The present invention relates to a sensor positioning device for use on a vial in a lyophilisation process comprising a stopper configured for clos ing a neck opening of the vial when mounted thereon, said stopper compris ing: a first part configured for extending into the vial and a second part config ured for extending over the neck opening of the vial, said first part extending away from the second part and having a distal end opposite the second part, and said second part forming an exterior surface of the stopper and having an outer rim delimiting the stopper in a plane extending in parallel with the exte rior surface; a cable passage having a first passage section extending from the distal end towards the exterior surface and allowing a cable of a sensor to pass through the first part of the stopper and a second passage section be tween the first passage section and the outer rim; and at least one vapour opening allowing vapour to escape from the vial. The invention further relates to a sensor unit and to a method of mounting a sensor in a stopper for a vial thereby creating a sensor unit.

A reliable monitoring and validation of lyophilisation processes is cru cial for example within the pharmaceutical industry, where products must be of high and uniform quality. For this purpose, it is important that the sensors used are positioned correctly within the vials during the entire measuring pe riod, and sensor positioning devices have been designed to ensure that this is the case.

One sensor positioning device of the type mentioned above, which has found widespread use, is described in US5,689,895. This positioning de vice relies on a cable probe being arranged in a tube extending from the stopper into the cavity of the vial and being fixated in relation to the stopper and/or the vial. The fixation may be achieved either by clamping the cable in the second passage section, which is an open groove extending away from the first passage section towards the outer rim, or by applying an elastic 0- ring around the neck of the vial so that the cable is clamped between the vial and the O-ring. In practice, clamping the cable in the cable passage has proven to provide an insufficient protection against pull on the cable, and the O-ring is therefore considered necessary to achieve a reliable positioning. The mounting of the O-ring may, however, be difficult since it usually has to be done in a sterile environment where the operator is required to wear thick gloves. It therefore happens that the probe is pulled out of position during the mounting of the O-ring or that the O-ring is not used.

Another positioning device, which does not require the use of an 0- ring, is described in US5,447,374. This positioning device instead relies on a clamping device on the first part of the stopper, and there is some concern that the presence of the clamping device within the cavity of the vial may add thermal mass, which may influence on the readings from the sensor.

It is therefore the object of the invention to provide a sensor position ing device, which reduces the risk of displacement of the sensor with a low risk of influencing on the readings of the sensor.

This object is achieved with a sensor positioning device of the type described above, where the second passage section or a first sub-section thereof extends away from the exterior surface towards the interior surface and is located at a distance from the first passage section in a direction paral lel to the exterior surface. This orientation and position of at least a sub section the second passage section means that when the cable is passed through the cable passage in a tight manner, at least one bent is formed on the cable in addition to the bent occurring where the cable leaves the first passage section. This bent entails that a pull acting on the part of the cable projecting from the sensor positioning device will result in the part of the cable extending from the first passage section to the second passage section or first sub-section thereof being pulled into a tighter contact with the stopper. In contrast a pull acting at an angle to the length direction of the groove serving as the second passage section in US5,689,895 would result in the cable be ing pulled out of the groove. In combination with the bent found where the first and second passage section meet, the bent resulting from the orientation and position of at least a sub-section the second passage section according to the present invention thus serves as a pull relief preventing a displacement of the sensor. Notably, this is achieved using very simple means affecting neither the space available in the vial nor the thermal mass of the sensor positioning device.

In the following, reference will be made primarily to the use of probes, which are essentially cables in themselves, as sensors. It is, howev er, to be understood that it is also possible to use other types of sensors to which a cable is connected, and where the cable is passed through the cable passage, while the sensor itself does not extend into the second passage section.

To maximize the effect, the second passage section or the first sub section thereof may extend in a direction, which is substantially perpendicular to the exterior surface. Any angle of more than 45 degrees between the exte rior surface and the second passage section or the first sub-section thereof will, however, provide some relief.

The elasticity and frictional characteristics of the material used for the stopper will be important factors with respect to determining the pull relief ca pacity. At present silicone, ethylene propylene diene monomer (EDPM), and other synthetic rubbers are considered advantageous as they will allow the entire stopper to be made from one material. It is, however, within the scope of the invention to make the first and second parts of the stopper from differ ent materials and/or to coat the cable passage wholly or partially with a mate rial providing desired frictional characteristics. It is noted that the friction be tween the cable passage and the cable will of course also depend on the sur face characteristics of the cable and that the use of different types of probes or cables may therefore potentially require the use of different stoppers.

In one embodiment, the second passage section or the first sub section thereof extends from an opening in the exterior surface to an opening in the interior surface, i.e. all the way through the second part of the stopper. This will facilitate the insertion of the cable into the cable passage, but it is not a requirement. A more closed cable passage may provide a better protection of the cable and it is even within the scope of the invention to first arrange the cable in the desired shape and then mould the stopper around it. Likewise, the second part of the stopper may be made by arranging the cable in or on a base part and then adding a cover layer onto it, for example by moulding or welding or by means of a glue, an adhesive, or even mechanical fastenings means, such as snap-locking.

A second sub-section of the second passage section extending away from the first passage section towards the outer rim may be provided to ac commodate the cable section extending away from the first passage section. Likewise, a third sub-section of the second passage section may extend from the first sub-section to the outer rim to accommodate another cable section. These sub-sections of the second passage section may help to guide the ca ble during assembly of a sensor unit and/or keep the cable in place ones mounted thus potentially contributing to the fixation of the cable in relation to the stopper.

In one embodiment the second sub-section of the second passage section is a groove in the exterior side of the second part of the stopper and the third sub-section of the second passage section is a groove in the interior side of the second part of the stopper. In use this allows the cable to be mounted in at least two different ways, where a first cable section extends from the first passage section in a direction towards the outer rim, a second cable section extends through the second passage section or the first sub section thereof, and at least one further cable section extending along the second part of the stopper, all cable sections being separated from each oth er by at least one bent.

The first way is to let a first cable section extend in a second sub section of the second passage section from the first passage section to a first sub-section of the second passage section, from there a second cable section extends through the first sub-section of the second passage section, and from there a third cable section extends in a third sub-section from the first sub section of the second passage section to the outer rim. The first, second, and third cable sections are thus arranged in continuation of each other when seen along the length of the cable, and the path followed by the cable has the overall shape of the letter Z. The second way is to let a first cable section extend in a second sub section of the second passage section from the first passage section to the outer rim, from there a fourth cable section extends from the first cable sec tion across the outer rim to the third cable section, from there the third cable section extends in a third sub-section of the second passage section from the fourth cable section at the outer rim to the first sub-section of the second pas sage section, and from there the second cable section extends from the third cable section through the first sub-section of the second passage section. When exiting the first sub-section of the second passage section the cable thus passes by the first cable section and the path followed by the cable has the overall shape of the Greek letter a.

Other ways of mounting the cable, including more complex paths than those described above, are of course possible, but it should be ensured that at least two bents are formed on the cable.

The second part of the stopper may comprise a tab configured for projecting over the neck of the vial in a mounted state, said tab projecting in a direction parallel to the exterior surface of the stopper and substantially in continuation of the second passage section. Such a tab may facilitate han dling of the stopper during mounting of the sensor as the presence of the tab may allow a bigger distance between the first passage section and the sec ond passage section or a first sub-section thereof. This will allow longer cable sections and less bending of the cable during the mounting process. Another advantage of such a tab may be that the additional material provides more space for the second passage section, which may particularly be advanta geous when it comprises two or more sub-sections, and in one embodiment a third sub-section of the second passage section extends into the tab.

A tab as described above may also facilitate handling of the assem bled sensor unit and the mounting of the sensor unit on the vial.

In one embodiment the tab is provided with at least one projection on the interior side, said projection being configured for extending down along an outer side of the neck of the vial in the mounted state of the sensor position ing device. If only a single projection is provided, the second passage section may end on an inner side of the projection so that the cable may be sand wiched between the projection and the outer surface of the neck of the vial, or the second passage section may end in an opening in the projection. Alterna tively, two projections may be provided closely side-by-side so that the cable existing from the second passage section may be clamped between them, thus providing an extra hold on the cable where it exits the second passage section.

The sensor positioning device may form part of a sensor unit further comprising a sensor extending from the first part of the stopper and a cable of the sensor. In such a sensor unit a first cable section extends from the first passage section in a direction towards the outer rim and a second cable sec tion extends through the second passage section or the first sub-section thereof, at least one bent being present on the cable between said first and second cable sections, and at least one further cable section, which extends along the second part of the stopper, is separated from the first and second cable sections by at least one bent.

As described with reference to the sensor positioning device above, the cable may then extend in at least two different ways, which will both result in a fixation of the cable without the need for additional elements. One being where the first cable section extends from the first passage section to a first sub-section of the second passage section, where the second cable section extends through the first sub-section of the second passage section, and where a third cable section extends from the first sub-section of the second passage section to the outer rim, said first, second, and third section being arranged in continuation of each other when seen along the length of the ca ble. Another being where the first cable section extends from the first passage section to the outer rim, where a fourth cable section extends from the first cable section across the outer rim to the third cable section, where the third cable section extends from the fourth cable section at the outer rim to the first sub-section of the second passage section, and where the second cable sec tion extends from the third cable section through the first sub-section of the second passage section. To facilitate the mounting of the cable, the first cable section may ex tend along the exterior surface of the second part of the stopper and the third cable section extend along the interior surface of the second part of the stop per.

In a second aspect of the invention the object of the invention is achieved with a method of mounting a sensor including a cable in a stopper for a vial thereby creating a sensor unit for use on a vial in a lyophilisation process, where said stopper is configured for closing an opening in a neck of the vial when mounted thereon, said stopper comprising: a first part configured for extending into the vial and a second part configured for extending over the opening of the vial, said first part extending away from the second part and having a distal end opposite the second part, and said second part having an exterior surface forming an exterior surface of the stopper in the mounted state, an interior surface opposite the exterior sur face configured for abutting on the neck of the vial, and an outer rim delimiting the stopper in a plane extending in parallel with the exterior surface, a cable passage having a first passage section extending from the distal end towards the exterior surface and a second passage section be tween the first passage section and the outer rim, and at least one vapour opening allowing vapour to escape from the vial, said method comprising the following steps:

A) arranging the sensor so that it projects from the distal end of the first part of the stopper, and

B) passing the cable of the sensor through the cable passage, characterized in that step B) comprises the following sub-steps: arranging a first cable section so that it extends from the first pas sage section in a direction towards the outer rim, arranging a second cable section so that it extends through the sec ond passage section or a first sub-section thereof, said second passage sec tion or first sub-section thereof extending away from the exterior surface to wards the interior surface and being located at a distance from the first pas sage section in a direction parallel to the exterior surface, creating at least one bent on the cable between said first and second cable sections, arranging at least one further cable section so that it extends along the second part of the stopper, and creating at least one further bent on the cable between the at least one further cable section and the first and/or second cable sections.

The sub-steps of step B) do not necessarily need to be performed in the order mentioned and it is to be understood that the creation of the bents may include further sub-steps. The insertion of the cable may result in the creation of a soft bent, which is later made sharper by tightening the cable so that it follows the shape of the cable passage and/or surfaces of the stopper.

The embodiments and advantageous of the invention described with reference to the first aspect of the invention also applies to the second as pect.

In the following the invention will be described in more detail with ref erence to embodiments shown in the drawing, where:

Fig. 1 is a cross-sectional view of a sensor unit mounted on a vial,

Fig. 2 is a perspective view of the sensor unit and vial in Fig. 1 ,

Fig. 3 is a perspective view of the stopper used in the sensor unit in Figs 1 and 2,

Fig. 4 is a cross-sectional view of another sensor unit mounted on a vial,

Fig. 5 is a perspective view of the sensor unit and vial in Fig. 4, and Fig. 6 is a perspective view of the stopper used in the sensor unit in Figs 4 and 5.

A sensor unit 1 comprising a sensor positioning device 2 mounted on a vial 3 for use in a lyophilisation process is shown in a cross-sectional Fig. 1 and in a perspective view in Fig. 2. The sensor positioning device comprising a stopper 4 closing the opening in the neck 31 of the vial by being arranged with a first part 41 extending into the vial and a second part 42 extending over the opening of the vial. The second part 42 has an exterior surface 421 form ing an exterior surface of the stopper in the mounted state, an interior surface 422 opposite the exterior surface abutting on the neck 31 of the vial, and an outer rim 423 delimiting the stopper in a plane extending in parallel with the exterior surface.

A sensor 5 extends from a distal end 411 of the first part opposite the second part, and a cable 51 of the sensor extends through a cable passage 6 in the stopper. In this embodiment the sensor 5 is a probe in the form of a thermo couple comprising two dissimilar electrical conductors forming an electrical junction. Such a sensor may be said to constitute a cable in itself, and in the following reference will therefore only be made to the cable 51. In this embodiment a tube 7 extends from the distal end 411 of the stopper 4 towards the bottom 32 of the vial and supports the cable 51 such that the end of the cable, and hence the sensing point of the sensor, is kept in a well- defined position above the bottom 32 of the vial.

The cable passage 6 consists of a first passage section 61 extending through the first part 41 of the stopper and a second passage section 62 ex tending through the second part 42 of the stopper. In this embodiment the tube 7 extends into the first passage section 61 and the part of it, which ex tends away from the stopper, serves as a continuation of the first passage section 61. This provides good support for and protection of the probe, but the tube is not strictly necessary, particularly not if using a different type of sen sor.

In this embodiment the stopper 4 and the tube 7 together constitute a sensor positioning device 2 as seen in Fig. 3, but a stopper may also consti tute a sensor positioning device on its own.

While the first passage section 61 extends from the distal end 411 towards the exterior surface 421 and follows a linear path, the second pas sage section 62 is found between the first passage section and the outer rim and allows the cable to follow a non-linear path. In the embodiment shown in Fig. 1 the second passage section 62 comprises three sub-sections 621, 622, 623 each accommodating a section of the cable. A first cable section 511 ex tends from the first passage section 61 to a first sub-section 621 of the sec ond passage section, a second cable section 512 extends through the first sub-section 621 of the second passage section, and where a third cable sec tion 513 extends from the first sub-section 621 of the second passage section to the outer rim 423. The path followed by the cable through the second pas sage section thus has the overall shape of the letter Z, and is bent at 90 de gree angles where it enters and exits the first sub-section 621 of the second passage section.

In this embodiment the first cable section 511 is accommodated in a second sub-section 622 of the second passage section, which is a groove in the exterior side of the second part of the stopper, as may be seen in Fig 3, and which extends away from the first passage section towards the outer rim. It is, however, also possible to simply let the first cable section 511 extend over the exterior surface 421 of the stopper without being inserted in a groove or the like. Likewise, the third cable section 513 is here accommodated in a third sub-section 623 of the second passage section, which is a groove in the interior side of the second part of the stopper and extends from the first sub section to the outer rim, but it might instead simply be sandwiched between the interior side of the stopper and neck of the vial in the mounted state.

In the embodiment shown in Figs. 1-3 the second part of the stopper comprises a tab 424 projecting in a direction parallel to the exterior surface and over the neck 31 of the vial 3 in a mounted state. The tab projects sub stantially in continuation of the second passage section and the third sub section 623 continues into the tab. As best seen in Figs. 1 and 3 the presence of the tab 424 allows that first sub-section 621 of the second passage section to be provided at a bigger distance D from the first passage section 61 than would otherwise have been possible considering that a certain amount of ma terial must be present between the first sub-section and the outer rim 423. This allows the second and third sub-sections 622, 623 to be longer than oth erwise possible, which facilitates the mounting of the cable 51 on the stopper 4. Another advantage of the tab 424 is that it may facilitate handling of the sensor unit.

The tab 424 is here provided with two projection 425 on the interior side, one on each side of the third sub-section 623 of the second passage section. In the mounted state these projections extend down along an outer side 33 of the neck 31 of the vial 3 as is seen in Fig. 1, thus potentially con tributing to the positioning of the sensor unit in relation to the vial. The two projections further serve as a fixation for the cable 51 , which can be clamped between them where it exits the stopper. In this way they contribute to keep ing the cable in the third sub-section of the second passage section and they may further provide a strain relief reducing the risk of damages to the cable. The latter particularly applies if the stopper 4 or at least the projections 425 are made from an elastic material, such as rubber.

Turning now to Figs 4-6 a second embodiment of the invention is shown. Figs 4-6 correspond to Figs 1-3 except for showing a different embod iment, and the same reference numbers have been used for features being identical and/or having the same function. In the following, only the features which are different from the embodiment in Figs. 1-3 will be described.

In Figs 4-6 the second sub-section 622 of the cable passage 6 ex tends all the way from the first passage section 61 to the outer rim 423 of the second part 42 of the stopper 4 and a fourth sub-section 624 of the second passage section extends across the outer rim down to the third sub-section 623. The cable extends the from the first passage section through second sub-section 622, then down through the fourth sub-section 624 across the outer rim, then through the third cable section, and finally through the first sub-section 621 to the exterior side. In this embodiment the cable is bent three times, each over approximately 90 degree, and the path followed by the cable resembles the Greek letter a.

As the cable exits the stopper at the exterior side there is no need for the clamping function of the projections 425 described with reference to Figs 1-3 and they have therefore been left out in this embodiment.

As is best seen in Figs 3 and 6 the cable passages 6 are in both stoppers 4 independent of the vapour openings 44, which are configured for allowing vapour to escape from the vial during a lyophilisation process, so that escape of vapour is not affected by the presence of the cable.

Further embodiments and combinations of features are possible with- in the scope of the claims.