CN112986603A - Anti-leakage reagent dropper for antigen detection and biological sampling method - Google Patents
Anti-leakage reagent dropper for antigen detection and biological sampling method Download PDFInfo
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- CN112986603A CN112986603A CN202110192555.0A CN202110192555A CN112986603A CN 112986603 A CN112986603 A CN 112986603A CN 202110192555 A CN202110192555 A CN 202110192555A CN 112986603 A CN112986603 A CN 112986603A
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- upper cover
- tube body
- swab
- antigen detection
- tube
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- 239000003153 chemical reaction reagent Substances 0.000 title claims abstract description 34
- 239000000427 antigen Substances 0.000 title claims abstract description 26
- 102000036639 antigens Human genes 0.000 title claims abstract description 26
- 108091007433 antigens Proteins 0.000 title claims abstract description 26
- 238000001514 detection method Methods 0.000 title claims abstract description 26
- 238000005070 sampling Methods 0.000 title claims abstract description 24
- 238000000034 method Methods 0.000 title claims abstract description 12
- 239000007788 liquid Substances 0.000 claims abstract description 34
- 239000000243 solution Substances 0.000 claims description 21
- 238000007789 sealing Methods 0.000 claims description 16
- 239000006166 lysate Substances 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- 230000007704 transition Effects 0.000 claims description 8
- 238000004898 kneading Methods 0.000 claims description 5
- 230000009089 cytolysis Effects 0.000 claims description 3
- 238000001746 injection moulding Methods 0.000 claims description 2
- 239000000523 sample Substances 0.000 abstract description 24
- 239000012488 sample solution Substances 0.000 abstract description 7
- 238000003860 storage Methods 0.000 description 8
- 230000000694 effects Effects 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 3
- 239000002504 physiological saline solution Substances 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000005429 filling process Methods 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000012460 protein solution Substances 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 239000010902 straw Substances 0.000 description 1
Images
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
-
- 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
- B01L3/02—Burettes; Pipettes
-
- 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
- B01L2200/06—Fluid handling related problems
- B01L2200/0689—Sealing
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N2035/1027—General features of the devices
- G01N2035/1032—Dilution or aliquotting
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- Physics & Mathematics (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Clinical Laboratory Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Sampling And Sample Adjustment (AREA)
Abstract
The invention discloses an antigen detection leak-proof reagent dropper, which comprises a tube body and an upper cover, wherein the upper cover is sealed on the tube body, a liquid outlet channel communicated with the tube body is arranged in the inner cavity of the upper cover, an upper cover breaking point is arranged on the upper cover, and the liquid outlet channel is communicated with the outside after the upper cover is broken at the upper cover breaking point; the tube body is composed of a multi-taper tube body and a small-diameter tube bottom, and the swab after sampling is arranged in the tube body and is closed by an upper cover after being broken. The whole process of storing and transporting the sample solution and collecting, releasing and adding the sample can be realized.
Description
Technical Field
The invention relates to the technical field of antigen detection kits, in particular to an antigen detection leakproof reagent dropper and a biological sampling method.
Background
Respiratory disease antigen detection kit, used with swab cooperation, for biological sampling, take new crown antigen kit as an example, the operational flow is summarized as follows: sampling by using a matched sampling swab in the kit; putting the sampled swab into lysate for release; the lysate containing the sample is added dropwise to the reaction plate.
In the prior art, the storage and transportation of the sample solution and the collection, release and addition of the sample can be completed only by stages and multiple steps of special straws, droppers and closed tubes, the operation process is complicated, and no reagent dropping bottle capable of simultaneously completing the storage and transportation of the sample solution and the collection, release and addition of the sample exists at present in China.
In order to achieve the above purpose, the following technical problems are faced: firstly, storage and transportation of a sample solution ensure environmental sealing, prevent liquid leakage and avoid volatilization of effective components; secondly, how to ensure good release of the sample; and thirdly, dripping the sample solution.
Disclosure of Invention
The technical problems to be solved by the invention are as follows: the invention aims to overcome the problems in the prior art and provides an antigen detection leakproof reagent dropper. It is another object of the present invention to provide a biological sampling method.
The technical scheme is as follows: in order to achieve the purpose, the technical scheme provided by the invention is as follows: an antigen detection leakproof reagent dropper comprises a tube body and an upper cover, wherein the upper cover is sealed at the upper opening of the tube body, a liquid outlet channel communicated with the tube body is arranged in the inner cavity of the upper cover, an upper cover breaking point is arranged on the upper cover, and the liquid outlet channel is communicated with the outside after the upper cover is broken at the upper cover breaking point; the tube body is composed of a multi-taper tube body and a small-diameter tube bottom, and the swab after sampling is arranged in the tube body and is closed by an upper cover after being broken.
As a further improvement of the invention, the upper cover is screwed with the upper opening of the tube body, and the lower end of the upper cover extends to form a threaded lantern ring screwed with the upper opening of the tube body.
As a further improvement of the invention, a water sealing ring is arranged at the contact part of the upper cover and the upper opening end surface of the pipe body, and the water sealing ring is secondarily injected on the upper cover.
As a further improvement of the invention, the taper of the upper part of the tube body is not more than 0.5 degrees, the taper of the lower part of the tube body is 2-4.4 degrees, the upper part and the lower part of the tube body are connected with a transition section, the taper of the transition section is 15 degrees, the taper of the transition section is not more than 15 degrees, the diameter of the tube bottom is 4-4.72mm, and the diameter is in negative correlation with the taper of the lower tube body.
As a further improvement of the invention, the width of the liquid outlet channel is not less than 1.8mm, and the diameter of the upper cover at the breaking point is not more than 3.2 mm.
As a further improvement of the invention, the outer walls of the tube body and the upper cover are both provided with anti-skid grains.
A biological sampling method comprising the steps of:
a. the anti-leakage reagent dropper for antigen detection is adopted, and lysis solution is pre-filled in the reagent dropper in advance;
b. sampling by using a swab, putting the sampled swab into lysate of a reagent dropper, breaking the swab at a breaking point of the swab, and covering an upper cover to squeeze a swab head;
c. kneading the position of the swab head in the tube to facilitate release of the sample in the swab head;
d. breaking the upper cover at the breaking point of the upper cover;
e. the tube body is inverted, and the lysate dissolved with the sample flows out of the liquid outlet channel of the upper cover and is dripped onto the reaction plate.
Has the advantages that: compared with the prior art, the technical scheme provided by the invention has the following beneficial effects:
(1) the anti-leakage reagent dropper for antigen detection, disclosed by the invention, has the advantages that the upper cover seals the upper opening of the dropper body, the airtight and leakage-free solution storage environment is ensured, and the volatilization of effective components is avoided.
(2) The anti-leakage reagent dropper for antigen detection can accommodate an effective sampling section of a swab, and reduces the biological pollution risk of naked and discarded swabs.
(3) The leakproof reagent dropper for antigen detection, disclosed by the invention, has the advantages that the dropper body is tapered, the wiper head is immersed in a small-volume dosage solution, so that the wiper head is fully contacted, and the release rate of a sample is improved.
(4) According to the anti-leakage reagent dropper for antigen detection, the tube body has kneading performance, and a sample can be effectively released without an additional sample release auxiliary instrument.
(5) The upper cover of the leakproof reagent dropper for antigen detection is provided with the liquid outlet channel which is convenient for solution to flow out and drip, so that the solution containing a sample can be quickly and effectively dripped onto a reaction plate.
(6) The anti-leakage reagent dropper for antigen detection can realize the whole processes of storage and transportation of a sample solution and collection, release and addition of a sample.
Drawings
FIG. 1 is a schematic view of an anti-leakage reagent dropper for antigen detection according to the present invention;
fig. 2 is an enlarged view of a point a in fig. 1.
The reference numerals in the schematic drawings illustrate:
11, a tube body; 12. a tube bottom; 100. a transition section; 2. an upper cover; 21. sealing a water seal ring; 22. a threaded collar; 23. a liquid outlet channel; 24. and the upper cover is broken.
Detailed Description
For a further understanding of the invention, reference should be made to the following detailed description taken in conjunction with the accompanying drawings.
In the description of the present invention, it is to be understood that the terms "center", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", and the like indicate orientations or positional relationships based on those shown in the drawings, and are only for convenience of description and simplicity of description, and do not indicate or imply that the referenced devices or elements must have a particular orientation, be constructed and operated in a particular orientation, and thus, are not to be construed as limiting the present invention.
In the description of the present invention, the meaning of a plurality of means is one or more, the meaning of a plurality of means is two or more, and larger, smaller, larger, etc. are understood as excluding the number, and larger, smaller, inner, etc. are understood as including the number. If the first and second are described for the purpose of distinguishing technical features, they are not to be understood as indicating or implying relative importance or implicitly indicating the number of technical features indicated or implicitly indicating the precedence of the technical features indicated.
In the description of the present invention, unless otherwise explicitly limited, terms such as arrangement, installation, connection and the like should be understood in a broad sense, and those skilled in the art can reasonably determine the specific meanings of the above terms in the present invention in combination with the specific contents of the technical solutions.
As shown in fig. 1-2, an anti-leakage reagent dropper for antigen detection comprises a tube body and an upper cover 2, wherein the upper cover 2 is sealed at the upper opening of the tube body, a liquid outlet channel 23 communicated with the tube body is arranged in the inner cavity of the upper cover 2, an upper cover breaking point 24 is arranged on the upper cover 2, and the liquid outlet channel 23 is communicated with the outside after the upper cover 2 is broken at the upper cover breaking point 24; the tube body is composed of a multi-taper tube body 11 and a small-diameter tube bottom 12, and the swab after sampling is placed in the tube body and is closed by the upper cover 2 after being broken.
The lysate is pre-filled in the reagent dropper in advance, a sealed space is needed during transportation, and when the lysate is not used, the lysate is sealed on the upper opening of the tube body through the upper cover 2 to achieve a sealing effect; during detection, the upper cover 2 is opened, the sampled swab is placed in lysate in the tube body, the swab is broken off, the upper cover 2 is covered again, the swab head is kneaded through the outer wall of the tube body, the sample is released, the upper cover 2 is broken off at the broken point of the upper cover, and liquid flows out of the liquid outlet channel 23 to the reaction plate.
Compared with the prior art, the reagent dropper provided by the invention can accommodate the broken swab sampling part (effective sampling section) after the swab is sampled, thereby reducing the biological pollution risk caused by the naked swab discarding; meanwhile, the upper cover 2 is sealed at the upper opening of the tube body, so that the sealing performance of the solution storage environment is ensured.
In a preferred embodiment, the upper cover 2 is screwed with the upper opening of the tube body, the lower end of the upper cover 2 extends to form a threaded collar 22 screwed with the upper opening of the tube body, and the tube body is connected with the upper cover 2 through threads to realize sealing effect.
In a preferred embodiment, the contact part of the upper cover 2 and the upper opening end surface of the tube body is provided with a water sealing ring 21, and the water sealing ring 21 is fixed on the upper cover 2 through secondary injection molding. The water sealing ring 21 is fixed on the upper cover 2 to form a whole, so that the water sealing ring 21 is prevented from being extruded out of a contact surface by complex stress when the upper cover 2 is screwed. In addition, the water sealing ring 21 has excellent leakage-proof effect, can ensure no leakage in a negative pressure environment, and is suitable for the air transportation environment of liquid, because most of the transportation bin is in the negative pressure environment during air transportation.
The upper cover 2 is in threaded connection with the upper opening of the pipe body, and the water sealing ring 21 is matched, so that the sealing performance of storage and transportation environments is further guaranteed, leakage is avoided, and volatilization of effective components is avoided.
In order to achieve good release of the sample, firstly the volume of solution associated with the release of the sample must not be too large, to prevent the occurrence of false negative due to excessive dilution, generally 350 μ L, and in addition, it is necessary to ensure sufficient contact between the small volume of the dose of solution and the swab head, which requires that the diameter of the bottom of the dropper must not be too large, to achieve a high level of the small volume of the dose of solution, so as to immerse the swab head and bring it into sufficient contact with the solution. In combination with the currently commercially available containers, a volume small enough to ensure that 350 μ L of solution is submerged in the swab head (approximately 15.9mm high), cannot accommodate a sampling swab 80mm long; can accommodate an 80mm sampling swab without ensuring that the lysate is above the swab head. Based on this, the applicant has made improvements to the tube body.
Preferably, the taper of the upper part of the tube body 11 is not more than 0.5 degrees, the taper of the lower part of the tube body 11 is 2-4.4 degrees, the upper part and the lower part of the tube body 11 are connected with a transition section, the taper of the transition section is not more than 15 degrees, and the diameter of the tube bottom 12 is 4-4.72mm and is negatively related to the taper of the lower tube body 11.
The design that many tapers pipe shaft 11 cooperation small diameter tube end 12 guarantees that under the condition of small volume dose liquid, liquid level height can reach a definite value, under the condition of tube end 12 diameter 4-4.72mm, 350 mu L liquid volume, liquid height can reach a definite value, can submerge the common swab head in the market, the experiment contrast is as follows:
| D(mm) | X(°) | V(μL) | H(mm) |
| 4.00 | 4.40 | 350.00 | 15.99 |
| 4.30 | 3.40 | 350.00 | 15.99 |
| 4.60 | 2.40 | 350.00 | 15.97 |
| 4.72 | 2.00 | 350.00 | 15.95 |
the following steps: d is the diameter of the bottom of the tube, X is the taper of the lower part of the tube body, V is the volume of the liquid, and H is the height of the solution.
The pipe shaft 11 has the tapering, and the effect of filling in advance is better, and straight pipe shaft is when the filling lysate, and liquid has viscidity, exists tension between the molecule, very easily forms the liquid film among the filling process, and the existence of liquid film has formed the hindrance, makes liquid be difficult to continue down to the bottom of the tube, and the filling effect is poor.
The pipe body 11 has taper, the sample is mixed and released effectually, the diameter of the swab head is between 2.5-4mm, the diameter of the existing straight pipe body is about 4mm, if the diameter of the used swab head is just 4.0mm, when the swab head is placed into the pipe bottom 12, the pipe bottom 12 is divided into an upper part and a lower part by the swab head, so that the liquid at the upper part and the lower part of the swab head can not be mixed evenly, and when the liquid dropping is inverted, the high-concentration solution at the lower part blocked by the swab head can not be dropped out. The improved tube body avoids the defects, only the tube body needs to be kneaded, and no additional sample release auxiliary instrument (such as an oscillator blending instrument) is needed, so that the release requirement of the sample can be met, and the effective release rate of the sample is increased by 50-70%.
Two existing tubes (labeled 1, 2) were taken for comparative experiments to verify sample release rates, experimental methods: 350 microliters of physiological saline is taken and placed in the tubes 1 and 2 and the present invention, a swab is used for sampling in a protein solution with the concentration of 10 micrograms/mL, then the tube 1 and 2 containing 350 microliters of physiological saline and the present invention are placed, the swab is broken and the cover is covered, and after three times of kneading, the protein concentration in the dripped liquid drop is measured, and the results are as follows:
| pipe and method for producing the same | Release Rate of protein sample from droplet |
| 1 | 30％-40％ |
| 2 | 35％-45％ |
| The invention | 55％-70％ |
In a preferred embodiment, the width of the liquid outlet channel 23 is not less than 1.8mm, and the diameter of the upper cover breaking point 24 is not more than 3.2 mm. The liquid outlet channel 23 is convenient for the solution to drip out, the single side of the liquid outlet channel 23 is 0.9mm, the caliber is small, and the solution cannot drip out from a drip opening when the dropper is not applied with pressure; when the solution is dripped, the solution can be quickly and effectively dripped on the reaction plate by using external force.
In a preferred embodiment, the outer walls of the tube body 11 and the upper cover 2 are provided with anti-slip lines. Effectively prevent the slippage risk that leads to because of frictional force is not enough in the use.
A biological sampling method comprising the steps of:
a. an antigen detection reagent kit is selected, wherein the kit contains the reagent dropper, and the reagent dropper is pre-filled with lysis solution in advance;
b. opening the upper cover 2, sampling by using a swab, putting the sampled swab into lysate of a reagent dropper, breaking the swab at a swab breaking point, and covering the upper cover 2 to extrude a swab head;
c. kneading the position of the swab head in the tube to facilitate release of the sample in the swab head;
d. the upper cover 2 is broken off at the upper cover breaking point 24;
e. the tube body is inverted, and lysate dissolved with the sample flows out of the liquid outlet channel 23 of the upper cover 2 and then is dripped onto the reaction plate.
The reagent dropper provided by the invention is matched with the sampling swab, and can realize the whole processes of storage and transportation of a sample solution and collection, release and addition of a sample.
The present invention and its embodiments have been described above schematically, without limitation, and what is shown in the drawings is only one of the embodiments of the present invention, and the actual structure is not limited thereto. Therefore, if the person skilled in the art receives the teaching, without departing from the spirit of the invention, the person skilled in the art shall not inventively design the similar structural modes and embodiments to the technical solution, but shall fall within the scope of the invention.
Claims (7)
1. The utility model provides an antigen detection leak protection reagent burette, includes body and upper cover, its characterized in that: the upper cover is sealed at the upper opening of the pipe body, the inner cavity of the upper cover is provided with a liquid outlet channel communicated with the pipe body, the upper cover is provided with an upper cover breaking point, and the liquid outlet channel is communicated with the outside after the upper cover is broken at the upper cover breaking point; the tube body is composed of a multi-taper tube body and a small-diameter tube bottom, and the swab after sampling is arranged in the tube body and is closed by an upper cover after being broken.
2. The antigen detection leakproof reagent dropper of claim 1, wherein: the upper cover is screwed with the upper opening of the tube body in a threaded manner, and the lower end of the upper cover extends to form a threaded lantern ring screwed with the upper opening of the tube body in a threaded manner.
3. The antigen detection leakproof reagent dropper of claim 1, wherein: and a water sealing ring is arranged at the contact part of the upper cover and the upper end face of the pipe body, and the water sealing ring is subjected to secondary injection molding on the upper cover.
4. The antigen detection leakproof reagent dropper of claim 1, wherein: the taper of the upper part of the tube body is not more than 0.5 degrees, the taper of the lower part of the tube body is 2-4.4 degrees, the upper part and the lower part of the tube body are connected with a transition section, the taper of the transition section is not more than 15 degrees, the diameter of the tube bottom is 4-4.72mm, and the diameter of the tube bottom is in negative correlation with the taper of the tube body at the lower part.
5. The antigen detection leakproof reagent dropper of claim 1, wherein: the width of the liquid outlet channel is not less than 1.8mm, and the diameter of the broken point of the upper cover is not more than 3.2 mm.
6. The antigen detection leakproof reagent dropper of claim 1, wherein: the outer walls of the pipe body and the upper cover are both provided with anti-skid lines.
7. A biological sampling method, characterized by: the method comprises the following steps:
a. the antigen detection leakage-proof reagent dropper of claims 1 to 4 is used, and the reagent dropper is pre-filled with lysis solution in advance;
b. sampling by using a swab, putting the sampled swab into lysate of a reagent dropper, breaking the swab at a breaking point of the swab, and covering an upper cover to squeeze a swab head;
c. kneading the position of the swab head in the tube to facilitate release of the sample in the swab head;
d. breaking the upper cover at the breaking point of the upper cover;
e. the tube body is inverted, and the lysate dissolved with the sample flows out of the liquid outlet channel of the upper cover and is dripped onto the reaction plate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110192555.0A CN112986603A (en) | 2021-02-20 | 2021-02-20 | Anti-leakage reagent dropper for antigen detection and biological sampling method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110192555.0A CN112986603A (en) | 2021-02-20 | 2021-02-20 | Anti-leakage reagent dropper for antigen detection and biological sampling method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112986603A true CN112986603A (en) | 2021-06-18 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110192555.0A Withdrawn CN112986603A (en) | 2021-02-20 | 2021-02-20 | Anti-leakage reagent dropper for antigen detection and biological sampling method |
Country Status (1)
| Country | Link |
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| CN (1) | CN112986603A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113604346A (en) * | 2021-09-02 | 2021-11-05 | 浙江仅一医疗科技有限公司 | Detection device with reagent and method for detecting nucleic acid by using detection device |
| CN115701345A (en) * | 2021-08-02 | 2023-02-10 | 上海妙灵生物工程有限公司 | Biochemical test tube and biochemical reaction assembly |
-
2021
- 2021-02-20 CN CN202110192555.0A patent/CN112986603A/en not_active Withdrawn
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115701345A (en) * | 2021-08-02 | 2023-02-10 | 上海妙灵生物工程有限公司 | Biochemical test tube and biochemical reaction assembly |
| CN113604346A (en) * | 2021-09-02 | 2021-11-05 | 浙江仅一医疗科技有限公司 | Detection device with reagent and method for detecting nucleic acid by using detection device |
| CN113604346B (en) * | 2021-09-02 | 2023-11-17 | 浙江仅一医疗科技有限公司 | Detection device containing reagent and method for detecting nucleic acid using detection device |
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Application publication date: 20210618 |
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| WW01 | Invention patent application withdrawn after publication |