WO2021093750A1

WO2021093750A1 - Sample processing device

Info

Publication number: WO2021093750A1
Application number: PCT/CN2020/127930
Authority: WO
Inventors: Adrian Wai Ming Lim; Hon Keung Lai; Yu Sun WONG
Original assignee: Jacobson T&D Limited
Priority date: 2019-11-12
Filing date: 2020-11-11
Publication date: 2021-05-20
Also published as: TW202127032A

Abstract

A sample processing device (1A) comprising a sample container (2A), a partition (23A), an inlet (24A), a partition breaker (30A) and a sampler (4A). The sample container comprises a lower compartment (20A) adapted to contain a first fluid, and an upper compartment (21A) located above the lower compartment (20A) and adapted to contain a second fluid. The partition (23A) separates the upper compartment (21A) from the lower compartment (20A). The partition breaker (30A) is operable to break the partition (23A) such that the upper (21A) and lower compartments (20A) are in fluid communication with each other. The sampler (4A) extends sealingly through the inlet (24A) and comprises a sample collector (40A) adapted to collect a sample and to be moved into the lower compartment (20A). The device (1A) is preferably used to test a urine sample for prostate cancer.

Description

Sample Processing Device

Related Applications

This application claims priority of United States Provisional Patent Application No. 62/934,006, filed November 12, 2019, the entire contents of which are incorporated herein by reference.

Technical Field

The present invention is in general directed to a sample processing device for both collecting a sample and processing the sample in a contained environment. In a preferred embodiment, the device is used for in vitro diagnostics, such as for detecting prostate cancer based on a urine sample.

Background

Methods for prostate cancer screening are known. Currently, the two most widely adopted screening methods are digital rectal examination (DRE) and serum prostate-specific-antigen (PSA) . These methods, however, are grossly inaccurate. Other screening methods for prostate cancer are also either inaccurate, expensive, inconvenient or invasive.

There is a need to develop a screening tool that performs significantly better than PSA as an initial screening test that is affordable, non-invasive, convenient and easy to use, and stable when stored on over-the-counter shelves and in transport.

There is also a general need for developing a tool (device) that is capable of collecting a sample and processing that sample in a contained environment.

Summary

The present invention provides a sample processing device for in vitro diagnostics, such as for detecting prostate cancer based on a urine sample. The present invention also has much broader application, for both collecting a sample and processing the sample in a contained environment.

According to a first aspect of the present invention, there is provided a sample processing device comprising:

a sample container comprising:

a lower compartment adapted to contain fluid;

an upper compartment located above the lower compartment, and adapted to contain fluid;

a partition separating the upper compartment from the lower compartment; and

an inlet to the lower compartment;

a partition breaker operable to break the partition such that the upper and lower compartments are in fluid communication with each other; and

a sampler extending sealingly through the inlet and comprising a sample collector adapted to collect a sample and to be moved into the lower compartment.

It is to be appreciated that, when collecting a sample, the upper compartment is typically located above the lower compartment. However, if the device were to be used other than in a substantially vertical disposition, the terms ‘upper compartment’ and ‘lower compartment’ could be substituted for other relative terms such as ‘first compartment’ and ‘second compartment’ .

The sample collector can be movable between a sample collecting position and sample processing position. In the sample collecting position, the sample collector can be located externally of the inlet and can collect a sample. When moving to the sample processing position, the sample collector can be moved through the inlet to a final location within the lower compartment.

The sampler can be of any suitable size, shape and construction, and can be made of any suitable material or materials. The sample collector can collect any suitable kind, mass, size or volume of sample, be it a fluid such as a gas, liquid, slurry or suspension, a semi-solid such as a gel, or a solid such as a coherent mass or a powder.

In some embodiments the sample collector can comprise at least one void (or cavity, recess, groove, cut-out or divot etc) for collecting or containing a fluid, a semi-solid and/or solid. In some embodiments the sample collector can comprise a single void. In some embodiments the sample collector can comprise two voids. In some embodiments the sample collector can comprise three voids. In some embodiments the sample collector can comprise four voids. The voids can be of identical size to each other or of differing sizes. In some embodiments, if a single void, then the void can be sized to collect approximately 0.1 mL of fluid, such as a liquid. In some embodiments, if having multiple voids, then the total volume collected by the voids can also be approximately 0.1 mL of fluid, preferably a liquid.

It is to be appreciated that the void or voids can be sized to collect fluid samples ranging from about 0.03, 0.04, 0.05 to about 5 mL, including all 0.001 mL increments between 0.03 and 5 mL, including 0.031, 0.032, 0.033, 0.034, 0.035 mL etc.

Preferably the one or more voids are fillable with a fluid. Preferably, the sample is a liquid having good flowability. In some embodiments the fluid can be a biological fluid. The biological fluid can be a liquid such as urine, blood or saliva, for example. Preferably the sample to be collected is urine.

In some embodiments the sample collector can comprise an absorbent material, such as a sponge or gauze, for absorbing liquid.

In some embodiments the sample collector can comprise at least one void containing an absorbent material, for absorbing liquid.

In some embodiments the sample collector can comprise a swab, scoop or swipe for collecting a fluid, a semi-solid or solid.

In some embodiments the sampler is in the form of a piston assembly that extends sealingly through the inlet. In some embodiments the piston assembly comprises a piston shaft that is slideable within the inlet.

In some embodiments the piston assembly comprises a respective piston stop located at each end of the piston shaft, each of which functions as a travel stop. A first piston stop extending adjacent the inlet within the lower compartment can prevent the piston shaft from moving completely through the inlet to a location externally of the device. A second piston stop located externally of the device can prevent the piston shaft from moving completely into the lower compartment. Each piston stop can, for example, be in the form of a head, shoulder or flange that overhangs the shaft.

One or more of the piston stops can be detachably connected to the piston shaft, for example, by way of a threaded connection or friction fit. Preferably the second piston stop is detachably connected to the piston shaft, preferably by way of a threaded connection. The second piston stop can have a flat surface so as to make good contact with a container containing a sample, such as a base of a cup.

The sample processing device can comprise a protective cap that houses at least some of the piston assembly. The protective cap can be of any suitable size, shape and construction, and can be made of any suitable material or materials. In some embodiments the protective cap prevents the sampler from being unintentionally moved to the sample processing position. In some embodiments the protective cap connects to the piston assembly or other part of the device, such as the sample container, by way of a friction fit or threaded connection, for example. The sample processing device can comprise a protective cap that friction fits to the second piston stop. In some embodiments the protective cap extends over the second piston stop and further extends to the inlet or sample container, so as to prevent the sampler from being unintentionally moved to the sample processing position. That is, the protective cap can have a cap base extending alongside the second piston stop, and a cap side wall extending from the cap base that extends to and abuts the inlet or sample container.

The piston assembly can comprise a central axis extending longitudinally through the piston shaft from one piston stop to the other. The piston shaft can comprise an outer cylindrical surface extending about the central axis. In some embodiments, the at least one void of the sample collector can be formed in the outer surface of the piston shaft between the piston stops. Put another way, the at least one void can be a recess, divot, cavity, groove or cut-out of the piston shaft/outer cylindrical surface. Preferably the at least one void is located approximately equidistantly between the piston stops.

If a single void, it can extend as a groove about, laterally of and relative to the central axis. For example, the outer cylindrical surface can comprise a circumferentially extending groove. The at least one void, but preferably three voids, can be equidistantly spaced about the central axis within the same plane, and each void can be formed in the outer cylindrical surface of the piston shaft. The void/scan be filled by immersing the piston shaft within the fluid to be sampled. Preferably, the void/scan be filled by immersing the piston shaft as well as a lower part of the inlet within the fluid to be sampled (with an excess of fluid usually being contained within a sampling cup) .

When sampling fluid, the void or outer cylindrical surface can be shaped, angled or tapered so as to more easily release air bubbles unintentionally trapped within the void. For example, air bubbles can be dislodged from the void by gently tapping the piston shaft or other part of the device. For example, an upper surface of the void can slope or taper upwardly as it extends away from the central axis.

The piston assembly can comprise sealing elements extending around the outer cylindrical surface perpendicularly of the central axis, such that the lower compartment cannot unintentionally leak fluid via the inlet. For example, the outer cylindrical surface can comprise a circumferentially extending groove within which extends an O-ring. The piston assembly can comprise one, two or three sealing elements located between the at least one void and the first piston stop, but preferably three sealing elements. The piston assembly can comprise one, two or three sealing elements located between the at least one void and the second piston stop, but preferably three sealing elements.

The sample container can be of any suitable size, shape and construction, and can be made of any suitable material or materials. The sample container can comprise a side wall, a top wall and a base wall.

The lower compartment can contain any suitable volume of fluid or fluids. The fluid can be a gas. The fluid can be a liquid. The fluid can include both a gas and a liquid. The gas can be air, oxygen or inert, such as nitrogen. The liquid can be, for example, compatible with the collected sample, such as a buffer, diluent, reagent or the like. Preferably the first compartment contains both a liquid (which usually cannot be compressed) and a gas such as air (which can be compressed) .

In some embodiments, the lower compartment has a void volume of between about 5 mL and about 25 mL, including all 0.1 mL increments between 5 and 25 mL. Preferably the lower compartment has a void volume of about 15 mL. Preferably the lower compartment is not completely filled with liquid because movement of the sample collector to the sample processing position will cause displacement of some of the fluid and so a headspace is needed (eg. air pocket) above the liquid. It may be important to have a headspace (air pocket) so that the sample collector does not “rebound” after being pushed into the lower compartment.

In some embodiments the ratio of sample to total liquid volume from both the upper and lower compartments ranges from about 1: 1 to 1: 200, including all numerical values therebetween, eg. 2, 3, 4, 5…195, 196, 197, 198 and 199 etc. In some embodiments, the lower compartment can contain approximately 8.9 mL of liquid, approximately 6 mL of air (above the liquid) , can receive approximately 0.1 mL of sample, and movement of the sample collector within the lower compartment can create a displacement volume of approximately 0.4 mL. It is to be appreciated that air pressure will vary according to temperature. In some embodiments, the upper compartment can contain approximately 1 mL of liquid.

The sample container can comprise a central axis extending centrally through the lower and upper compartments and inlet. That central axis preferably axially aligns with the central axis of the piston assembly.

The lower compartment can comprise a continuous lower compartment side wall. The lower compartment can comprise a lower compartment base wall extending between and to the side wall. The lower compartment can comprise a top wall extending between and to the side wall. The lower compartment can have any suitable geometric cross-section (ie. perpendicular to the central axis) , eg. round, oval, square, oblong, triangular, hexagonal et cetera. In some embodiments, the continuous lower compartment side wall is elongate and is tubular or substantially cylindrical. In some embodiments, the continuous lower compartment side wall is elongate and is substantially cylindrical but having an opposed pair of flattened lateral faces. In some embodiments, the continuous lower compartment side wall is elongate and in the form of a barrel, preferably a substantially cylindrical barrel. In some embodiments, the continuous lower compartment side wall is elongate and in the form of a barrel, preferably a substantially cylindrical barrel but having an opposed pair of flattened lateral faces. The lower compartment top wall and the partition can be one and the same, but this need not be the case. The lower compartment base wall can comprise a central opening. The lower compartment top wall can comprise a central opening. In some embodiments, the lower compartment top wall can comprise a shoulder, neck or narrowing. In some embodiments, the lower compartment top wall can comprise a shoulder or neck providing a central opening. In some embodiments, the lower compartment can comprise at least one retainer, such as a flange, extending perpendicularly of and outwardly from the side wall. In some embodiments, the lower compartment can comprise at least one spacer extending perpendicularly of and outwardly from the side wall and along a length of the side wall.

In some embodiments, with the exception of the lower compartment top wall, the lower compartment walls together with the inlet can comprise an elongate barrel having a restricted end from which the inlet extends.

The lower compartment walls can be made of any suitable material or materials, such as plastics material or glass. Although the lower compartment walls can be opaque, preferably they are transparent. In some embodiments, the inlet and lower compartment walls are of unitary construction. In some embodiments, the inlet and lower compartment walls are of unitary construction, with the exception of the lower compartment top wall. These can be made of moulded plastics material.

The inlet can be of any suitable size, shape and construction, and can be made of any suitable material or materials. In some embodiments, the inlet extends as a ring or annular wall from the lower compartment base wall. The inlet can have a central opening that coincides with the central opening in the lower compartment base wall. The inlet ring or annular wall can have an inlet rim.

The first piston stop can be adapted to abut the lower compartment base wall. The second piston stop can be adapted to abut the inlet rim.

The upper compartment can contain any suitable volume of fluid or fluids. The fluid can be a gas. The fluid can be a liquid. The fluid can include both a gas and a liquid. The fluid could be a solid, such as a powder or fine granular material, provided that it has good flowability. The gas can be air, oxygen or inert, such as nitrogen. The liquid can be, for example, compatible with the collected sample or fluid of the lower compartment, such as a buffer, diluent, reagent or the like. Preferably the upper compartment contains liquid.

Preferably the upper compartment has a void volume of between about 0.5 mL and 5 mL, including all 0.01 mL increments between 0.5 and 5 mL. Preferably the upper compartment is capable of containing up to about 1 mL of liquid.

The upper compartment can comprise a continuous upper compartment side wall, an upper compartment base wall extending between and to the side wall, and an upper compartment top wall extending between and to the side wall. The upper compartment can have any suitable geometric cross-section (ie. perpendicular to the central axis) , eg. round, oval, square, oblong, triangular, hexagonal, notched circular et cetera. The geometric cross-section can generally match the cross-section of the lower compartment. The upper compartment side wall can have a stepped periphery (between the base and top walls) . The upper compartment base wall and the partition can be one and the same or partly one and the same, but this need not be the case. The upper compartment top wall can be convex or dome-shaped, sloping upwardly and away from the upper compartment base wall. The upper compartment can comprise a flange, such as a sealing flange, extending perpendicularly of and outwardly from the side wall. The flange and side wall can be of unitary construction. The flange together with the base wall, as well as possibly part of the side wall, can form the partition separating the upper compartment from the lower compartment. The flange can seal tightly against the top wall or top wall neck of the lower compartment.

The upper compartment walls can be made of any suitable material or materials, such as plastics material, metal (eg. coated aluminium) , rubber, glass or composite materials. The upper compartment walls can be in the form of thin plastic, metal, glass or rubber walls, membranes, films or foils. The upper compartment top wall can be made of flexible material, such as a rubber, plastic or metal wall, membrane, film or foil. The upper compartment base wall/partition can be in the form of a thin plastic, metal, glass or rubber wall, membrane, film or foil.

If the partition is separate from the upper compartment base wall, then it can be of any suitable size, shape and construction. The partition can be made of any suitable material or materials, such as plastics material, metal (eg. coated aluminium) , glass or composite materials. The partition can be in the form of a thin plastic, metal or glass wall, membrane, film or foil.

In some embodiments the upper compartment is in the form of a capsule or pod prefilled with fluid, and having a flexible top wall and a tear away film or foil base wall (partition in some embodiments) .

In some embodiments the upper compartment walls are made of plastics material, with the top wall being made of flexible plastics material, and the base wall being made of a tear-away or otherwise breakable plastic film (cap) .

In some embodiments, a region or regions of the upper compartment wall or walls bear against the lower compartment side wall and/or lower compartment top wall. In some embodiments, the sealing flange or stepped periphery of the upper compartment side wall bears against a shoulder or neck of the lower compartment top wall in a sealed manner.

In some embodiments, the upper and lower compartment side walls can be of unitary construction. In some embodiments, the upper compartment can be detachably connected to the lower compartment, and this can be achieved in any suitable way.

The sample container can comprise a connecting mechanism for connecting the upper and lower compartments together. Any suitable type of connecting mechanism can be used. For example, a screw thread mechanism can be used, or a friction fit connecting mechanism can be used.

In some embodiments, the connecting mechanism comprises a cap assembly adapted to hold the upper and lower compartment together. The cap assembly can comprise a cap having a cap top wall having a central opening, and a continuous cap side wall extending downwardly from the cap top wall.

In some embodiments, the connecting mechanism comprises a sealing member, such as an O-ring, extending between the upper compartment retainer and upper compartment base wall/partition. The cap side wall can have a screw thread, the lower compartment side wall can have a screw thread, and these can be screwed together. When screwed together, the upper compartment top wall can extend through and proud of the cap top wall central opening, the retainer of the upper compartment can rest atop a rim of the lower compartment side wall, and the sealing member can extend between the retainer and base wall/partition.

In some embodiments, the connecting mechanism comprises a part or parts of the partition breaking mechanism, as discussed later.

The partition breaker can be moved from a resting position to a breaking position, and this can be achieved in any suitable way. The partition breaker can be of any suitable construction. For example, the partition breaker can comprise a working end shaped to pierce, cut, puncture, perforate, dislodge or break the partition.

In some embodiments, the partition breaker can comprise a working end extending from the upper compartment top wall towards the partition. In some embodiments, the partition breaker can further extend upwardly from the upper compartment top wall as a projection. In some embodiments, the partition breaker can be of integral construction with the upper compartment top wall –for example, both being made of rubber or plastics material. The upper compartment top wall can be flexible so that pressing down on the top wall moves the partition breaker working end towards and into contact with the partition. In some embodiments, the partition breaker working end is shaped to cut, puncture, pierce, break away or otherwise unseal the partition. In some embodiments, the partition is in the form of a foil or film, such as a metal foil or plastic film that can be pierced or broken away by the partition breaker. If the upper compartment base wall and partition are separate features of the device, then the partition breaker can break both the base wall and partition. In some embodiments, the working end is made of relatively harder plastic than the material used in the compartment top wall, which is flexible. In some embodiments the partition breaker is not of integral construction with the top wall, is sealed within the upper compartment, and is movable into contact with the partition when the top wall is pressed downwardly towards the partition.

The partition breaker can be a component of a larger partition breaking mechanism.

In some embodiments, the partition breaking mechanism can comprise an upper housing and lower housing, each of which envelops the sample container. The upper and lower housings can be of any suitable size, shape and construction, and can be made of any suitable material or materials.

The upper housing can comprise an upper cover that envelops the upper compartment and part of the lower compartment. The upper cover can comprise an apical region. In the resting position the apical region can extend above the upper compartment top wall and in contact with the partition breaker. In the breaking position, the apical region can move towards the upper compartment and press the partition breaker into engagement with the partition.

The upper cover can comprise two or more cover pieces that can be connected together by way of threaded fasteners or adhesive, for example.

The upper housing can comprise spacers that extend internally of the upper cover, that help position the upper cover relative to the lower compartment, especially when moving from the resting position to the breaking position.

The upper cover can be made of transparent material such that the lower compartment within is visible. The upper cover can be made of non-transparent or opaque material such that the lower compartment within is not visible or is kept in darkness. Some types of processing steps may need to be carried out in darkness, for example. The upper housing can comprise one or more viewing or inspection windows within the upper cover such that the lower compartment within is visible. The viewing or inspection window can be a cut-out or transparent area of the upper cover.

The partition breaking mechanism can comprise a lower housing that extends around the lower compartment. The lower housing can further extend around the inlet.

The lower housing can comprise a lower cover that envelops the lower compartment and optionally the inlet. The lower cover can extend partway between the upper cover of the upper housing and the lower compartment, so that the upper cover can slide relative to the lower cover.

The lower cover can comprise two or more cover pieces that can be connected together by way of threaded fasteners or adhesive, for example.

The lower cover can be made of transparent material such that the lower compartment within is visible. The lower cover can be made of non-transparent or opaque material such that the lower compartment within is not visible or is kept in darkness. The lower housing can comprise one or more viewing or inspection windows within the lower cover such that the lower compartment within is visible. The viewing or inspection window can be a cut-out or transparent area of the lower cover.

The lower cover can be connected to the sample container such that it does not move when the partition breaker and upper cover move to the breaking position. This can be achieved in any suitable way. In some embodiments, the lower housing comprises internal walls or spacers that extend inwardly of the lower cover. The lower compartment can comprise a retainer, such as a flange, extending perpendicularly of and outwardly from the lower compartment side wall. This retainer can locate between the internal walls or spacers.

Preferably, the partition breaker is movable only from the resting position to the breaking position. This can be achieved in any suitable way. In some embodiments, the partition breaking mechanism comprises a ratchet and pawl mechanism for unidirectional movement. Preferably the partition breaking mechanism comprises a linear ratchet and a pawl that is engagable with teeth of the ratchet. In some embodiments, the upper housing has at least one linear ratchet, preferably a pair of a linear ratchets, and the lower housing has at least one pawl, preferably a pair of pawls. In some embodiments a pair of linear ratchets extend along an inner surface of the upper cover, and a pair of pawls in the form of sprung hooked legs are connected to and extend upwardly from the lower cover and the hooked legs engage teeth of the linear ratchets.

In some embodiments, in order to move the partition breaker from the resting position to breaking position, the upper cover is slid relative to the lower cover until a viewing or inspection window of the upper housing coincides with a viewing or inspection window of the lower housing, such that the lower compartment is visible to a user of the device.

The sample processing device can comprise indicia, such as a colour legend, key, colour chart or colour wheel, for example located adjacent the viewing or inspection window of the upper housing, so as to help interpret a test result for the processed sample within the lower compartment.

In some embodiments, the partition breaking mechanism can comprise a housing that envelops the sample container. The housing can be of any suitable size, shape and construction, and can be made of any suitable material or materials.

The housing can comprise a cover that envelops the upper compartment and part of, most of, or all of, the lower compartment. The cover can comprise an apical region. The cover can comprise a side wall region extending from the apical region towards the inlet. In the resting position the apical region can extend above the upper compartment top wall and in contact (direct or indirect) with the partition breaker. In the breaking position, the apical region can move towards the upper compartment and press the partition breaker into engagement with the partition.

The cover can comprise two or more cover pieces that can be connected together by way of threaded fasteners or adhesive, for example.

The cover can be shaped so as to slide relative to the upper and lower compartments in a specific manner, especially when moving from the resting position to the breaking position. In this regard, both an inner surface of the cover and sample container or lower compartment side wall can have flattened lateral surfaces.

The cover can be made of transparent material such that the lower compartment within is visible. The cover can be made of non-transparent or opaque material such that the lower compartment within is not visible or is kept in darkness. The housing can comprise one or more viewing or inspection windows preferably within the cover side wall, preferably such that the lower compartment within is visible. The housing can comprise one or more viewing or inspection windows preferably within the cover side wall such that the upper and/or lower compartment side wall is visible. The viewing or inspection window can be a cut-out or transparent area of the cover.

The housing can comprise a connecting mechanism for connecting the cover to the sample container. Any suitable type of connecting mechanism can be used. In some embodiments, the connecting mechanism comprises a ratchet and pawl mechanism. In some embodiments, the connecting mechanism comprises a clip retaining or fastening mechanism.

This connecting mechanism and cover can also be used to hold the upper and lower compartments in a fluid-tight relationship. For example, an apical region of the cover can press against the top wall of the upper compartment and so sandwich walls of the upper and lower compartments together.

Preferably, the partition breaker is movable only from the resting position to the breaking position. This can be achieved in any suitable way. In some embodiments, the partition breaking mechanism comprises a ratchet and pawl mechanism for unidirectional movement. In some embodiments, the housing has a first part of the ratchet and pawl mechanism connected to the cover and a second part of the ratchet and pawl mechanism is connected to the sample container, such as to the lower compartment, eg. the side wall and/or base wall.

In some embodiments, the partition breaking mechanism comprises a clip retaining or fastening mechanism for unidirectional movement. In some embodiments, the partition breaking mechanism comprises a clip retaining mechanism for unidirectional movement. In some embodiments, the housing has a first part of a clip retaining mechanism connected to the cover and a second part of the clip retaining mechanism is connected to the sample container, such as to the side wall and/or base wall of the lower compartment.

In some embodiments, in order to move the partition breaker from the resting position to breaking position, the cover is slid relative to the sample container until at least one viewing or inspection window of the housing allows inspection of the lower compartment and/or viewing of indicia located on the upper and/or lower compartment side wall/s.

The sample processing device can comprise indicia located on the upper and/or lower compartment side wall/s, so as to indicate when the partition breaker has been successfully moved to the breaking position.

The sample processing device can comprise a peel off label that extends along the upper and lower covers, so as to prevent accidental movement of the upper cover relative to the lower cover.

In some embodiments the sample processing device is used to process and store a sample.

In some embodiments the sample processing device is used as an in vitro diagnostics device.

In some embodiments the sample processing device is used for qualitative analysis of a sample.

In some embodiments the sample processing device is used for quantitative analysis of a sample.

In some embodiments the sample processing device is used to test urine for a least one type of marker of prostate cancer, such as a polyamine. Examples of suitable polyamines include spermine, spermidine and putrescine. In some embodiments, the sample can be urine tentatively containing spermine. The first fluid can be a buffer for diluting the urine. The second fluid can be a sensor that, when mixed with the buffer and urine, produces a coloured solution (a colorimetric reaction) indicative of whether or not the at least one type of prostate cancer marker is present.

In some embodiments, the sensor can comprise a gold nanoparticle suspension. The gold nanoparticle suspension can interact with spermine via electrostatic force, wherein the gold nanoparticles are drawn together and aggregate, followed by red-shifting of the surface plasmon resonance related absorption to longer wavelengths. This alteration can be observed by a significant colour change of the gold nanoparticle suspension from red to blue/purple due to the presence of spermine in a urine sample.

Examples of suitable techniques for the detection of polyamines such as spermine in urine samples using gold nanoparticle suspensions are described in the following references, the contents of each of which are incorporated herein in their entirety: Tsoi T-H, Chan C-F, Chan W-L, Chiu K-F, Wong W-T, Ng C-F, et al. (2016) Urinary Polyamines: A Pilot Study on Their Roles as Prostate Cancer Detection Biomarkers. PLoS ONE 11 (9) : e0162217. doi: 10.1371/journal. pone. 0162217; Jornet Martínez, Neus &González-Béjar, María &Moliner-Martínez, Yolanda &Campíns-Falcó, Pilar &Pérez-Prieto, Julia. (2014) . Sensitive and Selective Plasmonic Assay for Spermine as Biomarker in Human Urine. Analytical chemistry. 86. 10.1021/ac404165j.; Kim, Tae-Il &Park, Jihye &Kim, Youngmi. (2011) . A Gold Nanoparticle-Based Fluorescence Turn-On Probe for Highly Sensitive Detection of Polyamines. Chemistry (Weinheim an der Bergstrasse, Germany) . 17. 11978-82. 10.1002/chem. 201102060.

According to a second aspect of the present invention, there is provided a method of processing a sample utilising the sample processing device of the first aspect, comprising the steps of:

(1) collecting a sample using the sample collector;

(2) moving the sample collector into the lower compartment such that the sample is in contact with fluid located within the lower compartment; and

(3) moving the partition breaker to break the partition such that the fluid located within the upper compartment contacts fluid of the lower compartment and collected sample.

Prior to step (1) , the method can comprise the step of removing the protective cap from the sample collector.

Prior to step (1) , in some embodiments, the method can comprise the step of removing the peel-off label from the upper and lower covers, and to expose the viewing window.

Prior to step (1) , the method can comprise the step of collecting 20-50 mL of sample in a cup.

Prior to step (1) , the method can comprise the step of standing the sample collector and inlet within the cup containing the sample.

Steps (2) and (3) can be carried out in succession by continuously pressing down the cover (upper cover in some embodiments) whilst the sample collector rests against the base of the cup.

After step (3) , the method can comprise (4) shaking the device to thoroughly mix the fluids and sample.

After step (4) , the method can comprise the step of (5) laying the device on its side for a predetermined reaction time.

After step (5) , the method can comprise viewing the lower compartment via the viewing window for a test result.

In some embodiments the method is used to test urine for prostate cancer. In this case, the sample can be urine tentatively containing at least one type of prostate cancer marker. The first fluid can be a buffer. The second fluid can be a marker sensor that, when mixed with the buffer and urine, produces a coloured solution indicative of whether or not the at least one type of prostate cancer marker is present.

Any of the forms of the invention or its features described above can be combined in any combination with any one or more of the other forms of the invention or features described below within the scope of the invention. For example, features described for the device can be recast as method steps and vice-versa.

Other forms and advantages of the invention will become apparent from a reading of this specification.

Preferred features, embodiments and variations of the invention may be discerned from the following Detailed Description which provides sufficient information for those skilled in the art to perform the invention. The Detailed Description is not to be regarded as limiting the scope of the preceding Summary in any way. The Detailed Description will make reference to a number of drawings as follows.

Brief Description of the Drawings

Figure 1 is a perspective view of an in vitro diagnostics kit, showing packaging, a sampling cup and sample processing device (pre-use) .

Figure 2 is a perspective view of the device shown in figure 1, (pre-use) with protective features in place.

Figure 3 is another perspective view of the device shown in figure 2.

Figure 4 is a front elevation view of the device shown in figure 2.

Figure 5 is a side elevation view of the device shown in figure 2.

Figure 6 is a sectional view taken through plane C-C of the device shown in figure 5. The figure also shows a lower compartment containing fluid (shown in crosshatch) , and an upper compartment also containing fluid (shown in crosshatch) . Between the upper and lower compartment fluids is a headspace of air.

Figure 7 is a partially exploded perspective view of the device shown in figure 2, (pre-use) but with the protective features removed.

Figure 8 is a perspective view of the device shown in figure 7 ready for collecting a liquid sample contained within a sampling cup.

Figure 9 is a front elevation view of that shown in figure 8.

Figure 10 is a side elevation view of that shown in figure 8.

Figure 11 is a sectional view taken through plane C-C of the device shown in figure 10.

Figure 12 is a perspective view of the device shown in figure 8 but showing the collected sample having been moved and processed within a lower compartment of the device.

Figure 13 is a front elevation view of that shown in figure 12.

Figure 14 is a side elevation view of that shown in figure 12.

Figure 15 is a sectional view taken through plane C-C of the device shown in figure 14.

Figure 16 is a perspective view of the device shown in figure 12 but showing the collected sample having been further processed within the device itself.

Figure 17 is a front elevation view of that shown in figure 16.

Figure 18 is a side elevation view of that shown in figure 16.

Figure 19 is a sectional view taken through plane C-C of the device shown in figure 16.

Figures 20 to 23 are the same as figures 16 to 19, except not showing the sampling cup.

Figure 24 is an exploded view showing the features of the device shown in figure 2.

Figures 25 and 26 are enlarged views of parts of figure 24.

Figure 27 is an enlarged view of part of figure 11.

Figure 28 is an enlarged view of part of figure 15.

Figure 29 is an enlarged view of part of figure 19.

Figure 30 is a perspective view of an in vitro diagnostics kit, showing packaging, a sampling cup and sample processing device (pre-use) , according to another embodiment of the invention.

Figure 31 is a perspective view of the device shown in figure 30, (pre-use) with a protective cap in place.

Figure 32 is another perspective view of the device shown in figure 31.

Figure 33 is a front elevation view of the device shown in figure 31.

Figure 34 is a side elevation view of the device shown in figure 31.

Figure 35 is a sectional view taken through plane A-A of the device shown in figure 34.

Figure 36 is a partially exploded perspective view of the device shown in figure 31, (pre-use) but with the protective cap removed.

Figure 37 is a perspective view of the device shown in figure 36 ready for collecting a liquid sample contained within a sampling cup.

Figure 38 is a front elevation view of that shown in figure 37.

Figure 39 is a side elevation view of that shown in figure 37.

Figure 40 is a sectional view taken through plane A-A of the device shown in figure 39.

Figure 41 is a perspective view of the device shown in figure 37 but showing the collected sample having been moved and processed within a lower compartment of the device.

Figure 42 is a front elevation view of that shown in figure 41.

Figure 43 is a side elevation view of that shown in figure 41.

Figure 44 is a sectional view taken through plane A-A of the device shown in figure 43.

Figure 45 is a perspective view of the device shown in figure 41 but showing the collected sample having been further processed within the device itself.

Figure 46 is a front elevation view of that shown in figure 45.

Figure 47 is a side elevation view of that shown in figure 45.

Figure 48 is a sectional view taken through plane A-A of the device shown in figure 45.

Figure 49 is an exploded view showing the features of the device shown in figure 31.

Figure 50 is an enlarged view of parts of figure 49.

Figure 51 is an enlarged view of the device shown in figure 48.

Figure 52 is a front elevation view of the device shown in figure 31.

Figure 53 is a sectional view taken through plane A-A of the device shown in figure 52.

Figure 54 is a side elevation view of the device shown in figure 51.

Figure 55 is a sectional view taken through plane B-B of the device shown in figure 54.

Detailed Description

In the figures, like reference numerals refer to like features.

First Embodiment

Figure 1 shows an in vitro diagnostics kit for detecting prostate cancer based on a urine sample, complete with packaging, a sampling cup 6 and sample processing device 1, according to an embodiment of the present invention.

The sample processing device 1 includes a sample container 2, a partition breaking mechanism 3, a sampler 4 and pre-use protective features 5 in the form of a protective cap 50 and peel-away label 51, as generally depicted in figure 24.

As seen in figures 6 and 11, the sample container 2 includes a lower compartment 20 adapted to contain fluid 8 (preferably liquid and gas) , an upper compartment 21 located above the lower compartment 20 and adapted to contain fluid 9 (preferably liquid) , a partition 23 separating the upper compartment 21 from the lower compartment 20, and an inlet 24 to the lower compartment 20.

SAMPLER

The sampler 4 extends sealingly through the inlet 24 and includes a sample collector 40 adapted to collect a liquid sample and to be moved into the lower compartment 20. This is best seen in figures 6, 7, 11, 15, 19, 23, 24 and 26-29. The sample collector 40 is movable between a sample collecting position, as seen in figure 11 and 27, and sample processing position, as seen in figures 15, 19, 23, 28 and 29. In the sample collecting position (figure 11) , the sample collector 40 is located externally of the inlet 24 and can collect a sample. When moving to the sample processing position, the sample collector 40 is moved through the inlet 24 to a final location within the lower compartment 20.

The sampler 4 includes a piston assembly 42 that extends sealingly through the inlet 24. The piston assembly 42 includes a piston shaft 421 that is slideable within the inlet 24.

The piston assembly 42 includes a first piston stop 422 extending adjacent the inlet 24 within the lower compartment 20 and a second piston stop 423 located externally of the device 1. These piston stops 422, 423 prevent the piston shaft 421 from disengaging the inlet 24.

The second piston stop 423 is detachably connected to the piston shaft 421 by way of a threaded connection. The second piston stop 423 has a flat surface so as to make good and stable contact with a base 60 of the sampling cup 6, as seen in figures 8-19.

The protective cap 50 friction fits to the second piston stop 423, as best seen in figures 6 and 7. The protective cap 50 has a cap base 501 extending alongside the second piston stop 423, and a cap side wall 502 extending from the cap base 501 that extends to and abuts the inlet 24.

The piston assembly 42 comprises a central axis 424 (as seen in figures 24 and 26) extending longitudinally through the piston shaft 421 from one piston stop to the other 422, 423. The piston shaft 421 has an outer cylindrical surface 425 extending about the central axis 424.

The sample collector 40 has three voids 401, each of which can be filled with about 0.033 mL of liquid sample (total approximately 0.1 mL) . The three voids 401 of the sample collector 40 are formed in the outer surface 425 of the piston shaft 421 and are located approximately equidistantly between the piston stops 422, 423. The three voids 401 are equidistantly spaced about the central axis 424 within the same plane. The voids 401 can be filled by immersing the piston shaft 421 within the liquid of the sampling cup 6.

The voids 401 are shaped so as to more readily release air bubbles unintentionally trapped within the voids. An upper surface of each void 401 slopes or tapers upwardly as it extends away from the central axis 424. Air bubbles can be dislodged from the voids 401 by gently tapping the piston shaft 421 or other part of the device 1.

The piston assembly 42 includes sealing elements 426 (see figure 23) extending around the outer cylindrical surface 425 perpendicularly of the central axis 424, such that the lower compartment 20 cannot unintentionally leak fluid via the inlet 24. The piston assembly 42 include two O-rings 426 located between the voids 401 and the first piston stop 422, and two O-rings 426 located between the voids 401 and the second piston stop 423. The outer cylindrical surface 425 has circumferentially extending grooves, within each of which extends an O-ring 426.

SAMPLE CONTAINER

The sample container 2 comprises a central axis 26 (see figures 24 and 26) extending centrally through the lower 20 and upper compartments 21 and inlet 24. That central axis 26 axially aligns with the central axis 424 of the piston assembly 42.

The lower compartment 20 has a void volume of about 15 mL. As seen in figure 6, the lower compartment 20 is not completely filled with liquid 8 because movement of the sample collector 40 to the sample processing position (as seen in figures 15, 19 and 23) will cause displacement of some of the liquid 8 and so a headspace 80 (see figure 6) is needed (ie. air pocket 80) above the liquid 8. It is important to have a headspace 80 (air pocket) so that the sample collector 40 does not “rebound” after being pushed into the lower compartment 20.

The lower compartment 20 has an elongate circular side wall 200, a base wall 201 and top wall 23. The top wall 23 and partition 23 are one and the same. The base wall 201 has a central opening (not labelled) . The lower compartment 20 has a retainer flange 203 extending perpendicularly of and outwardly from the side wall 200. With the exception of the top wall 23, the

lower compartment walls

200, 201 together with the inlet 24 form an elongate flanged barrel having a restricted end from which the inlet 24 extends.

The

lower compartment walls

200, 201 are made of transparent moulded plastics material.

The inlet 24 extends as an annular wall 240 from the base wall 201. The inlet 24 has a central opening 241 (see figures 24 and 26) that coincides with the central opening in the base wall 201. The annular wall 240 has a rim 242. (See figure 26. )

The upper compartment 21 has a void volume of about 1 mL.

The upper compartment 21 includes a circular side wall 210, base wall 23 and top wall 211. The base wall 23 and the partition 23 are one and the same. The top wall 211 is convex or dome-shaped pre-use, as seen in figures 6, 11 and 15. The upper compartment 21 also includes a retainer flange 212 extending perpendicularly of and outwardly from the side wall 210.

The upper compartment 21 is in the form of a capsule prefilled with liquid 9, and having a flexible plastic top wall 211 and a tear-away plastic film base wall/partition 23.

The sample container 2 includes a connecting mechanism 27 for connecting the upper 21 and lower compartments 20 together, as best seen in figures 15 and 27-29. The connecting mechanism 27 includes a cap assembly that includes a cap 270 having a cap top wall 271 having a central opening 272, and a continuous cap side wall 273 extending downwardly from the cap top wall 271.

The connecting mechanism 27 includes an O-ring 274 extending between the retainer flange 212 and base wall/partition 23 (as seen in figure 28) . The cap side wall 273 has a screw thread, the lower compartment side wall 200 has a screw thread, and these are screwed together (see figure 26) . When screwed together, the upper compartment 21 top wall 211 extends through and proud of the cap top wall 271 central opening 272, the retainer 212 rests atop a rim of the lower compartment side wall 200, and the O-ring 274 extends between the retainer 212 and base wall/partition 23.

PARTITION BREAKER

The partition breaking mechanism 3 includes a partition breaker 30 operable to break the partition 23 such that the upper 21 and lower 20 compartments are in fluid communication with each other, as seen in figures 19 and 23. The partition breaker 30 can be moved from a resting position, as seen in figures 6, 11, 15, 27 and 28, to a breaking position, as seen in figures 19, 23 and 29.

The partition breaker 30, made of hard plastics material, has a working end 300 extending from the upper compartment top wall 211 towards the partition 23. The working end 300 is shaped to cut, puncture, pierce, break away or otherwise unseal the partition 23. The partition breaker 30 further extends upwardly from the upper compartment top wall 211 as a projection 301. The partition breaker 30 is of integral construction with the top wall 211, however this need not be the case. The top wall 211 is made of flexible plastics material so that pressing down on the top wall 211 moves the partition breaker working end 300 towards and into contact with the partition 23. The partition 23 is in the form of a plastic film that can be pierced or broken away by the partition breaker 30.

The partition breaking mechanism 3 further includes an upper housing 32 and lower housing 33, each of which envelops the sample container 2.

The upper housing 32 includes an upper cover 320 that envelops the upper compartment 21 and part of the lower compartment 20. The upper cover 320 has an apical region 321. In the resting position the apical region 321 extends above the upper compartment top wall 211 and in contact with the partition breaker 30. In the breaking position, the apical region 321 moves towards the upper compartment 21 and presses the partition breaker 30 into engagement with the partition 23, as best seen in figures 19, 23 and 29.

The upper cover 320 comprises two cover pieces that are connected together by way of threaded fasteners (not labelled) , as best seen in figure 24.

The upper housing 32 includes spacers 323 that extend internally of the upper cover 320, that help position the upper cover 320 relative to the lower compartment 20, especially when moving from the resting position to the breaking position.

The upper cover 320 is made of opaque plastics material. The upper housing 32 has a viewing or inspection window 325 within the upper cover 320 such that the lower compartment 20 within is visible. The viewing or inspection window 325 is a cut-out of the upper cover 320.

The lower housing 33 includes a lower cover 330 that extends around the lower compartment 20 and inlet 24. The lower cover 330 extends partway between the upper cover 320 and the lower compartment 20, so that the upper cover 320 can slide alongside the lower cover 330.

The lower cover 330 comprises two cover pieces that are connected together by way of threaded fasteners, as best seen in figure 24.

The lower cover 330 is made of opaque plastics material such that the lower compartment 20 within is not visible. The lower housing 33 has a viewing or inspection window 332 such that the lower compartment 20 within is visible. The viewing or inspection window 332 is a cut-out of the lower cover 330.

The lower cover 332 is connected to the sample container 2 such that it does not move when the partition breaker 30 and upper cover 320 move to the breaking position. The lower housing 33 comprises internal walls or spacers 335 that extend inwardly of the lower cover 33. The lower compartment 20 has the retainer flange 203 that locates between the internal walls or spacers 335, as best seen in figure 19.

The partition breaker 30 is movable only from the resting position to the breaking position. The partition breaking mechanism 3 includes the upper housing 32 having a pair of a linear ratchets 327 having two teeth (best seen in figures 24 and 25) and the lower housing 33 having a pair of pawls 337 (best seen in figures 24 and 25) . The linear ratchets 327 extend along an inner surface of the upper cover 320, and the pair of pawls 337 are in the form of sprung hooked legs 337 that are connected to/pinned between pins 338 of the lower cover 330, and extend upwardly from the lower cover 330, and the hooked legs 337 engage teeth of the linear ratchets 327.

In order to move the partition breaker 30 from the resting position (figures 6, 11, 15, 27 and 28) to breaking position (figures 19, 23 and 29) , the upper cover 320 is slid relative to the lower cover 330 until the viewing or inspection window 325 of the upper housing 32 coincides with the viewing or inspection window 332 of the lower housing 33, such that the lower compartment 20 is visible from outside of the device 1.

The sample processing device 1 includes indicia (not shown) , such as a colour legend or key, located adjacent the viewing or inspection window 325 of the upper housing 32, so as to help interpret the test result for the processed sample within the lower compartment 30.

The sample processing device 1 includes the protective peel-away label 51 that extends along the upper 320 and lower 330 covers (as shown in figure 2) , so as to prevent accidental movement of the upper cover 320 relative to the lower cover 330.

USE

In use, the in vitro diagnostics kit 1 is unpackaged as shown in figure 1. The kit includes a sampling cup 6 and the sample processing device 1. The lower compartment 20 of the sample processing device 1 is partially pre-filled with a first test liquid 8 (see figure 6) that is suitable for the collected sample, and the upper compartment 21 of the sample processing device 1 is pre-filled with a second test liquid 9 that can react with the first test liquid 8 and sample in a known manner to produce a desired test result.

The protective cap 50 and peel-away label 51 are first removed by a user as shown in figure 7.

Up to about 50 mL of liquid sample is deposited into the sampling cup 6. The sample processing device 1 is inserted into the sampling cup 6 so as to fully submerge the sample collector voids 401, as shown in figures 9-11. The user holds the device 1 substantially vertically by way of the upper cover 320, such that the piston stop 423 rests against the cup base 60. The sample collector 40 is in the sample collecting position, as seen in figures 11 and 27.

Next, the user applies a downwards force on the upper cover 320, which results in the sample collector 40 moving through the inlet 24 to a final location within the lower compartment 20, to the sample processing position (as seen in figures 12-15 and 28) . The sample then mixes with the first test liquid 8 within the lower compartment 20. In the sample processing position the second piston stop 423 abuts the rim 242 of the inlet 24, as shown in figures 12-15 and 28.

The user continues to apply a downwards force on the upper cover 320, and since the sample collector 40 can move no further, this force results in the upper cover 320 sliding downwardly over the lower cover 330. Since the upper cover 330 bears against the partition breaker 30, the partition breaker 30 moves into contact with the partition 23 and dislodges it or tears it open (as seen in figures 19, 23 and 29) . The second test liquid 9 can then flow into the lower compartment 20 and mix with the first test liquid 8 and sample. The ratchet and pawl mechanism 327, 337 (spring-loaded hooked legs and teeth) ensures that the upper cover 320 can only slide downwardly to a predetermined position, after which the upper cover 320 is no longer slidable relative to the lower cover 330. In this regard, side by side figures 27-29 help visualise this.

When the upper 320 and lower 330 covers are properly aligned, their viewing or

inspection windows

325, 332 are also properly aligned such that the liquid contents of the first compartment 20 can be seen.

The user then may shake the device 1 so that the sample and

liquids

8, 9 from the

different compartments

20, 21 mix thoroughly. The device 1 may then be laid on its side (window 325 facing up) and left for a predetermined period of time depending on what test is being carried out. If a colorimetric reaction, then indicia appearing next to the window 325 may help interpret the test result.

Example 1 –Urine Test for Prostate Cancer

This Example will explain how the sample processing device 1 can be used to test urine for prostate cancer. In this Example, the sample will be tested for the prostate cancer marker spermine, which is a polyamine, using a suitable gold nanoparticle suspension.

In this Example, a gold nanoparticle suspension is used as a sensor. The gold nanoparticle suspension can interact with spermine via electrostatic force, wherein the gold nanoparticles are drawn together and aggregate, followed by red-shifting of the surface plasmon resonance related absorption to longer wavelengths. This alteration can be observed by a significant colour change of the gold nanoparticle suspension from red to blue/purple due to the presence of spermine in the urine sample.

The first compartment 20 can be prefilled with an ionic buffer 8. The second compartment can be prefilled with a gold nanoparticle suspension sensor, as described above. The sensor to buffer ratio can be 0.5 mL to 9.4 mL.

In use, up to about 50 mL of urine is deposited into the sampling cup 6.

An appropriate ratio of urine sample to total liquid volume from both the upper 21 and lower 20 compartments is used. The lower compartment contains approximately 8.9 mL of buffer, approximately 6 mL of air (above the liquid) , can receive approximately 0.1 mL of sample, and movement of the sample collector within the lower compartment can create a displacement volume of approximately 0.4 mL.

The sample processing device 1 is inserted into the urine (up to about 50 mL) so as to fully submerge the sample collector voids 401, as shown in figures 9-11. The user holds the device 1 substantially vertically by way of the upper cover 320, such that the piston stop 423 rests against the cup base 60, as best seen in figure 11. The sample collector 40 is in the sample collecting position.

Next, the user applies a downwards force on the upper cover 320, which results in the urine moving through the inlet 24 to within the lower compartment 20, to mix with the buffer 8, as seen in figure 15.

The user continues to apply a downwards force on the upper cover 320, and since the sample collector 40 can move no further, this force results in the upper cover 320 sliding downwardly over the lower cover 330. Since the upper cover 320 (apical region 321) bears against the

partition breaker

30, 301, the

partition breaker

30, 300 moves into contact with the partition 23 and dislodges it or tears it open. The sensor 9 then flows into the lower compartment 20 and mixes with the buffer 8 and sample.

When the upper 330 and lower 320 covers are properly aligned, their viewing or

inspection windows

325, 332 are also properly aligned such that the colorimetric reaction result can be seen.

The user then shakes the device 1 five times so that the sample, buffer 8 and sensor 9 mix thoroughly. The device 1 is then laid on its side (window 325 facing up) and left for a 15 minute reaction time.

The sensor 9, when mixed with the buffer 8 and urine, produces a coloured solution indicative of whether or not spermine is present. A red/purple test colour indicates a high risk of prostate cancer. A blue test colour indicates a low risk of prostate cancer. Indicia, a color wheel or a color chart appearing next to the window 325 helps interpret the test result.

Second Embodiment

Figures 30 to 51 show an in vitro diagnostics kit for detecting prostate cancer based on a urine sample, complete with packaging, a sampling cup 6A and sample processing device 1A, according to a second embodiment of the present invention.

The sample processing device 1A includes a sample container 2A, a partition breaking mechanism 3A, a sampler 4A and a pre-use protective feature 5A in the form of a protective cap 50A.

The sample container 2A includes a lower compartment 20A adapted to contain fluid (preferably liquid and gas) , an upper compartment 21A located above the lower compartment 20A and adapted to contain fluid (preferably liquid) , a partition 23A separating the upper compartment 21A from the lower compartment 20A, and an inlet 24A to the lower compartment 20A.

SAMPLER

The sampler 4A extends sealingly through the inlet 24A and includes a sample collector 40A adapted to collect a liquid sample and to be moved into the lower compartment 20A. The sample collector 40A is movable between a sample collecting position, as seen in figures 35, 36 and 40, and sample processing position, as seen in figures 44 and 48. In the sample collecting position (figure 40) , the sample collector 40A is located externally of the inlet 24A and can collect a sample. When moving to the sample processing position, the sample collector 40A is moved through the inlet 24A to a final location within the lower compartment 20A.

The sampler 4A includes a piston assembly 42A that extends sealingly through the inlet 24A. The piston assembly 42A includes a piston shaft 421A that is slideable within the inlet 24A.

As best seen in figure 51, the piston assembly 42A includes a first piston stop 422A extending adjacent the inlet 24A within the lower compartment 20A and a second piston stop 423A located externally of the device 1A. These piston stops 422A, 423A prevent the piston shaft 421A from disengaging the inlet 24A.

The second piston stop 423A is detachably connected to the piston shaft 421A by way of a threaded connection. The second piston stop 423A has a flat surface so as to make good and stable contact with a base 60A of the sampling cup 6A, as seen in figure 40.

The protective cap 50A friction fits to the second piston stop 423A, as best seen in figures 32 to 35. The protective cap 50A has a cap base 501A extending alongside the second piston stop 423A, and a cap side wall 502A extending from the cap base 501A that extends to and abuts the sampling container 2A.

The piston assembly 42A comprises a central axis 424A (as seen in figure 50) extending longitudinally through the piston shaft 421A from one piston stop to the other 422A, 423A. The piston shaft 421A has an outer cylindrical surface 425A extending about the central axis 424A.

The sample collector 40A has a circular void 401A which can be filled with about 0.1 mL of liquid sample. The void 401A of the sample collector 40A is formed in the outer surface 425A of the piston shaft 421A and is located approximately equidistantly between the piston stops 422A, 423A. The void 401A can be filled by immersing the piston shaft 421A within the liquid of the sampling cup 6A.

The void 401A is shaped so as to more readily release air bubbles unintentionally trapped within the void. An upper surface of the void 401A slopes or tapers upwardly as it extends away from the central axis 424A. Air bubbles can be dislodged from the void 401A by gently tapping the piston shaft 421A or other part of the device 1A.

The piston assembly 42A includes sealing elements 426A (see figures 50 and 51) extending around the outer cylindrical surface 425A perpendicularly of the central axis 424A, such that the lower compartment 20A cannot unintentionally leak fluid via the inlet 24A. The piston assembly 42A include three O-rings 426A located between the void 401A and the first piston stop 422A, and three O-rings 426A located between the void 401A and the second piston stop 423A. The outer cylindrical surface 425A has circumferentially extending grooves, within each of which extends an O-ring 426A.

SAMPLE CONTAINER

The sample container 2A comprises a central axis 26A (see figure 50) extending centrally through the lower 20A and upper compartments 21A and inlet 24A. That central axis 26A axially aligns with the central axis 424A of the piston assembly 42A.

The lower compartment 20A has a void volume of about 15 mL. The lower compartment 20A is not completely filled with liquid because movement of the sample collector 40A to the sample processing position (as seen in figures 44, 48 and 51) will cause displacement of some of the liquid and so a headspace is needed (ie. air pocket) above the liquid. It is important to have a headspace (air pocket) so that the sample collector 40A does not “rebound” after being pushed into the lower compartment 20A.

The lower compartment 20A has an elongate generally circular side wall 200A but with opposed flattened faces 2000A, a base wall 201A and top wall 23A. The base wall 201A overhangs the

side wall

200A, 2000A. The top wall 23A and partition 23A are, to a large extent, one and the same. The base wall 201A has a central opening (not labelled) . The lower compartment 20A has a spacer flange 203A extending perpendicularly of and outwardly from each circular side wall portion 200A.

The

lower compartment walls

200A, 2000A, 201A are made of transparent moulded plastics material.

The inlet 24A extends as an annular wall 240A from the base wall 201A. The inlet 24A has a central opening 241A that coincides with the central opening in the base wall 201A. The annular wall 240A has a rim 242A.

The upper compartment 21A has a void volume of about 1 mL.

The upper compartment 21A includes a generally circular side wall 210A, base wall 23A and top wall 211A. The base wall 23A and the partition 23A are one and the same. The top wall 211A is convex or dome-shaped pre-use, as seen in figures 35, 40 and 44. The upper compartment 21A also includes a sealing flange 212A extending perpendicularly of and outwardly from the side wall 210A.

The upper compartment 21A is in the form of a capsule or pod prefilled with liquid and having a flexible plastic top wall 211A and a tear-away plastic film base wall/partition 23A.

PARTITION BREAKER

The partition breaking mechanism 3A includes a partition breaker 30A operable to break the partition 23A such that the upper 21A and lower 20A compartments are in fluid communication with each other, as seen in figures 48 and 51. The partition breaker 30A can be moved from a resting position, as seen in figures 35, 40 and 44, to a breaking position, as seen in figures 48 and 51.

The partition breaker 30A, made of hard plastics material, has a working end 300A extending from the upper compartment top wall 211A towards the partition 23A. The working end 300A is shaped to cut, puncture, pierce, break away or otherwise unseal the partition 23A. The partition breaker 30A is connected to the top wall 211A. The top wall 211A is made of flexible plastics material or rubber so that pressing down on the top wall 211A moves the partition breaker working end 300A towards and into contact with the partition 23A. The partition 23A is in the form of a plastic film that can be pierced or broken away by the partition breaker 30A.

The partition breaking mechanism 3A further includes a housing 32A which envelops the sample container 2A. The housing 32A includes a cover 320A that envelops the upper compartment 21A and most of the lower compartment 20A. The cover 320A has an apical region 321A. In the resting position the apical region 321A extends above the upper compartment top wall 211A. In the breaking position, the apical region 321A moves towards the upper compartment 21A and presses the partition breaker 30A into engagement with the partition 23A, as best seen in figures 48 and 51.

The cover 320A is made of opaque plastics material. The housing 32A has a first viewing or inspection window 325A within the cover 320A such that the lower compartment 20A within is visible. The viewing or inspection window 325A is a cut-out of the upper cover 320A. The housing 32A has a second viewing or inspection window 326A within the cover 320A such that a label present on the lower compartment flattened side wall 2000A is visible. The viewing or inspection window 326A is a cut-out of the cover 320A.

The cover 320A is shaped so as to slide relative to the upper 21A and lower compartments 20A /sample container 2A in a specific uni-directional manner, when moving from the resting position to the breaking position.

The housing 32A comprises a connecting mechanism that connects the cover 320A to the sample container 2A. The connecting mechanism comprises a pair of clips 322A connected to the lower compartment side wall 2000A and base wall 201A, and a pair of clip retainers 324A connected to an inner surface of the cover 320A. Each clip 322A has a hooked end 3220A that can hook behind and be retained by the retainer 324A. Each clip 322A also has a pair of laterally spaced hooks 3221A that face one another and that can engage and retain opposed sides of the retainer 324A.

Initially, the hooked end 3220A is hooked above and behind each retainer 324A so that the cover 320A cannot disengage the sample container 2A by accident. In order to move the partition breaker 30A from the resting position to breaking position, the cover 320A is slid relative to the sample container 2A, at which time each hooked end 3220A slides upwardly relative to each retainer 324A, until window 325A allows inspection of the lower compartment 20A, and until window 326A aligns with the label to indicate that the partition breaker 30A has been successfully moved to the breaking position. At this point, the pair of laterally spaced hooks 3221A engage and retain opposed sides of the retainer 324A such that the cover 320A remains locked in position relative to the container sample 2A.

USE

In use, the in vitro diagnostics kit 1A is unpackaged as shown in figure 30. The kit includes a sampling cup 6A and the sample processing device 1A. The lower compartment 20A of the sample processing device 1A is partially pre-filled with a first test liquid that is suitable for the collected sample, and the upper compartment 21A of the sample processing device 1A is pre-filled with a second test liquid that can react with the first test liquid and sample in a known manner to produce a desired test result.

The protective cap 50A is first removed by a user as shown in figure 36.

Up to about 50 mL of liquid sample is deposited into the sampling cup 6A. The sample processing device 1A is inserted into the sampling cup 6A so as to fully submerge the sample collector void 401A, as shown in figures 38-40. The user holds the device 1A substantially vertically by way of the cover 320A, such that the piston stop 423A rests against the cup base 60A. The sample collector 40A is in the sample collecting position, as seen in figure 40.

Next, the user applies a downwards force on the cover 320A, which results in the sample collector 40A moving through the inlet 24A to a final location within the lower compartment 20A, to the sample processing position (as seen in figures 41 to 44) . The sample then mixes with the first test liquid within the lower compartment 20A. In the sample processing position the second piston stop 423A abuts the rim 242A of the inlet 24A, as shown in figures 41 to 44.

The user continues to apply a downwards force on the cover 320A, and since the sample collector 40A can move no further, this force results in the cover 320A sliding downwardly over the sample container 2A. Since the cover 330A bears against the partition breaker 30A, the partition breaker 30A moves into contact with the partition 23A and dislodges it or tears it open (as seen in figures 48 and 51) . The second test liquid can then flow into the lower compartment 20A and mix with the first test liquid and sample. The connecting

clip mechanism

322A, 324A ensures that the upper cover 320A can only slide downwardly to a predetermined position, after which the cover 320A is no longer slidable relative to the sample container 2A.

When the cover 320A is properly aligned, its window 325A is also properly aligned such that the liquid contents of the lower compartment 20A can be seen. The label visible through window 326A indicates that the partition 30A has been breached.

The user then may shake the device 1A so that the sample and liquids from the

different compartments

20A, 21A mix thoroughly. The device 1A may then be laid on its side (window 325A facing up) and left for a predetermined period of time depending on what test is being carried out. If a colorimetric reaction, then indicia appearing next to the window 325A may help interpret the test result.

Advantages of the present invention as exemplified include:

A single-use home-based in vitro diagnostic medical device which is available over-the-counter for users to carry out a prostate cancer screening test.

Upon activation of the device, it takes about 15 minutes for a coloured result to appear in a clear window, indicating low to high risks of prostate cancer.

The device is non-invasive.

The device is safe to use.

The device is hygienic.

A prostate cancer screening result appears in about 15 minutes.

The device can be used by users of all ages.

The device can collect a very small and precise volume of urine.

In the present specification and claims, the word ‘comprising’ and its derivatives including ‘comprises’ and ‘comprise’ include each of the stated integers but do not exclude the inclusion of one or more further integers.

Reference throughout this specification to ‘one embodiment’ or ‘an embodiment’ means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, the appearance of the phrases ‘in one embodiment’ or ‘in an embodiment’ in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more combinations.

The articles ‘a’ and ‘an’ are used herein to refer to one or to more than one of the article.

The term ‘about’ is to be understood as referring to a range of numbers that a person of skill in the art would consider equivalent to the recited value in the context of achieving the same function or result.

In compliance with the statute, the invention has been described in language more or less specific to structural or methodical features. It is to be understood that the invention is not limited to specific features shown or described since the means herein described comprises preferred forms of putting the invention into effect. The invention is, therefore, claimed in any of its forms or modifications within the proper scope of the appended claims appropriately interpreted by those skilled in the art.

Claims

A sample processing device comprising:

a sample container comprising:

a lower compartment adapted to contain fluid;

an upper compartment located above the lower compartment, and adapted to contain fluid;

a partition separating the upper compartment from the lower compartment; and

an inlet to the lower compartment;

a partition breaker operable to break the partition such that the upper and lower compartments are in fluid communication with each other; and

a sampler extending sealingly through the inlet and comprising a sample collector adapted to collect a sample and to be moved into the lower compartment.
The device of claim 1, wherein the sample collector comprises at least one void for collecting a fluid.
The device of claim 2, wherein the sampler is in the form of a piston assembly that extends sealingly through the inlet.
The device of claim 3, wherein the piston assembly comprises a piston shaft and a respective piston stop located at each end of the piston shaft, each of which functions as a travel stop.
The device of claim 4, wherein one of said piston stops has a flat surface so as to make good contact with a base of a container containing a sample.
The device of claim 5, wherein the piston assembly comprises a central axis extending longitudinally through the piston shaft from one said piston stop to the other, the piston shaft comprises an outer cylindrical surface, and the at least one void of the sample collector is formed in the outer surface of the piston shaft between the piston stops.
The device of claim 6, wherein three voids are equidistantly spaced about the central axis within the same plane, and each said void is formed in the outer cylindrical surface of the piston shaft.
The device of claim 7, wherein each said void or said outer cylindrical surface is shaped, angled or tapered so as to more easily release air bubbles unintentionally trapped within the void.
The device of any one of the preceding claims, wherein the lower compartment comprises a continuous elongate lower compartment side wall, a lower compartment base wall extending between and to the side wall, and a lower compartment top wall extending between and to the side wall.
The device of claim 9, wherein the lower compartment top wall or part thereof and the partition are one and the same.
The device of claim 10, wherein the upper compartment comprises a continuous upper compartment side wall, an upper compartment base wall extending between and to the side wall, and an upper compartment top wall extending between and to the side wall.
The device of claim 11, wherein the upper compartment base wall or part thereof and the partition are one and the same.
The device of claim 12, wherein the upper compartment top wall is flexible and is dome-shaped, sloping upwardly and away from the upper compartment base wall.
The device of claim 13, wherein the partition breaker is movable from a resting position to a breaking position.
The device of claim 14, wherein the partition breaker comprises a working end shaped to pierce, cut, puncture, perforate, dislodge or break the partition.
The device of claim 15, wherein the partition breaker comprises a working end extending from the upper compartment top wall towards the partition, and optionally the partition breaker further extends upwardly from the upper compartment top wall as a projection.
The device of claim 16, wherein the partition breaker is a component of a larger partition breaking mechanism comprising a housing which envelops the sample container.
The device of claim 17, wherein the housing comprises a cover that envelops the upper compartment and part of the lower compartment, and the cover comprises an apical region.
The device of claim 18, wherein in the resting position the apical region extends above the upper compartment top wall and in contact with the partition breaker, and in the breaking position the apical region moves towards the upper compartment and presses the partition breaker into engagement with the partition.
The device of claim 19, wherein the housing comprises an inspection window within the cover such that the lower compartment is visible.
The device of any one of claims 14 to 20, wherein the partition breaker is movable only from the resting position to the breaking position.
The device of claim 21, wherein the partition breaking mechanism comprises a ratchet and pawl mechanism for unidirectional movement of the cover relative to the sample container.
The device of claim 21, wherein the partition breaking mechanism comprises a clip retaining mechanism for unidirectional movement of the cover relative to the sample container.
The device of any one of the preceding claims, wherein the sample processing device is used as an in vitro diagnostics device.
The device of claim 24, wherein the sample processing device is used to test a urine sample for a least one type of marker of prostate cancer.
The device of claim 25, wherein the at least one type of marker is spermine.
A method of processing a sample utilising the sample processing device of any one of claims 1 to 26, comprising the steps of:

(1) collecting a sample using the sample collector;

(2) moving the sample collector into the lower compartment such that the sample is in contact with fluid located within the lower compartment; and

(3) moving the partition breaker to break the partition such that fluid located within the upper compartment contacts the fluid of the lower compartment and collected sample.
The method of claim 27, wherein the method is used to test a urine sample for prostate cancer.
The method of claim 28, wherein the urine sample tentatively contains at least one type of prostate cancer marker, the lower compartment contains a buffer and an air headspace, the upper compartment contains a marker sensor that, when mixed with the buffer and urine, produces a coloured solution indicative of whether or not the at least one type of prostate cancer marker is present.
The method of claim 29, wherein the at least one type of prostate cancer marker is spermine.