WO2005046485A1

WO2005046485A1 - Sampling device, method of producing a sampling device and use of a sampling device

Info

Publication number: WO2005046485A1
Application number: PCT/SE2004/001646
Authority: WO
Inventors: Klas Stoltz
Original assignee: FäRGKLäMMAN AB
Priority date: 2003-11-12
Filing date: 2004-11-12
Publication date: 2005-05-26

Abstract

Abstract The present invention relates to a sampling device (2) for obtaining samples of substances, which device (2) allows a sample of the substance to enter the device (2) through inlet opening(s) (4) into an inner chamber (8) of the device (2). The inlet opening(s) (4) are provided with sealing means (3) that is disposed to preserve a vacuum or substantial underpressure in the inner chamber (8) when the inlet opening(s) (4) are sealed. The sealing means (3) is adapted to be in a sealing position at a first predetermined location at which flow (6) of substance through the inlet opening(s) (4) is prevented and is adapted to be in an opening position at a second predetermined location at which flow (6) of substance is permitted through said inlet opening(s) (4) and into the inner chamber (8).

Description

Sampling device, method of producing a sampling device and use of a sampling device

Field of the invention The present invention relates to a sampling device for obtaining samples of substances in places where sampling is particularly inaccessible, for instance the digestive system of humans or animals, the sample obtained being a sample of internal body substance. The sampling device allows a sample of the substance to enter the device through a number of inlet opening(s) which are sealed when the sampling device is at a first predetermined location and open when the sampling device is at a second predetermined location. The invention also relates to a method of producing the sampling device and use of said sampling device for obtaining samples of internal body substances.

Background of the invention Obtaining samples of substances in places which are particularly inaccessible is a problem in many situations. For instance the sampling of internal body substances, gases or solid particles in the digestive system or the gastrointestinal tract in the human or animal body. These substances provide essential medical information for diagnosing and treatment. Examination of a sample of the gastric fluid of a patient provides important information of pH, acid contents, abdominal enzyme activity as well as information for diagnosing gastric ulcer and gastritis, cancer and tumour diseases, etc. A gastroscopic examination gives the physician who is treating a patient important information and plays a great role for a diagnosis. These intubation examinations are thus used extensively. A gastroscopic examination, in which a tube, having a diameter of a little finger, is inserted into the patient's mouth or nose, through the oesophagus and to the gastrointestinal system, is difficult to perform and demands the assistance of a physician. For the patient, the intubation of the digestive tract using these methods is a very un- pleasant intervention, both physically and psychologically, especially during the insertion of the tube and also when it is pulled out. The intubation demands that the patient is given a local anaesthetic and in some instances even tranquilliser or a general anaesthetic to overcome the stress to which the patient is subjected. The intubation examination methods described above are disadvantageous since they are very time- consuming for a qualified physician and thus expensive and a very unpleasant intervention for the patient. WO 02/ 102243 Al describes a sampling device for obtaining samples of internal body substances, which allows a sample of the body substance to enter the device through an inlet opening which is opened at predetermined position of the digestive tract following contact with the body substance to be collected. This is accomplished through the sealing of the inlet opening with a plug made of a material which is chosen depending on the specific body fluid to be collected. Following contact with said fluid the plug is dissolved and fluid flows into the device by the force of a substantial underpressure in the device. When the device is filled, the inlet opening is automatically closed, sealing it from the inside of the device, such that the sample remains in the device. This is accomplished through an elastic blocking member , resiliently movable between a flow permitting and a flow preventing configuration. The sampling device of WO 02/ 102243 Al is advantageous in many ways. However, the method of producing the device requires the assembling of the different parts of the device in a vacuum chamber, which results in unnecessarily complicated production steps and thus high production costs. Summary of the invention The object of the present invention is to provide a sampling device being just as reliable and easy to use as the sampling device of WO 02/ 102243 Al but which is simpler and less expensive to produce.

The sampling device according to the present invention is not limited for use in the digestive system or the gastrointestinal tract in the human or animal body, but can be used for obtaining samples of substances in many otherwise inaccessible places.

These objects are achieved by a device according to the preambles of the independent claims and provided by the features according to the characterising portions of the independent claims. Preferred embodiments are set forth in the dependent claims.

Moreover, if the device of the present invention would get caught in the body of the patient, it contains, according to a preferred embodiment, a minor part of an X-ray opaque material which ensures that the position of the sampling device is detectable during an X-ray examination.

In accordance with the present invention, the sampling device is provided with sealing means that, when at a first predetermined location, is in a sealing position of a number of inlet opening(s) of the sampling device. When the sampling device is at a second predetermined location, the sealing means is moved to an opening position of the inlet opening(s). The sample of the substance to be taken flows into an inner chamber of the device through the inlet opening(s) by the force caused by a vacuum or substantial underpressure in the inner chamber when the sealing means is in the opening position. The sampling device according to the invention is simple and is ^• made of a few parts. The parts can be assembled in practically any environment of choice, with only one step requiring vacuum. Short description of the drawings The invention will be described in greater detail below with reference to the attached drawings, in which: Figure 1 is a schematic sectional view of a sampling device of the invention, in a first closed and sealed state, Figure 2 shows the sampling device of Figure 1 in a second, open state, with the substance flowing into the device, Figure 3 shows the top part of the sampling device, partly from above. Figure 4 shows a schematic sectional view of the sampling device according to a first preferred embodiment of the present invention, Figure 5 shows a schematic sectional view of the sampling device in a variation of the first preferred embodiment of the present invention, Figure 6 shows the membrane, from above, Figure 7 shows the pushing part partly from above. Figure 8 shows a schematic sectional view of the sampling device in an embodiment with assisting pushing means, Figure 9 shows a schematic sectional view of the sampling device in an alternative embodiment, Figure 10 shows the sampling device in another alternative embodiment with the device having inlet openings at each side. Figure 11 shows the sampling device in a second preferred embodiment, the left hand side shows the device in an open state and the right hand side shows the device in a closed and sealed state. Figure 12 shows a schematic sectional view of the sampling device in yet an alternative embodiment. Detailed description of embodiments of the invention As seen from Figure 1 the sampling device 2 is preferably elongated with rounded end portions and preferably has a circular or oval- shaped cross-section. The device 2 further comprises sealing means 3 which is in a sealing position of inlet opening(s) 4 of the device 2 when said device 2 is in the closed and sealed state and which is in an opening position of the inlet opening(s) 4 when the device 2 is in the open state shown in Figure 2, in which open state a flow 6, indicated by arrows, of substance is permitted through the inlet opening(s) 4 and into an inner chamber 8 of the device 2, defined by a device wall and the sealing means 3. As long as the device 2 is in the closed and sealed state, a vacuum or substantial underpressure prevails in the inner chamber 8 but when the device 2 is in the open state, a suction effect is generated by the pressure difference between the external environment of the device 2 and the inner chamber 8. This suction effect forces substance in the external environment of the device 2 to flow 6 into the inlet opening(s) 4.

As seen from Figure 3, a number of inlet opening(s) 4 are arranged on the top part 9, marked out by the dashed lines in Figure 1-2, as well as along the circumference of the mantle part of the top part 9. Preferably, the inlet opening(s) are equally distributed on the top part 9. The number of inlet openings is preferably 1- 10. The movement of the sealing means 3 from the sealing position to the opening position of the inlet opening(s) 4 is accomplished by a moving means, which in a first preferred embodiment comprises temperature activated element 10, 11 in Figure 1-2, 4, 8-10 and Figure 5, respectively. The temperature activated element 10, 11 is made of a material, which upon reaching a certain temperature range, i.e. a second predetermined temperature range, undergoes a predefined deformation. Preferably, the deformed shape will be kept until the material returns to the original temperature range, i.e. the first temperature range, in which the material regains it original shape. Such a material is known as a shape memory material with a two way memory, and is for instance a metal, a bimetal, an alloy of for instance TiNi or a polymer. The deformation can be for instance an elongation, a shortening, a bending, a torsion etc. The temperature at which the material starts to deform, i.e. lower limit of the second temperature range, varies from one material to another but lies within the wide temperature range of -20°C to +120°C.

The temperature activated element 10, 11 can also be made of a shape memory material with a one way memory. In this case, the temperature activated element 10, 11 undergoes said deformation upon reaching the lower limit of the second temperature range but will not regain its original shape when returning to the first temperature range but stay in the deformed shape.

The present invention according to a first preferred embodiment is shown in Figure 4 in the closed and sealed state, i.e. when within the first temperature range. In figure 4, the temperature activated element 10 is in the shape of a helix- formed spring comprised in the inner chamber 8 of the device 2. When the device is subjected to the second temperature range, the temperature activated element 10 performs a movement, acting on the sealing means 3 such that it moves from the sealing position to the opening position. The movement is in this case the elongation of the temperature activated element 10 in the shape of a helix-formed spring, i.e. the helix-formed spring pushes the sealing means 3 in an upwards directed motion.

In figure 5, which shows the present invention according to the first preferred embodiment, the temperature activated element 11 is in the shape of one or many rods, for instance, three or four rods 11 are fastened in the same plane at the inner surface of the inner chamber 8 at equally distributed positions. Preferably, the rods 11 are attached by welding or brazing approximately in the radial direction at the inner periphery of a circular ring-shaped member (not shown) supported in a recess of the inner wall of the inner chamber 8. The movement in this case, i.e. when the device 2 is subjected to the second temperature range, is the upwards directed bending of the rods 11 , moving or pushing the sealing means 3 from the sealing position to the opening position.

The helix- formed spring 10, or the rods 11, are preferably made of a temperature activated material with a two way memory and regain the shape they had before being subjected to the second temperature range when once again subjected to the first temperature range, the movement acting on the sealing means 3 which causes it to move to the sealing position.

There are of course several other possible designs of the temperature activated element, regardless whether the temperature activated material has a one way memory or a two way memory, provided that the temperature activated element is able to perform the movement acting on the sealing means moving it from the sealing position to the opening position. Naturally, the structural design of the sealing means 3 and of the temperature activated element 10, 11 are adopted to each other.

In the embodiment shown in Figure 4, a membrane 12 having a two-way valve function is positioned between the inlet opening(s) 4 and the sealing means 3. The membrane 12, as seen in greater detail in

Figure 6, is preferably a disc made of an elastic material, such as Siθ2, provided with one or more foldable, normally sealed, openings achieved by foldable parts 14 . When the sealing means 3 moves to the opening position, the suction effect generated by the pressure difference between the external environment of the device 2 and the inner chamber 8, causes the foldable parts 14 to fold downwards along the dashed lines 15 admitting flow 6 of substance into the inner chamber 8 as long as there is a pressure difference between the external environment of the device 2 and the inner chamber 8. As the external and internal pressure of the device 2 equalise and the substance fills up the inner chamber 8, the foldable parts 14 gradually folds back to its original shape. As soon as the substance has filled up the inner chamber 8, the membrane secures that essentially all flow of substance out from the inner chamber 8 is prevented.

Moreover, in the embodiment shown in Figure 4, the sealing means 3 is made of two parts, i.e. a sealing part 16 and a pushing part 17. The sealing part 16 is preferably somewhat elastic to ensure a tight fit against protrusions 18 on the inner side of the device wall and the pushing part 17, which is the part that the temperature activated element 10, 11 acts on, are more firm. Naturally, the sealing means 3 can be made in one piece that includes the sealing part 16 and the pushing part 17.

Figure 7 shows the pushing part 17 in greater detail. The pushing part 17 preferably has the shape of a "top hat", i.e. a hollow cylindrical part 19 with a wider bottom or "brim" 20. The pushing part 17 has openings 21 equally distributed around the brim 20 as well as around the mantle of the cylindrical part 19, through which openings 21 substance is flowing into the inner chamber 8 of the device 2 when the sealing means 3 is in the opening position and as long as a pressure difference prevails between the external environment of the device 2 and the inner chamber 8. Moreover, in the embodiment shown in Figure 4 as well as in the alternative embodiment of Figure 9, the device 2 is made of a cap member 23 and a body member 25 to facilitate assembling of the device which will be described below. However, these members 23, 25 can naturally be in one piece.

Also shown in the embodiment of Figure 4, a recess 26 is made in a section of the device wall, preferably at the bottom end, which is filled with for instance a soft, easily penetratable material, such as silicon rubber. This recess 26 can be used when the substance in the inner chamber 8 shall be evacuated from the device 2. An evacuation needle then, directly or indirectly connected to an instrument for examination and analysis of the substance, penetrates the recess 26 of the chamber wall and empties the inner chamber 8. The recess 26 can also be made not all the way through the device wall but saving a thin partition 30 of said wall, as seen in Figure 9, which partition 30 is thin enough to be penetrated by conventionally used evacuation needles. The recess 26 seen in Figure 9, is optionally filled with the above mentioned soft, easily penetratable material.

In the embodiment shown in figure 8, second moving means 27, preferably in the shape of a helix- formed spring, is arranged between the membrane 12 and the sealing means 3. When the sealing means 3 is in the sealing position, the second moving means 27 is in a first tensed state and when the sealing means 3 moves to the opening position, the second moving means 27 is forced to a second tensed state, i.e. the pressure load on the second moving means 27 is greater in the second tensed state than in the first tensed state. However, the pressure load on the second moving means 27 in the first tensed state, may not be greater than that the temperature activated element 10, 11 may be able to move the sealing means 3 from the sealing position to the opening position when said element 10, 11 adopts a temperature within the second temperature range. Thus, when the sealing means 3 is about to return to the sealing position, i.e. when the substance has filled up the inner chamber 8 and/ or when the device 2 is subjected to the first temperature range, the second moving means 27 spontaneously assists the movement of the sealing means 3 back to the sealing position. This is particularly preferred when the temperature activated element 10, 11 is made of a shape memory material with a one way memory, since the temperature activated element 10, 11 spontaneously will not regain its original shape when once again being subjected to the first temperature range when being in the second temperature range. The second moving means 27 may of course have other possible designs other than in the shape of a helix-formed spring, as long as it is adopted to spontaneously assist the movement of the sealing means 3 to the sealing position. For instance in the shape of one or more resilient rods.

Moreover, also shown in the embodiment of Figure 8, plugs 28 are arranged in the opening(s) 4. A plug 28 is made of at least one material which is chosen depending on the application of device and which will dissolve upon contact with the substance that is to flow 6 into the inner chamber 8 of the device 2. This will be described in greater detail below. Naturally, the plugs 28 are not restricted to be arranged in the embodiment of the device 2 shown in Figure 8, but can be arranged in all embodiments of the present invention.

An alternative embodiment is shown in Figure 9, in which the temperature activated element 10 is positioned above the inner chamber 8 and the membrane 12 is positioned inside the inner chamber 8. In this embodiment the membrane 12 may have the shape of a disc that has a slit 29, preferably at the centre, which admits flow 6 of substance into the inner chamber 8 as long as there is a pressure difference between the external environment of the device 2 and the inner chamber 8. As soon as the external and internal pressure of the device 2 have been equalised and the substance has filled up the inner chamber 8, the membrane 12 secures that flow of substance out from the inner chamber 8 is prevented.

Naturally, in this embodiment the temperature activated element can be in the form of rods 11 as shown in Figure 5, and the membrane 12 can be positioned between the sealing means 3 and the inlet opening(s) 4 as in the preferred embodiment of Figure 4. Likewise, the membrane 12 can have the design as shown in Figure 6.

Another alternative embodiment of the device 2 is shown in Figure 10. In this embodiment the device has a second inlet opening(s) 4, provided with second sealing means 3 and a second membrane 12. The sampling device 2 has an elongated cylindrical form with a first end and a second end, with said second inlet opening(s) 4, said second sealing means 3 and said second membrane 12 provided in said second end.

In still another alternative embodiment of the invention, protrusions are disposed externally on the device 2 at the inlet opening(s) 4, not shown in any figure, such that laterally directed inlet grooves are formed between the protrusions.

A second preferred embodiment of the present invention is shown in figure 11 , the left hand side showing the sampling device in an open state and the right hand side showing the sampling device in a closed and sealed state. In this second preferred embodiment, the moving means comprises pushing means 31 arranged in the upper part of the device 2 in connection with the sealing means 3. The pushing means 31 consists of, for instance a spring as shown in figure 11 , which is in the tensed state as well as a non-moving state when the sealing means 3 is in the sealing position. The spring is held in the tensed and non-moving state by holding means (not shown). The holding means may for instance be a glue or the like and/ or one or more threads, holding the pushing means 31 in the tensed and non-moving state. The glue and/ or the threads is /are preferably made of at least one material that is chosen depending on the application of device. This material(s) will dissolve upon contact with the substance that is to flow 6 into the inner chamber 8 of the device 2, which results in the removal of the holding means whereupon the pushing means 31 shifts to its relaxed state, pushing/ moving the sealing means 3 to the opening position, i.e. a moving state of the pushing means 31. The material of the glue /thread is in the preferred use, i.e. collecting a sample of internal body substance from the digestive system of humans or animals, for example, gelatine, molten sugar, salt, glue, organic edible materials or any other suitable material. In this second preferred embodiment, the device 2 is preferably provided with a membrane 12 inside the inner chamber 8, preferably interposed in the protrusions 18, in order to secure a tight sealing fit, preserving the vacuum in the inner chamber 8. Sealing joints 33 may also be present in order to further secure the preserving of said vacuum. The membrane 12 preferably having the design as shown in Figure 6 or as explained in connection with Figure 9. Also in this second preferred embodiment, a recess 26 is made in a section of the device wall, preferably at the bottom end, which is filled with for instance a soft, easily penetratable material, such as silicon rubber, as explained above in reference with figure 4. The filled recess 26 may optionally be replaced by a non-return valve (not shown).

In the second preferred embodiment the sealing means 3 is designed in accordance with the pushing means 31. The sealing means 3 secures that flow 6 into and out from the inner chamber 8 is prevented when the sampling device is in the closed and sealed state and that flow 6 into the inner chamber 8 is effectively established when the device 2 is in the open state (as long as there is a pressure difference between the external environment of the device 2 and the inner chamber 8 as explained above), i.e. when the holding means has been removed and the pushing means 31 has pushed the sealing means 3 in a upwards directed motion, establishing a flow path from the external environment of the device 2, through the inlet opening(s) 4 and into the inner chamber 8, through the membrane 12.

Also in the second preferred embodiment, second moving means 27 may be arranged in connection with the sealing means 3, for instance arranged inside the device 2 between the sealing means 3 and the top of device 2 as seen in figure 11. The second moving means 27, preferably in the shape of a helix-formed spring, is in a first tensed state when the sealing means 3 is in the sealing position and when the sealing means 3 moves to the opening position, the second moving means 27 is forced to a second tensed state, i.e. the pressure load on the second moving means 27 is greater in the second tensed state than in the first tensed state. However, the pressure load on the second moving means 27 in the first tensed state may not be greater than that the pushing means 31 may be able to move the sealing means 3 from the sealing position to the opening position when the holding means has been removed. Thus, when the substance has filled up the inner chamber 8, the second moving means 27 spontaneously assists the movement of the sealing means 3 back to the sealing position.

In yet another embodiment, shown in figure 12, the inlet opening(s) 4 is provided with a plug 28 made of a material that will dissolve upon contact with the substance to be collected, as described above. A sealing plug 35 is provided inside the device 2 in a sealing contact with the inlet opening provided at the top of the device 2, thus the sealing plug 35 is preferably made of a soft, air- and watertight material, such as silicon rubber. The sealing plug 35 is further designed in order to co- operate with a preferably conically shaped spring 37, arranged between the sealing plug 35 and the inner chamber 8. In this embodiment, the device is further provided with the membrane 12 above the inner chamber 8 and optionally a screen 39 preferably arranged above the membrane 12. The membrane 12 preferably having the design as shown in Figure 6 or as explained in connection with Figure 9. Also in this embodiment, a recess 26 is made in a section of the device wall, preferably at the bottom end, which is filled with for instance a soft, easily penetratable material, such as silicon rubber, as explained above in reference with figure 4. The filled recess 26 may optionally be replaced by a non-return valve (not shown).

When the plug 28 dissolves upon contact with the substance to be collected, the underpressure inside the inner chamber 8 is sufficient enough to compress the spring 37 which pulls the sealing plug 35 in a downwards directed motion, allowing a flow of substance to enter the device 2. The screen 39 effectively prevents large particles or the like to block the membrane 12, which due to the suction effect generated by the underpressure allows substance to enter the device, as explained in closer detail in reference to figure 4. When the substance has filled up the inner chamber and thus equalised the external and internal pressure of the device 2, the spring 37 returns to its initial state pushing the sealing plug 35 back to its sealing position of the inlet opening at the top of the device 2.

When collecting a sample of a substance, the sampling device 2 is taken from a first predetermined location and put at the particular location from which environment a sample is to be taken, i.e. the second predetermined location. In the preferred use of the sampling device 2, i.e. sampling of internal body substance from the digestive system of humans or animals as discussed below, this is accomplished by simply swallowing the device 2. The second predetermined location, must secure that, in the first preferred embodiment of the invention, the temperature activated element 10, 11 reaches the said second temperature range, at which the element performs the above mentioned deformation, such that the sealing means 3 moves to the opening position of the inlet opening(s) 4.

In the second preferred embodiment of the invention, the environment of the second predetermined location must ensure removal of the holding means so that the pushing means 31 may be able to pull the sealing means 3 to the opening position of the inlet opening(s) 4.

As soon as the substance has filled up the inner chamber 8, the device 2 can be removed from the second predetermined location where the sample was taken. In the preferred use of the sampling device 2, the device 2 is removed from the second predetermined location by ways of natural means, i.e. the device 2 is fed through the gastrointestinal tract and is recovered from the fecies of the patient. If the temperature activated element 10, 11 in the first preferred embodiment is made of a temperature activated material with a two way memory, the temperature activated element 10, 11 regains its original shape when again subjected to the first temperature range and the sealing means 3 moves to the sealing position of the inlet opening(s) 4. If the temperature activated element 10, 11 is made of a temperature activated material with a one way memory, the membrane 12 still secures flow of substance out from the inner chamber 8 of the device 2. Also in the second preferred embodiment, the membrane 12 effectively prevents flow of substance out from the inner chamber 8 of the device 2. In a preferred use of the sampling device 2 according to the present invention, the substance to be taken is a sample of internal body substance from the digestive system of humans or animals. The sampling device 2 preferably having the shape of a swalloable capsule, such as a conventional pharmaceutical capsule, and thus suitable for ingestion. When an examination of a body fluid in the digestive system is required, the patient swallows the sampling device 2, which is in the closed and sealed state of Figure 1, without any stress or pain. The device 2 passes the oesophagus and enters into the stomach. During the passage of the device 2 from the mouth to the stomach the patient feels no more discomfort than he feels when he swallows an ordinary pharmaceutical capsule, i.e. a discomfort which is principally non- existing.

The sampling device 2 is according to the present invention provided with features preventing it from getting stuck, for instance in the intestines, by the suction forces generated by the internal underpressure. This is achieved by inlet opening(s) 4 distributed along the circumference of the mantle part of the top part 9 of the device 2 that secure that flow of substance always is permitted and accordingly the device 2 will not get stuck by the forces of vacuum inside the device 2. Moreover, by having several inlet opening(s) 4 it is secured that substance may enter the device 2 even though one of the inlet opening(s) 4 is being blocked by for instance a large particle of some sort.

Also the embodiment seen in Figure 10 with the device 2 having inlet opening(s) 4 at the first and at the second end of the device, secure the device 2 from being adhered to, for instance the walls of the digestive system in a similar way.

Even the embodiment with protrusions disposed externally on the device 2 at the inlet opening(s) 4, prevent the device 2 from getting stuck since the protrusions always secure a free flow of substance through the inlet grooves into the device 2. The size of the device 2 may vary depending on the volume of body fluid required for the examination and analysis. A suitable size of a device 2 which is easy to swallow has, for example, a length of about 25 mm and a width of about 10 mm. Thus, a typical volume that is to be collected is approximately 0,4 -1 ml.

In the preferred use of the present invention according to the first preferred embodiment, the temperature activated element 10, 11 may be of such a material, that the temperature of the human or animal body, that is typically 35-40°C, is within the second temperature range of said temperature activated material, so that the sealing means 3 moves from the sealing position to the opening position in the gastrointestinal tract of the body. The device 2 then is filled up with body substance, in a way previously described, is fed through the gastrointestinal tract and is recovered from the fecies of the patient. Once outside of the body, the temperature activated element 10, 11 is subjected to the first temperature range and, if the temperature activated element 10, 11 is made of a temperature activated material with a two way memory, regains its original shape and the sealing means 3 moves to the sealing position. If the temperature activated element 10, 11 is made of a temperature activated material with a one way memory the membrane 12 still secures flow of substance out from the inner chamber 8 of the device 2 and if the device 2 is provided with the second moving means 27, said second moving means 27 will assist the movement of the sealing means 3 back to the sealing position.

The temperature activated element 10, 11 may also be of such a material, that a temperature within the second temperature range is substantially higher than the temperature of the human or animal body. In that case, the temperature activated element 10, 11 is an electrically conducting material, which may reach the second temperature range by means of inductive heating. For instance, if the present invention according to the first preferred embodiment is used in its preferred use, an induction coil or the like may be applied adjacent to the patients body, preferably in the abdominal region. When the coil is operated in a suitable way, the generated electromagnetic field will increase the temperature of the temperature activated element 10, 11 to a temperature within the second temperature range. The position of the sampling device 2 inside the body may be visible, for instance by means of X-ray, so that the electromagnetic field induced by the coil is applied at a suitable time, i.e. when the sampling device is localized at a suitable place, for instance in the small intestine where sampling otherwise is extremely difficult.

In the preferred use of the present invention according to the second preferred embodiment, the material(s) of the holding means may for instance be of (a) material(s) that dissolve(s) in the order of a couple of minutes when subjected to the substance that is to flow into the device 2, i.e. a substance specifically contained in the environment of the second predetermined location, for instance the stomach or the small intestine. Alternatively, the material(s) of the holding means may be of (a) material(s) that is (are) dissolved when subjected to a substance that is contained in the whole gastrointestinal region. In that case, the material(s) of the holding means will dissolve gradually during the passing of the sampling device through the gastrointestinal system. The amount(s) or the thickness(es) of the material(s) of the holding means is (are) calculated so that the final removal of the holding means will take place at the second predetermined location, for instance in the small intestine.

As mentioned, the inlet opening(s) 4 can in an alternative embodiment further be sealed by plugs 28 (Figure 8). The plug 28 in the device 2 is made of a material which is chosen depending on the application of the device 2, in the preferred use i.e. depending on the specific body fluid to be collected, in which body fluid the plug 28 is dissolved after a short period of time. Thus, the material of the plug 28 is adapted to the specific fluid or substance in the external environment of the device 2 where the sample is to be collected. The material of the plug 28 is in the preferred use, for example, gelatine, molten sugar, salt, glue, organic edible materials or any other suitable material. The plug 28 can also be made of two or more layers of different materials, which dissolve gradually upon contact with different substances in the external environment of the device 2, for instance during its passage through the digestive system. The innermost layer dissolving upon contact with substance to be collected by the device 2, for instance a substance contained in the small intestine. Alternatively, instead of having plugs 28, the entire device 2 can be coated with the material(s) described above. Either way, the sealing means 3 in the first preferred embodiment moves from the sealing position to the opening position when reaching the second temperature range as previously described.

The sampling device 2 may initially be provided with a substance in the inner chamber 8, which substance is used in the analyzing of the substance of which a sample is taken.

The sampling device 2 according to the invention is in the preferred embodiments made of a few parts, i.e. the cap member 23, the body member 25, the sealing means 3, the membrane 12, the temperature activated element 10, 11 /the pushing means 31 and optionally the second moving means 27 and the plugs 28. All these parts, in the first preferred embodiment apart from the plugs 28, may initially be fully or partly assembled in practically any environment of choice. The cap member 23 and the body member 25 are permanently joined together, preferably by ultrasonic welding and are preferably made of injection- moulded thermoplastic, such as Macrolon® D for example, which is a strong, acid resistant and transparent material and thus suitable for the preferred use. The mounting of the sealing means 3, the membrane 12 and the temperature activated element 10, 11 /the pushing means 31 is carried out with conventional methods.

The assembly- step that finally seals off the inner chamber 8 of the device 2 from the external environment is however in the first preferred embodiment carried out in an vacuum-oven or the like, i.e. a device that is settable at predetermined temperatures and which at the same time is capable to create and maintain a vacuum. This is in order to achieve a vacuum or substantial underpressure in the inner chamber 8, such that sufficient suction forces are generated to suck substance into and fill the device 2 when in use. The assembled device 2 according to the first preferred embodiment, comprising the above mentioned components, is arranged in a vacuum-oven, either previously set at a temperature within the second temperature range or the setting of said temperature is performed after the arranging of the device 2. Also, the device 2 can already have a temperature that is within the second temperature range before being arranged in the oven. Either way the temperature of the vacuum-oven being in the second temperature range results in the sealing means 3 being in the opening position of the inlet opening(s) 4. In connection to the temperature setting, a vacuum is established in the oven. This can be done prior to, or after the temperature setting, as long as the sampling device 2 is arranged in the vacuum-oven. Subsequently, the temperature is set to be within the first temperature range of the temperature activated material while maintaining the vacuum. If the temperature activated element 10, 11 is made of temperature activated material with a two way memory, this will result in the sealing means 3 moving to the sealing position of the inlet opening(s) 4, sealing off the inner chamber 8. If the temperature activated element 10, 11 is made of temperature activated material with a one way memory, then the device 2 preferably is provided with the second moving means 27 that will assist the movement of the sealing means 3 back to the sealing position, as previously described in connection to Figure 8. Either way, the device 2 can be removed from the vacuum-oven when the sealing means 3 is in the sealing position and the inner chamber 8 of the device 2 has a vacuum or substantial underpressure. The step that creates a vacuum in the inner chamber 8 of the device 2 in the second preferred embodiment of the present invention, comprises for instance introducing a syringe or the like through the recess 26, filled with for instance a soft, easily penetratable air- and watertight material, such as silicon rubber. The syringe is adapted to remove air from the inner chamber 8 whereupon it is retracted from the inner chamber 8 and the recess 26, whereupon the material filled in the recess 26, preserves the underpressure in the inner chamber 8.

Said vacuum or substantial underpressure inside the inner chamber 8 may not have a magnitude greater than that the temperature activated element 10, 11 or the pushing means 31 can overcome the forces that keep the sealing means 3 in the sealing position and move this to the opening position when said element 10, 11 adopts a temperature within the second temperature range or when the holding means has been removed. A typical magnitude of said vacuum being ca 0, 1 bar.

However, the area over which the forces generated by the vacuum act is small in comparison with the total cross section of the device 2. Thus the magnitude of the vacuum in the inner chamber 8 of the device 2 may very well be greater than that. Moreover, in the first preferred embodiment, the greater the difference between the temperature within the first temperature range at which the sampling device initially is at, i.e. the temperature that the temperature activated element 10, 11 initially has, and the origin of the second temperature range, the greater the forces that will act on the sealing means 3 generated by the temperature activated element 10, 11 when subjected to the second temperature range. Therefore, for the preferred use, it might be necessary to store the sampling device in for instance a refrigerator, i.e. typically 4°C, and keep the device at this temperature just prior to the swallowing of said device in order to generate a temperature difference of approximately 30°C.

The plugs 28 can optionally be applied with conventional methods without the need of a vacuum-chamber. If the present invention is in its first preferred embodiment, this is the final step.

The device 2 may further be provided with an additional outer coating. In the preferred use this might for instance be a covering film of gelatine or any other suitable material, which is dissolved in the digestive system. The film may be applied in order to minimise the resistance when the device 2 is swallowed by the patient.

It will be understood that the invention is not restricted to the above-described exemplifying embodiments thereof and that several conceivable modifications of the invention are possible within the scope of the following claims.

For instance the temperature activated element 10, 11 and the pushing means 31 can have practically any design as long as the deformation of said element 10, 11 upon reaching the second temperature, or the upwards directed motion of the pushing means 31, secures the movement of the sealing means 3 to the opening position. Also the design of the sealing means 3 and the membrane 12 may vary from the description and the drawings of this present application as long as they perform the functions of the present invention which is defined by the appended claims.

Claims

1. A sampling device (2) for obtaining samples of substances, which device (2) allows a sample of the substance to enter the device (2) through at least one inlet opening (4) into an inner chamber (8) defined by a device wall, said inlet opening(s) (4) is provided with at least one sealing means (3) that is disposed to preserve a vacuum or substantial underpressure in the inner chamber (8) when the inlet opening (4) is sealed characterised in that said sealing means (3) is adapted to be in a sealing position when the sampling device (2) is at a first predetermined location in which flow (6) of substance through the inlet opening (4) is prevented and is adapted to be in an opening position when the sampling device is at a second predetermined location in which flow (6) of substance is permitted through said inlet opening (4) and into the inner chamber (8), wherein the device (2) comprises at least one moving means (31, 10, 11) which is adapted to move the sealing means (3) from the sealing position to the opening position when the device (2) is at the second predetermined location.

2. A sampling device according to claim 1, characterised in that the moving means comprises pushing means (31) adapted to move the sealing means (3) from the sealing position to the opening position when the sampling device (2) is at the second predetermined location.

3. A sampling device according to claim 2, characterised in that the pushing means (31) is a held in a non-moving state by means of a holding means when the sampling device (2) is at the first predetermined location.

4. A sampling device according to claim 3, characterised in that the holding means consists of at least one material that dissolves when subjected to the substance that is to enter the inner chamber (8) of the device 2, said substance is contained in the environment surrounding the device (2) in the second predetermined location.

5. A sampling device according to claim 1, characterised in that the moving means comprises at least one temperature activated element (10, 11), made of at least one temperature activated material which is adapted to move the sealing means (3) from the sealing position to the opening position when the device (2) is at the second predetermined location, said first predetermined location ensures that the temperature activated element is subjected to a temperature within a first predetermined temperature range and said second predetermined location ensures that the temperature activated element (10,11) is subjected to a temperature within a second predetermined temperature range.

6. A sampling device according to claim 5, characterised in that the temperature activated element (10, 11) is adapted to move the sealing means (3) from the opening position to the sealing position when the device (2) is at the first predetermined location.

7. A sampling device according to any of claims 5-6, characterised in that said temperature active material is a shape memory material with a two way memory.

8. A sampling device according to any of claims 5-7, characterised in that said temperature active material is a memory metal and/ or memory alloy.

9. A sampling device according to any of claims 5-8, characterised in that said temperature active material is an electrically conducting material and in that the temperature activated element (10, 11) is at the second predetermined location subjected to a temperature within the second predetermined temperature range by means of inductive heating.

10. A sampling device according to claims 5-9, characterised in that the sealing means (3) comprises a sealing part (16) and a pushing part (17).

11. A sampling device according to any of claims 1- 10, characterised in that the moving means is a helix- shaped spring.

12. A sampling device according to any of claims 1-11, characterised in that there are several inlet openings arranged along the circumference of the mantle part of the top part (9) of the device (2) .

13. A sampling device according to claims 1-12, characterised in that said device (2) is provided with at least one membrane (12), arranged such that it allows a flow (6) of substance into the inner chamber (8).

14. A sampling device according claim 13, characterised in that the membrane (12) is made of an elastic material.

15. A sampling device according to claims 1-14, characterised in that said device (2) is provided with second moving means (27) which is adapted to assist the movement of the sealing means (3) from the opening position to the sealing position.

16. A sampling device according to claim 15, characterised in that said second moving means (27) is in a first tensed state when the sealing means (3) is in the sealing position and in a second tensed state when the sealing means (3) is in the opening position, wherein the pressure load on the second moving means (27) is greater in the second tensed state than in the first tensed state.

17. A sampling device according to claims 1-16, characterised in that the device (2) initially comprises at least one substance, which is used in the analyzing of the substance of which a sample is taken.

18. A sampling device according to claims 1-17 characterised in that the under pressure level in the inner chamber (8) is 0 - 0,8 bar, preferably 0, 1 bar.

19. A method for producing a sampling device according to claims 1, 5- 18 characterised in that said method comprises the steps (a) -(d) in arbitrary order, provided that step (a) is previous to step (c) and step (d) is the last step, said steps (a)-(d) being:

(a) arranging the sampling device (2) in a vacuum chamber,

(b) changing the temperature of the vacuum chamber to said second temperature range in which the sealing means (3) is in the opening position,

(c) lowering the pressure to a preset pressure level, (d) changing the temperature to said first temperature range in which the sealing means (3) is in the sealing position,

20. Use of the sampling device according to any of the claims 1-18 characterised in that said sampling device (2) is used for sampling of body substances from the digestive tract of a patient.