JP2011033465A - Device for analysis - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a miniaturized device for analysis having a reduced weight. <P>SOLUTION: The device includes: a reaction vessel having an opening formed thereon, for storing a sample and a reagent inside through the opening; a dispensation chip holding the sample and the reagent inside and having a discharge hole for the sample and the reagent, which is a dispensation chip engageable with the reaction vessel to seal the opening of the reaction vessel in the state where the discharge hole is inserted into the reaction vessel; a dispenser on which the dispensation chip is mounted, for sucking the sample and the reagent into the dispensation chip through the discharge hole and discharging the sample and the reagent into the dispensation chip; and a moving means for moving the dispenser on which the dispensation chip engaged with the reaction vessel is mounted. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to an analysis apparatus.

  Conventionally, biochemical analysis using an enzyme reaction, immunological analysis using an antigen-antibody reaction, and molecular biological analysis using a nucleic acid amplification reaction have been widely used for examining viruses and microorganisms present in a sample. Has been done. In such an analysis, an apparatus having a dispensing function for dispensing a sample or a reagent to be mixed into the sample is usually used. For example, Patent Document 1 proposes a nucleic acid detection device having a reaction container in which a sample is stored, a reagent container in which a reagent is stored, and a dispenser with a dispensing tip attached to the tip. In this apparatus, the reagent in the reagent container is sucked into the dispensing tip by the above dispenser, the tip of the dispensing tip is immersed in the sample in the reaction container, the reagent is discharged, and then the dispensing tip is used as the sample. The sample and the reagent are mixed in the reaction container by performing suction and discharge several times while being immersed. Then, the dispenser is moved to take out the dispensing chip from the reaction container, and after performing the nucleic acid amplification reaction, the nucleic acid in the reaction container is detected.

JP 2009-77639 A

  By the way, in the apparatus as described above, after dispensing a reagent with a dispenser and taking out a dispensing chip from the reaction container, a nucleic acid amplification reaction is performed, and a separately prepared lid is attached to the reaction container. Hold and move the reaction vessel. For this reason, it is necessary to provide a mechanism for attaching a lid to the reaction vessel, a mechanism for holding the reaction vessel, and a mechanism for moving the reaction vessel, in addition to the dispenser. There is a problem of increasing the weight and weight.

  Therefore, an object of the present invention is to provide a device that is reduced in size and weight with a small number of mechanisms.

  An apparatus according to the present invention has been made to solve the above-described problems, and has an opening formed therein, and a reaction container that accommodates the sample and the reagent therein through the opening, and the sample and the reagent inside. A dispensing tip that holds and has a sample and reagent discharge hole, and is engageable with the reaction container so as to seal the opening of the reaction container in a state where the discharge hole is inserted into the reaction container. A dispensing tip, and a dispensing device that is mounted with the dispensing tip and causes the sample and reagent to be sucked into the dispensing tip through the discharge hole and to discharge the sample and reagent in the dispensing tip; Moving means for moving a dispenser equipped with a dispensing tip engaged with the reaction vessel.

  In the above apparatus, the discharge hole of the dispensing tip attached to the dispenser is inserted into the reaction container, and the sample and the reagent held in the dispensing tip are discharged into the reaction container. At this time, the reaction container is engaged with the opening sealed by the dispensing tip. Thus, in the above apparatus, the dispensing tip serves as a lid for sealing the opening of the reaction vessel, and it is not necessary to prepare a separate lid for the reaction vessel, so the dispensing tip is removed from the reaction vessel. The reaction vessel can be moved to the next step without any problems. Therefore, it is not necessary to separately provide a mechanism for attaching the lid to the reaction container or a mechanism for holding the reaction container for movement, and the apparatus can be reduced in size and weight. In addition, the sample in the reaction container is not scattered and contamination between the reaction containers can be prevented.

  In the above apparatus, the dispensing tip may have a breathable filter that prevents a sample and a reagent held inside when the dispensing tip is attached to the dispensing device from coming into contact with the dispensing device. According to this configuration, since the dispensing tip is sealed by the filter so that the sample and the reagent are not scattered from the upper part of the dispensing tip, it is possible to more reliably prevent contamination between the reaction vessels. It is also possible to prevent the reagent from evaporating.

  The apparatus may include a heating / cooling device and a detector, and may be configured such that a reaction vessel connected to the dispenser via the dispensing tip can reach them. In this apparatus, a reaction vessel connected to a dispenser via a dispensing tip is moved to a heating / cooling device by a moving means, and heated or cooled to generate a reaction product in the reaction vessel. Thereafter, the reaction vessel is moved to the detector by the moving means, and the generated reaction product is detected. As described above, the apparatus can carry out the reaction vessel for reaction and detection with only one moving means, so that the apparatus can be reduced in size and weight.

  According to the present invention, the device can be reduced in size and weight.

It is a plane schematic diagram of the device concerning this embodiment. It is front sectional drawing of the dispensing tip which concerns on this embodiment. It is front sectional drawing of the reaction container which concerns on this embodiment. It is front sectional drawing of the dispensing chip | tip and reaction container which concern on this embodiment. It is a front schematic diagram of the dispenser concerning this embodiment. It is a front schematic diagram of a dispenser and a dispensing tip concerning this embodiment. It is the schematic which shows a part of apparatus which concerns on this embodiment.

  Hereinafter, an embodiment in which the present invention is applied to a nucleic acid detection device will be described with reference to the drawings. For convenience of explanation, in FIG. 1, the lower side is referred to as the front side and the upper side is referred to as the back side.

  The nucleic acid detection apparatus 1 according to the present embodiment is an apparatus for detecting nucleic acids in a sample after mixing a necessary reagent in the sample and performing a nucleic acid amplification reaction. As shown in FIG. 1, the apparatus 1 includes a rack 6 that holds various containers, a dispenser 7 that dispenses samples and reagents from the containers held in the rack 6, and a movement that moves the dispenser 7. Means 9 are provided. The apparatus 1 includes a centrifuge 10 for applying a centrifugal force to a sample and a reagent, a nucleic acid amplification detector 11 for generating a nucleic acid amplification reaction of the sample and detecting a nucleic acid, a used dispensing tip, and the like. A disposal box 13 for disposal is provided.

  As shown in FIG. 1, the rack 6 includes a dispensing tip 2 a for dispensing the sample and the first to third reagents, a sample container 3 in which the sample is stored, Sixteen unretained first to third reagent containers 41 to 43 and 16 empty reaction containers 5 are placed. In addition, three dispensing tips 2b for supplying reagents to the first to third reagent containers 41 to 43 are placed on the left side of the rack 6, and the first to third reagent chips are placed in the back thereof. First to third supply source reagent containers 81 to 83 in which reagents are accommodated are placed.

  As shown in FIG. 2, the dispensing tip 2 a is formed in a substantially conical cylinder shape, and an upper end is opened so that the dispensing tip 2 a can be attached to a dispensing device 7 described later. The dispensing tip 2a has a discharge hole at the lower end so that the sample and the first to third reagents can be sucked and discharged and the sucked sample and the first to third reagents can be held inside. 21. The dispensing tip 2a is preferably covered at the top with a breathable filter in order to prevent scattering of the held sample and reagent. The dispensing tip 2b has the same configuration as the dispensing tip 2a, and the dispensing tips 2a and 2b are disposable types.

  As shown in FIG. 3, the reaction vessel 5 is closed at the lower end, and an opening 51 is formed at the upper end so that the dispensing tip 2 a can be inserted into the reaction vessel 5. The reaction vessel 5 has an elongated storage part 52 for storing the sample and the first to third reagents in the lower part, and a dispensing tip storage part 53 for storing the dispensing chip 2a in the upper part. ing. As shown in FIG. 4, the reaction container 5 is configured such that when the dispensing tip 2a is inserted, the opening 51 is blocked by the dispensing tip 2a and is not easily separated from the dispensing tip 2a. The means for preventing the reaction vessel 5 and the dispensing tip 2a from being easily separated is preferably formed in a shape such that the reaction vessel 5 and the dispensing tip 2a can be fitted to each other. The force for pressing 2a against the reaction vessel 5 is preferably 1 to 30N. The material for the reaction vessel 5 is preferably a thermoplastic resin or glass, but is not particularly limited. When the material of the reaction vessel 5 is a thermoplastic resin, polypropylene, polyolefin, polymethylpentene, cyclic polyolefin, polyethylene, polystyrene, polycarbonate, polyacetal, polyamide, polyimide, polyamideimide, liquid crystal polymer, polyether ether ketone, polyether sal It is preferably a polymer alloy or a polymer blend comprising any one of phon, polyethylene terephthalate, polyphenylene ether, polysulfone, polyphenylene sulfide, polybutylene terephthalate, methacrylic resin, ABS resin and polyvinyl chloride, or two or more thereof.

  As shown in FIG. 5, the dispenser 7 has a general dispensing mechanism 71 such as a syringe or a pipette, and the dispensing tips 2 a and 2 b are attached to the tip by the dispensing mechanism 71. In this state (FIG. 6), the sample and the first to third reagents are aspirated and discharged. The dispenser 7 includes a cylindrical portion 72 that can move up and down at the tip portion. When the cylindrical portion is moved downward, the dispensing tip 2a with the lower end of the cylindrical portion attached to the tip portion is provided. The dispensing tip 2a can be removed by pushing down. The mechanism for moving the cylindrical portion 72 up and down is not particularly limited.

  As shown in FIG. 1, the moving means 9 can move the dispenser 7 in the apparatus 1. Specifically, in the apparatus 1, the moving means 9 includes a Y-axis arm 9y extending in the depth direction, an X-axis arm 9x extending in the width direction and sliding on the surface of the Y-axis arm 9y, and in the height direction. The Z-axis arm 9z slides in the width direction on the surface of the extending X-axis arm 9x. The dispenser 7 is attached to the Z-axis arm 9z so as to slide in the height direction. With such a configuration, the moving means 9 can move the dispenser 7 freely in the depth direction, the width direction, and the height direction.

  As shown in FIG. 1, the centrifuge 10 is installed on the back side of the rack 6, and moves the sample and the reagent in the reaction vessel 5 to the lower part of the storage unit 52 by centrifugal force. There is no particular limitation. The centrifuge 10 may include, for example, a rotating part 101 in which a plurality of reaction container accommodation holes 102 for accommodating reaction containers are formed, and a motor 103 that rotates the rotating part 101.

  As shown in FIGS. 1 and 7, the nucleic acid amplification detector 11 is installed on the right side of the centrifuge 10, and includes a reaction container storage unit 111 that can store a plurality of reaction containers 5, and a hot air generation unit having a heater. (Not shown) and a fluorescence detection unit (not shown) for fluorescence detection of nucleic acids. The nucleic acid amplification detector 11 generates hot air and cold air at the hot air generator by switching the heater ON / OFF. The hot air and the cold air are introduced into the reaction container storage unit 111, and the storage unit 52 of the reaction container 5 stored in the reaction container storage unit 111 is heated and cooled, whereby the nucleic acid amplification reaction of the sample is performed. At this time, in the storage unit 52, for example, the fluorescence is generated by dissociation of the labeled probe and the target nucleic acid after the hybridization, and by detecting this fluorescence with the fluorescence detection unit, the target in the reaction vessel 5 is detected. Detect the presence of nucleic acid. The excitation light irradiation method and the fluorescence detection method are not particularly limited.

  As shown in FIG. 1, the disposal box 13 is installed on the right side of the detector 12 so that the used dispensing tips 2a and 2b and the reaction vessel 5 can be discarded.

  Next, a method for using the nucleic acid detection device 1 will be described.

  First, by moving the X-axis arm 9x of the moving means 9 along the Y-axis arm 9y in the depth direction of the device 1 and moving the Z-axis arm 9z along the X-axis arm 9x in the width direction of the device 1, The dispenser 7 is moved above the dispensing tip 2b in the rack 6. The dispenser 7 is lowered along the Z-axis arm 9z, and the tip of the dispenser 7 is inserted into the dispenser tip 2b on the rack 6, whereby the dispenser tip 2b is attached to the tip of the dispenser 7. Wear (FIG. 6). Next, the dispenser 7 to which the dispensing tip 2b is attached is raised along the Z-axis arm 9z and moved to the first supply source reagent container 81 on the rack 6, and then the tip of the dispensing tip 2b. Is inserted into the first supply source reagent container 81, and a predetermined amount of the first reagent in the first supply source reagent container 81 is sucked into the dispensing tip 2b by the dispensing mechanism 71 of the dispenser 7. Hold on. In this state, the dispenser 7 is moved to the first reagent container 41 on the rack 6, the tip of the dispensing tip 2 b is inserted into the first reagent container 41, and the first reagent is removed by the dispensing mechanism 71. Discharge into the first reagent container 41. This operation is repeated, and after supplying the first reagent to all the first reagent containers 41, the first reagent container 41 is moved to the disposal box 13 and the dispensing tip 2b attached to the dispensing device 7 is discarded. Thereafter, the dispensing tip 2b is replaced with a new one again, and the second reagent in the second supply source reagent container 82 is supplied to all the second reagent containers 42 in the same manner as described above. Similarly, the dispensing tip 2 b attached to the dispensing device 7 is replaced, and the third reagent in the third supply source reagent container 83 is supplied to all the third reagent containers 43. Then, the dispensing tip 2 b used for supplying the third reagent is removed from the dispenser 7 and discarded in the disposal box 13.

  Next, using a certain dispensing tip 2a held in the rack 6, the sample container 3 and the first to third reagent containers 41 to 43 arranged in the same row as the dispensing tip 2a are arranged in the same row. A sample and a reagent are dispensed into the reaction vessel 5. That is, the dispensing device 7 is moved to the dispensing tip 2 a by the moving means 9, the dispensing device 7 is lowered, and the dispensing tip 2 a is attached to the tip of the dispensing device 7. The dispenser 7 to which the dispensing tip 2a is attached is moved to the sample container 3 on the rack 6, and the sample stored in the sample container 3 is discharged from the dispensing tip 2a by the dispensing mechanism 71 of the dispensing device 7. A predetermined amount is sucked from the hole 21 to hold the sample in the dispensing tip 2a. Subsequently, while the sample is held in the dispensing tip 2a, the dispenser 7 is moved to the first reagent container 41, and the dispensing reagent 71 discharges the first reagent in the first reagent container 41 by the dispensing mechanism 71. A fixed amount is aspirated from 21 to hold the first reagent in the dispensing tip 2a. Further, the second and third reagents are sucked in order from the second and third reagent containers 42 and 43 by the dispensing mechanism 71 while holding the sample and the first reagent in the dispensing tip 2a. The second and third reagents are held in the dispensing tip 2a. Thereafter, the dispenser 7 is moved to the reaction vessel 5 on the rack 6 while holding the sample and the first to third reagents in the dispensing tip 2a, and the dispensing tip 2a is moved to the dispensing tip of the reaction vessel 5. It accommodates in the accommodating part 53 and seals the opening 51 (FIG. 4). At this time, the dispensing tip 2a and the reaction vessel 5 are not easily separated.

  Next, the dispenser 7 is moved to the centrifuge 10 by the moving means 9 together with the reaction vessel 5 whose opening 51 is blocked by the dispensing tip 2 a, and the reaction vessel 5 is accommodated in the reaction vessel accommodation hole 102. The dispensing tip 2a is removed from 7 and only the dispensing device 7 is raised. At this time, the reaction container 5 keeps the state in which the opening 51 is sealed by the dispensing tip 2a. Then, the motor 103 of the centrifuge 10 is driven to rotate the rotating unit 101, and a centrifugal force is applied to the sample and the first to third reagents in the reaction vessel 5, whereby the sample and the first to third samples are added. The reagent is moved to the lower end side of the storage unit 52. Thereafter, the dispenser 7 is lowered and the dispensing tip 2 a is mounted again on the tip of the dispenser 7.

  Next, the dispenser 7 together with the dispensing tip 2 a and the reaction container 5 is moved to the nucleic acid amplification detector 11 by the moving means 9, and the reaction container 5 is accommodated in the reaction container accommodating portion 111, and dispensed from the dispenser 7. The tip 2a is removed and only the dispenser 7 is raised. Then, hot air and cold air are generated in the hot air generation unit by switching the heater ON / OFF, a predetermined temperature cycle is applied to the storage unit 52 of the reaction vessel 5, and the nucleic acid amplification reaction of the sample in the storage unit 52 Give rise to At this time, for example, the labeled probe and the target nucleic acid are dissociated after the hybridization, whereby fluorescence is generated in the reservoir 52. This fluorescence is measured by the fluorescence detection unit, and the target nucleic acid present in the storage unit 52 is detected.

  After the above processing is completed, the dispenser 7 is lowered, the dispensing tip 2 a is attached to the dispensing device 7, and the dispensing tip 2 a and the reaction vessel 5 are taken out from the reaction vessel 111. Then, when the dispenser 7 is moved to the disposal box 13 together with the dispensing tip 2a and the reaction vessel 5, and the dispensing tip 2a is removed from the dispensing device 7, the opening 51 is blocked by the dispensing tip 2a and the dispensing tip 2a. The reaction container 5 is discarded in the disposal box 13.

  As described above, according to the embodiment described above, the dispensing tip 2a attached to the dispenser 7 is inserted into the reaction vessel 5, and the reaction vessel 5 is sealed with the opening 51 of the reaction vessel 5 by the dispensing tip 2a. A sample and first to third reagents are injected into 5. Since the reaction vessel 5 can move in the apparatus 1 while the opening 51 is blocked by the dispensing tip 2a and can perform nucleic acid amplification reaction or nucleic acid detection, it is necessary to take out the dispensing tip 2a from the reaction vessel 5. There is no. Thereby, it is possible to prevent the sample and reagent adhering to the dispensing tip from being scattered in the apparatus, and it is possible to prevent contamination from occurring between the reaction containers. Further, in the above apparatus, the sample, the reagent, and the reaction container can be transported by only one moving means, so that the apparatus can be reduced in size and weight.

  As mentioned above, although embodiment of this invention was described, this invention is not limited to these, A various change is possible unless it deviates from the meaning of this invention. For example, in the apparatus of the above-described embodiment, the first to third reagent containers 41 to 43 are provided. However, the present invention is not limited to this, and the number of reagent containers is changed according to the type of necessary reagent. You can also.

  Moreover, in the said embodiment, although 16 sample containers 3 which accommodated the sample were prepared, it is not limited to this, The number of sample containers is changed according to the number of samples to be detected. You can also. Note that the numbers of the first to third reagent containers 41 to 43, the reaction container 5, and the dispensing tips 2a may be changed according to the increase or decrease of the reaction containers.

  Moreover, in the said embodiment, the dispensing tip 2a, the sample container 3, the 1st-3rd sample containers 41-43, and the reaction container 5 are mounted from the right front side of the rack 6 to the back, and the left side. Although the dispensing tip 2b and the first to third supply source sample containers 81 to 83 are placed from the front to the back, the present invention is not limited to this, and the positions of the various containers in the rack can be changed as appropriate.

  Moreover, in the said embodiment, although the centrifuge 10 and the nucleic acid amplification detector 11 (a heating cooler, a detector) were installed in the back | inner side of the rack 6, it is not limited to this, A centrifuge, a heating cooling The position of the detector and the detector can be changed as appropriate.

  In the above embodiment, the moving means 9 is constituted by the XYZ axis arms 9x, 9y, 9z. However, the moving means serves as a dispenser as a sample container, a reagent container, a plurality of reaction containers, a heating / cooling machine, And if it can be made to reach | attain all of a detector, it will not be limited to this, For example, a robot arm, a rotation mechanism, etc. may be sufficient.

  In the above embodiment, the present invention is applied to the nucleic acid detection device. However, the present invention is not limited to this. For example, the present invention can also be applied to an immunoassay method, a biochemical analysis method, or the like. In this case, the nucleic acid amplification detector 11 of the above embodiment can be replaced with a photomultiplier tube or the like in the immunoassay, and can be replaced with a spectrophotometer or the like in the biochemical analysis method.

  Moreover, when applying this invention to an immunoassay method, a biochemical analysis method, etc., the centrifuge 10 in the said embodiment does not need to be provided. In this case, the storage part may not be formed long and narrow like the reaction container 5 in the above embodiment.

DESCRIPTION OF SYMBOLS 1 Apparatus 2a, 2b Dispensing tip 21 Discharge hole 5 Reaction container 51 Opening 7 Dispenser 9 Moving means 10 Centrifugal machine 11 Nucleic acid amplification detector (warming cooler, detector)

Claims (3)

An opening is formed, and a reaction container for storing a sample and a reagent therein through the opening;
A dispensing tip that holds a sample and a reagent therein and has a discharge hole for the sample and the reagent, wherein the reaction container is configured to seal the opening of the reaction container in a state where the discharge hole is inserted into the reaction container. Said dispensing tip engageable with,
A dispenser that is mounted with the dispensing tip and causes the sample and reagent to be sucked into the dispensing tip through the discharge hole and to discharge the sample and reagent in the dispensing tip;
A moving means for moving a dispenser equipped with a dispensing tip engaged with the reaction vessel.   The dispensing tip has an air-permeable filter for preventing a sample and a reagent held therein when the dispensing tip is attached to the dispensing device from coming into contact with the dispensing device. The device described in 1. A heating and cooling machine for heating or cooling the sample to produce a reaction product;
A detector for detecting the reaction product,
The apparatus according to claim 1 or 2, wherein the moving means can cause a reaction vessel connected to a dispenser via the dispensing tip to reach the heating cooler and the detector.

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