WO1993015402A1

WO1993015402A1 - An apparatus for indicating the presence of co2 and a method of measuring and indicating bacterial activity within a container or bag

Info

Publication number: WO1993015402A1
Application number: PCT/DK1993/000040
Authority: WO
Inventors: Bo Holte
Original assignee: Bo Holte
Priority date: 1992-02-04
Filing date: 1993-02-04
Publication date: 1993-08-05
Also published as: DK13492D0; AU3492793A

Abstract

The biological activity within a container or bag containing a foodstuff or a human thrombocyte concentrate is monitored by means of an apparatus (10) for indicating the partial pressure of carbon dioxide. The apparatus (10) comprises a first foil (24) of a light-transparent material substantially impermeable to gas and water, a second foil (20) constituting a CO2-permeable membrane, and an indicator system contained within a sponge (22) which is enclosed within a chamber defined between the first and second foils (24 and 20, respectively). As CO2 permeates into the chamber defined between the first and the second foils (24 and 20, respectively), the indicator system generates a visible indication in response to exposure to CO, which indication is visible through the first foil (24).

Description

An Apparatus for Indicating the Presence of CO- and a Method of Measuring and Indicating Bacterial Activity within a Container or Bag.

The present invention relates to the technique of measuring and indi- eating bacterial activity within containers or bags, such as containers or bags containing biological material or samples, such as blood sam¬ ples, urine samples, blood products, blood fractionation products, infu¬ sion fluids, such as enteral or parenteral infusion fluids or nutrients, or biologically degradable materials, or foodstuff.

The present invention more precisely relates to a novel technique of measuring and indicating bacterial activity within containers or bags by measuring and indicating the content of C0₂ within the container or bag in question or permeating from the container or bag in question, which CO is generated by bacterial activity within the container or bag.

The present invention consequently relates to the technique of measuring and indicating the partial pressure of carbon dioxide.

A particular technical field within which the novel technique according to the present invention is particularly applicable is within the field of handling and storing blood samples or products made thereof and blood products or blood fractionation products, such as thrombocyte concen¬ trates or red blood cell concentrates produced in blood banks.

Thrombocyte concentrates are routinely produced in blood banks from freshly donated blood, by well-known separation procedures. The thrombo¬ cyte concentrates can be used for the treatment of patients for up to five days from the date of production, during which period they are stored in sterile containers or bags made from a semi-permeable material that allows passage of oxygen (0-) and carbon dioxide (CO-). The cells in the thrombocyte concentrate sustain their life exactly the same way as cells within the human body, through a metabolic process, consuming 0- and producing C0₂- As thrombocyte concentrates are used for infusion into the blood stream of certain patients, maintenance of the sterility of the thrombocyte concentrate during storage is essential to the pa¬ tients. Thrombocyte concentrates, or e.g. red blood cell concentrates, infected by bacteria or other microorganisms may cause severe complica- tions such as bactere ia, sepsis, and shock. An infection of the throm¬ bocyte concentrate by bacteria or other microorganisms accidentally in¬ troduced during the production or handling of the thrombocytes, or from contaminated bags, tubes, etc., will cause an increase of the metabolic generation of CO-. Furthermore, it has been realized that an infection may give no other detectable sign than an increase of the production of CO-, and infected thrombocyte concentrates may thus accidentally be used for patient treatment.

Hitherto, the quality control of thrombocyte concentrates has been done by the blood banks by spot testing: A number of samples are tested, to represent the quality of the total number of thrombocyte units produced. The number of thrombocyte units that are accidentally infected is pre¬ sumably very low, compared to the total number of units produced; the probability of identifying an infected thrombocyte unit by spot testing is thus very low.

An object of the present invention is to provide a novel technique ren¬ dering it possible to carry out a non-invasive measurement and indica- tion of any bacterial activity within containers or bags containing bio¬ logical material or samples, such as blood samples, urine samples, blood products, blood fractionation products, infusion fluids, such as enteral or parenteral infusion fluids or nutrients, or biologically degradable materials, or foodstuff, in particular containers or bags containing thrombocyte concentrates.

A particular advantage of the present invention relates to the fact that the novel technique according to the present invention renders it possible to monitor and measure biological activity of bacteria or other microorganisms, such as aerobe and anaerobe bacteria within containers or bags which may be hermetically sealed containers or bags, or con¬ tainers or bags made from permeable or semi-permeable materials allowing the exchange of oxygen and carbon dioxide from the interior of the con¬ tainer or bag in question and the environment.

A further particular advantage of the present invention relates to the fact that the monitoring and measuring of biological activity of bacte¬ ria or other m croorganisms in accordance with the present invention is of a quantitative or at least semi-quantitative nature, and not only of a qualitative nature.

A particular feature of the present invention relates to the applicabi- lity of the novel technique according to the present invention, as the novel technique renders it possible to provide a low cost indicator ap¬ paratus or device which provides a highly accurate measurement and indi¬ cation, and which may be used within numerous technical fields, such as within the technical field of monitoring patients or persons by transcu- taneously measuring the partial pressure of carbon dioxide, and of pro¬ viding a visual indication of containers or bags containing foodstuff providing an accurate and reliable indication to the customer regarding the freshness of the foodstuff contained within the container in quest¬ ion.

The above object, advantage and feature, and numerous other objects, ad¬ vantages, and features which will be obvious to a person having ordinary skill in the art and which will be evident from the below detailed de¬ scription of preferred embodiments implemented in accordance with the, teaching of the present invention are in accordance with a first aspect of the present invention obtained by means of an apparatus for indica¬ ting the partial pressure of carbon dioxide, comprising: a first foil of a light-transparent material substantially imper¬ meable to gas and water, a second foil of a CO--permeable material, and an indicator system generating a visible indication in response to exposure to CO-, said first and second foils being joined together so as to define an inner chamber between said first and second foils, and said indicator system being enclosed within said inner chamber and being visible through said first foil.

In the present context, the term "substantially impermeable" defines in relation to the term "gas-permeable" that the substantially impermeable material exhibits barrier properties as the permeability of the substan¬ tially impermeable material is a factor at least 10 smaller than the permeability of the gas-permeable material, such as a factor 10-100 or more. Basically, the apparatus according to the first aspect of the present invention constitutes a CO- indicator which contains an indicator system generating a visible indication in response to exposure to CO-. The se- cond foil of the apparatus serves the purpose of providing a COg-perme- able membrane which is preferably impermeable to water and consequently to a substantial extent blocks the transmission of water through the CO--permeable membrane, and through which CO- may permeate into contact with the indicator system and further serves the purpose of defining an inner chamber enclosing the -indicator system with the first foil, which first foil serves the dual purpose of preventing CO- and any other gases or water from permeating into contact with the indicator system from the environment, and consequently of preventing constituents different from carbon dioxide from permeating into contact with the indicator system through a transmission path different from the C0--permeable second foil, and of providing a window through which the indicator system may be monitored and through which any indication generated by the indicator system in response to exposure to CO- may be monitored.

An example of an impermeable material is a composite foil comprising a 25 μm thick nylon foil and a 60 μm thick polyethylene foil, which foil exhibits a transmission to CO- of the order of 16.0 cm³/m^z/24 h at a temperature of 25°C and a relative humidity of 75%, and a transmission to water vapour of the order of 9.2 g/m²/24 h at a temperature of 40°C and a relative humidity of 90%. Similarly, a C0--permeable material is a polyethylene foil of a thickness of 95 μm exhibiting a permeability or transmission to CO- of the order of 11600 cm³/m²/24 h at a temperature of 25°C and a relative humidity of 75%, and a transmission to water va¬ pour of the order of 4.4 g/m²/24 h at a temperature of 40°C and a rela- tive humidity of 90%. This PE-foil is a CO--permeable, yet water-imper¬ meable foil or material. Preferably, the permeability of the first foil is approx. 100-1000 times less than the permeability of the second foil to C0-. Furthermore, a foil or material exhibiting a transmission or permeability to CO- of the order of 2500 cm³/m²/24 h at a temperature of 25°C and a relative humidity of 75% is considered a fairly permeable foil or material, whereas a foil or material exhibiting a permeability of transmission of the order of 150 cm³/m²/24 h at a temperature of 25°C and a relative humidity of 75% is considered a fairly impermeable foil or material .

The indicator system of the apparatus may be implemented in accordance with any appropriate technique, however, preferably comprises an aqueous solution of a pH-sensitive indicator material generating a visible indi¬ cation in response to a change of pH. Alternatively, the indicator sy¬ stem may comprise a glycerine-based solution of a pH-sensitive indicator material. The indicator material may e.g. be dibromthy olsulfonphthale- in, also known as Bromethymol Blue, and the aqueous solution may prefer¬ ably comprise a buffer, such as NaHCO-. The pH-sensitive indicator mate¬ rial and the buffer are preferably selected so as to create a pH indica¬ tor system in which a state of equilibrium is created corresponding to the normal partial pressure of CO- and so as to create an indicator sy¬ stem in which a change of the pCO- from a normal state to an abnormal state results in the generation of a clearly visual indication of the pH-sensitive indicator material.

Provided a thrombocyte concentrate is monitored by means of the appara¬ tus according to the first aspect of the present invention, the equili- brium partial pressure of carbon dioxide corresponding to the normal me¬ tabolic generation of CO- by the thrombocytes is of the order of 20-30 m Hg. Provided the partial pressure of CO- increases, a threshold is ex¬ ceeded, resulting in the generation of a visual indication by the indi¬ cator system and consequently by the pH-sensitive indicator material. For most biological materials or substances, e.g. blood products or blood fraction products, the indicator system is preferably provided as a mirror image of a biological liquid in which indicator system a pH of the order of approx. 7.00-7.40 and a concentration of bicarbonate ions of the order of 5-25 mM/1, substantially corresponding to the pH and the concentration of bicarbonate ions, respectively, of biological liquids. It is believed that a more accurate and precise indicator system is pro¬ vided by providing an indicator system constituting a mirror image of the material or substance to be monitored, as secondary reactions or substitutions are eliminated from influencing the relevant chemical re- action of the indicator system. Generally speaking, however, the indica¬ tor system has to be adjusted to react, causing a visible indication at a specific pCO- level. Thus, for alternative applications, the indica¬ tion system is to be optimized to provide a specific colour change at the relevant level of pCO-.

Various alternative and relevant indicator materials are dichlorosulfon- phthalein or phenolsulfonphthalein or other acid or base indicators, e.g. those indicators which are listed in Ullmanns "Encyklopadie der technischen Chemie", Verlag ChemierⁿVol. 13, 4th Edition, p_* 185. Further preferably, the aqueous solution comprises NaCl for providing a mirror image of the biological liquid as discussed above, and in the aqueous solution, the pH depends on the pCO- according to the following equation:

pH = - log pCO-, where

K is a constant, provided that the concentration of NaHCO- is between

_3 _1 ^ύ 10 M and 10 M. The chemical balance is adjusted by the provision of the buffer, and is, provided thrombocyte concentrates are to be monitor¬ ed, adjusted in such a way that the indication being Bromethymol Blue is blue at low and normal pCO- values (0 - 30 m Hg) and provides a colour change from blue to green and further to yellow at higher pCO- values.

According to a particular embodiment of the apparatus according to the present invention, the apparatus further comprises a sponge of an ab¬ sorbing material, which sponge is concealed within the inner chamber de¬ fined within the apparatus, and the indicator system is soaked in the sponge.

In order to render it possible to fixate the apparatus according to the present invention to a container or bag, such as a container or bag con¬ taining a thrombocyte concentrate, the apparatus according to the first aspect of the present invention preferably further comprises a support foil having a through-going aperture, which support foil is circumferen- tially joined to the inner foil of the apparatus in facial contact therewith through a first side surface of the support foil so as to ex¬ pose the second foil constituting the C0--permeable membrane of the ap- paratus in the aperture of the support foil. Further preferably, the support foil is provided with an adhesive layer provided at a side sur¬ face of the support foil opposite to the first side surface thereof. In order to render it possible to handle and store the apparatus prior to use, the apparatus may advantageously comprise a release foil cover¬ ing the adhesive layer and the second foil exposed in the aperture of the support foil in order to prevent that contamination, such as dust, unintentionally adheres to the adhesive layer, and further for prevent¬ ing that the C0--permeable membrane, and consequently the indicator sy¬ stem of the apparatus, is exposed to gases or even CO- prior to use, which gases might jam or ruin the operation of the apparatus.

As stated above, the apparatus according to the first aspect of the pre¬ sent invention may comprise a sponge in which the indicator system is soaked. Whether or not the apparatus comprises a sponge, the first foil is preferably shaped with an outwardly protruding dome, below which the inner chamber containing the indicator system and further the sponge, if any, is defined.

In the presently preferred embodiment of the apparatus according to the first aspect of the present invention, the apparatus constitutes a single or stand-alone apparatus which may be easily adhered or fixated to a container within or outside the container in question, optionally by means of the support foil of the apparatus. Alternatively, the appa¬ ratus according to the first aspect of the present invention may be in¬ tegrated into the container or bag, the content of which is to be moni¬ tored as the first foil of the apparatus may constitute a wall component of the container or bag in question.

Further alternatively, the apparatus according to the first aspect of the present invention may be integrated into the container or bag, the content of which is to be monitored as the second foil of the apparatus may constitute a wall component of the container or bag in question. Thus, in accordance with alternative embodiments of the apparatus according to the first aspect of the present invention, the first foil, and a second foil, respectively, are constituted by a foil constituting a wall component of the container or bag in question, containing the ma- terial or the sample, the bacteriological activity of which is to be mo¬ nitored by means of the apparatus.

In accordance with the concept of integrating the apparatus according to the first aspect of the present invention into the container or bag con¬ taining the material or the sample, the bacteriological activity of which is to be monitored by means of the apparatus, the indicator system may advantageously be contained within an adhesive layer through which the apparatus is adhered to the foil constituting a wall component of the container or bag, i.e. adhered to the inner surface of the foil constituting the wall component of the container or bag, provided the foil constitutes the first foil of the apparatus according to the first aspect of the present invention, and adhered to the outer surface of the foil constituting the wall component of the container or bag, provided the foil constitutes the second foil of the apparatus according to the first aspect of the present invention, respectively.

In accordance with the presently preferred embodiment of the apparatus according to the first aspect of the present invention, the first foil is a multi-layer film comprising at least one layer of nylon and at least one layer of polyethylene, the second foil is a polyethylene foil or alternatively a silicone rubber foil, the support foil is a PVC foil, and the sponge, if any, is preferably made of a filter paper material, or alternatively made from woven material or mesh material. Alternative¬ ly, the first foil may comprise a polyester foil, and the second foil may comprise a silicone foil.

As stated above, the apparatus according to the first aspect of the pre- sent invention is advantageously applied to or within containers or bags containing biological material or samples, such as blood samples, urine samples, blood products, blood fractionation products, infusion fluids, such as enteral or parenteral infusion fluids or nutrients, or biologic¬ ally degradable materials. Alternatively, the apparatus according to the first aspect of the present invention may be used for transcutaneously monitoring the partial pressure of carbon dioxide of a patient or per¬ son, such as a prematurely born infant. Furthermore, as stated above, the apparatus according to the first aspect of the present invention may be used within the foodstuff industry, providing a low cost, yet reli- able and precise indicator, rendering it possible to provide an objec¬ tive indication to the customers regarding the freshness of the food¬ stuff contained within a foodstuff container, such as a plastic con¬ tainer containing meat, or a meat container or tray wrapped into a plastic foil .

According to a second aspect of the present invention, an apparatus is provided which may be integrated into or enclosed within a sealed con- tainer, which container may be made from a permeable or impermeable ma¬ terial, dependent on the application. The apparatus for indicating the partial pressure of CO- according to the second aspect of the present invention comprises: a foil of a light-transparent, C0--permeable material, and an indicator system generating a visible indication in response to exposure to CO-, said foil being folded and sealed so as to define a sealed inner chamber, and said indicator system being enclosed within said inner chamber and being visible through said light-transparent foil.

According to the preferred embodiment of the apparatus according to the second aspect of the present invention, the foil defines a tubular seg¬ ment sealed at opposite ends thereof. Like the above described apparatus according to the first aspect of the present invention, the apparatus according to the second aspect of the present invention may be imple¬ mented according to the above embodiments and comprising the above fea¬ tures.

According to the first and second aspects of the present invention, ap- paratuses are provided for indicating the partial pressure of carbon di¬ oxide, in particular apparatuses for measuring and indicating the parti¬ al pressure of carbon dioxide generated by biological activity within containers or bags containing biological material or samples, such as blood samples, urine samples, blood products, blood fractionation pro- ducts, infusion fluids, such as enteral or parenteral infusion fluids or nutrients, or biologically degradable materials, or foodstuff. The appa¬ ratuses according to the present invention provide semi-quantitative in¬ formation, apart from a quality information, e.g. a quality information regarding the freshness of foodstuff contained within a container or bag. Furthermore, the biological material or sample contained within a container or sample may be monitored without providing access to the content of the container or bag in question, i.e. to the biological ma¬ terial or sample, and consequently without compromising the sterility of the material or sample.

According to a third aspect of the present invention, a method of measuring and indicating bacterial activity within a container or bag of a gas-permeable material containing a biological material or sample, such as a blood sample, a urine sample, a blood product, a blood frac¬ tionation product, e.g. a thrombocyte concentrate, an infusion fluid, such as an enteral or parenteral infusion fluid or nutrient, or a bio¬ logically degradable material, or a foodstuff, is provided, which method comprises the steps of: a) providing an apparatus for indicating the partial pressure of CO-, comprising: a first foil of a light-transparent material substantially imperme¬ able to gas and water, a second foil of a C0--permeable material, and an indicator system generating a visible indication in response to exposure to CO-, said first and second foils being joined together so as to define an inner chamber between said first and second foils, and said indicator system being enclosed within said inner chamber and being visible through said first foil, and b) arranging said apparatus in facial contact with said wall of said container or bag so as to arrange said second foil in gas-communi¬ cating relationship with said wall and said material or sample contained within said container or bag for causing CO- generated within said con¬ tainer or bag by bacterial activity therein to permeate through said wall and through said second foil of said apparatus causing a visible indication of said indicator system representing the bacterial activity within said container or bag.

According to a fourth aspect of the present invention, a method of mea¬ suring and indicating bacterial activity within a container or bag of a gas-impermeable material containing a biological material or sample, such as a blood sample, a urine sample, a blood product, a blood frac- tionation product, e.g. a thrombocyte concentrate, an infusion fluid, such as an enteral or parenteral infusion fluid or nutrient, or a bio¬ logically degradable material, or a foodstuff, is provided, which method comprises the following steps: a) providing an a^ aratus for indicating the partial pressure of CO-, comprising: a first foil of a ^" ght-transparent material substantially imperme¬ able to gas and water, a second foil of a CO--permeable material, and an indicator system generating a visible indication in response to exposure to CO-, said first and second foils being joined together so as to define an inner chamber between said first and second foils, and said indicator system being enclosed within said inner chamber and being visible through said first foil, and b) arranging said apparatus within said container or bag so as to arrange said second foil in gas-communicating relationship with said ma¬ terial or sample contained within said container or bag for causing C0- generated within said container or bag by bacterial activity therein to permeate through said second foil of said apparatus causing a visible indication of said indicator system representing the bacterial activity within said container or bag, and so as to expose said first foil through a light-transparent section or wall of said container or bag.

According to a fifth aspect of the present invention, a method of measuring and indicating bacterial activity within a container or bag of a gas-impermeable material containing a biological material or sample, such as a blood sample, a urine sample, a blood product, a blood frac- tionation product, e.g. a thrombocyte concentrate, an infusion fluid, such as an enteral or parenteral infusion fluid or nutrient, or a bio¬ logically degradable material, or a foodstuff, is provided, which method comprises the steps of: a) providing an apparatus for indicating the partial pressure of CO-, comprising: a first foil of a light-transparent material substantially imperme¬ able to gas and water, constituting at least a wall section of said con¬ tainer or bag, a second foil of a C0--permeable material, and an indicator system generating a visible indication in response to exposure to CO-, said first and second foils being joined together so as to define an inner chamber between said first and second foils, and said indicator system being enclosed within said inner chamber and being visible through said first foil, and b) arranging said apparatus so as to arrange said first foil con¬ stituting said wall section of said container or bag and so as to ar- range said second foil in gas-communicating relationship with said ma¬ terial or sample contained within said container or bag for causing C0- generated within said container or bag by bacterial activity therein to permeate through said second foil of said apparatus causing a visible indication of said indicator system representing the bacterial activity within said container or bag.

According to a sixth aspect of the present invention, a method of measuring and indicating bacterial activity within a container or bag of a gas-impermeable material containing a biological material or sample, such as a blood sample, a urine sample, a blood product, a blood frac¬ tionation product, e.g. a thrombocyte concentrate, an infusion fluid, such as an enteral or parenteral infusion fluid or nutrient, or a bio¬ logically degradable material, or a foodstuff, is provided, which method comprises the following steps: a) providing an apparatus for indicating the partial pressure of CO-, comprising: a foil of a light-transparent, C0--permeable material, and an indicator system generating a visible indication in response to exposure to CO-, said foil being folded and sealed so as to define a sealed inner chamber, and said indicator system being enclosed within said inner chamber and being visible through said light-transparent foil, and b) arranging said apparatus so as to arrange said foil in gas-com¬ municating relationship with said material or sample contained within said container or bag for causing CO- generated within said container or bag by bacterial activity therein to permeate through said foil of said apparatus causing a visible indication of said indicator system repre¬ senting the bacterial activity within said container or bag, and so as to expose said foil through a light-transparent section or wall of said container or bag.

The methods according to the third, fourth, fifth, and sixth aspect of the present invention constitute novel measuring and indicating tech- niques according to which the apparatuses according to the first and se¬ cond aspects of the present invention are employed.

Within the literature, various measuring techniques and measuring de- vices of somewhat different structure and fulfilling different purposes are described. Thus, US Patent No. 4,732,156 describes a transdermal do¬ simeter, and US Patent No. 4,821,733 describes a transdermal detection system for detecting ethanol or glucose. Reference is made to these US patents, and both US patents are herewith incorporated in the present specification by reference. -A transdermal dosimeter structure is dis¬ closed in International Patent Application, International Publication No. WO 87/00744. International Patent Application, International Publi¬ cation No. WO 89/04630, also describes a transdermal vapour collection method and apparatus. International Patent Application, International Publication No. W090/02511, European Patent Application, Publication No. 0083 941 and European Patent Application, Publication No. 0 143 550, describe various measuring and indicator techniques. A carbon diox¬ ide indicator is known from International Patent Application, Interna¬ tional Publication No. W090/01695, to which reference is made.

The technique of transcutaneously measuring the partial pressure of a blood gas constituent, such as the partial pressure of carbon dioxide, is extensively described in the literature, e.g. in numerous patents, such as Danish Patent No. 143.246 and Danish Patent No. 139.895. Furthermore, it is known to use C0--monitors or indicators for respira¬ tion monitoring, vide e.g. US Patent No. 4,728,499, to which reference is made and which is hereby incorporated in the present specification by reference.

Within the container and packaging industry, various techniques for in¬ dicating the sterility or the lack of sterility of a sealed container are known, e.g. from French Patent No. 2 461 662, US Patent No. 4,049,121, GB Patent Application No. 2 208287, German Published Patent Application No. DE OS 39 19405 and Japanese Patent Application, Appln. No. 62-206290, published under Publication No. 1-58670, to which patent specifications reference is made, and which above-mentioned US patent is hereby incorporated in the present specification by reference. The present invention will now be further described with reference to the drawings, in which

Fig. 1 is an exploded, perspective view of a first, presently preferred embodiment of a pCO- indicator implemented in accordance with the teach¬ ing of the present invention,

Fig. 2 is a perspective view of the assembled first embodiment of the pCO- indicator implemented in accordance with the teaching of the pre- sent invention, further including reference indicator codings,

Fig. 3 is a perspective view of a strip carrying or supporting two pCO- indicators according to the first embodiment of the present invention also shown in Fig. 1, illustrating the technique of assembling the pCO- indicators in a production plant,

Fig. 4 is a vertical sectional view of a second, slightly modified embo¬ diment of the pCO- indicator as compared to the first embodiment shown in Figs. 1-3, arranged on a skin surface part of a patient or person for transcutaneously indicating the partial pressure of CO- of the patient or person,

Fig. 5 is a perspective view of an assembly of a third embodiment of the pCO- indicator implemented in accordance with the teaching of the pre- sent invention, and a bio-electric signal-sensing electrode, i.e. an electrode for sensing a bio-electric signal, such as the ECG, the EEG, the heart rate or the like of a patient or person,

Fig. 6 is a perspective view of a presently preferred application of the first embodiment of the pCO- indicator shown in Figs. 1-3, within the field of monitoring live human thrombocytes enclosed within a container or bag,

Fig. 7 is a perspective view of an alternative application of the first embodiment of the pCO- indicator shown in Figs. 1-3, within the field of monitoring biological samples or fluids, such as blood samples, urine samples, blood products, blood fractionation products, infusion fluids, such as enteral or parenteral infusion fluids or nutrients, or biologic- ally degradable materials, or foodstuff, growth substrates, etc., or al¬ ternatively within the technical field of monitoring foodstuff,

Fig. 8 is a perspective view of a further alternative application of the pCO- indicator according to the present invention, illustrating a sample-containing bottle comprising a sealed cap in which a further al¬ ternative embodiment of the pCO- indicator implemented in accordance with the teaching of the present invention is integrated,

Figs. 9 and 10 are perspective views of further alternative applications of the pCO- indicator technique according to the present invention with¬ in the field of monitoring foodstuff, such as meat contained within a tray-shaped container, by means of two alternative embodiments of the pCO- indicator implemented in accordance with the teaching of the pre- sent invention,

Figs. 11 and 12 are exploded, perspective views similar to the view of Fig. 1 of still further alternative embodiments of the pCO- indicator implemented in accordance with the teaching of the present invention, and

Figs. 13 and 14 are perspective views similar to the views of Figs. 6 and 10, respectively, of the application of the alternative embodiment of the pCO- indicator shown in Figs. 11 and 12, respectively.

In Figs. 1 and 2, a first, presently preferred embodiment of a pCO- in¬ dicator is shown, implemented in accordance with the teaching of the present invention. The first embodiment is designated the reference nu¬ meral 10 in its entirety and comprises an annular support foil 12 in which a central circular aperture is defined and which is provided with adhesive coatings 14 and 16 on opposite side surfaces thereof. The annu¬ lar support foil 12 is provided with an outwardly protruding flap which is also provided with the adhesive coating 16 and covered by a flap com¬ ponent, designated the reference numeral 18 in order to render it possible to grasp the pCO- indicator.

The pCO- indicator further comprises a circular C0--permeable, yet water-impermeable membrane 20 which defines an outer diameter larger than the inner diameter of the through-going aperture of the support foil 12. The C0--permeable membrane 20 is arranged in contact with the adhesive coating 16 of the support foil 12 covering the through-going circular aperture of the support foil 12.

On top of the C0--permeable membrane 20, a sponge 22 is arranged which sponge comprises an indicator system, e.g. a pH indicator which gene¬ rates a visible indication when exposed to carbon dioxide, in accordance with the shift of the equilibrium of the equation:

H₂0 + C0₂ - H⁺ + HC0₃ ^"

Examples of indicator systems or compounds are listed below.

The sponge 22 and further an exposed annular rim part of the C0--perme- able membrane 20, which rim part is not covered by the sponge 22, and also the uncovered main part of the adhesive coating 16 of the support foil 12 is covered by a light-transparent, yet gas- and water-imperme¬ able cover foil 24 which is provided with a central, upwardly protruding dome, below which the sponge 22 and the pCO- indicator system or com¬ pound is enclosed. It is to be realized that the sponge 22 may be omit¬ ted, as the dome of the cover foil 24 may in itself define a chamber above the C0--permeable membrane 20, in which chamber the CO- indicator system is enclosed.

The adhesive coating 14 exposed at the lower or outer side surface of the support foil 12 is preferably a water-based adhesive or glue which is compatible with the material, such as the skin surface of a patient or person, or a container or bag made from a plastic material with which the pCO- indicator is to be brought into contact. The adhesive coating 16 may also be made from a water-based glue, provided the cover foil 24 is welded to the C0--permeable membrane 20 which is further preferably welded to the support foil 12 defining a sealed chamber below the dome of the cover foil 24 and above the C0--permeable membrane 20, which chamber communicates with the environment through the C0--permeable mem¬ brane exclusively due to the circumferential weld and further the imper¬ meable properties of the cover foil 24. In a slightly modified embodi¬ ment, the C0--permeable membrane 20 and the support foil 12 are integra- ted into a single component.

In Fig. 2, the pCO- indicator 10 is shown in the assembled state, ready for use, and further provided with colour codings 26, 27, 28, and 29, which colour codings are printed on an exposed circumferential rim part of the cover foil 24 adjacent to the dome of the cover foil 24. The co¬ lour codings 26-29 represent reference markings or indications with which the CO- indicator system visible through the light-transparent co¬ ver foil 24 may be compared for determining a specific partial pressure of carbon dioxide corresponding to a specific colour coding, i.e. one of the colour codings 26-29, of the material, patient, person, or sample, to which the pCO- indicator is applied or arranged.

In Fig. 3, two pCO- indicators of the above described structure, i.e. implemented in accordance with the first embodiment described above, are shown designated the reference numerals 10' and 10", respectively, ap¬ plied to a release foil 80.

The pCO- indicator 10 is preferably produced in an automatic production apparatus in which a length of the support foil material is provided with adhesive coatings on opposite side surfaces and cut into the annu¬ lar configuration shown in Fig. 1, also defining the flap to which the flap component 18 is applied. The flap component 18 may constitute a segment of a strip covering the length from which the annular support foil 12 is cut.

Similarly, the pCO--permeable membrane 20 is cut from a continuous length of the pCO--permeable membrane material. The sponge 22 and the cover foil 24 are also cut from continuous lengths of those materials, whereupon the sponge 22 is soaked with the pC0₂ indicator system. The support foil 12 having the adhesive coatings applied to opposite side surfaces thereof, the C0--permeable membrane 20, the sponge 22, and the cover foil 24 are arranged in registration and assembled optionally omitting the sponge 22, and preferably providing a sealing by providing a circumferential weld seam, welding the support foil 12, the C0₂~perme- able membrane 20 and the cover foil 24 together.

After or at the stage of assembling the pCO- indicator 10, the indicator is applied to the release foil 80, as shown in Fig. 3, which release foil 80 serves the purpose of protecting the adhesive coating 14 which is exposed at the lower side surface of the support foil 12 from unin¬ tentionally adhering to materials or substances and from being contami- nated by particles, dust, etc.

In Fig. 4, a second, or slightly modified embodiment of the pC0₂ indica¬ tor is shown, designated the reference numeral 40. The second embodiment of the pCO- indicator implemented in accordance with the teaching of the present invention basically a support foil 42 of an annular configura¬ tion defining a central, circular aperture. The support foil 42 basical¬ ly corresponds to the support foil 12 described above and is provided with adhesive coatings 44 and 46 corresponding to the adhesive coatings 14 and 16 described above. The pCO- indicator 40 further comprises a C0₂-permeable membrane 50 and a sponge 52 corresponding to the membrane 20 and the sponge 22, respectively, described above. Similar to the pC0₂ indicator 10 described above, the pCO- indicator 40 is provided with a cover foil designated the reference numeral 54. As is evident from Fig. 4, the cover foil 54, the C0--permeable membrane 50 and the support foil 42 are welded together along a circular or circumferential weld seam de¬ signated the reference numeral 48.

The pCO- indicator 40 shown in Fig. 4 is adapted to be used for moni¬ toring the partial pressure or carbon dioxide of a patient or person, such as a prematurely born child, a skin surface section of which is shown in Fig. 4 designated the reference numeral 30. The skin surface section 30 comprises three sections, viz. a hypodermic section or layer 32, an epidermic section or layer 34, and a dermic section or layer 36. As is evident from Fig. 4, a chamber 56 is defined above the layer 36 adjacent to the lower side surface of the C0--permeable membrane 50. The chamber 56 may be filled by a contact liquid, such as a CO- transfer li¬ quid.

In Fig. 5, an assembly 60 is shown, which assembly is assembled from a bio-electric signal-sensing electrode and a pC0₂ indicator implemented in accordance with the teaching of the present invention. The pCO- indi¬ cator is designated the reference numeral 66 in its entirety and is ar¬ ranged within a circular aperture of an electrically conductive plate 62 which may be made from a metal, such as a noble metal, or from carbon fibre material. A lower side surface of the plate 62 is provided with an electrically conductive glue 64, and the upper side surface of the plate 62 is covered by a C0₂-permeable foil 68 which constitutes a component of the pC0₂ indicator 66 similar to the cover foils 24 and 54 described above with reference to Figs. 1 and 4, respectively. A conductor 70 is connected in electrically conductive connection with the electrically conductive plate 62 through a rivet or soldering connection 72.

Whereas the second and third embodiments of the pC0₂ indicator according to the present invention discussed above with reference to Figs. 4 and 5 are preferably used for monitoring or measuring the partial pressure of a person or patient, the above described first, and presently preferred embodiment of the pCO- indicator according to the present invention is adapted to be used for detecting bacteriological activity of biological samples or systems, such as blood or urine samples, e.g. live human thrombocytes. Thus, in Fig. 6, the pC0₂ indicator 10 is applied to an outer side surface of a container or bag 90 containing live human throm¬ bocytes. The bag 90 is composed of two oxygen and carbon dioxide perme- able foils 92 and 94 which are welded together along a circumferential weld 96, together constituting the bag 90 and also integrally connected to an eyelet 98 by means of which the bag 90 may be hung on a wire, or hook or similar suspension means. The bag 90 is further provided with an outer label 100 on which information is printed or written, identifying the thrombocyte content of the bag 90 and the relevant data thereof, such as the date of production of the human thrombocyte sample and of the maximum period of time of storing of the sample. In case the live human thrombocytes are exposed to bacteriological activity, carbon diox¬ ide is generated by the bacteria, which carbon dioxide is easily detect¬ ed by means of the pC0₂ indicator 10, as the carbon dioxide permeates through the foil or membrane 92 of the bag 90 and into the indicator 10.

In Fig. 7, a similar application of the pC0₂ indicator is shown, in ac¬ cordance with which application the above described first, presently preferred embodiment of the pCO- indicator 10 is arranged on a container 110, which container is composed of a cover part 112 and a bottom part 114. The cover part 112 and the bottom part 114 may be welded together along a circumferential rim part of the cover part 112 in order to pro- vide a hermetically sealed container. Provided the cover part 112 of the container 110 is made from a C0₂-permeable material, the pCO- indicator 10 may be arranged on the outer side surface of the container 110. In case the cover part 112 of the container 110 is made from a C0₂- i per- meable material, the pC0₂ indicator 10 is arranged within the chamber defined within the container 110.

According to the teaching of the present invention, the pC0₂ indicator, such as the pC0₂ indicator designated the reference numeral 10 shown in Figs. 6 and 7, may be integrated into the container or bag which con¬ tains a sample or system which is to be monitored by means of the pC0₂ indicator. Thus, the cover foil of the pC0₂ indicator, such as the cover foil 24 shown in Figs. 1 and 2, may constitute a wall component of the container or bag which contains the sample or system which is to be mo- nitored. Reference is made to the description below referring to the em¬ bodiment shown in Fig. 9 which illustrates the technique of integrating the pCO- indicator into a wall component of the container or bag.

In Fig. 8, an alternative application of the teaching of the indicator technique according to the present invention is shown. Thus, in Fig. 8, a bottle 150 containing a biological substrate or material, e.g. a growth medium or substrate, is shown. The bottle 150 is sealed by means of a closure 152 which is provided with an integral pC0₂ indicator 154 implemented in accordance with the teaching of the present invention. Thus, provided the biological material or substance contained within the bottle 150 generates carbon dioxide, e.g. due to bacteriological growth within the bottle 150, the pCO- indicator 154 indicates an increase of the partial pressure of carbon dioxide generated within the hermetically sealed bottle 150.

In Figs. 9 and 10, a further alternative application of the pC0₂ indica¬ tor technique according to the present invention is illustrated. In Figs. 9 and 10, a container 120 is shown comprising a tray-shaped sup¬ port component 122, e.g. a plastic or cardboard tray component. Within the tray 122, chopped meat 124 is contained and covered by means of a light-transparent, oxygen and carbon dioxide impermeable foil 126. A la¬ bel 128 is applied to the outer side surface of the foil 126. In order to inform the customer about the quality of the content of the container 120, i.e. the quality of the chopped meat, pC0₂ indicators implemented in accordance with the teaching of the present invention are provided.

In Fig. 9, two pC0₂ indicators are integrated into the foil 126, one of which pC0₂ indicators is designated the reference numeral 130 in its en¬ tirety. The pC0₂ indicator 130 basically comprises a tray-shaped compo¬ nent 132 of a C0₂-permeable material, which component 132 is welded to the foil 126 along a rim part 134. Within the rim part 134, a pC0₂ indi¬ cator system 136 is enclosed, which indicator system may inform the cu- stomer about any bacteriological activity within the chopped meat 124 giving origin to an increase of the partial pressure of carbon dioxide within the container 120 and consequently within the indicator system contained within the carbon dioxide permeable tray 132.

In Fig. 10, an alternative embodiment of the pCO- indicator is shown designated the reference numeral 140 in its entirety. The pC0₂ indicator 140 basically comprises a tubular segment of a C0₂-permeable plastic ma¬ terial, within which tubular segment a pC0₂ indicator compound 144 is enclosed. The tubular segment 142 is cut from a continuous length of a tube containing the pC0₂ indicator system 144 as the individual tubular segments, such as the tubular segment 142, is sealed by means of con¬ strictions 146.

In accordance with the applications shown in Figs. 9 and 10, the label 148 may be provided with information regarding a specific visual indica¬ tion of the pC0₂ indicators 130 and 140, which visible indication -ay correspond to a specific increased bacteriological activity withir, the chopped meat 124. Thus, the pC0₂ indicators 130 and 140 may inform the customer that a specific chopped meat sample has been exposed to in- creased bacteriological activity and should consequently not be pur¬ chased.

In Fig. 11, a seventh embodiment of the pC0₂ indicator is shown, imple¬ mented in accordance with the teaching of the present invention. The se- venth embodiment is designated the reference numeral 160 in its entirety and is adapted to be adhered to a gas-permeable foil of a bag or con¬ tainer, the content of which is to be monitored by means of the pCO- in¬ dicator 160, e.g. as shown in Fig. 13 illustrating the application of the pC0₂ indicator 160 within the field of monitoring the bacteriolo¬ gical activity within a human thrombocyte sample as described above with reference to Fig. 6.

The seventh embodiment 160 comprises a light-transparent and gas-imper¬ meable plastic foil 162 of a circular configuration which is provided with an annul r covering 164 which defines a central window 166 of the foil 162. The foil 162 constitutes a foil similar to the cover foil 24 of the first embodiment 10 described above with reference to Figs. 1-3. The seventh embodiment 160 comprises in accordance with the teaching of the present invention a pH indicator generating a visible indication when exposed to carbon dioxide as discussed above with reference to Fig. 1. The pH indicator is bonded to a support body 168 which may be consti¬ tuted by a sponge or, alternatively and preferably, be constituted by a glue layer. The support body 168 is adhered to the lower side surface of the foil 162, i.e. the side surface of the foil 162 opposite the annular covering 164. Provided the support body is constituted by a sponge, the sponge is adhered to the foil 162 by means of an adhesive, and provided the support body is constituted by a glue layer, the support body ad- heres directly to the support foil through the glue or adhesive of the support body.

The reference numeral 172 designates an adhering surface of the support body, which adhering surface may be constituted by an adhesive or glue layer applied to the support body, provided the support body is consti¬ tuted by a sponge. Alternatively, provided the support body is constitu¬ ted by a glue layer, the adhering surface is constituted by an exposed surface of the support body 168. For protecting the support body 168 from being contaminated prior to use, a release foil 174 is provided. The support body 168 may comprise the pH indicator in a homogeneous sus¬ pension throughout the support body. Alternatively, the pH indicator may be concentrated within the central part of the support body 168, which central part is visible through the window 166 of the foil 162.

The seventh embodiment 160 shown in Fig. 11 is highly advantageous from a production point of view as the embodiment is easily produced from a first continuous web of the foil material from which the foil 162 is produced. The first web is sandwiched between a second continuous web which is provided with apertures defining the windows of the individual pC0₂ indicators from which second web the covering 164 is produced and a glue layer from which the support body 168 is produced integrally com¬ prising the pH indicator. The glue layer is covered by a third conti- nuous web of the release foil material from which the release foil 174 is produced. After the production of the sandwich comprising the three continuous webs and the adhesive layer, the circular pC0₂ indicators are cut or punched from the sandwich.

The seventh embodiment 160 of the pC0₂ indicator implemented in accord¬ ance with the teaching of the present invention may be used for moni¬ toring bacteriological activity within e.g. a bag containing human thrombocytes, such as the bag 90 shown in Fig. 13, or alternatively be used for monitoring bacteriological activity within a bag or a container in which a sample or foodstuff product is enclosed within a foil of a gas-permeable material. It is to be realized that the seventh embodiment 160 of the pC0₂ indicator shown in Fig. 11 differs from the above de¬ scribed embodiments in that the indicator employs the gas-permeable foil of the bag or container in which a material or a sample is contained and the bacteriological activity in which is to be monitored. Thus, the em¬ bodiment 160 may alternatively be used in connection with e.g. con¬ tainers or bags similar to the containers or bags shown in Figs. 7-10.

In Fig. 12, an eighth embodiment of the pCO- indicator is shown imple- mented in accordance with the teaching of the present invention. The eighth embodiment is designated the reference numeral 180 in its entire¬ ty. The eighth embodiment 180 of the pCO- indicator comprises a foil 182 of a gas-permeable material, which foil constitutes a foil similar to the C0--permeable membrane 20 of the first embodiment 10 of the pC0₂ in- dicator described above with reference to Figs. 1-3. The eighth embodi¬ ment 180 further comprises a support body 184 similar to the support bo¬ dy 168 of the seventh embodiment 160 described above with reference to Fig. 11. The support body 184, thus, may be constituted by a sponge or, alternatively and preferably, be constituted by a glue layer. Within a central area 186 of the support body 184, the pH indicator of the pC0₂ indicator is provided.

The pH indicator of the central area 186 may be constituted by any ap- propriate pH indicator system, such as the systems described below in the examples. The pH indicator may alternatively be provided as a homo¬ geneous suspension of the adhesive layer 184, in which instance, how¬ ever, the pH indicator may be brought into contact with a biological ma- terial, such as a foodstuff which for toxic reasons may be non-avanta- geous. Therefore, the pH indicator is preferably provided within the central area 186 of the support body 184, exclusively. The support body 184 is at its lower side surface adhered to the gas-permeable foil 182 and provides an exposed adhering surface 188 which may be constituted by the adhesive material of the support body 184 itself. Alternatively, in case the support body 184 is constituted by a sponge, a glue layer may be provided defining the adhering surface 188. In case a separate glue layer or adhsive is provided, constituting the adhering surface 188, the adhesive may be constituted by a non-light-transparent adhesive defining a central window similar to the window 166 shown in Fig. 11, which win¬ dow is provided in registration with the central area 186 of the support body 184 for providing a window through which the pH indicator of the central area 186 is visible. A release foil 190 is further provided for protecting the adhering surface 188 of the pC0₂ indicator 180 prior to use. The eighth embodiment 180 of the pC0₂ indicator is, like the above described seventh embodiment 160, advantageously produced from a web as¬ sembly sandwiching the glue material from which the support body 184 is produced.

The eighth embodiment 180 may advantageously be used for the same pur¬ pose as the above described embodiments 130 and 140, described above with reference to Figs. 9 and 10, viz. the purpose of monitoring any bacteriological activity within a foodstuff, such as chopped meat 124, contained within a container 120. The eighth embodiment 180 is, as is evident from Fig. 14, adhered to the inner side surface of the foil 126 of the container 120. Thus, the intentional application of the eighth embodiment 180 of the pC0₂ indicator differs from the intentional appli¬ cation of the seventh embodiment 160 of the pC0₂ indicator in that the eighth embodiment 180 is to be arranged within the container or bag which is constituted by a gas-impermeable foil, whereas the seventh em¬ bodiment 160 is arranged at the outer side surface of the foil of the bag or container, which foil is made from a gas-permeable material. The seventh embodiment 160 and the eighth embodiment 180 may, apart from the adhesion to the foil of the bag or container, be fixated at the foil through a circumferential weld seam along the outer rim of the embodi¬ ment in question, which weld seam seals the foil 162 and the foil 182 of the embodiments 160 and 180, respectively, to the foil of the container or bag.

Example 1

A prototype implementation of the pCO- indicator 10 described above with reference to Figs. 1-3 was made from the following components: the sup¬ port foil 12 was a 145 μm thick PVC foil of an outer diameter of 30 mm and having a through-going aperture of a diameter of 15 mm. The adhesive coating 14 was an acrylic adhesive applied as a coating or layer of a thickness of 50 μm, and the adhesive coating 16 was an acrylic adhesive applied as a coating or layer of a thickness of 50 μm. The pC0₂-perme- able membrane 20 was a semi-permeable membrane made from polyethylene of a thickness of 95 μm of an outer diameter of 22 mm. The sponge 22 was omitted. The cover foil 24 was provided with a central dome of a diame- ter of 18 mm and a height of 0.5 mm. The outer diameter of the cover foil was identical to the outer diameter of the support foil 12 and con¬ sequently measured 30 mm. The cover foil 24 was made from a composite multilayer film comprising a single 25 μm thick layer of nylon and a single 60 μm thick layer of polyethylene and had an overall thickness of 85 μm. The indicator system contained within the pC0₂ indicator was 0.15 ml of a saturated aqueous solution of Bromethymol Blue, which aqueous solution contained 150 mM NaCl and 15 mM NaHCO-, constituting a buffer. The release foil was a 75 μm silicone-coated paper foil.

Provided the partial pressure of carbon dioxide was low, the Bromethymol Blue indicator was blue, and as the partial pressure of carbon dioxide shifted beyond 30 mmHg, the indicator system shifted from blue to green, and at higher levels of pC0₂ further to yellow. The prototype implemen¬ tation was tested in a blood bank and also used for transcutaneously measuring the partial pressure of carbon dioxide of a test person. The prototype implementation responded correctly when exposed to carbon di¬ oxide. Example 2

Alternative relevant materials are: the membrane of the pC0₂ indicator may be made from any semi-permeable material, such as silicone rubber, polyethylene, polypropylene, polytetrafluorethylene, or combinations thereof, that allows the transmission of C0₂, but excludes transmission of H₂0 to any substantial extent in order to guarantee that the pCO- on either side of the membrane is the same when the indicator is in a state of equilibrium. In the state of equilibrium, the pCO- inside the pCO- indicator is identical to the pC0₂ outside the pC0₂ indicator, and con¬ sequently within the material or sample contained within the container or bag which is monitored by means of the pC0₂ indicator. A change of pC0₂ within the material or sample gives origin to a change of the pC0₂ outside the pC0₂ indicator, and after a new state of equilibrium has been reached, results in an identical change of pC0₂ within the pCO- in¬ dicator. The change of pC0₂ within the pC0₂ indicator gives rise to a pH change causing a colour change of the indicator system.

The indicator system may constitute any pH indicator system capable of generating a visible colour change within the relevant pCO- and pH range. Examples of relevant indicator systems are listed in the below Table 1 and in Ullmanns "Encyklopadie der technischen Chemie", Verlag Chemie, Vol. 13, 4th Ed., p. 185.

Table 1

Table 1 (continued)

pH Indicators

Range Indicator Colour Change Indicator Solution of acidic alkaline (eth. * ethanol, visible w = water) colour change

9.3-10.5 thymolphthalein

10.0-12.1 alizarin yellow G.G., C.I. 14025 11.6-13.0 epsilon blue

The cover foil of the pC0₂ indicator may be made from any material im¬ permeable to C0₂ fulfilling the requirements as to the light transparen¬ cy of the cover foil. Preferably, the material of the cover foil is a thermoplastic material in order to render it possible to provide a dome of the cover foil, below which dome the indicator system containing in¬ ner chamber of the pC0₂ indicator is defined.

Claims

1. An apparatus for indicating the partial pressure of C0₂, com¬ prising: a first foil of a light-transparent material substantially imperme¬ able to gas and water, a second foil of a C0₂-permeable material, and an indicator system generating a visible indication in response to exposure to C0₂, said first and second foils being joined together so as to define an inner chamber between said first and second foils, and said indicator system being enclosed within said inner chamber and being visible through said first foil.

2. The apparatus according to Claim 1, said indicator system com- prising an aqueous solution of a pH-sensitive indicator material gene¬ rating a visible indication in response to a change of pH.

3. The apparatus according to Claim 2, said indicator material be¬ ing Bromethymol Blue, and said aqueous solution comprising a buffer, such as NaHCO,.

4. The apparatus according to any of the Claims 1-3, further com- pising a sponge of an absorbing material, said sponge being concealed within said inner chamber, and said indicator system being soaked in said sponge.

5. The apparatus according to any of the Claims 1-4, further com- prising a support foil having a through-going aperture, said support foil being circumferentially joined to said first foil in facial contact therewith through a first side surface of said support foil so as to ex¬ pose said second foil in said aperture of said support foil.

6. The apparatus according to Claim 5, said support foil being pro- vided with an adhesive layer provided at a side surface of said support foil opposite to said first side surface thereof.

7. The apparatus according to Claim 6, further comprising a release foil covering said adhesive layer and said second foil exposed in said aperture of said support foil.

8. The apparatus according to any of the Claims 1-7, said first foil having a dome, said inner chamber being defined below said dome of said first foil .

9. The apparatus according to any of the Claims 1-8, said first foil being constituted by a foil of a container or bag containing a ma¬ terial or a sample, the bacteriological activity of which is to be moni¬ tored by means of the apparatus.

10. The apparatus according to any of the Claims 7-8, said second foil being constituted by a foil of a container or bag containing a ma¬ terial or a sample, the bacteriological activity of which is to be moni¬ tored by means of the apparatus.

11. The apparatus according to Claim 9 or 10, said indicator system being contained within an adhesive layer through which said apparatus is adhered to said foil of said container or bag.

12. The apparatus according to any of the Claims 1-11, further com¬ prising a reference colour coding provided at an outer side surface part of said first foil .

13. The apparatus according to any of the Claims 1-12, said first foil being a multi-layer film comprising at least one layer of nylon and at least one layer of polyethylene.

14. The apparatus according to any of the Claims 1-13, said second foil being a polyethylene foil, said support foil being a PVC foil, and said sponge being a filtre paper sponge, or alternatively a sponge made from woven material or mesh material.

15. An apparatus for indicating the partial pressure of C0₂, com¬ prising: a foil of a light-transparent, C0₂-permeable material, and an indicator system generating a visible indication in response to exposure to C0₂, said foil being folded and sealed so as to define a sealed inner chamber, and said indicator system being enclosed within said inner chamber and being visible through said light-transparent foil.

16. The apparatus according to Claim 15, said foil defining a tubu- lar segment sealed at opposite ends thereof.

17. The apparatus according to Claim 15 or 16, said indicator sy¬ stem comprising an aqueous solution of a pH-sensitive indicator material generating a visible indication in response to a change of pH.

18. The apparatus according to Claim 17, said indicator material being Bromethymol Blue, and said aqueous solution comprising a buffer, such as NaHCO.,.

19. The apparatus according to any of the Claims 15-18, further comprising a sponge of an absorbing material, such sponge being conceal- ed within said inner chamber, and said indicator system being soaked in said sponge.

20. The apparatus according to any of the Claims 15-19, said foil being a polyethylene foil, and said sponge being a filter paper sponge, or alternatively a sponge made from a woven material or mesh material.

21. A method of measuring and indicating bacterial activity within a container or bag having a wall of a gas-permeable material and con¬ taining a biological material or sample, comprising the steps of: a) providing an apparatus for indicating the partial pressure of C0₂, comprising: a first foil of a light-transparent material substantially imperme¬ able to gas and water, a second foil of a C0₂-permeable material, and an indicator system generating a visible indication in response to exposure to CO-, said first and second foils being joined together so as to define an inner chamber between said first and second foils, and said indicator system being enclosed within said inner chamber and being visible through said first foil, and b) arranging said apparatus in facial contact with said wall of said container or bag so as to arrange said second foil in gas-communi¬ cating relationship with said wall and said material or sample contained within said container or bag for causing C0₂ generated within said con¬ tainer or bag by bacterial activity therein to permeate through said wall and through said second foil of said apparatus causing a visible indication of said indicator system representing the bacterial activity within said container or bag.

22. The method according to Claim 21, said apparatus further com¬ prising any of the features of the apparatus according to any of the Claims 2-14.

23. The method according to any of the Claims 21 or 22, said con¬ tainer or bag being a bag containing a thrombocyte suspension.

24. A method of measuring and indicating bacterial activity within a container or bag of a gas-impermeable material containing a biological material or sample, comprising the following steps: a) providing an apparatus for indicating the partial pressure of C0₂, comprising: a first foil of a light-transparent material substantially imperme- able to gas and water, a second foil of a C0₂-permeable material, and an indicator system generating a visible indication in response to exposure to C0₂, said first and second foils being joined together so as to define an inner chamber between said first and second foils, and said indicator system being enclosed within said inner chamber and being visible through said first foil, and b) arranging said apparatus within said container or bag so as to arrange said second foil in gas-communicating relationship with said ma¬ terial or sample contained within said container or bag for causing C0₂ generated within said container or bag by bacterial activity therein to permeate through said second foil of said apparatus causing a visible indication of said indicator system representing the bacterial activity within said container or bag, and so as to expose said first foil through a light-transparent section or wall of said container or bag.

25. The method according to Claim 24, said apparatus further com¬ prising any of the features of the apparatus according to any of the Claims 2-11.

26. A method of measuring and indicating bacterial activity within a container or bag of a gas-impermeable material containing a biological material or sample, comprising the steps of: a) providing an apparatus for indicating the partial pressure of C0₂, comprising: a first foil of a light-transparent material substantially imperme¬ able to gas and water, constituting at least a wall section of said con¬ tainer or bag, a second foil of a C0₂-permeable material, and an indicator system generating a visible indication in response to exposure to C0₂, said first and second foils being joined together so as to define an inner chamber between said first and second foils, and said indicator system being enclosed within said inner chamber and being visible through said first foil, and b) arranging said apparatus so as to arrange said first foil con¬ stituting said wall section of said container or bag, and so as to ar¬ range said second foil in gas-communicating relationship with said mate¬ rial or sample contained within said container or bag for causing C0₂ generated within said container or bag by bacterial activity therein to permeate through said second foil of said apparatus causing a visible indication of said indicator system representing the bacterial activity within said container or bag.

27. The method according to Claim 26, said apparatus further com¬ prising any of the features of the apparatus according to any of the Claims 2-14.

28. The method according to any of the Claims 26-27, said container or bag being a bag containing foodstuff.

29. The method of measuring and indicating bacterial activity with¬ in a container or bag of a gas-impermeable material containing a biolo¬ gical material or sample, comprising the following steps: a) providing an apparatus for indicating the partial pressure of C0₂, comprising: a foil of a light-transparent, C0--permeable material, and an indicator system generating a visible indication in response to exposure to C0₂, said foil being folded and sealed so as to define a sealed inner chamber, and said indicator system being enclosed within said inner chamber and being visible through said light-transparent foil, and b) arranging said apparatus so as to arrange said foil in gas-com¬ municating relationship with said material or sample contained within said container or bag for causing C0₂ generated within said container or bag by bacterial activity therein to permeate through said foil of said apparatus causing a visible indication of said indicator system repre¬ senting the bacterial activity within said container or bag, and so as to expose said foil through a light-transparent section or wall of said container or bag.

30. A method according to Claim 29, said apparatus further com- prising any of the features of the apparatus according to any of the Claims 16-20.