Preventing sample degradation from transient temperature fluctuations

Abstract

Methods and devices can protect samples maintained at controlled temperatures from degradation due to transient temperature fluctuations.

Description

RELATED APPLICATIONS[0001]This application claims priority to United States Provisional Patent Application Ser. No. 61 / 512,816, entitled PREVENTING SAMPLE DEGRADATION FROM TRANSIENT TEMPERATURE FLUCTUATIONS, filed on Jul. 28, 2011, which is incorporated herein by reference in its entirety.BACKGROUND[0002]The storage of sensitive laboratory samples and reagents in controlled temperature conditions, for example, in upright refrigerators or freezers or in incubators, presents numerous opportunities for temperature cycle-dependent degradation. Biological samples typically contain a complex solution that may include salts, buffering components, stabilizers, reducing agents, and cryo-protectants, in addition to organic isolates and purified macromolecular components. Repeated, transient temperature fluctuations of such samples during periods at which they are being held at controlled temperatures can damage them.[0003]For example, during frozen storage, migration of smaller molecular spec...

AI Technical Summary

Benefits of technology

The present invention aims to provide solutions for problems caused by temporary temperature fluctuations in cooling devices, such as refrigerators and freezers. The invention involves using a method to suppress those fluctuations in samples placed in sample containers, such as tubes or vials, which are then placed in aluminum or aluminum alloy racks in the cooling device. This method helps to maintain consistent temperatures and minimizes the space occupied by the container holder.

Problems solved by technology

The storage of sensitive laboratory samples and reagents in controlled temperature conditions, for example, in upright refrigerators or freezers or in incubators, presents numerous opportunities for temperature cycle-dependent degradation.

Repeated, transient temperature fluctuations of such samples during periods at which they are being held at controlled temperatures can damage them.

The small molecule migrations can lead to focal changes in salt concentration, pH, and macromolecular hydration, leading to undesired effects, such as protein denaturation and aggregation.

Although the samples may never become fully thawed during storage, cyclic variation in temperature will impose progressive damage to many types of biological samples, particularly to protein solutions such as cells and cellular components, such as preparations of antibodies, vaccines, and / or proteins with enzymatic activity.

Under normal laboratory operation conditions, at least four sources of temperature fluctuation present a challenge to sample integrity of samples being held at controlled temperatures below freezing, and several of these sources are present in other temperature control devices, i.e., incubators that control temperatures at above room temperature and refrigerators that control temperatures at below room temperature and above freezing.

With time, the ice layer thickness can become substantial and can interfere with sample access and reduce the useful volume of the freezer interior.

This problem exists not only with freezers that are designed to operate in the −25° C. to 0° C. range but with freezers that operate (control the temperature) at lower temperatures, i.e., −80° C. freezers.

The third source of temperature fluctuation derives from user access and can result in the most extreme temperature fluctuations.

This problem exists with all temperature control devices, including incubators designed to control temperature at room temperature and above and refrigerators and freezers designed to control temperature at below room temperature.

This problem also exists with refrigerators.

Laboratory freezers are often shared property with multiple users, which results in frequent opening of the freezer compartment to the outside air.

The duration of an open door search for a specific item can easily result in an unintentional and severe rise in archived sample temperatures with warming to the point of visible melting of frost on container surfaces.

In addition, co-workers that are unaware that the freezer has been recently accessed often compound the warming problem by near term subsequent accession of the freezer compartment.

While these solutions serve to return the freezer interior to the desired temperature more quickly upon closure, the low thermal conductivity of the air separating the samples from the thermal sinks delays the heat transfer from the samples, resulting in poor protection against transient spikes in temperature.

This solution has limitations in that the containers are subject to rupture and vulnerable to impact damage, and the relatively low density of the gels provides sub-optimal protection for a given rack volume.

An effective thickness of insulation can greatly reduce the usable storage volume.

In addition, placement of room temperature samples in an insulated box will increase the length of time required to freeze the sample and subject all previously frozen samples to a spike in temperature as the thermal energy dissipates.

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