Patent Application
20240190627
The accompanying drawings, which are incorporated into and constitute a part of this specification, illustrate disclosed embodiments and, together with the description, serve to explain the disclosed embodiments. In the drawings:
Exemplary embodiments are described with reference to the accompanying drawings. While examples and features of disclosed principles are described herein, modifications, adaptations, and other implementations are possible without departing from the spirit and scope of the disclosed embodiments. Exemplary embodiments described herein may be independent of each other. Also, the words “comprising,” “having,” “containing,” and “including,” and other similar forms are intended to be equivalent in meaning and be open ended in that an item or items following any one of these words is not meant to be an exhaustive listing of such item or items, or meant to be limited to only the listed item or items. It should also be noted that as used herein and in the appended claims, the singular forms “a,” “an,” and “the” include plural references unless the context clearly dictates otherwise. For convenience, the term “disclosed embodiments” or “exemplary embodiment” may be used herein to refer to a single embodiment or multiple embodiments of the disclosure.
Materials for use in diagnostic testing are often packaged and stored in containers (e.g., reagent materials may be packaged in a sealed vial). A probe system, e.g., an automated probe system, may interface with such a container during use (e.g., to aspirate reagent materials from the vial in preparation for one or more tests). A probe system may perform multiple tests using materials stored in the same containers, requiring multiple aspirations from these containers. Multiple aspirations may require repeated penetrations of the seal. But repeated penetrations of conventional seals, (e.g., stoppers or the like) can reduce the reliability of diagnostic testing. For example, repeated penetrations of conventional stoppers can cause stopper coring and fragmentation. Stopper coring and fragmentation can interfere with reagent aspiration; expose reagent materials in the container to the ambient environment (e.g., through air holes in the stopper), which can reduce the lifetime (e.g., following the initial penetration of the stopper) of the reagent materials stored inside the primary container (e.g., the onboard stability of the reagent materials); and can interfere with subsequent testing and analyses (e.g., by causing errant measurement results due to undetected debris mixed with materials under test).
An improved sealing system (which can also be called an improved stopper or stopper assembly) can support repeated probe penetration without creating fragments that might interfere with diagnostic testing. The sealing system can include a plug to provide a seal between the side and part of the top of the container and sealing system. The plug can include a central opening (which can also be called a plug cavity) through which the probe may travel. The sealing system can include a pierceable membrane to provide a seal on the top of the plug cavity. The pierceable membrane can isolate materials in a container from the ambient environment prior to initial penetration of the membrane. Including the initial penetration, the pierceable membrane can be configured to support 1-1500 penetrations without fragmentation. The plug, membrane, and an insert placed below the membrane can together form an insert cavity in the stopper. This insert cavity can reduce evaporation of reagent materials within the container (and extend the lifetime or onboard stability of the reagent materials) following initial penetration of the seal. In some embodiments, the sides of the insert can also form a mechanical supporting or centering means for the probe system such that the probe, even when slightly off-axis, can reliably access the materials in the lower compartment through the cavity. In some embodiments, the sides of the insert can form a bushing that reduces lateral displacement of the probe within the container. In some embodiments, the sealing system can include a diaphragm that provides an additional barrier between materials within the container and the ambient environment.
The sealing systems can be suitable for containers storing liquid or dry (e.g., lyophilized, or the like) materials. The sealing system can have sufficient venting capability (e.g., through cutouts in the plug, or other suitable venting mechanisms) to support the lyophilization process. The pierceable membrane can be strong enough to withstand the pressures involved in the lyophilization process and any residual pressure which remains inside the container upon completion of the lyophilization process.
The present disclosure relates generally to sealing systems for use in testing, e.g., diagnostic testing including but not limited to medical (disease/drug), chemical, and/or biological testing/analysis, and systems, devices, and methods of using such sealing systems in such testing. Although the present disclosure describes multiple components (e.g., an insert, a pierceable membrane, a plug, a cap, a diaphragm, etc.) that can be implemented in combination, e.g., assembled or formed as an integral part, in a system, each aspect can be used independently with systems and devices that are not described in this disclosure (e.g., conventional systems and devices). A benefit arising from implementation of one of the multiple aspects can be independent of the implementation of another of the multiple aspects. The present disclosure merely describes the various aspects in a related manner for convenience.
As used herein, the term “probe” may be used interchangeably with the term “needle.” The term “probe” may refer to the probe system, or a specific component therein such as a needle. For example, the term “probe” may refer to a needle comprising a thin, hollow metal tube through which fluid can be aspirated and dispensed. Accordingly, the term “probe” may refer generally to a needle or any elongated component comprising a hollow cavity that is capable of puncturing, piercing, and penetrating a structure and aspirating material through the hollow cavity. A probe system may include the probe alone or the probe and other components.
Turning now to the drawings,
Consistent with disclosed embodiments, the sealing system can include a stopper and optionally a cap 160. The stopper can include a plug 120 that conforms to an inside surface of container 110. In some embodiments, plug 120 can be configured to conform to an inner wall of a neck of the container (e.g., container neck 112). For example, when container neck 112 has a cylindrical cross-section, a portion of plug 120 can have a conforming cylindrical cross-section. An outer diameter of the cylindrical portion of plug 120 can be larger than the inner diameter of container neck 112, such that inserting plug 120 into container neck 112 forms a seal between the outer wall of plug 120 and the inner wall of container neck 112. In some embodiments, a portion of plug 120 can remain outside container 110 when plug 120 is inserted into container neck 112. This portion can include a plug flange 114 that extends beyond container neck 112. In some embodiments, a lower surface of plug flange 114 can form a seal with an upper surface of container flange 116 when plug 120 is inserted into container neck 112. Consistent with disclosed embodiments, plug 120 can include a plug cavity 122. The stopper can include an insert 140 that extends into plug cavity 122 and forms the walls of insert cavity 124. The stopper can further include a membrane 130 that seals insert cavity 124. Plug 120, insert 140, and membrane 130 can seal the interior of container body 113. Insert 140 can include an opening 142 between insert cavity 124 and the interior of container body 113 (e.g., to allow a probe to extend from outside container 110, through membrane 130, insert cavity 124, and opening 142 to reach the interior of container body 113 to access the stored material(s) 180). In some embodiments, plug 120 (and optionally insert 140) can be secured within container 110 using cap 160. In the depicted embodiment, membrane 130 can isolate material(s) 180 from the ambient environment until penetrated by probe 170. Compared to a stopper that lacks a cavity formed between membrane 130 and opening 142 (e.g., insert cavity 124), the stopper disclosed in
In some embodiments, an insert 203 can be disposed within plug 201. In some embodiments, insert 203 can be positioned (e.g., using a compression fit, an adhesive, one or more restraints, or another suitable method) within plug 201 (e.g., as shown in
Consistent with disclosed embodiments, insert cavity 204 can be formed within insert 203 between pierceable membrane 207 and lower opening 209. In some embodiments, insert cavity 204 can be coaxial with plug 201 (or coaxial with plug cavity 202). In some embodiments, the inner surface of insert 203 can form walls of insert cavity 204. Upper opening 205 can form a top opening of insert cavity 204 and lower opening 209 can form a bottom opening of insert cavity 204. In some embodiments, a sidewall of insert cavity 204 can taper in from the top opening to the bottom opening of insert cavity 204. During aspiration of material from or deposition of material into the interior of container body 113, the aspirating or depositing probe can be advanced through insert cavity 204 into the container. Insert cavity 204 can assist in isolating the interior of the interior of container body 113 from the external environment.
In some embodiments, pierceable membrane 207 can seal the container (e.g., by sealing that portion of the opening of the container that remains unsealed by the plug). For example, the pierceable membrane 207 seals the upper opening 205 of insert 203. A portion of membrane 207 can overlap and be bonded to a corresponding portion of insert 203. In some embodiments, membrane 207 can include multiple layers of different materials. Constructing membrane 207 using multiple layers can enable selection of layers having different desired characteristics. For example, one layer of membrane 207 can be selected based on permeability and another layer of membrane 207 can be selected based on the ability to bond to insert 203.
In some embodiments, pierceable membrane 207 can include an upper impermeable layer and a lower bonding layer. In some embodiments, the lower bonding layer (e.g. an adhesive layer, heat-sealable polymer layer, or the like) can be the bottom layer of pierceable membrane 207. In some embodiments, additional layers can be disposed above the lower bonding layer. For example, one such additional layer (e.g., a polymer layer, or the like) can provide structural strength or support to pierceable membrane 207. This additional layer can be disposed between the upper impermeable layer and the lower bonding layer, or above the upper impermeable layer.
In some embodiments, the pierceable membrane 207 can include an upper metal layer and a lower polymer layer. The upper metal layer can exhibit reduced permeability and the lower polymer layer can be suitable for bonding to insert 203. In some embodiments, the metal layer can be a metal film, such as an aluminum film. In some embodiments, the polymer layer can be polypropylene, polyethylene, polyethylene terephthalate (PET) nylon, thermoplastic adhesive, or another suitable polymer. In various embodiments, membrane 207 can be a laminated metal film or a metallized film. In some embodiments, membrane 207 can be bonded using an adhesive (e.g., an adhesive applied to insert 203 or membrane 207, or an adhesive layer of membrane 207). In various embodiments, membrane 207 can be heat-sealed to insert 203. Such bonding can be performed before or after the insert in placed in plug cavity 202. In some embodiments, an impermeable polymer layer can be used in place of the upper metal layer.
Consistent with disclosed embodiments, plug 201 can include cutouts, such as cutout 213. Such cutouts can extend through the sides of plug 201. In some applications, such cutouts can provide an egress path for sublimated vapor during lyophilization.
Consistent with disclosed embodiments, plug 225 can be configured to conform to an interior wall of container neck 223. In some embodiments, plug 225 can be dimensioned such that a compression fit 228 maintains plug 225 within container neck 223, regardless of the shape and size of the container neck. In some embodiments, plug 225 can form a seal with container neck 223.
Consistent with disclosed embodiments, a lower surface of plug flange 226 can contact an upper surface of container flange 224. In some embodiments, plug flange 226 can form a seal with container flange 224.
Consistent with disclosed embodiments, a recess in the upper surface of plug 225 can form shelf 227. In some embodiments, shelf 227 can be configured to receive insert flange 233. A bottom surface of insert flange 233 can contact a top surface of shelf 227. The dimensions of shelf 227 (e.g., depth and width) can correspond to the dimensions of insert flange 233. In some embodiments, shelf 227 can have a depth in a range between about 0.25 mm to about 5 mm, e.g., 1 mm to 2 mm. In some embodiments, shelf 227 can have a width (e.g., an annular ring width, or the like) of 3 to 20 mm, e.g., 8 mm to 12 mm. In some embodiments, when insert flange 233 is an annulus, shelf 227 can include a corresponding annular recessed shelf. In various embodiments, when insert flange 233 comprises multiple tabs or projections, shelf 227 can comprise multiple corresponding recesses. In some embodiments, the depth of shelf 227 can be selected such that insert flange 233 (or membrane 235) does not project above shelf 227. In various embodiments, the depth of shelf 227 can be selected such that cap 237 compresses insert flange 233 into shelf 227, forming a seal between shelf 227 and insert flange 233.
Consistent with disclosed embodiments, insert 229 can be disposed within plug 225. In some embodiments, insert 229 can be secured within plug 225 using restraints. One or more such restraints can be attached to or integrally molded into insert 229 (e.g., restraint 231). In some embodiments, plug 225 can be formed with recess(es) corresponding to these restraint(s). The restraint(s) on insert 229 can interlock with the recess(es) on plug 255 to secure insert 229 to plug 225. Alternatively or additionally, restraint(s) on insert 229 can lack corresponding recess(es) on plug 225. Instead, these restraint(s) can form a compression fit that secures insert 229 to plug 255. In some embodiments, the one or more restraints can be attached or integrally molded into plug 225. The corresponding recess(es) can be formed on insert 229. Additionally or alternatively, insert 229 can be secured within plug 225 using adhesives or a compression fit.
Consistent with disclosed embodiments, pierceable membrane 235 can be located over insert 229. In some embodiments, membrane 235 can be bonded to insert flange 233 of insert 229 (e.g., bonded adhesively, heat-sealed, or in another suitable manner).
Optionally, cap 237 can be disposed around the container neck 223 and the stopper. The disclosed embodiments are not limited to caps made using any particular material or combination of materials. In some embodiments, cap 237 can be made from metal, polymer, or another suitable material. In some embodiments, cap 237 can be crimped around container flange 224, as depicted in
The disclosed embodiments are not limited to embodiments in which the stopper seals the container. In some embodiments, cap 237 can be configured to seal the container by compressing insert flange 233 against shelf 227, or by compressing plug flange 226 against container flange 224. In some embodiments, a portion of cap 237 can overlap with a portion of insert 229, such that cap 237 can apply a compressive force to insert 229. In such embodiments, this compressive force can secure (or assist in the securing of) insert 229 within plug 225, or seal insert 229 against plug 225 (e.g., seal insert flange 233 against plug flange 226). In some embodiments, cap 237 can be configured to prevent the stopper from becoming dislodged.
Consistent with disclosed embodiments, a displaceable secondary cover for pierceable membrane 239 (not depicted in
Consistent with disclosed embodiments, insert 310 includes an insert flange 313. The walls of insert 310 include a tapering portion 311 that ends in a lower opening 315 and a vertical portion 317 that connects to insert flange 313. Both the outer and inner walls of insert 310 taper.
Consistent with disclosed embodiments, insert 320 includes an insert flange 323. The walls of insert 320 include a tapering portion 321 connected to insert flange 323 and a vertical portion 327 the ends in a lower opening 325. Both the outer and inner walls of insert 320 taper.
Consistent with disclosed embodiments, insert 330 does not include an insert flange. In embodiments using an insert that lacks an insert flange, the plug (e.g., plug 225 or the like) may lack a recessed shelf (e.g., shelf 227 or the like). The walls of insert 330 include a tapering portion 331 disposed between two vertical portions 337, one of which ends in a lower opening 335. Both the outer and inner walls of insert 330 taper.
Consistent with disclosed embodiments, insert 340 does not include an insert flange. Furthermore, unlike inserts 310 to 330, the outer wall of insert 310 does not taper. Instead, an outer diameter of insert 340 remains approximately constant, while the inner wall of insert 340 tapers. In some embodiments, the constant diameter of insert 340 may support an improved seal between insert 340 and a plug containing insert 340.
Consistent with disclosed embodiments, insert 350 includes an insert flange 353. Unlike inserts 310 to 340, insert 350 includes a single vertical portion 357 but does not include a taper. Similar to insert 340, the constant diameter of insert 350 may support an improved seal between insert 350 and a plug containing insert 350. Furthermore, insert 350 may be simpler to manufacture than an insert that include tapering walls.
Consistent with disclosed embodiments, insert 360 includes an insert flange 356. Unlike inserts 310 to 350, insert 360 does not include a vertical portion but does includes taper 361. In some instances, insert 360 may provide a steeper interior wall angle for a given stopper height and diameter. The steeper interior wall angle may provide superior alignment capabilities for probes passing through insert 360.
The envisioned embodiments are not limited to embodiments including an insert. In some embodiments, the pierceable membrane may be bonded directly to the plug. In some such embodiments, the plug can be molded (and/or shaped) to include an upper opening and a lower opening formed, for example, by tapering the inner plug wall(s) to provide a plug cavity similar in shape to the insert cavities depicted in
Envisioned embodiments that include an insert are not limited to embodiments in which the pierceable membrane is bonded to the insert. In some embodiments that include an insert, the membrane may be bonded directly to the plug. For example, the membrane can be bonded to an upper surface of the plug above the recessed shelf (e.g., shelf 227, or the like) that contains the insert flange (e.g., insert flange 233, or the like). As an additional example, the membrane can be bonded to the cap, as opposed to being bonded to the insert or the plug. Accordingly, in some embodiments, the membrane can be over the insert and bonded to the insert (e.g., as in
In some embodiments, as depicted in
In some embodiments, as depicted in
As described above, in some embodiments the stopper may not include the insert. In such embodiments, a cavity can be formed between the pierceable membrane and the pre-sliced or pre-pierced diaphragm. The lower opening bounding the cavity can be formed by the pre-sliced or pre-pierced diaphragm (or the penetrated diaphragm following introduction of the probe into the container).
The embodiments may further be described using the following clauses:
Moreover, while illustrative embodiments have been described herein, the scope includes any and all embodiments having equivalent elements, modifications, omissions, combinations (e.g., of aspects across various embodiments), adaptations or alterations based on the present disclosure. The elements in the claims are to be interpreted broadly based on the language employed in the claims and not limited to examples described in the present specification or during the prosecution of the application, which examples are to be construed as non-exclusive. Further, the steps of the disclosed methods can be modified in any manner, including by reordering steps or inserting or deleting steps. It is intended, therefore, that the specification and examples be considered as example only, with a true scope and spirit being indicated by the following claims and their full scope of equivalents.
