CN114752475A - Reagent container, operation method thereof and reagent processing system - Google Patents

Reagent container, operation method thereof and reagent processing system Download PDF

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Publication number
CN114752475A
CN114752475A CN202110023377.9A CN202110023377A CN114752475A CN 114752475 A CN114752475 A CN 114752475A CN 202110023377 A CN202110023377 A CN 202110023377A CN 114752475 A CN114752475 A CN 114752475A
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CN
China
Prior art keywords
plug
diameter section
inner diameter
section
outer diameter
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN202110023377.9A
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Chinese (zh)
Inventor
占伟
杨毅
吴德忠
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
XIAMEN ZEESAN BIOTECH CO Ltd
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XIAMEN ZEESAN BIOTECH CO Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by XIAMEN ZEESAN BIOTECH CO Ltd filed Critical XIAMEN ZEESAN BIOTECH CO Ltd
Priority to CN202110023377.9A priority Critical patent/CN114752475A/en
Priority to US18/260,547 priority patent/US20240050952A1/en
Priority to EP22736599.6A priority patent/EP4276168A1/en
Priority to PCT/CN2022/070755 priority patent/WO2022148438A1/en
Priority to KR1020237026967A priority patent/KR20230147607A/en
Priority to JP2023541688A priority patent/JP2024504086A/en
Publication of CN114752475A publication Critical patent/CN114752475A/en
Pending legal-status Critical Current

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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above

Abstract

The invention relates to a reagent container, an operation method thereof and a reagent processing system. A reagent container comprising: the pipe comprises a pipe body and an elastic pipe plug, wherein the pipe body comprises a pipe plug accommodating section, the pipe plug accommodating section comprises a first inner diameter section and a second inner diameter section along the depth direction of the pipe body, and the inner diameter of the second inner diameter section is smaller than that of the first inner diameter section; the elastic pipe plug is provided with a through channel along the direction extending into the pipe body; the elastic pipe plug can be in non-interference fit with the first inner diameter section or in a first interference fit, and the elastic pipe plug can be in a second interference fit with the second inner diameter section; when the elastic pipe plug can be matched with the first inner diameter section in a non-interference mode, the second interference magnitude is larger than zero, and when the elastic pipe plug can be matched with the first inner diameter section in the first interference magnitude, the second interference magnitude is larger than the first interference magnitude; wherein the through passage is configured to be compression sealed with radial contraction of the elastomeric plug when the elastomeric plug is mated with the second inner diameter section with the second interference.

Description

Reagent container, operation method thereof and reagent processing system
Technical Field
The present disclosure relates to the field of biological detection technologies, and in particular, to a reagent container, an operating method thereof, and a reagent processing system.
Background
Polymerase Chain Reaction (PCR) is a molecular biology technique that can be used to amplify specific DNA fragments. The method can be used for carrying out in-vitro efficient amplification on the selective fragment of the gene, thereby realizing the detection of the target gene.
In the operation of nucleic acid amplification, it is sometimes necessary to add or remove a part of the preparation to or from the container, and in this case, it is necessary to manually open the lid of the reagent container and manually close the lid after adding or removing the reagent.
Disclosure of Invention
The present disclosure provides a novel reagent container whose novel structure makes it particularly suitable for automated operation.
In some aspects, the present disclosure provides a reagent container comprising:
the pipe body comprises a pipe plug accommodating section, the pipe plug accommodating section comprises a first inner diameter section and a second inner diameter section along the depth direction of the pipe body, and the inner diameter of the second inner diameter section is smaller than that of the first inner diameter section;
the elastic pipe plug is provided with a through channel along the direction extending into the pipe body;
the elastic pipe plug can be in non-interference fit with the first inner diameter section or in a first interference fit, and the elastic pipe plug can be in a second interference fit with the second inner diameter section;
When the elastic pipe plug can be in non-interference fit with the first inner diameter section, the second interference magnitude is larger than zero, and when the elastic pipe plug can be in non-interference fit with the first inner diameter section with the first interference magnitude, the second interference magnitude is larger than the first interference magnitude;
wherein the through passage is configured to be compression sealed with radial contraction of the elastomeric plug when the elastomeric plug is mated with the second inner diameter section with the second interference.
In some embodiments, the first amount of interference and the second amount of interference are both greater than zero.
In some embodiments, the non-interference fit (interference greater than or equal to zero) is a transition fit (interference equal to zero/clearance equal to zero) or a clearance fit (clearance greater than zero).
In some embodiments, the through-passage is compression sealed, meaning that at least part or all of the through-passage is compression sealed.
In some embodiments, the through passage is open or naturally closed in a non-interference fit state. Natural closure refers to the closed state that the through channel assumes only under the elastic pressure of the elastic plug itself when the latter is not subjected to radial pressure. When the through channel is in a natural closed state, the through channel can be penetrated by a liquid suction device.
In some embodiments, the first inner diameter section has an inner diameter greater than or equal to at least one outer diameter of the elastomeric plug.
In some embodiments, the second inner diameter section has an inner diameter less than at least one outer diameter of the elastomeric plug.
In some embodiments, the elastomeric plug does not have an interference fit or fit with a first interference with a first inner diameter section at a first depth into the tubular body and fits with a second interference with a second inner diameter section at a second depth into the tubular body, the second depth being greater than the first depth.
In some embodiments, the first inner diameter section and the second inner diameter section are directly adjacent.
In some embodiments, a chamfered surface is provided between the first inner diameter section and the second inner diameter section.
In some embodiments, the first inner diameter section tapers in inner diameter adjacent the second inner diameter section.
In some embodiments, the second inner diameter section has a gradually increasing inner diameter adjacent the first inner diameter section.
In some embodiments, the inner diameter at the intersection of the first and second inner diameter sections transitions smoothly.
In some embodiments, the second inner diameter section is deeper in the tubular body than the first inner diameter section.
In some embodiments, the tube body and/or the elastic tube plug are provided with a limiting structure for preventing the elastic tube plug from ascending and/or descending in the depth direction relative to the tube body.
In some embodiments, the tube body and/or the elastic tube plug are provided with one or more of the following limiting structures:
-a first stop structure for preventing the elastic plug from coming out of the nozzle of the tube body;
-a second stop formation preventing the resilient plug from passing from the first inner diameter section into the second inner diameter section;
-a third stop formation preventing the depth of the resilient plug from exceeding the plug receiving section.
In some aspects, the present disclosure provides a reagent container comprising:
a tube body including a plug receiving section;
the elastic pipe plug comprises a third outer diameter section and a fourth outer diameter section according to the sequence of the elastic pipe plug extending into the pipe plug accommodating section, the outer diameter of the fourth outer diameter section is larger than that of the third outer diameter section, and a through channel is arranged in the direction of the elastic pipe plug extending into the pipe body;
the third outer diameter section can be in non-interference fit or fit with the pipe plug accommodating section in a first interference manner, and the fourth outer diameter section can be in fit with the pipe plug accommodating section in a second interference manner;
when the third outer diameter section is capable of non-interference fit with the plug receiving section, the second interference is greater than zero, and when the third outer diameter section is capable of interference fit with the plug receiving section, the second interference is greater than the first interference;
wherein the through passage is configured to be compression sealed with radial contraction of the fourth outer diameter section when the fourth outer diameter section is mated with the plug receiving section with the second interference.
In some embodiments, at least one inner diameter of the plug receiving section is greater than or equal to the outer diameter of the third outer diameter section.
In some embodiments, at least one inner diameter of the plug receiving section is less than an outer diameter of the fourth outer diameter section.
In some embodiments, the resilient plug is at a third depth into the tubular body, the third outer diameter section is in a non-interference fit or fit with a first interference with the plug receiving section, the resilient plug is at a fourth depth into the tubular body, the fourth outer diameter section is in a fit with a second interference with the plug receiving section, and the fourth depth is greater than the third depth.
In some embodiments, the resilient plug is at a first depth into the tubular body, and the third outer diameter section is non-interference fit or fits with a first interference fit with the plug receiving section; the second degree of depth of body is being stretched into to the elasticity stopcock, and fourth external diameter section holds the section with the cooperation of second magnitude of interference with the stopcock, and the second degree of depth is greater than first degree of depth.
In some embodiments, the average outer diameter of the third outer diameter section is less than the average outer diameter of the fourth outer diameter section.
In some embodiments, the third outer diameter section and the fourth outer diameter section are directly adjacent.
In some embodiments, a chamfered surface is provided between the third and fourth outer diameter sections.
In some embodiments, the third outer diameter section has a gradually increasing outer diameter adjacent the fourth outer diameter section.
In some embodiments, the fourth outer diameter section tapers in outer diameter adjacent the third outer diameter section.
In some embodiments, the tube body and/or the elastic tube plug are/is provided with a limiting structure for preventing the elastic tube plug from ascending and/or descending relative to the tube body along the depth direction.
In some embodiments, the spacing structure comprises one or more of:
-a first stop structure for preventing the elastic plug from coming out of the nozzle of the tube body;
-a third stop formation preventing the depth of the elastomeric plug from exceeding the plug receiving section;
-a fourth stop formation preventing the fourth outer diameter section of the elastomeric plug from entering the elastomeric plug receiving section.
In some embodiments, the reagent container is configured such that when the resilient plug is extended into the tubular body to a first depth, the resilient plug is in a non-interference fit or a fit with a first interference with the plug receiving section, the through passage is not compressed to form a sealed state or is compressed to form a first sealed state; when the elastic pipe plug extends into the pipe body to a second depth, the elastic pipe plug is matched with the pipe plug accommodating section by a second interference magnitude, and the penetrating channel is compressed to form a second sealing state; the second depth is larger than the first depth, and the sealing degree of the second sealing state of the through channel is larger than that of the first sealing state.
In some embodiments, the second sealed state is a hermetic seal.
In some embodiments, the through passage comprises a second passage section and a first passage section in the order in which the elastomeric plug extends into the tubular body.
In some embodiments, the cross-sectional area of the first channel section is greater than the cross-sectional area of the second channel section.
In some embodiments, the cross-sectional shape of the channels of the first channel section is a two-dimensional shape and the cross-sectional shape of the channels of the second channel section is a one-dimensional shape.
In some embodiments, the elastomeric plug further comprises a sealing element for sealing the through passage;
in some embodiments, the sealing element is removable.
In some embodiments, the sealing element is pierceable.
In some aspects, the present disclosure provides a method of operating a reagent container, comprising the steps of:
a) providing a reagent container according to any of the above, the reagent container having an elastomeric stopple that has been engaged with the first inner diameter section but has not yet been interference fitted with the second inner diameter section;
b) penetrating a through channel of the elastic pipe plug by using a liquid transfer gun, and injecting a reagent into the pipe body and/or extracting the reagent from the pipe body;
c) pushing the elastic pipe plug to move along the depth direction of the pipe body, so that the elastic pipe plug is in interference fit with the second inner diameter section;
Preferably, also comprises
d) Placing the reagent container in a preset environment, and enabling the reagent in the container to react, such as a reaction related to nucleic acid amplification or nucleic acid detection;
preferably, the method of manipulating the reagent vessel is a nucleic acid amplification method or a nucleic acid detection method.
In some aspects, the present disclosure provides a method of operating a reagent container, comprising the steps of:
a) providing a reagent container according to any of the above, the reagent container having an elastic stopcock with a third outer diameter section already engaged with the stopcock receiving section, but a fourth outer diameter section not yet interference-engaged with the elastic stopcock receiving section;
b) penetrating a through channel of the elastic pipe plug by using a liquid transfer gun, and injecting a reagent into the pipe body and/or extracting the reagent from the pipe body;
c) pushing the elastic pipe plug to a deeper part of the pipe body to enable the fourth outer diameter section to be in interference fit with the accommodating section of the elastic pipe plug;
preferably, also comprises
d) Placing the reagent container in a preset environment, and enabling the reagent in the container to react, such as a reaction related to nucleic acid amplification or nucleic acid detection;
preferably, the method of manipulating the reagent vessel is a nucleic acid amplification method or a nucleic acid detection method.
In some aspects, the present disclosure provides a reagent processing system comprising
-a reagent container according to any of the above;
-a pipetting gun configured for penetrating a through passage on the elastic plug, injecting reagents into the tube and/or extracting reagents from the tube; and
-a ram configured for urging the elastomeric plug to move in a direction of the depth of the tubular body;
preferably, the reagent processing system further comprises a robotic arm on which the pipetting gun and/or the indenter are mounted.
In some embodiments, the first inner diameter section, the second inner diameter section is a section of the pipe body that varies in inner diameter less than or equal to ± 3% along the depth of the pipe body, such as less than or equal to ± 2%, such as less than or equal to ± 1%.
In some embodiments, the third outer diameter section, the fourth outer diameter section is a section of the tubular body of the elastomeric plug that varies in outer diameter less than or equal to ± 3%, such as less than or equal to ± 2%, such as less than or equal to ± 1%, in the direction of extension into the tubular body.
In some embodiments, the first channel section and the second channel section are channels on the elastic plug, and the inner diameter of the channels in the direction of the elastic plug extending into the pipe body varies by less than or equal to ± 3%, such as less than or equal to ± 2%, such as less than or equal to ± 1%.
In some embodiments, the first inner diameter section is adjacent to the second inner diameter section.
In some embodiments, the third outer diameter section is adjacent to the third outer diameter section.
In some embodiments, the first channel segment is adjacent to the second channel segment.
In some embodiments, the first inner diameter section does not overlap the second inner diameter section.
In some embodiments, the third outer diameter section does not overlap the third outer diameter section.
In some embodiments, the first channel segment does not overlap with the second channel segment.
In some embodiments, the inner diameter refers to the average inner diameter.
In some embodiments, the outer diameter refers to the average outer diameter.
Description of the terms:
if the following terms are used in the present invention, they may have the following meanings:
various relative terms such as "front," "back," "top," and "bottom," "upper," "lower," "above," "below," and the like may be used to facilitate description of various embodiments. Relative terms are defined with respect to conventional orientations of the structure and do not necessarily indicate an actual orientation of the structure at the time of manufacture or use.
As used in the description and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.
The term "container" relates to a vessel adapted to receive, store, transport and/or release the contents such as a test sample (e.g., blood, urine, serum, plasma or liquefied biopsy sample, etc.), a test reagent (e.g., a reagent for immunochemical testing, clinical chemistry testing, coagulation testing, hematological testing, molecular biology testing, etc.), or a combination thereof.
The term "tube" may be a vessel having a cylindrical, conical, or rectangular parallelepiped shape. The tube may have a closed bottom and an open top. The closed bottom of the cylindrical vessel may be circular. Non-limiting examples of a single cylindrical or conical separation vessel are primary or secondary tubes as known in the art. Alternatively, two or more tubes may be arranged as a multi-tube assembly. A non-limiting example of such a multi-manifold assembly is a multi-well plate, which is well known in the art.
The term "inner diameter" refers to its diameter for a circular cross-section and its diameter for a non-circular cross-section as a circle of the same area.
The term "outer diameter" refers to its diameter for a circular cross-section and its diameter for a non-circular cross-section for a circle of the same area.
The term "through channel" may be a through hole or a slit. The cross-section of the through channel may be a two-dimensional shape, such as a circle, a polygon, or a one-dimensional shape (e.g., a slit), which may be a "-" shape, a "+" shape, a "z" shape, a "+" shape, or the like.
The term "elastic" may be a property that returns to its original size and shape after deformation. The elastic plug may be made of a material having an elastic modulus (Young's modulus) of 10 4~108Pa, e.g. 105~107Pa, e.g. 106~107Pa of a material. The material of the elastic pipe plug can be an elastomer polymer, such as rubber or silicon rubber.
The term "limiting mechanism" can be a bump, a stop block, a boss, a convex ring, a concave-convex embedding structure of the elastic pipe plug and the pipe body, and a clamping structure of the elastic pipe plug and the pipe body.
The depth of a particular location in the tube body is the distance from that location to the orifice. For example, "depth of the elastomeric plug" refers to the distance from the lowermost end of the elastomeric plug to the nozzle. For example, "the depth of the first inner diameter section" refers to the distance from the lower edge of the first inner diameter section to the nozzle.
Unless otherwise specified, the term "depth direction" refers to the direction from the nozzle to the bottom of the tube.
The term "interference" refers to: the elastic plug is larger than the pipe body which is in interference fit with the elastic plug in the radial direction by a size Delta D, and the largest Delta D is taken as a standard.
The term "pipette" refers to a sharp device capable of injecting/extracting reagents through a through channel.
The term "ram" refers to an element capable of applying pressure to an elastic plug.
The term "robotic arm" is a device capable of displacing a target object. The displacement may be in any direction in three-dimensional space, such as a horizontal direction or a vertical direction.
The term "nucleic acid amplification" generally refers to a technique that increases the copy number of nucleic acid molecules in a sample or specimen. Techniques that can be used for nucleic acid amplification are well known in the art. An example of nucleic acid amplification is the Polymerase Chain Reaction (PCR), in which a nucleic acid sample collected from a subject is contacted with a primer (which may be single-stranded or double-stranded, if the nucleic acid sample is double-stranded, the double strand is dissociated first and then annealed in contact with the primer) under conditions that allow the primer to hybridize to a nucleic acid template in the sample, the primer is extended under suitable conditions, and the steps of dissociating (denaturing), annealing and extending are then repeated to amplify the copy number of the nucleic acid. Other examples of in vitro amplification techniques include strand displacement amplification, transcriptionless isothermal amplification, repair strand reaction amplification, ligase chain reaction, gap-fill ligase chain reaction amplification, coupled ligase detection and PCR, and RNA transcriptionless amplification, among others.
The term "nucleic acid" generally refers to a polymeric form of nucleotides of any length (deoxyribonucleotides (dntps) or ribonucleotides (rNTP)) or analogs thereof. The nucleic acid can have any three-dimensional structure and can perform any known or unknown function. Non-limiting examples of nucleic acids for the invention to which this application relates include DNA, RNA, coding or non-coding regions of a gene or gene fragment, one or more loci determined by linkage analysis, exons, introns, messenger RNA (mrna), transfer RNA (trna), ribosomal RNA (rrna), short interfering RNA (sirna), short hairpin RNA (shrna), micro RNA (mirna), ribozymes, cDNA, recombinant nucleic acids, branched nucleic acids, plasmids, vectors, DNA of any isolated sequence, RNA of any isolated sequence, nucleic acid probes, and primers. Nucleic acids may comprise one or more modified nucleotides, such as methylated nucleotides and nucleotide analogs. The nucleotide sequence of a nucleic acid may be interrupted by non-nucleotide components. The nucleic acid may be further modified after polymerization (e.g., by coupling or binding to a reporter).
The term reagent refers to any substance in a gaseous, liquid or solid state. The reagent may be a liquid.
Advantageous effects
One or more technical schemes of the present disclosure have one or more of the following beneficial effects:
(1) the liquid-transferring gun penetrates through the through channel of the elastic pipe plug, so that the reagent can be added and taken out without taking the elastic pipe plug out of the pipe body;
(2) the elastic pipe plug is pushed to the deep part of the pipe body, so that the through passage can be compressed and sealed;
(3) the automatic operation is convenient;
(4) the structure is simple;
(5) the cost is low.
Drawings
FIG. 1 is a schematic view of a reagent vessel of one embodiment;
FIG. 2 is a schematic view of a reagent vessel of yet another embodiment;
FIG. 3 is a schematic view of a reagent vessel and an elastic tube stopper according to yet another embodiment;
FIG. 4 is a schematic view of a reagent vessel of yet another embodiment;
FIG. 5 is a schematic view of a reagent vessel of yet another embodiment;
FIG. 6 is a schematic view of a reagent processing system of an embodiment.
Detailed Description
Embodiments of the present invention will be described in detail below with reference to examples, but those skilled in the art will appreciate that the following examples are only illustrative of the present invention and should not be construed as limiting the scope of the present invention. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products commercially available.
Fig. 1 shows a schematic view of a reagent container, wherein (a) and (b) show the plug at different depths in the tube. As shown in fig. 1 (a) and (b), the reagent vessel includes a tubular body 10 and an elastic tube stopper 20; the pipe body 10 comprises a pipe plug accommodating section 16, the pipe plug accommodating section 16 comprises a first inner diameter section 11 and a second inner diameter section 12 along the depth direction of the pipe body 10, and the inner diameter of the second inner diameter section 12 is smaller than that of the first inner diameter section 11; the elastic pipe plug 20 is provided with a through channel 21 along the direction extending into the pipe body 10; the elastic pipe plug 20 can be in non-interference fit with the first inner diameter section 11, the elastic pipe plug 20 can be in interference fit with the second inner diameter section 12 by a second interference magnitude, and the second interference magnitude is larger than zero; wherein, when elastomeric plug 20 is mated with second inner diameter section 12 with a second interference, elastomeric plug 20 is radially compressed and through passage 21 is pressure sealed.
As shown in fig. 1 (a), the depth of the elastic plug 20 extending into the tubular body 10 is a first depth. The elastomeric plug 20 is located in the first inner diameter section 11 and has not yet entered the second inner diameter section 12. The outer diameter of the elastic pipe plug 20 is smaller than the inner diameter of the first inner diameter section 11, and the relationship between the elastic pipe plug 20 and the first inner diameter section 11 is a non-interference fit (clearance fit). The elastomeric plug 20 is not radially compressed and the through passage 21 is not compressively sealed. The through channel 21 is open (in some embodiments the through channel 21 is naturally closed). When the reagent container is in this state, the pipette gun is used to penetrate through the through passage 21 of the elastic plug 20, and it is possible to inject a reagent into the tube 10 and/or extract a reagent from the tube 10.
As shown in fig. 1 (b), the depth of the elastic plug 20 extending into the tubular body 10 is a second depth, and the second depth is greater than the first depth. A portion of the elastomeric plug extends into the second inner diameter section 12. The outer diameter of the elastic pipe plug 20 is larger than the inner diameter of the second inner diameter section 12, and the elastic pipe plug 20 is in interference fit with the second inner diameter section 12. When the reagent vessel is in this state, the elastic plug 20 is radially compressed and the through passage 21 is pressure-sealed. The reagent vessel is well sealed.
In some embodiments, there is provided a method of operating the reagent container described above, comprising the steps of:
a) providing the reagent container, wherein the elastic plug 20 of the reagent container is matched with the first inner diameter section 11 but not matched with the second inner diameter section 12 in an interference fit manner;
b) using a pipette to penetrate through the through channel 21 of the elastic plug 20, injecting reagents into the tube 10 and/or extracting reagents from the tube 10;
c) pushing the elastic pipe plug 20 to move along the depth direction of the pipe body 10 (towards the deep part of the pipe body), so that the elastic pipe plug 20 is in interference fit with the second inner diameter section 12;
preferably, also comprises
d) The reagent container is placed in a preset environment, and the reagent in the container is subjected to reaction, such as reaction related to nucleic acid amplification or nucleic acid detection.
In some embodiments, the method of manipulating a reagent container is a nucleic acid amplification method or a nucleic acid detection method.
In some embodiments, as shown in fig. 1, the elastomeric plug 20 comprises a cylindrical plug body having a constant outer diameter in the direction of insertion into the tubular body.
In some embodiments, the first inner diameter section 11 and the second inner diameter section 12 are directly adjacent. In some embodiments, a chamfered surface is provided between the first inner diameter section 11 and the second inner diameter section 12. In some embodiments, the first inner diameter section 11 tapers in inner diameter adjacent the second inner diameter section 12. In some embodiments, the second inner diameter section 12 gradually increases in inner diameter adjacent to the first inner diameter section 11. In some embodiments, the inner diameter at the intersection of first inner diameter section 11 and second inner diameter section 12 is smoothly transitioned. In the above aspect, the elastic plug 20 can be switched between the first inner diameter section 11 and the second inner diameter section 12 more smoothly.
In one embodiment, the second inner diameter section 12 is deeper in the tubular body 10 than the first inner diameter section 11. The second inner diameter section 12 and the first inner diameter section 11 may be adjacent, but do not overlap.
Fig. 2 shows a reagent container having a stopper structure, and as shown in fig. 2, the reagent container is provided with stopper structures (13,14,15) for preventing the elastic plug 20 from being raised and/or lowered in the depth direction with respect to the tubular body 10.
In one embodiment, as shown in fig. 2, the tube 10 is provided with a first limiting structure 13 (e.g. a limiting block or a limiting ring) for preventing the elastic plug 20 from coming out of the tube opening. During use of the reagent vessel, it is sometimes necessary to use a pipette to penetrate through the through passage 21 of the elastomeric plug 20 in order to inject reagents into the tube 10 and/or extract reagents from the tube. When the pipette is pulled out from the through channel 21, the elastic pipe plug 20 can be taken out from the pipe body 10, and the first limiting structure 13 can effectively prevent the elastic pipe plug 20 from being taken out from the pipe body 10.
In one embodiment, as shown in fig. 2, the tube 10 is provided with a second limiting structure 14 (e.g., a limiting block or a limiting ring) for preventing the elastic tube plug 20 from entering the second inner diameter section 12 from the first inner diameter section 11. During use of the reagent container, it is sometimes necessary to use a pipette to penetrate through the through channel 21 of the elastic plug 20 to inject and/or extract reagents into and/or from the tube 10. Upon insertion of the pipette, there is the potential to push the plug 20 deeper into the body 10, for example, into the second inner diameter section 12. The second limiting structure 14 can effectively prevent the elastic pipe plug 20 from being pushed to the second inner diameter section 12.
In one embodiment, as shown in fig. 2, the tube body 10 is provided with a third limiting structure 15 (e.g., a limiting block or a limiting ring) for preventing the depth of the elastic plug 20 from exceeding the plug accommodating section 16. During use of the reagent vessel, it is sometimes necessary to push the elastic plug 20 deeper into the tubular body 10 so that the elastic plug 20 is in interference fit with the second inner diameter section 12. In pushing elastomeric plug 20, there may be a potential for plug 20 to be pushed deeper into plug receiving section 16. Third stop structure 15 is effective to prevent elastomeric plug 20 from being pushed deeper than plug receiving section 16.
It will be appreciated that the stop formations (e.g. the first stop formation, the second stop formation and the third stop formation) may be resilient stop formations, i.e. resilient plugs are able to break through the stop formations when an applied stress exceeds the load of the stop formations.
Fig. 3 shows a schematic diagram of yet another reagent container, where (a) and (c) show a longitudinal sectional view of the reagent container and a cross-sectional view of the resilient stopcock, respectively, when the resilient stopcock is located in a first inner diameter section, and (b) and (d) show a longitudinal sectional view of the reagent container and a cross-sectional view of the resilient stopcock, respectively, when the resilient stopcock is located in a second inner diameter section. As shown in fig. 3, the through passage 21 includes a second passage section 212 and a first passage section 211 in the order in which the elastic tube plug 20 is inserted into the tube body 10, and the first passage section 211 has a larger cross-sectional area than the second passage section 212. During use of the reagent vessel, it is sometimes necessary to use a pipette to penetrate through the through passage 21 in the elastomeric plug 20 to inject and/or extract reagents into and/or from the tube 10. The pipette can easily pass through if the through-channel has a larger inner diameter. Meanwhile, during the process of using the reagent container, after the required reagent is injected and extracted, the elastic pipe plug 20 is sometimes required to be in interference fit with the second inner diameter section 12, so that the elastic pipe plug 20 is radially compressed and the through channel 21 is tightly pressed and sealed. The through-channel can easily be pressure-sealed if it has a smaller inner diameter. According to the above solution, the first channel section 211 of the through channel 21 has a larger cross-sectional area, which makes it easier for the pipette to pass through, and the second channel section 212 has a smaller cross-sectional area, which makes it easier for it to be tightly pressed. This arrangement improves the ease of use and sealing of the reagent vessel.
As shown in fig. 3 (a), the depth of the elastic plug 20 extending into the tubular body 10 is a first depth. The elastomeric plug 20 is located in the first inner diameter section 11 and has not yet entered the second inner diameter section 12. The outer diameter of the elastic pipe plug 20 is smaller than the inner diameter of the first inner diameter section 11, and the relation between the elastic pipe plug 20 and the first inner diameter section 11 is non-interference fit (clearance fit). Neither the first channel section 211 nor the second channel section 212 has yet been compression sealed.
As shown in fig. 3 (b), the depth of the elastic plug 20 extending into the tubular body 10 is a second depth, and the second depth is greater than the first depth. A portion of the elastomeric plug extends into the second inner diameter section 12. The outer diameter of the elastic pipe plug 20 is larger than the inner diameter of the second inner diameter section 12, and the elastic pipe plug 20 is in interference fit with the second inner diameter section 12. When the reagent vessel is in this state, the resilient plug 20 is radially compressed and the second channel section 212 of the through channel 21 is pressure-sealed. The reagent vessel is well sealed.
As shown in fig. 3 (c) and (d), the cross-sectional shape of the first channel section 211 is a two-dimensional shape, such as a circle, and the cross-sectional shape of the second channel section 212 is a one-dimensional shape, such as a "-" shape. Due to the elasticity of the elastic plug, the pipette can penetrate through the second channel section 212 even if the cross-section of the channel is one-dimensional. In this arrangement, the first channel section 211 is shaped to facilitate passage of a pipette and the second channel section 212 is shaped to facilitate compression sealing, which improves the ease of use and sealing of the reagent container.
Figure 4 shows a schematic view of yet another reagent container. As shown in the figure, the elastic plug 20 of the reagent vessel is provided with a sealing element 25, and the sealing element 25 seals the through passage 21. The sealing element 25 is a pierceable sealing element. For reagent containers that have not yet been put into use, the elastic plug 20 can be fitted in advance to the first inner diameter section 11, with the sealing element 25 being able to seal the through-passage 21 from impurities entering the interior of the container. When it is desired to inject and/or extract reagents into and/or from the tube 10, the sealing element 25 is pierced using a reagent gun.
Figure 5 shows a schematic view of yet another reagent container. As shown, the reagent vessel includes a tubular body 10 and an elastic stopcock 20. The tubular body 10 includes a plug receiving section 16. The elastic plug 20 comprises, in the order in which it projects into the plug receiving section 16, a third outer diameter section 23 and a fourth outer diameter section 24, wherein the outer diameter of the fourth outer diameter section 24 is greater than the outer diameter of the third outer diameter section 23. The elastic plug 20 is provided with a through passage 21 in a direction extending into the tube body. The third outer diameter section 23 can be in non-interference fit with the plug receiving section 16, and the fourth outer diameter section 24 can be in interference fit with the plug receiving section 16 with a second interference magnitude that is greater than zero. Elastomeric plug 20 is configured such that when fourth outer diameter section 24 is mated with plug receiving section 16 with a second interference, fourth outer diameter section 24 is radially compressed and through passage 21 is compressively sealed.
As shown in fig. 5 (a), the depth of the elastic plug 20 extending into the tubular body 10 is a first depth. Third outer diameter section 23 of elastomeric plug 20 extends into plug receiving section 16 and fourth outer diameter section 24 does not yet extend into plug receiving section 16. The outer diameter of the third outer diameter section 23 is smaller than the inner diameter of the plug accommodating section 16, and the relationship between the plug accommodating section 16 and the third outer diameter section 23 is a non-interference fit (clearance fit). The third outer diameter section 23 is not radially compressed and the through-passage 21 is not pressure sealed. The through channel 21 is open and penetrable by the pipette. In this state, a pipette may be used to inject a reagent into the tube 10 and/or extract a reagent from the tube 10 by penetrating the through passage 21 of the elastic plug 20.
As shown in fig. 5 (b), the elastic plug 20 extends into the tubular body 10 to a second depth, which is greater than the first depth. At least a portion of the fourth outer diameter section 24 of the elastomeric plug extends into the plug receiving section 16. The outer diameter of the fourth outer diameter section 24 is greater than the inner diameter of the plug receiving section 16, and the relationship between the fourth outer diameter section 24 and the plug receiving section 16 is an interference fit. The fourth outer diameter section 24 is radially compressed and the through passage 21 is pressure sealed. In this state, the reagent vessel is well sealed.
In some embodiments, there is provided a method of operating the above reagent container, comprising the steps of:
a) providing the reagent container described above, the third outer diameter section 23 of the resilient plug 20 of the reagent container having been mated with the plug receiving section 16, but the fourth outer diameter section 24 has not been interference fitted with the resilient plug receiving section 16;
b) using a pipette to penetrate through the through channel 21 of the elastic plug 20, injecting reagents into the tube 10 and/or extracting reagents from the tube 10;
c) pushing the elastic plug 20 to a deeper position of the pipe body 10, so that the fourth outer diameter section 24 is in interference fit with the elastic plug accommodating section 16;
preferably, the method of operating a reagent vessel further comprises
d) The reagent container is placed in a preset environment, and the reagent in the container is subjected to reaction, such as reaction related to nucleic acid amplification or nucleic acid detection.
In some embodiments, the method of handling reagent containers is a nucleic acid amplification method or a nucleic acid detection method.
In some embodiments, as shown in fig. 5, plug receiving section 16 includes a cylindrical lumen of constant internal diameter along the depth of the body.
In some embodiments, as shown in fig. 5 (a), the reagent container is provided with a stopper structure 17 for preventing the elastic plug 20 from being raised and/or lowered in the depth direction with respect to the tubular body 10. Limiting structure 17 includes the recess that is located third external diameter section 23 and the lug that is located stopcock receiving section 16, and recess and lug can inlay the block. The stop structure 17 prevents the resilient plug 20 from being removed from the nozzle.
In some embodiments, the third outer diameter section 23 and the fourth outer diameter section 24 are directly adjacent. In some embodiments, a chamfered surface is provided between the third and fourth outer diameter sections 23, 24. In some embodiments, the third outer diameter section 23 has a gradually increasing outer diameter adjacent the fourth outer diameter section 24. In some embodiments, the fourth outer diameter section 24 tapers in outer diameter adjacent the third outer diameter section 23. In the above aspect, the fitting state of the elastic plug 20 and the plug fitting section 16 can be switched more smoothly. In the above embodiment, the elastic plug can be easily switched over in the fitting relationship with the plug housing section.
FIG. 6 shows a schematic of a reagent processing system. In some embodiments, there is provided a reagent processing system comprising:
a reagent container comprising a tube body 10 and an elastic plug 20, the tube body 10 comprising a plug accommodating section 16, the plug accommodating section 16 comprising a first inner diameter section 11 and a second inner diameter section 12 along the depth direction of the tube body 10, the second inner diameter section 12 having an inner diameter smaller than that of the first inner diameter section 11; the elastic pipe plug 20 is provided with a through channel 21 along the direction extending into the pipe body 10; the elastic pipe plug 20 can be matched with the first inner diameter section 11 with a first interference magnitude, the elastic pipe plug 20 can be matched with the second inner diameter section 12 with a second interference magnitude, and the second interference magnitude is larger than the first interference magnitude; wherein when the elastomeric plug 20 is mated with the second inner diameter section 12 with a second interference, the elastomeric plug 20 is radially compressed and the through passage 21 is pressure sealed;
A pipetting gun 30 configured for penetrating the through channel 21 on the elastic plug 20, injecting reagents into the tube 10 and/or extracting reagents from the tube; and
a ram 40 configured for pushing the elastic plug 20 to move in the depth direction of the tubular body 10.
The method of operating the reagent processing system described above comprises the steps of:
a) providing the reagent container, wherein the elastic plug 20 of the reagent container is matched with the first inner diameter section 11 but not matched with the second inner diameter section 12 in an interference fit manner;
b) using a pipette to penetrate through the through channel 21 of the elastic plug 20, injecting reagents into the tube 10 and/or extracting reagents from the tube 10;
c) pushing the elastic pipe plug 20 to move along the depth direction of the pipe body 10 (towards the deep part of the pipe body), so that the elastic pipe plug 20 is in interference fit with the second inner diameter section 12;
preferably, also comprises
d) The reagent container is placed in a preset environment, and the reagent in the container is subjected to reaction, such as reaction related to nucleic acid amplification or nucleic acid detection.
In some embodiments, as shown in fig. 6 (a), the tube body 10 is provided with a second limiting structure 14 for preventing the elastic tube plug 20 from entering the second inner diameter section 12 from the first inner diameter section 11. The second stop structure 14 prevents the elastic plug 20 from being brought deeper when the pipette passes through the through-channel 21. As shown in fig. 6 (b), the stress applied by the ram 40 exceeds the load of the stopper structure 14, and the elastic plug 20 breaks through the stopper structure 14 under the pressure of the ram 40 and reaches the second inner diameter section 12.
In some embodiments, the reagent processing system further comprises a robotic arm 50, and the pipette gun 30 and/or the ram 40 are mounted on the robotic arm 50.
While specific embodiments of the invention have been described in detail, those skilled in the art will understand that: various modifications may be made in the details within the teachings of the disclosure, and these variations are within the scope of the invention. The full scope of the invention is given by the appended claims and any equivalents thereof.

Claims (15)

1. A reagent container comprising:
a pipe body (10) comprising a plug receiving section (16), the plug receiving section (16) comprising a first inner diameter section (11) and a second inner diameter section (12) in the direction of the depth of the pipe body (10), the second inner diameter section (12) having a smaller inner diameter than the first inner diameter section (11);
the pipe plug (20) is elastic, and a through channel (21) is arranged on the elastic pipe plug (20) along the direction extending into the pipe body (10);
wherein the elastic pipe plug (20) can be matched with the first inner diameter section (11) in a non-interference fit mode or in a first interference fit mode, and the elastic pipe plug (20) can be matched with the second inner diameter section (12) in a second interference fit mode;
when the elastic pipe plug can be matched with the first inner diameter section in a non-interference mode, the second interference magnitude is larger than zero, and when the elastic pipe plug can be matched with the first inner diameter section in the first interference magnitude, the second interference magnitude is larger than the first interference magnitude;
Wherein the through passage (21) is configured to be compression sealed with radial contraction of the elastomeric plug (20) when the elastomeric plug (20) is mated with the second inner diameter section (12) with a second interference.
2. A reagent container according to claim 1 having one or more of the following features:
-the first inner diameter section (11) has an inner diameter greater than or equal to at least one outer diameter of the elastic plug (20);
-the second inner diameter section (12) has an inner diameter smaller than at least one outer diameter of the elastomeric plug (20);
-said elastic plug (20) is fitted with said first inner diameter section (11) without interference or with said first interference at a first depth into the tubular body (10) and with said second interference at a second inner diameter section (12), the second depth being greater than the first depth.
3. A reagent container according to claim 1 having one or more of the following features:
-the first inner diameter section (11) and the second inner diameter section (12) are directly adjacent;
-a chamfer is provided between the first inner diameter section (11) and the second inner diameter section (12);
-the first inner diameter section (11) tapers in inner diameter adjacent the second inner diameter section (12);
-the second inner diameter section (12) has a gradually increasing inner diameter adjacent to the first inner diameter section (11);
-a smooth transition of the inner diameter at the intersection of the first inner diameter section (11) and the second inner diameter section (12);
-the second inner diameter section (12) is deeper in the tubular body than the first inner diameter section (11).
4. The reagent container according to claim 1, wherein the tube body (10) and/or the elastic tube plug (20) is/are provided with a limiting structure for preventing the elastic tube plug (20) from ascending and/or descending in the depth direction relative to the tube body (10);
preferably, one or more of the following limit structures are arranged on the pipe body (10) and/or the elastic pipe plug (20):
-a first stop structure (13) for preventing the elastic plug (20) from coming out of the orifice of the tubular body (10);
-a second stop formation (14) for preventing the resilient plug (20) from passing from the first inner diameter section (11) into the second inner diameter section (12);
-a third stop formation (15) preventing the depth of the resilient plug (20) from exceeding the plug receiving section (16).
5. A reagent container comprising:
a tubular body (10) comprising a plug receiving section (16);
the elastic pipe plug (20) comprises a third outer diameter section (23) and a fourth outer diameter section (24) according to the sequence of the elastic pipe plug extending into the pipe plug accommodating section (16), the outer diameter of the fourth outer diameter section (24) is larger than that of the third outer diameter section (23), and a through channel (21) is formed in the direction of the elastic pipe plug (20) extending into the pipe body;
Wherein the third outer diameter section (23) is capable of non-interference fit or first interference fit with the plug receiving section (16), and the fourth outer diameter section (24) is capable of interference fit with the plug receiving section (16) second interference fit;
when the third outer diameter section is capable of non-interference fit with the plug receiving section, the second interference is greater than zero, and when the third outer diameter section is capable of interference fit with the plug receiving section, the second interference is greater than the first interference;
wherein the through-passage (21) is configured such that, when the fourth outer diameter section (24) is mated with the plug receiving section (16) with the second interference, the through-passage (21) is compressively sealed with radial contraction of the fourth outer diameter section (24).
6. The container of claim 5, having one or more of the following features:
-at least one inner diameter of the plug receiving section (16) is greater than or equal to the outer diameter of the third outer diameter section (23);
-at least one inner diameter of the plug receiving section (16) is smaller than an outer diameter of the fourth outer diameter section (24);
-the resilient plug (20) is non-interference fitted or fitted with the first interference with the plug receiving section (16) at a first depth into the body (10) and a third outer diameter section (23); the second depth that elasticity stopcock (20) stretched into body (10), fourth external diameter section (24) and stopcock accommodate section (16) with the cooperation of second interference magnitude, the second depth is greater than the first depth.
7. The container of claim 5, characterized by one or more of the following:
-the third outer diameter section (23) and the fourth outer diameter section (24) are directly adjacent;
-a chamfer is provided between the third outer diameter section (23) and the fourth outer diameter section (24);
-the third outer diameter section (23) has a gradually increasing outer diameter adjacent the fourth outer diameter section (24);
-the fourth outer diameter section (24) tapers in outer diameter adjacent the third outer diameter section (23).
8. The reagent container according to claim 5, wherein the tube body (10) and/or the elastic tube plug (20) is provided with a limiting structure for preventing the elastic tube plug (20) from ascending and/or descending in the depth direction relative to the tube body (10);
preferably, the spacing structure comprises one or more of:
-a first stop structure (13) for preventing the elastic plug (20) from coming out of the orifice of the tubular body (10);
-a third stop formation (13) preventing the depth of the resilient plug (20) from exceeding the plug receiving section (16);
-a fourth stop formation to prevent the fourth outer diameter section (24) of the elastomeric plug (20) from entering the elastomeric plug receiving section.
9. The reagent container of any of claims 1 to 8, configured such that when the resilient plug (20) is extended into the tubular body (10) to a first depth, the resilient plug (20) is fitted with the plug receiving section (16) in a non-interference fit or with the first interference, the through passage (21) is not compressed into a sealed state or is compressed into a first sealed state; when the elastic pipe plug (20) extends into the pipe body (10) to a second depth, the elastic pipe plug (20) is matched with the pipe plug accommodating section (16) with the second interference, and the through channel (21) is compressed to form a second sealing state;
Wherein the second depth is greater than the first depth and the penetration channel (21) is sealed to a greater extent in the second sealed state than in the first sealed state;
preferably, the second sealed state is a hermetic seal.
10. Reagent container according to any one of claims 1 to 8, wherein the through channel (21) comprises a second channel section (212) and a first channel section (211) in the order in which the resilient plug (20) projects into the tubular body (10), which channel has one or more of the following characteristics:
-the cross-sectional area of the first channel section (212) is larger than the cross-sectional area of the second channel section (211);
-the channel cross-sectional shape of the first channel section (211) is a two-dimensional shape and the channel cross-sectional shape of the second channel section (212) is a one-dimensional shape.
11. Reagent container according to any one of claims 1 to 8, the resilient plug (20) further comprising a sealing element (25), the sealing element (25) being adapted to seal the through-going passage (21);
preferably, the sealing element (25) is removable;
preferably, the sealing element (25) is pierceable.
12. A reagent vessel according to any one of claims 1 to 8 which is a PCR tube.
13. A method of operating a reagent vessel comprising the steps of:
a) Providing a reagent container according to any one of claims 1 to 12, the resilient plug (20) of the reagent container having been fitted with the first inner diameter section (11) but not yet having been interference fitted with the second inner diameter section (12);
b) penetrating a through passage (21) of the elastic tube plug (20) using a pipette gun to inject reagents into the tube (10) and/or extract reagents from the tube (10);
c) the elastic pipe plug (20) is pushed to move along the depth direction of the pipe body (10), so that the elastic pipe plug (20) is in interference fit with the second inner diameter section (12);
preferably, also comprises
d) Placing the reagent container in a preset environment, and enabling the reagent in the container to react, such as a reaction related to nucleic acid amplification or nucleic acid detection;
preferably, the method of manipulating a reagent vessel is a nucleic acid amplification method or a nucleic acid detection method.
14. A method of operating a reagent container comprising the steps of:
a) providing a reagent container according to any one of claims 1 to 12, the third outer diameter section (23) of the resilient plug (20) of the reagent container having been fitted with the plug receiving section (16), but the fourth outer diameter section (24) having not been interference fitted with the resilient plug receiving section (16);
b) -penetrating a through channel (21) of the elastic plug (20) using a pipette gun, injecting reagents into the tube (10) and/or extracting reagents from the tube (10);
c) Pushing the elastic pipe plug (20) to a deeper position of the pipe body (10) to enable the fourth outer diameter section (24) to be in interference fit with the elastic pipe plug accommodating section (16);
preferably, also comprises
d) Placing the reagent container in a preset environment, and enabling the reagent in the container to react, such as a reaction related to nucleic acid amplification or nucleic acid detection;
preferably, the method of manipulating a reagent vessel is a nucleic acid amplification method or a nucleic acid detection method.
15. A reagent processing system comprising
-a reagent container according to any one of claims 1 to 12;
-a pipette gun configured for penetrating a through channel (21) on the elastic plug (20), injecting reagents into the tube (10) and/or extracting reagents from the tube (10); and
-a ram configured for pushing the elastic plug (20) in a direction of the depth of the tubular body (10);
preferably, the reagent processing system further comprises a robotic arm on which the pipette gun and/or the ram are mounted.
CN202110023377.9A 2021-01-08 2021-01-08 Reagent container, operation method thereof and reagent processing system Pending CN114752475A (en)

Priority Applications (6)

Application Number Priority Date Filing Date Title
CN202110023377.9A CN114752475A (en) 2021-01-08 2021-01-08 Reagent container, operation method thereof and reagent processing system
US18/260,547 US20240050952A1 (en) 2021-01-08 2022-01-07 Reagent container and operation method therefor, and reagent treatment system
EP22736599.6A EP4276168A1 (en) 2021-01-08 2022-01-07 Reagent container and operation method therefor, and reagent treatment system
PCT/CN2022/070755 WO2022148438A1 (en) 2021-01-08 2022-01-07 Reagent container and operation method therefor, and reagent treatment system
KR1020237026967A KR20230147607A (en) 2021-01-08 2022-01-07 Reagent container and its operating method and reagent processing system
JP2023541688A JP2024504086A (en) 2021-01-08 2022-01-07 Reagent containers and their operating methods, and reagent handling systems

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202110023377.9A CN114752475A (en) 2021-01-08 2021-01-08 Reagent container, operation method thereof and reagent processing system

Publications (1)

Publication Number Publication Date
CN114752475A true CN114752475A (en) 2022-07-15

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CN202110023377.9A Pending CN114752475A (en) 2021-01-08 2021-01-08 Reagent container, operation method thereof and reagent processing system

Country Status (1)

Country Link
CN (1) CN114752475A (en)

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