AIRWAY SAMPLING DEVICE AND ASSOCIATED METHODS

Abstract

The present application discloses a variety of airway sampling devices and associated methods. According to an embodiment, an airway sampling device for taking a sample from a subject's airway is provided with a handle to be gripped by a user when taking the sample and a sampling head carried by the handle, the sampling head comprising a cavity with an opening for entry by the sample and a sample collection membrane located within the cavity for receiving the sample.

Claims

1. An airway sampling device for taking a sample from a subject's airway, the device comprising a handle to be gripped by a user when taking the sample and a sampling head carried by the handle, the sampling head comprising a cavity with an opening for entry by the sample and a sample collection membrane located within the cavity for receiving the sample.

2. An airway sampling device according to claim 1, wherein the sample collection membrane comprises absorbent and/or adsorbent material.

3. An airway sampling device according to claim 1, wherein the sample collection membrane is detachable from the sampling head.

4. An airway sampling device according to claim 1, wherein the cavity has a gutter provided at least partly around its opening.

5. An airway sampling device according to claim 1, wherein the cavity is defined within a peripheral wall provided at least partly around the sampling head, and wherein outer surfaces of the peripheral wall are configured to be perpendicular to the tonsils of the subject when the sampling head is inserted into and/or removed from the subject's pharynx.

6. An airway sampling device according to claim 1, wherein the cavity is defined within a peripheral wall provided at least partly around the sampling head, and wherein an outer surface of the peripheral wall is configured to be perpendicular to the uvula and/or posterior wall of the oropharynx of the subject during capture of the sample.

7. An airway sampling device according to claim 6, wherein an outer surface of the peripheral wall is configured to deflect the uvula of the subject, allowing the sampling head to enter the pharynx from the oral cavity.

8. An airway sampling device according to claim 1, wherein the handle is provided with a chamber, and the sampling head is movable relative to the handle between a first condition in which the sampling head is distal from the handle and a second condition in which the cavity is located over the chamber to define an enclosure which encloses the sample collection membrane between the interior of the cavity and the interior of the chamber.

9. An airway sampling device according to claim 8, wherein the enclosure is fluid-tight.

10. An airway sampling device according to claim 8, wherein a weakened area is provided in one of the chamber or the cavity.

11. An airway sampling device according to claim 10, wherein the weakened area is configured to rupture when pressure is applied to the enclosure.

12. An airway sampling device according to claim 11, wherein the weakened area is provided in the chamber, and the chamber is formed from a deformable material to allow a user to apply pressure to the enclosure.

13. An airway sampling device according to claim 8, wherein the interior of the chamber is provided with one or more protrusions which contact the sample collection membrane when the sampling device is placed into its second condition.

14. An airway sampling device according to claim 1, wherein the interior of the cavity is provided with one or more protrusions on which the sample collection membrane is located.

15. An airway sampling device according to claim 1, wherein the sampling device further comprises an illumination module, and the sampling head is configured as a light guide to guide and emit light emitted from the illumination module.

16. An airway sampling device according to claim 15, wherein the illumination module is removably mounted on the sampling device.

17. An airway sampling device according to claim 1, wherein the sampling head is provided at a first end of the sampling device distal from a second end of the sampling device at which the handle is provided, and the sampling device further comprises a shield mounted between the first and second ends of the sampling device, for shielding the user from sample from the subject.

18. An airway sampling device according to claim 1, wherein the airway sampling device is shaped and dimensioned so as to locate the opening of the cavity over the vocal cords and within the oropharynx posterior to the uvula of a subject when the sampling head is located at a sampling position in the patient's airway for taking the sample.

19. An airway sampling device according to claim 1, wherein the sampling head is angled relative to the handle, so as to present a plane of the opening of the cavity at an angle of between 25° to 45° downwardly from horizontal when the sampling head is located at the sampling position in the patient's airway.

20. An airway sampling device according to claim 1, wherein the depth of the sampling device, from an uppermost surface of the handle to a lowermost tip of the sampling head, is from 17 mm to 23 mm.

21. An airway sampling device according to claim 1, wherein the maximum width of the sampling head is between 10 mm to 16 mm.

22. An airway sampling device for taking a sample from a sampling position within a subject's airway, the device comprising a handle to be gripped by a user when taking the sample and a sampling head for insertion into the subject's airway and being carried by the handle, the sampling head comprising a cavity with an opening for entry by the sample, and wherein the airway sampling device is shaped and/or dimensioned so as to locate the opening over the vocal cords and within the oropharynx, posterior to the uvula, of a subject when the sampling head is located at the sampling position in the patient's airway.

23. An airway sampling device for taking a sample from a subject's airway, the device comprising a handle to be gripped by a user when taking the sample and a sampling head carried by the handle, wherein the handle is provided with a chamber, and the sampling head is movable relative to the handle between a first condition of the sampling device in which the sampling head is distal from the handle and a second condition of the sampling device in which the sampling head is located adjacent the chamber.

24. A method of taking a sample from a subject's airway, the method comprising collecting a sample from a sampling position located above the vocal cords and within the oropharynx and posterior to the uvula of a subject.

25. A method of preparing a sample from a subject taken using the airway sampling device of claim 1, the method comprising exposing the sample collection membrane to an elution buffer to elute the sample into the elution buffer.

Description

LIST OF FIGURES

[0137] In order that the present invention may be more readily understood, embodiments thereof will now be described, by way of example only, with reference to the accompanying drawings, of which:

[0138] FIG. 1 is a schematic view showing a detail of part of the muco-ciliary escalator of a human subject;

[0139] FIGS. 2A TO 2E schematically illustrate the cough function of a human subject;

[0140] FIG. 3 shows a first embodiment of a sampling device according to the present invention;

[0141] FIGS. 4A to 4C show details of a sampling head of the first embodiment;

[0142] FIGS. 5A and 5B show the sampling device of the first embodiment in a sampling position within a subject;

[0143] FIGS. 6 to 10 describe various preferable dimension and angling features of the first embodiment;

[0144] FIG. 11 shows a protective hood of the sampling device of the first embodiment;

[0145] FIG. 12 is a flow chart of a first sampling method according to an embodiment of the present invention;

[0146] FIGS. 13 to 15 show a second embodiment of a sampling device according to the present invention and various details thereof;

[0147] FIG. 16 shows assembly of the second embodiment;

[0148] FIGS. 17 and 18 show various preferable dimension and angling features of the second embodiment;

[0149] FIGS. 19A to 19E show the second embodiment in various free standing conditions;

[0150] FIG. 20 shows the second embodiment being held by a user;

[0151] FIG. 21 is a flow chart illustrating a second embodiment of a sampling method according to the present invention, with FIGS. 22 to 27 illustrating various steps of that method;

[0152] FIG. 28 shows a third embodiment of a sampling device according to the present invention;

[0153] FIGS. 29 to 31 shows a fourth embodiment of a sampling device according to the present invention;

[0154] FIG. 32 shows a fifth embodiment of a sampling device according to the present invention;

[0155] FIGS. 33 and 34 illustrate alternative sampling methods according to further embodiments of the present invention; and

[0156] FIGS. 25 and 36 show details of the second embodiment.

DESCRIPTION OF EXEMPLARY EMBODIMENTS

[0157] FIG. 1 is a schematic diagram showing a detail of a small section of the Muco-Ciliary Escalator (MCE) (shown generally at 1) in a human subject 3. The MCE 1 transports Mucosal Lining Fluid (MLF) from the small airways up to the larynx and the vocal cords. In particular, ciliary beating carries MLF upwards from small bronchioles to larger bronchi and onwards to the trachea and to the larynx through the vocal cords. The MLF is then normally swallowed (at a rate of approximately 30 ml/day).

[0158] The vocal cords (in the larynx) are “the gateway to the lower respiratory tract” and airways. The MLF provides the body with a barrier against infection clearing out the airways carrying with it foreign particles and microorganisms. Due to the MCE, vocal cord MLF (from part of the larynx) reflects large and small airway molecular events. The surface MLF reflects information in the underlying airway wall and peripheral airway. This is relevant to biomarkers for example for vaccination, lung cancer, infection (whether viral, bacterial or fungal), inflammation, asthma/chronic obstructive pulmonary disease (COPD)/lung fibrosis/cystic fibrosis.

[0159] Embodiments of the present invention aim to collect pure vocal cord MLF, free (or with only minimal contamination) from saliva. To do so, embodiments of the present invention take advantage of the fact that the cough function of the human body expels MLF from the vocal chords to the oropharynx. By sampling this expelled MLF from a position within the oropharynx, pure vocal cord MLF, uncontaminated (or with only minimal contamination) by saliva, may be obtained, e.g. to allow analysis of biomarkers contained in the MLF.

[0160] The cough function is schematically illustrated with reference to FIGS. 2A to 2E. Coughing forces air through the vocal cords at high speed (typically, air is expelled in a cough at velocities ranging from around 75 to 100 miles/hour). Tracheal and vocal cord MLF is expelled from the mouth by coughing, along with saliva from the uvula, tongue and oropharynx.

[0161] In more detail, FIG. 2A illustrates an inhalation phase of the cough function (typically triggered by airway irritation), which fills the lungs (generally at 5) with air. In the next stage of the cough function, shown in FIG. 2B, the glottis is closed, and the abdominal muscles are compressed, to create pressure. In the following stage of the cough function, shown in FIGS. 2C and 2E (the latter being a cross-sectional view through the oropharynx, at the position indicated by the arrowhead in FIG. 2D), the glottis is opened and a cough-cloud 7 is emitted. As part of this process, MLF 9 is transmitted from the vocal cords to the oropharynx (see FIG. 2E).

[0162] A first embodiment of an airway sampling device 11 is shown in FIG. 3. The device 11 comprises a handle 13 to be gripped by a user (facilitated by a locator 14 provided on the upper surface of the handle 13 for contact with the user's forefinger), a stem 15 extending from the handle 13 and a sampling head 17 provided at the end of the stem distal from the handle 13, and angled relative to the longitudinal axis of the handle 13.

[0163] In the present embodiment, the handle 13, stem 15 and sampling head 17 are provided as an integrally formed, unitary body e.g. by moulding. An integrally formed stem 15, handle 13 and sampling head 17 is preferred to minimise the chances of any one of those components coming loose and being swallowed. However, in other embodiments, one or more of these parts of the sampling device 11 may be formed as separate parts which may then be attached, releasably or non-releasably, to the other parts to assemble the device. Also in the present embodiment, the sampling device 11 may be formed for example from plastics materials such as acrylonitrile butadiene styrene (ABS) or polypropylene (PP); however, different materials (either plastics or otherwise) may be used, as appropriate.

[0164] As shown in FIG. 4A (and in cross section in FIG. 4B), the sampling head 17 is provided with a perimeter wall 19 which extends generally perpendicularly to the axis of the stem 15 to create a protective hood 21 having a cavity or recess 22 to accommodate a sample collection membrane 23 in the form of a patch or small piece of (preferably absorbent and/or adsorbent) sampling material 23, to collect the sample from the subject 3. The perimeter wall 19 includes a gutter 25 around its upper edge, the purpose of which is explained later.

[0165] The sample collection membrane 23 of the present embodiment preferably comprises absorbent and/or adsorbent material, and may for example be Synthetic Absorptive Matrix (SAMT™) material. More generally, the sample collection membrane 23 materials could for example include, without limitation, a variety of synthetic and functionalised polymers in foam, fibrous or solid format. For example, and without limitation: polyurethane, fibrous hydroxylatred polyester (FHPE), polycaprolactone (PCL), nylon, cellulose acetate, cellulose, nitrocellulose, polyethersulfone, polysulfone, polypropylene, polyvinylidene fluoride (PVDF), polytetrafluoroethylene (PTFE), acrylic copolymer, white blood cell isolation media; also assay membranes for Point-of-Care (POC) diagnostics, lateral flow and flow through assays, blotting; also materials with antibodies and/or aptamers for diagnostic assays; and the like.

[0166] The sample collection membrane 23 is retained within the hood 21 by, but not limited to, adhesive bond, chemical weld, ultrasonic weld, or an overmoulding.

[0167] The sample collection membrane 23 is provided with an integral perforation 26 for its removal, post sample collection, with forceps or tweezers T, e.g. for analysis or retention by a clinician or other user (see FIG. 4C). To this end, the sample collection membrane 23 further includes a notch 27 at one end, to allow ready insertion of e.g. tweezers, to facilitate removal.

[0168] FIGS. 5A and 5B show the sampling device 11 in situ according to an airway sampling method aspect of the present invention. In this condition, the sampling head 17 is located at a sampling position according to the present embodiment, which sampling position is above (for example, a few centimetres above) the vocal cords of a subject 3, within the oropharynx and posterior to the uvula of the subject 3. This allows for MLF, uncontaminated (or with only minimal contamination) by saliva, to be adsorbed or absorbed onto the sample collection membrane 23 carried by the sampling head 17 when the subject is prompted to give a small cough or forced expiration (i.e. a short, sharp breath out).

[0169] The sampling device 11 of the present embodiment is specifically designed to facilitate the placement of the sampling head 17 into the sampling position shown in FIGS. 5A and 5B.

[0170] Firstly, various features of the sampling device 11 are dimensioned, angled and/or shaped to facilitate placement of the sampling head 17 into the sampling position shown in FIGS. 5A and 5B. In a preferred embodiment, different variants of the sampling device 11 are provided, each version being dimensioned, angled and/or shaped for usage with a subject, allowing ready placement by a user of the sampling head at the sampling position, based upon an age grading of the subject. Ultimately, the decision of which sized sampling device 11 to use will be determined by a clinician e.g. to account for a subject who is significantly larger or smaller than average for their age. However, the present embodiment seeks to provide, for example, three different sizes, intended for use by subjects coarsely graded according to three different age groups.

[0171] FIGS. 6A and 6B show dimensions (all in millimetres) and angles according to a currently most preferred embodiment for usage with an adult human subject (aged 16 or over); FIGS. 7A and 7B show preferred ranges for these dimensions (all in millimetres) and angles; FIGS. 7C and 7D show currently preferred dimensions (all in millimetres) and angles for a large-sized sampling device 11 intended for an adult subject (aged 16 or over); FIGS. 7E and 7F show currently preferred dimensions and angles for a medium-sized sampling device 11 intended for a subject aged between 12 to 15; and FIGS. 7G and 7H show currently preferred dimensions and angles for a small-sized sampling device 11 intended for a child subject (aged 8 to 11).

[0172] According to the present embodiment, the width of the sampling head 17 (this width being the dimension labelled in FIGS. 7C, 7E and 7G) is selected to maximise sampling material size (and hence maximising sample capture), without causing undue discomfort for a patient or subject 3. In particular, the width X of the sampling head 17 is designed so as to comfortably clear the corresponding distance X′ between the tonsils of the subject 3 (see FIG. 8A) and especially to avoid and/or minimise interreference with the tonsils of a subject during the sample collection process, especially for a subject suffering from a viral or bacterial infection causing the tonsils to swell. In the present embodiment, the width ranges from 10 mm to 16 mm and, as an illustrative example only, may preferably be 16 mm for an adult/large sized device, 14 mm for an intermediate aged/medium sized device and 12 mm for a child/small sized device. A head width of 10 mm or more is advantageous, as it maximises sample capture and allows for a good-sized sample collection membrane 23 to be located within the protective hood 21 of the sampling head 17. A head width of 16 mm or less is also desirable, to avoid discomfort for the subject, and especially to avoid and/or minimise interreference with the tonsils of a subject during the sample collection process, especially for a subject suffering from a viral or bacterial infection causing the tonsils to swell.

[0173] Next, and referring to FIGS. 8C and 8B, respectively, the open angle θ of the sampling head 17, along with the overall vertical depth Z of the sampling device 11 (measured from the uppermost point of the sampling device handle 11 to the lower-most point (the tip) of the downwardly-angled sampling head 17), are designed to maximise the sampling material sampling area (i.e. to maximise the exposure to expelled MLF), without significantly restricting airflow. Here, the “open angle” of the head 17 means the angle θ of the sampling head 17, and more specifically the plane of the opening of the recess 22 within the hood 21 (which plane also preferably corresponds to the plane of the sample collection membrane 23) relative to horizontal, when the sampling device 11 is positioned in situ in the sampling position shown in FIG. 8C, with the sampling head 17 located at the desired sampling position (i.e. above the vocal cords within the oropharynx, posterior to the uvula). In the present embodiment, the preferred range of open angle θ° of the sampling head 17 is 25° to 45°, with a most preferred angle of 39°, regardless of the age of the subject.

[0174] Here, and as explained with reference to FIG. 9, an open angle of at least 25° relative to horizontal is preferred, to avoid significantly restricting the airflow of the subject (and hence to avoid reducing the volume of the airborne sample). On the other hand, an open angle of 45° or less relative to horizontal is preferred, to avoid reducing the amount of airborne sample landing on the sample collection membrane, either as a result of sample escaping around the back of the sampling head 17, without coming into contact with the sample collection membrane 23, or simply impinging upon the protective hood 21 of the sampling device 11. As shown in FIG. 10, the preferred angling and length of the sampling head 17 maximise airflow and the amount of sample impacting on the sample collection membrane 23.

[0175] The overall depth Z of the sampling device 11 is preferably varied according to the age of the subject; purely as an illustration, for a sampling device 11 intended for use with an adult (aged 16 or over), the depth Z may for example be 23 mm; for a sampling device 11 intended for use with an intermediate-aged subject adult (aged 12 to 15), the depth Z may for example be 20 mm or 21 mm; for a sampling device 11 intended for use with a child (aged 8 to 11), the depth Z may for example be 17 mm.

[0176] The following table 1 recites currently preferred optimal values for the head width X, depth Z and sampling head angle θ. It is however to be appreciated that the following preferred optimal values, as well as all of the foregoing described angles and dimensions, are strictly non-limiting and illustrative only, and that other angles and dimensions may be used as appropriate.

TABLE-US-00001 TABLE 1 Optimal Sizes Age X Z θ Small  8-11 12 17 39° Medium 12-15 14 20 39° Large 16+ 16 23 39°

[0177] Next, and also with reference to FIG. 10, the outside surface 29 of the sampling head 17 is smooth and radiused so as to readily deflect the uvula 31 of the subject 3 towards the rear of the oropharynx, allowing the sampling head 17 to adopt the optimal sampling position shown in FIG. 10, centrally above the airway of the subject. For example, and simply as an illustration, a mid-point of the outside surface of the sampling head 17 may present the angles such as shown in FIGS. 7D and 7F (38° and 36° relative to horizontal when in the sampling position, respectively) to facilitate deflection of the uvula. However these angles are merely illustrative and other angles nay be used, as appropriate.

[0178] The sampling head 17 is further configured to minimise and/or eliminate sample collection membrane contamination e.g. from saliva or from lymph fluid from the tonsils. Firstly, and as explained above, the sampling head 17 is provided with a wrap-around hood 21 which encloses the sample collection membrane 23 on all sides (other than at the opening to the recess within the hood 21), and hence enables the sampling head 17 to push past the tonsils, to upwardly deflect the uvula, and potentially to also contact the back of a subject's throat, without any (or with only minimal) fluid contamination of the sample collection membrane 23. To prevent direct surface contact contamination from these areas the outer surface of the hood 21 is designed to be perpendicular to these landmarks, as shown in FIG. 11, during placement, sample capture, and removal of the sampling device 11 from the subject's airway.

[0179] As a further measure, and as noted above, the hood 21 is provided with an integral gutter 25. When the sampling device 11 is inverted for sample processing, there is a risk that fluids such as saliva or lymph fluid could flow over the peripheral edge of the sampling head 17, potentially contaminating the sample collection membrane 23. The integral gutter 25 avoids or ameliorates this risk by capturing these fluids, and allowing them to safely drain away as indicated by the pointed arrows in FIG. 4A. Flow is gravity fed and dependent on fluid viscosity, and allows fluid to drain off safely outside of the sampling area of the sampling device 11.

[0180] In addition to the design of the sampling head 17, the stem 15 is designed to be thin to minimise contact with the tongue and mouth of a subject 3, thus minimising the gag reflex. For example, and as illustrated in FIG. 6A, the stem width may preferably be 8 mm, for a sampling device 17 intended for use with an adult. Also, the sampling device 11 is preferably flexible, to minimise accidental trauma to the subject under testing.

[0181] In summary, the sampling device 11 of the present embodiment is designed to position the sample collection membrane in the oropharynx (behind the uvula), protected from saliva and other fluids from the mouth, tongue and uvula. On coughing, the sample collection membrane 23 catches (by impingement) tiny droplets of MLF from the vocal cords and originating from the lower airways.

[0182] An airway sampling method according to an embodiment of the present invention, using the sampling device 11 described above, will now be described with reference to FIG. 12.

[0183] As a preliminary step 1201, the back of the subject's throat is sprayed with lignocaine or other local anaesthetic, to minimise discomfort and to reduce the risk of a gag-reflex.

[0184] Next, at step 1202, and with the subject's mouth wide open, the sampling head 17 of the sampling device 11 is inserted into the patient's mouth, taking care to avoid saliva contamination to the sampling material from the tongue. Although not necessary, a tongue depressor may optionally be used during this step, to depress the tongue of the subject for greater visibility of the mouth and throat.

[0185] At step 1203, the rear surface of the sampling head 17 is used to upwardly lift the uvula, as necessary, so that the sampling head 17 is positioned centrally over the subject's airway, and in particular over the subject's vocal chords, within the oropharynx and posterior to the uvula.

[0186] Next, at step 1204, the subject is prompted to cough or give a forcible expiration (i.e. a sharp exhalation). As explained above, this results in MLF expelled from the vocal cords to be collected, uncontaminated (or with only minimal contamination) from saliva and other fluids.

[0187] Finally, at step 1205, the sampling device is removed from the patient's airway, allowing the sample collection membrane 23 to be removed from the sampling head 17 e.g. for analysis or storage.

[0188] A second embodiment of a sampling device 11 according to the present invention is shown in FIG. 13, in which the same or similar features are given the same reference numerals, and only the differences from the first embodiment will be described. As explained in the following, the primary distinction is that the second embodiment allows for an integrated sample washing and elution function.

[0189] To this end, and unlike the first embodiment, the second embodiment is firstly provided with a washing and elution chamber 33 at the far end of the handle. As best shown in FIGS. 14A to 14C, the washing and elution chamber 33 has a perimeter wall 35 upstanding from and surrounding the entire circumference of a bottom wall 37, to define a cavity 39 within. Within the perimeter wall 35, a plurality of upstanding columns 41 are provided, spaced at regular intervals. In use, and as explained below, the chamber 33 is designed to be compressed (i.e. squeezed) by a user, as part of the sample washing and elution function. The 41 columns push in a spreading motion against the saturated sample collection membrane (e.g. SAM) to maximise the recovery of the eluted MLF, when the user compresses the chamber 33 e.g. with their thumb T, as shown in FIGS. 35 and 36. Accordingly, the chamber 33 is preferably formed from a deformable, resilient material (such as thermoplastic vulcanizate, TPV, although other suitable materials may equally be employed). In the present embodiment, the chamber 33 is further provided with a peripheral undercut feature 43 which locates over an annular flange 45 within the handle, holding the chamber 33 in place, with the bottom wall 37 protruding from the handle 13 to define a button, to facilitate squeezing of the chamber 33 by a user. The outer surface of the bottom wall 37 is provided with a roughened or textured area 41 to facilitate a user's steady grip on the bottom wall 37 during squeezing of the chamber 33. Preferably, the opening of the chamber 33 is closed by a removable protective cover 46 (see FIG. 14D), to prevent/reduce contamination risks prior to and during the sample collection process. The bottom wall 37 of the chamber 33 is further provided with a generally circular weakened area 47 of reduced thickness (see FIG. 13), the purpose of which is explained later.

[0190] Secondly, the device 11 of the present embodiment is provided with a hinge 49 connecting the handle 13 to the stem 15 (see FIG. 15A), and thus permitting the stem 15 and sampling head 17 to be rotated relative to the handle 13 between the unfolded condition shown in FIG. 13 or FIG. 15A (for use in sample collection) and a folded condition as shown in FIG. 15B (for sample washing and elution, as well as sample storage and, optionally, initial shipping).

[0191] As in the first embodiment, the sampling head 17 of the present embodiment is configured to carry a sample collection membrane 23 such as a piece of absorbent and/or adsorbent sampling material (e.g. SAM™), to collect a sample from a subject's airway. In this embodiment, however, the interior of the sampling head 17 is further provided with a series of protrusions 50, arranged in a chevron pattern (see FIGS. 15C and 15D), on which the sample collection membrane 23 is placed, with its edges located on a peripheral ledge 51 of the interior head surrounding the chevron-patterned protrusions (see FIG. 15E). The sample collection membrane 23 may be attached to the peripheral edge of the sampling head 17 by, but not limited to, adhesive bond, chemical weld, ultrasonic weld, an overmoulding. Again, the sample collection membrane 23 is provided with an integral perforation 26 for optional removal with forceps or tweezers T (see FIG. 15F); FIG. 15G shows the interior of the sampling head 17 with the sample collection membrane 23 removed.

[0192] As shown in FIGS. 16A to 16G, the hinge 49 is preferably a snap-fit hinge, in which the stem 15 and sampling head 17 assemble to the handle 11 via a snap-fit. To assemble, the hinge centre 51 of the stem 15 is pushed between hinge studs 53 provided in the handle 13, which causes the handle sides to flex rotate, allowing the stem 15 to pass the hinge studs. When the hole 55 at the hinge centre of the stem 15 and the hinge studs 53 in the handle 15 are in-line, the pre-loaded force within the flexible sides of the handle 15 force the hinge studs to snap-in, captivating the hinge assembly.

[0193] Preferably, tapered hinged studs 53 are used. Tapered studs offer two advantages—firstly, they significantly improves assembly; secondly, the increased surface area contact gives the hinge greater transverse stability.

[0194] In the present embodiment, the hinge centre of the stem 15 is designed with a deliberate interference, therefore, once assembled, there is a frictional contact between both components (stem 15 and handle 17).

[0195] Once assembled, and as shown in FIG. 16G, there are two positional snap-fits, 165° apart, one in the extended “sampling” position and the other in the housed “washing and elution” position. Movement between these positions is facilitated by the scalloped finger locater curves 57 provided in the handle 17 (see FIG. 16B).

[0196] As with the first embodiment, the present embodiment may be provided in different sizes, shapes and dimensions for usage with different sized-subjects, preferably based as a guideline on the age of the subject. As with the first embodiment, for example, an adult/large size sampling device 11 may be produced for preferred use with a subject aged 16 or over—see FIGS. 17A and 17B, 18C and 18D for (merely illustrative) preferred dimensions and angles, with a preferable range of dimensions and angles as shown by FIGS. 18A and 18B. Further, a medium sized device 11 may preferably be dimensioned and angled as shown in FIGS. 18E and 18F, for preferable usage with a subject of intermediate age (age 12 to 15) and a small sized device 11 may preferably be dimensioned and angled as shown in FIGS. 18G and 18H, for preferable usage with a subject of child age (age 8 to 11). Here, the benefits of using the angles and dimensions shown is the same as for the first embodiment described above, again all dimensions shown are in millimetres, and again, although preferable, all dimensions and angles shown are illustrative and non-limiting and other sizes and dimensions and angles may be used e.g. for different sized subjects.

[0197] FIGS. 19A to 19E show various free standing positions of the sampling device 11 of the present embodiment. As shown in FIG. 19A, the sides of the handle 13, stem 15 and sampling head 17 are designed to allow the sampling head 17 to stay motionless when placed on its side, without rolling. FIGS. 19B and 19C show the device 11 in its unfolded/sampling condition, and placed on a level surface so as to rest on the sampling head 17 and sides of handle 13. FIGS. 19D and 19E shows the sampling device 11 placed on a level surface in an inverted condition, resting on a finger-grip portion of the handle 13 and the button provided by the bottom wall 37 of the washing and elution chamber 33, e.g. for insertion of a washing and elution buffer as explained below in connection with FIG. 21.

[0198] FIG. 20 shows the sampling device 11 of the present embodiment in a hand grip position for a user to conduct the sampling process described below in connection with FIG. 21.

[0199] Operation of the second embodiment of the sampling device, according to a second embodiment of a sampling method of the present invention, will now be described with reference to the flow chart of FIG. 21.

[0200] Firstly, in step 2101, and aided by the scalloped finger locators 57, a user pinches/pulls the stem 15 to open device 11 (see FIG. 22), and rotates the stem 15 and sampling head 17 relative to the handle 11, to click it into the fully unfolded sampling position.

[0201] In Step 2102, to reduce the risk of a gag-reflex, the back of the subject's throat is sprayed with lignocaine or other local anaesthetic. As will be appreciated, the order of steps 2101 and 2102 may be reversed, or these steps may be performed simultaneously e.g. by two clinicians working in tandem.

[0202] In step 2103, with the subject's mouth wide open, the sampling head 17 of the device 11 is inserted into the subject's mouth (see FIG. 23), taking care to avoid saliva contamination from the tongue. Although the device is useable on its own, for greater visibility of the mouth and throat, the device 11 may optionally be inserted whilst the subject's tongue is depressed using a suitable tongue depressor.

[0203] In step 2104, the sampling head 17 is used to deflect the subject's uvula, as necessary, until the device 11 is position centrally over the subject's airway (see FIG. 24, with the stem shown in cross-section and the handle omitted, for clarity) and the sampling head located at the desired sampling position namely over the vocal cords, within the oropharynx and posterior to the uvula of the subject.

[0204] In step 2105, the subject 3 is asked to cough or give a forced expiration (a sharp exhalation), thus allowing a sample of MLF to be collected by the sample collection membrane 23 located within the sampling head 17 of the device 11, uncontaminated (or with only minimal contamination) by saliva or other fluids.

[0205] In step 2106, the sampling device 11 is entirely removed from the subject's airway.

[0206] If the sample is to be stored for future sample preparation, the process proceeds to step 2107, in which the protective cover 46 is removed from the chamber 33, and the stem 15 and sampling head 17 are rotated towards the handle 13 until the closed condition is adopted, protecting the sample from extraneous contamination; the closed sampling device 11, including its collected sample, may then be frozen.

[0207] On the other hand, if a user wishes to directly wash and elute the sample, the process proceeds to step 2108. In this step, the protective cover 46 is again removed from the chamber 33, and elution buffer is introduced into the chamber 33 e.g. via a pipette P as shown in FIG. 25A. In the present embodiment, the chamber 33 has, merely as an example, a maximum capacity of 504.1, although other sized chambers may of course be employed, as appropriate.

[0208] Next, in step 2109, the stem 15 and sampling head 17 are rotated towards the handle 13 to bring the device 11 into its fully folded condition (see FIG. 25B). As will be appreciated, the sample collection membrane 23 will now be located between the chevron-patterned protrusions of the sampling head 17 on one side, and the tops of the protruding columns 41 provided within the washing and elution chamber 33 on the other side.

[0209] Next, in step 2110, the user shakes the folded device 11, causing the elution buffer to wash the sampling material 23 now located within the chamber (see FIG. 26). Here, the washing of the sample collection membrane 23 is facilitated by the fact that the elution buffer is able to travel freely around and between the columns 41 within the chamber and the chevron-patterned protrusions within the sampling head 17, thus readily exposing both sides of the sampling material of the sample collection membrane 23 to the elution buffer and hence maximising MLF capture from the sample collection membrane 23.

[0210] Next, in step 2111, the user orientates the device 11 with the circular weakened area 47 located over a suitable collection vessel V (see FIG. 27A).

[0211] Finally, in step 2112, the user squeezes the button defined by the bottom wall 37 of the chamber 33. The resultant pressure increase within the chamber 33 causes the weakened area 47 to rupture, ejecting the liquid contents (i.e. the elution buffer containing MLF washed from the sampling material) (see FIG. 27B) into the collection vessel V, e.g. for analysis or storage.

[0212] Hence, the process described above provides a user with a ready and convenient means of sample extraction. However, the sample extraction process of FIG. 21 is only one example, and other sample extraction processes are possible. Some exemplary alternative sample extraction process are described later. First, some further sampling device embodiments are described, in which like features are given the same reference numerals, and the discussion will focus only on the distinctions from the first and/or second embodiments of the sampling device described above.

[0213] A third embodiment of a sampling device 11 is shown in FIGS. 28A to 28E. The sampling device 11 of the present embodiment is very similar to the second embodiment described above, but is additionally provided with a transverse slot or groove 57, located forward (i.e. towards the sampling head end) of the finger locator 14 of the handle, into which a generally circular cough shield 59 is located (as shown in FIGS. 28A and 28B) to form the completed device 11 shown in FIGS. 28C and 28D. The third embodiment is otherwise the same as the second embodiment.

[0214] The cough shield 59 is preferably made from a thin sheet of plastics material (e.g. Polyethylene Terephthalate Glycol (PETG) or Polycarbonate (PC)) although other suitable materials (e.g. metals) may be used, as appropriate. In the present embodiment, the cough shield 59 offers a user ≃315° protective coverage from the cough cloud generated by the subject during airway sampling, with the remaining ≃45° of the cough cloud passing underneath the winged sides of the handle. A slot 61 is provided in the cough shield 59, offering sufficient clearance for the sampling head 17 to be freely rotated between the folded and unfolded conditions of the sampling device 11 (see FIG. 28E).

[0215] As will be appreciated, the first embodiment of a sampling device 11 described above may likewise be modified to similarly include a cough shield 59, locating into a slot 57 to be provided, according to this modification, in the handle of the device 11.

[0216] A fourth embodiment of a sampling device 11 is shown in FIGS. 29 and 30. This embodiment modifies the second embodiment described above, to include an illumination module 65 within the handle 13, and to configure the stem 15 and sampling head 17 as a light guide device, beneficially allowing for the interior of a subject's mouth to be illuminated to facilitate the correct positioning of the sampling device 11 during the sampling process.

[0217] In more detail, and as shown in the various parts of FIG. 29, the stem 15 and sampling head 17 of the present embodiment are formed from a suitable light-transmissive material or materials so as to act as a light guide. For example, the stem 15 and sampling head 17 of the present embodiment may be formed from optically clear thermoplastic styrene-butadiene copolymers (SBC) or optically clear polycarbonates (PC) which are designed to glow with light from an external light source.

[0218] Next, the handle 13 of the present device is adapted to include a location groove 63 (see FIG. 29A) for accommodating an illumination module 65. In the present embodiment, the illumination module 65 includes a snap hook 67 (see FIG. 29b), and the handle 13 further comprises a snaphook hole (not shown) to receive the same, to securely retain the illumination module 65 in the handle 13 (see FIGS. 29C and 29D). In the present embodiment, the snap hook 67 may be disengaged from the snaphook hole, allowing the illumination module 65 to be removed for insertion into one or more other sampling devices 11; that is, one illumination module 65 may be re-used (after appropriate cleansing) and shared amongst a plurality of different illuminated sampling devices 11. The illumination module 65 is sealed against liquid and dirt ingress and for example may be constructed with an ABS moulded housing, with the necessary electronics potted in place using e.g. a TPE overmoulding process.

[0219] Preferably, the illumination module 65 may include a switch 71, which may be actuated by a light activating spigot optionally provided within the handle 13. This arrangement may for example allow for the light to be automatically switched on when the illumination module 65 is inserted into the handle 13 and switched off when the illumination module 65 is removed from the handle 13. Alternatively, the switch 71 may allow for the light to be automatically switched on when the sampling device 11 is brought into its unfolded (sampling) condition, and switched off when the sampling device 11 is in the folded condition. Alternatively, a manual on/off switch may be provided for manual activation by a user.

[0220] As for the illumination module 65, any suitable illumination device may be employed, but for example these may include e.g.:

[0221] 1) A laser light source, for example a laser with a wavelength between 450-500 nm (blue-cyan).

[0222] 2) An LED light source, for example an Ultrabright White directional LED.

[0223] An example of a laser light source is shown in FIG. 30A, with the light emitting element shown in detail in FIG. 30B. The latter may include, for example, a suitable power supply 69 such as two 3 Volt batteries wired in parallel, for example 5.5 mAh Lithium Manganese Silicon Batteries having Dimensions 06.8 mm, 2.1 mm thick (Part number: MS621). Also shown in FIG. 30B is a low profile, tactile, surface mount switch 71 e.g. for automatic activation by a light activating spigot optionally provided within the handle 11 as described above. The light emitting element further comprises a laser diode 73, for example a 3.3 mm laser diode with driver module.

[0224] An example of an LED light source is shown in FIG. 31A, with the light emitting element shown in detail in FIG. 31B. The latter may include, for example, a suitable power supply 69 such as two 1.55 Volt batteries wired in series, for example 16 mAh Silver Oxide Batteries having dimensions 06.8 mm, 1.65 mm thick (Part number: SR65). Also shown in FIG. 31B is a low profile, tactile, surface mount switch 71 e.g. for automatic activation by a light activating spigot optionally provided within the handle, as described above. The light emitting element further comprises an LED light source 75, for example a 3 mm ultra bright directional LED.

[0225] In the same way that the second embodiment may be modified to include an illumination feature, according to a fifth embodiment of the present invention, the first embodiment of the sampling device 11 described above may also be modified as shown in FIG. 32 to include a light module 65 within the handle 13, beneficially allowing for the interior of a subject's mouth to be illuminated to facilitate the correct positioning of the sampling device 11 during the sampling process. In this embodiment, as it is provided integrally with the sampling head 17 and stem 15 of the device 11, the handle 13 is also configured as a light guide device. In particular, the integral handle 13, stem 15 and sampling head 17 of the present embodiment are preferably formed from a suitable light-transmissive material or materials so as to act as a light guide. For example, the handle 13, stem 15 and sampling device 17 of the present embodiment may be integrally formed from optically clear thermoplastic styrene-butadiene copolymers (SBC) or optically clear polycarbonates (PC) which are designed to glow with light from the illumination module 65.

[0226] As the present fifth embodiment (like the first embodiment) does not have a folding function, a light activating spigot is not provided in the handle 11. However, a manual light switch is provided for activation by a user, so as to switch on the illumination device during the sampling process. In other respects, such as the nature of the illumination module, the fifth embodiment may generally be the same as for the fourth embodiment described above, and hence is not re-described here.

[0227] It will be appreciated that, according to further embodiments of the present invention, the cough shield feature of the third embodiment may also be combined with the fourth and fifth embodiments having the light guide feature.

[0228] The following describes some alternative sample extraction methods, suitable for usage with embodiments of the sampling device having a washing and elution chamber (e.g. the second, third and fourth embodiments described above).

[0229] According to a further embodiment of a sample extraction method, as shown in FIG. 33, rather than a user squeezing the chamber to cause rupture of the weakened area, a user may instead extract the liquid content (elution buffer containing MLF) by inserting a needle N of a syringe S into the weakened area, and pulling back on the plunger of the syringe to extract the sample. The extracted sample may then be processed as desired e.g. ejected from the syringe into a suitable vessel for direct analysis or transferred into a cryogenic storage container and frozen.

[0230] According to a still further embodiment of a sample extraction method, as shown in FIG. 34, a centrifuge method may for example be employed. According to this embodiment, after conducting the sample gathering process, introducing elution buffer introduced into the chamber and placing the sampling device into its folded condition, a user places the sampling device into a suitable centrifuge tube T (e.g. a cryogenic 50 ml centrifuge tube), with the tube then being closed by a cap C. The centrifuge tube is then located into a suitable centrifuge, which is then operated to spin the centrifuge tube e.g. to spin-down for 30 seconds @ 4000 rpm. This causes the weakened area to rupture, so that the liquid contents (elution buffer containing sampled MLF) collect at the bottom of the centrifuge tube T. A user then removes the cap from the tube, removes the device, and re-caps the tube e.g. for freezing or analysis.

[0231] The embodiments described above relate to airway sampling from a human subject. However, this is merely exemplary, and according to further embodiments the present invention may instead be applied to sampling devices and associated sampling methods for airway sampling performed on non-human subjects e.g. livestock such as cattle or pets such as cats and dogs.

[0232] The embodiments above assume that a user e.g. a nurse, doctor or other clinician would take a sample from a subject. However, potentially, a subject may take a sample from themselves, in which case the “user” and the “subject” are the same person.

[0233] The foregoing description has been given by way of example only and it will be appreciated by a person skilled in the art that modifications can be made without departing from the scope of the present invention as defined by the claims.