JP7343996B2 - Zirconium oxide ceramics and biochemical sample collection parts - Google Patents

Description

The present disclosure relates to zirconium oxide ceramics and members for collecting biochemical samples.

BACKGROUND ART Analyzers such as liquid chromatographs that analyze liquid samples are provided with a sample collection nozzle (hereinafter, this sample collection nozzle will be simply referred to as a nozzle) for collecting and transporting a liquid sample. Stainless steel whose main component is iron is mainly used for such nozzles. Since iron has the property of adsorbing hydroxyl groups, if the liquid sample contains hydroxyl groups, the liquid sample tends to stick to the surface of the nozzle. Biochemical samples such as blood that contain proteins tend to stick to the nozzle surface because the proteins contain hydroxyl groups, and even if you try to eject the collected biochemical sample from the nozzle, the stuck biochemical sample will remain inside the nozzle. As a result, there is a risk that the amount of ejection from the nozzle may be insufficient or that the amount of ejection may vary. As a nozzle that suppresses the adhesion of biochemical samples on the surface of such a nozzle, the applicant of the present application has proposed in Patent Document 1 a biochemical sample collection nozzle made of ceramics containing zirconium oxide as a main component. .

JP2018-87747A

Since the biochemical sample collection nozzle proposed in Patent Document 1 uses extrusion molding in its manufacturing process, the interval between open pores on the inner circumferential surface tends to become narrow, and the open pores may be closed depending on the biochemical sample. If it is eroded in such a way that it spreads out, there is a high risk that the parts where the distance between the open pores is narrow will fall off, and further improvement in corrosion resistance is required.

An object of the present disclosure is to provide a zirconium oxide ceramic with excellent corrosion resistance and a member for collecting biochemical samples.

The zirconium oxide ceramic of the present disclosure has a plurality of open pores, and the value obtained by subtracting the average value of the diameter of the open pores from the average value of the distance between the centers of gravity of the open pores is 70 μm or more.

Furthermore, the biochemical sample collection member of the present disclosure uses the above-mentioned zirconium oxide ceramic.

According to the present disclosure, it is possible to provide a zirconium oxide ceramic with excellent corrosion resistance and a member for collecting a biochemical sample.

An example of the member for collecting a biochemical sample according to the present disclosure is shown in FIG. 1 (a) is a perspective view, (b) is a cross-sectional view along the central axis, and (c) is an enlarged view of the enlarged diameter portion. (a) is a perspective view, and (b) is a cross-sectional view along the central axis, showing another example of the biochemical sample collecting member of the present disclosure.

Hereinafter, the zirconium oxide ceramic and biochemical sample collection member of the present disclosure will be described in detail with reference to the drawings.

FIG. 1 shows an example of the biochemical sample collection member of the present disclosure, in which (a) is a perspective view, (b) is a cross-sectional view along the central axis, and (c) is an enlarged view of (b). It is a diagram.

Further, FIG. 2 shows another example of the biochemical sample collection member of the present disclosure, in which (a) is a perspective view and (b) is a cross-sectional view along the central axis.

Note that in FIG. 2, the same components as in FIG. 1 are indicated by the same reference numerals as in FIG.

The biochemical sample collecting member shown in FIGS. 1 and 2 is a nozzle 10 for collecting a biochemical sample, and is used in an analysis device such as a liquid chromatograph that analyzes biochemical samples. The nozzle 10 is used in this analyzer to collect and transport a sample to be analyzed (hereinafter, this sample to be analyzed will be referred to as an analysis sample). The nozzle 10 uses a biochemical sample such as blood containing protein as an analysis sample. Specifically, a part of the first end 1a side of the nozzle 10 is immersed in the analysis sample, so that the nozzle 10 sucks up the analysis sample into the first through hole 1A and draws the analysis sample inside the first through hole 1A. Hold. This suction of the analysis sample is due to capillary action. In addition to the capillary phenomenon, the analysis sample can also be sucked up by creating a negative pressure inside the first through hole 1A and utilizing the pressure difference.

The nozzle 10 of the present disclosure includes a first through hole 1A extending from a first end 1a to a second end 1b, and has a first member 1 whose outer diameter becomes narrower toward the first end 1a. is made of ceramics whose main component is zirconium oxide (hereinafter, ceramics whose main component is zirconium oxide will be simply referred to as ceramics).

Here, the main component of ceramics refers to a component that accounts for 70% by mass or more out of a total of 100% by mass of the components constituting the ceramic. The content of zirconium oxide may be 75% by mass or more out of a total of 100% by mass of the components constituting the ceramic. Each component constituting the ceramic can be identified using an X-ray diffraction device, and its content can be determined using a fluorescent X-ray analyzer or an ICP emission spectrometer.

Moreover, the nozzle 10 may have the 2nd member 2 provided with 2 A of 2nd through-holes connected to 1 A of 1st through-holes on the 2nd end 1b side of 1 A of 1st through-holes. The inner diameter of the first through hole 1A may be smaller than the inner diameter of the second through hole 2A. When such a second member 2 is provided and the inner diameter of the first through hole 1A is smaller than the inner diameter of the second through hole 2A, an amount of analysis sample equal to or greater than the volume of the first through hole 1A of the first member 1 can be analyzed. can be held by the nozzle 10.

Further, the first end 1a side of the first through hole 1A is an inlet for an analysis sample to be collected, and is also an outlet for the collected analysis sample. When the analysis sample is discharged from the nozzle 10, the analysis sample becomes droplets, and if the inner diameter of the first through hole 1A is small, each droplet becomes small. The nozzle 10 can hold a relatively large amount of analysis sample through the second through hole 2A having a large inner diameter, and can accurately discharge small droplets through the first through hole 1A having a small inner diameter.

Further, the first member 1 has an insertion portion 11 inserted into the second through hole 2A on the second end 1b side, and the first through hole 1A has an inner diameter that decreases as it approaches the second end side 1b. It may have an enlarged diameter portion 12 that becomes larger. In the case of a configuration in which the insertion portion 11 is inserted into the second through hole 2A, the outer peripheral surface of the insertion portion 11 and the wide area of the inner peripheral surface of the second member 2 can be opposed, so that the second
The first member 1 can be firmly bonded to the member 2 via the bonding layer 13.

In addition, when it has the enlarged diameter portion 12 whose inner diameter increases as it approaches the second end side 1b, it becomes easier for the analysis sample to smoothly flow from the second through hole 2A toward the first through hole 1A. Generation of microbubbles at the boundary between the second through hole 2A and the first through hole 1A can be suppressed. Note that if there is no concern about the generation of microbubbles, etc., a configuration without the enlarged diameter portion 12 may be used as shown in FIG. The shape of the enlarged diameter portion 12 is, for example, a truncated cone shape, and the apex angle θ in a cross-sectional view along the central axis may be, for example, 70° or more and 110° or less.

When the first member 1 of the nozzle 10 has an insertion portion 11 inserted into the second through hole 2A on the second end 1b side, the outer circumferential surface of the insertion portion 11 and the inner circumference of the second through hole 2A A bonding layer 13 may be located between the surfaces. When such a configuration is satisfied, the first member 1 and the second member 2 are firmly joined, so that there is less possibility that the first member 1 will come off from the second member 2.

Further, when the insertion portion 11 has the stepped surface 14 on the first end 1a side, the stepped surface 14 and the second
A bonding layer 13 may also be located between the member 2 and the member 2 . The bonding layer 13 is located not only between the outer circumferential surface of the insertion portion 11 and the inner circumferential surface of the second member 2 but also between the step surface 14 and the end surface of the second member 2 on the first member 1 side. In some cases, the first member 1 and the second member 2 are more firmly joined, so that there is less possibility that the first member 1 will come off from the second member 2.

Bonding layer 13 may have silicon oxide as a main component and may also contain barium oxide, calcium oxide, and aluminum oxide. The bonding layer 13 containing silicon oxide as a main component is a so-called glass bonding layer. The bonding layer 13 containing barium oxide has relatively high water resistance, and also contains calcium oxide, so it has relatively high chemical durability. Furthermore, the bonding layer 13 containing aluminum oxide has a relatively high glass softening temperature and has relatively high heat resistance.

Note that the main component in the bonding layer 13 refers to the component that is present in the largest amount out of the total 100% by mass of the components constituting the bonding layer 13. Of the total 100% by mass of the components constituting the bonding layer 13, silicon oxide may account for 50% by mass or more. For example, the bonding layer 13 has a barium oxide content of 15% by mass or more and 30% by mass or less, a calcium oxide content of 5% by mass or more and 20% by mass or less, and an aluminum oxide content of 1% by mass or more and 10% by mass. The remainder is silicon oxide. The content of each component constituting the bonding layer 13 can be determined using an ICP emission spectrometer.

The first through hole 1A has a region in which the inner diameter (D1) is constant from the first end 1a to the second end 1b, and the ratio of the length (L1) of the first through hole 1A to the inner diameter (D1) is ( L1/D1) may be 50 or more. In the nozzle 10, the inner diameter (D1) of the first through hole 1A is, for example, 0.25 mm or more and 0.3 mm or less, the length (L1) of the first through hole 1A is, for example, 12 mm or more and 16 mm or less, and the ratio (L1 /D1) is 40 or more and 64 or less.

When this ratio (L1/D1) is 50 or more, the inner diameter (D1) of the first through hole 1A is sufficiently small, so that the analysis sample can be stably sucked up by capillary action. Furthermore, since the first through hole 1A is sufficiently long, a relatively large amount of analysis sample can be held and transported. In addition, in the first through hole 1A where the inner diameter D1 is sufficiently small relative to the length L1, turbulence is unlikely to occur in the sucked up analysis sample. Therefore, the generation of microbubbles due to turbulent flow is suppressed. Furthermore, when discharging droplets, it is possible to reduce variations in droplet size caused by turbulence.

The ceramic of the present disclosure used for biochemical sample collection members such as the nozzle 10 described above has a plurality of open pores, and the average value of the diameter of the open pores is subtracted from the average value of the distance between the centers of gravity of the open pores. The value L ( hereinafter, this L is referred to as the interval L ) is 70 μm or more.

If the spacing L is within this range, even if the analysis sample repeatedly touches the surface of the ceramic and undergoes erosion that enlarges the open pores, the spacing L is relatively large, so that the sample will not be sandwiched between adjacent open pores. The risk of parts falling off is reduced and corrosion resistance is improved.

Although the material of the second member 2 is not limited, it is preferable that it is made of ceramics whose main component is zirconium oxide, and that the distance L is 70 μm or more. If the second member 2 is made of ceramics and the interval L is within this range, even if the analysis sample repeatedly touches the ceramic surface of the second member 2 and is eroded to enlarge the open pores, the interval L will remain within this range. Since it is relatively large, the possibility that the portion sandwiched between adjacent open pores will fall off is reduced, and corrosion resistance is improved.

In this way, when the first member and the second member 2 are made of ceramics and the interval L is 70 μm or more, it is possible to suppress the incorporation of impurities, and therefore it is possible to quantify the analytical sample with high precision.

When determining the distance between the centers of gravity of open pores, the measurement range at one location is 7.1066×10 ⁵ μm ² using an optical microscope at a magnification of 200 times. By performing this measurement at four locations, the distance between the centers of gravity of the open pores can be determined.

Using this observation range as the measurement target, we applied a method called the center-of-gravity distance method of the image analysis software "A-zo-kun (Ver. 2.52)" (registered trademark, manufactured by Asahi Kasei Engineering Co., Ltd.) to measure the distance between adjacent open pores. The distance between the centers of gravity can be calculated. Note that the distance between the centers of gravity of open pores in the present disclosure is a straight line distance connecting the centers of gravity of open pores.

The measurement conditions were as follows: the brightness of the particles was dark, which is the setting condition for the center-of-center distance method, the binarization method was manual, the threshold was 190 to 220, the small figure removal area was 1 μm ² , and a noise removal filter was used. .

In addition, in the above measurement, the threshold value was set to 190 to 220, but the threshold value may be adjusted depending on the brightness of the image, which is the range. The threshold value may be adjusted manually, with a small figure removal area of 1 μm ² and a noise removal filter, so that the marker appearing in the image matches the shape of the open pore.

Furthermore, if the number of open pores observed in each measurement range is one or less, the measurement range may be expanded so that there are at least two or more open pores.

The kurtosis of the distance between the centers of gravity of open pores in the ceramic may be 0 or more.

If the kurtosis of the distance between the centroids of open pores is within this range, the variation in the distance between the centroids of open pores will be small, and the distance between the centroids of open pores will often show a value close to the average value, so The probability of suppressing the extension of microcracks in matching open pores increases, improving reliability.

In particular, the kurtosis of the distance between the centers of gravity of the open pores is preferably 0.05 or more.

Here, the kurtosis Ku is an index (statistic) that indicates how much the peak and tail of the distribution differ from the normal distribution.If the kurtosis Ku>0, the distribution has a sharp peak, and When the kurtosis Ku=0, the distribution becomes a normal distribution, and when the kurtosis Ku<0, the distribution becomes a distribution with a rounded peak.

The average value of the diameter of open pores in the ceramic may be 2.5 μm or less.

When the average value of the diameter of the open pores is 2.5 μm or less, the analysis sample is less likely to enter the inside of the open pores. When the amount of the analysis sample that enters the inside of the open pore decreases, the risk of damaging the wall of the open pore decreases, and new erosion is suppressed.

In particular, the average value of the diameter of open pores in ceramics is preferably 0.2 μm or less.

The kurtosis of the diameter of open pores in ceramics may be 0 or more.

When the kurtosis of the open pore diameter is within this range, the variation in the open pore diameter is small, and moreover, the open pore diameter often shows a value close to the average value, and there are open pores with an abnormally large diameter. Therefore, impurities generated from inside the open pores can be reduced.

In particular, the kurtosis of the distance between the centers of gravity of the open pores is preferably 0.5 or more.

The coefficient of variation of the diameter of open pores in the ceramic may be 0.7 or less.

When the coefficient of variation of the diameter of the open pores is 0.7 or less, the number of open pores with an abnormally large diameter is reduced, so that impurities generated from inside the open pores can be further reduced.

The area ratio of open pores in the ceramic may be 0.1% or less. The fewer open pores, the higher the corrosion resistance.

In particular, it is preferable that the area ratio of open pores is 0.05% or less.

The average value of the diameter of open pores other than the distance between centers of gravity, the coefficient of variation of the diameter of open pores, and the area ratio of open pores are obtained using the image analysis software "Win ROOF (Ver. 6.1.3)" (Mitani Co., Ltd.). (manufactured by Shoji), the measurement range at one location is 7.1066×10 ⁵ μm ² at a magnification of 200 times, and the threshold value of the circle equivalent diameter corresponding to the diameter is 0.21 μm. By performing this measurement at four locations, the average value, coefficient of variation, and area ratio of the open pore diameters can be determined.

Note that the distance between the centers of gravity of the open pores and the kurtosis Ku of the diameter may be determined using the function Kurt provided in Excel (registered trademark, Microsoft Corporation).

The average grain size of crystal grains in the ceramic may be 0.2 μm or more and 0.4 μm or less. When the average particle size is 0.2 μm or more, the thermal conductivity of the ceramic becomes high and the thermal uniformity of the ceramic becomes high. On the other hand, when the average grain size is 0.4 μm or less, it is possible to suppress the generation of abnormally grown crystal grains that reduce the mechanical strength of the ceramic, so that the mechanical strength can be increased.

The average grain size of the crystal grains was measured using a scanning electron microscope with the surface of the ceramic as the object of measurement, at a magnification of 1000 times, in a range of 112 μm in horizontal length and 80 μm in vertical length. It is determined by drawing four straight lines of the same length and dividing the number of crystals existing on these four straight lines by the total length of these straight lines. Note that the length of one straight line may be 20 μm. If the grain boundaries are difficult to identify on the baked surface and it is difficult to measure the grain size, the surface of the ceramic is polished until the arithmetic mean roughness Ra is 0.4 μm or less, and then the firing temperature is The measurement surface may be a polished surface that has been thermally etched at a temperature 100° C. lower than, for example, 1200° C. or higher and 1600° C.

Further, the ceramics constituting the first member 1 and the second member 2 may contain 2 mol% or more and 4 mol% or less of yttrium in terms of oxide. When the ceramic contains yttrium in the above range in terms of oxide, the first member 1 and the second member 2 made of this ceramic have higher mechanical strength.

Further, the ceramics constituting the first member 1 and the second member 2 may contain at least one of magnesium and calcium in an amount of 8 mol % or more and 12 mol % or less in terms of oxide. When the ceramic contains at least one of magnesium and calcium in the above range in terms of oxide, the first member 1 and the second member 2 made of this ceramic have higher thermal shock resistance.

Next, an example of the method for manufacturing the ceramics of the present disclosure will be described.

First, a powder containing zirconium oxide as a main component, a wax, a dispersant, and a plasticizer are prepared.

For 100 parts by mass of powder whose main component is zirconium oxide with a purity of 99% or more (hereinafter referred to as zirconium oxide powder), 10 parts by mass or more and 16 parts by mass or less of wax, and 0.1 parts by mass of a dispersant. The content of the plasticizer is 1.0 parts by mass or more and 1.8 parts by mass or less.

Here, in order to obtain ceramics containing 2 mol% or more and 4 mol% or less of yttrium in terms of oxide, the yttrium oxide powder should be 2 mol% or more and 4 mol% or less out of the total 100 mol% of the zirconium oxide powder and the yttrium oxide powder. The first blended powder may be obtained by blending the two powders.

In addition, in order to obtain ceramics containing 8 mol% or more and 12 mol% or less of Group 2 elements in terms of oxides, the Group 2 elements must be The second blended powder may be prepared by blending the oxide powder so that it is 8 mol% or more and 12 mol% or less.

Then, zirconium oxide powder, first blended powder, or second blended powder (hereinafter, a powder selected from these powders is referred to as ceramic powder), which are all heated to 90°C or higher, wax, a dispersant, and a plasticizer. and stored in a resin container. At this time, the wax, dispersant, and plasticizer are in liquid form.

To obtain ceramics in which the kurtosis of the distance between the centers of gravity of open pores is 0 or more, ceramic powder, wax, dispersant, and plasticizer are heated to 70°C or more and 130°C or less and placed in a resin container. good.

Next, this container is set in a stirrer, and the container is rotated around its axis for at least 1 minute (rotation-revolution kneading process), thereby stirring the ceramic powder, wax, dispersant, and plasticizer to obtain a slurry.

Here, in order to obtain ceramics in which the average particle size of crystal grains is 0.2 μm or more and 0.5 μm or less, the average particle size (D ₅₀ ) of the ceramic powder after rotational kneading treatment is, for example, 0.1 μm or more. The thickness should be 0.3 μm or less.

Then, the obtained slurry is filled into a syringe, and the slurry is defoamed using a defoaming jig while rotating and revolving the syringe for 1 minute or more.

Here, in order to obtain a ceramic in which the kurtosis of the open pore diameter is 0 or more, the slurry may be preheated at a temperature of 100° C. or more and 190° C. or less before the defoaming treatment.

Next, the syringe filled with the defoamed slurry is attached to an injection molding machine and molded while maintaining the temperature of the slurry at 90°C or higher to obtain a cylindrical first molded body having a first through hole. . A cylindrical second molded body having a second through hole is obtained using a method similar to the method described above.

Here, the channel through which the slurry passes in the injection molding machine is also preferably maintained at 90° C. or higher.

By sequentially degreasing and firing the obtained first molded body and second molded body, a first sintered body and a second sintered body are obtained, respectively, and these correspond to the ceramics of the present disclosure. Here, the firing atmosphere may be an air atmosphere, the firing temperature may be 1300° C. or more and 1700° C. or less, and the holding time may be 1.5 hours or more and 5 hours or less.

In addition, in order to obtain ceramics with an average open pore diameter of 2.5 μm or less, the firing atmosphere should be air atmosphere, the firing temperature should be 1400°C or more and 1700°C or less, and the holding time should be 1.5 hours or more and 5 hours or less. And it is sufficient.

In addition, in order to obtain ceramics with a coefficient of variation of open pore diameter of 0.7 or less, the firing atmosphere should be air atmosphere, the firing temperature should be 1400°C or more and 1700°C or less, and the holding time should be 2 hours or more and 5 hours or less. Bye.

In addition, in order to obtain ceramics with an open pore area ratio of 0.1% or less, the firing atmosphere should be air atmosphere, the firing temperature should be 1450°C or more and 1700°C or less, and the holding time should be 1.5 hours or more and 5 hours or less. do it.

Next, a first member is obtained by mechanically processing the surface of the first sintered body. Here, the insertion portion 11 may be formed by polishing the outer circumferential surface of the first end 1a side of the first sintered body so that it becomes narrower toward the tip, and grinding the second end 1b side. Further, the enlarged diameter portion 12 may be formed by processing a part of the opening end on the second end 1b side of the first through hole 1A.

Further, a second member is obtained by mechanically processing both end surfaces of the second sintered body.

Next, an example of a method for manufacturing the biochemical sample collection member of the present disclosure will be described.

First, align the central axis of the through hole of the first member with the central axis of the through hole of the second member, insert the insertion part of the first member 1 into the second through hole of the second member, and then and the second member are bonded to each other via a paste serving as a bonding layer. Prior to joining, powders of silicon oxide, barium oxide, calcium oxide, and aluminum oxide, cellulose resin, terpineol, etc. are applied to at least one of the outer peripheral surface of the insertion portion 11 of the first member and the inner peripheral surface of the through hole 2A. Apply a paste containing an organic solvent. Note that the total content of each oxide powder in 100% by mass of the paste is 72% by mass or more and 78% by mass or less. In addition, the content of barium oxide powder is 15% by mass or more and 30% by mass or less, and the content of calcium oxide powder is 5% by mass or more and 20% by mass or less in the total 100% by mass of the content of each powder of oxides. The content of the aluminum oxide powder may be 1% by mass or more and 10% by mass or less, with the remainder being silicon oxide.

In this state, when the insertion portion of the first member is inserted into the second through hole, there will be a gap between the outer peripheral surface of the insertion portion and the inner peripheral surface of the second member, and between the step surface and the end surface of the second member on the first member side. The paste spreads between. In this state, for example, the nozzle 10 in which the first member and the second member are bonded via the bonding layer is formed by heat treatment by raising the temperature to 850° C. or higher and 950° C. or lower, and then lowering the temperature to room temperature. can get.

In the present disclosure, as described above, the first member and the second member are manufactured by molding using an injection molding machine. For this reason, unlike the processing method in which through-holes are mechanically formed with a tool such as a drill after dry pressure forming, or the extrusion method is used, the spacing between the open pores becomes wider, resulting in biochemistry with excellent corrosion resistance. It can be used as a sample collection member.

Note that the present disclosure is not limited to the embodiments described above, and various changes, improvements, combinations, etc. can be made without departing from the gist of the present disclosure.

1: First member 1a: First end 1b: Second end 1A: First through hole 2: Second member 2A: Second through hole 10: Nozzle 11: Insertion part 13: Bonding layer 14: Step surface

Claims (6)

having a through hole for retaining a chemically erosive liquid and a surface in contact with the liquid ;
the surface has a plurality of open pores;
The value obtained by subtracting the average value of the diameter of the open pores from the average value of the distance between the centers of gravity of the open pores is 70 μm or more,
The average value of the diameter of the open pores is 2.5 μm or less,
Zirconium oxide ceramics, wherein the kurtosis of the distance between the centers of gravity of the open pores is 0 or more. having a through hole for retaining a chemically erosive liquid and a surface in contact with the liquid ;
the surface has a plurality of open pores;
The value obtained by subtracting the average value of the diameter of the open pores from the average value of the distance between the centers of gravity of the open pores is 70 μm or more,
The average value of the diameter of the open pores is 2.5 μm or less,
The zirconium oxide ceramic has a kurtosis of a diameter of the open pores of 0 or more. having a through hole for retaining a chemically erosive liquid and a surface in contact with the liquid ;
the surface has a plurality of open pores;
The value obtained by subtracting the average value of the diameter of the open pores from the average value of the distance between the centers of gravity of the open pores is 70 μm or more,
The average value of the diameter of the open pores is 2.5 μm or less,
The zirconium oxide ceramic has a coefficient of variation in diameter of the open pores of 0.7 or less. having a through hole for retaining a chemically erosive liquid and a surface in contact with the liquid ;
the surface has a plurality of open pores;
The value obtained by subtracting the average value of the diameter of the open pores from the average value of the distance between the centers of gravity of the open pores is 70 μm or more,
The average value of the diameter of the open pores is 2.5 μm or less,
A zirconium oxide ceramic whose crystal grains have an average grain size of 0.2 μm or more and 0.5 μm or less. The zirconium oxide ceramic according to any one of claims 1 to 4 , wherein the area ratio of the open pores is 0.1% or less. A member for collecting a biochemical sample, comprising the zirconium oxide ceramic according to any one of claims 1 to 5 .

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