An integrated fully automatic nucleic acid detection device

By designing an integrated fully automatic nucleic acid detection device, multiple institutions working together realize the automation of sample preprocessing, nucleic acid extraction and PCR amplification detection, solving the problems of slow detection speed and complex operation of the existing PCR detection system, and realizing the The demand for on-site instant high-throughput testing and large-scale epidemic screening.

CN113265328BActive Publication Date: 2025-02-18SUZHOU HELMEN PRECISION INSTR
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Patent Information

Application Number
CN202110746177.6
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2021-07-01
Publication Date
2025-02-18
Estimated Expiration
2041-07-01

AI Technical Summary

Technical Problem

The existing PCR detection system needs to be carried out in designated laboratories. The detection speed is slow and the operation is complicated, making it difficult to achieve instant high-throughput detection on site, which affects the detection efficiency and may lead to diagnosis lag.

Method used

An integrated fully automatic nucleic acid detection device is designed, including feeding mechanism, nucleic acid extraction mechanism, construction system mechanism, amplification detection mechanism, pipetting mechanism and cap transfer mechanism. Through the coordinated work of these mechanisms, the sample pre-pre-examination mechanism is achieved. Automation of treatment, nucleic acid extraction, reaction reagent construction and PCR amplification detection.

Benefits of technology

It realizes instant high-throughput detection on site, has high detection sensitivity, can meet the needs of large-scale epidemic screening, reduces the requirements for personnel and space, and basically realizes the automation of PCR experimental detection.

✦ Generated by Eureka AI based on patent content.

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Abstract

The present invention relates to an integrated fully automatic nucleic acid detection device, a workbench peripheral cover, a feeding mechanism for placing samples to be detected, a nucleic acid extraction mechanism for pretreatment and extraction of nucleic acids, a construction system mechanism for constructing reaction reagents and control samples, a liquid transfer mechanism for liquid transfer, an amplification detection mechanism for processing reaction reagents and control samples and detecting based on the processing results, a capping and capping transfer mechanism for opening and closing the cap and transferring the construction system mechanism to the amplification detection mechanism; a controller for controlling all mechanisms. The present invention integrates reagent preparation, specimen preparation and PCR amplification into one, and only simple operations are required to achieve on-site instant high-throughput detection, with high sensitivity, which can meet the needs of large-scale epidemic screening, high integration, small space occupation, low requirements for personnel, and only the work of placement and batch removal needs to be performed, and PCR experimental detection is basically automated.
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Description

Technical Field

[0001] The present invention relates to the technical field of enzymology or microbiology devices, and in particular to an integrated fully automatic nucleic acid detection device. Background Art

[0002] Polymerase chain reaction, also known as PCR, uses a segment of DNA as a template, and with the participation of DNA polymerase and nucleotide substrate, the segment of DNA is amplified to a sufficient amount for structural and functional analysis. The PCR detection method is extremely important in the rapid diagnosis of bacterial infectious diseases in the clinic.

[0003] The standard PCR detection system on the market must be tested in a designated laboratory or requires a complete PCR laboratory, usually a P2 laboratory. The detection speed is slow and the detection is not on-site. The reasons include high requirements for PCR laboratory site, high requirements for operators, and complex operating procedures. From sample reception and registration, laboratory environment preparation, personal protective equipment to laboratory testing and harmless treatment of waste, it takes about 5-7 hours. If the time for sampling, sample transportation, and queuing is also calculated, the time required will be longer, which greatly affects the detection efficiency and may also cause delays in diagnosis, which in turn brings greater difficulties to tracking patient dynamics. On-site real-time high-throughput detection is difficult to achieve.

[0004] The following alternatives are currently used:

[0005] (1) Test strip testing: Although it can achieve on-site instant high-throughput testing, the sensitivity of antigen detection is low, and antibody detection is not even suitable for early detection of the disease or for judging the status after recovery (antibodies will last for a long time);

[0006] (2) Although the on-site instant nucleic acid testing platform has a high accuracy rate, it relies on large and expensive equipment (fluorescence PCR instrument) and has a low throughput. Generally, only 1-4 samples can be tested per batch, which is far from meeting the needs of large-scale epidemic screening.

[0007] (3) The fully automatic fluorescent quantitative PCR detection system has a complicated operation process, requires many human operation steps, occupies a large space, and is not fully automated during the entire PCR experimental detection process. Summary of the invention

[0008] The present invention solves the problems existing in the prior art and provides an integrated fully automatic nucleic acid detection device with an optimized structure.

[0009] The technical solution adopted by the present invention is an integrated fully automatic nucleic acid detection device, comprising a workbench and an outer cover arranged outside the workbench; the outer cover is provided with:

[0010] A feeding mechanism, used for placing the sample to be tested;

[0011] A nucleic acid extraction mechanism, arranged in conjunction with the feeding mechanism, for pre-treating the sample to be tested and extracting nucleic acid;

[0012] A construction system mechanism for integrating the reaction reagents and control samples obtained by extracting nucleic acid;

[0013] A liquid transfer mechanism, used to cooperate in liquid transfer operations between the feeding mechanism and the nucleic acid extraction mechanism, and between the nucleic acid extraction mechanism and the construction system mechanism;

[0014] an amplification detection mechanism, used to process the reaction reagents and control samples in the construction system mechanism and perform detection based on the processing results;

[0015] A capping transfer mechanism, used for opening and closing the caps of the sample to be tested at the feeding mechanism and the reaction reagent or the container where the reaction reagent and the control sample are located at the construction system mechanism, and transferring the container where the reaction reagent and the control sample are located in the construction system mechanism to the amplification detection mechanism;

[0016] The feeding mechanism, nucleic acid extraction mechanism, system construction mechanism, amplification detection mechanism, liquid transfer mechanism and capping transfer mechanism are arranged in coordination with a controller.

[0017] Preferably, the feeding mechanism comprises a plurality of feeding sockets, a feeding carrier is provided in cooperation with any of the feeding sockets, one or more insertion holes are provided in cooperation with any of the feeding carriers, a sampling tube with a sample to be tested built therein can be loaded and unloaded in cooperation with any of the insertion holes, a first sealing cover is provided in cooperation with each sampling tube, and the first sealing cover is provided in cooperation with the screw cap transfer mechanism;

[0018] A scanning mechanism is arranged on the workbench matched with the feeding carrier plate, and the scanning mechanism is arranged in cooperation with the controller.

[0019] Preferably, the nucleic acid extraction mechanism includes a first X-axis transmission unit arranged on the workbench, one or more first guide blocks are provided in conjunction with the first X-axis transmission unit, one end of the first X-axis transmission unit is arranged toward the feeding mechanism, a substitute head seat cooperating with the pipetting mechanism and one or more extraction well plates with built-in nucleic acid extraction reagents are provided along the transmission direction of the first X-axis transmission unit, and a plurality of substitute heads are provided in the substitute head seat; a first vertical motion unit is connected in conjunction with any of the first guide blocks, a magnetic rod group cooperating with the extraction well plate is provided in conjunction with any of the first vertical motion units, and a magnetic source and a control motor are provided in conjunction with the magnetic rod group; the first X-axis transmission unit, the first vertical motion unit, the magnetic source and the control motor are provided in conjunction with the controller.

[0020] Preferably, there is at least one extraction well plate, the extraction well plate includes multiple rows parallel to the transmission direction of the first X-axis transmission unit, the magnetic rod group is one or more columns of magnetic rods, and the number of magnetic rods in each column is consistent with the number of rows of the extraction well plate; a waste frame is provided on the workbench that cooperates with the extraction well plate.

[0021] Preferably, the construction system mechanism includes at least one construction carrier and at least one sealing cover tray loaded with a second sealing cover, the construction carrier is provided with a control sample placed in a container and an empty container for placing a reaction reagent, the second sealing cover is arranged in cooperation with a screw-cap transfer mechanism, the empty container is arranged in cooperation with a pipetting mechanism, and the container or construction carrier for placing the control sample and the reaction reagent is arranged in cooperation with the screw-cap transfer mechanism.

[0022] Preferably, the amplification detection mechanism includes a track groove, and a plurality of air ducts are sequentially arranged in conjunction with the track groove, and the two ends of any air duct are respectively penetrated through the outer side of the track groove, and a heating unit and a fan are arranged in conjunction with any air duct; a trolley is arranged in conjunction with the track groove, and a detection carrier is mounted on the front and rear ends of the top of any trolley through pillars, and the trolley, the pillars and the detection carrier constitute a sub-air duct, and the two sides of the sub-air duct respectively correspond to the two ends of the air duct, and a second X-axis transmission unit is arranged in conjunction with the trolley, and the detection carrier is arranged in conjunction with the rotary cover transfer mechanism; the heating unit, the fan and the second X-axis transmission unit are arranged in conjunction with the controller.

[0023] Preferably, adjustable plug-in blocks are provided in the track groove to match the openings at both ends of any air duct.

[0024] Preferably, the pipetting mechanism comprises a pipetting gun, a second vertical motion unit is provided in cooperation with the pipetting gun, a first Y-axis transmission unit is provided in the horizontal direction in cooperation with the second vertical motion unit, and the first Y-axis transmission unit is provided in cooperation with the third X-axis transmission unit;

[0025] The third X-axis transmission unit and the first Y-axis transmission unit are horizontally arranged above the workbench through a bracket; the pipette gun, the second vertical motion unit, the third X-axis transmission unit and the first Y-axis transmission unit are arranged in cooperation with a controller.

[0026] Preferably, the capping transfer mechanism includes a third vertical motion unit, a rotating motor is provided at the bottom of the third vertical motion unit, a mechanical claw is provided at the bottom of the rotating motor, and a clamping mechanism is provided to cooperate with the mechanical claw; a second Y-axis transmission unit in the horizontal direction is provided at the upper part of the third vertical motion unit, and the second Y-axis transmission unit is arranged in conjunction with the third X-axis transmission unit; the second Y-axis transmission unit is horizontally arranged above the workbench through a bracket; the third vertical motion unit, the rotating motor, the mechanical claw, the clamping mechanism and the second Y-axis transmission unit are arranged in conjunction with a controller.

[0027] Preferably, a purple light lamp cooperating with the controller is provided in the outer cover.

[0028] The invention relates to an integrated fully automatic nucleic acid detection device with an optimized structure. An outer cover is arranged on the outer cover of a workbench. A feed mechanism is used to place a sample to be detected. A nucleic acid extraction mechanism cooperating with the feed mechanism pre-treats the sample to be detected and extracts nucleic acid. A system construction mechanism is used to integrate reaction reagents and control samples obtained by extracting nucleic acid. A liquid transfer mechanism is used to perform liquid transfer operations between the feed mechanism and the nucleic acid extraction mechanism and between the nucleic acid extraction mechanism and the system construction mechanism. An amplification detection mechanism is used to process the reaction reagents and control samples in the system construction mechanism and perform detection based on the processing results. A capping transfer mechanism is used to open and close the caps of the sample to be detected at the feed mechanism and the container where the reaction reagent is located at the system construction mechanism, and the system constructed in the system construction mechanism is transferred to the amplification detection mechanism. A controller is used to control the feed mechanism, the nucleic acid extraction mechanism, the system construction mechanism, the amplification detection mechanism, the liquid transfer mechanism and the capping transfer mechanism.

[0029] The present invention integrates reagent preparation, specimen preparation and PCR amplification into one. Only simple operations are needed to realize on-site instant high-throughput detection. It has high sensitivity and can meet the needs of large-scale epidemic screening. It has high integration and small space occupation and has low requirements for personnel. Only the insertion and batch clearing tasks need to be performed. PCR experimental detection is basically automated. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 It is a schematic diagram of the three-dimensional structure of the present invention from left to right;

[0031] Figure 2 It is a schematic diagram of the three-dimensional structure of the present invention from right to left;

[0032] Figure 3 It is a schematic diagram of the top view structure of the present invention;

[0033] Figure 4 It is a rear view structural schematic diagram of the present invention;

[0034] Figure 5 It is a left view structural schematic diagram of the present invention;

[0035] Figure 6 for Figure 5 AA section view structural diagram;

[0036] Figure 7 It is a schematic structural diagram of the first X-axis transmission unit and the liquid transfer mechanism in the present invention;

[0037] Figure 8 It is a structural schematic diagram of the capping transfer mechanism in the present invention;

[0038] Fig. 9 It is a schematic diagram of the stereoscopic structure of the amplification detection mechanism in the present invention;

[0039] Fig.10 It is a schematic diagram of the front view structure of the amplification detection mechanism in the present invention;

[0040] Fig.11 for Fig.10 BB section view structural schematic diagram;

[0041] Fig.12 It is a left view structural schematic diagram of the amplification detection mechanism in the present invention;

[0042] Fig.13 for Fig.12 Schematic diagram of the CC section view structure. DETAILED DESCRIPTION

[0043] The present invention is further described in detail below in conjunction with embodiments, but the protection scope of the present invention is not limited thereto.

[0044] The present invention relates to an integrated fully automatic nucleic acid detection device, comprising a workbench 1 and an outer cover (not shown in the figure) arranged outside the workbench;

[0045] A purple light 41 is arranged in the outer cover to match the controller.

[0046] In the present invention, the workbench 1 is generally arranged horizontally and includes an X-axis direction and a Y-axis direction, and the outer cover is used to ensure that the gas in a certain range above the workbench 1 does not overflow unnecessarily.

[0047] In the present invention, generally speaking, the gas is sucked out and filtered through the filter membrane and then discharged into the atmosphere; and in order to ensure that the gas does not move outward in the non-discharge stage, a pressure regulating mechanism can also be set in conjunction with the outer cover. The pressure regulating mechanism works during the entire process of nucleic acid detection to ensure that the outer cover is in a slightly negative pressure state. After the detection is completed, the pressure regulating mechanism works to adjust the outer cover to a non-negative pressure or slightly positive pressure state, so that the gas can quickly pass through the filter membrane for subsequent processing; wherein, the pressure regulating mechanism is content that is easy for technical personnel in this field to understand, and the gas source can be adjusted by the controller to complete the adjustment of the air pressure in the outer cover.

[0048] In the present invention, a UV lamp 41 is provided in conjunction with the outer cover, which may be one or more. After the detection is completed, it is turned on to process the environment inside the outer cover. The UV lamp 41 can be turned on manually, but is generally provided in conjunction with a controller to control the turning on.

[0049] In the present invention, some baffles 2 should be arranged on the workbench 1 in the outer cover based on actual needs to prevent pollution without affecting the work of each mechanism.

[0050] The outer cover is equipped with:

[0051] A feeding mechanism, used for placing the sample to be tested;

[0052] The feeding mechanism comprises a plurality of feeding sockets (arranged on the outer cover, not shown in the figure), a feeding carrier plate 3 is provided in cooperation with any of the feeding sockets, one or more insertion holes 4 are provided in cooperation with any of the feeding carrier plates 3, a sampling tube 5 with a sample to be tested built therein can be loaded and unloaded in cooperation with any of the insertion holes 4, a first sealing cover 6 is provided in cooperation with each sampling tube 5, and the first sealing cover 6 is provided in cooperation with the screw cap transfer mechanism;

[0053] A scanning mechanism 7 is provided on the workbench 1 that cooperates with the material feeding carrier plate 3 , and the scanning mechanism 7 is arranged in cooperation with a controller.

[0054] In the present invention, the feed socket is arranged on one side of the outer cover, generally on the front side of the workbench 1 , and a slot can be arranged on the workbench 1 that matches the feed socket to facilitate the placement of the feed carrier 3 .

[0055] In the present invention, the feed carrier plate 3 is generally a vertically placed plate structure, whose width is slightly larger than the outer diameter of the sampling tube 5, and the upper surface is located in the upper and middle part of the tube body of the sampling tube 5 and under the first sealing cover 6. Each feed carrier plate 3 is provided with a plug hole 4 on the top, generally multiple plug holes 4, and the sampling tube 5 containing the sample to be tested is placed in the plug hole 4 outside the device and sent into the device together with the feed carrier plate 3; the first sealing cover 6 of the sampling tube 5 is screwed up by the screw cap transfer mechanism before nucleic acid extraction and pipetted by the pipetting mechanism. After the pipetting is completed, the screw cap transfer mechanism re-tightens the first sealing cover 6.

[0056] In the present invention, in order to ensure normal operation, generally speaking, the sampling tube 5 adopts a polygonal bottom style, and the bottom of the jack 4 has a matching polygonal groove, so that the sampling tube 5 will not slip or rotate when the capping transfer mechanism is capping, ensuring the consistency of the results of each action.

[0057] In the present invention, a scanning mechanism 7 can be set on the workbench 1 on one side of the feed carrier plate 3. Obviously, the scanning mechanism 7 is facing the direction of the feed carrier plate 3. During the process of pushing the feed carrier plate 3, the scanning mechanism 7 can scan the barcodes attached to the tube wall of the sampling tube 5 on the feed carrier plate 3 one by one, which can not only confirm the position of the reagent to be detected corresponding to each barcode, facilitate subsequent tracking, but also serve as an error correction step before detection; the barcode includes but is not limited to a QR code, a barcode, etc. In order to match the barcode, the side wall of the feed carrier plate 3 is set to be open or have a long hole to expose the barcode; this is content that is easy for technical personnel in the field to understand, and technical personnel in the field can set it according to their needs.

[0058] A nucleic acid extraction mechanism, arranged in conjunction with the feeding mechanism, for pre-treating the sample to be tested and extracting nucleic acid;

[0059] The nucleic acid extraction mechanism includes a first X-axis transmission unit arranged on the workbench 1, and one or more first guide blocks 8 are arranged in conjunction with the first X-axis transmission unit. One end of the first X-axis transmission unit is arranged toward the feeding mechanism, and a substitute head seat 9 cooperating with the pipetting mechanism and one or more extraction well plates 10 with built-in nucleic acid extraction reagents are arranged along the transmission direction of the first X-axis transmission unit, and a plurality of substitute heads are arranged in the substitute head seat 9; a first vertical motion unit is connected to cooperate with any of the first guide blocks 8, and a magnetic rod group cooperating with the extraction well plate 10 is arranged in conjunction with any of the first vertical motion units, and a magnetic source and a control motor are arranged in conjunction with the magnetic rod group; the first X-axis transmission unit, the first vertical motion unit, the magnetic source and the control motor are arranged in conjunction with the controller.

[0060] There is at least one extraction well plate 10, and the extraction well plate 10 includes multiple rows parallel to the transmission direction of the first X-axis transmission unit. The magnetic rod group is one or more columns of magnetic rods 11, and the number of magnetic rods 11 in each column is consistent with the number of rows of the extraction well plate 10; a waste frame (not shown in the figure) is provided on the workbench 1 that cooperates with the extraction well plate 10.

[0061] In the present invention, in the nucleic acid extraction mechanism, the pipetting mechanism will first obtain the substitute head from the substitute head seat 9, extract the sample to be tested from the sampling tube 5, and place it into the first grid of a row of the extraction well plate 10, and then the first guide block 8 moves along the first X-axis transmission unit to perform subsequent operations.

[0062] In the present invention, the first guide block 8 can be one or more, and the extraction orifice plate 10 can also be one or more and obviously parallel, and the number of magnetic bars 11 of the magnetic bar group is also related to the extraction orifice plate 10, so an implementation method is given:

[0063] Taking the case where there are two first guide blocks 8 and two extraction well plates 10 as an example, each first guide block 8 drives two groups of magnetic rods, and the extraction well plate 10 generally adopts a 96-well plate (12 columns and 8 rows). Each magnetic rod group includes 2 columns of magnetic rods 11, and each column of magnetic rods 11 includes 8 magnetic rods 11, which are the same number of rows as the extraction well plate 10.

[0064] Before working, the rod sleeve is pre-installed on each column of magnetic rods 11, and then the first guide block 8 moves along the direction of the first X-axis transmission unit, and moves to the top of the corresponding 96-well plate, and the first vertical motion unit starts to work. The magnetic rod 11 moves up and down based on the preset workflow to complete the lysis (generally within 10 minutes), magnetic absorption, washing, secondary washing, elution (pre-setting the elution solution in the 96-well plate), and removal of magnetic beads of the sample to be tested. The technology of extracting nucleic acid and the time / process nodes of making the magnetic rod 11 magnetic by the magnetic source are well known to those skilled in the art, and this process can be set and implemented by those skilled in the art;

[0065] Since each column of magnetic bars 11 only needs to use 6 wells in the actual application process of nucleic acid extraction, each column of magnetic bars 11 only needs to use half of the wells of the 96-well plate. In this case, the liquid transfer mechanism actually moves the sample to be detected to the wells of the 1st column and the 7th column of the 96-well plate, that is, one magnetic bar group can complete two groups of nucleic acid extraction operations at each 96-well plate, and the configuration of two magnetic bar groups and two extraction well plates 10 can complete four groups of nucleic acid extraction, which greatly increases the detection throughput; based on this, it is obvious that the two columns of magnetic bars 11 of each magnetic bar group correspond to the wells of the 1st column and the 7th column of the 96-well plate, and the spacing between them is also fixed;

[0066] When finished, drop the magnetic rod cover into the waste basket on workbench 1.

[0067] In the present invention, an implementation method is provided for the transmission unit of the nucleic acid extraction mechanism:

[0068] The first X-axis transmission unit includes a first motor 12-1 disposed on the workbench 1, and an output end of the first motor 12-1 is provided with a driving wheel 12-2, a driven wheel 12-3 and a synchronous belt 12-4 disposed outside the two. The synchronous belt 12-4 is arranged along the X-axis direction, and the first guide block 8 is sleeved outside the synchronous belt 12-4 to drive the first vertical motion unit actually integrated with it to move in the X-axis direction; at the same time, a slide rail 12-5 cooperating with the first guide block 8 is arranged on the workbench 1 to ensure smooth sliding;

[0069] For the first vertical motion unit, it includes a vertical plate 13-1 that is actually integrated with the first guide block 8, a lead screw nut pair 13-2 is provided in conjunction with the vertical plate 13-1 and cooperates with the output end of the second motor 13-3, the second motor 13-3 works and drives the magnetic rod group combined with the lead screw nut pair 13-2 to complete the vertical movement; in order to ensure the stability of the vertical movement, a slide rail 13-4 is also configured, which is easy for a person skilled in the art to understand;

[0070] In the present invention, at least a local temperature control module should be provided in conjunction with the extraction well plate 10 to ensure smooth lysis.

[0071] A construction system mechanism for integrating the reaction reagents and control samples obtained by extracting nucleic acid;

[0072] The construction system mechanism includes at least one construction carrier plate 14 and at least one sealing cover tray 16 loaded with a second sealing cover 15. The construction carrier plate 14 is provided with a control sample placed in a container and an empty container for placing a reaction reagent. The second sealing cover 15 is arranged in cooperation with a screw-cap transfer mechanism, the empty container is arranged in cooperation with a pipetting mechanism, and the container for placing the control sample and the reaction reagent or the construction carrier plate 14 is arranged in cooperation with the screw-cap transfer mechanism.

[0073] In the present invention, in order to ensure the accuracy of transfer and the stability of the extracted nucleic acid without mutual interference, a construction system mechanism is set up.

[0074] In the present invention, generally at least one empty container is pre-placed on the construction carrier 14, and the reagents processed by the nucleic acid extraction mechanism are transferred here by the pipetting mechanism and correspond one to one. After one pipetting is completed, the second sealing cap 15 is picked up by the screw cap transfer mechanism for sealing operation until the solution for extracting nucleic acid is pipetted at one or two groups of nucleic acid extraction mechanisms.

[0075] In the present invention, the control sample can be prefabricated in a container on the construction carrier 14. Of course, in order to improve the universality of the whole machine, a reagent kit 17 can also be set near the initial position of the pipetting mechanism. In this case, the reagent is extracted by the pipetting mechanism, pipetted into the container, and then sealed by the screw cap transfer mechanism.

[0076] In the present invention, the construction carrier 14 can be separated on a temporary bracket, so that the screw-cap transfer mechanism can directly extract the construction carrier 14 and all the control samples and reaction reagents thereon and place them into the amplification detection mechanism at the same time. The construction carrier 14 can also be directly set to have a fixed structure, that is, the screw-cap transfer mechanism picks up all the control samples and reaction reagents on the construction carrier 14 one by one and places them into the amplification detection mechanism.

[0077] an amplification detection mechanism, used to process the reaction reagents and control samples in the construction system mechanism and perform detection based on the processing results;

[0078] The amplification detection mechanism includes a track groove 18, and a plurality of air ducts 19 are sequentially arranged in conjunction with the track groove 18. The two ends of any of the air ducts 19 are respectively arranged to penetrate the outer side of the track groove 18, and a heating unit and a fan 20 are arranged in conjunction with any of the air ducts 19; a trolley 21 is arranged in conjunction with the track groove 18, and a detection carrier 23 is mounted on the front and rear ends of the top of any trolley 21 through pillars 22. The trolley 21, the pillars 22 and the detection carrier 23 constitute a sub-air duct 24, and the two sides of the sub-air duct 24 correspond to the two ends of the air duct 19 respectively, and a second X-axis transmission unit is arranged in conjunction with the trolley 21, and the detection carrier 23 is arranged in conjunction with the capping transfer mechanism; the heating unit, the fan 20 and the second X-axis transmission unit are arranged in conjunction with the controller.

[0079] Adjustable plug-in blocks 25 are provided in the track groove 18 to match the openings at both ends of any air duct 19 .

[0080] In the present invention, amplification and detection are an important part of nucleic acid detection.

[0081] In the present invention, an implementation mode is provided:

[0082] The control samples and reaction reagents on the construction carrier 14 are moved one by one or together to the corresponding positions on the detection carrier 23; the detection carrier 23 is set on the trolley 21, and the second X-axis transmission unit is used to transport the trolley 21 in the X-axis direction, and the track groove 18 is used to guide the transportation of the trolley 21;

[0083] The second X-axis transmission unit includes a third motor 26-1 disposed at the bottom of the workbench 1. The output end of the third motor 26-1 penetrates the workbench 1 and is disposed upward. A driving wheel (not shown in the figure), a driven wheel 26-2 and a synchronous belt 26-3 disposed outside the third motor 26-1 are provided to cooperate with the output end of the third motor 26-1. The synchronous belt 26-3 is disposed along the X-axis direction. The bottom of the trolley 21 is sleeved outside the synchronous belt 26-3 to drive the trolley 21 to move in the X-axis direction, specifically, to move to the position of the designated air duct 19 to heat and complete the amplification. Based on this, there is obviously a long hole on the workbench 1 for the bottom of the trolley 21 to pass through, which is easily understood by those skilled in the art.

[0084] Generally speaking, the amplification detection mechanism should include at least three air ducts 19, and the real-time temperature should be obtained by the sensor. Based on the real-time temperature feedback, the controller controls the heating unit and the fan 20 to operate together, so that the wind in the air duct 19 is maintained at a preset temperature. The real-time temperature is obtained by the sensor, which is a well-known technology for those skilled in the art, and those skilled in the art can set it according to their needs.

[0085] For each air duct 19, the air duct 19 is actually an open annular channel structure, and its two ends are respectively arranged on the outside of the track groove 18; when the trolley 21 is not at the air duct 19, the adjustable connector block 25 is in the track groove 18, serving as a bridge between the openings at both ends of the air duct 19, so that the hot air always runs between the air duct 19 and the corresponding adjustable connector block 25 to prevent the hot air from overflowing; when the trolley 21 is at the air duct 19, the adjustable connector block 25 is not in the track groove 18, and the sub-air duct 24 composed of the trolley 21, the support 22 and the detection carrier plate 23 is used as a bridge between the openings at both ends of the air duct 19, and the hot air is output from one end of the air duct 19 to the air duct 19, acts on the container to be processed at the sub-air duct 24 and heats it, and then returns to the air duct 19 from the other end of the air duct 19 to circulate to prevent the hot air from overflowing.

[0086] In the present invention, the adjustment of the adjustable connector block 25 can be set according to the needs of technical personnel in this field, and an implementation method is given here; generally speaking, the outer diameter of the adjustable connector block 25 is equal to the inner diameter of the air duct 19, so when the trolley 21 is about to reach the detection carrier plate 23 with the detection carrier plate 23, the fourth motor 25-1 is output, and the output end of the fourth motor 25-1 acts as a latch and cooperates with the socket 25-2 at the top of the adjustable connector block 25 to bring the adjustable connector block 25 back into the air duct 19. At this time, the wind circulation in the air duct 19 is not affected, and at the same time, it acts on the sub-air duct 24. When the trolley 21 leaves with the detection carrier plate 23, the fourth motor 25-1 reverses, and the output end of the fourth motor 25-1 pushes the adjustable connector block 25 out of the air duct 19, and the wind circulation is also not affected.

[0087] In the present invention, the amplified sample is detected by an amplification detection mechanism. For example, the container of the reagent to be detected can be set as a translucent tube, and a convex mirror structure can be embedded in it, so that the detection device 38 can be used to intuitively detect its internal state; of course, other detection means are also applicable; the detection device 38 is set by technical personnel in this field based on actual needs.

[0088] In the present invention, further, the detection carrier 23 and the trolley 21 can be separated into several spaces by the partition 27, which respectively correspond to the control samples and reaction reagents on the construction carrier 14. In this case, the screw cap transfer mechanism can place the control samples and reaction reagents one by one in each separated space, or the construction carrier 14 together with the control samples and reaction reagents can be directly placed on the trolley 21, that is, the construction carrier 14 can be equivalent to the detection carrier 23.

[0089] In the present invention, the heating unit and the fan 20 are generally integrated, which is a technology that is easily understood by those skilled in the art, and those skilled in the art can configure them themselves or purchase them from outside according to their needs.

[0090] A liquid transfer mechanism, used to cooperate in liquid transfer operations between the feeding mechanism and the nucleic acid extraction mechanism, and between the nucleic acid extraction mechanism and the construction system mechanism;

[0091] The liquid transfer mechanism includes a liquid transfer gun 28, a second vertical motion unit is provided in cooperation with the liquid transfer gun 28, a first Y-axis transmission unit is provided in the horizontal direction in cooperation with the second vertical motion unit, and the first Y-axis transmission unit is provided in cooperation with the third X-axis transmission unit;

[0092] The third X-axis transmission unit and the first Y-axis transmission unit are horizontally arranged above the workbench through a bracket 29; the pipette gun 28, the second vertical motion unit, the third X-axis transmission unit and the first Y-axis transmission unit are arranged in cooperation with a controller.

[0093] A capping transfer mechanism, used for opening and closing the caps of the sample to be tested at the feeding mechanism and the reaction reagent or the container where the reaction reagent and the control sample are located at the construction system mechanism, and transferring the container where the reaction reagent and the control sample are located in the construction system mechanism to the amplification detection mechanism;

[0094] The capping transfer mechanism includes a third vertical motion unit, a rotating motor 30 is provided at the bottom of the third vertical motion unit, a mechanical claw 31 is provided at the bottom of the rotating motor 30, and a clamping mechanism (not shown in the figure) is provided to cooperate with the mechanical claw 31; a second Y-axis transmission unit in the horizontal direction is provided on the upper part of the third vertical motion unit, and the second Y-axis transmission unit is arranged in conjunction with the third X-axis transmission unit; the second Y-axis transmission unit is horizontally arranged above the workbench 1 through a bracket 29; the third vertical motion unit, the rotating motor 30, the mechanical claw 31, the clamping mechanism and the second Y-axis transmission unit are arranged in conjunction with the controller.

[0095] In the present invention, it should be first explained that, since the range of motion of the pipetting mechanism and the screw-cap transfer mechanism is relatively large, in fact, brackets 29 are provided at the four corner points of the workbench 1 in the outer cover, and two guide bars 32 arranged along the X-axis and two guide plates 33 arranged along the Y-axis are provided based on the four brackets 29; wherein the guide bars 32 can generally be provided in the form of guide rails, and of course can also be provided in any structure that satisfies the connection of the guide plates 33 and can move.

[0096] In the present invention, for the liquid transfer mechanism, an implementation method is provided:

[0097] The third X-axis transmission unit and the first Y-axis transmission unit are generally different from the aforementioned first X-axis transmission unit and the second X-axis transmission unit, and can be arranged above the workbench 1 in the outer cover, and the stability is ensured by the bracket 29 and the transverse beam, and the stable operation of the circuit is ensured by the towing cable, so as to ensure the convenience of the arrangement;

[0098] The pipette gun 28 uses conventional adsorption pipetting technology to absorb and transfer the pre-treated sample to be tested;

[0099] The pipette gun 28 is arranged on the second vertical motion unit, and the second vertical motion unit includes a vertical plate 34-1, a fifth motor 34-2 is arranged in cooperation with the vertical plate 34-1, and a driving wheel 34-3, a driven wheel 34-4 and a synchronous belt 34-5 outside the driving wheel 34-3 and the driven wheel 34-4 are arranged in cooperation with the fifth motor 34-2, and the synchronous belt 34-5 drives the pipette gun 28 to rise and fall;

[0100] The vertical plate 34-1 cooperates with the first Y-axis transmission unit, and the first Y-axis transmission unit includes a guide plate 33 arranged along the Y-axis, and the two ends of the guide plate 33 cooperate and support the two guide bars 32 respectively, and the sixth motor 35-1 is arranged in cooperation with the guide plate 33, and the driving wheel 35-3, the driven wheel (not shown in the figure) and the synchronous belt 35-2 outside the driving wheel 35-3 and the driven wheel are arranged in cooperation with the sixth motor 35-1, and the synchronous belt 35-2 drives the movement of the vertical plate 34-1;

[0101] Similarly, the third X-axis transmission unit includes a rear guide bar 32 (the front guide bar 32 is only used as a limit) arranged along the X-axis, and a seventh motor 36-1 is arranged in conjunction with the rear guide bar 32. A driving wheel 36-2, a driven wheel (not shown in the figure) and a synchronous belt 36-3 outside the driving wheel 36-2 and the driven wheel are arranged in conjunction with the seventh motor 36-1. The guide plate 33 of the first Y-axis transmission unit corresponds to the rear guide bar 32 at one end that cooperates with the third X-axis transmission unit, and moves along the X-axis through the connection with the synchronous belt 36-3.

[0102] In the present invention, the screw cap transfer mechanism needs to complete the screw capping action of the sampling tube 5 at the loading mechanism, including opening and closing the cap, and also needs to at least complete the opening and closing of the container where the reaction reagent is located at the construction system mechanism, and needs to transfer the container where the reaction reagent and the control sample are located in the construction system mechanism to the amplification detection mechanism.

[0103] In the present invention, during the capping operation, after the capping transfer mechanism is in place, the third vertical motion unit moves downward, the mechanical claw 31 is in place and clamped, and the rotating motor 30 works to complete the action of opening or closing the cap; and during the transfer operation, after the capping transfer mechanism is in place, the third vertical motion unit moves downward, the mechanical claw 31 is in place and clamped, and the third vertical motion unit moves directly upward; the setting of the clamping mechanism is a conventional technology in the field, and those skilled in the art can set it by themselves, such as using a mechanism including but not limited to a clamping cylinder.

[0104] In the present invention, the third vertical motion unit includes a guide frame 37-1 that cooperates with the second Y-axis transmission unit. An eighth motor 37-2 is arranged on the top of the guide frame 37-1. The eighth motor 37-2 is connected to the lifting frame 37-4 through a screw nut sub-mechanism 37-3. A rotating motor 30 is arranged in the lifting frame 37-4, and a mechanical claw 31 is arranged at the bottom of the lifting frame 37-4.

[0105] In the present invention, the second Y-axis transmission unit and its cooperation with the third X-axis transmission unit can refer to the pipetting mechanism, that is, the second Y-axis transmission unit includes a substrate 39, on which a ninth motor 39-1, a driving wheel 39-3 corresponding to the ninth motor 39-1, a driven wheel (not shown in the figure) and a synchronous belt 39-2 are arranged to realize the movement of the guide frame 37-1 connected to the synchronous belt 39-2. At the same time, a tenth motor 40-1 is arranged to cooperate with the rear guide bar 32, and a driving wheel 40-2, a driven wheel (not shown in the figure) and a synchronous belt 40-3 outside the driving wheel 40-2 and the driven wheel are arranged to cooperate with the tenth motor 40-1. One end of the substrate 39 of the second Y-axis transmission unit that cooperates with the third X-axis transmission unit corresponds to the rear guide bar 32, and moves along the X-axis through the connection with the synchronous belt 40-3.

[0106] In the present invention, the first Y-axis transmission unit and the second Y-axis transmission unit share two guide bars 32 and guide rails (if any) arranged along the X-axis. Under this premise, the synchronous belt 36-3 and the synchronous belt 40-3 can be arranged in parallel under the rear guide bar 32.

[0107] The feeding mechanism, nucleic acid extraction mechanism, system construction mechanism, amplification detection mechanism, liquid transfer mechanism and capping transfer mechanism are arranged in coordination with a controller.

[0108] In the present invention, all mechanisms cooperate with the controller, and the controller needs to control the actions of all mechanisms. This can be accomplished by a PLC program, etc. This is content that is easy for technical personnel in this field to understand. Technical personnel in this field can set the controller based on needs on the premise of understanding the technology.

[0109] The working principle of the present invention is:

[0110] The sample to be tested is placed on the feeding carrier plate 3 and then placed on the workbench 1 in the outer cover through the feeding port, and the scanning mechanism 7 scans and binds the sample;

[0111] The capping transfer mechanism moves to any sample to be tested, opens the cover, and the liquid transfer mechanism simultaneously obtains the substitute head and the extraction liquid, and the capping transfer mechanism closes the cover; the liquid transfer mechanism places the sample to be tested into a preset position of the preset extraction well plate 10, and removes the substitute head; the above is repeated several times until nucleic acid extraction can be started;

[0112] In the nucleic acid extraction mechanism, the magnetic rod group cooperates with the extraction well plate 10 to complete the operations of lysis, magnetic absorption, washing, secondary washing, elution (elution solution is pre-placed in the 96-well plate), and removal of magnetic beads;

[0113] The capping transfer mechanism moves to the sealing cap tray 16 of the construction system mechanism, removes the cap, and at the same time, the liquid transfer mechanism obtains the substitute head, extracts the liquid, and transfers the liquid to the preset empty container. The capping transfer mechanism closes the cap, and the liquid extraction mechanism removes the substitute head and returns to the extraction well plate 10; repeat several times until the nucleic acid amplification test can be started;

[0114] This process can be carried out together with the construction of the carrier plate 14; the capping transfer mechanism transfers the reaction reagents and the control sample to the trolley 21, starts heating amplification, and then performs detection after completion. After the detection is completed, the capping transfer mechanism discards the reaction reagents and the control sample;

[0115] Complete a single test and continue or stop.

[0116] In the present invention, one implementation is given for all sliding mechanisms and transmission mechanisms, but in actual applications, any other alternative implementation can be adopted as long as the functional requirements are met.

Claims

1. An integrated fully automatic nucleic acid detection device, characterized in that: It includes a workbench and an outer cover arranged outside the workbench; the outer cover is equipped with: A feeding mechanism, used for placing samples to be tested; the feeding mechanism includes a plurality of feeding sockets, a feeding carrier is provided in cooperation with any of the feeding sockets, one or more insertion holes are provided in cooperation with any of the feeding carriers, a sampling tube with a built-in sample to be tested can be loaded and unloaded in cooperation with any of the insertion holes, a first sealing cover is provided in cooperation with each sampling tube, and the first sealing cover is provided in cooperation with a capping transfer mechanism; a scanning mechanism is provided on the workbench in cooperation with the feeding carrier; A nucleic acid extraction mechanism, arranged in conjunction with a feeding mechanism, for pre-treating a sample to be detected and extracting nucleic acid; the nucleic acid extraction mechanism comprises a first X-axis transmission unit arranged on a workbench, one or more first guide blocks are arranged in conjunction with the first X-axis transmission unit, one end of the first X-axis transmission unit is arranged toward the feeding mechanism, a substitute head seat for cooperating with a pipetting mechanism and one or more extraction well plates with built-in nucleic acid extraction reagents are arranged along the transmission direction of the first X-axis transmission unit, and a plurality of substitute heads are arranged in the substitute head seat; a first vertical motion unit is connected in conjunction with any of the first guide blocks, a magnetic rod group arranged in conjunction with the extraction well plate is arranged in conjunction with any of the first vertical motion units, and a magnetic source and a control motor are arranged in conjunction with the magnetic rod group; A construction system mechanism, used to construct the reaction reagent and the control sample obtained by extracting nucleic acid into one; the construction system mechanism includes at least one construction carrier and at least one sealing cover tray loaded with a second sealing cover, the construction carrier is provided with a control sample placed in a container and an empty container for placing the reaction reagent, the second sealing cover is arranged in cooperation with a capping transfer mechanism, the empty container is arranged in cooperation with a liquid transfer mechanism, and the container or the construction carrier for placing the control sample and the reaction reagent is arranged in cooperation with the capping transfer mechanism; A liquid transfer mechanism, used for performing liquid transfer operations between the feeding mechanism and the nucleic acid extraction mechanism, and between the nucleic acid extraction mechanism and the construction system mechanism; the liquid transfer mechanism includes a liquid transfer gun, a second vertical motion unit is provided in cooperation with the liquid transfer gun, a first Y-axis transmission unit is provided in the horizontal direction in cooperation with the second vertical motion unit, and the first Y-axis transmission unit is provided in cooperation with the third X-axis transmission unit; the third X-axis transmission unit and the first Y-axis transmission unit are horizontally arranged above the workbench through a bracket; An amplification detection mechanism, used for processing the reaction reagents and control samples in the construction system mechanism and performing detection based on the processing results; the amplification detection mechanism includes a track groove, and a plurality of air ducts are sequentially arranged in conjunction with the track groove, and the two ends of any of the air ducts are respectively penetrated and arranged on the outside of the track groove, and a heating unit and a fan are arranged in conjunction with any of the air ducts; a trolley is arranged in conjunction with the track groove, and a detection carrier is arranged at the front and rear ends of the top of any trolley through pillars, and the trolley, the pillars and the detection carrier constitute a sub-air duct, and the two sides of the sub-air duct correspond to the two ends of the air duct respectively, and a second X-axis transmission unit is arranged in conjunction with the trolley, and the detection carrier is arranged in conjunction with the capping transfer mechanism; A capping transfer mechanism is used to open and close the caps of the sample to be tested at the feeding mechanism and the reaction reagent or the container where the reaction reagent and the control sample are located at the construction system mechanism, and transfer the container where the reaction reagent and the control sample are located in the construction system mechanism to the amplification detection mechanism; the capping transfer mechanism includes a third vertical motion unit, a rotating motor is provided at the bottom of the third vertical motion unit, a mechanical claw is provided at the bottom of the rotating motor, and a clamping mechanism is provided in cooperation with the mechanical claw; a second Y-axis transmission unit in a horizontal direction is provided at the upper part of the third vertical motion unit, and the second Y-axis transmission unit is arranged in cooperation with the third X-axis transmission unit; the second Y-axis transmission unit is horizontally arranged above the workbench through a bracket; the scanning mechanism, the first X-axis transmission unit, the first vertical motion unit, the magnetic source and the control motor, the construction system mechanism, the heating unit, the fan, the second X-axis transmission unit, the pipette gun, the second vertical motion unit, the third X-axis transmission unit, the first Y-axis transmission unit, the third vertical motion unit, the rotating motor, the mechanical claw, the clamping mechanism and the second Y-axis transmission unit are arranged in cooperation with the controller.

2. An integrated fully automatic nucleic acid detection device according to claim 1, characterized in that: There is at least one extraction well plate, which includes multiple rows parallel to the transmission direction of the first X-axis transmission unit. The magnetic rod group includes one or more columns of magnetic rods, and the number of magnetic rods in each column is consistent with the number of rows of the extraction well plate. A waste frame is provided on the workbench that cooperates with the extraction well plate.

3. An integrated fully automatic nucleic acid detection device according to claim 1, characterized in that: The track groove is provided with adjustable plug-in blocks in cooperation with the openings at both ends of any air duct.

4. An integrated fully automatic nucleic acid detection device according to claim 1, characterized in that: A purple light lamp matched with the controller is arranged inside the outer cover.

Citation Information

Patent Citations

  • Integrated full-automatic nucleic acid detection equipment

    CN217677569U