JP3927570B2 - container - Google Patents

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JP3927570B2
JP3927570B2 JP2004280215A JP2004280215A JP3927570B2 JP 3927570 B2 JP3927570 B2 JP 3927570B2 JP 2004280215 A JP2004280215 A JP 2004280215A JP 2004280215 A JP2004280215 A JP 2004280215A JP 3927570 B2 JP3927570 B2 JP 3927570B2
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container
portion
measurement
light
microplate
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JP2004280215A
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JP2005010179A (en
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秀二 田島
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プレシジョン・システム・サイエンス株式会社
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  TECHNICAL FIELD The present invention relates to a container suitable for analysis and inspection that requires strict quantitative accuracy. In particular, even when the tip of the pipette tip comes into contact with the inner bottom surface of the container, almost all of the sample in the container is aspirated. The present invention relates to a container that can improve the stirring efficiency by averaging the diffusion of the sample when the sample sucked into the container is discharged.

As is well known, in order to maintain the analysis accuracy at a high level, it is necessary to strictly maintain the quantitative accuracy by the dispensing device. In the case of a conventional container, the inner bottom is formed in a plane, or Because the cross-sectional shape is semicircular or substantially U-shaped, the sample / reagent cannot be aspirated / discharged when the tip of the pipette tip of the dispensing device is in contact with the inner bottom of the container. As a result, since the sample / reagent must always be aspirated while the tip of the pipette tip is slightly lifted from the inner bottom of the container, a small amount of sample / reagent always remains on the container side. In order to compensate, it is necessary to aspirate and discharge a larger amount of sample / reagent with the pipette tip than the actual aspiration amount, and it is unavoidable that the sample / reagent not aspirated remains in the container. Analysis Ukoto can not, had the problem.
As a conventional means for solving such a problem, for example, as shown in FIG. 16, the tip 2 of the pipette tip 1 is cut obliquely, and the tip 2 of the pipette tip 1 is placed on the container 3. A configuration in which the sample S can be sucked and discharged while being in contact with the inner bottom portion 4 or one or more horizontal holes 5 are opened at the lower end portion of the pipette tip 1 as shown in FIG. Some have also been proposed, and are devised so that the tip opening of the pipette tip 1 is not blocked by the inner bottom 4 of the container 3.
However, even when the tip portion 2 of the pipette tip 1 is cut obliquely, the portion below the water level W slightly below the upper end portion of the tip opening portion cut obliquely cannot be completely sucked. In addition, when the aspirated sample / reagent is discharged into the container 3, as shown in FIG. 17, one side of the container 3 is agitated by the discharge pressure. The opening side and the opposite side are not directly affected by the discharge pressure of the sample / reagent, and therefore the stirring efficiency is low. For this reason, it is difficult to obtain a uniform stirring effect, that is, a uniform reaction state. There was a problem that molding was difficult and cost was high.
Similarly, the one having the horizontal hole 5 opened at the lower end portion of the pipette tip 1 cannot suck the liquid S in the lower part from the opened portion of the horizontal hole 5, and also when discharging the sucked liquid, Since liquid is discharged only from the opening direction of the horizontal holes 5, it is difficult to obtain a uniform stirring effect, and moreover, a process of opening one or more horizontal holes 5 is added, so that molding becomes complicated and expensive. Had a problem.
In addition, when a liquid is sucked and discharged with the tip of the pipette tip floating from the inner bottom of the container, the sample / reagent is easily deposited on the outer surface of the pipette tip. Since the concentration fluctuated, there was a problem that it was difficult to obtain a highly accurate analysis result.

  The present invention has been developed in view of the present situation. The purpose of the present invention is, firstly, for processing, measuring, or dispensing tips having various capacities required for a series of processing. By providing a container for holding or the like in one container, a quick and efficient process is performed. Secondly, the mechanical drive required for the operation process from the start to the end of the process is reduced, and the process with few movable parts is performed.

In order to achieve the above object, a container according to a first aspect of the present invention includes a cartridge container or a microplate having a base portion and a plurality of storage portions respectively provided in a row or matrix form on the base portion. The plurality of storage units include a processing storage unit and a necessary number of measurement storage units that can be connected to a measuring instrument or a light receiving unit for optical measurement in a light-shielded state according to the processing. The upper end of the measurement housing portion is provided with a connecting portion composed of an annular convex portion that is connected to the optical measuring instrument or light receiving portion in a light-shielded state.
As a result, the process up to the optical measurement can be performed in one container, so that the mechanical driving is minimized, the distance and time of movement of the liquid etc. are shortened, and the process is quickly and reliably performed. Processing can be performed collectively.
A container according to a second invention is the container according to the first invention, wherein the base of the cartridge container or the microplate is formed of a translucent material such as a transparent material or a translucent material, and the measurement container is shielded from light It consists of a container holding hole for detachably holding the measurement container and a measurement container held in the container holding hole.
Since the measurement container that is shielded from light can be manufactured separately from the manufacturing of the microplate formed of a transparent material such as a transparent material, the manufacturing is easy and the manufacturing can be performed at low cost.
A container according to a third invention is the container according to the first invention, wherein a base part of the cartridge container or the microplate is formed of a light-shielding substance, and the measurement housing part is formed integrally with the base part.
A container according to a fourth invention is the container according to any one of the first invention and the second invention, wherein the measurement container held in the measurement container has a high inner wall of the measurement container due to white coloring or the like. It is formed so as to have a reflectance, and its outer side is covered with a light shielding material.
In order to “high reflectivity”, in addition to the white coloring, there are cases where the white material is used, a metallic color, and a metal.
This makes it possible to perform reliable measurement by blocking light from the outside and also making sure that light generated by light emission is incident on the light receiving unit or the measuring device.
A container according to a fifth invention is the container according to any one of the first invention to the fourth invention, wherein the microplate or cartridge container is provided in a substantially flat plate-like base and a matrix or series in the base. It has a plurality of accommodating portions and leg wall portions that protrude downward from the outer bottom portion of the accommodating portion toward the lower side from the periphery of the base portion and support the base portion.
A container according to a sixth invention is the container according to any one of the first to fifth inventions, wherein the upper surface of the base of the cartridge container or the microplate covers the opening of each accommodating part, so that the pipette tip enters. Possible seals are those provided by thermal welding or ultrasonic welding.
Here, the “seal into which the pipette tip can enter” is a thin film having a low strength and easily penetrates, and the seal itself has a high strength but a hole is formed in the seal itself. The chip may be one that can enter.
The seal may be not only transparent but also translucent or opaque, and is formed of aluminum foil or polyvinyl chloride.
Processing is performed by inserting the dispensing tip through the seal and into the receiving part.
As a result, evaporation and contamination of the liquid previously stored in each storage unit can be prevented, and intrusion of germs from the outside can be prevented, so that highly reliable processing can be performed efficiently.

Hereinafter, the present invention will be described in detail based on embodiments shown in the accompanying drawings.
1 to 6 show a container according to a first embodiment of the present invention. A container 10 according to this embodiment includes a container main body 11 integrally formed of glass, plastic or the like, and the container main body 11. The container main body 11 includes a plurality of (9 in the illustrated example) liquid storage portions 13A to 13I, and a cartridge container having a knob 12 formed at one end. A container holding hole 13J for detachably holding the measurement container 14 is formed.
In this embodiment, the liquid storage portions 13A to 13I are formed of a transparent plastic or glass so that the storage can be seen through from the outside. Therefore, a transparent body that is detachably held in the container holding hole 13J. The inner wall and the bottom of the measurement container 14 formed in step 1 are coated with a light-shielding film so as to reliably measure weak chemiluminescence. That is, the container 10 according to this embodiment is formed of two parts, a container body 11 that is a transparent body and a measurement container 14.
Of course, as another means for configuring the measurement container 14 so as to reliably measure weak chemiluminescence, the inner wall and the bottom of the container 14 are subjected to a process such as attaching a light shielding film or a light shielding plate, and assembled as a unit. The container main body 11 itself may be made opaque with a material excellent in light shielding properties, or may be integrally formed by coloring with excellent light shielding properties such as black or white. .
When the measurement container 14 is used as a transparent body, the container holding hole 13J is formed in a bottomed shape, and an inner surface of the container holding hole 13J is coated with a light-shielding film, or integrally molded, or It is desirable to assemble them integrally by stretching a light shielding plate, or to apply a color having excellent light shielding properties such as black or white.
Of course, as shown in FIG. 7, the measurement container 14 may be formed integrally with the liquid storage portion row formed in the container main body 11 as the measurement container hole portion 14A. The inner wall and bottom of the container hole 14A are coated and integrally molded with a light-shielding film, or assembled integrally by stretching a light-shielding plate, etc., or a color having excellent light-shielding properties such as black and white It is desirable to form the light shielding layer 14B by applying.
By forming the measurement container 14 or the measurement container hole 14A in this way, for example, when the measurement container 14 is used for chemiluminescence measurement, light other than the light generated by the reaction is blocked. Can do. Of course, depending on the measurement method such as the transmission measurement method, the spectroscopic measurement method, or the turbidimetric method, it may not be necessary to shield the light, and in this case, it is used as it is transparent.
It should be noted that the arrangement site of the measurement container 14 or the measurement container hole 14A is not limited to the illustrated embodiment, and can of course be formed at an appropriate position corresponding to the number of reaction steps of the measurement item. It is.
Each of the nine liquid storage portions 13A to 13I has a planar shape that is substantially elliptical, and each bottom portion 15 is substantially V-shaped in cross section (intersection angle is 90 ° in the illustrated example), and As shown in FIG. 1, a groove 16 having a substantially concave cross section is formed in the inner bottom portion 15a of each bottom portion 15 along the inclined surface of each inner bottom portion 15a.
As shown in FIGS. 8 and 9, the groove 16 has a width dimension d smaller than the diameter D of the tip 22 of the pipette tip 21 (D> d). 8 is formed longer than the diameter of the tip 22, so that even if the tip 22 of the pipette tip 21 abuts on the inner bottom 15 a, as shown in FIG. The sample / reagent contained in the parts 13A to 13I can flow through the groove 16 and be aspirated in the whole volume, so that it is possible to reliably guarantee the strict quantitativeness in this type of apparatus. Can be eliminated.
In this embodiment, a sample / reagent 18 containing magnetic fine particles 17 used in an analytical inspection of a chemiluminescence method such as a CLIA inspection method or a CLEIA inspection method is shown, but it is used in the present invention. The sample / reagent is not limited to this. For example, an antigen-antibody can be solid-phased on the inner wall surface of the liquid container 13 and used for EIA testing. Of course, it is not limited to the exemplified inspection method, and can be applied to other inspections.
Further, due to the presence of the groove 16, when the sample / reagent is discharged into each of the liquid storage portions 13A to 13I, the tip 22 of the pipette tip 21 contacts the inner bottom portion 15a of each of the liquid storage portions 13A to 13I. Even if the sample / reagent is discharged, the discharged sample / reagent flows out from the groove 16 into the liquid storage portions 13A to 13I on the average in the horizontal direction. Since the stirring flow is averaged in the liquid storage portions 13A to 13I, a uniform reaction state can be obtained.
Note that the number of the liquid storage portions 13A to 13I is not limited to the illustrated embodiment, and it is needless to say that the liquid storage portions 13A to 13I can be formed to an appropriate number corresponding to the number of reaction steps of the measurement item.
FIG. 10 is a plan view of the liquid storage portion 13 of the container 10 according to the second embodiment of the present invention. In this embodiment, the grooves 16A formed in the same manner as the grooves 16 of the first embodiment are radially formed. The other configurations and functions are the same as those in the first embodiment except that the entire amount of the sample / reagent in the liquid container 13 is aspirated / discharged more quickly and reliably. Since it is the same as that of an example, the detailed description is abbreviate | omitted here.
FIG. 11 is a plan view of the liquid storage portion 13 of the container 10 according to the third embodiment of the present invention. In this embodiment, a number of protrusions are used in place of the grooves 16 and 16A of the first and second embodiments. Alternatively, the concave hole 16B is formed, and the dimension between each of the protrusions or the concave holes 16B is smaller than the diameter of the tip 22 of the pipette tip 21 and slightly larger than the opening of the tip 22 of the pipette tip 21. Thus, except that it is configured so that the entire amount of sample / reagent can be aspirated / discharged, the other configurations / operations are the same as those in the first embodiment, and therefore detailed description thereof is omitted here.
Next, as a fourth embodiment of the present invention, a microplate 30 in which the liquid storage portions are arranged in a matrix (matrix) will be described with reference to FIGS.
When processing with a plurality of parallel liquid suction / discharge lines, the microplate 30 is used to separate, sort, dispense, dispense, clarify, concentrate, and dilute the target polymer material etc. at the same timing in each line. Or / and used for operations such as capture, extraction, isolation, amplification, labeling, and measurement.
As shown in FIGS. 12 and 13, the microplate 30 according to the present embodiment includes a substantially plate-like base portion 35 made of a transparent or translucent material, and a plurality of matrix-like base portions 35 provided on the base portion 35. It has accommodating parts 31A-31K, 32A-32K, 33A-33K, 34A-34K. The plurality of accommodating portions are composed of four accommodating portion groups 31A to 31K, 32A to 32K, 33A to 33K, and 34A to 34K divided for each row (column).
Among the storage unit groups divided for each row (column), the storage units 31K, 32K, 33K, and 34K at one end can be connected to a measuring instrument or a light receiving unit (not shown) for optical measurement in a light-shielded state. It is an accommodating part for measurement.
The measurement storage units 31K, 32K, 33K, and 34K include a container holding hole 330 that detachably holds the light-shielded measurement container 331 and a light-shielding measurement container 331. This is because the base portion 35 itself does not have a light shielding property, whereas the measurement housing portion needs a light shielding property, so that it is easier to manufacture than molding at once including the measurement housing portion.
The measurement container 331 is formed of a black light-blocking substance on the outside, and the inside is formed of a white light-blocking and highly reflective substance.
The upper end of the measurement container 331 is provided with a connecting portion 332 composed of an annular convex portion that is connected to a measuring device or a light receiving portion for optical measurement in a light-shielded state, and an elastic packing provided on the measuring device or the light receiving portion. The light is completely shielded by pressing.
As a result, the measurement container 331 can be formed more easily and cheaply than when the black measurement container 331 made of a light shielding material is formed integrally with the base 35 in advance.
As shown in FIG. 12, preferably, the upper surface of the microplate 30 covers each housing portion, and therefore a seal 300 made of a transparent thin film into which the tip of the dispensing tip can easily enter is thermally welded or ultrasonically. It is provided by welding. Accordingly, it is possible to prevent evaporation of the liquid stored in advance in each storage unit and prevent invasion of germs from the outside, so that highly reliable processing can be performed efficiently.
As shown in FIG. 13, the microplate 30 is provided with leg wall portions 36 that protrude from the outer bottom portions 39 of the respective housing portions and support the base portions 35 downward from the periphery of the base portion 35. Further, reinforcing ribs 38 are provided between the adjacent accommodating portions.
Thereby, the microplate can be stably placed on the stage of the dispensing device.
FIG. 14 shows a fifth embodiment of the present invention.
The microplate 40 according to the present embodiment is provided with eight rows of accommodating portion groups 41A to 41H, ... 48A to 48H.
One end of each storage unit group is a tip holding storage portion 41A to 48A that is held when the pipette tip 51 attached to and used by eight dispensing nozzles is detached, and the other end is the above-described measurement storage. Part 41H-48H. Moreover, each accommodating part 41B-41G except a both ends is formed so that it may have various capacity | capacitance corresponding to the required quantity of the liquid (reagent etc.) required according to a process.
In FIG. 14A, at the left end is eight interlocking pipettes attached to eight dispensing nozzles for performing a dispensing operation on each processing container of the microplate 40. By bringing the tip 51 and each pipette tip 51 close to or away from each other all at once, a magnetic field is applied to or removed from the medium-diameter liquid passage connecting the large-diameter reservoir of the pipette tip 51 and the tip. Thus, the eight permanent magnets 52 that simultaneously control the reaction, stirring, separation, washing, and transfer of the magnetic particles 53 and the moving body 50 that moves while holding the eight permanent magnets 52 are shown. Has been.
Between the eight adjacent permanent magnets, the SN polarities are arranged in a mutually inverted state.
Thereby, it is possible to prevent the magnetic field from interfering with adjacent magnets and perform stable control.
Also in the present embodiment, as shown in FIG. 14 and the like, as shown in FIG. 14, the inner bottom portion of each accommodating portion is formed with a groove having a substantially concave cross section along the inclined surface. is there.
Next, a sixth embodiment will be described based on FIG.
This embodiment is a container suitable for DNA inspection processing.
As shown in FIG. 15 (a), the microplate 60 according to the present embodiment has a plurality of cartridges 61, 62, 63, 64 each having a receiving portion provided for each column (row) and a predetermined space between adjacent cartridges. It has a coupling portion 66 which is arranged at intervals and coupled at one end thereof in a substantially comb-like shape.
The coupling portion 66 is provided with a knob 67 for gripping the microplate 60.
In this embodiment, each cartridge, the coupling portion and the like are integrally molded by a mold.
Here, the “predetermined interval” is set slightly larger than the thickness of the partition wall 65 so that the partition wall 65 provided on the stage on which the microplate 60 is placed can be inserted. When the partition wall 65 is inserted into the gap between the cartridges, adjacent cartridges are separated.
As shown in FIG. 5B, in this embodiment, the cartridge 63 for each row has a dispensing tip holding accommodating portion 63A for holding a dispensing tip 69 detached from the dispensing nozzle at one end. The other end is provided with a holding hole 63I for holding a PCR tube 635 used for DNA measurement.
The PCR tube 635 has a lid 633 that can be freely opened and closed to prevent evaporation of liquid at the upper end of the PCR tube 635 and is molded integrally with the PCR tube main body. It is supported by 63I.
Further, the present embodiment includes processing accommodating portions 63B, 63C, 63D, 63E, 63F, 63G, and 63H.
Among these, the accommodating parts 63G and 63H are provided at positions and sizes that can be accommodated in the constant temperature containers 631 and 632 as constant temperature means, and the constant temperature containers 631 and 632 provide a constant temperature, for example, 60 ° C, 90 °. C and so on. The housing portion is provided at a position away from the other housing portions to some extent so as not to affect the heat conduction. Further, in order to prevent the liquid from evaporating while keeping the constant temperature state for a long time, the accommodating portions 63G and 63H are covered with a lid 630 formed of an elastic body having slits in a cross shape. The tip of the dispensing tip can enter the accommodating portions 61G and 61H while the cross-shaped slit remains covered.
In order to use the container 60 according to the present embodiment, the container 60 is placed on the stage so that the partition wall 65 stands upright from above the partition wall 65 provided on the stage of the dispensing unit. Install in.
The partition walls 65 are arranged in parallel at predetermined intervals, and the cartridges 61 to 64 of the microplate 60 are located in the gaps between the partition walls 65. At that time, as shown in FIG. 15B, the accommodating portions 63G and 63H and the like are installed at predetermined positions of the constant temperature means 631 and 632.
Then, the dispensing tips attached to the four dispensing nozzles operate along the partition wall 65 and simultaneously perform suction and discharge of the four.
In FIG. 15B, reference numeral 70 denotes a filter. Also in this embodiment, as shown in FIG. 15A, a single groove having a substantially concave cross section is formed along the inclined surface in the inner bottom portion of each of the accommodating portions 61 </ b> B to 61 </ b> F.
According to this embodiment, the cartridges 61 to 64 are separated from each other by the partition wall 65, so that cross contamination due to mixing of other than the target DNA is prevented between the cartridges 61 to 64 of each processing line. be able to.
Further, in this embodiment, a description has been given of a rectangular partition that uses a rectangular plate. However, as an alternative to this partition, an air inhaler having a long air inlet in the line direction is provided between the lines. It can also be provided to perform air suction.
As a result, a downward air flow curtain is generated in each line, and the entrance and exit of air and the like between the adjacent lines is blocked in the same manner as in the case where the partition wall is provided, and the liquid from other lines is Mixing can be prevented.
In the embodiment described above, each of the containers 10 is not only provided with the liquid storage portions 13A to 13I in series, but also formed in a microplate shape, or in a row such as a loop shape or a zigzag shape. It may be configured in a shape. Or you may comprise a single container similarly to the said liquid accommodating part.
Moreover, in the above embodiment, the number or type of the accommodating portions provided in each microplate and cartridge is not limited to the above example, and it goes without saying that it can be increased or decreased as necessary.

It is a top view of the cartridge container which concerns on 1st Example of this invention. It is a front view of the cartridge container. It is a bottom view of the cartridge container. FIG. 3 is a left side view of the cartridge container. It is a right view of the same cartridge container. It is sectional drawing of the cartridge container. It is a partial expanded sectional view which shows the other structural example of the cartridge container. It is an expanded sectional view showing the suction state of the sample / reagent in the liquid storage part of the cartridge container. It is an expanded sectional view showing the discharge state of the sample and reagent in the liquid storage part of the cartridge container. It is a top view which expands and shows the structure of the liquid accommodating part of the cartridge container which concerns on 2nd Example of this invention. It is a top view which expands and shows the structure of the liquid accommodating part of the cartridge container which concerns on 3rd Example of this invention. It is a perspective view of the microplate which concerns on 4th Example of this invention. It is the top view and AA sectional view taken on the line of the microplate which concerns on 4th Example of this invention. It is the top view and BB sectional view taken on the line of the microplate which concerns on 5th Example of this invention. It is the top view and CC sectional view taken on the line of the microplate which concerns on 6th Example of this invention. It is sectional drawing which shows the example of the suction state of the sample and reagent in the conventional container. It is sectional drawing which shows the example of the discharge state of the sample and reagent in the conventional container. It is sectional drawing which shows the example of the suction state of the sample and reagent in the other conventional container.

Explanation of symbols

DESCRIPTION OF SYMBOLS 10 Cartridge container 13A thru | or 13I Liquid container 14 Measurement container 14A Measurement container hole 15 Liquid container bottom 15a Liquid container inner bottom 16, 16A Groove 16B Protrusion or concave hole 21 Pipette tip 22 Pipette tip tip d Groove width dimension D Diameter size of pipette tip 30, 40 Microplate 31A to 34K Housing 35 Base 36 Leg wall 300 Seal 41A to 48H Housing 51 Pipette chip 52 Permanent magnet 53 Magnetic particle 60 Microplate 61 to 64 Cartridge 65 Bulkhead 66 Bonding portion 635 PCR tube

Claims (6)

  1. The cartridge container or the microplate has a base portion and a plurality of storage portions respectively provided in a row or matrix form on the base portion, and the plurality of storage portions include a processing storage portion, and The necessary number of measurement storage units that can be connected to a measuring instrument or a light receiving unit for optical measurement in a light-shielded state is included according to the processing,
    The container according to claim 1, wherein an upper end of the measurement housing portion is provided with a connecting portion including an annular convex portion that is connected to the optical measuring instrument or the light receiving portion in a light-shielded state.
  2. The base of the cartridge container or the microplate is formed of a translucent material such as a transparent material or a translucent material, and the measurement housing portion is a container holding hole for detachably holding the light-shielded measurement container. The container according to claim 1, comprising a measuring container held in the container and the hole for holding the container.
  3. The container according to claim 1, wherein the base of the cartridge container or the microplate is formed of a light-shielding substance, and the measurement housing is formed integrally with the base.
  4. The measurement container held in the measurement container is characterized in that the inner wall of the measurement container is formed so as to have a high reflectance due to white coloring or the like, and the outside thereof is covered with a light shielding substance. The container described in either claim 1 or claim 2.
  5. The microplate or cartridge container includes a substantially flat base portion, a plurality of storage portions provided in a matrix or in series on the base portion, and an outer bottom portion of the storage portion facing downward from the periphery of the base portion. The container according to any one of claims 1 to 4, further comprising a leg wall portion that protrudes to support the base portion.
  6. The upper surface of the base part of the cartridge container or the microplate covers an opening of each accommodating part, and a seal into which a pipette tip can enter is provided by thermal welding or ultrasonic welding. The container in any one of Claim 5 thru | or 5 .
JP2004280215A 1995-07-31 2004-09-27 container Expired - Fee Related JP3927570B2 (en)

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