CN215924938U

CN215924938U - Sample introduction device

Info

Publication number: CN215924938U
Application number: CN202120859194.6U
Authority: CN
Inventors: 徐伟; 杨健雄; 方剑秋; 钟春梅
Original assignee: Hangzhou Depth Bio Tech Co ltd
Current assignee: Hangzhou Depth Bio Tech Co ltd
Priority date: 2021-04-25
Filing date: 2021-04-25
Publication date: 2022-03-01
Anticipated expiration: 2031-04-25

Abstract

The utility model provides a sample introduction device which comprises a Y-direction movement module, an X-direction movement module and a micro-porous plate loading module. The temperature control module with a specific structure is arranged on the microporous plate loading module, so that accurate temperature control can be performed on a nucleic acid microporous plate sample, the temperature control module is suitable for both an immune microporous plate and a nucleic acid microporous plate, the two microporous plates can be conveniently alternately matched for use, and great convenience is brought to sample introduction detection of an immune sample and a nucleic acid sample in the actual detection process; the driving motors of the Y-direction motion module and the X-direction motion module are driven by a synchronous belt transmission mechanism, the displacement and the speed of the microporous plate loading module on the Y-direction motion module and the X-direction motion module can be controlled, so that the microporous plate loading module is in high-speed centrifugal rotation motion above the Y-direction motion module and the X-direction motion module, the centrifugal rotation motion frequency is ensured to be more than 10HZ, the coded microspheres in a sample can be better mixed, and the detection accuracy and the sensitivity of the flow-type fluorescence instrument are further ensured.

Description

Sample introduction device

Technical Field

The utility model belongs to the technical field of biochemical analyzers, particularly relates to a sample feeding device, and particularly relates to a sample feeding device of a flow type fluorescence analyzer.

Background

Flow fluorescence, also known as suspension array, liquid phase chip, etc., is a multi-index joint diagnostic technique developed gradually over 20 years. The technology takes fluorescent coding microspheres as a core, integrates multiple technologies such as a current-collecting principle, laser analysis, high-speed digital signal processing and the like, performs multi-index parallel analysis, and can accurately and quantitatively detect 2-500 different biomolecules at most simultaneously by one tube; the method has the characteristics of high flux, high sensitivity, parallel detection and the like; can be used for various and multi-field researches such as immunoassay, nucleic acid research, enzymology analysis, receptor, ligand recognition analysis and the like.

The flow type fluorescence technology takes microspheres as a carrier required by detection reaction, utilizes different fluorescence to dye and code the microspheres, detects different indexes, can perform qualitative and quantitative analysis on a specific target by identifying the fluorescence color of the microspheres, and is a new generation of molecular diagnosis platform of high-throughput biochip technology developed on the basis of microsphere coding, flow type principle, laser technology and high-speed digital signal processing technology. The flow type fluorescence technology platform can be used for immunodetection and nucleic acid detection. In the immunoassay process, a microplate such as an immunological 96-well plate is usually used as a sample container. In the nucleic acid detection process, a microplate such as a nucleic acid 96-well plate is usually used as a sample container.

In the process of detecting nucleic acid by utilizing a flow type fluorescence technology platform, because the overall dimensions of an immune 96-pore plate and a nucleic acid 96-pore plate are different, and the temperature is generally controlled in the process of detecting nucleic acid, the existing sample feeding device is generally required to be firstly loaded into an adapter device and then loaded into a loading module when the nucleic acid 96-pore plate is placed in the nucleic acid item detection process, so that the constant temperature control is realized, and the operation is more complicated.

In the sample injection preparation detection process of the flow-type fluorescence instrument, both immunoassay and nucleic acid detection, the time for detecting all samples in a 96-well plate is about 1 hour, and in the process, the microspheres in the 96-well plate are likely to have a sedimentation phenomenon, so that the 96-well plate samples need to be uniformly mixed, and the microspheres are ensured to be in a suspension state. The existing sample feeding device is generally realized by adopting rotary motion in the horizontal direction and linear motion (such as US2016/0097707A1), and the positioning precision of the rotary motion is poor; or two linear or three linear motions in the horizontal direction are adopted for realizing the motion, but the transmission mechanisms of the motion adopt screw rod transmission (such as CN107643417A), the cost is higher, and the high-speed linkage in two directions of the 96-pore plate X, Y cannot be controlled, so that the uniform mixing effect of the coding microspheres in a 96-pore plate sample is difficult to ensure.

The sampling device is suitable for a flow-type fluorescence instrument, can be used for a nucleic acid microporous plate and an immune microporous plate, is simple in structure and convenient to use, can better mix coding microspheres in a sample, and can better guarantee detection accuracy and sensitivity.

SUMMERY OF THE UTILITY MODEL

In order to solve the above problems, the present invention provides a sample introduction device, which includes a microplate loading module, a Y-direction movement module and an X-direction movement module. The lower side of the microporous plate loading module is provided with the temperature control module which adopts a specially-made structure, so that a centrifuge tube at the lower part of the nucleic acid microporous plate can be completely embedded into the temperature control module to realize better temperature control, and the upper side of the microporous plate loading module can be directly used for placing the immune microporous plate, thereby realizing more convenient alternate placement of the immune microporous plate and the nucleic acid microporous plate; the driving motors of the Y-direction motion module and the X-direction motion module are driven by a synchronous belt transmission mechanism, the displacement and the speed of the microporous plate loading module on the Y-direction motion module and the X-direction motion module can be controlled, so that the microporous plate loading module is in high-speed centrifugal rotation motion above the Y-direction motion module and the X-direction motion module, the centrifugal rotation motion frequency is ensured to be more than 10HZ, the coded microspheres in a sample can be better mixed, and the detection accuracy and the sensitivity of the flow-type fluorescence instrument are further ensured.

The utility model provides a sample feeding device, which comprises a Y-direction moving module and an X-direction moving module which are vertical to each other; the X direction and the Y direction are both parallel to the ground; and the Y-direction motion module and the X-direction motion module are both driven by a synchronous belt drive mechanism.

As the microspheres have certain mass and have a descending trend, a large number of researches prove that only when the microporous plate keeps the centrifugal rotation movement with uniform temperature and the centrifugal rotation frequency reaches more than 10HZ, the microspheres in the sample can be always kept in a very uniform and stable state, thereby ensuring the accuracy and the sensitivity of a detection result.

However, the existing sample feeding device generally adopts screw rod transmission for positioning movement of the microporous plate, so that the cost is high, the speed is low, and the microspheres in the sample are difficult to keep a very uniform and uniform mixing state.

The high-speed linkage of the Y-direction motion module and the X-direction motion module can be realized only by adopting a synchronous belt transmission mechanism.

Furthermore, the Y-direction movement module comprises a Y-direction guide shaft, a Y-direction synchronous belt, a Y-direction drag chain, a Y-direction driving motor and a Y-direction base, the Y-direction guide shaft, the Y-direction synchronous belt and the Y-direction drag chain are located above the Y-direction base, and the Y-direction driving motor is located below the Y-direction base.

Furthermore, the X-direction motion module comprises an X-direction guide shaft, an X-direction synchronous belt, an X-direction drag chain, an X-direction driving motor and an X-direction base, and the X-direction guide shaft, the X-direction synchronous belt, the X-direction drag chain and the X-direction driving motor are all positioned above the X-direction base; the Y-direction movement module is positioned above the X-direction movement module, and an X-direction linear bearing is also arranged below the Y-direction base.

The Y-direction movement module is mainly used for driving a micropore plate (generally a 96-pore plate) in the micropore plate loading module to do linear movement along the Y direction, and the Y-direction driving motor drives the micropore plate loading module (together with the 96-pore plate) to do linear movement along the guiding device (Y direction) through a synchronous belt transmission mechanism. The cables of the devices on the 96-hole plate loading module are led out through a Y-direction drag chain; the X-direction motion module is mainly used for driving the 96 pore plate to do linear motion along the X direction, and the Y-direction motion module (together with the micropore plate loading module and the 96 pore plate) is driven to do linear motion along the guide device (the X direction) by the X-direction drive motor through the synchronous belt transmission mechanism. And the cable of the device on the Y-direction motion module is led out through the X-direction drag chain.

Therefore, the driving motor of the Y-direction movement module drives the microplate loading module to move along the Y direction through the synchronous belt transmission mechanism, and simultaneously, the driving motor of the X-direction movement module drives the Y-direction movement module and the microplate loading module to move together along the X direction through the synchronous belt transmission mechanism; the micro-porous plate loading module can do high-speed centrifugal rotation movement above the Y-direction movement module and the X-direction movement module by respectively controlling the displacement and the speed of the micro-porous plate loading module on the Y-direction movement module and the X-direction movement module.

When the microplate loading module is positioned above the Y-direction movement module and the Y-direction movement module is positioned above the X-direction movement module, the driving motor of the Y-direction moving module drives the microporous plate loading module to move along the Y direction through the synchronous belt transmission mechanism, meanwhile, a driving motor of the X-direction movement module drives the Y-direction movement module and the micropore plate loading module to move together along the X direction through a synchronous belt transmission mechanism, and at the moment, the micropore plate can realize high-speed deflection by accurately controlling the displacement and the speed of the micropore plate loading module on the Y-direction movement module and the X-direction movement module, so that the samples at the inner hole positions of the micropore plate are uniformly mixed, the high-speed linkage of X, Y linear motion makes the micropore board do high-speed centrifugal rotary motion around a preset shaft, the frequency of centrifugal rotary motion reaches more than 10HZ, and the sufficient mixing of microballon in the sample is ensured, thereby improving detection accuracy and sensitivity.

Furthermore, the sample feeding mechanism also comprises a microplate loading module, and the microplate loading module is positioned above the Y-direction movement module; the microplate loading module comprises a frame for placing an immunization microplate and a temperature control module for placing a nucleic acid microplate, and the temperature control module is positioned at the lower side in the frame; when the nucleic acid microporous plate is placed, the centrifuge tube at the lower part of the nucleic acid microporous plate can be embedded into the temperature control module.

Furthermore, a Y-direction linear bearing is arranged below the microplate loading module.

The micro-porous plate comprises a common 96-pore plate or a common 384-pore plate and the like, and the specification and the size of the sample feeding device can be accurately adjusted according to different specifications and sizes of the micro-porous plate, so that the micro-porous plate can be matched with a specific micro-porous plate for use.

The appearance structure of present commonly used immunity micropore board and nucleic acid micropore board exists differently, compares the nucleic acid micropore board, and the immunity micropore board has more regular lower surface, does not have one row of unsettled convex centrifuging tube of arranging, and the upper surface of nucleic acid micropore board is level and smooth, and the centrifuging tube of downside is unsettled protrusion respectively, and the one row of arranging of centrifuging tube is arranged neatly, specifically gives details to see fig. 1 and fig. 2.

The microplate loading module contained in the sample introduction device provided by the utility model can be used for placing an immune microplate and a nucleic acid microplate; when the nucleic acid microporous plate is placed, the centrifugal tube at the lower part of the nucleic acid microporous plate can be inserted into the temperature control module.

The core of flow-through fluorescence technology is to encode microspheres (usually micron-sized polystyrene beads, such as polystyrene beads with a diameter of 5.6 microns) by fluorescence staining, and then covalently cross-link the differently colored microspheres with probes, antigens or antibodies directed against a particular test substance. When the method is used, the coding microspheres for different detection objects are mixed, then a trace of sample to be detected is added, and the target molecules and the molecules crosslinked on the surfaces of the microspheres in suspension are specifically combined.

In the nucleic acid detection process using the flow fluorescence technology platform, in order to reduce the non-specificity of the nucleic acid probe hybridization reaction and to measure more accurately, temperature control of the sample in the nucleic acid 96-well plate is usually required.

The microspheres have certain mass and have a descending trend, and the sedimentation of the microspheres easily causes errors in detection results.

The inventors have surprisingly found through a large number of experiments that when the temperature of the nucleic acid detection sample is controlled to be 45 ℃, the nonspecific reaction of the nucleic acid probe hybridization reaction is reduced, and the sedimentation of the ball is reduced to the maximum extent, so that the detection result is more accurate, and the detection accuracy and sensitivity are improved. The reason for this may be that when the sample is controlled at 45 ℃, the liquid in the sample tends to move upwards due to the temperature rise, and the microspheres are also provided with an upward force, so that the sedimentation speed is slowed down and the suspension state is easier to maintain. However, if the temperature continues to rise, the probe hybridization reaction of nucleic acid detection is affected, and the accuracy of the detection result is affected, so that the temperature of the nucleic acid detection sample is accurately controlled to be 45 ℃ as the optimal control temperature, and the detection sensitivity and accuracy of the flow-type fluorescence instrument can be greatly improved.

The sample introduction device provided by the utility model is designed according to the characteristics of the immune microporous plate and the nucleic acid microporous plate respectively, the immune microporous plate can be directly placed on the upper side of the sample introduction device, the temperature control module is arranged on the lower side of the sample introduction device, the nucleic acid microporous plate can be placed in an embedded mode, and the centrifugal tube on the lower side of the nucleic acid microporous plate is directly contacted with the temperature control module.

Further, the temperature control module comprises a heating base and a heating film; the heating film is positioned below the heating base and provides heat for the heating base.

The heating film is a PI heating film, and the constant temperature of a nucleic acid detection sample can be kept at 45 ℃ through a temperature sensor, so that the non-specificity of the nucleic acid probe hybridization reaction is reduced, and the accuracy and the sensitivity of a detection result are improved.

Further, the heating base comprises a heat conducting plate and a base frame, and the heat conducting plate is vertically placed in the base frame.

Furthermore, the number of the heat conducting plates is set according to the row number of the centrifuge tubes of the nucleic acid microplate; the distance between two adjacent heat-conducting plates is consistent with the distance between two adjacent centrifuge tubes of the nucleic acid micro-porous plate; the height of the heat conducting plate is consistent with that of a centrifugal tube of the nucleic acid micropore plate.

The loading module of the microporous plate and the size of the temperature control module are controlled, so that the loading module of the microporous plate is completely matched with the microporous plate in size and is convenient to use.

Furthermore, the heat conducting plates account for 9 rows, and when the nucleic acid 96-well plate is placed, a centrifugal tube at the lower part of the nucleic acid 96-well plate can be embedded into a gap between the 9 rows of heat conducting plates.

The heat-conducting plate is made of a material with excellent heat-conducting property, and is in direct contact with a centrifugal tube at the lower part of the nucleic acid micropore plate, so that accurate temperature control is ensured.

Further, the temperature control module also comprises a temperature sensor and a temperature protection switch; the temperature sensor and the temperature protection switch are positioned inside the heating base.

The temperature sensor can feed back the temperature condition in time to help accurate temperature control; the temperature protection switch can perform emergency hardware power-off when the heating film is out of control in an accident condition, so that the heating base is prevented from being overheated.

Further, the frame includes thermal-insulated apron and thermal-insulated base, thermal-insulated apron is located accuse temperature module top, and thermal-insulated base is located accuse temperature module below.

Furthermore, the peripheries above the heat-insulating cover plates are provided with limiting blocks, and when the immune microporous plates are placed, the immune microporous plates are placed in the space surrounded by the limiting blocks, so that the positions of the immune microporous plates can be limited.

Furthermore, a sensor is arranged above the heat insulation cover plate and used for sensing whether the microporous plate is in place or not; the heat insulation cover plate, the heat insulation base and the limiting block are made of heat insulation materials; the heat conducting plate is made of metal materials.

On the other hand, the utility model also provides a loading module of the sample feeding device, which comprises a microplate loading module, wherein the microplate loading module comprises a frame and a temperature control module, and the temperature control module is positioned at the lower side in the frame; the micropore plate loading module can be used for placing an immune micropore plate and a nucleic acid micropore plate; when the nucleic acid microporous plate is placed, the centrifuge tube at the lower part of the nucleic acid microporous plate can be embedded into the temperature control module.

The loading module of the sample introduction device provided by the utility model is designed according to the characteristics of the immune microporous plate and the nucleic acid microporous plate respectively, the immune microporous plate can be directly placed on the upper side of the loading module, the temperature control module is arranged on the lower side of the loading module, the nucleic acid microporous plate can be placed in an embedded mode, and the centrifugal tube on the lower side of the nucleic acid microporous plate is directly contacted with the temperature control module.

Further, the temperature control module comprises a heating base and a heating film, wherein the heating film is located below the heating base and provides heat for the heating base.

Furthermore, the row number of the heat-conducting plate is set according to the row number of centrifuge tubes of the nucleic acid microplate; the distance between two adjacent heat-conducting plates is consistent with the distance between two adjacent centrifuge tubes of the nucleic acid micro-porous plate; the height of the heat conducting plate is consistent with that of a centrifugal tube of the nucleic acid micropore plate.

Furthermore, a sensor is arranged above the heat insulation cover plate and used for sensing whether the micro-pore plate is in place or not.

Furthermore, the heat insulation cover plate, the heat insulation base and the limiting block are made of heat insulation materials; the heat conducting plate is made of metal materials.

The sample injection device provided by the utility model has the following beneficial effects:

1. the temperature control module adopts a special structure, so that a centrifuge tube at the lower part of the nucleic acid micropore plate can be completely embedded into the temperature control module to realize better temperature control;

2. the kit is suitable for both an immune microporous plate and a nucleic acid microporous plate, is convenient for the alternate matching use of the two microporous plates, and brings great convenience for the sample introduction detection of immune samples and nucleic acid samples in the actual detection process;

3. the Y-direction motion module and the X-direction motion module are both driven by a synchronous belt drive mechanism, the displacement and the speed of the microporous plate loading module on the Y-direction motion module and the X-direction motion module can be controlled, so that the microporous plate loading module is in high-speed centrifugal rotary motion above the Y-direction motion module and the X-direction motion module, the centrifugal rotary motion frequency is ensured to be more than 10HZ, the coded microspheres in a sample can be better mixed, and the detection accuracy and the sensitivity of the flow-type fluorescence instrument are further ensured.

4. Simple structure, convenient to use has improved operating efficiency.

Drawings

FIG. 1 is a schematic view of a loading module of a sample injection device in embodiment 1

FIG. 2 is a schematic diagram of the loading module structure of the sample injection device in embodiment 1

FIG. 3 is a schematic cross-sectional view of a 96-well plate loading module in example 1

FIG. 4 is a schematic view of the sample injection device in embodiment 2

FIG. 5 is a schematic diagram showing the split structure of the microplate loading module of the sample injection device in embodiment 2

FIGS. 6, 7 and 8 are schematic diagrams illustrating different positioning of the 96-well plate loading module 1 on the Y-direction moving module 2 and the X-direction moving module 3 in embodiment 1

FIG. 9 is a schematic diagram of the mixing manner of a 96-well plate sample in high-speed centrifugal rotation around a predetermined axis

Detailed Description

In the following, preferred embodiments of the present invention will be described in further detail with reference to the accompanying drawings, it being noted that the following embodiments are intended to facilitate understanding of the present invention without any limitation thereto. The raw materials and equipment used in the examples of the present invention are known products and obtained by purchasing commercially available products.

Embodiment 1 Loading Module of sample injection device provided by the utility model

The loading module of the sample introduction device provided by the embodiment is shown in fig. 1, 2 and 3. Fig. 1 is a schematic structural diagram of a loading module of a sample injection device, fig. 2 is a schematic structural diagram of a loading module of a sample injection device, and fig. 3 is a schematic structural diagram of a cross section of a 96-well plate loading module 1.

The loading module of the sample injection device provided by the embodiment can be used with an immunization 96-well plate and a nucleic acid 96-well plate. As shown in fig. 1 and 2, the loading module of the sample injection device provided in this embodiment is a 96-well plate loading module 1, which includes a frame 4 and a temperature control module 5, where the temperature control module 5 is located at a lower side inside the frame 4; the 96-well plate loading module 1 can be used for placing an immune 96-well plate and a nucleic acid 96-well plate; when the nucleic acid microporous plate is placed, the centrifugal tube at the lower part of the nucleic acid microporous plate can be embedded into the temperature control module 5. Fig. 5 shows a schematic cross-sectional structure diagram of the 96-well plate loading module 1, in which an immune 96-well plate and a nucleic acid 96-well plate can be respectively placed at different positions of the 96-well plate loading module 1, wherein the immune 96-well plate is placed at an upper position, and the nucleic acid 96-well plate is placed at a lower position because a centrifuge tube at the lower part can be embedded into the temperature control module 5.

Preferably, the temperature control module 5 comprises a heating base 6, a heating film 7 and a temperature sensor 8; the heating film 7 is a PI heating film, is positioned below the heating base 6 and provides heat for the heating base 6; the temperature sensor 8 is located inside the heating base 6. The constant temperature of the sample is kept at 45 ℃ by the temperature control module 5, so that the non-specificity of the hybridization reaction of the nucleic acid probe is reduced, and the accuracy and the sensitivity of the detection result are improved. Heating base 6 includes heat-conducting plate 9 and heat conduction base 16, heat-conducting plate 9 adopts the material preparation that the thermal conductivity is excellent, heat-conducting plate 9 in this embodiment adopts stainless steel material to make, it is vertical and one row arrange to put together, the row number of heat-conducting plate 9 is confirmed by the row number of the centrifuging tube of nucleic acid 96 orifice plate, the centrifuging tube of nucleic acid 96 orifice plate counts 8 rows altogether, consequently, heat-conducting plate 9 needs 9 rows altogether and just can be the even heat supply of every sample of nucleic acid 96 orifice plate, interval between two adjacent heat-conducting plates 9 is unanimous with two adjacent centrifuging tube intervals of nucleic acid 96 orifice plate, the height of heat-conducting plate 9 is highly unanimous with the centrifuging tube height of 96 orifice plate, thereby make heat-conducting plate 9 can with the centrifuging tube direct contact of nucleic acid 96 orifice plate lower part, ensure accurate accuse temperature. The size of the 96-pore plate loading module 1 and the size of the temperature control module 5 are controlled, so that the 96-pore plate loading module is completely matched with the size of the 96-pore plate, and the use is convenient. The heating base 6 is internally provided with a temperature protection switch 10, so that emergency hardware power-off can be carried out when an accident that the heating film is out of control occurs, and the heating base 6 is prevented from being overheated.

Preferably, the frame 4 comprises an insulating cover 11 and an insulating base 12, the insulating cover 11 being located above the temperature control module 5 and the insulating base 12 being located below the temperature control module 5. When the heat insulation cover plate 11 and the heat insulation base 12 are combined together, the temperature control module 5 is wrapped inside. The periphery above the heat insulation cover plate 11 is provided with a limiting block 13, and when the immune 96-pore plate is placed, the immune 96-pore plate is placed in a space surrounded by the limiting block 13, so that the position of the immune 96-pore plate can be limited. A sensor 14 is arranged above the heat insulation cover plate 11 and used for sensing whether the 96-hole plate is in place or not; the heat insulation cover plate 11, the heat insulation base 12 and the limiting block 13 are made of heat insulation materials.

Embodiment 2 sample introduction device provided by the utility model

The sample injection device of the flow-type fluorometer provided in this embodiment is shown in fig. 3 and 4. Wherein, fig. 3 is a schematic structural diagram of the sample introduction device, and fig. 4 is a schematic structural disassembly diagram of the microplate loading module of the sample introduction device.

The sample injection device provided by the embodiment can be matched with an immune 96-well plate and a nucleic acid 96-well plate for use. As shown in fig. 3 and 4, the sample injection device provided in this embodiment includes a 96-well plate loading module 1, a Y-direction moving module 2, and an X-direction moving module 3; the X direction and the Y direction are both parallel to the ground; the 96-hole plate loading module 1 is positioned above the Y-direction moving module 2, a Y-direction linear bearing 17 is arranged below the 96-hole plate loading module 1, and the Y-direction moving module 2 is positioned above the X-direction moving module 3. The Y-direction motion module 2 and the X-direction motion module 3 are both driven by a synchronous belt drive mechanism 15, and the high-speed linkage of the Y-direction motion module 2 and the X-direction motion module 3 is realized by adopting the synchronous belt drive mechanism.

The 96-well plate loading module 1 comprises a frame 4 and a temperature control module 5, wherein the temperature control module 5 is positioned at the lower side inside the frame 4; the 96-well plate loading module 1 can be used for placing an immune 96-well plate and a nucleic acid 96-well plate; when the nucleic acid microporous plate is placed, the centrifugal tube at the lower part of the nucleic acid microporous plate can be embedded into the temperature control module 5. Fig. 3 shows a schematic cross-sectional structure diagram of the 96-well plate loading module 1, in which an immune 96-well plate and a nucleic acid 96-well plate can be respectively placed at different positions of the 96-well plate loading module 1, wherein the placement position of the immune 96-well plate is above 29, and the nucleic acid 96-well plate is below 30 because a centrifuge tube at the lower part can be embedded into the temperature control module 5.

Preferably, the temperature control module 5 comprises a heating base 6, a heating film 7 and a temperature sensor 8; the heating film 7 is a PI heating film, is positioned below the heating base 6 and provides heat for the heating base 6; the temperature sensor 8 is located inside the heating base 6. The constant temperature of the sample is kept at 45 ℃ by the temperature control module 5, so that the non-specificity of the hybridization reaction of the nucleic acid probe is reduced, and the accuracy and the sensitivity of the detection result are improved. Heating base 6 includes heat-conducting plate 9 and heat conduction base 16, heat-conducting plate 9 adopts the material preparation that the thermal conductivity is excellent, heat-conducting plate 9 in this embodiment adopts stainless steel material to make, it is vertical and one row arrange to put together, the row number of heat-conducting plate 9 is confirmed by the row number of the centrifuging tube of nucleic acid 96 orifice plate, the centrifuging tube of nucleic acid 96 orifice plate counts 8 rows altogether, consequently, heat-conducting plate 9 needs 9 rows altogether can be for the even heat supply of every sample of nucleic acid 96 orifice plate, interval between two adjacent heat-conducting plates 9 is unanimous with two adjacent centrifuging tube intervals of nucleic acid 96 orifice plate, the height of heat-conducting plate 9 is highly unanimous with the centrifuging tube height of 96 orifice plate, thereby make heat-conducting plate 9 can with the centrifuging tube direct contact of nucleic acid 96 orifice plate lower part, ensure accurate accuse temperature (as figure 4). The size of the 96-pore plate loading module 1 and the size of the temperature control module 5 are controlled, so that the 96-pore plate loading module is completely matched with the size of the 96-pore plate, and the use is convenient.

Preferably, the heating base 6 is internally provided with a temperature protection switch 10, so that emergency hardware power-off can be performed when an accident that the heating film is out of control occurs, and the heating base 6 is prevented from overheating.

Preferably, the frame 4 comprises an insulating cover 11 and an insulating base 12, the insulating cover 11 being located above the temperature control module 5 and the insulating base 12 being located below the temperature control module 5. When the heat insulation cover plate 11 and the heat insulation base 12 are combined together, the temperature control module 5 is wrapped inside. The periphery above the heat insulation cover plate 11 is provided with a limiting block 13, and when the immunization 96-pore plate is placed, the immunization 96-pore plate is placed in a space surrounded by the limiting block 13, so that the position of the immunization 96-pore plate can be limited (as shown in fig. 5). A sensor 14 is arranged above the heat insulation cover plate 11 and used for sensing whether the 96-hole plate is in place or not; the heat insulation cover plate 11, the heat insulation base 12 and the limiting block 13 are made of heat insulation materials.

Preferably, the Y-direction moving module 2 includes a Y-direction guide shaft 18, a Y-direction timing belt 19, a Y-direction drag chain 20, a Y-direction driving motor 21 and a Y-direction base 22, wherein the Y-direction guide shaft 18, the Y-direction timing belt 19 and the Y-direction drag chain 20 are located above the Y-direction base 22, and the Y-direction driving motor 21 is located below the Y-direction base 22. The X-direction motion module 3 comprises an X-direction guide shaft 23, an X-direction synchronous belt 24, an X-direction drag chain 25, an X-direction driving motor 26 and an X-direction base 27, wherein the X-direction guide shaft 23, the X-direction synchronous belt 24, the X-direction drag chain 25 and the X-direction driving motor 26 are all positioned above the X-direction base 27; the Y-direction motion module 3 is positioned above the X-direction motion module 2, and an X-direction linear bearing 28 is also arranged below the Y-direction base 22.

The 96-well plate loading module 1 is positioned above the Y-direction moving module 2, and the Y-direction moving module 2 is positioned above the X-direction moving module 3. The driving motor 21 of the Y-direction movement module 2 drives the 96-pore plate loading module 1 to move along the Y direction through the synchronous belt transmission mechanism 15, and meanwhile, the driving motor of the X-direction movement module 3 drives the Y-direction movement module 2 and the 96-pore plate loading module 1 to move together along the X direction through the synchronous belt transmission mechanism 15; through controlling displacement and speed of 96 orifice plate loading module 1 in Y to motion module 2 and X to motion module 3 respectively, make 96 orifice plate loading module 1 do high-speed centrifugal rotary motion to motion module 2 and X to motion module 3 top at Y, thereby make the interior hole site sample mixing of 96 orifice plate, through X, Y linear motion's high-speed linkage promptly, make the micropore board do high-speed centrifugal rotary motion around a preset axle, centrifugal rotary motion's frequency reaches more than 10HZ, guarantee the abundant mixing of microballon in the sample, thereby improve detection accuracy and sensitivity. FIG. 6, FIG. 7,

Fig. 8 is a schematic diagram of different positioning of the 96-well plate loading module 1 on the Y-direction movement module 2 and the X-direction movement module 3, respectively.

FIG. 9 is a schematic diagram of the mixing mode of a 96-well plate sample in high-speed centrifugal rotation around a preset axis.

Example 3

The sample feeding device provided in embodiment 1 is adopted in this embodiment, and the difference is that the Y-direction movement module and the X-direction movement module both adopt screw transmission.

EXAMPLE 4 Effect of different Transmission modes and temperature control on sample measurement results

Coupling macromolecular fluorescent coding microspheres anti-TAG with the diameter of 4.6 microns, crosslinking 200nm europium (Eu) time-resolved fluorescent microspheres with streptavidin, amplifying by using an amplification primer to obtain an amplification product, carrying out enzyme digestion treatment on the amplification product by using SAP enzyme and Exo-I enzyme, carrying out primer extension reaction on the amplified product after enzyme digestion by using an extension primer, doping biotin-labeled dCTP in the reaction process, carrying out hybridization reaction on the nucleic acid gene sequence of the extension product and macromolecular fluorescent coding microspheres which are coated by corresponding anti-TAG sequences and have different colors, adding streptavidin-time-resolved fluorescent microspheres (or quantum dot fluorescent microspheres) for incubation, and respectively entering a flow type fluorescence instrument for detection through the sample feeding devices provided by the embodiment 2 and the embodiment 3, wherein the temperature control modules of the embodiment 2 and the embodiment 3 respectively control the sample temperature to be 40 DEG, 45. and (2) conveying the reacted microsphere mixed liquid and sheath liquid to a flow chamber during detection at 50 ℃, sequentially passing through a capillary detection area of the flow chamber, exciting by a first laser, collecting a fluorescence signal by a fluorescence detector of the first laser, exciting by a second laser at the same time, wherein the excitation wavelength is 340nm, adjusting the delay time to be 5 nanoseconds to 8000 milliseconds, starting a time-resolved fluorescence detection unit of the second laser to record and collect the fluorescence signal, and analyzing and processing the collected signal by a data collection system. The results of 5 consecutive measurements are shown in table 1,

TABLE 1 influence of different drive modes on the results of sample testing

As can be seen from Table 1, when screw transmission is adopted, the highest centrifugal rotation frequency of a 96-well plate sample can only reach 2HZ, and at the moment, the fluorescent microsphere detection results are obviously different for five times continuously, so that the detection error is large; when the synchronous belt transmission mechanism is adopted, the centrifugal rotation frequency of the 96-pore plate sample reaches 10HZ, the microsphere mixing effect in the sample is better, the detection results are very close after five times of continuous detection, and therefore high-speed linkage can be realized when the synchronous belt transmission mechanism is adopted, the centrifugal rotation frequency reaches 10HZ, and the detection accuracy and the sensitivity of the 96-pore plate sample can be obviously improved.

When a synchronous belt transmission mechanism is adopted for comparison, the accuracy of detection results is greatly different under the condition that the temperature is controlled at 40 ℃, 45 ℃ and 50 ℃, when the temperature is controlled at 45 ℃, the detection results are very close to each other five times, the error is very small, and when the temperature is controlled at 40 ℃ or 50 ℃, the error is obviously increased; similarly, when the screw drive is adopted, the accuracy of the detection result is greatly different when the temperature is controlled at 40 ℃, 45 ℃ and 50 ℃ respectively, when the temperature is controlled at 45 ℃, the error of the five detection results is 9.11, and when the temperature is controlled at 40 ℃ or 50 ℃, the error is obviously increased and reaches 19.35 and 21.08 respectively, so that the detection result of the convection type fluorescence instrument with the temperature controlled at 45 ℃ also has the obvious effect of improving the detection accuracy, the reason may be that when the sample is controlled at 45 ℃, the liquid in the sample tends to move upwards due to the temperature increase, and meanwhile, the microspheres are provided with upward force, so that the sedimentation speed is slowed down, and the suspension state is more easily maintained. However, if the temperature continues to rise, the probe hybridization reaction of nucleic acid detection is affected, and the accuracy of the detection result is affected, so that the temperature of the nucleic acid detection sample is accurately controlled to be 45 ℃ as the optimal control temperature, and the detection sensitivity and accuracy of the flow-type fluorescence instrument can be greatly improved.

Although the present invention is disclosed above, the present invention is not limited thereto. For example, the application range of the medicine can be expanded. Various changes and modifications may be effected therein by one skilled in the art without departing from the spirit and scope of the utility model as defined in the appended claims.

Claims

1. A sample introduction device is characterized by comprising a Y-direction movement module and an X-direction movement module which are vertical to each other; the X direction and the Y direction are both parallel to the ground; the Y-direction motion module and the X-direction motion module are both driven by a synchronous belt drive mechanism; the device also comprises a microplate loading module, wherein the microplate loading module is positioned above the Y-direction movement module; the microplate loading module comprises a frame for placing an immunization microplate and a temperature control module for placing a nucleic acid microplate, and the temperature control module is positioned at the lower side in the frame; when the nucleic acid microporous plate is placed, the centrifuge tube at the lower part of the nucleic acid microporous plate can be embedded into the temperature control module.

2. The sample introduction device according to claim 1, wherein the Y-direction movement module comprises a Y-direction guide shaft, a Y-direction synchronous belt, a Y-direction drag chain, a Y-direction driving motor and a Y-direction base, the Y-direction guide shaft, the Y-direction synchronous belt and the Y-direction drag chain are located above the Y-direction base, and the Y-direction driving motor is located below the Y-direction base.

3. The sample introduction device according to claim 2, wherein the X-direction movement module comprises an X-direction guide shaft, an X-direction synchronous belt, an X-direction drag chain, an X-direction driving motor and an X-direction base, and the X-direction guide shaft, the X-direction synchronous belt, the X-direction drag chain and the X-direction driving motor are all located above the X-direction base; the Y-direction movement module is positioned above the X-direction movement module, and an X-direction linear bearing is also arranged below the Y-direction base.

4. The sample introduction device according to claim 3, wherein the temperature control module comprises a heating base, a heating membrane and a temperature sensor; the heating film is positioned below the heating base and provides heat for the heating base; the temperature sensor is located inside the heating base.

5. The sample introduction device according to claim 4, wherein the heating base comprises a heat conducting plate and a base frame, the heat conducting plate being vertically disposed within the base frame; and a temperature protection switch is also arranged in the heating base.

6. The sample introduction device according to claim 5, wherein the number of the heat conducting plates is set according to the row number of the centrifuge tubes of the nucleic acid microplate; the distance between two adjacent heat-conducting plates is consistent with the distance between two adjacent centrifuge tubes of the nucleic acid micro-porous plate; the height of the heat conducting plate is consistent with that of a centrifugal tube of the nucleic acid micropore plate.

7. The sample introduction device according to claim 6, wherein the frame comprises an insulating cover plate and an insulating base, the insulating cover plate is located above the temperature control module, and the insulating base is located below the temperature control module.

8. The sample introduction device according to claim 7, wherein the heat insulation cover plate is provided with a limiting block on the periphery thereof, and when an immunization microplate is placed, the immunization microplate is placed in a space surrounded by the limiting block, so that the position of the immunization microplate can be limited.

9. The sample introduction device according to claim 8, wherein a sensor is further provided above the heat insulation cover plate for sensing whether the micro-porous plate is in place; the heat insulation cover plate, the heat insulation base and the limiting block are made of heat insulation materials; the heat conducting plate is made of metal materials.