WO2008091194A1

WO2008091194A1 - Gastrointestinal sampling apparatus and method

Info

Publication number: WO2008091194A1
Application number: PCT/SE2008/000044
Authority: WO
Inventors: Anders Weilandt; Mikael Lindgren
Original assignee: Alimenta Medical Ab
Priority date: 2007-01-22
Filing date: 2008-01-21
Publication date: 2008-07-31

Abstract

An apparatus for sampling agents excreted by the gastrointestinal mucosa comprises a housing having a front wall and a side wall, one or more openings in the side wall, one or more flexible sampling feelers disposed displaceably in the housing, each having a front end and a rear end, and a means for guiding the front end(s) of each of the one or more sampling feelers towards and through a corresponding opening in the side wall. Also disclosed is a method of sampling agents excreted by the mucosa by means of the apparatus.

Description

GASTROINTESTINAL SAMPLING APPARATUS AND METHOD

FIELD OF THE INVENTION

The present invention relates to an apparatus for sampling agents excreted by the gastrointestinal mucosa, in particular by the colonic mucosa, and a corresponding method.

BACKGROUND OF THE INVENTION

While food allergy is widespread in modern society it is often difficult to identify the causative allergen (s) with certainty. Food allergy causes an inflammatory reaction of the gastrointestinal mucosa. The detection of such a reaction upon provocation with a suspected allergen is a decisive test in identifying the causative allergen. Provocation of the colonic mucosa is preferred since it can be easily accessed via the rectum. Inflammation of the colonic mucosa results in the excretion or increased excretion of agents (inflammation markers) that accompany inflammation, such as NO, cytokines, prostaglandins and plasma proteins. Their identification and quantification in clinical analysis provides a precise diagnostic tool. Except for the gaseous NO, once excreted these markers are found mainly in the aqueous layer covering the gastrointestinal mucosa. It is from this layer that they can be sampled. Methods and apparatus for procuring such intestinal samples are known in the art from US 5983899 A and US 6576429 B. A drawback with the apparatus disclosed in these documents is that they need to be inflated after insertion into the rectum to make them abut the colonic mucosa for sampling of mucosal fluid, and then deflated before their removal through the anus. There thus exists a need for improved methods and apparatus in this field. OBJECTS OF THE PRESENT INVENTION

One object of the invention is to provide an apparatus of the aforementioned kind that does not need to be inflated and deflated after insertion into the colon.

Another object of the invention is to provide a corresponding sampling method.

An additional object of the invention is to provide an apparatus of the aforementioned kind that is easy and safe to use even by inexperienced medical staff, and that, therefore, is also convenient to the patient.

Further objects of the invention will become apparent from the following short description of the invention, a number of preferred embodiments thereof illustrated in a rough drawing, and the appended claims.

SUMMARY OF THE INVENTION

According to the present invention is disclosed an apparatus of the aforementioned kind comprising a housing having a front wall and a side wall, one or more openings in the side wall, one or more flexible sampling feelers disposed displaceably in the housing, each having a front end and a rear end, and a means for guiding the front end(s) of each of the one or more sampling feelers towards and through a corresponding opening in the side wall. Thereby the front ends of the sampling feelers are guided into the lumen of the colon or other portion of the gastrointestinal lumen. The displacement of a sampling feeler is stopped by its front end abutting the mucosa. According to an important aspect of the invention a displacement of a sampling feeler is not stopped by another sampling feeler abutting the mucosa with its front end. During contact with the mucosa sampling materials with good wetting/capillary properties mounted at the front ends become imbued with gastrointestinal fluid. According to an important aspect of the invention the disposition of a sampling feeler within the housing during insertion of the apparatus into the colon protects the sampling feeler from contamination. According to another important aspect of the invention retraction of a sampling feeler into the interior of the housing after sampling fluid from the gastric mucosa protects the sampled fluid from contamination.

In this application "front end" or "distal end" is the insertion end of the apparatus into the anus, its opposite end being termed "rear end" or "proximal end". A "distal direction" thus is a direction towards the front end; a "proximal direction" is a direction towards the rear end. A "lateral direction" is a direction skew or perpendicular (radial) direction from the axis of the housing towards its side wall. In this application the openings in the side wall are also termed "lateral openings". "Radial" and "axial" relate to the axis of the housing, which is preferably generally rotationally symmetrical, in particular of oblong cylindrical form. It is made of a suitable polymer material such as polypropene, polystyrene, ABS (acrylonitrile- butadiene-styrene copolymer) , PVC (polyvinylchloride) , PET (poly (ethylene terephthalate) ) , POM (polyoxymethylene) , polyester or PC (polycarbonate) . Most or all other parts of the apparatus are also of suitable polymer material (s) . They can be formed by extrusion, moulding or other suitable polymer forming techniques known in the art.

The guide means of the invention is mounted in the housing or integral with the housing. When mounted in the housing the guide means is preferably a guide element provided with a number of guide channels corresponding to the number of sampling feelers or a number of guide elements each provided with one or several guide channels. The guide channels have a rear portion extending in an about axial direction of the housing and a front portion extending in a skew or radial direction away from the housing axis towards openings in the housing wall so as to deflect sampling feelers inserted into their rear ends in a skew or radial direction thereby directing each of them to an openings in the housing wall.

When integral with the housing the guide means comprises one or several faces capable of deflecting the sampling feeler towards a corresponding opening in the sidewall of the housing in the same manner as explained for the guide channels.

It is preferred for a sampling feeler to carry, at its front end, an element for sampling fluid from the intestinal mucosa, such as, for instance, a sampling pad of a woven or non-woven material such as cotton. A wide range of materials can be used with a sampling element, such as natural or semi-synthetic fibres like cellulose acetate fibres, and synthetic fibres like polyester or polyamide fibres. Useful materials for use with a sampling element include polymer matrices formed by, for instance, thermal or chemical bonding of fibres. Materials with good wetting properties are preferred. Also preferred are fibre materials that are inert to the sampled fluid and its constituents . According to a preferred aspect of the invention the sampling element material can be provided with one or more sample stabilizing agent, such as antimicrobial agents and enzyme inhibitors such as protease inhibitors. According to a further preferred aspect of the invention the sample stabilizing agent of the invention can be immobilized on the material for use with the sampling element. According to a particularly preferred aspect of the invention the sampling element comprises a support or base for the sampling element material. It is preferred for the support to comprise a means for attaching it to the sampling feeler, such as a barb or stem extending from the rear side of the support, which can be mounted in a terminal bore or lumen section of the sampling feeler.

At least a frontal portion of the sampling feeler of the invention is flexible to allow it to be deflected by the guide means from a generally axial direction to a generally skew or lateral direction. The sampling feeler need not to be and is preferably not resiliently extendable. In a preferred embodiment of the invention the sampling feeler has a preferred direction of bending, and is disposed in the apparatus in a manner to align the preferred direction of bending with the direction of deflection. A preferred direction of bending is one in which the resistance to bending is less than in another direction of bending, most preferred is at minimum in respect of other directions of bending. A preferred direction of bending can be imparted to a sampling feeler by, for instance, providing it with indentations along its one long side; its profile in a longitudinal direction then will be similar to that of a toothed belt. According to another preferred aspect of the invention the front portion sampling feeler is a plastic tube whereas its rear portion is a stiff rod that can be mounted in the lumen of the tube.

The sampling feeler of the invention is mounted in a means for its longitudinal displacement by the operator, preferably in a piston mounted displaceably in the housing, which can be actuated by means of a shaft extending from the rear end of the housing. It is preferred for the shaft to be provided at its rear end with a holding means such as a handle or knob. According to a preferred aspect of the invention the sampling feeler is mounted at the piston by means of a resilient element such as a metal coil disposed in a bore in the front face of the piston. This resilient element provides for compensation of differences in distance between the lateral openings and the mucosa. The contact of the sampling element of a sampling feeler with the mucosa does not bar the sampling element (s) of other sampling feeler (s) that have not yet contacted the mucosa from such contact. This important advantageous feature is due to the compressible design of at least a portion of a sampling element in an axial direction. It allows the portion of a sampling feeler disposed exteriorly of the housing seeking to make contact with the intestinal mucosa to adapt to the variation in distance of the mucosa from the housing. This variation in distance is determined by the position of the housing in the lumen of the intestine. In addition the resiliently compressible nature of a portion of a sampling feeler provides the sampling feeler with a means for coping with an unintended transverse displacement of the housing in respect of the intestinal wall during sampling. It is within the ambit of the invention to provide individual sampling feelers with resilient elements that differ in respect of their resilience. It is also within the ambit of the invention to integrate a resilient element or function in a sampling feeler.

It is preferred for the piston or other corresponding displacement means at which the rear end of a sampling feeler is mounted to be provided with a means for arresting the piston or the other means in respect of a displacement in the housing in a position at which the front end of the feeler is disposed within the housing. An arresting means may, for instance, comprise circumferential slots in the inner face of the housing and the cylindrical face of the piston, a ring of a resilient material, preferably natural or synthetic rubber, disposed in the slot of the piston superimposed by a radially slit polymer or metal ring, which is pressed against the housing inner wall by the spring action of the compressed resilient ring. In a ready-for-use state the piston is disposed distally of the slot in the housing wall and is displaceable by hand in a distal as well as in a proximal direction via the plunger/knob assembly. After sampling of mucosal fluid the piston is withdrawn to an arresting position proximal of the starting position. In the arresting position the slit ring is held in the slot of the housing by the resilient force of the compressed rubber ring and thereby hinders further displacement of the piston. The piston arresting means comprising the rubber ring, the slit ring and the slots can be dimensioned so that the piston can be fully withdrawn from the housing by applying a force sufficient to break the arrest of the slit ring at the cost of damaging the arresting means. This prevents the apparatus from further use, which is a desired property in regard of the risk of contamination of a patient or medical personnel by re-use of an apparatus that cannot be safely sterilized. In a variation of the aforementioned piston arresting means the combination of rubber ring and radially slit ring is exchanged for a single resilient radially slit ring, which is radially so dimensioned that its is mounted in the slot of the piston in a radially compressed state in which it abuts the inner wall of the housing. In the arresting position of the plunger the slit ring is partially disposed in the slot in the housing wall by its radial expansion. A further variation of the arresting means of the invention comprises a circumferential slit in the plunger and a matching bulge protruding from the inner face of the housing. In the arresting position the bulge is locked in the circumferential slit.

The sampling element guide means of the invention is preferably a channel in the housing in which the front portion of the sampling element is disposed. The guide means or channel has rear portion extending in a generally axial direction and a front portion extending in a generally lateral or radial direction, including a skew direction. A preferred angle enclosed by the front portion and the long axis of the housing in a distal direction is 60° or more, preferable 75° or more, most preferred from 80° to 100°, in particular about 90°. In the apparatus of the invention the front end portion of a guide means communicates with a bore in the side wall of the housing. If the apparatus of the invention comprises two or more sampling feelers it is preferred for their front end portions of their guide means to deflect in a skew or radial direction at different axial levels (different distances from the rear end of the housing) so as to make the corresponding openings in the side wall of the housing through which the sampling feelers are made to protrude during sampling to be disposed at different axial levels.

It is preferred for the housing to comprise radially extending flange means at its rear end for convenient holding of the apparatus by the operator. The closed front end of the housing is preferably rounded to provide for easy insertion into the anus. The housing may comprise metal or other markers to facilitate its orientation in the colon by means of imaging techniques such as ultrasound.

According to a further preferred aspect of the invention a guide element can be displaced with the housing in a rearward direction by displacement means fixed at the piston and co-operating with flange means arranged in the guide element accessible from the rear face thereof. By this displacement communication of the channel or channels in the guide element with the corresponding bore(s) in the side wall of the housing is interrupted; thereby the mucosal fluid samples on the sampling elements disposed in the channels are additionally protected from contamination during withdrawal of the apparatus from the colon.

According to a still further preferred aspect of the invention the sampling elements disposed in the channels can be protected from contamination during insertion and withdrawal of the apparatus of the invention by a shield arranged displaceable on the housing between a frontal position, in which it covers the bores in the housing side wall, and a rear position, in which it leaves the bores unshielded.

Since embodiments of the apparatus of the invention may not be suitable for sterilization after a first use, it is important to prevent such use independent of whether intended or not. The apparatus of the invention thus preferably comprises a means for self-destruction after sampling. It is of advantage to combine self-destruction with a compulsory step for removing the sample from the apparatus such as, for instance, withdrawal of the piston from the apparatus. Accordingly, it is preferred for the means for self- destruction to be operated by the piston or the piston shaft/rod.

The method of the invention for sampling fluid from the colonic mucosa comprises: inserting the housing of the apparatus of the invention with its front end foremost into the colon of a patient via the anus to a desired depth; displacing the one or more flexible sampling feelers in a frontal direction towards and through the opening (s) in the side wall until abutment of the sampling pad(s) comprised by their front ends with the gastric mucosa; holding the sampling pad(s) in abutment with the gastric mucosa for a selected period of time to sample gastric fluid from the mucosa; withdrawing the sampling feelers with their sampling pads loaded with gastric fluid into the housing; optionally locking the withdrawn sampling feelers against displacement within the housing; withdrawing the housing from the colon. It is preferred for the sampling feeler (s) to be withdrawn via a rear opening of the housing after withdrawal of the housing from the colon. It is furthermore preferred for a stop disposed within the housing or at the rear opening thereof to be broken during withdrawal of the feeler (s) from the housing, thereby making the apparatus unfit for re-use. It is particularly preferred for the stop to be broken by the piston or plunger or by an element disposable in a rearward direction by the piston or plunger.

SHORT DESCRIPTION OF THE DRAWINGS

The invention will now be explained in more detail by reference to a number of preferred embodiments illustrated in a rough drawing, in which radial dimensions are generally exaggerated in respect of axial dimensions for clarity of representation. In the drawing is shown in

Figs. Ia, Ib, Ic a first embodiment of the apparatus of the invention, with its sampling feelers shown in a retracted state, an extended state, and an arrested state, in a longitudinal section; Figs. Id, Ie, If enlarged detail views of arresting means integrated in the embodiment of Figs . Ia - Ic, in the arrested state of Fig. Ic, Figs. Ig, Ih the embodiment of Figs. Ia - Ic in a state inserted into the bowel of a patient, with the position of its sampling feelers corresponding to that of Figs Ia and Ib, respectively; Figs. 2, 2a, 2b, 2c enlarged detail views of another embodiment of a sampling feeler mounted in the apparatus of Figs. Ia - Ic and provided with two kinds of sampling pads; Figs. 3, 3a enlarged detail views of a still another embodiment of a sampling feeler mounted in the apparatus of Figs. Ia - Ic;

Figs. 4a-4c a second embodiment of the apparatus of the invention shown in states corresponding to those of Figs. Ia, Ib, and in a protected third state (Fig. 4c), in the same view as the embodiment of Figs. Ia, Ib; Figs. 5a-5c a third embodiment of the apparatus of the invention provided with a displaceable shield for protecting channels in which the sampling feelers are disposed, in the same view as the embodiment of Figs. Ia, Ib (Figs. 5a, 5b) or in a radial section B-B (Fig. 5c); Figs. 6a, 6b " a representation of the sampling feeler guide channels of a further embodiment of the apparatus of the invention with four sampling feelers, in a lateral (Fig. 6a) and an axial view (Fig. 6b); Fig. 7 a fourth embodiment of the apparatus of the invention in a state corresponding to that of Fig. Ia and in the same view.

DESCRIPTION OF PREFERRED EMBODIMENTS

The colonic mucosa sampling apparatus 1 of Figs. Ia, Ib comprises a cylindrical body 2 with a closed rounded front end 3 portion and a holding flange 4 extending in a radial direction from the rear end of the body 2. An sampling feeler guide element 5 is disposed in and fully fills the lumen of the body 2 in a frontal portion thereof extending from the rear end of the rounded front end portion 3 in a rearward direction. First and second guide channels 6, 7 of circular profile are arranged in the guide element 5; they first extend from the rear end of the guide element 5 in a axial direction so as to be parallel and mirrored in respect of the body axis A, and then bow off radially outwardly in the direction of the side wall of the guide element 5 at different axial levels so as to form openings in the side wall 2 of the guide element 5 at different axial levels B, C, respectively. Corresponding openings 8, 9 communicating with channels 6, 7, respectively, are provided in the side wall of the body 2. A piston 10 is displaceably arranged in the rear lumen of the body 2. The piston 10 has a shaft 11 extending out of the rear opening of the body 2 and ending in a knob or handle 12. The rear ends of first and second flexible sampling feelers 13, 14 of different length are fixed in two bores taken up in the front face of the piston 10. A front portion of the first sampling feeler 13 is disposed in the first guide channel 6, whereas a front portion of the second sampling feeler 14 is disposed in the second guide channel 7. By pushing or retracting the piston 10/shaft 11/knob 12 assembly the sampling feelers 13, 14 can be displaced in the guide channels 6, 7 so as to make their front ends protrude from the openings 8, 9 in the side wall of the body (Fig. Ib) . The length of the sampling feelers 13, 14 is adapted so as to make their front ends extend by the same length F from the bores 8, 9 for a given position of the piston 10. At their front end the sampling feelers 13, 14 carry sampling pads 15, 16 of a material that is easily soaked by mucosal fluid, such as non-woven cotton.

Sampling of fluid from the colonic mucosa M is shown in Figs. Ig, Ih. In Figs. Ig, Ih the state of the sampling apparatus corresponds to that in Figs Ia and Ib, respectively. For reference numbers omitted in Figs. Ig, Ih for clarity reasons reference is therefore made to Figs. Ia and Ib. Prior to sampling the bowel is rinsed well with water or saline. The sampling apparatus 1 is inserted into the bowel through the anus with the sampling feelers 13, 14 in a retracted position so that their sampling pads 15, 16 are located within channels 6, 7. After insertion to a desired depth a major portion of the main portion of the apparatus 1 including the front portion 3 is disposed within the colonic lumen L. The piston 10 is then pushed forwards by the operator by means of the knob 12/shaft 11. This makes the front end of the sampling feelers 13, 14 protrude from the openings 8, 9. When their movement is stopped by contact with the colonic mucosa M their ends with the pads 15, 16 become soaked with mucosal fluid within a few seconds. The sampling feelers 13, 14 are then retracted to dispose their ends with the soaked pads 15, 16 within the channels 6, 7. The pads 15, 16 are now protected from possible contamination by further contact with other parts of the mucosa or the anus (rectal sphincter RS) , and the apparatus 1 can be safely withdrawn. After withdrawal the antennae are pushed again forwards making their front ends accessible for removal of the soaked pads 15, 16 for analysis of their content of soaked mucosal fluid.

The sampling apparatus of Figs. Ia, Ib can be provided with a means for arresting the piston 10 against displacement in the housing 2 in a position (Fig. Ic) at which the feelers 13, 14 are completely disposed within the housing 2. The arresting means comprises circumferential slots 19, 24 in the inner face of the housing 2 and the cylindrical face of the piston 10, respectively, a ring 17 of a resilient material, such as rubber, disposed in the slot 24 of the piston 10 superimposed by a radially slit polymer or metal ring 18 (Fig. Id) . The slit ring 18 is pressed against the housing 2 inner wall by the spring action of the compressed resilient ring 17. In a ready-for-use state (Fig. Ia) the piston 10 is disposed distally of the slot 19 and is displaceable by hand in a distal as well as in a proximal direction via the plunger 11/knob 12 assembly. After sampling of mucosal fluid (Fig. Ib) the piston 10 is withdrawn to an arresting position (Fig. Ic) proximal of the starting position of Fig. Ia. In the arresting position the slit ring 18 is held in the slot 19 of the housing 2 by the expanded rubber ring 17 and thereby hinders further displacement of the piston 10. The piston arresting means comprising the rubber ring 17, the slit ring 18, and the slots 19, 24 can be dimensioned so that the piston 10 can be fully withdrawn from the housing 2 by applying a force sufficient to break the arrest of the slit ring 17 at the cost of damaging the arresting means Variations of the piston arresting means of the invention are show in Figs. Ie and If. The arresting means of Fig. Ie corresponds to that of Fig. Id except for that the combination of rubber ring 17 and radially slit ring 18 is exchanged for a single resilient radially slit ring 18', which radially so dimensioned that its is mounted in the slit 17 in a state radially compressed by the abutting inner face of the housing 2. In the arresting position of the plunger 10 shown in Fig. Ic the slit ring 18' is partially disposed in slot 19 by its radial expansion. The further embodiment of the arresting means of the invention shown in Fig. If comprises a circumferential slit in the plunger 10 and a matching bulge 25 that protrudes from the inner face of the housing 2. In the arresting position in Fig. If the bulge 25 is locked in the circumferential slit. This and other advantageous features can be provided by applying by state-of-the-art polymer design and manufacturing methods, taking into account the generally stiff but somewhat resilient nature of the polymer materials used in the invention.

The variation of the sampling feeler of the invention illustrated in Figs. 2 and 2a (partial enlargement) comprises a flexible front portion 20 and a comparatively stiff rear portion 21. The front portion 20 is toothed and has greater flexibility in the direction in which the teeth open up when bending the toothed portion, than in the other direction or in a plane perpendicular to the plane minimum bending resistance. With its rear portion 21 the sampling feeler is fixed at one end of a thin steel coil 22 loosely inserted into a bore 23 in the front face of the piston 23 and fixed to the bottom of the bore 25 with its other end. At its front end the sampling feeler has a flange 26 with central bore in which a pad element 27 is loosely mounted (Fig. 2a) . The pad element 27 (Fig. 2b) comprises a stiff base 28, a cotton pad 29 glued on the front face of the base 28 and a flexible barb element 30 extending from the rear face of the base 28. The variation of the pad element 27 shown in Fig. 2c lacks a base plate; its sampling pad 29' is fastened in the central bore of the terminal flange 26 of the feeler 20 by means of a barbed pin 30. Another variation of the sampling feeler of the invention is illustrated in Figs. 3 and 3a. The sampling feeler comprises a stiff rear element 40 on which a soft plastic tube 41 is mounted. The rear element 40 is held in a bore 42 in the front face of piston 43 by means of a steel coil 44 in a manner corresponding to the similar arrangement of the sampling feeler of Figs. 2, 2a, 2b. A pad element 45 comprising a stiff base 46, a cotton pad 47 glued on the front face of the base 46 and a mounting rod 48 with a thickened free end portion extending from the rear face of the base 46 is held inserted in the front opening of the plastic tube 41.

A second embodiment 101 of the colonic mucosa sampling apparatus of the invention is shown in Figs. 4a-4c in consecutive sampling stages. In Fig. 4a it is shown in a state prior to sampling and immediately after sampling with the front portions of the sampling feelers 113, 114 with their sampling pads disposed in channels 106, 108, respectively, of the guide element 105. The sampling stage, in which the sampling feelers 113, 114 project from lateral openings 108, 109 in the body 102 is illustrated in Fig. 4b. After sampling the 133, 114 are withdrawn into the channels 106, 108 by a rearward displacement of the piston/shaft/know assembly 110- 112; the apparatus is again in the state of Fig. 4a but with its sampling pads loaded with fluid sampled from the intestinal wall. The sampling states illustrated in Figs. 4a and 4b thus correspond to those of Figs. Ia and Ib. The embodiment 101 differs from the embodiment 1 in that its guide element 105 can be displaced in a rearward direction at the end of sampling by means of carrier pins 120, 123 ending in distal heads 121, 124 and which extend from the front face of the piston 110 in bores of which they are fixed into an annular compartment 122. The pins 120, 123 can be inserted into the compartment 122 by openings 125, 126 of a corresponding diameter (Fig. 4d, section B-B, Fig. 4b); a rotation of the piston 110 in respect of guide element 105 displaces the heads 121, 124 to^' positions at which they cannot be withdrawn from the compartment 122 by a rearward movement of the piston/shaft/knob assembly 110-112. In this embodiment the guide element is held in the position shown in Figs. 4a, 4b by friction between is cylindrical face and the inner face of the cylindrical wall of the body 102 or by any other suitable means such as minute co-operating circumferential flanges and notches arranged in facing walls of the guide element 105 and the body 102. By applying a force to the piston 110 via the knob/shaft 112, 111 sufficient for overcoming the friction or other resistance between the guide element 105 and the body 102 the guide element 105 is displaced in a rearward (proximal) by the heads 121, 124 abutting the bottom of compartment 122. Thereby the channels 106, 107 are also displaced in a rearward direction so that their communication with the openings 108, 109 is interrupted, and the sampling feelers 113, 114 are separated from the intestinal environment (Fig. 4c). The sampling apparatus 100 thus can be withdrawn without risking contamination of the collected intestinal mucosa fluid samples. Reference numbers 103, 104 identify elements corresponding to elements 3, 4 of the embodiment illustrated in Figs. Ia, Ib. After complete removal of the apparatus 101 from the patient the samples can be accessed by withdrawing the guide element 105 with the sampling feelers 113, 114 from the body 102 and then making their front ends protrude from the channels 106, 107 by pushing the piston 110 in the direction of the guide element 105. A third embodiment 201 of the colonic mucosa sampling apparatus of the invention is shown in Figs. 5a-5c. Elements identified by reference numbers 202 to 221, 223, and 224 correspond to functionally equivalent elements 102, 103, etc. of the embodiment of Figs. 4a-4c. The sampling apparatus 200 is a combination of a variation of the sampling apparatus 100 of the invention and an cylindrical shield 230, 231, 232 that is glidingly disposed on the cylindrical portion of the body 203 and, in a first position, Fig. 5a) covers the wall openings 208, 208 of the body 203 that communicate with the channels 206, 207 of the guide element 205 so as to protect the sampling pads mounted at the front ends of the sampling feelers 213, 214 disposed in the channels 206, 207 of the guide element 205 from contamination during insertion of the instrument into the colon via the anus. The shield comprises an intermediate cylindrical main portion 230 ending in a thinned front end portion 231 that is somewhat extendible and abuts, in the closed or protecting state of the shield, a section of the curved front end portion 203 that merging with the cylindrical main portion 230. A radial flange 232 extends form the rear (proximal) end of the shield to facilitate the displacement thereof by hand in a rearward direction to uncover openings 208, 209 after insertion of the instrument into the desired position in the colon. After sampling the shield 230, 231, 232 may be pushed back. to its position at start to make it again protect the openings 208, 209 during withdrawal of the instrument 201. The apparatus of Figs. Ia, Ib can be provided with a corresponding shield (not shown) . In a manner similar to that of the guide element 105 of the embodiment of Figs. 4a-4c the guide element 205 can be displaced in a proximal direction by means of heads 221, 224 of pins 220, 223 fixed at the piston 210. The heads 221, 224 are inserted into an annular compartment 222 through widened portions 226, 227 (Fig. 4c) of an annular slit 225 in the proximal face of the guide element 205 that opens into the compartment 222, followed by turning the knob/shaft/piston assembly 212, 211, 210 by a suitable angle such as, for instance, 90°. Withdrawal of the piston/shaft/know assembly 210, 211, 212 in a proximal direction makes proximal faces of the heads 221, 224 abut bottom flange sections bordering to the slit 225 and thereby displace the guide element 205 and the sampling feelers 213, 214 disposed in channels 206, 207 of the guide element 205 in a proximal direction. In the displaced position (not shown for the embodiment of Figs. 5a- 5c but corresponding to that of Fig. 4c) the lateral openings of the channels 206, 207 do no longer communicate with the openings 209, 209 in the cylindrical wall of the instrument body 203.

Figs. 6a and 6b illustrate the arrangement of four channels 301, 302, 303, 304 in the guide element 305 of a colonic mucosa sampling apparatus 300 of the invention accommodating a corresponding number of sampling feelers (not shown) . The channels 300-303 are symmetrically centred about the apparatus axis M. The lateral openings of the channels 300, 301, 302, 303 are disposed at different axial levels T, S, R, P, respectively, allowing to cover a larger portion of the colon.

In the fifth embodiment 401 of the colonic mucosa sampling apparatus of the invention shown in Fig. 7 the guide element is substituted by guide sections 405, 405', 405'', 405''' integral with the cylindrical housing 402, which conserves a rear flange 404 and a rounded front end portion 403. The sampling feelers 413, 414 are guided between paired guide sections 405, 405' and 405'', 405''' towards the lateral openings 408, 409 in the housing 402. The housing 402 is conveniently made in two mirroring halves of which the plane of section in Fig. 7 represents one of the mirroring faces at which they halves are joined adhesively or by thermal bonding,

Claims

1. An apparatus for sampling agents excreted by the gastrointestinal mucosa, in particular by the colonic mucosa, comprising a housing having a front wall and a side wall, one or more openings in the side wall, one or more flexible sampling feelers disposed displaceably in the housing, each having a front end and a rear end, and a means for guiding the front end(s) of each of the one or more sampling feelers towards and through a corresponding opening in the side wall.

2. The apparatus of claim 1, wherein the side wall comprises an oblong cylindrical section provided with said one or more openings.

3. The apparatus of claim 2 having two or more openings disposed radially and/or axially distant of each other.

4. The apparatus of claim 3, wherein said openings are radially and axially distant of each other.

5. The apparatus of any of claims 1-4, wherein the housing comprises two axially sectioned halves.

6. The apparatus of any of claims 1-5, wherein the guide means is integral with the housing.

7. The apparatus of claim 6, wherein the guide means comprises one or several faces capable of deflecting a sampling feeler in a radial or skew direction.

8. The apparatus of any of claims 1-5, wherein the guide means is mounted in the housing.

9. The apparatus of claim 7, wherein the guide means comprises a number of guide channels corresponding to the number of sampling feelers, which are disposed in the channels.

10. The apparatus of claim 8, wherein a guide channel has a rear portion extending in an about axial direction of the housing and a front portion extending in a skew or radial direction away from the housing axis towards one of said opening (s).

11. The apparatus of any of claims 1-10, wherein a sampling feeler carries, at its front end, an element for sampling fluid from the intestinal mucosa

12. The apparatus of claim 11, wherein the element for sampling comprised a sampling pad of woven or non-woven fibre .

13. The apparatus of claim 12, wherein the sampling pad is provided with a sample stabilizing agent selected from antimicrobial agent and enzyme inhibitor.

14. The apparatus of any of claims 12 or 13, wherein the sampling element comprises a support or base for the sampling pad.

15. The apparatus of claim 13, wherein the sampling element comprises a means for attaching it to the sampling feeler.

16. The apparatus of any of claims 1 to 15, wherein a sampling feeler is attached at its rear end to a piston mounted displaceable in the housing in an axial direction and which can be operated by means of a rod or shaft extending from a rear opening of the apparatus.

17. The apparatus of claim 16, wherein the attachment comprises resiliently a compressible damping means.

18. The apparatus of claim 17, wherein the damping means comprises a coil.

19. The apparatus of any of claims 1-18, wherein a sampling feeler has a preferred bending direction.

20. The apparatus of claim 19, wherein the sampling feeler is mounted in a guide channel so as to make its preferred bending direction coincide with the sampling feeler's direction of deflection.

21. The apparatus of any of claims 1-20, wherein the housing comprises a radially extending flange at its rear end.

22. The apparatus of any of claims 1-21, comprising a protective shield mounted displaceable in an axial direction on the housing.

23. The apparatus of any of claims 1-5 and 7-22, comprising a means for displacing the guide means in the housing in a rearward direction operable via the piston.

24. The apparatus of any of claims 16-23, wherein the piston can be locked in a position in which a sampling feeler is located within the housing.

25. The apparatus of any of claims 1-24, comprising a means for self-destruction after sampling to prevent the apparatus from being re-used.

26. The apparatus of claim 25, wherein the means for self- destruction is operated by any of piston, shaft or rod.

27. A method of sampling fluid from the colonic mucosa, comprising: inserting the housing of the apparatus of claims 1 to 26 with its front end foremost into the colon of a patient via the anus to a desired depth; displacing said one or more flexible sampling feelers in a frontal direction towards and through said opening (s) in the side wall until abutment of sampling pad(s) comprised by their front ends with the gastric mucosa; holding the sampling pad(s) in abutment with the gastric mucosa for a selected period of time to sample gastric fluid from the mucosa; withdrawing the sampling feelers with their sampling pads loaded with gastric fluid into the housing; optionally locking the withdrawn sampling feelers against displacement within the housing; withdrawing the housing from the colon.

28. The method of claim 27, comprising withdrawing the sampling feeler (s) via a rear opening of the housing after withdrawal of the housing from the colon.

29. The method of claim 28, comprising breaking a stop disposed within the housing or at the rear opening thereof during withdrawal of the feeler (s) from the housing, thereby making the apparatus unfit for re-use