Patent Application
20230165241
The present disclosure generally relates to apparatus to maintain at least temporarily maintain biological samples (e.g., eggs, sperm, embryos) at cryogenic temperatures, and to facilitate identification of stored biological samples.
Long-term preservation of cells and tissues through cryopreservation has broad impacts in multiple fields including tissue engineering, fertility and reproductive medicine, regenerative medicine, stem cells, blood banking, animal strain preservation, clinical sample storage, transplantation medicine, and in vitro drug testing. This can include the process of vitrification in which a biological sample (e.g., an oocyte, an embryo, a biopsy) contained in or on a storage device (e.g., a cryopreservation straw, cryopreservation tube, stick or spatula) is rapidly cooled by placing the biological sample and the storage device in a substance, such as liquid nitrogen. This results in a glass-like solidification or glassy state of the biological sample (e.g., a glass structure at the molecular level), which maintains the absence of intracellular and extracellular ice (e.g., reducing cell damage and/or death) and, upon thawing, improves post-thaw cell viability. To ensure viability, the vitrified biological samples must then be continuously stored in a liquid nitrogen dewar or other container containing the liquid nitrogen, which is at a temperature of negative 196 degrees Celsius.
There are, however, a number of concerns in how these biological samples are being stored, identified, managed, inventoried, retrieved, etc.
For example, each harvested embryo is loaded on a rigid embryo straw, stick or spatula. On the case of tube, the tube may be closed (e.g., plugged) at one end and open at the other end. The cryopreservation storage devices containing or holding the embryos are cooled as quickly as possible by plunging the cryopreservation storage device with the biological material into liquid nitrogen at a temperature of approximately negative 196 degrees Celsius, for example to achieve vitrification. More particularly, multiple cryopreservation storage devices are placed in a goblet for placement in the liquid nitrogen storage tank. The goblet attaches to the liquid nitrogen storage tank such that the multiple cryopreservation storage devices are suspended in the liquid nitrogen. Labels that are manually written-on using a suitable marker pen or printed using a custom printer are attached to the straw and/or the goblet. Such labels can include identification information corresponding to the individual that the embryo was harvested from and other suitable information (e.g., a cryopreservation storage device number, a practitioner number, etc.).
The size of the cryopreservation storage devices and the storage conditions in liquid nitrogen generally require special labels, and even then can adversely affect the persistence of markings on the respective cryopreservation storage devices. For instance, it is not uncommon for labels bearing identification information corresponding to the individual that the embryo was harvested from to separate from the corresponding cryopreservation storage device. Even if the goblet includes the identification information, it should also be noted that cryopreservation storage devices are often separated from the corresponding goblet, thereby resulting in one or more cryopreservation storage devices floating within the liquid nitrogen storage tank.
With regard to storage and management of these biological samples, facilities employ personnel that are required to maintain the liquid nitrogen storage tanks (e.g., by refilling them with liquid nitrogen when needed) and manage the inventory of stored biological samples (e.g., by performing periodic accountings). There is, however, little recordkeeping with regard to the proper storage of these biological samples. For example, subsequent identification or otherwise handling of the vitrified biological sample can involve removal of the sample from temperature-controlled storage and exposure of the sample to ambient temperature, thus potentially risking the viability of the sample.
Accordingly, it is desirable to provide new apparatus for preserving and identifying biological samples (e.g., vitrified biological samples) at suitably cold temperatures.
A container includes a vial, cap, and wireless transponders to store and identify samples of biological material at cryogenic temperatures (e.g., vitrified biological samples), for instance held by cryopreservation storage devices (e.g., straws, tubes, sticks, spatulas). A carrier includes a box, thermal shunt, thermal insulation to store and identify arrays of containers that hold cryopreservation storage devices with samples of biological material at cryogenic temperatures. Various apparatus include wireless transponders positioned and oriented to enhance range, and allow interrogation while retained in a carrier. Various apparatus can maintain the biological material at or close to cryogenic temperatures for prolonged period of times after being removed from a cryogenic cooler, and can allow wireless inventorying while maintaining the biological samples at suitably cold temperatures.
A carrier to carry vials of biological materials and extend cryogenic conditions may be summarized as including: a container having a top, a bottom and at least one side wall, the bottom having an inner facing surface and an outer facing surface, the at least one side wall having an inner facing surface and an outer facing surface, the inner facing surface of the bottom and the inner facing surface of the at least one side wall delineating an interior compartment having an interior compartment profile, the container having an opening at the top thereof; a thermal shunt, the thermal shunt comprising a substrate comprising a metal and having a first major face and a second major face, the second major face opposed from the first major face across a thickness of the substrate, the substrate having an array of a plurality of throughholes that extend through the thickness of the substrate, each of the throughholes of the substrate shaped and sized to receive at least a portion of a respective vial therethrough, the substrate closely receivable in the interior compartment of the container; at least one thermal insulator closely receivable in the interior compartment of the container and that overlies the first major face and underlies the second major face of the substrate of thermal shunt, the at least one thermal insulator having an array of a plurality of throughholes that extend therethrough, each of the throughholes of the at least one thermal insulator the shaped and sized to receive at least a portion of a respective vial therethrough; and a spacer closely receivable in the interior compartment of the container, the spacer having an array of a plurality of throughholes that extend therethrough, each of the throughholes of the spacer the shaped and sized to receive at least a portion of a respective vial therethrough, and wherein, when the spacer, the thermal shunt, the at least one thermal insulator are stacked in the interior compartment of the container, each of the throughholes of the spacer is axially aligned with a respective one of the throughholes of the thermal shunt and is axially aligned with a respective at least one of the throughholes of the at least one thermal insulator.
The vials may each carry a respective wireless transponder, and a combination of the bottom of the container, the thermal shunt, the at least one thermal insulator and the spacer positions the vials longitudinally to space the wireless transponders relatively above or relatively below the thermal shunt by a defined distance, for example positioning the vials longitudinally to space the wireless transponders relatively above or relatively below the thermal shunt by a distance of at least 3 millimeters. A combination of any of a thickness of the bottom of the container, the thermal shunt, the at least one thermal insulator and the spacer may position the vials longitudinally to space a bottom of the vials within a defined distance of an exterior surface of the bottom, for example a distance of less than 20 mm or more preferably less than 15 mm of an exterior surface of the bottom.
The at least one thermal insulator may comprise a thermal insulator tray and a thermal insulator plate, the substrate of the thermal shunt sandwiched between the thermal insulator tray and the thermal insulator plate. The tray may have a base having a periphery and a peripheral wall that extends from and about the periphery of the base, the base having an array of a plurality of throughholes, and the thermal insulator plate may have an array of a plurality of throughholes, the throughholes of the thermal insulator tray axially aligned with respective throughholes of the thermal insulator plate and axially aligned with respective throughholes of the substrate of the thermal shunt. The thermal insulator plate may be closely receivable by the peripheral wall of the thermal insulator tray to enclose the thermal shunt on all sides thereof by a combination of the thermal insulator tray and the thermal insulator plate, preventing thermal convection therethrough. The thermal insulator may comprise or consist of an aerogel.
The thermal shunt may be a heat sink in the form of a block of non-ferrous metal. The substrate of the thermal shunt may be a heat sink, for example, in the form of a block of aluminum or other non-ferrous metal. The substrate of the thermal shunt is may be a heat sink in the form of a block of non-ferrous metal impregnated polymer.
A bottom of the container may include an array of a plurality of receptacles that extend upwardly from the inner facing surface, each of the receptacles having a dimension sized to receive a bottom portion of a respective vial therein, and when the spacer, the thermal shunt, the at least one thermal insulator are stacked in the interior compartment of the container, each of the throughholes of the spacer, the thermal shunt, and the at least one thermal insulator is axially aligned with a respective one of the receptacles. The throughholes of the spacer, the thermal shunt, and the at least one thermal insulator may be arranged in a 2 by 2 array. The throughholes of the spacer, the thermal shunt, and the at least one thermal insulator may be arranged in a 7 by 7 array.
A carrier may include a cover coupleable to the container to seal the opening in the top of the container while the spacer, the thermal shunt, the at least one thermal insulator are stacked in the interior compartment of the container. The at least one side wall of the container is a thermally insulated side wall. The carrier may further include a handle.
A carrier may include one or more of: a passive temperature sensor fixed to a portion of the carrier, the temperature sensor operable to provide a signal representative of a temperature in the interior compartment of the container; a passive wireless transponder fixed to a portion of the carrier, the wireless transponder operable to withstand temperatures of approximately negative 150° C. and to subsequently or concurrently wireless transmit a unique identifier; a machine-readable symbol fixed to a portion of the carrier and which encodes a unique identifier; and/or a human-readable symbol fixed to a portion of the carrier and which encodes information.
A container for cryogenic storage of biological materials may be summarized as including: a vial having a first end, a second end, and a side wall, the second end opposed from the first end across a length of the vial, the side wall extending between the first and the second ends to delimit an interior cavity of the vial from an exterior thereof, the vial having an opening at the first end thereof; a cap sized and shaped to removably close the opening at the first end of the vial; a first wireless transponder having a first antenna, the first antenna having a beam axis aligned with a main lobe of a radiation plot of the first antenna, the first wireless transponder fixed to the vial with the beam axis thereof extending parallel to the length of the vial, the first wireless transponder operable to withstand temperatures of approximately negative 150° C. and to wireless transmit a unique identifier; and a second wireless transponder having a second antenna, the second antenna having a beam axis aligned with a main lobe of a radiation plot of the second antenna, the second wireless transponder fixed to the vial with the beam axis thereof extending perpendicularly to the beam axis of the first antenna, the second wireless transponder operable to withstand temperatures of approximately negative 150° C. and to wireless transmit a unique identifier.
The first antenna may be fixed at least proximate the second end of the vial, for secured thereto via an epoxy or encapsulant or modeled therein.
The second end of the vial may be a flat surface, the flat surface perpendicular to the length of the vial, and the first antenna of the first wireless transponder may extend parallel with the flat surface of the bottom of the vial. The first wireless transponder may be a radio frequency identification button cell that has a pair of major surfaces opposed across a thickness of the radio frequency identification button cell from one another and which extend parallel with the flat surface of the bottom of the vial. The second wireless transponder may be a radio frequency identification tag, and the radio frequency identification tag may wrap at least partially around an outer perimeter of the side wall of the vial.
The container may be sized to store sample cryopreservation storage devices with the biological materials retained by the sample cryopreservation storage devices. The container may further include a fixed thermal mass located in the interior cavity of the vial, the fixed thermal mass having a larger thermal mass than a thermal mass associated with the sample cryopreservation storage devices and the biological materials. The fixed thermal mass may take the form of a piece of non-ferrous metal or a metal impregnated polymer. The fixed thermal mass may be located along the length of the vial spaced from both the first wireless transponder and the second wireless transponder by at least a minimum defined distance. For example, the fixed thermal mass may be located along the length of the vial spaced from both the first wireless transponder and the second wireless transponder by at least a minimum defined distance of 0.3 mm.
The container may further include at least one passive temperature sensor carried by the vial, the passive temperature sensor operable to withstand temperatures of approximately negative 150° C. and to subsequently or concurrently provide a signal representative of a temperature in the interior compartment of the container. The at least one passive temperature sensor may be integral to at least one of the first or the second wireless transponders, and the first and the second wireless transponders may each be passive radio frequency identification transponders that encode at least one unique identifier or MEMS based identification transponders.
The container may further include at least one machine-readable symbol carried by the vial, the at least one machine-readable symbol encoding a unique identifier. The at least one machine-readable symbol may be carried by one or both of the wireless transponders
The wireless transponders may be fixed to a portion of the vial via an epoxy or encapsulant, or may be integrated into the vial, for instance by molding.
A container for cryogenic storage of biological materials may be summarized as comprising: a vial having a first end, a second end, and a side wall, the second end opposed from the first end across a length of the vial, the side wall extending between the first and the second ends to delimit an interior cavity of the vial from an exterior thereof, the vial having an opening at the first end thereof; a cap sized and shaped to removably close the opening at the first end of the vial, at least one of the cap or the vial including one or more through-holes to allow ingress of liquid (e.g., liquid nitrogen) into and/or to vent gas (e.g., air) from the interior cavity of the vial to the exterior while the cap is secured to the vial.
The container may include a first wireless transponder having a first antenna, the first antenna having a beam axis aligned with a main lobe of a radiation plot of the first antenna, the first wireless transponder fixed to the vial with the beam axis thereof extending parallel to the length of the vial, the first wireless transponder operable to withstand temperatures of approximately negative 150° C. and to wireless transmit a unique identifier. The through-holes may allow liquid nitrogen to fill the interior cavity of the vial when the vial is placed in a cryogenic bath, advantageously preventing the vial from floating to a surface of the liquid nitrogen bath.
A container for cryogenic storage of biological materials may be summarized as comprising: a vial having a first end, a second end, and a side wall, the second end opposed from the first end across a length of the vial, the side wall extending between the first and the second ends to delimit an interior cavity of the vial from an exterior thereof, the vial having an opening at the first end thereof; a cap sized and shaped to removably close the opening at the first end of the vial, and an elongated specimen holder having a distal end to carry a specimen and a proximate end, the elongated specimen holder attached to the cap at the proximate end of the elongated specimen holder. The elongated specimen holder may be integral with the cap, for example the elongated specimen holder and cap formed as a unitary, single piece construction (e.g., molded as a single unit), or may be secured to the cap via a friction or interference fit, or an adhesive capable of withstanding cryogenic temperatures.
A container for cryogenic storage of biological materials may be summarized as comprising: a vial having a first end, a second end, and a side wall, the second end opposed from the first end across a length of the vial, the side wall extending between the first and the second ends to delimit an interior cavity of the vial from an exterior thereof, the vial having an opening at the first end thereof; a cap sized and shaped to removably close the opening at the first end of the vial, and a jacket, sleeve or frame secured to an exterior of the vial. A wireless transponder may be carried on or by the jacket or sleeve, or frame, for example at tip thereof that is distal with respect to the cap.
A container for cryogenic storage of biological materials may be summarized as comprising: a vial having a first end, a second end, and a side wall, the second end opposed from the first end across a length of the vial, the side wall extending between the first and the second ends to delimit an interior cavity of the vial from an exterior thereof, the vial having an opening at the first end thereof; a cap sized and shaped to removably close the opening at the first end of the vial, and a wireless transponder may be carried on or by the cap.
In the drawings, identical reference numbers identify similar elements or acts. The sizes and relative positions of elements in the drawings are not necessarily drawn to scale. For example, the shapes of various elements and angles are not drawn to scale, and some of these elements are arbitrarily enlarged and positioned to improve drawing legibility. Further, the particular shapes of the elements as drawn are not intended to convey any information regarding the actual shape of the particular elements, and have been solely selected for ease of recognition in the drawings.
In the following description, certain specific details are set forth in order to provide a thorough understanding of various disclosed embodiments. However, one skilled in the relevant art will recognize that embodiments may be practiced without one or more of these specific details, or with other methods, components, materials, etc. In other instances, well-known structures associated with computer systems, actuator systems, and/or communications networks have not been shown or described in detail to avoid unnecessarily obscuring descriptions of the embodiments. In other instances, well-known computer vision methods and techniques for generating perception data and volumetric representations of one or more objects and the like have not been described in detail to avoid unnecessarily obscuring descriptions of the embodiments.
Unless the context requires otherwise, throughout the specification and claims which follow, the word “comprise” and variations thereof, such as, “comprises” and “comprising” are to be construed in an open, inclusive sense, that is as “including, but not limited to.”
Reference throughout this specification to “one embodiment” or “an embodiment” means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, the appearances of the phrases “in one embodiment” or “in an embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.
As used in this specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the content clearly dictates otherwise. It should also be noted that the term “or” is generally employed in its sense including “and/or” unless the content clearly dictates otherwise.
The headings and Abstract of the Disclosure provided herein are for convenience only and do not interpret the scope or meaning of the embodiments.
The container 100 includes a vial 104, a cap 106, a number of wireless transponders 108a, 108b (two shown), and optionally a number of sensors 110 (one shown).
The vial 104 has a first end 112a, a second end 112b, and a side wall 114. The second end 112b is opposed from the first end 112a across a length L of the vial 104, and the side wall 114 extends between the first and the second ends 112a, 112b to delimit an interior cavity 116 of the vial 104 from an exterior 118 thereof. The vial 104 has an opening 120 at the first end 112a thereof, and the second end 112b may be closed or sealable. The vial 104 takes the form of a tube, which may have a circular profile or cross section, or alternatively may have other shapes (e.g., rectangular, hexagonal, octagonal). The opening 120 of the vial 104 may, for example, be circular, although the opening 120 may have other shapes . The second end 112b of the vial 104 may, for example, have a flat surface 122, the flat surface 122 perpendicular to the length L or longitudinal axis of the vial 104. The vial 104 may be formed of any materials suitable to being deposited into a cryogenic bath, for example various polycarbonate, aromatic polyimidies (e.g., PMMA, Kapton, Upilex), and is preferably transparent.
The cap 106 is sized and shaped to removably close the opening 120 at the first end 112a of the vial 104. As best illustrated in
Returning to
The wireless transponders 108 are able to withstand cold temperatures (e.g., negative 150° C.; negative 196° C.) and continue to operate. In particular, the wireless transponders 108 are preferable able to withstand multiple instances of temperature cycling between cold temperatures (e.g., negative 150° C.; negative 196° C.) and relatively warmer temperatures to which the containers may be exposed when removed from a cryogenic cooler or dewar. The wireless transponders 108 may advantageously take the form of passive wireless transponders, which rely on power from interrogation signals to provide responses, for example via backscattering. MEMS transponders may be particularly suitable for operation at cold temperatures.
Each of a first and a second wireless transponder 108a, 108b encodes a unique identifier. The wireless transponders 108 respond to wireless interrogation signals with response signals encoding the unique identifiers, for example via backscattering. In some implementations, both the first and the second wireless transponders 108a, 108b may encode a same unique identifier as one another, which uniquely identifies the container 100. Alternatively, a nontransitory processor-readable medium may store a relationship between pairs of unique identifiers corresponding to pairs of wireless transponders 108 carried or born by a same respective container 100.
In particular, a first wireless transponder 108a has a respective antenna 138a (e.g., first antenna) which is coupled to a respective transponder circuit 139 (e.g., radio, transmitter, backscatter circuit, illustrated in
The first wireless transponder 108a is fixed to a portion of the vial 104, for example via an epoxy. The epoxy may encapsulate the first wireless transponder 108a, or the combination of the vial 104 and epoxy may encapsulate the first wireless transponder 108a, to securely attach and provide environmental protection thereto. Alternatively, the first wireless transponder 108a may be molded or encapsulated in a portion of the vial 104 itself. The second wireless transponder 108b is fixed to a portion of the vial 104, for example via an epoxy. The epoxy may encapsulate the second wireless transponder 108b, or the combination of the vial 104 and epoxy may encapsulate the second wireless transponder 108b, to securely attach and provide environmental protection thereto. Alternatively, the second wireless transponder 108b may be molded or encapsulated in a portion of the vial 104 itself.
As noted, the container 100 may also include or bear one or more sensors 110 (only one shown). The sensor(s) 110 may take a variety of forms, such as, for example, wireless sensors which not only sense conditions but also include an antenna and transponder circuit (e.g., radio, transmitter, backscatter circuit) to wirelessly transmit measurements or other indications of sensed condition from the sensors 110. The sensor(s) 110 are able to withstand cold temperatures (e.g., negative 150° C.; negative 196° C.) and continue to operate. In particular, the sensor(s) 110 are preferable able to withstand multiple instances of temperature cycling between cold temperatures (e.g., negative 150° C.; negative 196° C.) and relatively warmer temperatures to which the containers 100 may be exposed when removed from a cryogenic cooler or dewar.
The one or more sensors 110 may include one or more temperature sensors, and preferably passive temperature sensors, operable to sense temperature in the vial 104, at the vial 104 and/or external to the vial 104. Temperature sensors may include any one or more of optical based temperature sensors (e.g., laser temperature sensors, infrared temperature sensors); or thermocouples, thermistors and/or resistance temperature detectors, or MEMS based temperature sensors in which a frequency of mechanical vibration or oscillation of a vibratory element varies with temperature.
The sensor(s) 110 may be fixed to a portion of the vial 104, for example via an epoxy. The epoxy may encapsulate the sensor(s) 110, or the combination of the vial 104 and epoxy may encapsulate the sensor(s) 110, to securely attach and provide environmental protection thereto. Alternatively, the sensor(s) 110 may be molded or encapsulated in a portion of the vial 104 itself.
In at least some implementations, the sensor(s) 110 may be integral to the wireless transponders 108a, 108b, employing the antenna 138a, 138b and transponder circuits 109 of the wireless transponder 108a, 108b for transmitting information outward from the container 100. Alternatively, one or more sensor(s) 110 may be separate and distinct from the wireless transponders 108a, 108b.
The container 100 may also optionally include or bear one or more machine-readable symbols 144a, 144b. The machine-readable symbols 144a, 144b may take a variety of forms, for example one-dimensional machine readable symbols commonly referred to as barcode symbols, or two-dimensional machine-readable symbols for instance Matrix code symbols. The machine-readable symbols 144a, 144b can be composed of machine-readable symbol characters selected from any of a large variety of symbologies, and readable via any type of machine-readable symbol reader. The machine readable symbols (e.g., ink, media) 144a, 144b are able to withstand cold temperatures (e.g., negative 150° C.; negative 196° C.) and continue to operate. In particular, the machine readable symbols 144a, 144b are preferable able to withstand multiple instances of temperature cycling between cold temperatures (e.g., negative 150° C.; negative 196° C.) and relatively warmer temperatures to which the containers may be exposed when removed from a cryogenic cooler or dewar and remain optically readable.
Each of the one machine-readable symbols 144a, 144b encodes a unique identifier. In some implementations, both a first and a second one machine-readable symbol 144a, 144b may encode a same unique identifier as one another, which uniquely identifies the container 100. Alternatively, a nontransitory processor-readable medium may store a relationship between pairs of unique identifiers corresponding to pairs of one machine-readable symbol 144a, 144b carried or born by a same respective container 100.
The machine-readable symbols 144a, 144b may be fixed to a portion of the vial 104, for example via an epoxy. The epoxy may encapsulate the machine-readable symbols 144a, 144b, or the combination of the vial 104 and epoxy may encapsulate the machine-readable symbols 144a, 144b, to securely attach and provide environmental protection thereto. Alternatively, the machine-readable symbols 144a, 144b may be molded or encapsulated in a portion of the vial 104 itself. The epoxy and/or vial should be sufficiently transparent at a set of wavelengths (e.g., visible wavelengths, infrared wavelengths, ultraviolet wavelengths) that the machine-readable symbols 144a, 144b can be optically scanned or read.
While not illustrated, the container 100 may also optionally include or bear one or more human-readable symbols, for example alphanumeric characters or words or serial numbers.
In at least some implementations, the machine-readable symbols 144a, 144b may be integral to the wireless transponders 108a, 108b, e.g., printed, embossed, inscribed or otherwise applied thereto.
The container 100 may optionally include a fixed thermal mass 146 and a thermal insulator 148 that at least partially surrounds the thermal mass 146 to prevent or inhibit thermal conduction. The thermal mass 146 may be located in the interior cavity 116 of the vial 104. The thermal mass 146 has a larger thermal mass than a thermal mass associated with the sample cryopreservation storage device(s) 102 and the biological materials 103 held by the sample cryopreservation storage device(s) 102. The thermal mass 146 may take the form of a piece of non-ferrous metal or a metal impregnated polymer where the metal is in the form of small pieces, particles or strands that are sufficiently small and discontinuous as to prevent or retard the formation of currents therethrough. The thermal insulator 148 may take a variety of forms, including but not limited to an aerogel (e.g., a microporous solid in which the dispersed phase is a gas, a gel in which the liquid component is replaced with a gas, for instance silica-based, alumina-based, chromia-based, tin oxide-based and carbon based aerogels).
The thermal mass 146 is located along the length L of the vial 104, preferably spaced from both the first wireless transponder 108a and the second wireless transponder 108b by at least a minimum defined distance (e.g., 3 mm) to prevent interference with wireless communications via the wireless transponders 108a, 108b.
As best illustrated in
The carrier box 202 includes an array of receivers 218 (only one called out in
The number and arrangement of the receivers 218 may be based on the dimensions of the interior of the carrier box 202, the dimensions of the containers 100 and a desired spacing therebetween. In the illustrated implementation, the receivers 218 are arranged in a 7 by 7 array to accommodate a total of 49 containers 100. The array of receivers 218 may be an integral portion of the carrier box 202, for example molded as part of a molding the carrier box 202. Alternatively, the array of receivers 218 may be a separate and distinct structure, for instance press or friction fit into the carrier box, or even snap fit into the carrier box via tabs and slots or other engagement or securing mechanism. The array of receivers 218 may, for example be made of a polycarbonate.
As best illustrated in
The thermal shunt 204 has an array of through-holes 222 (only one called out in
As best illustrated in
Both the thermal insulation tray 206a and thermal insulation plate 206b has a respective array of through-holes 232, 234 (only one called out for ach array), respectively, extending therethrough. The through-holes 232, 234 are shaped and sized to closely receive respective ones of the containers 100 (
As best illustrated in
The top spacer 208 has an array of tubes 238 (only one called out) each with a respective through-hole 240. The through-holes 240 are shaped and sized to closely receive respective ones of the containers 100 (
The top spacer 208 may be made of any of a variety of materials, preferably polymers. The top spacer 208 may include a set of spacers 242, which extend laterally outwardly from tube 240 on an exterior of the top spacer to supportingly engage the walls 210 of the carrier box 202.
The carrier box 302 may be similar or even identical to the carrier box 202 of
The carrier box 202 includes an array of receivers 218 (only one called out in
As best illustrated in
The smaller “patient” carrier 303 includes an array of receivers 318 (only one called out in
The smaller “patient” carrier 303 may include structures that are similar to those discussed above with reference to the bulk carrier 200, for example a thermal shunt 304 (
As illustrated in
The thermal shunt 304 has an array of through-holes 322 (only one called out in
As illustrated in
Both the thermal insulation tray 306a and thermal insulation plate 306b has a respective array of through-holes 332, 334 (only one called out for ach array), respectively, extending therethrough. The through-holes 332, 334 are shaped and sized to closely receive respective ones of the containers 100 (
As best illustrated in
The top spacer 308 has an array of tubes 338 (only one called out) each with a respective through-hole 340. The through-holes 340 are shaped and sized to closely receive respective ones of the containers 100 (
The top spacer 308 may be made of any of a variety of materials, preferably polymers. The top spacer 308 may include a set of spacers 342 (only two called out), which extend laterally outwardly from tubes 340 on an exterior of the top spacer 308 to supportingly engage the walls 310 of the “patient” carrier 303.
As best illustrated in
As best illustrated in
The interior insert 412s may include an interior bottom 418 and at least one interior wall 410 extending upwardly from a periphery of the interior bottom 418, the interior bottom 418 and interior wall 420 delimiting a second cavity 422, having an opening 424 at a top thereof. The interior insert 412a may further include a ledge or shelf 426 extending laterally from an upper edge of the interior wall 420. The interior insert 412a is inserted or received in the first cavity of the exterior shell 410, an outer perimeter of the ledge or shelf 426 in contact with an inner surface of the exterior wall 416 at a top thereof. A space is formed between the exterior wall 416 of the exterior shell 410 and the interior wall 420 of the interior insert 412a, and between the exterior bottom 414 of the exterior shell 410 and the interior bottom 418 of the interior insert 412a. The space may be filled with a ridged or semi-ridged insulation, for example an aerogel. Less preferably, the space may evacuated or entrap a vacuum. Less preferably, the space may be filled with a fluid, for instance an inert gas, or even less preferably air.
The specimen holder 1102 has a distal end to carry a specimen 1103, such as biological materials and/or samples (e.g., eggs, sperm, and zygotes), and a proximate end which is attached to, or integral with, the cap 1106. In implementations, the specimen holder 1102 and the cap 1106 may be a single, unitary structure, and the specimen holder 1102 may include a spatula 1143 having a flat surface 1145 at the distal end of the specimen holder 1102, with the specimen 1103 being frozen to the flat surface 1145.
The cap 1106 may have a top portion 1125 and a side wall 1126 extending from the top portion 1125, the side wall 1126 delimiting a portion of the cap 1106 which is smaller in extent relative to the top portion 1125 in a direction transverse to the longitudinal axis of the vial 1104 so that the side wall 1126 can be inserted into the interior of the vial 1104, the top portion 1125 acting as a stopper to limit the depth of insertion of the side wall 1126 into the vial 1104. The cap 1106 may have threads 1132a, for example on an outer surface of the side wall 1126 to mate with corresponding threads 1132b on an inner surface of the side wall 1114 of the vial 1104.
Implementations may advantageously include a number of ports 1205 and/or vents 1210 (see
Although the term “vent” has been used herein to describe through-holes (which are not necessarily round), which allow gas (e.g., air) to escape the vial 1104 and the term “port” has been used to describe through-holes which allow liquid nitrogen into the vial 1104, these terms are interchangeable in some cases. For example, the structure of the through-holes used for the vents 1210 and ports 1205 may be simple apertures and therefore may function primarily as vents 1210 or ports 1205 depending on their position relative to the top and bottom of the container 1100 and depending on operational conditions (e.g., depending on whether a container 1100 is being lowered into or raised out of a cryogenic bath). In some implementations, the ports 1205 and vents 1210 may include valves, flaps, screens, filters, or other structures, to restrict the flow of gas or liquid to a specific direction vis-à-vis the interior of the vial 1104 and this may result in structures which act as dedicated ports 1205 or vents 1210. In some cases, the outer jacket 1107 (discussed below) may include through-holes in correspondence with the through-holes in the vial 1104 to facilitate ingress and egress of liquid and/or air.
The cap 1106 may be formed of any of a variety of materials, for example polymers, for instance thermoplastics, such as polypropylene or polyethylene, and/or any other suitable material that withstand temperatures common in cryogenic applications without significant degradation. An outer surface of the top portion 1125 of the cap 1106 may include a plurality of facets 1136 to facilitate gripping when tightening or loosening the cap 1106. While the cap 1106 is generally illustrated as having a portion thereof securely received within the opening of the vial 1104, in some implementations, the cap 1106 may alternatively be sized to receive a portion of the vial 1104 within an opening in the cap 1106, as in the example of
The container includes an outer jacket 1107 covering at least a portion of an exterior surface of the vial (see
The inner surface of the jacket 1107 may be attached to the exterior surface of the vial, e.g., friction fitted, heat fitted, and/or via adhesive, in implementations in which the outer jacket 1107 is to remain associated with the particular vial throughout the lifecycle of the container 1100. In some implementations, the inner surface of the jacket 1107 may be removably attached to the exterior surface of the vial 1104 to allow removal and replacement of the outer jacket 1107, e.g., if the outer jacket 1107 is to be associated with more than one vial 1104 (or vice versa). In such a case, there may be an elastic compression fit and/or a friction fit between the vial 1104 and the outer jacket 1107. In implementations, the inner surface of the jacket 1107 and/or the exterior surface of the vial 1104 may include deformable protrusions (not shown) which compress elastically to form a compression fit between the vial 1104 and the outer jacket 1107. In implementations, the inner surface of the jacket 1107 and/or the exterior surface of the vial 1104 may include opposing threads or ridges to secure the vial 1104 within the outer jacket 1107 (or, in other words, to secure the outer jacket to the vial). In implementations, outer jackets 1107 may be manufactured separately from vials 1100 and, for example, retrofitted onto existing vials 1104.
The outer jacket 1107 may have openings 1151 (see
In implementations, an arrangement of arms 1152 may extend from the bottom opening of the jacket 1107 in a longitudinal direction of the outer jacket 1107 to support a platform 1150, e.g., a solid, disk-shaped platform, which is oriented in a plane which is transverse to the longitudinal axis of the outer jacket 1107 (see
The container 1100 may include one or more wireless transponders 1108a, 1108b, 1108c (collectively 1108). As discussed above in the context of
In implementations, at least a portion of the platform 1150 itself may, for example, take the form of a radio frequency identification (RFID) button cell (see, e.g.,
In implementations, the circuitry of the first antenna 1138a, and possibly the transponder circuit 1139a, may be at least partially covered by a non-conductive label 1144a (see
In implementations, the circuitry of the second antenna 1138b and transponder circuit 1139b may be at least partially covered by a label 1144 (e.g., a label formed of a non-conductive material) with machine-readable symbols and/or human-readable information formed thereon (e.g., of the sort discussed above with respect to
Epoxy may encapsulate the second wireless transponder 1108b, or the combination of the jacket 1107 and the epoxy may encapsulate the second wireless transponder 1108b, to securely attach and provide environmental protection thereto. Alternatively, the second wireless transponder 1108b may be at least partially molded or encapsulated in a portion of the outer jacket 1107 itself.
In implementations, machine-readable symbol(s) may be fixed to other portions of the vial 1104, cap 1106, and/or outer jacket 1107, e.g., via epoxy. In at least some implementations, the machine-readable symbols may be integral to the wireless transponders 1108, e.g., printed, embossed, inscribed or otherwise applied thereto.
As discussed above, the first antenna 1138a may be fixed on an outer surface of the platform 1150 at the bottom end of the jacket 1107, in which case the beam axis of the first antenna 1138a of the first wireless transponder 1108a extends in a direction orthogonal to a plane of the platform 1105, which is in a direction along the longitudinal axis of the outer jacket 1107. As noted above, by providing the first and second wireless transponders 1108a, 1108b as separate and distinct substrates, the shape and features of the outer jacket 1107 may advantageously be employed to ensure that the beam axes are orthogonal to one another. Such an arrangement and positioning may facilitate interrogating or reading from below the vials, for example when held in storage in a cryogenic-cooled container.
In implementations, the circuitry of the third antenna 1138c and the transponder circuit 1139c may be at least partially covered by a non-conductive label with a machine-readable symbol(s) formed thereon so as to be visible on the top of the container 1100. In implementations, a label (not shown) with a machine-readable symbol formed thereon may be applied to the outer surface (e.g., the top surface 1124) of the cap 1106 without a wireless transponder being present. The label may be at least partially covered at a later time by attachable wireless transponder circuitry, such as, for example, circuitry formed on a carrier having an adhesive backing or a carrier which is attachable using adhesive, e.g., epoxy. The epoxy may encapsulate the third wireless transponder 1108c, or the combination of the cap 1106 and the epoxy may encapsulate the third wireless transponder 1108c, to securely attach and provide environmental protection thereto. Alternatively, the third wireless transponder 1108c may be molded or encapsulated in a portion of the cap 1106 itself.
Physically attaching a wireless transponder to a portion of a cap may be particularly advantageous where the elongated specimen holder (e.g. spatula, stick, or straw) is fixed to the cap, either as a single unitary piece structure or via adhesive or a weld (e.g., high frequency or radio frequency welding, ultrasonic welding). In such implementations, a wireless transponder encoding unique identifying information (e.g., a unique identifier) may be undetachably or permanently physically coupled to the elongated specimen holder via the cap, and hence undetachably or permanently physically associated with a specimen, even where the elongated specimen holder and/or specimen are withdrawn from a vial.
The container 1100 may include or bear one or more sensors 1110 (see
The various structures described herein may have dimensions conforming with a standardized format (e.g., American National Standards Institute (ANSI) format, Society for Biomolecular Screening (SBS) format, Society for Laboratory Automation and Screening format (SLAS), etc.). For example, in some embodiments, arrays of receptacles or other described structures can have a footprint that matches an SBS-format rack to facilitate use in an automated storage facility.
The various structures described herein may be comprised of any of a large variety of materials, although materials that would interfere with radio or microwave frequency communications will typically be avoided, or such materials spaced sufficient far (e.g., 3 mm) from antennas of wireless transponders and/or the anticipate location of interrogators or readers used to communicate with such wireless transponders. Further, the various structures described herein not only establish positioning or spacing in a two-dimensional plane (e.g., horizontal or XY plane), but also establish positioning or spacing in a third dimension (e.g., vertical or Z axis). At least some of the structures described herein support the containers 100 to ensure that a given location of the container (e.g., bottom surface with button coin RFID transponder) is spaced within a given distance or range (e.g., 20 mm; 15 mm) of an exterior of a carrier 200, 300, 400 and/or a location (i.e., interrogation station or reader station, e.g., located proximate a cryogenic cooler) at which an antenna of an interrogator or reader will be when the carrier 200, 300, 400 is placed at a reading location.
The various structures described herein as employing an aerogel may in some implementations consist of an aerogel. In other implementations, such structures may comprise an aerogel along with one or more other components. For example, some structures may employ a plastic (e.g., polypropylene) that is doped with an aerogel, which may advantageously enhance a dimensional stability of the structure. For instance, an array or cassette may include an aluminum bucket with an array of apertures sized and shaped to hold a plurality of containers, a top spacer of a plastic doped with aerogel with an array of apertures sized and shaped to hold a plurality of containers, and an outer sleeve of a plastic doped with aerogel that at least partially surrounds the aluminum bucket and top spacer.
The various implementations and embodiments described above can be combined to provide further implementations and embodiments. All of the commonly assigned US patent application publications, US patent applications, foreign patents, and foreign patent applications referred to in this specification and/or listed in the Application Data Sheet, including but not limited U.S. patent application 62/900,281, filed Sep. 13, 2019; U.S. patent application 62/880,786, filed Jul. 31, 2019; U.S. patent application 62/879,160, filed Jul. 26, 2019; U.S. patent application 62/741,986, filed Oct. 5, 2018; U.S. patent application 62/741,998, filed Oct. 5, 2018; and U.S. patent application Ser. No. 16/593,062, filed Oct., 4, 2019, are each incorporated herein by reference, in their entirety. These and other changes can be made to the embodiments in light of the above-detailed description.
Various changes can be made to the embodiments in light of the above-detailed description. For example, thermal insulators may consist of an aerogel or may comprise an aerogel and another non-aerogel thermal insulator (e.g., plastic). In some implementations, a thermal insulator may comprise an aerogel housed by a protective shell (e.g., plastic shell) or housing. One or more thermally insulative structures may additionally or alternatively be employed, for example one or more thermal breaks (e.g., walls defining cavities that a vacuum or near-vacuum, or holding an inert gas, or even a non-inert gas).
In general, in the following claims, the terms used should not be construed to limit the claims to the specific implementations and embodiments disclosed in the specification and the claims, but should be construed to include all possible implementations and embodiments along with the full scope of equivalents to which such claims are entitled. Accordingly, the claims are not limited by the disclosure.
| Number | Date | Country | |
|---|---|---|---|
| 62741986 | Oct 2018 | US | |
| 62741998 | Oct 2018 | US | |
| 62879160 | Jul 2019 | US | |
| 62880786 | Jul 2019 | US | |
| 62900281 | Sep 2019 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 16840720 | Apr 2020 | US |
| Child | 18100977 | US | |
| Parent | 16593062 | Oct 2019 | US |
| Child | 16840720 | US |
