CN110656024A - Micro-fluidic chip and biochemical detection device - Google Patents

Micro-fluidic chip and biochemical detection device Download PDF

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Publication number
CN110656024A
CN110656024A CN201810692234.5A CN201810692234A CN110656024A CN 110656024 A CN110656024 A CN 110656024A CN 201810692234 A CN201810692234 A CN 201810692234A CN 110656024 A CN110656024 A CN 110656024A
Authority
CN
China
Prior art keywords
gas
reaction chamber
microfluidic chip
reaction
cavity
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
CN201810692234.5A
Other languages
Chinese (zh)
Inventor
闵小平
葛胜祥
张师音
张东旭
苏晓崧
付达
翁振宇
陈文堤
翁祖星
宋浏伟
张军
夏宁邵
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 Wantai Kairui Biological Technology Co Ltd
Xiamen University
Original Assignee
Xiamen Wantai Kairui Biological Technology Co Ltd
Xiamen University
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 Wantai Kairui Biological Technology Co Ltd, Xiamen University filed Critical Xiamen Wantai Kairui Biological Technology Co Ltd
Priority to CN201810692234.5A priority Critical patent/CN110656024A/en
Publication of CN110656024A publication Critical patent/CN110656024A/en
Pending legal-status Critical Current

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Classifications

    • 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
    • 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
    • B01L3/502723Containers 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 venting arrangements
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • 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
    • B01L2200/12Specific details about manufacturing devices

Abstract

The invention relates to the technical field of biochemical detection, in particular to a micro-fluidic chip and a biochemical detection device. The invention provides a microfluidic chip, comprising: a reaction chamber; the reagent inlet flow channel is communicated with the reaction cavity liquid, and the reagent flows into the reaction cavity through the reagent inlet flow channel; the on-off control device is arranged on the reagent inlet flow passage and is used for controlling the on-off of the reagent inlet flow passage; and the gas accommodating device is provided with a gas accommodating cavity, the capacity of the gas accommodating cavity is variable, and the gas accommodating cavity is hermetically communicated with the reaction cavity and is used for accommodating gas exhausted from the reaction cavity. By arranging the gas containing device, the invention can form a flexible sealing mode, effectively reduce the pressure of the reaction cavity caused by expansion with heat and contraction with cold and improve the working reliability of the microfluidic chip.

Description

Micro-fluidic chip and biochemical detection device
Technical Field
The invention relates to the technical field of biochemical detection, in particular to a micro-fluidic chip and a biochemical detection device.
Background
The microfluidic chip is a technology for processing pipelines and reaction chambers on the chip and driving reagents to flow in the pipelines and the chambers so as to complete various biological and chemical processes. In recent years, micro-fluidic chips are rapidly developing towards functionalization and integration, and important biological and chemical processes such as nucleic acid amplification reaction, immune reaction and the like become new hot spots.
Along with the biochemical reaction on the chip, how to solve the problem that the reaction product leakage generated on the chip pollutes the outside is a very critical problem. At present, the common method is to seal the reaction cavity by a valve, open the valve, and seal the valve after the reagent enters, so as to achieve the sealing effect. However, at least two flow paths are required between the reaction chamber and the valve, one for the reagent and one for the air, and the design is complicated. Moreover, the seal in this case is a rigid seal, and if the reaction requires heat treatment, the reaction chamber and the valve are subjected to pressure due to thermal expansion and cold contraction, which is likely to cause problems and reduce the operational reliability of the microfluidic chip.
Disclosure of Invention
The invention aims to solve the technical problems that: the working reliability of the microfluidic chip is improved.
In order to solve the above technical problem, a first aspect of the present invention provides a microfluidic chip, including:
a reaction chamber;
the reagent inlet flow channel is communicated with the reaction cavity liquid, and the reagent flows into the reaction cavity through the reagent inlet flow channel;
the on-off control device is arranged on the reagent inlet flow passage and is used for controlling the on-off of the reagent inlet flow passage; and the combination of (a) and (b),
and the gas accommodating device is provided with a gas accommodating cavity, the capacity of the gas accommodating cavity is variable, and the gas accommodating cavity is in gas communication with the reaction cavity in a sealing mode and is used for accommodating gas exhausted from the reaction cavity.
Optionally, the walls of the gas containment chamber are non-elastic.
Optionally, the gas-containing means comprises a bag.
Optionally, the bag is a plastic bag.
Optionally, the gas inlet of the gas receiving chamber is disposed above the highest liquid level in the reaction chamber.
Alternatively, the gas-containing device communicates with one of the two corners of the upper portion of the reaction chamber, and the reagent-entering flow passage communicates with the other of the two corners of the upper portion of the reaction chamber.
Optionally, the gas-containing means is hot pressed or chemically bonded to the reaction chamber.
Optionally, the on-off control comprises a valve.
Optionally, the microfluidic chip is a nucleic acid amplification microfluidic chip.
The second aspect of the invention also provides a biochemical detection device which comprises the microfluidic chip of the invention.
The gas containing device is arranged, so that a flexible sealing mode can be formed, compared with the existing rigid sealing mode, the pressure of the reaction cavity caused by expansion with heat and contraction with cold can be effectively reduced, the influence of the expansion with heat and the contraction with cold on the reaction cavity is reduced, and the working reliability of the microfluidic chip is improved.
Other features of the present invention and advantages thereof will become apparent from the following detailed description of exemplary embodiments thereof, which proceeds with reference to the accompanying drawings.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to these drawings without creative efforts.
Fig. 1 shows a schematic diagram of the structure of a microfluidic chip according to an embodiment of the present invention.
In the figure:
1. a reaction chamber; 2. the reagent enters the flow channel; 3. a valve; 4. a plastic bag; 41. an air inlet.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. The following description of at least one exemplary embodiment is merely illustrative in nature and is in no way intended to limit the invention, its application, or uses. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without any inventive step, are within the scope of the present invention.
Techniques, methods, and apparatus known to those of ordinary skill in the relevant art may not be discussed in detail but are intended to be part of the specification where appropriate.
In the description of the present invention, it is to be understood that the orientation or positional relationship indicated by the orientation words such as "front, rear, upper, lower, left, right", "lateral, vertical, horizontal" and "top, bottom", etc. are usually based on the orientation or positional relationship shown in the drawings, and are only for convenience of description and simplicity of description, and in the case of not making a reverse description, these orientation words do not indicate and imply that the device or element being referred to must have a specific orientation or be constructed and operated in a specific orientation, and therefore, should not be considered as limiting the scope of the present invention; the terms "inner and outer" refer to the inner and outer relative to the profile of the respective component itself.
In the description of the present invention, it should be understood that the terms "first", "second", etc. are used to define the components, and are used only for the convenience of distinguishing the corresponding components, and if not otherwise stated, the terms have no special meaning, and thus, should not be construed as limiting the scope of the present invention.
Fig. 1 shows an embodiment of a microfluidic chip according to the present invention. Referring to fig. 1, the microfluidic chip provided by the present invention includes:
a reaction chamber 1;
the reagent inlet flow channel 2 is in liquid communication with the reaction cavity 1, and the reagent flows into the reaction cavity 1 through the reagent inlet flow channel 2;
the on-off control device is arranged on the reagent inlet flow channel 2 and is used for controlling the on-off of the reagent inlet flow channel 2; and the combination of (a) and (b),
and the gas accommodating device is provided with a gas accommodating cavity I, the capacity of the gas accommodating cavity I is variable, and the gas accommodating cavity I is in gas communication with the reaction cavity 1 in a sealing mode and is used for accommodating gas exhausted from the reaction cavity 1.
Based on the arrangement, when a reagent is required to enter the reaction chamber 1, the on-off control device can be opened, so that the reagent flows into the reaction chamber 1 through the reagent inlet runner 2, and gas exhausted by extrusion due to the inflow of the reagent in the reaction chamber 1 flows into the gas accommodating chamber I, namely, the gas accommodating chamber I accommodates the gas exhausted from the reaction chamber 1 in the process of the reagent entering the reaction chamber 1, so that the reagent can conveniently and smoothly enter, and the gas in the reaction chamber 1 can be prevented from leaking in the process; after the reagent enters, the on-off control device can be closed, and at the moment, the whole reaction chamber 1 is in a sealed state under the matching of the on-off control device and the gas containing device; and in the testing process, if the reaction needs to be heated, then in the heating process, the gas that is heated and expanded in the reaction chamber 1 can flow into in the gas holds chamber I, it holds chamber I to be held by the gas, make gas release the pressure that reaction chamber 1 increases because of being heated and expanded, and in the cooling process, the gas that gas holds in the chamber I can flow back to in the reaction chamber 1 again, fill the space that gas vacated because of the shrinkage that receives in the reaction chamber 1, make gas also compensate the pressure that reaction chamber 1 reduces because of the shrinkage that receives, it can see, gas accommodating device can release the pressure variation that is received because of expend with heat and contract with cold by sealed reaction chamber 1, prevent that reaction chamber 1 from appearing the problem because of bearing the pressure variation.
According to the analysis, the gas containing device can be matched with the on-off control device to form flexible sealing on the reaction cavity 1, so that the risk that the reaction cavity 1 is in a problem caused by pressure caused by expansion with heat and contraction with cold in the reaction process is reduced, and the working reliability of the microfluidic chip is effectively improved.
In addition, it is easy to understand that, besides the reaction chamber 1 can be prevented from bearing pressure due to expansion with heat and contraction with cold, the gas containing device provided by the invention can also be used for preventing the on-off control device from bearing pressure due to expansion with heat and contraction with cold, which is beneficial to further improving the working reliability of the microfluidic chip.
In addition, the gas accommodating device can accommodate the gas exhausted from the reaction cavity 1, so that a special flow channel for exhausting the air is not required to be additionally arranged between the on-off control device and the reaction cavity 1 like the prior art, the number of the flow channels can be effectively reduced, the structure is simplified, and the implementation is convenient.
According to the gas containing device, the cavity wall of the gas containing cavity I can be set to be inelastic, so that the capacity change of the gas containing cavity I does not depend on the elastic deformation of the cavity wall of the gas containing cavity I but completely depends on the inlet and outlet of gas relative to the condition that the cavity wall of the gas containing cavity I is elastic, the pressure of the reaction cavity 1 and the on-off control device is prevented from being influenced due to the reaction of the elastic deformation of the cavity wall of the gas containing cavity I on the reaction cavity 1 and the on-off control device, and therefore the pressure of the reaction cavity 1 and the on-off control device in the expansion and contraction process can be reliably reduced, and the working reliability of the microfluidic chip is effectively improved.
The microfluidic chip of the present invention is further described below with reference to the embodiment shown in fig. 1.
As shown in fig. 1, in this embodiment, the microfluidic chip includes a reaction chamber 1, a reagent inlet channel 2, a valve 3, and a plastic bag 4.
Wherein, the reaction chamber 1 is a place where the reagent reacts and provides a space for biochemical reaction. As can be seen from FIG. 1, the reaction chamber 1 of this embodiment has a rectangular longitudinal section.
The reagent inlet flow channel 2 is a flow-through channel through which the reagent enters the reaction chamber 1, and is in liquid communication with the reaction chamber 1 so that the reagent can flow into the reaction chamber 1 therethrough. As can be seen from FIG. 1, the reagent inlet channel 2 of this embodiment communicates with one of the two corners of the upper part of the reaction chamber 1 (specifically, the upper left corner of the reaction chamber 1 in FIG. 1).
The valve 3 is used as an on-off control means provided on the reagent inlet flow path 2 for controlling on-off of the reagent inlet flow path 2 to control whether or not the reagent is introduced into the reaction chamber 1. When the valve 3 is opened, the reagent inlet flow channel 2 is communicated, and the reagent can enter the reaction cavity 1 through the reagent inlet flow channel 2; when the valve 3 is closed, the reagent inlet channel 2 is disconnected, the reagent can not enter the reaction chamber 1 through the reagent inlet channel 2 any more, and the reaction chamber 1 is sealed at one side of the sample inlet. The valve 3 of this embodiment may be any valve that can perform the function of opening and closing a flow channel or connecting and disconnecting a flow channel and may be integrated on a microfluidic chip.
The plastic bag 4 serves as a gas containing means, and the inner cavity thereof serves as a gas containing chamber I which is in sealed gas communication with the reaction chamber 1 through a gas inlet 41 at the end thereof for containing the gas exhausted from the reaction chamber 1 and changes its volume as the gas enters and exits, so as to release the pressure change in the reaction chamber 1 and maintain the pressure in the reaction chamber 1 substantially constant. As can be seen from FIG. 1, the plastic bag 4 communicates with the other of the two corners of the upper part of the reaction chamber 1 (specifically, the upper right corner of the reaction chamber 1 in FIG. 1).
Initially, the plastic bag 4 is flat with almost no air inside. In the use process of the microfluidic chip, when liquid needs to be fed, the valve 3 is opened, liquid enters the reaction cavity 1 through the reagent inlet flow channel 2, and simultaneously discharged air enters the gas accommodating cavity I of the plastic bag 4, so that the plastic bag 4 is gradually inflated; after the liquid feeding is completed, the valve 3 is closed to close the liquid feeding port of the reaction chamber 1, at this time, the valve 3 and the plastic bag 4 together have a sealing effect on the whole reaction chamber 1, and the sealing is no longer a rigid sealing due to the effect of the plastic bag 4, but a flexible sealing, because in this case, if the reaction process needs heating or refrigeration, the gas accommodating chamber I of the plastic bag 4 can accommodate the gas exhausted from the reaction chamber 1 or re-exhaust the gas into the reaction chamber 1, and the pressure is released, so that the reaction chamber 1 and the valve 3 can not bear the internal or external pressure during the thermal expansion and cold contraction process due to the sealing, for example, during the heating reaction, the air expanded by heating can enter the gas accommodating chamber I of the plastic bag 4 to swell the plastic bag 4, at this time, the reaction chamber 1 still keeps sealing under the effect of the valve 3 and the valve 4, and the reaction chamber 1 and the valve 3 can not bear the pressure caused by the expanded air due to the sealing, and when the reaction chamber is cooled, the plastic bag 4 is flattened again, and the gas in the gas accommodating chamber I is released into the reaction chamber 1 again, so that the reaction chamber 1 and the valve 3 are prevented from bearing the pressure caused by the contracted air because of sealing.
It can be seen that the plastic bag 4 and the valve 3 of this embodiment play the effect of flexible seal jointly, it can not only make things convenient for reagent to get into reaction chamber 1 at the feed liquor in-process, can also keep whole reaction chamber 1 sealed at whole reaction process, prevent that reaction product from revealing and arousing the pollution, and can make reaction chamber 1 and valve 3 can not bear inside or outside pressure because of the expend with heat and contract with cold after the sealed, thereby can prevent effectively that reaction chamber 1 and valve 3 from appearing the problem in the reaction process that needs heating or refrigeration, and then can effectively improve micro-fluidic chip's operational reliability.
And, this embodiment adopts plastic bag 4 as the gas container, on the one hand, plastic bag 4 can obstruct air, water vapor and oxygen etc. to reach good sealed effect, on the other hand, plastic bag 4 can not react with biochemical reagent in the reaction chamber 1, the reliability of use is higher, life is longer, on the other hand, because plastic bag 4 is inelastic bag, the chamber wall of its gas accommodation chamber 1 is inelastic, therefore, it can avoid influencing the pressure that reaction chamber 1 and valve 3 bore because of gas accommodation chamber I chamber wall elastic deformation produces the reaction chamber 1 and valve 3 and produce the reaction, thereby can reduce the pressure that reaction chamber 1 and valve 3 received in the thermal contraction expend process more reliably, improve the operational reliability of micro-fluidic chip more effectively. Of course, it will be understood that instead of the plastic bag 4, other bags of other materials, or even other structures than bags, may be used as the gas containing means.
Meanwhile, because the plastic bag 4 can contain the gas discharged from the reaction chamber 1, only one flow channel for the reagent to enter is required to be arranged between the reaction chamber 1 and the valve 3, and no flow channel special for discharging the air is required to be additionally arranged, specifically, as shown in fig. 1, only the reagent entering flow channel 2 is arranged between the valve 3 and the reaction chamber 1 in the embodiment, so that the use requirement can be met, and the structure is simpler.
As mentioned above, in this embodiment, the plastic bag 4 and the reagent inlet channel 2 are respectively connected to one and the other of two corners of the upper portion of the reaction chamber 1, so that the plastic bag 4 and the reagent inlet channel 2 are both connected to the upper portion of the reaction chamber 1 and located on two sides of the vertical center line of the reaction chamber 1, the arrangement is reasonable, the space is saved, the reagent is convenient to enter the reaction chamber 1, the gas can enter and exit the gas accommodating chamber I, and the reagent is also prevented from entering the plastic bag 4 to corrode the plastic bag 4 and other chemical damages.
In addition, as can be seen from fig. 1, in this embodiment, the air inlet 41 is set higher than the top wall of the reaction chamber 1, which enables the air inlet 41 to be always located above the highest liquid level in the reaction chamber 1, and can more effectively prevent the liquid in the reaction chamber 1 from entering the plastic bag 4 through the air inlet 41 to damage the plastic bag 4, and prolong the service life of the plastic bag 4.
In order to make the gas accommodating chamber I hermetically and pneumatically communicate with the reaction chamber 1, the plastic bag 4 of the embodiment is thermally pressed on the reaction chamber 1, specifically, the plastic bag 4 is thermally pressed on the upper right corner of the reaction chamber 1, so that the sealing effect is good, and the process is simple. However, it should be noted that, in addition to the hot pressing method, other methods such as chemical bonding may be used to achieve the sealed gas communication between the gas accommodating chamber I and the reaction chamber 1.
From the above, the microfluidic chip of the present invention has good sealing performance and high reliability, and is suitable for various microfluidic chips, especially for microfluidic chips requiring a reaction chamber capable of allowing a reagent to enter and maintaining a seal in a subsequent reaction process, such as a nucleic acid amplification microfluidic chip.
The micro-fluidic chip is applied to a biochemical detection device, and is matched with a sample feeding device and the like, so that the biochemical detection device can realize a safer and more reliable biochemical detection or test process. Therefore, the invention also provides a biochemical detection device which comprises the microfluidic chip.
The above description is only exemplary of the present invention and should not be taken as limiting the invention, as any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims (10)

1. A microfluidic chip, comprising:
a reaction chamber (1);
a reagent inlet channel (2) which is in liquid communication with the reaction chamber (1), and through which the reagent flows into the reaction chamber (1) via the reagent inlet channel (2);
the on-off control device is arranged on the reagent inlet flow channel (2) and is used for controlling the on-off of the reagent inlet flow channel (2); and the combination of (a) and (b),
the gas containing device is provided with a gas containing cavity (I), the gas containing cavity (I) is variable in volume and is in gas communication with the reaction cavity (1) in a sealing mode, and the gas containing cavity is used for containing gas exhausted from the reaction cavity (1).
2. Microfluidic chip according to claim 1, characterized in that the walls of the gas containment chamber (I) are inelastic.
3. The microfluidic chip according to claim 1, wherein the gas-containing means comprises a bag.
4. Microfluidic chip according to claim 3, wherein the bag is a plastic bag (4).
5. Microfluidic chip according to claim 1, characterized in that the gas inlet (41) of the gas containment chamber (I) is arranged above the highest liquid level in the reaction chamber (1).
6. The microfluidic chip according to claim 1, wherein the gas-containing device is connected to one of the two corners of the upper portion of the reaction chamber (1), and the reagent inlet flow channel (2) is connected to the other of the two corners of the upper portion of the reaction chamber (1).
7. The microfluidic chip according to claim 1, wherein the gas-containing means is thermally pressed or chemically bonded to the reaction chamber (1).
8. Microfluidic chip according to claim 1, characterized in that said on-off control means comprise a valve (3).
9. The microfluidic chip according to claim 1, wherein the microfluidic chip is a nucleic acid amplification microfluidic chip.
10. A biochemical detection device comprising the microfluidic chip according to any one of claims 1 to 9.
CN201810692234.5A 2018-06-29 2018-06-29 Micro-fluidic chip and biochemical detection device Pending CN110656024A (en)

Priority Applications (1)

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CN201810692234.5A CN110656024A (en) 2018-06-29 2018-06-29 Micro-fluidic chip and biochemical detection device

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CN106237934A (en) * 2010-08-30 2016-12-21 恩特格里斯公司 Prepared compound or its intermediate by solid material and use this compound and the equipment of intermediate and method
CN106669873A (en) * 2017-02-17 2017-05-17 深圳韦拓生物科技有限公司 Micro-fluidic chip for cell freezing, mixing system and control method of mixing system
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