Urine sample preparation device

Abstract

A liquid sample preparation device 100 comprising: a concentrator tube 40 comprising an internal pocket 48 having formed at an open end thereof a seat 50; and a pipette tip 20 comprising an open-ended

Description

FIELD OF THE INVENTION The present invention relates to a sample preparation device. The invention finds advantageous application in the preparation, processing and analysis of liquid medical samples for diagnostic purposes, in particular, but not exclusively, urine. BACKGROUND OF THE INVENTION In the analysis and processing of liquid medical samples, such as urine, for diagnostic purposes, a sample may be centrifuged in order to concentrate proteins or other molecules present in the liquid sample. The concentrated sample is then analysed for the diagnosis and monitoring of disorders and diseases in humans and animals. In certain diagnostic processing methodologies, it is required to extract a precise and small quantity of the concentrated sample. It is also required to carefully recover, that precise and small quantity of concentrated sample, and transfer it, without risk of cross-contamination, for analysis. A pipette is typically used to conduct the recovery and transfer steps. This processing step can be slow and labour intensive. A skilled technician is required to use the pipette to carefully withdraw the correct quantity, which may be in the region of a few hundred pl, and ensure that only the concentrated macromolecular retentate is recovered with the pipette and not any of the supernatant. Whilst pipette tips with specified volumes can be used to assist in the recovery of a correct quantity of the concentrated retentate, in some methodologies it is necessary to remove all or most of the supernatant before recovery of the concentrated retentate. This additional step of pouring off the excess sample liquid is not easy to perform accurately, repeatedly, quickly, and increases the manual processing time. It is desirable for the time and skill in the supernatant removal and retentate recovery to be reduced. It is desirable for the accuracy of repeated retentate recovery after supernatant removal to be improved. Accordingly, the present invention seeks to provide an improvement in the processing of centrifuged liquid samples and accurate recovery of low volumes of concentrate, that has particular application for determining a disease or disorder due to the presence of particular proteins in the urine. The invention may be utilised in applications other than for protein detection and for analysis of substances other than urine, for example it is foreseen that the invention may have application in a wide variety of diagnostics and provide improvements to healthcare for humans and other animals. SUMMARY OF THE INVENTION Aspects of the invention provide a urine sample preparation device, a system and a method as claimed in the appended claims. According to a first aspect of the invention for which protection is sought, there is provided a liquid sample preparation device comprises: a pipette tip; and a concentrator tube. The concentrator tube comprises an internal concentration pocket having formed at an open end thereof a seat. The pipette tip comprises means for attaching the pippette tip to a pipette filler (which may also be referred to as a pipette barrel); and, at an opposite end thereof, an open ended tip that is shaped and sized to fit into the concentration pocket of the concentrator tube. The pipette tip also comprises a plug proximate to said open ended tip. The plug is shaped and configured for location in said seat at the open end of the concentration pocket for closing and / or sealing the concentration pocket. The concentration pocket is located at a bottom end of the concentrator tube and is a receptacle with one open end. The concentration pocket may also be considered as and / or referred to as a bowl, bucket and / or V-shaped bucket. Optionally, the plug is generally annular in shape. The plug may be considered as being at least partially disc-shaped. Optionally, at least a circumferential edge of the plug is shaped in a complementary manner to the shape of the seat formed at the top of the concentration pocket, such that when the plug is located in the seat, the open end of the concentration pocket is closed and / or sealed and any sample disposed therein is securely retained therein. Optionally, the concentration pocket is defined by a wall, wherein the seat is formed in an internal portion of said wall proximate to the open end of the concentration pocket. Optionally, in use, a liquid medical sample is disposed in the concentrator tube and centriguged; wherein once said plug is located in and maintained in said seat, the liquid medical sample contained in the concentrator tube above the plug can be poured off, out of the open-end of the concentrator tube; and the concentrator tube can be angled sufficiently steeply to remove all of the liquid medical sample contained in the concentrator tube whilst retaining the liquid medical sample contained in the concentration pocket within the concentration pocket. Preferably, the concentration pocket has a volume of about 300pl. More preferably, the concentration pocket has a volume of about 300pl (+ / - 50 pl). In dependence upon the capacity of the concentration pocket a volume of the concentrated liquid medical sample remaining in the concentration pocket can be determined. Optionally the concentrated liquid medical sample remaining in the concentration pocket may have a volume of between about 10pl and about 500pl. Optionally, the pipette tip is operable to recover the concentrated liquid medical sample from the concentration pocket. Optionally, the recovered concentrated liquid medical sample has a volume of 20pl. Optionally, the means for attaching the pippette tip to a pipette filler comprises, on an outer surface of the pipette tip, one or more ribs, ridges or other mouldings. Optionally, the device is formed completely or substantially from plastic. According to another aspect of the invention for which protection is sought, there is provided a pipette tip for use in the liquid sample preparation device according to the above relevant paragraphs. The pipette tip comprises means for attaching the pippette tip to a pipette barrel or pipette filler; and, at an opposite end thereof, an open ended tip, shaped and sized to fit into a concentration pocket of a concentrator tube. The pipette tip comprises a plug proximate to said open ended tip. The plug is shaped and configured for location in a seat at the open end of the concentration pocket for closing and / or sealing the concentration pocket. Optionally, at least a portion of the plug may have a disc-shape. According to yet another aspect of the invention for which protection is sought, there is provided a concentrator tube for use in the liquid sample preparation device according to the above relevant paragraphs. The concentrator tube comprises an internal concentration pocket having formed at an open end thereof a seat that is sized, shaped and configured for locating a plug of the pipette tip therein, for closing and / or sealing the concentration pocket. According to yet an even further aspect of the invention for which protection is sought, there is provided a method of preparing a concentrated liquid medical sample, the method comprises: providing a liquid sample preparation device according to the above relevant paragraphs, having a liquid sample deposited in the concentrator tube, said sample being of a volume greater than the capacity of the concentration pocket. Centrifuging said sample in the concentrator tube. Inserting the pipette tip into the concentrator tube, such that the open ended tip is disposed in the concentration pocket and such that the plug is located in said seat at the open end of the concentration pocket for closing and / or sealing the concentration pocket. The method may also comprise the step of pouring off liquid medical sample contained in the concentrator tube above the plug; and maintaining the location of the plug in said seat such that the concentrator tube can be angled sufficiently to pour the portion of the liquid medical sample above the plug out of the concentrator tube whilst maintaining the concentrated sample within the concentration pocket. The concentrated liquid medical sample remaining in the concentration pocket may have a volume of 300pl (+ / - 50 pl). The method may comprise the step of using the pipette tip to recover at least a portion of the concentrated liquid medical sample from the concentration pocket. The recovered concentrated liquid medical sample may have a volume of 20pl (+ / - 0.5pl). The recovered concentrated liquid medical sample may have a volume determined by the pipette tip and / or diagnostic application and may be between about 0.1 pl and about 300pl. Within the scope of this application, it is expressly intended that the various aspects, embodiments, examples and alternatives set out in the preceding paragraphs, in the claims and / or in the following description and drawings, and in particular the individual features thereof, may be taken independently or in any combination. That is, all embodiments and / or features of any embodiment can be combined in any way and / or combination, unless such features are incompatible. The applicant reserves the right to change any originally filed claim or file any new claim accordingly, including the right to amend any originally filed claim to depend from and / or incorporate any feature of any other claim although not originally claimed in that manner. BRIEF DESCRIPTION OF THE DRAWINGS Embodiments of the invention will now be described, by way of example only, with reference to the accompanying drawings, in which: FIGURE 1 is a perspective view of a two-part urine sample preparation device comprising a urine concentrator tube and a pipette tip according to a first embodiment of the invention; FIGURE 2 is a second perspective view of the two parts of the urine sample preparation device shown in Figure 1; FIGURE 3A shows: a plan-view of the first side of the pipette tip of the urine sample preparation device device according to the first embodiment; FIGURE 3B shows a cut-away view of the pipette tip shown in Figure 2; FIGURE 4A shows: a plan-view of the first side of the urine concentrator tube (also referred to herein as tube), of the urine sample preparation device shown in Figures 1 and 2; FIGURE 4B shows a cut-away view of the urine concentrator tube shown in Figure 4A; and FIGURE 5 shows a cut-away view of the urine concentrator tube having the pipette tip placed therein, with a plug of the pipette tip located in a seat defined in a concentration pocket. DETAILED DESCRIPTION OF EMBODIMENTS Detailed descriptions of specific embodiments of the urine sample preparation devices of the present invention are disclosed herein. It will be understood that the disclosed embodiments are merely examples of the way in which certain aspects of the invention can be implemented and do not represent an exhaustive list of all of the ways the invention may be embodied. Indeed, it will be understood that the urine sample preparation devices described herein may be embodied in various and alternative forms. The figures are not necessarily to scale and some features may be exaggerated or minimised to show details of particular components. Well-known components, materials or methods are not necessarily described in great detail in order to avoid obscuring the present disclosure. Any specific structural and functional details disclosed herein are not to be interpreted as limiting, but merely as a basis for the claims and as a representative basis for teaching one skilled in the art to variously employ the invention. Referring to Figure 1, there is shown perspective views of a pipette tip 20 and urine concentrator tube 40 of a two-part urine sample preparation device 100 according to various embodiments of the disclosure. The pipette tip 20 and / or urine concentrator tube 40 may be moulded or otherwise suitably manufactured from plastic or other suitable material. Optionally, the pipette tip 20 and / or urine concentrator tube 40 may be formed from translucent, transparent or opaque material. Optionally in the presently illustrated embodiment, the pipette tip 20 and / or urine concentrator tube 40 is a plastic moulded, construct which is formed of translucent or transparent plastics material. The pipette tip 20 comprises a generally tapered body 22, having ribs 30 formed on the exterior surface of the tapered body 22 proximate to a bulb-end 32. The “bulb-end” or first open end 32 is, in use, coupled to a pipette filler (also referred to as a pipette barrel), such as a bulb, thumb-wheel type filler, syringe or the like. At the other end of the tapered body is a tip 26 and a tip opening 28. Additionally, above the tip opening 28 between tip 26 and the tapered body 22 a plug is provided. The plug 24 may be an integrally moulded piece such that the pipette tip 20 is a unitary construct. The plug 24 is optionally annular and is configured and arranged for co-operation with the concentrator tube 40. In the embodiment illustrated in the Figures, in particular in Figures 1 and Figure 4B, it can be seen that the concentrator tube 40 has a generally cylindrical wall 46, having an open end 42. Opposite to the open end of the cylindrical wall 46, a concentration pocket 48 is provided. The concentration pocket 48 is closed at a bottom end thereof; and open at the other, upper end. At the open end of the concentration pocket 48, a seat 50 for locating the plug 24 of the novel pipette 20 is provided and is formed by shaping or moulding of a main wall 52 that defines the concentration pocket 48. The main wall 52 extends downwardly from the seat 50 and tapers toward a closed and optionally rounded bottom 45. The concentration pocket 48 is shaped sized and configured to have a specific capacity. The capacity of the concentration pocket 48 may be defined differently in concentrator tubes 40 for different applications. The presently illustrated concentrator tube 40 has been shaped sized and configured such that it can contain a total liquid medical sample, of optionally urine, of a about 3ml. The concentration pocket 48 has been shaped sized and configured such that, once the tip 26 is inserted therein and the plug seated in the seat 50; the concentration pocket 48 can contain a total liquid medical sample of 300pl. The pipette tip 20 and urine concentrator tube 40 are specifically configured to co-operate with one another. Referring to Figures 4A and 4B, the concentrator tube 40 is shown in plan and cut-away views. In Figures 3A and 3B, the pipette tip 20 is shown in plan and cut-away views. In Figure 2, the two components 20, 40 are shown side by side. In use, a liquid medical sample for analysis is deposited into the concentrator tube 40. The concentrator tube 40 may optionally have a lid or cap deposited on the open end 42; or optionally, the open end 42 may remain open during the step of centrifuging the sample (not shown). If a cap is used, it must be removed before the next step. No cap is shown and in many applications the concentrator tube does not require a lid or cap. Once the step of centrifuging is complete, in some methodologies, as discussed above, it is necessary or desirable to remove the supernatant before recovery of the concentrate. Typically, this can be done by carefully removing the supernatant liquid with a pipette or pouring it off; pipetting can be slow and care needs to be taken not to extract the concentrate. Pouring off can lead to mixing of the concentrate and supernatant; pouring off the concentrate; or not pouring off all of the supernatant. Advantageously the present invention provides a novel pipette tip 20 having an integral plug 24 which is carefully and accurately seated within a co-operatively shaped, sized and configured seat 50 provided at the top of a concentration pocket 48 in the concentrator tube 40. Once the step of centrifuging is complete, in some methodologies, it is necessary or desirable to recover a precise and low volume of the concentrate. In some methodologies, a volume of concentrate may be specified as 20pl. In other methodologies, a volume of recovered concentrate, from the concentrate contained in the concentration pocket 48, of between 20pl and 300pl may be required. The maximum volume of concentrate that may be recovered from the concentration pocket 48 is determined by the capacity of the concentration pocket 48, which, in envisaged embodiments could be greater than 300pl, for example, in some applications a volume of recovered concentrate, from the concentrate contained in the concentration pocket 48 may be greater than 0.1 pl and may be as much as 500pl or even greater. By inserting the pipette tip 20 into the concentrator tube 40, such that the tip 26 is disposed within the concentration pocket 48; and such that the concentration pocket 48 is closed off, or sealed, by seating the plug 24 in the seat 50 at the top of the concentrator reservoir, the volume of concentrate in the concentration pocket 48 is accurately defined and fixed in dependence upon the volume of the concentration pocket 48, position of the plug 24 and volume of the tip 26. In the illustrated, optional and non-limiting embodiment, the pipette tip 20 and concentrator tube 40 have been specifically configured to defined a concentrate volume of 300pl. From that remaining specific volume of concentrated liquid sample, a precise and low volume of the concentrate can be recovered. This is referred to as the “recovered concentrate”. Further beneficially, including the plug 24 on the pipette tip 20 for co-operation with the seat 50 at the top of the concentration pocket 48 to seal the defined concentrate volume of 300pl therein, enables a user to easily and quickly pour off the supernatant out of the open end 42 of the concentrator tube 40 whilst optionally applying just a little downward pressure to the pipette tip 20 to ensure that the plug 24 remains snuggly located within the seat 50. Immediately, a pipette filler (not shown) connected to the pipette tip 20 can be operated to withdraw the defined volume of concentrate (20pl) from the concentration pocket 48 Advantageously the present invention provides a concentrator tube 40 having a concentration pocket 48 or sample reservoir, in which a precisely determined volume of concentrate will be held. It can be appreciated that various changes may be made within the scope of the present invention, for example, in other embodiments of the invention it is envisaged that the wall 52 of the concentration pocket may be sized and configured to create a concentration pocket capable of holding a different maximum volume of concentrated sample. It will be appreciated that the maximum volume of concentrated sample that can be retained in the closed concentration pocket 48, is different to the maximum volume of concentrated sample that can be retained in the open concentration pocket 48 due to the presence of the tip 26 and plug 24 and that in configuring the liquid sample preparation device 100, the applicant has carefully configured the a pipette tip 20; and a concentrator tube 40 such that when the are in use and co-operating, the retained concentrated liquid sample sealed in the closed concentration pocket will be accurately defined for the particular analysis methodology for which the liquid sample preparation device has been prodcued. Accordingly, where as in the present arrangement the pipette tip 20 is configured for recovery of 20pl and whereas the maximum volume of concentrated sample that can be retained in the closed concentration pocket 48 is specifically determined to be 300pl (within a manufacturing tolerance of +1- 50pl); in other embodiments, the pipette recovery volume and maximum volume of concentrated sample that can be retained in the closed concentration pocket may be different to 20pl and 300p respectively.

Claims

1. A liquid sample preparation device comprising: a pipette tip; and a concentrator tube, the concentrator tube comprising an internal concentration pocket having formed at an open end thereof a seat; andthe pipette tip comprising: means for attaching the pippette tip to a pipette barrel or pipette filler; at an opposite end thereof, an open ended tip, shaped and sized to fit into the concentration pocket of the concentrator tube; and a plug proximate to said open ended tip, the plug being shaped and configured for location in said seat at the open end of the concentration pocket for closing and / or sealing the concentration pocket.

2. A liquid sample preparation device according to claim 1 wherein the plug is generally annular in shape.

3. A liquid sample preparation device according to claim 1 or 2 wherein at least a circumferential edge of the plug is shaped in a complementary manner to the shape of the seat formed at the top of the concentration pocket, such that when the plug is located in the seat, the open end of the concentration pocket is closed and / or sealed and any sample disposed therein is securely retained therein.

4. A liquid sample preparation device according to claim 3 wherein the concentration pocket is defined by a wall, wherein the seat is formed in an internal portion of said wall proximate to the open end of the concentration pocket.

5. A liquid sample preparation device according to any preceding claim wherein, in use, a liquid medical sample is disposed in the concentrator tube and centriguged; wherein once said plug is located in and maintained in said seat, the liquid medical sample contained in the concentrator tube above the plug can be poured off, out of the open-end of the concentrator tube; and the concentrator tube can be angled sufficiently steeply to remove all of the liquid medical sample contained in the concentrator tube whilst retaining the liquid medical sample contained in the concentration pocket within the concentration pocket.

6. A liquid sample preparation device according to claim 5 wherein the concentrated liquid medical sample remaining in the concentration pocket has a volume of between about 300pl and 1000pl (+ / - 50 pl).

7. A liquid sample preparation device according to claim 6 wherein the pipette tip is operable to recover the concentrated liquid medical sample from the concentration pocket.

8. A liquid sample preparation device according to claim 7 wherein the recovered concentrated liquid medical sample has a volume of between about 0.1 pl and about 20pl.

9. A liquid sample preparation device according to any of claim 5 to 8, wherein the means for attaching the pippette tip to a pipette filler or pipetter barrel comprises, on an outer surface of the pipette tip, one or more ribs, ridges or other mouldings.

10. A liquid sample preparation device according to any preceding claim, wherein the device is formed completely or substantially from plastic.

11. A pipette tip for use in the liquid sample preparation device according to any of claims 1 to 10, the pipette tip comprising:means for attaching the pippette tip to a pipette filler or pipette barrel;at an opposite end thereof, an open ended tip, shaped and sized to fit into a concentration pocket of a concentrator tube; and a plug proximate to said open ended tip,the plug being shaped and configured for location in a seat at the open end of the concentration pocket for closing and / or sealing the concentration pocket.

12. A concentrator tube for use in the liquid sample preparation device according to any of claims 1 to 10, the concentrator tube comprising an internal concentration pocket having formed at an open end thereof a seat sized, shaped and configured for locating a plug of the pipette tip of claim 11 therein, for closing and / or sealing the concentration pocket.

13. A method of preparing a concentrated liquid medical sample, the method comprising: (i) providing a liquid sample preparation device according to any preceding claims having a liquid sample deposited in the concentrator tube, saidsample being of a volume greater than the capacity of the concentration pocket;(ii) centrifuging said sample in the concentrator tube;(iii) inserting the pipette tip into the concentrator tube, such that the open ended tip is disposed in the concentration pocket and such that the plug is located in said seat at the open end of the concentration pocket for closing and / or sealing the concentration pocket.

14. The method of claim 13 further comprising the step of pouring off liquid medical sample contained in the concentrator tube above the plug; and maintaining the location of the plug in said seat such that the concentrator tube can be angled sufficiently to pour the portion of the liquid medical sample above the plug out of the concentrator tube whilst maintaining the concentrated sample within the concentration pocket.

15. The method of claim 14 wherein the concentrated liquid medical sample remaining in the concentration pocket has a volume of 300pl (+ / - 50 pl).

16. The method of claim 15 further comprising the step of using the pipette tip to recover at least a portion of the concentrated liquid medical sample from the concentration pocket.

17. The method of claim 16 wherein the recovered concentrated liquid medical sample has a volume of between about 0.1 pl and about 20pl or greater.12

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