-05-08
Tanner, Harry B. (Department: 3744)
Refrigeration
With indicator or tester
Condition sensing
C062S457900, C340S586000
Reexamination Certificate
active
06226997
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to a method and to an associated device or apparatus for maintaining the temperature integrity of cryogenically preserved materials. More particularly, this invention relates to a method and to an associated apparatus for safeguarding the cryogenic preservation of biological specimens during transfer of the specimens to or from a long-term storage container.
BACKGROUND OF THE INVENTION
When properly treated, biological specimens including human tissue and cell lines may be viably stored almost indefinitely at temperatures approaching that of liquid nitrogen, so long as that temperature is maintained. As long as a specimen is stored in a bulk storage facility it is relatively easy to maintain that specimen at a steady liquid nitrogen temperature. However, once the temperature of a specimen is raised significantly, the integrity of the specimen suffers. More specifically, unintended (upward) temperature excursions (UTE's), even falling far short of thawing, may permit the growth of ice crystals inside stored biological samples. Ice crystals may disrupt cell membranes, destroy cellular organelles and genetic material, and render the biological samples inviable. Such damage is irreversible and, if not recorded or reported at the time, may go undetected until the samples are deliberately thawed for use, years or possibly decades later.
When it becomes necessary to move or transfer a specimen, the possibility for uncontrolled and unrecorded temperature excursions occurs. The problem is compounded because an operator may not be aware that a removed specimen has undergone an unacceptable temperature excursion, or, inadvertently allowing such an excursion to occur, may not wish to record such an event out of concern for his or her continued employment and the possibly accurate perception that the damage is unlikely to be discovered during his or her tenure, or possibly, lifetime.
For these reasons, any installation undertaking the long-term cryogenic storage of viable tissue samples and cell lines must embody quality control and quality assurance measures, both to render unintended upward temperature excursions of stored material improbable, and to assure end-users of the improbability of such excursions and of the over-all reliability of the storage facility, to which irreplaceable samples may be entrusted. There is a continuing need for improved devices which will assist in maintaining the temperature integrity of biological samples undergoing cryogenic processing, and in particular, during operations which require the temporary removal of individual specimens from a controlled bulk storage facility and exposure to ambient conditions during such transfer, transportation, or other intermediate steps prior to a final deliberate thawing and use. There is yet a further need for methods and devices which will assure the temperature integrity of a multitude of portable individual samples within a bulk storage facility without the necessity of expensive sensing devices or permanent sensor leads affixed to each cell.
OBJECTS OF THE INVENTION
An object of the present invention is to provide a method and/or an apparatus for assisting in maintaining the temperature integrity of specimens stored at or within a preselected temperature range.
A more particular object of the present invention is to provide such a method and/or apparatus which will facilitate the maintenance of temperature integrity of cryogenically preserved biological specimens temporarily removed from a low-temperature storage container for processing or transport.
Yet another object of the present invention is to provide such a method and/or apparatus which will minimize possibilities for operator error during a processing operation requiring temporary removal of a cryogenically preserved biological specimen from a storage apparatus.
These and other objects of the present invention will be apparent from the drawings and descriptions herein.
SUMMARY OF THE INVENTION
The present invention addresses methods and devices for overcoming these limitations of bulk cryogenic storage facilities and in providing temperature control assurance, particularly for the storage of a multitude of small sub-containers (e.g., vials or ampules) which may be intermittently moved among units of the storage facility or between the facility and portable transport containers.
A bulk cryogenic storage facility includes one or more bulk containers or storage units each containing a multitude of addressable storage locations or receptacles for the receipt of vials or ampules. Such a bulk storage facility is disclosed in U.S. Pat. No. 5,921,102. A transfer operation comprises removing one or more vials containing cryogenically preserved biological material from respective storage locations and subsequently inserting the vials in different storage locations in the same or different bulk container or in a portable cryogenic storage unit. A portable cryogenic storage unit is a portable device capable of maintaining the temperature of one or more vials or other sub-containers in a cryogenic temperature range during transport. Typically, a portable cryogenic storage unit will take the form of an insulated container including a reservoir for liquid nitrogen, identifiable storage locations for one or more sub-containers, and a temperature monitoring device.
A method in accordance with the present invention for maintaining temperature integrity of a cryogenic specimen during a transfer operation comprises triggering an automatic process tracking the temperature of an individual specimen container upon removal of that container from a storage location in a bulk or portable cryogenic storage unit. In general, the temperature of the individual specimen container will rise following removal from a bulk or portable cryogenic storage unit. Upon exceeding a critical temperature T
c
, irreversible damage is presumed to begin accumulating in the specimen. Therefore, prior to reaching temperature T
c
, action is initiated at an alarm temperature T
A
=T
c
−&Dgr;, where &Dgr; is a temperature increment pre-chosen to allow time for corrective action to be completed prior to incipient accumulation of irreversible specimen damage at temperature T
c
.
Action initiated automatically upon determining that the temperature of a vial in transit has exceeded temperature T
A
may include sounding an audible alarm to alert a human operator to return the specimen to the bulk or portable cryogenic storage facility. Action initiated may also include issuance of instructions to a robotic arm to return the specimen to a storage location in a bulk or portable cryogenic storage facility, in conjunction with an audible alarm to alert a human operator to the impending automatic operation. In addition to operator or machine action, the temperature excursion may be recorded as an isolated event or as a portion of a complete temperature profile by a microprocessor associated with the bulk cryogenic storage facility (the “mainframe”, although it may in general be a workstation or PC), or temporarily recorded by a microprocessor associated with the portable cryogenic storage facility, for subsequent transfer to the mainframe associated with the bulk cryogenic storage facility.
A temperature tracking operation in accordance with the present invention is implemented by a microprocessor or computer and may include extrapolation of a current temperature of a vial or other container exposed to ambient conditions from an initial temperature of the vial as maintained in the storage location. This extrapolation may be based upon an empirical study of a standard vial containing a material with thermal properties similar to those of a representative biological specimen. In that case, the extrapolation consists of a timing operation coupled with a look-up operation on a standard temperature curve.
Use may be made in implementation of the present invention of Newton's Law of Constant Cooling. The Law of Constant Cooling states roughly that heat tr
Coleman Henry D.
Cryo-Cell International Inc.
Sudol R. Neil
Tanner Harry B.
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