PIERCING DEVICE AND SYSTEMS FOR LIQUID AND GAS HANDLING

1. CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the priority benefit of U.S. provisional application no.

62/549,574, filed August 24, 2017, the contents of which are incorporated herein in their entireties by reference thereto.

2. BACKGROUND

2.1. Field of the Invention

[0002] The present disclosure relates to the handling of liquids and gases, both extraction from and injection into, containers that can remain closed, if necessary, with the sampling needle of the disclosure being able to pierce through the top, bottom or side walls of the container.

2.2. Description of the Related Art

[0003] Manual handling of containers for extracting liquid or gas samples can be very problematic, particularly if the containers were not designed for automation in terms of sample handling. A device capable of manipulating samples from containers not designed for automation is extremely desirous as more is learned regarding the functionality of the human genome and proteome and the demand for diagnostic testing increases. With increased demands for testing follows demands for more high-throughput capability and automation. There are a few examples in the prior art in terms of anti-coring and venting sampling devices that begin to address this need.

[0004] Mehra et al. (Pipette Sampling System, US 6,817,256) describe a pipette tip functionalised with a piercing tip for removal of aliquots of liquids from sample tubes that have an orifice at the top which can be pierced. The preferred sample container is a Vacutainer™ as manufactured by Becton Dickenson and the device, which is preferentially described as being disposable, functions by drawing sample into a hollow chamber within the pipette tip. Some embodiments of the pipette tip contain a side vent. The function of the side vent is to substantially prevent or block excess fluid from passing to a filter barrier within the pipette tip. No provision is made in the pipette tip of Mehra et al. to permit for pressure equilibration between the sample tube and outside atmosphere nor to prevent material of the sample tube from entering or blocking the needle or piercing tip.

[0005] Motadel (Liquid Sampling Utilizing Ribbed Pipette Tip for Barrier Penetration, US patent application publication no. 2006/0171851) describes a pipette tip functionalised with ribs extending down the length of the pipette tip for piercing a resilient barrier sealing a container. In addition to providing the tip with sufficient rigidity for barrier piercing, the ribs along the length of the also serve to keep the resilient barrier of the sample container from contacting the surface of the pipette tip so as to permit for the ambient air to flow into and from the interior of the container during aspiration of the liquid sample. While the concept of venting is addressed, no provision is made in the device of Motadel to prevent material of the sample tube from entering or otherwise blocking the needle or piercing tip.

[0006] Raines (Vented needle with sideport, United States Patent No. 4,787,898) describes a device consisting of a needle within a needle wherein the inner needle may sample a liquid from a container and the second outer needle of shorter length provides for venting of the container. While the concept of venting is addressed, no provision is made in the device of Raines to prevent material of the sample tube from entering or otherwise blocking the needle or piercing tip.

[0007] Goldenberg (Aspiration needle with venting feature, US Patent No. 7,207,950) also describes a dual lumen needle in which a first lumen provides for sample aspiration and the second lumen a channel for venting, as preferentially required for bone marrow and other tissue sampling. While the concept of venting is addressed, no provision is made in the needle of Goldenberg to prevent material of the sample tube from entering or blocking the needle or piercing tip, particularly as the needle is generally designed for sampling of tissues (i.e. biopsy style sampling).

[0008] Choksi ei al. (Vented Needle for Medical Liquids, US Patent No. 4,058, 121) describes a thermoplastic needle with a closed forward end to prevent coring of the stopper material through which the needle is inserted. Alchas (Self-venting, non-coring needle assembly, US Patent No. 4,537,593) similarly has disclosed a non-coring needle assembly. Both Choksi and Alchas utilize a needle with a solid distal tip for penetrating stopper material and side apertures to allow aspiration of liquids. A disadvantage of the Choksi and Alchas needles is that the apertures do not reach the distal tips of the needles and therefore the needles are unable to withdraw small volumes of liquids in the bottom of a container.

[0009] Accordingly, the need persists for a device that is capable of sampling from containers which can pierce the container without having the bore of a needle of the device being filled or otherwise occluded with material from the container cap or walls. Preferably the device is capable of venting of the container to permit pressure equilibration between the inside and outside of the container while a sample is being aspirated from or dispensed into the container and permits quantitative or near-quantitative manipulation or recovery of samples. 3. SUM MARY

[0010] There is an increasing demand for equipment in laboratories and other environments in which handling of liquids and gasses in containers such as tubes and bottles is performed automatically by machinery rather than human operators. It is faster, cheaper, and in many cases more reliable, to design handling equipment that pierces the caps or walls of containers made of pierceable materials, for example rubber or plastic, to obtain access to the container to inject or extract fluids or gasses.

[001 1] An important example of a field where such handling is important is in high- throughput analysis of the products of Polymerase Chain Reaction (PCR) processes, which are typically done in-situ in 0.2 ml polyethylene tubes. These tubes have a snap cap on top, which is convenient for a human operator to use, but difficult for a robot to manipulate accurately and reliably in applications where space and expense are a concern.

Furthermore, opening a snap cap is known to aspirate a portion of the tube contents, particularly some of the nucleic acids generated during the PCR process, which may lead to contamination of the general area that may deleteriously effect the integrity subsequent samples. PCR samples also provide the challenge of being of small volume, typically of approximately 100 μΙ or less (e.g., approximately 25 μΙ, approximately 50 μΙ, approximately 75 μΙ, or approximately 100 μΙ,), that necessitates the sampling device being able to withdraw or inject close to the container walls in order to provide for quantitative or near- quantitative manipulation of the sample. A simpler solution is to withdraw a sample of the liquid by inserting a needle straight through the cap without the bore of the needle getting occluded or filled with material from the cap or walls of the container. The present disclosure solves this problem by providing a sampling needle and systems comprising the sampling needle, where the sampling needle has (1 ) a hollow shaft with a proximal end and a distal end, (2) a piercing tip at the distal end, and (3) an anti-coring component in or near the distal end of the shaft, said anti-coring component configured such that when the needle is pushed through the lid or wall of the container a flap is created that is displaced by the anti-coring component but remains attached to the lid or wall. In some embodiments, the anti-coring component is configured such that when the needle is pushed through the lid or wall of the container, the needle cuts a section of the lid or wall that is about 50% to 90%, preferably about 60% to 80%, and more preferably about two thirds to three quarters, of the perimeter of the distal end of the needle, thereby forming a flap that remains attached to the lid or wall by a section of lid or wall material that is about 10% to 50%, more preferably about 20% to 40%, and most preferably about one third to one quarter, of the perimeter of the distal end of the needle (e.g., as shown in Fig. 12). [0012] The container can be sealed after withdrawal of the needle, for example when storage of the contents of the container is desired. For example, the hole (with attached flap) can be closed with tape (e.g., Scotch™ tape). In another example, the flap can be pushed back to its original position and then sealed with tape or glue (e.g., a cyanoacrylate glue). In yet another example, the flap can be pushed back to its original position and sealed with glue (e.g., a cyanoacrylate glue) placed under tape. Sealing of the container for storage can be desirable for high value samples (e.g., rare or irreplaceable samples).

[0013] The needle is preferably configured so as to avoid positive or negative pressure build up in the container. This is achieved by a venting component that allows the pressure inside and outside the container to equalize.

[0014] The sampling needle of the disclosure preferably provides for quantitative or near quantitative manipulation of the sample within the container by being able to extract or deliver fluid materials near a wall of the container (e.g., a bottom wall of the container).

[0015] The sampling needle of the disclosure can also be configured to withstand the stress of piercing and withdrawal through thousands of cycles without failing due to modes such as snapping, bending or blunting. In order to avoid damage to a sampling needle of the disclosure upon insertion into a container, the force applied (e.g., by a gas or liquid handling robot) is preferably sufficient to penetrate a lid or wall of the container but insufficient to damage the sampling needle (e.g., by bending the piercing tip). It was found that slowly inserting a sampling needle of the disclosure into a container provides the most effective cutting/coring action without bending the needle tip, whereas hitting the cap of a container hard and fast with the sampling needle would result in a bent needle tip.

[0016] The sampling needle of the disclosure enables automated insertion and withdrawal of needles and transfer of fluid materials, whether liquids or gasses, to be performed at high speed, with high recovery yields and with high reliability. This is achieved by introducing an anti-coring component, such as, for example, an open tubular insert, into the needle tip. The anti-coring insert prevents the bore of the needle from being occluded or filled with material from the container by causing the material cut by the tip to be pushed down and away from the needle shaft as the terminus of the anti-coring section traverses the cap of the container. By creating a first cut in the container wall or cap, followed by pushing the cut section away by folding the container material, this anti-coring system also provides the benefit of not having a section of container material liberated from the container, which may interfere with manipulation of the sample. On insertion of the needle tip to the correct sampling depth in the container, an optional venting component situated in or on the needle then traverses the container wall or cap to provide a mechanism for gas to enter or escape from the container. This permits for more accurate and precise sampling by preventing overpressure or underpressure developing within the container when material is injected into or withdrawn from the container. Alternatively, the venting component could be attached to a vacuum system and/or a gas delivery system to provide for atmospheric pressure and composition control within the container.

[0017] The sampling needle and systems of the disclosure provide the advantage of being able to acquire sample directly through an opening present at the distal tip of the needle while not necessarily introducing venting components that require differential insertion forces to be applied.

[0018] The sampling needle and systems of the disclosure can also be used to deliver liquids or gases to a container (e.g., containing a biological sample). For example, a container can be pierced with the sampling needle and a liquid added to the container. The contents of the container can then optionally be mixed by withdrawing all or a portion of the liquid into the needle and reintroducing the withdrawn liquid into the sample tube one or more times (e.g., 1 to 5 times, 1 to 4 times, 1 to 3 times, 1 to 2 times, 2 to 5 times, 2 to 4 times, 2 to 3 times, 3 to 5 times, 3 to 4 times or 4 to 5 times). All or a portion of the mixed liquid can then be withdrawn from the container and moved to a different container or instrument for reaction or analysis (e.g., thermal cycling or hybridization to an array).

[0019] The sampling needle of the disclosure permits for quantitative or near-quantitative manipulation or recovery of samples. This is made possible as the distal terminus is open and available for the transfer of liquids at or near the walls of the container. This is particularly desirous in the case where sampling of small volumes is required, such as, for example, removal of PCR products (typically of 20 μΙ volumes or less) from PCR tubes.

[0020] The dimensions of the sampling needles of the disclosure can be varied to facilitate sampling of liquids and gasses from different types of containers and varied to facilitate use with different liquid and gas handling devices. For example, a sampling needle that can be used to inject or extract liquids from PCR tubes using a liquid handling robot can be 3 to 5 inches in length (e.g., about 3 to 4 inches or about 4 to 5 inches). Such needles can have a venting section from about ¼ of an inch to ¾ of an inch in length (e.g., about 0.3 inches to about 0.7 inches or about 0.4 inches to about 0.6 inches), which can be located, for example, ¼ to ¾ of an inch (e.g., about 0.3 inches to about 0.7 inches or about 0.4 inches to about 0.6 inches) from the distal end of the needle. The tip of the needle can be cut, for example, at an angle ranging from about 10° to about 20° relative to the wall of the needle shaft (e.g., 15°, for example as shown in Fig. 10D). The anti-coring insert can be positioned in the shaft of the needle so that the distal end of the anti-coring insert is approximately 0.07 to 0.1 1 inches from the distal end of the shaft. In some embodiments, the sampling needle of the disclosure has dimensions each varying by 0% to 50% (larger or smaller) from the dimensions shown in Fig. 10 (e.g., 0% to 40%, 0% to 30%, 0% to 20%, 0% to 10%, 10% to 50%, 10% to 40%, 10% to 30%, 10% to 20%, 20% to 50%, 20% to 40%, 20% to 30%, 30% to 50%, 30% to 40%, or 40% to 50%).

4. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] FIG. 1 is a schematic diagram of an exemplary non-coring, venting needle comprised of a shaft 1 , piercing tip 2, anti-coring insert 3 that prevents the bore of needle from being filled with material from the cap of the container, reduced diameter venting section 4, tubing attachment section 5 and a section used to secure and align the needle within a liquid/gas handling device 6.

[0022] FIG. 2 is a schematic diagram of an exemplary non-coring, venting needle comprised of a shaft 1 , a piercing tip 2, an anti-coring insert 3 that prevents the bore of needle from being filled with material from the cap of the container, a single venting groove 4, a tubing attachment section 5 and a section used to secure and align the needle within a liquid/gas handling device 6.

[0023] FIG. 3 is a schematic diagram of an exemplary non-coring, venting needle comprised of a shaft 1 , a piercing tip 2, an anti-coring insert 3 that prevents the bore of needle from being filled with material from the cap of the container, a multiplicity of venting grooves 4, a tubing attachment section 5 and a section used to secure and align the needle within a liquid/gas handling device 6.

[0024] FIG. 4 is a schematic diagram of an exemplary non-coring, venting needle situated within a container 2 partially filled with a liquid 3. The needle is comprised of a shaft 1 , a piercing tip 4, an anti-coring insert 5 that prevents the bore of needle from being filled with material from the cap of the container, a second venting needle affixed to the main shaft 6 with a second anti-coring insert 7 that prevents the bore of venting needle from being filled with material from the cap of the container, a tubing attachment section 8 and a section used to secure and align the needle within a liquid/gas handling device 9.

[0025] FIG. 5. is a close-up view of an exemplary needle tip, showing the anti-coring component 2 comprised of an open tubular insert immobilised within the bore of the needle tip. The anti-coring insert 2 prevents the bore of needle from being occluded or filled with material from the cap of the container by causing the material cut by the tip 1 to be pushed down and away from the syringe shaft as the terminus of the anti-coring section traverses the cap of the container. On insertion of the needle tip to the correct sampling depth in the container, the reduced diameter venting section 3 of the needle traverses the container lid and a ring of exposed air around the needle exists that prevents overpressure or underpressure developing within the container when liquids are being injected into or withdrawn from the container, since air in the container can exchange with atmospheric air.

[0026] FIG. 6. is a close-up view of an exemplary needle tip, showing the anti-coring component 2 comprised of a linear segment spanning the region between the needle tip 1 and a second point along the needle opening. The anti-coring insert 2 prevents the bore of needle from being occluded or filled with material from the cap of the container by causing the material cut by the tip 1 to be pushed down and away from the syringe shaft as the cutting faces of the needle traverse the cap of the container. On insertion of the needle tip to the correct sampling depth in the container, the reduced diameter venting section 3 of the needle traverses the container lid and a ring of exposed air around the needle exists that prevents overpressure or underpressure developing within the container when liquids are being injected into or withdrawn from the container, since air in the container can exchange with atmospheric air. In a particular embodiment, the linear segment that bisects the inner needle bore and spans the region between the needle tip 1 and a second point along the needle opening.

[0027] FIG. 7. is a close-up view of an exemplary needle tip, showing the anti-coring component 2 comprised of a rod situated within the inner needle bore that protrudes into the chamfered cutting section of the needle terminus. The anti-coring insert 2 prevents the bore of needle from being occluded or filled with material from the cap of the container by causing the material cut by the tip 1 to be pushed down and away from the syringe shaft as the anti- coring insert traverse the cap of the container. On insertion of the needle tip to the correct sampling depth in the container, the reduced diameter venting section 3 of the needle traverses the container lid and a ring of exposed air around the needle exists that prevents overpressure or underpressure developing within the container when liquids are being injected into or withdrawn from the container, since air in the container can exchange with atmospheric air.

[0028] FIG. 8 is a schematic diagram of an exemplary non-coring, venting needle comprised of a shaft 1 , a piercing tip 2, an anti-coring component 3 that prevents the bore of needle from being occluded or filled with material from the cap of the container, a reduced diameter venting section 4, and a female luer connector 5 for attachment to a male luer connector.

[0029] FIG. 9 is a schematic diagram of an exemplary non-coring, venting needle inserted into a PCR tube 1 containing a sample 2. The needle is comprised of a shaft 3, a piercing tip 4, an anti-coring component 5 that prevents the bore of needle from being occluded or filled with material from the cap 6 of the container, a reduced diameter venting section 7, and a tapered pipette terminus 8 for attachment to a pipetting device and to contain a desired volume of fluid material. The pipette terminus may be functionalised with depth stop features 9 that limit the depth of penetration of the needle into the container so that a second section of the container wall is not pierced while also permitting for repeatable sampling. The anti- coring component of the needle is designed to retain the portion 10 of the container wall or cap cut by the needle connected to the container. After the needle has been inserted through the plastic of the cap and the venting section 7 remains traversing the cap when the needle is inserted to the sampling depth, a ring of exposed air 11 around the needle exists that prevents overpressure or underpressure developing within the tube when material is being injected into or withdrawn from the tube, since air in the tube can exchange with atmospheric air.

[0030] FIG. 10A-D show dimensions of an exemplary sampling needle having a venting groove. FIG. 10A shows lengths of the various sections of the sampling needle. FIG. 10B shows the widths of the various sections of the sampling needle. FIG. 10C shows a detailed view of the section of the needle represented by circle A in FIG 10A. FIG 10D shows a detailed view of the section of the needle represented by circle B in FIG 10B. The dimensions shown in FIG. 10A-D are in inches.

[0031] FIG. 11 is a photograph of an exemplary needle of the disclosure mounted to a Tecan liquid handling robot.

[0032] FIG. 12 is a photograph of a tube cap pierced with an exemplary needle of the disclosure showing that when the needle was pushed through the lid of the tube the piercing tip was prevented from penetrating the entire lid by the anti-coring component.

5. DETAILED DESCRIPTION

[0033] In one aspect, the disclosure provides a sampling needle for injecting or extracting a sample into or from a container, where the sampling needle comprises (1) a hollow shaft with a proximal end and a distal end, (2) a piercing tip with a cutting point at the distal end of the hollow shaft, and (3) an anti-coring component in the piercing tip, said anti-coring component configured such that when the needle is pushed through the lid or wall of the container the piercing tip is prevented from penetrating the entire lid or wall.

[0034] In another aspect, the disclosure provides systems comprising one or more sampling needles of the disclosure and a mechanical device for pushing the needle(s) through lids or walls of a container (e.g., a plastic container). The mechanical device can be manual or automated. The mechanical device preferably includes a device for injecting or extracting a sample into or from the container through the needle(s), e.g., a pressure and/or vacuum source such as an electric pump or manually operated pump (e.g., a syringe).

[0035] Preferably, the mechanical device, whether manual or automated, should provide steady, consistent pressure on the lid or wall of the container as the needle is pushed through the lid or wall so as to avoid bending the needle. Once the needle has penetrated the lid or wall, sudden movement of the needle should preferably be avoided to prevent the needle from contacting or puncturing an inner wall of the container. Providing steady, consistent pressure and controlling movement of the needle following lid/wall puncture can be difficult with a handheld device such as a pipette or syringe and, therefore, the mechanical device is preferably not a handheld device. Mechanical devices can be configured to provide consistent pressure and insert the needle to a desired depth (for example, close to, but not touching a bottom surface of the container). Thus, the systems of the disclosure can avoid drawbacks associated with handheld devices, for example the difficulty in providing consistent pressure to the lid or wall of a container, and the difficulty in controlling movement of the needle after the needle has penetrated the lid or wall.

[0036] Preferably, the mechanical device is automated. For example, the mechanical device can be a liquid and/or gas handling robot (e.g., a Tecan MSP 9000, MSP 9250 or MSP 9500, a Tecan Cavro® Omni Flex, a Tricontinent TriTon (XYZ), or an Aurora Versa™). In some embodiments, the liquid and/or gas handling robot can be an autosampler such as a gas chromatography (GC) autosampler (e.g., a ThermoFisher TriPlus™ RSH, TriPlus™ 100 LS, or TriPlus™ 300 autosampler) or a liquid chromatography (LC) autosampler (e.g., a ThermoFisher Vanquish™ or UltiMate™ autosampler). The systems of the disclosure can be used to handle any type of liquid or gas traditionally handled by liquid and/or gas handling robots. In some embodiments, the mechanical device is a liquid handling robot.

[0037] Although automated mechanical devices are preferred, manually operated mechanical devices can also be used. For example, a manually operated device similar to a drill press can be used. In such a device, the sampling needle can be mounted at a position corresponding to the position where a drill bit would be mounted on a drill press, and tubing, pumps, fluid reservoirs, etc. can be mounted above the needle at a location analogous to the location housing the motor of a drill press. The use of such a device can allow the user to apply a larger and/or more consistent force on the lid or wall of a container as compared to the force that could be applied using a handheld device (e.g., a handheld pipette or syringe). A manually operated mechanical device can be configured to stop the insertion of the needle at a desired depth (e.g., at a desired height above a bottom surface of the container) so as to prevent overinsertion of the needle. For example, a drill press-type mechanical device can have a height adjustable platform for holding the container so that the user can adjust the height of the platform when using different sized needles and/or containers.

[0038] The systems of the disclosure can comprise one or more needles (e.g., 1 to 10 needles, 1 to 8 needles, 1 to 6 needles, 1 to 4 needles, 1 to 2 needles, 4 to 10 needles, 4 to 8 needles, 4 to 6 needles, 6 to 10 needles, or 6 to 8 needles) . In some embodiments, the systems of the disclosure comprise 1 needle. In some embodiments, the systems of the disclosure comprise 2 needles. In some embodiments, the systems of the disclosure comprise 3 needles. In some embodiments, the systems of the disclosure comprise 4 needles. In some embodiments, the systems of the disclosure comprise 5 needles. In some embodiments, the systems of the disclosure comprise 6 needles. In some embodiments, the systems of the disclosure comprise 7 needles. In some embodiments, the systems of the disclosure comprise 8 needles. In some embodiments, the systems of the disclosure comprise 9 needles. In some embodiments, the systems of the disclosure comprise 10 needles.

[0039] As the number of needles simultaneously inserted through lids or walls of containers increases (e.g., when attached to a single robot arm), the total force required to push the needles through the lids or walls increases. The force that can be provided by different mechanical devices can be different and, therefore, the number of needles that can be simultaneously used can vary between devices. Similarly, the forces needed to push a needle through different containers (e.g., containers made of different materials or of different thickness) can vary and the number of needles that can be used simultaneously with a given device can vary depending on the container type. If the device is incapable of providing sufficient force to simultaneously push a given number of needles through the walls or lids of a given container type, the number of needles can be reduced until the force provided by the mechanical device is sufficient to push the needles through the walls or lids.

[0040] The systems of the disclosure are useful for extracting and/or injecting samples in plastic containers, such as laboratory plastic storage containers. Such containers include test tubes, vials, centrifuge tubes and multiwell plates. Preferred containers include domed or flat top tubes (such as, but not limited to, 0.1 - 0.5 ml PCR tubes (in some embodiments 0.1 ml, 0.2 ml or 0.5 ml PCR tubes), 0.1 ml PCR tubes strips; 0.5-2 ml microcentrifuge tubes (in some embodiments 0.6 ml, 1 .5 ml, 1.7 ml or 2 ml microcentrifuge tubes) and multiwell plates (e.g., a 6, 12, 24, 48 or 96 well plate). The plastic containers can be made from, for example, polypropylene, polyethylene, polycarbonate, polystyrene, poly(methyl

methacrylate) (PMMA), or cyclic olefin copolymer (COC). [0041] The systems of the disclosure are useful for handling {e.g., extracting and/or injecting) small volumes, for example volumes less than 1 ml (e.g., 0.1 ml to 0.9 ml, 0.3 ml to 0.9 ml, 0.5 ml to 0.9 ml, 0.5 ml to 0.9 ml, or 0.7 ml to 0.9 ml), less than 0.5 ml (e.g., 0.1 ml to 0.5 ml, 0.1 ml to 0.4 ml, or 0.2 ml to 0.3 ml), or less than 0.25 ml (e.g., 0.05 ml to 0.2 ml, 0.05 ml to 0.1 ml, or 0.1 ml to 0.2 ml). In certain applications, the systems of the disclosure are useful for handling (e.g., extracting and/or injecting) even smaller volumes, e.g., for sampling PCR reaction mixtures and PCR products. In some embodiments the PCR reaction mixtures handled are 100 μΙ or less, 80 μΙ or less, 60 μΙ or less, 40 μΙ or less, or 20 μΙ or less.

[0042] The systems of the disclosure can be used to prepare and mix samples, e.g., mixtures of template nucleic acids and PCR reagents, prior to a reaction and/or analysis. For example, a PCR buffer can be delivered by a system of the disclosure to a container containing or suspected of containing template nucleic acids. The contents of the tube can then be mixed by drawing all or part of the contents of the tube in and out of the needle one or more times (e.g., 1 to 5 times, 1 to 4 times, 1 to 3 times, 1 to 2 times, 2 to 5 times, 2 to 4 times, 2 to 3 times, 3 to 5 times, 3 to 4 times or 4 to 5 times). After mixing, some or all of the mixture can then be withdrawn from the tube by the needle and moved to another container (e.g., a PCR tube or multiwell plate) or instrument for reaction and/or analysis.

[0043] The systems of the disclosure can be used to mix different liquids prior to use, for example drugs, vaccines or chemicals. For example, the systems can be used to combine and mix two, three, four, or more than four different liquids (e.g., 2 to 5 liquids, 2 to 4 liquids or 2 to 3 liquids). Each of the different liquids can comprise a different drug, vaccine component or chemical, for example.

[0044] The systems of the disclosure can be used to extract or transfer liquids (e.g., high value liquids) where it is not desirable to disturb the resting state of the liquid (e.g., where the liquid comprises liquids of different phases or densities, or where the container contains one or more liquid phases and a solid phase).

[0045] The systems of the disclosure can be used to add or extract a liquid from a container where it is desirable to add or extract liquid so that the level of the liquid in the container after addition or extraction is at a desired level and when it is not desirable to disturb the original contents of the container, for example by opening a cap of the container.

[0046] The systems of the disclosure can also be used to extract an amount of a drug from a container such as a vial, e.g., for administration via an IV infusion pump. 5.1. DESCRIPTION OF PREFERRED EMBODIMENTS

[0047] In one embodiment where the needle is inserted from the top, referring to the drawing of FIG. 4, a polyethylene tube with cap closed on top 2 is immobilized within a holder, a sampling needle 1 is oriented vertically, aimed downward toward the cap of the tube. An actuator moves the sampling needle toward the surface of the polyethylene tube, where the actuator is secured to section 8 of the needle, pushing the needle tip through the plastic of the cap. The venting needle 6 is also pushed through the plastic cap, but not so far as to contact the liquid in the container. The venting needle 6 prevents overpressure or underpressure developing within the tube when liquids are being injected into or withdrawn from the container, since air in the tube can exchange with atmospheric air. The anti-coring inserts 5 prevents material from the cap from entering or otherwise blocking the flow of liquid or gas through the opening at the distal end of the needles. The anti-coring insert can be of the type from, but not limited to, any of the examples shown in FIGS. 5-7.

[0048] In a second embodiment, the needle of FIG. 1 may be used in a similar fashion as described in the first embodiment, above. The shaft 1 has a smaller diameter section 4. After the needle tip 2 has passed through the plastic of the cap and the venting section 4 remains traversing the cap when the needle is inserted to the sampling depth, a ring of exposed air around the needle exists that prevents overpressure or underpressure developing within the tube when liquids are being injected into or withdrawn from the container, since air in the tube can exchange with atmospheric air. The anti-coring insert 3 prevents material from the cap from entering or otherwise blocking the flow of liquid or gas through the distal terminus of the needle. The anti-coring insert can be of the type from, but not limited to, any of the examples shown in FIGS. 5-7.

[0049] In a third embodiment, the needle of FIG. 2 may be used in a similar fashion as described in the first and second embodiments, above. After the needle tip 2 has passed through the plastic of the cap and the venting groove 4 remains traversing the cap when the needle is inserted to the sampling depth, a passageway for air exists that prevents overpressure or underpressure developing within the tube when liquids are being injected into or withdrawn from the container, since air in the tube can exchange with atmospheric air through the venting groove. The anti-coring insert 3 prevents material from the cap from entering or otherwise blocking the flow of liquid or gas through the distal terminus of the needle. The anti-coring insert can be of the type from, but not limited to, any of the examples shown in FIGS. 5-7.

[0050] In a fourth embodiment, the needle of FIG. 3 may be used in a similar fashion as described in the first, second and third embodiments, above. After the needle tip 2 has passed through the plastic of the cap and the multiplicity of venting grooves 4 are traversing the cap when the needle is inserted to the sampling depth, multiple passageways for air exist that prevents overpressure or underpressure developing within the tube when liquids are being injected into or withdrawn from the container, since air in the tube can exchange with atmospheric air through the venting grooves. The anti-coring insert 3 prevents material from the cap from entering or otherwise blocking the flow of liquid or gas through the distal terminus of the needle. The anti-coring insert can be of the type from, but not limited to, any of the examples shown in FIGS. 5-7.

[0051] In a fifth embodiment, the liquid handling robot is a Tecan MSP 9000, MSP 9250 or MSP 9500 equipped with a robotic arm capable of manipulating a liquid handling tip. The probe tip normally affixed to the z-axis of the robot arm is replaced with any of the needles of FIGS. 1 - 4, fitted with any of the anti-coring elements of FIGS. 5-7, with the sampling tube of the liquid handling robot connected to the tubing attachment section of the needle.

[0052] In a sixth embodiment, the proximal terminus of the needle is fitted with a tapered connector, such as a luer type connector, FIG. 8, for attachment of the needle to a syringe or other fluid handling device equipped with a male luer connector.

[0053] In a seventh embodiment, as illustrated in FIG. 9, the proximal terminus of the needle is fitted with a tapered connector for attachment of the needle to a pipettor or other fluid handling device capable of using pipette tips. The tapered pipette compatible connector at the proximal terminus of the needle contains a region between the needle and the pipette connection area which can hold a desired volume of sample withdrawn from the container or substance to be dispensed into the container. The pipette tip portion of the needle may optionally be functionalized with depth stops that control the depth to which the needle may enter the container so that a second section of the container wall is not pierced and to permit for repeatable sampling.

6. SPECIFIC EMBODIMENTS

[0054] The present disclosure is exemplified by the specific embodiments below.

WHAT IS EMBODIMENTED IS:

1. A system for injecting or extracting a sample into or from a container comprising:

(a) a sampling needle; and

(b) a mechanical device for pushing the needle through a lid or wall of a container,

wherein the sampling needle comprises:

(i) a hollow shaft with a proximal end and a distal end, (ii) a piercing tip with a cutting point at the distal end of the hollow shaft, and

(iii) an anti-coring component in the piercing tip, said anti-coring component configured such that when the needle is pushed through the lid or wall of the container the piercing tip is prevented from penetrating the entire lid or wall.

2. The system of embodiment 1 , wherein when the needle is pushed through the lid or wall a flap is created that is displaced by the anti-coring component but remains attached to the lid or wall.

3. The system of embodiment 2, wherein when the needle is pushed through the lid or wall the needle makes a cut in the lid or wall that is 50%-90% of the perimeter of the distal end of the sampling needle.

4. The system of embodiment 3, wherein when the needle is pushed through the lid or wall the needle makes a cut in the lid or wall that is 60%-80% of the perimeter of the distal end of the sampling needle.

5. The system of embodiment 3, wherein when the needle is pushed through the lid or wall the needle makes a cut in the lid or wall that is about two thirds to three quarters of the perimeter of the distal end of the sampling needle.

6. The system of embodiment 3, wherein the cut is about two thirds of the perimeter of the distal end of the sampling needle.

7. The system of embodiment 3, wherein the cut is about three quarters of the perimeter of the distal end of the sampling needle.

8. The system of any one of embodiments 1 to 7, wherein the anti-coring component comprises an open tubular insert immobilized within the piercing tip.

9. The system of any one of embodiments 1 to 7, wherein the anti-coring component comprises a rod immobilized at the piercing tip.

10. The system of any one of embodiments 1 to 7, wherein the anti-coring component comprises a disk immobilized at the piercing tip. 11. The system of any one of embodiments 1 to 7, wherein the anti-coring component comprises a linear segment of material spanning from the cutting point to a point at or near the distal tip of the shaft.

12. The system of any one of embodiments 1 to 7, wherein the anti-coring component bisects the piercing tip.

13. The system of any one of embodiments 1 to 12, wherein the sampling needle further comprises a venting component.

14. The system of embodiment 13, wherein the venting component comprises a section of the shaft proximal to the piercing tip that is smaller than the diameter of the shaft at its distal tip.

15. The system of embodiment 13, wherein the venting component comprises a single venting groove on the exterior surface of the shaft between the proximal and distal ends.

16. The system of embodiment 13, wherein the venting component comprises a plurality of venting grooves on the exterior surface of the shaft between the proximal and distal ends.

17. The system of embodiment 15 or embodiment 16, wherein the diameter of the shaft is constant from the section of the shaft comprising the venting groove(s) to the distal tip of the shaft.

18. The system of embodiment 13, wherein the venting component comprises a venting needle affixed to the exterior surface of the shaft, wherein the venting needle comprises a hollow shaft with openings at the proximal and distal ends.

19. The system of embodiment 18, wherein the sampling needle further comprises an anti-coring component at the opening of the distal end of the venting needle.

20. The system of any one of embodiments 1 to 19, wherein the proximal end of the shaft comprises a tubing attachment section. 21. The system of any one of embodiments 1 to 19, wherein the sampling needle further comprises a connector at the proximal end of the shaft for connecting the sampling needle to the mechanical device.

22. The system of embodiment 21 , wherein the connector is a Luer connector.

23. The system of embodiment 21 , wherein the connector is a tapered connector for attaching the needle to the mechanical device.

24. The system of any one of embodiments 1 to 23, wherein the shaft comprises a section between the proximal and distal ends for securing and/or aligning the needle with the mechanical device.

25. The system of embodiment 24, wherein the section for securing and/or aligning the needle with the mechanical device has an outer diameter that is greater than the outer diameter of the distal end of the needle.

26. The system of any one of embodiments 1 to 25, wherein the mechanical device is an automated device.

27. The system of embodiment 26, wherein the automated device is a liquid and/or gas handling robot, which is optionally an autosampler, which is optionally a gas chromatography (GC) autosampler or a liquid chromatography (LC) autosampler.

28. The system of embodiment 27, wherein the liquid and/or gas handling robot is an autosampler.

29. The system of embodiment 28, wherein the autosampler is a GC

autosampler.

30. The system of embodiment 28, wherein the autosampler is a LC autosampler.

31. The system of any one of embodiments 1 to 30, which comprises 1 to 10 sampling needles.

32. The system of embodiment 31 , which comprises a single sampling needle. 33. The system of any one of embodiments 1 to 32, wherein the container is a plastic container.

34. The system of any one of embodiments 1 to 33, wherein the container is a polypropylene container.

35. The system of any one of embodiments 1 to 33, wherein the container is a polyethylene container.

36. The system of any one of embodiments 1 to 33, wherein the container is a polycarbonate container.

37. The system of any one of embodiments 1 to 33, wherein the container is a polystyrene container.

38. The system of any one of embodiments 1 to 33, wherein the container is a poly(methyl methacrylate) (PMMA) container.

39. The system of any one of embodiments 1 to 33, wherein the container is a cyclic olefin copolymer (COC) container.

40. The system of any one of embodiments 1 to 39, wherein the container is a tube having a lid and wherein the needle is configured and dimensioned to penetrate the lid of the tube.

41. The system of embodiment 40, wherein the tube is a 0.1 ml to 2 ml tube.

42. The system of embodiment 41 , wherein the tube is a 0.6 ml tube.

43. The system of embodiment 41 , wherein the tube is a 1.5 ml tube.

44. The system of embodiment 41 , wherein the tube is a 1.7 ml tube.

45. The system of embodiment 41 , wherein the tube is a 2 ml tube.

46. The system of any one of embodiments 41 to 45, wherein the tube is a microcentrifuge tube. 47. The system of embodiment 40, wherein the tube is a 0.1 ml to 0.5 ml tube.

48. The system of embodiment 47, wherein the tube is a 0.1 ml tube.

49. The system of embodiment 47, wherein the tube is a 0.2 ml tube.

50. The system of embodiment 47, wherein the tube is a 0.5 ml tube.

51. The system of any one of embodiments 47 to 50, wherein the tube is a PCR tube.

52. The system of embodiment 51 , wherein the tube is part of a PCR tube strip.

53. The system of any one of embodiments 40 to 52, wherein the lid of the tube is a domed cap.

54. The system of any one of embodiments 40 to 52, wherein the lid of the tube is a flat cap.

55. The system of any one of embodiments 1 to 39, wherein the container is a multiwell plate and wherein the needle is configured and dimensioned to penetrate a lid or wall of the multiwell plate.

56. The system of embodiment 55, wherein the multiwell plate is a 6 - 96 well plate.

57. The system of embodiment 55, wherein the multiwell plate is a 6 well plate.

58. The system of embodiment 55, wherein the multiwell plate is a 12 well plate.

59. The system of embodiment 55, wherein the multiwell plate is a 24 well plate.

60. The system of embodiment 55, wherein the multiwell plate is a 48 well plate.

61. The system of embodiment 55, wherein the multiwell plate is a 96 well plate. 62. A method for sampling a liquid or gas from a container, comprising inserting a sampling needle of a system according to any one of embodiments 1 to 61 into the lid or wall of a container containing a liquid or gas using the mechanical device and withdrawing a sample of the liquid or gas.

63. The method of embodiment 62, which further comprises adding a liquid or gas to the container through the needle prior to withdrawing the sample.

64. The method of embodiment 62 or embodiment 63, which further comprises mixing the contents of the container by withdrawing all or a portion of the liquid or gas from the container into the needle and returning the withdrawn liquid or gas to the container one or more times prior to withdrawing the sample.

65. The method of any one of embodiments 62 to 64, wherein the volume of the sample is less than 1 ml, less than 0.5 ml or less than 0.25 ml.

66. The method of embodiment 65, wherein the volume of the sample is less than

1 ml.

67. The method of embodiment 65, wherein the volume of the sample is less than

0.5 ml.

68. The method of embodiment 65, wherein the volume of the sample is less than 0.25 ml.

69. The method of any one of embodiments 65 to 68, wherein the volume of the sample is at least 0.05 ml.

70. The method of any one of embodiments 65 to 68, wherein the volume of the sample is at least 0.1 ml.

71. The method of any one of embodiments 65 to 68, wherein the volume of the sample is at least 0.2 ml.

72. The method of any one of embodiments 62 to 64, wherein the volume of the sample is 100 μΙ or less, 80 μΙ or less, 60 μΙ or less, 40 μΙ or less, or 20 μΙ or less. 73. The method of embodiment 72, wherein the volume of the sample is 100 μΙ or less.

74. The method of embodiment 72, wherein the volume of the sample is 80 μΙ or less.

75. The method of embodiment 72, wherein the volume of the sample is 60 μΙ or less.

76. The method of embodiment 72, wherein the volume of the sample is 40 μΙ or less.

77. The method of embodiment 72, wherein the volume of the sample is 20 μΙ or less.

78. The method of any one of embodiments 72 to 77, wherein the volume of the sample is at least 1 μΙ.

79. The method of any one of embodiments 72 to 77, wherein the volume of the sample is at least 5 μΙ.

80. The method of any one of embodiments 72 to 77, wherein the volume of the sample is at least 10 μΙ.

81. The method of any one of embodiments 62 to 80, wherein the container comprises a liquid.

82. The method of embodiment 81 , wherein the liquid comprises a biological or environmental sample.

83. The method of embodiment 81 or embodiment 82, wherein the liquid comprises nucleic acid molecules and/or polypeptide molecules.

84. The method of embodiment 81 or embodiment 82, wherein the liquid comprises nucleic acid molecules. 85. The method of embodiment 84, wherein the liquid comprises primers designed to amplify DNA using PCR.

86. The method of embodiment 85, wherein the primers are designed to amplify DNA from a pathogen.

87. The method of embodiment 86, wherein the pathogen is a human pathogen.

88. The method of any one of embodiments 81 to 87, wherein the liquid sample comprises probes.

89. The method of any one of embodiments 81 to 88, wherein the liquid comprises PCR amplicons.

90. The method of embodiment 89, wherein the PCR amplicons contain pathogen sequences.

91. The method of embodiment 90, wherein the pathogen sequences are amplified from a biological sample.

92. The method of embodiment 91 , wherein the biological sample is human blood or peritoneal dialysis fluid.

93. The method of any one of embodiments 83 to 92, which further comprises performing PCR prior to withdrawing the sample.

94. A method for adding a liquid or gas to a container, comprising inserting a sampling needle of a system according to any one of embodiments 1 to 61 into the lid or wall of a container using the mechanical device and adding a liquid or gas to the container through the sampling needle.

95. The method of embodiment 94, further comprising mixing the contents of the container after adding the liquid or gas by withdrawing all or a portion of the liquid or gas from the container into the needle and returning the withdrawn liquid or gas to the container one or more times. 96. The method of embodiment 94 or embodiment 95, further comprising withdrawing a sample of the liquid or gas from the container.

97. The method of any one of embodiments 62 to 93 or 96, wherein the sample is a portion of the liquid or gas in the container.

98. The method of any one of embodiments 62 to 93 or 96, wherein the sample is all of the liquid or gas in the container.

99. The method of any one of embodiments 94 to 98, wherein the volume of the liquid or gas added to the container is less than 1 ml, less than 0.5 ml or less than 0.25 ml.

100. The method of embodiment 99, wherein the volume of the liquid or gas added to the container is less than 1 ml.

101. The method of embodiment 99, wherein the volume of the liquid or gas added to the container is less than 0.5 ml.

102. The method of embodiment 99, wherein the volume of the liquid or gas added to the container is less than 0.25 ml.

103. The method of any one of embodiments 99 to 102, wherein the volume of the liquid or gas added to the container is at least 0.05 ml.

104. The method of any one of embodiments 99 to 102, wherein the volume of the liquid or gas added to the container is at least 0.1 ml.

105. The method of any one of embodiments 99 to 102, wherein the volume of the liquid or gas added to the container is at least 0.2 ml.

106. The method of any one of embodiments 94 to 98, wherein the volume of the liquid or gas added to the container is 100 μΙ or less, 80 μΙ or less, 60 μΙ or less, 40 μΙ or less, or 20 μΙ or less.

107. The method of embodiment 106, wherein the volume of the liquid or gas added to the container is 100 μΙ or less. 108. The method of embodiment 106, wherein the volume of the liquid or gas added to the container is 80 μΙ or less.

109. The method of embodiment 106, wherein the volume of the liquid or gas added to the container is 60 μΙ or less.

110. The method of embodiment 106, wherein the volume of the liquid or gas added to the container is 40 μΙ or less.

11 1. The method of embodiment 106, wherein the volume of the liquid or gas added to the container is 20 μΙ or less.

112. The method of any one of embodiments 106 to 11 1 , wherein the volume of the liquid or gas added to the container is at least 1 μΙ.

113. The method of any one of embodiments 106 to 11 1 , wherein the volume of the liquid or gas added to the container is at least 5 μΙ.

114. The method of any one of embodiments 106 to 11 1 , wherein the volume of the liquid or gas added to the container is at least 10 μΙ.

115. The method of any one of embodiments 94 to 115, which comprises adding a liquid to the container.

116. The method of embodiment 1 15, wherein the container comprises a biological or environmental sample to which the liquid is added.

117. The method of embodiment 115 or embodiment 116, wherein the container comprises nucleic acid molecules and/or polypeptide molecules.

118. The method of embodiment 115 or embodiment 116, wherein the container comprises nucleic acid molecules.

119. The method of embodiment 1 18, wherein the liquid added to the container comprises primers designed to amplify DNA using PCR. 120. The method of embodiment 119, wherein the primers are designed to amplify DNA from a pathogen.

121. The method of embodiment 120, wherein the pathogen is a human pathogen.

122. The method of any one of embodiments 115 to 121 , wherein the liquid added to the container comprises probes.

123. The method of any one of embodiments 115 to 122, wherein the container contains a biological sample.

124. The method of embodiment 123, wherein the biological sample is human blood or peritoneal dialysis fluid.

125. The method of any one of embodiments 117 to 124, which further comprises performing PCR after adding the liquid to the container.

126. The method of embodiment 125, when depending directly or indirectly from embodiment 96, wherein the PCR is performed before withdrawing the sample from the container.

127. The method of any one of embodiments 62 to 126, wherein the needle is inserted with a force that is sufficient to penetrate the lid or wall of the container but insufficient to bend the piercing tip.

128. The method of any one of embodiments 62 to 127, wherein

(a) if the surface of the container into which the needle is inserted is flat, then the needle is inserted into the container at an angle of 75° to 105°, preferably at an angle of 85° to 95°, relative to the surface, and

(b) if the surface of the container into which the needle is inserted is curved, then the needle is inserted at a point on the surface of the container and at an angle of 75° to 105°, preferably at an angle of 85° to 95°, relative to a tangent plane at the point of insertion.

[0055] The present disclosure is further exemplified by the specific embodiments below. V. A sampling needle for injecting or extracting a sample into or from a container, comprising: (1) a hollow shaft with a proximal end and a distal end, (2) a piercing tip with a cutting point at the distal end of the hollow shaft, and (3) an anti-coring component in the piercing tip, said anti-coring component configured such that when the needle is pushed through the lid or wall of the container the piercing tip is prevented from penetrating the entire lid or wall.

2'. The sampling needle of embodiment 1 ', wherein when the needle is pushed through the lid or wall a flap is created that is displaced by the anti-coring component but remains attached to the lid or wall.

3'. The sampling needle of embodiment 2', wherein when the needle is pushed through the lid or wall the needle makes a cut in the lid or wall that is 60%-80% of the perimeter of the distal end of the sampling needle.

4'. The sampling needle of embodiment 3', wherein the cut is about two thirds of the perimeter of the distal end of the sampling needle.

5'. The sampling needle of embodiment 3', wherein the cut is about three quarters of the perimeter of the distal end of the sampling needle.

6'. The sampling needle of any one of embodiments V to 5', wherein the anti- coring component comprises an open tubular insert immobilized within the piercing tip.

7'. The sampling needle of any one of embodiments V to 5', wherein the anti- coring component comprises a rod immobilized at the piercing tip.

8'. The sampling needle of any one of embodiments V to 5', wherein the anti- coring component comprises a disk immobilized at the piercing tip.

9'. The sampling needle of any one of embodiments V to 5', wherein the anti- coring component comprises a linear segment of material spanning from the cutting point to a point at or near the distal tip of the shaft.

10'. The sampling need of any one of embodiments V to 5', wherein the anti- coring component bisects the piercing tip.

11 '. The sampling needle of any one of embodiments V to 10', further comprising a venting component. 12'. The sampling needle of embodiment 11 ', wherein the venting component comprises a section of the shaft proximal to the piercing tip that is smaller than the diameter of the shaft at its distal tip.

13'. The sampling needle of embodiment 11 ', wherein the venting component comprises a single venting groove on the exterior surface of the shaft between the proximal and distal ends.

14'. The sampling needle of embodiment 11 ', wherein the venting component comprises a plurality of venting grooves on the exterior surface of the shaft between the proximal and distal ends.

15'. The sampling needle of embodiment 13' or embodiment 14', wherein the diameter of the shaft is constant from the section of the shaft comprising the venting groove(s) to the distal tip of the shaft.

16'. The sampling needle of embodiment 11 ', wherein the venting component comprises a venting needle affixed to the exterior surface of the shaft, wherein the venting needle comprises a hollow shaft with openings at the proximal and distal ends.

17'. The sampling need of embodiment 16', further comprising an anti-coring component at the opening of the distal end of the venting needle.

18'. The sampling needle of any one of embodiments 1' to 17', wherein the proximal end of the shaft comprises a tubing attachment section.

19'. The sampling needle of any one of embodiments 1' to 17', further comprising a connector at the proximal end of the shaft.

20'. The sampling needle of embodiment 19', wherein the connector is a Luer connector.

21 '. The sampling needle of embodiment 19', wherein the connector is a tapered connector for attaching the needle to a pipettor or other fluid handling device capable of using pipette tips.

22'. The sampling needle of any one of embodiments 1' to 21', wherein the shaft comprises a section between the proximal and distal ends for securing and/or aligning the needle with a liquid/gas handing device. 23'. The sampling needle of embodiment 22', wherein the section for securing and/or aligning the needle with a liquid/gas handling device has an outer diameter that is greater than the outer diameter of the distal end of the needle.

24'. The sampling needle of any one of embodiments V to 23' which is attached to a pipetting device.

25'. The sampling needle of embodiment 24', wherein the pipetting device is automated.

26'. The sampling needle of any one of embodiments V to 25', wherein the container is a plastic container.

27'. The sampling needle of any one of embodiments V to 25', wherein the container is a polypropylene container.

28'. The sampling needle of any one of embodiments V to 25', wherein the container is a polyethylene container.

29'. The sampling needle of any one of embodiments V to 25', wherein the container is a polycarbonate container.

30'. The sampling needle of any one of embodiments V to 25', wherein the container is a polystyrene container.

31 '. The sampling needle of any one of embodiments V to 25', wherein the container is a poly(methyl methacrylate) (PMMA) container.

32'. The sampling needle of any one of embodiments V to 25', wherein the container is a cyclic olefin copolymer (COC) container.

33'. The sampling needle of any one of embodiments V to 32', wherein the container is a tube and wherein the needle is configured and dimensioned to penetrate the lid of the tube.

34'. The sampling needle of embodiment 33', wherein the tube is a 0.2 ml tube. 35'. The sampling needle of embodiment 33', wherein the tube is a 0.5 ml tube.

36'. The sampling needle of any one of embodiments 33' to 35', wherein the lid of the tube is a domed cap. 37'. The sampling needle of any one of embodiments 33' to 35', wherein the lid of the tube is a flat cap.

38'. The sampling needle of any one of embodiments 33' to 37', wherein the tube is a PCR tube.

39'. The sampling needle of any one of embodiments V to 32', wherein the container is a multiwell plate and wherein the needle is configured and dimensioned to penetrate a lid or wall of the multiwell plate.

40'. A method for sampling a liquid or gas from a container, comprising inserting a needle of any one of embodiments V to 39' into the lid or wall of a container containing a liquid or gas and withdrawing a sample of the liquid or gas.

41 '. The method of embodiment 40', wherein the container comprises a liquid.

42'. The method of embodiment 41', wherein the liquid comprises a biological or environmental sample.

43'. The method of embodiment 41' or embodiment 42', wherein the liquid comprises nucleic acid molecules.

44'. The method of embodiment 43', wherein the liquid comprises primers designed to amplify DNA using PCR.

45'. The method of embodiment 44', wherein the primers are designed to amplify DNA from a pathogen.

46'. The method of embodiment 45', wherein the pathogen is a human pathogen.

47'. The method of any one of embodiments 41 ' to 46', wherein the liquid sample comprises probes.

48'. The method of any one of embodiments 41 ' to 47', wherein the liquid comprises PCR amplicons.

49'. The method of embodiment 48', wherein the PCR amplicons contain pathogen sequences.

50'. The method of embodiment 49', wherein the pathogen sequences are amplified from a biological sample. 51 '. The method of embodiment 50', wherein the biological sample is human blood or peritoneal dialysis fluid.

52'. The method of any one of embodiments 40' to 51', wherein the needle is inserted with a force that is sufficient to penetrate the lid or wall of the container but insufficient to bend the piercing tip.

53'. The method of any one of embodiments 40' to 52', wherein

(a) if the surface of the container into which the needle is inserted is flat, then the needle is inserted into the container at an angle of 75° to 105°, preferably at an angle of 85° to 95°, relative to the surface, and

(b) if the surface of the container into which the needle is inserted is curved, then the needle is inserted at a point on the surface of the container and at an angle of 75° to 105°, preferably at an angle of 85° to 95°, relative to a tangent plane at the point of insertion.

[0056] The present disclosure is further exemplified by the specific embodiments below.

1 ". A piercing device, or needle, for injection or extraction of liquids or gasses into or out from containers after piercing the cap or bottom or walls of said container, comprising: a) a shaft, b) a piercing tip, and c) an anti-coring component.

2". The device of embodiment 1" that includes a component for venting the container.

3". The device of embodiment 1 " that includes a venting component that can be attached to a vacuum system and/or a gas delivery system to provide for atmospheric pressure and composition control within the container.

4". The device of any of embodiments 1 ", 2" and 3", that includes a section for the connection of tubing to the needle for delivery or removal of liquids or gasses to and from the container.

5". The device of any of embodiments 1 ", 2", 3" and 4" that includes a section along the needle body which can be used to secure the needle within a liquid handling device. 6". The device of any of embodiments 1 ", 2" and 3" that includes a luer connector for connection of the needle to a device fitted with a male luer connector.

7". The device of any of embodiments 1 ", 2" and 3" that includes a tapered connector at the proximal terminus for connection to a pipetting device.

8". The device of any of embodiments 2"-7" where the venting component, illustrated in FIG. 1 , is comprised of a reduced diameter section 4 of the needle body that enables venting of gas to permit equilibration between the container and the outside atmosphere; wherein the shaft diameter is reduced beyond the tip so that after complete penetration, an open ring around the narrower portion of the shaft exposes the interior of the container to atmospheric pressure so that gas can exit or enter the container to prevent build-up of positive or negative pressure

9". The device of any of embodiments 2"-7" where the venting component, illustrated in FIG. 2, is comprised of a single groove 4 in the needle body that enables venting of gas to prevent overpressure or underpressure when liquids are being injected into or withdrawn from the container; wherein the venting groove is situated along the needle shaft, above the level of liquid in the container and on the section of the needle traversing the container wall or cap material.

10". The device of any of embodiments 2"-7" where the venting component, illustrated in FIG. 3, is comprised of a multiplicity of grooves 4 in the needle body that enable venting of gas to prevent overpressure or underpressure when liquids are being injected into or withdrawn from the container; wherein the venting grooves are situated along the needle shaft, above the level of liquid in the container and on the section of the needle traversing the container wall or cap material.

11 ". A piercing device according to any of embodiments 2"-7", 9" and 10", with a constant diameter tip section functionalized with one or a multiplicity of venting grooves, illustrated in FIG. 2 and FIG. 3, that increases reliability by preventing bending of the shaft.

12". A piercing device according to any of embodiments 2"-7", referring to FIG. 4, with a venting component comprised of a second needle 6 affixed to the main needle.

13". A piercing device according to any of embodiments 1 "-12", referring to FIG. 5, with an anti-coring component 2 comprised of an open tubular insert immobilised within the bore of the needle tip that prevents the bore of needle from being occluded or filled with material from the cap or walls of the container by causing the material cut by the tip 1 to be pushed away from the syringe shaft as the terminus of the anti-coring section traverses the cap or walls of the container.

14". A piercing device according to any of embodiments 1 "-12", referring to FIG.

6, with a anti-coring component 2 comprised of a linear segment spanning the region between the needle tip 1 and a second point along the needle opening that prevents the bore of needle from being occluded or filled with material from the cap or walls of the container by causing the material cut by the tip 1 to be pushed away from the syringe shaft as the cutting faces of the needle traverse the cap or walls of the container.

15". A piercing device according to any of embodiments 1 "-12", referring to FIG.

7, with a anti-coring component 2 comprised of a linear segment that bisects the inner needle bore and spans the region between the needle tip 1 and a second point along the needle opening that prevents the bore of needle from being occluded or filled with material from the cap or walls of the container by causing the material cut by the tip 1 to be pushed away from the syringe shaft as the cutting faces of the needle traverse the cap or walls of the container.

16". A piercing device according to any of embodiments 1 "-12", with an anti-coring component comprised of a rod situated within the inner needle bore that protrudes into the chamfered cutting section of the needle terminus that prevents the bore of needle from being occluded or filled with material from the cap or walls of the container by causing the material cut by the tip to be pushed away from the syringe shaft as the anti-coring insert traverses the cap or walls of the container.

17". A piercing device according to any of embodiments 1"-16" for piercing PCR tubes.

18". A piercing device according to any of embodiments 1"-16" for piercing flat- capped PCR tubes.

19". A piercing device according to any of embodiments 1"-16" for piercing domed- capped PCR tubes.

20". A piercing device according to any of embodiments 1"-16" for piercing a PCR tube situated within a 96 PCR tube plate and sealed with a sealing film.

21 ". A piercing device according to any of embodiments 1"-20" which maintains the portion of container material cut by the needle attached to the container. [0057] While various specific embodiments have been illustrated and described, it will be appreciated that various changes can be made without departing from the spirit and scope of the disclosure(s).

7. CITATION OF REFERENCES

[0058] All publications, patents, patent applications and other documents cited in this application are hereby incorporated by reference in their entireties for all purposes to the same extent as if each individual publication, patent, patent application or other document were individually indicated to be incorporated by reference for all purposes. In the event that there is an inconsistency between the teachings of one or more of the references

incorporated herein and the present disclosure, the teachings of the present specification are intended.