A nucleic acid detection device and method

Abstract

The present application relates to the technical field of automation, and especially relates to a nucleic acid detection device and a method thereof, which comprises a rack, a sample pretreatment device enclosed in a lower layer of the rack, a sample preparation device to be detected enclosed in an upper layer of the rack and a PCR instrument. The nucleic acid detection device and the method thereof adopt full-automatic mechanical operation, and integrate a series of functions such as identity verification, sample information collection, sample enrichment and sample lysis. Full-automatic mechanical operation can greatly reduce the demand for relevant professionals, save medical resources and reduce epidemic prevention cost.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of automation, in particular to a nucleic acid detection device and method thereof. BACKGROUND

[0002] In recent years, new and emerging infectious diseases have shown characteristics of multiple sources, rapid spread, and wide impact, posing great challenges to infectious disease prevention and control and social stability. In particular, for places such as customs and primary medical institutions, it is particularly crucial to establish and improve a major infectious disease pathogen nucleic acid detection system.

[0003] However, the existing nucleic acid detection system still has a lot of room for improvement. Nucleic acid detection mainly relies on professional institutions, and large, high-throughput, and automated equipment are mostly used. The sample pretreatment step is complicated and time-consuming, making it difficult to apply to on-site rapid diagnosis. In recent years, a series of pathogen nucleic acid detection platforms with automatic "sample in-result out" characteristics have emerged, but they are either costly (requiring enzymatic amplification), or have limited throughput (mostly single target), or have insufficient key detection performance (such as sensitivity not reaching single copy / test), and still cannot fully meet the needs of on-site rapid real-time diagnosis.

[0004] The global outbreak of the novel coronavirus (2019-nCoV) has brought "nucleic acid detection" into the public eye. Among the global COVID-19 diagnosis methods, nucleic acid detection is recognized as the "gold standard". Currently, conventional nucleic acid detection includes four processes: sampling and pre-treatment, nucleic acid extraction, PCR amplification, and data analysis, and must rely on professional laboratories, precise PCR equipment, and professional operators, but it is still inevitable to have medical staff infections, virus / reagent cross-contamination, multiple independent spaces for detection processes, and unsatisfactory consistency of detection results, making the development of nucleic acid rapid detection integrated machines imminent.

[0005] Existing nucleic acid detection integrated machines are mainly divided into three categories: pipeline automation systems, cartridge-type integrated machines, and other types of integrated machines (amplification-free, extraction-free nucleic acid, etc.). The pipeline automation system is the most mature integrated nucleic acid detection instrument. The development is mainly based on the concept of replacing manual operation with mechanical automation, reducing the manual operation part to only placing reagent consumables and sample tubes, and consisting of four modules: sample import, sample transfer, sample separation and purification, and amplification and detection. It can realize the automation of sample pipetting, sample preparation, amplification and detection, result calculation and uploading, effectively improve the protection of operators and avoid external contamination, but the size of the equipment limits its potential application in POCT.

[0006] Roche cobas 8800, its 24h detection flux up to 2880; domestic above Shanghai Jiang's "greening No. 1" as representative, 24 hours continuous work only needs 4 times manual consumables to move and place, can save professional detection manpower greatly, daily single tube detection flux reaches 4500. The card box type integrated machine integrates all functions of the assembly line type system in a card box, greatly reduces the equipment volume, speeds up the detection process and improves the portability.

[0007] The cepheid infinity80-80 defines the molecular POCT product concept of "sample in, result out", which is composed of special microfluidic reagent cartridges and block type cumulative reaction modules. Sample processing, nucleic acid extraction and purification, system configuration and amplification detection are all completed in special reagent cartridges. The 24h detection flux can reach 768, and the on-site detection can be realized;

[0008] The domestic Automolec 3000 is the peak of the current domestic molecular diagnosis integrated machine, which integrates nucleic acid extraction, purification, amplification and detection into one machine, and realizes "sample on-site detection". It breaks through the previous limitation of batch detection of high-throughput integrated machine.

[0009] With the increasing demand for detection speed and portability, non-amplification and non-extraction nucleic acid integrated detection equipment has emerged. Through optimization of the lysis process and the rear end amplification reagent, Tsinghua University has developed a nucleic acid extraction-free integrated microfluidic cartridge, which can realize "sample in, result out" in 30 minutes. Based on the characteristics of CRISPR-Cas13a system target specific recognition and activation of non-specific cutting function, Japan has developed a device for automatic detection of new coronavirus within 9 minutes.

[0010] In summary, there are a large number of related products at home and abroad. The foreign products have slight advantages in mechanical precision control and new technology development and application, but most of them are still at the research and development stage, and there is a lack of related data and practice for large-scale application on the market, which indicates that there is still a lot of room for improvement. Domestic products have more thinking in PCR amplification module, throughput expansion and protection module, especially in the practical promotion and application of automatic integrated machine at the grassroots level, which still needs more research.

[0011] In view of the frequent outbreak of new and emerging infectious diseases, the development trend of nucleic acid rapid detection integrated machine will be from large volume assembly line automation to miniature automatic card box type detection device, and finally integrate new detection methods and new technologies to promote its development towards fast, accurate, high-throughput, integrated, fully automated and miniature molecular diagnostic equipment. SUMMARY

[0012] In view of the above, the present application provides a nucleic acid detection device and method, which at least partially solve the problems in the prior art.

[0013] A nucleic acid detection device, comprising a frame, a sample pretreatment device enclosed in the lower layer of the frame, a sample preparation device enclosed in the upper layer of the frame and a PCR instrument, wherein:

[0014] The sample pretreatment device comprises the following devices arranged on the frame:

[0015] A sample enrichment device for processing a sample containing a sample to be tested and a nanoscale magnetic particle enrichment tube to enrich the target components in the sample to be tested;

[0016] A sample lysis device for placing the enriched sample to be tested into a lysis tube containing a lysis solution to obtain a nucleic acid extraction tube, and sending the nucleic acid extraction tube to a test tube magazine;

[0017] The sample preparation device comprises the following devices arranged in the frame from back to front:

[0018] A tube moving device for moving the nucleic acid extraction tube containing the lysed sample in the test tube magazine to a liquid taking table and opening the cap;

[0019] A pipetting device for pipetting the sample to be tested in the nucleic acid extraction tube to an eight-way tube to obtain a sample to be tested and send it to the PCR instrument.

[0020] Preferably, it further comprises a lifting device enclosed in the rear part of the frame for conveying the test tube magazine between the sample pretreatment device and the sample preparation device, the test tube magazine being used to provide a lysis tube containing a lysis solution and a nucleic acid extraction tube containing a sample to be tested.

[0021] Preferably, the sample enrichment device comprises the following devices arranged therein:

[0022] A placement table for placing the enrichment tube;

[0023] An overturning manipulator for overturning the enrichment tube on the placement table on the overturning rack;

[0024] An overturning rack for overturning and placing the enrichment tube.

[0025] Preferably, the placement table is a rack structure, provided with an X-axis driver one for driving it to move left and right along the frame.

[0026] Preferably, the placement table further comprises a clamping jaw one for clamping the enrichment tube, and a rotating jaw one for tightening the enrichment cap of the enrichment tube.

[0027] Preferably, the upper part of the placement platform is further provided with an image recognition device for detecting whether the enrichment cover is installed on the enrichment tube.

[0028] Preferably, the turnover manipulator comprises:

[0029] an X-axis driver two for driving the enrichment tube to move along the left-right direction of the rack;

[0030] a Z-axis driver two for driving the enrichment tube to move along the up-down direction of the rack;

[0031] a gripper two for clamping the enrichment tube;

[0032] a rotary driver one for driving the gripper two to turn along the direction of gravity.

[0033] Preferably, the sample lysis device comprises:

[0034] a double-position rotary table provided with two test tube installation positions for respectively installing the enrichment tube and the lysis tube containing the lysis solution;

[0035] a lysis manipulator for covering the enrichment cover of the enrichment tube on the lysis tube containing the lysis solution on the double-position rotary table, obtaining the nucleic acid extraction tube and moving it to the test tube magazine.

[0036] Preferably, the double-position rotary table is a rack structure, and two test tube installation positions are respectively arranged on the rack structure, and a rotary gripper two for clamping and rotating the test tube is arranged below each test tube installation position.

[0037] Preferably, the double-position rotary table comprises:

[0038] a test tube rack provided with two test tube installation positions for respectively installing the enrichment tube and the lysis tube;

[0039] two grippers three respectively for clamping the enrichment tube and the lysis tube;

[0040] two rotary grippers two respectively for rotating the tube body of the enrichment tube and the lysis tube;

[0041] an X-axis driver three for driving the two rotary grippers two to move along the left-right direction of the rack.

[0042] Preferably, the lysis manipulator comprises:

[0043] an X-axis driver four for driving the lysis manipulator to move along the left-right direction of the rack;

[0044] a Y-axis driver four for driving the lysis manipulator to move along the front-back direction of the rack;

[0045] a Z-axis driver four for driving the lysis manipulator to move along the up-down direction of the rack.

[0046] a fourth gripper for clamping the enrichment tube;

[0047] a second rotary driver for driving the fourth gripper to flip along the direction of gravity,

[0048] a fifth gripper for clamping the lysis tube.

[0049] Preferably, the fourth gripper is provided with a magnetic device.

[0050] Preferably, the tube moving device comprises a liquid taking table and a tube moving robot provided above the liquid taking table, the tube moving robot being used to move the nucleic acid extraction tube with the lysis sample in the tube magazine to the liquid taking table and open the cap.

[0051] Preferably, the liquid moving device comprises a liquid dropping table, a consumable magazine and a liquid moving robot provided above the liquid dropping table, the liquid moving robot being used to move the eight-way tube in the consumable magazine to the liquid dropping table, and drop the liquid taken from the nucleic acid extraction tube into the eight-way tube to obtain the sample to be tested.

[0052] Preferably, the liquid taking table is a table structure, and a lower part of the table structure is provided with a sixth gripper for clamping the nucleic acid extraction tube.

[0053] Preferably, the tube moving robot comprises:

[0054] a fifth X-axis driver for driving the tube moving robot to move along the left-right direction of the rack;

[0055] a fifth Y-axis driver for driving the tube moving robot to move along the front-back direction of the rack;

[0056] a fifth Z-axis driver for driving the tube moving robot to move along the up-down direction of the rack;

[0057] a third rotary gripper for clamping the nucleic acid extraction tube and rotating to open the cap.

[0058] Preferably, the consumable magazine comprises at least one of the following consumables:

[0059] an eight-way tube for containing the sample to be tested taken from the nucleic acid extraction tube;

[0060] an eight-way cap for capping the eight-way tube;

[0061] a liquid moving cannula for taking liquid from the nucleic acid extraction tube and dropping into the eight-way tube.

[0062] Preferably, the liquid moving robot comprises:

[0063] a sixth X-axis driver for driving the liquid moving robot to move along the left-right direction of the rack;

[0064] Y-axis driver six for driving the movement of the eight-tube along the front-to-back direction of the rack;

[0065] Z-axis driver six for driving the movement of the eight-tube along the up-to-down direction of the rack;

[0066] Clamp jaw seven for moving the eight-tube to the droplet table;

[0067] Pipette for pipetting the nucleic acid from the nucleic acid extraction tube on the liquid taking table and into the eight-tube on the droplet table.

[0068] Preferably, the pipetting robot further comprises clamp jaw eight for moving the eight-cap to the eight-tube.

[0069] Preferably, the pipetting robot further comprises capping device, which comprises:

[0070] Capping table for placing the eight-tube with the eight-cap, wherein a linear driver is arranged at the lower part of the capping table for driving the movement of the capping table to the lower part of the capping machine;

[0071] Capping machine for capping the eight-cap to the eight-tube.

[0072] Preferably, the pipetting robot further comprises pipette recovery device, which is filled with disinfectant for storing the used pipette.

[0073] Preferably, the pipetting robot further comprises waste collection device, which is filled with disinfectant for storing the cap of the lysis tube and the body of the enrichment tube.

[0074] Preferably, the pipetting robot further comprises sterilization device for sterilization before and after the detection to avoid the contamination or leakage of the sample.

[0075] Preferably, the consumable storage is in the form of drawer, which can be pulled out of the rack along the left-to-right direction of the rack for replacing the consumable.

[0076] Preferably, the pipetting robot further comprises identification verification device, which comprises code scanning device for identifying the bar code information on the enrichment tube, and / or identity authentication device for identifying the identity information of the subject, and / or image recognition device for identifying whether the operation of the subject is standard.

[0077] Preferably, the pipetting robot further comprises isolation door device arranged in front of the sample enrichment device for closing the sample enrichment device to avoid the contamination of the sample.

[0078] Preferably, any one of the X-axis driver one, X-axis driver two, X-axis driver three, X-axis driver four, X-axis driver five, X-axis driver six, Y-axis driver four, Y-axis driver five, Y-axis driver six, Z-axis driver two, Z-axis driver four, Z-axis driver five, Z-axis driver six is an electric, pneumatic or hydraulic driven linear motion mechanism.

[0079] A method for nucleic acid detection according to the nucleic acid detection device described above, mainly including the following steps:

[0080] The sample enrichment step mainly inverts the enrichment tube containing the sample to be tested and nanoscale magnetic particles by the overturning manipulator, so that the formed components in the sample to be tested are enriched with the enrichment cover of the enrichment tube;

[0081] The sample lysis step mainly covers the lysis tube containing the lysis solution by the lysis manipulator, so as to obtain the nucleic acid extraction tube;

[0082] The tube moving step mainly moves the nucleic acid extraction tube containing the lysed sample in the tube magazine to the liquid taking table and opens the cover by the tube moving manipulator;

[0083] The pipetting step mainly moves the eight-way tube in the consumable magazine to the droplet table by the pipetting manipulator, and takes the liquid from the nucleic acid extraction tube and drops it into the eight-way tube;

[0084] The cover pressing step mainly tightly presses the eight-way cover into the eight-way tube by the cover pressing machine;

[0085] The machine detection step mainly sends the eight-way tube with the eight-way cover to the PCR instrument for detection by the pipetting manipulator.

[0086] Preferably, the sample enrichment step includes the following steps:

[0087] Step one, place the enrichment tube containing the mouthwash and nanoscale magnetic particles into the placing table;

[0088] Step two, overturn the enrichment tube along the gravity direction by the overturning manipulator, invert it in the inversion rack, and stand still for a preset time;

[0089] Step three, set a magnetic device on the enrichment cover of the enrichment tube and / or the clamping jaw four of the overturning manipulator, so that the nanoscale magnetic particles adsorbed with the formed objects of the sample to be tested are enriched in the enrichment cover.

[0090] Preferably, the sample lysis step includes the following steps:

[0091] Step one, the fifth gripper of the lysis manipulator takes a lysis tube containing lysis solution from the tube magazine and places it in one of the two tube holding positions of the double-position rotary table, and the fifth gripper holds the cap of the lysis tube, the third gripper of the corresponding tube holding position holds the body of the lysis tube, and the second rotary gripper of the corresponding tube holding position rotates the body of the lysis tube to remove the cap of the lysis tube;

[0092] Step two, the fourth gripper of the lysis manipulator takes the enrichment tube from the inverted rack, flips it in the direction of gravity, and then places it in the other tube holding position of the double-position rotary table, and the fourth gripper holds the enrichment cap of the enrichment tube, the third gripper of the corresponding tube holding position holds the body of the enrichment tube, and the second rotary gripper of the corresponding tube holding position rotates the body of the enrichment tube to remove the enrichment cap of the enrichment tube;

[0093] Step three, the lysis manipulator moves the enrichment cap to cover the lysis tube, and the nucleic acid extraction tube is obtained and moved to the tube magazine.

[0094] Preferably, the sample lysis link includes the following steps:

[0095] Step one, the fifth gripper of the lysis manipulator takes a lysis tube containing lysis solution from the tube magazine and places it in one of the two tube holding positions of the double-position rotary table, and the fifth gripper holds the cap of the lysis tube, the third gripper of the corresponding tube holding position holds the body of the lysis tube, and the second rotary gripper of the corresponding tube holding position rotates the body of the lysis tube to remove the cap of the lysis tube;

[0096] Step two, the fourth gripper of the lysis manipulator takes the enrichment tube from the inverted rack, flips it in the direction of gravity, and then places it in the other tube holding position of the double-position rotary table, and the fourth gripper holds the enrichment cap of the enrichment tube, the third gripper of the corresponding tube holding position holds the body of the enrichment tube, and the second rotary gripper of the corresponding tube holding position rotates the body of the enrichment tube to remove the enrichment cap of the enrichment tube;

[0097] Step three, the X-axis driver three drives the two second rotary grippers to move along the left and right directions of the rack, so that the body of the lysis tube moves below the enrichment cap, and the corresponding second rotary gripper of the lysis tube drives the body to rotate, so that the enrichment cap covers the lysis tube, and the nucleic acid extraction tube is obtained.

[0098] Preferably, the sample lysis link further includes the following steps:

[0099] Step four, the fourth gripper of the lysis manipulator takes the nucleic acid extraction tube from the double-position rotary table, and the rotary driver two flips the nucleic acid extraction tube a predetermined number of times to fully lyse the sample on the enrichment cap;

[0100] Step five, the lysis manipulator places the nucleic acid extraction tube upright in the tube magazine.

[0101] Preferably, it further includes a waste collection link, which includes one of the following actions:

[0102] Action one, through the gripper five of the lysis mechanical hand, the tube cover of the removed lysis tube is covered into the enrichment tube from which the enrichment cover has been removed, to obtain a waste tube, and then through the movement of the lysis mechanical hand, the waste tube is put into the waste collection device filled with disinfectant;

[0103] Action two, through the X-axis driver three to drive the two rotating grippers two to move along the left and right directions of the rack, the tube body of the enrichment tube is moved to below the tube cover of the lysis tube, the enrichment tube corresponding rotating gripper two drives the tube body to rotate, so that the tube cover of the lysis tube is covered into the enrichment tube to obtain a waste tube, and then through the movement of the lysis mechanical hand, the waste tube is put into the waste collection device filled with disinfectant.

[0104] Preferably, the tube moving link includes the following steps:

[0105] Step one, the tube moving mechanical hand moves the nucleic acid extraction tube filled with lysis samples in the test tube warehouse to the liquid taking table;

[0106] Step two, the gripper six of the liquid taking table clamps the nucleic acid extraction tube;

[0107] Step three, the rotating gripper three of the tube moving mechanical hand unscrews the enrichment cover of the nucleic acid extraction tube.

[0108] Preferably, the tube moving link further includes the following steps:

[0109] Step four, after the liquid taking is completed, the rotating gripper three of the tube moving mechanical hand covers back the tube cover of the nucleic acid extraction tube;

[0110] Step five, the gripper six of the liquid taking table clamps the nucleic acid extraction tube, and the rotating gripper three drives the enrichment cover to rotate to tighten the enrichment cover;

[0111] Step six, the gripper six of the liquid taking table loosens the nucleic acid extraction tube, and the tube moving mechanical hand sends the nucleic acid extraction tube back to the test tube warehouse.

[0112] Preferably, the liquid moving link includes the following steps:

[0113] Step one, the gripper seven of the liquid moving mechanical hand moves the eight-way tube in the consumable warehouse to the droplet table;

[0114] Step two, the liquid moving device of the liquid moving mechanical hand loads the liquid moving sleeve from the test tube warehouse;

[0115] Step three, the liquid moving device of the tube moving mechanical hand operates the liquid moving sleeve to take liquid from the nucleic acid extraction tube on the liquid taking table and drop into the eight-way tube on the droplet table.

[0116] Preferably, the pipetting link further comprises the following steps:

[0117] Step four, the pipette of the pipetting manipulator throws the used pipetting sleeve into the sleeve recycling device.

[0118] Preferably, the capping link comprises the following steps:

[0119] Step one, the gripper eight of the pipetting manipulator moves the eight-capped cap in the test tube magazine to the eight-capped tube on the droplet table;

[0120] Step two, the gripper six of the pipetting manipulator moves the eight-capped tube capped with the eight-capped cap from the droplet table to the capping table;

[0121] Step three, the capping table sends the eight-capped tube capped with the eight-capped cap to the lower part of the capping machine through the linear driver;

[0122] Step four, the capping machine presses the eight-capped cap tightly onto the eight-capped tube.

[0123] Preferably, it further comprises an identification verification link, which comprises the following steps:

[0124] Step one, the identity information of the examinee is identified through the identity authentication device, and after the authentication is passed, the isolation door is opened, and the examinee is prompted to put the enrichment tube into the placement table;

[0125] Step two, the bar code information of the enrichment tube placed on the placement table is identified through the code scanning device, and after the identification is successful, the isolation door is closed and a prompt is issued.

[0126] Preferably, step one of the sample enrichment link further comprises the following actions:

[0127] Through the image recognition device arranged above the placement table, it is identified whether the enrichment cap is capped on the enrichment tube, if yes, the enrichment cap is tightened through the cooperation of the gripper one and the rotating claw one, and if not, the operation is interrupted and an alarm is issued.

[0128] Preferably, it further comprises a disinfection link, that is, before and after the sample pretreatment, at least one of ultraviolet rays, high-temperature steam and disinfectant is used to disinfect the sample pretreatment device.

[0129] The nucleic acid detection device and method provided by the application have the following advantages compared with the prior art:

[0130] (1) Fully automated mechanical operation saves medical resources and reduces the need for professional personnel. The nucleic acid detection described in this invention integrates a series of functions such as identity verification, sample information collection, sample enrichment, sample lysis, sample transfer, sample pipetting, and capping. The fully automated mechanical operation can greatly reduce the need for relevant professional personnel, save medical resources, and reduce epidemic prevention costs.

[0131] (2) Operation in a closed space with complete disinfection measures to avoid cross-infection. The nucleic acid testing device described in this invention is completed in a relatively closed space within the rack and has a series of sterilization and disinfection measures that meet national standards, such as high-temperature sterilization and ultraviolet lamp sterilization. This can effectively prevent cross-contamination, greatly improve the efficiency of epidemic prevention and control, and reduce the risk of infection in the population.

[0132] (3) The structure is compact and can be deployed quickly with multiple nodes and multiple levels. The nucleic acid detection method described in this invention is compact, occupies a small area, is lightweight, and can be flexibly arranged. It can be used to form a fully automated unmanned nucleic acid sampling and detection system. The system has a high degree of modularity. It is easy to deploy in response to the current complex, multi-level, distributed, and sudden epidemic prevention and control needs in China. It can be quickly promoted to urban communities, schools, industrial parks, hotels, construction sites, transportation entrances, large supermarkets, urban-rural fringe areas, and vast rural areas, thus building a strong fortress for grassroots epidemic prevention and control. Attached Figure Description

[0133] To more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0134] Figure 1 This is a schematic diagram of the overall structure of the nucleic acid detection device according to an embodiment of the present invention;

[0135] Figure 2 This is a schematic diagram of the structure of the sealing plate hidden on the frame of the nucleic acid detection device according to an embodiment of the present invention;

[0136] Figure 3 This is a schematic diagram of the hidden bottom structure of the nucleic acid detection device according to an embodiment of the present invention. Figure 1 ;

[0137] Figure 4 This is a schematic diagram of the hidden bottom structure of the nucleic acid detection device according to an embodiment of the present invention. Figure 2 ;

[0138] Figure 5 This is a schematic diagram of the sample preprocessing device in the nucleic acid detection apparatus described in this embodiment of the invention. Figure 1;

[0139] Figure 6 Structure of a sample pretreatment device in a nucleic acid detection device according to an embodiment of the present application Figure 2 ;

[0140] Figure 7 Structure of a sample enrichment device in a sample pretreatment device according to an embodiment of the present application Figure 1 ;

[0141] Figure 8 Structure of a sample enrichment device in a sample pretreatment device according to an embodiment of the present application Figure 2 ;

[0142] Figure 9 Structure of a sample lysis device in a sample pretreatment device according to an embodiment of the present application Figure 1 ;

[0143] Figure 10 Structure of a sample lysis device in a sample pretreatment device according to an embodiment of the present application Figure 2 ;

[0144] Figure 11 Structure of a sample preparation device in a nucleic acid detection device according to an embodiment of the present application Figure 1 ;

[0145] Figure 12 Structure of a sample preparation device in a nucleic acid detection device according to an embodiment of the present application Figure 2 ;

[0146] Figure 13 Structure of a pipette device in a sample preparation device according to an embodiment of the present application Figure 1 ;

[0147] Figure 14 Structure of a pipette device in a sample preparation device according to an embodiment of the present application Figure 2 ;

[0148] Figure 15 Structure of a pipette device in a sample preparation device according to an embodiment of the present application Figure 1 ;

[0149] Figure 16 Structure of a pipette device in a sample preparation device according to an embodiment of the present application Figure 2 .

[0150] BRIEF DESCRIPTION OF THE DRAWINGS

[0151] 1 - frame

[0152] 11 - waste collection device

[0153] 12-Disinfection device;

[0154] 13-Identification verification device;

[0155] 14-Isolation door device;

[0156] 2-Sample pretreatment device;

[0157] 21-Sample enrichment device;

[0158] 211-Storage platform;

[0159] 2111-X-axis driver one;

[0160] 2112-Clamping jaw one;

[0161] 2113-Rotary jaw one;

[0162] 2114-Image recognition device;

[0163] 212-Inversion manipulator;

[0164] 2121-X-axis driver two;

[0165] 2122-Z-axis driver two;

[0166] 2123-Clamping jaw two;

[0167] 2124-Rotary driver one;

[0168] 213-Inversion rack;

[0169] 22-Sample lysis device;

[0170] 221-Biposition rotary table;

[0171] 2211-Tube rack;

[0172] 2212-Clamping jaw three;

[0173] 2213-Rotary jaw two;

[0174] 2214-X-axis driver three;

[0175] 222-Lysis manipulator;

[0176] 2221-X-axis driver four;

[0177] 2222-Y-axis driver four;

[0178] 2223-Z-axis driver four;

[0179] 2224-Clamping jaw four;

[0180] 2225-Rotary driver two;

[0181] 2226-Claw six;

[0182] 3-Preparation device for sample to be tested;

[0183] 31-Transfer device;

[0184] 311-liquid taking table;

[0185] 3111-Claw six;

[0186] 312-Transfer robot;

[0187] 3121-X-axis driver five;

[0188] 3122-Y-axis driver five;

[0189] 3123-Z-axis driver five;

[0190] 3124-Rotary claw three;

[0191] 32-Pipetting device;

[0192] 321-Drop table;

[0193] 322-Consumable material bin;

[0194] 3221-Eight connecting tubes;

[0195] 3222-Eight connecting covers;

[0196] 3223-Pipetting sleeve;

[0197] 3224-Sleeve recovery device;

[0198] 323-Pipetting robot;

[0199] 3231-X-axis driver six;

[0200] 3232-Y-axis driver six;

[0201] 3233-Z-axis driver six;

[0202] 3234-Claw seven;

[0203] 3235-Pipettor;

[0204] 3236-Claw eight;

[0205] 33-Capping device;

[0206] 331-Capping table;

[0207] 3311-Straight line driver;

[0208] 332-Capping machine;

[0209] 4-PCR instrument;

[0210] 5-tube magazine;

[0211] 51-enrichment tube;

[0212] 511-enrichment cover;

[0213] 52-lysis tube;

[0214] 53-nucleic acid extraction tube;

[0215] 6-lifting device. DETAILED DESCRIPTION

[0216] The embodiments of the present application will be described in detail below with reference to the drawings.

[0217] It should be noted that the following embodiments and features in the embodiments can be combined with each other without conflict; and all other embodiments obtained by those skilled in the art based on the embodiments in the present disclosure without creative labor are within the scope of protection of the present disclosure.

[0218] It should be noted that the various aspects of the embodiments described below are within the scope of the appended claims. It should be apparent that the aspects described herein can be embodied in a wide variety of forms and that any specific structure and / or function described herein is merely illustrative. Based on the teachings herein one skilled in the art should appreciate that an aspect described herein can be implemented independently of any other aspects and that two or more aspects can be combined in various ways. For example, an apparatus can be implemented and / or a method practiced using any number of the aspects described herein. In addition, an apparatus can be implemented and / or a method practiced using other structure and / or functionality in addition to or other than one or more of the aspects described herein.

[0219] It should be noted that the steps described below, with the suffix of the number, are only to distinguish different steps, and do not represent the order of the steps.

[0220] Figure 1 The overall structure of the nucleic acid detection device described in the present embodiment is shown in the figure, Figure 2 The structure of the cover plate on the rack 1 is shown in the figure, Figure 1 As shown in the figure, Figure 1 , 2 The nucleic acid detection device disclosed in the present embodiment comprises a rack 1, a sample pretreatment device 2 arranged in the lower layer of the rack 1 and closed by a cover plate, a sample preparation device 3 to be detected arranged in the upper layer of the rack 1 and closed by a cover plate, and a PCR instrument 4. In the bottom layer of the rack 1, a waste bin and other devices for collecting waste are also arranged.

[0221] Figure 3 、 Figure 4 For Figure 2 Two schematic diagrams of the bottom structure of the rack 1 are shown in the figure. The core of the sample pretreatment device 2 is a sample enrichment and lysis device, which mainly includes a sample enrichment device and a sample lysis device 22 arranged on the rack 1. The core of the sample preparation device 3 is a sample pipetting and capping device, which mainly includes a pipetting device 31, a capping device 33 and a pipetting device 32 arranged in sequence from back to front on the rack 1.

[0222] The lifting device 6 is also arranged at the back of the rack 1. The lifting device 6 is used to transfer the test tube magazine 5 between the sample pretreatment device 2 and the sample preparation device 3. The test tube magazine 5 is used to provide lysis tubes 52 containing lysis solution and nucleic acid extraction tubes 53 containing samples to be tested.

[0223] The sample enrichment device is used to process the sample enrichment tube 51 containing the sample to be tested and nanoscale magnetic particles, so as to enrich the target components in the sample to be tested. The sample lysis device 22 is used to place the enriched sample to be tested into the lysis tube 52 containing lysis solution, so as to obtain the nucleic acid extraction tube 53, and then send the nucleic acid extraction tube 53 to the test tube magazine 5. The pipetting device 31 is used to transfer the nucleic acid extraction tube 53 containing the lysis sample in the test tube magazine 5 to the liquid taking table 311 and open the cap. The pipetting device 32 is used to pipette the sample to be tested in the nucleic acid extraction tube 53 to the eight-way tube 3221, so as to obtain the sample to be tested and send it to the PCR instrument 4.

[0224] Figure 5 、 Figure 6 Two structural schematic diagrams of the sample pretreatment device 2 of the embodiment are shown in the figure. The sample enrichment device 21 includes a placement table 211, a turnover manipulator 212 and an inverted stand 213 arranged therein. The placement table 211 is used to normally place the enrichment tube 51. The inverted stand 213 is used to inversely place the enrichment tube 51. The turnover manipulator 212 is arranged above the placement table 211 and the inverted stand 213, and is used to invert the enrichment tube 51 on the placement table 211 to the inverted stand 213.

[0225] The sample lysis device 22 includes a double-position rotary table 221 and a lysis manipulator 222 arranged therein. The double-position rotary table 221 is provided with two test tube placement positions, which are used to respectively place the enrichment tube 51 and the lysis tube 52 containing lysis solution. The lysis manipulator 222 is used to cover the enrichment cap 511 of the enrichment tube 51 on the lysis tube 52 containing lysis solution on the double-position rotary table 221, so as to obtain the nucleic acid extraction tube 53 and move it to the test tube magazine 5.

[0226] Figure 7 、 Figure 8Two structural diagrams of the sample enrichment device 21 in the embodiment are shown in the figures. The support platform 211 is a rack structure. An X-axis driver 2111 is arranged below the rack to drive the support platform 211 to move along the left-right direction of the rack 1. The support platform 211 further includes a gripper 2112 for clamping the enrichment tube 51 and a rotating gripper 2113 for tightening the enrichment cover 511 of the enrichment tube 51. An image recognition device 2114 is arranged on the upper part of the support platform 211 to detect whether the enrichment cover 511 is installed on the enrichment tube 51.

[0227] In the embodiment, the image recognition device 2114 is a camera. When the subject places the enrichment tube 51 on the support platform 211, the camera starts to work to identify whether the enrichment cover 511 is on the enrichment tube 51. If yes, the gripper 2112 clamps the enrichment tube 51, and the support platform 211 is driven by the X-axis driver 2111 to move along the left-right direction of the rack 1 to the position below the rotating gripper 2113. The rotating gripper 2113 clamps and rotates to tighten the enrichment cover 511 of the enrichment tube 51. If the camera identifies that the enrichment cover 511 is not on the enrichment tube 51, the operation is interrupted and an alarm is issued.

[0228] The turnover manipulator 212 includes an X-axis driver 2121, a Z-axis driver 2122, a gripper 2123, and a rotating driver 2124. The X-axis driver 2121 is used to drive the turnover manipulator 212 to move along the left-right direction of the rack 1. The Z-axis driver 2122 is used to drive the turnover manipulator 212 to move along the up-down direction of the rack 1. The gripper 2123 is used to clamp the enrichment tube 51. The rotating driver 2124 is used to drive the gripper 2123 to turn 180° along the direction of gravity.

[0229] In specific operation, the turnover manipulator 212 is driven by the X-axis driver 2121 to move along the left-right direction, so that the gripper 2123 moves to the position of the enrichment tube 51 and clamps the enrichment tube 51. Then, the gripper 2123 is driven by the rotating driver to turn 180° along the direction of gravity. Then, the gripper 2123 is driven by the Z-axis driver 2122 to move along the up-down direction of the rack 1, so that the enrichment tube 51 is inverted and placed on the inverted rack 213, so that the tangible objects in the subject sample are deposited on the enrichment cover 511. In order to speed up the process, a magnetic device can be arranged on the enrichment cover 511 or the gripper 2224 of the lysis manipulator 222, or both, so that the subject sample adsorbed by the nano-sized magnetic particles is accelerated to be enriched on the enrichment cover 511.

[0230] Figure 9 、 Figure 10Two structural diagrams of the sample lysing device 22 are shown in the figure. The double-position rotary table 221 includes a test tube rack 2211, two clamping jaws three 2212, two rotary jaws two 2213, and an X-axis driver three 2214. The test tube rack 2211 is provided with two test tube installation positions respectively for placing the enrichment tube 51 and the lysing tube 52. The two clamping jaws three 2212 are used for clamping the enrichment tube 51 and the lysing tube 52 respectively. The two rotary jaws two 2213 are used for rotating the tube body of the enrichment tube 51 and the lysing tube 52 respectively. The X-axis driver three 2214 is used for driving the two rotary jaws two 2213 to move along the left-right direction of the machine frame 1.

[0231] The lysing manipulator 222 includes an X-axis driver four 2221, a Y-axis driver four 2222, a Z-axis driver four 2223, a clamping jaw four 2224, a rotary driver two 2225, and a clamping jaw five 2226. The X-axis driver four 2221 is used for driving the lysing manipulator 222 to move along the left-right direction of the machine frame 1. The Y-axis driver four 2222 is used for driving the lysing manipulator 222 to move along the front-rear direction of the machine frame 1. The Z-axis driver four 2223 is used for driving the lysing manipulator 222 to move along the up-down direction of the machine frame 1. The clamping jaw four 2224 is used for clamping the enrichment tube 51. The rotary driver two 2225 is used for driving the clamping jaw four 2224 to flip along the direction of gravity. The clamping jaw five 2226 is used for clamping the lysing tube 52.

[0232] Specifically, there are two implementation modes, which are as follows.

[0233] Implementation mode one

[0234] The clamping jaw five 2226 of the lysing manipulator 222 takes out a lysing tube 52 containing lysing solution from the test tube warehouse 5 and places it into one test tube installation position of the double-position rotary table 221. The clamping jaw five 2226 keeps clamping the tube cover of the lysing tube 52. The clamping jaw three 2212 corresponding to the test tube installation position clamps the tube body of the lysing tube 52. The rotary jaw two 2213 corresponding to the test tube installation position drives the tube body of the lysing tube 52 to rotate, so as to take off the tube cover of the lysing tube 52.

[0235] The clamping jaw four 2224 of the lysing manipulator 222 takes off the enrichment tube 51 from the inverted rack 213, flips it by 180° along the direction of gravity, and then places it into the other test tube installation position of the double-position rotary table 221. The clamping jaw four 2224 keeps clamping the enrichment cover 511 of the enrichment tube 51. The clamping jaw three 2212 corresponding to the test tube installation position clamps the tube body of the enrichment tube 51. The rotary jaw two 2213 corresponding to the test tube installation position drives the tube body of the enrichment tube 51 to rotate, so as to take off the enrichment cover 511 of the enrichment tube 51.

[0236] Finally, the X-axis driver three 2214 drives the two rotating claws two 2213 to move along the left and right directions of the rack 1, so that the body of the lysis tube 52 moves below the enrichment cover 511. The corresponding rotating claw two 2213 of the lysis tube 52 drives the body to rotate, so that the enrichment cover 511 covers the lysis tube 52, and the nucleic acid extraction tube 53 is obtained.

[0237] The main advantage of this method of keeping the enrichment cover 511 stationary and moving the body of the lysis tube 52 to obtain the nucleic acid extraction tube 53 is that it avoids possible falling and contamination of the test sample, thereby ensuring the authenticity of the nucleic acid detection result.

[0238] Embodiment two

[0239] Compared with the first embodiment, the core of this embodiment is that the test tube is stationary and the cover is moving. Specifically, the lysis robot 222 takes out the lysis tube 52 and the enrichment tube 51 from the test tube warehouse 5 and the inverted rack 213 respectively and places them on the double-position rotating table 221. Then, through the cooperation of the clamp jaw three 2212 and the rotating claw two 2213, the cover is twisted off. Finally, the enrichment cover 511 is covered into the lysis tube 52 by the movement of the lysis robot 222, and the nucleic acid extraction tube 53 is obtained.

[0240] After obtaining the nucleic acid extraction tube 53 by one of the above two methods, the lysis robot 222 also flips the nucleic acid extraction tube 53 back and forth several times through the clamp jaw four 2224 and the rotating driver two 2225, so that the test sample is fully lysed and then placed in the test tube warehouse 5.

[0241] For the remaining enrichment tube 51 body and lysis tube 52 cover, one of the above two methods is used to cover the lysis tube 52 cover into the enrichment tube 51 body to obtain a waste tube, and then the waste tube is thrown into the waste collection device 11 containing a disinfectant by the movement of the lysis robot 222.

[0242] Figure 11 And Figure 12 Two structural schematic diagrams of the pre-preparation device 3 for the test sample are shown in the figure. The pre-preparation device 3 includes a tube moving device 31, a cover pressing device 33, and a pipetting device 32 arranged from back to front, wherein:

[0243] The tube moving device 31 comprises a liquid taking table 311 and a tube moving manipulator 312 arranged above the liquid taking table 311, the tube moving manipulator 312 is used to move the nucleic acid extraction tube 53 containing the lysed sample in the test tube magazine 5 to the liquid taking table 311 and open the cap; the capping device 33 is used to cap and tightly cap the eight-connection cap 3222 into the eight-connection tube 3221, the pipetting device 32 comprises a liquid dropping table 321, a consumable magazine 322 and a pipetting manipulator 323 arranged above the liquid dropping table 321, the pipetting manipulator 323 is used to move the eight-connection tube 3221 in the consumable magazine 322 to the liquid dropping table 321, and drop the liquid taken from the nucleic acid extraction tube 53 into the eight-connection tube 3221 to obtain the sample to be detected.

[0244] Figure 13 and Figure 14 Two structural diagrams of the tube moving device 31 are shown in Figures 11-14 , the liquid taking table 311 of the tube moving device 31 is a rack structure, and the lower part is provided with a clamping jaw six 3111 for clamping the nucleic acid extraction tube 53. The tube moving manipulator 312 comprises an X-axis driver five 3121, a Y-axis driver five 3122, a Z-axis driver five 3123 and a rotating jaw three 3124, the X-axis driver five 3121 is used to drive it to move left and right along the rack 1, the Y-axis driver five 3122 is used to drive it to move forward and backward along the rack 1, the Z-axis driver five 3123 is used to drive it to move up and down along the rack 1, and the rotating jaw three 3124 is used to clamp and rotate the cap of the nucleic acid extraction tube 53.

[0245] In specific operation, the tube moving manipulator 312 moves the nucleic acid extraction tube 53 containing the lysed sample in the test tube magazine 5 to the liquid taking table 311, the clamping jaw six 3111 of the liquid taking table 311 clamps the nucleic acid extraction tube 53, the rotating jaw three 3124 rotates the enrichment cap 511 of the nucleic acid extraction tube 53 to open for the pipettor 3235 of the pipetting manipulator 323 to take liquid, after the liquid taking is completed, the rotating jaw three 3124 caps and tightens the tube cap of the nucleic acid extraction tube 53, the clamping jaw six 3111 loosens the nucleic acid extraction tube 53, and the tube moving manipulator 312 sends the nucleic acid extraction tube 53 back to the test tube magazine 5.

[0246] Figure 15 and Figure 16 Two structural diagrams of the pipetting device 32 are shown in Figure 16 , the X-axis driver six 3231 and the Y-axis driver of the pipetting device 32 are hidden, and the structural diagram of the capping device 33 is shown. Referring to Figure 11 , Figure 12 , Figure 15 and Figure 16As shown, the material consumption bin 322 of the pipetting device 32 is in the form of a drawer, which can be pulled out of the rack 1 in the left-right direction of the rack 1 to replace the consumable. The consumable includes eight multi-tubes 3221 for containing the samples to be tested taken from the nucleic acid extraction tubes 53, eight multi-covers 3222 for covering the eight multi-tubes 3221, and pipetting sleeves 3223 for taking drops from the nucleic acid extraction tubes 53 and dropping into the eight multi-tubes 3221. On the material consumption bin 322, a sleeve recovery device 3224 is also provided, which contains a disinfectant and is used to store the used pipetting sleeves 3223.

[0247] The pipetting manipulator 323 of the pipetting device 32 includes an X-axis driver six 3231, a Y-axis driver six 3232, a Z-axis driver six 3233, a gripper seven 3234, a gripper eight 3236, and a pipettor 3235, wherein:

[0248] The X-axis driver six 3231 is used to drive the movement of the pipetting manipulator 323 in the left-right direction of the rack 1, the Y-axis driver six 3232 is used to drive the movement of the pipetting manipulator 323 in the front-back direction of the rack 1, the Z-axis driver six 3233 is used to drive the movement of the pipetting manipulator 323 in the up-down direction of the rack 1, the gripper seven 3234 is used to move the eight multi-tubes 3221 to the drop table 321, the gripper eight 3236 is used to move the eight multi-covers 3222 to the eight multi-tubes 3221, and the pipettor 3235 is used to operate the pipetting sleeves 3223 to take drops from the nucleic acid extraction tubes 53 on the drop table 321 and drop into the eight multi-tubes 3221 on the drop table 321.

[0249] The capping device includes a capping table 331 and a capping machine 332. The capping table 331 is used to place the eight multi-tubes 3221 with the eight multi-covers 3222, and a linear driver 3311 is arranged at the lower part of the capping table 331 to drive the movement of the eight multi-tubes 3221 with the eight multi-covers 3222 to the lower part of the capping machine 332. The capping machine 332 is used to tightly cap the eight multi-covers 3222 to the eight multi-tubes 3221.

[0250] In specific operation, the gripper seven 3234 of the pipetting manipulator 323 moves the eight multi-tubes 3221 in the material consumption bin 322 to the drop table 321, the pipettor 3235 takes the pipetting sleeves 3223 from the test tube bin 5, takes drops from the nucleic acid extraction tubes 53 on the drop table 321, and drops into the eight multi-tubes 3221 on the drop table 321. After the drop taking is completed, the gripper eight 3236 moves the eight multi-covers 3222 in the test tube bin 5 to the eight multi-tubes 3221 on the drop table 321, the gripper seven 3234 moves the eight multi-tubes 3221 with the eight multi-covers 3222 from the drop table 321 to the capping table 331, the capping table 331 drives the eight multi-tubes 3221 with the eight multi-covers 3222 to the lower part of the capping machine 332 through the linear driver 3311, and the capping machine 332 presses down to tightly cap the eight multi-covers 3222 to the eight multi-tubes 3221.

[0251] The pipette 3235 will also throw the used pipette sleeve 3223 into the sleeve recycling device 3224 after the liquid taking is completed.

[0252] As shown in Figure 1 , Figure 2 The nucleic acid detection device also includes an identification verification device 13 and an isolation door device 14. The identification verification device 13 includes a code scanning device for identifying the barcode information on the enrichment tube 51, and / or an identity authentication device for identifying the identity information of the subject, and / or an image recognition device 2114 for identifying whether the operation of the subject is standardized. In this embodiment, all the above-mentioned identification verification devices 13 are included, and in other embodiments, only one or two of them can be provided.

[0253] The isolation door device 14 is arranged in front of the sample enrichment device 21 and is used to close the sample enrichment device 21 to avoid contamination of the subject sample.

[0254] As shown in Figures 5-8 The nucleic acid detection device also includes a disinfection device 12 for disinfection before and after detection to avoid contamination or leakage of the subject sample. In this embodiment, the disinfection device 12 is mainly a 222 nanometer new type ultraviolet excimer intelligent disinfection lamp, which is not only arranged on the lower layer of the rack 1, but also arranged in multiple places in the upper layer of the rack 1 (not shown in the figure). In other embodiments, the disinfection device 12 can also include high-temperature steam disinfection equipment, disinfectant spraying equipment, etc.

[0255] In the nucleic acid detection device, the X-axis driver one 2111, the X-axis driver two 2121, the X-axis driver three 2214, the X-axis driver four 2221, the X-axis driver five 3121, the X-axis driver six 3231, the Y-axis driver four 2222, the Y-axis driver five 3122, the Y-axis driver six 3232, the Z-axis driver two 2122, the Z-axis driver four 2223, the Z-axis driver five 3123, and the Z-axis driver six 3233 are linear drive mechanisms, and their driving modes are electric, pneumatic or hydraulic driving modes, which will not be described in detail.

[0256] The embodiment also discloses a method for nucleic acid detection according to the above-mentioned nucleic acid detection device, mainly including the following steps:

[0257] The sample enrichment step mainly inverts the mechanical arm 212 to invert the enrichment tube 51 containing the subject sample and the nanoscale magnetic particles, so as to enrich the formed elements in the subject sample with the enrichment cover 511 of the enrichment tube 51;

[0258] The sample lysing link mainly covers the enrichment cover 511 into the lysing tube 52 containing lysing solution through the lysing mechanical hand 222, to obtain the nucleic acid extraction tube 53;

[0259] The tube moving link mainly moves the nucleic acid extraction tube 53 containing the lysed sample in the test tube warehouse 5 to the liquid taking table 311 and opens the cover through the tube moving mechanical hand 312;

[0260] The pipetting link mainly moves the eight-way tube 3221 in the consumable warehouse 322 to the liquid dropping table 321 through the pipetting mechanical hand 323, and drops the liquid taken from the nucleic acid extraction tube 53 into the eight-way tube 3221;

[0261] The cover pressing link mainly tightly presses the eight-way cover 3222 into the eight-way tube 3221 through the cover pressing machine 332;

[0262] The machine detection link mainly sends the eight-way tube 3221 with the eight-way cover 3222 to the PCR instrument 4 for detection through the pipetting mechanical hand 323.

[0263] The sample enrichment link includes the following steps:

[0264] Step one, the enrichment tube 51 containing mouthwash and nanoscale magnetic particles is placed in the placing table 211, whether the enrichment tube 51 is covered with the enrichment cover 511 is identified through the image recognition device 2114 arranged above the placing table 211, if yes, the enrichment cover 511 is tightly screwed through the cooperation of the first jaw 2112 and the first rotating jaw 2113, if not, the operation is interrupted and an alarm is sent;

[0265] Step two, the enrichment tube 51 is inverted in the inverted frame 213 along the gravity direction through the overturning mechanical hand 212, and is statically placed for a preset time, in the embodiment, the preset time is 3 minutes;

[0266] Step three, the nanoscale magnetic particles adsorbing the shaped objects of the sample under test are enriched in the enrichment cover 511 through the magnetic device arranged on the enrichment cover 511 of the enrichment tube 51 and / or the fourth jaw 2224 of the overturning mechanical hand 212.

[0267] The sample lysing link has two implementation modes, which are as follows:

[0268] The first implementation mode includes the following steps:

[0269] Step one, the lysing tube 52 containing lysing solution is taken out from the test tube warehouse 5 through the fifth jaw 2226 of the lysing mechanical hand 222, and is placed in one test tube placement position of the double-position rotating table 221, and the tube cover of the lysing tube 52 is removed;

[0270] Step two, the enrichment tube 51 is taken off from the inverted rack 213 by the gripper four 2224 of the lysis mechanical arm 222, and after being turned over along the direction of gravity, it is placed into another test tube placement position of the double-position rotary table 221, and the gripper four 2224 keeps holding the enrichment cover 511 of the enrichment tube 51, the test tube placement position corresponds to the gripper three 2212 holding the tube body of the enrichment tube 51, and the test tube placement position corresponds to the rotary gripper two 2213 driving the tube body of the enrichment tube 51 to rotate, so as to take off the enrichment cover 511 of the enrichment tube 51;

[0271] Step three, the enrichment cover 511 is covered into the lysis tube 52 by the movement of the lysis mechanical arm 222, so as to obtain the nucleic acid extraction tube 53 and move it to the test tube magazine 5.

[0272] The second embodiment includes the following steps:

[0273] Step one, a lysis tube 52 containing lysis solution is taken out from the test tube magazine 5 by the gripper five 2226 of the lysis mechanical arm 222, and is placed into a test tube placement position of the double-position rotary table 221, and the gripper five 2226 keeps holding the tube cover of the lysis tube 52, the test tube placement position corresponds to the gripper three 2212 holding the tube body of the lysis tube 52, and the test tube placement position corresponds to the rotary gripper two 2213 driving the tube body of the lysis tube 52 to rotate, so as to take off the tube cover of the lysis tube 52;

[0274] Step two, the enrichment tube 51 is taken off from the inverted rack 213 by the gripper four 2224 of the lysis mechanical arm 222, and after being turned over along the direction of gravity, it is placed into another test tube placement position of the double-position rotary table 221, and the gripper four 2224 keeps holding the enrichment cover 511 of the enrichment tube 51, the test tube placement position corresponds to the gripper three 2212 holding the tube body of the enrichment tube 51, and the test tube placement position corresponds to the rotary gripper two 2213 driving the tube body of the enrichment tube 51 to rotate, so as to take off the enrichment cover 511 of the enrichment tube 51;

[0275] Step three, the tube body of the lysis tube 52 is moved to below the enrichment cover 511 by driving the two rotary gripper twos 2213 to move along the left and right directions of the rack 1 by the X-axis driver three 2214, and the tube body of the lysis tube 52 is driven to rotate by the corresponding rotary gripper two 2213, so as to cover the enrichment cover 511 into the lysis tube 52, thereby obtaining the nucleic acid extraction tube 53.

[0276] Compared with the first embodiment, the enrichment cover 511 is kept stationary and the tube body of the lysis tube 52 is moved to obtain the nucleic acid extraction tube 53, and the most important advantage is that, since the enrichment cover 511 is kept stationary, the possible falling, contamination and other interference factors of the test sample are avoided as much as possible, so as to ensure the authenticity of the nucleic acid detection result.

[0277] After the above two embodiments, the sample lysis link further includes the following steps:

[0278] Step four, the gripper four 2224 of the lysis robot 222 takes out the nucleic acid extraction tube 53 from the double-position rotary table 221, and overturns the nucleic acid extraction tube 53 for a predetermined number of times by the rotary driver two 2225, so that the sample on the enrichment cover 511 is fully lysed, and in the embodiment, the predetermined number of times is 5 times;

[0279] Step five, the lysis robot 222 places the nucleic acid extraction tube 53 upright into the test tube magazine 5.

[0280] The sample lysis process also includes a waste collection process, which includes one of the following actions:

[0281] Action one, through the gripper five 2226 of the lysis robot 222, the tube cover of the lysis tube 52 taken out is covered on the enrichment tube 51 from which the enrichment cover 511 has been taken off, to obtain a waste tube, and then through the movement of the lysis robot 222, the waste tube is put into the waste collection device 11 containing a disinfectant;

[0282] Action two, through the X-axis driver three 2214, the two rotary claws two 2213 are driven to move along the left and right directions of the rack 1, so that the tube body of the enrichment tube 51 moves to below the tube cover of the lysis tube 52, the tube body of the enrichment tube 51 corresponding to the rotary claw two 2213 is driven to rotate, so that the tube cover of the lysis tube 52 is covered on the enrichment tube 51 to obtain a waste tube, and then through the movement of the lysis robot 222, the waste tube is put into the waste collection device 11 containing a disinfectant.

[0283] The tube moving process includes the following steps:

[0284] Step one, the tube moving robot 312 moves the nucleic acid extraction tube 53 containing a lysed sample in the test tube magazine 5 to the liquid taking table 311;

[0285] Step two, the gripper six 3111 of the liquid taking table 311 clamps the nucleic acid extraction tube 53;

[0286] Step three, the rotary claw three 3124 of the tube moving robot 312 unscrews the enrichment cover 511 of the nucleic acid extraction tube 53;

[0287] Step four, after the liquid taking is completed, the rotary claw three 3124 of the tube moving robot 312 covers the tube cover of the nucleic acid extraction tube 53 back;

[0288] Step five, the gripper six 3111 of the liquid taking table 311 clamps the nucleic acid extraction tube 53, and the rotary claw three 3124 drives the enrichment cover 511 to rotate to tighten the enrichment cover 511;

[0289] Step six, the gripper six 3111 of the liquid taking table 311 releases the nucleic acid extraction tube 53, and the tube moving robot 312 sends the nucleic acid extraction tube 53 back to the test tube magazine 5.

[0290] The pipetting process includes the following steps:

[0291] Step one, the pipetting robot 323's gripper eight 3234 moves the eight-tube 3221 in the consumable warehouse 322 to the droplet table 321;

[0292] Step two, the pipetting robot 323's pipette 3235 loads the pipette 3223 from the test tube warehouse 5;

[0293] Step three, the pipette 3235 of the pipetting robot 312 operates the pipette 3223 to take liquid from the nucleic acid extraction tube 53 on the liquid taking table 311 and drop it into the eight-tube 3221 on the droplet table 321;

[0294] Step four, the pipette 3235 of the pipetting robot 312 throws the used pipette 3223 into the pipette recycling device 3224.

[0295] The capping process includes the following steps:

[0296] Step one, the pipetting robot 323's gripper eight 3236 moves the eight-tube cap 3222 in the test tube warehouse 5 to the eight-tube 3221 on the droplet table 321;

[0297] Step two, the pipetting robot 323's gripper six 3111 moves the eight-tube 3221 capped with the eight-tube cap 3222 from the droplet table 321 to the capping table 331;

[0298] Step three, the capping table 331 sends the eight-tube 3221 capped with the eight-tube cap 3222 to the capping machine 332 below through the linear actuator 3311;

[0299] Step four, the capping machine 332 presses down to tightly cap the eight-tube cap 3222 into the eight-tube 3221.

[0300] The nucleic acid detection method described in this embodiment also includes a recognition verification process, which includes the following steps:

[0301] Step one, through the identity authentication device, identify the identity information of the examinee, after authentication, open the isolation door, and prompt the examinee to put the enrichment tube 51 into the object table 211;

[0302] Step two, through the code scanning device, identify the barcode information of the enrichment tube 51 placed on the object table 211, after successful identification, close the isolation door and issue a prompt.

[0303] The nucleic acid detection method described in the embodiment further includes a disinfection link, that is, before and after the sample pretreatment, the sample pretreatment device 2 is disinfected by at least one of ultraviolet, high-temperature steam and disinfectant.

[0304] The nucleic acid detection device and method described in the application have the following advantages compared with the prior art:

[0305] (1) Full-automatic mechanical operation, saving medical resources and reducing the demand for professionals. The nucleic acid detection device described in the application has a series of functions such as identity verification, sample information collection, sample enrichment, sample lysis, sample transfer, sample pipetting and cap pressing, and is operated fully automatically and mechanically, which can greatly reduce the demand for related professionals, save medical resources and reduce epidemic prevention costs.

[0306] (2) Operation in a closed space, complete disinfection measures and avoidance of cross infection. The nucleic acid detection device described in the application is completed in a relatively closed space in the rack, and has a series of disinfection and sterilization measures such as high-temperature sterilization and ultraviolet lamp sterilization in line with national standards, which can effectively prevent cross contamination, greatly improve the efficiency of epidemic prevention and control, and reduce the risk of population infection.

[0307] (3) Compact structure, multi-node, multi-level and rapid deployment. The nucleic acid detection device described in the application has a compact structure, small footprint, light weight and flexible arrangement, and can form a full-automatic unmanned nucleic acid sampling and detection system. The system has high modularity, and can be easily deployed for the current complex, multi-level, distributed and sudden epidemic prevention and control needs, and can be quickly promoted to urban communities, schools, parks, hotels, construction sites, transportation entrances, large supermarkets, urban-rural junctions and rural areas, to build a strong fortress for grassroots epidemic prevention and control.

[0308] The above is only a specific embodiment of the application, but the protection scope of the application is not limited thereto. Any changes or replacements within the technical scope disclosed in the application can be easily thought of by those skilled in the art, and should be covered within the protection scope of the application. Therefore, the protection scope of the application should be subject to the protection scope of the claims.

Claims

1. A nucleic acid detection device, characterized by, The device comprises a rack, a sample pretreatment device enclosed in the lower layer of the rack, a sample preparation device enclosed in the upper layer of the rack, and a PCR instrument, wherein: The sample pretreatment device comprises: a sample enrichment device for processing a sample containing a target sample and a nanoscale magnetic particle enrichment tube to enrich the target sample; a sample lysis device for placing the enriched target sample into a lysis tube containing a lysis solution to obtain a nucleic acid extraction tube, and sending the nucleic acid extraction tube to a test tube magazine; The sample preparation device comprises: a test tube moving device for moving the nucleic acid extraction tube containing the lysed sample in the test tube magazine to a liquid taking table and opening the cap; a pipetting device for pipetting the target sample in the nucleic acid extraction tube to an eight-way tube to obtain a target sample and send it to the PCR instrument; The device further comprises a lifting device enclosed in the rear part of the rack for transferring the test tube magazine between the sample pretreatment device and the sample preparation device, the test tube magazine being used to provide a lysis tube containing a lysis solution and a nucleic acid extraction tube containing a target sample; The device further comprises a waste collection device enclosed below the sample pretreatment device, the waste collection device containing a disinfectant for storing the cap of the lysis tube and the body of the enrichment tube; The device further comprises a disinfection device for disinfection before and after detection to avoid contamination or leakage of the target sample; The device further comprises an identification verification device, which comprises a code scanning device for identifying the barcode information on the enrichment tube, and / or an identity authentication device for identifying the identity information of the target person, and / or an image recognition device for identifying whether the operation of the target person is standardized; The sample enrichment device comprises: a placement table for placing the enrichment tube; an overturning manipulator for overturning the enrichment tube on the placement table on an overturning rack; The sample lysis device comprises: a double-position rotating table provided with two test tube placement positions for placing the enrichment tube and the lysis tube containing the lysis solution, respectively; a lysis manipulator for placing the enrichment cap of the enrichment tube on the lysis tube containing the lysis solution on the double-position rotating table to obtain a nucleic acid extraction tube and move it to the test tube magazine; The double-position rotating table is a rack structure, and two test tube placement positions are respectively arranged on the double-position rotating table, and a rotating claw two for clamping and rotating a test tube is arranged below each test tube placement position; The double-position rotating table comprises: a test tube rack provided with two test tube placement positions for placing the enrichment tube and the lysis tube, respectively; two clamping claws three for clamping the enrichment tube and the lysis tube, respectively; two rotating claws two for rotating the body of the enrichment tube and the lysis tube, respectively; an X-axis driver three for driving the two rotating claws two to move along the left-right direction of the rack; The lysis manipulator comprises: an X-axis driver four for driving the lysis manipulator to move along the left-right direction of the rack; a Y-axis driver four for driving the lysis manipulator to move along the front-rear direction of the rack; a Z-axis driver four for driving the lysis manipulator to move along the up-down direction of the rack; ​ a fourth gripper for clamping the enrichment tube; a second rotary driver for driving the fourth gripper to flip over along the direction of gravity, a fifth gripper for clamping the lysis tube; The pipetting device comprises a droplet table, a consumable material bin and a pipetting manipulator arranged thereon, the pipetting manipulator is used to move the eight-way tube in the consumable material bin to the droplet table, and to take liquid from the nucleic acid extraction tube and drop it into the eight-way tube to obtain the sample to be tested. The pipetting manipulator comprises: a sixth X-axis driver for driving the pipetting manipulator to move along the left-right direction of the rack; a sixth Y-axis driver for driving the pipetting manipulator to move along the front-back direction of the rack; a sixth Z-axis driver for driving the pipetting manipulator to move along the up-down direction of the rack; a seventh gripper for moving the eight-way tube to the droplet table; a pipettor for operating the pipetting cannula to take liquid from the nucleic acid extraction tube on the liquid taking table and drop it into the eight-way tube on the droplet table.

2. The nucleic acid detection device of claim 1, wherein The rack structure is provided with a first X-axis driver for driving the rack structure to move along the left-right direction of the rack.

3. The nucleic acid detection device of claim 2, wherein The rack structure further comprises a first gripper for clamping the enrichment tube and a first rotary gripper for tightening the enrichment cap of the enrichment tube.

4. The nucleic acid detection device of claim 1, wherein The upper part of the rack structure is further provided with an image recognition device for detecting whether the enrichment cap is installed on the enrichment tube.

5. The nucleic acid detection device of claim 1, wherein The flipping manipulator comprises: a second X-axis driver for driving the flipping manipulator to move along the left-right direction of the rack; a second Z-axis driver for driving the flipping manipulator to move along the up-down direction of the rack; a second gripper for clamping the enrichment tube; a first rotary driver for driving the second gripper to flip over along the direction of gravity.

6. The nucleic acid detection device of claim 1, wherein, The fourth gripper is provided with a magnetic device.

7. The nucleic acid detection device of claim 1, wherein, The tube moving device comprises a liquid taking table and a tube moving manipulator arranged above the liquid taking table, the tube moving manipulator is used to move the nucleic acid extraction tube containing the lysis sample in the tube bin to the liquid taking table and open the cap.

8. The nucleic acid detection device of claim 7, wherein, The rack structure is provided with a sixth gripper for clamping the nucleic acid extraction tube.

9. The nucleic acid detection device of claim 7, wherein, The tube moving manipulator comprises: a fifth X-axis driver for driving the tube moving manipulator to move along the left-right direction of the rack; a fifth Y-axis driver for driving the tube moving manipulator to move along the front-back direction of the rack; a fifth Z-axis driver for driving the tube moving manipulator to move along the up-down direction of the rack; a third rotary gripper for clamping the nucleic acid extraction tube and rotating to open the cap.

10. The nucleic acid detection device of claim 1, wherein, The consumable material bin comprises at least one of the following consumables: an eight-way tube for containing the sample to be tested taken from the nucleic acid extraction tube; an eight-way cap for sealing the eight-way tube; a pipetting cannula for taking liquid from the nucleic acid extraction tube and dropping it into the eight-way tube.

11. The nucleic acid detection device of claim 1, wherein, The pipetting manipulator is further provided with an eighth gripper for moving the eight-way cap to the eight-way tube.

12. The nucleic acid detection device of claim 1, wherein, Further comprising a cap pressing device, which comprises: a cap pressing table for placing the eight-way tube with the eight-way cap, a linear driver is arranged at the lower part of the cap pressing table to drive the cap pressing table to move below the cap pressing machine; a cap pressing machine for pressing the eight-way cap tightly into the eight-way tube.

13. The nucleic acid detection device of claim 1, wherein, Further comprising a cannula recycling device, the cannula recycling device is filled with disinfectant and is used to store used pipetting cannulas.

14. The nucleic acid detection device of claim 10, wherein, The consumable material bin is in the form of a drawer, which can be pulled out of the rack along the left-right direction of the rack to replace the consumables.

15. The nucleic acid detection device of claim 1, wherein, It also includes an isolation door device arranged in front of the sample enrichment device for closing the sample enrichment device to avoid the test sample being contaminated.

16. A nucleic acid detection method for a purpose other than disease diagnosis, based on the nucleic acid detection device according to any one of claims 1 to 15, characterized by, It mainly includes the following steps: The sample enrichment step, through the overturning manipulator, the enrichment tube containing the test sample and nanoscale magnetic particles is inverted to enrich the test sample with the enrichment cover of the enrichment tube; The sample lysis step, through the lysis manipulator, the enrichment cover is covered into the lysis tube containing the lysis solution to obtain the nucleic acid extraction tube; The tube moving step, through the tube moving manipulator, the nucleic acid extraction tube containing the lysed sample in the tube warehouse is moved to the liquid taking table and the cover is opened; The pipetting step, through the pipetting manipulator, the eight-way tube in the consumable warehouse is moved to the droplet table, and the liquid in the nucleic acid extraction tube is taken and dropped into the eight-way tube; The cap pressing step, through the cap pressing machine, the eight-way cap is tightly pressed into the eight-way tube; The machine detection step, through the pipetting manipulator, the eight-way tube with the eight-way cap is sent into the PCR instrument for detection; The sample enrichment step includes the following steps: Step one, place the enrichment tube containing the mouthwash and nanoscale magnetic particles into the placement table; Step two, overturn the enrichment tube along the gravity direction through the overturning manipulator, invert it on the inverted frame, and stand still for a preset time; Step three, set a magnetic device on the enrichment cover of the enrichment tube and / or the clamping jaw four of the overturning manipulator, so that the nanoscale magnetic particles adsorbing the test sample have shape are enriched in the enrichment cover; It also includes an identification and verification step, which includes the following steps: Step one, through the identity authentication device, identify the identity information of the test person, and after authentication, open the isolation door and prompt the test person to place the enrichment tube into the placement table; Step two, through the code scanning device, identify the barcode information of the enrichment tube placed on the placement table, and after successful identification, close the isolation door and issue a prompt; The step one of the sample enrichment step also includes the following actions: Through the image recognition device arranged above the placement table, identify whether the enrichment tube is covered with an enrichment cover.

17. The method of claim 16, wherein the nucleic acid is DNA. The sample lysis step includes the following steps: Step one, through the clamping jaw five of the lysis manipulator, take out a lysis tube containing a lysis solution from the tube warehouse and place it into a test tube placement position of the double-position rotating table, and remove the tube cover of the lysis tube; Step two, through the clamping jaw four of the lysis manipulator, take down the enrichment tube from the inverted frame, after overturning along the gravity direction, place it into another test tube placement position of the double-position rotating table, and remove the enrichment cover of the enrichment tube; Step three, through the movement of the lysis manipulator, cover the enrichment cover into the lysis tube to obtain the nucleic acid extraction tube and move it to the tube warehouse.

18. The method of claim 16, wherein the nucleic acid is DNA. 17 The sample lysis step includes the following steps: Step one, through the clamping jaw five of the lysis manipulator, take out a lysis tube containing a lysis solution from the tube warehouse and place it into a test tube placement position of the double-position rotating table, and the clamping jaw five keeps clamping the tube cover of the lysis tube, the test tube placement position corresponds to the clamping jaw three clamping the tube body of the lysis tube, and the test tube placement position corresponds to the rotating jaw two driving the tube body of the lysis tube to rotate to remove the tube cover of the lysis tube; Step two, the fourth gripper of the lysis robot removes the enrichment tube from the inverted rack, flips it over in the direction of gravity, and places it in the other test tube placement position of the double-position rotary table, with the fourth gripper still holding the enrichment cap of the enrichment tube, and the third gripper of the corresponding test tube placement position holding the body of the enrichment tube, and the second rotary gripper of the corresponding test tube placement position driving the body of the enrichment tube to rotate, so as to remove the enrichment cap of the enrichment tube; Step three, the two second rotary grippers are driven by the third X-axis driver to move along the left-right direction of the rack, so that the body of the lysis tube moves below the enrichment cap, and the corresponding second rotary gripper of the lysis tube drives the body to rotate, so that the enrichment cap is covered on the lysis tube, and the nucleic acid extraction tube is obtained.

19. The nucleic acid detection method according to claim 17 or 18, wherein, The sample lysis link further includes the following steps: Step four, the fourth gripper of the lysis robot removes the nucleic acid extraction tube from the double-position rotary table, and flips the nucleic acid extraction tube a predetermined number of times by the second rotary driver, so that the sample under test on the enrichment cap is fully lysed; Step five, the lysis robot places the nucleic acid extraction tube in the test tube magazine.

20. The method of claim 19, wherein the nucleic acid is DNA. It also includes a waste collection link, which includes one of the following actions: Action one, the fifth gripper of the lysis robot covers the removed lysis tube cap on the enrichment tube that has been removed from the enrichment cap to obtain a waste tube, and then moves the waste tube into the waste collection device filled with disinfectant by the lysis robot; Action two, the two second rotary grippers are driven by the third X-axis driver to move along the left-right direction of the rack, so that the body of the enrichment tube moves below the lysis tube cap, and the corresponding second rotary gripper of the enrichment tube drives the body to rotate, so that the lysis tube cap is covered on the enrichment tube to obtain a waste tube, and then the waste tube is moved into the waste collection device filled with disinfectant by the lysis robot.

21. The method of claim 20, wherein the nucleic acid is DNA. 20 The tube moving link includes the following steps: Step one, the tube moving robot moves the nucleic acid extraction tube containing the lysed sample in the test tube magazine to the liquid taking table; Step two, the sixth gripper of the liquid taking table clamps the nucleic acid extraction tube; Step three, the third rotary gripper of the tube moving robot unscrews the enrichment cap of the nucleic acid extraction tube.

22. The nucleic acid detection method according to claim 21, wherein, The tube moving link further includes the following steps: Step four, after the liquid taking is completed, the third rotary gripper of the tube moving robot screws back the cap of the nucleic acid extraction tube; Step five, the sixth gripper of the liquid taking table clamps the nucleic acid extraction tube, and the third rotary gripper drives the enrichment cap to rotate to tighten the enrichment cap; Step six, the sixth gripper of the liquid taking table releases the nucleic acid extraction tube, and the tube moving robot sends the nucleic acid extraction tube back to the test tube magazine.

23. The method of claim 16, wherein the nucleic acid is DNA. The pipetting link includes the following steps: Step one, the seventh gripper of the pipetting robot moves the eight-way tube in the consumable magazine to the droplet table; Step two, the pipettor of the pipetting robot loads the pipetting sleeve from the test tube magazine; Step three, the pipettor of the tube moving robot operates the pipetting sleeve to take liquid from the nucleic acid extraction tube on the liquid taking table and drop it into the eight-way tube on the droplet table.

24. The nucleic acid detection method according to claim 23, wherein, The pipetting link further includes the following steps: Step four, the pipette of the pipette manipulator, puts the used pipette tip into the tip recycling device.

25. The method of claim 16, wherein the nucleic acid is DNA.

26. The method of claim 16, wherein the nucleic acid is RNA. The capping process comprises the following steps: Step one, the gripper eight of the pipette manipulator moves the eight-capped cap in the test tube magazine to the eight-tube on the droplet table; Step two, the gripper six of the pipette manipulator moves the eight-tube capped with the eight-capped cap from the droplet table to the capping table; Step three, the capping table sends the eight-tube capped with the eight-capped cap to the lower part of the capping machine through the linear driver; Step four, the capping machine presses the eight-capped cap tightly into the eight-tube.

26. The method of claim 16, wherein the nucleic acid is a DNA. It also includes a disinfection process, which disinfects the sample pretreatment device by at least one of ultraviolet light, high-temperature steam, and disinfectant before and after sample pretreatment.

Images