Patent Description:
Low temperature specimen carriers, such as cryopreservation devices, are used in the field of assisted reproductive technology (ART) to store and preserve living reproductive cells (e.g., oocytes, embryos, and blastocysts). Cryopreservation refers to a process where cells are preserved over extended periods of time by cooling to sub-zero temperatures. For example, a cryopreservation device can house and support cells undergoing vitrification, which is the rapid transition of a substance from a liquid phase to a solid phase (e.g., glass) without the formation of ice crystals.

Vitrifying reproductive cells using a cryopreservation device includes immersing the cells in a vitrification medium and loading the cells, suspended in a volume of the vitrification medium, onto a support member of the cryopreservation device. The support member may then be capped and plunged into a container of cooling medium (e.g., liquid nitrogen), causing the cells loaded thereon to rapidly cool to a glass state before ice crystals can form within the cells. The cryopreservation device can be stored in the cooling medium until the cells are ready to be used in reproductive procedures. At that time, the cells, which have been preserved in a viable state, can be thawed via standard warming protocols in which the cryopreservation device is removed from the cooling medium and the support member is uncapped to provide access to the cells.

<CIT> describes a cryopreservation container that comprises a tapered body with a proximal open end and a sealed distal end and a lumen extending there between, a closure for removable attachment to the body, and a least two projections extending radially outwardly from the external surface of the lumen and forming an outer container surface that has a substantially constant external diameter.

<CIT> describes a storing instrument for vitrification and storing of biological specimen. The storing instrument includes a storing member which is made of a liquid nitrogen-resistant material, and a tubular protection member for protecting said storing member, the tubular protection member being also made of a liquid nitrogen-resistant material.

<CIT> describes a cryopreservation storage and processing container for cryogenic material. It incorporates the functions of both storage container and centrifuge tubes, provides self-sealing mechanism, and accommodates higher cooling/warming rates. The storage container includes both a vessel body and a cap.

<CIT> describes a closing device to create a seal in a cryocontainer for a biological specimen utilizes the temperature-induced phase transformation of shape memory materials to cause an actuator to toggle between a sealed and unsealed state.

<CIT> describes a storing instrument for vitrification and storing of biological specimen, specifically sperm, oocytes, embryos, morulae or blastocysts comprising: a storing member which is made of a liquid nitrogen-resistant material, and a tubular protection member for protecting said storing member, the tubular protection member being also made of a liquid nitrogen-resistant material, wherein said storing member comprises a cylindrical body part having a cell storing part at a front portion, and having a rear end part at an end portion, wherein the cell storing part is formed as a recess in the body part, and wherein the storing member having a smaller outer diameter that the inner diameter of the tubular protection member so that the storing member may be inserted and accommodated in the tubular protection member.

<CIT> describes a cryopreservation storage and processing container for cryogenic material.

In general, this disclosure relates to low temperature specimen carriers that are sealable via various sealing features, such as dissimilar component materials, sealing rings, and tapered interferences, as well as related methods. Such specimen carriers can be used for preserving living specimens in a viable state over a prolonged period of time.

In one aspect, a specimen carrier is defined in claim <NUM>.

Embodiments may provide one or more of the following features.

In some embodiments, the cap further defines an internal channel forming the region of the cap that surrounds the specimen when the cap is passed over the portion of the elongate member, the internal sealing surface forming a part of the internal channel.

In certain embodiments, the external and internal sealing surfaces have a frustoconical shape.

In some embodiments, the first and second coefficients of thermal expansion are independent of a dimensional unit of the first and second materials, respectively.

In certain embodiments, the first material is a transparent or translucent material.

In some embodiments, the hermetic seal prevents organisms and particulates as small as about <NUM> from entering the region of the cap that surrounds the specimen when the cap is passed over the portion of the elongate member and the portion of the elongate member and the cap are together disposed in the cooling substance.

In certain embodiments, the elongate member includes a shaft configured for handling of the elongate member.

In some embodiments, the shaft includes multiple surface facets.

In certain embodiments, the shaft defines a recess that provides a tactile feedback to a user of the specimen carrier.

In some embodiments, the cap includes a rounded end that provides a tactile feedback to a user of the specimen carrier.

In certain embodiments, the elongate member defines a vertical wall that shields the support surface.

In certain embodiments, the cap further includes a third material surrounding the second material, the third material having a third coefficient of thermal expansion that is greater than the second coefficient of thermal expansion.

In some embodiments, the second and third materials together provide an aggregate coefficient of thermal expansion that is greater than the second coefficient of thermal expansion and less than the third coefficient of thermal expansion.

In certain embodiments, the specimen carrier is configured to preserve the specimen in a viable state within the cooling substance over a period of at least <NUM> years.

With the elongate member in a capped state while submerged in the cooling substance, the internal sealing surface of the cap shrinks against the external sealing surface of the elongate member, thereby increasing the extent of closure (e.g., tightness) of the region the cap to form a tight, intimate fit (or, in some cases, a tighter intimate fit) along the interface, such that the hermetic seal (e.g., an airtight seal) is formed at the interface between the external and internal sealing surfaces. The hermeticity of the seal is sufficient to prevent particulates and organisms (e.g., the HIV or Hepatitis B viruses) of sizes as small as about <NUM> from penetrating the seal and therefore preventing the particulates and organisms from entering the region of the cap and from contaminating the specimen contained therein. The seal provided along the interface has a greater hermeticity than would otherwise be achieved for an equivalently dimensioned interfacing cap and elongate member formed of the same material. The hermetic seal along the interface remains intact as long as the specimen carrier remains submerged within the cooling substance.

In some embodiments, when a specimen carrier including a cap with an internal sealing feature (e.g., one or more circumferential sealing rings or a tapered wall) is pressed onto the tip of a stick member, the interference fit formed along an interface between the sealing feature of the cap and the external sealing surface of the tip causes the cap to expand slightly in the region of the internal sealing feature, such that the cap experiences localized frictional forces in the region without stretching of the entire cap. Providing the internal sealing feature at a sufficient distance away from the open end of the cap advantageously avoids stress-induced fractures that may otherwise result if such a sealing feature was located closer to the open end of such a cap. Furthermore, the interference fit formed along the interface may provide a dual functionality of hermetic sealing that prevents contamination of the internal channel of the cap and retention of the cap on the stick member.

In some embodiments, serial placement of one sealing ring forward of one or more additional sealing rings along the internal channel of the cap provides one or more additional degrees of sealing that can prevent passage of particulates and organisms that manage to penetrate rearward sealing rings. In some embodiments, as the elasticity of the material from which the sealing rings is made increases, the elastic deformation that occurs upon pressing the cap onto the tip increases, providing more friction at the interfaces formed at the sealing rings, tighter seals, and improved retention of the cap on the stick member.

In some embodiments, a specimen carrier advantageously includes a sealing structure (e.g., a tapered wall-to-wall interface) and a retention feature (e.g., a snap ring and an associated recess) that are isolated from each other. In such embodiments, an interference fit formed between a tapered wall of the cap and the tip of the stick member provides a hermetic seal that prevents contamination of the internal channel of the cap, while a snap ring on the tip of the stick member and a recess within the tapered wall of the cap together provide a securement feature that retains the cap on the stick member. Furthermore, when the cap is passed over the tip, seating of the snap ring within the recess with can provide a tactile feedback and/or an audible feedback to a user indicating that the cap is properly secured to the stick member.

In some embodiments, a specimen carrier may include a relief area on a tip of the stick member that provides a retention capability. For example, in some embodiments, the external sealing surface of a tip of the stick member may define a circumferential relief positioned rearward of a tapered portion of the external sealing surface, and a tapered wall of the associated cap is formed to interfere with the tapered portion of the external sealing surface when the cap is passed fully over the tip. When the specimen carrier is immersed in the low temperature substance, the rear portion of the tapered wall of the cap relaxes (e.g., collapses) into a gap formed between the circumferential relief of the tip and the wall of the cap to retain the cap on the stick member. Thus, the rear portion of the tapered wall and the circumferential relief together provide a securement feature that further retains the cap on the stick member, while the interference fit between a forward portion of the tapered wall of the cap and the tip provides a hermetic seal that prevents contamination of the internal channel of the cap.

In some embodiments, a specimen carrier includes both a cap with sealing rings and a stick member with a relief area. When the cap of such a specimen carrier is passed over the tip of the stick member, the sealing ring provides a tactile feedback and/or an audible feedback to a user as the sealing ring passes along the tapered portion of the external sealing surface of the tip into a rearward relief formed on the external sealing surface. The feedbacks indicate to the user that the cap has been passed over the tip of the stick member by at least a minimum distance. A rear portion of the wall of the cap and the rearward relief of the tip together provide a securement feature that retains the cap on the stick member. That is, when the specimen carrier is immersed in the low temperature substance, the rear portion of the wall of the cap relaxes (e.g., collapses) into the gap formed by the relief to retain the cap on the stick member.

In some embodiments, a relief extending inwardly from the open end of the cap of the specimen carrier serves to avoid generation of excessive frictional forces that may otherwise result between the cap and the tip, thereby reducing the generation or propagation of any resulting stress fractures in the cap near the open end. In some embodiments, the cap defines a relief positioned along a central portion of the wall of the cap that alleviates forward frictional forces formed between the wall of the cap and the external sealing surface of the tip of the stick member.

For embodiments in which the coefficient of thermal expansion (CTE) of one or more materials from which the cap is made is greater than the CTE of the material from which the tip is made, the sealing structure of the cap (e.g., one or more sealing rings or a tapered wall) moves with respect to (e.g., shrinks against) the external sealing surface of the tip such that the interfaces become dynamic upon submersion in the low temperature substance. In this manner, the sealing provided by the interference fits formed at the interfaces may be tightened even further due to thermal affects. In some embodiments, the wall of the cap may include two or more layers made of different, respective materials providing an aggregate CTE that is greater than the CTE of the material from which the tip is made. In such embodiments, one or more outer layers of the cap may enforce the behavior of one or more inner layers of the cap relative to the tip, thereby providing a tighter closure between the external sealing surface of the tip and an inner-most layer of the wall of the cap.

Other aspects, features, and advantages will be apparent from the description, the drawings, and the claims.

<FIG> illustrates a specimen carrier <NUM> adapted for submersion and storage in a low temperature substance. The specimen carrier <NUM> is a cryopreservation device that is configured to house and store a variety of specimens (e.g., cellular samples and tissue samples) in a viable and vitrified state within the low temperature substance until the specimens are desired for use (e.g., over a period of up to about <NUM> years). The specimens may include reproductive specimens, such as oocytes, embryos (e.g., cleavage stage embryos), and blastocysts, or other samples, such as T-cells. Such specimens may be mammalian samples or non-mammalian samples. The low temperature substance (e.g., liquid nitrogen or cryogenic plasma) maintains the specimens in a vitrified state and has a temperature of about -<NUM> to about -<NUM> (e.g., about -<NUM>).

Referring to <FIG> and <FIG>, the specimen carrier <NUM> includes a stick member <NUM> (shown in a capped state and an uncapped state, respectively) and a cap <NUM> that can be passed over a portion of the stick member <NUM>. The stick member <NUM> includes a shaft <NUM> by which the stick <NUM> can be handled and a tip <NUM> extending from the shaft <NUM>.

The shaft <NUM> has a surface defined by hexagonal facets <NUM> that prevent the stick member <NUM> from rolling on a surface. Accordingly, the shaft <NUM> has a hexagonal cross-sectional shape. The shaft <NUM> defines a flat, elongate recess <NUM> that provides tactile feedback indicating that the specimen carrier <NUM> is being handled at the appropriate end of the specimen carrier <NUM>. The recess <NUM> further provides a visual indication that the specimen carrier <NUM> is oriented correctly while the specimen carrier <NUM> is being submerged in the low temperature substance or removed from a storage container. The recess <NUM> also provides a surface on which information (e.g., patient identification information, specimen identification information, a date, or other information) can be written or otherwise printed. A texture (e.g., a light frosting or a matt finish) of the surface of the recess <NUM> facilitates writing and printing, legibility of writing and printing, and retention of ink on the recess <NUM>. Markings may also be printed on a surface of an end portion <NUM> of the shaft <NUM>. Such markings may indicate information such as patient identification information, specimen identification information, a date, or other information. The shaft <NUM> typically has a length of about <NUM> to about <NUM> (e.g., about <NUM>) and a maximum width of about <NUM> to about <NUM> (e.g., about <NUM>). The shaft <NUM> may be manufactured via an injection molding process or a casting process. The shaft <NUM> is made of one or more materials that can withstand the low temperature substance, including but not limited to polymers such as polystyrene, polypropylene, polyvinyl acetate, and polycarbonate.

<FIG> illustrates an enlarged view of the tip <NUM> of the stick member <NUM>. The tip <NUM> is formed as a generally conical member that may be slid into the cap <NUM> (e.g., at an ambient temperature) to form an interface between the tip <NUM> and the cap <NUM>. The tip <NUM> defines an external sealing surface <NUM> configured to form the interface with the cap <NUM> and a tip extension <NUM> that extends from the external sealing surface <NUM>. The external sealing surface <NUM> has a generally frustoconical shape. The tip extension <NUM> defines a loading surface <NUM> (e.g., a support surface) upon which a specimen can be deposited and a vertical wall <NUM> that protects (e.g., shields) the loading surface <NUM>. The loading surface <NUM> is formed as a concave surface that extends from the vertical wall <NUM> to an end <NUM> of the tip <NUM>. The loading surface <NUM> is sized to hold one or two cells (e.g., reproductive cells). The tip <NUM> is also transparent or translucent to allow easy viewing of the cells under a microscope while the cells are supported on the loading surface <NUM>.

The loading surface <NUM> of the tip <NUM> typically has a length of about <NUM> to about <NUM> (e.g., about <NUM>) and a width of about <NUM> to about <NUM> (e.g., about <NUM>), allowing for easy placement of the cells, which typically have widths ranging from about <NUM> to about <NUM>. A thickness of the loading surface <NUM> is designed to allow maximum cell cooling rates when the specimen carrier <NUM> is submerged in the low temperature substance and maximum warming rates when the specimen carrier <NUM> is removed from the low temperature substance. The external sealing surface <NUM> of the tip <NUM> typically has a length of about <NUM> to about <NUM> (e.g., about <NUM>), a maximum diameter of about <NUM> to about <NUM> (e.g., about <NUM>), and a minimum diameter of about <NUM> to about <NUM> (e.g., about <NUM>). The tip <NUM> typically has a total length of about <NUM> to about <NUM> (e.g., about <NUM>). The tip <NUM> may be manufactured via a casting process or via an injection molding process (e.g., via a single injection molding process in which both the shaft <NUM> and the tip <NUM> are manufactured as an integral component or via a separate injection molding process, following which the tip <NUM> is subsequently joined to the shaft <NUM> as a subcomponent of the stick member <NUM>). The tip <NUM> is made of one or more materials that can withstand the low temperature substance, including but not limited to polymers such as polystyrene, polypropylene, polyvinyl acetate, and polycarbonate. In some embodiments, the one or more materials are translucent or transparent. The tip <NUM> and the shaft <NUM> may be made of the same material or made of different materials, depending on the process used to manufacture the tip <NUM> and the shaft <NUM>.

Referring again to <FIG> and <FIG>, the cap <NUM> is sized to be passed over the tip <NUM> to form an interface between the tip <NUM> and the cap <NUM>. The cap <NUM> forms a generally conical shaped internal channel <NUM> defined by an internal surface <NUM>. The internal surface <NUM> includes an internal sealing surface <NUM> configured to interface with the external sealing surface <NUM> of the tip <NUM>. Accordingly, the internal sealing surface <NUM> has a generally frustoconical shape. A rounded end <NUM> of the cap <NUM> provides a tactile feedback that tactilely differentiates the cap <NUM> from the stick member <NUM>. The internal sealing surface <NUM> of the cap <NUM> typically has a length, a maximum diameter, and a minimum diameter that are about equal to the length, the maximum diameter, and the minimum diameter, respectively, of the external sealing surface <NUM> of the tip <NUM>. In some embodiments, the internal sealing surface <NUM> has a length that is longer than the length of the external sealing surface <NUM>, a maximum diameter that is larger than the maximum diameter of the external sealing surface <NUM>, and a minimum diameter that is smaller than the minimum diameter of the external sealing surface <NUM>. The internal channel <NUM> of the cap <NUM> has a length that is about equal to the length of the tip <NUM> of the stick member <NUM>, a maximum diameter that is about equal to the maximum diameter of the external and internal sealing surfaces <NUM>, <NUM>, and a minimum diameter of about <NUM> to about <NUM> (e.g., about <NUM>). The cap <NUM> typically has a total length of about <NUM> to about <NUM> (e.g., about <NUM>).

As discussed above, the cap <NUM> may be passed over the tip <NUM> (e.g., loaded with a specimen) at room temperature to provide the interface between the internal sealing surface <NUM> of the cap <NUM> and the external sealing surface <NUM> of the tip <NUM>. Depending on the extent to which the cap <NUM> is passed over the tip <NUM>, and according to a tapered geometry of the cap <NUM> and the tip <NUM>, the interface may provide different levels of closure. For example, when the cap <NUM> is passed over the tip <NUM> to the extent that a distal end of the internal sealing surface <NUM> remains distal to a distal end of the external sealing surface <NUM>, the interface provides a clearance (e.g., a small gap) between the external and internal sealing surfaces <NUM>, <NUM> along an area in which the external and internal sealing surfaces <NUM>, <NUM> overlap. When the cap <NUM> is passed over the tip <NUM> to the extent that corresponding ends of the external and internal sealing surfaces <NUM>, <NUM> are substantially aligned, the interface provides an interference fit (e.g., a mild press fit) that frictionally, releasably secures the cap <NUM> to the stick member <NUM>. In some examples, the cap <NUM> is passed over the tip <NUM> to the extent that the distal end of the internal sealing surface <NUM> is proximal to the distal end of the external sealing surface <NUM>, thereby providing an intimate fit (e.g., a strong press fit) that frictionally, releasably, secures the cap <NUM> to stick member <NUM> along an area in which the external and internal sealing surfaces <NUM>, <NUM> overlap.

When the temperature of the specimen carrier <NUM> changes (e.g., when the specimen carrier <NUM> is heated or cooled), each component of the specimen carrier <NUM> undergoes a dimensional change by an amount that is proportional to the original dimension of the component and to the change in temperature. For example, when the specimen carrier <NUM> is cooled (e.g., submerged in the low temperature substance), the cap <NUM> and the stick member <NUM> contract (e.g., shrink), whereas when the specimen carrier <NUM> is heated (e.g., allowed to thaw upon removal from the low temperature substance), the cap <NUM> and the stick member <NUM> expand. This effect can be described by a coefficient of thermal expansion (CTE), which defines how the size of an object changes with a change in temperature. The CTE is defined as the ratio of a fractional change in one or more dimensions per unit (e.g., degree) change in temperature at a constant pressure, as provided in EQU. <NUM>, where α is the CTE, D is the original length (for the case of a one-dimensional length CTE), the original area (for the case of a two-dimensional area CTE), or the original volume (for the case of a three-dimensional volumetric CTE); ΔD is the change in D, ΔT is the change in the temperature, and p denotes a constant pressure. <MAT> In some cases, the CTE of a material varies as a function of the absolute temperature. However, the CTE is often assumed to be a constant value for the purpose of simplifying analyses.

<FIG> illustrates a cross-sectional perspective view of the specimen carrier <NUM> with the stick <NUM> in the capped state at a relatively high temperature (e.g., a room temperature of about <NUM>). At the relatively high temperature, the cap <NUM> is typically passed over the stick <NUM> to the extent that an interface <NUM> between the external and internal sealing surfaces <NUM>, <NUM> provides an interference fit, as described above. The cap <NUM> is made of a material that has a CTE that is greater than a CTE of the material from which the tip <NUM> is made, such that when the specimen carrier <NUM> is submerged in the low temperature substance (e.g., liquid nitrogen at a temperature of about -<NUM>), the cap <NUM> contracts to a greater extent per degree temperature change (e.g., at a faster rate) than does the tip <NUM>, causing the internal sealing surface <NUM> of the cap <NUM> to shrink against (e.g., compress) the external sealing surface <NUM> of the tip <NUM>. For the example specimen carrier <NUM>, the materials from which the cap <NUM> and the tip <NUM> are made behave substantially the same in all three dimensions with respect to thermal expansion, such that the cap <NUM> and the tip <NUM> can be described with respect to CTEs that are independent of a dimensional unit (e.g., length, area, or volume) of the respective materials. In some embodiments, the CTE of the material from which the cap <NUM> is made is about [<NUM> x <NUM>-<NUM>]/°C to about [<NUM> x <NUM>-<NUM>]/°C (e.g., about [<NUM> x <NUM>-<NUM>]/°C), and the CTE of the material from which the tip <NUM> is made is about [<NUM> x <NUM>-<NUM>]/°C to about [<NUM> x <NUM>-<NUM>]/°C (e.g., about [<NUM> x <NUM>-<NUM>]/°C).

<FIG> illustrates a cross-sectional view of the specimen carrier <NUM> with the stick <NUM> in the capped state while submerged in the low temperature substance. Within the low temperature substance, the internal sealing surface <NUM> of the cap <NUM> shrinks against the external sealing surface <NUM> of the tip <NUM>, thereby increasing the extent of closure (e.g., tightness) to form a tight, intimate fit (or, in some cases, a tighter intimate fit) along the interface <NUM>, such that a hermetic seal (e.g., an airtight seal) is formed at the interface <NUM> between the external and internal sealing surfaces <NUM>, <NUM>. The hermeticity of the seal (e.g., the extent to which the seal is able to prevent air from penetrating the seal) is sufficient to prevent particulates and organisms (e.g., the HIV and Hepatitis B viruses) of sizes as small as about <NUM> from penetrating the seal and therefore preventing the particulates and organisms from entering the internal channel <NUM> of the cap <NUM> and from contaminating the specimen contained therein. In some examples, the seal is defined as hermetic at an air leak rate of less than <NUM>-<NUM> atm-cc/sec. The seal provided along the interface <NUM> has a greater hermeticity as compared to a specimen carrier including a tip and a cap of the same geometries as the tip <NUM> and the cap <NUM> and formed of the same material. The hermetic seal along the interface <NUM> remains intact as long as the specimen carrier <NUM> remains submerged within the low temperature substance.

Upon removal of the specimen carrier <NUM> from the low temperature substance (e.g., in order to use the specimen in a reproductive procedure), the components of the specimen carrier <NUM> will stress relax over time. Accordingly, the cap <NUM> and the tip <NUM> will expand such that the interface <NUM> between the external and internal sealing surfaces <NUM>, <NUM> loosens, thereby reducing the level of closure of the internal channel <NUM> and releasing the hermetic seal.

The specimen carrier <NUM> is a sterile, single-use device that is non-toxic to cellular and tissue specimens. The specimen carrier <NUM> may be individually packaged, and both the specimen carrier <NUM> and the packaging will remain sterile for a guaranteed shelf-life of the specimen carrier <NUM>. The specimen carrier <NUM> typically has a total length (e.g., in a capped state) of about <NUM> to about <NUM> (e.g., about <NUM>), which allows the specimen carrier <NUM> to fit within standard storage containers and other standard equipment used in ART protocols.

In order to vitrify reproductive cells using the specimen carrier <NUM>, the cells are first immersed in an equilibrium medium and then in a vitrification medium containing high concentrations of cryoprotectants. Permeation of the cryoprotectants into the cells replaces water within the cells, thereby dehydrating the cells and increasing the intracellular viscosity of the cells. A micropipette is then used to load one or two cells, suspended in a minimally adequate volume of vitrification medium, onto the loading surface <NUM> of the specimen carrier <NUM>. The stick member <NUM> is slid inside of the cap <NUM>, thereby providing the interface <NUM> between the internal sealing surface <NUM> of the cap <NUM> and the internal sealing surface <NUM> of the tip <NUM> to close the internal channel <NUM> of the cap <NUM>. In a capped state, the specimen carrier <NUM> is then plunged into a container of the low temperature substance (e.g., a cooling substance), causing the cells to rapidly cool to a glass state before ice crystals can form within the cells to preserve the cells in a viable state. The specimen carrier <NUM> can be stored in the low temperature substance until the cells are ready to be used in reproductive procedures. At such a time, the specimen carrier <NUM> can be removed from the low temperature substance. The cells can subsequently be thawed via standard warming protocols in which the stick member <NUM> of the specimen carrier <NUM> is uncapped and the cells are exposed to one or more warming solutions.

While certain embodiments have been described above, other embodiments are possible.

For example, while the specimen carrier <NUM> has been described as including the cap <NUM> formed of one material, a specimen carrier may have a cap that is formed of two or more materials providing an aggregate CTE that is greater than a CTE of the material form which the tip is made. In some embodiments, as shown in <FIG>, a specimen carrier <NUM> includes the stick member <NUM> and a cap <NUM>. The cap <NUM> is substantially similar in size and shape to the cap <NUM> of the specimen carrier <NUM>, except that the cap <NUM> is made of two different materials. The cap <NUM> includes an outer layer <NUM> made of a first material and an inner layer <NUM> made of a second material. The outer and inner layers <NUM>, <NUM> may be made of one or more materials, including but not limited to polymers (e.g., polystyrene, polypropylene, polyvinyl acetate, polycarbonate, and polysulfone), composite materials, ceramics, and metals (e.g. steel or titanium).

The inner layer <NUM> has an internal sealing surface <NUM> (e.g., of substantially the same size and shape of the internal sealing surface <NUM> of the cap <NUM>) that forms an interface <NUM> with the external sealing surface <NUM> of the tip <NUM> when the cap <NUM> is passed over the tip <NUM>. The first material of the outer layer <NUM> has a CTE that is greater than a CTE of the second material from which the inner layer <NUM> is made, and the CTE of the second material is greater than the CTE of the material from which the tip <NUM> is made. Thus, an aggregate CTE provided by the first and second materials of the cap <NUM> (e.g., describing a behavior at an interface <NUM> between the outer and inner layers <NUM>, <NUM>) is greater than the CTE of the material from which the tip <NUM> is made.

When the specimen carrier <NUM> is submerged in the low temperature substance, the outer layer <NUM> contracts at a faster rate than does the inner layer <NUM>, causing the outer layer <NUM> to shrink against (e.g., compress) the inner layer <NUM>, and the inner layer <NUM> contracts at a faster rate than does the tip <NUM>, causing the internal sealing surface <NUM> to shrink against (e.g., compress) the external sealing surface <NUM> of the tip <NUM>. In this manner, the outer layer <NUM> of the cap <NUM> enforces the behavior of the inner layer <NUM> with respect to the tip <NUM>, thereby providing a tighter closure (e.g., a seal of a greater hermeticity) between the external sealing surface <NUM> of the tip <NUM> and the internal sealing surface <NUM> of the inner layer <NUM>, as compared to a seal that would otherwise form between the cap <NUM> and the tip <NUM> of the specimen carrier <NUM> in a case where the cap <NUM> is made of the same material from which the inner layer <NUM> of the specimen carrier <NUM> is formed.

While the specimen carrier <NUM> has been described as including the tip <NUM> with the concave loading surface <NUM>, in some embodiments, a specimen carrier may have a tip including feature geometries that are different from the those of the tip <NUM>. For example, as shown in <FIG>, a specimen carrier <NUM> includes a stick member <NUM> that has a tip <NUM> that is substantially similar in function and size and similar in construction to the tip <NUM> of the specimen carrier <NUM>, except that the tip <NUM> includes a flat, rectangular loading surface. In particular, the tip <NUM> defines an external sealing surface <NUM> that is equivalent in geometry to the external sealing surface <NUM> of the tip <NUM> and a tip extension <NUM> that extends from the external sealing surface <NUM>. The tip extension <NUM> defines a loading surface <NUM> upon which a specimen can be deposited and a vertical wall <NUM> that protects (e.g., shields) the loading surface <NUM>. The loading surface <NUM> is formed as a flat channel that extends from the vertical wall <NUM> to an end flange <NUM> of the tip <NUM>. The end flange <NUM> is configured to provide additional protection of the loading surface <NUM> and to provide a structure for supporting a pipette cannula during loading. Similar to the loading surface <NUM> of the tip <NUM>, the loading surface <NUM> is sized to hold one or two cells. The tip <NUM> may be manufactured using the techniques and made of the materials as described above with respect to the tip <NUM> of the specimen carrier <NUM>.

In some embodiments, as shown in <FIG>, a specimen carrier <NUM> includes a stick member <NUM> that has a tip <NUM> that is substantially similar in function and size and similar in construction to the tips <NUM>, <NUM> of the specimen carriers <NUM>, <NUM>, except that the tip <NUM> includes a loading surface that further defines a loading platform. For example, the tip <NUM> defines an external sealing surface <NUM> that is equivalent in geometry to the external sealing surface <NUM> of the tip <NUM> and a tip extension <NUM> that extends from the external sealing surface <NUM>. The tip extension <NUM> defines a loading surface <NUM> that further defines a loading platform <NUM> indicating where a specimen may be deposited. The loading platform <NUM> includes convex end regions <NUM>. The loading platform <NUM> is configured to guide placement of the cells on the loading surface <NUM> with more locational specificity. In some embodiments, the loading platform <NUM> may reduce the thermal mass of the tip extension <NUM>. In some embodiments, the loading platform <NUM> may also provide a region that is thinner or more light transmissive than the surrounding loading surface <NUM>. The tip extension <NUM> further defines a vertical wall <NUM> that protects (e.g., shields) the loading surface <NUM>. The loading surface <NUM> is formed as a flat, rectangular surface that extends from the vertical wall <NUM> to an end <NUM> of the tip <NUM>. Similar to the loading surfaces <NUM>, <NUM> of the tips <NUM>, <NUM>, the loading surface <NUM> is sized to hold one or two cells. The tip <NUM> may be manufactured using the techniques and made of the materials as described above with respect to the tip <NUM> of the specimen carrier <NUM>.

In some embodiments, as shown in <FIG>, a specimen carrier <NUM> includes a stick member <NUM> that has a tip <NUM> that is substantially similar in function and size and similar in construction to the tips <NUM>, <NUM>, <NUM> of the specimen carriers <NUM>, <NUM>, <NUM> except that the tip <NUM> includes a loading pocket near an end of the tip <NUM>. For example, the tip <NUM> defines an external sealing surface <NUM> that is equivalent in geometry to the external sealing surface <NUM> of the tip <NUM> and a tip extension <NUM> that extends from the external sealing surface <NUM>. The tip extension <NUM> defines a loading surface <NUM> and a loading pocket <NUM> where a specimen may be deposited. The loading surface <NUM> is formed as a flat channel that extends from a vertical wall <NUM> to an end <NUM> of the tip <NUM>. The loading pocket <NUM>, located near the end <NUM> of the tip <NUM>, is sized to hold one or two specimens that each includes one or more cells. The tip <NUM> may be manufactured using the techniques and made of the materials as described above with respect to the tip <NUM> of the specimen carrier <NUM>.

While the specimen carriers <NUM>, <NUM>, <NUM>, <NUM>, <NUM> have been described as being sealable via dissimilar component materials, in some embodiments, a specimen carrier may alternatively or additionally include other sealing features. For example, as shown in <FIG>, a specimen carrier <NUM> includes circumferential sealing rings <NUM>, <NUM>. The specimen carrier <NUM> includes the stick member <NUM> of the specimen carrier <NUM>, described above, and a cap <NUM> that is substantially similar in exterior geometry to the cap <NUM> of the specimen carrier <NUM>. Accordingly, the cap <NUM> defines a rounded end that is substantially similar in construction and function to the rounded end <NUM> of the cap <NUM>. The cap <NUM> also forms a generally conical shaped internal channel <NUM> defined by an internal surface <NUM>. The internal surface <NUM> includes an internal sealing surface <NUM> configured to interface with the external sealing surface <NUM> of the tip <NUM> of the stick member <NUM>. Accordingly, the internal sealing surface <NUM> has a generally tapered, frustoconical shape. The internal sealing surface <NUM> defines a forward sealing ring <NUM> and a rearward sealing ring <NUM> that serve as hermetic barriers. The internal sealing surface <NUM> further defines a circumferential relief <NUM> that extends axially from an open end <NUM> of the cap <NUM> and that also defines a rearward end <NUM> of the internal sealing surface <NUM>.

The internal channel <NUM> has a length and a minimum diameter that are about equal to the length and the minimum diameter of the internal channel <NUM> of the cap <NUM>, described above. The internal sealing surface <NUM> has a length and a minimum diameter that are about equal to the length and the minimum diameter of the internal sealing surface <NUM> of the cap <NUM>, described above. The relief <NUM>, defining the maximum diameter of the internal sealing surface <NUM> at the rearward end <NUM>, typically has a maximum diameter of about <NUM> to about <NUM> (e.g., about <NUM>) and a length of about <NUM> to about <NUM> (e.g., about <NUM>). The forward sealing ring <NUM> typically has a radius of curvature (i.e., with respect to a central, circular arc of the sealing ring <NUM>) of about <NUM> to about <NUM> (e.g., about <NUM>), has an interior circumferential diameter (i.e., extending through a longitudinal axis of the cap <NUM>) of about <NUM> to about <NUM> (e.g., about <NUM>), and is located about <NUM> to about <NUM> (e.g., at least about <NUM>) from the open end <NUM> of the cap <NUM>. The rearward sealing ring <NUM> typically has a radius of curvature (i.e., with respect to a central, circular arc of the sealing ring <NUM>) of about <NUM> to about <NUM> (e.g., about <NUM>), has an interior circumferential diameter (i.e., extending through the longitudinal axis of the cap <NUM>) of about <NUM> to about <NUM> (e.g., about <NUM>), and is located about <NUM> to about <NUM> (e.g., at least about <NUM>) from the open end <NUM> of the cap <NUM>. The cap <NUM> has a total length that is about equal to the total length of the cap <NUM>, described above.

The cap <NUM> may be passed over and pressed onto the tip <NUM> of the stick member <NUM> (e.g., loaded with a specimen) at room temperature to provide interfaces <NUM>, <NUM> that form respective interference fits between each of the sealing rings <NUM>, <NUM> and the external sealing surface <NUM> of the tip <NUM>. When the cap <NUM> is pressed onto the tip <NUM>, the interference fits at the sealing rings <NUM>, <NUM> cause the cap <NUM> to expand slightly in the regions of the sealing rings <NUM>, <NUM> (e.g., the cap <NUM> is pushed radially outward by the tip <NUM> at the interfaces <NUM>, <NUM>). Accordingly, the cap <NUM> experiences localized frictional forces in the regions of the sealing rings <NUM>, <NUM> without stretching of the entire cap <NUM>. Providing the sealing rings <NUM>, <NUM> (and therefore, the localized forces generated by the sealing rings <NUM>, <NUM>) at a sufficient distance (e.g., at least about <NUM> to at least about <NUM>) away from the open end <NUM> of the cap <NUM> can reduce or prevent stress-induced fractures that may otherwise result if such rings were located closer to the open end of such a cap. The interference fits between the sealing rings <NUM>, <NUM> and the tip <NUM> provide both hermetic seals that prevent contamination of the internal channel <NUM> and frictional interfaces (e.g., securement features) that retain the cap <NUM> on the stick member <NUM>.

The hermeticity of the seals can be sufficient to prevent particulates and organisms of sizes as small as about <NUM> from penetrating the seals and from therefore entering the internal channel <NUM> of the cap <NUM> and contaminating a specimen contained therein. Serial placement of the sealing ring <NUM> forward of the sealing ring <NUM> provides an additional degree of sealing that can prevent passage of particulates and organisms that manage to penetrate the sealing ring <NUM>. The hermetic seals formed along the interfaces <NUM>, <NUM> remain intact as long as the cap <NUM> remains pressed onto the tip <NUM> of the stick member <NUM>. Furthermore, the relief <NUM> serves to reduce or prevent generation of excessive frictional forces that may otherwise result between the cap <NUM> (e.g., near the open end <NUM> of the cap <NUM>) and the tip <NUM>, thereby reducing the generation or propagation of any resulting stress fractures in the cap <NUM> near the open end <NUM>.

In some embodiments, the two sealing rings <NUM>, <NUM> may be made of the same material, which is different from a material of which a wall <NUM> of the cap <NUM> is made. In some embodiments, the two sealing rings <NUM>, <NUM> may be made of two different, respective materials, where one or neither of the materials is the same as the material from which the wall <NUM> of the cap <NUM> is made. In some embodiments, as the elasticity of the material from which the sealing rings <NUM>, <NUM> is made increases, the elastic deformation that occurs upon pressing the cap <NUM> onto the tip <NUM> increases, providing more friction at the interfaces <NUM>, <NUM>, a tighter seal, and improved retention of the cap <NUM> on the stick member <NUM>.

In some embodiments, the cap <NUM> and the tip <NUM> of the stick member <NUM> may be made of the same material, thereby providing a fixed system for which, upon submersion in the low temperature substance, the interfaces <NUM>, <NUM> remain fixed such that the sealing rings <NUM>, <NUM> do not move substantially with respect to the external sealing surface <NUM> of the tip <NUM>. In such embodiments, sealing of the specimen carrier <NUM> is provided by the interference fits formed at the interfaces <NUM>, <NUM>.

In some embodiments, any of the wall <NUM> and the sealing rings <NUM>, <NUM> of the cap <NUM> may be made of one or more materials that are different from the material from which the tip <NUM> of the stick member <NUM> is made, thereby providing a dynamic system. For such embodiments in which the coefficient of thermal expansion (CTE) of one or more materials from which the wall <NUM> or the sealing rings <NUM>, <NUM> are made is greater than the CTE of the material from which the tip <NUM> is made, the sealing rings <NUM>, <NUM> move with respect to (e.g., shrink against) the external sealing surface <NUM> of the tip <NUM> such that the interfaces <NUM>, <NUM> become dynamic upon submersion in the low temperature substance. In this manner, the sealing provided by the interference fits formed at the interfaces <NUM>, <NUM> may be tightened even further due to thermal affects (e.g., as described above with respect to the specimen carrier <NUM>) resulting from a difference in the CTE of one or more of the wall <NUM> and the sealing rings <NUM>, <NUM> of the cap <NUM> and CTE of the tip <NUM>. In some embodiments, the CTE of the one or more materials from which the wall <NUM> and the sealing rings <NUM>, <NUM> of the cap <NUM> are made falls in a range of about [<NUM> x <NUM>-<NUM>]/°C to about [<NUM> x <NUM>-<NUM>]/°C (e.g., about [<NUM> x <NUM>-<NUM>]/°C), and the CTE of the material from which the tip <NUM> is made is about [<NUM> x <NUM>-<NUM>]/°C to about [<NUM> x <NUM>-<NUM>]/°C (e.g., about [<NUM> x <NUM>-<NUM>]/°C).

While the specimen carrier <NUM> has been described as including the cap <NUM> with two sealing rings <NUM>, <NUM>, in some embodiments, a specimen carrier includes a cap that has a different number of sealing rings (e.g., one, three, or four sealing rings). For example, as shown in <FIG>, a specimen carrier <NUM> includes the stick member <NUM> of the specimen carrier <NUM> and a cap <NUM> that is substantially similar in construction and function to the cap <NUM> of the specimen carrier <NUM>, except that the cap <NUM> includes four sealing rings <NUM>, <NUM>, <NUM>, <NUM> that form interference fits with the external sealing surface <NUM> of the tip <NUM> along interfaces <NUM>, <NUM>, <NUM>, <NUM> when the cap <NUM> is pressed onto the stick member <NUM>. Serial placement of the sealing rings <NUM>, <NUM>, <NUM>, <NUM> provides multiple degrees of sealing that can prevent passage of particulates and organisms that manage to penetrate any rearward sealing rings <NUM>, <NUM>, <NUM>. The sealing rings <NUM>, <NUM>, <NUM>, <NUM> may be spaced equally or unequally apart from one another. With the exception of the additional number of seals provided by the four sealing rings <NUM>, <NUM>, <NUM>, <NUM>, the specimen carrier <NUM> is substantially similar in construction and function to the specimen carrier <NUM>. Accordingly, the interference fits between the sealing rings <NUM>, <NUM>, <NUM>, <NUM> and the tip <NUM> provide both hermetic seals that prevent contamination of an internal channel <NUM> of the cap <NUM> and frictional interfaces that retain the cap <NUM> on the stick member <NUM>.

While the specimen carriers <NUM>, <NUM> have been described as including caps with circumferential rings <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> that effect sealing, in some embodiments, a specimen carrier includes a cap with a different feature that effects sealing, such as a tapered wall. For example, as shown in <FIG>, a specimen carrier <NUM> includes the stick member <NUM> of the specimen carrier <NUM> and a cap <NUM> that provides a tapered wall <NUM> formed to interfere with the external sealing surface <NUM> of the tip <NUM> of the stick member <NUM>. The cap <NUM> is substantially similar in exterior geometry to the cap <NUM>, described above, and accordingly defines a rounded end that is substantially similar in construction and function to the rounded end <NUM> of the cap <NUM>. The cap <NUM> forms a generally conical shaped internal channel <NUM> defined by an internal surface <NUM>. The internal surface <NUM> includes an internal sealing surface <NUM> that extends along the tapered wall <NUM> of the cap <NUM>. Accordingly, the internal sealing surface <NUM> and the tapered wall <NUM> have a generally frustoconical shape. The tapered wall <NUM> is dimensioned to interfere with a portion of the external sealing surface <NUM> of the stick member <NUM> when the cap <NUM> is pressed onto the tip <NUM> of the stick member <NUM>. The internal sealing surface <NUM> further defines a circumferential relief <NUM> that extends axially from an open end <NUM> of the cap <NUM> and that therefore defines a rearward end <NUM> of the internal sealing surface <NUM>.

The internal channel <NUM> has a length and a minimum diameter that are about equal to the length and the minimum diameter of the internal channel <NUM> of the cap <NUM>, described above. The internal sealing surface <NUM> has a length that is about equal to the length of the internal sealing surface <NUM> of the cap <NUM>. At a forward end <NUM>, the internal sealing surface <NUM> typically has a minimum diameter of about <NUM> to about <NUM> (e.g., about <NUM>). The relief <NUM>, defining the maximum diameter of the internal sealing surface <NUM> at the rearward end <NUM>, typically has a maximum diameter of about <NUM> to about <NUM> (e.g., about <NUM>). The relief <NUM> has a length that is about equal to the length of the relief <NUM> of the cap <NUM>. The cap <NUM> has a total length that is about equal to the total length of the cap <NUM>.

The cap <NUM> may be passed over and pressed onto the tip <NUM> of the stick member <NUM> (e.g., loaded with a specimen) at room temperature to provide an interface <NUM> that forms an interference fit between the internal sealing surface <NUM> and the external sealing surface <NUM>. When the cap <NUM> is passed fully over the tip <NUM>, the interference fit extends from a forward end <NUM> of the external sealing surface <NUM> to about a midway point <NUM> of the external sealing surface <NUM>. At the midway point <NUM>, the interference between the internal sealing surface <NUM> and the external sealing surface <NUM> diminishes to about zero. The interference fit causes the cap <NUM> to expand slightly in the region of the interference fit along the interface <NUM>, such that the cap <NUM> experiences localized frictional forces in the region without stretching of the entire cap <NUM>. Providing the interference fit at a sufficient distance (e.g., at least about <NUM> to at least about <NUM>) away from the open end <NUM> of the cap <NUM> can reduce or prevent stress-induced fractures that may otherwise result if such an interference was located closer to the open end of such a cap. The interference fit between the tapered wall <NUM> and the tip <NUM> provides both a hermetic seal that prevents contamination of the internal channel <NUM> and a securement feature that retains the cap <NUM> on the stick member <NUM>.

The hermeticity of the seal can be sufficient to prevent particulates and organisms of sizes as small as about <NUM> from penetrating the seal and from therefore entering the internal channel <NUM> of the cap <NUM> and contaminating a specimen contained therein. The hermetic seal formed along the interface <NUM> remains intact as long as the cap <NUM> remains pressed onto the tip <NUM> of the stick member <NUM>. Furthermore, the relief <NUM> functions substantially similarly to the relief <NUM> of the cap <NUM>, thereby reducing the generation or propagation of any resulting stress fractures in the cap <NUM> near the open end <NUM>.

In some embodiments, the cap <NUM> and the tip <NUM> of the stick member <NUM> may be made of the same material, thereby providing a fixed system for which, upon submersion in the low temperature substance, the interface <NUM> remains fixed such that the tapered wall <NUM> does not move substantially with respect to the external sealing surface <NUM> of the tip <NUM>. In such embodiments, sealing of the specimen carrier <NUM> is provided by the interference fit formed at the interface <NUM>.

In some embodiments, the cap <NUM> may be made of one or more materials that are different from the material from which the tip <NUM> of the stick member <NUM> is made, thereby providing a dynamic system. For embodiments in which the CTE (or an aggregate CTE) of the one or more materials from which the cap <NUM> is made is greater than the CTE of the material from which the tip <NUM> is made, the tapered wall <NUM> moves with respect to (e.g., shrinks against) the external sealing surface <NUM> of the tip <NUM> such that the interface <NUM> becomes dynamic upon submersion in the low temperature substance. In this manner, the sealing provided by the interference fit formed at the interface <NUM> may be tightened due to thermal affects (e.g., as described above with respect to the specimen carrier <NUM>) resulting from a difference in the CTE of the cap <NUM> and CTE of the tip <NUM>. In some embodiments, the CTE of the one or more materials from which the cap <NUM> is made is about [<NUM> x <NUM>-<NUM>]/°C to about [<NUM> x <NUM>-<NUM>]/°C (e.g., about [<NUM> x <NUM>-<NUM>]/°C), and the CTE of the material from which the tip <NUM> is made is about [<NUM> x <NUM>-<NUM>]/°C to about [<NUM> x <NUM>-<NUM>]/°C (e.g., about [<NUM> x <NUM>-<NUM>]/°C).

While the specimen carriers <NUM>, <NUM>, <NUM> have been described as including features that effect both sealing and securement of the caps <NUM>, <NUM>, <NUM> onto the stick member <NUM>, in some embodiments, a specimen carrier includes sealing features and securement features that are isolated from one another. For example, as shown in <FIG>, a specimen carrier <NUM> includes a tapered sealing structure and a retention ring that are spaced apart from each other. The specimen carrier <NUM> includes a stick member <NUM> and a cap <NUM>.

The stick member <NUM> is similar in construction and function to the stick member <NUM> of the specimen carrier <NUM>, described above, except that an external sealing surface <NUM> of a tip <NUM> of the stick member <NUM> defines a small circumferential step <NUM> and a circumferential snap ring <NUM> that are formed to engage the cap <NUM>. The tip <NUM> includes a tip extension <NUM> that is substantially similar in construction and function to the tip extension <NUM> of the stick member <NUM>, described above. The external sealing surface <NUM> is formed to interface with the cap <NUM> and has a generally frustoconical shape that has a small increase in diameter at the circumferential step <NUM> of the tip <NUM>. The snap ring <NUM> is located near a rearward end <NUM> of the external sealing surface <NUM>.

The external sealing surface <NUM> of the tip <NUM> typically has a length, a maximum diameter (excluding the diameter of the snap ring <NUM>), and a minimum diameter that are about equal to the length, the maximum diameter, and the minimum diameter of the external sealing surface <NUM> of the tip <NUM>, described above. The circumferential step <NUM> typically has a diameter of about <NUM> to about <NUM> (e.g., about <NUM>) and is located about <NUM> to about <NUM> (e.g., about <NUM>) from the rearward end <NUM> of the external sealing surface <NUM>. The snap ring <NUM> typically has a radius of curvature (i.e., with respect to a central, circular arc of the snap ring <NUM>) of about <NUM> to about <NUM> (e.g., about <NUM>), has a maximum circumferential diameter (i.e., with respect to a longitudinal axis of the external sealing surface <NUM>) of about <NUM> to about <NUM> (e.g., about <NUM>), and is located about <NUM> to about <NUM> (e.g., about <NUM>) from the rearward end <NUM> of the external sealing surface <NUM>. The tip <NUM> has a total length that is about equal to the total length of the tip <NUM>, described above.

The tip <NUM> may be manufactured via a casting process or via an injection molding process (e.g., via a single injection molding process in which both a shaft of the stick member <NUM> and the tip <NUM> are manufactured as an integral component or via a separate injection molding process, following which the tip <NUM> is subsequently joined to the shaft as a subcomponent of the stick member <NUM>). The tip <NUM> is made of one or more materials that can withstand the low temperature substance, including but not limited to polymers such as polystyrene, polypropylene, polyvinyl acetate, and polycarbonate. In some embodiments, the one or more materials are translucent or transparent. The tip <NUM> and the shaft may be made of the same material or made of different materials, depending on the process used to manufacture the tip <NUM> and the shaft of the stick member <NUM>.

The cap <NUM> of the specimen carrier <NUM> is substantially similar in exterior geometry to the cap <NUM> of the specimen carrier <NUM>, described above, and accordingly defines a rounded end that is substantially similar in construction and function to the rounded end <NUM> of the cap <NUM>. The cap <NUM> provides a tapered wall <NUM> that is formed to interfere with a portion of the external sealing surface <NUM>. The cap <NUM> forms a generally conical shaped internal channel <NUM> defined by an internal surface <NUM>. The internal surface <NUM> includes an internal sealing surface <NUM> that extends along the tapered wall <NUM>. Accordingly, the internal sealing surface <NUM> and the tapered wall <NUM> have a generally frustoconical shape. The internal sealing surface <NUM> defines a small circumferential relief <NUM>, and the tapered wall <NUM> is dimensioned to interfere with a portion of the external sealing surface <NUM> that extends between a forward end <NUM> of the external sealing surface <NUM> and the relief <NUM> along the internal sealing surface <NUM> when the cap <NUM> is passed fully over the tip <NUM>. The internal sealing surface <NUM> further defines a circumferential recess <NUM> that is positioned near an open end <NUM> of the cap <NUM> and is sized to accept the snap ring <NUM> of the tip <NUM> when the cap <NUM> is passed fully over the tip <NUM>. The internal sealing surface <NUM> also defines a circumferential relief <NUM> that extends from the open end <NUM> of the cap <NUM> to the recess <NUM>.

The internal channel <NUM> has a length and a minimum diameter that are about equal to the length and the minimum diameter of the internal channel <NUM> of the cap <NUM>, described above. The internal sealing surface <NUM> has a length that is about equal to the length of the internal sealing surface <NUM> of the cap <NUM>. At a forward end <NUM>, the internal sealing surface <NUM> typically has a minimum diameter of about <NUM> to about <NUM> (e.g., about <NUM>). The relief <NUM>, defining the maximum diameter of the internal sealing surface <NUM>, typically has a maximum diameter of about <NUM> to about <NUM> (e.g., about <NUM>). The relief <NUM> typically has a maximum diameter that is about equal to the maximum diameter of the circumferential step <NUM>, has a length of about <NUM> to about <NUM> (e.g., about <NUM>), and is located of about <NUM> to about <NUM> (e.g., about <NUM>) from the open end <NUM> of the cap <NUM>. The recess <NUM> has a radius of curvature that is about equal to the radius of curvature of the snap ring <NUM>, has a maximum circumferential diameter that is about equal to the maximum circumferential diameter of the snap ring <NUM>, and is typically located of about <NUM> to about <NUM> (e.g., about <NUM>) from the open end <NUM> of the cap <NUM>. The relief <NUM> typically has a length of about <NUM> to about <NUM> (e.g., about <NUM>). The cap <NUM> has a total length that is about equal to the total length of the cap <NUM>.

The cap <NUM> may be passed over and pressed onto the tip <NUM> of the stick member <NUM> (e.g., loaded with a specimen) at room temperature to provide an interface <NUM> that forms an interference fit between the internal sealing surface <NUM> and the external sealing surface <NUM>. When the cap <NUM> is passed fully over the tip <NUM>, the interference fit extends from the forward end <NUM> of the external sealing surface <NUM> to the relief <NUM>. In this configuration, a gap is formed between the internal sealing surface <NUM> and the external sealing surface <NUM> and extends from the relief <NUM> to the circumferential step <NUM>. The interference between the internal sealing surface <NUM> and the external sealing surface <NUM> is about zero from the circumferential step <NUM> to the snap ring <NUM>. The interference fit causes the cap <NUM> to expand slightly in the region of the interference fit along the interface <NUM>, such that the cap <NUM> experiences localized frictional forces in the region without stretching of the entire cap <NUM>. Providing the interference fit at a sufficient distance (e.g., at least about <NUM> to at least about <NUM>) away from the open end <NUM> of the cap <NUM> avoids stress-induced fractures that may otherwise result if such an interference was located closer to the open end of such a cap. The interference fit between the tapered wall <NUM> and the tip <NUM> provides a hermetic seal that prevents contamination of the internal channel <NUM> and provides a frictional interface (e.g., a securement feature) that retains the cap <NUM> on the stick member <NUM>, while the recess <NUM> and the snap ring <NUM> together provide additional securement of the cap <NUM> to the stick member <NUM>.

Furthermore, isolating the rearward snap ring <NUM> from the tapered wall <NUM> allows for hermetic sealing along the interface <NUM> without compromise of the seal integrity. Owing to manufacturing effects (e.g., parting lines in a mold) generated when forming the snap ring <NUM> on the tip <NUM>, the integrity of the seal formed along the interface <NUM> could be compromised if the snap ring <NUM> was located closer to the tapered wall <NUM>. Sufficiently separating the snap ring <NUM> from the tapered wall <NUM> allows the additional retention provided by the snap ring <NUM> without compromise of the hermetic seal formed along the interface <NUM>. Additionally, when the cap <NUM> is passed over the tip <NUM>, seating of the snap ring <NUM> within the recess <NUM> can provide a tactile feedback and/or an audible feedback to a user indicating that the cap <NUM> is properly secured to the stick member <NUM>.

The hermeticity of the seal can be sufficient to prevent particulates and organisms of sizes as small as about <NUM> from penetrating the seals and from therefore entering the internal channel <NUM> of the cap <NUM> and contaminating a specimen contained therein. The hermetic seal formed along the interface <NUM> remains intact as long as the cap <NUM> remains pressed onto the tip <NUM> of the stick member <NUM>. Furthermore, the relief <NUM> serves to reduce or prevent generation of excessive frictional forces that may otherwise result between the cap <NUM> (e.g., near the open end <NUM> of the cap <NUM>) and the tip <NUM>, thereby reducing the generation or propagation of any resulting stress fractures in the cap <NUM> near the open end <NUM>.

In some embodiments, the cap <NUM> and the tip <NUM> of the stick member <NUM> may be made of the same material, thereby providing a fixed system for which, upon submersion in the low temperature substance, the interface <NUM> remains fixed such that the tapered wall <NUM> does not move substantially with respect to the external sealing surface <NUM> of the tip <NUM>. In such embodiments, sealing of the specimen carrier <NUM> is provided by the interference fit formed at the interface <NUM>. In some embodiments, the cap <NUM> may be made of one or more materials that are different from the material from which the tip <NUM> is made, thereby providing a dynamic system. For such embodiments in which the CTE (or an aggregate CTE) of the one or more materials from which the cap <NUM> is made is greater than the CTE of the material from which the tip <NUM> is made, the tapered wall <NUM> moves with respect to (e.g., shrinks against) the external sealing surface <NUM> such that the interface <NUM> becomes dynamic upon submersion in the low temperature substance. In this manner, the sealing provided by the interference fit formed at the interface <NUM> may be tightened due to thermal affects (e.g., as described above with respect to the specimen carrier <NUM>) resulting from a difference in the CTE of the cap <NUM> and CTE of the tip <NUM>. In some embodiments, the CTE of the one or more materials from which the cap <NUM> is made is about [<NUM> x <NUM>-<NUM>]/°C to about [<NUM> x <NUM>-<NUM>]/°C (e.g., about [<NUM> x <NUM>-<NUM>]/°C), and the CTE of the material from which the tip <NUM> is made is about [<NUM> x <NUM>-<NUM>]/°C to about [<NUM> x <NUM>-<NUM>]/°C (e.g., about [<NUM> x <NUM>-<NUM>]/°C).

While the specimen carriers <NUM>, <NUM>, <NUM>, <NUM> have been described as including relief areas <NUM>, <NUM>, <NUM>, <NUM>, <NUM> on the caps <NUM>, <NUM>, <NUM>, <NUM>, in some embodiments, a specimen carrier may include a relief area on a tip of the stick member. For example, as shown in <FIG>, a specimen carrier <NUM> includes a tip with a relief area that provides a retention capability. The specimen carrier <NUM> includes a stick member <NUM> and a cap <NUM>.

The stick member <NUM> is similar in construction and function to the stick member <NUM> of the specimen carrier <NUM>, described above, except that an external sealing surface <NUM> of a tip <NUM> of the stick member <NUM> defines a circumferential relief <NUM> positioned rearward of a tapered portion <NUM> of the external sealing surface <NUM>. The tip <NUM> includes a tip extension <NUM> that is substantially similar in construction and function to the tip extension <NUM> of the stick member <NUM>, described above. The external sealing surface <NUM> is formed to interface with the cap <NUM> and has a generally frustoconical shape that has a small decrease in diameter along the relief <NUM>. The external sealing surface <NUM> of the tip <NUM> has a length and a minimum diameter that are about equal to the length and the minimum diameter of the external sealing surface <NUM> of the tip <NUM>. The external sealing surface <NUM> typically has a maximum diameter of about <NUM> to about <NUM> (e.g., about <NUM>) and extends about <NUM> to about <NUM> (e.g., about <NUM>) from a rearward end <NUM> of the external sealing surface <NUM>. The tip <NUM> has a total length that is about equal to the total length of the tip <NUM>, described above.

The cap <NUM> of the specimen carrier <NUM> is substantially similar in exterior geometry to the cap <NUM> of the specimen carrier <NUM>, described above, and accordingly defines a rounded end that is substantially similar in construction and function to the rounded end <NUM> of the cap <NUM>. The cap <NUM> provides a tapered wall <NUM> that is formed to interfere with a portion of the external sealing surface <NUM>. The cap <NUM> forms a generally conical shaped internal channel <NUM> defined by an internal surface <NUM>. The internal surface <NUM> includes an internal sealing surface <NUM> that extends along the tapered wall <NUM>. Accordingly, the internal sealing surface <NUM> and the tapered wall <NUM> have a generally frustoconical shape. The tapered wall <NUM> is dimensioned to interfere with a portion of the external sealing surface <NUM> that extends between a forward end <NUM> of the external sealing surface <NUM> and the relief <NUM> when the cap <NUM> is passed fully over the tip <NUM>. The internal sealing surface <NUM> also defines a circumferential relief <NUM> that extends from the open end <NUM> of the cap <NUM>.

The internal channel <NUM> has a length and a minimum diameter that are about equal to the length and the minimum diameter of the internal channel <NUM> of the cap <NUM>, described above. The internal sealing surface <NUM> has a length that is about equal to the length of the internal sealing surface <NUM> of the cap <NUM>. At a forward end <NUM>, the internal sealing surface <NUM> has a minimum diameter of about <NUM> to about <NUM> (e.g., about <NUM>). The relief <NUM>, defining the maximum diameter of the internal sealing surface <NUM> at the rearward end <NUM>, has a maximum diameter of about <NUM> to about <NUM> (e.g., about <NUM>). The relief <NUM> typically has a length of about <NUM> to about <NUM> (e.g., about <NUM>). The cap <NUM> has a total length that is about equal to the total length of the cap <NUM>.

The cap <NUM> may be passed over and pressed onto the tip <NUM> of the stick member <NUM> (e.g., loaded with a specimen) at room temperature to provide an interface <NUM> that forms an interference fit between the internal sealing surface <NUM> and the external sealing surface <NUM>, as shown in <FIG>. When the cap <NUM> is passed fully over the tip <NUM>, the interference fit extends from the forward end <NUM> of the external sealing surface <NUM> to the relief <NUM>. In this configuration, a gap is formed between the internal sealing surface <NUM> and the external sealing surface <NUM> and extends from the relief <NUM> to the open end <NUM> of the cap <NUM>. The interference fit causes the cap <NUM> to expand slightly in the region of the interference fit along the interface <NUM>, such that the cap <NUM> experiences localized frictional forces in the region without stretching of the entire cap <NUM>. Providing the interference fit at a sufficient distance (e.g., at least about <NUM> to at least about <NUM>) away from the open end <NUM> of the cap <NUM> can reduce or prevent stress-induced fractures that may otherwise result if such an interference was located closer to the open end of such a cap.

The interference fit between the tapered wall <NUM> and the tip <NUM> provides a hermetic seal that can reduce or prevent contamination of the internal channel <NUM> and a frictional interface (e.g., a securement feature) that secures the cap <NUM> to the stick member <NUM>, while a rear portion of the tapered wall <NUM> and the relief <NUM> together provide additional securement that retains the cap <NUM> on the stick member <NUM>. That is, when the specimen carrier <NUM> is immersed in the low temperature substance, the rear portion of the tapered wall <NUM> relaxes (e.g., collapses) into the gap formed by the relief <NUM> to retain the cap <NUM> on the stick member <NUM>, as shown in <FIG>.

The hermeticity of the seal can be sufficient to prevent particulates and organisms of sizes as small as about <NUM> from penetrating the seals and from therefore entering the internal channel <NUM> of the cap <NUM> and contaminating a specimen contained therein. The hermetic seal formed along the interface <NUM> remains intact as long as the cap <NUM> remains pressed onto the tip <NUM> of the stick member <NUM>. Furthermore, the relief <NUM> serves to avoid generation of excessive frictional forces that may otherwise result between the cap <NUM> (e.g., near the open end <NUM> of the cap <NUM>) and the tip <NUM>, thereby reducing or preventing the generation or propagation of any resulting stress fractures in the cap <NUM> near the open end <NUM>.

In some embodiments, the cap <NUM> and the tip <NUM> of the stick member <NUM> may be made of the same material, thereby providing a fixed system for which, upon submersion in the low temperature substance, the interface <NUM> remains fixed such that the a forward portion of the tapered wall <NUM> does not move substantially with respect to the tapered portion <NUM> of the external sealing surface <NUM>. In such embodiments, sealing of the specimen carrier <NUM> is provided by the interference fit formed at the interface <NUM>. In some embodiments, the cap <NUM> may be made of one or more materials that are different from the material from which the tip <NUM> is made, thereby becomes dynamic upon submersion in the low temperature substance. For such embodiments in which the CTE (or an aggregate CTE) of the one or more materials from which the cap <NUM> is made is greater than the CTE of the material from which the tip <NUM> is made, the forward portion of the tapered wall <NUM> moves with respect to (e.g., shrinks against) the tapered portion <NUM> of the external sealing surface <NUM> such that the interface <NUM> is provided as dynamic interface. In this manner, the sealing provided by the interference fit formed at the interface <NUM> may be tightened due to thermal affects (e.g., as described above with respect to the specimen carrier <NUM>) resulting from a difference in the CTE of the cap <NUM> and CTE of the tip <NUM>. In some embodiments, the CTE of the one or more materials from which the cap <NUM> is made is about [<NUM> x <NUM>-<NUM>]/°C to about [<NUM> x <NUM>-<NUM>]/°C (e.g., about [<NUM> x <NUM>-<NUM>]/°C), and the CTE of the material from which the tip <NUM> is made is about [<NUM> x <NUM>-<NUM>]/°C to about [<NUM> x <NUM>-<NUM>]/°C (e.g., about [<NUM> x <NUM>-<NUM>]/°C).

In some embodiments, a specimen carrier includes both a cap with sealing rings and a stick member with a relief area. For example, as shown in <FIG>, a specimen carrier <NUM> includes the cap <NUM> of the specimen carrier <NUM>, described above, and the stick member <NUM> of the specimen carrier <NUM>, described above.

The cap <NUM> may be passed over and pressed onto the tip <NUM> of the stick member <NUM> (e.g., loaded with a specimen) at room temperature to provide an interface <NUM> that forms an interference fit between the forward sealing ring <NUM> and the tapered portion <NUM> of the external sealing surface <NUM>, as shown in <FIG>. When the cap <NUM> is pressed onto the tip <NUM>, the interference fit at the sealing ring <NUM> causes the cap <NUM> to expand slightly in the region of the sealing ring <NUM> (e.g., the cap <NUM> is pushed radially outward by the tip <NUM> at the interface <NUM>). Accordingly, the cap <NUM> experiences localized frictional forces in the region of the sealing ring <NUM> without stretching of the entire cap <NUM>. Providing the sealing ring <NUM> (and therefore, the localized forces generated by the sealing ring <NUM>) at a sufficient distance (e.g., at least about <NUM> to at least about <NUM>) away from the open end <NUM> of the cap <NUM> can reduce or prevent stress-induced fractures that may otherwise result if such a ring was located closer to the open end of such a cap. The interference fit between the sealing ring <NUM> and the tip <NUM> provides both a hermetic seal that prevents contamination of the internal channel <NUM> and a frictional interface that retains the cap <NUM> on the stick member <NUM>.

Furthermore, when the cap <NUM> is passed over the tip <NUM> of the stick member <NUM>, the sealing ring <NUM> can provide a tactile feedback and/or an audible feedback to a user as the sealing ring <NUM> passes along the tapered portion <NUM> of the external sealing surface <NUM> into the relief <NUM>. The feedbacks indicate to the user that the cap <NUM> has moved at least a certain distance with respect to the stick member <NUM>. A rear portion of the wall <NUM> and the relief <NUM> together provide additional securement that retains the cap <NUM> on the stick member <NUM>. That is, when the specimen carrier <NUM> is immersed in the low temperature substance, the rear portion of the wall <NUM> relaxes (e.g., collapses) into the gap formed by the relief <NUM> to retain the cap <NUM> on the stick member <NUM>, as shown in <FIG>.

The hermeticity of the seal can be sufficient to prevent particulates and organisms of sizes as small as about <NUM> from penetrating the seals and from therefore entering the internal channel <NUM> of the cap <NUM> and contaminating a specimen contained therein. The hermetic seal formed along the interface <NUM> remains intact as long as the cap <NUM> remains pressed onto the tip <NUM> of the stick member <NUM>. Furthermore, the relief <NUM> serves to avoid generation of excessive frictional forces that may otherwise occur between the cap <NUM> (e.g., near the open end <NUM> of the cap <NUM>) and the tip <NUM>, thereby reducing or preventing the generation or propagation of any resulting stress fractures in the cap <NUM> near the open end <NUM>.

In some embodiments, the cap <NUM> and the tip <NUM> of the stick member <NUM> may be made of the same material, thereby providing a fixed system for which, upon submersion in the low temperature substance, the interface <NUM> remains fixed such that the a forward portion of the wall <NUM> does not move substantially with respect to the tapered portion <NUM> of the external sealing surface <NUM>. In such embodiments, sealing of the specimen carrier <NUM> is provided by the interference fit formed at the interface <NUM>.

In some embodiments, the cap <NUM> may be made of one or more materials that are different from the material from which the tip <NUM> is made, thereby becomes dynamic upon submersion in the low temperature substance. For such embodiments in which the CTE (or an aggregate CTE) of the one or more materials from which the cap <NUM> is made is greater than the CTE of the material from which the tip <NUM> is made, the forward portion of the wall <NUM> moves with respect to (e.g., shrinks against) the tapered portion <NUM> of the external sealing surface <NUM> such that the interface <NUM> becomes dynamic upon submersion in the low temperature substance. In this manner, the sealing provided by the interference fit formed at the interface <NUM> may be tightened due to thermal affects (e.g., as described above with respect to the specimen carrier <NUM>) resulting from a difference in the CTE of the cap <NUM> and CTE of the tip <NUM>. In some embodiments, the CTE of the one or more materials from which the cap <NUM> is made is about [<NUM> x <NUM>-<NUM>]/°C to about [<NUM> x <NUM>-<NUM>]/°C (e.g., about [<NUM> x <NUM>-<NUM>]/°C), and the CTE of the material from which the tip <NUM> is made is about [<NUM> x <NUM>-<NUM>]/°C to about [<NUM> x <NUM>-<NUM>]/°C (e.g., about [<NUM> x <NUM>-<NUM>]/°C).

In some embodiments, the caps <NUM>, <NUM>, <NUM>, <NUM>, <NUM> of the specimen carriers <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> may be manufactured via a casting process or via an injection molding process. The caps <NUM>, <NUM>, <NUM>, <NUM>, <NUM> may be made of one or more materials that can withstand the low temperature substance, including but not limited to polymers (e.g., polystyrene, polypropylene, polyvinyl acetate, polycarbonate, and polysulfone), composite materials, ceramics, and metals (e.g. steel or titanium).

In some embodiments, the walls <NUM>, <NUM>, <NUM>, <NUM>, <NUM> of the caps <NUM>, <NUM>, <NUM>, <NUM>, <NUM> may include two or more layers made of different, respective materials providing an aggregate CTE that is greater than a CTE of the material from which the respective tips <NUM>, <NUM>, <NUM> are made, as discussed above with respect to the specimen carrier <NUM>. In such embodiments, one or more outer layers of the caps <NUM>, <NUM>, <NUM>, <NUM>, <NUM> may enforce the behavior of one or more inner layers of the caps <NUM>, <NUM>, <NUM>, <NUM>, <NUM> relative to the respective tips <NUM>, <NUM>, <NUM>, thereby providing a tighter closure between the external sealing surfaces <NUM>, <NUM>, <NUM> of the tips <NUM>, <NUM>, <NUM> and an inner-most layer of the walls <NUM>, <NUM>, <NUM>, <NUM>, <NUM> of the caps <NUM>, <NUM>, <NUM>, <NUM>, <NUM>.

As discussed above with respect to the specimen carrier <NUM>, the specimen carriers <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> are sterile, single-use devices that are non-toxic to cellular and tissue specimens. The specimen carriers <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> may be individually packaged, and both the specimen carriers <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> and the packaging will remain sterile for a guaranteed shelf-life of the specimen carriers <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>. The specimen carriers <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> fit within standard storage containers and other standard equipment used in ART protocols and may be used in the manner described above with respect to the specimen carrier <NUM> to vitrify and store reproductive cells over a period of up to about <NUM> years.

While the specimen carriers <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> have been described as including the tips <NUM>, <NUM>, <NUM> of the stick members <NUM>, <NUM>, <NUM>, in other embodiments, a specimen carrier may include any one of the caps <NUM>, <NUM>, <NUM>, <NUM>, <NUM> in combination with a stick member that has any one of the tips <NUM>, <NUM>, <NUM>, <NUM>.

In some embodiments, a specimen carrier may include any one of the tips <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> and a cap that is similar in construction and function to any of the caps <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, except that the cap further includes a frangible interface that prevents multiple uses of the cap. Prior to and during securement of the cap to the stick member, the frangible interface may remain intact. However, upon removal of the secured cap, the frangible interface may tear or separate, indicating to a user that the single-use cap has been previously used.

Claim 1:
A specimen carrier (<NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>) configured to house and store specimens for cryopreservation, the specimen carrier comprising:
an elongate member (<NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>) defining an external sealing surface (<NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>) and a support surface (<NUM>, <NUM>, <NUM>, <NUM>) upon which a specimen can be carried, the elongate member made of a first material having a first coefficient of thermal expansion; and
a cap (<NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>) having a region configured to surround a specimen, wherein the cap is configured to be passed over a portion of the elongate member in an ambient environment of a first temperature to close the region of the cap that surrounds the specimen when the cap is passed over the portion of the elongate member, the cap defining an internal sealing surface (<NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>) formed complementary to the external sealing surface defined by the elongate member, the elongate member and the cap being configured such that, at the first temperature, an interface formed between the external and internal sealing surfaces comprises an interference fit, and the cap being made of a second material having a second coefficient of thermal expansion that is greater than the first coefficient of thermal expansion,
such that when the portion of the elongate member is covered with the cap and the portion of the elongate member and the cap are together placed in a cooling substance of a second temperature that is lower than the first temperature, the cap contracts to a greater extent per degree temperature change than does the elongate member causing the internal sealing surface of the cap to compress the external sealing surface of the elongate member and increase tightness of the interference fit at the interface (<NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>) between the external and internal sealing surfaces to form a hermetic seal along the interface.