Sample transfer element, kit and method

Abstract

A sample transfer element for transferring a sample from a first sample vessel to a second sample vessel, the sample transfer element comprising: a first interface configured to engage with the first sample vessel; and a second interface configured to engage with the second sample vessel.

Description

SAMPLE TRANSFER ELEMENT, KIT AND METHODFIELD OF THE INVENTION

[0001] The application relates to sample transfer elements for transferring a sample. The application also relates to kits comprising sample transfer elements. The application also relates to methods using such transfer elements or kits, including methods for collection, preparation, and / or storage of samples.

[0002] Such transfer elements and kits are used in a variety of fields including but not limited to medical testing in humans and animals, medicines manufacturing, quality control for biological and bio-mimicking enzymes, monitoring for environmental nucleic acid detection, and biotechnology research and development.BACKGROUND

[0003] In traditional medical practice, a collected sample must be handled using laboratorygrade tools, such as high-precision pipettes for liquid transfer. Given the biohazardous nature of the materials involved (e.g., samples and reagents), this work must be carried out by trained laboratory technicians. As a result, gold-standard testing is restricted to laboratory settings, which are often distant from patients who require timely results, and to facilities with the resources to maintain such laboratories.

[0004] Similarly, in non-medical fields, tests for biological or bio-similar indicators, such as nucleic acids, as well as non-biological agents such as engineered RNA sequences, face similar restrictions. The reliance on laboratory environments and skilled personnel makes it difficult for these tests to provide a sample-to-answer experience for environmental, industrial, or research applications, especially at the point and time of need.

[0005] As a result, it is desirable to provide methods, apparatus and / or kits which minimize handling of a sample, e.g., avoiding manual processes such as pipetting, liquid sample handling, mixing with reagents or solvents.

[0006] For example, traditional nucleic acid amplification and detection technologies (NAAT) such as polymerase chain reaction (PCR) require a sample to be collected and processed at a dedicated laboratory, often requiring expensive technician time and laboratory infrastructure. This commonly requires a laborious protocol of filtration, lysis, washing, and elution performed manually to extract and concentrate DNA from the sample, and mix the sample with NAAT reagents.

[0007] There exists a need for a sample collection device, apparatus or kit that integrates at least some of the steps highlighted above, while avoiding excess processing and user input during sample preparation from collection to testing. Desirably, such solutions would enable preparation of a sample for NAAT in a single, contained, process, while enabling features of a conventional protocol of sample or target collection for NAAT for both medical or nonmedical uses.SUMMARY

[0008] The application provides sample transfer elements, kits and methods as set out in the attached claims.

[0009] According to a first aspect, a sample transfer element is provided for transferring a sample from a first sample vessel to a second sample vessel. The sample transfer element comprises: a first interface configured to engage with the first sample vessel; and a second interface configured to engage with the second sample vessel. Optional features of the sample transfer element are set out in dependent claims 2 to 17.

[0010] According to a second aspect, a kit is provided. The kit comprises: a sample transfer element according to the first aspect, and the second sample vessel. Optional features of the kit are set out in dependent claims 2 to 17 and 19 to 34.

[0011] According to a third aspect, a method is provided for processing a sample. The method comprises: collecting a sample in a first sample vessel; using a sample transfer element according to the first aspect or a kit according to the second aspect, transferring the sample from the first sample vessel to a second sample vessel; and processing the sample in the second vessel. Optional features of the method are set out in dependent claims 2 to 17, 19 to 34 and 36 to 45.

[0012] The claimed features address the problems set out in the background section. Further advantages associated with the claimed features are identified in the following description.BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Figure 1 schematically illustrates stages of using a kit comprising a sample transfer element, in an embodiment;

[0014] Figure 2 provides photos and schematic illustrations of an embodiment;

[0015] Figure 3 schematically illustrates a kit comprising a sample transfer element, in an embodiment;

[0016] Figure 4 schematically illustrates a cross-section of an assembled kit, in an embodiment;

[0017] Figures 5A to 5C schematically illustrate a mechanical linkage for a plurality of drive mechanisms;

[0018] Figures 6A to 6C schematically illustrate a method of processing a sample;

[0019] Figure 7 schematically illustrates a cross-section of an assembled kit, in another embodiment;

[0020] Figure 8 schematically illustrates a cross-section of an assembled kit, in another embodiment;

[0021] Figure 9 schematically illustrates a cross-section of an assembled kit, in another embodiment;

[0022] Figure 10A schematically illustrates a cross-section of an assembled kit, in another embodiment; and Figure 10B is a photo illustration of this embodimentDETAILED DESCRIPTION

[0023] Figure 1 is a conceptual drawing showing a single apparatus or single step sample collection or storage and processing kit for nucleic acid amplification and / or detection.

[0024] At a first stage, a sample is collected using a first sample vessel. The first sample vessel may be a standard collection tube, such as a tube for samples containing nucleic acid.

[0025] The first sample vessel may be initially capped or sealed as per general procedure, or may be left uncapped.

[0026] A sample transfer element is then fitted to the first sample vessel. The sample transfer element may replace any cap that was previously applied to the first sample vessel. The sample transfer element may be configured as a cap or seal. The sample transfer element may comprise a filter. The filter may, for example, be a microfluidic filter. The sample transfer element may comprise one or more process agents such as reagents, solvents, or other components for mixing with and / or processing the sample. The sample transfer element may comprise a valved tube.

[0027] A second sample vessel is fitted to an opposing side of the sample transfer element. The second sample vessel may be a vessel suitable for insertion in devices such as a PCR amplification system and / or a centrifuge.

[0028] Inverting the sealed kit transfers a portion of the sample from the first sample vessel into the second sample vessel. The portion of the sample may have a fixed volume, where the volume is controlled by a valve of the sample transfer element and / or a valve of the second sample vessel. Inverting the sealed kit may also cause the portion of the sample to mix with process agent(s) and / or pass through a filter.

[0029] Figure 2 shows one example application of the above-described sample transfer element and kit. Panel A is a photo of the collection kit in an embodiment. Panel B is a schematic illustration of the kit components in this embodiment. Panel C shows a kit according to this embodiment, arranged to position the second sample vessel in a nucleic acid amplification machine.

[0030] In this example, the sample is a urine sample, as an example of human tissue collection. The sample is collected using a standard urine or human tissue collection space by the user. A standard seal or cap is then replaced with a sample transfer element according to the invention. The sample transfer element in this example is fitted with a filter, lyophilised reagents, and a multi-valved PCR tube (figure 2A and 2B). Inverting the sealed kit filters the sample, dispenses a fixed volume (guided by valving) into a nucleic acid amplification, reaction or detection tube where it mixes with reagents in the tube. The tube and the overall kit are configured to fit directly into a nucleic acid amplification for detection device (figure 2C), entirely removing the need for manual sample (e.g., urine) handling.

[0031] Embodiments which reduce or avoid the need for manual sample handling may be particularly useful for plasmonic PCR, which is a PCR technique that has minimum requirements for sample processing. Plasmonic PCR is one of the fastest PCR detection processes which benefits greatly from fast sample preparation.

[0032] Figure 3 shows an example internal structure of a sample transfer element according to the invention.

[0033] Referring to Figure 3, the sample transfer element 100 is configured as a cap or a sealing mechanism. An inner side of the cap / seal comprises an inlet 110 configured to receive a portion of a sample from a first sample vessel 10.

[0034] The first sample vessel 10 and the sample transfer element 100 have complementary screw threads 11 , 101 to hold the first sample vessel 10 together with the sample transfer element 100. In other embodiments, the first sample vessel 10 and the sample transfer element 100 may engage using another known mechanism, such as an interference fit. The sample transfer element 100 may also have a sealing element on the inner side to reduce the risk of leakage between the first sample vessel 10 and the sample transfer element 100. In other examples, any suitable interface may be used for connecting the first sample vessel 10 to the sample transfer element 100.

[0035] The inlet 110 connects to an inner volume of the sample transfer element 100 in which an (optional) filter 130 and an (optional) process agent 140 are arranged. The process agent may comprise one or more reagents, solvents, distillation fluids, or other components for mixing with and / or processing the sample. The filter 130 and the process agent 140 may be combined into a single element, for example by impregnating a filter material with a predetermined quantity of the process agent. The process agent may be configured as a lining or a seal, such that the sample flows past the process agent or breaks through the process agent as it is transferred through the sample transfer element 100.

[0036] The inner volume also connects to an outlet 120 on an outer side of the cap. The outlet 120 is configured to engage with a second sample vessel 20.

[0037] The sample transfer element 100 may also comprise one or more valves. The one or more valves may comprise a valve for controlling a volume of the portion of the sample that is transferred to the second sample vessel 20. The valves may comprise a one-way valve configured to prevent flow in an unintended direction through the transfer element, such as preventing flow from the second sample vessel to the first sample vessel.

[0038] In some embodiments, the portion of the sample is driven by gravity through the sample transfer element 100, when the kit is assembled and appropriately oriented.

[0039] Fig. 4 shows a schematic cross section of a kit according to a further detailed embodiment A. In this embodiment, the kit comprises a sample transfer element A100, a first sample vessel A10, a second sample vessel A20, a driving element A30 a valve A40 and a seal A50.

[0040] The first sample vessel A10 is configured to store a sample A1 .

[0041] The sample A1 may be an unprocessed sample when it is initially received in the first sample vessel A10.

[0042] In some cases, the first sample vessel A10 is also configured to be used for collection and / or initial processing of the sample. The first sample vessel may be a standardized sample vessel.

[0043] In various uses, the sample A1 may be collected as a liquid sample. In other use cases, the sample A1 may be a processed sample obtained by collecting a solid sample, and processing the solid sample in order to produce a liquid sample product A1.

[0044] The sample A1 may have any volume depending on the application. In typical examples, the sample A1 may have a volume of less than 500 ml. In typical examples, the sample A1 may have a volume of more than 100 pl, or more than 1 ml, or more than 10 ml.

[0045] The sample A1 may be subjected to various processes while in the first sample vessel A10. For example, the sample A1 may be mixed with a solvent such as a buffer (such as PBS phosphate buffer solution) or water and / or mixed with a reagent.

[0046] The sample transfer element A100 is configured to transfer at least a portion of the sample A1 (in an original collected state or a processed state) from the first sample vessel A10 to a second sample vessel A20.

[0047] The second sample vessel A20 may, for example, be a vessel suitable for retaining the sample while a process is applied, such as an NAAT process. For example, the second sample vessel A20 may be a standard vessel for performing PCR. In some embodiments, the second sample vessel A20 and the sample transfer element A100 may be configured such that the second sample vessel A20 can remain attached to the sample transfer element A100 while the NAAT process is performed. For example, a combined shape of the second sample vessel A20 and the sample transfer element A100 may be adapted to fit with a PCR or qPCR apparatus.

[0048] The second sample vessel A20 may additionally contain one or more process agents, in a liquid or solid form, prior to receiving a sample. For example, the second sample vessel may contain one or more PCR reagents. These process agents will mix with the sample as received via the sample transfer element A100.

[0049] The second sample vessel A20 may additionally or alternatively comprise one or more protective elements configured to protect the sample after it is received in the second sample vessel. In one example, a protective element may be configured to inhibit evaporation, such that the sample remains in liquid form within the second sample vessel. This may be particularly useful in embodiments where the second sample vessel is to be subjected to aprocess that involves heating, such as PCR. The protective element may be provided within the second sample vessel A20. For example, the protective element may comprise a liquid stored in the second sample vessel. In one case, the second sample vessel A20 may be provided with a relatively low density liquid as the protective element, such that the protective element can be expected to rise to a surface of the sample and protect the surface of the sample from contacting air, thus inhibiting evaporation. The protective element may, for example, comprise an oil, a wax or a petroleum jelly. In another example, a protective element may be configured to facilitate a process in the second sample chamber. For example, the protective element may be configured to prevent reagents from sticking to an inner wall of the second sample chamber, such as a bottom end of the second sample chamber. This may be achieved by providing an initially solid or rigid element in the second sample vessel. For example, the solid or rigid element may comprise an oil, wax or petroleum jelly which initially acts as a solid or rigid barrier for one or more components (such as process agents) stored in the second sample vessel. Furthermore, the initially solid or rigid element may be configured to act as a container for one or more components (such as process agents) within the second sample vessel.

[0050] The volume of sample received in the second sample vessel A20 will typically be on the scale of microliters. For example, the volume of sample received in the second sample vessel A20 may be less than 1 ml, less than 100 pl, or less than 40 pl, or less than 10 pl.

[0051] The second sample vessel A20 may additionally comprise a seal in an initial state. The seal may be broken when the second sample vessel is assembled with the sample transfer element. For example, the outlet A120 may comprise an element such as a sharp edge suitable for breaking the seal. Alternatively, the seal may be manually removed prior to using the second sample vessel with the sample transfer element.

[0052] In this embodiment, the sample transfer element A100 comprises an inlet A110 for receiving the sample from the first sample vessel A10, an outlet A120 for supplying the sample to the second sample vessel A20, and a process agent supply A150. The inlet A110, outlet A120 and process agent supply A150 may each comprise a tube, which may for example be constructed from an inert, medically safe material. In some embodiments, these tubes may be macrofluidic tubes (as opposed to microfluidic channels). In many embodiments, which at least partly rely on gravity to transfer the sample, the inlet A110 and outlet A120 are generally at opposite ends of the sample transfer element A100, such that the sample transfer element can be oriented vertically with the inlet A110 higher than the outlet A120. However, the inlet A110 and outlet A120 need not be at extreme ends of the sample transfer element A100. Furthermore, in embodiments which do not rely on gravity to transfer the sample from the inletto the outlet, the inlet A110 and outlet A120 need not be at opposite ends, and may, for example, be located at a same end of the sample transfer element.

[0053] The inlet A110, outlet A120 and process agent supply A150 are each connected to a mixing chamber A170, such that the sample can be mixed with a process agent before being delivered to the second sample vessel A20. The mixing chamber A170 may simply be a junction between the inlet A110, outlet A120 and process agent supply A150, as shown in Fig. 4. Alternatively, the mixing chamber may be more of a dedicated chamber, as shown in the previous example of Fig. 3.

[0054] The sample transfer element may further comprise a mix enhancing element (not shown), to enhance mixing in the mixing chamber A170. For example, the mix enhancing element may comprise a stirring element, a vibrating element or a heating element for convective mixing. The mix enhancing element may be externally driven. For example, the mix enhancing element may be a magnetic element, similar to a magnetic stirrer. The mix enhancing element may be confined in the mixing chamber A170, for example by using a mix enhancing element that is too large to pass through the inlet A110 or the outlet A120.

[0055] Alternatively, even if the sample transfer element does not specifically include a mix enhancing element, mixing may be stimulated by external processes such as vibrating, shaking, flicking, heating, or inverting the sample transfer element A100. These external processes may be performed manually or (more preferably in many circumstances) using a suitable machine for holding the transfer element and applying the required motion. As a further alternative, diffusion may be sufficient to mix the sample with the process agent when they meet in the mixing chamber A170, in which case it is not necessary to stimulate further mixing.

[0056] The embodiment of Fig. 4 is particularly applicable to cases where the sample A10 needs to be mixed with a liquid process agent A2. The process agent A2 may, for example, comprise a dilution agent or solvent, such as water. The process agent A2 may additionally or alternatively comprise a reagent intended to chemically or biologically interact with the sample. In some cases, a component of the process agent may be stored in a solid form (such as a lyophilised form) prior to mixing.

[0057] The sample transfer element A100 may comprise a process agent chamber A160 for storing the process agent A2 or a component of the process agent. The process agent chamber A160 may be filled with the relevant process agent at a manufacturing stage. Additionally or alternatively, the sample transfer element A100 may comprise a port foraccessing and filling the process agent chamber A160. In cases where multiple processes need to be applied to the sample, or multiple process agents need to be stored separately prior to mixing with the sample, the sample transfer element A100 may comprise multiple process agent chambers A160. In some embodiments, the process agent A2 (or a component of the process agent A2) may be stored in the mixing chamber A170, such that a separate process agent chamber A160 is not needed for the process agent (or at least not needed for that component of the process agent A2).

[0058] As shown in the example of Fig. 4, the process agent A2 may be retained in the process agent chamber A160 without a seal. For example, surface tension or capillary tube effects may be used to retain the process agent A2. Alternatively, the process agent chamber A160 may comprise a valve or seal which can be breached or released at an appropriate time in order to supply the process agent A2 to the mixing chamber A170 via the process agent supply A150.

[0059] The sample transfer element may comprise one or more filters arranged to filter any of the liquids that move within the sample transfer element. The filter(s) may, for example, include microfluidic filter(s). In Fig. 4, a filter A130 is provided in the inlet A110, in order to filter the sample before it reaches the mixing chamber A170. In other embodiments, it may be useful to include a filter in the outlet A120, after the mixing chamber A170, if it is expected that the mixing may produce sample components that are not to be delivered to the second sample vessel A20 as part of the transferred sample A3. Furthermore, it may be useful to filter the process agent A2 in some embodiments, especially if there is a possibility that the process agent will be stored for an extended period before use - this filtering may extend the shelf-life of a sample transfer element A100 that is manufactured with a reservoir of the process agent A2.

[0060] The sample transfer element may further comprise one or more valves A40. The one or more valves may comprise a valve for controlling a volume of the portion of the sample that is transferred to the second sample vessel 20. The valves may comprise a one-way valve configured to prevent flow in an unintended direction through the transfer element, such as preventing flow from the second sample vessel to the first sample vessel. A valve which fulfils both of the "direction-controlling" and "volume-controlling" properties may, for example, comprise a floating-seal-type valve in which a floating element travels upstream towards a valve point as fluid passes the valve point, until the floating element meets and blocks the valve point. For example, as illustrated in Fig. 4, a one-way volume-controlling valve may be provided at the outlet A120, in order to control the volume delivered to the second sample vessel A20 and also prevent any fluid from moving from the second sample vessel A20 to themixing chamber A170. The valve A40 may be provided as part of the sample transfer element A100, as part of the second sample vessel A20, or as a separate component which must be positioned between the outlet A120 and the second sample vessel A20 when assembling a kit embodiment More generally, volume-controlling valves and / or direction-controlling valves may be provided at any suitable location in the sample transfer element A100, including the inlet A110, the outlet A120 , the process agent supply A150, or within the mixing chamber A170.

[0061] As also shown in Fig. 4, the second sample vessel A20 may be attached to the transfer element A100. In some embodiments, a sealing protective film A50 may be used to attach the second sample vessel A20, as well as sealing the attachment against any liquid leaks.

[0062] In some embodiments, the transfer element A100 may be provided as part of a kit, together with the first sample vessel A10 and / or the second sample vessel A20 (and optionally any other separately provided components such as the plunger(s) A30, the valve A40 and / or the protective film A50). For such embodiments, an end user (such as a laboratory technician) is expected to assemble a combined system, for example as shown in Fig. 4. This assembly nevertheless requires less labour from the technician, by comparison to less integrated and enclosed systems, and carries a lower risk of contamination.

[0063] In some embodiments, the second sample vessel may be permanently attached to the sample transfer element. Such permanent attachment may be suitable if, for example, the combined sample transfer element A100 and second sample vessel A20 are suitable for use together in a PCR apparatus. Herein, the term "permanent" should be understood in terms of the purpose of the sample transfer element and the second sample vessel. In other words, a permanent attachment means that it is not expected or possible that the second sample vessel will be separated from the sample transfer element during normal usage, and they are attached in such a way that separating the second sample vessel from the sample transfer element is likely to damage either or both of these parts, such that they are likely to no longer be suitable for use in sample handling, processing or analysis. As examples of permanent attachment, the second sample vessel A20 could, for example, be formed as a sealed end to the outlet 120.

[0064] As further shown in Fig. 4, a plunger A30 may be provided in order to actuate the sample transfer. The plunger may be provided as a separate component, as part of a kit, or may be attached to the sample transfer element at a manufacturing stage. In some embodiments, the plunger may be permanently attached to the sample transfer element. Forexample, when a kit is assembled, the plunger may attach to the sample transfer element with a snap-fit connection that is irreversible without risking damage to the plunger and / or damage to the sample transfer element.

[0065] The plunger A30 may be configured to perform one or more different functions.

[0066] In some embodiments, the plunger A30 comprises a first drive mechanism A31 configured to drive the sample A1 from the first sample vessel A10 and into the sample transfer element. Additionally or alternatively, the plunger A30 may comprise a second drive mechanism A32 configured to drive the process agent A2 from the process agent chamber A160 to the mixing chamber A170.

[0067] In some embodiments, the first and second drive mechanisms may be mechanically linked (either via the plunger, or via another mechanical linkage). In other embodiments, the first and second drive mechanisms may each be provided with a separate plunger, so that they can be controlled individually.

[0068] Referring now to Figs 5A to 5C, in embodiments where the first and second drive mechanisms are linked together, the drive mechanisms may nevertheless be configured to allow some independent movement, within a movement range.

[0069] More specifically, as shown in Fig. 5A, each of the first and second drive mechanisms may comprise an actuation element A31 , A32 configured to move along a respective guide A33, A34. The actuation elements may be linked together using a pin and slot linkage A35, A36 such that the first drive mechanism A31 can move relative to the second drive mechanism A32 (and vice versa) within a first range of motion.

[0070] The motion between Figs. 5A and 5B illustrates this first range of motion. This represents a stage in which one of the sample A1 and the process agent A2 is being driven towards the mixing chamber A170, while the other is not being driven. For example, a portion of the process agent A2 may be pre-loaded into the mixing chamber A170 before the sample A1 is driven into the sample transfer element A100, or vice versa.

[0071] As further shown in Fig. 5C, when the pin A35 abuts an end of the slot A36, the first and second drive mechanisms move simultaneously in a second range of motion. This represents a stage at which both of the sample A1 and the process agent A2 are being driven towards the mixing chamber A170.

[0072] In general, in embodiments which use multiple drive mechanisms, the drive mechanisms may be operated in any order, and with any relative offset, using linkages such as shown in Figs. 5A to 5C.

[0073] The plunger(s) may be configured to operate as a mechanical pressure creation mechanism (such as a locally, physically-driven pneumatic linkage). For example, when the first drive mechanism is operated, it may push air into the first sample vessel A10, and thereby displace a corresponding volume of the sample A1 into the inlet A110 of the sample transfer element A100. This may require airtight interfaces between the sample transfer element A100 and the other components (including tight fit between drive mechanism(s) and the sample transfer element). Such airtight interfaces may, for example, comprise threaded interfaces, interference fits, rubberised o-rings or gaskets, and / or skirts or convoluted paths. These locally-applied mechanical pressure creation mechanisms may be contrasted with other systems that rely on an external pressure source (such as a gas or liquid supply). In general, embodiments of this application preferably do not require an external pressure supply or external apparatus to function.

[0074] Each driving mechanism may be configured to displace a predetermined volume of fluid. For example, the predetermined volume may be calculated based on a surface area of a fluid-facing end of the actuation element 31 , 32, and based on a range of motion of the actuation element 31 , 32.

[0075] As shown in Fig. 4, the plunger(s) may be operated using a push action; equally, the plunger(s) may be configured to drive the sample and / or a process agent based on a pull action - the skilled person would be able to envisage a variety of mechanical linkages for controlling the drive mechanisms using any relevant motion of a plunger, handle etc. and in any direction relative to (towards, away from, perpendicular, around etc.) the sample transfer element, and the invention is not limited to any specific user interaction implementation. Indeed, in some examples, the transfer is driven by gravity and a user-controlled drive mechanism is unnecessary.

[0076] Figs. 6A to 6C schematically illustrate an example method for processing a sample, using the sample transfer element of Fig. 4.

[0077] Referring to Fig. 6A, at a first step S1 , the sample A1 is obtained and stored in the first sample vessel A10. As mentioned above, the first sample vessel may be a standardized sample vessel. Many types of sample vessel are designed to interface with a cap, lid or other seal, in order to prevent leakage or contamination of the sample. During storage, the firstsample vessel A10 is typically oriented with its (sealed) opening upward, to reduce the risk of spills or leakage.

[0078] As also shown in Fig. 6A, at this point in the process, the sample transfer element A100 may be detached from the first sample vessel A10. Alternatively, the sample transfer element may be used instead of the cap / lid / seal, to seal the sample in the first sample vessel A10, until the user is ready to transfer the sample to a second sample vessel A20. For example, a first interface of the sample transfer element A101 , adjacent to the inlet A110, may be designed to match a standard sealing mechanism of the first sample vessel A10, for example by imitating the interface of a cap that is normally supplied with the first sample vessel A10.

[0079] Additionally, as shown in Fig. 6A, at this point in the process, the second sample vessel A20 may already be attached to the first sample vessel A10. For example, as described above, the second sample vessel and the sample transfer element may be manufactured, sold or stored as a single unit, until they are needed to receive a sample.

[0080] Referring to Fig. 6B, at a second step S2, the first sample vessel A10 is engaged with the first interface A101 of the sample transfer element A100. Typically, at this stage, the first sample vessel is still oriented with its opening upward, to avoid spillage of the sample. Accordingly, the first interface A101 of the sample transfer element A100 is oriented to face downward. This forms a completed kit in which the sample transfer element has a (preferably sealed) fluid connection with both of the first sample vessel and the second sample vessel. If a cap was previously used to seal the first sample vessel A10, then the cap may be removed in order to engage with the first interface A101. Alternatively, the first interface A101 may be configured to engage with the first sample vessel A10, even without removing its standard cap. For example, the first sample vessel A10 may comprise a valve configured to engage with inlet A110. Furthermore, the sample transfer element may be connected to the first and second sample vessels in any order, so the second sample vessel may be connected to the sample transfer element before or after the illustrated step S2.

[0081] Referring to Fig. 6C, at a third step, the fully assembled kit is inverted, such that the first interface A101 of the sample transfer element A100 now faces upward, and the first sample vessel A10 is raised above the second sample vessel A20, such that gravity can assist transfer of the sample.

[0082] However, in this embodiment, because the connection between the first interface A101 and the first sample vessel A10 is airtight, the sample A1 does not immediately flow into the sample transfer element, allowing the user control of the transfer process.

[0083] At fourth step, also shown in Fig. 6C, the user operates the plunger A30. In this embodiment, the single plunger is connected to both of the first sample vessel A10 and the process agent chamber A160. As a result, at fifth step (labelled 5a) the plunger operation drives both of a portion of the sample A1 and a portion of the process agent A2 towards the mixing chamber A170 where they mix together (labelled 5b) before passing through the valve A40 into the second sample vessel A20 (labelled step 5c).

[0084] This may be viewed as a surprising effect. Even if there is air in the first sample vessel A10, and even though it is expected that there may be air in the inlet A110 tube, the inventors have found, when using a drive mechanism, that this technique enables precise control of when and what volume of sample is dispensed into the sample transfer element and ultimately into the second sample vessel.

[0085] After the method steps of Figs. 6A to 6C are completed, the method may continue with inserting the second sample vessel A20 into a sample processing apparatus for further processing of the sample while it is stored in the second sample vessel. For example, the second sample vessel may be inserted into a PCR apparatus or a centrifuge.

[0086] Fig. 7 schematically illustrates an alternative detailed embodiment B. Features which are comparable to the embodiment A of Fig. 4 are indicated by using the same numeral for the B embodiment. For example, figure labels A1 and B1 both refer to the sample as initially stored in the first sample vessel B10 (A10). For conciseness, details which are shared with embodiment A are not repeated, and the following description of Fig. 7 relates only to the differences between embodiments A and B. Accordingly, it may be assumed that the features of embodiment A (including the method of using embodiment A, as illustrated in Figs 6A to 6C) are equally applicable to embodiment B, unless stated otherwise below.

[0087] Embodiment B as shown in Fig. 7 differs from embodiment A in that the process agent B2 is stored directly in the mixing chamber B170, and the process agent chamber A160, and the process agent supply A150, are omitted from this embodiment. Nevertheless, the sample transfer element B100 is configured such that similar mixing occurs when the sample B1 is introduced into the mixing chamber B170, as described above for embodiment A.

[0088] Additionally, embodiment B differs from embodiment A in that the sample transfer element B100 is not configured to use a plunger. Instead the assembled kit uses gravity totransfer the sample B1 from the first sample vessel B10, through the filter B130 and the mixing chamber B170 to the second sample vessel B20.

[0089] For embodiment B it is envisaged that a valve B40 at the outlet of the sample transfer element may be implemented as a floating-seal-type valve (as described in more detail above). Furthermore, the second sample vessel B20 may initially comprise a sealed protective film. This protective film may be calibrated to break under the weight of the processed sample, or to break when the sample transfer element B100 and the second sample vessel B20 are pushed together. For example, the seal may be configured such that inserting the assembled kit into a sample processing apparatus (such as a PCR apparatus) can be expected to break the seal.

[0090] Fig. 7 also illustrates how the sample transfer element B100 may itself be distributed as a kit of smaller parts, and assembled for use. As an example, in Fig. 7, a snap fit connection is shown between an inlet-and-first-interface section B101 , which is configured to engage with the first sample vessel B10, and a filter section B130. Furthermore, different cross-section hatching is used to illustrate several different sections of the mixing chamber B170 which are configured to engage with each other in the assembled sample transfer element B100.

[0091] Fig. 8 schematically illustrates an alternative detailed embodiment C. Features which are comparable to the embodiment A of Fig. 4 are indicated by using the same numeral for the C embodiment. For example, figure labels A1 and C1 both refer to the sample as initially stored in the first sample vessel C10 (A10). For conciseness, details which are shared with embodiment A are not repeated, and the following description of Fig. 8 relates only to the differences between embodiments A and C. Accordingly, it may be assumed that the features of embodiment A (including the method of using embodiment A, as illustrated in Figs 6A to 6C) are equally applicable to embodiment C, unless stated otherwise below.

[0092] Embodiment C as shown in Fig. 8 differs from embodiment A in that the process agent C2 is stored directly in the mixing chamber C170, and the process agent chamber A160, and the process agent supply A150, are omitted from this embodiment. Nevertheless, the sample transfer element C100 is configured such that similar mixing occurs when the sample C1 is introduced into the mixing chamber C170, as described above for embodiment A.

[0093] Additionally, embodiment C differs from embodiment A in that the sample transfer element C100 is configured to use a different combination of drive mechanisms. More specifically, drive mechanism C31 performs a function similar to drive mechanism A31 , and isconfigured to drive the transfer of the sample C1 from the first sample vessel C10 into the sample transfer element C100.

[0094] On the other hand, drive mechanism C33 is configured to perform a different function from the drive mechanisms of embodiment A. More specifically, drive mechanism C33 is configured to drive the mixed sample from the mixing chamber C170 into the second sample vessel C20. This can be used to allow the user to control the length of a mixing time in which the sample C1 mixes with the process agent C2, before being transferred to the second sample vessel C20. One or more one-way valves C180 may be provided in order to ensure that the driving force provided by drive mechanism C33 acts to push the mixed sample towards the second sample vessel C20, and not back along the inlet 0110. The valves may also be configured to resist opening sufficiently to prevent the mixed sample from flowing to the second sample vessel C20 before the user actuates the drive mechanism C33.

[0095] Fig. 9 schematically illustrates an alternative detailed embodiment D. Features which are comparable to the embodiment C of Fig. 8 are indicated by using the same numeral for the D embodiment. For example, figure labels C1 and D1 both refer to the sample as initially stored in the first sample vessel D10 (C10). For conciseness, details which are shared with embodiment C are not repeated, and the following description of Fig. 9 relates only to the differences between embodiments C and D. Accordingly, it may be assumed that the features of embodiments A and C (including the method of using embodiment A, as illustrated in Figs 6A to 60) are equally applicable to embodiment D, unless stated otherwise below.

[0096] Embodiment D as shown in Fig. 9 differs from embodiment C in that the sample transfer element comprises multiple outlets D120-1 to D120-n, each of which is configured to engage with a respective second sample vessel D20-1 to D20-n. More specifically, in this example, the outlet comprises a single initial section D120 connected to the mixing chamber D120. This initial section branches out into the plurality of outlets D120-1 to D120-n. This enables a single sample transfer element to fill multiple second sample vessels D20-1 to D20- n using a single simplified process, further reducing the time and labour taken from laboratory technicians when preparing samples for further processing (such as PCR or centrifugation).

[0097] In other embodiments such branching may be configured at a different part of the sample transfer element. For example, the sample transfer element could be configured with a branching point in the inlet D110, and a mixing chamber for each of the plurality of outlets, with each mixing chamber being connected to a respective outlet.

[0098] Figs. 10A and 10B schematically illustrate an alternative detailed embodiment E. Features which are comparable to the embodiment A of Fig. 4 are indicated by using the same numeral for the E embodiment. For example, figure labels A1 and E1 both refer to the sample as initially stored in the first sample vessel E10 (A10). For conciseness, details which are shared with embodiment A are not repeated, and the following description of Figs. 10A and 10B relates only to the differences between embodiments A and E. Accordingly, it may be assumed that the features of embodiment A (including the method of using embodiment A, as illustrated in Figs 6A to 6C) are equally applicable to embodiment E, unless stated otherwise below.

[0099] Embodiment E as shown in Figs. 10A and 10B differs from embodiment A in that the mixing chamber A170 is entirely omitted, along with the process agent supply A150, the process agent chamber A160 and the second drive mechanism A32. In other words, the sample transfer element E100 comprises an inlet E110 which is directly connected to the outlet E120 without any intermediate mixing.

[0100] In embodiment E, the first drive mechanism E31 and a valve E180 are used together to control dispensing of a portion of the sample E1 from the first sample vessel E10 into the second sample vessel E20.

[0101] This embodiment may be particularly useful in scenarios where it is desirable to dispense a small portion of a sample from a larger vessel into a smaller vessel, while avoiding the need for a pipette, a simple syringe or another manual process. This may help to reduce workload and also decrease the risk of contamination or wastage of a sample.

[0102] As mentioned above, any of the described embodiments, and other embodiments falling within the claim scope, may be configured such that the second sample vessel can be subjected to further sample processing, while remaining attached to the sample transfer element.

[0103] For example, the combined kit (with or without the original first sample vessel) may be inserted into a sample processing apparatus, such as a PCR apparatus.

[0104] Such processing apparatuses may have means for identifying an inserted sample vessel, such as an RFID tag reader, a barcode reader, or other passive or active communication means for obtaining data from the sample vessel. Such identifiers can additionally or alternatively be used for identifying further details such as identifying a protocol to run on the sample, identifying reaction parameters and so on.

[0105] With respect to sample transfer elements and kits according to the invention, the sample transfer element may comprise an identifier, in addition to or alternative to the second sample vessel. This identifier may include any of an active electronic communication system (for wireless communication with the sample processing apparatus, or wired communication using appropriate electrical contacts), a passive electronic communication system (such as an RFID tag), and / or a non-electronic identifier (such as a bar code or other visual identifier).

[0106] Including an identifier on the sample transfer element may have advantages over including an identifier on the second sample vessel. For example, in many embodiments, the sample transfer element may be larger than the second sample vessel, providing more space for a larger or more complex identifier. Additionally, when the second sample vessel is positioned for sample processing in the sample processing apparatus, it may be difficult to for the apparatus to read the identifier. On the other hand, a sample transfer element which is attached to the second sample vessel, but is not fully inserted for sample processing (e.g. PCR processing) may be more readily accessible to automatically or manually read an identifier.

[0107] The above described embodiments have been provided as examples only. Many other combinations of the described features are possible within the scope of the attached claims.

Claims

Claims1. A sample transfer element for transferring a sample from a first sample vessel to a second sample vessel, the sample transfer element comprising: a first interface configured to engage with the first sample vessel; and a second interface configured to engage with the second sample vessel.

2. A sample transfer element according to claim 1, configured as a cap or as a partial seal for the first sample vessel.

3. A sample transfer element according to claim 2, wherein the cap comprises an inner face and an outer face, the inner face comprising an inlet for receiving liquid from the first sample vessel and the outer face comprising an outlet for delivering liquid to the second sample vessel.

4. A sample transfer element according to any of claims 1 to 3, wherein the first interface comprises an engagement element for holding the first sample vessel and / or for forming a sealed connection to the first sample vessel.

5. A sample transfer element according to claim 4, wherein the first interface comprises a screw thread for engaging with a corresponding screw thread of the first sample vessel, or wherein the first interface is configured to form an interference fit with the first sample vessel.

6. A sample transfer element according to any of claims 1 to 5, comprising a mixing element configured to mix a process agent with the sample as the sample is transferred from the first sample vessel to the second sample vessel, wherein the process agent comprises one or more of a reagent and / or a solvent.

7. A sample transfer element according to claim 6, wherein the mixing element is a mixing chamber.

8. A sample transfer element according to claim 7, wherein the transfer element is configured to dispense the process agent into the mixing chamber.

9. A sample transfer element according to claim 8, further comprising a process agent reservoir.

10. A sample transfer element according to any of claims 6 to 9, further comprising a mix enhancing element configured to enhance mixing of the sample with the process agent in the mixing element.

11. A sample transfer element according to any of claims 1 to 10, comprising a filter configured to filter the sample as the sample is transferred from the first sample vessel to the second sample vessel.

12. A sample transfer element according to any of claims 6 to 10 and claim 11 , wherein the filter is the mixing element.

13. A sample transfer element according to any of claims 6 to 12, wherein the mixing element and / or the filter is replaceable.

14. A sample transfer element according to any of claims 1 to 13, wherein the sample transfer element is configured to transfer the sample under gravity.

15. A sample transfer element according to any of claims 1 to 14, further comprising a volume-controlling valve for controlling a volume of the sample transferred from the first sample vessel to the second sample vessel and / or a direction-controlling valve configured to control a direction of transfer of the sample.

16. A sample transfer element according to any of claims 1 to 15, further comprising a sample identification element configured to be passively or actively read by a sample processing apparatus that is also configured to receive and process the sample while stored in the second sample vessel.

17. A sample transfer element according to any of claims 1 to 16, comprising a plurality of second interfaces configured to engage with a plurality of second sample vessels.

18. A kit comprising: a sample transfer element according to any of claims 1 to 17, and the second sample vessel.

19. A kit according to claim 18, wherein the second sample vessel is permanently attached to the sample transfer element.

20. A kit according to claim 18 or claim 19, further comprising the first sample vessel.

21. A kit according to claim 20, wherein a volume of the first sample vessel is greater than a volume of the second sample vessel.

22. A kit according to any of claims 18 to 21 , wherein the second sample vessel comprises a volume-controlling valve.

23. A kit according to any of claims 18 to 22, wherein the second sample vessel is suitable for performing a PCR reaction on the sample, while the sample is contained in the second sample vessel.

24. A kit according to any of claims 18 to 23, wherein the second sample vessel comprises a protective element configured to protect the sample after it is received in the second sample vessel.

25. A kit according to claim 24, wherein the protective element is configured to inhibit evaporation, such that the sample remains in liquid form within the second sample vessel.

26. A kit according to claim 25, wherein the protective element comprises a liquid.

27. A kit according to any of claims 18 to 26, further comprising a first drive mechanism, wherein the first drive mechanism is configured to drive the transfer of the sample from the first sample vessel into the sample transfer element.

28. A kit according to any of claims 18 to 27, wherein the transfer element comprises a process agent and a mixing chamber, and the kit further comprises a second drive mechanism, wherein the second drive mechanism is configured to drive the process agent into the mixing chamber.

29. A kit according to any of claims 18 to 28, wherein the transfer element comprises a process agent and a mixing chamber for mixing the process agent with the sample to produce a mixed sample, and the kit further comprises a third drive mechanism, wherein the third drive mechanism is configured to drive the mixed sample to the second sample vessel.

30. A kit according to any of claims 27 to 29, wherein two or more drive mechanisms are connected as a combined drive mechanism.

31. A kit according to claim 30, wherein the combined drive mechanism comprises a sliding linkage configured such that one of the drive mechanisms is configured to move relative to another drive apparatus in a first range of motion, and the connected drive mechanisms are configured to move simultaneously in a second range of motion.

32. A kit according to any of claims 27 to 31 , wherein the first drive mechanism, the second drive mechanism, the third drive mechanism and / or the combined drive mechanism are permanently attached to the sample transfer element.

33. A kit according to any of claims 27 to 32, wherein the first drive mechanism, the second drive mechanism and / or the third drive mechanism is a mechanical pressure creation mechanism.

34. A kit according to any of claims 27 to 33, wherein the first drive mechanism, the second drive mechanism and / or the third drive mechanism comprises a manual plunger.

35. A method of processing a sample, the method comprising: collecting a sample in a first sample vessel; using a sample transfer element or kit according to any of claims 1 to 34, transferring the sample from the first sample vessel to a second sample vessel; and processing the sample in the second vessel.

36. A method according to claim 35, wherein the sample initially comprises biological tissue in the first sample vessel.

37. A method according to claim 35 or claim 36, wherein the processing in the second sample comprises a PCR reaction.

38. A method according to claim 37, wherein the processing in the second sample comprises a plasmonic PCR reaction.

39. A method according to any of claims 35 to 38, comprising mixing the sample with one or more process agents, the process agents comprising one or more of a reagent and / or a solvent.

40. A method according to claim 39, wherein the sample is mixed with a process agent in the first sample vessel.

41. A method according to claim 39 or claim 40, wherein the sample is mixed with a process agent in the second sample vessel.

42. A method according to any of claims 39 to 41, wherein the sample is mixed with a process agent during the transfer from the first sample vessel to the second sample vessel.

43. A method according to claim 42, wherein the sample is mixed with a process agent in a mixing chamber of the transfer element.

44. A method according to claim 43, further comprising dispensing the reagent into the mixing chamber.

45. A method according to any of claims 35 to 44, wherein the second sample vessel comprises a protective element such that, after the sample is received in the second sample vessel, the protective element protects the sample.

46. A method according to claim 45, wherein the protective element is configured to inhibit evaporation, such that the sample remains in liquid form within the second sample vessel.

47. A method according to claim 46, wherein the protective element comprises a liquid.

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