WO2020145896A1

WO2020145896A1 - Sample collection device

Info

Publication number: WO2020145896A1
Application number: PCT/SG2020/050010
Authority: WO
Inventors: Ching Chiuan YEN; Tai Wei David LEONG; Wai Tung CHOW; Suresh GOVINDARAJAN; Sui Ming Raymond HON; Jo Hanan LAU; Win Sen KUAN
Original assignee: National University Of Singapore; National University Hospital (Singapore) Pte Ltd
Priority date: 2019-01-11
Filing date: 2020-01-10
Publication date: 2020-07-16

Abstract

Disclosed is a sample collection device comprising an inlet, an outlet and an undeviating conduit. The undeviating conduit has an internal surface extending between the inlet and outlet, the internal surface having a profile change through which a breath expelled into the inlet passes towards the outlet. The profile change slows the expelled breath to cause lower respiratory tract substances to deposit on the internal surface of the conduit. In specific embodiments, the profile change increases an area of the internal surface, comprises a plurality of ridges constricting an internal cross-section of the conduit, forms a plurality of channels, has a polygonal cross-section, comprises a spiralling ridge or increases a length of the conduit. In a more specific embodiment, the sample collection device comprises at least one reversed output channel and at least one transverse outlets for directing flow from the at least one reversed output channels transversely of the conduit.

Description

SAMPLE COLLECTION DEVICE

Technical Field The present invention relates, in general terms, to a sample collection device. More specifically, the present invention may be used in the collection of samples from coughed and/or sneezed expulsions of lower respiratory tract substances.

Background

Many infections and conditions of the respiratory tract involve the harbouring of pathogens, e.g. microorganisms, in the lower respiratory tract. One such condition is community-acquired pneumonia (CAP). CAP is an acute lung infection brought about from the community and resulting from defects in the host's (e.g. subject's) defences or immunity, or by exposure to an overwhelming amount of virulent pathogen. Globally, the annual incidence is approximately 6 cases per 1,000 people. Mortality rates range from 13.6% in hospitalised patients to 36.5% in patients admitted to the intensive care unit. Infiltrates or consolidation on chest X-ray, combined with clinical features - e.g. fever, cough, sputum production and shortness of breath - confirm the diagnosis of CAP. For various authorities, the guidelines for treatment then suggest initiation of empiric presumptive antibiotic therapy. However, the recent emphasis on limiting antibiotic overuse, reducing resistance, improving care and preventing complications such as Clostridium difficile infection has driven the initiative for more pathogen-directed treatment.

Diagnostic testing is not routinely done for most outpatients with less severe presentation of CAP. Those hospitalised have higher likelihood of resistant pathogens and require microbiological characterisation to determine the responsible pathogen strain and resistance patterns. Currently, the non- invasive method involves sputum collection, either spontaneously or through induction, which is carried out through inhalation of nebulised hypertonic saline solution that can cause discomfort and severe coughing reaction. These specimens are subsequently sent for culturing, which takes at least 24 hours to present the identity of the pathogen and its antimicrobial susceptibility. Sputum samples oftentimes are contaminated with saliva and oral flora, producing false positive results that may complicate or confound interpretation and management of a subject's condition.

The most representative samples should come directly from the lower respiratory tract, which likely has a higher yield in positive identification of the culprit pathogen for CAP since it hones in on the organ involved - the lungs. Breathing is typically insufficient to expel sufficient amounts of the responsible bacteria from the lower lung where the infection occurs. Established clinical procedures for specimen extraction involves, e.g., tracheal aspirate, bronchoalveolar lavage fluid or pleural fluid which may cause discomfort, be laborious to administer, be invasive, tedious, and require specialised technical skill and equipment.

Therefore, there is a need for a more rapid, non-invasive, atraumatic and simpler point-of-care procedure for collecting representative samples of lower respiratory tract origin that can be used in tandem with current diagnostic methods to facilitate expeditious and precise treatment of CAP and other conditions. This is particularly important for hospitalised patients. There is similarly a need for earlier identification of the organism, so targeted therapy can be provided to reduce the risk of systemic inflammatory response from the host and mutation of the pathogen that may enhance resistance to antimicrobial agents. Summary

Disclosed herein is a sample collection device comprising : an inlet;

an outlet; and

an undeviating conduit having an internal surface extending between the inlet and outlet, the internal surface having a profile change through which a breath expelled into the inlet passes towards the outlet, the profile change slowing or changing a direction of the expelled breath to cause lower respiratory tract substances to deposit on the internal surface of the conduit. In some embodiments, the profile change may slow and change the direction of the expelled breath.

As used herein, the term "undeviating" refers to the conduit having only a path or paths that lead from the inlet to the outlet, and no paths that branch off the conduit - e.g. to a reservoir or chamber. In embodiments, this can be referred to as the conduit having a "single" inlet and "single" outlet, or being "unbranched", "linear" and other terms as context permits.

The terms "expelled breath" and similar are distinguished from normal breathing. In particular, "expelled" is used herein to refer to a cough, sneeze or other sufficiently strong/violent expulsion of breath from the lungs that lower respiratory tract substances (sputum, droplets etc - also referred to as products) are liberated from the lungs and entrained or otherwise drawn into the exiting breath. The expelled breath is sufficiently strong to carry those lower respiratory tract substances (also referred to as products) past the oral mucosa without significant contamination. The breath itself is therefore not analysed and instead serves as a carrier for lower respiratory tract substances. Where context dictates, "expelled breath", "breath expelled" and similar refer to a cough and/or sneeze.

By comparison, such products may not be liberated during normal breathing, or would not be liberated in significant quantities. As a consequence, the smaller quantities (if any) liberated during normal breathing are susceptible to dilution and contamination from oral flora and saliva that interfere with analysis - this comparison between "normal breathing" and "expelling" is discussed further with reference to Figure 10.

The inlet may be configured for the collection of cough and/or sneeze expulsions. The device is generally configured for the collection of cough and/or sneeze samples - e.g. the inlet of some embodiments is widened to fit around a coughing mouth of a subject (e.g. comprise a mouthpiece), or the nose of the subject (e.g. comprise a nasal mask), or both the mouth and nose (e.g. comprise a face mask) - and the change in profile is for slowing and/or changing a direction of an expelled cough or sneeze. Thus, the expelled breath passing through the conduit will generally be an expelled cough or sneeze.

The profile change may increase an area of the internal surface. The profile change may comprise a plurality of ridges constricting an internal cross-section of the conduit. The plurality of ridges may extend circumferentially, and be spaced longitudinally, of the conduit. The plurality of ridges may progressively reduce the internal cross-section of the conduit. Thus, the plurality of ridges slow the expelled breath and cause small deviations or changes in direction of at least part of the expelled breath.

The profile change may form a plurality of channels. Each channel may have a polygonal cross-section.

The profile change may comprise a spiralling ridge.

The profile change may increase a length of the conduit.

The sample collection device may further comprise a distal end comprising the outlet, and an output cap configured to be attached at the distal end, the output cap being configured to transversely redirect the expelled breath. The output cap may be considered part of the profile change which would then change the direction of the expelled breath to cause lower respiratory tract substances to deposit in the device. The sample collection device may further comprise a proximal end comprising the inlet, and at least one reversed output channel for directing flow from the output cap towards the proximal end. The sample collection device may further comprise one or more transverse outlets for directing flow from the one or more reversed output channels transversely of the conduit. The output cap may be removable.

The inlet may be configured to taper from a wider portion into which a subject coughs or sneezes, to a narrower portion at the conduit.

The inlet may be part of a proximal end configured to attach to a distal end of a detachable mouthpiece, the detachable mouthpiece widening proximally to a diameter sufficient to surround a subject's mouth during coughing or sneezing. The inlet may be part of a proximal end configured to attach to a distal end of a detachable nasal mask, the detachable nasal mask widening proximally to a diameter sufficient to surround a subject's nose during sneezing. Alternatively, the inlet may be part of a proximal end configured to attach to a distal end of a detachable face mask, the detachable face mask widening proximally to a diameter sufficient to surround a subject's mouth and nose during coughing or sneezing.

At least part of the internal surface may be hydrophobic. The internal surface may be entirely hydrophobic. The hydrophobicity encourages coalescence of droplets of lower respiratory tract substances, facilitating easier collection than for embodiments having non-hydrophobic internal surfaces.

It will be appreciated that the hydrophobic properties may be conferred by a coating on an internal surface of the sample collection device, as well as by forming the sample collection device or conduit thereof from a material having hydrophobic properties. The profile change may be configured to drain the lower respiratory tract substances towards one of the inlet and outlet.

The sample collection device may be used for collecting viral pneumonia samples, or for collecting tuberculosis samples, or for collecting samples for the detection of any lower respiratory tract conditions.

Current devices typically collect only samples of breath rather than the droplets entrained in the breath during expulsion. By contrast and advantageously, the present invention can be used to non-invasively obtain droplets expelled while a subject coughs or sneezes. Embodiments work by coalescing droplets expelled during coughing and sneezing, to facilitate their collection and analysis. As a result, the device affords analysis of the lower respiratory tract substances (e.g. droplets/sputum) rather than breath per se.

Advantageously, the inlet, nasal mask, face mask or mouthpiece of relevant embodiments is designed and intended to completely but comfortably cover a coughing nose, mouth or both nose and mouth to prevent loss of cough and/or sneeze materials to surroundings and to reduce the discomfort experienced by the user. This also reduces the potential for infection of the medical practitioner. Also, for embodiments involving a mouthpiece or face mask, by completely covering the mouth of the subject, the subject does not need to grip - e.g. with their lips - an inserted mouthpiece which can otherwise make it difficult to cough or sneeze. Instead, the present inlet or mouthpiece of relevant embodiments, by covering (i.e. surrounding) the mouth, allows the subject to cough or sneeze naturally during sample collection.

Advantageously, the conduit - which can interchangeably be referred to as a tube - is designed to slow down and stop, or change the direction of, droplets expelled during coughing or sneezing.

Advantageously, the conduit of various embodiments enables breath to be conveyed through the device - e.g. through the profile change (which may include an angled end cap) - substantially unhindered, while lower respiratory tract substances fall out of the expelled breath. Brief description of the drawings

Embodiments of the present invention will now be described, by way of non limiting example, with reference to the drawings in which : Figure 1 is a side view of an embodiment of a device in accordance with present teachings;

Figures 2A, 2B and 2C are side, cross-section perspective and end views of another embodiment of a device in accordance with present teachings;

Figures 3A, 3B and 3C are side, cross-section perspective and end views of another embodiment of a device in accordance with present teachings;

Figures 4A and 4B cross-section perspective and end views of another embodiment of a device in accordance with present teachings;

Figures 5A and 5B cross-section perspective and end views of another embodiment of a device in accordance with present teachings; Figure 6 is a cross-section side view of another embodiment of a device in accordance with present teachings;

Figure 7 is a side view of another embodiment of a device in accordance with present teachings;

Figures 8A and 8B are end and perspective views of components for substitution into the device of Figure 7; Figure 9 is a perspective, cross-sectional view of components for substitution into the device of Figure 7; Figure 10 shows Ponceau S stain and Western blot results for confirming the presence of Streptococcus Pneumoniae in cough samples; and

Figure 11 illustrates a workflow for use of traditional methods and the present devices.

Detailed description

Described below are sample collection devices that can be used in the detection of all major respiratory diseases, illnesses and conditions including, but not limited to, pneumonia such as viral pneumonia. The devices operate by non- invasively collecting lower respiratory tract substances, particularly those expelled during coughing or sneezing.

The cough or sneeze or an infected subject - e.g. a patient or other subject with a respiratory condition, that term including within its scope respiratory diseases and illnesses referred to above - contains virulent as well as fragments of organisms causing particular conditions, such as pneumonia. The sample collection device collects an adequate sample for subsequent rapid analysis using, e.g., molecular techniques. In the case of pneumonia, such as viral pneumonia, through the devices disclosed herein clinicians are better able to accurately diagnose or identify microorganisms responsible for pneumonia for faster and pathogen-directed treatment as well as the avoidance of bacterial resistance. For the purpose of illustration, the description below will be made in the context of the detection of pneumonia. It will be appreciated that the same teachings may be used to detect other conditions, such as tuberculosis, where pathogens and other relevant sample material is expelled during coughing or sneezing, from the lower respiratory tract.

As CAP is spread through pathogen-containing droplets, cough or sneeze condensates could provide useful clinical material that is representative of the condition of the lower respiratory tract. Compared to sputum, cough condensates have a higher probability of bypassing the oral mucosa, thereby lowering the risk of contamination with saliva and oral flora. Cough condensates from CAP patients, that consist of droplets containing pathogens (whole and fragments) and their protein secretions, can be used to address current gaps in pneumonia diagnosis. Consider, for example, the objective to rapidly select or switch to targeted antibiotics for CAP. Current methodologies have inherent issues such as sputum contamination - e.g. from oral flora - and the cultures used to then determine the contents of the sputum take a considerable period to process. Urinary assays are limited to two pathogens and tracheal aspirate and bronchoalveolar lavage are invasive.

Figure 1 is a general illustration of a sample collection device 100 in accordance with present teachings. The sample collection device broadly comprises an inlet 102, an outlet 104 and a conduit 106.

The inlet 102 is for receiving an expelled (e.g. coughed or sneezed) breath of a subject (not shown). The inlet 102 may take many forms and presently is in the form of an aperture. The aperture opens directly into the conduit 106 to enable the expelled breath to pass directly into the conduit 106.

The outlet 104 allows the expelled breath to exit the conduit 106. As with the inlet 102, the outlet 104 of the present embodiment comprises an aperture. The aperture opens directly into the conduit 106. Thus an expelled breath passing through the conduit 106 has free passage through the outlet 104, and out of the conduit 106. With reference to Figures 2A, 2B and 2C, the device 200 may be configured with a distal end 202, comprising the outlet 204, that may take a variety of forms or shapes depending on the desired use of the device 200. While the distal end 108 of Figure 1 has a smooth external surface 110 to which nothing may attach, or that may be attached, for example by friction fit, to an output cap the external surface 206 of distal end 202 is configured with a helical or screw thread. The external surface 206 is thereby configured to engage or attach to an output cap 208 of device 200. The output cap 206 therefore comprises a mating thread 214 on an internal surface. The output cap 206 may, in some instances, be considered part of, or an extension of, the conduit and thus the profile change may include any change in direction or cross-section of the conduit afforded by the output cap 206. The output cap 206 is configured to transversely redirect the expelled breath - i.e. change its direction from a trajectory parallel with arrow X to a trajectory parallel with arrow Y. This sharp change of direction can significantly reduce the speed of the expelled breath. Moreover, heavier entrained substances such as droplets will naturally have greater difficulty changing direction when compared with the lighter exhaled air. Those droplets and other substances are consequently likely to be deposited on the distal internal surface 208 of the output cap 206.

The output cap 206 of the present embodiment comprises an outlet 210 and the outlet 210 is positioned proximally of the distal internal surface of the output cap 206, thereby forming a reservoir or recess 212. The recess 212 collects droplets driven out of the expelled breath by the transverse change in direction caused by the output cap 206. The conduit 216 of Figures 2A, 2B and 2C is undeviating. Depending on interpretation the inlet 218 may simply be an aperture at a proximal end 220 of the device 200, or the proximal end 220 and inlet 218 therein may extend up to a profile change 222 of the conduit 216. All such interpretations are intended to fall within the scope of the present disclosure.

In some embodiments, the conduit may be straight in the present embodiments, conduit 216 has a small taper distally, to progressively reduce the overall cross-sectional dimensions of the conduit 216. The progressive constriction further inhibits the passage of the expelled breath through the conduit 216, causing more droplets to fall out of the expelled breath. The conduit 216 has an internal surface 224 extending between the inlet 218 and outlet 204. The internal surface 224 includes the profile change 222 through which a breath expelled into the inlet 218 passes towards the outlet 204. The profile change 222 slows the expelled breath to cause lower respiratory tract substances to deposit on the internal surface 224 of the conduit 216.

The profile change 222 increases the surface area of the internal surface 224. This increases the resistance to flow of the expelled breath, thereby causing a greater proportion of lower respiratory tract substances to fall out of the expelled breath and onto the internal surface 224.

The profile change 222 of the device 200 forms a plurality of channels 226 as best seen in the end view Figure 2B. The channels 226 have a polygonal cross- section. The polygonal cross-section creates a larger surface area of each channel than, for example, a circular cross-section. However, in some embodiments a circular cross-section may also be used. The present polygonal cross-section of each channel 226 is hexagonal. This enables the channels 226 to be generally tessellated (e.g. form a honeycomb type structure), with only a small bridge or web 228 therebetween. Figures 3A, 3B and 3C illustrate an alternative device 300 in which the inlet 302 and outlet 304 have substantially the same function as the inlets 102, 218 and outlets 104, 204 of Figures 1, 2A, 2B and 2C. The profile change 308 of the conduit 306 comprises a plurality of ridges 310. The ridges 310 constrict the internal cross-section of the conduit 306. The ridges 310 provide an abrupt barrier to passage of the expelled breath. Droplets and other substances drawn from the lower respiratory tract and caught in the expelled breath have greater inertia that the surrounding air or gas in the expelled breath. Those substances therefore deposit on the ridges 310 while the air continues along the conduit 306 and out the outlet 304. The ridges 310 extend circumferentially around the internal surface 309 of the conduit 306. Moreover, the ridges 310 are spaced longitudinally of the conduit 306 - i.e. along an axis from the inlet 302 to the outlet 304. Rather than constrict and then broaden the internal cross-section of the conduit 306, which may be appropriate in some embodiments, the ridges 310 progressively reduce the internal cross-section of the conduit 306 as shown in Figure 3B. This progressively slows the expelled breath to increase the likelihood that substances will fall from the expelled breath and coalesce on the internal surface 309. Where it is desired to drain coalesced substances that have collected in the conduit 306 towards the distal end 312 of the device 300, there may be a gap or slot (not shown) in each of the ridges 310. The gaps or slots may be aligned such that the coalesced substances will drain towards the distal end 312 if the device 300 is tilted appropriately. In other embodiments, the profile change may instead be configured to drain the lower respiratory tract substances towards the inlet.

The distal end 312 again incorporates a thread 314 for engaging an output cap 316 in the same manner as that shown in Figures 2A, 2B and 2C. Figures 4A and 4B illustrate a further embodiment of a device 400 in which the inlet 402 and outlet 404 are again substantially the same as those shown in Figures 2A, 2B and 2 C. The conduit 406 includes a profile change 408 comprising a helical or spiralling nested waveform or ridge. As is evident in Figure 4A, profile change 408 substantially increases the surface area of the internal surface 310, but also obstructs the conduit 406 and forces the expelled breath to spiral. The spiralling action causes substances entrained in the expelled breath to be thrown from the expelled breath against the internal surface 410.

Figures 5A and 5B illustrate a further embodiment of a device 500 for collecting samples of lower respiratory tract substances. While the inlets of all embodiments disclosed herein are intended for the collection of cough and/or sneeze expulsions, the inlet 502 is specifically configured to comfortably capture cough and/or sneeze expulsions - i.e. expelled breaths.

The inlet 502 is fluted. It is configured with a taper from a wider portion - at its proximal-most end 504 - into which a subject coughs or sneezes, to a narrower portion at the conduit 506. The inlet 502 at its proximal end 504 is wide enough to surround the mouth and/or nose (depending on the largest internal diameter of the proximal end 504) of a coughing or sneezing subject, while narrowing distal ly to direct the expelled cough or sneeze into the conduit 506. The outlet 508 is configured to engage - e.g. by thread or friction fit - an output cap 510. The output cap 510 includes a lateral slit 512 through which expelled breath exits the output cap 510, the lateral slit 512 causing the expelled breath to again redirect transversely to cause substances to deposit on the internal surface 514 of the output cap 510.

Conduit 506 includes a profile change 516 comprising a plurality of nested tubes 518. The nested tubes are supported within the device 500 by braces 520. The device 200 of Figures 2A, 2B, 2C, 3A, 3B, 3C, 4A, 4B, 5A and 5B thus provide a tapered, cylindrical or generally cylindrical cough channel 216, 306, 406, 506 with internal structures in the form of a profile change 222, 308, 408, 516 intended to increase the surface area for condensate or substances - e.g. droplet - catchment or collection for specimen acquisition from the lower respiratory tract. The threaded-on angled air output cap 206, 316 and output cap 510 guides upper respiratory tract substances out during the expulsion process - e.g. coughing or sneezing - and can be taken off or removed for analysis - e.g. placed in a centrifuge to gather the specimen from the recess 212 (which will be similarly recognised in the other output caps 316 and 510).

Figure 6 illustrates a device 600 capable of at least partial disassembly for analysis and, where multiple uses of the device 600 are desired, sterilisation. The device 600 comprises a proximal end 602 comprising the inlet 604, an outlet 606, a conduit 608 for conveying an expelled breath from the inlet 604 to the outlet 606 as described above, an output cap 610 and a pair of reversed output channels 612 for directing flow from the output cap 610 towards the proximal end 602 (the output cap and reversed output channels may, in some cases, be considered to extend the conduit and the profile change therein or may, in other cases, be considered a separate feature - in the former case the outlet may be considered to be at location 614). It will be understood that other embodiments will permit one or more reversed output channels to be used. The output cap 610 does not include any output that directly connects the internal volume of the output cap 610 to the surrounding environment. Instead, the output cap 610 serves to redirect the expelled breath from the conduit 608 to the reversed output channels 612. The distal-most end 620 of the reversed output channels 612 is shaped like a funnel to assist directing the expelled breath into the reversed output channels 612. The conduit 608 includes a profile change that results in a general taper from the inlet 604 to the outlet 606. Again, this progressive reduction in cross- sectional area of the conduit 608 results in deposition of substances from the expelled breath onto the internal surface of the conduit 608.

The conduit 608 may also be considered to comprise the reversed output channels 612. In this case, the profile change, which comprises the reversed output channels 612, increases the length of the conduit 608. This increased length provides extra opportunity for the expelled breath to slow before exiting the device 600, and further increases the internal surface area of the conduit 608.

The expelled breath exits the reversed output channels 612 through one or more, and presently one, transverse outlets 614. The transverse outlet 614 directs the flow from the reversed output channels 612 transversely of the conduit 608. The transverse outlet 614 includes a circumferential recess 616 so that expelled breath from all reversed output channels 612 converge to the transverse outlet 614. Having a single transverse outlet 614 ensures the transverse outlet 614 can be directly upwardly during use. This prevents cough or sneeze substances from dripping downwardly out of the device 600.

After use, the device 600 can be angled downwardly (i.e. lifting the proximal end relative to the distal end 618). Substances taken from the expelled breath will therefore drain into the output cap 610.

The output cap 610 is detachably attached to the distal end 618 as discussed in relation to Figures 2A, 2B and 2C. It can therefore be removed for analysing the samples collected therein. The proximal end 602 is configured to attach to a distal end 622 of a detachable mouthpiece 624 of the device 600. The detachable mouthpiece 624 widens proximally to a diameter sufficient to surround a subject's mouth during coughing or sneezing. The detachability of the mouthpiece 624 enables it to be selected to fit the size of the mouth of the subject - e.g. the proximal end 626 of the mouthpiece 624 will be smaller for a child than for an adult - or to be substituted for a nasal mask or face mask. This allows passage of air - i.e. expelled breath - at high velocity and pressure to be comfortably captured. Sneezes or coughs can exit the body at speeds greater than lOOkm/h.

As shown in Figure 7, the arrow Z, defining the trajectory of airflow, progresses firstly into the conduit, reaches the distal end (output cap) and then returns along the reversed output channels back to the outlets - e.g. outlet 614 - near or at the proximal end of the device.

The detachability of the components of the device 600 also enables substitution for other forms of output cap and conduit. Figures 8A, 8B and 9 show forms of conduit having the inlet and outlet at opposite ends both of which are configured to attach to respective output caps and mouthpieces.

The conduit 800 of Figures 8A and 8B includes a profile change comprising an extension of the honeycomb concept described with reference to Figures 2A, 2B and 2C. Figure 9 depicts a conduit for substitution into the devices of, for example, Figures 6 and 7.

The embodiments in Figures 6, 7, 8A, 8B and 9 are modular concepts enabling separation of the main cylinder - i.e. the conduit - from the L-bend chamber or output cap for further processing and analysis or sputum or other substances collected. Cough or sneeze condensates can then be analysed using existing molecular methods, such as polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), Western blot methods and others. Each of the device embodiments described herein can employ a transverse redirection of flow of expelled breath. This transverse redirection can cause upper respiratory tract breath to pass cleanly through the device, while capturing lower respiratory tract substances. Moreover, by capturing cough and sneeze exhalations rather than normal breathing exhalations, lower respiratory tract substances are liberated from the lung and entrained in the breath being expelled. Consequently, the devices disclosed herein capture predominantly the substances from the lower respiratory tract and, due to the speed of expulsion - coughs and sneezes can travel over lOOkm/h - the lower respiratory tract substances substantially avoid the confounding effects of saliva and oral flora contamination.

In all of the present embodiments at least part of the internal surface of the conduit can be, or be made, hydrophobic. In some embodiments, the entire internal surface of the conduit is hydrophobic. The hydrophobicity can result either from application of a hydrophobic coating or by forming the conduit from a hydrophobic material. The output cap can similarly be formed from hydrophobic material or have a hydrophobic coating applied to its internal surface.

Similarly, any one of the above embodiments is condition agnostic. The devices may be used to collect samples for the detection of pneumonia, tuberculosis or any other condition of the lower respiratory tract.

In preliminary experiments the ridged funnel embodiment - Figures 3A, 3B and 3C - was employed. This demonstrated the effect of progressively narrowing the cross-sectional area of the conduit and the use of circumferential ridges to retard the velocity of droplets in the expelled breath and to increase coalescence of the droplets into bigger drops that are then more easily extracted for analysis.

The ridged funnel prototype was used to collect exhaled breath (control) and cough condensates from a subject - i.e. a patient - in the emergency department with a radiologically-proven CAP as a pilot clinical trial. A total of 15 exhaled breaths lasting 2 seconds each and 15 coughs from the same patient were collected in two separate but identical apparatus that were 3D-printed. The entire process of sample collection from the patient lasted approximately 5 minutes with no discomfort, sedation or paralysis, or use of any invasive methods. The cylinders - i.e. conduits - were inverted from the sputum collection chamber, placed into 50ml falcon tubes, and centrifuged at 20,000 rpm for 5 minutes to obtain the condensates. Without additional processing, protein comparison of the exhaled breath (12mI_) and cough condensates (9mI_) was made by Western blot using synthetic PspA (pneumococcal surface protein A) peptide and Streptococcus pneumoniae (SP) lysates as controls - the results are shown in Figure 10.

The amount of protein collected from cough condensates was at least 2000% more abundant than for breath condensates. The results from cough condensates exhibited the presence of potential PspA of activated SP, despite having a lower collected volume compared with exhaled breath - 9mI_ compared with 12mI_. PspA and cough shared a band at ~67 kDa (kilodaltons). In contrast, no such band was shared with breath - note: PspA peptide is generally between ~67 kDa and 99kDa depending on the origin of the strain. SP is likely only coughed out by the patient but not breathed out. Therefore, the apparatus, being configured to capture cough condensates, was able to capture some bacteria including SP.

The pilot trial using the ridged funnel prototype demonstrated that cough condensates, particularly those collected using the devices disclosed herein, can be a new non-invasive representative specimen for demonstrating the microbiology of the lower respiratory tract. Moreover, the results evidenced that such microbiological information cannot be reliably obtained by exhaled breath condensates.

The current state-of-the-art workflow for microbiological identification of culprit organisms causing respiratory tract conditions - e.g. in CAP - may cause discomfort - e.g. sputum collection - are invasive - e.g. bronchoalveolar lavage or tracheal aspirates - and have substantially longer turnaround time than the present methods - e.g. require culturing. The present apparatus is non- invasive, does not cause discomfort to the patient, and the microbiological material collected can be used by the existing molecular methods such as PCR, ELISA, and Western blot in hospitals and diagnostic laboratories. Moreover, the collection of microbiological material from the present devices is simple.

Figure 11 illustrates the incorporation of the present devices into the clinical workflow 1100. In practice, a patient undergoes X-ray to detect the potential presence of pneumonia - 1102. The current clinical workflow then bifurcates between non-invasive and invasive procedures. The non-invasive procedure involves sputum induction 1104, which causes significant discomfort to the patient. The sputum collected may also be contaminated with oral flora and saliva. The sputum is then Gram stained and cultured for 24 to 72 hours 1106, before microorganism detection 1108. In the invasive procedure, samples are taken by bronchoalveolar lavage or tracheal aspirates 1110 that are then Gram stained and cultured for 24 to 72 hours 1112 before microorganism detection 1114.

In contrast, the methods available by the present devices enable a post-X-ray (if performed) use of the device to capture cough or sneeze samples 1116. These samples are then analysed using methods such as PCR, ELIZA and Western blot tests - step 1118. The patient experiences no discomfort, and a more rapid analysis that facilitates earlier confirmation and accurate treatment administration than current methods.

It will be appreciated that many further modifications and permutations of various aspects of the described embodiments are possible. Accordingly, the described aspects are intended to embrace all such alterations, modifications, and variations that fall within the spirit and scope of the appended claims. Throughout this specification and the claims which follow, unless the context requires otherwise, the word "comprise", and variations such as "comprises" and "comprising", will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps.

The reference in this specification to any prior publication (or information derived from it), or to any matter which is known, is not, and should not be taken as an acknowledgment or admission or any form of suggestion that that prior publication (or information derived from it) or known matter forms part of the common general knowledge in the field of endeavour to which this specification relates.

Claims

1. A sample collection device comprising:

an inlet;

an outlet; and

an undeviating conduit having an internal surface extending between the inlet and outlet, the internal surface having a profile change through which a breath expelled into the inlet passes towards the outlet, the profile change slowing or changing a direction of the expelled breath to cause lower respiratory tract substances to deposit on the internal surface of the conduit.

2. The sample collection device of claim 1, wherein the inlet is configured for the collection of cough and/or sneeze expulsions.

3. The sample collection device of claim 1 or 2, wherein the profile change increases an area of the internal surface.

4. The sample collection device of claim 3, wherein the profile change comprises a plurality of ridges constricting an internal cross-section of the conduit.

5. The sample collection device of claim 4, wherein the plurality of ridges extend circumferentially, and are spaced longitudinally, of the conduit.

6. The sample collection device of claim 4 or 5, wherein the plurality of ridges progressively reduce the internal cross-section of the conduit.

7. The sample collection device of any preceding claim, wherein the profile change forms a plurality of channels.

8. The sample collection device of claim 7, wherein each channel has a polygonal cross-section.

9. The sample collection device of any preceding claim, wherein the profile change comprises a spiralling ridge.

10. The sample collection device of any preceding claim, wherein the profile change increases a length of the conduit.

11. The sample collection device of any preceding claim, further comprising a distal end comprising the outlet, and an output cap configured to be attached at the distal end, the output cap being configured to transversely redirect the expelled breath.

12. The sample collection device of claim 11, further comprising a proximal end comprising the inlet, and at least one reversed output channel for directing flow from the output cap towards the proximal end.

13. The sample collection device of claim 12, further comprising one or more transverse outlets for directing flow from the one or more reversed output channels transversely of the conduit.

14. The sample collection device of any one of claims 10 to 12, wherein the output cap is removable.

15. The sample collection device of any preceding claim, wherein the inlet is configured to taper from a wider portion into which a subject coughs or sneezes, to a narrower portion at the conduit.

16. The sample collection device of any one of claims 1 to 14, wherein the inlet is part of a proximal end configured to attach to a distal end of a detachable mouthpiece, the detachable mouthpiece widening proximally to a diameter sufficient to surround a subject's mouth during coughing or sneezing.

17. The sample collection device of any preceding claim, wherein at least part of the internal surface is hydrophobic.

18. The sample collection device of any preceding claim, wherein the profile change is configured to drain the lower respiratory tract substances towards one of the inlet and outlet.

19. The sample collection device of any preceding claim, being used for collecting viral pneumonia samples.

20. The sample collection device of any preceding claim, being used for collecting tuberculosis samples.