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Rate-controlled freezer and cooling methods thereof

a temperature control and freezer technology, applied in the field of cooling devices, can solve the problems of inability to uniformly cool samples within the device, inability to accept and irreversible damage to cells, and inability to control the temperature of the sample, so as to reduce the temperature differential, increase the total sample volume or sample, and reduce the effect of temperature differential

Inactive Publication Date: 2005-11-03
GENENTECH INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0009] The present disclosure, in embodiments, provides a freezer system including a temperature monitored and temperature controlled freezer characterized by being capable of producing and maintaining uniform temperatures within individual samples and uniform temperatures among samples. The freezer system is also characterized by being capable of producing constant rate-controlled cooling within individual samples and among samples. The freezer system is also characterized by being capable of minimizing the temperature differential among samples and the temperature differential between samples and the chamber. The minimized temperature differentials are believed to enable more uniform sample temperatures and more uniform sample cooling-rates. Thus, the freezer system can provide superior cryo-preserved samples having little or no lot-to-lot variability in sample temperature, relative cooling-rate, and sample quality or efficacy.
[0010] The present disclosure, in embodiments, also provides a rack system comprising one or more trays adapted to receive and hold items, such as sample vials or ampoules, within the freezer to further enable the above-mentioned temperature and cooling characteristics of the freezer system and cooling methods of the disclosure. The freezer system incorporating the rack system is characterized by being able to accommodate a plurality of same or different sized items. The freezer system incorporating the rack system is further characterized by having an increased total sample volume or sample load capacity for simultaneously and rate-controllably cooling items compared to commercially available freezers.

Problems solved by technology

As external ice forms, liquid water is depleted from the extra-cellular environment and an osmotic imbalance can occur across the cell membrane or cell wall, which imbalance may cause intracellular water to migrate out of the cell and lead to solute concentration within the cell.
However, rapid cooling typically produces more intracellular ice, which may cause unacceptable and irreversible damage to the cells.
However, the ThermoForma freezer and other commercially available rate-controlled cooling devices experience problems which include, for example, non-uniform cooling of samples within the device, such as, considerable relative-temperature variability among samples; considerable relative-temperature variability between the freezer's chamber and samples and within individual samples; and considerable cooling-rate variability among samples.
These problems are exacerbated for large total volume sample loads.

Method used

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  • Rate-controlled freezer and cooling methods thereof

Examples

Experimental program
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Effect test

example 4

[0122] Evaluation of Cryomed Freezer to Provide Rate-Controlled Cooling Comparative Example 2 was repeated with the exception that the sample trays were filled with ampoules as shown in FIG. 6 having alternate or every-other main openings filled with an ampoule and all minor openings vacant for a total of 45 openings per tray filled with ampoules of the 162 available openings, such that no filled opening, that is an ampoule occupied opening, has a nearest-neighbor opening that is filled or occupied with an ampoule. A cooling rate of about −1° C. per minute produced nearly uniform cooling and freezing results.

example 5

[0123] Evaluation of Kryosave Freezer to Provide Rate-Controlled Cooling Example 4 was repeated with the exception that the freezer was a Kryosave 750-30 having a laminar flow pattern characteristic. A cooling-rate program was used which automatically compensates for the total number of sample ampoules in the chamber and their collective impact on the total heat of fusion sample load. A cooling rate of about −1° C. per minute produced nearly uniform cooling and freezing results.

example 6

[0124] Evaluation of ThermoForma Freezer to Provide Rate-Controlled Cooling Example 4 was repeated with the exception that the sample trays had a slightly different configuration and capacity. The trays were filled with ampoules as shown in FIG. 7 and a ThermoForma Model 7454 freezer, see the abovementioned U.S. Pat. No. 6,044,648, was used having a larger fan, a higher capacity fan motor capable of providing greater convection, a larger chamber, a heat transfer coil based on liquid nitrogen “spray,” and capable of accomplishing the following instruction “hold chamber at temperature X until sample temperature is Y”.

[0125] In preliminary experimental trials with this freezer in several configurations, such as using one, two, or three trays, it was apparent from the sample temperature data and the cooling-rate measurements that the cooling pattern within in the chamber can be markedly affected by the rack and tray configuration. This observation prompted further modification of the a...

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Abstract

The disclosure provides a freezer system including a temperature and cooling-rate controlled freezer having a rack system having a tray adapted for freezing and preserving temperature-sensitive items. The disclosure also provides methods for cooling and preserving items in the freezer system.

Description

CROSS REFERENCE TO RELATED APPLICATIONS [0001] This application is a United States non-provisional application and is related to and claims priority to co-pending U.S. provisional application Ser. No. 60 / 527,131, filed Dec. 3, 2003, the disclosure of which is incorporated herein by reference in its entirety.BACKGROUND OF THE INVENTION [0002] The present disclosure generally relates to cooling devices, such as low-temperature freezers, which utilize a directly injected refrigerant, such as liquid nitrogen, to cool various products, such as temperature sensitive biological samples. [0003] One common cryo-preservation method of biological materials involves rate-controlled freezing to minimize ice-crystal formation and to prevent osmotic effects. During cooling, ice can form at different rates depending upon, for example, the nature of the sample, such as cell permeability, and the sample's constituents and its surrounding matrix. During slow cooling, for example of biological cells, f...

Claims

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Application Information

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IPC IPC(8): A01N1/02F25D3/10F25D17/04F25D17/06F25D25/02F25D29/00G01N1/42
CPCA01N1/02A01N1/0257F25D3/102F25D17/06F25D25/028F25D29/001G01N1/42F25D2317/0655F25D2331/812F25D2700/122F25D2700/123F25D2700/16F25D2317/0651
Inventor HAMILTON, ROBERT WARREN
Owner GENENTECH INC
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