Apparatus and method for in vitro diagnostic testing

Abstract

A filter device (70) comprising: a head end (20); an attachment means (22) for mating with an internal portion of an open-end of a mixing tube for use with the filter device; a filter body (26) comprising a matrix of pores, sized to facilitate segregation of particles; a measuring scoop extending from a bottom of the filter body; and a bore (30) extending from an opening in the head end through the filter body and to a bottom opening proximate the measuring scoop.

Description

[0001] APPARATUS AND METHOD FOR IN VITRO DIAGNOSTIC TESTING

[0002] FIELD OF THE INVENTION

[0003] The present invention relates to apparatus and a method for in vitro diagnostic testing. The invention finds advantageous application in the preparation, processing and analysis of medical samples for diagnostic purposes, in particular, but not exclusively, faecal or other solid biological samples.

[0004] BACKGROUND OF THE INVENTION

[0005] In vitro diagnosis (IVD) refers to a field of technology that facilitates the diagnosis of health conditions by analysing objects such as blood, urine, or cells collected from an animal body, for example a human or cow. In vitro diagnostics can include, but is not limited to, immunodiagnostics, and molecular diagnostic techniques. Molecular diagnosis is a method of diagnosing diseases by detecting and analysing genetic information material, for example DNA or RNA. Immunodiagnostics uses the ability of antibodies to bind to an antigen. Specific antibodies that are easy to identify, can provide indirect proof of the presence of an antigen, which can lead to the accurate diagnosis of a medical condition. A fast and accurate diagnosis is an important factor in improved treatment of any ailment.

[0006] For the collection and analysis of a bovine faecal specimen, a conventional methodology may include the steps of: firstly, confining the animal to be tested; removing faecal material from the animal’s rectal; and isolating the specimen in a container labelled with the animal’s ID. The specimen is then transported to a laboratory. At the point of collection and / or at a laboratory, the specimen may be frozen and stored for analysis at a later date. Additional processing steps may then be required to process the frozen specimen. The subsequent testing protocol may involve transferring a quantity, i.e. an amount (e.g. 1 ml) of the faecal specimen to a sterile Eppendorf tube containing diagnostic reagent and mixing the quantity of specimen with the diagnostic reagent. An agitation mixing method may be performed, for example, vortexing, followed by centrifuging to remove large solids. Then, an amount of the resulting processed specimen may be extracted via pipette and transferred for RNA analysis, for example Differential Gene Expression (DGE) analysis which may enable the identification of diseasedriver genes for precise diagnosis.

[0007] It is difficult to practically conduct such tests in locations that are easily accessible to patients or care providers. As a result, patients or care providers (for example veterinarians and medical professionals) are unable to perform in vitro diagnostic tests in the early stages of the disease, which can result in delays in appropriate treatment. Accordingly, the present invention seeks to provide an improvement in the diagnostic testing processing of biological specimens. The present invention aims to provide an apparatus and method for in vitro diagnostic testing that could be utilised in Point-of-Care (POC) testing services; and / or which could be used in other testing services yet reduce the amount of laboratory analysis and / or away from patient processing of the diagnostic specimen, in order to provide for faster, but nevertheless accurate diagnostic testing.

[0008] The invention may be utilised in applications other than for bovine faecal specimen analysis, 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.

[0009] SUMMARY OF THE INVENTION

[0010] Aspects of the invention provide apparatus for in vitro diagnostic testing, a kit for diagnostic testing a system and a method as claimed in the appended claims.

[0011] According to a first aspect of the invention for which protection is sought, there is provided a filter device comprising: a head end; an attachment means for mating with an internal portion of an open-end of a mixing tube for use with the filter device; a filter body comprising a matrix of pores, sized to facilitate segregation of particles; a measuring scoop extending from a bottom of the filter body; and a bore extending from an opening in the head end through the filter body and to a bottom opening proximate the measuring scoop.

[0012] Optionally, the bore is a central bore extending entirely through the filter device.

[0013] Optionally, the central bore is sized to receive a pipette therethrough.

[0014] Optionally, the filter body is tapered.

[0015] Optionally, the filter device further comprises a circumferential seal between the attachment means and filter body.

[0016] According to a second aspect of the invention for which protection is sought, there is provided the filter device of any preceding paragraph and a mixing tube, the mixing tube having a tubular body with an open top end and a closed tapered end providing an agitation pocket, the mixing tube comprising an internal attachment means such that the attachment means of the filter device can couple to the internal attachment device of the mixing tube. Optionally, said filter device is inserted into and attached to the mixing tube, and the measuring scoop may terminate above the closed tapered end of the mixing tube.

[0017] Optionally, a pipette tip is inserted into the bore of the filter device and extends into the closed tapered end of the mixing tube.

[0018] According to another aspect of the invention there is provided a biological specimen preparation kit comprising: a filter device according to any of the relevant preceding paragraphs; a mixing tube; and a pipette.

[0019] Optionally, the biological specimen preparation kit further comprises: milling media and a reagent.

[0020] According to yet another aspect of the invention there is provided a method of preparing a biological specimen for testing or analysis, comprising the steps of:

[0021] (i) using the measurement scoop provided on the end of the filter device according to any of the relevant preceding paragraphs, for obtaining a controlled quantity or amount of biological specimen;

[0022] (ii) transferring the controlled amount of biological specimen to the mixing tube;

[0023] (iii) inserting the filter device into and connecting the filter device to the mixing tube;

[0024] (iv) agitating the combined unit of the connected filter device and mixing tube;

[0025] (v) inserting a pipette tip into a central bore in the filter device, and into an agitation space in the mixing tube to extract a quantity of supernatant therefrom; and

[0026] (vi) transferring the extracted quantity of supernatant for analysis.

[0027] Optionally, the method further comprises the steps of:

[0028] (vii) using the measurement scoop provided on the end of the filter device for obtaining a controlled amount of milling media; and

[0029] (viii) transferring the milling media to a mixing tube.

[0030] Optionally, said analysis includes Differential Gene Expression (DGE) analysis.

[0031] 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.

[0032] BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Embodiments of the invention will now be described, by way of example only, with reference to the accompanying drawings, in which:

[0034] FIGURE 1 A is a plan view from the side of a filter device apparatus for diagnostic testing;

[0035] FIGURE 1 B is a plan view from the rear of the filter device apparatus of Figure 1 A;

[0036] FIGURE 1 C is a plan view from the top of the filter device apparatus of Figures 1A and 1 B;

[0037] FIGURE 2A is a perspective view from the top and side of the filter device apparatus of Figures 1A and 1 B;

[0038] FIGURE 2B is a perspective view from the top and side of the filter device apparatus of Figure 2A once it has been received in and securably attached to a mixing tube which forms part of a diagnostic testing kit;

[0039] FIGURE 2C is a further perspective view of the filter device apparatus of Figures 1 A and 1 B;

[0040] FIGURE 3A shows a plan view from the front of the filter device apparatus of Figure 2B securably attached to a sample tube;

[0041] FIGURE 3B shows a cross-sectional view through the line A-A denoted in Figure 3A;

[0042] FIGURE 4A shows a plan view from the front of the filter device apparatus of Figure 3A securably attached to a sample tube and with a first pipette tip inserted into the filter device;

[0043] FIGURE 4B shows a cross-sectional view through the line B-B denoted in Figure 4A (the first pipette tip is not fully inserted into the mixing tube); FIGURE 5A shows a plan view from the front of the filter device apparatus of Figure 3A securably attached to a sample tube and with a second pipette tip inserted into and through the filter device;

[0044] FIGURE 5B shows a cross-sectional view through the line C-C denoted in Figure 5A (the second pipette tip is not fully inserted into the mixing tube); and

[0045] FIGURE 6 shows a specimen preparation kit according to various embodiments of the invention.

[0046] DETAILED DESCRIPTION OF EMBODIMENTS

[0047] Detailed descriptions of specific embodiments of the apparatus, methods and kits for diagnostic testing 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 apparatus, methods and kits for diagnostic testing 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.

[0048] A specimen preparation and testing kit 100 for in vitro diagnostic testing according to an embodiment of the present disclosure is illustrated schematically in Figure 6. The kit 100 in some embodiments may also include a vortex mixing device 1 10 (also shown in Figure 6); though this is optional, it is more likely, that the specimen preparation and testing kits 100 will be provided separately to the vortex mixing device 110, for use therewith.

[0049] The specimen preparation and testing kit 100 for in vitro diagnostic testing shown in Figure 6 comprises an optional specimen collection tube 50; an optional reagent 60; milling media (also called mixing beads 90); a mixing tube 40; a filter device 70 and a pipette or pipette tip 80.

[0050] A biological specimen, for example, but not exclusively, a faeces specimen taken from an animal, such as livestock, may be contained in the optional specimen collection tube 50. The optional reagent 60 may be contained in a separate container 60; or in some embodiments, a measured quantity of test reagent 60 may, already be contained in the specimen mixing receptacle 40, which may be provided in the kit 100 in a sealed condition.

[0051] To prepare a biological specimen ready for testing or analysis, the specimen preparation and testing kit 100 for in vitro diagnostic testing may be used as follows:

[0052] • a measurement scoop 10 provided on the end of the filter device 70 may be used to extract a controlled amount of milling media or mixing beads 90 from the quantity of milling media 90 provided in the kit 100;

[0053] • the controlled quantity of milling media 90 may be transferred to the mixing tube 40;

[0054] • the measurement scoop 10 provided on the end of the filter device 70 may be used to extract a controlled amount of biological specimen from the optional collection tube 50;

[0055] • the measured amount of biological specimen is transferred to the mixing tube 40;

[0056] • if the reagent 60 is not already contained in the mixing tube 40, then the reagent 60 is added to the mixing tube 40;

[0057] • the filter device 70 is inserted into and connected to the mixing tube 40;

[0058] • the combined unit 70 / 40 of the connected filter device 70 and mixing tube 40, with the specimen, reagent 60, and milling media 90 contained therein, is inserted into a vortex apparatus 110 for mixing of the specimen and reagent 60 with the mixing beads 90;

[0059] • the pipette tip 80 is inserted into a central bore 30 in the filter device 70, and into the mixing tube 40 to extract a quantity of supernatant of the mixed, milled and filtered specimen-reagent solution; and

[0060] • the extracted quantity of the mixed specimen-reagent solution is transferred to another testing apparatus for further analysis. The further analysis may include microscope analysis, RNA analysis, for example Differential Gene Expression (DGE) analysis which may enable the identification of disease-driver genes for precise diagnosis and may optionally include an Al powered analytics platform to facilitate rapid and accurate analysis.

[0061] The testing technique provided by the kit 100 and the various components thereof allows for an efficient processing protocol that is well contained; thus, reducing the risk of contamination of the test as well as making the test process safer for the user. Further beneficially the apparatus provided in the kit 100 provides for a test process that is simple enough for less skilled personnel to undertake and / or that is simple and quick enough to be conducted outside of a laboratory. In this way the test kit 100 can be used at a point-of-care (POC) by a carer, pharmacist or other medical professional such as a veterinarian, nurse or doctor. The test can be conducted effectively in-situ with the patient during a consultation and results of the test obtained in a very short time frame rather than requiring days, weeks or even longer, as is typically the case when a specimen is collected and then sent away to a specialist laboratory for testing.

[0062] Referring to Figures 1A and 1 B, the filter device apparatus 70 is shown in more detail. The filter device 70 is for use with the mixing tube 40 (see Figures 2B, and 3A to 5B) and a pipette tip 80, 80’ such as that shown in Figures 4A to 5B, that may optionally be included in the kit 100.

[0063] The filter device 70 comprises a head end 20 which may optionally have ribs or other surface features to aid gripping by a user. The filter device 70 comprises an attachment means 22, which optionally in the presently illustrated arrangement is an external screw-thread, sized, configured and arranged for mating with an internal screw thread provided proximate to an open-end of and internally of the mixing tube 40. The attachment means 22 may terminate at or near to a circumferential seal 24, which may serve to further close and seal an annular region of the open end of the mixing tube 40, once the filter device 70 has been inserted therein and secured thereto (see Figure 3B). Extending from the circumferential seal 24 a filter body 26 is provided. Optionally, the filter body 26 may comprise a matrix of pores, sized to facilitate segregation of particles contained in the mixed specimen / reagent solution.

[0064] In the illustrated example, the filter body 26 of the filter device 70 comprises a lattice structure of crossing internal and external elongated elements. A cross-sectional view of the filter device 70 is shown in Figure 3B. The filter body 26 may take various forms and is not limited to that shown in the Figures and described herein. For example, a filter body 26 may be structured in a similar manner to the filter bodies 12 and 13, of the filter devices of EP3436197 and GB2321857B. In other embodiments pores of the filter body 26 may be formed in a variety of ways; may take a variety of shapes, sizes configurations and formats; and may be configured or tailored for the filtration, extraction, or segregation of specific physical features from a biological specimen. For example, the filter body 26 may have stepped shaped pores, square or circular pores and / or other features to prevent, for example, large stool debris from being contained in the supernatant.

[0065] However, in contrast to the filter bodies 12 and 13 of the filter devices of EP3436197 and GB2321857B; the filter device 70 of the present invention is open at both ends and has a central bore 30 extending entirely therethrough. In other words, the filter device 70 has an open top end; and open bottom end and a hollow bore 30 between the two. This is illustrated in Figure 1 C which shows a plan view from the top of the filter device 70 showing the bore 30 extending from the top of the head 20, through the centre of the filter body 26 and out near the measuring scoop 10. The bore 30 can also be seen in the cross-sectional view of Figure 3B.

[0066] It can also be seen in Figure 3B that the filter body 26 of the present invention is tapered. The filter device 70 is for use with and co-operates with the mixing tube 40 (see Figures 2B, 3A and 3B). The sample mixing device 40 is a generally tubular structure with an open top end 41 , a tubular body and a closed tapered end 42. The open top-end 41 is provided with an attachment means 41 , which optionally in the presently illustrated arrangement is an internal screw-thread 41 , sized, configured and arranged for mating with the external screw thread 22 of the filter device 70. The attachment means 41 may terminate at or near to a circumferential tapered ledge or seat 43, which may serve to guide the seal 24 of the filter device 70 into its sealing location whereat it closes and seals about the open end of the mixing tube 40. The bore 30 prevents the combined unit 70 / 40 (of the filter device 70 when inserted into and secured to the mixing tube 40) from being completely closed. During the test procedure outlined above, it is necessary to keep the combined unit 70 / 40 (as shown in Figure 3B) in a generally upright condition. However, the seating of the seal 24 and sealing of an annulus about the top of the combined unit 70 / 40 (using the screw-threaded fittings 22 / 41 and the additional seal 24 seated beneath seat 43) ensures that during the vortexing of the specimen, for mixing the specimen (and releasing small features such as RNA, whilst causing larger particles to be caught by the filter body 26), the vortexing solution does not spill out from the mixing tube 40.

[0067] As can best be seen in Figure 3B, when the filter device 70 is inserted into and screw-fitted to the mixing tube 40, the end of the measuring scoop 10 terminates above an agitating or mixing pocket 42 provided in the internal space between the tapered end 42 of the mixing tube 40; and the end of the measuring scoop 10. The milling media 50 will tend to be located in this mixing pocket. The milling media 50 beneficially help to breakdown the biological specimen to release small features, such as RNA from the specimen mixture. This increases the amount of RNA accessible for Differential Gene Expression (DGE) analysis or other analysis and this increases the sensitivity or accuracy of the analysis.

[0068] The mixing pocket 42 or agitation space 42 is also the location from which supernatant is extracted, using a pipette 80, 80’ (as shown in Figures 4B and 5B). The pipette 80, 80’ fits into and is guided by the bore 30 such that the withdrawn supernatant is taken from the specimen mixture where the concentration of released RNA is likely to be highest. Additionally, the pipette 80, 80’ fits into and is guided by the bore 30 such that the withdrawn supernatant is taken from the specimen mixture where the concentration of specimen debris is lowest (due to the specimen debris having been filtered out by the filter body 26).

[0069] As shown in Figures 6, 4B and 5B, the pipette tip 80, 80’ comprises a generally tapered body. In some embodiments, the pipette tip 80, 80’ may have ribs or other formations formed on the exterior surface proximate to an upper (wide end) - also known as a “bulb-end”. The “bulbend” or first open end may, in use, be 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 and a tip opening, configured, sized and arranged for insertion into the agitating or mixing pocket 42.

[0070] The kit 100 of Figure 6 provides apparatus in the form of the mixing tube 40, filter device 70, pipette 80, 80’, and optional milling media 90 and reagent 60, which are easily operated together to provide a well-mixed biological specimen in which:

[0071] • larger particles are filtered out of the solution by the body 26 of the filter device 70;

[0072] • RNA, DNA or other smaller features are extracted out of the biological specimen by the milling media 90 acting on the vortexed specimen in the provided agitation space 42, so that they are more readily detectable or provide more sensitive analysis and better testing; and

[0073] • the supernatant is easily and accurately extracted from the agitation space 42 by direct insertion of the pipette 80, 80’ through the mixing apparatus 70 / 40 by means of the provided bore 30.

[0074] The secure and convenient connection of the mixing tube 40 with the filter device 70 makes the apparatus 100 easy for an operator to use. The measuring scoop 10 provides a convenient, safe and easy to use way of measuring a controlled amount of milling media and biological specimen.

[0075] 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 agitation pocket 42 may be sized and configured to create a concentration pocket capable of holding a different volume of mixed specimen and milling media. The filter device and sample tube may be formed completely or substantially from plastic.

Claims

CLAIMS1 . A filter device (70) comprising: a head end (20); an attachment means (22) for mating with an internal portion of an open-end of a mixing tube for use with the filter device; a filter body (26) comprising a matrix of pores, sized to facilitate segregation of particles; a measuring scoop extending from a bottom of the filter body; and a bore (30) extending from an opening in the head end through the filter body and to a bottom opening proximate the measuring scoop.

2. The filter device (70) of claim 1 wherein the bore (30) is a central bore (30) extending entirely through the filter device (70).

3. The filter device of claim 2 wherein the central bore is sized to receive a pipette therethrough.

4. The filter device (70) of claim 1 , 2 or 3, wherein the filter body (26) is tapered.

5. The filter device (70) of any preceding claim further comprising a circumferential seal (24) between the attachment means (22) and filter body (26).

6. The filter device of any claim 1 to 5 and a mixing tube (40), the mixing tube (40) having a tubular body with an open top end (41 ) and a closed tapered end (42) providing an agitation pocket, the mixing tube (40) comprising an internal attachment means such that the attachment means of the filter device (70) can couple to the internal attachment device of the mixing tube (40).

7. The filter device (70) and mixing tube (40) of claim 6 wherein said filter device is inserted into and attached to the mixing tube, and wherein the measuring scoop terminates above the closed tapered end of the mixing tube.

8. The filter device (70) and mixing tube (40) of claim 7 wherein a pipette tip is inserted into the bore of the filter device and extends into the closed tapered end (42) of the mixing tube.

9. A biological specimen preparation kit comprising: a filter device (70) according to any of claims 1 to 5; a mixing tube; and a pipette.

10. A biological specimen preparation kit according to claim 9 further comprising: milling media and a reagent.

11. A method of preparing a biological specimen for testing or analysis, comprising the steps of:(i) using the measurement scoop (10) provided on the end of the filter device (70) according to any of claims 1 to 5, for obtaining a controlled amount of biological specimen;(ii) transferring the controlled amount of biological specimen to the mixing tube (40);(iii) inserting the filter device (70) into and connecting the filter device to the mixing tube 40;(iv) agitating the combined unit (70 / 40) of the connected filter device (70) and mixing tube (40);(v) inserting a pipette tip (80; 80’) into a central bore (30) in the filter device (70), and into an agitation space (42) in the mixing tube (40) to extract a quantity of supernatant therefrom; and(vi) transferring the extracted quantity of supernatant for analysis.

12. The method of claim 11 further comprising the steps of:(vii) using the measurement scoop (10) provided on the end of the filter device (70) according to any of claims 1 to 5 for obtaining a controlled amount of milling media (90); and(viii) transferring the milling media (90) to a mixing tube (40).

13. The method of claim 11 or claim 12 wherein said analysis includes Differential Gene Expression (DGE) analysis.

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