WO2000074853A1

WO2000074853A1 - Container, closure and method of mixing two materials

Info

Publication number: WO2000074853A1
Application number: PCT/GB2000/002173
Authority: WO
Inventors: Eva Widenoja
Original assignee: Axis-Shield Poc As; Stevens, Jason, Paul
Priority date: 1999-06-04
Filing date: 2000-06-05
Publication date: 2000-12-14
Also published as: WO2000074853A8; AU5094800A

Abstract

A container (10), particularly for use with biological or similar samples, contains a container body (12) for containing a diluent or similar and a closure (14), one of which carries a metering device (16). The metering device is used to draw up a metered amount of a first material, and the material enters the container body (12) as the container (10) is closed by the closure (14). Further, the closure is configured such that the parts which a use can come into contact with after the closure is subsequently opened are not contacted by the first material, either before or after mixing with the diluent or similar material. The invention also extends to a method of mixing materials in this way, and a closure of this type.

Description

CONTAINER, CLOSURE AND METHOD OF MIXING TWO MATERIALS

The present invention relates to a container, to a closure for a container, and to a method of mixing two materials .

A large number of ailments can be diagnosed through testing of biological samples, such as saliva, expectorate, tear fluid, spinal liquid, wound drainage fluid, lavage, tissue or cell extracts, faecal samples, and especially bodily fluids such as blood and urine. One common form of testing involves measurement of the amount of a particular substance in a known amount of blood. Abnormal concentrations of certain substances are indicative of certain illnesses or deviant physiological conditions.

A known method of measuring the amount of a substance in a sample is "affinity binding", where a chemical binds to the substance in question to produce a direct or indirect signal, such as a colour change. The eventual colour of the sample under test indicates the concentration of the substance in question in the biological sample under examination. However, in order to produce a standardized result, it is necessary for the biological sample to be diluted to a particular concentration before it is tested.

Previously, methods for diluting the biological sample have consisted of introducing a known amount of the biological sample and a known amount of diluent into a test tube or similar container. For example, in one known method for testing the level of glycated haemoglobin in human blood, it is necessary to dilute 25 μl of whole blood with 1000 μl of diluent. 25 μl of the diluted blood is then used to perform the test. Measurement of these volumes requires the use of graduated micro pipettes or similar metering devices. The use of such devices requires a certain degree of manual dexterity in order to dispense the required amount of liquid. It is quite possible to dispense too much or too little of the biological sample or of the diluent from the metering device, and this can spoil the test procedure. It may then be necessary to obtain a further sample of the biological sample from the patient, which can be time-consuming and inconvenient. Even if the tube where the biological sample and the diluent are mixed is supplied pre-filled with the appropriate amount of diluent, it is still necessary to measure the amount of blood correctly, using a suitable metering device, such as a graduated micro pipette or a capillary tube . This is an intricate procedure for a user, who has to take care to avoid spillage when dispensing the blood into the tube. If there is spillage the test is spoiled and there is an increased risk of user contact with the blood. This can be particularly problematic if the blood or other biological sample being tested contains or is suspected to contain infectious material.

A further disadvantage of the known method is that the person carrying out the test is exposed to the mixture of biological sample and diluent until such time as the test tube is closed. In addition, it is necessary to thoroughly mix the biological sample, e.g. blood, and the diluent in order to achieve the proper degree of dilution. This is most easily done by closing the tube and then shaking it vigorously. However, if this is done, the diluted sample will coat the entire inner surface of the tube. If the tube is closed by means of a cap or plug, then the part of the cap or plug which is exposed to the inside of the tube will also be coated with diluted sample. This can lead to a risk of contamination when the tube is opened, as the wetted part of the cap or plug could be touched by or otherwise come into contact with the person conducting the test . It would be preferable to reduce this risk by avoiding contact between the sample and the cap during mixing.

According to a first aspect of the present invention, there is provided a container comprising a container body for containing a first material, a closure, and a metering device for holding a metered amount of a second material, one of the container body and the closure carrying or being adapted to carry the metering device, and the container and closure cooperating such that when the closure is used to close the container, the metering device enters the container body, thus allowing the first material to be mixed with the second material, where the parts of the closure which can be contacted by a user after opening of the closure are prevented from coming into contact with the mixture of the first material and the second material . Since prior to closing of the container, the metering device is carried by the container body or the closure, the container is easy to use. Once the container contains the first material and the metering device holds the second material, the next logical step for a user is to close the container and, according to the first aspect of the invention, this step advantageously also results in entry of the metering device into the container body thereby allowing mixing of the first and second materials to take place. There is less chance that the user will come into contact with the second material, as compared to known systems in which a metering device is used to add the second material to the first material and then the container is closed in a separate step. Further, there is a reduction in the number of separate parts which a user has to handle to effect mixing of the materials.

Since there is a reduced chance of the user coming into contact with the second material, the container is also suitable for use with any material with which it is hazardous to come into contact. For example, the container can also be used in the handling of biological samples as mentioned above, microbiological samples, for example after culturing, and non-biological samples whose toxicity or the like poses a hazard to the user.

In one example of the use of the container, the first material is a diluent and the second material is a biological sample such as blood or urine requiring dilution in the diluent before carrying out a diagnostic test. Once the metering device which may, for example, be a capillary, has been used to gather the metered amount of biological sample, it is a simple and logical procedure for the user to close the container and at the same time cause the metering device to enter the container body. The potential for exposure of the user to the biological sample is minimised, reducing the chance of contamination of the sample or infection for the user.

Further, since the container is closed at the same time as the second material is introduced thereinto, the length of time during which the materials are exposed to the air can be reduced. In the prior art methods, the second material was introduced into the container, and the container was then closed in a separate step. By contrast, according to this aspect of the invention, the introducing and closing steps take place substantially at the same time. The invention also extends to a method of using the container to mix materials, and so according to a second aspect of the present invention, there is provided a method of mixing a first material and a second material, said method comprising the steps of providing a container body containing a certain amount of said first material, providing a metering device holding a metered amount of said second material, and introducing said metering device into said container body and simultaneously closing said container body, said container also having a closure such that the parts of the closure which can be contacted by a user after opening of the closure are prevented from coming into contact with the mixture of the first material and the second material .

By means of this method, the risk of the mixture inadvertently escaping from the container body, and thus the risk that a person carrying out the method will come into contact with the mixture, is considerably reduced. This is of course an advantage in cases where the mixture is in some way hazardous, for example infectious .

In a preferred method, the first material is a diluent, and the second material is a biological sample, such as blood. The method will then reduce the chance of any infection arising from contact with infectious agents in the biological sample and the resulting mixture of biological sample and diluent . The first material may be placed in the container body by the end user, i.e. the person who requires the materials to be mixed, preferably in a measured amount. Preferably, however, the container is pre-filled with a known amount of the first material . Since the metering device will hold a metered amount of the second material, it is possible to ensure that the resulting mixture of materials is in the correct proportions. This leads to a simpler overall procedure, as there is less need for manual skill or dexterity in measuring the amount of the first material.

The mixture of materials can be removed from the container in a number of ways,- for example, the container could be pierced by a hypodermic needle or similar, or could be provided with a line of weakness along which it could be broken. As an alternative, when the mixture is liquid, the container could be provided with an opening through which drops of the mixture could be squeezed out. It is however preferred that the closure can be opened after the metering device has entered the container, to allow access to the mixture of the materials. Such a closure will generally be reclosable and this has the advantage that after gaining access to the mixture of materials by opening the closure it can then be reclosed, to seal the container and prevent spillage.

Further, since the parts of the closure which can be contacted by a user after opening of the closure are prevented from coming into contact with the mixture of the first material and the second material, this reduces the risk of exposure to the mixture for a user and is thus advantageous where hazardous materials, e.g. potentially infectious biological samples, are involved. Protection for the user contactable parts of the closure may be provided by a protective member which is left behind in the container body when the closure is opened. As an alternative, the closure may open to reveal an orifice, which is initially sealed by a puncturable film. Access to the contents of the container can then be attained by puncturing this film with a pipette or the like. The film thus protects the user-contactable parts of the closure from contact with the mixture of the first material and the second material.

The metering device may remain attached to the container body or closure during mixing and after opening of the container. Preferably, however, the container body or the closure is arranged to carry the metering device detachably. Thus, the metering device may be arranged to detach from its carrier, i.e. the container body or the closure, when the closure is used to close the container or alternatively when the closure is opened. The metering device will then remain in the container. As the metering device is in a preferred embodiment intended to meter the amount of a biological sample, such as blood or urine, it is desirable to reduce the risk of contamination from the sample as much as possible. If the metering device is retained within the container, then there is far less risk that it will come into contact with anyone using the container than if it remains attached to e.g. the closure when the closure is opened. The metering device can thus advantageously comprise a portion which serves as the protective member for the user contactable parts of the closure.

In certain preferred embodiments, it is the closure which carries or is adapted to carry the metering device prior to closing of the container. This can result in a simple container construction in which introducing the metering device and closing the container are effectively carried out as a single step. In fact, such a combined closure and metering device can be used with known containers, and accordingly viewed from another aspect the invention provides a closure for a container, in combination with a metering device for holding a metered amount of a material, the closure carrying or being adapted to carry the metering device in such a way that when the closure is used to close a container the metering device is inserted into the container, and where the parts of the closure which can be contacted by a user after opening of the closure are prevented from coming into contact with the material.

Preferably, opening of the closure to gain access to the mixture detaches the metering device from the closure. The metering device will then be retained in the container when the closure is opened. In one preferred form, the metering device engages with a part of the container body when the closure is opened, and this engagement serves to detach the metering device from the closure. Alternatively, the metering device may engage with a part of the closure itself when the closure is opened to detach the metering device from the closure . Arranging the metering device and the closure in this way can simplify the construction of the container body and indeed enable the closure and metering device to be designed for use on known containers.

It is further preferred that the metering device and the closure be formed integrally with each other. This can simplify manufacture. In addition, if the metering device is intended to be detachable from the closure, an integral construction reduces the risk that the metering device could be detached from the closure prematurely, as it is actually necessary to fracture the connection between the metering device and the closure. In alternative embodiments, it is the container body which carries or is adapted to carry the metering device prior to closing of the container. This again can give ease of use and a reduced likelihood that a user will come into contact with the second material, as compared to known systems in which a metering device for the second material is provided separately of the container .

In the situation where the metering device is attached to the container body, it is preferred that the metering device be detached from the container body when the closure is used to close the container. The detachment of the metering device can then take place automatically as the container is closed. Preferably, the metering device is connected to a region of the wall of the container body, and the said region of the wall is detached from the remainder of the container body when the closure is used to close the container. By using this arrangement, the metering device, which is initially on the outside of the body, can be pushed through the hole made in the wall of the body to introduce the metering device into the container.

The region of wall can be removed by any suitable means. For example, the region could be bounded by a line of weakness, adapted to break as the region is pushed on. However, it may be difficult for there to be sufficient weakness whilst still maintaining a seal along the line of weakness, as is desirable when for example the container body is pre-filled with the first material and sterility is to be maintained.

Accordingly, it is preferred that the region of the wall be detached by a cutting member on the closure. The cutting member can engage with the region of the wall when the closure is used to close the container, which ensures that the container is closed at the same time as the metering device is detached. Further, provision of a cutting member helps to ensure that the region of wall is reliably removed.

The cutting member may be formed as a separate member from the closure and may be detachably attached thereto, so that it is detached from the closure when the closure is opened. Since the cutting member cuts a region of the wall away, the hole made is virtually the same size as the cutting member itself. It is thus possible for the cutting member to jam in the hole, which can make it difficult to open the closure. Forming the cutting member as a separate and separable member avoids this problem.

It is preferred that the metering device comprises a capillary passage for receiving the second material . This allows accurate metering of very small amounts of biological samples. An open capillary split may be preferred in some cases.

The container may further comprise means for mixing a third material with the first and second materials. This increases the range of possible mixtures which can be produced using the container, and thus increases its versatility.

As mentioned above, the body and the closure are arranged such that the parts of the closure which can be contacted by a user after opening of the closure are prevented from coming into contact with the mixture of the first material and the second material. The idea of using a protective member to avoid the closure being exposed to the contents of the container is considered to be of independent inventive merit, and so according to another aspect of the present invention, there is provided a container comprising a closure and a protective member for protecting the closure from exposure to the contents of the container, the arrangement being such that when the closure is opened the protective member is left behind in the container whilst allowing access to the contents of the container. Such an arrangement is advantageous in the context of containers for a single material, as well as those where two materials are to be mixed together. It is also advantageous for containers for materials which are to be mixed, where a separate metering device (i.e. one not carried by the container body or the closure) is to be used. In ordinary containers, there is no such protective member, and so there is nothing to prevent contact between the closure and the contents of the container. This does not cause a problem with most containers, as their contents are generally harmless. However, with certain products, for example bleaches and other caustic or otherwise hazardous materials, contact with the material should be minimized and preferably avoided altogether. If the closure has come into contact with the material, then it is quite possible for the user to come into contact with any material remaining on the closure, and this can have adverse consequences .

Provision of a protective member avoids this problem. The closure is protected from the contents of the container by the protective member, and so when the closure is opened, the parts of the closure with which the user can come into contact have not been exposed to the contents of the container. Since the protective member is left inside the container, a person opening the closure can avoid coming into contact with the protective member accidentally.

Preferably, the protective member and the closure are initially attached to each other, and are detached as a result of opening the closure. The protective member will then prevent contact between the closure and the contents of the container while the closure is closed, but will be detached to ensure that the opened closure is not contaminated with any of the contents of - li the container. This reduces the risk of inadvertent contact between the person opening the container and the contents thereof .

In a further preferred embodiment, the protective member also protects a mouth of the container from exposure to the contents of the container. This further reduces the chance that the user will come into contact with the contents of the container.

Certain preferred embodiments of the invention will now be described by way of example only and with reference to the accompanying drawings, in which:

Figure 1 shows a first embodiment;

Figures 2a to 2d show how the first embodiment operates ,- Figure 3 shows a first variant of the first embodiment ;

Figures 4a to 4d show how the first variant of the first embodiment operates;

Figure 5 shows a second variant of the first embodiment;

Figures 6a to 6d show how the second variant of the first embodiment operates;

Figure 7 shows a second embodiment;

Figures 8a to 8d show how the second embodiment operates;

Figure 9 shows a first variant of the second embodiment ;

Figures 10a to lOd show how the first variant of the second embodiment operates,- Figure 11 shows a second variant of the second embodiment ;

Figures 12a to 12d show how the second variant of the second embodiment operates,-

Figure 13 shows a third variant of the second embodiment ;

Figures 14a to 14d show how the third variant of the second embodiment operates;

Figure 15 shows a sample handling device which does not fall within the scope of the invention;

Figures 16a to 16d show how the sample handling device of Figure 15;

Figure 17 shows a variant of the sample handling device of Figure 15, which also does not fall within the scope of the invention;

Figures 18a to 18d show how the variant of the sample handling device operates;

Figure 19 shows a third embodiment; Figures 20a to 20d show how the third embodiment operates ;

Figure 21 shows a variant of the third embodiment ,-

Figures 22a to 22d show how the variant of the third embodiment operates; Figures 23a to 23e show the operation of a fourth embodiment .

Figure 24 shows a fifth embodiment; and

Figures 25a to 25f show thew operation of the fifth embodiment . It should be noted that, although the sample handling devices shown in Figures 15, 16a to 16d, 17 and 18a to 18d do not fall within the scope of the invention, they are here described to aid in understanding of subsequent embodiments. With regard to Figures 1 and 2a to 2d, the first embodiment comprises a container 10 with a body 12, and a closure 14 carrying a sampling device 16. The body 12 has a narrowed mouth 18, which is closed by a seal 20. The mouth is at least wide enough to allow a pipette or similar apparatus to be inserted into the body. The mouth is also formed with tracks 22 along its inner surface (see Figure 2c) . The body as supplied contains a certain amount of diluent .

The sampling device 16 includes a member having a capillary passage 24, and is detachably connected to a cap 26 which forms the closure 14. The member is formed as a solid member with a narrow split in it, the narrow split forming the capillary passage; such members are termed "capillary splits". The split is open on all but one of its sides, and so it is much easier to wash fluid out of the capillary split than it is with a normal capillary tube. The capillary split 16 is connected to the underside of the cap, so that when the cap 26 is connected to the body 12, the split 16 projects into the body 12. The split 16 also has a projecting collar 28. The collar 28 co-operates with the tracks 22 on the inside of the mouth 18, in a manner to be described later.

The first embodiment is used as follows: The container is initially as shown in Figure 2a. As a first step, the open end of the capillary passage is contacted with the sample which is to be tested. As a result, a certain amount of the sample is drawn up into the capillary passage through capillary action. This step can be repeated if necessary until a desired amount of the sample has been drawn up into the capillary passage. The required amount of sample may be indicated by a mark on the outside of the passage.

In addition, since the capillary split is connected to the cap, the user can hold the cap during this stage. In previous methods using capillary tubes, it was necessary to hold the tube itself, which is small and relatively fragile. Providing a larger member to be gripped makes this step easier for the user.

When the desired amount of sample has been drawn up into the capillary split, any sample adhering to the outer surface of the capillary split can be removed if desired, for example by wiping the outer surface. The removal of any excess sample from the outer surface ensures that the amount of sample to be diluted corresponds as closely as possible to the volume of the capillary split, which as mentioned above can be calibrated. Of course, care should be taken to prevent the user coming into contact with the sample when the split is wiped in the event that the sample is hazardous . Alternatively, or additionally, the outer surface of the capillary split may be such that it is not wet by the sample, thus preventing the adherence of liquid to the outer surface of the capillary split in the first place. The non-wettability of the outer surface may be achieved by forming it from a particular material, or by chemical or other treatment of the surface.

When the desired amount of sample has been drawn up, the seal 20 is removed from the body 12. The area of the seal 20 which confronts the inside of the body 12 should be made as small as possible, in order to reduce the amount of diluent which may adhere to it when it is removed. Obviously, since the body is supplied containing a certain amount of diluent, which amount has been calibrated to the degree of dilution required, it is desirable to maintain the amount of diluent as near to the original amount as possible.

The cap 26, with the capillary split 16 attached, is then fitted onto the body 12. In the course of this, the capillary split 16 passes through the mouth 18 of the body 12. The collar 28 of the capillary split 16 cooperates with the tracks 22 as it passes through the mouth 18. When the collar 28 emerges from the mouth 18 into the inside of the body 12, it "snaps" into place beneath the mouth 18, and this provides a tactile signal to the user that the cap 26 is located correctly. The body 12 with the cap 26 attached is shown in Figure 2b.

When the cap 26 and capillary split 16 have snapped into place, the container 10 can then be shaken or otherwise agitated, so that the diluent flushes the sample from the capillary passage. Of course, other ways of agitating the container, such as mechanical agitation, stirring, vibration, rotation, inversion, rolling and swirling can also be used rather than shaking, and the agitation may be done by hand or using some form of apparatus .

Since the amount of diluent is set when the body 12 is filled, and the amount of sample introduced can be set by marking the capillary split appropriately, the degree of dilution of the sample can be closely controlled. Further, the collar 28 of the capillary split 16 prevents the diluted sample from contacting the cap 26 when the container 10 is shaken.

In order to gain access to the diluted sample in the container 10, the cap 26 is twisted. As this is done, the tracks 22 engage with the collar 28 of the capillary split 16 to force it downwards, away from the cap 26. The capillary split 16 thus detaches from the cap 26 and falls into the body 12. It will thus be seen that no part of the cap 26 has come into contact with the sample, whether diluted or undiluted, at any time. The cap 26 thus poses no risk of contamination. In addition, the collar 28 of the capillary split 16 prevents sample from contacting the mouth 18 of the body 12, and so this is also not contaminated.

The cap 26 can also be provided with means which cooperate with the tracks 22 to force the cap 26 upwardly when it is rotated. This assists in separating the capillary split 16 from the cap 26, and also assists in removing the cap 26 from the body 12. The container 10 with the cap 26 removed from the body 12 and the capillary split 16 inside the body 12 is shown in Figure 2c.

Once the cap 26 has been removed, the desired amount of diluted sample can be removed from the body 12 using a pipette or similar apparatus.

When the desired amount of diluted sample has been removed and the test has been completed, there is no further use for the diluted sample remaining in the body 12, and so the body 12 can then be discarded. In order to avoid contamination, the original seal 20 or the cap 26 is refitted onto the body 12 to close it, to prevent diluted sample from leaving the container 10. The closed container 10 can then be discarded. The closed container 10 is shown in Figure 2d.

This system can be used with a number of variants . Figures 3 and 4a to 4d show the system of the first embodiment in use with a body 12a formed and filled by a blow-fill-seal process. In this variant, the body 12a is formed as a closed body, as is standard with blow- fill-seal processes. The body 12a is formed around a previously moulded mouth part 30a. A line of weakness 32a is formed in the body 12a around the mouth 30a, so that the body 12a can be broken to allow access to its mouth 30a. Further, rather than the capillary split and the cap being formed as separate members, in this variant they are moulded integrally. However, the connection 34a between the cap 26a and the capillary split 16a is frangible . When the capillary split 16a containing the sample to be tested is inserted into the mouth 30a (see Figures 4a and 4b) , the periphery of a collar 28a at its uppermost end snaps beneath a track 36a in the mouth 30a of the body. This prevents the capillary split 16a from being removed from the body 12a when the cap 26a is taken off. As a result, when the cap 26a is taken off the frangible connection 34a between the cap 26a and the capillary split 16a is broken, and the capillary split 16a falls into the body (see Figure 4c) . Once again, no part of the cap 26a comes into contact with the sample before the cap is removed.

A second variant is shown in Figures 5 and 6a to 6d. Here, the body 12b is formed from laminated films, connected to a moulded mouth 30b, which has an opening 18b initially closed by a seal 20b. The cap 26b and the capillary split 16b are integrally formed and connected at 28b, as in the first variant. The operation is similar to the first embodiment, and will not be described further. It will be noted that the base of the body 12b is rounded, in contrast to the flat bases of the bodies in the first embodiment and the first variant thereof . It is thus not possible to stand the body 12b up by itself. This problem can easily be overcome by providing a stand for the body, or simply by changing the shape of the body.

A second embodiment is shown in Figures 7 and 8a to 8d. Once again, it comprises a container 110 formed from a body 112 and a closure 114. The body 112 has at its upper end a peripheral groove 116, whose purpose will be described later. The body itself is sealed at its upper end by a tear-off sheet 118, although any other suitable means, such as a removable cap as used in the first embodiment, could be employed. Further, as an alternative to a tear-off sheet, a puncturable or penetrable membrane or the like may be provided. As in the first embodiment, the body as supplied contains a certain amount of diluent.

The closure 114 for the container fits over the upper end of the body 112, and has a downwardly extending skirt 120. The skirt 120 of the closure 114 fits around the upper end of the body 112. To ensure that the closure 114 is held securely on the body 112, an inwardly-extending rib 122 is provided on the inner surface of the skirt 120, and this rib 122 co-operates with the peripheral groove 116 to retain the closure. The closure 114 comprises two generally planar members 124, 126, one (126) overlying the other (124). The members are hinged together. Opposite the hinge, the upper member 126 has a lip 128 which extends outwardly further than the lower member 124. The upper member 126 is also provided with a boss 130, which extends through a corresponding aperture 132 in the lower member 124. The height of the boss 130 is the same as the thickness of the lower member 124.

The boss 130 is also provided with means for engaging a capillary split 134, such as a recess 136 for engaging with a pin 138 on the capillary split 134, as shown. The capillary split 134 has a collar 140, which has a greater width than the aperture 132 in the lower member 124. The second embodiment is used as follows-. Firstly, as in the first embodiment, the open end of the capillary passage in the capillary split 134 is contacted with the sample which is to be tested, until a desired amount of the sample has been drawn up into the capillary passage.

When the desired amount of sample has been drawn up, the tear-off sheet 118 is removed from the body 112. The closure 114 is then fitted onto the body 112, and the rib 122 on the closure 114 snaps into place on the groove 116 on the body 112. Again, the "snap" provides a tactile signal to the user that the closure 114 is located correctly. The body 112 with the closure 114 attached is shown in Figure 8b. When the closure 114 has been snapped into place, the container 110 can be shaken to dilute the sample to the desired concentration .

In order to gain access to the diluted sample in the container, the lip 128 of the upper member 126 is lifted. As this is done, the boss 130 of the upper member 126 moves upwardly. Since the capillary split 134 is connected to the boss 130, it also attempts to move upwardly. However, the collar 140 of the capillary split 134 contacts the lower surface of the lower member 124, and so the capillary split 134 is prevented from moving upwardly. As a result, the pin 138 of the capillary split 134 is pulled from the recess 136 in the boss 130, and the capillary split 134 thus detaches from the boss 130 and falls into the body 112. The aperture 132 in the lower member 124 then allows access to the diluted sample in the container 110. The container 110 with the closure 114 open and the capillary split 134 inside the body 112 is shown in Figure 8c.

Since the lower surface of the boss 130 is covered by the collar 140 of the capillary split 134 when the container 110 is shaken, no sample comes into contact with it during the shaking. The lower surface of the boss 130 is therefore clean, and poses no risk of contact with the diluted sample for a user. In addition, no sample contacts the aperture 132 in the lower member 124.

Once the upper member 126 has been lifted to allow access through the aperture 132 in the lower member 124, the desired amount of diluted sample can be removed from the container 110 using a pipette or similar apparatus. When the desired amount of diluted sample has been removed and the test has been completed, the upper member 126 can be pushed downwardly until the boss 130 engages in the aperture 132 to close the container 110. The closed container 110 can then be discarded. The closed container 110 is shown in Figure 8d.

In an alternative version (not shown in the Figures) , the upper and lower members 126, 124 of the closure 114 could be formed as separate members, rather than being hinged together. This gives the advantage of making the aperture 132 in the lower member 124 easier to access, as the upper member 126 can be completely removed rather than still being connected to the lower member 124. However, it is then possible to mislay the upper member 126, and thus not be able to use it to close the container 110. This problem can be avoided by attaching the upper member to the lower member by means of a long flexible member such as a strap or similar, which holds the members together but still effectively allows the upper member to be removed.

As with the first embodiment, the second system can be used on a number of variants . Figures 9 and 10a to lOd show the system used with a body 112a formed by a blow-fill-seal process. The body 112a is formed around a previously moulded mouth part 146a, and has a line of weakness 148a around the mouth 146a, analogous with the first variant of the first embodiment. In the current variant, the upper part of the mouth 146a is formed with a groove 150a for engaging with the rib 122a on the skirt 120a of the closure 114a. There is no need to provide a tear-off sheet, as the body 112a remains sealed until the upper part of it is broken away. As before, the closure has an upper member 126a and a lower member 124a, with a capillary split 134a initially connected to the upper member 126a. A second variant is shown in Figures 11 and 12a to 12d. In this variant, the body 112b is formed from laminated films, which are attached to a previously moulded mouth part 146b. The body is initially closed by a tear-off sheet 118b. As in the first variant, the upper part of the mouth has a groove 150b for cooperating with the rib 122b on the skirt 120b of the closure 114b, and the closure has an upper member 126b and a lower member 124b, with a capillary split 134b initially connected to the upper member 126b. A third variant is shown in Figures 13 and 14a to 14d. Here the body 112c is formed from a suitable plastics material by moulding. As in the second embodiment described above, a groove 116c is provided around the upper part of the body 112c, for engagement with a rib 122c on the skirt of the closure 114c. The body is sealed by means of a tear-off sheet 118c, and the closure has an upper member 126c and a lower member 124c, with a capillary split 134c initially connected to the upper member 126c. A further version of the sample handling device, which does not fall within the scope of the present invention, is shown in Figures 15 and 16a to 16d. It comprises a container 210 formed from a sealed body 212, to which a capillary split 214 is attached, and a removable cap 216.

The body 212 is formed by a blow-fill-seal process, and contains a certain amount of diluent . At the upper end of the body 212 is an external screw thread 218, for engagement with a corresponding internal screw thread 220 on the cap 216. Beneath the external screw thread 218 is a projecting ring 222, whose purpose will be described later.

Projecting from the upper part of the body 212 is a capillary split 214, which points away from the body. The capillary split 214 is fixedly attached to the body 212, in contrast to the first and second embodiments where the split was detachable. The split 214 can be attached to the body 212 during the blow-fill-seal process, by forming the body 212 around the end of the capillary split 214, or can be attached later by conventional fixing means.

The cap 216 has a downwardly extending skirt 224 with an internal screw thread 220, as mentioned above. A tear-off ring 226 is removably attached to the lower end of the skirt 224. The tear-off ring 226 has an inwardly projecting lip 228, which engages beneath the projecting ring 220 on the body 212 to hold the cap 214 in place. The threads 218, 220 on the body and the cap are arranged such that when the lip 228 engages beneath the ring 222, the threads do not engage.

The upper part of the cap 216 is provided with a downwardly projecting annular portion 230, the diameter of which is greater than the capillary split 214. In the version of the sample handling device as shown, the capillary split 214 is mounted on an upwardly projecting region 232, and the diameter of the annular portion 230 on the cap is slightly greater than that of the upwardly projecting region 232. The lower end of the annular portion 230 is formed as a cutting edge 236.

The container 210 as supplied has the cap 216 already connected to the body 212, with the lip 228 of the cap 216 engaged beneath the ring 222 on the body 212. As mentioned above, in this situation the threads 218, 220 on the cap and body are not engaged.

Use of this version of the sample handling device is as follows :

The container 210 as supplied is shown in Figure 16a. As a first step, the user removes the tear-off ring 226. This disengages the lip 228 on the tear-off ring 226 from the ring 222 on the body 212, and since the threads 218, 220 on the body and cap are not engaged the cap 216 can be removed. This exposes the capillary split 214, which is then used to draw up the required amount of sample, as in the first and second embodiments. The container 210 in this state is shown in Figure 16b.

When the required amount of sample has been drawn up, the cap 216 is screwed onto the body 212. As the cap 216 is screwed down, the annular portion 230 of the cap 216 is brought near to the upper part of the body 212. In particular, the cutting edge 236 at its lower end is initially brought into contact with the upper surface, and then further screwing of the cap 216 forces the cutting edge 236 through the upper part of the body 212. As the cutting edge 236 is annular, it cuts a region out of the upper part of the body 212. This region, to which the capillary split 214 is attached, then falls into the inside of the body 212. The cap 216 is screwed onto the body 212 as far as possible, to properly close the container 210. The container 210 with the cap 216 attached and the region of the wall holding the capillary split 214 inside the container 212 is shown in Figure 16c.

The container 210 is then shaken to mix the sample and diluent, and thus dilute the sample to the desired concentration. In order to gain access to the diluted sample, the cap 216 is unscrewed from the body 212. A pipette or similar apparatus can then be inserted through the hole in the upper surface of the body 212 where the region cut out by the cutting edge 236 used to be.

Once the required amount of diluted sample has been withdrawn, the cap 216 can be reattached to the body 212 to close it, and the closed container 210 can then be discarded. The closed container 210 is shown in Figure 16d.

A variant of this version of the sample handling device, which also does not fall within the scope of the present invention, is shown in Figures 17 and 18a to 18d. In this variant, the body 212a of the container is formed from laminated films, to which a preformed mouth portion 238a is attached. The mouth portion has an external thread 218a for engagement with the internal thread 220a on the cap 216a and a groove 240a for retaining the inwardly-projecting lip 228a on the tear- off ring 226a. It also has a weakened portion 242a around the region where the capillary split 214a is attached, to facilitate the removal of the region by the cutting edge 236a. Of course, such a weakened portion 242a can also be used on the body 212 of the version of the sample handling device shown in Figure 15. The operation of the variant is the same as that of the sample handling device shown in Figure 15. A third embodiment is shown in Figures 19 and 20a to 20d. The third embodiment operates in a similar way to the version of the sample handling device shown in Figure 15, but includes additional features.

In the version of the sample handling device shown in Figure 15, in order to mix the diluent and the sample, the container 210 is shaken after the capillary split 214 has been cut free and has dropped into the body 212. During this shaking, the whole of the inner surface of the container 210, including the inner part of the annular portion 230 of the cap 216, is exposed to, and may come into contact with, diluted sample. When the cap 216 is removed to access the diluted sample, its inner surface may be contaminated with diluted sample, and this can pose a risk if the sample contains infectious agents. It is preferable for the cap to be "clean" when it is removed, which requires that no part of the cap as removed comes into contact with the sample, either diluted or undiluted, before it is removed. This is achieved in the third embodiment by modifying the annular portion of the cap. The third embodiment is shown in use on a container 310 whose body 312 is formed from laminated films, as in the sample handling device shown in Figure 17. The preformed mouth 314, the body 312 itself and the capillary split 316 are all generally similar to those used in the device shown in Figure 17, and so will not be described further. However, the annular portion 318 of the cap 320 is formed in a different manner.

In the device shown in Figure 17, the annular portion was formed integrally with the cap. In the third embodiment, there is a separate annular member 318. At its lower end 322, the annular member 318 is barbed, and the barb has a cutting edge 324. The cutting edge is designed to cut through the upper part of the body 312, and the barb is designed to engage underneath the cut part of the wall to hold the annular member 318 in place.

At its upper end, the annular member 318 has a radially inwardly extending portion 326. This lies flush against the inner surface of the top of the cap 320 when the annular member 318 is attached to the cap 320. The annular member 318 is held in place by a retainer 328. The retainer 328 engages against the lower surface of the radially inwardly extending portion 326, and is connected to the cap 320 by means of a pin 330 on the retainer 328 engaging in a recess 332 in the cap 320.

The third embodiment is used in the same manner as the device as shown in Figure 17, up to the stage where the container 310 is shaken to dilute the sample. When the container 310 of the third embodiment is shaken, the inner surface of the container 310 is again coated with diluted sample. The inner surface of the annular member 318 and the lower surface of the retainer 328 are also exposed to the diluted sample. However, it will be noted that no portion of the cap 320 itself is exposed to the diluted sample. This is best shown in Figure 20c.

When the cap 320 is unscrewed to allow access to the diluted sample, the barbs of the annular member 318 retain the annular member in position as the cap 320 moves up. As a result, the annular member 318 is pulled away from the cap 320, and this force is transmitted to the retainer 328. The force is sufficient to pull the pin 330 on the retainer 328 from the recess 332 in the cap 320. Once the pin 330 has been pulled fully out of the recess 332, the retainer 328 falls into the body 312, and the cap 320 can then be fully removed, as there is no longer any engagement between the cap 320 and the annular member 318. Since the annular member 318 and the retainer 328 prevented the cap 320 from being contacted by the diluted sample, the cap as removed is clean and uncontaminated . This is best shown in Figure 20d. Once sufficient of the diluted sample has been removed from the container 310 for the test to be carried out, the container 310 can be closed by screwing the cap 320 onto it. The closed container 310 can then be discarded with no risk of leakage. A variant of the third embodiment is shown in

Figures 21 and 22a to 22d. In the variant, the cap 320a and the mouth 314a of the body 312a of the container are generally similar to the those used in the third embodiment, with the cap having an annular member 318a with a cutting edge 324a and a retainer 328a held in place by pin 330a, and the body having a capillary split 316a. However, the body of the container 312a is formed from a plastics material by moulding. The mouth 314a can be integrally moulded with the body 312a. The operation of the variant is analogous to that of the third embodiment .

A problem which can arise in any of the embodiments and variants stems from the fact that the capillary split drops into the body of the container. As mentioned, the usual way of removing mixture from the container involves the use of a pipette or similar apparatus. However, the presence of the capillary split in the body may cause problems when inserting the pipette into the body, as the capillary split can get in the way of the pipette. In some cases, it may even be necessary to increase the diameter of the body in order to give sufficient room for the pipette to be used. To overcome this, it is possible to arrange for the capillary split to be retained in a particular position in the container, out of the way of a pipette. For example, in the first and second embodiments, the capillary split can be retained to one side of the cap. As an alternative, the split can be broken into pieces when the container is opened. Since these pieces are smaller than the split as a whole, they are less likely to interfere with the pipette.

A further alternative approach to this problem is taken in the fourth embodiment, shown in Figures 23a to 23e. This embodiment comprises a container 410 with a body 412, a closure 414 carrying a capillary member 416, and a spacer member 418. The body 412 has an external screw thread 420 extending around its mouth, which co- operates with an internal screw thread 422 formed on a skirt 424 of the closure 414 to hold the closure on the body. Of course, a rib-an -groove arrangement could also be used, as in the second embodiment.

As best seen in Figures 23b and 23e, the closure is formed from two generally planar members 426 and 428, one (426) overlying the other (428) and hingedly connected at 430, in a similar manner to the closure of the second embodiment. However, unlike the second embodiment, the capillary member 416 is attached to the lower (428) of the planar members. It is therefore unaffected by the opening and closing of the closure, and remains attached to the closure at all times.

In addition, an orifice 430 is formed in the lower member 428. When the closure is in its closed condition, the upper member 426 overlies this orifice 430 and prevents access to the contents of the container. The orifice is initially sealed by a puncturable film. The operation of the fourth embodiment is as follows :

The container is shown in its initial state in Figure 23a. As a first step, the closure 414 is removed from the spacer 418 (see Figure 23b) , and the spacer 418 is removed from the body 412 (see Figure 23c) . The capillary member 416 on the closure is then contacted with the sample to be tested, and a certain amount of the sample is drawn up into the capillary member. The closure 414 is then screwed onto the body 412, and the screw threads 422 and 420 co-operate to ensure that the closure 414 is retained on the body 412 (see Figure 23d) . The container 410 is then shaken or otherwise agitated to ensure that the sample and the diluent are well mixed.

When it is desired to remove some of the diluted sample from the container for testing, the closure 414 is opened by lifting the upper member 426 from the lower member 428, in a similar manner to the second embodiment. This exposes the orifice 430 in the lower member. However, since the orifice is initially sealed by the puncturable film, the container remains sealed after the closure is opened. It is necessary to puncture the film with a pipette 432 or the like before any of the diluted sample can be removed from the container (see Figure 23e) . In addition, the presence of the puncturable film prevents any of the sample in the container from passing through the orifice 430 contacting the upper member 426 of the closure when the container is agitated, and thus ensures that the parts of the closure which a user can come into contact with remain clean.

When the film has been punctured, the pipette 432 can be used to remove diluted sample for testing. Once the testing has been completed, the container 410 is reclosed, and can be discarded.

It will be appreciated that, because the capillary member is retained on the lower member of the closure and does not fall into the body of the container, it does not interfere with the pipette. Thus the process of removing material from the container is made easier. The problem of the capillary member interfering with the pipette when sample is to be removed from the container can also be avoided through the provision of alternative means allowing the mixture in the container to be removed. A passage in the container allowing a drop of calibrated size to be squeezed from the container could for example be used.

A fifth embodiment, which also initially uses a spacer member to prevent the capillary member from coming into contact with the diluent in the sample handling device, is shown in Figure 24. This embodiment comprises a container 510 with a generally cup- shaped body 512, a closure 514 carrying a capillary holder 516, which in turn holds a capillary member 517, and a generally cup-shaped spacer member 518. The spacer member 518 is initially positioned between the body 512 and the closure 514, and the three parts can be retained together as a single item by any convenient means, such as rib-and-groove arrangements as described above. When retained together, the capillary member 517 held by capillary holder 516 projects into a hollow region 520 of the cup-shaped spacer member 518.

The closure itself is generally similar to that of the second embodiment, in that it comprises two generally planar members (522 and 524) which are hingedly attached to each other. A boss 526 on the upper member 522 projects into an orifice 528 on the lower member 524, and a lug 530 on capillary holder 516 fits into a blind bore 532 in the boss 526. A collar 534 on the capillary holder 516 engages with the periphery of the orifice 524. The operation of the fifth embodiment is as follows :

The device is supplied in the state shown in Figure 25a. As a first step, the closure 514 is removed from the spacer member 518 (see Figure 25b) , and since the capillary holder 516 and the capillary member 517 are attached to the closure 514, they are also removed. The spacer member 518 is then removed from the container body 512, as shown in Figure 25c. This exposes the diluent which is held in the container body 512.

The capillary member 517 is then contacted to the sample which must be diluted, to draw up a metered amount. This step is shown schematically in Figure 25d. The closure is then fitted onto the body 512, as shown in Figure 25e. In this state, the material in the capillary member 517 mixes with the diluent in the container body 512, and is diluted to the required amount .

In order to access the diluted sample, the upper member 522 of the closure is lifted from the lower member 524. As in the second embodiment, the boss 526 is pulled upwardly from the orifice 528, but the collar 534 on the capillary holder prevents from moving upwardly with the boss. As a result, the lug 530 is pulled from the blind bore 532, and the capillary holder 516 and capillary member 517 drop into the body 512. It will also be appreciated that the collar 534 prevents any of the sample (diluted or undiluted) from coming into contact with the boss 526, and so the parts of the closure which a user can come into contact with after the closure is opened are clean.

The diluted sample can then be removed from the container using a pipette or the like, as shown in Figure 25f.

Of course, each of the embodiments can be used on various forms of body, and the particular variants illustrated are examples only. In particular, each of the embodiments can be used on bodies formed by laminating films, by blow-fill -seal processes or by moulding plastics material. The shapes of the bodies can be such as to allow them to stand by themselves, or alternatively the bodies can be placed in racks or similar apparatus when it necessary to put them down.

In addition, a number of other variations are possible. For instance, normal capillary tubes can be used instead of capillary splits. The capillary tubes can be connected to the caps or bodies by push-fitting, gluing or the like, or can be integrally moulded in. As an alternative, the tubes can be supplied separately, as in the known methods, and the containers can still have the advantage of being formed such that the cap is protected from contact with the contents of the container by a protective member.

With regard to the first and second embodiments, these are shown as having the sealed container bodies and the closure supplied separately. However, the bodies and closures can of course be packaged together. In addition, it may be possible to supply the closure already on the body, although it is then necessary to ensure that the closure can be removed from the body initially without detaching the metering device therefrom.

In each embodiment and variant, space is provided on the surface of the body for data to be written. These data may, for example, relate to the patient when the container is used in medical testing or the like.

An indication of the manufacturer and such data as batch numbers can also be put on the container.

An important feature is the fact that the cap removed from the container can be "clean", that is, uncontaminated by the mixture in the container. This is achieved through the use of a protective member which shields the cap from the inside of the container, and remains in or attached to the container when the cap is removed . This arrangement can also be used in the first embodiment on the seal . As was mentioned in the description relating to the first embodiment, the body is supplied containing a known amount of diluent. This amount of diluent is such that when a given amount of blood or the like is introduced into it, the blood will be diluted to a given concentration. The amount of diluent is controlled so as to give a desired concentration when the required amount of blood is introduced .

Of course, if the amount of diluent changes, for example because some is lost through spillage or similar, then the concentration of the diluted blood will change. A change in the concentration can affect the results of any test carried out on the diluted blood, which is obviously undesirable, as it can lead to incorrect diagnoses being made. One way in which the amount of diluent can change is through the removal of the seal. If the sealed body has been agitated before use, for example during transport, then the diluent can splash onto the inside of the seal. When the seal is removed, any residual diluent adhering thereto is also removed, and is lost. This can affect the concentration of the diluted sample, and thus the results of any tests carried out thereon. While the effect of this is admittedly likely to be small, it is preferable to avoid it altogether.

One way of avoiding it is to use a protective member to shield the seal from contact with the diluent. The protective member can be attached to the seal in much the same way as the capillary split is attached to the cap. The protective member will then fall into the body of the container when the seal is removed, and any diluent adhering thereto will be mixed in with the remainder. No part of the seal as removed will have come into contact with the diluent, and so there is no risk that any diluent may be lost as a result.

Of course, there are a number of other situations where it is important that a closure, when removed from a container, does not carry any of the contents of the container away with it . This is important not only where it is necessary for the amount of the contents to be conserved, but also when contact with the contents of the container is hazardous, for example when the contents are caustic or otherwise harmful . The use of a protective member on such containers can not only ensure that the closure as removed is "clean", but also ensure that the opening in the container exposed by the removal of the closure is "clean".

In addition, although all of the embodiments and variants have been described in the context of mixing two materials together, more particularly a sample and a diluent fluid, it is possible to adapt the closure to allow more than two materials to be mixed. For example, the closure can have a separate compartment holding a third material, for example a dry powder. The compartment could be opened by twisting part of the closure relative to the rest of the closure to align apertures and allow the third material to flow out. Alternatively, the third material could be disposed in the closure such that when the closure is opened, the material is allowed to enter the container. For example, in the variants of the second embodiment, the third material could occupy the volume 152a, 152b, 152c between the collar on the capillary split and the lower member and the boss of the upper member. Removal of the capillary split from the closure, which occurs as the closure is opened, would then allow the third material to enter the container. Similarly, in the third embodiment and its variant, the third material could be disposed in the volume 334, 334a between the retainer 328, 328a and the lower surface of the top of the cap

320, 320a. As the retainer is pulled away from the top of the cap when the cap is removed, the third material is allowed to enter the container. Several variants of this idea can be envisaged, depending on the particular requirements of any situation.

Claims

1. A container comprising a container body for containing a first material, a closure, and a metering device for holding a metered amount of a second material, one of the container body and the closure carrying or being adapted to carry the metering device, and the container and closure co-operating such that when the closure is used to close the container, the metering device enters the container body, thus allowing the first material to be mixed with the second material, where the parts of the closure which can be contacted by a user after opening of the closure are prevented from coming into contact with the mixture of the first material and the second material .

2. A container as claimed in claim 1, wherein the container body or the closure is arranged to carry the metering device detachably.

3. A container as claimed in claim 1 or 2 , wherein the closure carries or is adapted to carry the metering device prior to closing of the container.

4. A container as claimed in claim 3, wherein opening of said closure to gain access to said mixture detaches said metering device from said closure.

5. A container as claimed in claim 4, wherein said metering device engages with a part of the container body when said closure is opened, this engagement serving to detach said metering device from said closure .

6. A container as claimed in claim 4, wherein said metering device engages with a part of the closure when said closure is opened, this engagement serving to detach said metering device from said closure.

7. A container as claimed in any of claims 3 to 6, wherein said metering device and said closure are formed integrally with each other.

8. A container as claimed in any of claims 3 to 7 , wherein said closure is initially supplied connected to the container body.

9. A container as claimed in claim 8, wherein said closure is connected to a spacer member which is in turn connected to said container body.

10. A container as claimed in claim 1 or claim 2, wherein the container body carries or is adapted to carry the metering device prior to closing of the container .

11. A container as claimed in claim 10, wherein said metering device is detached from the container body when said closure is used to close said container.

12. A container as claimed in claim 11, wherein said metering device is connected to a region of a wall of the container body, said region of said wall being detached from the remainder of said container body when said closure is used to close the container.

13. A container as claimed in claim 12, wherein said region of the wall is detached by a cutting member on said closure.

14. A container as claimed in claim 13 , wherein said cutting member is formed as a separate member from and is detachably attached to said closure, and is detached from said closure when said closure is opened.

15. A container as claimed in any preceding claim, wherein said metering device comprises a capillary passage for receiving said second material .

16. A container as claimed in claim 1, wherein opening of the closure exposes an orifice, said orifice initially being sealed by a puncturable film.

17. A method of mixing a first material and a second material, said method comprising the steps of: providing a container body containing a certain amount of said first material; providing a metering device holding a metered amount of said second material ; and introducing said metering device into said container body, and simultaneously sealing said container body, said container also having a closure such that the parts of the closure which can be contacted by a user after opening of the closure are prevented from coming into contact with the mixture of the first material and the second material .

18. A method as claimed in claim 17, wherein said first material is a diluent, and said second material is a biological sample.

19. A container comprising a closure and a protective member for protecting the closure from exposure to the contents of the container, the arrangement being such that when the closure is opened the protective member is left behind in the container whilst allowing access to the contents of the container.

20. A container as claimed in claim 19, wherein said protective member and said closure are initially attached to each other, and are detached as a result of opening said closure.

21. A container as claimed in claim 19 or 20, wherein said protective member also protects a mouth of the container from exposure to the contents of the container .

22. A closure for a container, in combination with a metering device for holding a metered amount of a material, the closure carrying or being adapted to carry the metering device in such a way that when the closure is used to close a container the metering device is inserted into the container, and where the parts of the closure which can be contacted by a user after opening of the closure are prevented from coming into contact with the material .