WO2010131140A1

WO2010131140A1 - Biological sample collection device

Info

Publication number: WO2010131140A1
Application number: PCT/IB2010/051819
Authority: WO
Inventors: Billy Wai-Hon Chan; Joseph Kwok-Fai Chow; Rachel Ching-Yee Yeung
Original assignee: Diagcor Bioscience Incorporation Limited
Priority date: 2009-05-09
Filing date: 2010-04-26
Publication date: 2010-11-18

Abstract

The present invention relates to a clinical sample collection device comprising a sample retention arrangement enclosed within a housing, wherein the sample retention arrangement is capable of trapping or retaining a quantity of sample contained in a sample containing fluid when the sample containing fluid transits through the sample retention arrangement, and wherein the housing comprises an inlet for ingress of sample containing fluid and an outlet for egress of residual or excessive sample containing fluid, wherein the housing is closable to isolate the quantity of sample trapped or retained. The device facilitates convenient self-collection of body liquid sample, so that a patient could collect body liquid samples conveniently at the persons home and enjoy privacy. In addition, a closable housing facilitates user convenience while at the same time mitigating the risks of contamination during transport to a laboratory.

Description

Biological Sample Collection Device

Field of the Invention

The present invention relates to biological sample or specimen collection devices and methods, and more particularly, to body liquid sample collection devices and methods for clinical purposes. More specifically, although of course not solely limited thereto, the present invention relates to urine sample collection devices and methods.

Background of the Invention

Body liquid samples of a person, such as urine, blood, or saliva samples, are frequently obtained and analyzed to determine the health conditions of a person. For example, urine samples are frequently collected and are then processed to extract bio-molecules such as DNAs, cells, bacteria and/or granule particles for pathological analysis. More recently, urine samples are also used for rapid evaluation of sexually transmitted diseases, for example, by use of nucleic acid amplification tests (NAATs) which faciliates detection with a low copy number of specific nucleic acids. The use of urine samples, instead of the use of female cervical or male urethral swap for culture or enzyme-linked immunosorbent assays (ELISAs) evaluations, have made such evaluations more convenient and less uncomfortable for patients.

Currently, collection of urine samples for laboratory testing typically requires personal attendance of patients at clinics or laboratories. This could be inconvenient and somewhat embarrassing for busy or well-known people. On the other hand, the travelling time and costs to get to a clinic with conventional body liquid sampling arrangements would its diminish the willingness of less well-off people in less developed countries to know identify their problems, to get cured and to prevent spreading of diseases. Therefore it will be desirable if improved means and methods for collection body fluid samples are made available.

Summary of Invention

According to the present invention, there is provided a clinical sample collection device comprising a sample retention arrangement enclosed within a housing, wherein the sample retention arrangement is capable of trapping or retaining a quantity of sample contained in a sample containing fluid when the sample containing fluid transits through the sample retention arrangement, and wherein the housing comprises an inlet for ingress of sample containing fluid and an outlet for egress of residual or excessive sample containing fluid, wherein the housing is closable to isolate the quantity of sample trapped or retained.

The clinical sample to be collected includes, for example, bio-liquid such as blood, urine, saliva, etc; and bio-particles including bio-molecules such as cells, DNA, RNA, etc. In the present context, the term sample and specimen is used interchangeably without loss of generality.

The device facilitates convenient self-collection of body liquid sample, so that a patient could collect body liquid samples conveniently at the person's home and enjoy privacy. In addition, a closable housing facilitates user convenience while at the same time mitigating the risks of contamination during transport to a laboratory.

The sample retention arrangement may comprise an exclusion glass microfiber filter. An exclusion glass microfiber filter is capable of isolating cells from the body liquid sample, and at the same time provides means for storage of the sample.

The sample collection device may comprise a container which is adapted for collecting a quantity of liquid sample and for coupling to the housing so that collect liquid sample could be delivered to the sample retention arrangement in a clean and hygienic manner. The container may be compressively collapsible so that liquid sample could be forced through to arrive at the sample retention arrangement upon application of a force to compress the container. Such an arrangement provides a convenient and expeditious sample to obtain a sufficient quantity of sample.

According to another aspect of the present invention, there is provided a method of obtaining biological samples from a sample containing fluid using a sample collection device as described herein, the method comprising:

- Filling a sample collection container with a sample fluid,

- Coupling the sample collection container with the inlet of the device,

- Passing the collected sample fluid into the housing and through the sample retention arrangement of the device,

- Draining excessive sample fluid at the outlet, and

- Closing or sealing the inlet and the outlet.

In an embodiment, the sample collection container is a syringe and the method further comprises injecting the sample fluid from the syringe into the housing of the device through the inlet.

The sample collection container may include coupling means for water-tight coupling with the housing, and the method further may comprise inverting the coupled assembly of the device and the sample collection container such that the sample fluid passes through the sample retention arrangement and is then discharged at the outlet due to gravity.

Such a method provides a convenient, hygienic and expeditious way to obtain a sufficient quantity of bio-samples for laboratory testing.

Brief Description of Drawings

Exemplary embodiments illustrating the practice or implementation of the present invention will be explained below by way of example with reference to the accompanying drawings, in which:-

Figure 1 is a schematic front elevation view of a sample collection device depicting a first embodiment of the present invention,

Figure 2 & 2A are schematic diagrams depicting the various component or parts of the sample collection device of Figure 1

Figure 3 & 3A is a schematic view showing the container of Figure 2A respectively in a compressed state and an expanded state,

Figures 4-9 are schematic diagrams illustrating an exemplary process of collecting urine sample using the sample collection device of Figures 1 & 2.

Figure 10 is a sample collection device illustrating a second embodiment of the present invention,

Figure 10A & 10B respectively show a container for use with the sample collection device of Figure 10 in an expanded state and a compressed or contracted state,

Figure 11 illustrates the attachment of a container of Figure 1OB to the underside of the sample retention device of Figure 10, and

Figure 12 depicts the sample collection device of Figure 11 in an inverted state and illustrating the direction of subsequent compression to cause biological liquid to pass through the sample retention device.

Figure 13 depicts a sample containing sample collection device of Figure 10 packed in a sterile pack for laboratory dispatch.

Figures 14 & 14A are respectively top and bottom perspective views of a sample collection device illustrating a third embodiment of the present invention,

Figure 14B is a perspective view showing a sample retention device of the sample collection device of Figure 14,

Figure 14C shows a container for use with the sample collection device of Figure 10,

Figures 15 and 15A are respectively front and perspective view of a sample collection device according to a fourth embodiment,

Figures 16-18 shows various view of a fifth embodiment of a sample collection device according to the invention.

Detailed Description of Preferred Embodiments

Referring to the Figures, the sample collection device comprises a main housing and a sample retention device. The main housing is moulded of hard plastics and defines a compartment or cavity of a sample retention volume for receiving the sample retention arrangement. The main housing comprises an upper side, a lower side, and a peripheral wall interconnecting the upper and bottom sides which collectively defines a sample retention compartment. An inlet and an outlet are formed on the upper and lower sides of the housing respectively for ingress and egress of body fluid sample. The inlet and outlet are arranged such that liquid sample entering the housing through the inlet and exiting via the outlet must pass through the sample retention compartment before exiting. Biological particles or liquid to be collected will be retained by the sample retention device. The sample contained sample retention device will then be processed and analyzed.

Referring more specifically to Figures 1 , 2 and 2A in which a first embodiment of the present invention is shown. The sample collection device 100 comprises a tubular body 110 as an example of a main housing, and a filter assembly 120 as an example of a sample retention device. The tubular body is cylindrical and comprises an inlet 112 and an outlet 114. The device further comprises accessories including a stopper 140, a plunger 142, a patient information label 144, a container 150 as shown in Figures 2A & 3.

The filter assembly comprises a top filter 122, a main filter 124 and a bottom filter 126 which are assembled with the main filter 124 disposed intermediate the top 122 and bottom 124 filters. The main filter comprises a threaded housing 128 so that the filter assembly could be tightened as a single unit. The filter assembly, especially the main filter, is closely fit-able and slidable within the tubular housing, which is in a cylindrical tubular body part of a clinical syringe. The main filter 124 comprises nitrocellulose membranes which are adapted as a size exclusion filter and used as an example of a sample retention device when placed within the sample retention volume of the main housing. The filter is disposed within the tubular body such that sample fluid must pass through the filter on transit from the inlet to the outlet.

The stopper 140 is for fitting onto the outlet of the tubular body and has a valve-like arrangement such that fluid or liquid container within the tubular body 110 will not egress through the stopper or the outlet except with application of a threshold pressure.

The container 150 is transparent and made of clear plastics. The container is collapsible and extendable along the axial direction, and is adapted for coupling to the stopper so that liquid egress from the stopper will be held by the container. A plurality of parallel creases is formed on the container to facilitate bellows-like axial expansion and contraction.

Application of the sample collection device will be described below with reference to Figures 1 to 9.

Firstly, a sample collection device is assembled as schematically shown in Figure 1 with the filter assembly closely fitted within the tubular body in a piston manner. The stopper is tightly fitted at the outlet of the tubular housing. A quantity of urine sample collected and stored in the container is then dispensed into the tubular body through the inlet. The stopper, through its valve-like arrangement, stops the urine sample from leaving the tubular body. The container is then coupled to the underside of the stopper by screw-threaded engagement and is then tightened onto the lower end of the stopper. A syringe plunger is then inserted into the tubular body via the inlet and is then depressed downwards towards the stopper. After the plunger has been fully depressed, as shown in Figure 7, the collected urine sample will have passed through the filter assembly and residual and excesses liquid will be retained by the container. The tubular body is then detached from the stopper and the sample containing filter assembly is then removed and further tightened as a sample containing assembly as shown in Figures 8-9. The filter assembly is then put inside, for example, a sterile container such as a zip-lock plastic bag, for transport to a laboratory.

The biological sample containing sample collection device would then be sent to a testing laboratory and processed. For example, Cells are lysed and DNA and

RNA will be stabilized using purpose specific formulated buffer. The collected cell lysate can then be subjected to nucleic acid isolation and detection of predetermined substances which may be found within the sample. Preliminary data shows that human DNA and Chlamydia trachomatis DNA from urine can be extracted by this method, and detected by a real-time PCR testing.

At the laboratory, incoming specimens are opened, registered and tested. Typical testing includes the following steps:

Individually opening the specimen bags under sterile conditions in a biohazard hood using decontaminated instruments.

- Elute the content trapped on the filter by elution buffer.

- Subject the eluted content for nucleic acid purification.

- Subject the purified nucleic acid for testing.

- Generating a report. In the embodiments below, parts which correspond to parts of the embodiment of Figures 1-9 above and have same or similar function will be referred to by numerals which has the same value but added with multiple or multiples of 100 for brevity.

Referring to Figures 10 to 13, there is shown a bio-liquid sample collection device 200 illustrating a second exemplary embodiment of the present invention. The sample collection device 200 of Figure 11 comprises a sample retention device of Figure 10 and a main housing of Figures 10A & 10B. The sample retention device comprises a filter assembly 220 as an example of a sample retention device which is mounted within a generally cylindrical filter housing 228. The filter assembly 220 is similar to the filter assembly 120 of Figure 9 except that the filter elements are now contained within the filter housing 228 which includes an inlet and an outlet arranged such that liquid entering the filter housing from the inlet and exiting from the outlet must pass through the main filter elements contained within the filter assembly. A main difference between the filter assembly 220 and that of the filter assembly 120 of the first embodiment is that the filter housing of this filter assembly is provided with threaded arrangements at its outlet end for releasable liquid-tight engagement with the container 250.

The container 250 comprises a compressively collapsible container having a threaded neck portion for liquid-tight engagement with the filter housing. Both the neck portion and the container have a generally circular cross-section by easy handgrip.

Application of the sample collection device 200 will be described next. Firstly, a quantity of body liquid sample or other bio-liquid sample is collected in the container 250 when the container is in an expanded state. The sample filled container 250 is then coupled to the filter assembly 220 with the threaded portions on the filter housing 228 engaged with the threaded neck portion of the container 250 in a liquid-tight manner. In this arrangement, the filter assembly is on top of the container with the inlet of the filter housing in direct communication with the internal volume of the container.

Secondly, the sample containing sample collection device 200 comprising the container and the filter assembly in liquid tight engagement is then inverted so that the container is now vertically above the filter assembly. A longitudinal compressive force is then applied to the upper end of the container and to press the container to contract towards the filter assembly below, as shown in Figure 12. This compression of the container forces the liquid sample to pass through the filter assembly and the biological samples will be collected and retained by the filter assemblies. Residual liquid will then pass through the outlet of the sample retention device and could be disposed of. After sufficient liquid sample has been collected by the sample retention device, the container could be removed from the sample retention device and the sample containing sample retention device then sealed and pass on to a laboratory for testing liquidness according to usual established laboratory protocols.

A third embodiment of the sample collection device 300 as shown in Figures 14 & 14A comprises a main housing which defines a sample compartment inside which a filter assembly 320 as an example of a sample retention device is mounted. The main housing is generally cylindrical having an upper end, a lower end and a peripheral wall interconnecting the lower and upper ends. The lower end, the upper end and the peripheral wall collectively define the sample compartment within which a filter assembly as an example of a sample retention device is housed. To facilitate ingress of sample liquid and egress of excessive or residual liquid, a liquid inlet 312 and a liquid outlet 314 are respectively formed on the top side of the upper end and bottom side of the lower end. The inlet, outlet, the sample compartment and the filter assembly are arranged such that liquid entering the inlet must pass through the sample compartment and the filter assembly before exiting through the outlet.

The filter assembly 320 is a modular filter comprising a moulded filter housing within which filter elements are enclosed. The filter housing also defines moulded inlet and outlet for guided ingress and egress of liquid.

To facilitate controlled liquid ingress, the inlet comprises an inlet nozzle which is arranged to tightly receive an elongate nozzle of a syringe such that a quantity of bio-liquid sample could be injected into the sample compartment when the syringe nozzle is inserted and tightly received by the inlet. The inlet nozzle is a chimney-like nozzle protruding above the upper end of the top and has an aperture or an inlet bore adapted to tightly receive the elongate nozzle of a syringe. An outlet bore is formed on the bottom surface of the lower end and is disposed axially distal from the inlet nozzle to permit egress of residual liquid after passing through the filter assembly. In general, the structure of this sample collection device is the same as that of Figure 10, except that the inlet and outlet bores are substantially smaller than the cross-sectional dimension of the sample compartment.

In addition, the sample collection device 300 further includes a pair of plugs 330 as example of closure means. The plugs 330 are provided such that the sample collection device could be closed and/or isolated from outside environment after a sufficient quantity of liquid sample has been collected to mitigate the risks of contamination when the sample containing device is dispatched to a laboratory. The reduced apertures of the inlet and outlet bores are arranged to facilitate closure of the inlet and outlet with a convenient stopper, such as plugs of a few millimeter in width, as well as a guided and/or controlled liquid passage.

Use of the sample collection device 300 will be explained next. Firstly, a quantity of bio-liquid sample is collected and the collected liquid is delivered into a syringe. Secondly, the sample liquid filled syringe is caused to engage with the sample collection device by inserting the elongate syringe nozzle into tight engagement with the inlet nozzle. After the syringe nozzle and the inlet bore have been engaged, an operator will then inject the liquid inside the syringe into the sample collection device 300 via the inlet. Because of the liquid path arrangement of the sample collection device, the injected liquid will enter the sample compartment and arrive at the filter assembly. At the filter assembly, liquid and other over-sided bio-particles will be retained and residual or excessive liquid will exit via the outlet. After a sufficient quantity of sample has been collected, the inlet and outlet will be sealed by the closure arrangements and then delivered for laboratory analyses.

The container 350 of Figure 14C may be attached to the lower end of the main housing 310 to receive residual or excessive liquid upon egress.

The combination of the device 300 of Figures 14 & 14A and the container of Figure 14C would constitute a sample collection device 400 which is a variation of the device 300. When using the device 400, it is possible to inject sample liquid into the inlet and collect residual liquid by the container. Alternatively, use of the device 400 could be similar to that of the device of Figure 11 & 12. More specifically, a quantity of liquid sample is first collected by the container and the container is attached to the main housing. The entire device is then inverted and the sample liquid is forced through the sample compartment for retention by the filter assembly. After a sufficient quantity of liquid samples have passed through, the inlet and outlets will be sealed by the closure plus.

It will be noted that the closure plugs are attached by flexible links such as plastic straps to the outer side of the peripheral wall so that the links do not obstruct engagement between the container and the main housing. The closure means could be provided with anti-tampering means to mitigate tampering or contamination. Labels, especially patient information labels, are attached to the sample collection device prior to sample collection to ensure proper handling.

Figures 16-18 show a further variation to the embodiment of Figures 15A. The sample collection device 500 is substantially identical to that of the device 400 of Figure 15A, except that an intermediate insert 560 is provided between the container 550 and the main housing 510 for better coupling.

Sample Retention Device

Filter based technology has a wide range of application in biological sample processing. The size exclusion ability of filters enables capturing of cells or tissue from different biological fluid, like urine as described herein. Other applications include isolation of cells from sputum, whole blood, or processed clinical samples like cervical brushing in Thinprep Liquid Based Cytology Preservative. The captured cells are then disrupted and the cell lysate is collected for the downstream process such as nucleic acid purification. The current device can also be utilized for the direct immobilization of specific molecules in the biological fluid onto filter membranes. Different molecules have been captured on filter membranes through simple adsorption. Out of many porous filter membrane materials such as nylon, nitrocellulose, hydrophobic polyvinylidinefluoride (PVDF); glass microfiber have been used for noncovalent nucleic acid immobilization; and has been shown to specifically bind nucleic acids from a variety of nucleic acid containing sources effectively. Under the correct salt and buffering conditions, nucleic acids will bind to glass or silica, or released from the filter membrane matrix for analysis.

An alternative embodiment of the current device can be modified as using conjugate matrix, capable to specifically bind the target molecules in the sample. In this case the filter membrane serves to retain the conjugate matrix, which is captured and stays on top of the membrane. The conjugate molecules can be nucleic acid, antibody, antigen or any affinity ligand serving as capturing agent for target molecules collection for subsequent assay.

While the present invention has been explained with reference to exemplary embodiments described above, it will be appreciated that the embodiments are only non-limiting examples which are provided to help illustrate the invention. It will be appreciated to persons skilled in the art that the invention could be practiced through other embodiments or implementation means. For example, while a filter comprising nitrocellulose membranes is used as an example above, filters comprising a glass fibre membrane, or polypropylene could also be used as a size exclusion filter. Furthermore, while a bore size of 1.6um has been used above, it will be appreciated that the bore size is variable and commensurate with the size of the bio-particles, including bio-molecules, which are the target of collection.

For example, while the embodiments have been described with reference to urine samples, the invention could be used for collecting blood, saliva or other body samples without loss of generality.

Claims

1. A clinical sample collection device comprising a sample retention arrangement enclosed within a housing, wherein the sample retention arrangement is capable of trapping or retaining a quantity of sample contained in a sample containing fluid when the sample containing fluid transits through the sample retention arrangement, and wherein the housing comprises an inlet for ingress of sample containing fluid and an outlet for egress of residual or excessive sample containing fluid, wherein the housing is closable to isolate the quantity of sample trapped or retained.

2. A collection device according to Claim 1 , wherein both the inlet and the outlet are closable or sealable, preferably re-closable or re-sealable.

3. A collection device according to Claims 1 or 2, further comprising plugs or caps for sealing or closing the inlet and the outlet, preferably with anti-tampering means.

4. A collection device according to Claim 3, wherein the housing comprises an upper end and a lower end respectively on which the inlet and the outlet is disposed, and a peripheral side wall interconnecting the upper and lower ends; an wherein the plugs or caps are attached to the peripheral side wall of the housing by a flexible link, such as a plastic strap.

5. A collection device according to any of Claims 1 to 4, wherein the inlet is adapted to receive and tightly engage with an outlet nozzle of a syringe such that the sample containing fluid inside the syringe could be injected into the housing via the inlet.

6. A collection device according to any of the preceding Claims, wherein the inlet and the outlet respectively define an inlet aperture and an outlet aperture, and the housing defines a sample retention aperture which is intermediate the inlet and outlet apertures and in fluid communication therewith; the bore size of the sample retention aperture being a substantial enlargement of the inlet aperture to provide for an enlarged sample retention surface.

7. A collection device according to any of the preceding Claims, further comprising a sample fluid collector, the sample fluid collector being detachably attachable to the inlet side of the housing.

8. A collection device according to any of the preceding Claims, further comprising a residual sample fluid collector, the residual sample fluid collector being detachably attachable to the outlet side of the housing.

9. A collection device according to Claims 7 or 8, wherein the sample fluid collector and/or the residual sample fluid collector is attachable to the housing by releasable coupling means such as screw threads.

10. A collection device according to Claim 9, wherein the releasable coupling means is arranged to form a water-tight coupling between the housing and the sample fluid collector and/or the residual sample fluid collector when coupled.

11. A collection device according to any of Claims 7 to 10, wherein the sample fluid collector and/or the residual sample fluid collector is axially retractable and/or axially expandable.

12. A collection device according to Claim 11 , wherein the sample fluid collector and/or the residual sample fluid collector comprises circumferentially extending corrugations such as bellows like corrugations so that the sample fluid collector is axially expandable.

13. A collection device according to any of the preceding Claims, wherein the sample retention arrangement comprises a filter, preferably glass fiber filter, nitrocellulose filter, nylon filter, hydrophobic polyvinylidinefluoride (PVDF) filter, or a filter pad such as a membrane type filter.

14. A collection device according to Claim 13, wherein the filter is adapted to retain bio-fluid, and/or bio-particles, such as bio-molecules including DNA, RNA and other protein molecules.

15. A collection device according to Claim 14, wherein the filter comprises a nitrocellulose membrane adapted to filter DNA, RNA and other protein molecules by size exclusion or affinity binding.

16. A collection device according to any of Claims 13 to 15, wherein the filter is a size exclusion filter.

17. A collection device according to any of Claims 13 to 16, wherein the filter has a bore size of 1.6 μm or below.

18. A collection device according to any of the preceding claims which is configured as a urine sample collection device.

19. A collection device according to any of the preceding claims, wherein the filter contains a buffering agent for maintaining the stability of the sample during storage and/or transportation.

20. A method of obtaining biological samples from a sample containing fluid using a sample collection device of any of the preceding Claims, the method comprising:

Filling a sample collection container with a sample fluid, - Coupling the sample collection container with the inlet of the device,

Draining excessive sample fluid at the outlet, and

- Closing or sealing the inlet and the outlet.

21. A method according to Claim 20, wherein the sample collection container is a syringe and the method further comprises injecting the sample fluid from the syringe into the housing of the device through the inlet.

22. A method according to Claims 20 or 21 , wherein the sample collection container includes coupling means for water-tight coupling with the housing, and the method further comprises inverting the coupled assembly of the device and the sample collection container such that the sample fluid passes through the sample retention arrangement and is then discharged at the outlet due to gravity.

23. A method according to Claim 22, wherein the sample collection container is collapsible, and the method further comprising compressing the collapsible sample collection container to force the collected sample fluid into the housing and through the filter.