CN115943202A - Gene Analysis Device - Google Patents

Abstract

In a gene analyzer, a reagent holder (22) holds a plurality of reagent bottles containing reagents to be injected into a plurality of reaction vessels, respectively, in a bottle area (221). More specifically, the reagent support (22) comprises: a reagent bottle hole (221A) for holding a1 st reagent bottle containing a predetermined reagent; and a reagent bottle hole (221G) for holding a2 nd reagent bottle for storing a predetermined reagent.

Description

Gene analysis device

Technical Field

The present disclosure relates to a gene analyzer, and more particularly, to a gene analyzer for analyzing a sample generated by injecting a sample in a sample container into the sample container with a needle.

Background

Conventionally, various techniques have been proposed for apparatuses used for gene analysis. For example, japanese patent No. 5504797 (patent document 1) discloses an arrangement of an optical sensor for accurately detecting an object to be detected in a nucleic acid amplifier using a detector for detecting the object to be detected by fluorescence of a fluorescent substance.

Documents of the prior art

Patent document

Patent document 1: japanese patent No. 5504797

Disclosure of Invention

Problems to be solved by the invention

In the gene analysis process, various reagents such as enzymes and primers can be used. A gene analyzer is provided with a reagent bottle containing such a reagent, and when preparing a sample, a required amount of reagent is dispensed from the reagent bottle every time.

When a plurality of samples are analyzed in succession, the gene analyzer sometimes requires a reagent bottle to contain a reagent in an amount corresponding to the entire plurality of samples, so as to avoid opening and closing of the door of the analyzer during the continuous analysis. In such a case, when the remaining amount of the reagent in the reagent bottle is small, the small amount of the reagent may be discarded without being used.

The present disclosure has been made in view of the above-described background, and an object thereof is to provide a technique for efficiently utilizing a reagent in a gene analyzer.

Means for solving the problems

According to one aspect of the present disclosure, there is provided a gene analyzer including a rack holding a plurality of reagent bottles containing reagents to be injected into a plurality of reaction containers, respectively, the rack including: a1 st vial hole for holding a1 st reagent vial containing a predetermined reagent; and a2 nd bottle hole holding a2 nd reagent bottle accommodating a given reagent.

The gene analysis device may further include: a dispenser that dispenses a predetermined reagent into a plurality of vials that contain the reagents to be injected into the plurality of reaction vessels, respectively; and a controller that controls the operation of the dispenser. The plurality of tubes may also include a1 st tube and a2 nd tube. The controller may control as follows: the method includes the steps of specifying a predetermined amount of a reagent required for dispensing into the 1 st and 2 nd vials, dispensing the predetermined reagent from the 1 st reagent bottle into the 1 st and 2 nd vials if the remaining amount of the predetermined reagent stored in the 1 st reagent bottle is equal to or more than the predetermined amount, and dispensing the predetermined reagent from the 1 st and 2 nd reagent bottles into the 1 st and 2 nd vials if the remaining amount of the predetermined reagent stored in the 1 st reagent bottle is less than the predetermined amount.

The 1 st reagent bottle may also contain a given reagent that expires earlier in terms of life than the given reagent contained by the 2 nd reagent bottle.

The 1 st reagent bottle may be held in the 1 st well before the 2 nd reagent bottle is held in the 2 nd well.

The controller may include a memory for storing information indicating that the 1 st reagent bottle is preferentially used compared to the 2 nd reagent bottle.

The stent may also contain a1 st designation to the 1 st well and a2 nd designation to the 2 nd well. The 1 st and 2 nd identifiers may also contain common information.

ADVANTAGEOUS EFFECTS OF INVENTION

According to the present disclosure, in the case where a predetermined reagent is used for analyzing a plurality of samples, even if the remaining amount of the reagent in the 1 st reagent bottle is small enough to cope with only a part of the plurality of samples, the plurality of samples can be continuously analyzed by using the reagent stored in the 2 nd reagent bottle. Thus, a small amount of the reagent in the 1 st reagent bottle can be effectively used.

Drawings

FIG. 1 is a diagram showing the external appearance of an example of a gene analysis device.

FIG. 2 is a schematic cross-sectional view of the gene analyzer 1.

FIG. 3 is a schematic longitudinal sectional view of the gene analyzer 1.

FIG. 4 is a schematic longitudinal cross section of the nucleic acid amplifier 6 and the detector 7.

Fig. 5 is an enlarged view of the vicinity of the irradiation portion 71 and the light sensor 72.

Fig. 6 is a diagram schematically showing the directions of the excitation light and the detected fluorescence in the detector 7.

Fig. 7 is an enlarged view of the vicinity of the sample preparation region 2 in fig. 1.

Fig. 8 is a longitudinal cross-section of a dispensing tip.

Fig. 9 is a diagram showing an arrangement of dispensing tips of the dispensing tip cartridge.

Fig. 10 is a schematic diagram showing a longitudinal section of the reaction vessel 11.

Fig. 11 is a schematic diagram showing a longitudinal section of the dispensing tip 8 and the reaction vessel 11.

Fig. 12 is a front view of the dispenser 3.

Fig. 13 is a diagram showing a state in which the dispensing tip 8 is attached to the dispenser 3.

FIG. 14 is a diagram showing the hardware configuration of the gene analyzer 1.

Fig. 15 is a diagram showing an example of the data structure of the reagent management information.

Fig. 16 is a diagram showing an example of a data structure of sample modulation information.

FIG. 17 is a flowchart of the processing executed by the gene analyzer 1 to detect a target nucleic acid.

Fig. 18 is a flowchart of a subroutine of the reagent dispensing (step S30) of fig. 17.

Fig. 19 is a diagram showing a structure of a1 st modification of the reagent management information.

FIG. 20 is a diagram showing a structure of a2 nd modification of the reagent management information.

FIG. 21 is a diagram showing the structure of a modification 3 of the reagent management information.

Fig. 22 is a flowchart of a subroutine of the sample preparation (step S40) of fig. 17.

Fig. 23 is a diagram showing an example of a clean area when preparing the sample of test No. 1.

Fig. 24 is a diagram for explaining an example of the movement path of the dispenser 3 in preparation of the sample of test number 1.

Fig. 25 is a diagram for explaining an example of the movement path of the dispenser 3 in preparation of the sample of test number 1.

Fig. 26 is a diagram for explaining an example of the movement path of the dispenser 3 in preparation of the sample of test number 1.

Fig. 27 is a diagram for explaining an example of the movement path of the dispenser 3 in preparation of the sample of test number 1.

Fig. 28 is a diagram showing an example of a clean area when the sample of test No. 8 was prepared.

Fig. 29 is a diagram showing a modification of the sample modulation information.

Detailed Description

Hereinafter, embodiments of the technical idea of the present disclosure will be described with reference to the drawings. In the following description, the same components are denoted by the same reference numerals. The names and functions of these components are also the same. Thus, detailed description about these components will not be repeated.

[ appearance of Gene analysis apparatus ]

FIG. 1 is a view showing the external appearance of an example of a gene analyzer. The gene analyzer 1 houses a controller 10 for controlling operations of each element in the gene analyzer 1, a sample, and a device for analyzing the sample in the main body 1A thereof. The main body 1A is provided with a door 15 for opening and closing the main body 1A.

[ Structure of Gene analysis apparatus ]

FIG. 2 is a schematic cross-sectional view of the gene analyzer 1. The gene analyzer 1 is provided with a sample preparation region 2. Elements for preparing a sample from a sample and/or a reagent are arranged in the sample preparation region 2. Details of the elements in the sample preparation region 2 will be described later with reference to fig. 7 and the like.

The gene analyzer 1 includes a dispenser 3, a transfer unit 4, a centrifuge 5, and a waste box 12. The dispenser 3 suctions and ejects the specimen and the reagent. The moving unit 4 moves the dispenser 3. The centrifuge 5 applies a centrifugal force to the sample. The disposal container 12 stores used dispensing needles and the like.

The gene analysis apparatus 1 further includes a nucleic acid amplifier 6 and a detector 7. The nucleic acid amplification unit 6 generates a nucleic acid amplification reaction of a sample. The detector 7 detects nucleic acids in the sample.

FIG. 3 is a schematic longitudinal cross-sectional view of the gene analysis device 1. The nucleic acid amplifier 6 includes a casing 61, a hot air generator 64, and a fan 65.

The housing 61 includes a chamber 611 having an opening and a turntable 612 arranged in such a manner as to cover the opening of the chamber 611. The chamber 611 is formed in a bottomed cylindrical shape, and the opening is located at an upper end of the chamber 611.

The turntable 612 is rotatable about a central axis, and has a plurality of 2 nd holding holes 62 formed on the same circumference for holding the reaction vessels 11, and the reaction vessels 11 will be described later with reference to fig. 5 and the like. When the reaction container 11 is disposed in the 2 nd holding hole 62, the storage portion 112 of the reaction container 11 is disposed in the chamber 611.

A circular discharge port 63 for discharging air in the chamber 611 is formed in the center of the turntable 612. In one embodiment, the size of the chamber 611 is preferably 68mm to 106mm in diameter and 45mm to 70mm in height, in which case the discharge port 63 of the turntable 612 is preferably 50mm to 65mm in diameter.

The hot air generator 64 is formed in a cylindrical shape and has a heater 641 inside. The hot air generator 64 is provided inside the discharge port 63 so that an upper end thereof protrudes above the turntable 612. The lower end of the hot air generator 64 is opened in the chamber 611.

The fan 65 is provided below the hot air generator 64 in the chamber 611, and is configured to blow out the air in the chamber 611 from the outlet 63.

FIG. 4 is a schematic longitudinal sectional view of the nucleic acid amplifier 6 and the detector 7. The detector 7 includes an irradiation part 71 disposed on the right side of the nucleic acid amplifier 6 and an optical sensor 72 disposed on the rear side of the nucleic acid amplifier 6. Fig. 5 is an enlarged view of the vicinity of the irradiation portion 71 and the light sensor 72. Fig. 6 is a diagram schematically showing the directions of the excitation light and the detected fluorescence in the detector 7.

The irradiation unit 71 includes a plurality of light sources 711 for irradiating the reservoir 112 of the reaction vessel 11 with excitation light. The light source 711 is disposed parallel to the axial direction of the reaction container 11, and irradiates the excitation light toward the 1 st side surface 114 of the quadrangular prism-shaped reservoir 112 of the reaction container 11. In order to condense the plurality of light source beams on a straight line in the axial direction of the reaction container 11, a cylindrical lens or the like is preferably used.

The optical sensor 72 is disposed so as to face the 2 nd side surface 115 adjacent to the 1 st side surface 114, and detects fluorescence generated in the reaction container 11 and transmitted through the 2 nd side surface 115. In one embodiment, an LED (Light Emitting Diode) or the like is used as the Light source 711, and a photodiode or the like is used as the Light sensor 72.

Fig. 7 is an enlarged view of the vicinity of the sample preparation region 2 in fig. 1. The sample preparation area 2 includes a cartridge installation area 20. Two frames 20A, 20B are formed in the cassette setting region 20, and a dispensing tip cassette in which two or more dispensing tips are unitized is provided in the two frames 20A, 20B. In fig. 7, dispensing tip cartridges 200A and 200B are attached to frames 20A and 20B, respectively. The dispenser tip cassettes 200A and 200B each include a total of 48 dispenser tips arranged in a matrix of 4 dispenser tips in the lateral direction and 12 dispenser tips in the vertical direction. The sample preparation region 2 may have a structure having 3 or more frames so that 3 or more dispensing tip cartridges can be mounted thereon. The number of the dispensing tips included in the dispensing tip cartridge is not limited, and a dispensing tip cartridge including 96 to 384 dispensing tips may be used, for example.

Fig. 8 is a longitudinal section of a dispensing tip. The dispensing tip 8 is formed in a substantially conical tube shape, and has an upper end opening so as to be attachable to a distal end portion of the dispenser 3 described later. The dispensing needle 8 has an ejection hole 81 at a lower end thereof so as to be able to aspirate and eject a sample or a reagent, and is configured to be able to hold the aspirated sample or reagent therein. The dispensing needle 8 is preferably covered at the top with an air-permeable filter to prevent scattering of the held sample and reagent.

Fig. 9 is a diagram showing an arrangement of dispensing tips of the dispensing tip cartridge. The dispensing tip cartridges 200A and 200B each include a frame 201. The 48 dispensing tips 8 are fitted into the frame 201. The frame 201 has a substantially rectangular parallelepiped shape, and has two chamfered corners CN1 and CN 2. The frames 20A and 20B of the sample preparation area 2 are also chamfered in the same manner. The dispensing tip cartridges 200A and 200B can be easily set in the frames 20A and 20B by aligning the chamfered portions of the dispensing tip cartridges 200A and 200B with the chamfered portions of the frames 20A and 20B, respectively. The shape of the frame may be a substantially cubic shape instead of a rectangular parallelepiped, or may be a shape chamfered at 1 or 3 corners.

Returning to fig. 7, a specimen holder 21 is provided in a region other than the cassette setting region 20 in the sample preparation region 2. In the example shown in fig. 7, the specimen holder 21 includes 12 specimen holes 211 arranged in a horizontal row. Each sample hole 211 is provided with a container for storing a sample. The number of sample holes of the sample holder 21 is not limited, and for example, 16 to 48 sample holes may be formed.

In the sample preparation region 2, a reagent holder 22 is provided in a region other than the cartridge installation region 20. The reagent holder 22 is provided with a vial region 221 and a sample region 222. In the example shown in fig. 7, 8 reagent bottle holes 221A, 221B, 221C, 221D, 221E, 221F, 221G, and 221H are formed in the bottle region 221, in which bottles can be set, respectively. The reagent bottle wells 221A, 221B, 221C, 221D, 221E, 221F, 221G, and 221H are provided with the character strings "KOD1", "KOD2", "P1", "P2", "P3", "P4", "S1", and "S2", respectively. These text columns are each an example of a logo. The number of reagent bottle wells in the bottle area is not limited, and may be, for example, 6 to 12 reagent bottle wells.

In the example of FIG. 7, the vial region 221 is provided with vials of two enzymes (labeled "KOD01" and "KOD02" as an example) and vials of 4 primer/probe reagents (labeled "primer A", "primer B", "primer C" and "primer D" as an example). More specifically, a bottle with KOD01 is provided in the reagent bottle well 221A, a bottle with KOD02 is provided in the reagent bottle well 221B, a bottle with primer A is provided in the reagent bottle well 221C, a bottle with primer B is provided in the reagent bottle well 221D, a bottle with primer C is provided in the reagent bottle well 221E, and a bottle with primer D is provided in the reagent bottle well 221F. The "primer probe reagent" refers to a reagent containing a reagent for a primer and a reagent for a probe.

The types of enzymes used for analyzing the sample in the gene analyzer 1 are not limited to the two types shown in fig. 7 as long as they are 1 or more. The types of the primer/probe reagents used for analyzing the sample in the gene analyzer 1 are not limited to the 4 types shown in FIG. 7 as long as they are 1 or more.

The bottle area 221 may be configured such that a bottle containing the same kind of reagent as that contained in a bottle provided in another reagent bottle hole can be provided in the reagent bottle hole 221G or 221H. For example, a bottle of KOD01 can be provided in the reagent bottle hole 221G. A bottle of KOD02 can be provided in the reagent bottle hole 221H. In order to use the reagent bottle hole 221G in this manner, a character string including the same characters as those attached to the reagent bottle hole 221A may be attached to the reagent bottle hole 221H, or a character string including the same characters as those attached to the reagent bottle hole 221B may be attached to the reagent bottle hole 221H. In the example of fig. 7, the character string "KOD1" attached to the reagent bottle well 221A and the character string "S1" attached to the reagent bottle well 221G include the common character "1", and the character string "KOD2" attached to the reagent bottle well 221B and the character string "S2" attached to the reagent bottle well 221H include the common character "2". Here, the common characters are an example of "common information".

In the example shown in fig. 7, a total of 72 holes of 12 in each row are formed in 6 rows in the lateral direction in the sample region 222. The 6 rows of wells in the transverse direction are identified as the 1 st, 2 nd, capillary holes 222A, 222B, 222C, 222D, 222E, 222F from below. The number of holes formed in the sample region 222 is not limited to the number shown in fig. 7. The holes may be formed in 10 to 20 rows in 6 rows in the lateral direction, or may be formed in such a manner that the number of rows is further increased (for example, 9 rows or 12 rows).

A tube for dispensing a reagent is provided in each of the 12 1 st reagent wells 222A and the 12 2 nd reagent wells 222B. The reaction containers 11 are provided in the 12 capillary holes 222C, respectively. The reaction container 11, which is arranged in the vertical direction and includes a tube provided in the 1 st reagent well 222A, a tube provided in the 1 nd 2 nd reagent well 222B, and a tube provided in the 1 capillary hole 222C, is involved in sample preparation. For example, the reagent contained in the tube provided in the leftmost first reagent well 222A and the reagent contained in the tube provided in the leftmost second reagent well 222B are injected into the reaction container 11 provided in the leftmost capillary hole 222C.

A tube for dispensing a reagent is provided in each of the 12 1 st reagent wells 222D and the 12 2 nd reagent wells 222E. The reaction containers 11 are provided in the 12 capillary holes 222F, respectively. The reaction container 11, which is arranged in the vertical direction and is provided with the 1 st reagent well 222D, the 1 nd 2 nd reagent well 222E, and the 1 capillary hole 222F, participates in sample preparation. For example, the reagent contained in the tube provided in the leftmost first reagent well 222D and the reagent contained in the tube provided in the leftmost second reagent well 222E are injected into the reaction container 11 provided in the leftmost capillary hole 222F.

That is, in the example shown in fig. 7, 12 tubes and reaction containers 11 for preparing a sample are provided in the sample region 222 in the lower 3 rows of holes out of the 6 rows of holes in the lateral direction. The upper 3 rows of wells were provided with 12 tubes and reaction vessels 11 for sample preparation. Therefore, 24 tubes and reaction vessels 11 for preparing a sample can be provided in the sample region 222. In addition, as a modification, the number of the prepared samples can be increased by increasing the number of the 1-row reagent wells and capillary wells or increasing the number of the rows.

In the gene analyzer 1, the specimen container, the tube for storing the reagent, and the reaction container 11 for storing the sample may be held in 1 holder. In the example shown in fig. 7 and the like, the sample container is held by the sample holder 21, and the tube for storing the reagent and the reaction container 11 for storing the sample are held by the reagent holder 22. That is, the sample container is held by a holder different from the holder holding the tube and the reaction container 11. This makes it possible to fit the lateral intervals of the sample holes 211 of the sample holder 21 to the size of the sample container, and fit the lateral intervals of the 1 st, 2 nd, and capillary holes 222A, 222D, 222B, 222E, and 222C, 222F of the reagent holder 22 to the size of the tube and the reaction container 11. In the example of fig. 7, the intervals in the lateral direction of the 1 st reagent wells 222A and 222D, the 2 nd reagent wells 222B and 222E, and the capillary holes 222C and 222F of the reagent holder 22 are narrower than the intervals in the lateral direction of the sample wells 211 of the sample holder 21. That is, in the example of fig. 7, the space inside the gene analyzer 1 can be effectively used by minimizing the hole interval of the reagent holder 22.

The reference line L1 is shown in fig. 7. In the gene analyzer 1, the specimen holder 21 and the reagent holder 22 are positioned on one side of the reference line L1, and the cassette setting region 20 is positioned on the other side of the reference line L1. Thus, the cassette installation region 20 holding the unused dispensing tip 8 is more reliably separated from the region where the sample and the reagent are installed, and contamination of the dispensing tip 8 can be more reliably avoided.

Next, the reaction vessel 11 will be explained. Fig. 10 is a schematic diagram showing a longitudinal section of the reaction vessel 11.

As shown in fig. 10, the reaction vessel 11 has a closed lower end and an opening 111 formed at an upper end thereof so that the dispensing tip 8 can be inserted thereinto. The reaction vessel 11 has an elongated storage portion 112 formed in a lower portion thereof for storing a sample and a reagent, and a storage portion 113 formed in an upper portion thereof for storing the dispensing tip 8.

Fig. 11 is a schematic diagram showing a longitudinal section of the dispensing tip 8 and the reaction vessel 11. The reaction container 11 is configured to be fitted to the dispensing tip 8 with the opening 111 closed by the dispensing tip 8 when the dispensing tip 8 is inserted. The material of the reaction vessel 11 is preferably a thermoplastic resin or glass, and is not particularly limited, but in the case of a thermoplastic resin, it is preferably any one of polypropylene, polyolefin, polymethylpentene, cyclic polyolefin, polyethylene, polystyrene, polycarbonate, polyacetal, polyamide, polyimide, polyamideimide, liquid crystal polymer, polyetheretherketone, polyethersulfone, polyethylene terephthalate, polyphenylene oxide, polysulfone, polyphenylene sulfide, polybutylene terephthalate, methacrylic resin, ABS resin, and polyvinyl chloride, or a polymer alloy or polymer blend composed of two or more of these.

Next, the dispenser 3 will be explained. Fig. 12 is a front view of the dispenser 3. Fig. 13 is a diagram showing a state in which the dispensing tip 8 is attached to the dispenser 3.

As shown in fig. 12, the dispenser 3 includes a normal dispensing mechanism 31 such as a syringe or a pipette, and the dispensing mechanism 31 suctions and discharges a sample or a reagent in a state where the dispensing needle 8 is attached to the tip end portion.

The dispenser 3 has a vertically movable cylindrical portion 32 at the distal end portion, and is configured to be able to remove the dispensing tip 8 by moving the cylindrical portion 32 downward and pressing the dispensing tip 8 attached to the distal end portion.

Next, the mobile unit 4 will be explained. As shown mainly in fig. 2 and 3, the moving unit 4 includes a Y-axis arm 4Y extending in the depth direction, an X-axis arm 4X extending in the width direction and sliding in the depth direction on a surface of the Y-axis arm 4Y, a Z-axis arm 4Z extending in the height direction and sliding in the width direction on a surface of the X-axis arm 4X, and a driving section (e.g., a motor or the like) for sliding these arms. The dispenser 3 is mounted on the Z-axis arm 4Z. With such a configuration, the moving means 4 can freely move the dispenser 3 in the depth direction, the width direction, and the height direction.

Next, the centrifuge 5 will be explained. The centrifuge 5 moves the sample in the reaction vessel 11 toward the lower end by centrifugal force. As shown mainly in fig. 2, the centrifuge 5 is provided on the back side of the sample preparation region 2. In one embodiment, as shown mainly in fig. 3, the centrifuge 5 includes a rotating part 53, and the rotating part 53 is formed with a plurality of 1 st holding holes 531 for holding the reaction vessels 11. The rotating portion 53 may be attached to the rotating shaft 51 rotated by the driving portion 52.

[ operation of analyzing a sample of a Gene analysis apparatus ]

Next, the operation of the gene analyzer 1 for analyzing a sample will be described.

(1) Dispensing of reagents

First, a necessary reagent is dispensed from the vial in the vial region 221 to the vials provided in the 1 st reagent well 222A, 222D and the 2 nd reagent well 222B, 222E, respectively.

(2) Preparation of sample

The sample in the sample container provided in the sample holder 21 and the reagents in the tubes provided in the 1 st reagent well 222A, 222D and the 2 nd reagent well 222B, 222E are injected into the reaction container 11 provided in the capillary holes 222C, 222F.

More specifically, the moving means 4 moves the X-axis arm 4X in the depth direction of the gene analyzer 1 along the Y-axis arm 4Y, and moves the Z-axis arm 4Z in the width direction of the gene analyzer 1 along the X-axis arm 4X. Thereby, the dispenser 3 moves above the dispensing tip 8 held in the cartridge setting region 20.

Next, the moving unit 4 lowers the dispenser 3 along the Z-axis arm 4Z, and inserts the tip of the dispenser 3 into the dispensing tip 8. Thus, a dispensing tip 8 is attached to the tip of the dispenser 3.

Next, the moving unit 4 moves the dispenser 3 to which the dispensing needle 8 is attached to the sample container of the sample holder 21 (in the example shown in fig. 7, any one of 12 sample containers provided in 12 sample wells 211, respectively), and the controller 10 sucks a certain amount of the sample in the sample container from the discharge port 81 into the dispensing needle 8 by the dispensing mechanism 31 of the dispenser 3.

Next, the moving unit 4 moves the dispenser 3 to the 1 st reagent well 222A provided in the reagent holder 22 (in the example shown in fig. 7, any one of the 12 tubes provided in the 12 1 st reagent wells 222A, respectively), and the controller 10 causes the dispenser 3 to aspirate a certain amount of the reagent in the tube.

Next, the moving unit 4 moves the dispenser 3 to the tube provided in the 2 nd reagent well 222B of the reagent holder 22 (in the example shown in fig. 7, any one of the 12 tubes provided in the 12 2 nd reagent wells 222B, respectively), and the controller 10 causes the dispenser 3 to aspirate a certain amount of the reagent in the tube.

Next, the moving unit 4 moves the dispenser 3 to the reaction cuvette 11 (in the example shown in fig. 7, any one of the reaction cuvettes 11 provided in the 12 capillary holes 222C, respectively) provided in the capillary hole 222C of the reagent holder 22, and inserts the dispensing tip 8 at the tip end of the dispenser 3 into the reaction cuvette 11. Thereby, the dispensing tip 8 and the reaction vessel 11 are fitted to each other.

Subsequently, the controller 10 causes the dispenser 3 to discharge the sample and the reagent into the reaction container 11.

When a sample is prepared in the reaction container 11 provided in the capillary hole 222F, the 1 st reagent well 222A, the 2 nd reagent well 222B, and the capillary hole 222C are changed to the 1 st reagent well 222D, the 2 nd reagent well 222E, and the capillary hole 222F.

That is, the moving unit 4 moves the dispenser 3 to the tube provided in the 1 st reagent well 222D (in the example shown in fig. 7, any one of 12 tubes provided in the 12 1 st reagent wells 222D, respectively), the controller 10 sucks the reagent in the tube, the moving unit 4 moves to the tube provided in the 2 nd reagent well 222E (in the example shown in fig. 7, any one of 12 tubes provided in the 12 2 nd reagent wells 222E, respectively), the controller 10 sucks the reagent in the tube, the moving unit 4 then moves to the reaction container 11 provided in the capillary well 222F (in the example shown in fig. 7, any one of the reaction containers 11 provided in the 12 capillary wells 222F, respectively), and the controller 10 ejects the sample and the reagent to the reaction container 11.

Next, the transfer unit 4 moves the dispenser 3, to which the reaction container 11 and the dispensing needle 8 are attached, to the centrifuge 5, inserts the reaction container 11 into the 1 st holding hole 531 through the opening 5A, detaches the dispensing needle 8 from the dispenser 3, and raises only the dispenser 3.

Next, the controller 10 drives the driving unit 52 of the centrifuge 5. The rotating unit 53 is thereby rotated, and the sample and the reagent in the reaction container 11 are moved to the lower end side of the reaction container 11 by applying a centrifugal force, and are filled in the reservoir unit 112. The process of filling the sample and the reagent into the reservoir 112 in this way will be described as follows as the process by the centrifuge 5 in step S50 in fig. 17.

When the operation by the centrifuge 5 is completed, the transfer unit 4 lowers the dispenser 3, and reattachs the dispensing tip 8 attached to the 1 st holding hole 531 to the tip end of the dispenser 3.

Subsequently, the transfer unit 4 moves the dispenser 3, to which the reaction vessel 11 and the dispensing tip 8 are attached, to the nucleic acid amplifier 6, inserts the reaction vessel 11 into the 2 nd holding well 62, and removes the dispensing tip 8 and the reaction vessel 11 from the dispenser 3 to lift only the dispenser 3.

The moving means 4 repeats the above-described steps, and thereby a required number of reaction containers 11 filled with the sample and the reagent are set in the nucleic acid amplifier 6.

In the process of preparing a plurality of samples, the transfer unit 4 attaches the dispensing tip 8 to the dispenser 3 from one of the dispensing tip magazine 200A and the dispensing tip magazine 200B provided in the magazine installation region 20. In one embodiment, the moving unit 4 first uses the dispensing tip 8 provided in the dispensing tip cartridge 200A, and uses the dispensing tip 8 provided in the dispensing tip cartridge 200B when the dispensing tip 8 provided in the dispensing tip cartridge 200A is used up.

At the time of sample preparation, the gene analyzer 1 supplies the dispensing tip 8 from the dispensing tip cartridge 200A or the dispensing tip cartridge 200B. Thus, in the gene analyzer 1, the user does not need to set the dispensing tips 8 to the holder one by one using fingers, tweezers, or the like.

Further, the gene analyzer 1 may be provided with a plurality of dispensing tip cartridges. Thus, even if the dispensing tip cartridge 200A becomes empty during a certain inspection (detection of a target nucleic acid), the user does not have to interrupt the inspection. In this examination, the user can cause the mobile unit 4 to replace the empty dispensing tip cartridge 200A with a new one after the end of this examination by using the dispensing tip 8 provided in the dispensing tip cartridge 200B.

(3) Detection of target nucleic acids

After the nucleic acid amplifier 6 is provided with a desired number of reaction containers 11 as described above, the gene analyzing apparatus 1 performs control for the nucleic acid amplification reaction of the sample. Then, the gene analysis apparatus 1 detects the target nucleic acid using a labeled probe labeled with a fluorescent substance. As the fluorescent substance, for example, a substance that is quenched upon hybridization with a target nucleic acid can be used, and a substance that is quenched at the base pair of guanine and cytosine at the end of the label probe, such as fluorescein or a derivative thereof, BODIPY (registered trademark) series, rhodamine, or a derivative thereof, is preferable.

The control includes a modification step, an annealing step, and an elongation step. Hereinafter, each step will be described.

(3-1) modification step

In the reforming step, the controller 10 turns on the heater 641 of the hot air generator 64 and drives the fan 65 to discharge the air in the chamber 611 through the discharge port 63 of the turntable 612. Accordingly, the air pressure in the chamber 611 becomes low, and thus the air outside the chamber 611 is heated by the heater 641 and introduced into the chamber 611 through the inside of the hot air generator 64. By raising the temperature in the chamber 611 to a predetermined temperature (for example, 90 to 105 ℃) in this manner, the sample in the reaction vessel 11 held in the 2 nd holding hole 62 is heated, and double-stranded nucleic acids contained in the sample in the reaction vessel 11 are dissociated into single strands.

(3-2) annealing step

In the annealing step, the controller 10 turns off the heater 641 and drives the fan 65 to discharge the high-temperature air in the chamber 611 through the discharge port 63. Thus, the air at the normal temperature outside the chamber 611 is introduced into the chamber 611 via the hot air generator 64. In this way, by lowering the temperature in the chamber 611 to a predetermined temperature (for example, 35 ℃ to 65 ℃), the sample in the reaction vessel 11 is cooled, and the primer is annealed to the 5' -end of each single-stranded nucleic acid in the sample in the reaction vessel 11. In this case, when the target nucleic acid is present in the sample, the label probe hybridizes to the target nucleic acid. After a lapse of a certain time (for example, 0.01 to 5 minutes) while the temperature in the chamber 611 is maintained at the above-mentioned predetermined temperature (for example, 35 to 65 ℃), the light source 711 of the irradiation unit 71 irradiates the 1 st side surface 114 of the reaction vessel 11 with excitation light. Since the label probe has a property of quenching when it is hybridized with the target nucleic acid, only the label probe that is not hybridized with the target nucleic acid is excited in the reaction vessel 11 to generate fluorescence. Among the fluorescence, the fluorescence transmitted through the 2 nd side 115 of the reaction container 11 is detected by the photosensor 72. Thereafter, the turntable 612 is rotated to irradiate light and detect fluorescence also on the reaction cuvette 11 held in the other 2 nd holding well 62.

(3-3) elongation step

In the extension step, the controller 10 raises the temperature in the chamber 611 to a predetermined temperature (for example, 40 to 80 ℃, preferably 45 to 75 ℃) to heat the sample in the reaction vessel 11, as in the modification step. Thus, the primer annealed to the 5' -end of the single-stranded nucleic acid in the reaction vessel 11 is extended, and a double-stranded nucleic acid replica is generated. At this time, the labeled probe hybridized with the target nucleic acid is dissociated from the target nucleic acid.

By repeating the modification step, the annealing step, and the extension step as described above, the nucleic acid in the sample in the reaction vessel 11 is amplified. When the target nucleic acid is included in the sample, the target nucleic acid also increases, and therefore the number of labeled probes hybridized with the target nucleic acid increases in the annealing step, and the amount of fluorescence detected by the photosensor 72 decreases. The presence or absence of the target nucleic acid contained in the sample in the reaction vessel 11 is determined based on the decrease in the fluorescence amount.

The step of determining the presence or absence of the target nucleic acid in this manner will be described as follows after the nucleic acid detection by the nucleic acid amplifier 6 in step S60 in FIG. 17.

After the detection of the nucleic acid is completed, the transfer unit 4 attaches the reaction vessel 11 and the dispensing tip 8 in the 2 nd holding well 62 of the nucleic acid amplifier 6 to the dispenser 3. Then, the moving means 4 moves the dispenser 3 to the disposal container 12, and operates to detach the dispensing tip 8 and the reaction vessel 11 from the dispenser 3. Thereby, the dispensing tip 8 and the reaction vessel 11 are discarded in the discard box 12.

[ hardware configuration ]

FIG. 14 is a diagram showing the hardware configuration of the gene analyzer 1.

As shown in FIG. 14, in the gene analyzer 1, the controller 10 is connected to the display 17, the dispenser 3, the movement unit 4, the centrifuge 5, the nucleic acid amplifier 6, and the detector 7, and controls the operations of these components.

The gene analysis apparatus 1 further includes an input device 14 and a communication interface (I/F) 16. The input means 14 are realized by operating buttons and/or software buttons displayed on the display 17. The controller 10 accepts input of information via the input device 14. For example, the communication I/F16 is implemented by a network card. The controller 10 communicates with an external device via a communication I/F.

In the example of fig. 14, the controller 10 includes a processor 101 and a memory 102. The memory 102 can store a program executed by the processor 101 and various data used for the operation of the gene analyzer 1.

[ data Structure of reagent management information ]

Fig. 15 is a diagram showing an example of the data structure of the reagent management information. The reagent management information is information for managing the remaining amount of 8 bottles set in the bottle area 221. The reagent management information is stored in the memory 102, for example.

As shown in fig. 15, the reagent management information associates the position, the reagent type, and the remaining reagent amount. The positions indicate reagent bottle holes of 8 bottles, respectively, in the bottle region 221. For example, position "221A" represents reagent bottle well 221A.

The reagent type indicates the type of reagent in the bottle provided in each well. In the example of FIG. 15, "KOD01" and "KOD02" represent the types of enzymes, respectively. "primer A", "primer B", "primer C" and "primer D" each represent the type of primer (or the combination of a primer reagent and a probe reagent when a probe reagent is contained).

The remaining reagent amount indicates that the reagent in the bottle provided in each well can be used for sample preparation several times thereafter. For example, "10" indicates a margin that can be used for sample preparation 10 times later. In one embodiment, when 4. Mu.L of the reagent is used for 1 sample preparation, the "10" remaining amount means that the remaining amount of the reagent is 40. Mu.L.

[ data Structure of sample modulation information ]

Fig. 16 is a diagram showing an example of a data structure of sample modulation information. The sample modulation information indicates the contents of each of the 24 samples. The 24 samples are composed of samples in 12 reaction containers 11 provided in the 12 capillary holes 222C, respectively, and samples in 12 reaction containers 11 provided in the 12 capillary holes 222F, respectively. The sample modulation information is stored in the memory 102, for example.

As shown in fig. 16, the sample preparation information associates a test number, a sample number, a1 st reagent, and a2 nd reagent. The test numbers define 12 capillary holes 222C and 12 capillary holes 222F, respectively. For example, 12 capillary holes 222C are assigned with any one of test numbers 1 to 12, and 12 capillary holes 222F are assigned with any one of test numbers 13 to 24.

The specimen numbers define 12 specimen holes 211, respectively. The sample numbers may be assigned in accordance with the numbers assigned to the 12 sample holes 211 in fig. 7, for example.

The 1 st reagent and the 2 nd reagent are each limited to the type of enzyme and primer used for preparation of each sample (or the type of combination of a primer and a probe when the primer reagent also includes a probe).

In one example, the 1 st reagent of each of test numbers 1 to 12 is dispensed into each of the 12 vials disposed in the 1 st reagent well 222A. The 2 nd reagent of each of test nos. 1 to 12 was dispensed into the 12 vials provided in the 2 nd reagent well 222B. The 1 st reagent of each of test nos. 13 to 24 was dispensed into a pipette provided in each of the 12 1 st reagent wells 222D. The 2 nd reagent of each of test nos. 13 to 24 was dispensed into the 12 nd reagent wells 222E.

In the example of FIG. 16, for example, test number "1", sample number "1", 1 st reagent "KOD01", and 2 nd reagent "primer A" are related. This means that the reagent specified by test number "1" includes the sample specified by sample number "1" (the sample disposed in the leftmost one of the 12 sample wells 211), the enzyme specified by "KOD01", and the primer specified by "primer a".

The sample modulation information is generated by a user, for example. That is, the user inputs information of each prepared sample as sample preparation information to the gene analyzer 1.

In the example of fig. 16, the test numbers "23" and "24" do not relate to the specimen number, the 1 st reagent, and the 2 nd reagent. This means that the preparation of the test pieces was not predetermined for test numbers "23" and "24". That is, the example in fig. 16 means that, when a user can prepare 24 samples at maximum in the gene analyzer 1, preparation of only 22 samples is scheduled at that time.

Fig. 29 shows a modification of the sample modulation information. In fig. 29, test numbers are given as run-numbers when the same sample is measured a plurality of times. That is, for example, the sample of sample number "1" is used for test number "1" and test number "2". By generating the sample modulation information in such a manner that the same sample is used for consecutive test numbers, there is an advantage that it is possible to more reliably avoid a situation in which a clean area including an area in which a sample container containing an unmodulated sample is held is contaminated with another sample, which will be described later.

[ procedure of treatment ]

(1) Main process

Fig. 17 is a flowchart of processing executed for detection of a target nucleic acid in the gene analysis apparatus 1. The gene analysis device 1 may realize the processing of fig. 17 by causing the processor 101 to execute a predetermined program, for example. The above-described processing may be executed by a dedicated Circuit such as a Field-Programmable Gate Array (FPGA) or an Application Specific Integrated Circuit (ASIC).

Referring to fig. 17, in step S10, the gene analyzer 1 receives input of information such as sample modulation information via the input device 14 and/or the communication I/F16.

In step S20, the gene analysis device 1 determines whether or not an instruction to start detection is received by an operation of the start button or the like. The gene analyzer 1 stops the control until the instruction is received in step S20 (no in step S20), and proceeds to step S30 if the instruction is received (yes in step S20).

In step S30, the gene analyzer 1 dispenses a reagent from the bottles set in the reagent bottle wells 221A to 221F to the vials set in the 1 st reagent wells 222A and 222D and the 2 nd reagent wells 222B and 222E, respectively. The type of reagent dispensed into each tube is specified based on the sample preparation information (see fig. 16). Next, the contents of reagent dispensing in step S30 will be described with reference to fig. 18.

In step S40, the gene analyzer 1 prepares a sample in the reaction cuvette 11 provided in the capillary holes 222C and 222F, respectively. The contents of the sample preparation in step S40 will be described later with reference to fig. 19.

In step S50, the gene analyzer 1 processes the prepared sample (reaction vessel 11) with the centrifuge 5.

In step S60, the gene analysis device 1 performs nucleic acid detection using the nucleic acid amplifier 6 on the prepared sample.

In step S70, the gene analyzer 1 performs post-processing such as disposal of the dispensing tip 8 and the reaction vessel 11, and the processing shown in fig. 17 is ended.

(2) Reagent dispensing

Fig. 18 is a flowchart of a subroutine of the reagent dispensing (step S30) of fig. 17.

Referring to fig. 18, in step S300, the gene analysis device 1 sets the value of the variable M to 1. The variable M identifies each reagent dispensed into a pipette provided in the 1 st reagent well 222A, 222D and the 2 nd reagent well 222B, 222E. According to the example of FIG. 16, the reagents dispensed into the 1 st reagent wells 222A and 222D and the 2 nd reagent wells 222B and 222E are 6 types, i.e., "KOD01", "KOD02", "primer A", "primer B", "primer C", and "primer D". The variables M correspond to these 6 reagents, respectively.

In step S302, the gene analyzer 1 specifies the amounts of the respective reagents necessary for dispensing the 1 st and 2 nd reagent wells 222A and 222D and 222B and 222E with respect to the M-th reagent with reference to the sample preparation information (fig. 16). For example, in the case where the reagent No. M is "KOD01", 16 samples (test Nos. 1 to 16) are required, and thus the required amount is specified as "16". When the reagent No. M is "primer A", the required amount is specified to be "12" since it is required for 12 samples (test Nos. 1 to 12).

In step S304, the gene analyzer 1 refers to the reagent management information (fig. 15), and determines whether or not the remaining amount of the reagent No. 1 bottle is equal to or more than the required amount specified in step S300. When the reagent No. M is "primer A", the required amount is "12" and the remaining amount of the reagent is "12", and therefore the remaining amount of the bottle No. 1 is equal to or more than the required amount. On the other hand, in the case where the reagent No. M is "KOD01", the required amount is "16", but the remaining amount of the vial No. 1 (for example, number 1 in numbers 1 and 7 in FIG. 15) is "10", and therefore the remaining amount of the vial No. 1 is not more than the required amount.

If it is determined that the remaining amount of the bottle No. 1 is equal to or larger than the required amount (yes in step S304), the gene analyzer 1 proceeds to step S306, and if not (no in step S304), proceeds to step S308.

In step S306, the gene analyzer 1 determines whether or not the value of the variable M reaches the number P of types of reagents to be dispensed to the 1 st reagent wells 222A and 222D and the 2 nd reagent wells 222B and 222E ("6" in the example of fig. 16). If it is determined that the value of the variable M has reached the number P of types of the reagent (yes in step S306), the gene analyzer 1 proceeds to step S314, otherwise (no in step S306), the control proceeds to step S312.

In step S312, the gene analyzer 1 updates the value of the variable M by adding 1, and returns control to step S302.

In step S308, the gene analyzer 1 determines whether or not the total remaining amount of the No. 1 vial and the No. 2 vial is equal to or more than the required amount specified in step S302 with respect to the M-th reagent. For example, in the case where the reagent No. M is "KOD01", the total amount is equal to or more than the required amount because the remaining amount in the vial No. 1 (e.g., the number 1 in FIG. 15) is "10", the remaining amount in the vial No. 2 (e.g., the number 7 in FIG. 15) is "50", and the required amount is "16".

If it is determined that the sum is equal to or larger than the required amount (yes in step S308), the gene analyzer 1 proceeds to step S306, and if not (no in step S308), proceeds to step S310.

In step S310, the gene analyzer 1 notifies an error and ends the process of fig. 18 (fig. 17). The error notification may be a sound or a display (for example, a display of the display 17).

In step S314, the gene analysis device 1 causes the dispenser 3 to dispense a reagent into the vials disposed in the 1 st reagent wells 222A and 222D and the 2 nd reagent wells 222B and 222E, respectively, in accordance with the sample preparation information (fig. 16). Thereafter, the gene analyzer 1 returns the control to fig. 17.

In step S314, the gene analyzer 1 allows the dispenser 3 to use the reagents in the vials when the reagents of a certain type are stored in 1 vial in an amount necessary for sample preparation for the test numbers 1 to 24 registered in the sample preparation information. In the example shown in fig. 15 and 16, the gene analyzer 1 causes the dispenser 3 to dispense a reagent stored in a bottle No. 3 to each of the vials for test nos. 1 to 12 requiring a reagent "primer a".

On the other hand, when the amounts necessary for preparing the samples of test numbers 1 to 24 registered in the sample preparation information are not stored in 1 bottle but in a plurality of bottles with respect to a certain type of reagent, the gene analyzer 1 causes the dispenser 3 to use the reagents stored in the plurality of bottles. In the example shown in fig. 15 and 16, the gene analyzer 1 causes the dispenser 3 to dispense the reagent stored in the vial No. 1 to 10 to each of the vials No. 1 and No. 7 to each of the vials No. 11 to 16 for the test nos. 1 to 16 requiring the reagent "KOD 01". Thus, when preparing the samples of test nos. 1 to 24 (test nos. 1 to 22 in the example of fig. 16) in 1 examination (detection of target nucleic acid), the examination does not need to be interrupted as long as the required amount of reagent is contained in a plurality of vials in the vial region 221, even if the required amount of reagent is not contained in 1 vial in the vial region 221. The user may simply replace the bottle after the examination is completed. Further, if a reagent bottle that becomes empty after the end of the examination is provided, a configuration may be adopted in which the status of the empty reagent bottle and/or the status of the reagent bottle that needs to be replaced before the next examination is notified by a sound, a display (for example, a display on the display 17), or the like.

When a plurality of bottles containing the same type of reagent are held in the bottle area 221, the controller 10 can determine which of the plurality of bottles is the No. 1 bottle by various methods (step S304). In one embodiment, the order of priority is determined in advance for 8 reagent bottle wells 221A, 221B, 221C, 221D, 221E, 221F, 221G, and 221H, and a bottle held in a reagent bottle well having a higher order of priority among the plurality of bottles may be determined as "bottle No. 1".

In one embodiment, the controller 10 may also determine "vial No. 1" based on data in the reagent management information. Fig. 19 is a diagram showing a structure of a1 st modification of the reagent management information. In the example of fig. 19, the reagent management information further includes the expiration date of the reagent in each bottle. The term of use may be input by the user, or may be read from information printed on the bottle by a reader (not shown) mounted on the gene analyzer 1 and registered in the reagent management information.

The controller 10 determines a bottle whose lifetime is the earliest out of a plurality of bottles containing the same type of reagent as "bottle No. 1". In the example of FIG. 19, the reagent "KOD01" was defined as "bottle No. 1" in the vial No. 1 (expiration date: 2020, 4/16), and "bottle No. 2" in the vial No. 7 (expiration date: 2020, 4/20).

FIG. 20 is a diagram showing a structure of a2 nd modification of the reagent management information. In the example of fig. 20, the reagent management information further includes the date (setting start date) at which each vial starts to be set in each well of the vial region 221. The installation start date may be input by the user, or may be registered by the controller 10 as a date when the installation of the bottle is started by a sensor (not shown) provided in each hole of the bottle region 221.

The controller 10 determines, as the "No. 1 bottle", the bottle having the earliest installation start date among a plurality of bottles containing the same type of reagent. In the example of FIG. 20, the reagent "KOD01" was designated as "bottle No. 1" (day of start of set: 2020, 4/16), and the reagent "7" (day of start of set: 2020, 4/20) was designated as "bottle No. 2".

FIG. 21 is a diagram showing the structure of a modification 3 of the reagent management information. In the example of fig. 21, the reagent management information further includes the order of priority of the bottles in the respective wells provided in the bottle area 221. In one embodiment, the priority order of each vial is set to "1" by default, and when a plurality of vials are held in the vial region 221 for the same reagent, the priority order value of each vial can be set by the user.

The controller 10 determines a bottle having a priority order value "1" as a "No. 1 bottle" among a plurality of bottles containing the same type of reagent. In the example of FIG. 21, the reagent "KOD01" was defined as "bottle No. 1" (priority order: 1) and "bottle No. 2" (priority order: 2).

(3) Preparation of sample

Fig. 22 is a flowchart of a subroutine of the sample preparation (step S40) of fig. 17.

Referring to fig. 22, in step S400, the gene analyzer 1 sets the value of the variable N to 1. The variable N is a variable corresponding to the test number of the sample modulation information (fig. 16).

In step S402, the gene analyzer 1 moves the dispenser 3 to the dispenser tip cartridge 200A or the dispenser tip cartridge 200B.

In step S404, the gene analyzer 1 fits the tip of the dispenser 3 into the dispensing tip 8, thereby setting the dispensing tip 8 to the dispenser 3.

In step S406, the gene analyzer 1 moves the dispenser 3 to the sample corresponding to the test number N. For example, when N is 1, the dispenser 3 moves to the sample of sample number 1 corresponding to test number 1 (for example, the sample container held in the leftmost sample hole 211 of the sample holder 21). When N is 2, the dispenser 3 moves to the sample of sample number 2 corresponding to the test number 2 (for example, the sample container held in the 2 nd sample hole 211 counted from the left side of the sample holder 21). In the example based on the sample modulation information shown in fig. 16, when N is 13, the dispenser 3 also moves to the sample of sample number 1 corresponding to the test number 13.

In step S408, the gene analyzer 1 causes the dispenser 3 to aspirate the specimen.

In step S410, the gene analyzer 1 moves to the 1 st reagent tube corresponding to the test number N (in the example shown in fig. 7, the 1 st reagent well 12A and the 1 st reagent well 12D are provided in one tube).

In step S412, the gene analyzer 1 causes the dispenser 3 to aspirate the 1 st reagent.

In step S414, the gene analyzer 1 moves the dispenser 3 to the 2 nd reagent tube corresponding to the test number N (in the example shown in fig. 7, the tube provided in any one of the 12 2 nd reagent wells 222B and 12 2 nd reagent wells 222E).

In step S416, the gene analysis apparatus 1 causes the dispenser 3 to aspirate the 2 nd reagent.

In step S418, the gene analyzer 1 moves the dispenser 3 to the reaction container 11 corresponding to the test number N (in the example shown in fig. 7, the reaction container provided in either one of the 12 capillary holes 222C and 12 capillary holes 222F), and inserts the dispensing needle 8 at the tip of the dispenser 3 into the reaction container 11. Thereby, the (dispensing tip 8 at the tip of the) dispenser 3 is fitted into the reaction vessel 11.

In step S420, the gene analyzer 1 moves the dispenser 3 to the opening 5A of the centrifuge 5.

In step S422, the gene analyzer 1 inserts the reaction container 11 into the 1 st holding well 531, removes the dispensing tip 8 from the dispenser 3, and raises only the dispenser 3.

In step S424, it is determined whether or not the value of the variable N has reached the maximum number Q of trial numbers ("22" in the example of fig. 16). If it is determined that the variable N has reached the maximum number Q (yes at step S424), the gene analyzer 1 proceeds to step S428, and if not (no at step S424), proceeds to step S426.

In step S426, the gene analysis device 1 updates the value of the variable N by adding 1, and returns the control to step S402. Thus, samples are prepared in order from test No. 1, and the reaction vessel 11 for storing the prepared samples is provided in the centrifuge 5.

In step S428, the gene analysis apparatus 1 moves the dispenser 3 to a predetermined initial position. Thereafter, the gene analysis apparatus 1 returns the control to fig. 17.

(4) Moving path of dispenser

Next, the moving path of the dispenser 3 will be described.

In the process described with reference to fig. 21, the dispenser 3 is fitted to the dispensing tip 8 in the cassette setting area 20 for each test number, sucks the sample and the reagent (the 1 st reagent and the 2 nd reagent), discharges the sample and the reagent into the reaction container 11, is fitted to the reaction container 11, inserts the dispensing tip 8 and the reaction container 11 into the 1 st holding hole 531 of the centrifuge 5, and then is detached from the dispensing tip 8 and the reaction container 11.

In the gene analyzer 1, the movement path of the dispenser 3 during preparation of each sample can be appropriately set based on the arrangement of the dispensing tip cartridge 200A or the dispensing tip cartridge 200B of the dispensing tip 8 to be used, the arrangement of the specimen container to be used, the arrangement of the 1 st reagent and the 2 nd reagent tubes to be used, and the arrangement of the reaction container 11 to be used. In one embodiment, paths may also be preset for all combinations of the arrangement of these elements.

The movement path of the dispenser 3 from the fitting to the dispensing tip 8 to the removal from the dispensing tip 8 (and the reaction container 11) in the 1 st holding hole 531 of the centrifuge 5 can be set so as to avoid the dispensing tip 8, the sample, and the tube associated with the preparation of the sample that has not been prepared in the current test. The avoided area may also be defined as a "clean area".

Fig. 23 is a diagram showing an example of a clean area when the sample of test No. 1 was prepared. In fig. 23, the cleaning region includes regions 901, 902, 903. The clean area when preparing the sample of test No. 1 includes elements related to the samples of preparation test No. 2 and onward. The cleaning region may be a region including only one of the regions 901 to 903, or may be a region including only two of the regions 901 to 903 (for example, regions 901 and 903).

More specifically, the region 901 includes the cartridge installation region 20 and the bottle region 221 and the vicinity thereof. The region 902 includes the specimen hole 211 of the specimen holder 21 holding the specimen other than the specimen corresponding to the specimen of test number 1 and the vicinity thereof. The region 903 includes the tubes and reaction vessels 11 of the reagent cartridge 22 other than the elements (tubes and reaction vessels 11) related to the sample of test No. 1 and the vicinity thereof. In one embodiment, the vicinity means that each region, each region of the sample well, tube, or reaction vessel, and the peripheral region of the sample well, tube, or reaction vessel are contaminated when scattered droplets are scattered from the discharge hole 81 of the moving dispensing tip 8. In order to provide sufficient expansion to each region, sample well, tube or reaction vessel, the vicinity may be, for example, a region defined by a width of about 5mm from the outer periphery of each region, sample well, tube or reaction vessel, but is not limited thereto.

Fig. 24 to 27 are diagrams for explaining an example of the movement path of the dispenser 3 in preparation of the sample of test No. 1.

A path from the cassette setting area 20 to the specimen holder 21 is shown as a path A1 in fig. 24. In the path A1, after 1 dispensing tip 8 is fitted in the cassette setting area 20, the dispenser 3 moves in the cleaning area so as not to pass over the remaining dispensing tips 8 in the cassette setting area 20.

Fig. 25 shows a path from the specimen holder 21 to the 1 st reagent well 222A as a path A2. For reference, the shortest path from the specimen holder 21 to the 1 st reagent well 222A is shown as a path B2 in fig. 25. While route B2 passes through region 901, route A2 avoids region 901.

In fig. 26, a path from the 1 st reagent well 222A to the 2 nd reagent well 222B is shown as a path A3, and a path from the 2 nd reagent well 222B to the capillary hole 222C is shown as a path A4.

A path from the capillary hole 222C to the opening 5A is shown as a path A5 in fig. 27. For reference, the shortest path from the capillary hole 222C to the opening 5A is shown as a path B5 in fig. 27. While route B5 passes through region 901, route A5 avoids region 901.

Fig. 28 is a diagram showing an example of a clean area when the sample of test No. 8 was prepared. In fig. 28, the cleaning region includes regions 901, 904, and 905. The region 904 includes the specimen hole 211 of the specimen holder 21 for storing the specimen used for sample preparation of test numbers 9 to 24 (substantially test numbers 9 to 22) and the vicinity thereof. The region 905 includes the wells of the reaction container 11 and the tubes for holding the samples of test numbers 9 and thereafter, among the 1 st reagent well 222A, the 2 nd reagent well 222B, the capillary hole 222C, the 1 st reagent well 222D, the 2 nd reagent well 222E, and the capillary hole 222F.

Fig. 28 shows a path from the capillary hole 222C to the opening 5A as a path A6 for the test sample No. 8. For reference, the shortest path from the capillary hole 222C to the opening 5A is shown as a path B6 in fig. 28. While path B6 passes through region 901 and region 905, path A6 avoids region 901 and region 905.

As described above, in the gene analyzer 1, the controller 10 can control the movement path of the dispenser 3 during preparation of each sample. This allows the user to omit the troublesome operation of setting the movement path. The movement path is set to avoid the cleaning region as described above. This can more reliably avoid the contamination of 1 sample by another sample.

The embodiments disclosed herein are to be considered in all respects as illustrative and not restrictive. The scope of the present invention is indicated by the claims rather than by the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are intended to be embraced therein.

Description of the reference numerals

1. A gene analysis device; 1A, a main body; 2. a sample preparation area; 3. a dispenser; 4. a mobile unit; 4X, 4Y, 4Z, an axial arm; 5. a centrifuge; 5A, 111, opening; 6. a nucleic acid amplifier; 7. a detector; 8. a dispensing needle; 10. a controller; 11. a reaction vessel; 12. a waste box; 14. an input device; 15. a door; 16. a communication I/F; 17. a display; 20. a cartridge setting area; 20A, 20B, frame; 21. a specimen holder; 22. a reagent support; 31. a dispensing mechanism; 32. a cylindrical portion; 51. a rotating shaft; 52. a drive section; 53. a rotating part; 61. a housing; 62. a2 nd holding hole; 63. an outlet port; 64. a hot air generator; 65. a fan; 71. an irradiation unit; 72. a light sensor; 81. an ejection hole; 101. a processor; 102. a memory; 112. a storage section; 113. a storage section; 114. a1 st side; 115. a2 nd side; 200A, 200B, a needle box; 201. a frame; 211. a subject well; 221. a bottle region; 221A, 221B, 221C, 221D, 221E, 221F, 221G, 221H, reagent bottle well; 222. a sample area; 222A, 222D, 1 st reagent well; 222B, 222E, and 2 nd reagent well; 222C, 222F, capillary holes.

Claims (6)

1. A gene analysis device, wherein,

the gene analyzer includes a holder for holding a plurality of reagent bottles containing reagents to be injected into a plurality of reaction containers,

the stent comprises:

a1 st vial hole for holding a1 st reagent vial containing a predetermined reagent; and

a2 nd vial well holding a2 nd reagent vial containing the given reagent.

2. The gene analysis apparatus according to claim 1,

the gene analysis device further includes:

a dispenser that dispenses the predetermined reagent to a plurality of vials that contain the reagents to be injected into the plurality of reaction vessels, respectively; and

a controller that controls an operation of the dispenser,

the plurality of tubes comprises a1 st tube and a2 nd tube,

the controller controls in the following manner:

specifying the predetermined amount of the reagent required for dispensing into the 1 st and 2 nd cuvettes,

dispensing the predetermined reagent from the 1 st reagent bottle into the 1 st and 2 nd vials when the remaining amount of the predetermined reagent contained in the 1 st reagent bottle is equal to or more than the predetermined amount,

and dispensing the predetermined reagent from the 1 st and 2 nd reagent bottles into the 1 st and 2 nd vials if the remaining amount of the predetermined reagent contained in the 1 st reagent bottle is smaller than the predetermined amount.

3. The gene analysis apparatus according to claim 2,

the 1 st reagent bottle contains the given reagent that expires earlier in terms of life than the given reagent contained by the 2 nd reagent bottle.

4. The gene analysis apparatus according to claim 2,

the 1 st reagent bottle is held in the 1 st bottle well before the 2 nd reagent bottle is held in the 2 nd bottle well.

5. The gene analysis apparatus according to claim 2,

the controller includes a memory for storing information indicating that the 1 st reagent bottle is used in preference to the 2 nd reagent bottle.

6. The gene analysis apparatus according to any one of claims 1 to 5,

the bracket comprises a1 st mark assigned to the 1 st bottle hole and a2 nd mark assigned to the 2 nd bottle hole,

the 1 st identification and the 2 nd identification contain common information.

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