The present invention relates to cartridges and systems for preparing and analysing samples and methods of preparing and analysing samples using such devices. The invention provides fast and accurate preparation and analysis of samples, and a quick and convenient disposal of samples after use.
In the field of diagnostics there has been a growing need to provide sample preparation devices that can be used in the analysis of a sample from a patient. In particular there has been a growing need for ‘point-of-care’ medical diagnostic devices that enable a sample to be analysed at the location of a patient to ensure rapid analysis and to improve overall care for the patient.
One analytical approach which is desired to be implemented in such a point-of-care device is polymerase chain reaction (PCR). PCR is a technique in which small samples of segments of DNA and RNA are amplified or copied to provide larger quantities of the sample to study in detail. During this process a purified eluate containing the DNA or RNA in question is thermal cycled to amplify and detect the DNA or RNA in question.
Such analysis often uses a cartridge that contains wet and dry reagents to perform the DNA/RNA extraction, purification and amplification. The dry reagents are either in the form of cakes, that are directly lyophilised in the cartridge, or small beads, that are placed into the cartridge. In both cases, they are extremely hydroscopic.
To be effective over the shelf life of the product, the lyophilised reagent must be stored in a very low moisture environment (<5% RH). Unfortunately, such cartridges are typically manufactured from materials with poor moisture barrier properties, such as polypropylene. Consequently, the design of the dry chamber within the cartridge faces several potential challenges.
They must maintain a low RH within the dry chamber during assembly and must prevent moisture migrating from the fluid reagent chambers into the dry chamber over the specified shelf life. They should provide the ability for the system to open the chambers during use and must keeping the system simple, by not asking the user to carry out additional assembly tasks when performing a test (such as snapping in a separate chamber from a secondary foil pouch)
Existing cartridges use different methods to improve shelf life but these all have drawbacks.
One approach is to employ large amounts of desiccant, stored within the cartridge packaging, to maintain a low moisture environment within the cartridge. However, this requires additional volumes of fluid reagents which increases the overall size and cost of the cartridge. Also, it is shelf life limited and the desiccant adds to overall cost.
Another approach is to have desiccant stored within the dry chamber, to maintain a low moisture environment. However, this requires a large ratio of desiccant to lyophilised reagent and can make rehydration difficult due to the need to avoid desiccant mixing with the elution. It is also, shelf life limited.
Yet a further approach is to store the dry reagents separately from the wet reagents and ask the user to assemble both prior to use. This significantly impacts the risk of the user making a mistake. It also adds to the packaging costs.
In accordance with an aspect of the invention there is provided a cartridge according to the claims.
The present invention takes advantage of the provision of a liner formed from a low permeability material to enable formation of the main housing of the sample analysis cartridge from low cost and readily available plastics materials whilst improving dry reagent shelf life within the cartridge through use of lined and sealed dry reagent storage chambers. The invention can also simplify and improve manufacture by enabling production of the liner component as a separate sealed unit prior to assembly of the cartridge.
Specific examples of the invention will now be discussed with reference to the following drawings:
An example sample analysis cartridge 1 according to the invention is shown in expanded plan view in
The sample analysis cartridge 1 comprises base moulding 2 covered by a dip tube moulding 3.
The base moulding 2 forms part of a housing for the sample analysis cartridge 1 and is moulded to define at least one liquid reagent chamber 4 and at least one dry reagent chamber 5. In the examples shown plural chambers 4,5 of both type are provided. During manufacture liquid reagent is placed in the chamber or chambers 4, the dip tube moulding 3 is sealed, preferably by welding, on to the base moulding 2 and an optional low fluid permeability barrier 6 placed over apertures 7 in the dip tube moulding 3 to seal the liquid contained within the liquid reagent chambers 4 in place and prevent leakage of those liquid reagents during transport and handling. Other apertures 8 within the dip tube moulding 3 sit above the dry reagent chambers 5. Liners 9 are inserted via the apertures 8 and sit within and line of the dry reagent chambers 5. The liners 9 are also made of a low fluid permeability material, such as a metal. One particularly cost effective and functionally effective metal is aluminium. Dry reagent is provided or placed inside each of the liners 9, either during manufacture of the sample analysis cartridge 1, or prior to insertion of the liners 9 into the apertures 8. Held within each liner 9 may be other components, such as a small amount of desiccant to improve shelf life of the dry reagents, as well as other components such as reagent dip tubes 10 that are used during operation of the sample analysis cartridge 1 during use. Each of the linings 9 is then sealed with a cover 11 as will be described in more detail below.
seen in
In this particular example, during use the sample analysis cartridge 1 is inserted into a system (not shown) and a driving mechanism is passed via the central core of the base moulding 2 to engage with the pipette moulding 14 and raise and rotate it to selectively engage with desired liquid reagent and dry reagent chambers 4, 5 as required by a particular analysis. Thus the pipette moulding 14 acts as a reagent supply mechanism and may selectively supply reagent from the dry and fluid storage chambers 4, 5 (e.g. to the reaction chamber 3a and/or other chambers within the housing). The pipette moulding 14 may comprise one or more pipettes configured to receive and supply reagent(s). It will be appreciated by a person skilled in the art that other methods of accessing the reagent chambers 4, 5 are possible whilst still employing the concept of ensuring reliable storage of dry and/or liquid reagents in accordance with the invention. Referring to FIG. 2, the structure of the liners 9 which comprise the low fluid permeability material is shown in more detail. In this example aluminium is used, but other metals or high barrier plastics (such as LCP) can be employed. In this particular example dip tubes 10 are inserted into each liner 9. The dip tubes can be formed of a plastics material, and may comprise desiccant within that material to help absorb moisture within the liner 9. In addition, or as an alternative, the liner 9 or the dip tube 10 can include a pocket to contain desiccant therein. Once the dip tube 10 has been inserted then dry reagent may be placed within the dip tube. Alternatively, reagent may be introduced, wet, down the dip tube 10, and subsequently lyophilised (i.e. freeze-dried) in situ so as to form dry reagent. After dry reagent is provided within the liner 9 a seal 11 is placed over the liner 9 to provide a sealed lining unit which can line a dry reagent chamber 5 within the sample analysis cartridge 1. The seal component 11 should also be formed of a low fluid permeability material, such as aluminium foil, and can be joined (e.g. adhered or welded) to the main body of the liner 9. The liner 9 can be formed separate to the sample analysis cartridge 1 and then inserted into its respective dry reagent chamber 5 during manufacture of the sample analysis cartridge 1. Individual sealing components 11 can be coloured differently to aid in such
assembly so as to indicate different reagent types contained therein. As will be appreciated, the seal 11 may be structured so that it can be pierced in use so that during operation the dry reagent can be removed from its respective dry reagent chamber 5, normally by rehydration of the dry reagent and then drawing up into the system.
At present sample analysis cartridges are usually made of a low cost plastics material such as polyethylene or polypropylene. These have reasonably low rates of moisture permeability, as shown in
Metals, particularly aluminium, are not affected in the same way and are virtually impermeable to fluids, particularly moisture, when they are above a certain thickness. The present invention takes advantage of this by providing the liner 9 formed from such a material as it enables formation of the main housing of the sample analysis cartridge 1 from low cost and readily available plastics materials whilst improving dry reagent shelf life within the cartridge through use of sealed chambers 5. As will be appreciated, whilst an aluminium liner 9 with the appropriate seal 11 should be virtually impermeable to moisture, in practice a sealing layer 18 (
Alternatively, the seal 11 may be joined directly to the liner 9 by welding. As such, a sealing layer 18 may not be necessary between the seal 11 and the liner 9, and moisture ingress into the dry reagent chamber 5 may be significantly reduced. This approach is especially effective where the seal 11 and liner 9 are both metals (e.g. aluminium), and preferably the same metal. To further reduce moisture ingress, desiccant may be introduced into the liner 9 before it is welded closed using any of the techniques discussed above.
As mentioned above, the materials used in conventional sample analysis cartridges do have significant issues with fluid permeability, particularly in relation to moisture ingress. As shown in
Number | Date | Country | Kind |
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2017920.6 | Nov 2020 | GB | national |
The present application is a national stage application under 35 U.S.C. § 371 of International Application No. PCT/GB2021/052930, filed Nov. 12, 2021, which claims priority to Great Britain Patent Application No. 2017920.6, filed Nov. 13, 2020. The above referenced applications are hereby incorporated by reference in their entirety.
Filing Document | Filing Date | Country | Kind |
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PCT/GB2021/052930 | 11/12/2021 | WO |