A sample transfer member, kit and method

Abstract

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

Description

Technical Field

[0001] This application relates to sample transfer devices for transferring samples. This application also relates to kits comprising sample transfer devices. This application further relates to methods of using such transfer devices or kits, including methods for collecting, preparing, and / or storing samples.

[0002] These transfer devices and kits are used in a variety of fields, including but not limited to medical testing for humans and animals, drug manufacturing, quality control of bioenzymes and biomimetic enzymes, monitoring of environmental nucleic acid detection, and biotechnology research and development. Background Technology

[0003] In traditional medical practice, collected samples must be handled using laboratory-grade equipment such as high-precision pipettes for fluid transfer. Given the biohazardous nature of the materials involved (such as samples and reagents), this work must be performed by trained laboratory technicians. Therefore, gold standard testing is limited to laboratory environments, often located far from patients requiring timely results, and to institutions with the resources to maintain such laboratories.

[0004] Similarly, in non-medical fields, the detection of biological or bio-like indicators such as nucleic acids and non-biological agents such as engineered RNA sequences faces similar limitations. Reliance on laboratory environments and skilled personnel makes it difficult for these tests to provide a "sample in, result out" experience for environmental, industrial, or research applications, especially at the time and place where testing is required.

[0005] Therefore, there is an urgent need to provide methods, devices, and / or kits that minimize sample handling (e.g., avoid manual handling such as pipetting, liquid sample handling, and mixing with reagents or solvents).

[0006] For example, traditional nucleic acid amplification and detection techniques (NAAT) such as polymerase chain reaction (PCR) require the collection and processing of samples in a dedicated laboratory, which typically requires laboratory infrastructure and consumes a significant amount of technicians' time. This often necessitates the manual execution of tedious procedures involving filtration, lysis, washing, and elution to extract and concentrate DNA from the sample and mix it with NAAT reagents.

[0007] There is an urgent need for a sample collection device, apparatus, or kit that integrates at least some of the steps highlighted above while avoiding excessive processing and user input during sample preparation from collection to detection. Ideally, such a solution would be able to prepare samples for NAAT in a single, closed-loop process, while also supporting routine functions for the collection of NAAT samples or targets for medical or non-medical purposes. Summary of the Invention

[0008] This application provides sample transfer devices, kits, and methods as set forth in the appended claims.

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

[0010] According to a second aspect, a reagent kit is provided. The kit includes a sample transfer device according to the first aspect and a second sample container. Optional features of the kit are set forth in dependent claims 2-17 and dependent claims 19-34.

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

[0012] The claimed feature resolves the problems described in the background section. Further beneficial effects associated with the claimed feature will be explained in the following description. Attached Figure Description

[0013] Figure 1 The various stages of using the kit, including the sample transfer element, in the embodiments are illustrated schematically. Figure 2 Images and diagrams of embodiments are provided; Figure 3 The kit, including a sample transfer element, is illustrated schematically in the embodiments; Figure 4 A cross-section of the assembled kit in the embodiment is shown schematically; Figure 5 A to Figure 5 C schematically illustrates a mechanical linkage used for multiple drive mechanisms; Figures 6A to 6C The method for processing samples is illustrated schematically; Figure 7 A cross-section of the assembled kit is schematically shown in another embodiment; Figure 8 A cross-section of the assembled kit is schematically shown in yet another embodiment; Figure 9 A cross-section of the assembled kit is schematically shown in another embodiment; Figure 10A A cross-section of the assembled kit is schematically shown in another embodiment; and Figure 10B These are examples of images used in this embodiment. Detailed Implementation

[0014] Figure 1 This is a conceptual diagram illustrating a single device for nucleic acid amplification and / or detection, or a single-step sample collection or storage and processing kit.

[0015] In the first stage, samples are collected using a first sample container. The first sample container can be a standard collection tube, such as a tube used for samples containing nucleic acids.

[0016] The first sample container can be initially covered or sealed according to the usual procedure, or it can be left uncovered.

[0017] The sample transfer device is then assembled onto the first sample container. The sample transfer device can replace any cover previously used on the first sample container. The sample transfer device can be configured as a cover or a seal. The sample transfer device may include a filter. For example, the filter may be a microfluidic filter. The sample transfer device may include one or more processing agents, such as reagents, solvents, or other components for mixing with and / or processing the sample. The sample transfer device may include a valved tubing.

[0018] The second sample container is fitted onto the opposite side of the sample transfer unit. The second sample container may be a container suitable for insertion into a device such as a PCR amplification system and / or a centrifuge.

[0019] Inverting the sealed kit transfers a portion of the sample from the first sample container to the second sample container. This portion of the sample can have a fixed volume, which is controlled by a valve on the sample transfer device and / or a valve on the second sample container. Inverting the sealed kit also allows this portion of the sample to be mixed with the treatment agent and / or passed through a filter.

[0020] Figure 2 An example application of the above-described sample transfer device and kit is shown. Subfigure A is an image of the kit collection in one embodiment. Subfigure B is a schematic diagram of the kit components in this embodiment. Subfigure C shows the kit according to this embodiment, arranged to position the second sample container in a nucleic acid amplification instrument.

[0021] In this example, the sample is a urine sample, used as an example of human tissue collection. The user collects the sample using a standard urine or human tissue collection space. The standard seal or cover is then replaced with the sample transfer device according to the invention. The sample transfer device in this example is equipped with a filter, lyophilized reagents, and a multi-valve PCR tube. Figure 2 A and Figure 2 B). The inverted-sealed kit filters the sample and (via valve guidance) dispenses a fixed volume of sample into nucleic acid amplification, reaction, or detection tubes, where it mixes with reagents in the tubes. The tubes and the entire kit are designed for direct assembly into nucleic acid amplification detection devices. Figure 2 C), no manual sample processing (e.g., urine) is required.

[0022] Examples that reduce or eliminate the need for manual sample handling are particularly useful for plasma PCR, a PCR technique with minimal sample preparation requirements. Plasma PCR is one of the fastest PCR assay procedures, greatly benefiting from rapid sample preparation.

[0023] Figure 3 An example of the internal structure of the sample transfer device according to the present invention is shown.

[0024] Reference Figure 3 The sample transfer member 100 is configured as a cover or sealing mechanism, and the inside of the cover / seal includes an inlet 110 configured to receive a portion of the sample from the first sample container 10.

[0025] The first sample container 10 and the sample transfer member 100 have complementary threads 11, 101 for holding the first sample container 10 and the sample transfer member 100 together. In other embodiments, the first sample container 10 and the sample transfer member 100 may be engaged using another known mechanism, such as an interference fit. The sample transfer member 100 may also have a seal on its inner side for reducing the risk of leakage between the first sample container 10 and the sample transfer member 100. In other examples, any suitable interface may be used to connect the first sample container 10 to the sample transfer member 100.

[0026] Inlet 110 connects to the internal volume of sample transfer member 100, in which (optional) filter 130 and (optional) treatment agent 140 are arranged. The treatment agent may contain one or more reagents, solvents, distillates, or other components for mixing with and / or processing the sample. Filter 130 and treatment agent 140 may be combined into a single element, for example, by impregnating filter material with a predetermined amount of treatment agent. The treatment agent may be configured as a liner or seal such that the sample flows through or permeates the treatment agent during transfer through sample transfer member 100.

[0027] The internal volume is also connected to an outlet 120 on the outside of the cover. The outlet 120 is configured to engage with the second sample container 20.

[0028] The sample transfer member 100 may also include one or more valves. The one or more valves may include valves for controlling the volume of the portion of the sample transferred to the second sample container 20. Such valves may include one-way valves configured to prevent flow through the sample transfer member in unintended directions, such as preventing flow from the second sample container to the first sample container.

[0029] In some embodiments, when the kit is assembled and properly oriented, the portion of the sample is driven by gravity through the sample transfer element 100.

[0030] Figure 4 A schematic cross-section of a kit according to another detailed embodiment A is shown. In this embodiment, the kit includes a sample transfer element A100, a first sample container A10, a second sample container A20, a drive element A30, a valve A40, and a seal element A50.

[0031] The first sample container A10 is constructed to store sample A1.

[0032] When sample A1 is initially received in the first sample container A10, sample A1 may be an unprocessed sample.

[0033] In some cases, the first sample container A10 is also configured for sample collection and / or initial processing. The first sample container may be a standard sample container.

[0034] In various applications, sample A1 can be collected as a liquid sample. In other applications, sample A1 can be a processed sample obtained by collecting a solid sample and processing the solid sample to produce the liquid sample product A1.

[0035] Depending on the application scenario, sample A1 can have any volume. In a typical example, the volume of sample A1 can be less than 500 mL. In a typical example, the volume of sample A1 can be greater than 100 μL, greater than 1 mL, or greater than 10 mL.

[0036] While in the first sample container A10, sample A1 can undergo various treatments. For example, sample A1 can be mixed with solvents such as buffers (such as PBS phosphate buffer) or water and / or with reagents.

[0037] The sample transfer device A100 is configured to transfer at least a portion of the sample A1 (in its original collected state or processed state) from the first sample container A10 to the second sample container A20.

[0038] The second sample container A20 may be, for example, a container suitable for preserving samples during processing such as NAAT procedures. For instance, the second sample container A20 may be a standard container for performing PCR. In some embodiments, the second sample container A20 and the sample transfer device A100 may be configured such that the second sample container A20 can remain attached to the sample transfer device A100 during the NAAT procedure. For example, the combined shape of the second sample container A20 and the sample transfer device A100 may be adaptable to PCR or qPCR equipment.

[0039] Before receiving the sample, the second sample container A20 may additionally contain one or more processing agents in liquid or solid form. For example, the second sample container may contain one or more PCR reagents. These processing agents will be mixed with the sample received via the sample transfer device A100.

[0040] The second sample container A20 may additionally or alternatively include one or more protective elements configured to protect the sample after it has been received by the second sample container. In one example, the protective element may be configured to inhibit evaporation, such that the sample remains in liquid form within the second sample container. This is particularly useful in embodiments where the second sample container will undergo treatments involving heat, such as PCR. Protective elements may be provided within the second sample container A20. For example, the protective element may comprise a liquid stored within the second sample container. In one case, a relatively low-density liquid may be provided to the second sample container A20 as a protective element, such that the protective element is expected to float to the surface of the sample and protect the sample surface from contact with air, thereby inhibiting evaporation. The protective element may, for example, comprise oil, wax, or petroleum jelly. In another example, the protective element may be configured to facilitate processes within the second sample container. For example, the protective element may be configured to prevent reagents from adhering to the inner walls of the second sample container, such as the bottom of the second sample container. This can be achieved by providing an initial solid or rigid element within the second sample container. For example, the solid or rigid element may include oil, wax, or petrolatum, which initially acts as a solid or rigid barrier for one or more components (such as a treatment agent) stored in the second sample container. Furthermore, the initial solid or rigid element may be configured to act as a container for one or more components (such as a treatment agent) within the second sample container.

[0041] The volume of the sample received in the second sample container A20 is typically in the microliter range. For example, the volume of the sample received in the second sample container A20 may be less than 1 mL, less than 100 μL, less than 40 μL, or less than 10 μL.

[0042] The second sample container A20 may additionally include a seal in its initial state. The seal may be damaged when the second sample container is assembled with the sample transfer device. For example, the outlet A120 may include elements such as sharp edges adapted to damage the seal. Alternatively, the seal may be manually removed before using the second sample container with the sample transfer device.

[0043] In this embodiment, the sample transfer device A100 includes an inlet A110 for receiving a sample from a first sample container A10, an outlet A120 for supplying the sample to a second sample container A20, and a processing agent supply device A150. The inlet A110, outlet A120, and processing agent supply device A150 may each include a tube, for example, made of an inert medical-safe material. In some embodiments, these tubes may be macrofluidic tubes (as opposed to microfluidic channels). In many embodiments where sample transfer relies at least partially on gravity, the inlet A110 and outlet A120 are typically located at opposite ends of the sample transfer device A100, allowing the sample transfer device to be vertically oriented with the inlet A110 higher than the outlet A120. However, the inlet A110 and outlet A120 need not be at the ends of the sample transfer device A100. Furthermore, in embodiments where the sample is transferred from the inlet to the outlet without relying on gravity, the inlet A110 and outlet A120 need not be at opposite ends and may, for example, be located at the same end of the sample transfer device.

[0044] Inlet A110, outlet A120, and reagent supply A150 are each connected to mixing chamber A170, allowing the sample to be mixed with the reagent before being transported to the second sample container A20. Mixing chamber A170 may simply be a junction between inlet A110, outlet A120, and reagent supply A150, such as... Figure 4 As shown. Alternatively, the mixing room can be more of a dedicated room, as previously described. Figure 3 As shown in the example.

[0045] The sample transfer element may further include a mixing enhancer (not shown) for enhancing mixing in the mixing chamber A170. For example, the mixing enhancer may include a stirrer, vibrator, or heater for convective mixing. The mixing enhancer may be externally driven. For example, the mixing enhancer may be a magnetic element, similar to a magnetic stirrer. The mixing enhancer may be confined within the mixing chamber A170, for example, by using a mixing enhancer that is too large to pass through the inlet A110 or outlet A120.

[0046] Alternatively, even if the sample transfer element does not specifically include a mixing enhancer, mixing can be stimulated by external treatments such as vibration, shaking, tapping, heating, or inverting the sample transfer element A100. These external treatments can be performed manually or (more preferably in many cases) using a suitable machine for holding the sample transfer element and applying the desired motion. As a further alternative, diffusion may be sufficient to mix the sample and the treatment agent when they meet in the mixing chamber A170, in which case further stimulation of mixing is unnecessary.

[0047] Figure 4 The embodiments described are particularly suitable for situations where sample A10 needs to be mixed with liquid treatment agent A2. Treatment agent A2 may, for example, contain a diluent or solvent, such as water. Treatment agent A2 may additionally or alternatively contain reagents intended to chemically or biologically interact with the sample. In some cases, the components of the treatment agent may be stored in solid form (such as lyophilized form) prior to mixing.

[0048] The sample transfer device A100 may include a treatment agent chamber A160 for storing treatment agent A2 or components thereof. Treatment agent chamber A160 may be filled with the relevant treatment agent during the manufacturing stage. Additionally or alternatively, the sample transfer device A100 may include a port for accessing and filling the treatment agent chamber A160. Where multiple treatments need to be applied to the sample or where multiple treatment agents need to be stored separately before mixing with the sample, the sample transfer device A100 may include multiple treatment agent chambers A160. In some embodiments, treatment agent A2 (or components thereof) may be stored in a mixing chamber A170, such that a separate treatment agent chamber A160 is not required for the treatment agent (or at least for components thereof).

[0049] like Figure 4 As shown in the example, the treatment agent A2 can be stored in a treatment agent chamber A160 without a seal. For example, surface tension or capillary effect can be used to store the treatment agent A2. Alternatively, the treatment agent chamber A160 may include a valve or seal that can be opened or released at appropriate times to supply the treatment agent A2 to the mixing chamber A170 via the treatment agent supply A150.

[0050] The sample transfer element may include one or more filters arranged to filter any liquid moving within the sample transfer element. Filters may, for example, include microfluidic filters. Figure 4In this embodiment, a filter A130 is provided in inlet A110 to filter the sample before it reaches mixing chamber A170. In other embodiments, it may be useful to include a filter in outlet A120 after mixing chamber A170 if the mixing is expected to produce sample components that are not transported to second sample container A20 as part of transfer sample A3. Furthermore, in some embodiments, filtering treatment agent A2 may be useful, especially if the treatment agent may be stored for a long time before use—this filtration can extend the shelf life of sample transfer piece A100 manufactured with the reservoir of treatment agent A2.

[0051] The sample transfer element may further include one or more valves A40. The one or more valves may include valves for controlling the volume of the portion of the sample transferred to the second sample container 20. The valves may include one-way valves configured to prevent flow through the sample transfer element in an unintended direction, such as preventing flow from the second sample container to the first sample container. A valve satisfying both "direction control" and "volume control" characteristics may, for example, include a floating-seal valve, wherein as fluid passes through the valve point, the floating element travels upstream toward the valve point until it encounters and blocks the valve point. For example, as... Figure 4 As shown, a one-way volume control valve can be provided at outlet A120 to control the volume of sample transported to the second sample container A20 and also to prevent any fluid from moving from the second sample container A20 to the mixing chamber A170. Valve A40 can be provided as part of the sample transfer unit A100, part of the second sample container A20, or as a separate component that must be located between outlet A120 and the second sample container A20 when assembling the kit embodiment. More generally, the volume control valve and / or directional control valve can be provided at any suitable location in the sample transfer unit A100, including inlet A110, outlet A120, and treatment agent supply unit A150, or within the mixing chamber A170.

[0052] Or as Figure 4 As shown, the second sample container A20 can be fixed to the sample transfer member A100. In some embodiments, a sealing protective film A50 can be used to adhere to the second sample container A20 and seal the adhesion to prevent any liquid leakage.

[0053] In some embodiments, the sample transfer unit A100, along with a first sample container A10 and / or a second sample container A20 (and optionally any other separately provided components, such as a piston A30, a valve A40, and / or a protective membrane A50), may be supplied as part of the kit. For such embodiments, it is anticipated that the end user (such as a laboratory technician) will assemble a combined system, for example... Figure 4 As shown. However, compared to less integrated and closed systems, this assembly requires less labor from technicians and carries a lower risk of contamination.

[0054] In some embodiments, the second sample container may be permanently connected to the sample transfer element. Such permanent attachment may be suitable if, for example, the combined sample transfer element A100 and the second sample container A20 are suitable for use in a PCR device. In this document, the term "permanent" should be understood according to the intended use of the sample transfer element and the second sample container. In other words, permanent attachment means that it is neither expected nor possible to separate the second sample container from the sample transfer element during normal use, and that they are attached in such a way that separating the second sample container from the sample transfer element would damage one or both of these components, making them potentially unsuitable for sample handling, processing, or analysis. As an example of permanent attachment, the second sample container A20 may, for example, be formed as a sealed end of an outlet 120.

[0055] like Figure 4 As further shown, a piston A30 can be provided to facilitate sample transfer. The piston can be provided as a separate component, as part of the kit, or it can be attached to the sample transfer element during the manufacturing stage. In some embodiments, the piston can be permanently attached to the sample transfer element. For example, during kit assembly, the piston can be attached to the sample transfer element via an irreversible snap-fit ​​connection without the risk of damaging the piston and / or the sample transfer element.

[0056] Piston A30 can be configured to perform one or more different functions.

[0057] In some embodiments, piston A30 includes a first drive mechanism A31 configured to drive sample A1 from first sample container 10 into sample transfer member. Additionally or alternatively, piston A30 may include a second drive mechanism A32 configured to drive treatment agent A2 from treatment agent chamber A160 into mixing chamber A170.

[0058] In some embodiments, the first and second drive mechanisms may be mechanically linked (either via a piston or via another mechanical link). In other embodiments, the first and second drive mechanisms may each be provided with separate pistons, allowing them to be controlled independently.

[0059] Now for reference Figure 5 A to Figure 5 C. In embodiments where the first and second drive mechanisms are linked together, the drive mechanisms can still be configured to allow some independent movement within the range of motion.

[0060] More specifically, such as Figure 5As shown in Figure A, the first drive mechanism and the second drive mechanism may each include actuators A31 and A32, which are configured to move along their respective guides A33 and A34. The actuators may be linked together using a pin link A35 and a slot link A36, such that the first drive mechanism A31 can move relative to the second drive mechanism A32 within a first range of motion (and vice versa).

[0061] Figure 5 A and Figure 5 The movement between B indicates the range of this first movement. This represents a stage in which one of the sample A1 and the treatment agent A2 is driven toward the mixing chamber A170 without driving the other. For example, a portion of the treatment agent A2 may be pre-loaded into the mixing chamber A170 before the sample A1 is driven into the sample transfer unit A100, or vice versa.

[0062] like Figure 5 As further shown in C, when the pin connector A35 abuts the end of the slot connector A36, the first drive mechanism and the second drive mechanism move simultaneously within a second range of motion. This indicates that both sample A1 and treatment agent A2 are being driven towards the mixing chamber A170.

[0063] Typically, in embodiments using multiple drive mechanisms, mechanisms such as... Figure 5 A to Figure 5 The links shown in C operate the drive mechanism in any order and with any relative offset.

[0064] The piston can be configured to operate as a mechanical pressure generating mechanism, such as a pneumatic linkage with localized physical actuation. For example, when operating a first drive mechanism, it can push air into a first sample container A10, thereby moving a sample A1 of a corresponding volume into the inlet A110 of a sample transfer member A100. This may require an airtight interface between the sample transfer member A100 and other components (including a tight fit between the drive mechanism and the sample transfer member). Such an airtight interface may include, for example, a threaded interface, an interference fit, a rubber-coated O-ring or washer, and / or a skirt or labyrinth path. These locally applied mechanical pressure generating mechanisms can contrast with other systems that rely on an external pressure source, such as a gas or liquid supply. Typically, embodiments of this application preferably do not require an external pressure supply or external equipment to function.

[0065] Each drive mechanism can be configured to move a predetermined volume of fluid. For example, the predetermined volume can be calculated based on the surface area of ​​the fluid-facing ends of actuators 31 and 32 and the range of motion of actuators 31 and 32.

[0066] like Figure 4As shown, a pushing action can be used to operate the piston; similarly, the piston can be configured to drive the sample and / or treatment agent based on a pulling action—those skilled in the art will be able to envision various mechanical linkages for controlling the drive mechanism using any relevant movement of the piston, handle, etc., relative to (towards, away from, perpendicular to, around, etc.) the sample transfer member, and the invention is not limited to any particular user interaction implementation. In fact, in some examples, the transfer is driven by gravity and does not require user control of the drive mechanism.

[0067] Figures 6A to 6C The use is illustrated schematically. Figure 4 An example method for processing samples using sample transfer components.

[0068] refer to Figure 6A In the first step S1, sample A1 is obtained and stored in a first sample container A10. As mentioned above, the first sample container can be a standard sample container. Many types of sample containers are designed to engage with a cover, cap, or other seal to prevent leakage or contamination of the sample. During storage, the first sample container A10 is typically oriented with its (sealed) opening facing upwards to reduce the risk of spillage or leakage.

[0069] Or as Figure 6A As shown, in this process, the sample transfer piece A100 can be removed from the first sample container A10 at this point. Alternatively, the sample transfer piece can be used instead of the cover / cap / seal to seal the sample in the first sample container A10 until the user is ready to transfer the sample to the second sample container A20. For example, the first interface of the sample transfer piece A101 adjacent to the inlet A110 can be designed to match the standard sealing mechanism of the first sample container A10, for example, by mimicking the interface of the cover that is typically supplied with the first sample container A10.

[0070] In addition, such as Figure 6A As shown, in this process, the second sample container A20 may already be fixed to the first sample container A10. For example, as described above, the second sample container and the sample transfer device may be manufactured, sold, or stored as a single unit until they are needed to receive samples.

[0071] refer to Figure 6BIn the second step S2, the first sample container A10 engages with the first interface A101 of the sample transfer member A100. Typically, at this stage, the first sample container remains oriented upwards to prevent sample spillage. Therefore, the first interface A101 of the sample transfer member A100 is oriented downwards. This forms a complete kit in which the sample transfer member is in fluid communication with both the first and second sample containers (preferably sealed). If a cover was previously used to seal the first sample container A10, the cover can be removed to engage with the first interface A101. Alternatively, the first interface A101 can be configured to engage with the first sample container A10, without even removing the standard cover of the first sample container A10. For example, the first sample container A10 may include a valve configured to engage with the inlet A110. Furthermore, the sample transfer member can be connected to the first and second sample containers in any order, so the second sample container can be connected to the sample transfer member before or after the illustrated step S2.

[0072] refer to Figure 6C In the third step, the fully assembled kit is inverted so that the first interface A101 of the sample transfer component A100 is now facing upwards, and the first sample container A10 is raised above the second sample container A20, so that gravity can assist in sample transfer.

[0073] However, in this embodiment, since the connection between the first interface A101 and the first sample container A10 is airtight, the sample A1 will not immediately flow into the sample transfer device, thereby allowing the user to control the transfer process.

[0074] Still Figure 6C As shown, in the fourth step, the user operates piston A30. In this embodiment, a single piston is connected to both the first sample container A10 and the treatment agent chamber A160. Therefore, in the fifth step (labeled 5a), the piston operation drives a portion of sample A1 and a portion of treatment agent A2 toward the mixing chamber A170, where they are mixed together (labeled 5b) before passing through valve A40 into the second sample container A20 (labeled step 5c).

[0075] This can be considered an unexpected effect. The inventors have discovered that even if air is present in the first sample container A10, and even if air is expected to be present in the inlet pipe A110, the technology can still precisely control when and how much volume of sample is dispensed into the sample transfer piece and finally into the second sample container when using the drive mechanism.

[0076] After completion Figures 6A to 6CFollowing the method steps, the method can continue by inserting a second sample container A20 into a sample processing device, thereby further processing the sample while it is stored in the second sample container. For example, the second sample container can be inserted into a PCR device or a centrifuge.

[0077] Figure 7 Optional detailed embodiment B is illustrated schematically. (With) Figure 4 The same features as in Embodiment A are designated using the same reference numerals in Embodiment B. For example, reference numerals A1 and B1 both refer to the sample initially stored in the first sample container B10 (A10). For the sake of brevity, details common to Embodiment A will not be repeated, and the following description... Figure 7 The description only relates to the differences between Embodiment A and Embodiment B. Therefore, it can be assumed that the features of Embodiment A (including the method of using Embodiment A, such as...) Figures 6A to 6C The same applies to Example B (as shown), unless otherwise stated below.

[0078] like Figure 7 The difference between Embodiment B and Embodiment A is that the treatment agent B2 is stored directly in the mixing chamber B170, and the treatment agent chamber A160 and the treatment agent supply unit A150 are omitted in this embodiment. However, the sample transfer unit B100 is configured such that similar mixing occurs when the sample B1 is introduced into the mixing chamber B170, as described in Embodiment A above.

[0079] Furthermore, Example B differs from Example A in that the sample transfer device B100 is configured not to use a piston. Instead, the assembled kit uses gravity to transfer sample B1 from the first sample container B10 to the second sample container B20 through filter B130 and mixing chamber B170.

[0080] For Embodiment B, it is conceivable that the valve B40 at the sample transfer outlet could be implemented as a floating-seal valve (as described in more detail above). Furthermore, the second sample container B20 may initially include a sealed protective membrane. This protective membrane may be calibrated to rupture under the weight of the processed sample, or to rupture upon pressure of the sample transfer device B100 and the second sample container B20. For example, the seal may be configured such that insertion of the assembled kit into a sample processing device (such as a PCR device) is expected to damage the seal.

[0081] Figure 7 The sample transfer component B100 itself, as a smaller part of the kit, is also shown in how it can be distributed and assembled for use. As an example, in Figure 7The image shows a snap-fit ​​connection between the inlet and first interface integrated segment B101 and the filter segment B130, with the inlet and first interface integrated segment B101 configured to engage with the first sample container B10. Furthermore, different cross-sectional shading lines are used to illustrate several different segments of the mixing chamber B170, which are configured to engage with each other within the assembled sample transfer assembly B100.

[0082] Figure 8 An optional detailed embodiment C is illustrated schematically. (Compared to...) Figure 4 The same features as in Embodiment A are designated using the same reference numerals in Embodiment C. For example, reference numerals A1 and C1 both refer to the sample initially stored in the first sample container C10 (A10). For the sake of brevity, details common to Embodiment A will not be repeated, and the following description... Figure 8 The description only relates to the differences between Embodiment A and Embodiment C. Therefore, it can be assumed that the features of Embodiment A (including the method of using Embodiment A, such as...) Figures 6A to 6C The same applies to Example C (as shown), unless otherwise stated below.

[0083] like Figure 8 The difference between Embodiment C and Embodiment A is that the treatment agent C2 is stored directly in the mixing chamber C170, and the treatment agent chamber A160 and the treatment agent supply unit A150 are omitted in this embodiment. However, the sample transfer unit C100 is configured such that similar mixing occurs when the sample C1 is introduced into the mixing chamber C170, as described in Embodiment A above.

[0084] Furthermore, Embodiment C differs from Embodiment A in that the sample transfer member C100 is configured to use a different combination of drive mechanisms. More specifically, drive mechanism C31 performs a similar function to drive mechanism A31 and is configured to drive sample C1 from the first sample container C10 to sample transfer member C100.

[0085] On the other hand, the drive mechanism C33 is configured to perform a different function than the drive mechanism of Embodiment A. More specifically, the drive mechanism C33 is configured to drive the mixed sample from the mixing chamber C170 into the second sample container C20. This can be used to allow the user to control the mixing time of the sample C1 with the treatment agent C2 before it is transferred to the second sample container C20. One or more one-way valves C180 may be provided to ensure that the driving force provided by the drive mechanism C33 is used to push the mixed sample into the second sample container C20, rather than returning along the inlet C110. The valves may also be configured to resist opening before the user actuates the drive mechanism C33 to prevent the mixed sample from flowing into the second sample container C20.

[0086] Figure 9 An optional detailed embodiment D is schematically illustrated. (With) Figure 8 The same features as in Embodiment C are designated using the same reference numerals in Embodiment D. For example, reference numerals C1 and D1 both refer to the sample initially stored in the first sample container D10 (C10). For the sake of brevity, details common to Embodiment C will not be repeated, and the following description... Figure 9 The description only relates to the differences between Embodiment C and Embodiment D. Therefore, it can be assumed that the features of Embodiment A and Embodiment C (including the method of using Embodiment A, such as...) Figures 6A to 6C The same applies to Example D (as shown), unless otherwise stated below.

[0087] like Figure 9 The difference between Example D and Example C is that the sample transfer device includes multiple outlets D120-1 to D120-n, each outlet configured to engage with a corresponding second sample container D20-1 to D20-n. More specifically, in this example, the outlet includes a single initial segment D120 communicating with the mixing chamber D120. This initial segment branches off to the multiple outlets D120-1 to D120-n. This allows a single sample transfer device to fill multiple second sample containers D20-1 to D20-N using a single simplified process, further reducing the time and effort spent by laboratory technicians preparing samples for further processing, such as PCR or centrifugation.

[0088] In other embodiments, such branching paths can be constructed in different parts of the sample transfer member. For example, the sample transfer member can have a branch point in the inlet D110 and a mixing chamber for each of a plurality of outlets, wherein each mixing chamber is connected to a corresponding outlet.

[0089] Figure 10A and Figure 10B An optional detailed embodiment E is schematically illustrated. (With) Figure 4 The same features as in Embodiment A are designated using the same reference numerals in Embodiment E. For example, reference numerals A1 and E1 both refer to the sample initially stored in the first sample container E10 (A10). For the sake of brevity, details common to Embodiment A will not be repeated, and the following description... Figure 10A and Figure 10B The description only relates to the differences between Embodiment A and Embodiment E. Therefore, it can be assumed that the features of Embodiment A (including the method of using Embodiment A, such as...) Figures 6A to 6C The same applies to Example E (as shown), unless otherwise stated below.

[0090] like Figure 10A and 10BThe difference between Embodiment E and Embodiment A is that the mixing chamber A170 is completely omitted, as are the treatment agent supply unit A150, the treatment agent chamber A160, and the second drive mechanism A32. In other words, the sample transfer unit E100 includes an inlet E110 that is directly connected to the outlet E120 without any intermediate mixing.

[0091] In embodiment E, the first drive mechanism E31 and the valve E180 together are used to control the distribution of a portion of sample E1 from the first sample container E10 to the second sample container E20.

[0092] This embodiment can be particularly useful when you want to distribute a small portion of a sample from a larger container to a smaller one while avoiding the need for pipettes, simple syringes, or other manual handling. This helps reduce workload and also reduces the risk of sample contamination or waste.

[0093] As described above, any of the embodiments described herein, as well as other embodiments falling within the scope of the claims, can be configured such that the second sample container can undergo further sample processing while remaining fixed to the sample transfer device.

[0094] For example, a combination kit (with or without the original first sample container) can be inserted into a sample processing device such as a PCR device.

[0095] Such processing equipment may have means for identifying inserted sample containers, such as RFID tag readers, barcode readers, or other passive or active communication devices for obtaining data from the sample containers. Such identifiers may be additionally or alternatively used for further identification details, such as identifying the protocol to be performed on the sample, identifying response parameters, etc.

[0096] Regarding the sample transfer device and kit according to the present invention, in addition to or in lieu of the second sample container, the sample transfer device may include an identifier. This identifier may include any of the following: an active electronic communication system (for wireless communication with sample processing equipment 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 barcode or other visual identifier).

[0097] Including an identifier on the sample transfer device is preferable to including it on the second sample container. For example, in many embodiments, the sample transfer device can be larger than the second sample container, thus providing more space for a larger or more complex identifier. Furthermore, when the second sample container is positioned for sample processing in a sample processing apparatus, the apparatus may have difficulty reading the identifier. On the other hand, a sample transfer device attached to but not fully inserted into the second sample container for sample processing (e.g., PCR processing) is more convenient for automatic or manual reading of the identifier.

[0098] The above embodiments are provided as examples only. Within the scope of the appended claims, the features can be combined in a variety of other ways.

Claims

1. A sample transfer device for transferring a sample from a first sample container to a second sample container, the sample transfer device comprising: The first interface is configured to engage with the first sample container; as well as The second interface is configured to engage with the second sample container.

2. The sample transfer device according to claim 1, wherein the sample transfer device is configured as a cover or partial seal for the first sample container.

3. The sample transfer device of claim 2, wherein the cover includes an inner surface and an outer surface, the inner surface including an inlet for receiving liquid from the first sample container, and the outer surface including an outlet for conveying liquid to the second sample container.

4. The sample transfer device according to any one of claims 1 to 3, wherein the first interface includes a coupling for retaining the first sample container and / or for forming a sealing connection with the first sample container.

5. The sample transfer device according to claim 4, wherein the first interface includes a thread for engaging with a corresponding thread of the first sample container, or wherein the first interface is configured to form an interference fit with the first sample container.

6. The sample transfer device according to any one of claims 1 to 5, the sample transfer device comprising a mixing element configured to mix a treatment agent with the sample when the sample is transferred from the first sample container to the second sample container, wherein the treatment agent comprises one or more of a reagent and / or a solvent.

7. The sample transfer device according to claim 6, wherein the mixing device is a mixing chamber.

8. The sample transfer device of claim 7, wherein the sample transfer device is configured to dispense the treatment agent into the mixing chamber.

9. The sample transfer device according to claim 8, further comprising a treatment agent reservoir.

10. The sample transfer device according to any one of claims 6 to 9, further comprising a mixing enhancer configured to enhance the mixing of the sample and the treatment agent in the mixing device.

11. The sample transfer device according to any one of claims 1 to 10, comprising a filter configured to filter the sample as it is transferred from the first sample container to the second sample container.

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

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

14. The sample transfer member according to any one of claims 1 to 13, wherein the sample transfer member is configured to transfer the sample under the action of gravity.

15. The sample transfer device according to any one of claims 1 to 14, further comprising a volume control valve for controlling the volume of the sample transferred from the first sample container to the second sample container and / or a direction control valve configured to control the transfer direction of the sample.

16. The sample transfer device according to any one of claims 1 to 15, further comprising a sample identification device configured to be passively or actively read by a sample processing device, the sample processing device being further configured to receive and process the sample when the sample is stored in the second sample container.

17. The sample transfer device according to any one of claims 1 to 16, the sample transfer device comprising a plurality of second interfaces configured to engage with a plurality of second sample containers.

18. A reagent kit comprising: The sample transfer device according to any one of claims 1 to 17, and The second sample container.

19. The kit of claim 18, wherein the second sample container is permanently attached to the sample transfer device.

20. The kit according to claim 18 or claim 19, wherein the kit further comprises the first sample container.

21. The kit of claim 20, wherein the volume of the first sample container is greater than the volume of the second sample container.

22. The kit according to any one of claims 18 to 21, wherein the second sample container includes a volume control valve.

23. The kit according to any one of claims 18 to 22, wherein the second sample container is adapted to perform a PCR reaction on the sample while the sample is contained in the second sample container.

24. The kit according to any one of claims 18 to 23, wherein the second sample container includes a protective element configured to protect the sample after it has been received in the second sample container.

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

26. The kit of claim 25, wherein the protective element comprises a liquid.

27. The kit according to any one of claims 18 to 26, the kit further comprising a first drive mechanism, wherein the first drive mechanism is configured to drive the sample from the first sample container to the sample transfer member.

28. The kit according to any one of claims 18 to 27, wherein the sample transfer element comprises a processing agent and a mixing chamber, and the kit further comprises a second drive mechanism configured to drive the processing agent into the mixing chamber.

29. The kit according to any one of claims 18 to 28, wherein the sample transfer element includes a processing agent and a mixing chamber for mixing the processing agent with the sample to produce a mixed sample, and the kit further includes a third drive mechanism configured to drive the mixed sample to the second sample container.

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

31. The kit of claim 30, wherein the combined drive mechanism includes a sliding link configured such that one drive mechanism of the drive mechanism is configured to move relative to another drive device within a first range of motion, and a connected drive mechanism is configured to move simultaneously within a second range of motion.

32. The kit according to any one 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 fixed to the sample transfer device.

33. The kit according to any one of claims 27 to 32, wherein the first drive mechanism, the second drive mechanism and / or the third drive mechanism are mechanical pressure generating mechanisms.

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

35. A method for processing a sample, the method comprising: The samples were collected in the first sample container; Using the sample transfer device or kit according to any one of claims 1 to 34 The sample is transferred from the first sample container to the second sample container; and the sample is processed in the second sample container.

36. The method of claim 35, wherein the sample initially comprises biological tissue in the first sample container.

37. The method of claim 35 or claim 36, wherein the treatment in the second sample container comprises a PCR reaction.

38. The method of claim 37, wherein the treatment in the second sample container comprises a plasma PCR reaction.

39. The method according to any one of claims 35 to 38, the method comprising mixing the sample with one or more treatment agents, the treatment agents comprising one or more of reagents and / or solvents.

40. The method of claim 39, wherein the sample is mixed with the treatment agent in the first sample container.

41. The method of claim 39 or claim 40, wherein the sample is mixed with the treatment agent in the second sample container.

42. The method according to any one of claims 39 to 41, wherein the sample is mixed with the treatment agent during the transfer from the first sample container to the second sample container.

43. The method of claim 42, wherein the sample is mixed with the treatment agent in the mixing chamber of the sample transfer member.

44. The method of claim 43, further comprising dispensing the reagent into the mixing chamber.

45. The method according to any one of claims 35 to 44, wherein the second sample container includes a protective element such that the protective element protects the sample after the sample has been received in the second sample container.

46. ​​The method of claim 45, wherein the protective element is configured to inhibit evaporation, such that the sample remains in liquid form within the second sample container.

47. The method of claim 46, wherein the protective element comprises a liquid.

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