Reclosable septum cap for medical sample transport and processing

Abstract

A pierceable lid 720 can be used to hold a sample. The pierceable lid 720 can prevent the sample from escaping before it is transferred by the transfer device 43. The pierceable lid 720 can be mounted on a container 730. An access port in the housing of the pierceable lid 730 can allow the transfer device 43 to pass through the pierceable lid 730. The housing houses a septum 700 having four semi-dome notches 715, each defining a quadrant within the septum. The notches are separated by a septum bottom layer 795, which extends along respective first and second diameters of the septum 700 and intersects at approximately ninety degrees. The semi-dome notches guide the transfer device to the partially slotted portion of the septum bottom layer 795.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to and the benefit of U.S. Provisional Application No. 62 / 861,043, filed June 13, 2019, which is incorporated herein by reference. Commonly owned U.S. Patent Application Serial No. 11 / 785,144, filed April 16, 2007, and entitled “Pierceable Cap,” issued March 5, 2013 as U.S. Patent No. 8,387,810, and U.S. Patent Application Serial No. 11 / 979,713, filed November 7, 2007, and entitled “Pierceable Cap,” issued March 5, 2013 as U.S. Patent No. 8,387,811, are related to this application and are incorporated herein by reference in their entireties. The entire contents of International Application PCT / US2012 / 024993, filed February 14, 2012 (published as WO 2012 / 112505), which claims priority to U.S. Provisional Application Serial No. 61 / 442,676 (filed February 14, 2011) and U.S. Provisional Application Serial No. 61 / 442,634 (filed February 14, 2011), are also incorporated herein by reference. U.S. Patent No. 9,545,632, issued January 17, 2017 (application serial No. 13 / 985,177, filed February 14, 2012), and U.S. Patent Application No. 15 / 372,021, filed December 7, 2016, both entitled “Pierceable Cap,” are commonly owned patents and applications, the entire contents of which are incorporated herein by reference. Background Art

[0003] The cap and container combination is often used to receive and store specimens. In particular, biological and chemical specimens may be analyzed to determine the presence of specific biological or chemical agents. The types of biological specimens commonly collected and delivered to clinical laboratories for analysis may include blood, urine, sputum, saliva, pus, mucus, cerebrospinal fluid, and others. Because these specimen types may contain pathogenic organisms or other harmful components, it is important to ensure that the container is substantially leak-proof during use and transport. Substantially leak-proof containers are particularly important in situations where the clinical laboratory and collection facility are separate.

[0004] To prevent leakage from the container, the cap is typically screwed, snapped, or otherwise frictionally fitted onto the container, thereby forming a substantially leak-proof seal between the cap and the container. In addition to preventing sample leakage, the substantially leak-proof seal formed between the cap and the container can reduce the sample's exposure to potential contaminants from the surrounding environment. The leak-proof seal prevents the introduction of contaminants that could alter the qualitative or quantitative results of the assay and prevents the loss of material that may be important to the analysis.

[0005] Although a substantially leak-proof seal can prevent sample leakage during transport, physically removing the cap from the container prior to sample analysis presents another opportunity for contamination. When the cap is removed, any material that may have accumulated on the underside of the cap during transport may come into contact with the user or equipment, potentially exposing the user to harmful pathogens present in the sample. If a film or bubble forms around the mouth of the container during transport, the film or bubble may burst when the cap is removed from the container, thereby dispersing the sample into the environment. Sample residue from one container may have been transferred to the user's gloved hand, which may also come into contact with the specimen in another container through routine or accidental removal of the cap. Another risk is the generation of contaminated aerosols when the cap and container are physically separated from each other, which may cause false positives or inflated results through cross-contamination in other samples assayed simultaneously or subsequently in the same general working area.

[0006] The problem of cross-contamination is particularly severe when the assay being performed involves nucleic acid detection and amplification procedures, such as the well-known polymerase chain reaction (PCR) or transcription-based amplification systems (TAS), such as transcription-mediated amplification (TMA) or strand displacement amplification (SDA). Because the purpose of amplification is to increase assay sensitivity by increasing the amount of target nucleic acid sequence present in a sample, even the transfer of a very small amount of target nucleic acid from a sample or positive control sample from another container to an otherwise negative sample can result in a false-positive result.

[0007] The pierceable lid can alleviate the labor of removing the screw cap before testing, which may be quite large in the case of high-throughput equipment. The pierceable lid can minimize the possibility of generating aerosols of contaminated samples and can limit direct contact between samples and people or the environment. Some lids that only cover the container opening with a fragile layer (such as foil) may cause pollution by ejecting the droplets of the contents in the container into the surrounding environment when pierced. When the sealed container is penetrated by the transfer device, the amount of space occupied by the fluid transfer device will displace an equal volume of air from the collecting device. In addition, temperature changes can cause the pressure of the sealed collection container to be greater than the surrounding air, which can be released after piercing the lid. This air displacement can release a part of the sample into the surrounding air by aerosols or bubbles. It is desirable to have a lid that allows air to be transferred out from the container in a manner that reduces or eliminates the generation of aerosols or bubbles that may be harmful or contaminated.

[0008] Other existing systems have used an absorbent, permeable material above the frangible layer to contain any possible contamination, but the equipment required to apply and retain this material adds cost. In other systems, the cap may use pre-cut elastomer for a pierceable seal, but these caps can leak. Other designs with valve-type seals have been tried, but valve-type seals can cause dispensing accuracy issues.

[0009] Ideally, the cap can be used in both manual and automated applications and is suitable for use with pipette tips made of plastic material.

[0010] Generally, there is a need for improved apparatus and methods for sealing containers with caps during transport, inserting transfer devices, resealing and storing samples after initial testing, additionally transferring samples from containers after storage, or transferring samples. Also described are improvements for replacement caps that have already been used and may need to be sealed and stored for future use. Summary of the Invention

[0011] Described herein are reclosable septum caps for medical sample transport and processing. Embodiments of the present invention solve some problems and / or overcome many of the shortcomings and drawbacks of the prior art by providing an apparatus and method for sealing a container having a pierceable cap, wherein a transfer device is inserted through the seal for transporting a sample to or from the container, and the pierceable cap reseals when the transfer device is withdrawn from insertion through the septum cap.

[0012] Certain embodiments of the present invention achieve this by providing a pierceable cover device comprising: a housing; an access port in the housing for allowing at least a portion of a transfer device to pass through the access port, wherein the transfer device transfers a sample; a lower frangible layer disposed across the access port for preventing the sample from being transferred through the access port prior to insertion of at least a portion of the transfer device; one or more upper frangible layers disposed across the access port for preventing the sample from being transferred through the access port after at least a portion of the transfer device is inserted through the lower frangible layer; one or more extensions between the lower frangible layer and the one or more upper frangible layers, and wherein the one or more extensions move and pierce the lower frangible layer when pressure is applied from the transfer device.

[0013] In an embodiment of the present invention, the lower frangible layer may be coupled to one or more extensions. The one or more upper frangible layers may contact the conical tip of the transfer device during rupture of the lower frangible layer.

[0014] Embodiments of the present invention may include one or more upper frangible layers that are peripherally or otherwise vented.

[0015] In an embodiment of the present invention, the upper and lower fragile layers may be made of foil or other materials. The upper and lower fragile layers may be constructed of the same material and have the same dimensions. Either or both of the upper and lower fragile layers may be pre-scored.

[0016] Embodiments of the present invention may include an external recessed portion within the access port and between the top of the housing and the one or more extensions.

[0017] The one or more upper frangible layers may be offset from the top of the housing or may be flush with the top of the housing.

[0018] A peripheral groove may be provided for securing the lower frangible layer within the housing. A gasket may be provided for securing the lower frangible layer within the housing and creating a seal between the pierceable lid and the container.

[0019] In an embodiment of the present invention, movement of one or more extensions may create airways to allow air to move through the inlet port. One or more upper frangible layers may be ventilated at the periphery to create a labyrinthine path for air to move through the inlet port.

[0020] Alternative embodiments of the present invention may include a housing, an access port extending through the housing, a lower frangible layer disposed across the access port, an upper frangible layer disposed across the access port, and one or more extensions between the lower frangible layer and the upper frangible layer, wherein the one or more extensions are coupled to a wall of the access port via one or more coupling regions.

[0021] In another alternative embodiment, a single frangible seal is positioned within the housing. In these embodiments, the seal is configured to address the problem caused by the fact that the volume of air displaced in the container by a transfer device (e.g., a pipette) may be greater than the headspace in the container containing the sample. In certain embodiments, such a seal is made of a material that forms a seal around the transfer device upon initial puncture (to prevent backsplash of fluid from the container during puncture), but only allows venting from the container after the initial puncture. In other embodiments, a frangible seal is not required to seal around the transfer device to prevent atomization upon puncture, as the narrowed portion of the seal itself serves to prevent unwanted backsplash, as described in further detail below. To facilitate venting, the seal is provided with a preferably asymmetrical tearable portion disposed on a structural rib on the underside of the seal. However, symmetrical tearable portions are also contemplated. The weakened portion tears in a manner that does not allow venting during initial puncture, but venting will occur when the transfer device is advanced through the seal due to the asymmetry of the tearable portion. This design takes advantage of the use of a tapered transfer device, where the tip (distal portion) of the transfer device has the smallest diameter. The increased thickness of the transfer device causes the weakened portion to tear, and those tears allow for the desired venting during transfer, but not during the initial puncture of the frangible seal. During the initial puncture, venting from the container can only be achieved through the transfer device (not through the frangible seal). In an alternative embodiment, the seal and housing are a unitary structure as contemplated herein.

[0022] In another alternative embodiment, the frangible seal is configured so that its perimeter narrows as it extends from the lid in which it is located into the container. This narrowing serves a dual purpose, namely, to guide the transfer device to the weakened portion for insertion through the seal and (as described above) to prevent the sample from splashing back during the initial puncture. The narrowed portion can have a circumferential band that is integral with the seal or configured as an O-ring that applies upward pressure to the narrowed portion, thereby closing the transfer device when it is removed from the container, thereby substantially resealing the transfer device after the sample transfer. After the initial puncture, the walls of the narrowed portion can also close together to achieve a closed reseal.

[0023] Embodiments of the present invention may also include a method of piercing a cover, the method comprising: providing a pierceable cover, the pierceable cover comprising a shell, an access port passing through the shell, a lower fragile layer arranged across the access port, an upper fragile layer arranged across the access port, and one or more extensions between the lower fragile layer and the upper fragile layer, wherein the one or more extensions are coupled to the wall of the access port through one or more coupling areas; inserting a transfer device into the access port, applying pressure to the one or more upper fragile layers to rupture the one or more upper fragile layers, and applying pressure to the one or more extensions with the transfer device, wherein the one or more extensions rotate about the one or more coupling areas to contact the lower fragile layer and rupture the lower fragile layer, and further inserting the transfer device through the access port.

[0024] In another embodiment, the pierceable cover can include a housing adapted to be coupled to a sample container, and the housing can further include an access port in the housing that allows passage of a fluid transfer device, such as a pipette. The cover can also include a penetrable seal having walls, wherein those walls form a bottom surface having an openable slitted portion adapted to be closed when the pierceable cover is secured to the sample container. As used herein, bottom refers to the container side of the septum. As used herein, top refers to the cover side of the septum.

[0025] In other embodiments, the pierceable lid may include an annular ring from which a wall extends and has a lower surface having a protrusion that can be configured to compress against the sample container when the pierceable lid is fastened to the sample container. This compression occurs when the lid is screwed onto the container and causes the openable slit portion to close. The openable slit portion can be a tearable slit portion or an unconnected slit.

[0026] In yet another embodiment, the pierceable cap may include an elastomeric housing including a locking structure for securing the housing to the container and may also include a resilient access port in the housing to allow passage of at least a portion of a transfer device. The cap may also include a frangible layer having cross slits disposed across the access port, which may prevent transfer of a sample specimen through the access port prior to insertion of at least a portion of the transfer device.

[0027] The fragile layer may also have a ribbed portion extending inward and downward into the container, the ribbed portion terminating in a bottom surface on which the weakened portion is disposed. This bottom surface is referred to herein as the septum floor. These cross slits may be tearable mesh cross slits or unconnected cross slits. Other slit configurations include scored portions in which the scores do not extend through the entire thickness of the pierceable septum. These partially scored portions are referred to herein as partial slits. The partial slits are oriented so that the slits on the bottom surface of the septum extend upward and only partially through the thickness of the septum floor. The lid may also include an O-ring disposed on the housing, the O-ring being disposed between the housing and the sample container when the housing is positioned on the sample container. The fragile layer and the O-ring may be integral, and the ribbed portion of the fragile layer may be used to guide the transfer device to the slit portion during insertion and to close each other when the transfer device is removed. This structural arrangement allows the slit portion to be openable.

[0028] In one embodiment, the frangible seal is a diaphragm made of an elastomeric material located within the cap. The diaphragm engages a tube to which the cap is fastened. Typically, both the cap and the tube are threaded. The cap is fastened to the tube by a threaded engagement. The diaphragm is configured to have a retaining ring that is at least partially received by a complementary recess in the cap. The recess is defined by a cap wall on one side and a rib extending from the side of the cap wall. The protrusion of the diaphragm retaining ring fits into the gap defined by the cap wall and the rib. Fitting the retaining ring protrusion into this recess in the transverse extension of the cap wall ensures that the diaphragm remains in place when a pipette is inserted into or removed from the diaphragm.

[0029] In this embodiment, the septum retention ring further includes transversely extending barbs extending toward the cover wall. When the cover with the septum is assembled onto the nozzle, the barbs deform and become lodged between the nozzle's outer wall and the cover. When the cover is not tightened onto the tube, the barbs secure the septum in the cover. The inner wall of the cover has a slightly wider inner diameter in the area of ​​the barbs and tapers to a slightly smaller inner diameter, so that the barbs are accommodated within the wider inner diameter of the cover and retained within the cover by the narrower inner diameter of the cover.

[0030] In this embodiment, the tearable or weakened portion of the septum is defined by four semi-dome structures extending from the periphery of the septum to the interior of the septum, where a pipette passes through the septum to aspirate or dispense a sample from or into a tube. In one embodiment, the semi-dome structures are configured as cusps that intersect halfway up the second cusp. The septum wall is configured as two slanted triangles bifurcated by the semi-arches. After the pipette is withdrawn from engagement with the septum, the arch structures force the septum closed.

[0031] Also described herein is a method for piercing a septum lid. According to the method, a container having a pierceable lid is obtained. The pierceable lid comprises a housing and an access port in the housing adapted to allow at least a portion of a transfer device to pass through the access port. The septum seal comprises a collar and a plurality of semi-dome notches extending from the periphery of the septum toward its center. The notches extend inwardly and downwardly toward a substantially planar septum substrate. The septum substrate has a thickness, wherein the housing is adapted to accommodate the septum seal, and wherein the substantially planar septum substrate includes a slotted portion that only partially extends through the thickness of the septum substrate. A pipette tip is positioned over the septum seal. The pipette tip is advanced into contact with the septum substrate, thereafter further advanced through the septum substrate such that the pipette tip initially advances through an unslotted portion of the thickness of the septum substrate and subsequently further advances through the slotted portion. According to the method, the access port comprises a first frangible layer positioned within the access port. The pipette tip is advanced through the frangible layer, and subsequently the pipette tip is advanced through the septum substrate.

[0032] Additional features, advantages, and embodiments of the present invention are set forth or become apparent by considering the following detailed description, the accompanying drawings, and the appended claims. In addition, it should be understood that the foregoing summary of the present invention and the following detailed description are exemplary and are intended to provide further explanation without limiting the scope of the invention as claimed. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] The accompanying drawings are included to provide a further understanding of the present invention and are incorporated in and constitute a part of this specification. The accompanying drawings illustrate preferred embodiments of the present invention and, together with the detailed description, serve to explain the principles of the present invention. In the drawings:

[0034] Figure 1A A perspective view of a pierceable cap having a septum frangible layer.

[0035] Figure 1B for Figure 1A A top view of the pierceable cover.

[0036] Figure 1C for Figure 1A Side view of the pierceable cover.

[0037] Figure 1D for Figure 1A A cross-sectional view of a pierceable cover.

[0038] Figure 1E for Figure 1A Bottom view of a pierceable cover with a septum (not shown) being pierced.

[0039] Figure 1F for the reason Figure 1A A top view of the pierceable cover molded into place.

[0040] Figure 1G is a cross-sectional view of a pierceable cap coupled to a container with a pipette tip inserted through the cap.

[0041] Figure 2A A perspective view of a possible weak layer diaphragm.

[0042] Figure 2B for Figure 2A Cross-sectional view of the fragile layer.

[0043] Figure 3A A perspective view of a pierceable lid having a foil frangible layer.

[0044] Figure 3B for Figure 3A A top view of the pierceable cover.

[0045] Figure 3C for Figure 3A Side view of the pierceable cover.

[0046] Figure 3D for Figure 3C A cross-sectional view of a pierceable cover.

[0047] Figure 3E for Figure 3A Bottom view of the pierceable cover molded into it.

[0048] Figure 3F for Figure 3A Bottom view of a pierceable cover, wherein the pierceable cover with a foil not shown is pierced.

[0049] Figure 3G For coupling to the container Figure 3A Cross-sectional view of a pierceable cap with a pipette tip inserted through the cap.

[0050] Figure 4A is a perspective view of a pierceable cap having a lower frangible layer and extensions in a flat star-shaped pattern.

[0051] Figure 4B for Figure 4A A perspective cutaway view of a pierceable cover.

[0052] Figure 5A A perspective view of a pierceable cap having a conical molded frangible layer and extensions in a flat star pattern.

[0053] Figure 5B for Figure 5A A cross-sectional view of a pierceable cover.

[0054] Figure 6A A perspective top view of a pierceable lid having two frangible layers and a slightly concave upper frangible layer.

[0055] Figure 6B for Figure 6A A perspective bottom view of the pierceable cover.

[0056] Figure 6C for Figure 6A A cross-sectional view of a pierceable cover.

[0057] Figure 6D for Figure 6A A perspective view of the pierceable lid with a pipette tip inserted through the two fragile layers.

[0058] Figure 6E for Figure 6A Cross-sectional view of the pierceable cap with the pipette tip inserted through the two fragile layers.

[0059] Figure 7A A perspective view of a pierceable cap having a V-shaped frangible layer.

[0060] Figure 7B for Figure 7A A top view of the pierceable cover.

[0061] Figure 7C for Figure 7B A cross-sectional view of a pierceable cover.

[0062] Figure 8A is a perspective top view of a pierceable cover having two frangible layers and a slightly concave upper frangible layer.

[0063] Figure 8B for Figure 8A A perspective bottom view of the pierceable cover.

[0064] Figure 8C for Figure 8A A cross-sectional view of a pierceable cover.

[0065] Figure 8D for Figure 8A A perspective view of the pierceable lid with a pipette tip inserted through the two fragile layers.

[0066] Figure 8E for Figure 8D Cross-sectional view of the pierceable cap with the pipette tip inserted through the two fragile layers.

[0067] Figure 9 A top view and a cross-sectional view of a one-piece pierceable cover having a thin pierceable webbing.

[0068] Figure 10 A top view and a cross-sectional view of a two-piece pierceable cover with a thin webbing.

[0069] Figure 11 is a perspective view of a pierceable cap configured to be locked onto a container.

[0070] Figure 11 a is a cross-sectional view of a pierceable cap with an integrated sealing ring.

[0071] Figure 11 b is Figure 11 a. Cross-sectional view of the pierceable cap assembled with the sample container.

[0072] Figure 12 A perspective bottom view of the ribbed frangible seal.

[0073] Figure 13 A perspective top view of a ribbed frangible seal.

[0074] Figure 14 A top view of a ribbed frangible seal assembled with a sample container.

[0075] Figure 15 A cross-sectional view of a ribbed frangible seal assembled with a sample container.

[0076] Figure 16 FIG. 1 is a top view of a housing and a seal according to an embodiment of the present invention.

[0077] Figure 17 FIG. 1 is a cross-sectional view of a housing and a seal in one embodiment of the present invention.

[0078] Figure 18 for Figure 17 Exploded view of a seal showing a seal having an opening on the bottom surface.

[0079] Figure 19 for Figure 17 Exploded view of an alternative embodiment showing a seal with a frangible membrane.

[0080] Figure 20 A cross-sectional view of the housing and seal assembled with the sample container.

[0081] Figure 21 is a cross-sectional view of the housing and seal before assembly with the sample container.

[0082] Figure 22A A diaphragm according to one embodiment of the present invention is shown.

[0083] Figure 22B Shown is suitable for accommodating Figure 22A The diaphragm cover.

[0084] Figure 22C Shown with Figure 22B The cover is assembled together Figure 22A diaphragm.

[0085] Figure 22D Detailed view of a portion of the diaphragm collar housed in the cap.

[0086] Figure 22E Detailed view of the gap in the laterally extending surface of the cover that accommodates the protrusion from the diaphragm retention ring.

[0087] Figure 22F For the cover assembly Figure 22A Detailed view of the diaphragm.

[0088] Figure 23A for Figure 22A Perspective view of the diaphragm in.

[0089] Figure 23B for Figure 23A Detailed view of a cross section of a diaphragm arch is shown.

[0090] Figure 24 is a bottom view of one embodiment of a diaphragm described herein.

[0091] Figure 25 is a cross-sectional view of the diaphragm showing a weakened portion in the bottom of the diaphragm. DETAILED DESCRIPTION

[0092] Some embodiments of the present invention are discussed in detail below. Although specific exemplary embodiments can be discussed, it should be understood that this is done for illustrative purposes only. Those skilled in the relevant art will recognize that other components and configurations can be used without departing from the spirit and scope of the present invention.

[0093] Embodiments of the present invention may include a pierceable lid for sealing a container for holding a sample specimen. The sample specimen may include a diluent for transporting and testing the sample specimen. A transfer device such as, but not limited to, a pipette may be used to transfer an accurate amount of sample from the container to a testing device. The pipette tip may be used to pierce the pierceable lid. The pipette tip is preferably plastic, but may be made of any other suitable material. Scoring the top of the container may make piercing easier. The sample specimen may be a liquid patient sample or any other suitable sample that needs to be analyzed.

[0094] The pierceable lid of the present invention can be combined with a container to receive and store a sample sample for subsequent analysis, including analysis based on nucleic acid determination or the immunodiagnostic analysis of a specific pathogenic organism. When the sample sample is a biological fluid, the sample sample can be, for example, blood, urine, saliva, sputum, mucus or other body secretions, pus, amniotic fluid, cerebrospinal fluid or semen. However, the present invention also contemplates materials other than these specific biological fluids, including but not limited to water, chemicals and assay reagents, and solid materials (for example, tissue samples, tissue culture cells, feces, environmental samples, food, powders, particles and granules) that can be dissolved in a fluid environment in whole or in part. The container used with the pierceable lid of the present invention is preferably capable of forming a substantially leakproof seal with the pierceable lid, and can have any shape or composition, as long as the shape of the container can receive and maintain the substance of interest (for example, fluid sample or assay reagent). In the case of comprising a sample to be measured in a container, it is important that the composition of the container is substantially inert, so that it does not significantly interfere with the performance or result of the assay.

[0095] Embodiments of the present invention can inherently sterilize the cell type contained in the container. In this way, large cell cultures can be automatically screened and maintained. Where cell culture is intended, the leak-proof seal is preferably of a type that allows gas exchange across the membrane or seal. In other cases, where the container is pre-filled with a transport medium, the stability of the medium may be crucial. Therefore, the membrane or seal may have very low permeability.

[0096] Figures 1A to 1G An embodiment of a pierceable cap 11 is shown. The pierceable cap 11 may include a housing 13, a frangible layer 15, and optionally a gasket 17.

[0097] The shell 13 can be a generally cylindrical shape or any other shape suitable for covering the opening 19 of the container 21. The shell 13 is preferably made of plastic resin, but can be made of any suitable material. The shell 13 can be formed by injection molding or other similar processes. Based on the guidance provided herein, those skilled in the art will be able to select a resin or resin mixture with hardness and permeability that is suitable for a specific application without having to perform any operation other than routine experimentation. In addition, those skilled in the art will recognize that the range of acceptable lid resins will also depend on the properties of the resin or other materials used to form the container 21, because the properties of the resin used to form these two parts will affect the good degree to which the lid 11 and the container 21 can form a leak-proof seal and the ease with which the lid can be securely screwed onto the container. In order to change the rigidity and permeability of the lid, those skilled in the art will understand that the molding material can be processed by, for example, heating, irradiation or quenching. The shell 13 can have ridges or grooves to facilitate coupling the lid 11 to the container 21.

[0098] The cap 11 may be injection molded as a single piece using procedures well known to those skilled in the art of injection molding, including a multi-gating process to promote uniform flow of resin into the cap cavity used to form the cap shape.

[0099] The container 21 may be a test tube, but may be any other suitable vessel for holding a sample specimen.

[0100] Frangible layer 15 can be a layer of material located within access port 23. For purposes of the present invention, "frangible" means pierceable or tearable. Preferably, access port 23 is an opening through housing 13 from a top end 37 of housing 13 to an opposite bottom end 38 of housing 13. If housing 13 is generally cylindrical, access port 23 can extend through the end of the generally cylindrical housing 13. Access port 23 can also be generally cylindrical and can be concentric with the generally cylindrical housing 13.

[0101] The frangible layer 15 may be disposed within the inlet port 23 such that transfer of sample specimen through the inlet port is reduced or eliminated. Figures 1A to 1G In the embodiment, the fragile layer 15 is a membrane. Preferably, the fragile layer 15 is a thin multilayer film with a uniform cross section. Alternative fragile layers 15 are possible. For example, Figures 2A to 2B(Not shown to scale) is an exemplary frangible layer 15 in the form of a diaphragm. The frangible layer 15 is preferably made of rubber, but can be made of plastic, foil, combinations thereof, or any other suitable material. The frangible layer 15 can also be a mylar or metal-coated mylar that is melted, rests, or partially rests on the elastic diaphragm. The diaphragm can also be used to close the access port 23 after transfer of the sample sample to delay evaporation of any sample sample remaining in the container 21. The frangible layer 15 can be thinner in the center 57 of the frangible layer 15 or at any location closest to where a break in the frangible layer 15 is desired. The frangible layer 15 can be thicker at the edge 59 where it contacts the housing 13 and / or the optional gasket 17. Alternatively, the frangible layer 15 can be thicker at the edge 59 so that the edge 59 of the frangible layer 15 forms a functional gasket within the housing 13, without the need for the gasket 17. The frangible layer 15 is preferably symmetrical in the radial direction and from top to bottom so that the frangible layer 15 can be inserted into the cap 11 with either side facing the well 29 in the container 21. The frangible layer 15 can also be used to close the access port 23 after use of the transfer device 25. A peripheral groove 53 can be molded into the housing 13 to secure the frangible layer 15 in the cap 11 and / or to retain the frangible layer 15 in the cap 11 when the frangible layer 15 is punctured. The peripheral groove 53 in the cap 11 can prevent the frangible layer 15 from being pushed downwardly into the container 21 by the transfer device 25. One or more pre-formed scores or slits 61 can be provided in the frangible layer 15. The one or more pre-formed scores or slits 61 can facilitate rupturing the frangible layer 15. The one or more pre-formed scores or slits 61 can be arranged radially or otherwise to facilitate rupturing the frangible layer 15.

[0102] The frangible layer 15 may be ruptured upon insertion of the transfer device 25. Rupture of the frangible layer 15 may include puncturing, tearing, or otherwise disrupting the structural integrity and seal of the frangible layer 15. The frangible layer 15 may be ruptured by movement of the one or more extensions 27 around or along the coupling region 47 toward the aperture 29 in the container 21. When the one or more extensions 27 are in an initial position, the frangible layer 15 may be disposed between the one or more extensions 27 and the container 21.

[0103] In some embodiments, the frangible layer 15 and the one or more extensions 27 can be of unitary construction. In some embodiments, the one or more extensions 27 can be positioned in a manner to guide or realign the transfer device 25 so that the transfer device 25 can enter the container 21 in a precise orientation. In this manner, the transfer device 25 can be guided down the inside of the container 21 or in any other desired orientation to the center of the hole 29.

[0104] In an embodiment of the present invention, one or more extensions 27 can be generated by pre-engraving a pattern (e.g., a "+") in the material of the pierceable cover 11. In an alternative embodiment, one or more extensions 27 can be separated by gaps. The gaps can have various shapes, sizes, and configurations depending on the desired application. In certain embodiments, the pierceable cover 11 can be coated with a metal such as gold by a vacuum metal exhaust device or by a coating. In this way, the pierced cover can be easily visualized and distinguished from the unpierced cover by deformation of the coating.

[0105] One or more extensions 27 can be integrally molded with the housing 13. The one or more extensions 27 can have different configurations depending on the application. The one or more extensions 27 can be connected to the housing 13 via one or more coupling areas 47. The one or more extensions 27 can include a point 49 facing the center of the cover 11 or toward the desired breaking point of the fragile layer 15. The one or more extensions 27 can be paired so that each blade faces the opposite blade. Preferred embodiments of the present invention may include four or six extensions arranged in opposing pairs. Figures 1A to 1G The one or more coupling regions 47 are preferably living hinges, but may be any suitable hinge or attachment that allows the one or more extensions to move and penetrate the frangible layer 15.

[0106] The inlet port 23 can be at least partially blocked by one or more extensions 27. The one or more extensions 27 can be thin and relatively flat. Alternatively, the one or more extensions 27 can be leaf-shaped. Other sizes, shapes, and configurations are also possible. The inlet port 23 can be aligned with the opening 19 of the container 21.

[0107] Gasket 17 may be an elastomeric ring between frangible layer 15 and opening 19 of container 21 or between frangible layer 15 and lid 11 to prevent leakage before rupture of frangible layer 15. In some embodiments of the present invention, gasket 17 and frangible layer 15 may be integrated into a single component.

[0108] When the lid 11 is coupled to the container 21, the surface 33 can hold the fragile layer 15 against the gasket 17 and the container 21. The external recess 35 at the top 37 of the lid 11 can be configured to keep the wet surface out of reach of the user's fingers during handling. During the transfer process, the surface of the access port 23 may become wetted by a portion of the sample sample. The external recess 35 can reduce or eliminate contamination by preventing the user or an automated capping / decapping device from coming into contact with the sample sample during the transfer process. The external recess 35 can offset the fragile layer 15 from the top 37 of the lid 11 toward the bottom 38 of the lid 11.

[0109] The housing 13 may include threads 31 or other coupling mechanisms for attaching the lid 11 to the container 15. The coupling mechanism preferably frictionally holds the lid 11 on the opening 19 of the container 21 without leaking. The housing 13 may hold the gasket 17 and the fragile layer 15 against the container 21 for sealing in the sample without leaking. The container 21 preferably has complementary threads 39 for securing and tightening the lid 11 to the container. Other coupling mechanisms may include complementary grooves and / or ridges, a snap-on arrangement, or other arrangements.

[0110] The cap 11 can initially be separated from the container 21, or can be shipped as a coupled pair. If the cap 11 and container 21 are shipped separately, a sample specimen can be added to the container 21, and the cap 11 can be screwed onto the complementary threads 39 on the container 21 before shipping. If the cap 11 and container 21 are shipped together, the cap 11 can be removed from the container 11 before adding the sample specimen to the container 21. The cap 11 can then be screwed onto the complementary threads 39 on the container 21 before shipping. At the testing site, the container 21 can be placed in an automated transfer apparatus without removing the cap 11. The transfer device 25 is preferably a pipette, but can be any other device for transferring a sample specimen to or from the container 21. When the transfer device tip 41 enters the access port 23, the transfer device tip 41 can push the one or more extensions 27 downward toward the aperture 29 of the container 21. The movement of the one or more extensions 27 and the associated point 49 can rupture the frangible layer 15. When the entire shaft 43 of the transfer device 25 enters the container 21 through the entry port 23, one or more extensions 27 can be pushed outward to form an airway or vent 45 between the fragile layer 15 and the shaft 43 of the transfer device 25. The airway or vent 45 can allow air displaced by the tip 41 of the transfer device to escape from the container 21. The airway or vent 45 can prevent contamination and maintain pipetting accuracy. The airway or vent 45 may or may not be used in any embodiment of the present invention.

[0111] The action and thickness of the one or more extensions 27 can create a sufficiently large airway or vent 45 to allow air to exit the aperture 29 of the container 21 at a low velocity. This low-velocity airflow preferably prevents the expulsion of aerosols or small droplets from the container. This low-velocity airflow can reduce contamination of other containers or surfaces on the pipetting apparatus. In some cases, droplets of sample material may adhere to the underside surface 51 of the lid 11. In existing systems, if droplets completely fill and block the airway in the lid, the sample material may form bubbles and burst, or otherwise generate aerosols and droplets that could escape from the container and cause contamination. In contrast, the airway and vent 45 formed by the one or more extensions 27 can be sufficiently large so that sufficient liquid cannot accumulate and block the airway or vent 45. A larger airway or vent 45 can prevent pressurization of the container 21 and the generation and expulsion of aerosols or droplets. This airway or vent 45 can allow for more accurate transfer of sample material.

[0112] One embodiment may include a molded plastic housing 13 to reduce costs. The housing 13 may be made of polypropylene to achieve sample compatibility and provide a resilient living hinge 47 for the one or more extensions 27. The lid 11 may preferably include three to six dart-shaped extensions 27 hinged at the periphery of the access portal 23. For moldability, the portal may have a flat closure with a gap of 0.030 inches between the extensions 27 and a draft depth of 10 degrees. The access portal 23 may be approximately twice the diameter of the tip 41 of the transfer device 25. The diameter of the access portal 23 may be wide enough to allow for adequate venting, but small enough to allow the one or more extensions 27 to have room to extend downward into the container 21. An external recess 25 in the top of the housing 13 may be approximately half the diameter of the access portal 23, which prevents any user's fingertips from contacting the access portal.

[0113] Figures 3A to 3G An alternative embodiment of a lid 71 is shown having a foil laminate serving as a frangible layer 75. The frangible layer 75 can be heat welded or otherwise coupled to the underside 77 of one or more inlet extensions 79. During insertion of the transfer device 25, the frangible layer 75 can be substantially torn apart when the one or more inlet extensions 79 are pushed toward the hole 29 in the container, or when the tips 81 of the one or more inlet extensions 79 spread apart. The foil laminate of the frangible layer 75 can be inserted or formed into a peripheral groove 83 in the lid 71. An O-ring 85 can also be positioned within the peripheral groove 83 to serve as a sealing gasket. When the lid 71 is coupled to the container 21, the peripheral groove 83 can retain the O-ring 85 above the opening 29 of the container 21. The lid 71 operates similarly to the lids described above.

[0114] Figure 4A and Figure 4B An alternative cover 91 is shown having an elastomeric sheet as a fragile layer 95. The fragile layer 95 can be made of an easily tearable silicone resin (such as a silicone sponge rubber with low tear strength, hydrophobic Teflon, or other similar material). The fragile layer 95 can be fixed near the cover 91 or adhered to the cover 91 to prevent the fragile layer 95 from undesirably moving during the sample transfer process. The elastomeric material can serve as a container gasket and fragile layer 95 in the rupture zone. One or more extensions 93 can rupture the fragile layer 95. The cover 91 operates similarly to the above-described cover.

[0115] Figures 5A to 5B An alternative cap 101 is shown having a conical molded frangible layer 105 covered by a plurality of extensions 107. Cap 101 operates similarly to the caps described above.

[0116] Figures 6A to 6E An alternative cap 211 is shown having multiple frangible layers 215, 216. The pierceable cap 211 may include a housing 213, a lower frangible layer 215, one or more upper frangible layers 216, and optionally a gasket 217. Where not specified, the operation and composition of the alternative cap 211 are similar to those described above.

[0117] As described above, the housing 213 can be generally cylindrical in shape or any other shape suitable for covering the opening 19 of the container 21. The housing 213, in place of the lid 211, can include provisions for securing two or more frangible layers. The following exemplary embodiment describes a pierceable lid 211 having a lower frangible layer 215 and an upper frangible layer 216, however, it is contemplated that more frangible layers can be arranged in series above the lower frangible layer 215.

[0118] Fragile layers 215, 216 may be located within access port 223. Lower fragile layer 215 is typically configured as described above. Preferably, access port 223 is an opening through housing 213 extending from a top end 237 of housing 213 to an opposite bottom end 238 of housing 213. If housing 213 is generally cylindrical, access port 223 may extend through the end of the generally cylindrical housing 213. Access port 223 may also be generally cylindrical and concentric with the generally cylindrical housing 213.

[0119] The frangible layers 215, 216 may be positioned within the entry port 223 such that transfer of sample specimens through the entry port is reduced or eliminated. Figures 6A to 6EIn the embodiment of the present invention, the fragile layers 215 and 216 may be foil. The foil may be any type of foil, but in preferred embodiments, it may be 100 microns, 38 microns, 20 microns, or any other size. More preferably, the foil used for the upper fragile layer 216 is 38 microns or 20 microns in size to prevent the tip 41 of the transfer device 25 from bending. Exemplary types of foil that can be used in the present invention include "Easy Puncture Heat Seal Foil" from ABGENE or "ThermoSeal Heat Seal Foil" from ABGENE. Other types of foil and fragile materials may be used. In preferred embodiments of the present invention, the foil may be a composite of several materials. The same or different selected materials may be used in the upper fragile layer 216 and the lower fragile layer 215. Furthermore, the upper fragile layer 216 and the lower fragile layer 225 may have the same or different diameters. The fragile layers 215 and 216 may be bonded to the lid by a heat treatment such as induction heating or heat sealing.

[0120] A peripheral groove 253 can be molded into the housing 213 to secure the lower frangible layer 215 in the pierceable lid 211 and / or to retain the lower frangible layer 215 in the lid 211 when the lower frangible layer 215 is pierced. The peripheral groove 253 in the lid 211 can prevent the lower frangible layer 215 from being pushed downwardly into the container 21 by the transfer device 25. One or more pre-formed scores or slits can be provided in the lower frangible layer 215 or the upper frangible layer 216.

[0121] One or more upper frangible layers 216 can be positioned within the housing 213 such that one or more extensions 227 are positioned between the lower frangible layer 215 and the upper frangible layer 216. Preferably, the distance between the lower frangible layer 215 and the upper frangible layer 216 is as large as possible. This distance can vary depending on several factors, including the size of the transfer device. In some embodiments, the distance between the lower frangible layer 215 and the upper frangible layer 216 is approximately 0.2 inches. More preferably, the distance between the lower frangible layer 215 and the upper frangible layer is approximately 0.085 inches. In a preferred embodiment of the present invention, the gap can be 0.085 inches. The upper frangible layer 216 is preferably recessed within the entry port 223 to prevent contamination from contact with the user's hand. Recessing the upper frangible layer 216 further minimizes contamination during manual transfer. Upon piercing the lower frangible layer 215, the upper frangible layer 216 can block any ejected liquid.

[0122] The upper frangible layer 216 may lie flush with the wall of the entry port 223, or may be vented through one or more vents 218. The one or more vents 218 may be formed by a septum 219. The one or more vents 218 may diffuse the ejected air during puncture and form a maze to capture any ejected air during puncture.

[0123] During piercing of the lower frangible layer 215, the upper frangible layer 216 preferably contacts the conical tip 41 of the transfer device 25. The upper frangible layer 216 can be ruptured prior to rupturing the lower frangible layer 215. During insertion of the transfer device 25 into the access port 223, the frangible layers 215, 216 can be ruptured. The rupture of the frangible layers 215, 216 can include puncturing, tearing, or otherwise disrupting the structural integrity and seal of the frangible layers 215, 216. The lower frangible layer 215 can be ruptured by movement of the one or more extensions 227 around or along the coupling region 247 toward the hole 29 in the container 21. When the one or more extensions 227 are in the initial position, the lower frangible layer 215 can be disposed between the one or more extensions 227 and the container 21.

[0124] The gasket 217 may be an elastomeric ring between the lower frangible layer 215 and the opening 19 of the container 21 to prevent leakage before the frangible layers 215, 216 rupture.

[0125] The external recessed portion 235 at the top 237 of the pierceable lid 211 can be configured to keep the wet surface out of reach of the user's fingers during processing. During the transfer process, the surface entering the inlet 223 may become wetted by part of the sample. The external recessed portion 235 can reduce or eliminate contamination by preventing the user or an automatic capping / opening device from coming into contact with the sample during the transfer process. The external recessed portion 235 can offset the fragile layers 215, 216 from the top 237 of the lid 211 toward the bottom 238 of the lid 211. The lid 211 can initially be separated from the container 21 until the sample is added thereto, or it can be combined with the container before adding the sample. It is contemplated herein that the lid 211 can be transported as a coupled pair. If the lid 211 and container 21 are transported separately, the sample can be added to the container 21 and then, before further transportation and processing, the lid 211 can be fixed to the complementary threads of the container 21. If the cap 211 and container 21 are secured and transported together for shipment, the cap 211 can be removed from the container 21 before adding the sample specimen to the container 21. The cap 211 can then be re-secured to the complementary threads on the container 21 before further transport and processing. At the testing site, the container 21 can be placed in an automated fluid transfer instrument to remove the sample without removing the cap 211.

[0126] As described above, the housing 213 may include threads 231 or other coupling mechanism for coupling the lid 211 to the container 15 .

[0127] The transfer device 25 is preferably a pipette, but can be any other device for transferring a sample specimen to or from the container 21. When the transfer device tip 41 enters the access port 223, the transfer device tip 41 can rupture the upper frangible layer. The transfer device tip 41 can be generally conical, while the shaft 43 can be generally cylindrical. As the transfer device conical tip 41 continues to advance through the ruptured upper frangible layer 216, the opening in the upper frangible layer 216 can expand as the diameter of the conical tip 41 increases.

[0128] The tip 41 of the transfer device 25 can then contact one or more extensions 227 and push it downward toward the aperture 29 of the container 21. The movement of the one or more extensions 227 and associated points can disrupt the lower frangible layer 215. At this point, the conical tip 41 of the transfer device may still be in contact with the upper frangible layer 216. As the conical tip 41 increases in diameter and the entire shaft 43 of the transfer device 25 enters the container 21 through the entry port 223, the one or more extensions 227 can be pushed outward to form an airway or vent between the lower frangible layer 215 and the shaft 43 of the transfer device 25. The formed airway or vent allows air displaced by the tip 41 of the transfer device 25 to escape from the container 21. The airway or vent prevents contamination and maintains pipetting accuracy. The upper frangible layer 216 prevents contamination by forming a seal with the transfer device tip 41 above the one or more extensions 227. The displaced air is exhausted from the container 215 to the external environment through a labyrinthine path.

[0129] The upper frangible layer 216 in the pierceable cap 211 can have a different function than the lower frangible layer 215. The lower frangible layer 215, which can be bonded to one or more extensions 227, can be torn in a manner that opens a relatively large opening in the lower frangible layer 215. The relatively large opening can form a relatively large vent in the lower frangible layer 215 to eliminate or reduce pressure generated by the insertion of the tip 41 of the transfer device 25. In contrast to the lower frangible layer 215, the upper frangible layer 216 can act as a barrier to prevent any liquid that may escape from the pierceable cap 211 after piercing the lower frangible layer 215. The upper frangible layer 216 can vent 215 at its periphery to prevent pressurization of the intermediate volume between the upper frangible layer 216 and the lower frangible layer 215. The upper frangible layer 216 may also be vented 218 at its periphery to diffuse any impinged liquid by forming a plurality of channels for the expelled liquid and / or air to escape from the intermediate volume between the upper frangible layer 216 and the lower frangible layer 215 .

[0130] The upper frangible layer 216 can act upon puncture and can be located within the aperture of the puncturable cap 211 at a height such that when the lower frangible layer 215 is punctured, the upper frangible layer 216 acts upon the conical tip 41 of the transfer device 25. Acting upon the conical tip 41 rather than upon the cylindrical shaft 43 of the transfer device 25 can ensure relatively intimate contact between the tip 41 and the upper frangible layer 216 and can maximize the effectiveness of the upper frangible layer 216 as a barrier.

[0131] The selected material of the upper frangible layer 216 may tear in a polygonal shape (typically a hexagon). When the conical tip 41 is fully engaged with the upper frangible layer 216, there is sufficient venting so that there is little or no effect on the transfer volume being drawn from or into the shaft 43 of the transfer device 25.

[0132] Alternatively, for Figures 6A to 6E In the pierceable cover 211 shown in FIG, the upper frangible layer 216 can be flush with the top 237 of the housing 213. When the upper frangible layer 216 is flush with the top 237 of the housing 213, venting may or may not be used. Preferably, the distance between the lower frangible layer 215 and the upper frangible layer is about 0.2 inches. The foil used for the upper frangible layer 216, which is flush with the housing top 237, can be a heavier or lighter foil or other material than the foil or other material used for the lower frangible layer 215. Venting may or may not be used in any embodiment of the present invention.

[0133] 7A to 7C An alternative pierceable cap 311 is shown having a V-shaped frangible layer 315 with a seal 317. The frangible layer 315 can be weakened in various patterns along the seal 317. In a preferred embodiment of the present invention, the seal 317 is sinusoidal in shape. Depending on the particular application, the seal 317 can be linear or have other shapes. The sinusoidal shape of the seal 317 can improve the seal around the tip 41 of the transfer device 25 or improve the resealing quality of the seal after the transfer device 25 is removed from the V-shaped frangible layer 317. Resealing any portion of the seal 317 can prevent contamination or improve the storage of the contents of the container 21. In addition, the sinusoidal shape of the seal 317 can allow air to escape from the container 21 during transfer of the contents of the container 21 using the transfer device 25. The frangible layer 315 can be weakened by scoring or perforating the frangible layer 315 to facilitate insertion of the transfer device 25. Alternatively, the fragile layer 315 may be configured such that the seal 317 is thinner than the surrounding material in the fragile layer 315 .

[0134] The pierceable cap 311 can include a housing 313, threads 319, and other components similar to those described above. Where not specified, the operation and composition of alternative caps 311 can include embodiments similar to those described above. In other alternative embodiments described below, the pierceable cap has a unitary elastomeric construction. Those skilled in the art will appreciate that the elastomeric seals described herein can also be adapted for incorporation into the housing and seal embodiments described herein.

[0135] One or more additional frangible layers can be added to the pierceable cap 311 to further prevent contamination. For example, one or more additional frangible layers can be positioned closer to the top 321 of the housing 313 within an external recess (not shown). The V-shaped frangible seal 315 can be recessed within the housing 313 so that an upper frangible seal is added above the V-shaped frangible seal 315. Alternatively, the additional frangible layer can be flush with the top 321 of the housing 313. The operation and advantages of the upper frangible seal have been discussed above.

[0136] Figures 8A to 8E An alternative cap 411 is shown having multiple frangible layers 415, 416. The pierceable cap 411 may include a housing 413, a lower frangible layer 415, one or more upper frangible layers 416, and optionally a gasket 417. Where not specified, the operation and composition of the alternative cap 411 are similar to those described above.

[0137] As described above, housing 413 can be generally cylindrical in shape or any other shape suitable for covering opening 19 of container 21. Housing 413, in place of lid 411, can include provisions for securing two or more frangible layers. The following exemplary embodiment describes a pierceable lid 411 having a lower frangible layer 415 and an upper frangible layer 416, however, it is contemplated that more frangible layers can be arranged in series above lower frangible layer 415.

[0138] Fragile layers 415, 416 may be located within access port 423. Lower fragile layer 415 is typically configured as described above. Preferably, access port 423 is an opening through housing 413 extending from a top end 437 of housing 413 to an opposite bottom end 438 of housing 413. If housing 413 is generally cylindrical, access port 423 may extend through the end of the generally cylindrical housing 413. Access port 423 may also be generally cylindrical and concentric with the generally cylindrical housing 413.

[0139] Fragile layers 415, 416 may be positioned within inlet port 423 to reduce or eliminate transfer of sample specimens through the inlet port. Fragile layers 415, 416 may be similar to those described above. In a preferred embodiment of the present invention, the foil may be a composite of several materials. The same or different selected materials may be used in upper fragile layer 416 and lower fragile layer 415. Furthermore, upper fragile layer 416 and lower fragile layer 425 may have the same or different diameters. Fragile layers 415, 416 may be bonded to the lid by a thermal process such as induction heating or heat sealing.

[0140] A peripheral groove 453 can be molded into the housing 413 to secure the lower frangible layer 415 in the pierceable lid 411 and / or to retain the lower frangible layer 415 in the lid 411 when the lower frangible layer 415 is pierced. The peripheral groove 453 in the lid 411 can prevent the lower frangible layer 415 from being pushed downwardly into the container 21 by the transfer device 25. One or more pre-formed scores or slits can be provided in the lower frangible layer 415 or the upper frangible layer 416.

[0141] One or more upper frangible layers 416 can be positioned within housing 413 such that one or more extensions 427 are located between lower frangible layer 415 and upper frangible layer 416. Preferably, the distance between lower frangible layer 415 and upper frangible layer 416 is as large as possible. This distance can vary depending on several factors, including the size of the transfer device. Preferably, upper frangible layer 416 is only slightly recessed from top end 437. Upon piercing lower frangible layer 415, upper frangible layer 416 can block any ejected liquid. Preferably, there is no vent associated with upper frangible layer 416; however, venting may be used depending on the specific application.

[0142] During piercing of the lower frangible layer 415, the upper frangible layer 416 preferably contacts the conical tip 41 of the transfer device 25. The upper frangible layer 416 can be ruptured prior to rupturing the lower frangible layer 415. During insertion of the transfer device 25 into the access port 423, the frangible layers 415, 416 can be ruptured. The rupture of the frangible layers 415, 416 can include puncturing, tearing, or otherwise disrupting the structural integrity and seal of the frangible layers 415, 416. The lower frangible layer 415 can be ruptured by movement of the one or more extensions 427 around or along the coupling region 447 toward the hole 29 in the container 21. When the one or more extensions 427 are in the initial position, the lower frangible layer 415 can be disposed between the one or more extensions 427 and the container 21.

[0143] The gasket 417 may be an elastomeric ring between the lower frangible layer 415 and the opening 19 of the container 21 to prevent leakage before the frangible layers 415, 416 break.

[0144] An external recess 435 at the top 437 of the pierceable cover 411 can be configured to keep the wet surface out of reach of the user's fingers during handling. During the transfer process, the surface of the access port 423 may become wetted by a portion of the sample. The external recess 435 can reduce or eliminate contamination by preventing the user or an automated capping / decapping device from coming into contact with the sample during the transfer process. The external recess 435 can cause the fragile layers 415, 416 to deflect from the top 437 of the cover 411 toward the bottom 438 of the cover 411.

[0145] As described above, the housing 413 may include threads 431 or other coupling mechanism for coupling the cap 411 to the container 15. The operation of the pierceable cap 411 is similar to those embodiments described above.

[0146] Embodiments of the present invention may utilize a relatively rigid extension in combination with a relatively fragile frangible layer. Both the frangible layer and / or the rigid extension may be scored or cut; however, embodiments in which neither is scored or cut are also contemplated. The frangible material itself is generally incapable of opening wider than the diameter of one or more piercing elements. In many cases, the frangible material may remain in close contact with the shaft of the transfer device. This arrangement may provide insufficient venting for displaced air. Without adequate airways or vents, the transferred volume may be inaccurate, and bubbling and splashing of contents may occur. Even with the use of stress wires and thin-walled sections to aid piercing, rigid components designed solely to seal leaks can be difficult to pierce. This problem can often be overcome, but it incurs additional costs in terms of quality control. Rigid components can be cut or scored to facilitate piercing, but cutting or scoring may result in leaks. Difficult-to-pierce materials may cause the tip on the transfer device to bend and / or prevent transfer altogether. Combining a frangible component with a rigid but movable component can provide both a readily breakable seal and sufficient airways or vents to enable accurate transfer of sample without contamination. Additionally, in some embodiments, the scribe lines of the fragile layer will not be aligned with the scribe lines of the stationary component. This is easily achieved by providing a self-aligned fragile layer and rigid component.

[0147] Additionally, changing the motion profile of the transfer device tip during the penetration process can reduce the likelihood of contamination. Possible changes to the motion profile include slowing the penetration speed to reduce the rate at which air is expelled. Alternative changes can include using a pipette or similar device to draw liquid into the transfer device tip during the initial penetration.

[0148] Figure 9Another embodiment of a pierceable lid having a single fragile membrane 502 is shown. The membrane 502 has elastomeric properties and includes a thin webbing 507 that provides a seal until pierced or otherwise ruptured by a transfer device. The webbing feature provides a structurally weakened membrane portion that controls the manner in which the seal opens, thereby ensuring the proper function of the lid. The weakened membrane portion is achieved by thinning the membrane in the portion designated for tearing. Alternatively, the membrane can be weakened by any other known method, such as perforation or scoring.

[0149] Figure 9 Shown are a pierceable cap housing 501, a frangible membrane 502, and a container (tube) 503. An o-ring feature 504 on the frangible membrane 502 is sealed to the tube by tightening the cap housing 501 along threads 505. The elastomeric membrane 502 has a cross slit 506 that is closed by a very thin webbing 507 of elastomeric material.

[0150] Figure 10 A further embodiment is shown, wherein Figure 9 The features shown may optionally be combined with an upper frangible layer such as foil seal 508 .

[0151] In the above embodiment, the cap can be composed of at least two parts, namely an outer shell and a fragile membrane having elastomeric properties. The outer shell 501 is used to fix the membrane to the container. In this embodiment, the membrane 502 provides a leak-proof seal, which is reinforced by the threads 505 of the shell 501.

[0152] The membrane 502 may be separate from or integral with the housing. The membrane contains a pre-formed slit geometry 506 which may be sealed by a film or elastomeric webbing 507 (wherein the webbing may be a separate layer) or may be integrated within the membrane 502. When accessed by the transfer device, the seal is broken by the webbing slit 506. The slit geometry 506 may be symmetrical, where the two slits are the same length, or asymmetrical (as shown), where the slits are of different lengths and / or proportions. Figures 9 to 11 As shown, in one embodiment, the slit geometry 506 can appear in a configuration similar to a cross. However, the present invention is in no way limited to any particular slit orientation or slit geometry. The profile of the slit orientation can also be thickened with more material to guide how the thin webbing tears.

[0153] exist Figure 9In an embodiment of the present invention, the cover can also be configured to accommodate an O-ring 504, which can fit within a recess 510 provided on the inner surface of the housing 501. The O-ring can be integral with the housing 501, or can be a separate component.

[0154] The purpose of this O-ring 504 is to form a liquid-tight seal between the housing 501 and the container 503. The seal formed by the O-ring 504 maintains the integrity of the sample while preventing atomization and contamination caused by the sample contents escaping from the container. It also provides a slit geometry without relying on features on the housing 501 to open the membrane 502, such as an extension from the housing itself. In contrast to other embodiments described herein, the membrane taught in this embodiment can be a single fragile layer, rather than a multi-layer one. The two-part design allows the seal to be controlled by a fixing mechanism on the outer housing 505.

[0155] When accessed by a manual or automated transfer device, the elastomeric material can be opened along a predetermined slit geometry 506. Because the elastomeric material used is generally resilient and compliant, it acts to tightly contact the tip of the transfer device, significantly reducing or eliminating aerosolization and potential contamination. As the transfer device is advanced further through the slit and into the container, the slit will begin to tear, allowing venting to occur. This venting further reduces aerosolization and contamination. The slit geometry and webbing also improve the efficiency of pumping any fluid from the container itself by preventing the creation of a vacuum.

[0156] Figure 11 Another alternative embodiment of a one-piece cover is shown having an integral frangible membrane 602 and O-ring 604. This embodiment differs from the other embodiments described herein in that the frangible membrane 602, O-ring 604, and housing 601 are constructed as a single piece, rather than as separate components. This embodiment also does not require an extension for piercing the frangible membrane 602. The one-piece locking cover of this embodiment includes a coupling structure ("locking structure") 605 for securing, snapping, or locking the cover to a container or tube. For the purposes of this disclosure, the terms "container" and "tube" are used interchangeably. As described above, the frangible membrane 602 can be incorporated into the assembly structure previously described.

[0157] Figure 11 A cross-sectional view of a single cap assembled on a container 606 is shown, as well as a bottom view of the cap. When the cap is attached to the container 606, a shoulder 610 at the top of the cap prevents the user from contacting the sample membrane 602. The thin section 603 of the membrane 602 defines the tear geometry of the cap. The inner O-ring 604 seals to the interior of the tube and is chamfered to guide the insertion of the cap on the container. Figure 11As shown, O-ring 604 is configured to sit flush with the inner wall of container 606. The juxtaposition of O-ring 604 and container 606 can form a seal, preventing aerosolization of the sample and thereby reducing or eliminating contamination.

[0158] In one variation, Figure 11 As shown, the cap 601 can include a locking structure such as a serration or ratchet-like protrusion 605 on the lower interior portion of the housing 601. A triangular "ratchet" feature is employed in the cap, with the "angled" portion oriented in the direction of insertion and the flat portion 615 oriented in the direction of cap removal. The flat portion 615 then contacts a ridge 617 on the container. The flat portion 615 of the top protrusion contacts the bottom surface of a corresponding recessed portion 607 on the container 606. In a preferred embodiment, there are three ridges 617 in place for sealing redundancy, however, the number of ridges can vary.

[0159] Although the embodiments described herein are described as triangular serrations or ratchet-like protrusions, the actual structure can be any known type of locking or securing the cap to the container, including but not limited to ridges and threads. By applying a downward axial force to the cap, a dynamic seal is formed between the cap and the container.

[0160] The seal may be due, at least in part, to an internal expansion of the locking structure 605 that engages beneath a locking structure or recess present on the container 607 .

[0161] like Figure 11A and Figure 11B As shown, in another preferred embodiment, the housing 608 can be configured with at least one elastomeric ridge 608, which is circumferentially disposed on the inner surface of the housing 601. As described above, the ridge can be in the shape of a sawtooth structure. Figure 11B As shown, in this embodiment, (one or more) elastomeric ridges 608 may not cooperate with corresponding structures on the sample container. Instead, a seal is provided between the container and the housing by (one or more) elastomeric ridges 608. In this embodiment, the outer diameter of the container is larger than the inner diameter of the housing. In an alternative embodiment, the container may include one or more annular ridges (not shown) that can be positioned above the (one or more) elastomeric ridges 608 of the housing when the housing is coupled to the container. Although the annular ridges on the container are not required, they can further prevent the cover from being accidentally removed from the container.

[0162] For example, in Figure 11A and Figure 11BThe embodiment of the lid shown in is designed to have a certain degree of flexibility, and the lid is preferably constructed of an elastomer or similar "springy" material. This property allows the lid to stretch or adapt to the outer diameter of the container. The lid described in this particular embodiment may be superior to traditional "hard lids" that require manual manipulation to open and close. The lid of this embodiment provides a liquid-tight seal that is maintained during handling and agitation of the container. The liquid in the sealed container can then be accessed by piercing the fragile membrane 602 of the lid. With the help of the locking mechanism described, the lid can remain on the container even when a separation force is applied. The lid can maintain a liquid-tight seal when torsional and / or vibration forces are applied to the container. The lid can be used as a primary lid or a replacement lid after the contents of the container have been accessed when the container was not otherwise sealed.

[0163] The lid is configured so that the liquid in the sample can be accessed without removing the lid. Accessing the liquid can be done manually or using liquid handling automation, which is an improvement over traditional screw lids. Such processing can be performed using any method known in the art, but in a preferred embodiment, it is accomplished using the transfer device described herein.

[0164] The integrated frangible membrane 602 is pierced in a manner designed to prevent the seal of the liquid handling device, thereby allowing accurate manipulation of the liquid. Thus, the cover can be handled without contaminating the membrane surface accessed by the liquid handling robot. The cover is easy to manufacture and requires no assembly.

[0165] Contamination of the integrated membrane is partially prevented by a shoulder 610 at the top of the cap that is smaller than the diameter of the pressure pad of a typical user's thumb or index finger. With this design, the user does not contact the frangible membrane 602 when applying the cap by exerting downward force on the top of the cap. Eliminating this contact substantially reduces or prevents any contamination on the user's part.

[0166] The coefficient of friction between the fragile membrane and the pipette tip is sufficient to allow the transfer device to be easily inserted into or removed from the membrane.

[0167] The mode (also referred to as tearing geometry) of the slit tearing of pierceable or fragile film is an important factor to keep suitable liquid-tight seal.The tearing geometry in the present embodiment is at least partially controlled by a film layer 603, and this film layer is in the geometry of accurate definition, and this film layer is several times thinner than the rest of film.But in other alternative embodiments, film portion 603 need not be thinner than the rest of film 602.This film portion 603 can be made of the material identical with the rest of film 602, or can be different materials.The geometry of film portion 603 will limit where film tears when film is pierced.In a preferred embodiment, the sealing around the pipette tip from liquid handling manipulator is controlled by providing the cross slit geometry that allows film to open in two directions.After being pierced by the transfer device such as automatic manipulator, slit closure is to form liquid-tight seal.

[0168] This is partially optimized by the fact that one slit is longer than the other. Figure 11 The embodiment shown. This configuration can further help reduce leakage and atomization. The geometry prevents the membrane from sealing to the pipette tip during sample entry. The slits are forced to open unevenly, creating air gaps along the long slits, preventing a vacuum seal around the tip. This slit geometry also provides venting, increasing the efficiency of pumping fluid from the container by reducing or eliminating the creation of a vacuum within the container itself.

[0169] In another embodiment, the cap uses an internal o-ring 604 on the lower surface of the membrane 602 and a triple-ridge redundant seal on the inner bottom of the cap, using a suitable elastomeric material that conforms to the container geometry. For ease of assembly, the ridges 607 and o-ring 604 are chamfered. The multi-surface redundant seal exists on both the inner and outer top surfaces of the tube, as well as below the locking structure on the tube at the pivot point of the dynamic movement of the cap on the tube during agitation.

[0170] The one-piece locking cover described herein can be used to eliminate multiple user steps for securing and removing screw caps on sample tubes (such as any commercially available buffer tubes). Once the sample is added to the sample container, the one-piece locking cover is placed on the container in a downward axial motion. The container is then agitated in a multi-tube vortex comprising a fixed plate and a movable plate, with the container and the one-piece locking cover positioned between the fixed plate and the movable plate.

[0171] Typical sample buffers used for molecular diagnostics contain high levels of detergents, which both reduce the surface tension of the liquid, allowing a higher incidence of leakage, and lubricate the surfaces of thermoplastic / elastomeric parts. After agitation, the sealed container can be entered / accessed by a transfer device (such as a BD MAX instrument). The instrument will pierce the integrated fragile membrane with the pipette tip, causing the thin webbing layer to tear along a cross-shaped pattern, allowing tearing in multiple directions and thus preventing the seal on the pipette tip. When the pipette tip is removed from the tube, a one-piece locking cap is retained on the tube. Once removed from the tube, the integrated membrane closes, forming a functional liquid-tight seal to prevent liquid from spilling during further processing of the sample tube.

[0172] The geometry of the membrane portion 603 shown in another embodiment is for a pierceable cap for a container that maintains a seal against spills, leaks, or vapor escape during sample transport and storage, and can be accessed by a manual or automated liquid handling robot that deploys a transfer device for aspirating the sample from the container. This embodiment mitigates the risk of sample splashing and atomization when the cap is pierced by the tip of the transfer device.

[0173] In this embodiment, if Figures 12 to 21 As shown, the cover may include an outer shell 634 ( Figure 15 ) and elastomeric seal 612. The housing and seal can be separate or integral structures. The seal in this embodiment is designed not to tear when inserted into the transfer device. Instead, the transfer device separates the walls 642 and 643 of the elastomeric seal, thereby forming a space 644 without permanently tearing the elastomeric material. This space enables the transfer device to access the sample contained in the container.

[0174] Housing 634 ( Figure 15 ) can be cylindrical in shape and include at least one outer surface and an inner surface extending in an axial direction. The housing can also include a proximal opening and a distal opening. In such an embodiment, the distal opening can be provided at the end that cooperates with the sample container, while the proximal opening can include an access port and can be provided at the end that receives the sample transfer device. In a preferred embodiment, the housing 634 and the seal 612 are elastomeric. In an alternative embodiment, the housing can be constructed of a harder material, and only the seal is elastomeric.

[0175] like Figure 15 As shown, the diameter of seal 612 is greatest where it falls into housing 634. In one embodiment, the outermost diameter of the seal is greater than the diameter of the inner wall of the housing so that when the cap is not on the container / sample tube, the seal is retained in the housing regardless of whether the seal is bonded or adhered to the housing.

[0176] Figure 15The seal 612 is shown after it has been punctured and the transfer device removed. In the embodiment shown, a support strip 636, shown in cross section as an O-ring, is provided below the periphery of the seal 612. The support strip 636 is shown as a separate component, but it can be integrally integrated and of the same material as the seal 612. Regardless of whether the support strip 636 is integral with the seal or a separate component, it has the function of sealing between the housing 634 and the nozzle. The support strip can contact at least three surfaces, namely, the top surface of the tube, the side wall of the housing, and the bottom surface of the housing wall or the inner surface of a groove in the housing. The groove 509 ( Figure 10 ) will maintain the seal or O-ring during pipette tip penetration. In other embodiments, the support band 636 can be set on top of the collar 623 instead of below it.

[0177] In other embodiments, seal 612 may include an annular ring, such as collar 623, and one or more ribs 620 and 621. Figures 12 to 15 The embodiment shown in shows two ribs 620 and 621, but more than two ribs may be deployed in alternative embodiments of the present technology. The seal may also include two major surfaces. A first surface 627 faces away from the interior of the container and receives a transfer device such as a pipette, and a second major surface 628 extends into the sample container. Each rib 620, 621 may include two peripheral walls 624 and 625. Each peripheral wall 624, 625 extends from the collar 623 in a generally axial direction. A bottom surface 626 may also connect each peripheral wall 624 and 625. Each rib may also include at least two lateral side walls 629 extending from the bottom surface 626 to the collar 623. The ribs 620 and 621 extend radially inward, axially downward, or distally from the collar 623 of the seal 612 into the container. The entire seal may be formed integrally by a method such as injection molding, or may be assembled separately and each separate component joined separately. In Figure 14 , a top perspective view of the seal 612 assembled with the housing 634 and the container is shown.

[0178] In embodiments where the various components of the seal are individually joined together, the joints where the various surfaces meet can form a fluid-tight seal. However, in alternative embodiments, these joints can be configured in accordance with aspects of the present technology described herein to include perforations or scores to allow for additional controlled venting along these joints when penetrated by a sample transfer device.

[0179] although Figure 12 and Figure 13A seal with two ribs is shown, but the seal can be configured with one or more ribs and can include 2, 3, 4, 5, or 6 ribs. Varying the number of ribs can change the size and dimensions of each rib and the tearable portion contained therein. Increasing the number of ribs can be used to increase the effectiveness of the kit in guiding the transfer device into the container.

[0180] In the embodiment shown, the ribs are arranged radially to achieve an intersection angle of 90. However, the ribs can be configured to intersect at any angle relative to each other.

[0181] In this embodiment, the bottom surface 626 can include a slit portion having a tearable portion 630, which can be symmetrical or asymmetrical. The tearable portion 630 can be fragile and designed to tear or puncture when the sample transfer device is inserted. According to the embodiments described in detail above, the tearable portion(s) 630 can be thinner than the rest of the seal and can also include webbing integrated into the seal.

[0182] Ribs 620 and 621 can extend both vertically and horizontally into the container. Thus, they serve to guide the transfer device through the seal, causing the tearable portion 630 to be pierced first. The seal that is initially pierced is made of a suitable resilient material and positioned around the transfer device. As a result, any venting of the container that occurs during the initial piercing can pass through the transfer device. As the transfer device advances through the seal, the tearable portion tears further, allowing venting around the transfer device and through the seal during sample transfer.

[0183] When the transfer device is removed, the support band, which may have a perimeter slightly smaller than the outer perimeter of the seal 612, exerts upward pressure on the inwardly extending sides 620, thereby causing them to join together and close over the tear formed by the puncture of the transfer device. In other embodiments, the outer perimeter of the support band and the outer perimeter of the seal may be substantially the same.

[0184] Figures 16 to 21 Another embodiment of a pierceable cap is shown consisting of at least one seal 641 and a housing 634 incorporating elements to improve resealing performance. The seal may include a slit portion 640, which may include one or both of an unattached openable portion 644 or a frangible portion 645. The seal 641 and the housing 634 may be coupled to form the pierceable cap. Figure 17As shown, seal 641 can include an annular ring or protrusion 646 that defines the outermost surface of seal 641 and protrudes upwardly from the surface of seal 641. A complementary annular protrusion 639 on the lower surface of seal 641 is offset from the periphery of seal 641. Furthermore, protrusion 639 can be positioned so that when assembled, protrusion 639 is located between the wall of tube 631 and the wall of housing 634.

[0185] Figure 20 The relationship of the cap to the container 631 is depicted before the cap is fully tightened onto the container, and Figure 21 The structure and function relationship of the cover after it is fully screwed onto the container is shown. The protrusion 639 cooperates with the wall of the container 631 (as shown in FIG. Figure 20 and 21 As shown), the sealing member side walls 642 and 643 are closed to each other and form a seal. Figure 21 As shown, as the lid is further screwed onto the container 631, internal stress is exerted on the side walls 642 and 643 of the seal 641, and more specifically, on the protrusion 639. The internal stress generates a force on the side walls of the seals 642 and 643 that pushes the side walls 642 and 643 toward each other and into contact with each other.

[0186] With the side walls 642 and 643 pressed against each other in this manner to form a liquid-tight seal, the design of the penetrable bottom of the seal can be achieved in at least two possible ways. Figure 18 As shown, the first is an openable seal. When the seal is in its natural configuration, the apexes of the side walls 642 and 643 do not touch each other at all but are openable, and instead form a very narrow slot 644 in the slotted portion 640, just wide enough to facilitate injection molding. Figure 21 As shown, when assembled with housing 634 and container 631, sidewalls 642 and 643 are forced together to form seal 650. This embodiment can have the advantage of not being torn during tip insertion / penetration, thereby limiting the possibility of debris falling into the sample tube caused by the tearing mechanism.

[0187] exist Figure 19 The second embodiment seen in the depicts a frangible seal 645 on or within the slit portion having a thin web of material that tears upon first penetration by the pipette tip. In all other respects, its performance is identical to the seal described in the previous paragraph.

[0188] Figure 18 and Figure 19 Both embodiments of the seal in Figure 20 The foil top seal 648 shown is used in conjunction to increase durability for shipping and handling and to serve as an additional barrier to aerosols during pipette insertion.

[0189] In certain embodiments, the seal can be made of any material that, when initially pierced, has sufficient resilience to form a seal around the outer periphery of a transfer device, such as a pipette. However, since the inwardly and downwardly sloping ribs or sidewalls mitigate the risk of atomization during initial piercing, it may not be necessary to seal around the transfer device during initial piercing. In the illustrated embodiment, the seals 612, 641 include elastomeric membranes 614, 645. During the initial piercing, the membranes 612, 645 conform to the periphery of the transfer device in a manner that prevents the aforementioned undesirable splashing or atomization of the sample from the container, thereby ensuring that the sample remains contained within the container during the initial piercing step.

[0190] In one embodiment, the liquid transfer device is a pipette tip that contains a filter (not shown). When the transfer device is inserted, its movement is paused after puncture to allow any air pressure within the container to escape. The seal provides a leak-proof barrier and forces any exhaust gas through the transfer device at this stage, rather than around it.

[0191] Figure 15 The seal 612 is shown in cross section as disposed within the container 521. The outer housing provides a locking mechanism for the liquid container and ensures that the seal remains in place during storage and transport and protects the seal from damage and consequential loss.

[0192] In yet another embodiment of the present invention, a method is provided for advancing at least a portion of a transfer device into an access port secured to a housing of a sample container. As the transfer device enters the access port, it is advanced distally and guided, in part, by one or more ribs. The transfer device is advanced toward a webbing contained within a bottom surface of a seal and ultimately pierces the webbing to access the sample.

[0193] Additionally, changing the motion profile of the transfer device tip during the penetration process can reduce the likelihood of contamination. Possible changes to the motion profile include slowing the penetration speed to reduce the rate at which air is expelled. Alternative changes can include using a pipette or similar device to draw liquid into the transfer device tip during the initial penetration.

[0194] Figure 22A Diaphragm 700 is shown in accordance with one embodiment of the present invention. Although described as a separate embodiment, diaphragm 700 may be inserted in place of the frangible layer described herein, the membrane described herein, and the elastomeric shield described herein. Figures 1A to 1G and Figures 2A to 2B Indicated as fragile layer 15; Figures 3A to 3G is shown as a fragile layer 75, Figures 4A to 4B is shown as a fragile layer 95, Figures 5A to 5Bis shown as a fragile layer 105, Figures 6A to 6E is shown as fragile layer 215, 7A to 7C is shown as fragile layer 315 and Figures 8A to 8E The film is shown as a fragile layer 415. Figure 9 502 in Figure 11 602 in the middle. Elastomer cover in Figures 12 to 21 The diaphragm is shown as 612. The diaphragm has a collar or lip 705. The collar or lip 705 has a barb 710. The diaphragm also has a recess 715 that defines the inner wall of the diaphragm. As shown, the recess 715 is shaped like an ogee. Because the ogee extends both radially and inwardly, the ogee defines a semi-dome recess.

[0195] Barb 710 is a septum feature that holds the septum in the cap 720 when the cap is not on the tube 730. Barb 710 is elastomeric and flexible enough to be forced through the narrower inner diameter portion 735 of the cap 720. The cap 720 and the tube 730 are in Figure 22B The septum barb 710 deflects during insertion and then extends into the wider inner diameter portion 740 of the cap 730. Once inserted, the barb 710 is retained in the wider diameter portion of the cap 730. Figure 22C and Figure 22D The barb 710 is resilient and deforms into the cap 720 but does not extend into the cap. Figure 22E The retention of the barbs 710 in the wider inner diameter portion 740 of the cap 720 maintains the planarity of the septum seal and the slit area of ​​the septum seal relative to the top 745 of the cap 720 and the top 750 of the tube 730 .

[0196] The cap undercut 755 thus has a wider inner diameter portion 740 for accommodating the barbs 710 , a narrower inner diameter portion 735 for retaining the septum 700 in the cap 720 , and a transition angle 760 for maintaining a coplanar relationship between the septum surface and the cap 720 .

[0197] Figure 22F Shown Figure 22A How is the diaphragm 700 placed in Figure 22B The diaphragm collar 705 has a vertically extending protrusion 765. The protrusion 765 is seated in a gap 770 in a laterally extending surface of the cover 720. The surface 775 extends inwardly from the cover wall 780. The gap 770 is defined by the cover wall 780 on one side and a rib 785 on the other side.

[0198] The septum collar 705 interfaces with the rib 785 to prevent the septum 700 from being pushed into the tube 730 when a pipette (not shown) is inserted through the septum 700 to access a sample in the tube 730. Because the collar protrusion 765 is retained in the gap 770, additional deflection of the protrusion 765 may be required to push or pull the septum 700 from its installed position during sample access. Figure 22F The structure in reduces axial misalignment of the cap 720 and tube 730 by locating the deflection of the diaphragm 700 when the cap is placed on the tube.

[0199] Figure 23A for Figure 22A 700 . The diaphragm 700 has four semi-dome structures 785 that are located on the diaphragm bottom layer 790 and rise upward and inward toward the inner wall 795 of the diaphragm 700. Each semi-dome structure 785 has two curved triangular faces 800 that share an arcuate boundary 805. The intersection of the faces 800 with the inner wall 795 of the diaphragm 700 forms a pointed arch 810. The arched boundary 805 has a semi-arched trajectory. The dome shape facilitates the reclosing of the diaphragm so that the pipette will not leak after it is withdrawn from the diaphragm. Similarly, the dome shape provides a structure that prevents the diaphragm from inverting during sample processing steps (such as pipette tip extraction and thermal cycling). The dome-shaped structure reduces insertion and extraction forces by deflecting the material rather than stretching it.

[0200] Figure 23B for Figure 23A Detailed view of a cross section of a diaphragm arch is shown. Figure 23A The arched boundary 805 of the semi-dome structure 785 is shown relative to the septum floor 790 and the septum inner wall 795.

[0201] Figure 24 FIG2 is a bottom view of one embodiment of a diaphragm described herein. The bottom layer 795 of the diaphragm 700 (including weakened portions 815) separates four semi-dome-shaped recesses 785. Pointed arches 810, along with triangular faces 800 and an arcuate border 805, are visible from the back. Pointed arches 810 extend along the periphery of the diaphragm, while arcuate border 805 extends inward toward the center of the diaphragm. As shown, the lateral extent of the weakened portion (e.g., a scored portion or slit extending only partially through the thickness of the bottom layer 795 of the diaphragm) is such that the weakened portion does not traverse the entire extent of the bottom layer 795.

[0202] Figure 25FIG is a detailed cross-sectional view of the diaphragm 700 showing a weakened portion 815 in the bottom layer 795 of the diaphragm. Note that in this embodiment, the weakened portion is a slit that extends approximately halfway through the thickness of the bottom layer 795 of the diaphragm. Furthermore, in this embodiment, the slit 815 traverses nearly the entire length of the bottom layer. This is illustrated by the extent of the cross slit 815A, which is shown in the lengthwise direction and intersects the slit 815 extending approximately perpendicular to the slit 815A. In this example, the lateral extent of the slit or scored portion 815 is approximately equal to the slit 815A. Figure 12 The lateral extent of the tearable portions 630 is shown to be the same. Figure 25 Also shown is a slit 815 extending upward from the bottom surface of the septum substrate (i.e., the surface facing the tube) through some portion of the thickness of the septum substrate, but not completely through that thickness. Because the slit or weakened portion is only in the bottom portion of the thickness of the septum substrate, the septum is able to maintain a seal even when the contents of the container in which the septum is placed are under pressure. In operation, this allows the pipette tip to exert a higher tensile stress on the septum when piercing the septum from above. As the pipette tip propagates through the septum substrate, the bending moment of the septum substrate changes, and the pipette tip requires less force to propagate through the slit portion. As described above, the dome structure reduces insertion and withdrawal forces by causing the material to deflect rather than stretch.

[0203] Although the foregoing description is directed to preferred embodiments of the present invention, it should be noted that other variations and modifications will be apparent to those skilled in the art and may be made without departing from the spirit or scope of the present invention. In addition, features described in conjunction with one embodiment of the present invention may also be used in conjunction with other embodiments even if not expressly stated above.

Claims

1. A pierceable cap comprising: case, an access port in the housing adapted to allow at least a portion of a transfer device to pass through the access port; a diaphragm comprising a collar and a plurality of semi-dome notches extending from a periphery of the diaphragm toward a center thereof, wherein the semi-dome notches extend inwardly and downwardly toward a substantially planar diaphragm bottom layer having a thickness, wherein the housing is elastomeric and adapted to receive the diaphragm; and wherein the substantially planar membrane bottom layer has a slotted portion that extends only partially through the thickness of the substantially planar membrane bottom layer, wherein the collar has a barbed portion extending laterally from the collar toward an inner wall of the housing that houses the diaphragm, wherein the housing has a wider inner diameter portion and a narrower inner diameter portion and a transition portion, and wherein when the diaphragm is inserted into the housing, the barb extends into the transition portion above the narrower inner diameter portion and is thereby retained in place in the housing.

2. The pierceable cap of claim 1 , comprising four semi-dome notches, each notch positioned in a quadrant of the septum defined by the substantially planar septum bottom layer and the periphery of the septum.

3. The pierceable cap of claim 2 , wherein the substantially planar septum bottom layer has a first portion having a length extending along a first diameter of the septum and a second portion having the same length extending along a second diameter, wherein the first portion and the second portion intersect to define the quadrant.

4. The pierceable cap of claim 3 , wherein a first slit extends along a portion of the length of the first portion of the substantially planar septum bottom layer, and a second slit extends along a portion of the length of the second portion of the substantially planar septum bottom layer, and wherein the first slit intersects the second slit.

5. The pierceable cap of claim 4, wherein the first slit has a first length and the second slit has a second length, and the first length is longer than the second length.

6. The pierceable cap of claim 4, wherein the first slit has a first length and the second slit has a second length, and the first length is equal to the second length.

7. The pierceable cap of claim 5 , wherein a first length of the first slit extends less than half the length of the first portion of the substantially planar septum bottom layer, and a second length of the second slit extends more than half the length of the second portion of the substantially planar septum bottom layer.

8. The pierceable cap of claim 6 , wherein a first length of the first slit extends over half the length of the first portion of the substantially planar septum bottom layer, and a second length of the second slit extends over half the length of the second portion of the substantially planar septum bottom layer.

9. The pierceable cap of claim 1, wherein the collar further includes an upwardly extending portion at a periphery thereof proximate the barbed portion.

10. The pierceable cap of claim 9, wherein the housing has an inner wall, wherein the housing has a surface extending laterally from a wider inner portion, wherein the laterally extending surface has a retaining rib extending from the laterally extending surface, and a gap is defined between the inner wall of the housing and the retaining rib, and wherein when the septum is inserted into the housing, a portion extending upwardly from the septum collar fits into the gap.

11. A method for piercing a septum, the method comprising: A container having a pierceable lid thereon is obtained, the lid comprising: case, an access port in the housing, the access port being adapted to allow at least a portion of a transfer device to pass through the access port; a septum comprising a collar and a plurality of semi-dome notches extending from a periphery of the septum toward a center thereof, wherein the semi-dome notches extend inwardly and downwardly toward a substantially planar septum bottom layer having a thickness, wherein the housing is adapted to receive the septum, and wherein the substantially planar septum bottom layer has a slotted portion extending only partially through the thickness of the substantially planar septum bottom layer, and wherein the collar has a barbed portion extending laterally from the collar toward an inner wall of the housing receiving the septum, wherein the housing has a wider inner diameter portion and a narrower inner diameter portion and a transition portion, wherein when the septum is inserted into the housing, the barbs extend into the transition portion above the narrower inner diameter portion and are thereby retained in position in the housing; positioning a pipette tip on the septum; advancing the pipette tip into contact with the substantially planar membrane substrate; and Further advancement of the pipette tip through the substantially planar membrane bottom layer causes the pipette tip to be initially advanced through an unslit portion of the thickness of the substantially planar membrane bottom layer and subsequently further advanced through the slotted portion.

12. The method of claim 11, wherein the access port further comprises a first frangible layer positioned in the access port, the method further comprising advancing the pipette tip through the frangible layer, whereupon the pipette tip is advanced through the substantially planar membrane substrate.

13. The method of claim 12, wherein upon advancement through the substantially planar septum substrate, the pipette tip is in fluid communication with the interior of the container.

14. The method of claim 13, further comprising aspirating at least a portion of the sample in the container with the pipette tip after the pipette tip has been advanced through the substantially planar membrane bottom layer.

15. The method of claim 13, further comprising dispensing liquid into the container through the pipette tip after the pipette tip has been advanced through the substantially planar membrane substrate.

16. The method of any one of claims 14 and 15, further comprising withdrawing the pipette tip from the container and through the septum, wherein the septum closes after the pipette tip is withdrawn therefrom.

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