WO2024155789A2

WO2024155789A2 - Color-change sensor assembly and transportation thereof

Info

Publication number: WO2024155789A2
Application number: PCT/US2024/011977
Authority: WO
Inventors: Gregory L. Heacock; Toby William ARMSTRONG
Original assignee: Shockwatch Inc D/b/a Spotsee
Current assignee: Shockwatch Inc D/b/a Spotsee
Priority date: 2023-01-18
Filing date: 2024-01-18
Publication date: 2024-07-25
Anticipated expiration: 2025-07-18
Also published as: WO2024155789A3; CN120693515A; EP4652447A2

Abstract

A color change sensor assembly which changes color depending on temperature or time since activation is disclosed. The sensor assembly comprises an indicator that changes color based on the concentration of a gas. The assembly comprises a porous material containing the gas at concentrations higher than the gas is found in the atmosphere and the assembly is configured to control diffusion of the gas for example carbon dioxide into the color change indicator. The assembly is enclosed in an impermeable container that has high concentrations of the gas found in the porous material, allowing the sensor assembly to be activated by removing it from the packaging, providing a time-sensitive and temperature-sensitive indicator.

Description

COLOR-CHANGE SENSOR ASSEMBLY AND TRANSPORTATION THEREOF T_{his invention relates to a color-} ^{change sensor assembly which changes color depending on} the temperature of the environment in which the sensor assembly is located and which provides an indicator response dependent upon time elapsed since the sensor assembly is ^^ activated or armed. The sensor assembly comprises an indicator that changes color based on the concentration of a gas contained therein which may be controlled by the presence of a local atmosphere comprising the gas. Many products may be susceptible to deterioration or inactivity due to the passage of time such that products may have a finite “shelf-life” or be subjected to undesirably low or high ^^^ temperatures. Such deterioration or inactivity may compromise product quality, utility and, in certain case, present a significant risk to health or safety. There are many examples of such products including medicines, vaccines, foods, nutraceuticals, temperature sensitive chemicals, pants, inks, electronic equipment, products in aerospace applications and medications. Indicators, of whether a product has been subjected to undesirable or ^^^ unacceptable temperatures or passage of time are important in various industries. Visual indicators are especially useful as they provide a means of readily determining whether a product has been subjected to adverse conditions by the human eye or scanning techniques which may facilitate automated control of product quality, safety and utility. Medical products, for example vaccines, and other products for human or animal consumption or use are ^^^ especially susceptible to impairment, inactivation or other adverse effect due to the passage of time or exposure to unacceptably high or low temperature in the supply chain, for example during storage or shipping. A product which is compromised may present a significant and potentially life-threatening risk to public or animal health due to exceeding an intended shelf- life for the product or by being subjected to temperature excessively low or high temperatures, ^^^ beyond the product specification. There is a particular need for a reliable indicator for medicines, particularly vaccines, to ensure they remain suitable for use, that is safe and effective, notwithstanding conditions that may arise during distribution, storage and use, often over a prolonged period and in varying prevailing atmospheric conditions arising between manufacture and the point and time of use. ^^^ Vaccines may be distributed globally in huge quantities and to regions with low or high prevailing temperatures and without appropriate means of controlling the temperature to which the vaccines may be subjected, risking inactivation of the vaccine. Vaccines are often supplied in small individual vials and hundreds of millions of such vaccine doses are typically distributed to areas without either air conditioning or heating and there have been attempts to develop ^^^ products that effectively provide an indication that vaccine doses may have been subjected to unacceptable temperatures or excessive delay since manufacture, rendering the vaccines ^ ^^^^^^^^^ ineffective. Such products or indicators are known as vaccine vial monitors (VVMs) and typically need to be able to be used with batches of vaccines or individual vials to provide reassurance for clinicians, medics or users at the point and time of use. Suitably, VVMs are small and may be applied to a vial so may need to have a small footprint, for example a label, ^^ be easy to apply to a vaccine vial, inexpensive and easy to monitor without special equipment. In an attempt to meet these various requirements, thermochromic inks printed on labels have been employed. An example of such a product is the HEATmarker VVM product from TempTime. These products use thermochromic inks that can be printed on a label and then attached to a vaccine vial. Colorimetric sensors or indicators based on polydiacetylene ^^^ technology are known for use in food and medical applications, for example in vaccines. However, costly or complex provision may need to be made to avoid activation during shipping and before being applied to a product. For example, polyacetylene-based colorimetric sensors may need to be shipped in dry ice and stored at temperatures below -20°C prior to application to a product otherwise the indicator becomes “active” and does not reflect the conditions to ^^^ which the product has been subjected. There is a need to provide indicators or sensors which may be “activated” or “armed” upon application of the indicator to the product whilst avoiding complex and costly supply chain logistics to avoid premature arming. Further, a continuing need exists for a sensor, particularly for a color-change sensor that may ^^^ be applied to a product or its packaging, suitably with a small footprint such as a label, is easy to apply, is inexpensive, may be readily read manually or by non-human means and which may be activated at or just before the indicator is applied to a product. In the case of medicines and vaccines, the attribute of being able to activate the indicator at the time or just before it is applied to a product is sometimes referred to as the indicator or monitor being “field armable”. ^^^ We have now found that a time-temperature color change sensor assembly that uses changes in the concentration of a gas to trigger the indicator ameliorates or addresses these drawbacks. The invention provides a color change sensor comprising a porous material containing a gas, referred to herein as a “gas layer” and an indicator, the color of which is affected by the presence or concentration of the gas wherein the color change sensor is ^^^ disposed in a container which is impermeable to the gas such that the environment in the container is sealed to the ambient environment. The gas is present in the gas layer at a concentration different to, preferably higher than, the concentration of the gas in the atmosphere. The gas may or may not be present in the atmosphere. The sensor assembly may include a further layer such as a semi-permeable barrier to regulate or control the flow of ^^^ the gas between the gas layer and the color change indicator. ^ ^^^^^^^^^ In a first aspect, the invention provides a color change sensor assembly, preferably a time- temperature color change sensor assembly, which comprises: (a) a color-change indicator, the color of which may be affected by the presence or absence or the concentration of a gas in contact with the indicator; ^^ (b) a gas layer comprising a porous material containing a gas capable of interaction with the indicator so as to produce a color change, the gas being present at a different, preferably higher, concentration than the gas is found in the ambient environment, typically the atmosphere; and (c) optionally, a further layer; ^^^ wherein the color change sensor assembly is disposed in a container which is impermeable to the gas and which contains the gas at a concentration which is different, preferably higher, to the concentration of the gas in the ambient environment. The color-change indicator may be separate from the gas layer or the indicator and the porous material of the gas layer may be mixed together. ^^^ The further layer may be impermeable to the gas or may comprise a semi-permeable barrier. Multiple further layers which are the same or different may be employed. In one embodiment, the semi-permeable barrier may be disposed between the gas layer and the color change indicator and control the flow of the gas between the gas layer and the color change indicator. In one embodiment the invention provides a color change sensor assembly, preferably a time- ^^^ temperature color change sensor assembly, which comprises: (a) a gas layer comprising a porous material containing a gas, the gas being present at a different, preferably higher, concentration than the gas is found in the ambient environment, typically the atmosphere; and (b) a color-change indicator adjacent to the gas layer or mixed with the porous material ^^^ of the gas layer, the indicator being capable of interaction with the gas so as to produce a color change; wherein the color change sensor assembly is disposed in a container which is impermeable to the gas and which contains the gas at a concentration which is different, preferably higher, to the concentration of the gas in the ambient environment. ^^^ In another embodiment, the invention provides a color change sensor assembly, preferably a time-temperature color change sensor assembly, which comprises: (a) a gas layer comprising a porous material containing a gas, the gas being present at a different, preferably higher, concentration than the gas is found in the ambient environment, typically the atmosphere; ^^^ (b) a further layer, preferably a semi-permeable barrier that controls the flow of the ^ ^^^^^^^^^ gas; and (c) a color-change indicator between the gas layer and the further layer, the indicator being capable of interaction with the gas so as to produce a color change; wherein the color change sensor assembly is disposed in a container which is impermeable ^^ to the gas and which contains the gas at a concentration which is different, preferably higher, to the concentration of the gas in the ambient environment. In a further embodiment, the invention provides a color change sensor assembly, preferably a time-temperature color change sensor assembly, which comprises: (a) a gas layer comprising a porous material containing a gas, the gas being present ^^^ at a different, preferably higher, concentration than the gas is found in the ambient environment, typically the atmosphere; (b) a semi-permeable barrier that controls the flow of the gas adjacent to the gas layer; and (c) a color-change indicator on the semi-permeable barrier, the indicator being ^^^ capable of interaction with the gas so as to produce a color change; wherein the color change sensor assembly is disposed in a container which is impermeable to the gas and which contains the gas at a concentration which is different, preferably higher, to the concentration of the gas in the ambient environment. ^^^ Upon opening the impermeable container, the sensor assembly is exposed to the atmosphere and the gas in the assembly will migrate out of the assembly and into the atmosphere depending on the construction of the assembly and the concentration of gas in the assembly and in the atmosphere. at some rate. In at least one embodiment after exposure to the ambient environment, the gas in the gas layer will migrate out of porous material, through the semi- ^^^ permeable barrier and into the indicator material and then eventually into the atmosphere. As the gas concentration that the indicator is exposed to changes, the indicator itself changes color. The higher the temperature the faster this gas migration may occur and the assembly provides an indication of the time and temperature to which the assembly has been subject, a “time-temperature indicator”. The material from which the semi-permeable barrier is ^^^ constructed and/or the thickness of the barrier (or including multiple layers of the barrier) the rate of migration of the gas into the indicator layer and eventually into the atmosphere may be controlled. At the point of use, the color change sensor is removed from the container and applied to a ^^^ product, for example a medical product, vaccine, food product or the like, and exposed to the ambient environment. The sensor is thereby “armed”. The concentration of the gas in the color change sensor may then change over time and, depending on the indicator and the ^ ^^^^^^^^^ concentration of gas in contact with the indicator, the indicator will change color providing an indication of the time elapsed since the sensor was armed. The color change sensor assembly is suitably in the form which may be readily applied to a ^^ product including product packaging. In a preferred embodiment, the sensor assembly is in the form of a label which may be applied to a product prior to the product being distributed to wholesalers, end users or other third party entities. The color change sensor according to the invention may be manufactured and stored or shipped independently of the product to which the assembly is to be applied. The assembly may be left in its unarmed state for any period ^^^ of time and, advantageously, does not require a low-temperature storage environment, thereby affording advantage as regards costs of storage or distribution and environmental advantage. The terms “color change sensor” and “indicator assembly” are employed interchangeably herein. Further, reference to a color change sensor assembly may or may not include the ^^^ impermeable container, according to the context. For example, where the indicator has been removed from the container and is armed, it may still be referred to a color change sensor assembly. In a second aspect, the invention provides a color change sensor assembly pack comprising: i) a closed container defining a chamber; ^^^ ii) at least one, preferably a plurality of a, color change sensor assemblies, preferably a time-temperature color change sensor assemblies, in the chamber wherein the or each assembly comprises: (a) a color-change indicator, the color of which is affected by the presence or absence or the concentration of a gas in contact with the indicator; ^^^ (b) a gas layer comprising a porous material containing a gas capable of interaction with the indicator so as to produce a color change, the gas being present at a different, preferably higher, concentration than the gas is found in the ambient environment, typically the atmosphere; and (c) optionally, a further layer; ^^^ wherein the container is openable to the ambient environment and constructed of a material which is impermeable to the gas and comprises the gas at a concentration which is different, preferably higher, to the concentration of the gas in the ambient environment. Suitably, the further layer is selected from an impermeable layer, a semi-permeable barrier ^^^ and aselectively permeable layer as described herein. ^ ^^^^^^^^^ In a further aspect, the invention provides a method of making a sensor assembly pack comprising: i) providing an impermeable container defining a chamber; ii) placing at least one and preferably a plurality of color change sensor ^^ assemblies in the container, wherein the or each assembly comprises: a. a color-change indicator, the color of which is affected by the presence or absence or the concentration of a gas in contact with the indicator; b. a gas layer comprising a porous material containing a gas capable of interaction with the indicator so as to produce a color change, the gas being ^^^ present at a different, preferably higher, concentration than the gas is found in the ambient environment, typically the atmosphere; and c. optionally, a further layer; wherein the or each color change sensor is placed in the container under an atmosphere of the said gas and the container is impermeable to the said gas; ^^^ iii) providing before or after step ii) an atmosphere in the chamber comprising the gas at a concentration which is different to, preferably higher than, the concentration of the gas in the ambient environment; and iv) closing the container. The sensor assembly pack enables at least one and preferably a plurality of sensor ^^^ assemblies to be manufactured and shipped or stored in a state where the indicator is not armed or activated and which does not require costly arrangements for shipping such as provision of very low temperature storage. The invention according provides significant cost savings and simplifies distribution and storage logistics and provides environmental advantage by not requiring the usage of refrigeration in the supply chain. ^^^ The container may be flexible, for example a pack and pouch ,especially a heat sealed pouch. The container is openable such that the environment in the chamber is in communication with the ambient environment. Alternatively, the container may be rigid and be openable by any suitable means, for example an openable aperture, a removable or pivotally openable cover or panel. ^^^ By enclosing the sensor assemblies in the impermeable container, the sensor assembly may be activated at a point in time selected by the user thereby avoiding the need to maintain the assembly under certain conditions such as very low temperature between its manufacture, during shipping and up to the point of being applied to the product. By providing the time- temperature color change sensor assembly in a container that is impermeable to the gas, the ^^^ sensor is field armable, in other words it may be activated when desired by an end user. ^ ^^^^^^^^^ Suitably, the impermeable container has a higher than concentrations of the gas than the concentration in the porous material in the gas layer whereby the gas does not migrate out of the gas layer or out of the semi-permeable barrier or the color change indicator and thereby become activated. ^^ In a further aspect, the invention provides a method or providing a plurality of color change sensor assemblies at a location remote from the location of manufacture of the assemblies comprising: i) providing an impermeable container defining a chamber; ii) placing a plurality of a color change sensor assemblies in the container, wherein ^^^ each assembly comprises: a. a color-change indicator, the color of which is affected by the presence or absence or the concentration of a gas in contact with the indicator; b. a gas layer comprising a porous material containing a gas capable of interaction with the indicator so as to produce a color change, the gas being ^^^ present at a different, preferably higher, concentration than the gas is found in the ambient environment, typically the atmosphere; and c. optionally, a further layer, for example a semi-permeable barrier; wherein the plurality of color change sensors are placed in the container under an atmosphere of the said gas and the container is impermeable to the said ^^^ gas; iii) providing before or after step ii), an atmosphere in the chamber comprising the gas at a concentration which is different to, preferably higher than, the concentration of the gas in the ambient environment; iv) closing the container; ^^^ v) transporting the container containing the plurality of sensor assemblies to a remote location, preferably in the absence of provision of cooling or refrigeration of the sensor assemblies; and vi) optionally storing the sensor assemblies until required for use and, at the time of use, opening the container such that the concentration of gas in the sensor ^^^ assembly changes and applying the sensor assemblies to products, thereby activating the sensor assembly. The semi-permeable barrier, if present , may be between the gas layer and the color change indicator to control the flow of the gas between the gas layer and the color change indicator and/or above the color change indicator to control the flow of gas between the color change ^^^ indicator and the ambient environment. ^ ^^^^^^^^^ Advantageously, a plurality, especially a large quantity or multitude of sensors may be contained in the container, enabling manufacture and distribution of large quantities of sensor assemblies which are dormant and only activated or armed upon removal from the container and application to the product. ^^ In a further aspect, the invention provides for use of a sensor assembly according to the invention to provide an indication of elapsed time and temperature exposure of at least one product comprising providing a sensor assembly pack according to the invention, opening the container of the said pack whereby the concentration of the gas in the chamber changes, retrieving at least one sensor assembly for the or each product from the chamber in the ^^^ container and applying the at least sensor assembly to the or each said product. In another aspect, the invention provides a temperature or time sensitive product comprising a product having a sensor assembly according to the present invention applied to the product or to packaging of the product or to a batch of the said products. The sensor assembly may be applied to any kind of product where it is essential, important or ^^^ desirable to have an indication of the age of the product or whether the product has been subjected to an undesirably high or low temperature. Examples of products with which the sensor assemblies of the present invention may be employed include vaccines, medicines, nutraceuticals, food products, any other products for human or animal consumption and to any other products which may be susceptible to deterioration in quality or safety over time or upon ^^^ exposure to undesirable temperatures. The invention provides a product, preferably a medical product or a vaccine, having secured on the product or its packaging an activated color-change sensor assembly which comprises: a) a color-change indicator, the color of which may be affected by the presence or absence or the concentration of a gas in contact with the indicator; ^^^ b) a gas layer comprising a porous material containing a gas capable of interaction with the indicator so as to produce a color change; and c) optionally, a further layer; wherein the gas is present in the gas layer at a different, preferably higher concentration than the gas is found in the ambient environment and the said concentration changes over ^^^ time to reach equilibrium with the ambient environment. The gas layer comprises a porous material suitable for holding or containing the gas or permeated with higher than atmospheric levels of gas, preferably carbon dioxide when exposed to an environment containing the gas at high levels and to release the gas when exposed to an ambient atmosphere. The gas layer may consist essentially of a porous material ^^^ suitable for containing a gas at concentrations higher than the gas is found in the ambient ^ ^^^^^^^^^ atmosphere. Any material that is porous or contains a matrix, passages, cavities or the like in which a gas may become entrapped, held, or otherwise contained may be employed including, for example, solid substances with permeable matrices or liquids, foam and the like. The porous ^^ material may act as a sponge such that gases are trapped, contained or otherwise held within the material. The porous material may be in any suitable form, for example in the form of a sheet or particulate or a combination thereof. Examples of suitable porous materials include silicone rubber, urethane foams, PVC, ^^^ polyalkylenes, especially polyethylene, particularly high density polyethylene for example TYVEK ™, available from Du Pont and polypropylene for example, available from Avery Dennison. The porous material may comprise surface-modified polymethylmethacrylate (PMMA) or open cell silicone In some embodiments the gas may be present in the ambient atmosphere at very low levels or not at all. ^^^ In a preferred embodiment, the color change indicator is applied, preferably printed, onto a porous material selected from porous polyethylene, for example TYVEK and porous polypropylene. The gas layer may have a thickness of 1 to 250 ^m, especially 2 to 100, for example 10 to 50 ^^^ The porous material may comprise a particulate material having internal voids or cavities which aids retention of the gas in the sensor assembly. The gas layer may comprise a porous sheet material, a porous particulate material or a mixture thereof. Examples of suitable materials include diatomaceous earth, for example Freshwater Diatomaceous Earth ™ ^^^ ^^^

^ ^^^^^^^^^ Suitably, the encapsulation layer comprises an organic material to provide selective permeability. Suitably, the organic material which is solid but which has a melting point of 0 to 50°C, preferably 10 to 40°C which provides an impermeable barrier to the gas in the solid form but which permits transmission of the gas through it upon melting as the sensor assembly is ^^ subjected to a temperature above the melting point of the organic material. Examples of suitable materials include fatty chain hydrocarbons, for example C14 to C22 hydrocarbons such as octadecane; esters of fatty acid especially short chain, for example C1 to C4 esters of C14 to C₂₂ carboxylic acids, for example methyl palmitate. The further layer is optionally present and is suitably an impermeable layer or a semi- ^^^ permeable barrier. Where the porous material of the gas layer provides adequate control over the passage of gas through that layer upon exposure of the assembly to the ambient environment, a further layer for control of transport of the gas is not essential. The sensor assembly need not comprise a further layer or an impermeable layer but the surface onto which the sensor assembly is applied or adhered, for example a product surface or packaging, ^^^ may act as a substrate during use although not a constituent part of the sensor assembly. In a preferred embodiment, the sensor assembly comprises a semi-permeable barrier. The semi-permeable barrier suitably controls or regulates the flow of the gas into the color change indicator The semi-permeable barrier may be located between the gas layer and the color change indicator. The semi-permeable layer may be a sheet or particulate. ^^^ Examples of suitable materials for the further layer include polypropylene, polyethylene including low density and high density polyethylene, polyvinyl chloride (PVC), polyethylene terephthalate (PET), rubber, cellulose, polylactic acid polyethylene, especially high density polyethylene for example TYVEK ™, available from Du Pont. The porous material may comprise surface-modified polymethylmethacrylate (PMMA) or open cell silicone. The polymer ^^^ for the further layer may be amorphous or oriented, for example biaxially oriented. The further layer may have a thickness of 1 to 250 ^m, especially 2 to 150, for example 10 to The sensor assembly may comprise a supercoat or top layer which overlies the at least one semi-permeable barrier overlying the gas layer and indicator. Preferably, the supercoat is ^^^ semi-permeable to permit diffusion of the gas from the gas layer to outside the sensor assembly. Examples of suitable materials for the supercoat include polypropylene, polyethylene including low density and high density polyethylene, polyvinyl chloride (PVC), polyethylene terephthalate (PET), cellulose, polylactic acid polyethylene, especially high density ^ ^^^^^^^^^ polyethylene for example TYVEK ™, available from Du Pont. The porous material may comprise surface-modified polymethylmethacrylate (PMMA) or open cell silicone. PET, polypropylene and polyethylene having a structure capable of permitting diffusion of the gas therethrough. ^^ In some embodiments, the supercoat comprises a material which is selectively permeable depending on the prevailing environmental conditions. The supercoat may be in an impermeable form or a permeable form and may pass between the two forms due to an external stimulus, such as temperature, ultra violet or chemical interaction, for example oxidation, contact with a solvent, or the like. ^^^ Preferably the supercoat comprises an organic material which is solid but which has a melting point of 0 to 50°C, preferably 10 to 40°C which provides an impermeable barrier to the gas in the solid form but which permits transmission of the gas through it upon melting as the sensor assembly is subjected to a temperature above the melting point of the organic material. Examples of suitable materials include fatty chain hydrocarbons, for example C₁₄ to C₂₂ ^^^ hydrocarbons such as octadecane; esters of fatty acid especially short chain, for example C1 to C4 esters of C14 to C22 carboxylic acids, for example methyl palmitate. The supercoat may have a thickness of 1 to 250 ^m, especially 2 to 150, for example 10 to 110 ^m. The sensor assembly may include a layer of a meltable organic material to provide selective ^^^ permeability by being impermeable when solid and permeable when liquid. In one embodiment, the sensor assembly may include an organic layer between any two layers of the sensor to provide selective permeability. Preferably, the sensor assembly comprises two adjacent semi-permeable barrier layers and a selectively permeable organic layer interposed between the two semi-permeable barrier layers. ^^^ In a further embodiment, the indicator dye or ink may be coated, for example encapsulated, by an organic material to provide selective permeability. Suitably, the organic material which is solid but which has a melting point of 0 to 50°C, preferably 10 to 40°C which provides an impermeable barrier to the gas in the solid form but which permits transmission of the gas through it upon melting as the sensor assembly is ^^^ subjected to a temperature above the melting point of the organic material. Examples of suitable materials include fatty chain hydrocarbons, for example C₁₄ to C₂₂ hydrocarbons such as octadecane; esters of fatty acid especially short chain, for example C1 to C4 esters of C14 to C₂₂ carboxylic acids, for example methyl palmitate. The gas in the assembly and in the container may be any gas which interacts with the indicator ^ ^^^^^^^^^ and thereby effects a detectable change in the color of the indicator. A single gas may be used or a mixture of gases. The interaction may be physical or chemical and suitably comprises a chemical interaction between the gas and the indicator. In some embodiments the gas may be present in the ambient atmosphere at very low levels or not at all. ^^ Examples of suitable gases include carbon dioxide, oxygen, nitrogen, argon and ammonia. In a preferred embodiment, the interaction provides a change in pH. Suitably, the gas comprises carbon dioxide and is preferably solely carbon dioxide and the indicator interacts or reacts with the carbon dioxide. Suitably, the container is saturated with respect to carbon dioxide. Depending on the concentration of carbon dioxide in contact with ^^^ the indicator, the indicator will exist in different states which are visually detectable. As the concentration of carbon dioxide in contact with the indicator changes due to the sensor being exposed to the ambient environment, the indicator will after a certain time change its color depending on the level of carbon dioxide. The level of carbon dioxide and its diffusion into contact with the indicator will depend on the concentration (change of concentration) of carbon ^^^ dioxide in the sensor which is influenced by the materials of construction of the gas layer and optional semipermeable layer and thickness of the layers. The user will be able to provide a tuneable sensor assembly by selection of materials and thickness of the layers as desired having regard to the desired elapsed time for color change and at what temperature by employing the color change indicator suitably comprises a ^^^ component, for example a dye or ink, that is able to change color based on interaction with the gas. Suitably, the color change arises due to a change in pH of the indicator, the pH change arising due to a change in the level of the gas in contact with the indicator. The color change indicator may be any appropriate color change indicator including, for example, an indicator that changes color based on changes in carbon dioxide levels (a carbon dioxide-based ^^^ indicator) or oxygen levels (an oxygen-based indicator) or ammonia-based indicators (an ammonia-based indicator). Examples of color change indicators have been described in prior patents and patent applications, for example, (U.S. Pat. Nos. 8,388,131; 9,134,285; 8,663,998; 9,746,421 and 11,467,422. In addition, US Pub. No.20180104017 (incorporated herein by reference) describes how color change indicators can be used with a gas layer. ^^^ The color change indicator may comprise color changeable dye. Color changeable dyes can include a redox indicator, a reduction reaction initiator, an electron donor, an oxygen scavenger, an indicator barrier agent, a thickening agent and an agent to facilitate mixing. The color changeable dye may be, for example, a first color in the presence of oxygen, capable of changing to a second color upon reduction in a substantially oxygen free environment, and ^^^ capable of changing back to the first color after exposure to oxygen for a period of time ^ ^^^^^^^^^ corresponding to the intended use time of a disposable or limited use product. U.S. Patent No. 9,746,421, presented, for example, use protocol indicators having a color changeable dye that changes color after exposure to a particular environment for a defined time. The color changeable dye may be varied in order to change color in response to a variety of ^^ different environments (e.g. time-temperature parameters). In one embodiment, the color change indicator may have a color changeable dye, the dye being translucent or having a first color upon immediate exposure to an environment and for a defined time thereafter and the dye changing color after exposure to the environment for the defined time. The environment can be an oxygen containing environment and the color changeable dye is an oxygen sensing ^^^ color changeable dye. The environment can also be a carbon dioxide containing environment and the color changeable dye can be a carbon dioxide sensing color changeable dye. The environment can be a carbon dioxide containing environment and the color changeable dye can be an oxygen sensing color changeable dye. Other environments are also appropriate. The environment to which the color changeable dye responds can be chosen based on the ^^^ environment in which the disposable, limited or restricted use product is intended to be used. An example of a color changeable dye that reacts based on carbon dioxide levels in its environment could include a carbon dioxide reactive dye such as cresol red (CR, o- cresolsulfonephthalein) example formulation of l:cresol red, 20: glycerol, 3: 10M KOH (aq), Texas red hydrazide (THR), bromothymol blue (BTB, hydroxy triarylmethane), or m-cresol ^^^ purple (MCP, hydroxyl triarylmethane). This carbon dioxide reactive dye could be mixed with a solvent such as alcohol, methanol or acetone. Bentonite nanoclay or diatomaceous earth could be added to give the color changeable dye desirable physical properties. Examples of carbon dioxide-based color change indicators are described in U.S. Patent No. 11,467,422 and US Pub. No.20180104017 which are both hereby incorporated by reference. ^^^ A color changeable dye may include a carbon dioxide status indicator, a solvent, a polymer wherein the carbon dioxide status indicator is dispersed, an optional plasticizer, and an optional agent to facilitate mixing wherein the color changeable dye changes to a warning color after exposure to a change in carbon dioxide environment for a predetermined period. A carbon dioxide status indicator is a compound that changes color because it is exposed to a ^^^ change in carbon dioxide environment, i.e., the additional presence or absence of carbon dioxide either before or after the color change is what triggers the change in color, and is used to indicate a change in the carbon dioxide environment. Examples of carbon dioxide status indicators include Cresol Red, Texas Red Hydrazine, Bromothymol Blue, M-Cresol Purple, Phenol Red, Congo Red and Natural Red. ^^^ The color changeable dye can be a first color in the presence of a higher than atmospheric ^ ^^^^^^^^^ carbon dioxide environment, and can be capable of changing to a second color after exposure to atmospheric conditions for a time-temperature environment that corresponds to a degradation of the product of interest (e.g. a vaccine). The exposure to atmospheric conditions will occur when indicator assembly is exposed to the ambient atmosphere upon opening the ^^ impermeable container . In one embodiment, the status indicator, for example a carbon dioxide status indicator is a pH status indicator. A pH status indicator is a compound that changes color when exposed to a change in pH and is used to indicate a change in environment. A pH status indicator can be incorporated into the present color changeable dye to allow for a color change upon exposure ^^^ to a change in carbon dioxide environment. That change could be either an increase or a decrease in the carbon dioxide concentration of the environment. Examples of possible pH status indicators and their corresponding colors are shown below in Table 1.

Texas Red or m-Cresol Purple could also be used. The acid low pH color for these dyes is a ^^^ light yellow. Texas Red transitions from yellow to red at about 4% CO.sub.2. m-Cresol purple transitions from yellow to purple at 14pprox.2% CO.sub.2. It is understood that other status indicators could be substituted in the color changeable dye of the present application. ^ ^^^^^^^^^ Preferred pH status indicators for use in the present solution are Cresol Red, m-Cresol Purple and Phenol Red. A pH status indicator is typically a halochromic chemical compound that is added in small amounts to a solution so that the pH of the solution can be determined visually. A pH status ^^ indicator is a chemical detector for hydronium ions (H3O+) or hydrogen ions (H+) in the Arrhenius model. Normally, the indicator causes the color of the solution to change depending on the pH. As an example of how the pH status indicators function in different carbon dioxide environments, for Cresol Red the acid or low pH color is yellow and the base or high pH color ^^^ is reddish purple. When the Cresol Red is in a carbon dioxide rich environment, for example a pure 100% carbon dioxide environment, it will be in the H Ind form which is the acid or low pH color of yellow. When placed in a lower carbon dioxide environment, for example an atmospheric environment with approximately 0.0397% carbon dioxide, the Cresol Red changes to its Ind− form which is the base or high pH color of reddish purple. This would apply ^^^ similarly to the other pH status indicators in the chart above with their respective high and low pH colors. A pH status indicator may be incorporated into the color changeable dye in the indicator in its acid or low pH form (the yellow form in the case of Cresol Red) in a carbon dioxide rich environment. The impermeable container may contain high levels of carbon dioxide so that ^^^ the indicator is in its acid or low pH form (the yellow form in the case of Cresol Red) in the carbon dioxide rich environment of impermeable container. When the color change indicator is actuated by removing sensor assembly from impermeable container and the indicator is exposed to atmospheric conditions with a lower carbon dioxide content (approximately 0.0397% carbon dioxide), the dye disposed on the product will change ^^^ from its acid or low PH state (yellow for Cresol Red) to its base or high pH state (reddish purple for Cresol Red) after a period of time that is controlled by all the various factors discussed above. The color change characteristics of the indicator may be tailored to provide an indicator that change color after exposure to different environment after different periods of time or at ^^^ different temperatures. Parameters that may be modified to alter color change characteristics include the particular dye or ink and its composition, the material and characteristics of the porous material in the gas layer (e.g. open cell foam pathways), the concentration of the gas in the gas layer, the thickness of the gas layer and other semi-permeable layers and the presence of other permeable layers.. ^ ^^^^^^^^^ A scavenger for the gas, such as oxygen scavengers, may be added to modify the color- change characteristics, for example iron (II) carbonate. Suitably, the color change indicator may be applied applied to the time-temperature color change sensor assembly by any suitable technique including by co-extrusion or by printing, ^^ for example UV ink jet, latex and letter press printing, provided that the application method does not compromise the functionality of the indicator, for example due to exposure to high processing temperatures. The sensor assembly may comprise an adhesive between any two layers of the sensor especially between the gas layer and indicator, between the gas layer and the further layer,^^^ preferably a semi-permeable barrier and between the further layer, preferably a semi- permeable barrier and the indicator. The sensor may comprise two or more layers of adhesive between multiple pairs of adjacent layers. Suitably, the adhesive is of a composition such as not to interfere with the color change of the indicator. For example, where the indicator changes color based on a change in pH due to ^^^ contact with an acidic gas such as carbon dioxide, the adhesive suitably has a pH which is higher than the pH at which the indicator changes color. In the case of an indicator which changes color with an increase in pH and the gas is alkaline, for example ammonia, the adhesive suitably has a pH which is lower than the pH at which the indicator changes color. Preferably, where the gas is carbon dioxide or another acidic gas and the indicator is activated ^^^ by acidic conditions, for example thymol blue, the adhesive has a neutral or alkaline pH. Examples of suitable adhesives include rubber, synthetic rubber, hot melt rubber and rubber resin. Where the gas is alkaline, the adhesive is suitably neutral or acidic. The adhesive may contain more than one adhesive provided that the components of the adhesive do not affect the pH of the indicator or otherwise participate in the mechanism of ^^^ color change of the indicator. The gas layer may be on an impermeable substrate which may be a component of the sensor assembly or, at the point of use, applied to a product and the product or its packaging may provide a substrate upon which the sensor assembly is mounted. The substrate allows the assembly to act as a label and be applied to a product of interest (e.g. a vaccine vial). ^^^ Example of suitable substrates include paper, plastic, metallic films, for example aluminium, Glass, for example glass vials for vaccines and combinations thereof. The sensor assembly may be applied to the product by hand or in an automated process. The sensor assembly may be in the form of a label for application to a product or packaging of a product. The label suitably comprises a plurality of layers including a gas layer, a further ^ ^^^^^^^^^ layer, preferably a semi-permeable barrier, and optionally at least one additional further layer. In a preferred embodiment, the indicator is applied to a material which acts as the gas layer and provides a reservoir for the gas by any suitable process, preferably by printing. The indicator and gas layer are suitably applied to an underlying semi-permeable barrier, ^^ preferably PET. Further layers suitably comprising at least one semi-permeable barrier overlie the indicator and gas-layer so as to provide a “sandwich” structure. In a preferred embodiment, the indicator and gas layer have two or more semi-permeable barrier layers applied on top of the indicator. The sensor assembly preferably comprises a supercoat or top layer which overlies the at least ^^^ one semi-permeable barrier overlying the gas layer and indicator as described above. Any further layers may be applied to any other layer through any appropriate mechanism known to those skilled in the field, for example, by vacuum deposition, lamination, paint, silk screen or any other appropriate manufacturing means. Adhesives may also be used to adhere adjacent layers. Preferably, the adhesive is selected from rubber, synthetic rubber, hot melt ^^^ rubber and natural rubber although any adhesive which does not detrimentally affect the color change properties of the indicator may be employed. In a preferred embodiment, the sensor assembly is part of a label which may be applied to a product or product packaging whether packaging for an individual product or a plurality of product units or for large quantities of product units, for example a palletised body of product ^^^ units. Preferably the impermeable container with a high concentration of gas, preferably carbon dioxide, contains a multitude of labels. The labels may be in any form for example as a pad or roll of labels which may need to be separated at the point of use. The sensor assembly may comprise at least two indicators, suitably adapted to provide a color change in response to different circumstances or conditions, for example upon being exposed ^^^ to a pre-determined temperature, after a certain time has elapsed from when the indicator was armed or in relation to other detectable changes in environment or circumstance. In a further aspect, the invention provides a color change sensor assembly according to the invention and which, in addition to the first indicator, further comprises a second color change indicator wherein the first color indicator and the second color indicator change color under ^^^ different circumstances or conditions or in response to different stimuli. The second indicator may be any type of known color change indicator or may be a color change indicator according to the invention. Suitably, the second color change indicator changes color based on the presence or absence or the concentration of a gas in contact with the said second indicator. ^ ^^^^^^^^^ Suitably, the first indicator and second indicator are mounted on a substrate to provide multiple indications for a product. Preferably, the first indicator changes color after elapsed time t₁ after being activated and the second indicator changes color at temperature T2; or after elapsed time t2 after being activated wherein t1 and t2 are different. ^^ In one embodiment, the first indicator is configured to provide a color change immediately upon activation, that is upon being removed from the impermeable container ie t₁ =0 days which provides a visual indication that the indicator is armed. In other embodiments, the first indicator may be configured to provide a color change after up to 40 days, for example, 0.5, 1, 2, 7, 11, 14, or 30 days ie t₁ is 0.5, 1, 2, 7, 11, 14 or 30 days. The second indicator may be _^^^ configured to provide a color change after an elapsed time t₂ from arming of up to 40 days, for example t2 is 0.5, 1, 2, 7, 11, 14 or 30 days provided that t2 is different to t1. Where the second indicator provides a color change based on temperature, the indicator may be configured to provide a color change at any desired temperature, preferably at a temperature T₂ in the range from -5°C to 70°C, for example -4°C, 0°C, 5°C, 10°C, 20°C, 25°C, 37°C, 50°C or 60°C. ^^^ In one embodiment, a sensor with multiple indicators provides an indication that the sensor is armed ie t1 is 0 and an indication of elapsed time consistent with the shelf life of the product, for example 30 days for a vaccine, t₂ is 30. In another embodiment, a sensor with multiple indicators provides an indication of elapsed time consistent with the shelf life of the product, for example 30 days for a vaccine, t1 is 30.and the second indicator provides a color change ^^^ at a pre-determined temperature, for example T₂ is 0°C. In addition to two or more indicators, the sensor assembly may further comprise a selectively permeable layer comprising a meltable organic compound as described above. The meltable organic layer may provide a temperature indication by melting at a pre-determined temperature in addition to indications provided by the first and second color change indicators. ^^^ Brief Description of the Drawings: Figure 1 shows a schematic of a time-temperature sensor assembly enclosed in an impermeable container where the semi-permeable barrier is between the gas layer and color indicator. Figure 2 shows a schematic of a time-temperature sensor assembly enclosed in an ^^^ impermeable container where the color indicator is between semi-permeable barrier and the gas layer. Figure 3 shows a schematic of a time-temperature sensor assembly without a semi-permeable barrier. Figure 4 shows a schematic of a time-temperature sensor assembly with a semi-permeable ^ ^^^^^^^^^ barrier below and two semipermeable layers above the indicator and gas layer and a supercoat. Figure 5 shows a schematic of a time-temperature sensor assembly of similar construction to that of Figure 4 with an organic fat layer interposed between the two semi-permeable layers ^^ above the indicator. Figure 6 shows a schematic of a time-temperature sensor assembly in particulate form. Figure 7 shows a schematic of a time-temperature sensor assembly of similar construction to that of Figure 6 with an encapsulation layer. Figure 8 shows a schematic of a time-temperature sensor assembly with two semipermeable ^^^ layers above the indicator and gas layer on an aluminium substrate. Figure 9 shows a schematic of a time-temperature sensor assembly with a selectively permeable layer above the gas layer/indicator. Figure 10 shows a schematic of a time-temperature sensor assembly in the form of a label having two indicators on a single substrate. ^^^ Figures 11 and 12 show results of experiments carried out in the Examples indicating a change in indicator color with time. DETAILED DESCRIPTION The present invention now will be described more fully hereinafter with reference to the accompanying drawings, in which some preferred embodiments of the invention are shown. ^^^ This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art. Like numbers refer to like elements throughout. FIG.1 is an illustration of one embodiment of the present invention. As shown in FIG.1, color ^^^ change sensor assembly 100 is enclosed in impermeable container 90. Impermeable container 90 contains both color change sensor assembly 100 and a gas used in the color change assembly 100. The gas in impermeable container 90 (e.g. a bag) is at a higher concentration than it is found in the ambient atmosphere. Impermeable container 90 is highly or entirely impermeable to the gas used in the color change assembly 100. Color change ^^^ assembly 100 comprises a substrate 10, a gas layer 20 which is a porous material with a higher concentration of gas than is found in the ambient atmosphere; a semi-permeable layer 30 and a color change indicator 40. The gas in impermeable container 90 and in gas layer 20 are the same gas. When the subject gas (e.g. carbon dioxide) is present in gas layer 20, ^ ^^^^^^^^^ gas layer 20 interferes with atmospheric gas migration into indicator 40 that triggers the color change chemistry. Or in other words, the high levels of the subject gas in gas layer 20, keep the concentration of the subject gas in indicator layer 40 higher for a longer period of time than if indicator layer 40 was exposed to the ambient atmosphere without also be exposed to the ^^ concentrated gas in gas layer 20. In some embodiments, like that shown in FIG 1, the interference of gas layer 20 with the migration of ambient atmosphere into indicator layer 40 is assisted by semi-permeable layer 30 that helps slow down the migration of gas out of assembly 100 and extend the higher concentrations of the subject gas in indicator layer 40. While the embodiment of FIG.1 depicts semi-permeable barrier 30 disposed on top of gas ^^^ layer 20, the user can select any method to help slow down the migrations of the gas in gas layer 20 once impermeable container 90 is opened, including those described herein (see FIG 2 and FIG 3 and their descriptions infra). Color change indicator 40 changes color as it is exposed to different concentrations of the concentrated gas found in both impermeable container 90 and in gas layer 20. When ^^^ impermeable container 90 is opened sensor assembly 100 is exposed to the ambient environment. Since the ambient environment has a lower level of the gas than is found in the now exposed sensor assembly 100 the gas will begin to migrate out of gas layer 20, through semi-permeable layer 30 and through indicator 40. As the concentration of the gas in indicator 40 becomes lower—or said another way, the concentration of atmospheric gases increase— ^^^ indicator 40 changes color. By changing the characteristics of various layers of assembly 100 one can fine tune the time-temperature color change. As just one example, by increasing or decreasing the thickness of semi-permeable layer 30 one can change the period of time it takes for indicator 40 to change color. The time-temperature color change could also be fine- tuned by changing the characteristics of the porous material in the gas layer (e.g. open cell ^^^ foam pathways) or the concentration of the gas in the gas layer or the thickness of the gas layer or the characteristics of the dye in indicator 40. The porous material in gas layer 20 for holding or containing the gas may be any suitable substrate that is able to contain or hold gases. For example, any substrate that is porous or contains a matrix or passages in which gaseous substances may become entrapped, held, or ^^^ otherwise contained would be suitable including, for example, solid substances with permeable matrices or liquids. The porous substrate may act as a sponge such that gases are trapped, contained or otherwise held within the substrate. Examples of appropriate substrates include silicone rubber, urethane foams, or PVC foam. In a preferred embodiment, the gas- containing substrate is surface-modified polymethylmethacrylate (PMMA) or open cell silicone ^^^ In some embodiments the gas may be either non-existent in an ambient atmosphere of found ^ ^^^^^^^^^ only at very low levels. For example, to achieve gas concentrations that are greater than atmospheric levels in gas layer 20, it can be flooded with the subject gas during manufacturing. For example, gas layer 20 may be placed in a container containing, for example, carbon dioxide or argon. Over time, ^^ the gas will permeate the matrix of the substrate and displace atmospheric gas with the subject gas. The subject gas can also be applied to the substrate under pressure to decrease amount of time needed for gas permeation into the matrix. The gas in the porous material in gas layer 20 can include any suitable gas that can permeate out of the porous material and effect the color of the indicator. Examples of appropriate gases ^^^ include oxygen, carbon dioxide, nitrogen, argon and ammonia. To inhibit or slow down permeation of ambient atmospheric gases to the indicator 40, the gas in gas layer 20 is initially at non-atmospheric levels, i.e., in concentrations or levels that are greater than or less than the concentration or level of the gas under normal atmospheric conditions. These non- atmospheric levels can be achieved before or after manufacturing of the sensor and/or its ^^^ components. In other embodiments, gas layer 20 is made from a material that itself contains the gas. As shown in FIG 1, sensor assembly 100 includes semi-permeable layer 30. Semi-permeable layer 30 may be directly or indirectly disposed on gas layer 20. Semi-permeable layer 30 assists in containing the gas in the gas layer 20 after impermeable container 90 has been ^^^ opened and sensor assembly 100 is exposed to the ambient environment. In one embodiment, semi-permeable layer 30 is disposed directly or indirectly on the gas layer or gas-containing substrate and contains the gas present in the layer or substrate. In this embodiment, the semi-permeable layer assists in inhibiting the gas from escaping from the gas layer. Semi-permeable layer 30 should generally be made from materials or combinations ^^^ of materials having low or very low gas diffusion rates that may appropriately help slow down the permeation of gas out of gas layer 20. Examples of materials from which semi-permeable layer 30 may be made include polyethylene, polypropylene, polyethylene terephthalate (PET), and polyamides. The thickness of semi-permeable layer 30 should be any thickness that will appropriately slow^^^ down the diffusion of the gas out of gas layer 20. In determining the thickness of semi- permeable layer 30, consideration should be given to the diffusion rates of materials which form the gas-containing substrate or gas layer and/or the diffusion rates of the materials which form the interface layer. It is noted that different gases also diffuse through materials at different rates. For example, hydrogen is a small molecule and would diffuse more quickly^^^ through many semi-permeable than other gases. Because sensor assembly 100 is a time- ^ ^^^^^^^^^ temperature indicator it is important to understand how temperature effects the diffusion of the gas out of semi-permeable layer 30. For example, if semi-permeable layer 30 is made from a material or materials with higher gas diffusion rate(s), the thickness of the interface layer may need to be increased or gas layer 20 ^^ may need to be formed of a material which is better able to contain gas to control the permeation of the ambient atmosphere into indicator 40 over time. Alternatively, if semi- permeable layer 30 is made from a material or materials with lower gas diffusion rate(s), the thickness of semi-permeable layer 30 may be decreased and there may be greater flexibility with the materials from which gas layer 20 is formed. Generally speaking, a thicker semi- ^^^ permeable layer 30 or more semi-permeable layers will result in greater gas containment in the gas layer 20. Conversely, thinner semi-permeable layer 30 or less semi-permeable layers will allow more gas to escape. Additionally using a material that has a higher or lower diffusion of gas will also shorten or lengthen the time respectively as different gases diffuse through materials at different rates. ^^^ Semi-permeable layer 30 may be applied to gas layer 20 or in some embodiments some other layers (see additional embodiments infra) through any appropriate mechanism. For example, the interface layer may be applied by vacuum deposition, lamination, paint, silk screen or any other appropriate manufacturing means. Adhesives may also be used as described further below. ^^^ Color change indicator 40 may be any appropriate color change indicator including, for example, an indicator that changes color based on changes in carbon dioxide levels (a carbon dioxide-based indicator) or oxygen levels (an oxygen-based indicator) or ammonia-based indicators (an ammonia-based indicator). The color change indicator can be disposed on the product itself by being screen printed or ^^^ otherwise deposited on the product or incorporated into the sensor assembly by having the indicator in a polymer composite that can be extruded into a sheet or layer. As shown in FIG 1, assembly 100 is positioned on substrate 10. The substrate may be may be any type of material as described above. The sensor assemblies 400, 500 are in a sealed pouch, container or bag 490, 590. Figures 4 ^^^ and 5 show a multi-layer sensor assemblies according to the invention. The sensor assembly has a substrate 410, 510, a gas layer including a porous material 420, 520 and a color change indicator 440, 540 which changes color under acidic conditions for example with changing levels of an acidic gas such as carbon dioxide, a semi-permeable barrier 430a, 530a beneath the gas layer and two semi-permeable barrier layers 430b, 430c and 530b, 530c above the ^ ^^^^^^^^^ gas layer. The semi-permeable layers are preferably selected from PET, polypropylene and rubber. In one example semi-permeable layers 430a, b, and c are made from 3M1577 double sided tape. In another example, layers 430a, b, and c are made from 3M1567 double sided tape. In another example, layers 430a and b are made from 3M1567 double sided tape and ^^ layer 430c is tissue paper (3M 9040 Beige Double Sided paper Tape). A supercoat 450, 550 is provided and this may comprise a material which may be in an impermeable form or a permeable form and may pass between the two forms due to an external stimulus, such as temperature, ultra violet or chemical interaction, for example oxidation, contact with a solvent, or the like. Preferably, the supercoat comprises a meltable ^^^ organic material such that it provides selective permeability by being impermeable in its solid form and permeable in its molten or liquid form. As the sensor assembly is subjected to a higher temperature, the supercoat may become permeable, thereby activating the sensor assembly and providing an indication that the product to which the sensor assembly is applied has been subjected to a temperature at a certain level. ^^^ In some embodiments, adhesive may be present between any two layers and suitably comprises a rubber, hot melt rubber, natural rubber or synthetic rubber and does not adversely affect the color change characteristics of the sensor assembly. Figures 6 and 7 show multi-layer sensor assemblies according to the invention in particulate form. The particles may be adhered to a substrate to provide a label comprising the particulate ^^^ indicator. The sealed container is not shown for clarity in these figures. The sensor assembly has a porous material 620, 720 at its core. This material may be diatomaceous earth or other suitable porous particulate materials as described above. The color change indicator 640, 740 is coated on porous material and a semi-permeable barrier 630, 730 is coated above the gas layer. The semi-permeable layers are preferably selected ^^^ from PET, polypropylene and rubber. The sensor assembly of Figure 7 also includes an encapsulation layer or supercoat 750. The encapsulation layer suitably may be in an impermeable for or a permeable form and may pass between the two forms due to an external stimulus, such as temperature, ultra violet or chemical interaction, for example oxidation, contact with a solvent, or the like. Preferably, the ^^^ encapsulation layer is made from a meltable organic material, for example a hydrocarbon or an ester having a melting point in the range 0 to 50°C. Figure 8 shows a multi-layer sensor assembly according to the invention (without the sealed container being shown). The sensor assembly has an aluminium substrate 810, a gas layer including a porous material 820 made from TYVEK (polyethylene fibre) with 25% by volume ^ ^^^^^^^^^ of diatomaceous earth or 50% of diatomaceous earth, and a color change indicator 840 and two semi-permeable barrier layers 830a, 830b above the gas layer. The semipermeable layers are made of PET (3M 396 tape) with a rubber resin adhesive such that adjacent layers are adhered. ^^ Figure 9 shows a sensor assembly (without the sealed container being shown) having a substrate 910 with a gas layer containing a porous material and indicator 920, 940 in particulate form adhered to the substrate with a selectively permeable barrier 930 made of a meltable organic compound. Whilst solid the selectively permeable barrier acts to seal the indicator from the ambient environment and upon melting, the gas layer is then exposed to ^^^ the environment and the sensor assembly is armed. The color change indicator then provides an indication of whether the sensor assembly, and hence the product to which it is adhered, has been activated and whether the product is still within or beyond its shelf life. Figure 10 shows a multiple indicator sensor assembly (without the sealed container being shown) having a first color indicator comprising an indicator/porous layer 1020a, 1040a made ^^^ of a color change ink coated on TYVEK and a semipermeable barrier 1030a which may be configured to provide a short indication of elapsed time since arming eg t1=0, and a second indicator comprising an indicator/porous layer 1020b, 1040b made of a color change ink coated on TYVEK which may be the same or different to that of the first indicator, and two semi permeable barriers 1030b1, 1030b2 which act to slow the transport of the gas from the ^^^ porous layer and thereby provide an indicator with a longer elapsed time or shelf life than the first indicator. One of the semipermeable barriers 1030b1, 1030b2 may be a selectively permeable barrier which seals the second indicator from the ambient environment until the assembly is subjected to a temperature at which the selectively permeable barrier becomes permeable, for example by melting. ^^^ The semi-permeable layers in the embodiments shown in the Figures and in any aspect of the invention may also be made from polypropylene and rubber and other materials as hereinbefore described. The addition of porous particulate material to the gas layer increases the recovery time of the sensor assembly as set out in the Examples. ^^^ In some embodiments, (not expressly shown), an adhesive or other separation layer may be disposed between semi-permeable layer 30 and gas layer 20 and/or gas layer 20 and color change indicator 40. In some embodiments, an adhesive is disposed between substrate 10 or gas layer 20 and color change indicator 40. In some embodiments, an adhesive may also be disposed between semi-permeable layer 30 and gas layer 20 and color change indicator 40. ^^^ In other embodiments, semi-permeable layer 30 is disposed directly on gas layer 20 substrate ^ ^^^^^^^^^ 10 is disposed directly on color change indicator 40. In some embodiments, layers or parts of layers may be heat fused together using various forms of heat and pressure, for example heat welding, ultrasonic welding, laser welding or radio frequency welding. ^^ The configuration of the various layers and their manner of being coupled together can be varied without departing from the scope of the disclosure. This is especially true if one of more of the non-color change indicator layers are transparent so that indicator 40 can be viewed by an end user even if there is another layer between the view point of an end user and indicator layer 40. ^^^ The invention is illustrated by the following non-limiting examples. Examples 1 to 4 Several sensor assemblies according to the invention were prepared by coating Thymol Blue indicator on a polyethylene fibre sheet (TYVEK ™ available from DuPont) in its blue form and. This assembly was tested for stability to determine whether components of the product had ^^^ an acidifying effect and so affected the indicator. The assembly was also was adhered to a tape (further layer) having an adhesive thereon as shown in Table 1. Table 1 Eg Tape Polymer Thickness Adhesive Thickness (µ) (µ) 1 3M Scotch Shipping Polypropylene Hot melt packaging tape rubber 2 3M Tape 5 Clear electrical PET 40 Rubber resin 60 3 3M 1577 double sided tape PET 20 Synthetic 35 rubber 4 3M 1567 double sided tape PET 20 Synthetic 50 rubber The TVEK/indicator product and the products in the Table were subjected to stability testing ^^^ by laminating the assembly to avoid exposure to external factors at room temperature. All products showed no sign of color change to yellow after 7 months indicating that the components of the assembly did not interfere with the indicator and were suitable for use in the sensor assembly. When used with carbon dioxide any color change would therefore be due to changes in the concentration of carbon dioxide.. ^^^ The shelf life of samples of the TVEK/indicator product and the products having TVEK/indicator adhered to a tape as listed in Table 1 were tested by storing the product in a ^ ^^^^^^^^^ closed plastic pouch made of non-gas permeable material under a carbon dioxide atmosphere at room temperature. All products showed no sign of colour change after 2 months indicating that the products had not been activated. Example 5 ^^ Color change indicators sensitive to carbon dioxide were prepared according to the procedures below and cast onto medical grade TYVEK film using K-bar 3 to provide sensor assemblies for use in the invention. After the blue ink film dried, the ink films were cut as 0.7 cm wide squares and placed on a clear plastic film (0.115 mm thick), as a support layer. 1, 2, and 3 layers of PET, 3M 396 tape (each layer of 3M 396 tape is 0.105 mm thick) were placed ^^^ on top of the indicator layer and attached on the support layer sandwiching the indicator layer in the following construction shown in Figure 9. Table 2 - Chemicals used in preparing the indicators Name Sigma Aldrich number Tetrabutylammonium hydroxide solution (1 M in methanol) 230189 Tetrabutylammonium hydroxide solution (~40% in water) 86854 Ethyl cellulose (viscosity 46 cP) 433837 Hydroxypropyl cellulose (average Mw ~80,000) 435007 Tributyl phosphate 240494 Glycerol G9012 CO2 sensitive solvent based ink: ^^^ Solution I was prepared by adding 0.036 g thymol blue sodium salt to 3 ml of methanol. A further 0.5 ml of tetrabutylammonium hydroxide (1M in methanol) was added to the solution and mixed well. Solution II was prepared in which 10 g of ethyl cellulose was dissolved in a solution containing 20 ml of ethanol and 80 ml of toluene. ^^^ The final solvent based ink solution comprised 2 ml of solution I, 10 g of solution II, 1 ml of tributyl phosphate, and 0.5 ml of tetrabutylammonium hydroxide (1M in methanol). CO2 sensitive water based ink: Solution I was prepared by dissolving 0.1 g thymol blue sodium salt in 2.5 ml DI water and 1 ml of tetrabutylammonium hydroxide solution (~40% in water) solution. ^^^ Solution II was prepared by dissolving 10 g of hydroxypropyl cellulose in 100 ml DI water. The final water based ink solution comprised 2 ml of solution I, 10 g of solution II, 1 ml of ^ ^^^^^^^^^ tetrabutylammonium hydroxide solution (~40% in water) solution and 1.5 g of glycerol. Testing The indicators were placed in a 100% CO2 purged heat sealed pouch. After all the indicators turned yellow, samples were then removed from the pouch thereby activating or arming the ^^ indicator, and placed in an incubator at 37^oC. The initially CO2-saturated indicator changed color as it lost CO₂ to the ambient air. This change in colour was monitored photographically as indicated by the images shown in Figure 11. Photos were taken hourly and RGB analysis of each of the photographs was used to provide a measure of the apparent absorbance, A’. The subsequent plot of ^A’ vs time after exposure to air, t, is illustrated in Figure 12 and shows ^^^ that with increasing diffuse layer thickness (i.e. number of adhesive layers), the 80% recovery time increases, so that with additional layers, the recovery time was 2h longer than with just one layer. Example 6 and 7 Sensor assemblies as shown in Figure 8, one having 25 % diatomaceous earth (Example 6) ^^^ and another having 50% (Example 7) of the same diatomaceous earth, were placed in an impermeable container under carbon dioxide were tested by removing the sensor assemblies from the container and observing the indicator change color. The sensor assembly having 25 % diatomaceous earth changed color after 14 days. The sensor assembly having 50 % diatomaceous earth changed color after 21 days. The higher ^^^ level of diatomaceous earth increased the recovery time of the sensor assembly. ^ ^^^^^^^^^

Claims

Claims 1. A color change sensor assembly which comprises: (a) a color-change indicator, the color of which may be affected by the presence or absence or the concentration of a gas in contact with the indicator; ^^ (b) a gas layer comprising a porous material containing a gas capable of interaction with the indicator so as to produce a color change, the gas being present at a different concentration than the gas is found in the ambient environment; and (c) optionally, a further layer; wherein the color change sensor assembly is disposed in a container which is ^^^ impermeable to the gas and which contains the gas at a concentration which is different to the concentration of the gas in the ambient environment. 2. A color change sensor assembly comprising: a) a gas layer that is a porous material containing a gas at concentrations higher ^^^ than the gas is found in the atmosphere; b) an indicator that changes color based upon the concentration of the gas; and c) a semi-permeable barrier between the gas layer and the color changing indicator that regulates the flow of the gas between the gas layer and the color changing indicator; and ^^^ wherein the color change sensor assembly is enclosed in an impermeable container with higher than atmospheric concentrations of the gas so that the time-temperature color change sensor assembly is not exposed to the atmosphere until the impermeable container is opened. ^^^ 3. A color change sensor assembly according to claim 1 or claim 2 wherein the gas is selected from carbon dioxide, oxygen, nitrogen, ammonia and argon. 4. A color change sensor assembly according to claim 3 wherein the gas is carbon dioxide and the indicator changes color based on pH changes caused by changes in ^^^ the concentration of carbon dioxide. 5. A color change sensor assembly according to any one of the preceding claims wherein the color change indicator and the gas layer are in separate layers. ^^^ 6. A color change sensor assembly according to any one of the preceding claims wherein the porous material comprises a matrix, passages or cavities in which a gas may become entrapped, held, or otherwise contained. 7. A color change sensor assembly according to claim 6 wherein the porous material is ^ ^^^^^^^^^ a foam, sponge or particulate material having pores capable of being permeated with higher than atmospheric levels of a gas and to release the gas when exposed to an ambient environment. ^^ 8. A color change sensor assembly according to any one of the preceding claims which comprises a further layer selected from an impermeable layer and a semi-permeable barrier. 9. A color change sensor assembly according to claim 8 wherein the further layer ^^^ comprises at least one of polypropylene, polyethylene including low density and high density polyethylene, polyvinyl chloride (PVC), polyethylene terephthalate (PET), rubber, cellulose, polylactic acid polyethylene. 10. A color change sensor assembly according to claim 8 or claim 9 having a semi- ^^^ permeable barrier which controls or regulates passage of the gas out of the gas layer and into the color changing indicator that changes the color of the indicator based upon the concentration of the gas. 11. A color change sensor assembly according to any one of the preceding claims wherein ^^^ the porous material is selected from a semi silicone rubber, urethane foams, PVC, polyethylene, and a surface-modified polymethylmethacrylate (PMMA) or open cell silicone and a porous particulate material and an encapsulated porous particulate material. ^^^ 12. A color change sensor assembly according to any one of the preceding claims wherein the color changing indicator comprises a dye, ink printed onto the color change sensor assembly. 13. A color change sensor assembly according to any one of the preceding claims wherein ^^^ the assembly is part of a label and wherein the impermeable container contains a plurality of the said labels. 14. A color change sensor assembly according to any one of the preceding claims which further comprises a supercoat. ^^^ 15. A color change sensor assembly according to claim 14 wherein the supercoat comprises a material which is selectively permeable depending on the prevailing environmental conditions. ^^^ 16. A color change sensor assembly according to any one of the preceding claims which further comprises a layer of a meltable organic material disposed between two other layers to provide selective permeability by being impermeable when solid and ^ ^^^^^^^^^ permeable when liquid. 17. A color change sensor assembly according to any one of the preceding claims which further comprises comprise an adhesive between any two layers of the sensor, the ^^ adhesive being of a composition such as not to interfere with the color change of the indicator. 18. A color change sensor assembly according to claim 17 wherein the adhesive is selected from rubber, synthetic rubber, hot melt rubber and rubber resin. ^^^ 19. A color change sensor assembly, which comprises: (a) a gas layer comprising a porous material containing a gas, the gas being present at a different concentration than the gas is found in the ambient environment; and (b) a color-change indicator adjacent to the gas layer or mixed with the porous material ^^^ of the gas layer, the indicator being capable of interaction with the gas so as to produce a color change; wherein the time-temperature color change sensor assembly is disposed in a container which is impermeable to the gas and which contains the gas at a concentration which is different to the concentration of the gas in the ambient environment. ^^^ 20. A color change sensor assembly which comprises: (a) a gas layer comprising a porous material containing a gas, the gas being present at a different concentration than the gas is found in the ambient environment; (b) a further layer, that controls the flow of the gas; and ^^^ (c) a color-change indicator between the gas layer and the further layer, the indicator being capable of interaction with the gas so as to produce a color change; wherein the time-temperature color change sensor assembly is disposed in a container which is impermeable to the gas and which contains the gas at a concentration which is different to the concentration of the gas in the ambient environment. ^^^ 21. A color change sensor assembly which comprises: (a) a gas layer comprising a porous material containing a gas, the gas being present at a different concentration than the gas is found in the ambient environment; (b) a semi-permeable barrier that controls the flow of the gas adjacent to the gas layer; ^^^ and (c) a color-change indicator on the semi-permeable barrier, the indicator being capable of interaction with the gas so as to produce a color change; wherein the time-temperature color change sensor assembly is disposed in a container which is impermeable to the gas and which contains the gas at a concentration which ^ ^^^^^^^^^ is different to the concentration of the gas in the ambient environment. 22. A color change sensor assembly according to any one of the preceding claims which comprises a second color change indicator wherein the said color indicator and the ^^ said second color indicator change color under different circumstances or conditions. 23. A color change sensor assembly according to claim 22 wherein the said second color change indicator changes color based on the presence or absence or the concentration of a gas in contact with the said second indicator. ^^^ 24. A color change sensor assembly according to claim 22 or claim 23 wherein: i) the first indicator changes color after elapsed time t1 after being activated; and ii) the second indicator changes color at temperature T_2; or after elapsed time t₂ after being activated ^^^ wherein t1 and t2 are different. 25. A color change sensor assembly according to any one of claims 22 to 24 wherein the first indicator and second indicator are mounted on a substrate. ^^^ 26. A color change sensor assembly pack comprising: i) a closed container defining a chamber; ii) at least one color change sensor assemblies in the chamber wherein the or each assembly comprises: (a) a color-change indicator, the color of which is affected by the presence or absence ^^^ or the concentration of a gas in contact with the indicator; (b) a gas layer comprising a porous material containing a gas capable of interaction with the indicator so as to produce a color change, the gas being present at a different concentration than the gas is found in the ambient environment; and (c) optionally, a further layer; ^^^ wherein the container is openable to the ambient environment and constructed of a material which is impermeable to the gas and comprises the gas at a concentration which is different to the concentration of the gas in the ambient environment. 27. A method of making a sensor assembly pack comprising: ^^^ i) providing an impermeable container defining a chamber; ii) placing at least one color change sensor assemblies in the container, wherein the or each assembly comprises: a. a color-change indicator, the color of which may be affected by the presence or absence or the concentration of a gas in contact with the ^ ^^^^^^^^^ indicator; b. a gas layer comprising a porous material containing a gas capable of interaction with the indicator so as to produce a color change, the gas being present at a different concentration than the gas is found in the ambient ^^ environment; and c. optionally, a further layer; wherein the color change sensor assembly is disposed in the container which is impermeable to the gas wherein the or each color change sensor is placed in the container under an atmosphere of the said gas and the ^^^ container is impermeable to the said gas; iii) providing before or after step ii) an atmosphere in the chamber comprising the gas at a concentration which is different to the concentration of the gas in the ambient environment ; and iv) closing the container. ^^^ 28. A method or providing a plurality of color change sensor assemblies at a location remote from the location of manufacture of the assemblies comprising: i) providing an impermeable container defining a chamber; ii) placing a plurality of a color change sensor assemblies in the container , wherein each assembly comprises: ^^^ a. a color-change indicator, the color of which is affected by the presence or absence or the concentration of a gas in contact with the indicator; b. a gas layer comprising a porous material containing a gas capable of interaction with the indicator so as to produce a color change, the gas being present at a different concentration than the gas is found in the ambient ^^^ environment; and c. optionally, a further layer; wherein the plurality of color change sensors are placed in the container under an atmosphere of the said gas and the container is impermeable to the said gas; ^^^ iii) providing before or after step ii) an atmosphere in the chamber comprising the gas at a concentration which is higher than the concentration of the gas in the ambient environment; iv) closing the container; v) transporting the container containing the plurality of sensor assemblies to a remote ^^^ location; and vi) optionally storing the sensor assemblies until required for use and, at the time of ^ ^^^^^^^^^ use, opening the container such that the concentration of gas in the sensor assembly changes and applying the sensor assemblies to products, thereby activating the sensor assembly. 29. Use of a sensor assembly according to any one of claims 1 to 25 to provide an ^^ indication of elapsed time and temperature exposure of at least one product comprising providing a sensor assembly pack according to any one of claims 1 to 25, opening the container of the said pack whereby the concentration of the gas in the chamber changes, retrieving at least one sensor assembly for the or each product from the chamber in the container and applying the at least sensor assembly to the or each said ^^^ product. 30. A product having secured on the product or its packaging an activated color-change sensor assembly which comprises: a) a color-change indicator, the color of which may be affected by the presence or ^^^ absence or the concentration of a gas in contact with the indicator; b) a gas layer comprising a porous material containing a gas capable of interaction with the indicator so as to produce a color change; and c) optionally, a further layer; wherein the gas is present in the gas layer at a different, concentration than the gas is found ^^^ in the ambient environment and the said concentration changes over time to reach equilibrium with the ambient environment. ^ ^^^^^^^^^