GB2605429A

GB2605429A - Collection device for bodily fluids

Info

Publication number: GB2605429A
Application number: GB2104622.2A
Authority: GB
Inventors: White Richard; Hurth Cedric
Original assignee: Mint Diagnostics Ltd
Current assignee: Mint Diagnostics Ltd
Priority date: 2021-03-31
Filing date: 2021-03-31
Publication date: 2022-10-05
Also published as: GB202104622D0

Abstract

A bodily fluid collection apparatus for collecting and storing a predetermined volume of bodily fluid such as saliva. The device comprises a collection tool 10 comprising at least one internal channel or cavity (11, fig 1) extending from a first end to a second end thereof. The first end of the tool is for receiving a bodily fluid directly from a person. A storage vessel 30 configured to couple to and decouple from the second end of the collection tool is provided. Fluid displacement means, preferably a plunger, are configured to fit the first end of the collection tool such that a movement thereof causes air displacement to transfer bodily fluid from the at least one internal channel or cavity of the collection tool into the storage vessel. A vent system 16 is configured to allow air to escape from the channel or cavity during the fluid displacement. A method of collecting saliva using said device is also claimed.

Description

Collection Device for Bodily Fluids

FIELD OF THE INVENTION

The present invention generally relates to a collection device for bodily fluids, in particular for collecting saliva

BACKGROUND TO THE INVENTION

Sample collection is the first and most important part in any Point-of-Care application. It is often done externally and rarely integrated into the final device whereas sample-inanswer-out systems are the most sought after and preferred diagnostic devices to limit user intervention.

Sample collection can be lengthy and cause distress to the user. Current methods for saliva collection include passive drooling and absorbent swabs. In passive drooling, saliva flows into a cylindrical receptacle and into a storage container. It can take several minutes to collect sufficient saliva. Furthermore, this method does not control the volume of collected saliva, and additional sample processing is required before testing.

When collecting saliva using absorbent swabs, the collected saliva volume is uncontrolled. Furthermore, the extracted sample of saliva typically requires centrifugation.

The field of saliva testing therefore needs an improved method to collect saliva to, e.g., allow greater convenience for the user being tested, speed of collection, easy testing and/or interfacing with a test device, collection of smaller and/or more precise volumes, improved safety by containment (thus e.g., reduced potential for contact to the saliva by a person assisting the user), and/or reduced storage volume requirements, etc..

For use in understanding the present invention, the following disclosures are referred to: -"Evaluation of saliva collection devices for the analysis of steroids, peptides and therapeutic drugs". Groschl et al., Journal of Pharmaceutical and Biomedical Analysis 47 (2008) 478 -486; -US9,198,641 B2, Slowey et al; -US9,498,191 B2, Granger at al.. -GB2585227 A, Borini et al.

SUMMARY

According to a first aspect of the invention, there is provided a bodily fluid collection apparatus for collecting and storing a predetermined volume of bodily fluid such as saliva, the device comprising: a collection tool comprising at least one internal channel or cavity extending from a first end to a second end of the collection tool, the first end of the tool for receiving a bodily fluid directly from a person; a storage vessel configured to couple to and decouple from the second end of the collection tool at one end of the storage vessel; a fluid displacement means configured to fit the first end of the collection tool such that a movement of the fluid displacement means causes air displacement to transfer bodily fluid from inside the at least one internal channel or cavity of the collection tool into the storage vessel; and a vent system configured to allow air to escape from the channel or cavity during the fluid displacement.

Advantageously, the apparatus may enable quick and/or accurate collection of bodily fluid and transfer into a separable storage vessel. The plunger may enable the movement of a controlled or predetermined volume into the vessel.

In an embodiment, the storage vessel comprises a removable seal at an end opposite the end that is configured to couple to the collection tool. The seal provides a means for accessing the bodily fluid for use in test devices.

Further, the seal may comprises a plug and the storage vessel is configured to couple with a test device such that when the storage vessel is coupled to the test device, the plug opens to allow the bodily fluid to move from the storage vessel to the test device. This provides efficient, quick and accurate movement of a volume of bodily fluid from a person to the test device.

In an embodiment, the storage vessel, when not coupled to the collection tool, is configured to be coupleable to a storage cap. If the collected bodily fluid does not need to be used in test(s) straight away, it can be stored separate from the collection tool. This de-coupling from the collection tool for storage may reduce the space needed to store the sample, for example, in a fridge.

In an embodiment, the fluid displacement means comprises a plunger. The plunger may provide an effective means of causing air displacement to move the predetermined volume of bodily fluid into the storage vessel.

In an embodiment, the fluid displacement means comprises a compressible member, wherein compression of the compressible member causes the air displacement. The compressible member may provide an additional or alternative means of causing air displacement relative to for example a plunger. In embodiments, the compressible member may comprise the collection tool in a compressible form, and/or a squeezable cap that can be fitted to the collection tool.

In an embodiment, the at least one internal channel or cavity comprises a capillary channel having a hydrophilic surface, eg material, coating or adhesive tape. The use of the hydrophilic surface may ensure that sufficient fluid volume can be acquired by a capillary effect. Further, the use of the capillary effect may improve the collection of the fluid, for example potentially reducing any need to for the saliva to be collected by passive means, such as drooling in the case of saliva.

Furthermore, the hydrophilic surface of the capillary channel preferably extends from the first end to a seal, eg plug, at the second end of the collection tool. The use of the hydrophilic surface may ensure that sufficient fluid volume can be acquired by a capillary effect, preferably such that the full available volume of the channel(s)/cavity becomes filled with bodily fluid.

In an embodiment, a diameter of the at least one internal channel or cavity progressively decreases from a first end to a second end. This feature may create a slowly increasing capillary force required that reduces the collection time required to fill the collection tool.

In an embodiment, the collection tool comprises a bubble trap, the trap comprising a widening of the channel or cavity at the first end of the tool. This feature may reduce or prevent bubbles from entering the collection tool. Such bubbles may affect the volume of fluid that would be possible to collect in the collection tool, and/or the flow of fluid through the apparatus.

In an embodiment, the hydrophilic material comprises hydrophilic tape. The use of hydrophilic tape may allow the tool to be made out of a non-hydrophilic material, and the tape applied afterwards.

In an embodiment, the hydrophilic material comprises glass. The use of glass may provide the desired hydrophilic properties, without needing to apply hydrophilic tape.

In an embodiment, the collection tool comprises hydrophilic tape configured to divide the at least one internal channel or cavity into at least two internal channels or cavities. The use of the hydrophilic tape in this way may achieve assembly of the two halves of collection tool into one piece.

In an embodiment, the first end of the collection tool comprises a mouthpiece, wherein the mouthpiece comprises two spacers for simultaneously contacting a tongue of the person, preferably wherein ends of the spacers are positioned relative to one another to match a curvature of the tongue such as around the tip of the tongue. This feature may prevent a tongue from blocking the inlet to the internal channel of cavity, which may otherwise impede the collection of the bodily fluid.

In an embodiment, the storage vessel comprises a filter to remove bubbles and/or particles from the bodily fluid, the filter preferably at the end to couple to the collection tool. The filter may prevent any particles or bubbles, which may affect the testing of the sample from entering the storage vessel, where the fluid sample is store before testing.

According to an embodiment, the storage vessel comprises reagents on at least part of its internal surface to buffer or treat collected fluid. Such reagents can provide a fluid sample more suitable for testing In an embodiment, the storage vessel comprises a microfluidic circuit, the microfluidic circuit comprising: a collection chamber for collecting the predetermined volume; a waste chamber; a one-way valve to allow excess fluid from the collection chamber to pass to the waste chamber; and a vent channel connected to the waste chamber.

The microfluidic circuit may allow for precise measuring of the bodily fluid, which is important for some testing devices and methods, eg biosensing test(s) in a test strip / device to be coupled to the storage vessel, for example such tests for detecting hormones such as cortisol.

According to an embodiment, the bodily fluid is saliva. Alternatively, the fluid may be eg blood or urine.

According to a second aspect of the invention there is provided a collection tool for use in the bodily fluid collection apparatus described above.

According to a third aspect of the invention there is provided a storage vessel for use in the bodily fluid collection apparatus described above.

According to a fourth aspect of the invention there is provided a fluid displacement means for use in the bodily fluid collection apparatus described above.

According to a fifth aspect of the invention there is provided a test device configured to couple with the storage vessel described above.

According to a sixth aspect of the invention there is provided a method of collecting saliva from a person using the apparatus described above. The method comprising: inserting the first end of the collection tool into a person's mouth; when the collection tool contains saliva, inserting the fluid displacement means into the first end of the collection tool; and moving the fluid displacement means to displace the saliva from the collection tool to the storage device.

BRIEF DESCRIPTION OF THE DRAWINGS

For a better understanding of the invention and to show how the same may be carried into effect, reference will now be made, by way of example, to the accompanying drawings, in which: Fig. 1(a) shows assembly of the collection tool according to an embodiment; Fig. 1(b) shows the spacers of the collection tool according to an embodiment; Fig. 1(c) illustrates a cross-section of the assembled collection tool according to an embodiment; Fig. 2 illustrates different capillary channel dimensions in accordance with various embodiments; Fig. 3 (a) illustrates the storage vessel according to an embodiment; Fig. 3(b) illustrates a cross-section of the storage vessel according to an embodiment; Fig. 4(a) illustrates the plug of the storage vessel according to an embodiment; Fig. 4 (b) illustrates a cross section of the test device interface according to an embodiment; Fig. 4 (c) illustrates the test device interface according to an embodiment; Fig. 5 illustrates how the collection tool and storage vessel are coupled according to an embodiment; Fig 6 illustrates a fluid displacement means according to an embodiment; Fig 7 illustrates a storage cap according to an embodiment; Fig. 8 illustrates an alternate collection tool and plunger arrangement according to an embodiment; Fig.9(a) illustrates a storage vessel according to an embodiment; Fig.9(b) illustrates a storage vessel according to an embodiment; Fig.9(c) illustrates a storage vessel according to an embodiment; Fig. 10(a) illustrates an alternate collection tool according to an embodiment; Fig. 10(b) illustrates an alternate collection tool according to an embodiment; Fig. 10(c) illustrates an alternate collection tool and fluid displacement means arrangement according to an embodiment; Fig. 10(d) illustrates an alternate collection tool and fluid displacement means arrangement according to an embodiment; Fig.11 shows the collection tool and storage vessel according to an embodiment; and Fig. 12 illustrates a method of collecting bodily fluid samples according to an embodiment.

DETAILED DESCRIPTION OF EMBODIMENTS

The present disclosure details apparatuses for collecting bodily fluids. The apparatus may comprises a collection tools and/or a storage vessel and/or a fluid displacement means (eg plunger) and/or a test device.

Collection tool In a preferred embodiment, the collection tool comprises an internal channel which is preferably (i.e., optionally) a capillary channel and may extend from a first end of the collection tool to a second end of the collection tool. The capillary channel enables the sampling of bodily fluid from a user using capillary forces. The geometry, the length, the internal dimensions and any possible surface modifications or treatments of the central capillary channel control the sampling speed and the volume of the fluid collected. The use of the capillary channel may allow a much faster collection than via conventional drooling methods or when using an absorbent swab material.

Zimmerman et al (LabChip, 2007, 7, 119-125, Capillary pumps for autonomous capillary systems) defines the capillary pressure Pc of a liquid-air meniscus in a microchannel as: where y is the surface tension of the liquid, chili are the contact angles of the liquid on the bottom, top, left, and right wall, respectively, and a and b are the depth and width of the microchannel, respectively.

References to capillary pressure herein generally relate to capillary pressure of a saliva-air interface, and may be approximated based on the above equation for capillary pressure Pc based on an assumption that the relevant structure, e.g., channel or chamber, can be approximated as having a substantially rectangular cross-section.

The above definition of a liquid-air capillary pressure Pc may generally be applied to references to capillary pressure throughout the present disclosure.

However, it is not essential that the internal channel is a capillary channel. Drawing of saliva through the channel may be primarily driven by surface wettability and/or capillary pressure. Thus, the drawing may be achieved by, e.g., a hydrophilic material or surface coating of at least an internal region along the length of the channel, and/or a hydrophilic element extending through the length of the channel such as may be provided by hydrophilic, preferably adhesive, tape. Thus, while preferred embodiments may have a capillary channel and/or hydrophilic tape, either or both of these features may be omitted.

Although saliva is referred to as the bodily fluid throughout this application, it may also be blood, urine etc. In an embodiment, a first end of the collection tool is preferably shaped to facilitate insertion in the mouth for the collection of saliva. In an embodiment the width of the device at this first end is between -4 and -15 mm. In addition, the external surface of the device is preferably smooth so that the discomfort to the user is kept at a minimum within the small sampling time (e.g. < 1 min).

The internal dimensions of the internal capillary can be calculated to match (e.g.) half the target volume of the sample to collect. The internal surface energy and geometry of the internal capillary can be suitable for drawing saliva by capillary action.

Fig. 1(a) illustrates the assembly of the collection tool 10 of an embodiment. Fig. 1 (c) illustrates a cross-section of the assembled collection tool 10 and includes dimensions of the internal channel 11 for saliva collection. The internal channel 11 contains a feature 12 near the inlet to capture bubbles. All dimensions in Fig.1(a) to Fig. 1(c) are in millimetres (mm). The collection tool 10 may be formed of two preferably identical halves 13. The two halves 13 of the tool may be 3D-printed or injection-molded and then assembled using a double-sided hydrophilic adhesive tape 14, thermal bonding or solvent bonding.

The central channel 11 in each half defines a capillary sub-channel of a set volume (e.g. -5--100 pL) that may include a feature to trap bubbles (e.g., a small section near the mouth side of the capillary about twice as wide as the internal channel, wider near the mouth side where bubbles can accumulate). In a preferred embodiment, each sub-channel (e.g., each half when divided by hydrophilic tape) has a diameter of up to -1.3mm, and may have a progressive taper from -1.3 mm on the mouth side (or first side) to -0.8 mm. A channel diameter (combined of the two sub-channels) of less than 3mm is preferable. The channel 11 also has a -3.0 mm wider part at the top to allow bubbles to accumulate. Alternatively, the channel 11 may not have a feature to trap bubbles, so that it provides a stronger capillary action. This is useful for when the collection tool 10 is used inverted with a pool of saliva at the bottom and the mouth end soaked in the pool. The overall device length is -61 mm. Different dimensions, e.g., channel diameters, may be appropriate for fluids of different viscosity, e.g. blood.The central part of each half defines a capillary sub-channel of a set volume. This volume is set to be half the target volume of the sample to collect. When the halves 13 are joined together using the hydrophilic adhesive tape 14, the tape forms a part of each capillary sub-channel. The properties of the hydrophilic adhesive tape provide adequate capillary forces to enable capillary action to collect the fluid. The hydrophilic tape preferably has a water contact angle of less than -5°, e.g. for a 5u L drop of water. The hydrophilic tape 14 should be pressure-activated rather than thermally activated to facilitate easy assembly. A double sided acrylic tape, such as ARFlow® 93687, which has a water contact angle of < 5° is suitable. Alternatively, two pieces of hydrophilic single sided tape, such as ARFlow® 93049 which has a water contact angle of < 5°, may be used joined. The two pieces of hydrophilic single sided tape can be joined together by a double sided tape such as ARFlow® 90445. As this double sided tape is not in contact with the fluid, the water contact angle is not of importance. However, other types of hydrophilic tape can be used.

In another embodiment, the collection tool 10 is focused towards collecting saliva within <1 min. In this embodiment, the internal capillary channel 11 is an inverted taper with a slowly decreasing diameter to create a slowly increasing capillary force required to rapidly fill the internal volume when the user slightly tilts his head forward with the collection tool in his/her mouth. Fig. 2 illustrates the adaptability of the design of the internal capillary channel 11 to allow the collection of bodily fluids with various viscosity ranges (blood or saliva) and with or without expected bubble formation at the collection point. Fig. 2 details several possible tapered designs with various capillary forces depending on the expected viscosity of the saliva to be collected as well as a wider taper at the inlet to allow possible bubbles to be accumulated in this area without affecting the accuracy of the collected volume. All dimensions in Fig.2 are in millimetres (mm). The channels with a decreasing taper from the mouth side are preferred unless the collection is done in a drooling configuration. The latter can tolerate a decreasing taper (extreme right). In a passive drooling configuration there is less need to assist the fluid to flow to the other end, so a decreasing taper can be used.

A feature 12 may be added to trap bubbles (Fig. 2: 2nd and 3rd from the left). When the collection tool 10 is placed horizontally, and liquid enters on the mouth side, the bubbles will go where the pressure is minimal. The 5-mm long pocket shown in Fig. 2 311 from the left was designed to serve that purpose.

When the collection tool 10 is placed in a mouth and pointing downwards, the bubbles will stay in the top section of the tool 10. The 6-mm deep tapered feature 12 shown in Fig. 2 second from the left provides an accumulation area for the bubbles. The same is true for the channel shown in Fig. 1(c).

In another embodiment, a glass capillary may be embedded within a plastic casing. The glass capillary defines the volume and may have preferential wetting properties compared with a plastic casing. This avoids using a hydrophilic tape for propagation since the glass capillary is hydrophilic enough to provide adequate capillary forces. The same two halves 13 presented in Fig. 1(a) can be used, but the glass capillary facilitates the fabrication of the collection tool 10 by inserting a glass capillary later during assembly.

Alternatively, the capillary channel 11 may be coated with a hydrophilic material. In this case, or in the case of the glass capillary, any adhesive, or adhesive method such as thermal bonding, may be used to assemble the two halves 13 of the collection tool 10 together.

Alternatively, the collection tool 10 may be fabricated as a single piece, or as two nonidentical halves. For example, only one of the two halves 13 may have a capillary channel.

Fig. 1 (b) shows the use of the spacers 15 (or protrusions) to prevent clogging of the collection tool 10 by the tongue of the operator. As illustrated in Fig. 1(b), the mouthpiece end includes two spacers 15 to avoid the direct contact of the tongue with the inlet of the internal capillary channel 11. In an embodiment, the spacers 13 are between -1 mm to -5 mm long. The spacers 13 are designed as two protrusions at the first end which is inserted in the mouth. When the collection tool 10 is pushed against the tongue, a cavity forms where the saliva is accumulated during a short time before collection starts. This pool is created because the spacers 15 keep the tongue close to the tool inlet without allowing to make contact and seal the capillary inlet. The length of the spacers 15 and the distance between them can be adjusted to create a larger pool if the test device for which the sample is being collected commands so or to reduce the bubbles during collection. Preferably, the distance between the spacers 15 is between -4 and -8 mm. The distance between the spacers 15 can be adjusted before manufacture to tune the pool of saliva and/or slightly adjust the pooled volume depending on the assay requirements, such as amount of saliva needed.

The collection tool 10 may comprise a vent system located in the collection tool, preferably close to or at the second end of the collection tool, and/or the storage vessel. It allows air to escape as the fluid/saliva fills the capillary channel. The vent system may comprise a notch 16 in the collection tool connecting the filter and the storage vessel underneath to the atmosphere. The vent notch 16 is shown in Fig. 1(c).

Alternatively or additionally, the vent system may be located in the storage vessel. Advantageously however provision of the vent system in the collection tool rather than the storage vessel may reduce contamination and/or leakage through a vent (e.g. hole) in the storage vessel. However, the vent system, e.g., in the storage vessel, may comprise a cap to open and/or close (preferably seal) the vent. (Regardless, a vent may be present in the fluid displacement means, e.g., as a vent in a plunger; in embodiments this is in addition to the above-mentioned vent system).

The storage vessel The storage vessel is included in the tool so that the user is not required to supply their own vial to collect the sampled fluid. The storage vessel may be coupled to the collection tool through friction fit, mechanical twist fit, by threaded ends, or by a Luer-type connection.

The storage vessel should be made of a material that reduces the wetting and interaction of the collected fluid with the internal walls, which could lead to volume and/or analyte losses (preferably polypropylene for saliva collection). The vessel has an internal volume of -50-250 pL to allow for the possible expansion of the content when freezing.

The material of the storage vessel may be optimized for several modes of storage, e.g.,: room temperature, in a refrigerated environment (e.g. 0-+10 °C), and/or frozen (e.g. -40-0 °C).

Fig. 3(a) and Fig. 3(b) show an example of a storage vessel 30 according to an embodiment. Fig. 3(a) illustrates details of the storage vessel 30 and the breakable opening 31 for insertion into the test device. Fig. 3(b) illustrates cross sections of the storage vessel 30 and the breakable opening 31. All dimensions in Fig. 3(a) and Fig. 3(b) are in millimetres (mm). During collection, the sampled volume is immediately transferred into a storage vessel 30 that can be kept at room temperature, in the fridge, or in a -20 °C freezer before analysis. It has a breakable 2x1 mm plug 31 with 0.2 mm thick tabs that allows it to be ejected when the storage vessel 30 is coupled to the test device (see below and Fig. 4(a) and (b)).

The storage vessel 30 may advantageously have dried, or wet reagents stored inside to be reconstituted or mixed with the saliva. The reagents may stabilize analytes within the stored fluid, add competing species for competitive assays, sequester interfering species within the sample, and/or prevent coagulation On the case of blood) or otherwise provide a sample more suitable for testing.

The storage vessel 30 may also comprise a filter to remove bubbles or unwanted debris or particles.

Fig. 5 illustrates how the collection tool 10 and storage vessel 30 are coupled according to an embodiment. In particular, Fig. 5 shows details of the assembly mechanism on the storage vessel 30 for the collection stage. A gasket 50 and a filter 51 are sandwiched between the collector tool 10 and the storage vessel 30. Assembly is achieved by twisting the collection tool 10 200 clockwise. All dimensions in Fig. 5 are in millimetres (mm). During collection, the storage vessel 30 and the collection tool 10 are mechanically connected using a 20-degree twist action that seals by aligning two tabs on the collection tool 10 into the corresponding slots on the storage vessel 30. A commercial off-the-shelf rubber gasket 50 (diameter 3-5 mm, e.g., polybutadiene) and a custom-cut filter membrane 51 are inserted between the collection tool 10 and the storage vessel 30 to, respectively, provide a seal and eliminate the bubbles that would remain from the collection into the capillary. The filter 51, which may have a low hydrophobicity, may have a reasonably tight pore structure to allow filtering out particles without significantly obstructing the flow, typically -1 --6 pm pore diameter. Too low a pore diameter may result in a need for too high pressure to allow the saliva to flow through the filter 51. It is made of a material that does not allow total wetting by the collected fluid that would result in volume and/or analyte losses. In the preferred embodiment, polyethersulfone (PES) or polyvinylidene difluoride (PVDF) are preferred materials for the filter 51.

After the fluid has been transferred to the storage vessel 30, the storage vessel 30 may be removed, or decoupled, from the collection tool 10. This can be achieved, for example, by a counterclockwise turn of the collection tool to free it from the storage vessel.

A storage cap made of the same material as the storage vessel 30 (e.g., polypropylene) can replace the collection tool 10 using the same locking mechanism. Fig. 7 illustrates the storage cap 70 according to an embodiment, wherein the locking mechanism is a mechanical twist lock. Fig. 7 shows details of the storage cap 70 and its assembly onto the storage vessel 30 by a user after the fluid has been transferred from the collection tool. All dimensions in Fig. 7 are in millimetres (mm). The storage cap 70 seals the storage vessel 30 to protect the stored saliva from contact with the outside environment. Preferably, the storage cap 70 is attached to the storage vessel 30 using a thin plastic tab that only requires the user to flip it onto the storage vessel 30 and twist-lock it, or otherwise couple it to the storage vessel 30.

The storage vessel 30 is configured to couple with a test device. The storage vessel 30 comprises a breakable plug 31 at the bottom of the storage chamber that is broken with minimal force on mating with a test device. On breaking the plug 31, the test device can contact the stored saliva and saliva flows from the storage vessel 30 into the test strip channel by capillary action.

Fig. 4(a) illustrates the plug, or breakable opening, in the storage vessel 30 according to an embodiment. All dimensions in Fig. 4(a) are in millimetres (mm). The plug 31 is shaped to prevent it from releasing into the test device 40 once it breaks off. For the same reason, the storage vessel 30 narrows at the bottom. The width and shape of the tabs can be modified to facilitate breaking generally within certain limits set by the fabrication process (e.g. injection molding). In the preferred embodiment, -200-micron thick rectangular tabs that are -0.45 mm wide around the plug (Fig. 4(a)) will break off easily when inserted into the mating part (Fig. 4(b)).

The collected and stored sample is dispensed via a mechanism integrated in the test device 40 while the liquid in the storage vessel 30 acts as a hydrostatic reservoir so that there is no requirement to use pipettes to transfer the sampled fluid into the diagnostic system thereby reducing handling time, the exposure to the operator, and possible contamination of the sample. Possible materials with surface properties that allow capillary action include polycarbonate, methacrylate, polystyrene, polypropylene, and glass.

The storage vessel 30 has a flat side that indicates to the user the way it should be inserted into the test device 40. The flat edge should mate with a corresponding flat edge on the test device 40. Inserting the storage vessel 30 into the test device 40 may initiate the transfer of the fluid to the test device 40 (Fig. 4(b)).

The storage vessel 30 may mate with the test device 40 by friction fit, mechanical twist fit, by threaded ends, or by a Luer-type connection.

A fluid displacement means Fig. 6 illustrates a fluid displacement means 60 according to an embodiment. Fig. 6 shows details of a plunger used to move the fluid from the collection tool 10 to the storage vessel 30 by a short sliding action. All dimensions in Fig. 6 are mm. The fluid displacement 60 means fits onto the first end of the collection tool and when moved causes a small air volume displacement to move the collected sample from the collection tool 10 to the storage vessel 30.

In an embodiment, the fluid displacement means 60 is a plunger. Once the collection by the internal capillary of the collection tool 10 is complete, the user is required to fit a plunger onto the end of the collection tool 10 opposite the storage vessel 30. The plunger is made of the same material as the collection tool 10 (e.g., polystyrene, polymethylmethacrylate, polypropylene or any material for which the collected fluid has a low affinity) and takes advantage of the smooth finish of the outside surface of the collection tool 10. Only a small sliding action is required to move the small volume collected, typically 1 -100 pL (Fig. 6 6). Alternatively, the fluid displacement 60 means can be made of a deformable, or compressible, material such as silicone or thermoplastic polyurethane and a squeezing action can provide the same required air displacement to transfer the fluid into the storage vessel 30.

Furthermore, as the volume of the channel or cavity of the collection tool 10 is known a predetermined volume of bodily fluid, such as saliva, can be determined for transfer from the collection tool 10 to the storage device 30 by air displacement. In an embodiment, a controlled volume can be realized by changing the plunger to have a controlled travel so that it sweeps a controlled predeterined volume.

In an embodiment, a full movement of the fluid displacement means from the first end to a preferably physical stop at or proximate the second end determines the predetermined volume. As shown in Fig. 1 (a) and Fig. 1(c), the stop 17 may be a groove in the collection tool configured to accept a raised inner portion 61 of the plunger 60 so as to stop the plunger from moving any further.

Providing a controlled predetermined volume to test devices such as assay strips is important for the analysis technique to work accurately. Too much or too little bodily fluid, and hence the analyte to be measured, in comparison to the active reagent on the test strip could result in errors.

Test Device The storage vessel 30 may connect or interface with a test device 40 (e.g. microfluidic test strip). In an embodiment, the test device 40 may be an assay strip such as for an ELISA or ELONA test and may have visual and/or audible user interface for indicating a test result, and/or a physical interface for communicating biosensing test results / values to a reader device, and/or a wireless interface for communicating such results/values to a portable device such as a mobile phone and/or to the Cloud to allow remote patient monitoring.

The test device 40 may be a test strip or assay to measure or assess hormones such as progesterone, estrogen, testosterone and/or cortisone. These test devices 40 may be used for menstrual cycle monitoring or monitoring health or performance of athletes. Other test devices 40 may be used to determine or assess viral diseases, including coronaviruses. Other test devices may be used to assess drug abuse.

Fig. 4(b) and Fig. 4(c) illustrate the test device 40 according to an embodiment. Fig. 4(b) shows the principle of the opening of the storage vessel 30 by insertion into the test device 40. All dimensions shown in Fig. 4 (a)-(c) are in millimetres (mm). The test device comprises a mating structure 44 configured to mate with the end of the storage vessel 30 comprising the plug 31. The test device 40 further comprises a platform 41 to raise the plug 31 to induce breaking. The test device 40 also comprises a drain channel 42 connected to a collection channel 43. When the plug 31 is raised, the fluid, or saliva, from within the storage vessel 30 exits under capillary force, and is accumulated in the collection channel 43 that surrounds the platform 41. The collection channel 43 is connected to the drain channel 42 such that the fluid in the collection channel 43 gradually drains away from the collection channel 43 to the drain channel 42. The drain channel 42 directs the fluid to the test device 40, for example a test strip.

Alternative implementation 1 Fig. 8 and Fig. 9 illustrate an alternate approach for the rapid (< 1 min) collection of small volume of bodily fluids. This approach allows for a precise metering (e.g., supplying a predetermined, measured or regulated amount) of the sample fluid after collection a larger volume than required, typically twice or thrice the target volume. The device is closely related to the preferred embodiment described above because it also involves the use of a slight positive pressure to displace the collected volume from a collection tool to a storage chamber but differs because the volume collected is done by passive drooling (Fig. 8).

Fig. 8 illustrates an alternate approach for saliva collection.

Stage 1: a hollow tube 80 is used for passive drooling into a collection body 81. It collects a volume around 1-2 mL. In Fig. 8 the diameter is 6 mm. For faster collection rates the diameter would decrease, and the length would set the collected volume. The tube is a separate part to the collection chamber (green).

Stage 2: The tube 80 is capped off with plunger cap 83 and becomes a plunger (fluid displacement means). It is placed inside the collection body to move the collected fluid into the storage vessel 82 that is made of a collection chamber of the desired volume and a waste chamber.

Stage 3: The storage vessel is decoupled from the collection body 81 and is coupled to a storage cap 84.

Fig. 9 shows the storage part comprising the collection chamber and the waste chamber. The collection chamber is the smaller chamber connected to the inlet channel.

Fig. 9 illustrates a microfluidic circuit inside the lower part of the device. The microfluidic circuit is used for metering, eg determining, providing or collecting a precise volume, and is comprised of several parts: * An inlet channel 93 (width: 250 pm, depth: 400 pm) wide enough to accept a sharp capillary channel, preferably with a hydrophilic inner surface, to retrieve the collected fluid and/or to couple to the test device 40. The capillary channel may be part of the test device and maybe inserted into inlet channel 93.

* A metered collection chamber 90 to collect a precise volume of fluid from the collected drool volume. The collection chamber 90 has recesses at the bottom on the sides to prevent the fluid from flowing out unexpectedly and reduce the metered volume, whose consistency is desirable for assay reproducibility.

* A stop valve 94 (depth: 0.4 mm) to prevent the liquid expelled from the collection chamber 90 from returning to it.

* A waste chamber 91 to collect the discarded sample volume. Similarly, the waste chamber 91 is defined by two symmetric halves that superimpose. The chamber has a flat bottom to stabilize the collected waste during operation.

* A vent channel 92 connected to the waste chamber 91 and facing on the front side of the lower part and the opening is matched by the storage cap 95 to seal off the vessl 82 during storage. The vent channel 92 allows the movement of the fluid under the action of the plunger. The vent 92 can be plugged up by a matching feature on the storage cap 95 to seal off the vessel 82.

To couple with the test device, the storage vessel 82 coupled the test device 40. Fig. 9(c) shows the storage vessel of Fig. 9(a) and Fig. 9(b) except it additionally includes a protruding part 96 which couples into a reservoir-shaped matching feature on the test device 40.

Alternative implementation 2 An alternative implementation exists whereby an uncontrolled and larger volume of saliva (e.g., 50-500 pL) is initially collected in the collection tool. An advantage of doing so is that an excess of saliva is collected, and the user can visually confirm that enough saliva has been collected -which is difficult to do with the preferred embodiment described above. The saliva is collected and then a controlled volume of saliva is transferred to the storage vessel, via the same filter/o-ring assembly as described above. The controlled volume may be realized by changing the plunger to have a controlled travel so that it sweeps a controlled volume.

Fig. 10 illustrates a collector tool and plunger arrangement for the alternative implementation 2. In Fig. 10(a), the saliva 1001 is collected in the channel or cavity of the collection tool 102. The collection tool 1002 may have a thinner section 1003 to promote wicking. In this way saliva may be sampled up to the fill line but may not move to the bottom of the channel/cavity initially.

In Fig. 10(b), the saliva moves to the bottom, where it is stopped by the filter (not shown). It may be left for a period of time to wick. In Fig. 10(b) the fluid displacement means 1004 is coupled with the collection tool 1002. The fluid displacement means may be a plunger or a deformable/compressible member, which when compressed or squeezed causes air displacement. The fluid displacement means comprises a vent 1005 that may ensure saliva isn't moved out of the collection tool before it is time. Alternatively or additionally, the vent 1005 may be located in the storage vessel to which the collection tool is attached or in the collection tool.

In Fig. 10(d), the fluid displacement 1004 means is activated and the saliva is pushed through the filter into the storage vessel (not shown).

Fig.11 shows the collection tool and storage vessel according to an embodiment. Fig. 11 illustrates production of the different elements of the device in a pre-assembled set for easier handling by the user. In this embodiment, the device may be manufactured by attaching each element with thin tabs so that the user can easily handle the entire device without losing any element.

Fig. 12 outlines a method of collecting saliva from a person using the apparatus described previously.

In 3121, the first end of the collection tool is inserted into a person's mouth. Saliva is then collected in the collection tool either through passive drooling or through capillary action. In S122, when the collection tool is contains saliva, the plunger is coupled with the first end of the collection tool. In an embodiment, the collection tool is preferably full of saliva. In S123, the fluid displacement means is moved so as to displace the saliva from the collection tool to the storage device.

Optionally, the storage device may be uncoupled from the collection tool (S124) and a cap placed on the storage vessel (S125). The storage vessel may then be coupled with a test device so that the saliva moves from the storage vessel to the test device (S126).

The described invention proposes a fast (< 30s) collection time and can directly be inserted in one-step into the processing device. Alternatively, it offers the possibility to be stored in a variety of conditions depending on the requirements.

In summary, embodiments of the disclosed invention may offer, e.g.,: a rapid (e.g. <30s) sampling of bodily fluid (e.g., saliva); a simple operation for untrained users; storage at room temperature or frozen (e.g. -20 °C); release into the corresponding test device for analysis; a design amenable to injection molding as well as 3D printing; and/or reduced storage volume requirements, e.g. the separable parts of an embodiment (collection tool, storage vessel, test device) may mean that only the storage vessel need by stored (e.g. in a freezer) for example before interfacing to a test device.

Any measurements indicated throughout the description or in the figures are for only example purposes, and other dimensions may be used.

Claims

CLAIMS: 1. A bodily fluid collection apparatus for collecting and storing a predetermined volume of bodily fluid such as saliva, the device comprising: a collection tool comprising at least one internal channel or cavity extending from a first end to a second end of the collection tool, the first end of the tool for receiving a bodily fluid directly from a person; a storage vessel configured to couple to and decouple from the second end of the collection tool at one end of the storage vessel, a fluid displacement means configured to fit the first end of the collection tool such that a movement of the fluid displacement means causes air displacement to transfer bodily fluid from inside the at least one internal channel or cavity of the collection tool into the storage vessel; and a vent system configured to allow air to escape from the channel or cavity during the fluid displacement.
2. A bodily fluid collection apparatus according to claim 1, wherein the storage vessel comprises a removable seal at an end opposite the end that is configured to couple to the collection tool.
3. A bodily fluid collection apparatus according to claim 2, wherein the seal comprises a plug, wherein the storage vessel is configured to couple with a test device such that when the storage vessel is coupled to the test device, the plug opens to allow the bodily fluid to move from the storage vessel to the test device
4. A bodily fluid collection apparatus according to any preceding claim wherein the storage vessel, when not coupled to the collection tool, is configured to be coupleable to a storage cap.
5. A bodily fluid collection apparatus according to any preceding claim wherein the fluid displacement means comprises a plunger.
6. A bodily fluid collection apparatus according to any preceding claim wherein the fluid displacement means comprises a compressible member, wherein compression of the compressible member causes the air displacement.
7. A bodily fluid collection apparatus according to any preceding claim wherein the at least one internal channel or cavity comprises a capillary channel having a hydrophilic surface.
8. A bodily fluid collection device according to claim 7, wherein the hydrophilic surface of the capillary channel extends from the first end to the second end of the collection tool.
9. A bodily fluid collection apparatus according to any preceding claim wherein a diameter of the at least one internal channel or cavity progressively decreases from a first end to a second end.
10. A bodily fluid collection apparatus according to any preceding claim wherein the collection tool comprises a bubble trap, the trap comprising a widening of the channel or cavity at the first end of the tool.
11. A bodily fluid collection apparatus according to any one of claims 1 to 10 wherein the hydrophilic material comprises hydrophilic tape.
12. A bodily fluid collection apparatus according to any one of claims 1 to 10 wherein the hydrophilic material comprises glass.
13. A bodily fluid collection apparatus according to any one of claims 1 to 10 wherein the collection tool comprises hydrophilic tape configured to divide the at least one internal channel or cavity into at least two internal channels or cavities.
14. A bodily fluid collection apparatus according to any preceding claim wherein the first end of the collection tool comprises a mouthpiece, wherein the mouthpiece comprises two spacers for simultaneously contacting a tongue of the person, preferably wherein ends of the spacers are positioned relative to one another to match a curvature of the tongue such as around the tip of the tongue.
15. A bodily fluid collection apparatus according to any preceding claim wherein the storage vessel comprises a filter to remove bubbles and/or particles from the bodily fluid, the filter preferably at the end to couple to the collection tool.
16. A bodily fluid collection apparatus according to any preceding claim wherein the storage vessel comprises reagents on at least part of its internal surface to buffer or treat collected fluid
17. A bodily fluid collection apparatus according to any preceding claim, wherein the storage vessel comprises a microfluidic circuit, the microfluidic circuit comprising: a collection chamber for collecting the predetermined volume; a waste chamber; a one-way valve to allow excess fluid from the collection chamber to pass to the waste chamber; and a vent channel connected to the waste chamber
18. A bodily fluid collection apparatus according to any preceding claim, wherein the bodily fluid is saliva
19. A collection tool for use in the bodily fluid collection apparatus of any one of claims 1 to 18.
20. A storage vessel for use in the bodily fluid collection apparatus of any one of claims 1 to 18.
21. A fluid displacement means for use in the bodily fluid collection apparatus of any one of claims 1 to 18
22. A test device configured to couple with the storage vessel of claims 3 to 18.
23. A method of collecting saliva from a person using the apparatus of any one of claims 1 to 17, the method comprising: inserting the first end of the collection tool into a person's mouth; when the collection tool contains saliva, fitting the fluid displacement means to the first end of the collection tool; and moving the fluid displacement means to displace the saliva from the collection tool to the storage device.