CN112371195A - Detection chip - Google Patents

Detection chip Download PDF

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Publication number
CN112371195A
CN112371195A CN202110051360.4A CN202110051360A CN112371195A CN 112371195 A CN112371195 A CN 112371195A CN 202110051360 A CN202110051360 A CN 202110051360A CN 112371195 A CN112371195 A CN 112371195A
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CN
China
Prior art keywords
detection chip
cavity
sealing
opening
chamber
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Granted
Application number
CN202110051360.4A
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Chinese (zh)
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CN112371195B (en
Inventor
王琛瑜
张玙璠
赵静
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BOE Technology Group Co Ltd
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BOE Technology Group Co Ltd
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Priority to CN202110051360.4A priority Critical patent/CN112371195B/en
Publication of CN112371195A publication Critical patent/CN112371195A/en
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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
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D19/00Degasification of liquids
    • B01D19/02Foam dispersion or prevention
    • 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
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/50273Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means or forces applied to move the fluids
    • 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
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502753Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02Adapting objects or devices to another
    • B01L2200/026Fluid interfacing between devices or objects, e.g. connectors, inlet details
    • B01L2200/027Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06Fluid handling related problems
    • B01L2200/0631Purification arrangements, e.g. solid phase extraction [SPE]
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/10Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/04Closures and closing means
    • B01L2300/046Function or devices integrated in the closure

Abstract

Provided is a detection chip including: a substrate having a first surface and comprising at least one cavity having a first opening in the first surface and at least one fluid channel leading to the at least one cavity; one of the at least one fluid passage has a switching valve for controlling connection and disconnection of the corresponding at least one fluid passage. An amplification chamber in communication with the at least one fluid channel; and a sealing cover connected with the base body and sealing the first opening of the base body.

Description

Detection chip
Technical Field
Embodiments of the present disclosure relate to a detection chip.
Background
The micro-fluidic chip technology integrates basic operation units related to sample preparation, reaction, separation, detection and the like in the fields of biology, chemistry, medicine and the like into a chip with a micro-channel with a micron scale, and automatically completes the whole process of reaction and analysis. The chip used in this process is called a microfluidic chip, and may also be called a Lab-on-a-chip (Lab-on-a-chip). The microfluidic chip technology has the advantages of small sample consumption, high analysis speed, convenience for manufacturing a portable instrument, suitability for real-time and on-site analysis and the like, and is widely applied to various fields of biology, chemistry, medicine and the like.
Disclosure of Invention
According to at least one embodiment of the present disclosure, there is provided a detection chip including: a substrate having a first surface and comprising at least one cavity having a first opening in the first surface and at least one fluid channel leading to the at least one cavity; one of the at least one fluid channel is provided with a switch valve for controlling the connection and disconnection of the corresponding at least one fluid channel; an amplification chamber in communication with the at least one fluid channel; and a sealing cover connected with the base body and sealing the first opening of the base body.
For example, at least one embodiment of the present disclosure provides a detection chip further including: at least one storage container received in the at least one cavity through the first opening, the at least one storage container including a second opening and a first sealing membrane sealing the second opening.
For example, at least one embodiment of the present disclosure provides a detection chip further including: at least one first sealing member disposed between the storage container and the cavity to seal a gap between the storage container and the cavity.
For example, at least one embodiment of the present disclosure provides a detection chip, wherein the outer surface of the storage container is provided with at least one groove, or the inner surface of the cavity is provided with at least one groove, and the at least one first sealing member is mounted in the at least one groove.
For example, at least one embodiment of the present disclosure provides a detection chip, wherein the at least one cavity includes a puncturing structure, and the puncturing structure is disposed in the cavity and is used for puncturing the first sealing film, so that a reagent in the storage container enters the at least one fluid channel.
For example, at least one embodiment of the present disclosure provides a detection chip further including: the mixing structure, wherein, among the plurality of cavities at least one pass through among the plurality of fluid passage at least one with mixing structure intercommunication, wherein, mixing structure including ventilative mouthful, barrier film, power chamber and with the mixing chamber of power chamber intercommunication, power chamber with communicate through many fluid passage respectively between the plurality of cavities, ventilative mouthful setting is in sealed covering, the barrier film covers ventilative mouthful, the base member passes through ventilative mouthful with barrier film and external atmosphere intercommunication.
For example, at least one embodiment of the present disclosure provides a detection chip, wherein the amplification chamber has a reaction region and a bubble removal region that are communicated with each other.
For example, at least one embodiment of the present disclosure provides a detection chip, wherein the bubble removing region is located at an upstream side and/or a downstream side of the reaction region.
For example, at least one embodiment of the present disclosure provides a detection chip, wherein the reaction region is formed in a shuttle shape, and the bubble removal region is formed in a circular shape.
For example, at least one embodiment of the present disclosure provides a detection chip further including: a drive chamber in fluid communication with the amplification chamber.
For example, at least one embodiment of the present disclosure provides a detection chip further including: a drive assembly movably received in the drive chamber, the drive assembly including a drive cap and a resilient member disposed between the drive cap and the drive chamber.
For example, in the detection chip provided by at least one embodiment of the present disclosure, the driving assembly further includes at least one second sealing member, the at least one second sealing member is disposed between the driving cover and the driving cavity to seal a gap between the driving cover and the driving cavity, an outer surface of the driving cover is provided with at least one groove, or an inner surface of the driving cavity is provided with at least one groove, and the at least one second sealing member is correspondingly mounted in the at least one groove.
For example, in the detection chip provided in at least one embodiment of the present disclosure, a sliding structure is disposed between the driving cavity and the driving cover, the sliding structure includes a buckle disposed on an outer surface of the driving cover and a groove structure disposed on an inner surface of the driving cavity, and the buckle cooperates with the groove structure to enable the buckle to slide in the groove structure and to be vertically limited.
For example, at least one embodiment of the present disclosure provides a detection chip in which the at least one storage container further includes a third opening and a second sealing film sealing the third opening, the first sealing film and the second sealing film defining a reservoir space therebetween for containing a reagent.
For example, at least one embodiment of the present disclosure provides a detection chip, wherein the puncturing structure is located at an end of the cavity opposite to the first opening.
For example, at least one embodiment of the present disclosure provides a detection chip, wherein the storage container includes a drainage channel and an inner wall having an inclined first angle toward an end of the second opening, and the drainage channel communicates the inner wall and the second opening.
For example, in the detection chip provided in at least one embodiment of the present disclosure, the first angle ranges from 5 degrees to 60 degrees.
For example, in the detection chip provided in at least one embodiment of the present disclosure, the cavity further includes a liquid guiding channel, and the substrate further includes a fluid channel, where the liquid guiding channel is disposed at the puncture structure and communicates the cavity and the fluid channel.
For example, at least one embodiment of the present disclosure provides a detection chip, wherein an inner diameter of the liquid guiding channel is the same as an inner diameter of the fluid channel.
For example, at least one embodiment of the disclosure provides a detection chip, wherein one end of the puncturing structure facing the storage container is provided with a needle-shaped protrusion, and a size of the needle-shaped protrusion is smaller than a size of the second opening.
For example, at least one embodiment of the present disclosure provides a detection chip, wherein the needle-shaped protrusion has a pyramid shape and has a plurality of side edges, and an opening of the liquid guiding channel in the cavity is located between two of the side edges and is connected to a bottom surface and a side surface of the pyramid.
For example, in the detection chip provided in at least one embodiment of the present disclosure, the needle-shaped protrusion is a cone, and an opening of the liquid guide channel in the cavity is connected to a bottom surface of the cone.
For example, at least one embodiment of the present disclosure provides a detection chip, wherein an opening of the liquid guiding channel in the cavity has an area smaller than an area of a bottom surface of the needle-shaped protrusion.
For example, in the detection chip provided in at least one embodiment of the present disclosure, the first sealing film and/or the second sealing film is a flexible film or a composite aluminum film, and a material of the flexible film includes at least one of PE, PP, or PS.
For example, at least one embodiment of the present disclosure provides a detection chip, wherein the sealing cap is clamped to the base.
For example, at least one embodiment of the present disclosure provides a detection chip, in which the sealing cover includes a cover body, and a clip assembly, the clip assembly includes at least one first clip disposed at an outer peripheral portion of the cover body and a second clip disposed at a central portion of the cover body.
For example, in the detection chip provided in at least one embodiment of the present disclosure, the sealing cover further includes a sealing ring disposed inside an outer peripheral portion of the cover body.
For example, at least one embodiment of the present disclosure provides a detection chip, wherein the cap body and the snap assembly are formed of a rigid material, and the sealing ring is formed of a flexible material.
For example, in the detection chip provided in at least one embodiment of the present disclosure, the sealing cover is provided with a cover film at the first opening.
For example, at least one embodiment of the present disclosure provides a detection chip, wherein the cover film is an elastic film.
For example, at least one embodiment of the present disclosure provides a detection chip, wherein a surface of the cover film facing the first opening is provided with a protrusion structure.
For example, at least one embodiment of the present disclosure provides a detection chip, wherein the protrusion structure includes a central protrusion portion and a plurality of peripheral protrusion portions distributed circumferentially around the central protrusion portion.
For example, in the detection chip provided in at least one embodiment of the present disclosure, the central protrusion is in a shape of a straight line, a cross, or a circle, and the plurality of peripheral protrusions are in a shape of a straight line or a circle.
For example, in the detection chip provided in at least one embodiment of the present disclosure, the base body is provided with a flow channel convergence structure between the power cavity and the at least one cavity.
For example, in the detection chip provided in at least one embodiment of the present disclosure, a central portion of the flow channel converging structure is circular, and a plurality of trapezoid structures are uniformly distributed around the central portion in a circumferential direction.
For example, at least one embodiment of the present disclosure provides a detection chip further including: and the magnetic bead capturing cavity is arranged between the power cavity and the mixing cavity and is respectively communicated with the power cavity and the mixing cavity.
For example, at least one embodiment of the present disclosure provides a detection chip, wherein an area or a size of a middle region of the magnetic bead capture cavity is larger than an area or a size of the two end regions.
Drawings
To more clearly illustrate the technical solutions of the embodiments of the present disclosure, the drawings that are required to be used in the embodiments will be briefly described below, it should be understood that the following drawings only illustrate some embodiments of the present disclosure and therefore should not be considered as limiting the scope, and for those skilled in the art, other related drawings may be obtained from the drawings without inventive effort.
FIG. 1 shows a perspective view of a detection chip according to at least one embodiment of the present disclosure;
FIG. 2 shows an exploded perspective view of the detection chip of FIG. 1;
FIG. 3 shows an exemplary schematic of a fluid channel;
FIG. 4A illustrates a flow path convergence structure;
FIG. 4B shows a magnetic bead capture chamber;
fig. 5 illustrates an exploded view of a storage container according to at least one embodiment of the present disclosure;
fig. 6 illustrates a cut-away perspective view of a storage container according to at least one embodiment of the present disclosure;
fig. 7A illustrates a perspective view of a cavity showing a breaching structure in accordance with at least one embodiment of the present disclosure;
FIG. 7B shows an enlarged partial top view of the breaching structure of FIG. 7A;
FIG. 7C illustrates an enlarged partial top view of another embodiment of a breaching structure;
FIG. 8 shows a perspective view of the storage container mounted within the cavity;
FIG. 9 shows a schematic view of the state of the storage container releasing the reagent;
FIG. 10 shows a top view of the sealing lid without the film adhered thereto;
FIG. 11 shows a top view of the sealing lid with the film adhered thereto;
FIGS. 12A-12C respectively illustrate a schematic view of an elastic membrane of a sealing lid in accordance with at least one embodiment;
13A-13F illustrate schematic diagrams of a drive component of a detection chip according to at least one embodiment;
FIGS. 14A and 14B show schematic diagrams of an amplification chamber of a detection chip according to at least one embodiment; and
FIG. 15 shows a detection device according to an embodiment of the present disclosure.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present disclosure more apparent, the technical solutions of the embodiments of the present disclosure will be described clearly and completely with reference to the drawings of the embodiments of the present disclosure. It is to be understood that the described embodiments are only a few embodiments of the present disclosure, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the described embodiments of the disclosure without any inventive step, are within the scope of protection of the disclosure.
Unless otherwise defined, technical or scientific terms used herein shall have the ordinary meaning as understood by one of ordinary skill in the art to which this disclosure belongs. The use of "first," "second," and similar terms in this disclosure is not intended to indicate any order, quantity, or importance, but rather is used to distinguish one element from another. The word "comprising" or "comprises", and the like, means that the element or item listed before the word covers the element or item listed after the word and its equivalents, but does not exclude other elements or items. "upper", "lower", "left", "right", and the like are used merely to indicate relative positional relationships, and when the absolute position of the object being described is changed, the relative positional relationships may also be changed accordingly.
In the design process of microfluidic chips, it is generally desirable to integrate as many functions of analytical tests on the chip as possible to reduce the dependence of the chip on external operations, thereby achieving automation and integration. The micro-fluidic chip is a disposable product, so that complex liquid path systems such as cleaning and waste liquid treatment can be omitted, and pollution caused by the liquid path systems can be avoided. In order to achieve integration, a reagent storage part may be provided in the microfluidic chip to store various reagents required for the analytical detection. For a common microfluidic chip with a reagent storage function, the chip structure is complex, or the preparation process is complex, so that the cost of the microfluidic chip as a consumable material is too high. Meanwhile, the process of the microfluidic chip capable of realizing multiple detections is more complicated and the cost is higher.
At least one embodiment of the present disclosure provides a detection chip including a base having a first surface and including at least one cavity having a first opening in the first surface and at least one fluid channel leading to the at least one cavity, and a sealing cover. The at least one storage container is received in the at least one cavity through a first opening, the at least one storage container including a second opening and a first sealing membrane sealing the second opening. The sealing cover is coupled to the base and seals the first opening of the base. Wherein the at least one cavity comprises a breaching structure disposed therein for breaching the first sealing membrane to allow reagent in the storage container to enter the fluid passageway. In the embodiment, the storage containers are arranged in a split manner, so that the sample and the reaction reagent can be pre-stored in the closed storage container and isolated from the outside, long-term storage is realized, and the sample and the reaction reagent are combined with the substrate of the detection chip as required, so that the manufacturing cost of the microfluidic chip can be reduced, and the application range of the microfluidic chip can be enlarged. The enclosed space within the reservoir is broken upon use, thereby releasing the reagent quantitatively. Meanwhile, the storage container can be simply and effectively isolated from the outside by arranging the sealing cover, so that pollution is prevented.
At least one embodiment of the present disclosure provides a detection chip, which may include one or more of an eluent chamber, a wash solution chamber, a sample chamber, a first mixing chamber, a second mixing chamber, a waste solution chamber, a venting chamber, and an amplification chamber as needed, and one or more of the eluent chamber, the first wash solution chamber, the second wash solution chamber, the third wash solution chamber, the sample chamber, the first mixing chamber, the second mixing chamber, the waste solution chamber, the venting chamber, and the amplification chamber may be configured to accommodate a storage container as described above. The detection chip can integrate all or part of the steps of the detection process, thereby facilitating the design and operation of the detection process, reducing the detection time, reducing the pollution in the detection process and the like.
At least one embodiment of the present disclosure provides a detection chip including a base body having a first surface and including at least one cavity having a first opening in the first surface and at least one fluid channel leading to the at least one cavity; one of the at least one fluid passage is provided with a switch valve for controlling the connection and disconnection of the corresponding at least one fluid passage; the amplification chamber is in communication with at least one fluid channel; the sealing cover is connected with the base body and seals the first opening of the base body.
For example, the at least one fluid passage includes a plurality of fluid passages, at least one of the plurality of fluid passages having an on-off valve, for example, each of the plurality of fluid passages having an on-off valve.
The following generally describes a detection chip according to an embodiment of the present disclosure with reference to the drawings.
FIG. 1 shows a perspective view of a detection chip according to at least one embodiment of the present disclosure; fig. 2 shows an exploded perspective view of the detection chip of fig. 1. Fig. 3 shows an exemplary schematic of a fluid channel. Fig. 4A shows a flow channel convergence structure. Figure 4B shows a magnetic bead capture chamber.
As shown in FIGS. 1 and 2, the detection chip according to at least one embodiment of the present disclosure includes a base 100, a sealing cover 20, a sealing layer 31, at least one storage container 40, a kneading structure 50, a driving assembly 60, and an amplification chamber 71.
The substrate 100 is formed with a plurality of cavities, a plurality of mixing chambers, a sample chamber, a waste chamber, a magnetic bead capture chamber, and a plurality of substrate grooves. The substrate 100 may be injection molded from a polymer material such as PMMA (polymethyl methacrylate), PC (polycarbonate), PP (polypropylene), or PS (polystyrene), which will not be described in detail herein.
The plurality of cavities includes a plurality of reservoirs that cooperate with corresponding reservoirs 40 and a drive chamber 1011 for injecting liquid into the amplification chamber 71. Wherein the amplification chamber 71 is a quantitative chamber, a fixed volume of liquid enters the quantitative chamber, and the excess liquid will overflow from the quantitative chamber as waste liquid. In addition, the PCR amplification lyophilized powder may be preloaded inside the amplification chamber 71. One or more of the lysis fluid chamber, the eluent chamber, the wash fluid chamber and the bead chamber are configured to receive a corresponding reservoir 40. Contain corresponding reagent in every corresponding storage container 40, for example, can hold the storage container that stores the lysate in the lysate chamber, the eluant chamber can hold the storage container that stores the eluant, the cleaning solution chamber can hold the storage container that stores the washing liquid, the magnetic bead chamber can hold the storage container that stores the magnetic bead.
As shown in fig. 3, the inlet 110 may be connected to any one of a plurality of cavities, a fluid passage 130 connects the any one cavity and the flow path convergence structure, and an on-off valve 120 may be provided in the fluid passage 130 for controlling opening and closing of the fluid passage.
The plurality of mixing chambers include a mixing chamber and a power chamber, which form a portion of the mixing structure 50 of the detection chip.
The magnetic bead capture cavity 1014 is arranged between the power cavity and the mixing cavity, and magnetic beads pass through the magnetic bead capture cavity 1014 and are captured under the attraction of an external magnet. As shown in fig. 4B, the bead capture chamber 1014 is a recessed shuttle. The depth of the indent is consistent with the depth of the flow channel.
The magnetic bead capture cavity 1014 is arranged in a shuttle shape, the area of the middle area of the magnetic bead capture cavity is large, more magnetic beads can be contained, and the blocking of a flow channel is avoided; and both ends are little, can avoid liquid to cut off the flow, and liquid can assemble simultaneously, avoids forming the magnetic bead piece that can't be mixed by the mixing.
The detection chip in this embodiment includes a sealing cap 20, and the sealing cap 20 is connected to the base 100 and seals the first opening of the base. As previously described, the cavity has a first opening in the first surface 100a of the base 100, and the storage container 40 is sealingly received in the first opening.
In the present embodiment, the base body 100 is provided with the flow path convergence structure 1013 between the power chamber and the plurality of cavities. As shown in fig. 4A, the central portion of the flow path converging structure 1013 is circular, and a plurality of trapezoidal structures are uniformly distributed around the circumference of the central portion.
The flow channel convergence 1013 functions to prevent liquid shut-off and liquid cross-over. When the power cavity pumps liquid from the liquid storage cavity, the reagent enters the runner convergence structure 1013, and the whole structure is infiltrated under the action of capillary force, so that the flow cutoff is avoided; on the other hand, due to the capillary force, the surrounding reagents will tend to converge towards the flow channel convergence structure 1013, and even if a small amount of reagents are connected into other flow channels, the reagents can finally converge and be drawn away by the power cavity.
The base body 100 and the sealing layer 31 collectively form a plurality of fluid passages including a plurality of flow paths and a plurality of on-off valves respectively provided on part or all of the flow paths. The switch valve is used for controlling the connection and disconnection of the corresponding at least part of the fluid passage.
Illustratively, the sealing cover 20 in this embodiment is configured to enclose at least one cavity, e.g., each cavity, thereby providing an enclosed environment for the cavities that is isolated from the outside, preventing contamination, and protecting the first surface 100a of the substrate 100.
The structure and operation of the storage container 40 will be described with reference to the accompanying drawings.
Fig. 5 illustrates an exploded view of a storage container according to at least one embodiment of the present disclosure. Fig. 6 illustrates a cut-away perspective view of a storage container according to at least one embodiment of the present disclosure. Fig. 7A illustrates a perspective view of a cavity showing a puncture structure in accordance with at least one embodiment of the present disclosure. Fig. 7B shows an enlarged partial view of the puncture structure of fig. 7A. Fig. 7C shows an enlarged partial top view of another embodiment of the breaching structure. Figure 8 shows a perspective view of the storage container mounted within the cavity. Fig. 9 shows a schematic view of the state of the storage container releasing the reagent.
As shown in fig. 5, 6, 7A-7C, and 8, the cavity has a first opening at the first surface 100a of the substrate 100. It should be noted that "cavity" refers to one or more of a sample chamber, an eluent chamber, a wash chamber, and a bead chamber hereinafter. For example, in the present embodiment, the sample chamber, the eluent chamber, the washing solution chamber, and the magnetic bead chamber have first openings on the first surface 100a of the substrate 100, respectively. The sealing layer 31 is attached to the second surface 100b of the base 100. The base 100 is provided with a base groove for forming a flow path on the surface of the second surface 100 b. The storage container 40 is received in the cavity through the first opening. The storage container 40 includes a second opening 4012 and a first sealing film 403 sealing the second opening 4012.
The cavity comprises a breaching structure 70, the breaching structure 70 being disposed within the cavity for breaching the first sealing membrane 403 to allow reagent in the reservoir 40 to enter the cavity.
The reservoir 40 further comprises a third opening 4011 and a second sealing membrane 402 sealing the third opening 4011, the first sealing membrane 403 and the second sealing membrane 402 defining a reservoir space therebetween through a sidewall of the reservoir 40 for containing a reagent. Thus, a certain amount of reagent can be kept sealed in the reservoir space. The first sealing film and the second sealing film are flexible films or composite aluminum films made of high polymer materials such as PE, PP or PS.
The detection chip may further include a first sealing member 404 disposed between the storage container 40 and the cavity of the base to seal a gap between the storage container 40 and the cavity. For example, the cylindrical outer circumference of the storage container 40 is provided with at least one first groove 405, and the first sealing member 404 is mounted in the first groove 405. Alternatively, the cylindrical inner periphery of the cavity may be provided with a first groove (not shown) in which the first seal 404 is mounted.
Illustratively, the first sealing element 404 is a silicone ring, which can form a stable and reliable seal.
The reservoir 40 is disposed coaxially with the cavity. The breaching structure 70 is located at an end of the cavity opposite the first opening, such as the bottom in fig. 7A.
Illustratively, the storage container 40 may include a drainage channel 406 and an inner wall 407 having an inclined first angle toward an end of the second opening 4012, the drainage channel 406 communicating the inner wall 407 and the second opening 4012. Optionally, the first angle ranges from 5 degrees to 60 degrees. The use of the inclined inner wall 407 helps to guide the reagent in the reservoir into the test chip through the drainage channel 406, preventing the reagent from remaining in the reservoir.
The inner diameter of the drainage channel must be larger than the size of the puncture structure to ensure that the puncture structure can be smoothly inserted into the drainage channel, so that the release of the reagent in the storage container is facilitated.
The cavity further comprises a drainage channel 1001 arranged at the puncture structure 70 and communicating the cavity with the fluid channel. The internal diameter of drainage channel 1001 may be equal to the internal diameter of drainage channel 406 to ensure uniform hydraulic pressure in the flow path.
The end of the puncturing structure 70 facing the storage container 40 is provided with a needle-like protrusion 701, the centre point 702 of which coincides with the orthographic projection of the centre of the bottom surface of the cavity. The needle projection 701 has a size smaller than that of the second opening 4012.
As shown in fig. 7A and 7B, in an exemplary embodiment, the needle-like protrusion 701 is approximately in the shape of a triangular pyramid, i.e., the outer profile resembles a triangular pyramid, having three lateral edges. The opening of liquid-conducting channel 1001 in the cavity is located between the two side edges of the triangular pyramid and connects the bottom face and one side face of the triangular pyramid.
Fig. 7C shows an enlarged partial top view of another embodiment of the breaching structure. The needle-like projection 701' may also have other pyramid shapes with multiple side edges, such as four side edges (as shown in fig. 7C), in accordance with the concepts of the present disclosure. The opening of the drainage channel 1001 in the cavity is located between two of the four side edges and connects the base and one side of the pyramid. The disclosure is not limited thereto, and those skilled in the art may also arrange other number of side edges and arrange the opening of the liquid guiding channel between two of the side edges.
In a further embodiment, not shown, the needle-like projection may also be formed as a cone, the opening of the liquid-conducting channel in the cavity being connected to the bottom surface of the cone.
Alternatively, the area of the opening of the liquid guiding channel in the cavity is smaller than the area of the bottom surface of the needle-like projection. This arrangement is beneficial to improving the efficiency of liquid entering the fluid channel and preventing liquid from being retained at other positions of the cavity.
Illustratively, the sealing cap 20 may snap (i.e., snap-fit) with the base 100. For example, the sealing cap 20 includes a cap body 201, a snap assembly, and a sealing ring.
For example, the snap assembly includes at least one first snap 2010 provided at an outer circumferential portion of the cap body 201 and a second snap (not shown) provided at a central portion of the cap body 201. The packing is provided inside the outer peripheral portion of the cap body 201.
Correspondingly, a first sealing groove along the periphery of the power cavity and a second sealing groove along the periphery of the plurality of cavities may be provided on the first surface 100a of the base 100, at least one third clip 1010 may be further provided on the periphery of the base 100 for clipping with the at least one first clip 2010 of the cover body 201, and a fourth clip may be further provided on the periphery of the power cavity of the base 100 for clipping with the second clip. Illustratively, the number of the first and third buckles is equal, for example, 1-100. A simple and reliable connection can be achieved using a snap connection.
Optionally, the cap body 201 and the snap assembly are formed of a rigid material and the sealing ring is formed of a flexible material. The rigid material is injection molding material such as ABS, PC, acrylic, etc., and is used for manufacturing the buckle in the buckle assembly and providing rigidity of the sealing cover. The flexible material is silica gel or TPU material, as the sealing washer. The second snap corresponds to the fourth snap position, so that the middle of the sealing cover 20 has rigidity.
Fig. 10 shows a top view of the sealing lid without the film adhered thereto. Fig. 11 shows a top view of the sealing lid when the film is adhered. Fig. 12A-12C respectively illustrate schematic views of an elastic membrane of a sealing cap in accordance with at least one embodiment.
The various membrane structures provided in the sealing lid 20 are described in detail below. As shown in fig. 10 to 11, the sealing cap 20 is provided with a sample port 2030 and a vent port 2050.
The sample port 2030 is used for adding a sample to the detection chip, and the upper end is covered with the first isolation film 1030. The first separation film 1030 may be adhered to the upper end of the sample port 2030, and the first separation film 1030 is completely impermeable to air so that the sample port 2030 may be sealed. In operation, the operator tears open the first release film 1030, adds the sample, and then reattaches the first release film 1030.
Preferably, the first release film 1030 is a single-sided adhesive having tackiness. Optionally, first isolation diaphragm 1030 has a diameter of 1-5mm, and first isolation diaphragm 1030 is sized to ensure complete coverage of sample port 2030.
The vent 2050 is an outlet through which the whole gas inside the detection chip is communicated with the atmosphere. The venting ports 2050 may be connected to a venting chamber, for example. A second isolation film 1050 is bonded to the vent port 2050, and the second isolation film 1050 is a gas permeable film. The second isolation film 1050 is preferably a sheet material such as a waterproof and breathable film, gauze, cotton sheet, etc., which prevents liquid leakage, but is breathable at the same time.
The sealing cap 20 is provided with an elastic film 2060 at the first opening, specifically, at the upper end of the storage container 40. In this embodiment, the elastic film 2060 is an air guide silicone.
When the second sealing film 402 is punctured by a kit, since the contact portion of the elastic film 2060 is silicone and has a thickness of 0.5 to 2mm, it is not punctured, so that the upper end of the storage container 40 is not directly exposed to air after being punctured.
Optionally, the surface of the elastic membrane 2060 facing the first opening is provided with a protruding structure. As shown in fig. 12A to 12C, the protruding structure may be a cross-shaped, a straight line-shaped, or a circular protruding structure with a width of 0.5mm to 5mm in the middle, so that the silicone rubber in this region is not in contact with two smooth surfaces of the second sealing film 402, but has a concave-convex structure, thereby forming air passages to facilitate air to enter the punctured holes of the second sealing film 402 through the air passages.
Fig. 13A-13F illustrate schematic diagrams of a driving assembly of a detection chip according to at least one embodiment.
The drive assembly 60 is movably received in the drive chamber 1011, the drive assembly 60 including a drive cap 6020 and a resilient member 6030, the resilient member 6030 being disposed between the drive cap 6020 and the drive chamber 1011. As used herein, the term "movable" refers to two elements that are capable of relative movement between the elements, including but not limited to sliding, rotating, screwing, and the like.
Illustratively, the drive assembly 60 further includes at least one second seal 6011, the at least one second seal 6011 being disposed between the drive cap 6020 and the drive chamber 1011 to seal a gap between the drive cap 6020 and the drive chamber 1011. Accordingly, the cylindrical periphery of the drive cap 6020 is provided with at least one second recess 6010. Alternatively, the cylindrical inner circumference of the drive chamber 1011 is provided with at least one second groove. The at least one second seal 6011 is correspondingly mounted in the at least one second groove. The at least one second seal 6011 may be, for example, a gasket.
Illustratively, a sliding structure may also be provided between the drive cavity 1011 and the drive cap 6020. Fig. 13A to 13F exemplarily show an alternative embodiment of the sliding structure. For example, the drive cap 6020 may include a snap 6021 disposed about the cylindrical periphery thereof that cooperates with the slot structure 1021 in the inner wall of the drive chamber 1011 to provide an upper and lower limit therebetween by the slot structure 1021 during a piston movement. A slot feature 1021 is provided on the upper side of the drive chamber 1011 and is rectangular in shape and sized to match the catch 6021. Other movable structures may be employed by those skilled in the art, and the present disclosure is not limited thereto.
The elastic member 6030 is loaded inside the drive chamber 1011 as shown in fig. 13A to 13F. After the drive chamber 1011, resilient member 6030 and drive cap 6020 are assembled together, the resilient member 6030 is in a compressed state due to the location of the catch 6021 and channel structure 1021. At this time, the external device presses the driving cap 6020 and the gas inside the driving chamber 1011 is exhausted. When the pressing force of the external device is removed, the driving cap 6020 automatically rebounds under the action of the elastic member 6030, and the external air enters the driving chamber 1011.
FIGS. 14A and 14B show schematic diagrams of an amplification chamber of a detection chip according to at least one embodiment. FIG. 14A is an exploded perspective view of an amplification chamber, and FIG. 14B is a top view of an amplification substrate of the amplification chamber.
Amplification chamber 71 may be configured to be removably mounted to base 100 and includes an upper membrane 701, an amplification substrate 702, and a lower membrane 703. The upper film 701 and the lower film 703 are bonded to the upper and lower surfaces of the amplification substrate 702, respectively, and assembled together, and the upper film 701 and the lower film 703 are made of a transparent film material, preferably a PC or PP material, and have a thickness in the range of 0.01 to 0.2 mm.
The amplification substrate 702 is a sheet having a cut structure with a thickness of 0.01 to 2 mm. The amplification substrate 702 has a reaction region 7022 and at least one bubble-removing region 7021 which are connected to each other, and the reaction region 7022 is a PCR amplification region and is formed in a shuttle shape. The bubble removal zone 7021 is located on the upstream side and/or the downstream side of the reaction zone 7022. In this embodiment, the amplification substrate 702 includes two bubble removal regions 7021, which are located on the upstream side and the downstream side of the reaction region 7022, respectively. For example, the bubble removal region 7021 may be circular with a diameter of 1-3mm to intercept bubbles in the reagent.
The detection chip of the embodiment of the present disclosure may be mounted to an appropriate position of the detection apparatus of the embodiment of the present disclosure to complete the detection process in cooperation with the detection apparatus.
FIG. 15 shows a detection device according to an embodiment of the present disclosure.
The detecting chip 1000 includes a first chip positioning structure 1040 for positioning the detecting chip 1000 to a suitable position of the detecting device 2000, for example, the detecting chip 1000 is fixed so as to be used for transmission and detection. For example, the first chip positioning structure 1040 may include a chip positioning hole provided in the base 100, which may be a circular through hole having a diameter in the range of 0.1-10mm, for cooperating with a positioning pin on the inspection device 2000 as the second chip positioning structure 2001 to position the inspection chip 1000 onto the inspection device 2000. For another example, the first chip positioning structure may include elongated chip positioning grooves on both sides of the detecting chip 1000 for matching with the fixing device on the detecting device 2000 to fix the chip onto the detecting device 2000.
The detection apparatus 2000 may include the jack 90 as described above as the first operating portion 2010 for changing the volume of the cavity. For example, the ejector 90 may be plural as needed, and the plural ejectors 90 are respectively disposed above different cavities to change the volumes of the cavities. Alternatively, the detection device 2000 may comprise a ram 90 that is movable over different cavities.
The scope of the present disclosure is not defined by the above-described embodiments but is defined by the appended claims and equivalents thereof.

Claims (37)

1. A detection chip, comprising:
a substrate having a first surface and comprising at least one cavity having a first opening in the first surface and at least one fluid channel leading to the at least one cavity; one of the at least one fluid channel is provided with a switch valve for controlling the connection and disconnection of the corresponding at least one fluid channel;
an amplification chamber in communication with the at least one fluid channel; and
a sealing cover coupled with the base and sealing the first opening of the base.
2. The detection chip of claim 1, further comprising:
at least one storage container received in the at least one cavity through the first opening, the at least one storage container including a second opening and a first sealing membrane sealing the second opening.
3. The detection chip of claim 2, further comprising:
at least one first sealing member disposed between the storage container and the cavity to seal a gap between the storage container and the cavity.
4. The detection chip according to claim 3,
the outer surface of the storage container is provided with at least one groove, or the inner surface of the cavity is provided with at least one groove,
the at least one first seal is mounted in the at least one groove.
5. The test chip of claim 2, wherein the at least one cavity comprises a breaching structure disposed in the cavity for breaching the first sealing membrane to allow the reagent in the reservoir to enter the at least one fluid channel.
6. The detection chip of claim 1, further comprising:
a mixing structure, wherein the at least one cavity is in communication with the mixing structure through at least one of the plurality of fluid passageways,
wherein, the mixing structure including ventilative mouthful, barrier film, power chamber and with the mixing chamber of power chamber intercommunication, the power chamber with communicate through many fluid passage respectively between a plurality of cavitys, ventilative mouthful setting is in sealed covering, the barrier film covers ventilative mouthful, the base member passes through ventilative mouthful with barrier film and external atmosphere intercommunication.
7. The detection chip according to claim 1, wherein the amplification chamber has a reaction region and a bubble removal region that are in communication with each other.
8. The detection chip according to claim 7, wherein the bubble removing region is located on an upstream side and/or a downstream side of the reaction region.
9. The detecting chip according to claim 7 or 8, wherein the reaction region is formed in a shuttle shape and the bubble removing region is formed in a circular shape.
10. The detection chip of claim 1, further comprising:
a drive chamber in fluid communication with the amplification chamber.
11. The detection chip of claim 10, further comprising:
a drive assembly movably received in the drive chamber, the drive assembly including a drive cap and a resilient member disposed between the drive cap and the drive chamber.
12. The detection chip according to claim 10,
the drive assembly further comprising at least one second seal disposed between the drive cap and the drive chamber to seal a void between the drive cap and the drive chamber,
the outer surface of the driving cover is provided with at least one groove, or the inner surface of the driving cavity is provided with at least one groove,
the at least one second seal is correspondingly mounted in the at least one groove.
13. The detection chip according to claim 11 or 12, wherein a sliding structure is disposed between the driving cavity and the driving cover, the sliding structure includes a buckle disposed on an outer surface of the driving cover and a groove structure disposed on an inner surface of the driving cavity, and the buckle cooperates with the groove structure to enable the buckle to slide in the groove structure and to be limited up and down.
14. The detection chip according to claim 2,
the at least one storage container further comprises a third opening and a second sealing membrane sealing the third opening,
the first sealing film and the second sealing film define a reservoir space therebetween for containing a reagent.
15. The detection chip of claim 5, wherein the breaching structure is located at an end of the cavity opposite the first opening.
16. The detection chip according to claim 15,
the storage container includes a drainage channel and an inner wall having an inclined first angle toward an end of the second opening, the drainage channel communicating the inner wall and the second opening.
17. The detection chip of claim 16,
the first angle ranges from 5 degrees to 60 degrees.
18. The detection chip according to claim 15,
the cavity further comprises a liquid guide channel, the substrate further comprises a fluid channel,
the liquid guide channel is arranged at the puncture structure and is communicated with the cavity and the fluid channel.
19. The detection chip of claim 18,
the inner diameter of the liquid guide channel is the same as that of the fluid channel.
20. The detection chip of claim 19,
one end of the puncture structure facing the storage container is provided with a needle-shaped protruding portion, and the size of the needle-shaped protruding portion is smaller than that of the second opening.
21. The detection chip of claim 20,
the needle-shaped protrusion is pyramid-shaped and has a plurality of side edges, and the opening of the liquid guide channel in the cavity is located between two of the side edges and is connected with the bottom surface and one side surface of the pyramid.
22. The detection chip of claim 20,
the needle-shaped protrusion part is a cone, and the opening of the liquid guide channel in the cavity is connected with the bottom surface of the cone.
23. The detection chip according to claim 21 or 22,
the area of the opening of the liquid guide channel in the cavity is smaller than the area of the bottom surface of the needle-shaped protrusion.
24. The detection chip of claim 14,
the first sealing film and/or the second sealing film are flexible films or composite aluminum films, and the materials of the flexible films comprise at least one of PE, PP or PS.
25. The detection chip according to claim 1,
the sealing cover is clamped with the base body.
26. The detection chip of claim 25,
the sealing cover comprises a cover body and a buckle assembly, wherein the buckle assembly comprises at least one first buckle arranged at the outer peripheral part of the cover body and a second buckle arranged at the central part of the cover body.
27. The detection chip of claim 26,
the sealing cover further comprises a sealing ring, and the sealing ring is arranged on the inner side of the peripheral portion of the cover body.
28. The detection chip of claim 27, wherein the cap body and snap assembly are formed of a rigid material and the sealing ring is formed of a flexible material.
29. The detection chip of claim 26, wherein the sealing cap is provided with a cover film at the first opening.
30. The detection chip of claim 29, wherein the cover film is an elastic film.
31. The detection chip according to claim 29, wherein a surface of the cover film facing the first opening is provided with a protrusion structure.
32. The detection chip of claim 31, wherein the protrusion structure comprises a central protrusion and a plurality of peripheral protrusions distributed circumferentially around the central protrusion.
33. The detecting chip according to claim 32, wherein the central protrusion has a straight shape, a cross shape, or a circular shape, and the plurality of peripheral protrusions have a straight shape or a circular shape.
34. The detection chip according to claim 6, wherein the substrate is provided with a flow channel convergence structure between the power cavity and the at least one cavity.
35. The detecting chip of claim 34, wherein the central portion of the flow channel converging structure is circular, and a plurality of trapezoid structures are uniformly distributed around the circumference of the central portion.
36. The detection chip of claim 6, further comprising:
and the magnetic bead capturing cavity is arranged between the power cavity and the mixing cavity and is respectively communicated with the power cavity and the mixing cavity.
37. The detection chip of claim 36, wherein the area or size of the middle region of the bead capture chamber is larger than the area or size of the two end regions.
CN202110051360.4A 2021-01-15 2021-01-15 Detection chip Active CN112371195B (en)

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