Airway sampling device and related methods

Abstract

The present application discloses a variety of airway sampling devices and related methods. According to one embodiment, an airway sampling device for sampling from a subject's airway has a handle that a user holds tightly when sampling and a sampling head carried by the handle, wherein the sampling head includes a cavity having an opening for sample entry and a sample collection membrane located in the cavity for accommodating the sample.

Description

Technical Field

[0001] The present invention relates to an airway sampling device and related methods. Embodiments of the present invention particularly seek to provide a non-invasive lower airway mucosal lining fluid sampling device and related methods. Background Art

[0002] Current methods for monitoring airway inflammation use samples obtained from blood, breath, sputum, nasal passages, and invasive bronchoscopy.

[0003] However, existing breath sampling techniques have various problems, and when measuring inflammation using non-invasive sampling methods (blood, breath, sputum and nasal methods) when studying lung diseases, existing techniques are flawed. Below is an example of measuring inflammation in asthma to illustrate the range of problems with blood, breath, sputum and nasal samples; but these samples are flawed in a range of lung diseases, not just asthma.

[0004] Blood analysis: The blood collection site is too far from the respiratory tract; blood is affected by many organs through the systemic circulation and there is a lot of dilution in about 5L of blood. In modern clinical practice of asthma, people tend to use blood eosinophil counts to assess the level of airway inflammation. This is reflected in the need for a minimum level of blood eosinophils before selecting asthma patients for monoclonal antibody treatment (anti-interleukin-5 or anti-IL-5). However, the eosinophil count in the blood varies greatly during the day due to exercise and steroid circadian rhythm.

[0005] Eosinophils are considered an important target in patients with asthma because they are proinflammatory cells that migrate from the blood to sites of inflammation in the respiratory tract and intestine (1, 2). Historically, the humble eosinophil count has been widely used in the treatment of asthma (3-5). Recently, there has been a renewed interest in the use of blood eosinophil counts to select patients with asthma for monoclonal antibody therapy (6-10). A mathematical algorithm has been developed to predict elevated sputum eosinophils: the eosinophil / lymphocyte and eosinophil / neutrophil index (ELEN) index (9). In addition, recent American Thoracic Society / European Respiratory Society international guidelines for severe asthma support blood eosinophil counts, suggesting that the utility of other biomarkers in identifying asthma phenotypes requires further validation (11). However, blood eosinophil counts are notoriously variable, with levels increasing during the day (12), and exercise can increase eosinophil counts (13). A recent study of 24-hour blood eosinophil counts found increased variability in blood eosinophil counts in patients with moderate asthma (14).

[0006] Breathed NO: Exhaled nitric oxide (NO or FENO) levels are a crude measure of airway inflammation in asthma. However, such levels are variable, very non-specific, and can be altered by treatment, dietary factors, and the menstrual cycle in women. They do not provide a specific marker for asthma, and we need to look at a range of protein, lipid, and prostanoid mediators.

[0007] Exhaled breath condensate (EBC) analysis is contaminated by condensation and oropharyngeal contamination; a major concern with current noninvasive sampling methods from the respiratory tract (including breath and sputum analysis) is contamination from the oral cavity (or oropharynx). Exhaled breath has been extensively studied as a noninvasive means of assessing airway inflammation, including by measuring mediators in exhaled breath condensate (EBC) (15). Richard Effros and colleagues elegantly highlighted the problems of salivary contamination and condensation dilution that occur during EBC collection (16–18); these can be serious obstacles to measuring EBC pH (19)(20) and levels of inflammatory mediators in breath droplets.

[0008] Breath volatile organic compound (VOC) analysis and metabolomics appear more promising (21–24). However, VOCs do not include proteins such as cytokines, chemokines, and antibodies.

[0009] Sputum contains dead and dying cells, and mediator levels are affected by bacteria, saliva, proteases, and mucins. The late Morrow Brown used sputum to measure eosinophilia in his initial studies in the 1950s, which demonstrated the efficacy of oral prednisolone in the treatment of asthma (25), although sputum had been of interest to clinicians before the time of Hippocrates (26). The late Freddy Hargreave pioneered the clinical use of quantitative determination of eosinophil levels in induced sputum (27). As an extension of this work, Ian Pavord and colleagues (Leicester and Oxford) have demonstrated that normalization of sputum eosinophil counts is effective in reducing asthma exacerbations (28). In addition, adult asthma phenotypes have been defined by sputum eosinophil to neutrophil percentages (29)(30). There are reports that blood eosinophil counts are poor substitutes for sputum eosinophil counts (31, 32), while another group has found that blood eosinophil counts can be used to predict sputum eosinophil counts (33, 34). Analysis of fluid-phase media from sputum samples presents numerous technical problems (35): these include protease and bacterial degradation, loss of protein secondary structure due to dithiothreitol (DTT) reduction, binding to mucus, contamination with saliva and oropharyngeal contents, and continuous leakage of mediators from dead and dying cells. Some elegant attempts have been made to validate the measurement of fluid-phase levels of IL-5 in sputum (36), highlighting the role of proteases (37).

[0010] Nasal sampling is from the airways or respiratory tract, but the mucociliary escalator (MCE) samples nasal molecules from the front to the back of the nose, from the nostrils to the pharynx. Therefore, nasal MCE is discontinuous, with MCE going from the lower airways up through the bronchi and trachea. However, nasal absorption is preferable to nasal lavage in measuring inflammatory mediators and does inform airway inflammation from the upper airways.

[0011] Bronchoscopy sampling includes bronchial biopsy, bronchoalveolar lavage (BAL), bronchial brushings, and bronchial suction. Performing bronchoscopy to obtain bronchial mucosal biopsy and bronchial brushing samples requires the presence of a team of experts in the endoscopy suite and the patient needs sedation and local anesthesia. Biopsy, bronchoalveolar lavage, bronchial brushings, and bronchial suction of the airways are useful samples for analysis, but they are too invasive for most patients with asthma. Bronchoscopy is usually performed in selected centers for patients with lung cancer, tuberculosis, and interstitial lung disease.

[0012] References

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[0059] 47. Jackson DJ, Glanville N, Trujillo-Torralbo MB, Shamji BW, Del-RosarioJ, Mallia P, Edwards MJ, Walton RP, Edwards MR, Johnston SL. Interleukin-18 is associated with protection against rhinovirus-induced colds and asthmaexacerbations. Clin Infect Dis 2015;60:1528-1531. Summary of the invention

[0060] Aspects of the present invention seek to provide improved airway sampling devices and methods that seek to overcome or ameliorate one or more problems associated with the prior art. Specifically, embodiments of the present invention are directed to providing a non-invasive airway sampling device and method for sampling airway mucosal lining fluid (MLF), particularly obtaining lower respiratory tract samples (from outside the vocal cords) with no (or minimal) saliva and oropharyngeal contamination.

[0061] One aspect of the invention is based on sampling droplets in the vocal cords and lower respiratory tract (peripheral airways outside the vocal cords). This aspect samples mucosal lining fluid (MLF) that is ejected from the lower respiratory tract by forceful exhalation or coughing. A key feature of one aspect of the invention is minimizing saliva contamination of the sample obtained. Another aspect of the invention is the non-invasive acquisition of lower respiratory tract specimens without the use of bronchoscopy. An important feature of the lower respiratory tract MLF is that it continues upward through the respiratory tract via the mucociliary escalator (MCE) and then passes through the vocal cords before swallowing. The MLF of the vocal cords therefore reflects airway events in the peripheral lower respiratory tract. The MLF in the small airways contains molecules and biomarkers that reflect disease in the underlying tissue. The small airway MLF is transmitted to the large airways via the MCE and all the way up to the vocal cords. The inventors of the present invention have recognized that capturing fluid from the vocal cords and lower respiratory tract in a non-invasive and accurate manner would be highly beneficial in assessing respiratory disease by obtaining samples from the lower respiratory tract (trachea, bronchi, bronchioles) that are not contaminated by saliva and oropharynx.

[0062] According to a first aspect of the present invention, there is provided an airway sampling device for sampling the airway of a subject, the device comprising a handle to be gripped by a user during sampling and a sampling head carried by the handle, the sampling head comprising a cavity with an opening for entry of the sample and a sample collection membrane located within the cavity for accommodating the sample.

[0063] Preferably, the sample collection membrane comprises an absorbent and / or adsorbent material.

[0064] Preferably, the sample collection membrane is detachable from the sampling head.

[0065] Preferably, the sample collection membrane includes a perforation to facilitate its removal from the sampling head.

[0066] Preferably, the sample collection membrane comprises a notch to facilitate grasping the sample collection membrane when separating the sample collection membrane from the sampling head.

[0067] Preferably, the cavity has a gutter disposed at least partially around its opening.

[0068] Preferably, the cavity is defined within a peripheral wall disposed at least partially around the sampling head, and wherein an outer surface of the peripheral wall is configured to be perpendicular to the subject's tonsils when the sampling head is inserted into and / or removed from the subject's pharynx.

[0069] Preferably, the cavity is defined within a peripheral wall disposed at least partially around the sampling head, and wherein an outer surface of the peripheral wall is configured to be perpendicular to the uvula and / or posterior oropharyngeal wall of the subject during capture of the sample.

[0070] Preferably, the outer surface of the peripheral wall is configured to deflect the uvula of the subject, allowing the sampling head to pass from the oral cavity into the pharynx.

[0071] Preferably, the sampling head is connected to the handle via a valve stem.

[0072] Preferably, the sampling head, the valve stem and the handle are integrally formed.

[0073] Preferably, the handle has a protruding portion for engagement by a user's fingers to facilitate gripping of the handle.

[0074] Preferably, the handle has a chamber, and the sampling head is movable relative to the handle between a first state (in which the sampling head is away from the handle) and a second state, wherein in the second condition, the cavity is located above the chamber to define a shell, which encloses the sample collection membrane inside the cavity and inside the chamber.

[0075] Preferably, the housing is fluid-tight.

[0076] Preferably, a weakened area is provided in one of the chambers or cavities.

[0077] Preferably, the weakened region is configured to rupture when pressure is applied to the housing.

[0078] Preferably, the weakened region is provided in the chamber and the chamber is formed from a deformable material to allow a user to apply pressure to the housing.

[0079] Preferably, the weakened region is configured to allow insertion of a syringe needle into the housing.

[0080] Preferably, the weakened region is configured to rupture when the sampling device is spun by a centrifuge.

[0081] Preferably, the cavity has one or more protrusions inside, and a sample collection membrane is provided on the protrusions.

[0082] Preferably, the interior of the cavity has a plurality of protrusions in a V-shaped pattern, and the sample collection membrane is located on the protrusions.

[0083] Preferably, the interior of the chamber is provided with one or more protrusions which come into contact with the sample collecting membrane when the sampling device is placed in its second state.

[0084] Preferably, the one or more protrusions are configured to push against the sample collection membrane when a user applies pressure to the housing.

[0085] Preferably, the sampling device comprises retaining means to retain the sampling device in its first and second states.

[0086] Preferably, the edge of the handle includes a scalloped region to facilitate moving the sampling device from the second state to the first state.

[0087] Preferably, the sampling device further comprises an illumination module, and the sampling head is configured as a light guide plate to guide and emit light emitted from the illumination module.

[0088] Preferably, the lighting module is detachably mounted on the sampling device.

[0089] Preferably, the lighting module comprises a switch, and the handle comprises a protrusion, and when the sampling device is mounted on the sampling device, the protrusion is used to operate the switch to the on position.

[0090] Preferably, the lighting module comprises a switch, the handle comprising a protrusion for actuating the switch to an on position when the sampling device is placed in its first state.

[0091] Preferably, the lighting module comprises an LED light source or a laser light source.

[0092] Preferably, the sampling head is arranged at the first end of the sampling device, away from the second end of the sampling device provided with a handle, and the sampling device also includes a protective cover installed between the first end and the second end of the sampling device for protecting the user from being affected by the sampling of the subject.

[0093] Preferably, the airway sampling device is shaped and sized to position the opening of the cavity within the oropharynx above the vocal cords and behind the uvula of the subject when the sampling head is in a sampling position in the patient's airway for sampling.

[0094] Preferably, the sampling head is angled relative to the handle so that when the sampling head is in a sampling position in the patient's airway, the plane of the cavity opening is presented at an angle of 25° to 45° downward from the horizontal.

[0095] Most preferably, the sampling head is angled relative to the handle so that the plane of the cavity opening is angled 39° downward from the horizontal when the sampling head is in the sampling position in the patient's airway.

[0096] Preferably, the depth of the sampling device from the uppermost portion of the handle to the lowermost portion of the sampling head is 17 mm to 23 mm.

[0097] Preferably, the length of the opening is between 15 mm and 30 mm.

[0098] Most preferably, the length of the opening is 26 mm.

[0099] Preferably, the maximum width of the sampling head is between 10 mm and 16 mm.

[0100] Most preferably, the maximum width of the sampling head is 16 mm.

[0101] Preferably, the outer surface of the sampling head is designed to be perpendicular to at least one of the tonsils, uvula, and back of the throat of a subject during placement, sample capture, and removal of the sampling device from the airway of the subject.

[0102] According to a second aspect of the present invention, there is provided an airway sampling device for sampling from a sampling position in the airway of a subject, the device comprising a handle grasped by a user during sampling and a sampling head for insertion into the airway of the subject and carried by the handle, the sampling head comprising a cavity with an opening for entry of the sample, wherein the shape and / or size of the airway sampling device is such as to ensure that when the sampling head is located at the sampling position in the patient's airway, the opening is located above the vocal cords and in the oropharynx of the subject, behind the uvula.

[0103] Preferably, the sampling head is angled relative to the handle so that when the sampling head is in a sampling position in the patient's airway, the plane of the cavity opening is presented at an angle of 25° to 45° downward from the horizontal.

[0104] Most preferably, the sampling head is angled relative to the handle so that the plane of the cavity opening is angled 39° downward from the horizontal when the sampling head is in the sampling position in the patient's airway.

[0105] Preferably, the depth of the sampling device from the uppermost portion of the handle to the lowermost portion of the sampling head is 17 mm to 23 mm.

[0106] Preferably, the length of the opening is between 15 mm and 30 mm.

[0107] Most preferably, the length of the opening is 26 mm.

[0108] Preferably, the maximum width of the sampling head is between 10 mm and 16 mm.

[0109] Most preferably, the maximum width of the sampling head is 16 mm.

[0110] Preferably, the outer surface of the sampling head is designed to be perpendicular to the tonsils, uvula and back of the throat of a subject during placement, sample capture and removal of the sampling device from the airway of the subject.

[0111] According to a third aspect of the present invention, there is provided an airway sampling device for sampling the airway of a subject, the device comprising a handle which is held by a user when sampling and a sampling head carried by the handle, the handle being provided with a chamber, the sampling head moving relative to the handle between a first state of the sampling device (wherein the sampling head is away from the handle) and a second state of the sampling device (wherein the sampling head is located near the chamber).

[0112] Preferably, when the sampling device is in the second state, a housing is defined between the sampling head and the chamber.

[0113] Preferably, the housing is fluid-tight.

[0114] Preferably, a weakened region is provided in one of the chamber or the sampling head.

[0115] Preferably, the weakened region is configured to rupture when pressure is applied to the housing.

[0116] Preferably, the weakened region is provided in the chamber and the chamber is formed from a deformable material to allow a user to apply pressure to the housing.

[0117] Preferably, the weakened region is configured to allow insertion of a syringe needle into the housing.

[0118] Preferably, the weakened region is configured to rupture when the sampling device is spun by a centrifuge.

[0119] Preferably, a sample collection membrane is located within the sampling head.

[0120] Preferably, one or more protrusions are provided inside the sampling head, and the sample collecting membrane is located on the one or more protrusions.

[0121] Preferably, the interior of the sampling head has a plurality of V-shaped protrusions, and the sample collection membrane is located on the plurality of V-shaped protrusions.

[0122] Preferably, the interior of the chamber is provided with one or more protrusions which come into contact with the sample collecting membrane when the sampling device is placed in its second state.

[0123] Preferably, the sampling device comprises retaining means to retain the sampling device in its first and second states.

[0124] Preferably, the edge of the handle includes a scalloped region to facilitate moving the sampling device from the second state to the first state.

[0125] According to a fourth aspect of the present invention, there is provided a method of sampling the airway of a subject, the method comprising collecting a sample from a sampling location located above the vocal cords, within the oropharynx and behind the uvula of the subject.

[0126] Preferably, the step of collecting samples comprises:

[0127] placing a sample collector at a sampling site within the airway of a subject; and prompting the subject to cough or forcefully exhale to produce a sample.

[0128] Preferably, the sample comprises mucosal lining fluid from the subject's vocal cords resulting from the subject coughing or forceful exhalation.

[0129] According to a fifth aspect of the present invention, there is provided a method for preparing a sample collected from a subject using the sampling device of the first aspect, the method comprising exposing a sample collection membrane to an elution buffer to elute the sample into the elution buffer.

[0130] Preferably, the method comprises removing the sample collection membrane from the cavity and placing the sample collection membrane in an elution buffer.

[0131] Preferably, the handle of the sampling device is provided with a chamber, and the sampling head moves relative to the handle between a first state and a second state, wherein in the first state, the sampling head is away from the handle, and in the second state, the cavity is located above the chamber to define a shell, which surrounds the sample collection membrane between the interior of the cavity and the interior of the chamber, wherein the method includes introducing an elution buffer into the chamber and placing the sampling device in its second state so that the sample collection membrane is exposed to the elution buffer.

[0132] Preferably, the method further comprises agitating the sampling device after placing the sampling device in its second state.

[0133] Preferably, a weakened region is provided in one of the chamber or the cavity, and the method further comprises applying pressure to the housing to rupture the weakened region to remove the elution buffer containing the eluted sample from the housing.

[0134] Preferably, the method further comprises inserting a needle of a syringe into the housing, and extracting an elution buffer containing the elution sample from the housing using the syringe.

[0135] Preferably, a weakened area is provided in one of the chambers or cavities, and the method further comprises placing the sampling device still in the second state into a container, and rotating the container using a centrifuge to break the weakened area and introduce an elution buffer containing the eluted sample into the container.

[0136] Preferably, the method further comprises freezing the sampling device still in the second state together with the elution buffer containing the eluted sample still within the housing. BRIEF DESCRIPTION OF THE DRAWINGS

[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, in which:

[0138] Figure 1 is a schematic diagram showing local details of the mucociliary escalator of a subject;

[0139] Figures 2A to 2E Schematic illustration of cough function in human subjects;

[0140] Figure 3 A first embodiment of a sampling device according to the present invention is shown;

[0141] Figures 4A to 4C shows details of the sampling head of the first embodiment;

[0142] Figure 5A and 5B The sampling device of the first embodiment is shown at a sampling site within a subject;

[0143] Figure 6 to Fig.10 Various preferred dimensional and angular features of the first embodiment are described;

[0144] Fig.11 A protective cover for 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] Figure 13 to Figure 1 5 shows a second embodiment of the sampling device according to the present invention and various details thereof;

[0147] Fig. 16 is an assembly diagram of the second embodiment;

[0148] 17 and 18 show various preferred dimensions and angle features of the second embodiment;

[0149] Figures 19A to 19E A second embodiment is shown under various independent conditions;

[0150] Fig. 20 A second embodiment is shown being held by a user;

[0151] Fig.21 is a flow chart showing a second embodiment of the sampling method according to the present invention, Fig. 22 27 show the various steps of the method;

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

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

[0154] Fig.32 A fifth embodiment of the sampling device according to the present invention is shown;

[0155] Fig.33 and 34 shows an alternative sampling method according to a further embodiment of the present invention; and

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

[0157] Figure 1 is a schematic diagram showing details of a short segment of a mucociliary escalator (MCE) (generally indicated at 1) in a human subject 3. The MCE 1 transports mucosal lining fluid (MLF) from the small airways to the larynx and vocal cords. In particular, ciliary beating transports the MLF from the small bronchioles upward to the large bronchi and then through the vocal cords to the trachea and larynx. The MLF is then swallowed normally (at a rate of approximately 30 ml / day).

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

[0159] Embodiments of the present invention are intended to collect pure vocal cord MLF that does not contain saliva (or is only slightly contaminated by saliva). To this end, embodiments of the present invention utilize the fact that the human body's coughing function discharges MLF from the vocal cords to the oropharynx. By sampling from a certain location within the oropharynx, pure vocal cord MLF that is not contaminated by saliva (or is only minimally contaminated) can be obtained, for example, for analyzing biomarkers contained in the MLF.

[0160] FIG. 2A to FIG. 2E The cough function is schematically shown. A cough forces air through the vocal cords at high speed (typically, air is expelled at about 75 to 100 mph during a cough). The trachea and vocal cord MLF are expelled from the oral cavity by a cough, with saliva also expelled from the uvula, tongue, and oropharynx.

[0161] In more detail, Figure 2A The inhalation phase of the cough function (usually triggered by airway stimulation) is shown, which fills the lungs with air (usually indicated by 5). In the next phase of the cough function, Figure 2B As shown, the glottis closes and the abdominal muscles are compressed to create pressure. In the next stage of the cough function, Figure 2C and 2E (the latter is a cross-sectional view through the oropharynx, in Figure 2D The position indicated by the arrow in the middle), opens the glottis and ejects the cough cloud 7. As part of this process, mlf9 is transported from the vocal cords to the oropharynx (see Figure 2E ).

[0162] The first embodiment of the airway sampling device 11 is as follows Figure 3 The device 11 includes a handle 13 for gripping by a user (facilitated by a detent 14 disposed on an upper surface of the handle 13 for contact with a user's index finger), a rod 15 extending from the handle 13, and a sampling head 17 disposed at the end of the rod at a distal end of the handle 13 and angled relative to the longitudinal axis of the handle 13.

[0163] In the present embodiment, the handle 13, the rod 15 and the sampling head 17 are integrally formed, for example, by molding. It is preferred to use an integrally formed rod 15, handle 13 and sampling head 17 to minimize the possibility of any of these components becoming loose and being swallowed. However, in other embodiments, one or more of these components of the sampling device 11 can be formed as separate components, which can then be connected to other components in a releasable or non-releasable manner to assemble the device. Also in the present embodiment, the sampling device 11 can be formed of a plastic material such as acrylonitrile butadiene styrene (ABS) or polypropylene (PP); however, different materials (plastic or other materials) can be used as appropriate.

[0164] like Figure 4A (as well as Figure 4B As shown in cross-section in Figure 1, the sampling head 17 has a peripheral wall 19 extending generally perpendicularly to the axis of the rod 15 to form a shield 21 having a cavity or recess 22 to accommodate a sample collection membrane 23 in the form of a sampling material in the form of a patch or a small piece (preferably absorbent and / or adsorbent) for collecting a sample from the subject 3. The peripheral wall 19 includes a drainage ditch 25 around its upper edge, the purpose of which will be explained later.

[0165] The sample collection membrane 23 of this embodiment preferably includes an absorbent and / or adsorbent material, and may be, for example, a synthetic adsorption matrix (SAM TM ) materials. More generally, the sample collection membrane 23 material may include, for example, but is not limited to, various synthetic and functionalized polymers in foam, fiber or solid form. For example, and not limited to: polyurethane, fibrous hydroxytryptamine polyester (FHPE), polycaprolactone (PCL), nylon, cellulose acetate, cellulose, nitrocellulose, polyethersulfone, polysulfone, polypropylene, polyvinylidene fluoride (PVDF), polytetrafluoroethylene (PTFE), acrylic copolymers, leukocyte isolation media; analytical membranes that can also be used for point-of-care (POC) diagnostics, lateral flow and flow-through analysis, blotting; materials with antibodies and / or aptamers that can also be used for diagnostic analysis; and the like.

[0166] The sample collection membrane 23 is held within the housing 21 by, but not limited to, adhesives, chemical welding, ultrasonic welding, or overmolding.

[0167] The sample collection membrane 23 is provided with a perforation 26 as an integral part for removal using forceps or forceps T after sample collection, for example for analysis or retention by a clinician or other user (see Figure 4C ). To this end, the sample collection membrane 23 further includes a notch 27 at one end so that tweezers can be inserted at any time for easy removal.

[0168] Figure 5A and 5B An in-situ sampling device 11 according to aspects of the airway sampling method of the present invention is shown. In this case, the sampling head 17 is located at a sampling position according to the present embodiment, which is located above the vocal cords of the subject 3 (e.g., a few centimeters above), in the oropharynx of the subject 3, and behind the uvula. When the subject is prompted to cough slightly or exhale forcefully (i.e., a short and rapid exhalation), the MLF that is not contaminated by saliva (or minimally contaminated) can be adsorbed or absorbed onto the sample collection membrane 23 carried by the sampling head 17.

[0169] The sampling device 11 of this embodiment is specially designed to facilitate the placement of the sampling head 17 Figure 5A and 5B Sampling locations shown.

[0170] First, the various features of the sampling device 11 are sized, angled, and / or shaped to facilitate placement of the sampling head 17 into the Figure 5A and Figure 5B . In a preferred embodiment, different variations of the sampling device 11 are provided, with each type of sampling device being sized, angled and / or shaped to be suitable for use by a subject, allowing the user to place the sampling head in the sampling position according to the age grade of the subject. Ultimately, which size of sampling device 11 to use will be determined by the clinician, for example, to consider a subject who is significantly larger or smaller than the average for their age. However, the present embodiment seeks to provide, for example, three different sizes for use by subjects roughly graded according to three different age groups.

[0171] Fig. 6A and 6B Dimensions (all in millimeters) and angles for use with adult human subjects (16 years of age or older) according to the presently most preferred embodiment are shown; Fig. 7A and 7B Preferred ranges for these dimensions (all in millimeters) and angles are shown; Figure 7C and 7D The currently preferred dimensions (all in millimeters) and angles of the large sampling device 11 for use with adult subjects (16 years of age or older) are shown; Fig. 7E and 7F shows the currently preferred dimensions and angles of a medium sampling device 11 for use with subjects between the ages of 12 and 15 years old; and Figure 7G and 7H The currently preferred dimensions and angles of a small sampling device 11 for use with pediatric subjects (8 to 11 years old) are shown.

[0172] According to this embodiment, the width of the sampling head 17 (the width is Figure 7C , 7E and 7G) to maximize the size of the sampled material (and thus maximize sample collection) without causing undue discomfort to the patient or subject 3. In particular, the width X of the sampling head 17 is designed to comfortably clear the corresponding distance X' between the tonsils of the subject 3 (see Fig. 8A), and in particular to avoid and / or minimize interference with the subject's tonsils during sample collection, especially for patients with swollen tonsils caused by viral or bacterial infections. In the present embodiment, the width ranges from 10 mm to 16 mm, and as an illustrative example only, for adult / large-sized devices, 16 mm may be preferred; for middle-aged and elderly / medium-sized devices, 14 mm may be preferred; and for children / small-sized devices, 12 mm may be preferred. A head width of 10 mm or greater is advantageous because it maximizes sample capture and allows a well-sized sample collection membrane 23 to be placed within the protective cover 21 of the sampling head 17. A head width of no more than 16 mm is also desirable to avoid discomfort to the subject, especially to avoid and / or minimize interference with the subject's tonsils during sample collection, especially for subjects with swollen tonsils caused by viral or bacterial infections.

[0173] Next, refer to Figure 8C and 8B , the opening angle θ of the sampling head 17, and the total vertical depth Z of the sampling device 11 (measured from the highest point of the sampling device handle 11 to the lowest point (tip) of the downwardly inclined sampling head 17), are designed to maximize the sampling area of ​​the sampled material (i.e., maximize exposure to the discharged MLF) without significantly restricting the airflow. Here, the "opening angle" of the head 17 refers to the angle θ of the sampling head 17, more specifically the angle of the opening plane of the groove 22 in the cover 21 (which plane also preferably corresponds to the plane of the sample collection membrane 23) relative to the horizontal plane, and the sampling device is located in the posterior oral and nasal region, as shown in Figure 17.8C, and the sampling device is located at the desired vocal cord position. In this embodiment, regardless of the age of the subject, the preferred range of the opening angle θ° of the sampling head 17 is 25° to 45°, and the most preferred angle is 39°.

[0174] Here, and as referenced Fig. 9 As described above, an opening angle of at least 25° relative to the horizontal is preferred to avoid significantly restricting the subject's airflow (and thereby reducing the volume of the sample in the air). On the other hand, an opening angle of 45° or less relative to the horizontal is preferred to avoid reducing the amount of sample in the air that lands on the sample collection membrane, which may be due to the sample escaping from behind the sampling head 17 without contacting the sample collection membrane 23, or simply hitting the sample collection membrane 23 of the sampling device 11 protective cover 21. Fig.10 As shown, the preferred angle and length of the sampling head 17 maximizes airflow and the amount of sample that impacts the sample collection membrane 23 .

[0175] The total depth Z of the sampling device 11 preferably varies depending on the age of the subject; purely by way of illustration, for a sampling device 11 intended for adults (16 years or older), the depth Z may, for example, be 23 mm; for a sampling device 11 intended for subjects of intermediate age (12 to 15 years), the depth Z may, for example, be 20 mm or 21 mm; for a sampling device 11 intended for children (8 to 11 years), the depth Z may, for example, be 17 mm.

[0176] Table 1 below lists currently preferred optimum values ​​for head width X, depth Z and sampling head angle θ. However, it should be appreciated that the following preferred optimum values ​​and all of the aforementioned angles and dimensions are strictly non-limiting and merely illustrative, and other angles and dimensions may be used as appropriate.

[0177] Optimal size age X Z 0 Small 8-11 12 17 39° medium 12-15 14 20 39° big 16+ 16 23 39°

[0178] Table 1

[0179] Next, also refer to Fig.10 The outer surface 29 of the sampling head 17 is smooth and radially shaped so as to easily deflect the uvula 31 of the subject 3 toward the back of the oropharynx, thereby allowing the sampling head 17 to adopt Fig.10 The best sampling position as shown is directly above the airway of the subject. For example, in simple terms, the midpoint of the outer surface of the sampling head 17 can be as shown in FIG. Fig.7D and 7F The angles shown (38° and 36°, respectively, relative to the horizontal direction in the sampling position) are to facilitate deflection of the uvula. However, these angles are merely illustrative and other angles may be used as appropriate.

[0180] The sampling head 17 is further configured to minimize and / or eliminate contamination of the sample collection membrane with, for example, saliva or lymph fluid from the tonsils. First, as described above, the sampling head 17 has a surrounding hood 21 that surrounds the sample collection membrane 23 from all sides (except at the recessed opening in the hood 21), thereby enabling the sampling head 17 to be pushed through the tonsils, deflect the uvula upward, and possibly also contact the back of the subject's throat without any (or only a small amount) of liquid contamination of the sample collection membrane 23. In order to prevent contamination from direct surface contact such as these, Fig.11 As shown, the outer surface of the protective cover 21 is designed to be perpendicular to these landmarks during placement, sample capture, and removal of the sampling device 11 from the airway of a subject.

[0181] As a further measure, as mentioned above, the cover 21 is provided with an integral drain 25. When the sampling device 11 is inverted for sample processing, there is a risk that liquids such as saliva or lymph fluid may flow over the peripheral edge of the sampling head 17, thereby potentially contaminating the sample collection membrane 23. The integral drain 25 collects these fluids and allows them to drain safely, such as Figure 4A The flow rate is gravity fed, depends on the fluid viscosity, and allows the fluid to be safely discharged outside the sampling area of ​​the sampling device 11.

[0182] In addition to the design of the sampling head 17, the sampling rod 15 is also designed to be thin to minimize contact with the tongue and mouth of the subject 3, thereby minimizing the gag reflex. Fig. 6A As shown, for a sampling device 17 intended for adults, the stem width is preferably 8 mm. In addition, the sampling device 11 is preferably flexible to minimize accidental trauma to the subject being tested.

[0183] In summary, the sampling device 11 of this embodiment is designed to position the sample collection membrane in the oropharynx (behind the uvula) to prevent saliva and other liquids from the mouth, tongue and uvula from entering. During coughing, the sample collection membrane 23 captures (by impact) the vocal cords and tiny MLF droplets from the lower respiratory tract.

[0184] Now refer to Fig.12 The airway sampling method using the sampling device 11 according to an embodiment of the present invention is described.

[0185] In a first step 1201, lidocaine or other local anesthetic is sprayed on the back of the subject's throat to minimize discomfort and reduce the risk of a gag reflex.

[0186] Next, at step 1202, with the subject's mouth wide open, the sampling head 17 of the sampling device 11 is inserted into the patient's oral cavity, taking care to avoid contamination of the sampling material with saliva from the tongue. Although not necessary, a tongue depressor may also be used in this step to lower the subject's tongue to make the mouth and throat more visible.

[0187] At step 1203, if necessary, the uvula is lifted upward using the rear surface of the sampling head 17 so that the sampling head 17 is located in the center of the subject's airway, specifically above the subject's vocal cords, in the oropharynx, and behind the uvula.

[0188] Next, the subject is prompted to cough or forcefully exhale (i.e., exhale vigorously) at step 1204. As described above, this causes the MLF to be expelled from the vocal cords and collected without (or only with minimal) contamination by saliva and other fluids.

[0189] 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, for example, for analysis or storage.

[0190] According to a second embodiment of the sampling device 11 of the present invention, Fig.13 1 and 2, wherein the same or similar features are given the same reference numerals and only the differences from the first embodiment are described. As described below, the main difference is that the second embodiment allows the integration of sample washing and elution functions.

[0191] To this end, and unlike the first embodiment, the second embodiment is first provided with a washing and elution chamber 33 at the distal end of the handle. Figures 14A to 14C As shown, the washing and elution chamber 33 has a perimeter wall 35 perpendicular to and around the entire perimeter of the bottom wall 37 to define a cavity 39 therein. Within the perimeter wall 35, a plurality of vertical posts 41 are provided, which are spaced at regular intervals. In use, as part of the sample washing and elution function, as described below, the chamber 33 is designed to be compressed (i.e., squeezed) by the user. When the user compresses the chamber 33 with the thumb T, the 41 posts are pushed toward the saturated sample collection membrane (e.g., SAM) to maximize the recovery of the eluted MLF, as described below. Fig.35 and 36 As shown. Therefore, the chamber 33 is preferably formed of a deformable elastic material (e.g., thermoplastic vulcanizate, TPV), although other suitable materials may be used equally). In this embodiment, the chamber 33 also has a peripheral bite edge feature 43, which is located above the annular flange 45 in the handle to hold the chamber 33 in place, and the bottom wall 37 protrudes from the handle 13 to define a button to facilitate the user to squeeze the chamber 33. The outer surface of the bottom wall 37 has a rough or textured area 41 to facilitate the user to grasp the bottom wall 37 stably during squeezing the chamber 33. Preferably, the opening of the chamber 33 is closed by a removable protective cover 46 (see Fig.14D ) to prevent / reduce the risk of contamination before and during the sample collection process. The bottom wall 37 of the chamber 33 also has a generally circular weakened area 47 of reduced thickness (see Fig.13 ), whose purpose is explained later.

[0192] Secondly, the device 11 of this embodiment has a hinge 49 connecting the handle 13 to the rod 15 (see Fig.15A ), thus allowing Fig.13 or Fig.15A The expanded state shown (for sample collection) and Fig. 15B The shaft 15 and sampling head 17 are rotated relative to the handle 13 between the collapsed positions shown (eg, for sample washing and elution, as well as sample storage and optional initial transport).

[0193] As in the first embodiment, the sampling head 17 of this 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 the airway of a subject. However, in this embodiment, the sampling head 17 is further provided with a series of protrusions 50 arranged in a V-shape (see FIG. Fig. 15C and 15D ), the sample collection membrane 23 is placed on the protrusions with its edge located on the peripheral boss 51 surrounding the inner head of the V-shaped pattern protrusions (see Fig.15E ). The sample collection membrane 23 may be connected to the peripheral edge of the sampling head 17 by, but not limited to, adhesives, chemical welding, ultrasonic welding, secondary molding, etc. Again, the sample collection membrane 23 has an integral perforation 26 for selective removal with forceps or forceps T (see Fig.15F ); Figure 15G The interior of the sampling head 17 is shown with the sample collection membrane 23 removed.

[0194] like Figures 16A to 16G As shown, the hinge 49 is preferably a snap-on hinge, wherein the rod 15 and the sampling head 17 are assembled to the handle 11 by a snap fit. During assembly, the hinge center 51 of the rod 15 is pushed between the hinge studs 53 in the handle 13, thereby bending and rotating the handle side so that the rod 15 passes through the hinge studs. When the hole 55 in the hinge center of the rod 15 is aligned with the hinge studs 53 in the handle 15, the preload in the flexible side of the handle 15 forces the hinge studs to snap in, making the hinge assembly more attractive.

[0195] Preferably, tapered hinge studs 53 are used. Tapered studs have two advantages - firstly, they significantly improve assembly and secondly, the increased surface area contact gives the hinge greater lateral stability.

[0196] In this embodiment, the hinge center of the rod 15 is designed to interfere intentionally.

[0197] Thus, after assembly, there is frictional contact between the two components (stem 15 and handle 17).

[0198] After assembly, Figure 16G As shown, there are two position snaps, 165° apart, one in an extended "sampling" position and the other in a closed "wash and elute" position. Movement between these positions is provided by a fan-shaped finger detent curve 57 in the handle 17 (see Fig. 16B )Promote.

[0199] As with the first embodiment, this embodiment can be provided in different sizes, shapes and dimensions for use with subjects of different sizes, preferably based on the age of the subject as a guideline. As with the first embodiment, for example, an adult / large size sampling device 11 can be used for subjects 16 years of age or older, preferably for use - see Fig.17A and 17B , 18C and 18D to obtain (illustrative only) preferred dimensions and angles, wherein the preferred range of dimensions and angles is Fig.18A and 18B In addition, the medium-sized device 11 can preferably be as shown in Fig.18E and 18F For better use with subjects of moderate age (ages 12 to 15 years), the small size device 11 may preferably be as shown in FIG. Figure 18G and Fig.18H The dimensions and angles are set as shown, preferably for pediatric subjects (8 to 11 years old).

[0200] Here, the benefits of using the angles and dimensions shown are the same as for the first embodiment described above, again, all dimensions shown are in millimeters, and again, although preferably all dimensions and angles shown are illustrative and non-limiting, and other dimensions and angles may be used, for example for objects of different sizes.

[0201] Figures 19A to 19E Various independent positions of the sampling device 11 of this embodiment are shown. Fig.19A As shown, the handle 13, the rod 15 and the sides of the sampling head 17 are designed to remain stationary when the sampling head 17 is placed on its side, without rolling. Fig.19B and 19C The display device 11 is in the unfolded / sampling state and is placed on a horizontal surface so as to be placed on the side of the sampling head 17 and the handle 13 . Fig.19D and 19E The sampling device 11 is shown placed in an inverted state on a horizontal surface, the sampling device 11 being located on the finger grip portion of the handle 13 and the button provided on the bottom wall 37 of the washing and elution chamber 33, for example for inserting the washing and elution buffer, as shown below in conjunction with Fig.21 described.

[0202] Fig. 20 The sampling device 11 of this embodiment is shown, which is located at the handle position so that the user can combine Fig.21 The sampling process described below is performed.

[0203] Now refer to Fig.21 The flowchart describes the operation of the second embodiment of the sampling device according to the second embodiment of the sampling method of the present invention.

[0204] First, in step 2101, with the help of the fan-shaped finger positioner 57, the user pinches / pulls the lever 15 to open the device 11 (see Fig. 22 ), and rotate the rod 15 and the sampling head 17 relative to the handle 11 to snap them into the fully extended sampling position.

[0205] In step 2102, lidocaine or other local anesthetic is sprayed on the back of the subject's throat to reduce the risk of a gag reflex. As will be appreciated, the order of steps 2101 and 2102 may be reversed, or the steps may be performed simultaneously, such as by two physicians working simultaneously.

[0206] In step 2103, when the subject's mouth is wide open, the sampling head 17 of the device 11 is inserted into the subject's oral cavity (see Fig.23 ), taking care to avoid saliva contamination of the tongue. Although the device can be used alone, in order to more clearly see the mouth and throat, one may choose to insert the device 11 while depressing the subject's tongue using a suitable tongue depressor.

[0207] In step 2104, the subject's uvula is deflected as needed using sampling head 17 until device 11 is centered in the subject's airway (for clarity, Fig.24 The rod is shown in cross-section in Figure 1, with the handle omitted), and the sampling head is positioned at the desired sampling location, i.e., above the vocal cords, within the oropharynx and behind the uvula.

[0208] In step 2105, the subject 3 is asked to cough or exhale forcefully (exhale vigorously) so that the sample collection membrane 23 located in the sample head 17 of the device 11 can collect the MLF sample without being contaminated by saliva or other liquids (or only being contaminated a little).

[0209] In step 2106, the sampling device 11 is completely removed from the airway of the subject.

[0210] 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 rod 15 and sampling head 17 are rotated toward the handle 13 until a closed state is adopted to protect the sample from external contamination; the closed sampling device 11, including the sample collected therein, can then be frozen.

[0211] On the other hand, if the 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 the elution buffer is passed through the chamber 33. Fig.25A The pipette P is shown introduced into the chamber 33. In the present embodiment, the maximum capacity of the chamber 33 is only 500 μl (this is just an example), and of course other chamber sizes can be used as appropriate.

[0212] Next, in step 2109, the rod 15 and the sampling head 17 are rotated toward the handle 13 to bring the device 11 into a fully folded state (see FIG. Fig.25BAs will be appreciated, the sample collection membrane 23 will now be located between the V-shaped protrusion of the sampling head 17 on one side and the top of the protruding post 41 within the wash and elution chamber 33 on the other side.

[0213] In the next step 2110, the user shakes the folded device 11 to allow the eluent to wash the sampling material 23 now located in the chamber (see Fig.26 Here, since the elution buffer can move freely between the column 41 in the chamber and the V-shaped protrusion in the sampling head 17, both sides of the sampling material of the sample collection membrane 23 are easily exposed to the elution buffer, thereby maximally capturing the MLF from the sample collection membrane 23.

[0214] Next, in step 2111, the user orients the device 11 using the circular weakened area 47 located above the appropriate collection container V (see Fig.27A ).

[0215] 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 region 47 to rupture, releasing the liquid contents (i.e., the elution buffer containing the MLF flushed from the sampled material) (see Fig.27B ) is ejected into a collection container V, for example for analysis or storage.

[0216] Therefore, the above process provides users with a convenient sample extraction method. Fig.21 The sample extraction process is only one example, and other sample extraction processes are possible. Some exemplary alternative sample extraction processes are described later. First, some further sampling device embodiments are described, in which like features are given like reference numerals, and the discussion will focus only on the differences from the first and / or second embodiments of the sampling device described above.

[0217] The third embodiment of the sampling device 11 is as follows Figures 28A to 28E The sampling device 11 of this embodiment is very similar to the second embodiment described above, but additionally includes a transverse groove or recess 57 located forward of the finger locator 14 of the handle (i.e., toward the sampling head end), in which a generally circular cough guard 59 (e.g., Fig.28A and 28B shown), to form Fig.28C and 28D The complete device shown in . The third embodiment is otherwise identical to the second embodiment.

[0218] The cough shield 59 is preferably made of a thin sheet of plastic material (such as polyethylene terephthalate glycol (PETG) or polycarbonate (PC)), but other suitable materials (such as metal) may be used as appropriate. In this embodiment, the cough shield 59 provides the user with 315° of protection coverage to prevent the cough cloud generated by the subject during airway sampling, and the remaining 45° of the cough cloud passes under the wing side of the handle. A slot 61 is provided in the cough shield 59, which provides sufficient clearance for the sampling head 17 to rotate freely between the folded and unfolded states of the sampling device 11 (see Fig.28E ).

[0219] As will be appreciated, the first embodiment of the sampling device 11 described above may also be modified to similarly include a cough shield 59 located in a slot 57 provided in the handle of the device 11 according to this modification.

[0220] 29 and 30 illustrate a fourth embodiment of the sampling device 11. This embodiment modifies the second embodiment described above by including an illumination module 65 within the handle 13 and configuring the rod 15 and sampling head 17 as a light guide, which advantageously allows illumination of the interior of the subject's mouth to facilitate proper positioning of the sampling device 11 during the sampling process.

[0221] In more detail, as shown in the various parts of Figure 29, the rod 15 and the sampling head 17 of the present embodiment are formed of one or more suitable light-transmitting materials so as to function as a light guide. For example, the rod 15 and the sampling head 17 of the present embodiment can be formed of an optically transparent thermoplastic styrene-butadiene copolymer (SBC) or an optically transparent polycarbonate (PC), which is designed to emit light using light from an external light source.

[0222] Next, the handle 13 of the present device is adapted to include a positioning slot 63 for accommodating the lighting module 65 (see Fig.29A In this embodiment, the lighting module 65 includes a hook 67 (see FIG. 29 b ), and the handle 13 also includes a spring hook hole (not shown) to receive the hook hole, so as to firmly fix the lighting module 65 in the handle 13 (see FIG. Fig.29C and 29D ). In this embodiment, the hook 67 is detachable from the hook hole, allowing the lighting module 65 to be removed for insertion into one or more other sampling devices 11; that is, one lighting module 65 can be reused (after proper cleaning) and shared between multiple different lighting sampling devices 11. The lighting module 65 is sealed to prevent the ingress of liquids and dust, for example, the lighting module 65 can be constructed using an ABS molded housing and the necessary electronic components can be encapsulated in place using a TPE secondary molding process.

[0223] Preferably, the lighting module 65 may include a switch 71 that may be actuated by a light-activated receptacle optionally disposed within the handle 13. For example, this arrangement may allow the light to automatically turn on when the lighting module 65 is inserted into the handle 13, and automatically turn off when the lighting module 65 is removed from the handle 13. Alternatively, the switch 71 may allow the light to automatically turn on when the sampling device 11 enters its deployed (sampling) state, and to turn off when the sampling device 11 is in its folded state. Alternatively, a manual on / off switch may be provided for manual activation by the user.

[0224] For the lighting module 65, any suitable lighting means may be used, but for example these may include, for example:

[0225] 1) A laser light source, such as a laser with a wavelength between 450-500 nanometers (blue-cyan).

[0226] 2) LED light sources, such as ultra-bright white directional LEDs.

[0227] Examples of laser sources are Fig. 30A As shown, the light emitting element is Fig. 30B The light emitting element may include, for example, a suitable power source 69, such as two 3 volt batteries connected in parallel, such as a 5.5 mAh lithium manganese silicon battery (part number: MS621) having dimensions of 6.8 mm diameter and 2.1 mm thickness. Fig. 30B Also shown is a low profile, tactile, surface mounted switch 71, for example, as described above, automatically activated by a light activated socket optionally provided in the handle 11. The light emitting element also includes a laser diode 73, for example a 3.3 mm laser diode with a driver module.

[0228] Examples of LED light sources include Fig.31A As shown, the light emitting element is Fig.31B The light emitting element may include, for example, a suitable power source 69, such as two 1.55 volt batteries connected in series, such as a 16 mAh silver oxide battery (part number: SR65) having dimensions of 6.8 mm diameter and 1.65 mm thickness. Fig.31B Also shown is a low profile, tactile, surface mounted switch 71, for example, as described above, automatically activated by a light activated socket optionally provided in the handle. The light emitting element also includes an LED light source 75, for example, a 3mm ultra bright directional LED.

[0229] In the same manner 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 Fig.32The handle 13 is modified to include a light module 65 in the handle 13, which is beneficial for allowing the subject's mouth to be illuminated to facilitate the correct positioning of the sampling device 11 during the sampling process. In the present embodiment, since the handle 13 is integrally provided with the sampling head 17 and the rod 15 of the device 11, the handle 13 is also configured as a light guide. Specifically, the integral handle 13, the rod 15 and the sampling head 17 of the present embodiment are preferably formed of one or more suitable light-transmitting materials so as to be used as a light guide. For example, the handle 13, the rod 15 and the sampling device 17 of the present embodiment can be integrally formed of an optically transparent thermoplastic styrene-butadiene copolymer (SBC) or an optically transparent polycarbonate (PC), which is designed to emit light using the light from the lighting module 65.

[0230] Since this fifth embodiment (like the first embodiment) does not have a folding function, no light activation socket is provided in the handle 11. However, a manual light switch is provided for user activation to turn on the lighting device during the sampling process. In other aspects, such as the nature of the lighting module, the fifth embodiment can be generally the same as the fourth embodiment described above, and therefore will not be re-described here.

[0231] It should be understood that according to other embodiments of the present invention, the cough guard feature of the third embodiment may also be combined with the fourth and fifth embodiments having light-guiding features.

[0232] Some alternative sample extraction methods are described below, which are applicable to embodiments of the sampling device having a washing and elution chamber (eg, the second, third and fourth embodiments described above).

[0233] According to another embodiment of the sample extraction method, Fig.33 As shown, the user can extract the liquid contents (elution buffer containing MLF) by inserting the needle N of the syringe S into the weakened area and pulling the plunger of the syringe backwards, rather than the user squeezing the chamber to cause the weakened area to rupture. The extracted sample can then be processed as needed, such as ejected from the syringe into a suitable container for direct analysis, or transferred to a cryogenic storage container and frozen.

[0234] According to another embodiment of the sample extraction method, Fig.34As shown, centrifugation can be used, for example. According to this embodiment, during the sample collection process, after introducing the elution buffer into the chamber and placing the sampling device in its folded state, the user places the sampling device into a suitable centrifuge tube T (e.g., a low-temperature 50 ml centrifuge tube) and then closes the tube with a cap C. The centrifuge tube is then placed in a suitable centrifuge, which is then operated to spin the centrifuge tube, for example, at 4000 rpm for 30 seconds. This causes the weakened area to rupture, so that the liquid contents (elution buffer containing the sampled MLF) gather at the bottom of the centrifuge tube T. The user then removes the cap from the tube, removes the device, and re-caps the tube, for example for freezing or analysis.

[0235] The above embodiments relate to airway sampling from humans. However, this is merely exemplary, and according to further embodiments, the present invention may alternatively be applied to sampling devices and related sampling methods for airway sampling performed on non-human subjects (e.g., livestock such as cattle or pets such as cats and dogs).

[0236] The above embodiments assume that a user (e.g., a nurse, doctor, or other clinician) will obtain a sample from a subject. However, potentially, a subject can take a sample from themselves, in which case the "user" and the "subject" are the same person.

[0237] The above description is given by way of example only, and those skilled in the art will appreciate that modifications may be made without departing from the scope of the present invention as defined in the claims.

Claims

1. An airway sampling device for sampling from the airway of a subject, the device comprising a handle that a user holds tightly when sampling and a sampling head carried by the handle, the sampling head comprising a cavity having an opening for sample entry and a sample collection membrane located in the cavity for receiving the sample; wherein, The sampling head is provided with a surrounding cover, which surrounds the sample collection membrane on all sides, including on the lateral sides of the sampling head and on the guiding side of the sampling head opposite to the handle, so that the sample collection membrane is surrounded on all sides except the opening of the cavity in the cover, so that the sampling head can be pushed through the tonsils of the subject to deflect the uvula of the subject without contaminating the sample collection membrane.

2. The airway sampling device according to claim 1, characterized in that: The sample collection membrane includes an absorbent and / or adsorbent material.

3. The airway sampling device according to claim 1 or 2, characterized in that: The sample collection membrane is detachable from the sampling head.

4. The airway sampling device according to claim 1, characterized in that: The cavity is at least partially provided with a gutter around its opening.

5. The airway sampling device according to claim 1, characterized in that: The cavity is defined within a peripheral wall forming the surrounding enclosure, and wherein an outer surface of the peripheral wall is configured to be perpendicular to the tonsils of the subject when the sampling head is inserted into the throat of the subject and / or when the sampling head is removed from the throat of the subject.

6. The airway sampling device according to claim 5, characterized in that: The outer surface of the peripheral wall is also configured to be perpendicular to the uvula and / or posterior oropharyngeal wall of the subject during capture of the sample from a sampling location in the airway of the subject, where the opening of the cavity is located above the vocal cords of the subject, within the oropharynx, and behind the uvula.

7. The airway sampling device according to claim 6, characterized in that: The outer surface of the peripheral wall is configured to deflect the uvula of the subject, thereby allowing the sampling head to pass from the oral cavity into the pharynx.

8. The airway sampling device according to claim 1, characterized in that: The handle has a chamber, and the sampling head moves relative to the handle between a first state and a second state, wherein the first state is that the sampling head is away from the handle, and the second state is that the cavity is located above the chamber to define a shell, and the shell encloses the sample collection membrane between the interior of the cavity and the interior of the chamber.

9. The airway sampling device according to claim 8, characterized in that: The housing is fluid-tight.

10. The airway sampling device according to claim 8, characterized in that: A weakened area is provided in one of the chamber or the cavity.

11. The airway sampling device according to claim 10, characterized in that: The weakened area is configured to rupture when pressure is applied to the housing.

12. The airway sampling device according to claim 11, characterized in that: The weakened area is disposed in the chamber, and the chamber is formed of a deformable material to allow a user to apply pressure to the housing.

13. The airway sampling device according to claim 8, characterized in that: The interior of the chamber is provided with one or more protrusions which are in contact with the sample collection membrane when the sampling device is placed in its second state.

14. The airway sampling device according to claim 1, characterized in that: One or more protrusions are arranged inside the cavity, and the sample collection membrane is arranged on the protrusions.

15. The airway sampling device according to claim 1, characterized in that: The sampling device further includes a lighting module, and the sampling head is configured as a light guide plate to guide and emit light emitted from the lighting module.

16. The airway sampling device according to claim 15, characterized in that: The lighting module is detachably mounted on the sampling device.

17. The airway sampling device according to claim 1, characterized in that: The sampling head is arranged at the first end of the sampling device, and the first end of the sampling device is far away from the second end of the sampling device provided with the handle. The sampling device also includes a shield installed between the first end and the second end of the sampling device to protect the user from being affected by the sample.

18. The airway sampling device according to claim 1, characterized in that: The airway sampling device is shaped and sized such that when the sampling head is located in a sampling position in the patient's airway for sampling, the opening of the cavity is located above the vocal cords behind the uvula of the subject and within the oropharynx.

19. The airway sampling device according to claim 1, characterized in that: The sampling head is angled relative to the handle so that when the sampling head is located at a sampling position in the airway of the subject, the plane of the opening of the cavity is at an angle of 25° to 45° to the horizontal direction, wherein the opening of the cavity is located above the vocal cords, within the oropharynx, and behind the uvula of the upright subject at the sampling position.

20. The airway sampling device according to claim 1, characterized in that The depth of the sampling device, ie the depth from the uppermost portion of the handle to the lowermost portion of the sampling head, is between 17 mm and 23 mm.

21. The airway sampling device according to claim 1, characterized in that The maximum width of the sampling head is between 10 mm and 16 mm.

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