CN110806491B - Full-automatic POCT multiple detection liquid phase chip system - Google Patents

Full-automatic POCT multiple detection liquid phase chip system Download PDF

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Publication number
CN110806491B
CN110806491B CN201911118125.3A CN201911118125A CN110806491B CN 110806491 B CN110806491 B CN 110806491B CN 201911118125 A CN201911118125 A CN 201911118125A CN 110806491 B CN110806491 B CN 110806491B
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magnetic separation
guide rail
assembly
magnetic
sample
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CN110806491A (en
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张兴鹏
常乐
韦润聃
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Chengdu Yilexin Biotechnology Co ltd
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Chengdu Yilexin Biotechnology Co ltd
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    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
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    • G01N21/6402—Atomic fluorescence; Laser induced fluorescence
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    • G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
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    • G01N35/1004—Cleaning sample transfer devices
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    • G01N35/1065—Multiple transfer devices
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    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
    • G01N2021/6439—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" with indicators, stains, dyes, tags, labels, marks
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Abstract

The utility model relates to a full automatization luminous field specifically is to relate to a full automatization POCT multiple detection liquid phase chip system, and it is including the mounting bracket, install application of sample arm, magnetic separation subassembly, optical path system and main control board on the mounting bracket respectively, optical path system and main control board are located the top of mounting bracket, and optical path system includes first laser instrument and the first mirror holder that corresponds with it, second laser instrument and the second mirror holder that corresponds with it, and second mirror holder is provided with the flow chamber by, is provided with two cemented lens between flow chamber and the second mirror holder, is provided with first side direction fluorescence collection subassembly, second side direction fluorescence collection subassembly and forward scattered light collection subassembly around the flow chamber. The optical path system adopts a modularized design, and can be flexibly configured according to the requirements of clients. The fluorescence collection system can adopt a single-chip aspheric focusing lens with large numerical aperture, and has simple and reliable structure and high stability.

Description

Full-automatic POCT multiple detection liquid phase chip system
Technical Field
The application relates to the field of full-automatic chemiluminescence, in particular to a full-automatic POCT (point of care testing) multiple detection liquid-phase chip system.
Background
Large-scale chemiluminescence has been widely used in clinic due to its high degree of automation and high sensitivity, and has been the mainstream methodology for immunodetection in recent years. However, since each test can only detect one index, the detection flux is much lower than that of a biochemical analyzer, the speed measurement of the main stream is generally 200T/H, and the highest speed of the biochemical analyzer can reach 2000T/H, from the perspective of detection projects, the immune detection index is much greater than the biochemical detection index, so that the requirement on high flux of immunity is a necessary trend, and for a single index detection system, the detection flux is very difficult to improve, because chemiluminescence involves magnetic separation cleaning, the step is the biggest bottleneck, and the detection flux is difficult to improve greatly. However, if the detection is multi-index detection, the detection flux can be increased to 20 times of the original detection flux under the assumption that 20 indexes can be detected at a time, and the speed of the detection is faster than that of the existing biochemical analyzer, so that the multi-immunity detection is an inevitable trend of clinical immunity development. At present, the main platform for multi-index detection is a Luminex liquid-phase chip system, and the perspective life is based on the platform to push out a full-automatic liquid-phase chip system, but the cost is high, the volume is huge, and the method is not suitable for middle and small hospitals. The existing POCT is basically based on the chromatography principle, the detection sensitivity is not enough, the precision is not high, and individual manufacturers release the chemiluminescence of the POCT, but the magnetic separation efficiency is not high, the degree of automation is low, and the detection flux is small.
Disclosure of Invention
In order to solve the problems in the prior art, a full-automatic POCT multiple detection liquid-phase chip system which can realize multiple detection, supports single reagent encapsulation, has small instrument size and full automation, does not need manual sample adding, has no carrying pollution and has higher detection efficiency is provided.
In order to achieve the technical effects, the specific scheme of the application is as follows:
a full-automatic POCT multiple detection liquid phase chip system is characterized in that: the device comprises a mounting frame, wherein a sample loading arm, a sample pipe rack, a TIP box assembly, a constant temperature control bin, a TIP head unloading frame, a magnetic separation assembly, a light path system and a main control board are respectively arranged on the mounting frame, the constant temperature control bin comprises a first reaction bin and a second reaction bin, the magnetic separation assembly comprises a first magnetic separation assembly and a second magnetic separation assembly, the first magnetic separation assembly is correspondingly arranged above the first reaction bin, and the second magnetic separation assembly is correspondingly arranged above the second reaction bin;
the optical path system and the main control board are positioned at the top of the mounting frame, the optical path system comprises a first laser and a first reflector bracket corresponding to the first laser, a second laser and a second reflector bracket corresponding to the second laser, a flow chamber is arranged beside the second reflector bracket, a double-gluing lens is arranged between the flow chamber and the second reflector bracket, and a first lateral fluorescence collecting assembly, a second lateral fluorescence collecting assembly and a forward scattering light collecting assembly are arranged around the flow chamber.
Further, the first laser is a 525nm laser, the second laser is a 638nm laser, or a 525nm laser; the first reflector frame and the second reflector frame are 45-degree reflector frames and two beam combining lenses; the double-cemented lens comprises a precision optical one-dimensional adjusting frame and a double-cemented lens.
Further, the first lateral fluorescence collection assembly and the second lateral fluorescence collection assembly each comprise a monolithic aspheric focusing lens, a dichroic mirror, an optical filter and a detector, wherein the aperture of the monolithic aspheric focusing lens is larger than 0.5; the forward scattered light collection assembly includes a lens, an optical filter, and a photodiode detector.
Further, the liquid path system comprises two plunger pumps, an electromagnetic valve, a sheath liquid filter and a diaphragm pump, wherein the two plunger pumps suck samples into the flow chamber through pressure difference, stable sheath liquid flow is provided, the samples flow through a detection area of the flow chamber under the wrapping of the sheath liquid, the electromagnetic valve is used for controlling the on-off of the liquid, the filter is used for filtering impurities in the sheath liquid, and the diaphragm pump is used for supplying cleaning liquid on the outer wall of the sample needle.
To the magnetic separation assembly, further, first magnetic separation assembly is the same with second magnetic separation assembly structure, first magnetic separation assembly and second magnetic separation assembly all include main lead screw motor and the guide rail slider connecting block that links to each other with it, guide rail slider connecting block cup joints on linear guide, guide rail slider connecting block is connected with bar magnet motor guide rail installing support, be fixed with bar magnet lead screw motor on the bar magnet motor guide rail installing support, be connected with the bar magnet installation piece on the bar magnet motor guide rail installing support, the bar magnet installation piece is connected with a plurality of bars magnet, bar magnet motor guide rail installing support bottom has the loading head that is used for loading disposable magnetic separation cover.
For the first magnetic separation component and the second magnetic separation component, further, the main screw motor is connected with the guide rail slide block through a T-shaped screw nut; the linear guide rail is positioned on the motor guide rail mounting bracket, and the main screw motor is mounted on the motor guide rail mounting bracket.
Aiming at the first magnetic separation component and the second magnetic separation component, further, the magnetic rod installation block is sleeved with at least one optical axis guide rail, and the bottom of the magnetic rod installation block is connected with a plurality of magnetic rods; the bottom of the motor guide rail mounting bracket is provided with a reflective photoelectric detection switch for detecting whether the disposable magnetic separation sleeve is normally loaded or unloaded, and the reflective photoelectric detection switch is arranged beside the disposable magnetic separation sleeve.
For the application of sample arm, further, the application of sample arm includes X axle and Z axle, installs the plunger pump on the Z axle motor slider of application of sample arm.
For the sample pipe support, further, the sample pipe support adopts crawler-type transmission structure.
Further to the TIP-box assembly, the TIP-box assembly moves in the Y-axis direction.
The first reaction bin and the second reaction bin are independent two constant temperature control bins, and can execute Y-axis direction movement.
For the TIP head unloading frame, further, the TIP head unloading frame is arranged above the constant temperature control bin, and a waste bin is arranged right below the constant temperature control bin and is in a drawer type structure.
Further, the device also comprises a flow type sample loading assembly and a light path support, wherein the light path support is positioned right above the flow type sample loading assembly, the light path support is connected with the light path system through a shockproof rubber seat, the flow type sample loading assembly is positioned above the two reaction bins, and the X-axis direction and the Z-axis direction movement are executed below the light path support.
Further, the intelligent instrument also comprises a control computer, an electric control assembly and an external electric interface, wherein the control computer is an industrial personal computer with a touch function, and the control computer is arranged on a front frame of the instrument shell. The electric control assembly comprises a switching power supply, a main control board, a motor driving board and a temperature control board, and the external electric interface comprises an alternating current power supply three-in-one switch, a USB and a network port.
Be provided with the handle on the reagent strip that matches with the system, be provided with two-dimensional code, magnetic separation cover and disposable rupture of membranes head by the handle, be provided with first diluent hole, second diluent hole, magnetic bead hole, first reagent hole, second reagent hole, third reagent hole, first washing liquid hole, second washing liquid hole, third washing liquid hole, fourth washing liquid hole and detection hole side by side on the reagent strip.
The application has the advantages that:
1. the optical path system adopts a modularized design, and can be flexibly configured according to the requirements of clients. The fluorescent collection system can adopt a single-chip aspheric focusing lens with large numerical aperture, and has simple and reliable structure and high stability; the SiPM is adopted for detection in side scattered light and fluorescence detection, so that the size is small, the cost is low, the quantum efficiency is high, and the PMT is even better than PMT in certain wavelengths, so that a higher signal-to-noise ratio can be obtained; meanwhile, due to the semiconductor technology, the consistency between chips is far better than that of PMT, the stability of the system is further improved, and the inter-table difference between different instruments is reduced.
2. The liquid path system is driven by the plunger pump, so that the precision is high, the service life is long, and the maintenance cost is low; the sample adopts a differential pressure sample loading mode, so that dead volume is avoided, and carrying pollution is less; specifically, two 2 plunger pumps can be adopted, one is used for supplying sheath liquid, one is used for extracting waste liquid from the outlet end of the flow chamber, when the extraction speed is higher than the sheath liquid supply speed, stable negative pressure can be generated between the 2 plunger pumps, accurate sample suction can be achieved by precisely controlling the speed of the plunger pumps, and the sample does not have any electromagnetic valve before entering the flow chamber.
3. The application adopts mutually independent first reaction bin and second reaction bin, and both can independently operate, have realized binary channels and have detected, can improve detection efficiency, compatible emergency call demand. The application adopts two active magnetic separation technologies of a first magnetic separation component and a second magnetic separation component, utilizes the cooperation of a disposable magnetic separation sleeve and a magnetic rod to directly adsorb magnetic beads at the bottom of the magnetic separation sleeve, achieves the effect of active magnetic separation, improves the cleaning efficiency, and reduces the background of a system.
4. The utility model provides a bar magnet motor drive magnetic separation cover in first magnetic separation subassembly and the second magnetic separation subassembly shake the mixing about lasting in the reaction process, has accelerated immune reaction process, has shortened reaction time, has avoided the subsidence of magnetic bead, has realized whole mixing, has promoted reaction efficiency, has avoided the magnetic bead subsidence, has improved the homogeneity of reaction.
5. The PMT reading device drives a rotating mechanism through the steering engine, the rotating mechanism can be provided with the shutter and the attenuation sheet with the transmittance of 1%, and the luminous value before attenuation and the luminous value after attenuation can be respectively read through switching, so that the dynamic range of detection is greatly improved, the reagent consumption is saved, and the detection efficiency is improved.
6. The sample injection system adopts crawler-type sample injection, so that compared with the traditional disc-type sample injection, the space is greatly saved, and meanwhile, the sample can be supported to be inserted at any time, so that the emergency call requirement is better supported. The disposable conductive TIP head can be adopted, and is provided with liquid level detection and air pressure detection, so that full-automatic sample feeding is realized, whole blood is supported, and no pollution is caused. At present, POCT chemiluminescence of domestic factories is manually sample-adding, has complicated steps, is easy to introduce human errors, and is not suitable for emergency treatment; the single reagent strip can be adopted, and all consumables are packaged in the reagent strip, so that the manual operation flow is simplified.
Drawings
Fig. 1 is a schematic structural diagram of the present application.
FIG. 2 is a schematic diagram of a matched reagent strip structure according to the present application.
FIG. 3 is a schematic view of the magnetic separation component of the present application.
Fig. 4 is a schematic view of the optical path structure of the present application.
Fig. 5 is a schematic view of the liquid path structure of the present application.
In the accompanying drawings: the device comprises a 1-sample adding arm, a 2-plunger pump, a 3-master control computer, a 4-sample pipe rack, a 5-TIP box assembly, a 6-first reaction chamber, a 7-second reaction chamber, a 8-waste chamber, a 9-TIP head unloading frame, a 10-reaction disc cable drag chain, a 11-first magnetic separation assembly, a 12-second magnetic separation assembly, a 13-light path support, a 14-external electric interface, a 15-flow sample adding assembly, a 16-light path system, a 17-master control board, a 20-handle, a 21-two-dimensional code, a 22-magnetic separation sleeve, a 23-disposable rupture head, a 24-first diluent hole, a 25-second diluent hole, a 26-magnetic bead hole, a 27-first reagent hole, a 28-second reagent hole, a 29-third reagent hole, a 30-first cleaning liquid hole, a 31-second cleaning liquid hole, a 32-third cleaning liquid hole, a 33-fourth cleaning liquid hole and a 34-detection hole.
101-a main screw motor, 102-a main motor guide rail mounting bracket, 103-a T-shaped screw nut, 104-a guide rail slide block connecting block, 105-a linear guide rail, 106-a reflective photoelectric detection switch, 107-a disposable magnetic separation sleeve, 108-a magnetic rod screw motor, 109-a magnetic rod motor guide rail mounting bracket, 110-a magnetic rod mounting block, 111-an optical axis guide rail and 112-a magnetic rod.
301-first laser, 302-second laser, 303-first mirror mount, 304-second mirror mount, 305-doublet lens, 306-first lateral fluorescence collection assembly, 307-second lateral fluorescence collection assembly, 308-flow cell, 309-forward scattered light collection assembly.
201-electromagnetic valve, 202-sheath liquid filter, 203-first plunger pump, 204-diaphragm pump.
Detailed Description
Example 1
As shown in fig. 1, a full-automatic POCT multiple detection liquid phase chip system includes a mounting frame, on which a sample loading arm 1, a sample pipe rack 4, a TIP box assembly 5, a constant temperature control bin, a TIP head unloading rack 9, a magnetic separation assembly, an optical path system 16 and a main control board 17 are respectively mounted, wherein the constant temperature control bin includes a first reaction bin 6 and a second reaction bin 7, the magnetic separation assembly includes a first magnetic separation assembly 11 and a second magnetic separation assembly 12, a first magnetic separation assembly 11 is correspondingly disposed above the first reaction bin 6, and a second magnetic separation assembly 12 is correspondingly disposed above the second reaction bin 7;
as shown in fig. 4, the optical path system 16 and the main control board 17 are located at the top of the mounting frame, the optical path system 16 includes a first laser 301 and a first reflector bracket 303 corresponding to the first laser, a second laser 302 and a second reflector bracket 304 corresponding to the first laser, a flow chamber 308 is provided beside the second reflector bracket 304, a double-cemented lens 305 is provided between the flow chamber 308 and the second reflector bracket 304, and a first lateral fluorescence collection component 306, a second lateral fluorescence collection component 307 and a forward scattering light collection component are provided around the flow chamber 308. When the microspheres in the sample pass through the detection area of the flow chamber 308 one by one, the microspheres are excited by the laser focused on the detection area to generate scattered light, coded fluorescence and fluorescence to be detected, the scattered light, the coded fluorescence and the fluorescence to be detected are respectively received by a scattered light detector and a fluorescence detector, and after being sampled by a high-speed ADC, the data are transmitted to the main control computer 3 for calculating a final result.
The optical path system 16 of the present application adopts a modular design, and can be flexibly configured according to the needs of customers. The fluorescent collection system can adopt a single-chip aspheric focusing lens with large numerical aperture, and has simple and reliable structure and high stability; the SiPM is adopted for detection in side scattered light and fluorescence detection, so that the size is small, the cost is low, the quantum efficiency is high, and the PMT is even better than PMT in certain wavelengths, so that a higher signal-to-noise ratio can be obtained; meanwhile, due to the semiconductor technology, the consistency between chips is far better than that of PMT, the stability of the system is further improved, and the inter-table difference between different instruments is reduced.
Example 2
As shown in fig. 1, the full-automatic POCT multiple detection liquid-phase chip system comprises a mounting frame, wherein a sample loading arm 1, a sample pipe rack 4, a TIP box assembly 5, a constant temperature control bin, a TIP head unloading frame 9, a magnetic separation assembly, a light path system 16 and a main control board 17 are respectively mounted on the mounting frame, the constant temperature control bin comprises a first reaction bin 6 and a second reaction bin 7, the magnetic separation assembly comprises a first magnetic separation assembly 11 and a second magnetic separation assembly 12, a first magnetic separation assembly 11 is correspondingly arranged above the first reaction bin 6, and a second magnetic separation assembly 12 is correspondingly arranged above the second reaction bin 7;
the light path system 16 and the main control board 17 are located at the top of the mounting frame, the light path system 16 comprises a first laser 301 and a first reflector bracket 303 corresponding to the first laser, a second laser 302 and a second reflector bracket 304 corresponding to the second laser, a flow chamber 308 is arranged beside the second reflector bracket 304, a double-cemented lens 305 is arranged between the flow chamber 308 and the second reflector bracket 304, and a first lateral fluorescence collection assembly 306, a second lateral fluorescence collection assembly 307 and a forward scattering light collection assembly are arranged around the flow chamber 308. When the microspheres in the sample pass through the detection area of the flow chamber 308 one by one, the microspheres are excited by the laser focused on the detection area to generate scattered light, coded fluorescence and fluorescence to be detected, the scattered light, the coded fluorescence and the fluorescence to be detected are respectively received by a scattered light detector and a fluorescence detector, and after being sampled by a high-speed ADC, the data are transmitted to the main control computer 3 for calculating a final result.
The first laser 301 is a 525nm laser, the second laser 302 is a 638nm laser, or a 525nm laser; the first reflector 303 and the second reflector 304 are 45-degree reflectors and two beam combining lenses; the doublet 305 includes a precision optical one-dimensional adjustment frame and a piece of doublet 305. The first lateral fluorescence collection assembly 306 and the second lateral fluorescence collection assembly 307 each comprise a monolithic aspheric focusing lens, dichroic mirror, optical filter, and detector having an aperture greater than 0.5; the optical filter and the dichroic mirror can be flexibly configured according to the coding requirement of the fluorescent channel; the forward scattered light collection assembly includes a lens, an optical filter, and a photodiode detector.
In addition to the above structure, the system further comprises a liquid path system, the liquid path system comprises two plunger pumps 2, an electromagnetic valve 201, a sheath liquid filter 202 and a diaphragm pump 204, the two plunger pumps 2 suck the sample into the flow chamber 308 through pressure difference, meanwhile, stable sheath liquid flow is provided, the sample flows through a detection area of the flow chamber 308 under the wrapping of the sheath liquid, the electromagnetic valve 201 is used for controlling on-off of the liquid, the filter is used for filtering impurities in the sheath liquid, the flow chamber 308 is prevented from being blocked, and the diaphragm pump 204 is used for supplying cleaning liquid on the outer wall of the sample needle.
The first magnetic separation assembly 11 and the second magnetic separation assembly 12 are identical in structure, the first magnetic separation assembly 11 and the second magnetic separation assembly 12 both comprise a main screw motor 101 and a guide rail slider connecting block 104 connected with the main screw motor, the guide rail slider connecting block 104 is sleeved on a linear guide rail 105, the guide rail slider connecting block 104 is connected with a magnetic rod motor guide rail mounting bracket 109, a magnetic rod screw motor 108 is fixed on the magnetic rod motor guide rail mounting bracket 109, a magnetic rod mounting block 110 is connected on the magnetic rod motor guide rail mounting bracket 109, the magnetic rod mounting block 110 is connected with a plurality of magnetic rods 112, and a loading head for loading the disposable magnetic separation sleeve 107 is arranged at the bottom of the magnetic rod motor guide rail mounting bracket 109. The loading head is loaded by friction and the disposable magnetic separation sheath 107 may be loaded with one or more. The first magnetic separation component 11 and the second magnetic separation component are respectively driven by a main screw motor 101 and a magnetic rod screw motor 108, and the two motors only do Z-axis motion for executing magnetic bead adsorption, magnetic bead transfer and magnetic bead mixing.
The magnetic separation assembly adopts an active magnetic separation mode, adopts a disposable magnetic separation sleeve 107, adsorbs magnetic beads from solution to the outer wall of the disposable magnetic separation sleeve 107 through matching with a magnetic rod 112, transfers the magnetic beads to other reaction hole sites, withdraws the magnetic rod 112, and resuspents the magnetic beads through up-and-down oscillation of the disposable magnetic separation sleeve 107, so that the magnetic adsorption time is short and only about 10-15S is needed. The traditional magnetic separation mode adopts passive magnetic separation, a magnetic field is outside a reaction cup, liquid is pumped by a waste liquid pump after long-time absorption, and other solutions are added for re-suspension and uniform mixing, so that the absorption efficiency is low, the absorption time is long, and the absorption time is generally more than 45S; in addition, in the whole reaction process, the magnetic rod 112 arm can continuously vibrate up and down, so that the settlement of the magnetic beads is prevented, the reaction is more sufficient, and the continuous vibration accelerates the movement and the contact probability of molecules, thereby accelerating the whole immune reaction and shortening the reaction time.
The main screw motor 101 is connected with the guide rail slide block through a T-shaped screw nut 103; the linear guide 105 is located on a motor guide mounting bracket on which the main lead screw motor 101 is mounted.
The magnetic rod mounting block 110 is sleeved with at least one optical axis guide rail 111, and the bottom of the magnetic rod mounting block 110 is connected with a plurality of magnetic rods 112; the bottom of the motor guide rail mounting bracket is provided with a reflective photoelectric detection switch 106 for detecting whether the disposable magnetic separation sleeve 107 is normally loaded or unloaded, and the reflective photoelectric detection switch 106 is arranged beside the disposable magnetic separation sleeve.
The sample adding arm 1 comprises an X axis and a Z axis, and is used for executing reciprocating motion of the X axis and the Z axis, a plunger pump 2 is arranged on a Z axis motor sliding block of the sample adding arm 1, and the plunger pump 2 is matched with the sample adding arm 1 to finish functions of TIP head loading, liquid level detection, air pressure detection, sample suction, sample addition, TIP head unloading and the like.
The sample pipe rack 4 adopts a crawler-type transmission structure. The sample tube rack 4 is used for loading the sample tube and driving the sample tube to rotate and transmit to the position where the sample needs to be added, thereby greatly saving the volume of the instrument and supporting the insertion of the sample at any time.
The TIP-box assembly 5 moves in the Y-axis direction. The TIP box assembly 5 is used to load TIP head consumables and drive the TIP box to run to the position where the TIP head needs to be loaded.
The first reaction bin 6 and the second reaction bin 7 are two independent constant temperature control bins, and can both execute Y-axis direction movement. The disposable reagent strips can be respectively loaded into 2 reaction bins and used for completing all immune reactions, cleaning and reading after sample addition, and sequentially completing the processes of penetrating and loading, penetrating a membrane, adding samples, diluting, loading the magnetic separation sleeve 22, transferring magnetic beads for multiple times, cleaning the magnetic beads, transferring the magnetic beads to a substrate reading and the like according to the process of programming.
The TIP head unloading frame 9 is arranged above the constant temperature control cabin, the waste cabin 8 is arranged right below the constant temperature control cabin, and the waste cabin 8 is in a drawer type structure. The film-penetrating head, the TIP head, the magnetic separation sleeve 22, etc. are automatically unloaded and dropped to the waste bin 8, wherein the used TIP head is automatically unloaded and dropped to the waste bin 8 by an unloading mechanism mounted on the TIP head unloading frame 9.
Besides the structure, the system further comprises a flow type sample loading assembly 15 and a light path support 13, wherein the light path support 13 is positioned right above the flow type sample loading assembly 15 and used for bearing the whole light path system 16, the light path support 13 is connected with the light path system 16 through a shockproof rubber seat and used for reducing the influence of external vibration on detection results, the flow type sample loading assembly 15 is positioned above two reaction bins, the light path support 13 is positioned below the reaction bins, and the X-axis direction and Z-axis direction movement is executed and used for detecting liquid to be detected in the reagent strip detection holes 34 after reaction is completed.
In addition to the above structure, the system also includes a control computer, an electrical control assembly and an external electrical interface 14, the control computer is an industrial personal computer with touch function, and the control computer is mounted on the front frame of the instrument housing. The control computer is used for controlling the whole instrument and providing a man-machine interaction interface. The electrical control assembly comprises a switching power supply, a main control board 17, a motor driving board and a temperature control board, and the external electrical interface 14 comprises an alternating current power supply three-in-one switch, a USB and a network port. The external electrical interface 14 is used for accessing the mains supply and connecting with USB peripherals, networks and the like; the electric control assembly is used for supplying power to the system and controlling the whole machine, the control system is communicated with the computer through USB, and the main control board 17 is communicated with other control modules through CAN buses.
The reagent strip matched with the system is provided with a handle 20, a two-dimensional code 21, a magnetic separation sleeve 22 and a disposable membrane breaking head 23 are arranged beside the handle 20, and a first diluent hole 24, a second diluent hole 25, a magnetic bead hole 26, a first reagent hole 27, a second reagent hole 28, a third reagent hole 29, a first cleaning liquid hole 30, a second cleaning liquid hole 31, a third cleaning liquid hole 32, a fourth cleaning liquid hole 33 and a detection hole 34 are arranged on the reagent strip side by side. The handle 20 is used for a user to take and put a reagent strip, the two-dimensional code 21 contains information such as a reagent code number, a lot number and the like, the automatic identification of a system is used, the disposable magnetic separation sleeve 107 is used for executing magnetic bead adsorption, uniform mixing and transfer, the disposable membrane breaking head 23 is used for breaking through an aluminum membrane seal of each hole of the reagent strip, the first diluent hole 24 and the second diluent hole 25 are used for executing dilution of a sample, the magnetic bead hole 26 is used for packaging magnetic bead components of a reagent, the first reagent hole 27, the second reagent hole 28 and the third reagent hole 29 are used for packaging other reagent components, the first cleaning liquid hole 30, the second cleaning liquid hole 31, the third cleaning liquid hole 32 and the fourth cleaning liquid hole 33 are used for executing cleaning of the magnetic beads, the detection hole 34 is used for re-suspending the magnetic beads, and detection is executed.
The optical path system 16 adopts a modularized design, and can be flexibly configured according to the requirements of customers. The fluorescent collection system can adopt a single-chip aspheric focusing lens with large numerical aperture, and has simple and reliable structure and high stability; the SiPM is adopted for detection in side scattered light and fluorescence detection, so that the size is small, the cost is low, the quantum efficiency is high, and the PMT is even better than PMT in certain wavelengths, so that a higher signal-to-noise ratio can be obtained; meanwhile, due to the semiconductor technology, the consistency between chips is far better than that of PMT, the stability of the system is further improved, and the inter-table difference between different instruments is reduced.
The liquid path system is driven by the plunger pump 2, so that the precision is high, the service life is long, and the maintenance cost is low; the sample adopts a differential pressure sample loading mode, so that dead volume is avoided, and carrying pollution is less; specifically, two 2 plunger pumps 2, one for supplying sheath fluid and one for extracting waste fluid from the outlet end of the flow chamber 308, and the extraction speed is higher than the sheath fluid supply speed, stable negative pressure can be generated between the 2 plunger pumps 2, accurate sample suction can be achieved by precisely controlling the speed of the plunger pumps 2, and the sample does not have any solenoid valve 201 before entering the flow chamber 308.
The first reaction bin 6 and the second reaction bin 7 which are mutually independent can independently operate, so that double-channel detection is realized, the detection efficiency can be improved, and the emergency requirements are met. The application adopts two active magnetic separation technologies of the first magnetic separation component 11 and the second magnetic separation component 12, utilizes the cooperation of the disposable magnetic separation sleeve 107 and the magnetic rod 112, directly adsorbs magnetic beads at the bottom of the magnetic separation sleeve 22, achieves the effect of active magnetic separation, improves the cleaning efficiency, and reduces the background of a system.
The magnetic rod 112 motor in the first magnetic separation component 11 and the second magnetic separation component 12 drives the magnetic separation sleeve 22 to vibrate and mix up and down continuously in the reaction process, so that the immune reaction process is accelerated, the reaction time is shortened, the sedimentation of magnetic beads is avoided, the whole-course mixing is realized, the reaction efficiency is improved, the sedimentation of the magnetic beads is avoided, and the uniformity of the reaction is improved.
The PMT reading device drives a rotating mechanism through the steering engine, and the rotating mechanism can be provided with a shutter and an attenuation sheet with the transmittance of 1%, and can respectively read the luminous value before attenuation and the luminous value after attenuation through switching, so that the dynamic range of detection is greatly improved, the reagent consumption is saved, and the detection efficiency is improved.
The sample injection system adopts crawler-type sample injection, so that compared with the traditional disc-type sample injection, the space is greatly saved, and meanwhile, the sample can be supported to be inserted at any time, so that the emergency call requirement is better supported. The disposable conductive TIP head can be adopted, and is provided with liquid level detection and air pressure detection, so that full-automatic sample feeding is realized, whole blood is supported, and no pollution is caused. At present, POCT chemiluminescence of domestic factories is manually sample-adding, has complicated steps, is easy to introduce human errors, and is not suitable for emergency treatment; the single reagent strip can be adopted, and all consumables are packaged in the reagent strip, so that the manual operation flow is simplified.

Claims (6)

1. A full-automatic POCT multiple detection liquid phase chip system is characterized in that: the device comprises a mounting frame, wherein a sample loading arm (1), a sample pipe rack (4), a TIP box assembly (5), a constant temperature control bin, a TIP head unloading frame (9), a magnetic separation assembly, a light path system (16) and a main control board (17) are respectively mounted on the mounting frame, the constant temperature control bin comprises a first reaction bin (6) and a second reaction bin (7), the magnetic separation assembly comprises a first magnetic separation assembly (11) and a second magnetic separation assembly (12), the first magnetic separation assembly (11) is correspondingly arranged above the first reaction bin (6), and the second magnetic separation assembly (12) is correspondingly arranged above the second reaction bin (7);
the sample adding arm (1) comprises an X axis and a Z axis, and a plunger pump (2) is arranged on a Z axis motor sliding block of the sample adding arm (1); the sample pipe rack (4) adopts a crawler-type transmission structure; the TIP box assembly (5) moves along the Y-axis direction; the first reaction bin (6) and the second reaction bin (7) are two independent constant temperature control bins, and can both execute Y-axis direction movement; the TIP head unloading frame (9) is arranged above the constant temperature control bin, a waste bin (8) is arranged right below the constant temperature control bin, and the waste bin (8) is in a drawer type structure;
the optical path system (16) and the main control board (17) are positioned at the top of the mounting frame, the optical path system (16) comprises a first laser (301) and a first reflector bracket (303) corresponding to the first laser, a second laser (302) and a second reflector bracket (304) corresponding to the second laser, a flow chamber (308) is arranged beside the second reflector bracket (304), a double-gluing lens (305) is arranged between the flow chamber (308) and the second reflector bracket (304), and a first lateral fluorescence collection assembly (306), a second lateral fluorescence collection assembly (307) and a forward scattering light collection assembly are arranged around the flow chamber (308);
the liquid path system comprises two plunger pumps (2), an electromagnetic valve (201), a sheath liquid filter (202) and a diaphragm pump (204), wherein the two plunger pumps (2) suck a sample into a flow chamber (308) through pressure difference, stable sheath liquid flow is provided, the sample flows through a detection area of the flow chamber (308) under the wrapping of the sheath liquid, the electromagnetic valve (201) is used for controlling the on-off of the liquid, the filter is used for filtering impurities in the sheath liquid, and the diaphragm pump (204) is used for supplying cleaning liquid on the outer wall of a sample needle;
the first magnetic separation assembly (11) and the second magnetic separation assembly (12) are identical in structure, the first magnetic separation assembly (11) and the second magnetic separation assembly (12) comprise a main screw motor (101) and a guide rail sliding block connecting block (104) connected with the main screw motor, the guide rail sliding block connecting block (104) is sleeved on a linear guide rail (105), the guide rail sliding block connecting block (104) is connected with a magnetic rod motor guide rail mounting bracket (109), a magnetic rod screw motor (108) is fixed on the magnetic rod motor guide rail mounting bracket (109), a magnetic rod mounting block (110) is connected on the magnetic rod motor guide rail mounting bracket (109), a plurality of magnetic rods (112) are connected to the magnetic rod mounting block (110), and a loading head for loading the disposable magnetic separation sleeve (107) is arranged at the bottom of the magnetic rod motor guide rail mounting bracket (109).
2. The fully automated POCT multiplexed detection liquid phase chip system of claim 1, wherein: the first laser (301) is a 525nm laser, the second laser (302) is a 638nm laser, or a 525nm laser; the first reflector frame (303) and the second reflector frame (304) are 45-degree reflector frames and two beam combining lenses; the doublet (305) comprises a precision optical one-dimensional adjustment frame and a piece of doublet (305).
3. The fully automated POCT multiplexed detection liquid phase chip system of claim 2, wherein: the first lateral fluorescence collection assembly (306) and the second lateral fluorescence collection assembly (307) each comprise a monolithic aspheric focusing lens with a numerical aperture greater than 0.5, a dichroic mirror, an optical filter, and a detector; the forward scattered light collection assembly includes a lens, an optical filter, and a photodiode detector.
4. The fully automated POCT multiplexed detection liquid phase chip system of claim 1, wherein: the main screw rod motor (101) is connected with the guide rail slide block through a T-shaped screw rod nut (103); the linear guide rail (105) is positioned on the motor guide rail mounting bracket, and the main screw motor (101) is mounted on the motor guide rail mounting bracket.
5. The fully automated POCT multiplexed assay liquid chip system of claim 4, wherein: the magnetic rod mounting block (110) is sleeved with at least one optical axis guide rail (111), and the bottom of the magnetic rod mounting block (110) is connected with a plurality of magnetic rods (112); the bottom of the motor guide rail mounting bracket is provided with a reflective photoelectric detection switch (106) for detecting whether the disposable magnetic separation sleeve (107) is normally loaded or unloaded, and the reflective photoelectric detection switch (106) is arranged beside the disposable magnetic separation sleeve.
6. The fully automated POCT multiplexed detection liquid phase chip system of claim 1, wherein: the device further comprises a flow type sample loading assembly (15) and a light path support (13), wherein the light path support (13) is positioned right above the flow type sample loading assembly (15), the light path support (13) is connected with a light path system (16) through a shockproof rubber seat, the flow type sample loading assembly (15) is positioned above the two reaction bins, and the light path support (13) is arranged below to execute X-axis direction and Z-axis direction movement.
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