Some biological products, for example vaccines, and other condition-sensitive products of commercial importance are not only subject to spoil, deteriorate or lose quality if exposed, even briefly, to a temperature near or below freezing but also age at ambient temperatures, and accordingly have a limited shelf life within which the product should be used to avoid spoilage. Thus, a vaccine distributed in a tropical climate may have a life of only a few weeks which is significantly shortened if the vaccine is extensively exposed to ambient temperatures in excess of about 25, or about 30° C. (about 77° F. or about 86° F. or more). Effective cumulative temperature indicators are known, such as the vaccine condition indicators supplied by the assignee of the present invention, TEMPTIME Corporation, which are specified for use in UNICEF/WHO vaccination programs.
Vaccines in the field in hot climates are commonly protected from excessive temperature exposure by keeping them in portable cold storage containers using blue ice or equivalent measures. However, such measures run the risk of causing freeze-related damage to vaccine samples in the vials or syringes from cold ambient temperatures in mountainous areas and the like or possibly in the bulk container, from adjacency to the blue ice or container walls contacting the blue ice or other coolant. Also, vaccines are commonly stored in refrigerators or refrigerated volumes for short or long periods of time, in some cases as much as three years. As is well known, refrigerators and refrigerated spaces are prone to cold spots where products can freeze notwithstanding that the refrigeration may be thermostatted to an above-freezing temperature of say 2-4° C. A bottle or glass of water can freeze in the top of many refrigerators. Thus, there is a significant possibility that in the course of normal handling, an individual vaccine vial may have suffered potentially damaging freeze exposure.
Such freeze-damaged samples may have lost immunological virulence and should be discarded yet may bear no visible signs of the damage. Accordingly, there is a need for a low-cost freeze indicator to indicate past exposure of a product to a freezing or, possibly, a near-freezing temperature. It is presently understood that the art lacks useful devices that will enable a medical technician, or other user, readily to determine, in such circumstances, in the field at the point of care, or elsewhere, which vaccine samples are in good condition and which are not.
Various freeze indicators are known or have been proposed. For example, U.S. Pat. No. 4,148,748 to Hanlon et al. (“Hanlon”) discloses a nonreversible freeze-thaw indicator intended to detect whether an article has been subjected to freezing or thawing conditions. Hanlon's indicator employs a colloidal dispersion of organic solid particles of a polymeric resinous material, which may be in latex form, for example, styrene polymers. Various other styrene, vinyl and vinylidine polymers and copolymers are mentioned. Hanlon's colloidal dispersions are described as becoming nonreversibly destabilized upon freezing, transforming a translucent dispersion to a substantially opaque dispersion.
U.S. Pat. No. 4,191,125 to Johnson (“Johnson”) discloses a freeze indicator which includes a frangible ampoule substantially filled with a mixture of water, a nucleating agent, and a surfactant. Upon reaching the freezing point of water, the water mixture freezes fracturing the frangible ampoule. According to Johnson: a nucleating agent can be used to overcome the undercooling effect; a dye-printed pad can be employed to show a color change; and deuterium oxide may be added to raise the freezing point.
U.S. Pat. No. 4,646,066 to Baughman (“Baughman”) discloses an indicator device employing a tuned electrical circuit interrogatable by an RF signal in the microwave range or lower. The tuned circuit includes an element having an electrical property that changes in a predetermined fashion in response to a particular environmental parameter. Baughman suggests that various freeze-induced phenomena such as rupture of saline-containing microcapsules or demulsification of liquids, for example, salad dressing, can provide a conductance change in the tuned circuit element which may be detected on interrogation, enabling freezing to be monitored.
Other freeze indicators based on comparable or different technologies are also known to those skilled in the art.
USPTO Backgrounds
USPTO Backgrounds