WO2020193267A1

WO2020193267A1 - Sampling device for collecting a microbiota sample

Info

Publication number: WO2020193267A1
Application number: PCT/EP2020/057202
Authority: WO
Inventors: Jacobo Paredes Puente
Original assignee: Universidad De Navarra
Priority date: 2019-03-22
Filing date: 2020-03-17
Publication date: 2020-10-01

Abstract

In a first aspect, a sampling device for collecting a microbiota sample from a gastrointestinal system configured to passively control the communication between an inside and an outside of the sampling device is provided. In a further aspect, a sampling device for collecting a microbiota sample from a gastrointestinal system configured to deliver an aqueous medium is provided. In yet a further aspect, a method for collecting a microbiota sample from a gastrointestinal system is provided.

Description

Samplinq device for collectinq a microbiota sample

The present application claims the benefit and priority of EP 19 382 203.8 filed on March 22, 2019.

The present disclosure relates to a sampling device for collecting a microbiota sample from a gastrointestinal system.

BACKGROUND

Microbiota is the aggregate of microorganisms that resides on or within some human tissues and biofluids, for example within the gastrointestinal tract. Microbiota may include bacteria, archaea, fungi, protists and viruses. Analyzing the properties of the gastrointestinal fluids or microbiota provides information about the health status of the gastrointestinal tract which may indicate physiological and in particular pathological conditions of a patient. This information may be used for doctors to diagnose gastrointestinal diseases, such as inflammatory bowels disease or colon cancer, or other diseases such as type II diabetes, obesity or brain-related disorders. In addition, the analysis of the microbiota may also be used to improve and control a personalized medicine program by modulating the microbiota by changing diet habits or by administering probiotics supplements or other medical actuations.

Samples of the microbiota of the gastrointestinal system may be taken using endoscopes. The use of endoscopes is very invasive and expensive. In addition, samples from the gastrointestinal cannot be routinely collected using endoscopes. Therefore, health status of the microbiota cannot be continuously monitored.

Capsules or sampling devices have been developed to collect microbiota samples in a less invasive manner. However, selectively collecting the samples in specific parts of the digestive tract and preserving the collected sample is still challenging. In particular, some of the most interesting intestine samples may be attached to internal walls of the small bowel. These intestine samples are difficult to detach from the internal walls of the small bowel and then absorbed by the capsule.

Sampling devices may be provided with electronic systems which control the aperture of an inlet for entering and storing the sample inside the device. In addition, sampling devices may also incorporate tracking or imaging systems to detect in which part of the digestive tract the capsule is located. These active sampling devices may additionally require power or battery systems. When the sampling device is detected in a particular location of the digestive tract, e.g. in a portion of the small bowel, the electronic system activates the aperture of the inlet for absorbing a sample of the microbiota. These active sampling devices are thus expensive and complex. In addition, the components of these active devices, e.g. battery or an electronic system, may imply a health risk inside the body if the sampling device is damaged.

The present disclosure provides examples of systems and methods that at least partially resolve some of the aforementioned disadvantages. SUMMARY

In a first aspect, a sampling device for collecting a microbiota sample from a gastrointestinal system configured to passively control the communication between an inside and an outside of the sampling device is provided. The sampling device comprises a reservoir for receiving the microbiota sample, an inlet providing a passage between the reservoir and an outside of the sampling device. Furthermore, the sampling device comprises an inlet closure assembly for passively controlling the communication between the reservoir and the outside of the sampling device through the inlet.

The inlet closure assembly comprises an outer closure for temporarily closing the inlet and being configured to dissolve at a sampling site for allowing the microbiota sample to enter into the reservoir through the inlet. The inlet closure assembly further comprises an inner closure configured to block the inlet after collecting the microbiota sample.

As the inlet closure assembly passively controls the communication between the reservoir and the outside of the device, a sample may passively enter into the reservoir. The outer closure is dissolved at a sampling site. The outer closure may be dissolved depending on an external parameter. This external parameter may be for example a parameter of the surrounding area of the sampling device, e.g. a temperature or a pH surrounding the sampling device, or a time of the sampling device inside the gastrointestinal system. This external parameter may trigger the dissolution of the outer closure. An external parameter, e.g. pH, may vary along the digestive track. Accordingly, this parameter may indicate the positon of the sampling device inside the digestive tract. The outer closure may thus be designed to be dissolved when the sampling device reaches a specific part of the digestive tract, e.g. a portion of the small bowel wherein the sample is to be collected. Accordingly, the activation of the dissolution of the outer closure may take place where the microbiota is present. The outer closure may be configured to dissolve in a predetermined range of pH and/or in a predetermined range of temperatures and/or in a predetermined period of time of the sampling device inside the gastrointestinal system.

In some examples, the outer closure may comprise biodegradable or dissolvable polymers for example dissolving at a predetermined pH range. Examples of these polymers may be polymethacrylate-based copolymers. These polymethacrylate- based copolymers may be derived from esters of acrylic and methacrylic acid.

When the inlet closure dissolves, the sample may thus be absorbed by the sampling device. In some examples, there is a differential pressure between the reservoir and the outside of the sampling device and this differential pressure may cause the sample to enter into the reservoir. In some examples, a piston may be moved to create the pressure difference and then to absorb the sample.

Tracking or imaging systems for detecting the position of the sampling device may thus be avoided. In addition, activating systems for actively opening the inlet when the sampling device reaches a predetermined position and active systems for absorbing a sample may also be avoided. A more reliable, economic and simpler sampling device may therefore be provided.

Furthermore, as the inner closure is configured to block the inlet after collecting the microbiota sample, the sample may be kept inside the reservoir. Contamination of the sample may thus be prevented.

The outer closure may be arranged outwardly with respect to the inner closure. Accordingly, when the outer closure is dissolved, at least a portion of the inner closure may come into contact with the outside of the sampling device.

In some examples, the inner closure may comprise an expandable element configured to expand in an aqueous medium. The expandable element may absorb a part of the aqueous medium, i.e. the expandable element may swell in an aqueous medium. The expandable element may thus change its shape by absorbing a liquid. Inside the gastrointestinal system, the sampling device may be surrounded by liquid when the outer closure has been dissolved. Some of this surrounding liquid can be absorbed by the expandable element. A change of a volume of the expandable can thereby block the inlet. In some examples, the expandable element of the inner closure may be configured to change an expansion rate after a change in pH. Changes in swelling rates may thus be triggered by a change in pH. These changes in swelling rates may thus allow controlling the expansion of the expandable element, i.e. the blocking of the inlet. For example, the expandable may slowly expand when the pH is stable, but may quickly expand when the pH changes.

Temperature or time may also be an external trigger to change the swelling or the expansion rate. For example, a predetermined time after the dissolution of the outer closure may trigger to change the expansion or swelling rate. These external triggers, e.g. a change in pH, may affect the swelling rate of the expandable element to increase the volume of aqueous medium to absorb by time. As the swelling rate is increased, the expandable element expands quicker. This expansion may block the inlet of the sampling device.

The inner closure may close the inlet to isolate the collected sampling. The sample may thus be conserved without being negatively affected by changes in the parameters outside of the sampling device. Contamination of the sample may thus be prevented.

For example, the inner closure may close the inlet when no more microbiota is to be collected or when the sampling device is no longer in a portion of the gastrointestinal system in which the microbiota sampling is to be collected, i.e. is no longer at a sampling site. A change in pH or in temperature or a time after the dissolution of the outer closure may indicate that sampling device is no longer at a sampling site. Elements present in the portions of the gastrointestinal system that are downstream from the sampling site are thus prevented from entering into the device.

In some examples, the expandable element may comprise hydrogel. In some of these examples, the expandable element may comprise polyacrylamide, poly(N- isopropylacrylamide), poly(methyl vinyl ether), poly(vinyl alcohol) or polyethylene glycol.

In some examples, a portion of the expandable element may be arranged inside the inlet. Liquid trying to enter into the reservoir may thus be absorbed by the expandable element. The expandable element may have a ring or a disc shape.

Alternatively or additionally, a portion of the expandable element may be arranged inside the reservoir for enclosing the microbiota sample when the expandable element expands. The portion of the expandable element inside the reservoir may act as a bag enclosing the microbiota sample. The expandable element may thus define an inner cavity for enclosing the microbiota sample. This portion of the expandable element may be arranged at a part of an internal wall of the reservoir. When the expandable element expands, the inner cavity defined by the expandable element may enclose the sample and may also block the inlet. Contamination of the stored sample may thus be prevented.

In some examples, the sampling device may be configured in such a way that a pressure in the reservoir is lower than a pressure outside of the sampling device when the outer closure closes the inlet. When the inlet closure is dissolved, this differential pressure between the reservoir and the outside of the sampling device may cause a sample to enter into the reservoir through the inlet. The sample may thus be absorbed by the sampling device.

In some of these examples, the reservoir may comprise a polydimethysiloxane (PDMS) element for maintaining a pressure inside the reservoir lower than a pressure outside the sampling device. Other materials having similar properties may alternatively be used. Because of the gas solubility and permeability of PDMS, air molecules can be evacuated from a PDMS substrate maintaining a vacuum environment for a certain period of time. As a result, vacuum or a low pressure may be stored in a PDMS substrate or element. When this PDMS substrate is brought to a higher pressure, e.g. an atmospheric pressure, air is reabsorbed by the PDMS substrate. A flow towards the PDMS substrate may thus be created. Liquids may be stored in the microfluidic channels of the PDMS substrate. Accordingly, the PDMS element may act as a pump for forcing a sample to enter into the reservoir.

In some examples, the sampling device may comprise a piston inside the reservoir configured to move from a closing positon to a receiving position. A closing position refers when the outer closure closes the inlet and a receiving position when the outer closure allows the microbiota to enter into the sampling device. The dissolution of the outer closure may trigger the piston releasing from the closing positon and moving to a receiving position. The piston may be retained in the closing position by for example, a portion of the outer closure or a dissolvable retainer. A deformable element may connect the piston and the sampling device. When the piston is no longer retained in the closing position, the deformable element may drive the movement of the piston inside the reservoir to a receiving position. In some examples, the deformable element may be a compression spring. This compression spring is compressed when the piston is in the closing position and extends to move the piston to the receiving position. In other examples, the deformable element may be a tension spring. This tension spring is extended when the piston is in the closing position and is in its nominal position when the piston reaches the receiving position.

In some examples, the sampling device may comprise an additional reservoir configured to contain an aqueous medium. This additional reservoir may be comprised inside the main reservoir or may be separated from the main reservoir.

An outlet may comprise a passage between the additional reservoir and the outside of the sampling device. An aqueous medium contained in the additional reservoir may be ejected through the outlet. This ejected aqueous medium may help to detach the microbiota from the walls of the digestive tract, e.g. from the walls of the small bowel. This aqueous medium injected from the sampling device may be mixed with the microbiota to be collected making the sample more liquid and reducing its viscosity. This may help to absorb the microbiota.

A piston inside the sampling device may separate the main reservoir (or a first reservoir) from the additional reservoir (or a second reservoir). This piston may be configured to move from a closing position to a receiving position. The movement of the piston from a closing position to a receiving position may force the aqueous medium contained in the additional reservoir to exit through the outlet.

The outlet may comprise an outlet closure assembly according to any of the examples described below.

In a further aspect, a sampling device for collecting a microbiota sample from a gastrointestinal system configured to deliver an aqueous medium is provided. The sampling device comprises a first reservoir for receiving the microbiota sample and a second reservoir comprising an aqueous medium. The sampling device further comprises a first reservoir inlet providing a passage between the first reservoir and an outside of the sampling device and a first reservoir inlet closure assembly for controlling the communication between the first reservoir and the outside. In addition, the sampling device comprises a second reservoir outlet providing a passage between the second reservoir and the outside of the sampling device and second reservoir outlet closures assembly for controlling the communication between the second reservoir and the outside. The second reservoir outlet closure assembly is configured to open when the first reservoir inlet closure assembly opens, such that the aqueous medium is delivered through the second reservoir outlet.

The aqueous medium may be delivered passively or actively. For example a passive valve or an active valve may be used. An active valve may be electrically or mechanically controlled. Ejecting an aqueous medium may allow detaching the microbiota from the internal walls of the bowels. This aqueous medium may thus be delivered at a sampling site.

In some examples, a pressure in the second reservoir is higher than a pressure outside of the sampling device when the second reservoir outlet closure assembly closes the second reservoir outlet, such that the aqueous medium is passively delivered when the second reservoir outlet is open. As the pressure inside the second reservoir is higher than outside, the aqueous medium is forced to exit through the second reservoir outlet.

In some examples, the sampling device may comprise a piston for delivering the aqueous medium. The piston may be configured to be moved from a closing position to a receiving positon. In the closing position the first reservoir inlet closure assembly closes the first reservoir inlet. When the piston is in the receiving position, the sampling device is configured to deliver an aqueous medium contained in the second reservoir and to receive the microbiota sample in the first reservoir. The movement of the piston may force the aqueous medium to exit from the second reservoir outlet and the microbiota sample to enter through the first reservoir inlet.

In some examples, the second reservoir outlet closure assembly may be passive. In some of these examples, the second reservoir outlet closure assembly may be configured to dissolve at the sampling site to deliver an aqueous medium contained in the second reservoir. For example, the second reservoir outlet closure assembly may comprise dissolvable or biodegradable polymers for example dissolving at a predetermined pH range, e.g. polymethacrylate-based copolymers derived from esters of acrylic and methacrylic acid.

The first reservoir inlet closure assembly may be according to any of the examples herein described. For example, it may comprise an outer closure and an inner closure.

In some examples, both the second reservoir outlet closure assembly and the outer closure of the first reservoir inlet may be dissolved at a sampling site. For example, the second reservoir outlet closure assembly and the outer closure of the first reservoir inlet may be configured to dissolve at a predetermined pH range and/or a predetermined temperature range. According to this aspect, the aqueous medium to detach the microbiota from the internal walls of the bowel may be delivered when a sample is allowed to enter into the sampling device. Both the first reservoir inlet and the second reservoir outlet may be substantially simultaneously open. In some these examples, the second reservoir outlet closure assembly and the inner closure of the first reservoir inlet may comprise biodegradable or dissolvable polymers.

The sampling device according to any of the examples herein disclosed may have a substantially cylindrical shape extending along a longitudinal axis. The ends of the sampling device may be rounded. The sampling device may thus have a capsule-like shape. This shape may allow a patient to easily swallow the sampling device. In addition, movements along the gastrointestinal system may be enhanced.

In yet a further aspect, a method for collecting a microbiota sample from a gastrointestinal system is provided. The system comprises administering a sampling device according to any of the examples herein described to an animal, e.g. a human. The sampling device enters through the mouth and passes through the pharynx to the oesophagus. When the sampling device arrives at a portion of the digestive tract wherein the microbiota is to be collected, the inlet opens and a sample of microbiota flows into the reservoir. Then, the sampling device may be excreted by the digestive system and the microbiota sample stored inside the sampling device may be analysed.

BRIEF DESCRIPTION OF THE DRAWINGS

Particular examples of the present disclosure will be described in the following by way of non-limiting examples, with reference to the appended drawings, in which:

Figure 1 schematically illustrates a sampling device according to one example of the present disclosure;

Figure 2 schematically illustrates the sampling device according to the example of Figure 1 after collecting a microbiota sample;

Figure 3 schematically illustrates a sampling device according to another example of the present disclosure;

Figure 4 schematically illustrates the sampling device according to the example of Figure 3 after collecting a microbiota sample;

Figure 5 schematically illustrates a sampling device according to another example of the present disclosure; Figure 6 schematically illustrates the sampling device according to the example of Figure 5 after collecting a microbiota sample.

DETAILED DESCRIPTION OF EXAMPLES The following description is merely exemplary in nature and is not intended to limit the present disclosure, application, or uses. It should be understood that throughout the drawings, corresponding reference numerals indicate like or corresponding parts and features.

Figure 1 and 2 schematically illustrate a sampling device according to one example of the present disclosure. The sampling device 1 illustrated in these figures comprises a reservoir 10 for receiving a microbiota sample 2 and an inlet 20 providing a passage between the reservoir 10 and an outside of the sampling device. This sampling device further comprises an inlet closure assembly 30 for passively controlling the communication between the reservoir 10 and the outside of the sampling device through the inlet 20. The inlet closure assembly 30 comprises an outer closure 31 and an inner closure 32.

Figure 1 illustrates the sampling device before collecting a microbiota sample. The outer closure 31 may temporarily close the inlet 20 and therefore no sample can be collected by the device of figure 1. The outer closure 31 may dissolve at a sampling site, for allowing the microbiota sample to enter into reservoir through the inlet. The outer closure may dissolve at a predetermined range of temperatures and/or pH. The outer closure 31 may, for example, comprise a degradable or dissolvable polymer for example dissolving at a predetermined pH range.

In these figures, the reservoir 10 comprises a PDMS element 1 1. When the outer closure 31 closes the inlet, a pressure inside the reservoir is lower than an outside of the sampling device. This lower pressure may be created and maintained by the PDMS element 1 1. When the outer closure 31 dissolves, the differential pressure between the reservoir and the outside may cause a microbiota sample to passively flow towards and along the inlet. The sample may then enter into the reservoir. After entering the sample 2 into the reservoir 10, the inner closure 32 may block the inlet 20. The inner closure 32 may comprise an expandable element which expands in an aqueous medium. In this example, the inner closure is arranged inside the inlet. In other examples, a portion of this expandable element may be arranged inside the reservoir for enclosing the sample. In these figures, the expandable element has a ring shape that may expand towards the walls of the inlet. In some examples, several expandable elements may be arranged inside the inlet. The expandable element may expand when aqueous medium present outside the sampling device intends to enter into the reservoir. The expandable element may absorb this liquid and may consequently expand.

In some examples, the absorption rate of the expandable element, e.g. hydrogel, may vary in function of for example changes in pH.

In some examples, the inlet and the inlet closure assembly may be according to any of the examples herein disclosed. For example, the inlet and/or the inlet closure assembly may be according to the example of figures 5 and 6.

Figure 2 shows the sampling device when the outer closure 32 blocks the inlet 30. In figure 2, the reservoir 10 stores the sample 2, preventing other particles, e.g. microorganisms, from entering into the reservoir.

Figure 3 and 4 schematically illustrate a sampling device according to one example of the present disclosure. The sampling device 1 illustrated in these figures comprises a piston 40 configured to move from a closing position (figure 3) to a receiving position (figure 4).

In Figure 3 the outer closure 31 closes the inlet and the piston is in the closing positon. The outer closure 31 may extend along a portion of the inlet 20. In this example, a portion of the outer closure retains the piston in a closing position. Alternative or in addition, the sampling device may comprise one or more retainers for maintaining the piston in the closing position. In these examples, the inlet 20 is arranged substantially at one end of the sampling device. The piston 40 may move from this end towards the opposite end.

The piston 40 may comprise a deformable element 41 , e.g. a spring, connecting the piston and the sampling device. In these figures the deformable element 41 is compressed when the piston is in the closing position. The piston 41 may move along a longitudinal axis of the sampling device from the closing position to a receiving position. In these figures, the deformable element 41 is compression spring.

In other examples, the deformable element may be traction spring. In these examples, the traction spring may connect the piston to an area of the sampling device arranged at opposite end.

As with respect to the examples of figures 1 and 2, the outer closure may dissolve in function of a predetermined pH, temperature or after a time from the administration of the sampling device. In this example, as the outer closure retains the piston in the closing position, the dissolution of the outer closure may release the compressible element. The piston may thus move towards the opposite end. The movement of the piston may cause the microbiota to enter into the reservoir.

The sampling device of these figures may also comprise an inner closure 32 expandable in an aqueous medium. The inner closure 32 may be according to any of the examples herein described. However, in this example, a portion of the inner closure is arranged inside the reservoir, rather than inside the inlet as illustrated in figures 1 and 2. After expanding, the inner closure may close the inlet.

In some examples, a PDMS element may be contained inside the reservoir to create a low pressure. Accordingly, when the retainer of the piston, e.g. the outer closure, dissolves, there is substantially no friction against the movement of the piston. The piston may further comprise an O-ring 42 for isolating the area of the reservoir containing the low pressure.

In figure 4, the microbiota sample is stored in the reservoir and the expansion of the expandable element 32 closes the inlet 20.

In figures 3 and 4, the piston may move axially and may substantially occupy a cross- section of the reservoir. However, in other examples the piston may move tangentially with respect to the axial axis of the sampling device. In these examples, a torsional spring may connect the piston with the sampling device. The piston may substantially close the inlet when the piston is in the closing position. When the torsional spring is released, the piston may be moved tangentially. This tangential movement may open the inlet. A sample may thus be forced to enter into the reservoir.

Figure 5 and 6 schematically illustrate a sampling device according to another example of the present disclosure. The sampling device 1 illustrated in these figures comprises a first reservoir 10 to receive the microbiota sample and a second reservoir 12 to contain an aqueous medium 51. The sampling device of these figures comprises a first reservoir inlet 20 and a second reservoir outlet 50. The first reservoir inlet 20 provides a passage between the first reservoir 10 and the outside and the second reservoir outlet 50 provides a passage between the second reservoir 12 and the outside.

The sampling device may also comprise a first reservoir inlet closure assembly 30 for controlling the communication between the first reservoir 10 and the outside through the inlet 20. In these figures, the inlet 20 comprises a main conduit 21 and a plurality of secondary conduits 22a, 22b. The plurality of secondary conduits 22a and 22b may extend from an opening arranged at outermost portion of the inlet to the main conduit 21. The main conduit 21 may extend from the plurality of secondary conduits 22a and 22 b to the first reservoir 10. However, in other examples the inlet may be according to any of the examples herein disclosed.

The first reservoir inlet closure assembly 30 of figures 5 and 6 comprises an outer closure 31 arranged inside the secondary conduits 22a and 22b. Similar to others examples herein disclosed, the outlet closure 31 may be configured to at a sampling site. The inlet closure assembly 30 of these figures further comprises an inner closure 32 arranged at the main conduit 21. The inner closure 32 may be configured to expand in presence of an aqueous medium. The inner closure 32 may be for example according to any of the examples herein disclosed.

In other examples, the first reservoir inlet closure assembly of a sampling device having a second reservoir for delivering an aqueous medium may be an active valve. An active valve may be controlled for example electrically or mechanically.

A second reservoir outlet closure assembly 52 controls the communication between the second reservoir 12 and an outside of the sampling device 1 through the outlet 50. The second reservoir outlet closure assembly 52 may be configured to dissolve at a sampling site. In some examples, the second reservoir outlet closure assembly may have a similar configuration to the outer closure of a first reservoir inlet closure assembly according to any of the examples herein disclosed. For example, the second reservoir outlet closure may comprise a dissolvable element to for example dissolve in function of a change in pH.

In addition, the sampling device 1 of figures 5 and 6 comprises a piston 40 separating the first reservoir 10 from the second reservoir 12. The piston 40 may be moved from a closing positon (figure 5) to a receiving position (figure 6). The movement of the piston from a closing position to a receiving position cause the sampling device to deliver an aqueous medium 51 contained in the second reservoir 12 and to absorb a sample into the first reservoir.

In the example of figures 5 and 6, the second reservoir outlet closure assembly 52 and the first reservoir inlet closure assembly 30 may open substantially at the same time because the dissolvable element of the second reservoir outlet closure assembly 52 and the outer closure 31 may be dissolved substantially at the same time. An aqueous medium 51 stored inside the second reservoir 12 may be ejected for detaching microbiota from an internal wall of the small bowel. This microbiota may then enter into the inlet 20 and may subsequently be stored in the first reservoir 10. As an aqueous medium is delivered, an area surrounding the sampling device is more aqueous. This may also help to block the first reservoir inlet 20 after collecting the microbiota if an inner closure being expandable in presence of a liquid is provided.

As in the example of figures 3 and 4, the piston comprises a deformable element connecting the piston to the sampling device. However, in the examples of figures 5 and 6 the piston is retained in a closing position by the action of one or more retainers 43, rather than by the inner closure of the inlet. The retainer 43 may be configured to be dissolved at a sampling site. For example, the retainer 43 may dissolve at a predetermined range of pH or at predetermined ranges of temperatures or after a time of the sampling device inside the gastrointestinal system. The retainer 43 may be made from a dissolvable element. The piston may additionally comprise an O-ring to substantially isolate the first reservoir 10 to the second reservoir 12.

In some examples, the piston may be connected to the sampling device by a torsional spring and the piston may move tangentially with respect to the longitudinal axis of the sampling device.

Figure 6 shows the sampling device of figure 5, in which the microbiota sample 2 is stored in the first reservoir 10 and the expansion of the expandable element 32 closes the first reservoir inlet 20. The aqueous medium 51 contained in the second reservoir 12 of figure 5 has been delivered, and therefore no substantially aqueous medium is contained in the second reservoir of figure 6.

In the examples of figure 5 and 6, the piston separates the first and the second reservoir. However, in other examples an internal wall may separate the first from the second reservoir. In further examples, the second reservoir may be comprised in the first reservoir.

For reasons of completeness, various aspects of the present disclosure are set out in the following numbered clauses:

Clause 1 . A sampling device for collecting a microbiota sample from a gastrointestinal system comprising: a reservoir for receiving the microbiota sample;

an inlet providing a passage between the reservoir and an outside of the sampling device;

an inlet closure assembly for passively controlling the communication between the reservoir and the outside of the sampling device through the inlet; the inlet closure assembly comprising:

an outer closure for temporarily closing the inlet, the outer closure configured to dissolve at a sampling site for allowing the microbiota sample to enter into the reservoir through the inlet; and

an inner closure configured to block the inlet after collecting the microbiota sample.

Clause 2. A sampling device according to clause 1 , wherein the inner closure comprises an expandable element configured to expand in an aqueous medium.

Clause 3. A sampling device according to clause 2, wherein at least a portion of the expandable element is arranged inside the inlet.

Clause 4. A sampling device according to clause 3, wherein the inlet comprises a main conduit and a plurality of secondary conduits, wherein the main conduit extends from the plurality of secondary conduits to the reservoir and each conduit of the plurality of secondary conduits extends from an opening to the main conduit.

Clause 5. A sampling device according to clause 4, wherein the expandable element is arranged inside the main conduit.

Clause 6. A sampling device according to any of clauses 3 - 5, wherein the expandable element has a ring shape.

Clause 7. A sampling device according to any of clauses 2 - 5, wherein at least a portion of the expandable element is arranged inside the reservoir for enclosing the microbiota sample when the expandable element expands.

Clause 8. A sampling device according to any of clauses 2 - 7, wherein the expandable element is configured to change an expansion rate after a change in pH.

Clause 9. A sampling device according to any of clauses 2 - 8, wherein the expandable element comprises hydrogel.

Clause 10. A sampling device according to clause 9, wherein the expandable element comprises polyacrylamide, poly(N-isopropylacrylamide), poly(methyl vinyl ether), poly(vinyl alcohol) or polyethylene glycol.

Clause 1 1 . A sampling device according to any of clauses 1 - 10, wherein the outer closure comprises a dissolvable polymer, optionally a polymethacrylate-based copolymer.

Clause 12. A sampling device according to any of clauses 1 - 1 1 , wherein the outer closure is configured to dissolve in a predetermined range of pH.

Clause 13. A sampling device according to any of clauses 1 - 12, wherein the outer closure is configured to dissolve in a predetermined range of temperatures.

Clause 14. A sampling device according to any of clauses 1 - 13, wherein the outer closure is configured to dissolve after a time of the sampling device inside the gastrointestinal system.

Clause 15. A sampling device according to any of clauses 1 - 14, wherein the sampling device is configured in such a way that a pressure in the reservoir is lower than a pressure outside of the sampling device when the outer closure closes the inlet.

Clause 16. A sampling device according to clause 15, wherein the reservoir comprises a polydimethylsiloxane (PDMS) element for maintaining a pressure inside the reservoir lower than a pressure outside the sampling device. Clause 17. A sampling device according to any of clauses 1 - 16, wherein the sampling device comprises a piston inside the reservoir configured to move from a closing position when the outer closure closes the inlet to a receiving position for allowing the microbiota sample to enter into the reservoir. Clause 18. A sampling device according to clause 17, wherein the sampling device comprises a deformable element connecting the piston and the sampling device. Clause 19. A sampling device according to clause 18, wherein the deformable element is compressed when the piston is in the closing position.

Clause 20. A sampling device according to clause 18, wherein the deformable element is extended when the piston is in the closing position.

Clause 21. A sampling device according to any of clauses 17 - 20, wherein the outer closure and/or a retainer dissolvable in function of a predetermined temperature or pH or a time of the sampling device inside the gastrointestinal system are configured to retain the piston in the closing position.

Clause 22. A sampling device according to any of clauses 17 - 21 , wherein the sampling device has a substantially cylindrical shape extending along an axial axis, and wherein the piston is configured to move along the axial axis from the closing position to the receiving position.

Clause 23. A sampling device according to clause 22, wherein the sampling device comprises a deformable element connecting the piston and the sampling device, the deformable element being an axial spring.

Clause 24. A sampling device according to clause 23, wherein the axial spring is a tension spring.

Clause 25. A sampling device according to clause 24, wherein the axial spring is a compression spring.

Clause 26. A sampling device according to any of clauses 17 - 21 , wherein the sampling device has a substantially cylindrical shape extending along an axial axis, and wherein the piston is configured to move tangentially with respect to the axial axis from the closing position to the receiving position.

Clause 27. A sampling device according to clause 26, wherein the sampling device comprises a deformable element connecting the piston and the sampling device, the deformable element being a torsional spring.

Clause 28. A sampling device according to any of clauses 1 - 27, wherein the sampling device further comprises: an additional reservoir configured to contain an aqueous medium, and an outlet providing a passage between the additional reservoir and the outside of the sampling device.

Clause 29. A sampling device according to clause 28, wherein a piston separates the additional reservoir from the reservoir.

Clause 30. A sampling device according to clause 29, wherein the piston is according to any of clauses 17 - 27.

Clause 31. A sampling device according to any of clauses 29 - 30, wherein the sampling device is configured to deliver an aqueous medium contained in the additional reservoir and to receive the microbiota sample in the reservoir when the piston is in the receiving position.

Clause 32. A sampling device according to any of clauses 28 - 31 , wherein sampling device comprise an outlet closure assembly for controlling the communication between the additional reservoir and the outside of the sampling device.

Clause 33. A sampling device according to clause 32, wherein the outlet closure assembly is passive.

Clause 34. A sampling device according to clause 33, wherein the outlet closure is configured to dissolve at a sampling site to deliver an aqueous medium contained in the additional reservoir.

Clause 35. A sampling device according to clause 34, wherein the outlet closure comprises a dissolvable polymer, optionally polymethacrylate-based copolymer.

Clause 36. A sampling device according to any of clauses 34 - 35, wherein the outlet closure is configured to dissolve in a predetermined range of pH.

Clause 37. A sampling device according to any of clauses 34 - 36, wherein the outlet closure is configured to dissolve in a predetermined range of temperatures.

Clause 38. A sampling device according to any of clauses 34 - 37, wherein the outlet closure is configured to dissolve after a time of the sampling device inside the gastrointestinal system.

Clause 39. A sampling device for collecting a microbiota sample from a gastrointestinal system comprising:

a first reservoir for receiving the microbiota sample;

a second reservoir comprising an aqueous medium;

a first reservoir inlet providing a passage between the first reservoir and an outside of the sampling device;

a first reservoir inlet closure assembly for controlling the communication between the first reservoir and the outside of the sampling device;

a second reservoir outlet providing a passage between the second reservoir and the outside of the sampling device;

a second reservoir outlet closure assembly for controlling the communication between the second reservoir and the outside of the sampling device;

wherein the second reservoir outlet closure assembly is configured to open when the first reservoir inlet closure assembly opens, such that the aqueous medium is delivered through the second reservoir outlet.

Clause 40. A sampling device according to clause 39, wherein the second reservoir outlet closure assembly is passive.

Clause 41 . A sampling device according to clause 40, wherein the second reservoir outlet closure assembly is configured to dissolve at a sampling site to deliver an aqueous medium contained in the second reservoir.

Clause 42. A sampling device according to clause 41 , wherein the second reservoir outlet closure assembly comprises a dissolvable polymer, optionally polymethacrylate-based copolymer. Clause 43. A sampling device according to any of clauses 41 - 42, wherein the second reservoir outlet closure assembly is configured to dissolve in a predetermined range of pH.

Clause 44. A sampling device according to any of clauses 41 - 43, wherein the second reservoir outlet closure assembly is configured to dissolve in a predetermined range of temperatures. Clause 45. A sampling device according to any of clauses 41 - 44, wherein the second reservoir outlet closure assembly is configured to dissolve after a time of the sampling device inside the gastrointestinal system.

Clause 46. A sampling device according to any of clauses 39 - 45, wherein the first reservoir inlet closure assembly is passive and comprises:

an outer closure for temporarily closing the first reservoir inlet, the outer closure configured to dissolve at sampling site for allowing the microbiota sample to enter into the first reservoir through the first reservoir inlet; and

an inner closure configured to block the first reservoir inlet after collecting the microbiota sample.

Clause 47. A sampling device according to clause 46, wherein the first reservoir inlet closure assembly is according to any of clauses 2 - 14.

Clause 48. A sampling device according to any of the clauses 39 - 47, wherein a pressure in the second reservoir is higher than a pressure outside of the sampling device when the second reservoir outlet closure assembly closes the second reservoir outlet, such that the aqueous medium is passively delivered when the second reservoir outlet is open.

Clause 49. A sampling device according to any of clauses 39 - 47, wherein the sampling device comprises a piston for delivering the aqueous medium.

Clause 50. A sampling device according to clause 49, wherein the piston separates the first reservoir from the second reservoir, the piston being configured to move form a closing positon to a receiving position;

wherein the sampling device is configured to deliver an aqueous medium contained in the second reservoir and to receive the microbiota sample in the first reservoir when the piston is in the receiving position.

Clause 51 . A sampling device according to clause 50, wherein the sampling device comprises a deformable element connecting the piston and the sampling device.

Clause 52. A sampling device according to clause 51 , wherein the deformable element is compressed when the piston is in the closing position. Clause 53. A sampling device according to clause 52, wherein the deformable element is extended when the piston is in the closing position.

Clause 54. A sampling device according to any of clauses 50 - 53, wherein the outer closure and/or a retainer dissolvable in function of a predetermined temperature or pH or after a time of the sampling device inside the gastrointestinal system is configured to retain the piston in the closing position.

Clause 55. A sampling device according to any of clauses 49 - 54, wherein the sampling device has a substantially cylindrical shape extending along an axial axis, and wherein the piston is configured to move along the axial axis from the closing position to the receiving position.

Clause 56. A sampling device according to clause 55, wherein the sampling device comprises a deformable element connecting the piston and the sampling device, the deformable element being an axial spring.

Clause 57. A sampling device according to clause 56, wherein the axial spring is a tension spring.

Clause 58. A sampling device according to clause 56, wherein the axial spring is a compression spring.

Clause 59. A sampling device according to any of clauses 49 - 54, wherein the sampling device has a substantially cylindrical shape extending along an axial axis, and wherein the piston is configured to move tangentially with respect to the axial axis from the closing position to the receiving position.

Clause 60. A sampling device according to clause 59, wherein the sampling device comprises a deformable element connecting the piston and the sampling device, the deformable element being a torsional spring.

Clause 61. A sampling device according to any of clauses 39 - 60, wherein the first reservoir contains the second reservoir.

Clause 62. A sampling device according to any of clauses 39 - 61 , wherein the second reservoir contains the first reservoir. Clause 63. A method for collecting a microbiota sample from a gastrointestinal system comprising administering a sampling device according to any of clauses 1 - 62 to an animal.

Clause 64. A method for collecting a microbiota sample according to clause 63, wherein the animal is a human.

Although only a number of examples have been disclosed herein, other alternatives, modifications, uses and/or equivalents thereof are possible. Furthermore, all possible combinations of the described examples are also covered. Thus, the scope of the present disclosure should not be limited by particular examples, but should be determined only by a fair reading of the claims that follow.

Claims

1 . A sampling device for collecting a microbiota sample from a gastrointestinal system comprising:

a reservoir for receiving the microbiota sample;

an outer closure for temporary closing the inlet, the outer closure configured to dissolve at a sampling site for allowing the microbiota sample to enter into the reservoir through the inlet; and

2. A sampling device according to claim 1 , wherein the inner closure comprises an expandable element configured to expand in an aqueous medium.

3. A sampling device according to claim 2, wherein at least a portion of the expandable element is arranged inside the inlet.

4. A sampling device according to any of claims 2 - 3, wherein at least a portion of the expandable element is arranged inside the reservoir for enclosing the microbiota sample when the expandable element expands.

5. A sampling device according to any of claims 2 - 4, wherein the expandable element is configured to change an expansion rate after a change in pH.

6. A sampling device according to any of claims 2 - 5, wherein the expandable element comprises hydrogel.

7. A sampling device according to any of claims 1 - 6, wherein the outer closure comprises a dissolvable polymer, optionally a polymethacrylate-based copolymer.

8. A sampling device according to any of claims 1 - 7, wherein the sampling device comprises a piston configured to move from a closing position when the outer closure closes the inlet to a receiving position for allowing the microbiota sample to enter into the reservoir.

9. A sampling device according to any of claims 1 - 7, wherein the sampling device is configured in such a way that a pressure in the reservoir is lower than a pressure outside of the sampling device when the outer closure closes the inlet.

10. A sampling device according to any of claims 1 - 9, wherein the sampling device comprises:

an additional reservoir configured to contain an aqueous medium, and an outlet providing a passage between the additional reservoir and the outside of the sampling device.

1 1 . A sampling device for collecting a microbiota sample from a gastrointestinal system comprising:

a first reservoir for receiving the microbiota sample;

a second reservoir comprising an aqueous medium;

12. A sampling device according to claim 1 1 , wherein the second reservoir outlet closure assembly and/or the first reservoir inlet closure assembly is passive.

13. A sampling device according to claim 12, wherein the second reservoir outlet closure assembly is configured to dissolve at a sampling site to deliver an aqueous medium contained in the second reservoir.

14. A sampling device according to any of claims 1 - 13, wherein the second reservoir outlet closure assembly is configured to dissolve in a predetermined range of pH and/or in a predetermined range of temperatures and/or after a time of the sampling device inside the gastrointestinal system.

15. A method for collecting a microbiota sample from a gastrointestinal system comprising administering a sampling device according to any of claims 1 - 14 to an animal, optionally a human.