Reagent cartridges may be used with, for example, sequencing platforms. The sequencing platforms may include syringe pumps that flow reagent from the reagent cartridges.
Shortcomings of the prior art can be overcome and advantages and benefits as described later in this disclosure can be achieved through the provision of reagent cartridges and related systems and methods. Various implementations of the apparatus and methods are described below, and the apparatus and methods, including and excluding the additional implementations enumerated below, in any combination (provided these combinations are not inconsistent), may overcome these shortcomings and achieve the advantages and benefits described herein.
In accordance with a first implementation, an apparatus includes a reagent cartridge receptacle, a pressure source, and a reagent cartridge interface having a reagent coupling and a pressure coupling fluidly coupled to the pressure source. The apparatus also includes a reagent cartridge having a first flexible container, a second flexible container, and a coupling. The first flexible container has an end and defines a first interior containing reagent. The second flexible container has an end and defines a second interior. The first flexible container is positioned within the second interior. The coupling has a first portion coupled to the end of the first flexible container and a second portion coupled to the end of the second flexible container. The coupling has a reagent port fluidly coupled to the first interior of the first flexible container and a pressure port fluidly coupled to the second interior of the second flexible container. The reagent coupling is to couple with the reagent port to enable reagent to flow out of the first flexible container to the reagent coupling of the reagent cartridge interface and the pressure coupling is to couple with the pressure port to enable the pressure source to change a pressure within the second flexible container to urge the reagent to flow out of the first flexible container.
In accordance with a second implementation, an apparatus includes a first flexible container, a second flexible container, and a coupling. The first flexible container has an end and defines a first interior containing reagent. The second flexible container has an end and defines a second interior. The first flexible container is positioned within the second interior. The coupling has a first portion coupled to the end of the first flexible container and a second portion coupled to the end of the second flexible container. The coupling has a reagent port fluidly coupled to the first interior of the first flexible container and a pressure port fluidly coupled to the second interior of the second flexible container.
In accordance with a third implementation, a method includes depositing reagent within a first flexible container having an end and defining a first interior and coupling a first portion of a coupling to the end of the first flexible container. The coupling has a reagent port fluidly coupled to the first interior of the first flexible container and a pressure port. The method also includes positioning the first flexible container within a second flexible container having an end and defining a second interior and coupling a second portion of the coupling to the end of the second flexible container. The pressure port fluidly coupled to the second interior of the second flexible container.
In accordance with a fourth implementation, a method includes coupling a reagent coupling of a reagent cartridge interface with a reagent port of a coupling of a reagent cartridge. The reagent cartridge has a first flexible container, a second flexible container, and the coupling. The first flexible container had an end and defines a first interior containing reagent. The second flexible container has an end and defines a second interior. The first flexible container is positioned within the second interior and the coupling is coupled to the end of the first flexible container and the end of the second flexible container. The method includes coupling a pressure coupling of the reagent cartridge interface with a pressure port of the coupling of the reagent cartridge, changing a pressure within the second flexible container, and urging the reagent to flow out of the first flexible container based on the change in the pressure.
In accordance with fifth implementation, an apparatus includes a system, comprising: a reservoir receptacle to receive a reservoir; a fluidic interface to be fluidly coupled to the reagent reservoir; and a pump fluidly coupled to the fluidic interface. The pump includes a housing including a pressure port and a flexible container disposed in the housing and including an inlet and an outlet. Each of the inlet and the outlet is externally accessible outside of the housing. The inlet is fluidly coupled to the fluidic interface. The system also includes a pressure source coupled with the pressure port and in fluid communication with the housing, and a flow cell receptacle to receive a flow cell and comprising a flow cell interface fluidly coupled to the outlet of the flexible container. Fluid is to flow from the reservoir to the inlet of the flexible container and the pressure source is to pressurize the housing and urge the fluid out of the outlet of the flexible container toward the flow cell receptacle.
In accordance with a sixth implementation, an apparatus includes a pump including a housing and a flexible container. The housing includes a pressure port and the flexible container is disposed in the housing and includes an inlet and an outlet. Each of the inlet and the outlet is externally accessible outside of the housing. Fluid is to flow from a reservoir to the inlet of the flexible container and the housing is to be pressurized to urge the fluid out of the outlet of the flexible container.
In accordance with a seventh implementation, an apparatus includes a pump including a housing defining a chamber; a flexible container having a first portion and a second portion and including an inlet and an outlet. The first portion and second portion are in fluid communication. Each of the inlet and the outlet is externally accessible outside of the housing. The pump includes a first actuator disposed in the housing and that is actuatable to act on the first portion of the flexible container; and a second actuator actuatable to act on the second portion of the flexible container. The flexible container, the first actuator, and the second actuator being disposed in the chamber. When the first actuator is actuated and the flexible container contains a first fluid and a second fluid, at least a portion of the first fluid and at least a portion of the second fluid is urged from the first portion of the flexible container to the second portion of the flexible container. When the second actuator is actuated and the flexible container contains a first fluid and a second fluid, at least a portion of the first fluid and at least a portion of the second fluid is urged from the second portion of the flexible container to the first portion of the flexible container.
In an eighth implementation, an apparatus includes a first flexible container including a pressure port and a second flexible container disposed in the first flexible container and including an aperture. The aperture is externally accessible outside of the pump. Fluid is to flow through the aperture to the second flexible container, and the first flexible container is to be pressurized to urge the fluid out through the aperture of the second flexible container.
In a ninth implementation, a method includes pumping fluid from a liquid reservoir to an inlet of a flexible container of a pump, the pump including: a housing; and the flexible container disposed in the housing and including the inlet and an outlet. The method also includes pressurizing the housing and urging the fluid out of the outlet of the flexible container toward a flow cell receptacle based the housing being pressurized.
In a tenth implementation, a method includes disposing a flexible container in a housing of a pump, the housing of the pump comprising an aperture and a pressure port and the flexible container disposed in the housing and including a coupling, an inlet, and an outlet. The method includes coupling the coupling of the flexible container to the aperture of the housing, and coupling a pressure source to the pressure port of the housing. The method includes filling the flexible container with a fluid, pressurizing the housing using the pressure source; and urging the fluid through the outlet of the flexible container, in response to the pressure source pressurizing the housing.
In an eleventh implementation, an apparatus includes a housing and a flexible container disposed in the housing and including an inlet and an outlet.
In further accordance with the foregoing first, second, third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, and eleventh implementations, an apparatus and/or method may further include or comprise any one or more of the following:
In an implementation, the pressure source provides positive pressure.
In accordance another implementation, the pressure source provides negative pressure.
In accordance another implementation, the apparatus includes a seal carried by the reagent port and a seal carried by the pressure port. The reagent coupling sealingly engages the seal carried by the reagent port and the pressure coupling sealingly engages the seal carried by the pressure port.
In accordance another implementation, the reagent includes liquid reagent.
In accordance another implementation, the apparatus includes a cover covering the pressure port and the reagent port.
In accordance another implementation, the cover has an impermeable barrier.
In accordance another implementation, the cover includes foil.
In accordance another implementation, the reagent coupling pierces the cover covering the reagent port and the pressure coupling pierces the cover covering the pressure port.
In accordance another implementation, the coupling further includes an extension coupled to the reagent port and extends into the first interior of the first flexible container.
In accordance another implementation, the extension includes a tube having a proximal end coupled to the first portion of the coupling and a distal end disposed within the first interior of the first flexible container.
In accordance another implementation, the tube is coupled with the coupling by an interference fit.
In accordance another implementation, the apparatus includes an insert positioned within the second interior of the second flexible container and between the second flexible container and the first flexible container.
In accordance another implementation, the reagent coupling is received within the reagent port and the pressure coupling is received within the pressure port.
In accordance another implementation, the reagent coupling has a reagent conduit having a distal end received within the reagent port and the pressure coupling has a pressure conduit having a distal end received within the pressure port.
In accordance another implementation, the first flexible container has a first pouch bag and the second flexible container has a second pouch bag.
In accordance another implementation, the first flexible container has a neck and the first portion of the coupling is coupled to the neck of the first flexible container and the second flexible container has a neck and the second portion of the coupling is coupled to the neck of the second flexible container.
In accordance another implementation, the first flexible container includes a first material and the second flexible container includes a second material.
In accordance another implementation, the first material is resistant to air permeability.
In accordance another implementation, the first flexible container is metalized.
In accordance another implementation, the coupling includes a pressure fluidic line and a reagent fluidic line. The pressure fluidic line extends between the pressure port and the first portion of the coupling and the reagent fluidic line extends between the reagent port and the second portion of the coupling.
In accordance another implementation, the pressure fluidic line extends through the first portion of the coupling to enable a pressure within the second flexible container to change and the reagent fluidic line extends through the first portion and the second portion of the coupling to enable the reagent to flow out of the first flexible container.
In accordance another implementation, the coupling includes a fitment.
In accordance another implementation, the coupling further includes spacers that are positioned between the first portion and the second portion.
In accordance another implementation, the first portion of the coupling has opposing first side walls that form a first canoe shape and the second portion of the coupling has opposing second side walls that form a second canoe shape.
In accordance another implementation, the first canoe shape is smaller than the second canoe shape.
In accordance another implementation, the first side walls define slots and the second side walls define slots.
In accordance another implementation, the coupling has a head having the pressure port and the reagent port and the coupling further includes a neck positioned between the head and the second portion of the coupling.
In accordance another implementation, the apparatus includes a plate defining a slot. The neck of the coupling is positioned within the slot.
In accordance another implementation, the method includes positioning a seal within the reagent port and positioning a seal within the pressure port.
In accordance another implementation, the method includes covering the reagent port and the pressure port with a cover.
In accordance another implementation, the method includes coupling an extension to the reagent port.
In accordance another implementation, the extension has a tube.
In accordance another implementation, the extension extends into the first interior of the first flexible container after the first portion of the coupling is coupled to the end of the first flexible container.
In accordance with another implementation, the pressure source positively pressurizes the housing.
In accordance with another implementation, the pressure source positively pressurizes the housing to about 5 pounds per square inch (psi) gauge.
In accordance with another implementation, the pump comprises a coupling comprising the inlet and the outlet and the housing comprises an aperture through which the coupling extends to enable the inlet and the outlet to be externally accessible outside of the housing.
In accordance with another implementation, the coupling comprises a fitment.
In accordance with another implementation, the pump comprises a seal disposed between the coupling and the housing.
In accordance with another implementation, the housing comprises a pressure chamber in which the flexible container is disposed and the seal hermetically seals the pressure chamber.
In accordance with another implementation, the coupling comprises an extension and the flexible container has an interior that the extension extends into.
In accordance with another implementation, the extension comprises a tube.
In accordance with another implementation, the reservoir receptacle is to receive a second reservoir and the fluidic interface to be fluidly coupled to the second reservoir.
In accordance with another implementation, the apparatus further comprises a valve to selectively control fluid flow from the reservoir to the inlet of the flexible container and from the second reservoir to the inlet of the flexible container.
In accordance with another implementation, the valve comprises a three-way valve.
In accordance with another implementation, the apparatus further comprises a pair of second pumps, each pump corresponding to the reservoir or the second reservoir.
In accordance with another implementation, the second pumps are configured to dispense the fluid into the flexible container to enable jet mixing.
In accordance with another implementation, the fluid is a first fluid and the apparatus further includes a second fluid that jet-mixes with the first fluid.
In accordance with another implementation, the apparatus also includes a second pump to flow fluid from the reservoir to the flexible container.
In accordance with another implementation, the second pump is positioned downstream from the pump.
In accordance with another implementation, the second pump is positioned upstream of the pump.
In accordance with another implementation, the housing comprises a lower portion and an upper portion and wherein the inlet and the outlet of the flexible container extend through the lower portion.
In accordance with another implementation, the pump includes a coupling and the flexible container includes an end, the coupling coupling the end of the flexible container to the upper portion of the housing.
In accordance with another implementation, the coupling includes a strap.
In accordance with another implementation, the pump includes a first coupling comprising the inlet and a second coupling includes the outlet.
In accordance with another implementation, the housing includes a first end and a second end, the first coupling coupled at the first end of the housing and the second coupling coupled at the second end of the housing.
In accordance with another implementation, the apparatus further includes a first valve and a second valve. The first valve to control fluid flow into the inlet of the flexible container and the second valve to control fluid flow out of the second container.
In accordance with another implementation, the inlet of the flexible container has a plurality of openings.
In accordance with another implementation, the openings have central axes that are positioned about 45 degrees relative to one another.
In accordance with another implementation, the inlet of the flexible container is a converging nozzle.
In accordance with another implementation, the housing includes a body having a base, a sidewall, and a lid. The base and sidewall define a chamber and the lid encloses the chamber when disposed on the sidewall.
In accordance with another implementation, the base and the sidewall are integrally formed.
In accordance with another implementation, the housing further includes a gasket and the sidewall has an end. The gasket is disposed between the sidewall and the lid at the end of the side.
In accordance with another implementation, the lid is removably secured to the sidewall.
In accordance with another implementation, the housing further includes a plurality of fasteners to removably secure the lid to the sidewall.
In accordance with another implementation, the fasteners are disposed about a perimeter of the lid and the sidewall.
In accordance with another implementation, the base further includes a plurality of posts having ends that extend from the base and are disposed in the chamber. The lid including corresponding apertures that receive the ends of the posts.
In accordance with another implementation, the posts secure corners of the flexible container in the aperture disposed partially through the lid.
In accordance with another implementation, each of the plurality of posts includes a cylindrical seat extending from the base and having a first diameter and a pole extending from the cylindrical seat and having a second diameter. The first diameter is greater than the second diameter.
In accordance with another implementation, the housing includes a first coupling having a first nozzle and a second coupling having a second nozzle.
In accordance with another implementation, the first coupling is positioned opposite the second coupling.
In accordance with another implementation, the first nozzle is received in the inlet of the flexible container.
In accordance with another implementation, an interference fit is formed between the first nozzle and the inlet and the second nozzle and the outlet.
In accordance with another implementation, the housing is a first housing defining a first chamber, a first flexible container disposed in the first chamber; and the apparatus further comprising a second housing defining a second chamber, a second flexible container disposed in the second chamber.
In accordance with another implementation, a conduit fluidly couples the first flexible container and the second flexible container.
In accordance with another implementation, the first actuator positively pressurizes the first housing and the second actuator positively pressurizes the second housing.
In accordance with another implementation, the first flexible container is compressed when the first housing is pressurized, and the second flexible container is compressed when the second housing is pressurized.
In accordance with another implementation, the second actuator is not actuated when the first actuator is actuated, and the first actuator is not actuated when the second actuator is actuated.
In accordance with another implementation, the first actuator comprises a first flexible container and the second actuator comprises a second flexible container.
In accordance with another implementation, the first flexible container is inflatable to actuate the first flexible container and the second flexible container is inflatable to actuate the second flexible container.
In accordance with another implementation, the first portion of the flexible container is compressed when the first flexible container is inflated and the second portion of the flexible container is compressed when the second flexible container is inflated.
In accordance with another implementation, the apparatus further comprises an airtight seam hermetically sealing the first flexible container.
In accordance with another implementation, the airtight seam also hermetically seals the second flexible container and further couples the second flexible container to the first flexible container.
In accordance with another implementation, air wells are disposed between the first flexible container and the second flexible container.
In accordance with another implementation, the second flexible container is made of an oxygen barrier material.
In accordance with another implementation, the oxygen barrier material comprises aluminum or an aluminum alloy.
In accordance with another implementation, pressurizing the housing includes pressurizing the housing to about 5 pounds per square inch (psi) gauge.
In accordance with another implementation, the method further includes actuating an inlet valve from a closed configuration to an open configuration when pumping the fluid from the liquid reservoir to the inlet.
In accordance with another implementation, the method further includes actuating an outlet valve from a closed configuration to an open configuration when urging the fluid out of the outlet of the flexible container.
In accordance with another implementation, pumping the fluid from the liquid reservoir also includes pumping a first fluid from a first liquid reservoir and also pumping a second fluid from a second liquid reservoir to the inlet of the flexible container of the pump.
In accordance with another implementation, further including actuating a three-way valve between a first position fluidly coupling the first liquid reservoir with the flexible container and a second position fluidly coupling the second liquid reservoir with the flexible container.
In accordance with another implementation, the method includes jet mixing the first fluid and the second fluid in the flexible container.
In accordance with another implementation, further including a second pump comprising: a second housing having a pressure port; and a second flexible container disposed in the second housing and including an inlet and an outlet. The method includes filling at least one of the first flexible container and the second flexible container with the first fluid and the second fluid.
In accordance with another implementation, coupling the coupling of the flexible container to the aperture of the housing further includes securing an end of the flexible container to a coupling of the housing, wherein the end is disposed opposite the coupling of the flexible container and the coupling of the housing is disposed opposite the aperture of the housing.
In accordance with another implementation, coupling the coupling of the flexible container to the aperture of the housing also includes disposing a seal between the coupling and the aperture.
In accordance with another implementation, the housing of the pump has a base, a sidewall, and a lid, and wherein disposing the flexible container in the housing of the pump further comprises removably securing the lid to the sidewall of the housing.
In accordance with another implementation, the base of the housing also has a post extending from the base into an aperture disposed in the lid. And, disposing the flexible container in the housing of the pump includes securing the flexible container in the housing by the post urging a portion of the flexible container into the aperture disposed in the lid.
In accordance with another implementation, the housing includes a nozzle, and coupling the coupling of the flexible container to the aperture of the housing includes forming an interference fit between the outlet of the flexible container and the nozzle.
It should be appreciated that all combinations of the foregoing concepts and additional concepts discussed in greater detail below (provided such concepts are not mutually inconsistent) are contemplated as being part of the subject matter disclosed herein and/or may be combined to achieve the particular benefits of a particular aspect. In particular, all combinations of claimed subject matter appearing at the end of this disclosure are contemplated as being part of the subject matter disclosed herein.
Although the following text discloses a detailed description of implementations of methods, apparatuses and/or articles of manufacture, it should be understood that the legal scope of the property right is defined by the words of the claims set forth at the end of this patent. Accordingly, the following detailed description is to be construed as examples only and does not describe every possible implementation, as describing every possible implementation would be impractical, if not impossible. Numerous alternative implementations could be implemented, using either current technology or technology developed after the filing date of this patent. It is envisioned that such alternative implementations would still fall within the scope of the claims.
The disclosed implementations relate to consumables and related systems that use a positive pressure source to urge fluid out of a flexible container. The flexible container may have a known volume and may refillable during one or more operations. The flexible container may alternatively be a consumable that is not refilled.
Dispensing the fluid out of a flexible container having a known volume may allow for the fluid to be accurately metered during the corresponding operations. An implementation of a system has a reservoir, a fluidic interface, and a pump. The pump is fluidly coupled to the reservoir through the fluidic interface. The pump includes a housing with a pressure port and a flexible container disposed in the housing. The flexible container of the pump includes an inlet and an outlet that are accessible outside of the housing. The flexible container receives fluid from the reservoir through the inlet, the housing is pressurized and expels the fluid from the flexible container through the outlet.
The flow cell 104 carries a sample of interest. The pressure source 106 may be used to pressurize the reagent cartridge 102 to flow the reagent 118 from the reagent cartridge 102 that interact with the sample. The pressure source 106 may be provided by the system 100 and/or may be carried by the reagent cartridge 102. Alternatively, the gas source 103 may be omitted.
A reversible terminator may be attached to the reagent 118 to allow a single nucleotide to be incorporated onto a growing DNA strand. One or more of the nucleotides has a unique fluorescent label that emits a color when excited in some implementations. The color (or absence thereof) is used to detect the corresponding nucleotide. The imaging system 114 excites one or more of the identifiable labels (e.g., a fluorescent label) and thereafter obtains image data for the identifiable labels. The labels may be excited by incident light and/or a laser and the image data may include one or more colors emitted by the respective labels in response to the excitation. The image data (e.g., detection data) may be analyzed by the system 100. The imaging system 114 may be a fluorescence spectrophotometer including an objective lens and/or a solid-state imaging device. The solid-state imaging device may include a charge coupled device (CCD) and/or a complementary metal oxide semiconductor (CMOS).
Another reaction component (e.g., a reagent) is flowed into the flow cell 104 after the image data is obtained that is thereafter received by the waste reservoir 109 and/or otherwise exhausted by the reagent cartridge 102. The reaction component may perform a flushing operation that chemically cleaves the fluorescent label and the reversible terminator from the sstDNA. The sstDNA is then ready for another cycle.
The reagent cartridge 102 has a first flexible container 124, a second flexible container 126, and a coupling 128. The first flexible container 124 may be referred to as a reagent reservoir and the second flexible container 126 may be referred to as a pressure chamber. The first flexible container 124 has an end 130 and defines an interior 132 that contains the reagent 118 and the second flexible container 126 also has an end 134 and defines an interior 136. The interior 132 may be referred to as a first interior and the interior 136 may be referred to as a second interior. The first flexible container 124 is positioned within the interior 136 of the second flexible container 126.
The coupling 128 has a first portion 138 coupled to the end 130 of the first flexible container 124 and a second portion 140 coupled to the end 134 of the second flexible container 126. The coupling 128 may be coupled to the first flexible container 124 and the second flexible container 126 using a heat sealing process. The coupling 128 also has a reagent port 142 fluidly coupled to the interior 132 of the first flexible container 124 and a pressure port 144 fluidly coupled to the interior 136 of the second flexible container 126. The reagent coupling 120 couples with the reagent port 142 in operation to enable the reagent 118 to flow out of the first flexible container 124 to the reagent coupling 120 of the reagent cartridge interface 108 and the pressure coupling 122 couples with the pressure port 144 to enable the pressure source 106 to change a pressure within the second flexible container 126 to urge the reagent 118 to flow out of the first flexible container 124. The pressure source 106 may provide positive pressure to the second flexible container 126 and/or the pressure source 106 may provide negative pressure to the second flexible container 126. The pressure source 106 changes a pressure within the second flexible container 126 and that pressure change compresses the first flexible container 124 and urges the reagent 118 out of the first flexible container 124 regardless of whether the pressure provided is a positive pressure or a negative pressure. The pressure within the second flexible container 126 may apply a relatively even force on the first flexible container 124. All, a majority, or most of the reagent 118 may be dispensed from the first flexible container 124 as a result and, thus, the reagent cartridges 102 disclosed have low amounts of dead volume.
A seal 146 is carried by the reagent port 142 and a seal 148 is carried by the pressure port 144. The seal 146 provides a fluid seal and the seal 148 provides a pressure seal. The reagent coupling 120 sealingly engages the seal 146 carried by the reagent port 142 and the pressure coupling 122 sealingly engages the seal 148 carried by the pressure port 144. The seals 146, 148 may be O-rings and/or may be include an elastomer.
The reagent cartridge 102 also includes a cover 150 that covers the reagent port 142 and the pressure port 144. The cover 150 may be an impermeable barrier 152 such as foil. The cover 150 retains the reagent 118 within the first flexible container 124 and/or prevents or inhibits ingress of moisture into the interior 132 of the first flexible container 124 and/or the interior 136 of the second flexible container 126. The cover 150 may be a pierceable or removable cover including thin metal foil, such as aluminum foil, or a thin plastic sheet(s), such as Saran™ wrap. The cover 150 may comprise or consist of other materials and/or other layering arrangements that substantially prevent moisture ingress. The cover 150 may be coupled to the insert reagent port 142 and the pressure port 144 by heat sealing, laser welding, ultrasonic welding, pressure-sensitive adhesive (PSA), or any other suitable method. The cover 150 may alternatively be omitted. A pierceable septum or resealing spring valve may be included in place of the cover 150, for example.
The system 100 may pierce the cover 150 or the cover 150 may be pierced by an individual prior to use. The reagent coupling 120 may pierce the cover 150 covering the reagent port 142 in implementations when the system 100 pierces the cover 150 and the pressure coupling 122 may pierce the cover 150 covering the pressure port 142. The reagent coupling 120 and/or the pressure coupling 122 may include a piercing member such as a conical protrusion that is used to pierce the cover 150 as and/or prior to the couplings being formed between the reagent coupling 120 and the reagent port 142 and between the pressure coupling 122 and the pressure port 144.
The coupling 128 includes an extension 154 in the implementation shown that is coupled to the reagent port 142 and extends into the interior 132 of the first flexible container 124. The extension 154 may be used to encourage more of the reagent 118 to flow out of the first flexible container 124 and, thus, for less dead volume to be left within the first flexible container 124 when emptied. The extension 154 may alternatively be omitted. The extension 154 may be a tube 155 having a proximal end 156 coupled to the first portion 138 of the coupling 128 and a distal end 158 disposed within the interior 132 of the first flexible container 124. The tube 155 may be referred to as a straw. The tube 155 may is coupled with the coupling 128 by an interference fit. The tube 155 may be coupled to the coupling 128 in other ways, however. Adhesive may be used to couple the tube 155 and the coupling 128, for example.
An insert 159 may be positioned within the interior 136 of the second flexible container 126 and positioned between the second flexible container 126 and the first flexible container 124. The insert 159 may be a structure and/or a mesh that allows the second flexible container 126 to slide and/or move relative to the first flexible container 124. Relative movement between the second flexible container 126 and the first flexible container 124 is helpful when the pressure source 106 applies negative pressure.
A regulator 160 can be positioned between the pressure source 106 and the reagent cartridge interface 108 and regulates a pressure provided to the reagent cartridge interface 108 and, thus, the second flexible container 126. The regulator 160 may alternatively not be included.
The reagent cartridge 102 is in fluid communication with the flow cell 104. A “flow cell” as used herein can include a device having a lid extending over a reaction structure to form a flow channel therebetween that is in communication with a plurality of reaction sites of the reaction structure, and can include a detection device that detects designated reactions that occur at or proximate to the reaction sites. The flow cell 104 is shown being received within a flow cell receptacle 162 of the system 100. The flow cell 104 may alternatively be carried by or otherwise integrated into the reagent cartridge 102.
While the above disclosure describes urging liquid and/or the reagent 118 into and out of the first flexible container 124 and/or through the flow cell 104 under positive pressure, liquid and/or the reagent 118 may alternatively be drawn through the flow cell 104 under negative pressure when, for example, the reagent cartridge(s) 102 is not pressurized. The system 100 may include a pump 164 positioned between the flow cell 104 and the waste reservoir 116 to do so. The waste reservoir 109 may be selectively receivable within a waste reservoir receptacle 165 of the system 100. The pump 164 may be implemented by a syringe pump, a peristaltic pump, a diaphragm pump, etc. While the pump 164 is shown being part of the system 100 and positioned between the flow cell 104 and the waste reservoir 1116 the pump 164 may be positioned upstream of the flow cell 104, may be part of the reagent cartridge 102, or omitted entirely, in other implementations.
Referring now to the drive assembly 110, in the implementation shown, the drive assembly 110 includes a pump drive assembly 166 that interfaces with the pump 164 to pump fluid through the reagent cartridge 102 and/or the flow cell 104.
The controller 112 includes a user interface 168, a communication interface 170, one or more processors 172, and a memory 174 storing instructions executable by the one or more processors 172 to perform various functions including the disclosed implementations. The user interface 168, the communication interface 170, and the memory 174 are electrically and/or communicatively coupled to the one or more processors 172.
In an implementation, the user interface 168 receives input from a user and provides information to the user associated with the operation of the system 100 and/or an analysis taking place. The user interface 168 may include a touch screen, a display, a key board, a speaker(s), a mouse, a track ball, and/or a voice recognition system. The touch screen and/or the display may display a graphical user interface (GUI).
In an implementation, the communication interface 170 enables communication between the system 100 and a remote system(s) (e.g., computers) via a network(s). The network(s) may include an intranet, a local-area network (LAN), a wide-area network (WAN), the intranet, etc. Some of the communications provided to the remote system may be associated with analysis results, imaging data, etc. generated or otherwise obtained by the system 100. Some of the communications provided to the system 100 may be associated with a fluidics analysis operation, patient records, and/or a protocol(s) to be executed by the system 100.
The one or more processors 172 and/or the system 100 may include one or more of a processor-based system(s) or a microprocessor-based system(s). In some implementations, the one or more processors 172 and/or the system 100 includes a reduced-instruction set computer(s) (RISC), an application specific integrated circuit(s) (ASICs), a field programmable gate array(s) (FPGAs), a field programmable logic device(s) (FPLD(s)), a logic circuit(s), and/or another logic-based device executing various functions including the ones described herein.
The memory 174 can include one or more of a hard disk drive, a flash memory, a read-only memory (ROM), erasable programmable read-only memory (EPROM), electrically erasable programmable read-only memory (EEPROM), a random-access memory (RAM), non-volatile RAM (NVRAM) memory, a compact disk (CD), a digital versatile disk (DVD), a cache, and/or any other storage device or storage disk in which information is stored for any duration (e.g., permanently, temporarily, for extended periods of time, for buffering, for caching).
The reagent coupling 120 is shown being received within the reagent port 142 and the pressure coupling 122 is shown being received within the pressure port 144. The reagent port 142 is formed of or comprises an annular wall 204 and the reagent port 142 is also formed of or comprises an annular wall 206. The reagent coupling 120 includes a reagent conduit 208 having a distal end 210 that is shown received within the reagent port 142 and the pressure coupling 122 similarly includes a pressure conduit 212 having a distal end 214 received within the pressure port 144.
The first flexible container 124 has a neck 310 and the first portion 138 of the coupling 128 is coupled to the neck 310 of the first flexible container 124. The second flexible container 126 also has a neck 312 and the second portion 140 of the coupling 128 is coupled to the neck 312 of the second flexible container 126. The first flexible container 124 and the second flexible container 126 are shown being symmetric about a central longitudinal axis 314.
The first flexible container 124 may include a first material in some implementations and the second flexible container 126 may include a second material. The first material may the same or different from the first material. The first material may be stiffer than the second material and may be resistant to air permeability. The first flexible container 124 may prevent or inhibit the gas used to pressurize the second flexible container 126 from passing through the first flexible container 124 and accessing the reagent 118 within the first flexible container 124. The first flexible container 124 may be metalized to deter the gas from passing into the interior 132 of the first flexible container 124, for example.
The coupling 128 has a pressure fluidic line 316 and a reagent fluidic line 318. The pressure fluidic line 316 is shown extending between the pressure port 144 and the second portion 140 of the coupling 128 and the reagent fluidic line 318 is shown extending between the reagent port 142 and the first portion 138 of the coupling 128. The pressure fluidic line 316 extends through the second portion 140 of the coupling 128 to enable the pressure source 106 of the system 100 of
The first portion 138 of the coupling 128 has opposing first side walls 326, 328 that form a first canoe shape 330 and the second portion 140 of the coupling 128 has opposing second side walls 332, 334 that form a second canoe shape 336. The first canoe shape 330 is smaller than the second canoe shape 336. The first canoe shape 330 has a smaller width and a smaller depth than the second canoe shape 336 shown. The first flexible container 124 and the second flexible container 126 can each form a coupling with the corresponding canoe shapes 330, 336 as a result of the sizing of the canoe shapes 330, 336, with the first flexible container 124 coupled to the first canoe shape 330 and the second flexible container 126 coupled to the second canoe shape 336. The first canoe shape 330 and the second canoe shape 336 may alternatively be similar or the same sizes. Manufacturing the coupling 128 may be simplified if the canoe shapes 330, 336 are similar or the same. The coupling 128 may be more easily coupled to the first flexible container 124 and the second flexible container 126 if the canoe shapes 330, 336 are similar or the same.
Each of the first portion 138 and the second portion 140 include ribs 338 that are separated by slots 340. The ribs 338 and the slots 340 may facilitate manufacturability of the coupling 128. The coupling 128 may be an injection molded part in some implementations.
The first portion 138 of the coupling 128 has a first width 344 and the second portion 140 of the coupling 128 has a second width 346 that is wider than the first width 344. The coupling 128 also a head 348 in the implementation shown having the pressure port 144 and the reagent port 142 and a neck 350 positioned between the head 348 and the second portion 140 of the coupling 128.
The process 700 of
The first portion 138 of the coupling 128 is coupled to the end 130 of the first flexible container 124 (Block 706). The coupling 128 has the reagent port 142 fluidly coupled to the interior 132 of the first flexible container 124 and a pressure port 144. The extension 154 extends into the interior 132 of the first flexible container 124 after the first portion 138 of the coupling 128 is coupled to the end 130 of the first flexible container 124.
The first flexible container 124 is positioned within the second flexible container 126 having the end 134 and defining the interior 136 (Block 708). The second portion 140 of the coupling 128 is coupled to the end 134 of the second flexible container 126 (Block 710). The pressure port 144 is fluidly coupled to the interior 136 of the second flexible container 126. A seal 146 is positioned within the reagent port 142 and a seal 148 is positioned within the pressure port 144 (Block 712). The reagent port 142 and the pressure port 144 are covered with the cover 150 (Block 714).
The process of
The pressure coupling 122 is coupled with the pressure port 144 of the coupling 128 of the reagent cartridge 102, 202, 300, 360, 450, 475, 500, 550 (Block 804). A pressure within the second flexible container 126 is changed (Block 806). The change in pressure may be an increase in pressure or a decrease in pressure. The reagent 118 is urged to flow out of the first flexible container 124 based on the change in the pressure (Block 808).
The pump 1306 is fluidly coupled to the fluidic interface 1304 and includes a housing 1316 having a pressure port 1315 and a flexible container 1318 disposed in the housing 1316 in the implementation shown. The flexible container 1318 may include and/or be formed by any number of panels that form a small pouch bag and/or a quad bag or other types of bags. The flexible container 1318 may be formed by two panels, three panels, four panels, five panels, for example. The pump 1306 is shown including one flexible container 1318 but may alternatively include more than one flexible container 1318.
The flexible container 1318 includes an inlet 1326 and an outlet 1328 in the implementation shown. The inlet 1326 may be referred to or associated with a coupling and the outlet 1328 may be referred to or associated with a coupling. The inlet 1326 and the outlet 1328 are each externally accessible outside of the housing 1316 to allow fluid 1314 to flow into the inlet 1326 of the flexible container 1318 and/or out of the outlet 1328 of the flexible container 1318. The inlet 1326 of the flexible container 1318 is fluidly coupled to the fluidic interface 1304. The fluid 1314 can accordingly flow from the reservoir 1312 to the inlet 1326 of the flexible container 1318.
The pressure source 106 is coupled with the pressure port 1315 and is in fluid communication with the housing 1316 in the implementation shown. The flow cell receptacle 162 receives a flow cell 104 and has a flow cell interface 1330 fluidly coupled to the outlet 1328 of the flexible container 1318.
The system 1300 further includes a flow cell receptacle 162 to receive a flow cell 104. The flow cell receptacle 162 and/or the system 100 may further include a flow cell interface 1330 fluidly coupled to the outlet 1328 of the flexible container 1318.
The fluid 1314 flows from the reservoir 1312 to the inlet 1326 of the flexible container 1318 in operation and the pressure source 106 pressurizes the housing 1316 and urges the fluid 1314 out of the outlet 1328 of the flexible container 1318 toward the flow cell receptacle 162. The pressure source 106 may positively pressurize the housing 1316 to urge the fluid out of the outlet 1328 of the flexible container 1318. The pressure source 106 may positively pressurize the housing 1316 to about 5 pounds per square inch gauge (psig). The pressure source 106 may pressurize the housing 1316 to less than 5 psig or greater than 5 psig, however. For example, the pressure source 106 may be configured to positively pressurize the housing 1316 to approximately more than 5 psig, 10 psig, 15 psig, etc. Alternatively, the pressure source 106 may reduce the pressure in the housing 1316. For example, the pressure source 106 may be configured to pull a vacuum in the housing 1316.
The flexible container 1318 has a coupling 1334 that includes the inlet 1326 and the outlet 1328 in the implementation shown. The inlet 1326 and the outlet 1328 may be separate as shown in
The pump 1306 includes a seal 1342 disposed between the coupling 1334 and the housing 1316 in the implementation shown. The seal 1342 may alternatively be omitted. The seal 1342 inhibits pressurized gas from exiting the housing 1316. The housing 1316 has a pressure chamber 1322 in which the flexible container 1318 is disposed and the seal 1342 hermetically seals the pressure chamber 1322. For example, the seal 1342 provides a hermetic seal between an outer surface of the coupling 1334 and a surface of the housing 1316 that defines the aperture 1336. The pressure port 1315 is in fluid communication with the chamber 1322 and is configured to pressurize the chamber 1322, as disclosed above.
The coupling 1334 in the implementation shown includes an extension 1344 and the flexible container 1318 has an interior 1346 that the extension 1344 extends into. The extension 1344 may be implemented by a tube 1348. The extension 1344 may be implemented in different ways or may be omitted (See,
The reservoir receptacle 1302 of the system 1300 of
The system 1300 is shown including a valve 1352 that selectively controls fluid flow from the reservoir 1312 to the inlet 1326 of the flexible container 1318 and from the second reservoir 1350 to the inlet 1326 of the flexible container 1318. The valve 1352 is shown being implemented by a three-way valve. The valve 1352 may be any type of valve used for controlling fluid flow, however. Additionally or alternatively, the system 1300 may include a Y-junction that may pass fluid from reservoir 1312 and the reservoir 1350 through the inlet 1326 during different times or a similar or the same time period.
The system 1300 includes a pair of second pumps 1356, 1357 in the implementation shown. The pump 1356 corresponds to the reservoir 1312 and is used to pump the fluid 1314 from the reservoir 1312 toward and into the flexible container 1318. The pump 1357 corresponds to the second reservoir 1350 and is used to pump the fluid 1317 from the second reservoir 1350 toward and into the flexible container 1318. The pumps 1356, 1357 are positioned upstream of the pump 1306. The pumps 1356, 1357 may be configured to dispense the fluid 1314, 1317 into the flexible container 1318 to enable jet mixing. For example, the second fluid 1317 may be jet-mixed with the first fluid 1314 within the flexible container 1318. In various examples, jet-mixing uses the kinetic energy of a pumped stream to blend the liquid contents in a container. As a result, the fluid 1314, 1317 may be passed into the flexible container 1318 at a high speed. In other examples, the system 1300 may include alternative apparatus to mix the fluid 1314 and the fluid 1317. For example, the system 1300 may include a magnetic stirrer and/or magnetic stir plate and a magnetic stirrer may be disposed in the flexible container 1318 of the pump 1306.
The system 1300 may alternatively include a single pump that is used to pump the fluid 1314 from the reservoirs 1312, 1350 toward the flexible container 1318. One of the pumps 1356, 1357 may be omitted in such an example, and the remaining pump 1356 or 1357 may be used to pump fluid 1314, 1317 from either or both of the reservoirs 1312, 1350. The system 1300 is shown including the pump 164 to flow fluid 1314 from the reservoir 1312, 1350 to the flexible container 1318. The pump 164 may be referred to as a second pump. The pump 164 is shown positioned upstream of the pump 1306. The pump 164 may alternatively be positioned downstream from the pump 1306.
In some examples, the pump 1306 is replaceable and is replaced after use or on a consistent basis. In other examples, the pump 1306 may be reusable. In such examples, sometimes the flexible container 1318 benefits from being washed or cleaned. For example, in some examples, the fluid 1314 or the fluid 1317 may partially crystallize in the flexible container 1318. In such examples, a washing fluid may be passed through the flexible container 1318 to flush the flexible container 1318.
The pump 1400 of
The pump 1306 of
The pump 1600 of
The pump 1800 receives the first fluid 1314 of the first reservoir 1312 from the pump 1356 in operation and receives the second fluid 1317 of the second reservoir 1350 from the second pump 1357. In some examples, the pump 1356 and the second pump 1357 are operated simultaneously, but the pump 1356 and the second pump 1357 may operate separately. As shown, the first fluid 1314 and the second fluid 1317 may pass through the valve 1352 before reaching the pump 1800.
The housing 2301 also includes a gasket 2324 and the sidewall 2314 has an end 2326. The gasket 2324 is disposed between the sidewall 2314 and the lid 2316 at the end 2326 of the sidewall 2314 when the lid 2316 is attached to the body 2302. In some examples, the lid 2316 may be hermetically sealed to the sidewall 2314 without the use of the gasket 2324. The lid 2316 may be removably secured to the sidewall 2314. The housing 2301 also is shown including a plurality of fasteners 2328 to removably secure the lid 2316 to the sidewall 2314. The fasteners 2328 are disposed about a perimeter 2330 of the lid 2316 and the sidewall 2314 but may be implemented in other positions.
The fasteners 2328 are shown being implemented by screws. The fasteners 2328 may be implemented by bolts, latches, hinges and/or other similar selective fasteners. In some examples, the lid 2316 can be hermetically sealed with the sidewall 2314 with as few as one or two fasteners 2328, but in other examples, there may be two or more fasteners 2328. Additionally, in some examples, the lid 2316 may be hingedly coupled to the sidewall 2314 and fasteners 2328 may be disposed on one side of the housing 2301, opposite the hinge. The fasteners 2328 may be screws and/or latches in such examples. The lid 2316 may additionally or alternatively be magnetically secured to the sidewall 2314. Alternatively, the lid may be integral with the sidewall 2314 or permanently secured to the sidewall 2314 (e.g., via adhesive, welding, etc.).
The base 2312 also includes posts 2340 having ends 2342 that extend from the base 2312 and are disposed in the chamber 2322. Each of the posts 2340 includes a cylindrical seat 2344 extending from the base 2312 and having a first diameter and a pole 2346 extending from the cylindrical seat 2344 and having a second diameter. The first diameter is greater than the second diameter. The lid 2316 may include corresponding apertures 2370 that receive the ends 2364 of the posts 2362. The interaction between the posts 2362 and the apertures 2370s can secure corners of the flexible container 1318 within the housing 2301 and/or deter the flexible container 1318 from moving when being filled with and/or dispensing the fluid 1314, 1317. The apertures 2370 may alternatively be omitted, however.
In some examples, the housing 2301 includes a first coupling 2372 including a first nozzle 2374 and a second coupling 2376 including a second nozzle 2378. In the example of
Additionally, the pump 2300 includes a pressure sensor port 2380. In various examples, the pressure sensor port 2380 permits a pressure sensor 2381 to measure a pressure within the chamber 2322. The system 1300 of
In other examples, the nozzle 2374 and the inlet 1326 are formed with different mechanical connection structures. For example, the nozzle 2374 and the inlet 1326 may be any other male-female coupling that can form a hermetic seal.
The flexible container 2704 includes a first portion 2712 and a second portion 2714. The first portion 2712 and the second portion 2714 are in fluid communication. A first fluid 2716 and a second fluid 2718 are shown disposed within the flexible container 2704. The flexible container 2704 may have more or fewer fluids, however.
The first actuator 2706 is actuated in operation to exert pressure on the first portion 2712 of the flexible container 2704 and the second actuator 2708 is actuated to exert pressure on the second portion 2714 of the flexible container 2704. As shown in
When the first actuator 2706 is actuated, at least a portion of the first fluid 2716 and at least a portion of the second fluid 2718 is urged from the first portion 2712 of the flexible container 2704 to the second portion 2714 of the flexible container 2704.
The first actuator 2706 may be actuated by inflating the first flexible container 2726 and the second actuator 2708 may be actuated by inflating the second flexible container 2728. The first portion 2712 of the flexible container 2704 is compressed when the first flexible container 2726 is inflated and the second portion 2714 of the flexible container 2704 is compressed when the second flexible container 2728 is inflated.
The flexible container 2916 is disposed in the first chamber 2914 and the first pressure source 2904 is fluidly coupled with the first chamber 2914. The flexible container 2926 is disposed in the second chamber 2924 and the second pressure source 2906 is fluidly coupled with the second chamber 2924. The pump 2900 also includes a conduit 2930 fluidly coupling the flexible container 2916 and the flexible container 2926.
The first pressure source 2904 positively pressurizes the first housing 2912 and the second pressure source 2906 positively pressurizes the second housing 2922. The flexible container 2916 is compressed when the first housing 2912 is pressurized, and the flexible container 2926 is compressed when the second housing 2922 is pressurized. During operation, alternating the actuation of the first pressure source 2904 and the second pressure source 2906 causes fluid to pass back and forth through the conduit 2930 from flexible container 2916 and the second container 2926 to mix the first fluid 2716 and the second fluid 2718.
The flexible container 2966 is disposed in the first chamber 2964 and the first pressure source 2954 is fluidly coupled with the first chamber 2964. The flexible container 2976 is disposed in the second chamber 2974 and the second pressure source 2956 is fluidly coupled with the second chamber 2974. The pump 2950 also includes a conduit 2980 fluidly coupling the flexible container 2966 and the flexible container 2976.
Based on the examples of
The first flexible containers 3002 each include a pressure port 3012. The pressure port 3012 may be coupled with the pressure source 3006 and in fluid communication with the first flexible container 3002 when the reagent reservoirs 3000 are installed in the system 1000, for example. The second flexible container 3004 is disposed in the first flexible container 3002 and includes an aperture 3014. The aperture 3014 may be referred to as a port, an inlet, and/or an outlet. The second flexible container 3004 may contain fluid. The aperture 3014 is externally accessible outside of the first flexible container 3002. Each of the flexible containers 3004 may contain fluid. Fluid may additionally or alternatively flow from a reservoir (e.g., reservoir 1312 or reservoir 1350 of
The corresponding reagent reservoirs 3000 includes an airtight seam 3022 hermetically sealing the first flexible container 3002. The airtight seam 3022 also hermetically seals the second flexible container 3004. In some examples, the airtight seam 3022 also couples the second flexible container 3004 to the first flexible container 3002.
The reagent reservoirs 3000 may be formed using a pair of first sheets 3122 and a second pair of sheets 3124 in the implementation shown. The first sheets 3122 are coupled at the couplings 3011 to form the first flexible containers 3002 and the second sheets 3124 are coupled at the couplings 3011 to form the second flexible containers 3004. The coupling 3011 may be formed by laser welding or hot plate welding and may be referred to as an airtight seal. Any number of sheets may be used to form the reagent reservoirs 3000, however.
The foregoing description is provided to enable a person skilled in the art to practice the various configurations described herein. While the subject technology has been particularly described with reference to the various figures and configurations, it should be understood that these are for illustration purposes only and should not be taken as limiting the scope of the subject technology.
As used herein, an element or step recited in the singular and proceeded with the word “a” or “an” should be understood as not excluding plural of said elements or steps, unless such exclusion is explicitly stated. Furthermore, references to “one implementation” are not intended to be interpreted as excluding the existence of additional implementations that also incorporate the recited features. Moreover, unless explicitly stated to the contrary, implementations “comprising,” “including,” or “having” an element or a plurality of elements having a particular property may include additional elements whether or not they have that property. Moreover, the terms “comprising,” including, “having,” or the like are interchangeably used herein.
The terms “substantially,” “approximately,” and “about” used throughout this Specification are used to describe and account for small fluctuations, such as due to variations in processing. For example, they can refer to less than or equal to ±5%, such as less than or equal to ±2%, such as less than or equal to ±1%, such as less than or equal to ±0.5%, such as less than or equal to ±0.2%, such as less than or equal to ±0.1%, such as less than or equal to ±0.05%.
The terms “connect,” “connected,” “contact” “coupled” and/or the like are broadly defined herein to encompass a variety of divergent arrangements and assembly techniques. These arrangements and techniques include, but are not limited to (1) the direct joining of one component and another component with no intervening components therebetween (i.e., the components are in direct physical contact); and (2) the joining of one component and another component with one or more components therebetween, provided that the one component being “connected to” or “contacting” or “coupled to” the other component is somehow in operative communication (e.g., electrically, fluidly, physically, optically, etc.) with the other component (notwithstanding the presence of one or more additional components therebetween). It is to be understood that some components that are in direct physical contact with one another may or may not be in electrical contact and/or fluid contact with one another. Moreover, two components that are electrically connected, electrically coupled, optically connected, optically coupled, fluidly connected or fluidly coupled may or may not be in direct physical contact, and one or more other components may be positioned therebetween.
There may be many other ways to implement the subject technology. Various functions and elements described herein may be partitioned differently from those shown without departing from the scope of the subject technology. Various modifications to these implementations may be readily apparent to those skilled in the art, and generic principles defined herein may be applied to other implementations. Thus, many changes and modifications may be made to the subject technology, by one having ordinary skill in the art, without departing from the scope of the subject technology. For instance, different numbers of a given module or unit may be employed, a different type or types of a given module or unit may be employed, a given module or unit may be added, or a given module or unit may be omitted.
Underlined and/or italicized headings and subheadings are used for convenience only, do not limit the subject technology, and are not referred to in connection with the interpretation of the description of the subject technology. All structural and functional equivalents to the elements of the various implementations described throughout this disclosure that are known or later come to be known to those of ordinary skill in the art are expressly incorporated herein by reference and intended to be encompassed by the subject technology. Moreover, nothing disclosed herein is intended to be dedicated to the public regardless of whether such disclosure is explicitly recited in the above description.
It should be appreciated that all combinations of the foregoing concepts and additional concepts discussed in greater detail below (provided such concepts are not mutually inconsistent) are contemplated as being part of the subject matter disclosed herein. In particular, all combinations of claimed subject matter appearing at the end of this disclosure are contemplated as being part of the subject matter disclosed herein.
This application claims the benefit of and priority to U.S. Provisional Patent Application No. 63/321,362, filed Mar. 18, 2022, the content of which is incorporated by reference herein in its entirety and for all purposes.
Filing Document | Filing Date | Country | Kind |
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PCT/US2023/015515 | 3/17/2023 | WO |
Number | Date | Country | |
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63321362 | Mar 2022 | US |