Quality inspection device and sample handling system

Abstract

A quality control device 10 measures the quality of a nucleic acid contained in a nucleic acid solution obtained during or after pretreatment. The quality control device 10 comprises: a PCR unit 100 for performing PCR on a nucleic acid; a chemiluminescence unit 100A for generating chemiluminescence for the nucleic acid; a light absorption unit 100B for determining the absorbance of the nucleic acid solution; and an electrophoresis unit 200 for performing electrophoresis of the nucleic acid. The quality control device 10 comprises: a measuring body 300 for measuring the fluorescence based on nucleic acid amplified in the PCR unit 100, the chemiluminescence from the chemiluminescence unit 100A, and the absorbance based on transmitted light from the light absorption unit 100B; and a control unit for controlling all units and the measuring body.

Description

Technical field

[0001] The present invention relates to a quality control device for measuring the quality of a target substance, such as a nucleic acid, during or after completion of a pretreatment for obtaining a target substance, such as a nucleic acid, from a sample, and to a sample treatment system equipped with this quality control device. State of the art

[0002] The PCR method is used to detect pathogens such as viruses. This method utilizes a polymerase chain reaction (PCR), which is widely used in the development of genetic engineering. A sample containing a pathogen is taken using a standard sampling kit. A nucleic acid (DNA or RNA) is extracted from the sample, amplified by the PCR process, and the pathogen is then tested based on the amplified nucleic acid.

[0003] The PCR procedure is primarily performed manually. However, it is difficult to continuously perform a large number of tests manually, and there is a possibility of errors and contamination during the process. Therefore, an automated PCR testing device has been proposed to automate the PCR procedure. For example, Precision System Science Co., Ltd. has launched the geneLEAD series, which is a fully automated PCR testing system (Non-Patent Literature No. 1). In this fully automated PCR testing system, a sample is extracted from a sample container without human intervention, pretreatment is performed, nucleic acid is extracted and purified, and then a PCR test can be performed.

[0004] During the PCR test, a PCR cycle is repeated several dozen times, using a reaction fluid containing purified nucleic acid and a reagent. A PCR cycle involves heating the reaction fluid to a predetermined temperature and holding it for a predetermined time, as well as cooling it to a predetermined temperature and holding it for a predetermined time. Repeating the PCR cycle several dozen times requires a comparatively long time until nucleic acid amplification is complete.

[0005] To shorten the duration of the PCR cycle, consideration has been given to reducing the time required for cooling and heating the reaction fluid to reach the specified temperature by decreasing the amount of reaction fluid. A standard PCR uses a relatively large amount of reaction fluid (e.g., 20 µl to 30 µl); however, reducing the amount of reaction fluid and performing the PCR with a comparatively small amount (e.g., 2 µl to 10 µl) is being explored.

[0006] In patent document 1 proposed by the inventor, a PCR device for performing PCR by sealing a PCR container with a lid was proposed. By accommodating and sealing a lower section of the lid within a lower section of the container, the volume of the reaction chamber is reduced, thereby enabling PCR to be performed with a comparatively small amount of reaction fluid. Cited documents Non-patent literature

[0007] Non-patent literature 1: geneLEAD series, [online], June 11, 2024,<URL: https: / / www.pss.co.jp / english / product / genelead / > Patent literature

[0008] Patent literature 1: WO 2023 / 032870 A1 Summary of the invention Technical problem of the invention

[0009] It is necessary to verify the quality of a target substance, such as a nucleic acid, during or after pretreatment before performing a treatment like PCR using a relatively large volume of reaction fluid. If the quality is inadequate, tasks such as nucleic acid amplification via PCR cannot be performed, resulting in wasted time for the PCR reaction. Therefore, when verifying the quality of a target substance like a nucleic acid during or after pretreatment, it is preferable to perform a quality check using a different, faster, and simpler instrument in addition to or instead of PCR.

[0010] The present invention provides a quality control device for measuring the quality of a target substance such as a nucleic acid during or after completion of a pretreatment, wherein a comparatively small amount of a solution of a target substance such as a nucleic acid is used. Solution to the task

[0011] The present invention comprises the following aspects: (Point of view 1)

[0012] A quality control device for measuring the quality of a target substance (such as a nucleic acid) contained in a target substance solution obtained during or after pretreatment, wherein the quality control device comprises at least one or a combination of two or more of the following components: at least one PCR unit for obtaining fluorescence from the target substance, at least one chemiluminescence unit for generating chemiluminescence on the target substance, at least one light absorption unit for obtaining the absorption of the target substance, and at least one electrophoresis unit for performing electrophoresis of the target substance, wherein the quality control device includes a measuring element for measuring the fluorescence from the fluorescence unit.the absorption based on the transmitted light from the light absorption unit and / or the chemiluminescence from the chemiluminescence unit and a control unit for controlling the fluorescence unit, the electrophoresis unit and / or the measuring body. (Point of view 2)

[0013] The quality inspection device described in point 1, wherein the measuring body comprises at least one or a combination of two or more of the following components: a fluorescence measuring unit for measuring the fluorescence based on a nucleic acid amplified by the fluorescence unit, an absorption measuring unit for measuring the absorption based on the light transmitted by the light absorption unit, and a chemiluminescence measuring unit for measuring the chemiluminescence from the chemiluminescence unit. (Point of view 3)

[0014] The quality inspection device described in point 1, wherein the quality inspection device comprises the fluorescence unit, the light absorption unit and the chemiluminescence unit. (Point 4)

[0015] The quality control device described in point 3, in which the measuring body comprises a PCR measuring unit for measuring fluorescence based on nucleic acid amplified by the fluorescence unit, an absorption measuring unit for measuring absorption based on light transmitted by the light absorption unit, and a chemiluminescence measuring unit for measuring chemiluminescence from the chemiluminescence unit. (Point 5)

[0016] The quality inspection device described in point 4, in which the measuring body comprises a scanning body that moves over the fluorescence measuring unit, the absorption measuring unit and the chemiluminescence measuring unit. (Point 6)

[0017] The quality inspection device described in point 5, in which the scanning element is connected to at least one optical fiber for transmitting light to guide excitation light from the fluorescence measuring unit to the fluorescence unit and / or to guide incident light from the absorption measuring unit to the light absorption unit; with an optical fiber for receiving light, for guiding fluorescence from the fluorescence unit or for guiding chemiluminescence from the chemiluminescence unit to the fluorescence measuring unit; and with an optical fiber for transmitted light to guide transmitted light from the light absorption unit to the absorption measuring unit. (Point 7)

[0018] The quality inspection device described in point 6, in which the fluorescence measuring unit and / or the absorption measuring unit is provided with a plurality of light sources with different wavelengths and a plurality of light receiving elements corresponding to the plurality of light sources, and the chemiluminescence measuring unit is provided with at least one light receiving element for receiving the chemiluminescence. (Point 8)

[0019] The quality inspection device described in point 6, comprising at least one light-transmitting and light-receiving nozzle with end sections of the optical fiber for transmitting light and the optical fiber for receiving light, wherein the light-transmitting and light-receiving nozzle is connected to the fluorescence unit, the chemiluminescence unit and the light absorption unit via the optical fiber for transmitting light and the optical fiber for receiving light. (Point 9)

[0020] The quality inspection device described in point 8, in which the fluorescence unit, the chemiluminescence unit and the light absorption unit each consist of a container and a lid for closing the container. (Point 10)

[0021] The quality inspection device described in point 9, wherein the container consists of a container top and a container bottom projecting downwards from the container top, the container bottom having a smaller diameter than the container top, the lid consisting of a lid top and a lid bottom projecting downwards from the lid top, the lid bottom having a smaller diameter than the lid top, and the lower part of the lid being received in the lower part of the container when the lid is placed on the container. (Point 11)

[0022] The quality inspection device described in point 10, wherein, when the lower part of the lid is received in the lower part of the container, the lower part of the lid is in close contact with the lower part of the container and forms a space that seals the nucleic acid solution. (Point 12)

[0023] The quality inspection device described in point 9, in which an inner surface of the container of the fluorescent unit is colored white or the container of the fluorescent unit is made of a white colored material. (Point 13)

[0024] The quality inspection device described in point 9, in which an inner surface of the container of the chemiluminescence unit is colored black or the container of the chemiluminescence unit is made of a black colored material. (Point 14)

[0025] The quality inspection device described in point 9, wherein the lid comprises a lid-side light-transmitting section for transmitting the excitation light, the fluorescence light and / or the chemiluminescence light, and the lid-side light-transmitting section is arranged such that it faces the light-transmitting and light-receiving nozzle. (Point 15)

[0026] The quality inspection device described in point 9, wherein the container of the light absorption unit comprises a container-side light-transmitting section and the container-side light-transmitting section is arranged such that it faces the end section of the optical fiber for transmitted light. (Point 16)

[0027] The quality control device described in point 1, in which the target substance is a nucleic acid or a protein. (Point 17)

[0028] The quality control device described in point 16, in which the fluorescence unit is a PCR unit for carrying out a PCR reaction of the nucleic acid. (Point 18)

[0029] The quality control device described in point 1, in which the control unit performs a qualitative and / or quantitative treatment of the target substance using the measured fluorescence, chemiluminescence and / or absorption. (Point 19)

[0030] The quality control device described in point 18, which further comprises an imaging unit for imaging an electrophoresis pattern obtained from electrophoresis, wherein the control unit performs a quality assessment of the target substance on the basis of the electrophoresis pattern. (Point of view 20)

[0031] A sample treatment system comprising: a sample treatment device for performing a treatment to extract a nucleic acid from a sample and to purify the nucleic acid, as well as a treatment to amplify the purified nucleic acid, and the quality control device described in point 1. (Point 21)

[0032] The sample treatment system described in point 20, including a moving device for moving a solution of nucleic acid from the sample treatment device to the quality control device. (Point of view 22)

[0033] A sequencer for performing the sequencing of a nucleic acid obtained from a sample, comprising: a sample treatment device with a pretreatment unit for extracting the nucleic acid from the sample and for purifying the nucleic acid, a PCR unit on the pretreatment side for amplifying the nucleic acid by PCR using a nucleic acid solution obtained from the pretreatment unit, and a first nozzle unit for moving the nucleic acid solution; the quality control device described in point 1 for measuring the quality of the nucleic acid using the nucleic acid solution obtained from the pretreatment unit; a movement device for moving the nucleic acid solution from the pretreatment unit to the quality control device; a flow cell unit for performing sequencing of the nucleic acid using the nucleic acid solution;and a control unit for controlling the sample treatment device, the quality control device, the movement device and a treatment in the flow cell unit, wherein, if the control unit determines that the quality of the nucleic acid measured by means of the quality control device meets at least one predetermined condition, the sequencing of the nucleic acid is carried out. (Point of view 23)

[0034] The sequencer described in point 22, in which the pretreatment unit comprises a nucleic acid extraction unit for extracting a nucleic acid from the sample, a size determination unit for performing a size determination of an extracted nucleic acid, and an adapter conjugation device for conjugating an adapter to both ends of a size-determined nucleic acid. Advantageous effects of the invention

[0035] The quality control device of the present invention can test the quality of a target substance such as a nucleic acid during or after completion of a pretreatment using a comparatively small amount of a solution of the target substance such as a nucleic acid, before a treatment such as PCR is carried out using a comparatively large amount of a solution of the target substance such as a nucleic acid. Brief description of the drawings Fig. Figure 1 is a perspective view from above showing a sample treatment system according to an embodiment of the present invention. Fig. 2 is a top view showing the sample handling system of Fig. 1 shows. Fig. Figure 3 is a top view showing a lid and container of the PCR unit. Fig. 1 shows. Fig. Figure 4 is a longitudinally sectioned view showing the PCR unit of Fig. 1 shows. Fig. Figure 5 is a longitudinally sectioned view showing a modified example of the PCR unit of Fig. 1 shows. Fig. Figure 6 is a top view showing a lid and a container of the chemiluminescence unit of Fig. 1 shows. Fig. Figure 7 is a longitudinally sectioned view showing the chemiluminescence unit of Fig. 1 shows. Fig. Figure 8 is a longitudinally sectioned view showing a modified example of the chemiluminescence unit of Fig. 1 shows. Fig. Figure 9 is a top view showing a lid and a container of the light absorption unit of Fig. 1 shows. Fig. Figure 10 is a longitudinally sectioned view showing the light absorption unit of Fig. 1 shows. Fig. Figure 11 is a longitudinally sectioned view showing a modified example of the light absorption unit of Fig. 1 shows. Fig. 12 includes (a) a top view and (b) a sectional view showing the stage of the quality inspection device of Fig. Show 1. Fig. Figure 13 is a perspective view showing the measuring body of Fig. Figure 1 shows the scanning element of the measuring body being located on the left rear side. Fig. Figure 14 is a perspective view showing the measuring body of Fig. Figure 1 shows the scanning element of the measuring body being located on the right front side. Fig. 15 is a top view of the measuring body of Fig. 11. Fig. 16 is a side view showing the sample handling system of Fig. 1 shows. Fig. Figure 17 is a perspective view from below, showing the second nozzle unit of Fig. 1 shows. Fig. Figure 18 is a perspective view from below, showing the light-transmitting and light-receiving nozzle of Fig. 17 shows. Description of the exemplary implementations

[0036] An embodiment of the quality control device and the sample treatment system equipped therewith according to the present invention is explained with reference to the drawings. In the drawings, identical components are provided with the same reference numerals, so their explanation is omitted here. In the present invention, a comparatively small quantity of a solution of a target substance, such as a nucleic acid, should be less than a comparatively large quantity of a solution of a target substance, such as a nucleic acid. Although there is no limitation in the present embodiment, a comparatively large quantity of a solution of a target substance, such as a nucleic acid, can be configured, for example, as 20 to 30 µl, and a comparatively small quantity of a solution of a target substance, such as a nucleic acid, can be configured, for example, as 2 to 10 µl.In the present embodiment, the target substance whose quality is to be tested has been configured as a nucleic acid; however, this is not limited to this, and any biologically related substance (e.g., a protein) can be used. Sample processing system (fully automated sequencer)

[0037] As in the Fig. 1 and Fig. As shown in Figure 2, a sample treatment system 1 (sequencer) of the present embodiment consists of a sample treatment measuring device 2, a quality control device 10, and a motion device 400 with pitch conversion. The sample treatment measuring device 2 comprises a pretreatment unit (pretreatment device) 20 for obtaining a nucleic acid solution by pretreating a sample such as blood or body fluid, a PCR unit 25 on the pretreatment side for performing a PCR reaction on the comparatively large quantity of nucleic acid solution obtained after pretreatment, a flow cell unit 21 for performing sequencing, and a first nozzle unit 30 that moves in the x-direction above the pretreatment unit 20, the flow cell unit 21, and the PCR unit 25 on the pretreatment side. The first nozzle unit 30 is provided with a plurality of metering nozzles arranged in the y-direction.

[0038] As in Fig. As shown in Figure 1, the motion device 400 with pitch conversion is equipped with a plurality of nucleic acid solution containers 401 to hold the comparatively small amount of nucleic acid solution obtained during or after completion of a pretreatment. The motion device 400 with pitch conversion moves the plurality of nucleic acid solution containers 401 from the pretreatment unit 20 to the quality control device 10. The motion device 400 with pitch conversion moves along a rail extending in the y-direction and can, as shown in Figure 1, be positioned as follows: Fig. Figure 1 shows a large pitch state for positioning on the side of the sample handling measuring device 2 and a small pitch state for positioning on the side of the quality control device 10. The large pitch state should be larger than the small pitch state, and there is no limit to the size of the pitches.

[0039] The quality control device 10 measures the quality of the comparatively small quantity of nucleic acid solution obtained during or after completion of a pretreatment. As in Fig. As shown in Figure 1, the quality inspection device 10 consists of a PCR unit (quality measurement side PCR unit) 100, a chemiluminescence unit 100A, a light absorption unit 100B, an electrophoresis unit 200, a second nozzle unit 60 that moves in the x-direction over each of the units 100, 100A, 100B, and a measuring body 300 for measuring the received light, etc., by each of the units 100, 100A, 100B. Fig. The optical fibers described below are not shown in Figure 1.

[0040] The quality control device 10 is on a stage 11 with one or more combinations of at least one of the PCR units 100 for amplifying a nucleic acid solution by means of a real-time PCR reaction ( Fig. 4 or Fig. 5), at least one of the chemiluminescence units 100A for generating a chemiluminescence of an immune reaction solution of the nucleic acid ( Fig. 7 or Fig. 8), at least one of the 100B light absorption units to obtain the transmitted light of the nucleic acid solution in order to measure the absorption of the nucleic acid solution ( Fig. 10 or Fig. 11) and at least one of the electrophoresis units 200 is equipped to perform electrophoresis of the nucleic acid solution ( Fig. 1) The quality inspection device 10 can preferably be provided on the stage 11 with a PCR unit 100, a chemiluminescence unit 100A, a light absorption unit 100B and an electrophoresis measurement unit 200. PCR unit

[0041] The PCR unit (fluorescence unit) 100 according to the present embodiment is based on the Fig. 3 to 5 explained. The PCR unit 100 consists of a PCR container (measuring container) 110, the inner surface of which is at least partially colored white, a lid (a common cap) 120 for the PCR container, a thermocycler 130 and a light-transmitting and light-receiving nozzle 40 or 40A.

[0042] The PCR container 110 is preferably made of a white-colored plastic. The PCR container 110 consists of: a container upper part 111 for receiving a lid middle part 123 of the lid 120; and a container lower part 112 for receiving a lid lower part 122 of the lid 120, a reagent, and a nucleic acid solution. The container upper part 111 preferably has a cylindrical shape. The container lower part 112 has a smaller diameter than the container upper part 111. The container lower part 112 preferably projects downwards from the container upper part 111 in a conical shape. The container lower part 112 is preferably provided with a bottommost container section 112a, which is round.

[0043] The lid 120 comprises the tubular upper lid section 121 for receiving the lower end of the light-transmitting and light-receiving nozzle 40, the tubular middle lid section 123, which is housed in the upper part 111 of the container, and the lower lid section 122, which is connected to an annularly inclined surface of the middle lid section 123. The lower lid section 122 projects conically downwards from the upper lid section 121. The lower lid section 122 has a smaller diameter than the upper lid section 121 and the middle lid section 123.

[0044] At the lower end of the lid base 122, a flat, light-transmitting part (lid-side light-transmitting part) 122a is formed. The lid base 122 is preferably conical in shape. In the lid base 122, at least the light-transmitting part 122a is made of a transparent material. A plastic that transmits the excitation light, fluorescent light, and / or chemiluminescent light described below can be used as the transparent material. The outer surface of the conical lid base 122 is in close contact with the inner surface of the conical container base 112 and forms a space S ( Fig. 4) for holding the reagent and the nucleic acid solution between the light-transmitting part 122a and the lowest container section 112a.

[0045] As in Fig. As shown in Figure 4, the lid base 122 is in close contact with the container base 112, and the nucleic acid solution is sealed in space S in a state in which the lid base 122 is received into the container base 112. In other words, when the lid base 122 is received into the container base 112 while the lid 120 is placed on the container 110, the nucleic acid solution dispensed into the container base 112 overflows between the lid base 122 and the container base 112, forcing the air upwards from where it is located between the lid base 122 and the container base 112. This allows a comparatively small amount of nucleic acid solution to be trapped in space S without an air layer. Because space S contains no air layer, no condensation forms on the surface of the light-transmitting section 122a during PCR.

[0046] The light-transmitting and light-receiving nozzle 40 is attached to a second nozzle unit 60 ( Fig. 1) provided, and the second nozzle unit 60 is arranged to be movable in the x-direction above the quality inspection device 10 by means of a second nozzle unit movement mechanism (e.g., a motor and a rail). A movement mechanism for the detection end section (e.g., a motor and an actuator) moves the light-transmitting and light-receiving nozzle 40 in the z-direction. The light-transmitting and light-receiving nozzle 40 can be mounted in the cover 120. The light-transmitting and light-receiving nozzle 40 can be moved by means of the second nozzle movement mechanism and the movement mechanism for the detection end section in a state in which the light-transmitting and light-receiving nozzle 40 is mounted in the cover 120.

[0047] One in Fig. The light-transmitting and light-receiving nozzle 40, shown in Figure 4, is of the lens type and consists of an optical fiber 41a for transmitting light, an optical fiber 41b for receiving light, an optical lens 42 arranged at the lower end of the optical fibers 41a and 41b, and an end cover 43 for enclosing the optical fibers 41a and 41b and the optical lens 42. The underside of the optical lens 42 is exposed within the cover 120. The space between the cover 120 and the light-transmitting and light-receiving nozzle 40 is preferably sealed with a sealing material, etc., to prevent fogging of the optical lens 42.

[0048] The in Fig. 5 The light-transmitting and light-receiving nozzle 40A of the direct light transmission and reception type is connected to the light-transmitting and light-receiving nozzle 40 of Fig. 4 interchangeable. For the light-transmitting and light-receiving nozzle 40A, only those parts that differ from the light-transmitting and light-receiving nozzle 40 are described. The light-transmitting and light-receiving nozzle 40A has no optical lens 42, wherein a lower end section 41a1 of the optical fiber 41a for transmitting light and a lower end section 41b1 of the optical fiber 41b for receiving light are arranged such that they are opposite the light transmission section 122a, in the vicinity of the light transmission section 122a. The lower end section 41a1 and the lower end section 41b1 are preferably arranged such that they abut the light transmission section 122a.

[0049] The thermocycler 130 performs a PCR reaction by repeatedly heating and cooling the nucleic acid solution, which contains a nucleic acid amplification reagent and a measurement reagent, such as a fluorescent dye, and is housed in chamber S. This process amplifies the nucleic acid. Since the amplified nucleic acid is conjugated to a fluorescent dye, it is excited by excitation light transmitted by optical fiber 41a and emits fluorescence. This fluorescence is received by optical fiber 41b. The measuring device 300, described below, supplies excitation light to optical fiber 41a and measures the fluorescence from optical fiber 41b. The PCR unit 100 preferably performs real-time PCR. Chemiluminescence unit

[0050] The chemiluminescence unit 100A for quality control according to the present embodiment is based on the Fig. Sections 6 to 8 are explained. For the chemiluminescence unit 100A, the parts that differ from the PCR unit 100 are explained, omitting the explanation of the same reference numerals assigned to identical parts. The chemiluminescence unit 100A does not have a thermocycler 130 and has a light-shielding container 110A. The container 110A is preferably made of a light-shielding material (e.g., black plastic) or provided with a light-shielding coating (black coating) on ​​its inner surface.

[0051] The light-transmitting and light-receiving nozzle 40, 40A is provided with an annular unit 44 (annular projecting unit) which is formed or arranged annularly around the outer circumference of the end cover 43, wherein the annular unit 44 has an annular light-shielding groove 41a for engaging with the annular upper end section of the cover 121. Apart from the light-transmitting section 122a, the cover 120 is preferably made of a light-shielding material (preferably black plastic); alternatively, the cover 120 can have a light-shielding coating (black coating) on ​​its inner surface.

[0052] The nucleic acid solution and a chemiluminescent substance, which emits light through an antigen-antibody reaction with the nucleic acid (predetermined base sequence), are housed in compartment S of the chemiluminescence unit 100A. The light-transmitting and light-receiving nozzle 40, 40A does not supply excitation light from the optical fiber 41a for light transmission, but rather transmits the chemiluminescent light received from the optical fiber 41b to the measuring body 300. A light detection element provided on the measuring body 300 measures the chemiluminescent light transmitted from the optical fiber 41b. For example, a photomultiplier tube (PMT) or the like can be used in the light detection element. Light absorption unit

[0053] The light absorption unit 100B according to the present embodiment is based on the Fig. Sections 9 to 11 are explained. For the light absorption unit 100B, the parts that differ from the PCR unit 100 are explained, omitting the explanation of the same reference numerals assigned to the same parts. The light absorption unit 100B does not have a thermocycler 130 and has a vessel 110B equipped with a light-transmitting section 113B (vessel-side light-transmitting section) and a lower measuring end section 50.

[0054] The light-transmitting section 113B is formed at the lower end of the container 110B. The light-transmitting section 113B is made of a transparent material and has a flat, transparent surface. Preferably, a transparent resin that transmits visible light (incident light) can be used as the transparent material. The lower measuring end section 50 consists of the end section of an optical fiber 51 for transmitted light and a cover 53 for covering the circumferential surface of the optical fiber 51 for transmitted light. The upper end surface 51a of the optical fiber 51 for transmitted light faces the light-transmitting section 113B.

[0055] The nucleic acid solution is contained in chamber S of the light absorption unit 100B. The light-transmitting and light-receiving nozzles 40, 40A supply incident light (e.g., visible light) from the optical fiber 41a for transmission to the nucleic acid solution within chamber S. The light transmitted through the nucleic acid solution and the light-transmitting section 113B is received by the upper end face 51a of the transmitted light fiber 51. The transmitted light is guided by the transmitted light fiber 51 to the measuring body 300, and a light-receiving element of the measuring body 300 measures the absorption or opacity of the transmitted light. Quality inspection device

[0056] As in Fig. As shown in Figure 12, the quality control device 10 is provided with a plurality of treatment lines (e.g., four treatment lines) extending in the x-direction on a flat quality measurement platform 11. Each treatment line is provided with a plurality of dispensing tips 12, at least one perforation tip 13, components of the PCR unit 100, components of the chemiluminescence unit 100A, components of the light absorption unit 100B, and the electrophoresis measurement unit 200. The second nozzle unit 60 ( Fig. 1 and Fig. 2) moves above the quality inspection device 10 in the x-direction. On the side of the quality measuring platform 11 (on the left side), several nucleic acid solution containers 401 are arranged according to each treatment line, which move in the y-direction by means of a pitch conversion mechanism 400.

[0057] The components of the PCR unit 100 are a container 130 for a PCR reagent, the lid 120, and the PCR vessel 110, arranged in a row in the x-direction. As shown in Fig. As shown in Figure 12(b), the thermocycler 130 is arranged on the underside of the PCR container 110. A dosing nozzle 65 of the second nozzle unit 60 ( Fig. 16) The PCR reagent is transferred from container 130A to PCR container 110. The dosing nozzle 65 transfers a relatively small amount of nucleic acid solution from the nucleic acid solution container 401 of the pitch-conversion motion device 400 into PCR container 110. The light-transmitting and light-receiving nozzle 40 or 40A fits the lid 120 into PCR container 110.

[0058] The components of the chemiluminescence unit 100A are a container 130A for a chemiluminescence reagent, the lid 120, and a light-shielding (black) chemiluminescence container 110A, arranged in a row in the x-direction. The metering nozzle 65 conveys the chemiluminescence reagent from the container 130A into the chemiluminescence container 110A. The metering nozzle 65 conveys a comparatively small amount of nucleic acid solution from the nucleic acid solution container 401 of the pitch-conversion motion device 400 into the chemiluminescence container 110A. The light-transmitting and light-receiving nozzle 40 or 40A fits the lid 120 into the chemiluminescence container 110A.

[0059] The components of the light absorption unit 100B are a container 130B for an absorption measurement reagent, the lid 120, and a light absorption container 110B, arranged in a row in the x-direction. As shown in Fig. As shown in Figure 12(b), the lower measuring end section 50 (the optical fiber 51 for transmitted light) is located on the underside of the light absorption vessel 110B. The metering nozzle 65 moves the absorption measuring reagent from the container 130B to the light absorption vessel 110B. The metering nozzle 65 moves a comparatively small amount of nucleic acid solution from the nucleic acid solution container 401 of the pitch-conversion motion device 400 into the light absorption vessel 110B. The light-transmitting and light-receiving nozzle 40 or 40A fits the lid 120 into the light absorption vessel 110B.

[0060] The components of the electrophoresis measuring unit 200 comprise a container 230 for an electrophoresis reagent and the electrophoresis unit 200. The electrophoresis unit 200 has one or more solution dispensing ports 201 corresponding to one or more treatment lanes, an electrophoresis gel 203, and a pair of electrophoresis electrodes 205 between which the electrophoresis gel 203 is arranged. The metering nozzle 65 moves the electrophoresis reagent from the container 230 to the electrophoresis unit 200. The metering nozzle 65 moves a comparatively small amount of nucleic acid solution from the nucleic acid solution container 401 of the pitch-conversion motion device 400 to the solution dispensing port 201. An electrophoresis control unit (not shown) applies a voltage between the pair of electrophoresis electrodes 205 to perform the electrophoresis. Measuring device (scanner for multiple measurements)

[0061] The measuring body 300 is based on the Fig. Figures 13 to 15 explain. The measuring body 300 consists of a PCR measuring unit (fluorescence measuring unit) 310 for measuring the fluorescence obtained by the PCR unit 100 during real-time PCR, an absorption measuring unit 320 for measuring the transmitted light obtained by the light absorption unit 100B, a chemiluminescence measuring unit 330 for measuring the chemiluminescence obtained by the chemiluminescence unit 100A, a scanning body 340 (holder for the end of the optical fiber) which is movable in the direction of the arrow while facing each of the units, a scanning body movement mechanism 350 for moving the scanning body 340, and a control unit (CPU) 360 for controlling each measuring unit and each scanning mechanism.

[0062] The scanning element 340 moves to positions along a guide rail 370, each facing the PCR measuring unit 310, the absorption measuring unit 320, and the chemiluminescence measuring unit 330, respectively. The scanning element 340 is connected to a first optical fiber group A, a second optical fiber group B, and a third optical fiber group C.

[0063] The first optical fiber group A consists of a plurality of optical fibers 41a for transmitting light, which are connected to a plurality of light-transmitting and light-receiving nozzles 40 or 40A of the second nozzle unit 60, as shown in the Fig. 15 and Fig. Figure 16 shows the first optical fiber group A transmits fluorescence from a light source of the PCR measuring unit 310 to space S of the PCR unit 100. The second optical fiber group B consists of a plurality of optical fibers 41b for receiving light, which are connected to the light-transmitting and light-receiving nozzle 40 or 40A, as shown in the Fig. 15 and Fig. Figure 16 shows that the second optical fiber group B transmits fluorescence or chemiluminescence obtained from the PCR unit 100 or the chemiluminescence unit 100A to the PCR measuring unit 310 or the chemiluminescence measuring unit 330. The third optical fiber group C consists of a plurality of transmitted light optical fibers 51 provided at the lower part of the light absorption unit 100B, as shown in the Fig. 15 and Fig. Figure 16 shows the third optical fiber group C transmits transmitted light received from the light absorption unit 100B to the absorption measurement unit 320.

[0064] As in the Fig. 13 and Fig. As shown in Figure 14, the scanning element motion mechanism 350 consists of a drive motor 351, a toothed belt 353, a pair of pulleys 354 which rotatably support the toothed belt 353, and a connecting plate 355 which is moved by the toothed belt 353. One of the two pulleys 354 is rotated by means of the drive motor 351. The scanning element 340 moves integrally with the connecting plate 355.

[0065] The measuring body 300 of the present embodiment can preferably perform several measurements successively and continuously by having the scanning mechanism 350 scan several of the parameters described in the following: Fig. The PCR units 100 shown in the diagram, several of the chemiluminescence units 100A and several of the light absorption units 100B are moved.

[0066] The measuring body 300 has a scanning line LA of the first optical fiber group A (the optical fiber 41a for transmitting light), as shown by the dashed lines in Fig. Figure 15 shows the absorption measurement unit 320, which is equipped with an arrangement that positions several light sources on the scanning line LA.

[0067] The absorption measuring unit 320 is preferably provided linearly with a light source position P1, at which a first light source (a light source of a first wavelength range) is arranged, a light source position P2, at which a second light source (a light source of a second wavelength range) is arranged, and a light source position P3, at which a third light source (a light source of a third wavelength range) is arranged, on the scanning line LA.

[0068] The PCR measuring unit 310 is provided with an arrangement in which several excitation light sources are positioned on the scanning line LA, wherein the PCR measuring unit 310 is preferably provided linearly with an excitation light position P4, at which a first excitation light source is arranged, an excitation light position P5, at which a second excitation light source is arranged, and an excitation light position P6, at which a third excitation light source is arranged, on the scanning line LA. The measuring body 300 has a scanning line LB of the second optical fiber group B (the optical fiber 41b for receiving light), as indicated by the dashed lines in Fig. Figure 15 shows the chemiluminescence measuring unit 330 being provided with an arrangement P7 of at least one light receiving element (PMT) on the scanning line LB.

[0069] The measuring body 300 has a scanning line LC of the third optical fiber group C (the optical fiber 51 for transmitted light), as shown by the dashed lines in Fig. Figure 15 shows the absorption measuring unit 320, which is provided with an arrangement for positioning a plurality of elements for receiving transmitted light on the scanning line LC. The absorption measuring unit 320 is preferably linearly provided with an arrangement P8 of a fourth light-receiving element, an arrangement P9 of a fifth light-receiving element, and an arrangement P10 of a sixth light-receiving element on the scanning line LC.

[0070] The PCR measuring unit 310 is provided with an arrangement that positions several light-receiving elements on the scanning line LB. The PCR measuring unit 310 is preferably linearly provided with a light-receiving position P11, at which a first light-receiving element (light-receiving element of the first wavelength) is arranged, a light-receiving position P12, at which a second light-receiving element (light-receiving element of the second wavelength) is arranged, and a light-receiving position P13, at which a third light-receiving element (light-receiving element of the third wavelength) is arranged on the scanning line LB.

[0071] The second nozzle unit 60 is selected based on the Fig. 16 and Fig. 17 explained. The second nozzle unit 60 is provided with a plurality of light-transmitting and light-receiving nozzles 40 or 40A arranged in a row in the y-direction, a first removal mechanism 63 for pressing down and removing a plurality of covers 120 attached to the plurality of light-transmitting and light-receiving nozzles 40 or 40A, several metering nozzles 65 arranged in a row in the y-direction, and a second removal mechanism 67 for pressing down and removing the several dispensing tips 12 attached to the several metering nozzles 65. The first removal mechanism 63 and the second removal mechanism 67 consist of a removal plate and a motor for driving the removal plate. As in Fig. As shown in Figure 18, the first removal mechanism 63 is provided with a light-shielding groove 44a around the circumference of the light-transmitting and light-receiving nozzle 40. Sample treatment measuring device

[0072] The sample treatment measuring device 2 is based on Fig. 2 explained. The sample treatment measuring device 2 consists of the pretreatment unit 20, the flow cell unit 21, the PCR unit 25 on the pretreatment side, and the first nozzle unit 30. The pretreatment unit 20 consists of a consumables intake unit 22, a nucleic acid extraction and purification cartridge 23a (nucleic acid extraction unit), a nucleic acid sizing cartridge 23b (sizing unit), and a ligation cartridge 23c (ligation unit). The consumables intake unit 22 receives consumables such as one or more dispensing tips, one or more sample tubes, and / or one or more perforation tips.

[0073] The nucleic acid extraction and purification cartridge 23a is equipped with a recess for receiving a nucleic acid extraction and - purification reagent and a well for nucleic acid extraction and - provided for cleaning. The nucleic acid sizing cartridge 23b consists of a well for receiving a nucleic acid sizing reagent and a well for performing the nucleic acid sizing, whereby the size determination of the extracted nucleic acid is carried out using the nucleic acid sizing reagent. The ligation cartridge 23c consists of a well for receiving a ligation reagent and a well for performing the ligation (adapter conjugation), whereby an adapter is conjugated to both ends of the sorted nucleic acid. Freeze-dried reagents are pre-sealed in the wells for storing the individual reagents by means of an aluminum seal or the like. The PCR unit 25 consists of a PCR cartridge for receiving a PCR well and a PCR reagent, as well as a thermocycler provided at the bottom of the PCR well.

[0074] If, after pretreatment, the quality of the nucleic acid obtained from the quality control device 10 meets at least one of the predetermined conditions described below, the nucleic acid (to which an adapter has been conjugated) is sequenced using a comparatively large quantity of a nucleic acid solution with the flow cell unit 21, as determined by a control unit. The flow cell unit 21 has a cluster of immobilized nucleic acids via an adapter for conjugation to the nucleic acid. The flow cell unit performs parallel, simultaneous sequencing of a large number of immobilized nucleic acids on the flow cell using four types of fluorescently labeled nucleotides and polymerase enzymes based on sequencing by synthesis (SBS), a one-base synthesis method.The flow cell unit is equipped with an excitation light source and a fluorescent light receiving element, which are not shown, with the control unit controlling the excitation light source and the fluorescent light receiving element. Real-time PCR measurement using the measuring body

[0075] The process is explained when the PCR measuring unit 310 of the measuring body 300 measures the fluorescence obtained from the several PCR units 100. As in Fig. As shown in Figure 12(a), the multiple PCR units 100 are arranged in the y-direction. Several nucleic acid solutions, obtained from several different samples, are placed in the space S within each of the multiple PCR units 100. The multiple light-transmitting and light-receiving nozzles 40 or 40A of the second nozzle unit 60 are moved along the x-direction onto the container 110, on which the lid 120 is attached, in order to bring the interior of the PCR unit 100 into a measurable state, as shown in Figure 12(a). Fig. 4 is shown.

[0076] During PCR testing in the state of Fig. 4. Light transmission and light reception are carried out in the several PCR units 100, while the scanning element 340 is caused to move along the scanning lines LA and LB of Fig. 15 above the PCR measuring unit 310. The optical fibers 41a for transmitting light and the optical fibers 41b for receiving light are grouped into one of the PCR units 100 and in groups A and B of Fig. The scanning element 340 is arranged substantially perpendicular (or vertically) to the scanning direction. When the scanning element 340 scans the excitation light positions P4, P5, P6 of the PCR measuring unit 310 along the scanning line LA and the light reception positions P11, P12, P13 of the PCR measuring unit 310 along the scanning line LB, excitation light of different wavelengths can be supplied to the multiple PCR units 100, while the fluorescence corresponding to the excitation light of different wavelengths can be measured. The control unit 360 performs a qualitative and / or quantitative treatment of a target substance, such as a nucleic acid, based on the fluorescence measured by the PCR measuring unit (fluorescence measuring unit) 310. The control unit 360 determines whether the quality (fluorescence intensity) of the measured target substance meets a predetermined condition.When the control unit 360 has determined that the predetermined condition (fluorescence intensity condition) is met, the control unit 360 registers that the quality meets the condition in a storage unit (such as a hard drive, etc.). Absorption measurement using the measuring body

[0077] The process by which the absorption measuring unit 320 of the measuring body 300 measures the absorption (transmitted light) received from the several light absorption units 100B is explained. As in Fig. As shown in Figure 12, the multiple light absorption units 100B are arranged in the y-direction. Several nucleic acid solutions, obtained from several different samples, are placed in the space S within each of the multiple light absorption units 100B. The multiple light-transmitting and light-receiving nozzles 40 of the second nozzle unit 60 are moved along the x-direction towards the container 110, on which the lid 120 is attached, in order to bring the interior of the light absorption unit 100B into a measurable state, as shown in the Fig. 10 or Fig. 11 is shown.

[0078] In the state of Fig. 10 or Fig. Light is transmitted from above into the majority of the light absorption units 100B, and light that has passed through space S is received from below, while the scanning element 340 is caused to scan along the scanning lines LA and LC above the absorption measurement unit 320. The optical fiber 41a for transmitting light and the optical fiber 51 for transmitted light are grouped into one of the light absorption units 100B and are substantially perpendicular (or vertical) to the scanning direction in groups A and C of Fig. 15. When the scanning element 340 scans the visible light positions P1, P2, P3 of the absorption measuring unit 320 along the scanning line LA and scans the light receiving positions P8, P9, P10 of the PCR measuring unit 310 along the scanning line LB, different types of visible light can be supplied to the multiple light absorption units 100B, while the transmitted light corresponding to the different types of visible light can be received and the absorption measured. The control unit 360 can calculate the turbidity from the measured absorption. The control unit 360 performs a qualitative and / or quantitative treatment of a target substance, such as a nucleic acid, based on the absorption measured by the absorption measuring unit 320. The control unit 360 determines whether the quality (absorption or turbidity) of the measured target substance meets a predetermined condition.When the control unit 360 has determined that the specified condition (absorption or turbidity condition) is met, the control unit 360 registers in the storage unit that the quality meets the condition. Chemiluminescence measurement using the measuring body

[0079] The process is explained when the chemiluminescence measuring unit 330 of the measuring body 300 measures the chemiluminescence obtained from the several chemiluminescence units 100A. As in Fig. As shown in Figure 12, the multiple chemiluminescence units 100A are arranged in the y-direction. Several nucleic acid solutions, obtained from several different samples, are placed in the space S within each of the multiple chemiluminescence units 100A. The multiple light-transmitting and light-receiving nozzles 40 or 40A of the second nozzle unit 60 are moved along the x-direction onto the container 110, on which the lid 120 is attached, in order to bring the interior of the chemiluminescence unit 100A into a measurable state, as shown in the Fig. 7 or Fig. 8 is shown.

[0080] In this state, chemiluminescent light is received by the majority of the chemiluminescence units 100A, while the scanning element 340 is caused to move along the scanning line LB. Fig. The scanning element 340 scans the light receiving position P7 of the chemiluminescence measuring unit 330 along the scanning line LB. When the scanning element 340 scans the light receiving position P7 of the chemiluminescence measuring unit 330 along the scanning line LB, the chemiluminescence obtained by the plurality of chemiluminescence units 100A can be measured. The control unit 360 performs a qualitative and / or quantitative treatment of a target substance, such as a nucleic acid, based on the chemiluminescence measured by the chemiluminescence measuring unit 313. The control unit 360 determines whether the quality (chemiluminescence intensity) of the measured target substance meets a predetermined condition. If the control unit 360 has determined that the predetermined condition (chemiluminescence intensity condition) is met, the control unit 360 records in the storage unit that the quality meets the condition. Measurement of electrophoresis using an electrophoresis unit

[0081] As in Fig.As shown in Figure 12, the electrophoresis unit 200 has a plurality of solution dispensing ports 201 arranged in the y-direction. A plurality of nucleic acid solutions, obtained from a plurality of different samples, are dispensed into each of the plurality of nucleic acid solution dispensing ports 201 via the plurality of dispensing nozzles 65. After the nucleic acid solutions have been dispensed, a voltage is applied between the electrode pair 205 for electrophoresis to move the nucleic acid along the electrophoresis sail 203. After a predetermined time, an electrophoresis pattern generated by the movement of the nucleic acid is imaged by an imaging unit (photographic element such as a CCD). The control unit 360 performs image recognition of the imaged electrophoresis pattern and can carry out a quality assessment of a target substance such as a nucleic acid.The imaging unit can be located on the second nozzle unit 60. The control unit 360 determines whether the quality (electrophoresis pattern) of the measured target substance meets a predetermined condition. If the control unit 360 has determined that the predetermined condition (electrophoresis condition) is met, the control unit 360 registers that the quality meets the condition.

[0082] In the exemplary embodiment of the present invention, the quality measurement of a nucleic acid during or after pretreatment was described; however, the quality control device of the present invention is not limited to the quality measurement of a nucleic acid by means of a PCR reaction. The quality control device of the present invention can be used for chemiluminescence measurement by means of fluorescence or an antigen-antibody reaction (immunoassay), absorption measurement by means of different absorption settings, and / or electrophoresis pattern measurement based on the size of an electrically charged target substance for a plurality of target substances (e.g., proteins, etc.) obtained during or after pretreatment.Furthermore, the quality control device of the present invention can perform multiple and highly sensitive quantitative and / or qualitative treatments on a target substance using the obtained measured values. Reference symbol list 1 Sample processing system (fully automated sequencer) 2 Sample treatment measuring device 10 Quality inspection device 20 pretreatment units 21 Flow cell unit 30 first nozzle unit 40 light-transmitting and light-receiving nozzles 60 second nozzle unit 100 PCR units 100A Chemiluminescence Unit 100B light absorption unit 200 electrophoresis units 300 measuring bodies 310 PCR measuring unit 320 Absorption measurement unit 330 Chemiluminescence measuring device 340 scanning elements 400 Motion device with pitch conversion QUOTES INCLUDED IN THE DESCRIPTION

[0000] This list of documents cited by the applicant was automatically generated and is included solely for the reader's convenience. The list is not part of the German patent or utility model application. The DPMA accepts no liability for any errors or omissions. Cited patent literature

[0000] WO 2023 / 032870 A1

[0008] Cited non-patent literature

[0000] https: / / www.pss.co.jp / english / product / genelead / >

[0007]

Claims

[1] Quality control device for measuring the quality of a target substance, such as a nucleic acid, contained in a target substance solution obtained during or after pretreatment, wherein the quality control device comprises at least one or a combination of two or more of the following components: at least one fluorescent unit to obtain fluorescence from the target substance, at least one chemiluminescence unit for generating chemiluminescence in the target substance, at least one light absorption unit to obtain absorption of the target substance solution and at least one electrophoresis unit for performing electrophoresis of the target substance, wherein The quality control device comprises a measuring body for measuring the fluorescence from the fluorescence unit, the absorption based on the transmitted light from the light absorption unit and / or the chemiluminescence from the chemiluminescence unit and a control unit for controlling the fluorescence unit, the electrophoresis unit and / or the measuring body. [2] Quality inspection device according to claim 1, wherein the measuring body comprises at least one or a combination of two or more of the following components: a fluorescence measuring unit for measuring the fluorescence from the fluorescence unit, an absorption measuring unit for measuring absorption based on the light transmitted by the light absorption unit and a chemiluminescence measuring unit for measuring the chemiluminescence from the chemiluminescence unit. [3] Quality inspection device according to claim 1, wherein the quality inspection device comprises the fluorescence unit, the light absorption unit and the chemiluminescence unit. [4] Quality inspection device according to claim 3, wherein the measuring body comprises a PCR measuring unit for measuring the fluorescence based on a nucleic acid amplified with the fluorescence unit, an absorption measuring unit for measuring the absorption based on the light transmitted by the light absorption unit and a chemiluminescence measuring unit for measuring the chemiluminescence from the chemiluminescence unit. [5] Quality inspection device according to claim 4, wherein the measuring body comprises a scanning body which moves over the fluorescence measuring unit, the absorption measuring unit and the chemiluminescence measuring unit. [6] Quality inspection device according to claim 5, wherein the scanning element is connected to at least one optical fiber for transmitting light in order to direct excitation light from the fluorescence measuring unit to the fluorescence unit and / or to direct incident light from the absorption measuring unit to the light absorption unit; with an optical fiber for receiving light, for transmitting fluorescence from the fluorescence unit or chemiluminescence from the chemiluminescence unit to the fluorescence measuring unit; and with an optical fiber for transmitted light to guide transmitted light from the light absorption unit to the absorption measurement unit. [7] Quality inspection device according to claim 6, wherein The fluorescence measuring unit and / or the absorption measuring unit comprises a plurality of light sources with different wavelengths and a plurality of light-receiving elements corresponding to the plurality of light sources. wherein the chemiluminescence measuring unit comprises at least one light receiving element for receiving the chemiluminescence. [8] Quality inspection device according to claim 6, comprising at least one light-transmitting and light-receiving nozzle with end sections of the optical fiber for transmitting light and the optical fiber for receiving light, wherein the light-transmitting and light-receiving nozzle is connected to the fluorescence unit, the chemiluminescence unit and the light absorption unit via the optical fiber for transmitting light and the optical fiber for receiving light. [9] Quality inspection device according to claim 8, wherein the fluorescence unit, the chemiluminescence unit and the light absorption unit each consist of a container and a lid for closing the container. [10] Quality inspection device according to claim 9, wherein the container consists of a container upper part and a container lower part projecting downwards from the container upper part, wherein the container lower part has a smaller diameter than the container upper part, the lid consists of a lid top and a lid bottom projecting downwards from the lid top, the lid bottom having a smaller diameter than the lid top, and The lower part of the lid is incorporated into the lower part of the container when the lid is placed on the container. [11] Quality inspection device according to claim 10, wherein when the lower part of the lid is received in the lower part of the container, the lower part of the lid is in close contact with the lower part of the container and forms a space that seals the nucleic acid solution. [12] Quality inspection device according to claim 9, wherein an inner surface of the container of the fluorescent unit is colored white or that the container of the fluorescent unit is made of a white colored material. [13] Quality inspection device according to claim 9, wherein an inner surface of the container of the chemiluminescence unit is colored black or the container of the chemiluminescence unit is made of a black colored material. [14] Quality inspection device according to claim 9, wherein the lid comprises a lid-side light-transmitting section for transmitting the excitation light, the fluorescence light and / or the chemiluminescence light, and the lid-side light-transmitting section is arranged such that it faces the light-transmitting and light-receiving nozzle. [15] Quality inspection device according to claim 9, wherein the container of the light absorption unit comprises a container-side light-transmitting section, and the container-side light-transmitting section is arranged such that it faces the end section of the optical fiber for transmitted light. [16] Quality control device according to claim 1, wherein the target substance is a nucleic acid or a protein. [17] Quality control device, wherein the fluorescence unit is a PCR unit for performing a PCR reaction of the nucleic acid. [18] Quality control device according to claim 1, wherein the control unit performs a qualitative and / or quantitative treatment of the target substance using the measured fluorescence, chemiluminescence and / or absorption. [19] Quality inspection device according to claim 18, further comprising an imaging unit for imaging an electrophoresis pattern obtained from electrophoresis, wherein The control unit performs a quality assessment of the target substance based on the electrophoresis pattern. [20] Sample treatment system, comprising a sample treatment device for performing a treatment to extract a target substance (such as a nucleic acid) from a sample and to purify the target substance, and the quality inspection device according to claim 1. [21] Sample treatment system according to claim 20, comprising a motion device for moving a solution of the target substance from the sample treatment device to the quality control device. [22] Sequencer for performing sequencing of a nucleic acid obtained from a sample, comprising a sample treatment device comprising a pretreatment unit for extracting the nucleic acid from the sample and for purifying the nucleic acid, a PCR unit on the pretreatment side for amplifying the nucleic acid by PCR using a nucleic acid solution obtained from the pretreatment unit, and a first nozzle unit for moving the nucleic acid solution; the quality control device according to claim 1 for measuring the quality of the nucleic acid using the nucleic acid solution obtained from the pretreatment unit; a moving device for moving the nucleic acid solution from the pretreatment unit to the quality control device; a flow cell unit for performing nucleic acid sequencing using the nucleic acid solution; and a control unit for controlling the sample treatment device, the quality control device, the movement device and a treatment in the flow cell unit, wherein If the control unit determines that the quality of the nucleic acid measured using the quality control device meets at least one predetermined condition, nucleic acid sequencing is performed. [23] Sequencer according to claim 22, wherein the pretreatment unit comprises a nucleic acid extraction unit for extracting a nucleic acid from the sample, a size determination unit for performing a size determination of an extracted nucleic acid and an adapter conjugation unit for conjugating an adapter to both ends of a size-determined nucleic acid.

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