CN113967492A - Multipurpose centrifugal micro-fluidic chip - Google Patents
Multipurpose centrifugal micro-fluidic chip Download PDFInfo
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- CN113967492A CN113967492A CN202111467101.6A CN202111467101A CN113967492A CN 113967492 A CN113967492 A CN 113967492A CN 202111467101 A CN202111467101 A CN 202111467101A CN 113967492 A CN113967492 A CN 113967492A
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- 239000007788 liquid Substances 0.000 claims abstract description 128
- 238000000926 separation method Methods 0.000 claims abstract description 58
- 238000001514 detection method Methods 0.000 claims abstract description 57
- 239000002699 waste material Substances 0.000 claims abstract description 31
- 238000006243 chemical reaction Methods 0.000 claims abstract description 25
- 239000000758 substrate Substances 0.000 claims abstract description 25
- 230000002209 hydrophobic effect Effects 0.000 claims abstract description 13
- 238000000034 method Methods 0.000 claims description 10
- 238000004026 adhesive bonding Methods 0.000 claims description 4
- 238000003860 storage Methods 0.000 claims description 4
- 238000003466 welding Methods 0.000 claims description 4
- 238000009826 distribution Methods 0.000 claims description 3
- 238000012827 research and development Methods 0.000 abstract description 4
- 238000009827 uniform distribution Methods 0.000 description 5
- 230000004907 flux Effects 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 238000012545 processing Methods 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 238000012935 Averaging Methods 0.000 description 1
- 238000005842 biochemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000008094 contradictory effect Effects 0.000 description 1
- 238000012864 cross contamination Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000005370 electroosmosis Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 244000000010 microbial pathogen Species 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 238000011896 sensitive detection Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers 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
- B01L3/50273—Containers 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
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/10—Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Dispersion Chemistry (AREA)
- Analytical Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Hematology (AREA)
- Clinical Laboratory Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Automatic Analysis And Handling Materials Therefor (AREA)
Abstract
The invention discloses a multipurpose centrifugal microfluidic chip, which comprises a cover plate, a hydrophobic breathable film and a substrate, wherein the cover plate is arranged on the substrate; the cover plate, the hydrophobic breathable film and the substrate are sequentially overlapped up and down to be combined into a whole; the substrate is provided with a rotating shaft connecting structure, liquid separating tanks are uniformly distributed around a geometric rotation center, and waste liquid tanks are arranged on the substrate around the geometric rotation center; the liquid separation tank and the waste liquid tank are respectively communicated through a detection tank, and a reaction tank is arranged in the detection tank or at the edge of one side of the detection tank; the substrate is provided with a waste liquid exhaust hole, a liquid separation tank exhaust hole and a sample inlet hole, the liquid separation tank exhaust hole and the sample inlet hole are communicated with the liquid separation tank, the waste liquid exhaust hole is communicated with a waste liquid tank through an exhaust channel, and the hole openings of the liquid separation tank exhaust hole and the waste liquid exhaust hole are respectively sealed through a hydrophobic breathable film; through holes are respectively arranged on the cover plate corresponding to the positions of the rotating shaft connecting structure, the sample inlet hole, the liquid separation tank exhaust hole and the waste liquid exhaust hole. The invention realizes the functions of evenly dividing and detecting the liquid by adopting low rotating speed, and reduces the research and development cost.
Description
Technical Field
The invention relates to the application in the fields of biomedicine and analytical chemistry, in particular to a multipurpose centrifugal microfluidic chip.
Background
In a micro total analysis system, the sharing, reaction and detection of a sample and a reagent are mainly realized by a micro-fluidic chip. With the development of microfluidic technology, the driving modes of microfluidic chips mainly include pressure driving, electroosmotic flow driving, surface tension driving, centrifugal driving and the like. The centrifugal driving mode is that a sample to be detected is conveyed to the interior of the chip by utilizing centrifugal force, has the characteristics of compact structure, wide range of applicable samples, large range of flow rate regulation and the like, and is widely applied to the fields of biomedicine and analytical chemistry.
At present, the scheme of utilizing centrifugal drive to realize liquid and equalling divide has a lot, mainly has two kinds of modes: one is to realize uniform distribution of liquid in a wave-shaped channel by utilizing high rotating speed, for example, the patent document with Chinese patent publication No. CN102369443A discloses a centrifugal sample analysis chip which is composed of a wave-shaped detection groove, a buffer hole and a reaction hole; the micro-fluidic chip detection groove is wavy, the channel structure is complex, the processing difficulty is high, the processing cost is high, each reaction hole is distributed at the edge of the circumferential micro-fluidic chip, and the sample detection flux is small; because the micro-fluidic chip only adopts one sample adding channel, the detection sample is single and cannot adapt to the situation of diversified detection samples; in addition, the microfluidic chip needs to use a higher rotation speed to drive the liquid to move, and the research and development cost and the manufacturing cost of the instrument are also increased. The other is to adopt the structure such as the quantitative component, sample-dividing component and siphon valve to realize the equipartition operation of the liquid, for example Chinese patent publication No. CN207586245U, disclose a detect the centrifugal micro-fluidic chip of the pathogenic microorganism, the micro-fluidic chip is made up of sample application pool, sample-dividing component and reaction element, utilize centrifugal force to transport the sample in the sample application pool to the reaction pool through siphon valve and sample-dividing component, the micro-fluidic chip can guarantee the homogeneity of the liquid equipartition time, but the number of the reaction pool is less, detect the flux is small, can't adapt to the occasion that the sample detects the index many too; meanwhile, the micro-fluidic chip is often driven by multiple stages of rotating speeds, so that the research and development and manufacturing costs are greatly increased.
Disclosure of Invention
The invention aims to provide a multipurpose centrifugal microfluidic chip with high throughput and diversified detection sample types, which realizes the uniform distribution and detection of liquid and has low manufacturing cost.
In order to achieve the purpose, the invention can adopt the following technical scheme:
the multipurpose centrifugal microfluidic chip comprises a cover plate, a hydrophobic breathable film and a substrate; the cover plate, the hydrophobic breathable film and the substrate are sequentially overlapped up and down and are combined into a whole through laser welding, hot-press bonding or gluing; a rotating shaft connecting structure is arranged on the substrate at the geometric rotation center, a plurality of liquid separation tanks are uniformly distributed around the geometric rotation center, and a waste liquid tank is arranged on the substrate around the geometric rotation center and used for collecting redundant samples; each liquid separation tank is communicated with the waste liquid tank through a detection tank, and a reaction tank is arranged in the detection tank or at the edge of one side of the detection tank; a waste liquid exhaust hole, a liquid separation pool exhaust hole and a sample inlet hole which are of an upper opening structure are formed in the substrate; the liquid separation pool vent hole is used for keeping the air pressure in the detection groove constant in the rotation process of the microfluidic chip; the exhaust hole of the liquid separation tank and the sample inlet hole are respectively communicated with the liquid separation tank, the waste liquid exhaust hole is communicated with the waste liquid tank through an exhaust channel, and the orifices of the exhaust hole of the liquid separation tank and the waste liquid exhaust hole are respectively sealed through the hydrophobic breathable film; through holes are respectively arranged on the cover plate corresponding to the positions of the rotating shaft connecting structure, the sample inlet hole, the liquid separation tank exhaust hole and the waste liquid exhaust hole.
Preferably, the detection groove is a straight groove or an arc-shaped groove, and a capillary passive valve is arranged at the joint of the detection groove and the liquid distribution pool; and the capillary passive valve is used for preventing liquid from entering the detection groove during sample adding.
Preferably, the reaction tank can be in a shape of a circular hole, a square hole, a kidney-shaped hole or the like which can realize a liquid storage function; the diameter of the circular hole or the width of the square hole is equal to, smaller than or larger than the width of the detection slot.
Preferably, the straight or arc-shaped groove is inclined clockwise or counterclockwise, i.e. the inclination direction is opposite to the rotation direction of the microfluidic chip during operation.
Preferably, the capillary passive valve is a structural valve.
Preferably, the sample inlet hole is a tapered hole matched with the standard pipette tip in size, and a flexible mould is covered above the sample inlet hole, so that the standard pipette tip can be inserted and sealed conveniently.
Preferably, a plurality of reaction tanks are arranged in each detection tank, and the volume of each liquid separation tank is equal to 1.2-1.5 times of the total volume of the reaction tanks communicated with the liquid separation tank, so as to realize primary uniform distribution of liquid.
Preferably, a plurality of the liquid separation tanks are communicated with each other, and the planar shape of each liquid separation tank can be a sector, a semicircle or a semi-ellipse.
The invention realizes the functions of liquid averaging and detection by adopting low rotating speed, is suitable for the range of 0-500 r/min, and reduces the research and development cost of instruments matched with the liquid. Compared with the prior art, the liquid storage tank and the liquid separation tank are combined, a siphon valve is not used, the structure is simple, and the processing difficulty is low; and the quantitative and uniform distribution operation of the liquid can be realized only by using one section of rotating speed, and the operation is convenient and fast. The arc-shaped detection tank structure is adopted, and centrifugal force in the rotation process is utilized to force liquid in the detection tank to flow along the wall, so that the uniform distribution operation of the liquid in the reaction tank is realized. Meanwhile, compared with the linear detection groove arranged along the radial direction, the length of the detection groove is prolonged, and the flux of sample detection is increased. A plurality of liquid separating pools are arranged, so that the uniform separation and detection of different types of samples are realized. The liquid separation pool is in radiation distribution from the geometric rotation center of the substrate to the periphery, so that cross contamination among samples of the liquid separation pool is avoided.
Drawings
Fig. 1 is a schematic axial view of the structure of embodiment 1 of the present invention.
Fig. 2 is a schematic view of the structure of the substrate of fig. 1.
Fig. 3 is a schematic view of the structure of a substrate in embodiment 2 of the present invention.
Fig. 4 is a schematic view of the structure of a substrate in embodiment 3 of the present invention.
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. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
It should be noted that all the directional indicators (such as up, down, left, right, front, and rear … …) in the embodiment of the present invention are only used to explain the relative position relationship between the components, the movement situation, etc. in a specific posture (as shown in the drawing), and if the specific posture is changed, the directional indicator is changed accordingly.
In the present invention, unless otherwise expressly stated or limited, the terms "connected," "secured," and the like are to be construed broadly, and for example, "secured" may be a fixed connection, a removable connection, or an integral part; can be mechanically or electrically connected; they may be directly connected or indirectly connected through intervening media, or they may be connected internally or in any other suitable relationship, unless expressly stated otherwise. The specific meanings of the above terms in the present invention can be understood by those skilled in the art according to specific situations.
In addition, the meaning of "and/or" appearing throughout is to include three juxtapositions, exemplified by "A and/or B," including either the A or B arrangement, or both A and B satisfied arrangement. In addition, technical solutions between various embodiments may be combined with each other, but must be realized by a person skilled in the art, and when the technical solutions are contradictory or cannot be realized, such a combination should not be considered to exist, and is not within the protection scope of the present invention.
Example 1:
as shown in figures 1 and 2, the multipurpose centrifugal microfluidic chip comprises a cover plate 1 in a disc structure, a hydrophobic breathable film 2 and a base plate 3 in a disc structure. The cover plate 1, the hydrophobic breathable film 2 and the substrate 3 are sequentially overlapped up and down and are combined into a whole through laser welding, hot-press bonding or gluing.
Three rotating shaft connecting holes 4 are uniformly distributed on the substrate 1 at the radius position set by the circle center point o and are used for realizing the fixation and rotation of the microfluidic chip.
Twelve liquid separation tanks 5 are uniformly distributed around the circle center o point of the substrate 1, the planar shape of each liquid separation tank 5 can be fan-shaped, semicircular or semi-elliptical, and all the liquid separation tanks 5 are sequentially communicated; of course, the liquid separation tank 5 can be divided into different chambers according to the type of the detected sample.
An annular waste liquid groove 7 is formed in the position, close to the edge, of the substrate 1 in a circle o mode, and is used for collecting redundant samples in the detection process.
Each liquid separation tank 5 is respectively communicated with a waste liquid tank 7 through a detection tank 8, the detection tank 8 is an arc-shaped tank arranged in the clockwise direction and is opposite to the rotation direction (anticlockwise) of the micro-fluidic chip during working, a plurality of reaction tanks 9 are arranged in the detection tank 8 at intervals in the clockwise direction, and the detection of a sample is realized by respectively pre-burying substances for biochemical reaction, immunodiagnosis or drug sensitive detection.
The arc-shaped grooves arranged in the clockwise direction aim to:
1. when the microfluidic chip rotates anticlockwise, the centrifugal force drives the liquid to flow along the curved side wall, so that the liquid can break through the tension between the detection groove 8 and the reaction tank 9 more easily and enter the reaction tank 9; 2. the length of the detection groove 8 is prolonged, and the flux of sample detection is increased.
The radian of the detection groove 8 can be a standard semicircular arc, an elliptic arc or an arc conforming to the archimedes spiral track; the reaction tank 9 can be any shape capable of realizing a liquid storage function, such as a circular hole, a square hole or a waist-shaped hole; the diameter of the circular hole or the width of the square hole is equal to, smaller than, or larger than the width of the detection slot 8.
The volume of each liquid separation pool 5 is equal to 1.2-1.5 times of the total volume of all reaction pools 9 in the detection tank 8 communicated with the liquid separation pool, and the liquid separation pool is used for realizing primary uniform separation of liquid.
A cross-shaped capillary passive valve 10 (a linear capillary passive valve or any other shape can be selected) is arranged at the joint of the detection tank 8 and the liquid separation tank 5; and the capillary passive valve is used for preventing liquid from entering the detection groove 8 during sample adding.
A waste liquid exhaust hole 11 with a step hole structure, a liquid separation tank exhaust hole 12 and a sample inlet hole 13 are formed in the substrate 3; the liquid separation pool vent hole 12 is used for keeping the air pressure in the detection groove 8 constant in the rotation process of the microfluidic chip; the liquid separation tank exhaust hole 12 and the sample inlet hole 13 are respectively communicated with the liquid separation tank 5, and the waste liquid exhaust hole 11 is communicated with the waste liquid tank 7 through the exhaust channel 6; the sample inlet hole 13 is a tapered hole matched with the standard pipette tip in size, and a flexible mold is covered above the sample inlet hole to facilitate the insertion and sealing of the standard pipette tip.
The diameter of the hydrophobic breathable film 2 is respectively matched with the waste liquid exhaust hole 11 and the liquid separation tank exhaust hole 12 of the corresponding step hole structure; in actual manufacturing, the hydrophobic breathable film 2 is respectively sealed in the waste liquid exhaust hole 11 and the liquid separation tank exhaust hole 12, and then is combined into a whole through laser welding, hot-press bonding or gluing.
Through holes 4.1, 13.1, 12.1 and 11.1 matched with the rotating shaft connecting hole 4, the sample inlet hole 13, the liquid separation tank exhaust hole 12 and the waste liquid exhaust hole 11 are respectively arranged on the cover plate 1.
Example 2:
as shown in FIG. 3, the present embodiment is different from embodiment 1 in that a reaction cell 9 is provided at one side edge of a detection tank 8 and is communicated with the detection tank 8; thus, the width of the arc detection groove 8 can be reduced.
Example 3:
as shown in fig. 4, the present embodiment is different from embodiment 1 in that the detection groove 8 is a straight groove arranged in a clockwise direction.
As shown in fig. 1 and 2, taking embodiment 1 as an example, the working process of the present invention is briefly described as follows:
1-4 ml of sample is added into the liquid separation tank 5 from the sample inlet hole 13, gas in the sample adding bin is discharged from the gas outlet hole 12 of the liquid separation tank in the sample adding process, no bubble appears in the liquid after the liquid separation tank 5 is filled with the liquid, and the liquid sequentially fills each liquid separation tank 5.
Placing the micro-fluidic chip added with the sample on a centrifugal detection platform, and rotating counterclockwise for 2-5 s at the rotating speed of 150-350 r/min; in rotatory in-process, liquid in the liquid separation pond 5 breaks through capillary passive valve 10 under centrifugal force's drive and enters into the arc and detects 8 in the groove, and under centrifugal force, liquid hugs closely the arc and detects 8 lateral walls flows, and when liquid flows to reaction tank 9 edges, because the influence of liquid surface tension, liquid flow is obstructed, and liquid produces and piles up, along with piling up the increase of liquid quality, liquid breaks through tension, enters into in the reaction tank 9.
The liquid amount in the liquid separation tank 5 is larger than the total liquid amount of all the reaction tanks 9 in the corresponding arc-shaped detection tank 8, and the residual liquid to be detected flows into the waste liquid tank 7. In the centrifugal process, gas in the microfluidic chip is discharged from the waste liquid exhaust hole 11, so that the balance of air pressure in the whole microfluidic chip is ensured during rotation.
Claims (8)
1. A multipurpose centrifugal microfluidic chip comprises a cover plate, a hydrophobic breathable film and a substrate; the cover plate, the hydrophobic breathable film and the substrate are sequentially overlapped up and down and are combined into a whole through laser welding, hot-press bonding or gluing; the method is characterized in that: a rotating shaft connecting structure is arranged on the substrate at the geometric rotation center, a plurality of liquid separation tanks are uniformly distributed around the geometric rotation center, and a waste liquid tank is arranged on the substrate around the geometric rotation center and used for collecting redundant samples; each liquid separation tank is communicated with the waste liquid tank through a detection tank, and a reaction tank is arranged in the detection tank or at the edge of one side of the detection tank; a waste liquid exhaust hole, a liquid separation pool exhaust hole and a sample inlet hole which are of an upper opening structure are formed in the substrate; the liquid separation pool vent hole is used for keeping the air pressure in the detection groove constant in the rotation process of the microfluidic chip; the exhaust hole of the liquid separation tank and the sample inlet hole are respectively communicated with the liquid separation tank, the waste liquid exhaust hole is communicated with the waste liquid tank through an exhaust channel, and the orifices of the exhaust hole of the liquid separation tank and the waste liquid exhaust hole are respectively sealed through the hydrophobic breathable film; through holes are respectively arranged on the cover plate corresponding to the positions of the rotating shaft connecting structure, the sample inlet hole, the liquid separation tank exhaust hole and the waste liquid exhaust hole.
2. The multipurpose centrifugal microfluidic chip of claim 1, wherein: the detection groove is a straight groove or an arc-shaped groove, and a capillary passive valve is arranged at the joint of the detection groove and the liquid distribution tank; and the capillary passive valve is used for preventing liquid from entering the detection groove during sample adding.
3. The multipurpose centrifugal microfluidic chip of claim 1, wherein: the reaction tank is in a shape of a circular hole, a square hole or a waist-shaped hole and realizes the liquid storage function; the diameter of the circular hole or the width of the square hole is equal to, smaller than or larger than the width of the detection slot.
4. The multipurpose centrifugal microfluidic chip of claim 2, wherein: the straight groove or the arc-shaped groove is obliquely arranged along the clockwise direction or the anticlockwise direction.
5. The multipurpose centrifugal microfluidic chip of claim 2, wherein: the capillary passive valve is a structural valve.
6. The multipurpose centrifugal microfluidic chip of claim 1 or 2, wherein: the sample inlet hole is a tapered hole matched with the standard pipette tip in size, and a flexible mould is covered above the sample inlet hole, so that the standard pipette tip can be conveniently inserted and sealed.
7. The multipurpose centrifugal microfluidic chip of claim 1 or 2, wherein: and a plurality of reaction tanks are arranged in each detection tank, and the volume of each liquid separation tank is equal to 1.2-1.5 times of the total volume of the reaction tanks communicated with the liquid separation tank in the detection tank, so that the primary uniform separation of liquid is realized.
8. The multipurpose centrifugal microfluidic chip of claim 1 or 2, wherein: the liquid separation tanks are mutually communicated, and the planar shape of each liquid separation tank is fan-shaped, semicircular or semi-elliptical.
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CN202111467101.6A CN113967492A (en) | 2021-12-03 | 2021-12-03 | Multipurpose centrifugal micro-fluidic chip |
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN117471092A (en) * | 2023-12-27 | 2024-01-30 | 湖南源流检测技术有限公司 | Centrifugal type immunodetection micro-fluidic chip and detection method |
CN117487649A (en) * | 2024-01-03 | 2024-02-02 | 嘉兴朝云帆生物科技有限公司 | Microfluidic chip and nucleic acid amplification analyzer |
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2021
- 2021-12-03 CN CN202111467101.6A patent/CN113967492A/en active Pending
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN117471092A (en) * | 2023-12-27 | 2024-01-30 | 湖南源流检测技术有限公司 | Centrifugal type immunodetection micro-fluidic chip and detection method |
CN117487649A (en) * | 2024-01-03 | 2024-02-02 | 嘉兴朝云帆生物科技有限公司 | Microfluidic chip and nucleic acid amplification analyzer |
CN117487649B (en) * | 2024-01-03 | 2024-03-29 | 嘉兴朝云帆生物科技有限公司 | Microfluidic chip and nucleic acid amplification analyzer |
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